Induced pluripotent stem cell-derived extracellular vesicles overexpressing SFPQ protect retinal Müller cells against hypoxia-induced injury.

Splicing factor proline/glutamine-rich (SFPQ) is expressed in induced pluripotent stem cells (iPSCs), which are reported to orchestrate hypoxic injury responses and release extracellular vesicles (EVs). Therefore, this study sought to explore the role of iPSC-derived EVs carrying SFPQ in hypoxia-induced injury to retinal Müller cells. We induced oxygen-glucose deprivation/reoxygenation (OGD/R) in Müller cells. SFPQ was overexpressed or knocked down in iPSCs, from which EVs were extracted. Müller cells were co-cultured with EVs, and the results indicated that SFPQ protein was transferred into retinal Müller cells by iPSC-derived EVs. We identified an interaction of SFPQ with HDAC1 in retinal Müller cells. Specifically, SFPQ recruited HDAC1 to downregulate HIF-2α by regulating its acetylation. The in vitro studies suggested that iPSC-derived EVs, SFPQ or HDAC1 overexpression, or HIF-2α silencing diminished cell injury and apoptosis but elevated proliferation in retinal Müller cells. The in vivo studies indicated that iPSC-derived EVs containing SFPQ curtailed apoptosis of retinal Müller cells, thus alleviating retinal ischemia/reperfusion (I/R) injury of rat model. Taken together, iPSC-derived EVs containing SFPQ upregulated HDAC1 to attenuate OGD/R-induced Müller cell injury via downregulation of HIF-2α.

Formulating win-win management plans in Protected Areas (PAs) based on Key Ecosystem services (KESs): An application in the Shennongjia National Park, China.

Exploring win-win approaches to ecological conservation and community development goals is a central issue in the management of PAs. Achieving sustainable management of ESs in PAs is more of a social governance issue, requiring the SES managers to understand the diverse tradeoffs among ESs and well-beings and design management plans with supportive governance processes and institutions. To solve this issue, ESs importance was chosen as the entry point, which is good at "understanding" but weak in "designing" in most cases. We proposed a "KESs-based PAs management plans formulating framework," which is born out of the ESs importance analysis and knowledge for win-win management in PAs. Through the six steps and two tools ("Identification Methodology for PAs KESs" and the "Standard Strategies for PAs KESs Management") embedded in the framework, the win-win management plan for dual goals could be formulated. By applying the framework in the Shennongjia National Park in China, we obtained three directions for adjusting strategies and eight directions for adjusting measures for the National Park Services to formulate management plans. The framework promotes the sustainable management of ESs in PAs by making up for the gap in applying ESs importance in designing feasible, specific, and systematic management plans with policies and institutions.

A phytoestrogen secoisolariciresinol diglucoside induces browning of white adipose tissue and activates non-shivering thermogenesis through AMPK pathway.

Secoisolariciresinol diglucoside (SDG) is the main phytoestrogen component of flaxseed known as an antioxidant. Current study focused on the effect of SDG in white adipose tissue (WAT) browning. Browning of WAT is considered as a promising treatment strategy for metabolic diseases. To demonstrate the effect of SDG as an inducer of browning, brown adipocyte markers were investigated in inguinal WAT (iWAT) of high fat diet-fed obese mice and genetically obese db/db mice after SDG administration. SDG increased thermogenic factors such as uncoupling protein 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha and PR domain containing 16 in iWAT and brown adipose tissue (BAT) of mice. Similar results were shown in beige-induced 3T3-L1 adipocytes and primary cultured brown adipocytes. Furthermore, SDG increased factors of mitochondrial biogenesis and activation. We also observed SDG-induced alteration of AMP-activated protein kinase α (AMPKα). As AMPKα is closely related in the regulation of adipogenesis and thermogenesis, we then evaluated the effect of SDG in AMPKα-inhibited conditions. Genetic or chemical inhibition of AMPKα demonstrated that the role of SDG on browning and thermogenesis was dependent on AMPKα signaling. In conclusion, our data suggest SDG as a potential candidate for improvement of obesity and other metabolic disorders.

Compound K Induces Endoplasmic Reticulum Stress and Apoptosis in Human Liver Cancer Cells by Regulating STAT3.

The ginsenoside compound K (20-O-ß-d-glucopyranosyl-20(S)-protopanaxadiol; CK) is an intestinal bacterial metabolite of ginseng protopanaxadiol saponin that has been reported to induce apoptosis in many cancer cells; however, the precise mechanisms of its activity in human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we demonstrated that CK inhibited the growth and colony formation of HepG2 and SMMC-7721 cells, phenotypes that were mediated by inducing apoptosis. Meanwhile, CK showed lower toxicity in normal hepatoma cells. After treating HepG2 and SMMC-7721 cells with CK, p-STAT3 levels decreased, the three branches of the unfolded protein response were activated, and levels of endoplasmic reticulum stress (ERS)-related proteins were increased. We also revealed that CK decreased the DNA-binding capacity of STAT3. Moreover, silencing STAT3 with CRISPR/Cas9 technology enhanced CK-induced ERS and apoptosis. Finally, we showed that CK inhibited the growth of liver cancer xenografts with little toxicity. Mice bearing human HCC xenografts that were treated with CK showed increased GRP78 expression and decreased p-STAT3 levels. Taken together, these data showed that CK induced ERS and apoptosis by inhibiting p-STAT3 in human liver cancer cells; thus, CK might be a potential therapeutic candidate for human HCC.

Sex effect on insulin secretion and mitochondrial function in pancreatic beta cells of elderly Wistar rats.

AIMS/HYPOTHESIS: Glucose tolerance progressively declines with age, and there is a high prevalence of type 2 diabetes in the elderly people. Previous studies have reported the sex differences in risk for type 2 diabetes, especially in the elderly people, whereas reasons for these sex differences remain poorly understood. This study aims to evaluate the effect of sex on glucose-stimulated insulin secretion and mitochondrial function in pancreatic beta cells of Wistar rats. METHODS: 3-month-old and 18-month-old Wistar rats of both sexes were used. Insulin secretion of islets was analyzed by glucose-stimulated insulin secretion and islet perifusion assays; ATP content and oxygen consumption rate of islets were determined to evaluate the mitochondrial function. RESULTS: Insulin secretion of islets under high glucose conditions declined significantly with age in both sexes. Glucose-stimulated insulin secretion of elderly female groups was markedly higher than that of male groups under high glucose conditions. Importantly, islets from elderly female groups showed higher mitochondrial function compared with male counterparts, evidenced by higher ATP content and oxygen consumption rate under high glucose conditions. It was also noted that mitochondrial biogenesis of islets from elderly female rats was significant higher compared with male rats. There were notable increases in expression of genes involved in mitochondrial biogenesis in islets from elderly female rats compared with male rats. CONCLUSION: This study demonstrates a sex dimorphism in the age-associated impairment of pancreatic beta cell function in elderly rats, while the potential mechanism may be related to the sexual differences in mitochondrial biogenesis and function.

Moderating AKT signaling with baicalein protects against weight loss by preventing muscle atrophy in a cachexia model caused by CT26 colon cancer.

Cancer cachexia is a type of energy-wasting syndrome characterized by fatigue, anorexia, muscle weakness, fat loss, and systemic inflammation. Baicalein, a flavonoid with bioactive properties, has demonstrated the ability to mitigate cardiac and skeletal muscle atrophy in different experimental settings. This effect is achieved through the inhibition of muscle proteolysis, suggesting its potential in preserving skeletal muscle homeostasis. In this study, we investigated the anti-cancer cachexia effects of baicalein in the regulation of muscle and fat wasting, both in vivo and in vitro. Baicalein attenuated body weight loss, including skeletal muscle and white adipose tissue (WAT), in CT26-induced cachectic mice. Moreover, baicalein increased muscle fiber thickness and suppressed the muscle-specific ubiquitin-protease system, including F-box only protein 32 and muscle RING-finger protein-1, by activating AKT phosphorylation both in vivo and in vitro. The use of LY294002, a particular inhibitor of AKT, eliminated the observed impact of baicalein on the improvement of muscle atrophy. In conclusion, baicalein inhibits muscle proteolysis and enhances AKT phosphorylation, indicating its potential role in cancer cachexia-associated muscle atrophy.

B(C6F5)3-catalyzed regio- and stereoselective thiosulfonylation of terminal alkynes with thiosulfonates.

Herein, a metal-free main-group catalysis system for thiosulfonylation of terminal alkynes with thiosulfonates has been established by using commercially available B(C6F5)3 as a catalyst. The protocol provides a highly regio- and stereoselective route for the synthesis of diverse (E)-(ß)-arylthiolvinyl sulfones under mild conditions with 100% atom-economy and exceptional functional group compatibility.

Investigation of the Fracture and Fragmentation of Implosively Driven Thin-Walled Cylindrical Shell: From Thermodynamic Analysis to CDEM Simulation.

The scattering of fragments is a notable characteristic of the explosive detonation of a shelled charge. This study examines the fracture and fragmentation of the shell and the process by which natural fragments form under the strains of implosion. The analysis takes into account both the explosive's energy output and the casing's dynamic response. For this purpose, utilizing a thermochemical code as an alternative to the conventionally employed cylinder test, the Jones-Wilkins-Lee equation of state (JWL EOS) was calibrated within a range of relative specific volume up to 13. The detonation of the shelled charge was subsequently analyzed using the continuum-discontinuum element method (CDEM). Following this, the formation mechanisms and scattering characteristics of natural fragments were scrutinized. The analysis found that the shell predominantly experiences shear failure with uniform evolution, displaying a "hysteresis effect" and two mutation stages in the evolution of tensile failure. Within the JWL EOS's calibrated range, the representation of fragment displacement and velocity improved by 47.97% and 5.30%, respectively. This study provides valuable guidance for designing the power field of warheads and assessing their destructive power.

Late Cambrian geomagnetic instability after the onset of inner core nucleation.

The Ediacaran Period marks a pivotal time in geodynamo evolution when the geomagnetic field is thought to approach the weak state where kinetic energy exceeds magnetic energy, as manifested by an extremely high frequency of polarity reversals, high secular variation, and an ultralow dipole field strength. However, how the geodynamo transitioned from this state into one with more stable field behavior is unknown. Here, we address this issue through a high-resolution magnetostratigraphic investigation of the ~494.5 million-year-old Jiangshanian Global Standard Stratotype and Point (GSSP) section in South China. Our paleomagnetic results document zones with rapid reversals, stable polarity and a ~80 thousand-year-long interval without a geocentric axial dipole field. From these changes, we suggest that for most of the Cambrian, the solid inner core had not yet grown to a size sufficiently large to stabilize the geodynamo. This unusual field behavior can explain paleomagnetic data used to define paradoxical true polar wander, supporting instead the rotational stability of the solid Earth during the great radiation of life in the Cambrian.

Circular RNA_0037128 aggravates high glucose-induced damage in HK-2 cells via regulation of microRNA-497-5p/nuclear factor of activated T cells 5 axis.

Circular RNAs (CircRNAs) were reported to play vital roles in the progression of DN. Herein, the action of circular RNA_0037128 (circ_0037128) was investigated in DN. The level of circ_0037128, microRNA-497-5p (miR-497-5p) and nuclear factor of activated T cells 5 (NFAT5) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The feature of circ_0037128 was tested by RNase R and Actinomycin D treatment assays. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining assays were conducted to evaluate the proliferation ability. The relative protein expression was determined via Western blot analysis. Levels of the inflammatory cytokines, like tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), were assessed by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) production, lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity were determined by the matched kits. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were conducted for evaluating the correlation between miR-497-5p and circ_0037128 or NFAT5. Circ_0037128 and NFAT5 were enhanced, while miR-497-5p was weakened in kidney tissues of DN patients and high glucose (HG)-cultured HK-2 cells. Circ_0037128 inhibition bated HG-caused inhibition effect on cell proliferation and promotion effects on oxidative stress, inflammation and fibrosis in HK-2 cells. Moreover, circ_0037128 knockdown alleviated HG-caused cell damage via regulating miR-497-5p. In addition, NFAT5 overexpression could reverse the influence of miR-497-5p on HG-induced injury in HK-2 cells. Mechanically, circ_0037128 sponged miR-497-5p to modulate NFAT5. Circ_0037128 downregulation could mitigate HG-stimulated cell damage via regulating the miR-497-5p/NFAT5 axis in HK-2 cells in vitro, providing a possible therapy target for DN.

[Environmental impact differences in Qingtian rice-fish culture system at different management scales in the context of land transfer: An empirical study with the carbon footprint method.] / åœŸåœ°æµè½¬èƒŒæ™¯ä¸‹ä¸åŒç»è¥è§„æ¨¡é’ç”°ç¨»é±¼å ±ç”Ÿç³»ç»Ÿçš„çŽ¯å¢ƒå½±å“å·®å¼‚­­åŸºäºŽç¢³è¶³è¿¹çš„å®žè¯ç ”ç©¶.

Under rapid industrialization and urbanization, the conservation and management of agricultural heritage systems is facing many threats and challenges, such as the massive outflow of working labor, land abandonment, and the difficulty in maintaining traditional knowledge systems. Promoting land transfer and carrying out moderate-scale management play an active role in the conservation of agricultural heritage systems. While land transfer brings economic benefits to heritage sites, its environmental impacts to heritage sites are worthy of attention. However, empirical studies are scarce. This study took Qingtian rice-fish culture system in Zhejiang Province as an example, which was designated as Globally Important Agricultural Heritage Systems (GIAHS) in 2005. Small farmer management model and land scale management model were distinguished, while the life cycle method was used to calculate the carbon footprints of two models. The results showed that the carbon footprints of small farmer management model and land scale management model were 6510.80 and 5917.00 kg CO2-eq·hm-2, respectively, while the carbon footprints per unit output were 0.13 and 0.10 kg CO2-eq·yuan-1, respectively. Compared with small farmer management model, land scale management model had lower greenhouse gas emission and lower environmental impact of per unit output. As farmers expanded the scale of land management, local greenhouse gas emissions had been reduced by 4097.20 kg CO2-eq. Furthermore, the accumulation of CH4 in agricultural production accounted for the largest proportion of carbon footprint. The input of compound fertilizer among agricultural production materials was next to CH4 accumulation, becoming the second largest source of greenhouse gas emission. Corn and wheat being used as fish feed also had a significant impact on greenhouse gas emission in small farmer management model. Therefore, the promotion of moderate scale land management is conducive to the win-win of economic and environmental benefits of traditional agricultural systems and plays an important role in the conservation of agricultural heritage systems.

Interleukin-37 sensitize the elderly type 2 diabetic patients to insulin therapy through suppressing the gut microbiota dysbiosis.

OBJECTIVE: The morbidity and prevalence of type 2 diabetes mellitus (DM) are increasing in the elderly population. Interleukin 37 (IL-37) play important roles in anti-inflammatory and anti-bacteria immune responses, but its role in the development of type 2 DM in the elderly is unclear. Therefore, we investigated whether IL-37 is associated with type 2 DM in the elderly and the underlying mechanism. METHODS: Hospitalized patients (aged 65-95 years) with recently diagnosed type 2 diabetes mellitus were studied retrospectively and compared with healthy subjects without glucose metabolism abnormalities. A diabetic mouse model was established by feeding ob/ob mice (C57BL/6) a high-fat, carbohydrate-free diet. Plasma glucose and insulin levels were determined by glucose oxidase assay and radioimmunoassay, respectively. The IL-37 expression level was determined by real-time PCR, western blot and ELISA (Enzyme-linked immunoassay). RESULTS: Statistic analysis showed that the IL-37 level was significantly associated with type 2 DM and insulin resistance in the elderly. The patients were then divided into insulin therapy sensitive and resistant group according to their response to insulin therapy. Data showed that the IL-37 was highly expressed in the insulin therapy sensitive group. And this was related to the less severe gut microbiota dysbiosis. In the mice model, overexpressing the IL-37 could suppress the gut microbiota dysbiosis and also the diabetes development. CONCLUSION: Thus our results showed that higher IL-37 was associated with increased insulin sensitive in elderly type 2 DM patients through suppressing the gut microbiota dysbiosis.

TTF1­NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells.

TTF1­NP is a flavonoid nanoparticle based on 5,2',4'­trihydroxy­6,7,5'­trimethoxyflavone (TTF1), which is derived from the medicinal plant Sorbaria sorbifolia that grows in the Changbai Mountain. We previously demonstrated antitumor effects of TTF1­NP in human hepatoma including induction of apoptosis and inhibition of angiogenesis, migration and invasion. Herein, we examined the effects of TTF1­NP on autophagy and its relationship with apoptosis, and explored potential underlying mechanisms in human hepatoma cell lines. We conducted cell viability assays, Annexin V/propidium iodide double staining, Hoechst staining, monodansylcadaverine staining, transmission electron microscopy, green fluorescent protein­light chain 3 plasmid transfection and western blots. We found that TTF1­NP induced apoptosis and autophagy in HepG2 and SMMC­7721 cells. Pretreatment with the autophagy inhibitor 3­methyladenine promoted TTF1­NP­induced apoptosis. TTF1­NP decreased levels of phosphorylated (p)­Akt, p­mTOR and p­ERK1/2 and increased p­JNK levels in the two cell lines. Treating cells with insulin, SP600125 and U0126 indicated that the Akt/mTOR pathway and JNK were involved in TTF1­NP­induced autophagy. Together, these findings suggest that TTF1­NP induced protective apoptosis­related autophagy by modulating the Akt/mTOR and JNK pathways in HepG2 and SMMC­7721 cells. Therefore, autophagy may be a potential target for TTF1­NP in human hepatoma therapy.

[Measuring water ecological carrying capacity with the ecosystem-service-based ecological footprint (ESEF) method: Theory, models and application].

Integrated watershed management based on aquatic ecosystems has been increasingly acknowledged. Such a change in the philosophy of water environment management requires recognizing the carrying capacity of aquatic ecosystems for human society from a more general perspective. The concept of the water ecological carrying capacity is therefore put forward, which considers both water resources and water environment, connects socio-economic development to aquatic ecosystems and provides strong support for integrated watershed management. In this paper, the authors proposed an ESEF-based measure of water ecological carrying capacity and constructed ESEF-based models of water ecological footprint and capacity, aiming to evaluate water ecological carrying capacity with footprint methods. A regional model of Taihu Lake Basin was constructed and applied to evaluate the water ecological carrying capacity in Changzhou City which located in the upper reaches of the basin. Results showed that human demand for water ecosystem services in this city had exceeded the supply capacity of local aquatic ecosystems and the significant gap between demand and supply had jeopardized the sustainability of local aquatic ecosystems. Considering aqua-product provision, water supply and pollutant absorption in an integrated way, the scale of population and economy aquatic ecosystems in Changzhou could bear only 54% of the current status.

[Effects of different rice farming systems on paddy field weed community].

Taking the paddy fields planted with glutinous rice and hybrid rice in the traditional agricultural region in Congjiang County of Guizhou Province as the case, and by using semi-experiment combined with random sampling investigation, this paper studied the characteristics of weed community in the paddy fields under rice monoculture (R), rice-fish culture (R-F), and rice-fish-duck culture (R-F-D). Under the three rice farming systems, glutinous rice had higher capability in inhibiting weeds, compared with hybrid rice. Farming system R-F-D decreased the weed density significantly, with the control effect on Monochoia vaginalis and Rotala indica being 100%. The overall weed-inhibiting effect of R-F-D was significantly higher than that of the other farming systems. Under R-F-D, the species richness and Shannon diversity index of weed community decreased markedly, while the Pielou evenness index increased, indicating that the species composition of weed community changed greatly, and the occurrence of native dominant weed species decreased. It was concluded that R-F-D was a feasible farming system for the control of paddy field weed community.