Kinase CPK10 regulates low light-induced tomato flower drop downstream of IDL6 in a calcium-dependent manner.

Flower drop is a major cause for yield loss in many crops. Previously, we found that tomato (Solanum lycopersicum) INFLORESCENCE DEFICIENT IN ABSCISSION-Like (SlIDL6) contributes to flower drop induced by low light. However, the molecular mechanisms by which SlIDL6 acts as a signal to regulate low light-induced abscission remain unclear. In this study, SlIDL6 was found to elevate cytosolic Ca2+ concentrations ([Ca2+]cyt) in the abscission zone (AZ), which was required for SlIDL6-induced flower drop under low light. We further identified that one calcium-dependent protein kinase gene (SlCPK10) was highly expressed in the AZ and up-regulated by SlIDL6-triggered [Ca2+]cyt. Over-expression and knockout of SlCPK10 in tomato resulted in accelerated and delayed abscission, respectively. Genetic evidence further indicated that knockout of SlCPK10 significantly impaired the function of SlIDL6 in accelerating abscission. Furthermore, Ser-371 phosphorylation in SlCPK10 dependent on SlIDL6 was necessary and sufficient for its function in regulating flower drop, probably by stabilizing the SlCPK10 proteins. Taken together, our findings reveal that SlCPK10, as a downstream component of the IDL6 signaling pathway, regulates flower drop in tomato under low light stress.

A SlCLV3-SlWUS module regulates auxin and ethylene homeostasis in low light-induced tomato flower abscission.

Premature abscission of flowers and fruits triggered by low light stress can severely reduce crop yields. However, the underlying molecular mechanism of this organ abscission is not fully understood. Here, we show that a gene (SlCLV3) encoding CLAVATA3 (CLV3), a peptide hormone that regulates stem cell fate in meristems, is highly expressed in the pedicel abscission zone (AZ) in response to low light in tomato (Solanum lycopersicum). SlCLV3 knockdown and knockout lines exhibit delayed low light-induced flower drop. The receptor kinases SlCLV1 and BARELY ANY MERISTEM1 function in the SlCLV3 peptide-induced low light response in the AZ to decrease expression of the transcription factor gene WUSCHEL (SlWUS). DNA affinity purification sequencing identified the transcription factor genes KNOX-LIKE HOMEDOMAIN PROTEIN1 (SlKD1) and FRUITFULL2 (SlFUL2) as SlWUS target genes. Our data reveal that low light reduces SlWUS expression, resulting in higher SlKD1 and SlFUL2 expression in the AZ, thereby perturbing the auxin response gradient and causing increased ethylene production, eventually leading to the initiation of abscission. These results demonstrate that the SlCLV3-SlWUS signaling pathway plays a central role in low light-induced abscission by affecting auxin and ethylene homeostasis.

SlBEL11 regulates flavonoid biosynthesis, thus fine-tuning auxin efflux to prevent premature fruit drop in tomato.

Auxin regulates flower and fruit abscission, but how developmental signals mediate auxin transport in abscission remains unclear. Here, we reveal the role of the transcription factor BEL1-LIKE HOMEODOMAIN11 (SlBEL11) in regulating auxin transport during abscission in tomato (Solanum lycopersicum). SlBEL11 is highly expressed in the fruit abscission zone, and its expression increases during fruit development. Knockdown of SlBEL11 expression by RNA interference (RNAi) caused premature fruit drop at the breaker (Br) and 3 d post-breaker (Br+3) stages of fruit development. Transcriptome and metabolome analysis of SlBEL11-RNAi lines revealed impaired flavonoid biosynthesis and decreased levels of most flavonoids, especially quercetin, which functions as an auxin transport inhibitor. This suggested that SlBEL11 prevents premature fruit abscission by modulating auxin efflux from fruits, which is crucial for the formation of an auxin response gradient. Indeed, quercetin treatment suppressed premature fruit drop in SlBEL11-RNAi plants. DNA affinity purification sequencing (DAP-seq) analysis indicated that SlBEL11 induced expression of the transcription factor gene SlMYB111 by directly binding to its promoter. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay showed that S. lycopersicum MYELOBLASTOSIS VIRAL ONCOGENE HOMOLOG111 (SlMYB111) induces the expression of the core flavonoid biosynthesis genes SlCHS1, SlCHI, SlF3H, and SlFLS by directly binding to their promoters. Our findings suggest that the SlBEL11-SlMYB111 module modulates flavonoid biosynthesis to fine-tune auxin efflux from fruits and thus maintain an auxin response gradient in the pedicel, thereby preventing premature fruit drop.

The HD-Zip transcription factor SlHB15A regulates abscission by modulating jasmonoyl-isoleucine biosynthesis.

Plant organ abscission, a process that is important for development and reproductive success, is inhibited by the phytohormone auxin and promoted by another phytohormone, jasmonic acid (JA). However, the molecular mechanisms underlying the antagonistic effects of auxin and JA in organ abscission are unknown. We identified a tomato (Solanum lycopersicum) class III homeodomain-leucine zipper transcription factor, HOMEOBOX15A (SlHB15A), which was highly expressed in the flower pedicel abscission zone and induced by auxin. Knocking out SlHB15A using clustered regularly interspaced short palindromic repeats-associated protein 9 technology significantly accelerated abscission. In contrast, overexpression of microRNA166-resistant SlHB15A (mSlHB15A) delayed abscission. RNA sequencing and reverse transcription-quantitative PCR analyses showed that knocking out SlHB15A altered the expression of genes related to JA biosynthesis and signaling. Furthermore, functional analysis indicated that SlHB15A regulates abscission by depressing JA-isoleucine (JA-Ile) levels through inhabiting the expression of JASMONATE-RESISTANT1 (SlJAR1), a gene involved in JA-Ile biosynthesis, which could induce abscission-dependent and abscission-independent ethylene signaling. SlHB15A bound directly to the SlJAR1 promoter to silence SlJAR1, thus delaying abscission. We also found that flower removal enhanced JA-Ile content and that application of JA-Ile severely impaired the inhibitory effects of auxin on abscission. These results indicated that SlHB15A mediates the antagonistic effect of auxin and JA-Ile during tomato pedicel abscission, while auxin inhibits abscission through the SlHB15A-SlJAR1 module.

Compound droughts slow down the greening of the Earth.

Vegetation response to soil and atmospheric drought has raised extensively controversy, however, the relative contributions of soil drought, atmospheric drought, and their compound droughts on global vegetation growth remain unclear. Combining the changes in soil moisture (SM), vapor pressure deficit (VPD), and vegetation growth (normalized difference vegetation index [NDVI]) during 1982-2015, here we evaluated the trends of these three drought types and quantified their impacts on global NDVI. We found that global VPD has increased 0.22 ± 0.05 kPa·decade-1 during 1982-2015, and this trend was doubled after 1996 (0.32 ± 0.16 kPa·decade-1 ) than before 1996 (0.16 ± 0.15 kPa·decade-1 ). Regions with large increase in VPD trend generally accompanied with decreasing trend in SM, leading to a widespread increasing trend in compound droughts across 37.62% land areas. We further found compound droughts dominated the vegetation browning since late 1990s, contributing to a declined NDVI of 64.56%. Earth system models agree with the dominant role of compound droughts on vegetation growth, but their negative magnitudes are considerably underestimated, with half of the observed results (34.48%). Our results provided the evidence of compound droughts-induced global vegetation browning, highlighting the importance of correctly simulating the ecosystem-scale response to the under-appreciated exposure to compound droughts as it will increase with climate change.

Fatty acid metabolism disorders and potential therapeutic traditional Chinese medicines in cardiovascular diseases.

Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid metabolism are crucial contributors in the development of cardiovascular diseases. The abnormal cardiac fatty acid metabolism usually leads to energy deficit, oxidative stress, excessive apoptosis, and inflammation. Targeting fatty acid metabolism has been regarded as a novel approach to the treatment of cardiovascular diseases. However, there are currently no specific drugs that regulate fatty acid metabolism to treat cardiovascular diseases. Many traditional Chinese medicines have been widely used to treat cardiovascular diseases in clinics. And modern studies have shown that they exert a cardioprotective effect by regulating the expression of key proteins involved in fatty acid metabolism, such as peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase 1. Hence, we systematically reviewed the relationship between fatty acid metabolism disorders and four types of cardiovascular diseases including heart failure, coronary artery disease, cardiac hypertrophy, and diabetic cardiomyopathy. In addition, 18 extracts and eight monomer components from traditional Chinese medicines showed cardioprotective effects by restoring cardiac fatty acid metabolism. This work aims to provide a reference for the finding of novel cardioprotective agents targeting fatty acid metabolism.

Effects of HMGA2 on the epithelial-mesenchymal transition-related genes in ACHN renal cell carcinoma cells-derived xenografts in nude mice.

BACKGROUND: The architectural transcriptional regulator high-mobility group AT-hook 2 (HMGA2) is an oncofetal protein which has been reported to be ectopically expressed in a variety of cancers. A high expression of HMGA2 in human renal cell carcinoma (RCC) is related with tumor invasiveness and poor prognosis. Recent in vitro studies have shown that HMGA2 knockdown was able to decrease cell proliferation and migration, and regulate the gene expression related to epithelial-mesenchymal transition (EMT). METHODS: To understand the HMGA2's effect in vivo, HMGA2 expression was knocked down in ACHN cells using small hairpin RNA (shRNA), then the HMGA2-deficient ACHN cells were xenografted into the BALB/c nude mice. Tumor growth was monitored and the expression of EMT-related genes was analyzed. RESULTS: HMGA2 expression was confirmed to be knocked down in the cultured and xenografted ACHN cells. The xenograft tumor of HMGA2-deficient cells demonstrated a retarded growth pattern compared with the control. The expression of E-cadherin was increased, whereas N-cadherin and Snail were decreased in the HMGA2-deficient xenograft tumors. CONCLUSIONS: In conclusion, to the best of our knowledge, for the first time, we have successfully developed an in vivo experiment using HMGA2-silencing ACHN cells to be grown as xenografts in nude mice. Our findings show that HMGA2 deficiency was sufficient to suppress the xenograft tumor growth in vivo, which support our hypothesis that HMGA2-induced renal carcinogenesis occurs at least in part through the regulation of tumor associated EMT genes.

Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial.

BACKGROUND AND PURPOSE: Tianzhi granule (TZ) is usually used for patients with vascular dementia (VaD) in China. The aim was to assess the effect of TZ by a randomized clinical trial (RCT). METHODS: A 24-week RCT was conducted in 16 centres. Participants were grouped into TZ, donepezil or placebo. The co-primary outcomes were the Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog) and Clinician's Interview-based Impression of Change-plus caregiver information (CIBIC-plus). RESULTS: A total of 543 patients with mild to moderate VaD were enrolled, of whom 242 took TZ granules, 241 took donepezil, and 60 took placebo. The least-squares mean changes from baseline and 95% CI were 6.20 (5.31, 7.09) (TZ group), 6.53 (5.63, 7.42) (donepezil group) and 3.47 (1.76, 5.19) (placebo group), both TZ and donepezil showed small but significantly improvement compared with placebo group. The percent of improvement on the global impression which was measured by CIBIC-plus was 73.71% in TZ and 58.18% in placebo, there was significant different between TZ and placebo group (P = 0.004). No significant differences were observed between TZ and donepezil. No significant differences of adverse events were found. CONCLUSIONS: TZ and donepezil could bring symptomatic benefit for mild to moderate VaD. Trial registration The protocol had retrospectively registered at clinical trial.gov, Unique identifier: NCT02453932, date of registration: May 27, 2015; https://www.clinicaltrials.gov/ct2/show/NCT02453932?term=NCT02453932&rank=1.

Rs7193343 polymorphism in zinc finger homeobox 3 (ZFHX3) gene and atrial fibrillation: an updated meta-analysis of 10 case-control comparisons.

BACKGROUND: The previous genome-wide studies have shown that rs7193343 single-nucleotide polymorphism (SNP) in zinc finger homeobox 3 (ZFHX3) gene correlate with risk of atrial fibrillation (AF). However, the distribution of this SNP differs significantly among various populations. The present study was to investigate whether combined evidence shows the association between ZFHX3 rs7193343 SNP and the risk of AF in various populations. METHODS: A systematic search of all studies published through Dec 2014 was conducted using the Medline, Embase, WanFang, ScienceDirect, CNKI, and OVID databases. The case-control studies that evaluated an association between rs7193343 SNP and risk of AF were identified. The association between the ZFHX3 rs7193343 SNP and AF susceptibility was assessed using genetic models. RESULTS: We collected 10 comparisons from six studies for rs7193343 SNP, including 1037 cases and 4310 controls in Asian, 5583 cases and 38215 controls in Caucasian, and then performed an updated meta-analysis and subgroup analysis based on ethnicity. In overall population, the occurrence of AF was found to be associated with T-allelic of rs7193343 SNP in ZFHX3 (OR =1.17, 95% CI 1.10-1.26). In subgroup analysis, we observed there was significant association between T-allele of rs7193343 and risk of AF in Caucasian subgroups (OR =1.20, 95% CI 1.12-1.30), but no statistically significance (OR = 1.07, 95% CI 0.92-1.24) in Asian population. CONCLUSION: In Caucasian population, genetic variant rs7193343 SNP is associated with risk of AF in Caucasian population. However, no association is found in Asian population based on the current evidence. Further studies with larger sample size involving case-control populations with multiple ethnics are still required in the future.

Analyzing nonlinear variations in terrestrial vegetation in China during 1982-2012.

Quantifying the long-term trends of changes in terrestrial vegetation on a large scale is an effective method for detecting the effects of global environmental change. In view of the trend towards overall restoration and local degradation of terrestrial vegetation in China, it is necessary to pay attention to the spatial processes of vegetative restoration or degradation, as well as to clarify the temporal and spatial characteristics of vegetative growth in greater geographical detail. However, traditional linear regression analysis has some drawbacks when describing ecological processes. Combining nonparametric linear regression analysis with high-order nonlinear fitting, the temporal and spatial characteristics of terrestrial vegetative growth in China during 1982-2012 were detected using the third generation of Global Inventory Modeling and Mapping Studies (GIMMS3g) dataset. The results showed that high-order curves could be effective. The region joining Ordos City and Shaanxi Gansu Ningxia on the Loess Plateau may have experienced restoration-degradation-restoration processes of vegetative growth. In the Daloushan Mountains, degradation-restoration processes of vegetative growth may have occurred, and the occurrence of several hidden vegetative growth processes was located in different regions of eastern China. Changes in cultivated vegetation were inconsistent with changes in other vegetation types. In southern China and some high-altitude areas, temperature was the primary driver of vegetative growth on an interannual scale, while in the north, the effect of rainfall was more significant. Nevertheless, the influence of climate on vegetation activity in large urban areas was weak. The trend types of degradation-restoration processes in several regions were inconsistent with the implements of regional land development and protection strategy. Thus, the role of human activity cannot be ignored. In future studies, it will be still necessary to quantify the effects of human management on spatial patterns, develop trend-fitting methods, and explore more refined methods of analyzing the driving forces affecting large-scale changes in vegetative growth.

[Evidence-based nursing practice for the prevention of nasal and facial pressure injuries in patients with non-invasive positive pressure ventilation].

OBJECTIVE: To investigate the evidence-based practice of prevention and care of nasal and facial pressure injuries in patients with non-invasive positive pressure ventilation (NPPV) using the knowledge to action framework (KTA), and to explore its effectiveness. METHODS: Using an evidence-based nursing approach, an evidence-based practice group was established to formulate a clinical problem, the literature from domestic and international databases were researched for relevant evidence, the evidence was introduced into clinical scenarios, an evidence-based practice plan was developed, and a strategy for applying the best evidence was constructed by conducting a baseline review of healthcare professionals and patients with NPPV, analyzing barriers and promoting factors, and making changes in clinical practice at the organizational level, the practitioner level, and the patient level. Purposive sampling method was used to select the healthcare staff of the cardiac surgical intensive care unit (CSICU) of the Shandong Provincial Hospital Affiliated to Shandong First Medical University, as well as the patients with NPPV admitted from October 1 to November 15, 2023 (pre-evidence-based practice) and November 16 to December 31 (post-evidence-based practice), as the subjects of the study. Through questionnaire analysis, the incidence of nasal and facial pressure injury of NPPV patients, the implementation rate of review indicators of medical staff, the score of the knowledge, belief and conduct of medical staff, and the compliance and comfort of patients before and after evidence-based practice were compared. RESULTS: A total of 52 medical staff were included, aged (28.54±6.50) years old, with 3.00 (1.00, 12.75) years of working experience; 2 doctoral degree holders (3.85%), 4 master degree holders (7.69%), 46 bachelor degree holders (88.46%); 2 with senior title (3.85%), 17 with intermediate title (32.69%), and 33 junior titles (63.46%). Fifty patient questionnaires were collected before and after evidence-based nursing practice; the differences between before and after evidence-based practice in terms of gender, age, body weight, duration of ventilator usage, 24-hour bleeding and total bleeding were not statistically significant and were comparable. Compared with the pre-evidence-based practice, after carrying out the corresponding evidence-based nursing practice, the incidence of nasal and facial pressure injuries of NPPV patients decreased from 16.00% (8/50) to 4.00% (2/50, P < 0.05), the total implementation rate of review indicators of medical staff increased from 79.73% to 94.08% (P < 0.01), and the total scores of knowledge, belief and conduct were significantly improved (141.96±13.88 vs. 114.65±19.72, P < 0.05), and compliance and comfort of patients were significantly improved (compliance score: 4.60±0.99 vs. 5.82±1.42, comfort score: 4.10±1.63 vs. 6.92±2.33, both P < 0.05). CONCLUSIONS: The application of an evidence-based nursing approach to obtain evidence related to the prevention of nasal and facial pressure injuries in patients with NPPV can be used to guide clinical practice, significantly reducing the incidence of nasal and facial pressure injuries in such patients, improving the implementation rate of review indicators and the knowledge, belief, and conduct scores of medical staff, and enhancing compliance and comfort of NPPV patients.

Investigation on the Gas Emission Law of Water-Containing Coal across the Rank Range.

Water commonly occurs in coal reservoirs, and it can block the gas flow channels. This has a significant influence on methane transportation within coal. To reveal the gas emission law of water-containing coal across the rank range, three typical coal samples with different coal ranks covering lignite to anthracite were selected in this work. The initial velocity of gas emission (ΔP) under the effect of moisture was measured, and the combination of scanning electron microscopy and mercury injection method was adopted to study the pores and fracture characteristics within coal. Distribution features of oxygen-containing groups in coal were explored by X-ray photoelectron spectroscopy. The microscopic influence mechanism of the water content on ΔP in coal was also comprehensively elucidated. The experimental results show that the moisture content has an obvious inhibitory effect on the ΔP of coal, but the degree of influence on different coal rank samples was different. As the pore space of anthracite (sample XJ) is developed with numerous gas transportation channels, the ΔP has less changes at the lower moisture content (<4.36%). When the moisture content is >4.36%, a large number of water molecules will band together to form water clusters, hindering the gas release, thus greatly reducing the ΔP. However, the change of lignite (sample SL) shows an inverse trend to that of anthracite. Its ΔP is sensitive to the moisture content due to the small number of pores and low porosity. In addition, a great number of oxygen-containing groups in lignite can also provide good surface hydrophilicity for water molecules, and even a small amount of the moisture content (<3.21%) can block most of the pore and facture channels within coal, leading to the remarkable decrease in ΔP. For bituminous coal (sample ML), the distribution of pores and oxygen-containing groups is the most uniform, and the ΔP decreases linearly with the increase in the moisture content.

Medicinal and edible polysaccharides from ancient plants: extraction, isolation, purification, structure, biological activity and market trends of sea buckthorn polysaccharides.

Sea buckthorn (Hippophae L.), a well-known medicinal and edible plant, is known as the "king of VC". Due to its excellent medicinal and nutritional value, it has been developed into a variety of functional products. Sea buckthorn polysaccharides (SPs), one of the important and representative active components, have attracted the attention of researchers in the fields of health food and medicine because of their potential beneficial effects on human health. Recently, SPs have shown various biological activities in in vitro and in vivo studies, such as anti-obesity, immunomodulatory, anti-tumor, antioxidant, anti-inflammatory, anti-fatigue, and hepatoprotective activities. This review provides a comprehensive and systematic summary of the extraction and purification methods, structural characterization, biological activity, and market trends of SPs to provide a theoretical basis for their therapeutic potential and sanitarian functions. A future scope is needed to further explore the medicinal and nutritional value of SPs and incorporate them in functional food products.

Nanomechanical behavior of coal with heterogeneous minerals and pores using nanoindentation.

The coal's mechanical properties have a significant influence on mining safety and the mine environment. Preparing a standard sample and conducting repeat mechanical testing are challenging because the coal is primarily soft, fragmented, and rich in developed fractures. This study used nanoindentation technology, combined with X-ray diffraction, small-angle X-ray, a high magnification microscope, and mechanical parameter scale-up analysis, to study the micromechanical of three coals being dominated by heterogeneous components and pores. The results show that load-displacement curves with different maximum loads (50 mN, 100 mN, and 200 mN) all appear the pop-in events, and coal heterogeneity affects the frequency of their occurrence. As the maximum load is increased, pop-in event of DSC appears once each, YW increases from zero to three times and HM decreases from four to two times. The heterogeneity of pore structure has little effect on residual displacement, which is mainly affected by hard minerals, and hard minerals reduce the law that residual displacement increases with the increase in maximum load. The micromechanical parameters of soft coals are mainly affected by large pores, while hard coals are mainly affected by hard minerals. The coal's heterogeneity does not affect the linear relationship between hardness and elastic modulus, but stronger heterogeneity will weaken the linear relationship between fracture toughness and elastic modulus. Compared to the mechanical parameters after scale-up, the values obtained based on nanoindentation are less than 15.588% larger, and the increase in the heterogeneity and hard minerals can make the predicted parameters more accurate. The nanoindentation technique can not only provide an efficient and accurate method for studying the mechanical properties of heterogeneous coal at the nanoscale, an important guide for large-scale coal.

The potential of herbal drugs to treat heart failure: The roles of Sirt1/AMPK.

Heart failure (HF) is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden. In addition to cardiac myocyte oxidative stress and apoptosis, which are considered mechanisms for the development of HF, alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF. Silent information regulator 1 (Sirt1) and adenosine monophosphate-activated protein kinase (AMPK) are nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases and phosphorylated kinases, respectively. They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), protein 38 mitogen-activated protein kinase (p38 MAPK), peroxisome proliferator-activated receptors (PPARs), and mammalian target of rapamycin (mTOR). We summarized the synergistic effects of Sirt1 and AMPK in the heart, and listed the traditional Chinese medicine (TCM) that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway, to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases (CVDs).

[Impact of Land Use Change on Carbon Storage in Urban Agglomerations in the Guanzhong Plain].

It is important to study the impact of land use change on terrestrial ecosystem carbon stocks in urban agglomerations for the optimization of land use structure and sustainable development in urban agglomerations. Based on the patch-generating land use simulation (PLUS) model and integrated valuation of ecosystem services and trade-offs (InVEST) model, a simulation was developed that predicted the land use change and carbon stock of the Guanzhong Plain urban agglomeration in 2040 under different scenarios and further analyzed the impact of land use change on carbon stock. The results showed that:① The land use types of the Guanzhong Plain urban agglomeration were mainly cultivated land, forest land, and grassland, which accounted for more than 90 % of the total study area. ② From 2000 to 2020, the carbon stock in the Guanzhong Plain showed a continuous downward trend, with cropland, woodland, and grassland being the main sources of carbon stock in the Guanzhong Plain, and the overall carbon stock declined by 15.12×106 t, with the spatial distribution presenting the distribution characteristics of "high in the north and south and low in the middle." ③ By 2040, the carbon stock would decrease the most under the urban development scenario, with a total reduction of 27.08×106 t, and the least under the ecological development scenario, with a total reduction of 4.14×106t. The research results can provide data support for the high-quality development and rational land use planning of the Guanzhong Plain urban agglomeration.

Huang-Lian-Jie-Du decoction drug-containing serum inhibits IL-1ß secretion from D-glucose and PA induced BV2 cells via autophagy/NLRP3 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du decoction (HLJDD), a famous traditional Chinese medicine prescription with heat-clearing and detoxifying effects, has been widely used to treat diabetes, dementia, stroke, and other diseases. However, the detailed mechanisms of HLJDD against type 2 diabetes associated cognitive dysfunction (DACD) through inhibiting interleukin-1ß (IL-1ß) mediated neuroinflammation remain to be further elucidated. AIM OF THE STUDY: The aim of this study was to investigate the effect and potential mechanism of HLJDD on IL-1ß secretion in a DACD model of BV2 cells induced by D-glucose and palmitic acid (PA). MATERIALS AND METHOD: sUltra-performance liquid chromatography-quadrupole/electrostatic field orbital well high-resolution mass spectrometry technology was used to analyze the compounds in HLJDD drug-containing serum. The cytotoxicity was detected by cell counting kit-8. Enzyme-linked immunosorbent assay was used to measure the secretion of IL-1ß in BV2 cells. Reactive oxygen species, glutathione, superoxide dismutase, and malondialdehyde kits were used to detect the intracellular oxidative stress levels. The autophagy level was determined by autophagy staining kit and transmission electron microscope. The expression levels of autophagy-related 7 (Atg7), P62, LC3, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3(NLRP3), Caspase1, and IL-1ß were detected by real-time PCR, immunofluorescence, and western blotting. The Atg7siRNA was transfected into BV2 cells to produce autophagy inhibitory effect. Then the effect of HLJDD drug-containing serum on IL-1ß secretion in D-glucose and PA induced BV2 cells and the potential mechanism of autophagy-NLRP3 inflammasome activation were further observed. RESULTS: Eighty-eight compounds were preliminarily identified in HLJDD drug-containing serum, among which geniposide, baicalin, palmatine, berberine, wogonoside, wogonin, and geniposidic acid were identified as the main prototype components of HLJDD into the blood. In this study, the DACD model of BV2 cells induced by high concentrations of glucose and PA was successfully constructed. HLJDD drug-containing serum significantly reduced the secretion of IL-1ß and the activity of NLRP3 inflammasome with improving the oxidative stress level. Interestingly, the enhanced autophagy level was also found. After transfection of Atg7siRNA into BV2 cells, the effect of HLJDD drug-containing serum on autophagy promotion was reversed, but the inhibitory effects on IL-1ß secretion, NLRP3 inflammasome activation, and oxidative stress were reduced. CONCLUSIONS: These results indicated that the inhibition of HLJDD drug-containing serum on the IL-1ß secretion in D-glucose and PA induced BV2 cells was related to autophagy promotion, the decreased NLRP3 inflammasome activation, and the improved oxidative stress. Moreover, the improvement of HLJDD drug-containing serum on IL-1ß secretion, NLRP3 inflammasome activation, and oxidative stress were all closely associated with Atg7 mediated autophagy promotion. Geniposide, baicalin, palmatine, berberine, wogonoside, wogonin, and geniposidic acid may be the potential active ingredients of HLJDD drug-containing serum.

Scutellarin ameliorates mitochondrial dysfunction and apoptosis in OGD/R-insulted HT22 cells through mitophagy induction.

Scutellarin (Scu), a flavonoid from herbal Erigeron breviscapus (Vaniot) Hand-Mazz, exerts neuroprotective effects against cerebral ischemia. However, whether the effects of Scu are related to mitochondrial protection needs further investigation. In this study, we aimed to clarify the mechanisms of Scu against HT22 cells injury caused by oxygen-glucose deprivation and reperfusion (OGD/R). Our results proved that Scu significantly reduced the overload of intracellular reactive oxygen species (cellar ROS) and mitochondria reactive oxygen species (mito-ROS), ameliorating oxidative stress damage. TUNEL positive rate, Caspase-3 activity, and Cytochrome c (Cyto-c) expression remarkably decreased following Scu treatment. Meanwhile, Scu could maintain mitochondrial morphology and reverse ultrastructure changes. And mitochondrial membrane potential (MMP), oxygen consumption rate (OCR), adenosine triphosphate (ATP) production and Na+/K+-ATPase activity were obviously promoted. Additionally, Scu was found to stimulate mitophagy level by increasing the expression of LC3, Beclin1, PINK1 and Parkin proteins, as well as promoting the degradation of p62. More importantly, the regulatory effects of Scu on mito-ROS, MMP, ATP, Na+/K+-ATPase, cell viability and lactate dehydrogenase (LDH) were markedly limited by Mdivi-1 (a mitophagy inhibitor). Of note, the inhibitor also reversed Scu-mediated apoptosis suppression, evidenced by the diminished apoptosis rate, the down-regulated expression activities of Cyto-c, Bax and cleaved Caspase-3, as well as the elevated level of Bcl-2 protein. Collectively, Scu could improve mitochondrial dysfunction and inhibit apoptosis by stimulating mitophagy, thereby attenuating OGD/R-induced HT22 cells injury.

Study on the Response Law of Coal Pore Structure and Permeability Affected by Acidification Time.

In order to study the pore alteration and permeability of coal affected by acid liquor, samples were collected from the Yuwu coal mine in the Qinshui basin, Shanxi Province, and taken as the study object. Hydrochloric acid (HCl) with a 10% volume concentration was used to treat these coal samples. The pore structure characteristics and gas permeability of this coal with different treatment times were measured by laboratory experiments. The fractal theory was introduced to analyze the complexity of the sample pore and the changing rules of coal permeability. The research results show that acid liquor has a significant influence on the pore structure of YW coal. Under the effect of acid treatment, the micropore volume of the coal sample is reduced, but both the mesopore and macropore volume are increased. The fractal dimension of acidulated coal samples changes in the range of 2.57-2.81, and it is exponentially decreased with the increase of the treatment time. This indicates that the acid treatment can make the YW coal surface become smooth, and the pore structure tends to be smooth. The acidification method is able to effectively enhance the coal permeability with a maximum increment of about 9.43 times. After 30 h of acid treatment, the total pore volume, fractal dimension, and gas permeability of this coal tend to be stable. The acid treatment time should be controlled at around 30 h.

Optimal radiotherapy modality sparing for cardiac valves in left-sided breast cancer.

Background: The cardiotoxicity caused by radiotherapy is a critical problem in the treatment of patients with breast cancer. The appropriate radiotherapy modality sparing for cardiac valves in left-sided breast cancer has not been well defined. The aim of this study was thus to compare the dosimetric differences in heart and cardiac valves of 3-dimensional conformal radiotherapy (3D-CRT), fixed-field intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) to find the optimal radiotherapy modality sparing for cardiac valves in patients with left breast cancer. Methods: From January 5, 2021, to March 15, 2021, 21 patients with left-sided breast cancer postmastectomy were included in this study, and 3 different plans for adjuvant radiation were created using 3D-CRT, IMRT, and VMAT for each patient. All patients received 50 Gy in 25 fractions. The mean dose (Dmean) of the heart; percentage volume of the heart receiving ≥5 Gy (V5), ≥30 Gy (V30), and ≥40 Gy (V40); and the Dmean and the near-maximum dose (D0.03cc) of cardiac valves were extracted from dose-volume histograms (DVHs) and compared. The correlations in dosimetric factors between cardiac valves and the whole heart were analyzed. Results: IMRT significantly decreased the values of V5, V30, V40, and Dmean in the whole heart compared to 3D-CRT and VMAT (P<0.001). Among the 3 different plans, IMRT had the lowest radiation dose to the Dmean and the D0.03cc of the aortic valve (1.27 Gy/1.75 Gy), pulmonary valve (3.44 Gy/6.89 Gy), tricuspid valve (1.02 Gy/1.14 Gy), and mitral valve (0.93 Gy/1.00 Gy). Pearson correlation analysis found that local parameters (Dmean and D0.03cc) within valves were strongly correlated to the global parameters (V5, V30, V40, and Dmean) of the heart. Conclusions: This study revealed that IMRT showed the lowest cardiac valves dose compared with 3D-CRT and VMAT in left-sided breast cancer radiotherapy. IMRT might be the optimal modality sparing for cardiac valves in this group of patients. Further studies need to be carried out in order to validate the protective role of IMRT on the cardiac valves.