Four new species of Russula from the Xizang Autonomous Region and other provinces of China.

Russula is the largest genus in the Russulales and is widespread throughout the world. Almost all Russula species are known to be ectomycorrhizal with high ecological and edible values, and some are lethal poisonous. In this study, four new species belonging to the subgenus Russula crown clade are identified based on morphological and phylogenetic evidence from the Xizang Autonomous Region and other provinces of China. Morphologically, Russula paragraveolens (sect. Polychromae, subsect. Xerampelinae) is mainly characterised by a cherry red to blood red pileus centre, a reddish orange pileus margin; R. pseudograveolens (sect. Polychromae, subsect. Xerampelinae) is characterised by a violet brown to brownish red pileus centre, a pale red to pastel red pileus margin and short basidia; R. shigatseensis (sect. Flavisiccantes, subsect. Lepidinae) is characterised by a brownish orange to madder red pileus centre, pinkish red pileus margin, and having lateral branches or branches of hyphal terminations in pileipellis; R. yadongensis (sect. Tenellae, subsect. Laricinae) is characterised by a dark purplish red pileus centre with brownish purple tints and having isolated to clustered spines of spore ornamentations. Their distinct taxonomic status is confirmed by the positions of the four new species in both the ITS and 4-locus (nucLSU, mtSSU, rpb2, tef1) phylogenetic trees.

Recent advances in potential therapeutic targets of ferroptosis­associated pathways for the treatment of stroke (Review).

Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis­associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.

Upregulated dual oxidase 1-induced oxidative stress and caspase-1-dependent pyroptosis reflect the etiologies of heart failure.

BACKGROUND: Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was designed to evaluate the potential role of DUOX1 in heart failure. MATERIALS AND METHODS: AC16 cells were treated with 2 µmol/L of doxorubicin (DOX) for 12, 24, and 48 h to construct a heart failure model. DUOX1 overexpression and silencing in AC16 cell were established. DUOX1 expression was detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pyroptosis and reactive oxygen species (ROS) production were measured by flow cytometry. RESULTS: Increased DUOX1 expression levels were observed after DOX treatment for 24 h in AC16 cells. DUOX1 silencing inhibited DOX-induced pyroptosis and ROS production. The release of IL-1ß, IL-18, and lactate dehydrogenase (LDH), and expression levels of pyroptosis-related proteins were also decreased. DUOX1 overexpression increased pyroptosis, ROS production, IL-1ß, IL-18, and LDH release, and pyroptosis-related protein expression. N-acetyl-cysteine (NAC) significantly reversed DUOX1-induced pyroptosis, ROS, and related factors. CONCLUSION: These results suggest that DUOX1-derived genotoxicity could promote heart failure development. In the process, oxidative stress and pyroptosis may be involved in the regulation of DUOX1 in heart failure.

N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis.

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.

Unravelling the Photoelectrochemical Water Splitting of Nanometer-Thick Carbon Nitride Layer.

Matching the thickness of the graphitic carbon nitride (CN) nanolayer with the charge diffusion length is expected to compensate for the poor intrinsic conductivity and charge recombination in CN for photoelectrochemical cells (PEC). Herein, the compact CN nanolayer with tunable thickness is in situ coated on carbon fibers. The compact packing along with good contact with the substrate improves the electron transport and alleviates the charge recombination. The PEC investigation shows CN nanolayer of 93 nm-thick yields an optimum photocurrent of 116 µA cm-2 at 1.23 V versus RHE, comparable to most micrometer-thick CN layers, with a low onset potential of 0.2 V in 1 m KOH under 1 sun illumination. This optimum performance suggests the electron diffusion length matches with the thickness of the CN nanolayer. Further deposition of NiFe-layered double hydroxide enhanced the surface water oxidation kinetics, delivering an improved photocurrent of 210 µA cm-2 with IPCE of 12.8% at 400 nm. The CN nanolayer also shows extended potential in PEC organic synthesis. This work experimentally reveals the PEC behavior of the nanometer-thick CN layer, providing new insights into CN in the application of energy and environment-related fields.

Five New Species of Gymnopilus from Xizang Autonomous Region of China and Surrounding Areas.

The species of Gymnopilus (Hymenogastraceae, Agricales) are commonly recognized as wood-decaying fungi. Certain members of this genus have been identified as psilocybin-producing mushrooms. Gymnopilus exhibits a diverse range and has a global distribution. In this study, a total of seventy-eight specimens were gathered from ten provinces in China. A comprehensive molecular phylogenetic analysis was conducted, employing gene sequences including ITS, nrLSU, nrSSU, rpb1, rpb2, and tef1-α. Additionally, morphological examinations were also carried out. The phylogenetic topology of Gymnopilus from this study generally agreed with previous studies and facilitated the identification of all those specimens. As a result, eleven species, including five newly discovered ones named Gy. gyirongensis, Gy. variisporus, Gy. tomentosiceps, Gy. tenuibasidialis, and Gy. aurantipileatus, were recognized. Significantly, four of the five newly identified species are native to the Xizang Autonomous Region, emphasizing their specialization in this distinctive habitat. This research contributes to our comprehension of Gymnopilus diversity and lays the groundwork for the conservation and sustainable utilization of Gymnopilus resources.

Therapeutic strategies targeting the NLRP3­mediated inflammatory response and pyroptosis in cerebral ischemia/reperfusion injury (Review).

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD­like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL­1ß and IL­18, as well as gasdermin­D­mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3­mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.

Clinical Significance and Potential Mechanisms of the RNA Methyltransferase KIAA1429 in Osteosarcoma.

Background: KIAA1429, a member of the RNA methyltransferase complex, is involved in cancer progression; however, the clinical significance and underlying mechanism of KIAA1429 in osteosarcoma (OS) remains to be reported. Methods: We evaluated the clinical significance of KIAA1429 in OS by performing RT-qPCR, microarray, and RNA sequencing and using published data as a reference. Two KIAA1429-targeting siRNA constructs were transfected into SW1353 cells. CCK-8 assay, colony formation assays, flow cytometry and the xenograft mouse model were conducted to investigate the biological function of KIAA1429 in OS. Results: The mRNA expression of KIAA1429 was markedly upregulated in 250 OS samples as compared to that in 71 non-cancer samples (standardized mean difference = 0.67). Summary receiver operating characteristic curve analysis revealed that KIAA1429 exhibited reliable diagnostic capacity to differentiate OS samples from non-cancer samples (area under the curve = 0.83). Further, survival analysis indicated that KIAA1429 overexpression was associated with shorter overall survival time. Knocking down KIAA1429 reduced m6A methylation levels, inhibited proliferation, prevented the growth of tumors in vivo and accelerated apoptosis of OS cells. In total, 395 KIAA1429-related genes were identified among co-expressed genes and differentially expressed genes, which were enriched in the cell cycle pathway. Protein-protein interaction network analysis showed that CDK1, CCNA2, and CCNB1 were KIAA1429-related genes, serving as major network hubs in OS. Conclusions: Our findings indicate that KIAA1429 plays an oncogenic role in OS and potentially facilitates OS progression via a mechanism that involves regulating CDK1, CCNA2, and CCNB1.

Hydrophobic Carbon Nitride Nanolayer Enables High-Flux Oil/Water Separation with Photocatalytic Antifouling Ability.

Efficient oil/water separation tackles various issues in occasions of oil leakage and oil discharge, such as environmental pollution, recollection of the oil, and saving the water. Herein, a compact superhydrophobic/superoleophilic graphitic carbon nitride nanolayer coated on carbon fiber networks (CNBA/CF) is designed and synthesized for efficient gravity-driven oil/water separation. The CNBA/CF shows excellent oil absorption and an impressive oil/water filtration separation performance. The flux reaches the state-of-art value of 4.29 × 105 L/m2/h for dichloromethane with separation efficiency up to 99%. Successive oil absorption tests, long-term filtration separation, and harsh conditions experiments confirm the remarkable separation and chemical structure stability of the CNBA/CF filter. Besides, the CNBA/CF demonstrates good photocatalytic antifouling ability thanks to the extended visible light absorption and improved charge separation. This work combines the material surface wettability modulation with a photocatalytic self-cleaning property in the fabrication of efficient oil/water separation materials while overcoming the filter fouling issue.

High precision measurements of lithium isotopic composition at sub-nanogram by MC-ICP-MS with membrane desolvation.

The geochemistry of Li and Li isotopes is a promising tracer of chemical weathering processes for both modern and ancient times. Therefore, accurate and precise determination of the isotopic composition of Li is required for a large variety of complex geological samples with different Li concentrations and matrix/Li ratios. Especially, geochemical studies of precious geological samples with ultra-low lithium content and high matrix. In this study, the accuracy and the precision corresponding to Li isotopic measurements of low-level samples using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) with membrane desolvation introduction system was evaluated. The method of MC-ICP-MS with membrane desolvation and a high-sensitivity X-skimmer cone, together with a simple one-step column separation enabled the high-precision isotopic analysis of Li quantities as small as 2 ng. The long-term instrumental external reproducibility of δ7Li values for the L-SVEC and SPEX-Li were 0.0 ± 0.1‰ (n = 20) and 12.1 ± 0.4‰ (n = 20), respectively. Based on the measurements on a series of international reference materials over the last two years. The measured δ7Li values for the standards with a variety of matrices, including BHVO-2, AGV-2 and seawater (NASS-6). The δ7Li values of BHVO-2 (4.58 ± 0.35‰), AGV-2 (6.85 ± 0.40‰) and NASS-6 (30.88 ± 0.20‰) are in agreement with the published data within the uncertainty. We also present analytical results for South China Sea surface seawater water, meteorite, limestones and rain water. These results demonstrate the validity of the method for obtaining highly precise and accurate outcomes.

TAF1D Functions as a Novel Biomarker in Osteosarcoma.

Background: The most frequent primary bone cancer in teenagers, osteosarcoma (OS), is particularly aggressive with a high mortality rate. Methods: By combining public databases, OS and non-cancer samples were obtained. The Wilcoxon test and standardized mean difference (SMD) were utilized to evaluate the mRNA expression level of TATA-box binding protein associated factor, RNA polymerase 1 subunit D (TAF1D). The potential of TAF1D to discriminate OS samples from non-cancer samples was revealed by summary receiver operating characteristic curve (sROC). To investigate the prognostic significance, Kaplan‒Meier curve and univariate Cox analysis were performed. Immunohistochemistry (IHC) was used to determine the TAF1D protein expression level. ESTIMATE algorithm and TIMER2.0 database were used to reveal the association between TAF1D expression and the immune microenvironment. Enrichment analysis and potential drug prediction were performed to clarify the underlying molecular mechanisms and possible therapeutic directions of TAF1D. Ultimately, the transcription factors (TFs) and the TAF1D binding site were predicted based on the Cistrome and JASPAR databases. Results: TAF1D was upregulated in OS at the mRNA and protein levels and possessed robust discriminatory power. TAF1D upregulation was suggestive of worse prognosis and enhancement of tumor purity in OS patients. The cell cycle was the most significantly enriched pathway, and NU.1025 was considered to be the potential target agent. Finally, MYC was identified as a TF that regulates the expression of TAF1D. Conclusions: Altogether, TAF1D has the potential to serve as a biological marker and therapeutic target in OS, which could offer new perspectives for OS treatment.

Lycium Barbarum polysaccharides ameliorates hyperglycemia-exacerbated cerebral ischemia/reperfusion injury via protecting blood-brain barrier.

BACKGROUND: Hyperglycemia exacerbates brain damage in cerebral ischemia/reperfusion injury. Previous study found that Lycium barbarum polysaccharides (LBP) has a neuroprotective effect on hyperglycemia-aggravated ischemic brain injury, which raising the possibility for treatment of neurodegenerative diseases. However, the underlying mechanism of LBP-induced protection by ameliorating hyperglycemia-aggravated ischemia/reperfusion injury needs to be tested. This study aimed to investigate the effects of LBP on blood-brain barrier (BBB) integrity with a hyperglycemia-aggravated cerebral ischemia/reperfusion injury model. METHODS: Sprague-Dawley male rats were randomly divided into three groups: normoglycemic (NG), hyperglycemic (HG), and LBP-pretreated hyperglycemic (HG + LBP). Animals underwent middle cerebral artery occlusion (MCAO) for 30 min, followed by 1-, 3-, and 7-day of reperfusion. RESULTS: Our results showed that the neurological deficit, infarct volume, cell apoptosis, and IgG leakage in the HG group significantly increased separately, compared with that of the NG group, (p < 0.05). Pre-treatment with LBP reversed these injury indicators (p < 0.05). And much more severe degree of swelling endothelium, swollen astrocyte, and decreased tight junctions in the micro-vessel were detected in the HG group comparing to that of the NG group. In addition, increased degree of basement membrane degradation, dissociation between the astrocyte endfeet and basement membrane, and tight junction's protein degradation was found in the HG group compared with the NG group (p < 0.05). However, when exposure to LBP therapy could reverse the above alterations (p < 0.05). CONCLUSIONS: These results demonstrated that LBP could ameliorate hyperglycemia-exacerbated cerebral ischemia/reperfusion injury via protecting the blood-brain barrier.

Chronic Obstructive Pulmonary Disease Patients With High Peripheral Blood Eosinophil Counts Have Better Predicted Improvement in 6MWD After Rehabilitation: A PRELIMINARY STUDY.

PURPOSE: The objective of this investigation was to determine whether chronic obstructive pulmonary disease (COPD) patients with high blood eosinophil (EOS) counts had better improvement in 6-min walk test (6MWT) after pulmonary rehabilitation (PR). METHODS: Fifty COPD patients were randomly assigned to either the rehabilitation group (RG) or the control group (CG). Patients in the RG (8 wk PR + routine medication) and the CG (routine medication) were followed for 32 wk. According to the blood EOS level, the RG was divided into an EOS ≥ 200 cells/µL group and EOS < 200 cells/µL group. The 6MWT distance, Borg Scale, and COPD Assessment Test (CAT) were evaluated before intervention and 8 wk and 32 wk later. RESULTS: After the 8-wk intervention, 37 patients (19 RG/18 CG) completed the study. At 8-wk and 32-wk follow-up from baseline, a statistically significant difference was found between these two groups in the 6MWT, Borg Scale, and CAT. Compared with baseline, the 6MWT in the RG increased 49.1 ± 40.2 m (95% CI, 29.7-68.5, P < .001) at 8 wk and 60.8 ± 42.1 m (95% CI, 40.5-81.6, P < .001) at 32 wk. In addition, the improvement of 6MWT in the EOS ≥ 200 cells/µL RG group was higher than that in the EOS < 200 cells/µL group (40.1 ± 17.6 m, 95% CI, 36.8-43.4; P = .036) at 32-wk follow-up from baseline. CONCLUSION: An 8-wk PR can improve the exercise capacity of COPD patients, and the benefits persistent for 24 wk. The improvement in the 6MWT was more significant in COPD patients with a high blood EOS count.

Antidepressant alkaloids from the rhizomes of Corydalis decumbens.

Two new alkaloids (1 and 2), named 1,7-dimethoxy-2'-prenyl-1',9-dihydropyrrolo-carbazole (1) and 1,7-dimethoxy-4',5'-dimethylcyclopenta-carbazole-1',3'-dione (2), along with thirteen known alkaloids (3-15) were isolated by means of silica gel, sephadex LH-20, and semi-preparative HPLC from the CHCl3 extraction of Corydalis decumbens for the first time. Their structures were determined by NMR, MS, IR, UV, and related references. Compounds (1-15) were evaluated for their antidepressant activities by measuring inhibition of monoamine neurotransmitter reuptake in vitro. Among them, compounds 1, 2, 4, and 6 showed certain antidepressant activities.

Characterization of Altered Oropharyngeal Microbiota in Hospitalized Patients With Mild SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by full-length 16S rRNA gene sequencing through the NANOPORE platform of oropharynx swab specimens from 10 mild COVID-19 patients and 10 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in mild COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Peptostreptococcus anaerobius and Pseudomonas stutzeri and depletion of Sphingomonas yabuuchiae, Agrobacterium sullae, and Pseudomonas veronii. Based on the relative abundance of the oropharyngeal microbiota at the species level, we built a microbial classifier to distinguish COVID-19 patients from healthy controls, in which P. veronii, Pseudomonas fragi, and S. yabuuchiae were identified as the most prominent signatures for their depletion in the COVID-19 group. Several members of the genus Campylobacter, especially Campylobacter fetus and Campylobacter rectus, which were highly enriched in COVID-19 patients with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and showed a significant correlation with disease status and several routine clinical blood indicators, indicate that several bacteria may transform into opportunistic pathogen in COVID-19 patients when facing the challenges of viral infection. We also found the diver taxa Streptococcus anginosus and Streptococcus alactolyticus in the network of disease patients, suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the microbial association patterns. In conclusion, the low sample size of SARS-CoV-2 infection patients (n = 10) here makes these results tentative; however, we have provided the overall characterization that oropharyngeal microbiota alterations and microbial correlation patterns were associated with COVID-19 severity in Anhui Province.

Does delaying ureteral stent placement lead to higher rates of preoperative acute pyelonephritis during pregnancy?

BACKGROUND: Pregnancy with renal colic may cause pyelonephritis, decreased renal function, systemic infection and even shock in pregnant women, and cause premature birth and other adverse pregnancy outcomes. When surgery is necessary, the relationship between timing of the operation and the outcome of the mother and child are not known. AIM: To investigate the association between time to ureteral stent placement and clinical outcomes of patients with renal colic during pregnancy. METHODS: In this retrospective study, pregnant women with renal colic who underwent surgery were studied. Maternal preoperative acute pyelonephritis (PANP), pregnancy outcome, and length of hospital stay (LOS) were compared between the two groups. RESULTS: 100 patients were included in the analysis, median age was 30 years. Median time to ureteral stent placement was 48 h (interquartile range, 25-96 h), and 32 patients (32%) were diagnosed with PANP. PANP was closely related to hospitalization costs, re-admission to the hospital due to urinary tract infection after surgery and premature delivery. Multivariate analysis found that stone location and time from pain to admission were related to PANP. CONCLUSION: Both early and delayed surgery are safe and effective for the treatment of renal colic during pregnancy. Early surgery may be superior to a delayed procedure due to shorter LOS. For pregnant patients with renal colic, delayed surgery within 48 h is not related to the clinical outcome of the mother and child. However, the time from pain to hospital admission was related to PANP.

Spatial distribution and potential sources of arsenic and water-soluble ions in the snow at Ili River Valley, China.

Trace elements and water-soluble ions in snow can be used as indicators to reveal natural and anthropogenic emissions. To understand the chemical composition, characteristics of snow and their potential sources in the Ili River Valley (IRV), snow samples were collected from 17 sites in the IRV from December 2018 to March 2019. Inverse distance weighting, enrichment factor (EF) analysis, and backward trajectory modelling were applied to evaluate the spatial distributions and sources of water-soluble ions and dissolved arsenic (As) in snow. The results indicate that Ca2+ and SO42- were the dominant ions, and the concentrations of As ranged from 0.09 to 0.503 µg L-1. High concentrations of As were distributed in the northwest and middle of the IRV, and the concentrations of the major ions were high in the west of the IRV. The strong correlation of As with F-, SO42-, and NO2- demonstrates that As mainly originated from coal-burning and agricultural activities. Principal component analysis showed that the ions originated from a combination of anthropogenic and crustal sources. The EFs showed that K+, SO42-, and Mg2+ were mainly influenced by human activities. Backward trajectory cluster analysis suggested that the chemical composition of snow was affected by soil dust transport from the western air mass, the unique terrain, and local anthropogenic activities. These results provide important scientific insights for atmospheric environmental management and agricultural production within the IRV.

Oxymatrine Alleviates Hyperglycemic Cerebral Ischemia/Reperfusion Injury via Protecting Microvessel.

Hyperglycemia aggravates cerebral ischemia/reperfusion (I/R) injury via vascular injury. There is still a lack of effective pharmaceutical preparations for cerebral I/R injury under hyperglycemia. This study aimed to investigate the effects of oxymatrine (OMT) on hyperglycemia-exacerbated cerebral I/R injury in vitro and in vivo. The middle cerebral artery occlusion (MCAO) and reperfusion was established in the rats under hyperglycemia. Meanwhile, oxygen-glucose deprivation and reoxygenation (OGD/R) with high glucose was used as an in vitro model of hyperglycemic cerebral I/R injury. The results showed that the neurological deficit score, mortality, infarct volume and penumbra apoptosis in hyperglycemia group were significantly higher than those in normal glucose group. OMT pre-treated obviously reduced the degree of neurological deficit, mortality, infarct volume, improve cerebral blood flow after I/R in rats with hyperglycemia, and increase the survival rate of human brain microvascular endothelial cells (HBMECs) in high glucose and OGD/R group. OMT significantly improved the ultrastructure changes of endothelial cells, and maintain the migration and angiogenesis potency of HBMECs in high glucose and OGD/R group. OMT obviously alleviated the down-regulating CD31 and CD105 expression in cerebral microvessels caused by hyperglycemia. It is concluded that OMT treatment might alleviate cerebral I/R injury under hyperglycemia via protecting microvessels.

Structurally diverse Monascus pigments with hypolipidemic and hepatoprotective activities from highland barley Monascus.

Highland barley Monascus has historically been used in solid state fermentation and traditional fermented foods in Tibet. It is possessed of the characteristics of medicine and food. Three new 8,13-unsaturated benzocyclodiketone-conjugated Monascus pigments (1-3), three new benzofuran Monascus pigments (4-6), three new butylated malonyl Monascus pigments (7-9), and eleven known Monascus pigment derivatives (10-20) were isolated from highland barley Monascus for the first time. Their structures were determined by analyzing NMR, MS, UV, and IR spectral data and compared with relevant references. Among them, compounds 2, 4, 6 showed important inhibition of pancreatic lipase activity, and decreased significantly FFA-induced lipid accumulation in HepG2 liver cells. Additionally, compounds 1, 10, 14, 16, 18 exhibited certain hepatoprotective activities against the damage in acetaminophen-induced HepG2 cells. The plausible biogenetic pathway and preliminary structure activity relationship of the selected compounds were scientifically summarized and discussed in this work.

Clinical Significance and Underlying Mechanisms of CELSR3 in Metastatic Prostate Cancer Based on Immunohistochemistry, Data Mining, and In Silico Analysis.

Background: The treatment and survival rate of patients with metastatic prostate cancer (MPCa) remain unsatisfactory. Herein, the authors investigated the clinical value and potential mechanisms of cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) in MPCa to identify novel targets for clinical diagnosis and treatment. Materials and Methods: mRNA microarray and RNA-Seq (n = 1246 samples) data were utilized to estimate CELSR3 expression and to assess its differentiation ability in MPCa. Similar analyses were performed with miRNA-221-3p. Immunohistochemistry performed on clinical samples were used to evaluate the protein expression level of CELSR3 in MPCa. Based on CELSR3 differentially coexpressed genes (DCEGs), enrichment analysis was performed to investigate potential mechanisms of CELSR3 in MPCa. Results: The pooled standard mean difference (SMD) for CELSR3 was 0.80, demonstrating that CELSR3 expression was higher in MPCa than in localized prostate cancer (LPCa). CELSR3 showed moderate potential to distinguish MPCa from LPCa. CELSR3 protein expression was found to be markedly upregulated in MPCa than in LPCa tissues. The authors screened 894 CELSR3 DCEGs, which were notably enriched in the focal adhesion pathway. miRNA-221-3p showed a significantly negative correlation with CELSR3 in MPCa. Besides, miRNA-221-3p expression was downregulated in MPCa than in LPCa (SMD = -1.04), and miRNA-221-3p was moderately capable of distinguishing MPCa from LPCa. Conclusions: CELSR3 seems to play a pivotal role in MPCa by affecting the focal adhesion pathway and/or being targeted by miRNA-221-3p.