Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
Tong LiHui-Min XingHai-Dong QianQiao GaoSheng-Lan XuHua MaZai-Long Chi
Quality is the core feature of cultivated land. In the face of deteriorating cultivated land quality and growing food demand, improving cultivated land quality is a top priority for guaranteeing the sustainable use of resources and national food security. Cultivated land quality in the new era can be considered in four dimensions: suitability, contiguity, resistance and ecological stress. Cultivated land suitability in China shows a decreasing trend from east to west, cultivated land contiguity is high in the north-east and low in the south-west. In terms of cultivated land resistance, the number of strongly and weakly resistant cropping fields is small and spatially clustered. Cultivated land with ecological stress is mainly located in the northern region. Based on the current situation of cultivated land quality and the strategic needs of national high-quality development, China's future goals for improving cultivated land quality include four aspects: promoting the sustainable use of resources,improving the economic benefits of farming, coping with extreme meteorological disasters and meeting the transition of the food system.Against the backdrop of a volatile international environment and high domestic demand for food, China should guarantee a safe supply of staples, a stable supply of animal feed and a moderate supply of high-nutrient food. In the future, China should create three major food production spaces: highstandard, low-to medium-yield, and marginal cultivated land. China urgently needs to construct three paths to implement the goal of improving cultivated land quality, namely the development of high-standard cultivated land with the core of spatial optimization, resilience enhancement and scale coupling,the transformation of low-to medium-yield cultivated land with the core of obstacle elimination, tenure adjustment, ecological sustainable, and the conservation development of marginal cultivated land with a focus on sustainable use.
BACKGROUND Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms(MiNENs)are rare malignancies affecting the pancreas.The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components,each constituting 30%or more of the tumor volume.Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination.A well-differentiated neuroendocrine tumor(NET)component is rarely reported in MiNENs.CASE SUMMARY Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas.The two tumors show distinct histology and significant differentiation discrepancy(poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET),and also present as metastases in separate lymph nodes.Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma,but no genetic alterations in the NET,suggesting divergent origins for these two components.Although tumors like this meet the diagnostic criteria for MiNEN,clinicians often find the diagnosis and staging confusing and impractical for clinical management.CONCLUSION Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.
Molecular weaving is a powerful approach to make molecularly woven materials that have showed unprecedented characteristics and properties intrinsically distinct to those of non-woven materials.We here report a facile and efficient approach for the synthesis of 2D woven supramolecular polymers by differentiated self-assembly through orthogonal noncovalent interactions.Importantly,the difference in binding strength of two orthogonal noncovalent interactions can be used to control the process of molecular weaving.Consequently,single-layered 2D woven supramolecular polymers were synthesized and fully characterized by various techniques.This study demonstrates a controllable method for molecular weaving,and will significantly hasten the development of molecularly woven materials.
This paper expounds upon a novel target detection methodology distinguished by its elevated discriminatory efficacy,specifically tailored for environments characterized by markedly low luminance levels.Conventional methodologies struggle with the challenges posed by luminosity fluctuations,especially in settings characterized by diminished radiance,further exacerbated by the utilization of suboptimal imaging instrumentation.The envisioned approach mandates a departure from the conventional YOLOX model,which exhibits inadequacies in mitigating these challenges.To enhance the efficacy of this approach in low-light conditions,the dehazing algorithm undergoes refinement,effecting a discerning regulation of the transmission rate at the pixel level,reducing it to values below 0.5,thereby resulting in an augmentation of image contrast.Subsequently,the coiflet wavelet transform is employed to discern and isolate high-discriminatory attributes by dismantling low-frequency image attributes and extracting high-frequency attributes across divergent axes.The utilization of CycleGAN serves to elevate the features of low-light imagery across an array of stylistic variances.Advanced computational methodologies are then employed to amalgamate and conflate intricate attributes originating from images characterized by distinct stylistic orientations,thereby augmenting the model’s erudition potential.Empirical validation conducted on the PASCAL VOC and MS COCO 2017 datasets substantiates pronounced advancements.The refined low-light enhancement algorithm yields a discernible 5.9%augmentation in the target detection evaluation index when compared to the original imagery.Mean Average Precision(mAP)undergoes enhancements of 9.45%and 0.052%in low-light visual renditions relative to conventional YOLOX outcomes.The envisaged approach presents a myriad of advantages over prevailing benchmark methodologies in the realm of target detection within environments marked by an acute scarcity of luminosity.
Climate change and rapid urbanization pose significant challenges to the conservation and management of agricultural heritage systems,including decline in agricultural land,loss of labor,and ecosystem degradation.Although existing studies have proposed general strategies with theoretical guidance and specific strategies for particular systems to promote the conservation of agricultural heritage systems,there remains a large knowledge gap in effective and differentiated management strategies at the regional level.This is especially so in China because of the clear regional differences in the natural and socioeconomic conditions of the widely distributed China Nationally Important Agricultural Heritage Systems(China-NIAHS).In this study,we integrated multi-source data and spatial analysis to reveal the distribution characteristics of existing China-NIAHS and proposed differentiated management strategies.Results show that there are four clustering distribution zones of China-NIAHS,i.e.,the northwest clustering zone west of the Heihe-Tengchong Line(ZoneⅠ),the clustering belt with‘Northeast-Hebei-Shandong'as core(ZoneⅡ),the Yangtze River Delta clustering zone(ZoneⅢ),and the Hunan-Chongqing-Yunnan-Guizhou clustering zone(ZoneⅣ).Different management strategies are proposed for the China-NIAHS in each clustering zone.Specifically,ZoneⅠshould focus on maintaining their ecological functions and services,while ZoneⅡshould aim for livelihood supply,sustainable resource use,and ecological protection.For ZoneⅢ,rapid urbanization could become a positive driving force for China-NIAHS conservation through sustainable tourism and reasonable urban zoning.ZoneⅣshould emphasize the mutual support between characteristic product development and the brand effect of the China-NIAHS.These findings will help establish regional and targeted management strategies for China-NIAHS and provide a reference for the conservation of agricultural heritage systems in other countries.
Kawasaki disease(KD)is a disorder of immune responses.The prevalence of KD among 100,000 children aged 0-4 years was 71.9-110.0 in China,170.9-194.9 in Korea,and 18.1-21.3 in the USA[1].The most severe complication of KD is coronary artery lesions(CALs),including coronary dilatation and coronary aneurysms,which may even lead to myocardial ischemia,myocardial infarction,and sudden death.
Background:The incidence of well-differentiated gastric neuroendocrine tumors(G-NET)is increasing annually,and while they have a good prognosis and low mortality rate,their high recurrence rate makes treatment options controversial.This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET.Methods:We performed a multicenter,retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union Medical College Hospital,Yantai Yuhuangding Hospital,and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023.Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis.Results:After a median follow-up of 49 months,the overall recurrence rate among the 94 G-NET patients was 14%(13/94).The recurrence rates of endoscopic mucosal resection(EMR),endoscopic submucosal dissection(ESD),somatostatin analog(SSA)therapy,and surgery were 43%(6/14),10%(5/49),5%(1/22),and 11%(1/9),respectively.Post-treatment recurrence rates were significantly different(P=0.014)among four treatments(EMR,ESD,SSA,and surgery),and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group.From the second month onward,SSA therapy considerably reduced the gastrin levels from 1081.0(571.5,2472.8)pg/mL to 461.5(255.3,795.0)pg/mL(Z=-3.521,P<0.001).Both chi-squared test and multifactorial logistic regression analysis suggested that among the clinicopathological parameters studied,only the pre-treatment gastrin level(P=0.018 and 0.005)and the type of treatment(P=0.014 and 0.017)were significantly associated with G-NET recurrence.Conclusions:Individualized treatment strategies may reduce the risk of relapse after G-NET treatment.Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions,and it substantially decreases the incidence of post-treatment recurrence.
Ju HuangHuimin LiuDekun YangTianming XuJing WangJingnan Li
