Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

Gas chromatography-ion mobility spectrometry (GC-IMS) technique and its recent applications in grain research.

Grains are the primary source of food for most people worldwide and constitute a major source of carbohydrates. Many novel technologies are being employed to ensure the safety and reliability of grain supply and production. Gas chromatography-ion mobility spectrometry (GC-IMS) can effectively separate and sensitively detect volatile organic compounds. It possesses advantages such as speed, convenience, high sensitivity, no pretreatment, and wide applicability. In recent years, many studies have shown that the application of GC-IMS technology for grain flavor analysis can play a crucial role in grains. This article elucidates the working principle of GC-IMS technology, reviews the application of GC-IMS in grains in the past 5 years. GC-IMS technology is mainly applied in four aspects in grains. In grain classification, it distinguishes varieties, quality, origin, production year, and processing methods based on the trace differences in volatile organic compounds, thereby fulfilling various grain classification requirements such as origin tracing, geographical indication product recognition, variety identification, production year identification, and detection of counterfeit and inferior grain samples. In optimizing the processing technology of grains and their products, it can improve food flavor, reduce undesirable flavors, and identify better processing parameters. In grain storage, it can determine the storage time, detect spoilage phenomena such as mold and discoloration during storage, eliminate pests affecting storage, and predict the vitality of seeds after storage. In aroma evaluation of grains and their processed products, it can assess the impact of new raw materials, new technologies, fermentation processes, and even oral processing on the quality of grain products. This article also summarizes the characteristics of GC-IMS technology, compiles typical grain flavor compounds, and provides prospects for the future application of GC-IMS. © 2024 Society of Chemical Industry.

Adaptation measures of the potential double cropping region in Northern China to future climate change.

In the context of climate change, the northern climate-based boundaries of the winter wheat-summer maize double cropping system (DCS) have moved northward and westward. The selection of spring maize single cropping system (SCS) or DCS in the potential DCS region in northern China directly affects the annual crop yield, resource use efficiency, and greenhouse gas (GHG) emissions. Reducing GHG emissions while improving yield and resource use efficiency is essential to green agricultural development. We used future climate data (2021-2060, SSP2-4.5 and SSP5-8.5), along with crop and soil data, to assess the applicability of the Denitrification-Decomposition Model (DNDC) for simulating crop yield and GHG emissions. Through simulation of DNDC, we identified a cropping system that prioritized high yield, resource use efficiency, and GHG emissions reduction, adapting to future climate change. Under this cropping system, we quantified the effects of various straw incorporation rates, irrigation, and nitrogen input on crop yield, resource use efficiency, and GHG emissions. We proposed optimal measures to adapt to future climate change while aiming for high yield, resource use efficiency, and GHG emissions reduction. The results show that the DNDC reliably simulated yield and GHG emissions for the (SCS) and the DCS. In counting for greenhouse gas emission intensity (GHGI) as GHG emissions normalized by crop yield, the GHGI was reduced by 86.4% and 89.2% in DCS than in SCS under the SSP2-4.5 and SSP5-8.5, respectively. In the study area, the DCS should be adopted for high yield, resource use efficiency, and GHG emissions reduction (increased by 28.4% and 34.4%) in the SSP2-4.5 and SSP5-8.5 with 1) straw incorporation rate for 100% of winter wheat and for 60% of summer maize; 2) total irrigating 240 mm for winter wheat at pre-sowing, jointing, booting, and filling stages; and 3) applying nitrogen of 168 kg·N/ha for both crops.

1 km-resolution gridded dataset of phosphorus rate for rice wheat and maize in China over 2004-2016.

Crop-specific, high-resolution phosphorus rate information is essential for sustainable agricultural fertilizer management in China. However, substantial uncertainties exist in the current phosphorus fertilizer dataset because of only coarse national statistics used in dataset development and no crop-specific information provided. This study harmonized provincial and county-level phosphorus and component fertilizer statistics and crop distribution data to generate 1 km gridded maps of phosphorus rate for rice, wheat and maize in the years of 2004-2016 (CN-P). CN-P provides a comparable estimate on phosphorus rate for each crop over 2004-2016, and demonstrates an improved spatial heterogeneity. Existing dataset developed using national statistics tends to smooth out the variability within country and significantly underestimates actual phosphorus rate. CN-P shows that, during 2004-2016, wheat received the most phosphorus rate (8.7 g P2O5 m-2), while maize showed the rapidest increasing trend (2.36% yr-1). The CN-P dataset has the potential to be widely applied in modeling studies on sustainable agricultural fertilizer management strategies and phosphorus pollution.

Spatial-temporal patterns of high-temperature and drought during the maize growing season under current and future climate changes in northeast China.

BACKGROUND: Under the background of global warming, the intensity and frequency of extreme meteorological events in the maize growing season in northeast China are increasing. In order to clarify the occurrence characteristics of extreme meteorological events in northeast China, this study focused on three extreme agrometeorological events, i.e., high temperatures, drought, and the compound events of high-temperature and drought during the maize growing season (May-September), impacting maize production. RESULTS: Based on historical (1981-2017) and future (2021-2060) climate data, we analyzed the spatial-temporal patterns of these three events with different intensities in northeast China. The results indicated that slight high-temperatures and moderate and severe droughts occurred more frequently in the study area during the historical period. The frequency of the different grades of the compound events of high-temperature and drought will exhibit an increasing trend in the future, as will the frequency of the compound events of high-temperature and drought. This is particularly evident in the northwest of the study area. CONCLUSION: The compound events of high-temperature and drought mainly occurred in late July and early August, encompassing the flowering stage of maize varieties. It is important to identify the area and time of major extreme weather events to implement the necessary preventive measures. © 2023 Society of Chemical Industry.

Impacts of mean climate and extreme climate indices on soybean yield and yield components in Northeast China.

Soybean is an important oil crop in China, and the national focus of soybean production is in Northeast China. In order to achieve high-stable yield, it is crucial to acknowledge the impacts of mean climate and extreme climate indices on soybean yield and yield components. In this study, based on the weather data from 61 counties from 1981 to 2017 in Northeast China, we assessed the impacts of mean climate and extreme climate indices on soybean observed yield and simulated yield. Mean climate include effective growing degree days (GDD10), precipitation (Pre), and solar radiation (SR); extreme climate indices include the number of cool days during seed-filling period (C15), the number of cool days during 15 days before anthesis (C17), the number of hot days (H30), maximum amount of 5 Day accumulated precipitation (P5), and consecutive dry days (CDD)). We used the DSSAT-CROPGRO-Soybean model to identify the main yield components for soybean. The results showed that observed soybean yield reduced by 3.57% due to the collective changes in the eight study climate indices. Increases in GDD10, decreases in Pre, and decreases in SR caused a 3.96%, -3.89%, and - 0.48% change in soybean yield, respectively. Decreases in C15 and C17 led to a 5.36% increase in soybean yield; increases in H30, P5, and CDD caused a 5.75%, 0.30%, and 1.14% reduction in soybean yield, respectively. By comparing the response of observed and simulated soybean yield to climate indices (excluding P5) in the DSSAT-CROPGRO-Soybean model, we identified the key yield components for soybean as the number of pods and seed weight. The negative impacts on the number of pods and seed weight were mainly attributed to changes in Pre and H30 from anthesis to podding and during seed-filling period. Our results could be used to assist the local soybean community adapt to climate change.

MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A.

Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mouse model of oxygen-induced proliferative retinopathy (OIR). We found that miR-18a-5p was highly expressed in the retina of pups as well as retinal endothelial cells, and was consistently down-regulated during retinal development. On the other hand, miR-18a-5p was increased significantly during pathologic neovascularization in the retinas of OIR mice. Moreover, intravitreal administration of miRNA mimic, agomiR-18a-5p, significantly suppressed retinal neovascularization in OIR models. Accordingly, agomir-18a-5p markedly suppressed human retinal microvascular endothelial cell (HRMEC) function including proliferation, migration, and tube formation ability. Additionally, we demonstrated that miR-18a-5p directly down-regulated known vascular growth factors, fibroblast growth factor 1 (FGF1) and hypoxia-inducible factor 1-alpha (HIF1A), as the target genes. In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization.

Sulfonated Binaphthyl-Containing Poly(arylene ether ketone)s with Rigid Backbone and Excellent Film-Forming Capability for Proton Exchange Membranes.

Sterically hindered (S)-1,1'-binaphthyl-2,2'-diol had been successfully copolymerized with 4,4'-sulfonyldiphenol and 4,4'-difluorobenzophenone to yield fibrous poly(arylene ether ketone)s (PAEKs) containing various amounts of binaphthyl unit, which was then selectively and efficiently sulfonated using ClSO3H to yield sulfonated poly(arylene ether ketone)s (SPAEKs) with ion exchange capacities (IECs) ranging from 1.40 to 1.89 mmol·g-1. The chemical structures of the polymers were confirmed by 2D ¹H⁻¹H COSY NMR and FT-IR. The thermal properties, water uptake, swelling ratio, proton conductivity, oxidative stability and mechanical properties of SPAEKs were investigated in detail. It was found that the conjugated but non-coplanar structure of binaphthyl unit endorsed excellent solubility and film-forming capability to SPAEKs. The SPAEK-50 with an IEC of 1.89 mmol·g-1 exhibited a proton conductivity of 102 mS·cm-1 at 30 °C, much higher than that of the state-of-the-art Nafion N212 membrane and those of many previously reported aromatic analogs, which may be attributed to the likely large intrinsic free volume of SPAEKs created by the highly twisted chain structures and the desirable microscopic morphology. Along with the remarkable water affinity, thermal stabilities and mechanical properties, the SPAEKs were demonstrated to be promising proton exchange membrane (PEM) candidates for potential membrane separations.

Xiayuxue Decoction ([symbols; see text]) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice.

OBJECTIVE: To investigate the effects of ancient Chinese medical formula Xiayuxue Decoction ([symbols; see text], XYXD) on activation of hepatic stellate cells (HSCs) and defenestration of sinusoidal endothelial cells (SECs) in CCl4-induced fibrotic liver of mice. METHODS: High performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCl4 exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 (CD31). Whole liver lysates were detected of α-smooth muscle actin (α-SMA) and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA, F-actin, DNA fragmentation through confocal microscopy, Western blot, terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan, respectively. RESULTS: Amygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% (P<0.01), as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% (P<0.05) respectively. In vitro, XYXD (12.5 µg/mL, 50 µg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent, demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% (P<0.05). Besides, XYXD induced the apoptosis of HSC-T6 cells by 20.0% (P<0.05) and 49.5% (P<0.01), evidenced by enhanced TUNEL positivity. Moreover, ultrastructural observation suggested XYXD inhibited defenestration of SECs, which was confirmed by 31.1% reduction of protein level of CD31 (P<0.05). CONCLUSIONS: XYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases.

[Effects of Chinese herbal medicine Xiaopi Pill in preventing rats from dimethylnitrosamine-induced liver fibrosis].

OBJECTIVE: To explore the intervention effects of Xiaopi Pill (XPW), a compound traditional Chinese herbal medicine, on the development progress of dimethylnitrosamine (DMN)-induced liver fibrosis in rats. METHODS: Liver fibrosis model was established by intraperitoneal injection of 0.5% DMN 2 mL/kg thrice a week for 4 weeks. Rats were divided into control group given saline and treatment group given XPW during the 3rd week of DMN injections. Rats were sacrificed at the end of the experiment, and then liver histological changes, liver function and mRNA expression of the liver fibrosis-associated markers were observed. RESULTS: (1) At the end of the 2nd and 4th weeks of DMN injection, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) increased significantly in rats (P<0.01 or P<0.05); content of total bilirubin (TBil) increased significantly compared with the normal group until the end of the 4th week (P<0.05); compared with the model group after 4 weeks of DMN injection, the serum levels of ALT, AST, ALP and TBil were decreased remarkably in the XPW-treated group (P<0.01 or P<0.05). (2) The hepatic inflammation and collagen deposition in hepatic tissues increased by different degrees in experimental rats. Parts of pathological changes in the rat liver were found at the end of the 4th week, including a complete round structure of false flocculus round, meantime, the hydroxyproline content of hepatic tissue was increased significantly at the end of the 2nd and 4th weeks (P<0.05). Compared with the 4-week model group, the hepatic inflammation, collagen deposition and hydroxyproline content in hepatic tissues were alleviated dramatically (P<0.05). (3) Compared with the normal and 2nd week groups, protein expression of alpha-smooth muscle actin (α-SMA) was gradually increased, and that of the 4th week group were aggrandized significantly (P<0.01). Compared with the normal group, the mRNA expression of α-SMA, transforming growth factor-ß1 (TGF-ß1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and heme oxygenase-1 (HO-1) was gradually increased. Further changes in above-mentioned abnormalities were found in the model rats at the end of the 4th week (P<0.01); while compared to the 4th week group, protein and mRNA levels of α-SMA and mRNA levels of TGF-ß1, TIMP-1, and HO-1 were decreased significantly in the XPW group (P<0.01 or P<0.05). CONCLUSION: Progressive DMN-induced liver fibrosis in rats can be suppressed by XPW; the mechanism may be associated with inhibition of the activated hepatic stellate cells.

[Dynamic change of lipid peroxidation-related protein expression and the intervention effects of Yiguanjian decoction in a rat model of CCl4-induced liver fibrosis].

To investigate the dynamic change of lipid peroxidation-related protein expression and the intervention effects of Yiguanjian (YGJ) Decoction on liver fibrosis induced by CCl4 in rat. Fifty-seven male Wistar rats were randomly divided into a liver fibrosis group (n = 39) and a normal group (n = 18). The liver fibrosis was treated with peritoneal injection of 50% CCl4 for nine weeks. At the end of weeks 3 and 6 of CCl4 treatment, six rats were sacrificed to assess the status of liver fibrosis. At the end of week 7, the remaining -fibrotic rats were randomly divided into an untreated model group (M, n=15) and a YGJ-treated group (n = 12). The YGJ group was administered daily, oral YGJ Decoction for three weeks, concomitant with continued CCl4 treatment. The M group and normal group received the same treatment oral regimen and volume of distilled water. At the end of week 8, four rats in group M were sacrificed to observed the fibrosis status. At the end of week 9, the fibrotic rats were sacrificed for sampling. Liver function, histological changes, contents of hydroxyproline (Hyp) and malondialdehyde (MDA), activity of super oxidase dismutase (SOD) and L-glutathione (GSH), protein expression of heat shock protein (HSP)70, heme oxygenase (HO)-1, transferrin, peroxiredoxin (Prxd) 6 and liver fatty acid binding protein (L-FABP) were detected. Compared with normal group-, the MDA content was increased significantly in M group at week 6 (M: 4.23+/-0.45 nmol/mg vs. normal: 2.22+/-0.59 nmol/mg, F = 60.13, P less than 0.01) and week 9 (M: 6.29+/-1.23 nmol/mg vs. normal: 2.22+/-0.59 nmol/mg, F = 66.99, P less than 0.01), but the SOD activity was decreased significantly at the same time points [week 6: (M: 196.94+/-39.20 U/mg vs. normal: 264.50+/-30.44 U/mg, F = 11.12, P less than 0.01]); [week 9: (M: 152.2+/-51.65 U/mg vs. normal: 264.50+/-30.44 U/mg, F = 23.11, P less than 0.01)], as were the GSH content [week 6: (M: 48.47+/-7.27 nmol/mg vs. 60.74+/-9.04 nmol/mg, F = 6.71, P less than 0.05]]; [week 9: (M: 37.89+/-9.01 nmol/mg vs. 60.74+/-9.04 nmol/mg, F = 24.06, P less than 0.01]]. Compared with group M at week 9, the YGH-treated model group had markedly decreased MDA (YGJ: 4.25+/-0.86 nmol/mg vs. M: 6.29+/-1.23 nmol/mg, F = 19.52, P less than 0.01], but significantly increased SOD (YGJ: 198.35+/-46.48 U/mg vs. 152.21+/-51.65 U/mg, F = 4.65, P less than 0.05] and GSH (YGJ: 53.73+/-7.54 nmol/mg vs. M: 37.89+/-9.01 nmol/mg, F = 19.23, P less than 0.01). Compared to normal rats at week 9, group M had significantly higher protein levels of HSP70 (normal: 1.21+/-0.06 vs. M: 0.58+/-0.07, F = 166.87, P less than 0.01) and HO-1 (normal: 1.11+/-0.06 vs. M: 0.58+/-0.06, F = 123.96, P less than 0.01), but significantly decreased levels of Prxd6 (normal: 0.04+/-0.05 vs. M: 1.49+/-0.05, F = 1215.85, P less than 0.01), transferrin (normal: 0.67+/-0.03 vs. M: 1.67+/-0.04, F = 301.35, P less than 0.01), and L-FABP (normal: 0.24+/-0.02 vs. M: 1.44+/-0.14, F = 219.05, P less than 0.01). Compared to group M at week 9, the YGJ treatment group showed significantly reduced HSP70 (YGJ: 0.82+/-0.04 vs. M: 1.21+/-0.06, F = 92.31, P less than 0.01) and HO-1 (YGJ: 0.90+/-0.04 vs. 1.11+/-0.06, F = 26.89, P less than 0.01), but significantly increased Prxd6 (YGJ: 0.88+/-0.11 vs. 0.04+/-0.05, F = 150.17, P less than 0.01), transferrin (YGJ: 1.36+/-0.13 vs. 0.24+/-0.02, F = 237.19, P less than 0.01), and L-FABP (YGJ: 1.04+/-0.12 vs. 0.67+/-0.03, F = 27.53, P less than 0.01). YGJ treatment of fibrotic liver rats reduces lipid peroxidation damage by preventing generation of oxidizing substances.

Platycoside O, a new triterpenoid saponin from the roots of Platycodon grandiflorum.

A new unusual minor triterpenoid saponin, platycoside O (1), was isolated from the 75% EtOH extract obtained from the roots of Platycodon grandiflorum, together with four known saponins: platycoside M-3 (2), platycoside J (3), platycoside F (4) and platycoside B (5). The structure of 1 was determined as 3-O-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl-2ß,3ß,16α,23-tetrahydroxyolean-12-en-24-methoxyl, 24-oxo-28-oic acid 28-O-ß-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside on the basis of spectral analysis and chemical evidence.

Simultaneous determination of five nucleosides and nucleobases of Rehmannia glutinosa Libosch. by high performance liquid chromatography.

This study is to establish a method for simultaneously determination of five nucleosides and nucleobases, including hypoxanthine, uridine, adenine, guanosine and adenosine in Rehmannia glutinosa Libosch. which was collected from different regions in China. A Diamonsil C18 column (250 mm x 4.6 mm, 5 microm) was used. Acetonitrile and 0.04 mol L(-1) potassium dihydrogen phosphate solution were adopted as mobile phase with gradient elution. The flow rate was 1 mL min(-1) and column temperature was 30 degrees C. The detection wavelength was at 254 nm. The method had good linearity over the range of 1.0 - 16.0 microg mL(-1) (r2 = 0.999 8), 5.0 - 80.0 microg mL(-1) (r2 = 0.999 8), 1.0 - 16.0 microg mL(-1) (r2 = 0.999 5), 1.25 - 20.0 microg mL(-1) (r2 = 0.999 8) and 1.0 - 16.0 microg mL(-1) (r2 = 0.999 8) for hypoxanthine, uridine, adenine, guanosine and adenosine, respectively. The average recoveries were between 98.8% and 100.7%. The content of hypoxanthine, uridine, adenine, guanosine and adenosine in Rehmannia glutinosa Libosch. from different regions was significantly different. This established method was sensitive and reliable for the quantification of five chemical constituents in Rehmannia glutinosa Libosch.

Pharmacokinetic behavior of 16-dehydropregnenolone after intramuscular administration in rats.

The pharmacokinetics of 16-dehydropregnenolone (16-DHP), a sterols compound isolated from Solanum lyratum Thunb., was investigated in rats following a Single intramuscular administration (40 mg/kg). The concentration of 16-DHP in rat plasma was determined by a high Performance liquid chromatography (HPLC) method with UV detection. Levonorgestrel was used as the internal Standard (IS). The pharmacokinetic parameters of 16-DHP were derived by non-compartmental method. After a Single intramuscular administration, the maximum plasma concentration (Cmax) was (289 ± 25) ng/mL, time to reach Cmax(tmax) was (0.38 ± 0.14) h, the elimination half-life (t1/2) was (2.5 ± 1.1) h, the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC(0-t)) was (544 ± 73)ng · h/mL. The results indicated that 16-DHP was absorbed quickly and eliminated rapidly in rats after the intramuscular injection.