Vernicia fordii leaf extract inhibited anthracnose growth by downregulating reactive oxygen species (ROS) levels in vitro and in vivo.

Background: Colletotrichum fructicola is a predominant anthracnose species in Camellia oleifera, causing various adverse effects. Traditional intercropping Vernicia fordii with C. oleifera may enhance anthracnose resistance, but the mechanism remains elusive. Methods: We utilized UPLC-MS/MS and acid-base detection to identify the major antimicrobial alkaloid components in the V. fordii leaf extract. Subsequently, by adding different concentrations of V. fordii leaf extract for cultivating C. fructicola, with untreated C. fructicola as a control, we investigated the impact of the V. fordii leaf extract, cell wall integrity, cell membrane permeability, MDA, and ROS content changes. Additionally, analysis of key pathogenic genes of C. fructicola confirmed that the V. fordii leaf extract inhibits the growth of the fungus through gene regulation. Results: This study discovered the alkaloid composition of V. fordii leaf extract by UPLC-MS/MS and acid-base detection, such as trigonelline, stachydrine, betaine, and O-Phosphocholine. V. fordii leaf extract successfully penetrated C. fructicola mycelia, damaged cellular integrity, and increased ROS and MDA levels by 1.75 and 2.05 times respectively, thereby inhibiting C. fructicola proliferation. By analyzing the key pathogenic genes of C. fructicola, it was demonstrated that the antifungal function of V. fordii leaf extract depends mainly on the regulation of RAB7 and HAC1 gene expression. Therefore, this study elucidates the mechanism of V. fordii -C. oleifera intercropping in strengthening anthracnose resistance in C. oleifera, contributing to efficient C. oleifera cultivation.

Machine learning integrated photocatalysis: progress and challenges.

Discovering efficient photocatalysts has long been the goal of photocatalysis, which has traditionally been driven by serendipitous or try-and-error strategies. Recent developments in photocatalysis integrated with machine learning techniques promise to accelerate the discovery of photocatalysts, but are also facing significant challenges. In this review, advances in machine learning integrated photocatalysis are first presented from the perspective of three main photocatalytic processes: light harvesting, charge generation and separation, and surface redox reactions. Next, progress in using machine learning to understand complex photoactivity-structure relationships and identify the factors governing activity follows. A future photocatalysis paradigm is then provided with the integration of artificial intelligence, robots and automation. Lastly, we discuss the current challenges in machine learning integrated photocatalysis. This review aims to provide a systematic overview and guidelines to the broad scientific community interested in photocatalysis and artificial intelligence for solar fuel synthesis.

Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division.

Objective This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH). Methods Sixty rats were randomly divided into three groups: normal control (NC) group, CIH group, and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure, we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT), examined and compared the adenosine triphosphate (ATP) levels, mitochondrial membrane potential (MMP) levels, reactive oxygen species (ROS) levels, enzymes gene expression levels of Ant1, Cs, Hmox1, and Cox4i1 which represented mitochondrial tricarboxylic acid cycle function, the protein and gene expression levels of DRP1, FIS1, MFN1, and OPA1 which represented mitochondrial fusion and division, and the protein expression levels of BAX, BCL-2, cleaved Caspase-3, and cleaved PARP which represented mitochondrial associated apoptosis pathway of pancreatic islet. Results OGTT and IRT showed blood glucose and insulin levels had no differences among the NC, CIH and CIH+APN groups (both P>0.05) at 0 min, 20 min, 30 min, 60 min, 120 min. However, we found that compared to NC group, CIH increased the ROS level, reduced ATP level and MMP level. The islets of CIH exposed rats showed reduced gene expression levels of Ant1, Cs, Hmox1, and Cox4i1, decreased protein and gene expression levels of MFN1 and OPA1, increased protein and gene expression levels of DRP1 and FIS1, increased protein expression levels of cleaved Caspase-3 and cleaved PARP, with lower ratio of BCL-2/BAX at protein expression level. All the differences among three groups were statistically significant. APN treated CIH rats showed mitigated changes in the above measurements associated with islet injuries. Conclusion APN may ameliorate the pancreatic islet injury induced by CIH via inhibiting the imbalance in mitochondrial fusion and division.

Klotho alleviates chronic intermittent hypoxia-induced genioglossus myocyte apoptosis by inhibiting endoplasmic reticulum stress.

Chronic intermittent hypoxia (CIH) has been shown to induce cell apoptosis in multiple organs of the human body. The present study aimed to assess the effects of exogenous klotho on CIH-induced genioglossus muscle injury, as well as the involvement of endoplasmic reticulum stress (ERS) in this process. A total of 36 adult C57BL/6 male mice were assigned to normoxia control (NC), CIH and CIH + klotho groups (n=12 mice/group). ELISA was performed to detect the level of klotho protein in the serum and in the genioglossus muscle tissue samples. Apoptosis was evaluated using the TUNEL assay. Reactive oxygen species (ROS) levels were quantified using a dihydroethidium assay kit, and the protein and mRNA levels of ERS-associated proteins (namely, glucoseregulated protein 78, C/EBP homologous protein, cleaved caspase-12 and cleaved caspase-3) in genioglossus samples were assessed using immunoblot assay and reverse transcription-quantitative PCR, respectively. Compared with the NC group, the quantities of klotho protein in the serum and genioglossus muscle tissue samples in the CIH group were significantly decreased, whereas the apoptotic rate, ROS levels and protein and mRNA levels of the ERS-associated proteins in the genioglossus muscle were significantly increased. Following supplementation with exogenous klotho protein, the klotho protein levels in the serum and genioglossus muscle tissue of mice were found to be markedly increased, and the apoptotic rate, ROS levels and protein and mRNA levels of the ERS-associated proteins in the genioglossus muscle were decreased compared with those in the CIH group. Taken together, the results of the present study have demonstrated that exogenous klotho may inhibit apoptosis of genioglossus myocytes in mice by inhibiting ROS-associated ERS.

Globular adiponectin alleviates chronic intermittent hypoxia-induced H9C2 cardiomyocytes apoptosis via ER-phagy induction.

This study evaluated the effects of endoplasmic reticulum autophagy (ER-phagy) and globular adiponectin (gAPN) on chronic intermittent hypoxia (CIH)-induced H9C2 cardiomyocytes injury while investigating potential mechanisms of action. The CIH model of H9C2 cardiomyocytes was established in this study. CCK-8 assay was used to determine cell viability post-exposure to various CIH times and gAPN concentrations. Flow cytometry was used to observe H9C2 cardiomyocytes apoptosis and immunofluorescence was used to measure ER-phagy and SEC62 activation. Western blot was used to observe ER stress and AMPK pathway. Results indicated that ER stress was activated in H9C2 cardiomyocytes exposed to CIH. Inhibition of ER stress reduced CIH-induced cell apoptosis. gAPN attenuated CIH-induced ER stress and H9C2 cardiomyocytes apoptosis. ER-phagy and SEC62 protein level were induced by CIH, while gAPN highly enhanced these changes. Inhibition of SEC62 expression reduced ER-phagy and increased ER stress and H9C2 cardiomyocytes apoptosis. Moreover, gAPN induced AMPK expression. Inhibition of AMPK expression reduced SEC62-mediated ER-phagy and increased the H9C2 cardiomyocytes apoptosis. Altogether, our study suggested that gAPN upregulated SEC62-mediated ER-phagy to extenuate ER stress, and mitigated H9C2 cardiomyocytes apoptosis induced by CIH through AMPK activation.

Altered amplitude of low-frequency fluctuation in basal ganglia correlates to pulmonary ventilation function in COPD patients: A resting-state fMRI study.

INTRODUCTION: Patients under chronic obstructive pulmonary disease (COPD) has been reported to be associated with a higher prevalence of cognitive impairment (CI). However, it is still largely unknown whether the aberrant resting-state spontaneous neuronal activity pattern reflected by the amplitude of low-frequency fluctuation (ALFF) analysis will be associated with the CI in COPD patients. MATERIALS: A total of 28 COPD patients and 26 healthy controls were enrolled in this study. Of all the subjects, structural and functional MRI data, spirometry tests performance and neuropsychological assessments of different cognitive domains were collected. Voxel-based two-sample t tests were used to detect brain regions showing differences in the ALFF value between COPD patients and healthy controls. An additional fMRI runs with supplementary oxygen delivery were employed to explore the impact of elevated partial pressure of oxygen (PaO2 ) or moderate hyperoxia on ALFF in COPD patients and healthy controls respectively. RESULTS: More extensive white matter lesion was detected in COPD patients. COPD patients exhibit decreased ALFF value in bilateral basal ganglia areas and right thalamus, and aberrant ALFF value is correlated with PaO2 and pulmonary ventilation function (FEV1%pred). COPD patients performed worse in the Digit Span Test (reverse), Digit Symbol Substitution Test, Trail-making test (A and B) than controls. After supplementary oxygen inhalation, the ALFF value of basal ganglia and right thalamus significantly increased in the controls, but not in the COPD patients. CONCLUSIONS: COPD patients mainly exhibit impaired executive function but not long-term memory in cognitive function assessment. Aberrant ALFF alteration in the deep brain may be directly related to lower PaO2 in COPD patients.

The prognostic impact of serum bilirubin in stage IV colorectal cancer patients.

BACKGROUND: Bilirubin played a great role in antioxidation and anticancer and has been considered as a promising prognostic factor of non-liver disease-related death in various cancers. The aim of this study was to assess the prognostic value of pre-treatment serum bilirubin in stage IV CRC patients. METHODS: Serum bilirubin including TBIL, DBIL, and IBI which were tested at pre-treatment were investigated in 154 stage IV CRC patients in Zhongda Hospital, Nanjing, China, from July 2005 to July 2011. X-tile program was used to determine the optimal cut-off values of these three biomarkers. Kaplan-Meier analysis, univariate, and multivariate cox regression as well as time-dependent ROC curve analysis were performed to evaluate the relations between serum bilirubin and survival outcomes. RESULTS: We got the results that the optimal cut-off points of serum TBIL, DBIL, and IBI levels were 12.9, 6.1, and 4.8 µmol/L, respectively. Univariate analysis showed that elevated TBIL, DBIL, and CEA were significantly associated with poor 5-year OS in stage IV CRC patients. Multivariate cox analysis indicated that the high DBIL (HR=1.603, 95%CI=1.053-2.442, P<.028) and CEA (HR=1.785, 95%CI=1.123-2.837, P=.014) could be identified as independent factors for poor OS. Furthermore, time-dependent ROC curves demonstrated that high DBIL had similar prognostic efficacy as elevated CEA for poor OS (AUC=0.63 and 0.61, respectively). CONCLUSIONS: Pre-treatment elevated TBIL and DBIL levels were associated with poor OS in stage IV CRC patients. Moreover, DBIL could be considered as an independent prognostic biomarker for OS. Furthermore, DBIL had similar prognostic efficacy as CEA for OS.