Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

Associations between new obesity indices and abnormal bone density in type 2 diabetes mellitus patients.

The clinical data analysis found that, compared with the traditional obesity index, the waist-weight ratio (WWR) has more advantages in predicting abnormal bone mineral density in subjects with type 2 diabetes. WWR may serve as a new predictive indicator for osteoporosis in T2DM patients. PURPOSE: This study was designed to explore the correlation between obesity-related indices and bone mineral density (BMD) and its influencing factors in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 528 patients with type 2 diabetes were recruited. Glucose tolerance, insulin stimulation, and blood biochemical tests were conducted on all participants. All subjects underwent dual-energy X-ray bone density testing and were grouped based on the bone density results. RESULTS: Compared with those in the normal BMD group, the waist-to-body weight ratio (WWR) and weight-adjusted-waist index (WWI) in the osteopenia and osteoporosis groups were significantly greater, while body mass index (BMI) was significantly lower (P < 0.05). The logistic regression results showed that the WWR, WWI, and BMI were independently correlated with abnormal BMD in T2DM patients (P < 0.05). WWR and the WWI were negatively correlated with the T-value of bone density in various parts of the body, while BMI was positively correlated with the T-value of bone density (P < 0.05). The area under the working characteristic curve (AUC) for T2DM patients with abnormal bone mass predicted by the WWR [0.806, 95% CI = (0.770-0.843), P < 0.001] was greater than that for patients with other obesity indicators, such as the WWI and BMI. CONCLUSION: We found a positive correlation between the WWR and bone density in T2DM patients. Compared with other obesity indicators, such as BMI and WWI, the WWR has a stronger discriminative ability for T2DM patients with abnormal bone density. Therefore, more attention should be given to the WWR in T2DM patients.

Genetic insights into the relationship between immune cell characteristics and ischemic stroke: A bidirectional Mendelian randomization study.

BACKGROUND AND PURPOSE: Ischemic stroke, a major contributor to global disability and mortality, is underpinned by intricate pathophysiological mechanisms, notably neuroinflammation and immune cell dynamics. Prior research has identified a nuanced and often paradoxical link between immune cell phenotypes and ischemic stroke susceptibility. The aim of this study was to elucidate the potential causal links between the median fluorescence intensity (MFI) and morphological parameters (MP) of 731 immune cell types and ischemic stroke risk. METHODS: By analyzing extensive genetic datasets, we conducted comprehensive Mendelian randomization (MR) analyses to discern the genetic correlations between diverse immune cell attributes (MFI and MP) and ischemic stroke risk. RESULTS: Our study identified key immune cell signatures linked to ischemic stroke risk. Both B cells and T cells, among other immune cell types, have a bidirectional influence on stroke risk. Notably, the regulatory T-cell phenotype demonstrates significant neuroprotective properties, with all odds ratio (OR) values and confidence intervals (CIs) being less than 1. Furthermore, CD39 phenotype immune cells, particularly CD39+ CD8+ T cells (inverse variance weighting [IVW] OR 0.92, 95% CI 0.87-0.97; p = 0.002) and CD39+ activated CD4 regulatory T cells (IVW OR 0.93, 95% CI 0.90-0.97; p < 0.001), show notable neuroprotection against ischemic stroke. CONCLUSION: This investigation provides new genetic insights into the interplay between various immune cells and ischemic stroke, underscoring the complex role of immune processes in stroke pathogenesis. These findings lay a foundation for future research, which may confirm and expand upon these links, potentially leading to innovative immune-targeted therapies for stroke prevention and management.

Structure and Defect Engineering Synergistically Boost High Solar-to-Chemical Conversion Efficiency of Cerium oxide/Au Hollow Nanomushrooms for Nitrogen Photofixation.

Photocatalytic nitrogen fixation using solar illumination under ambient conditions is a promising strategy for production of the indispensable chemical NH3 . However, due to the catalyst's limitations in solar energy utilization, loss of hot electrons during transfer, and low nitrogen adsorption and activation capacity, the unsatisfactory solar-to-chemical conversion (SCC) efficiencies of most photocatalysts limit their practical applications. Herein, cerium oxide nanosheets with abundant strain-VO defects were anchored on Au hollow nanomushroom through atomically sharp interfaces to construct a novel semiconductor/plasmonic metal hollow nanomushroom-like heterostructure (denoted cerium oxide-AD/Au). Plasmonic Au extended the absorption of light from the visible to the second near-infrared region. The superior interface greatly enhanced the transfer efficiency of hot electrons. Abundant strain-VO defects induced by interfacial compressive strain promoted adsorption and in situ activation of nitrogen, and such synergistic promotion of strain and VO defects was further confirmed by density functional theory calculations. The judicious structural and defect engineering co-promoted the efficient nitrogen photofixation of the cerium oxide-AD/Au heterostructures with a SCC efficiency of 0.1 % under simulated AM 1.5G solar illumination, which is comparable to the average solar-to-biomass conversion efficiency of natural photosynthesis by typical plants, thus exhibiting significant potential as a new candidate for artificial photosynthesis.

The Structural Changes of Frontal Subregions and Their Correlations with Cognitive Impairment in Patients with Alzheimer's Disease.

BACKGROUND: The frontal lobe is affected by Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, we still lack sufficient understanding of subregion atrophy in the frontal cortex, and the relationship between subregions volume and cognitive decline in AD or MCI remains unclear. METHODS: This study enrolled 434 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 150 cognitively normals (CN), 187 subjects with MCI, and 97 patients with AD. The gray matter of frontal regions and subregions was divided based on the BNA-246 atlas and its volume was measured by voxel-based morphometry (VBM). Analysis of covariance was performed to compare the differences in frontal regions and subregions volume. Then, receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to analyze the discriminative ability of subregion volume to distinguish the three groups. In addition, we investigated the association of subregion volume with Mini-Mental State Examination (MMSE) score and Alzheimer's Disease Assessment Scale-Cognitive Behavior section (ADAS-cog) scores with age, gender, education, and the estimated total intracranial volume (eTIV) as covariates. RESULTS: In addition to the regions of frontal lobe atrophy found in previous studies, atrophy of the precentral gyrus (PrG) and some of its subregions were found in MCI. The volume of the right dorsal area 9/46 (MFG_7_1) was the best index to differentiate AD from CN, with an AUC value of 0.7. Moreover, we found that some subregions are associated with cognition in patients with MCI and AD. CONCLUSIONS: Frontal lobe atrophy in MCI is more extensive than we assumed. In addition, the volume of right MFG_7_1 has the potential to distinguish AD from CN.

Sleep Duration Positively Correlates with Global Cognition in the Non-Demented Older Adults with High School or above Education.

BACKGROUND: Sleep disturbance is common in the elderly. The effect of sleep duration on cognitive function in the non-demented older adults with high school or above education needs to be clarified. Here, we conducted a cross-sectional study to explore the correlation between sleep duration and multi-domain cognitive function in non-demented older adults. METHODS: A total of 226 adults aged 60 years and over who have an educational background over 9 years, received a battery of neuropsychological evaluations. The Mini-Mental State Examination (MMSE) was used to assess global cognitive function, the Auditory Verbal Learning Test (AVLT), Verbal Fluent Test (VFT), Trial Making Test-A/B (TMT-A/B), Symbol Digit Modalities Test (SDMT), and Rey-Osterriech Complex Figure Test (CFT) were used to assess the memory, language, attention and executive, and visuospatial functions respectively. Sleep characteristics were collected by questionnaire. RESULTS: Subjects with sleep disturbance performed worse in visuospatial ability as compared with those with normal sleep. A significant correlation between nocturnal/total sleep duration and MMSE scores and CFT scores was found in overall subjects using linear regression models after adjusting for age, gender, education and BMI. Consistently, the nocturnal/total sleep duration positively correlated with MMSE scores after controlling for age, gender, education, BMI, hypertension, diabetes, hyperlipidemia, coronary artery disease and household conditions. CONCLUSIONS: The results indicate that shorter sleep duration impairs the global cognition and visuospatial ability in the older adults with high school or above education, even in the very early non-demented stage.

Relationship between FGF21 and drug or nondrug therapy of type 2 diabetes mellitus.

Sedentary and high-calorie diets are associated with increased risk of obesity and type 2 diabetes mellitus, while exercise and diet control are also important nondrug treatments for diabetes. Fibroblast growth factor 21 (FGF21) is an important cytokine, which is mainly expressed in liver, fat and muscle tissue responding to nutrition and exercise, and plays an important role in the improvement of glucose and lipid metabolism. Due to the increasing serum FGF21 level in obesity and diabetes, FGF21 can be used as a predictor or biomarker of diabetes. A variety of clinical antidiabetic drugs can reduce the content of FGF21, possibly for the improvement of FGF21 sensitivity. In this paper, we reviewed the interactions between FGF21 and nondrug therapy (diet and exercise) for diabetes and explored the potential value of the combined application of clinical antidiabetic drugs and FGF21.

The relationship between Schistosoma and glycolipid metabolism.

Diabetes and obesity have become the most popular metabolic diseases in the world. A large number of previous studies have shown that glucose and lipid metabolism disorder is an important risk factor and a main cause of diabetes and obesity. Schistosoma is a parasite transmitted by freshwater snails. It can induce a series of inflammatory and immune reactions after infecting the human body, causing schistosomiasis. However, in recent years, studies have found that Schistosoma infection or Schistosoma related products can improve or prevent some immune and inflammatory diseases, such as severe asthma, inflammatory bowel disease, diabetes and so on. Further experiments have also revealed that Schistosoma can promote the secretion of anti-inflammatory factors and regulate the glucose and lipid metabolism in the host body by polarizing immune cells such as T cells, B cells and dendritic cells (DCs). In this review, we summarize studies that investigated Schistosoma and Schistosoma-derived products and their relationship with glycolipid metabolism and related diseases, highlighting potential protective mechanisms.

Association of Hepatic Steatosis Index and Fatty Liver Index with Carotid Atherosclerosis in Type 2 Diabetes.

Background/aim: Previous studies have suggested that the hepatic steatosis index (HSI) and fatty liver index (FLI) can be used as a predictor of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to determine whether non-invasive indices of hepatic steatosis (HSI and FLI) are associated with carotid atherosclerosis in type 2 diabetes mellitus (T2DM). Methods: This was a cross-sectional study conducted in the T2DM patients (n=768). Carotid intima-media thickness (CIMT) was measured by the Color Doppler ultrasound. The HSI was calculated based on gender, body mass index (BMI), and transaminases level. The FLI was based on BMI, waist circumference (WC), triacylglycerols (TG) and g-glutamyl transferase (GGT). Results: Raised HSI and FLI levels was associated with increased CIMT levels in T2DM patients. Patients with greater CIMT had higher HSI (39.10 ± 5.70 vs 36.10 ± 4.18, P < 0.001) and FLI (46.35 (29.96, 65.54) vs 36.93 (18.7, 57.93), P < 0.001) than those with lower CIMT. Subjects with existing carotid plaque had higher HSI (38.28 ± 5.63 vs 35.69 ± 3.45 P < 0.001) and FLI (47.41 (27.77, 66.62) vs 37.19 (17.71, 51.78), P < 0.001) accordingly. HSI (r = 0.343, P < 0.001) and FLI (r = 0.184, P < 0.001) were positively related with the CIMT. In the linear regression, after full adjustment metabolic risk factors, smoking, and measures of insulin resistance, HSI and FLI were independently associated with CIMT (HSI: ß = 0.011, FLI: ß = 0.001, all P < 0.01). Further, logistic regression analyses showed that higher HSI and FLI had an impact on the risk for carotid atherosclerosis [HSI: OR (95%CI): 1.174 (1.123-1.228), FLI: OR (95%CI): 1.011(1.004-1.019), all P < 0.01]. Overall, increasing values of HSI and FLI were associated with CIMT (P < 0.05) significantly across different categories of age and hypertension. Conclusion: Current data suggest HSI and FLI are independently correlated with carotid atherosclerosis in T2DM. They may be a simple and useful marker for assessing the progression of diabetic macrovascular complications.

Cytosolic glyceraldehyde-3-phosphate dehydrogenase 2/5/6 increase drought tolerance via stomatal movement and reactive oxygen species scavenging in wheat.

Drought is a major threat to wheat growth and crop productivity. However, there has been only limited success in developing drought-hardy cultivars. This lack of progress is due, at least in part, to a lack of understanding of the molecular mechanisms of drought tolerance in wheat. Here, we evaluated the potential role of three cytosolic glyceraldehyde-3-phosphate dehydrogenases (TaGAPC2/5/6) under drought stress in wheat and Arabidopsis. We found that TaGAPC2/5/6 all positively responded to drought stress via reactive oxygen species (ROS) scavenging and stomatal movement. The results of yeast co-transformation and electrophoretic mobility shift assay showed that TaWRKY33 acted as a direct regulator of TaGAPC2/5/6 genes. The dual luciferase reporter assay indicated that TaWRKY33 positively activated the expression of TaGAPC2/5/6. The results of bimolecular fluorescence complementation and yeast two-hybrid system demonstrated that TaGAPC2/5/6 interacted with phospholipase Dδ (PLDδ). We then demonstrated that TaGAPC2/5/6 positively promoted the activity of TaPLDδ in vitro and in vivo. Furthermore, lower PLDδ activity in RNAi wheat could lead to less PA accumulation, causing higher stomatal aperture sizes under drought stress. In summary, our results establish a new positive regulatory mechanism of TaGAPCs which helps wheat fine-tune their drought responses.

Keap1-targeting microRNA-941 protects endometrial cells from oxygen and glucose deprivation-re-oxygenation via activation of Nrf2 signaling.

BACKGROUND: Mimicking ischemia-reperfusion injury, oxygen and glucose deprivation (OGD)-re-oxygenation (OGDR) applied to endometrial cells produces significant oxidative stress and programmed necrosis, which can be inhibited by nuclear-factor-E2-related factor 2 (Nrf2) signaling. MicroRNA (miRNA)-induced repression of Keap1, a Nrf2 suppressor protein that facilitates Nrf2 degradation, is novel strategy to activate Nrf2 cascade. METHODS: MicroRNA-941 (miR-941) was exogenously expressed in HESC and primary human endometrial cells, and the Nrf2 pathway examined by Western blotting and real-time quantitative PCR analysis. The endometrial cells were treated with OGDR, cell programmed necrosis and apoptosis were tested. RESULTS: MiR-941 is a novel Keap1-targeting miRNA that regulates Nrf2 activity. In T-HESC cells and primary human endometrial cells, ectopic overexpression of miR-941 suppressed Keap1 3'-UTR (untranslated region) expression and downregulated its mRNA/protein expression, leading to activation of the Nrf2 cascade. Conversely, inhibition of miR-941 elevated Keap1 expression and activity in endometrial cells, resulting in suppression of Nrf2 activation. MiR-941 overexpression in endometrial cells attenuated OGDR-induced oxidative stress and programmed necrosis, whereas miR-941 inhibition enhanced oxidative stress and programmed necrosis. MiR-941 overexpression and inhibition were completely ineffective in Keap1-/Nrf2-KO T-HESC cells (using CRISPR/Cas9 strategy). Restoring Keap1 expression, using an UTR-depleted Keap1 construct, abolished miR-941-induced anti-OGDR activity in T-HESC cells. Thus Keap1-Nrf2 cascade activation is required for miR-941-induced endometrial cell protection. CONCLUSIONS: Targeting Keap1 by miR-941 activates Nrf2 cascade to protect human endometrial cells from OGDR-induced oxidative stress and programmed necrosis. Video Abstract.

Inheritance and expression of Bt cry1Ba3 gene in progeny from transformed cabbage plants.

Stable inheritance and expression of transgene are important parameters for successful use of a transgenic crop. We previously transformed a Bt cry1Ba3 gene into cabbage inbred line CA21-3. To evaluate the stability of our Bt cabbage lineages, transgene inheritance and expression were examined in four successive generations under greenhouse conditions. In our study, T1, T2 and T3 progenies of the three independent transgenic lineages (YA-1, YA-2 and YA-3) were generated and then the inheritance and expression of cry1Ba3 were analyzed in sexually derived progeny. Segregation ratio of 2.81:1, 3.27:1 and 3.07:1 was found in T1 progeny of lineages YA-1, YA-2 and YA-3, respectively. Chi-square analysis indicated that these segregation ratios of corresponding population fit the 3:1 ratio. Segregation ratios of the transgene in T2 progeny showed either 3:1 or all expression of cry1Ba3. These data suggest that cry1Ba3 in CA21-3 can be inherited in a Mendelian manner. ELISA analysis of transgenic plants from four generations demonstrated that cry1Ba3 had been stably transmitted to the T3 progeny. Additionally, under artificial infestation conditions, the homozygous T3-YA-1-2-1 line exhibited excellent resistance to Plutella xylostella as compared with un-transformed CA21-3. All these results imply that the three cabbage lineages are genetically stable and can be used to inhibit damage on cabbage caused by P. xylostella.

Higher body mass index deteriorates postoperative outcomes of pancreaticoduodenectomy.

BACKGROUND: Previous studies presented controversies in impact of body mass index (BMI) on perioperative complications in pancreatectomy, and mainly focused on Western population. This study aimed to explore the impact of BMI on perioperative outcomes in Chinese patients undergoing pancreaticoduodenectomy. METHODS: Seven hundred and seven adult patients undergoing open pancreaticoduodenectomy between January 2005 and December 2016 at Ruijin Hospital were studied retrospectively and categorized as obese (BMI ≥25 kg/m2), overweight (BMI ≥23 kg/m2 and <25 kg/m2), or normal weight (BMI ≥18.5 kg/m2 and <23 kg/m2). Associations of these BMI groups with perioperative outcomes were evaluated. RESULTS: The overweight and obese groups experienced higher risk of clinically related postoperative pancreatic fistula (CR-POPF) (7.6% vs. 9.9% vs. 17.6%, P = 0.002) and re-operation (1.1% vs. 2.5%  vs. 5.1%, P = 0.017), and longer systemic inflammation response syndrome (SIRS) duration [2 (1-9) d vs. 2 (1-7) d vs. 3 (1-10) d, P = 0.003] and postoperative hospital stay [19 (2-84) d vs. 19 (7-158) d vs. 23 (8-121) d, P = 0.023] than the normal weight group did. The multiple logistic regression models showed obese as an independent risk factor for CR-POPF (P = 0.013). The multiple linear regression analysis confirmed BMI as a predictor for prolonged postoperative hospital stay (P = 0.005). CONCLUSIONS: Higher BMI results in higher morbidity of Chinese patients undergoing open pancreaticoduodenectomy. Pancreaticoduodenectomy is still a safe surgery procedure for overweight and obese patients, with intensive perioperative management.

Correction: Xixi, Li., et al. The Plastidial Glyceraldehyde-3-Phosphate Dehydrogenase Is Critical for Abiotic Stress Response in Wheat. Int. J. Mol. Sci. 2019, 20, 1104.

The author wishes to make the following correction to this paper [...].

[The Efficacy of 17 Cases of Pancreaticoduodenectomy Combined with Vascular Resection and Reconstruction by Using Robotic Operation System (with Video)].

OBJECTIVE: To explore the clinical efficacy of pancreaticoduodenectomy (PD) combined with vascular resection and reconstruction under robotic surgery system in the treatment of borderline resectable pancreatic cancer. METHODS: The clinical data of 17 patients with borderline resectable pancreatic cancer who underwent PD combined with vascular resection and reconstruction (see the Video 1 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/20200760202) under robotic surgery system between August 2011 and September 2018 was analyzed retrospectively. RESULTS: There were 4 cases required conversion because of serious tumor invasion and soft pancreas texture, the other 13 cases were successfully completed. 16 cases (94%) achieved margin-negative resection (R0 resection), 14 cases combined with vein resection, and 3 cases combined with arterial resection. The mean operation time was (401±170) min, the mean blood loss was (647±345) mL, the mean postoperative length of hospital stay was (20±8) d. There was no perioperative death. Postoperative pathology findings and follow-up outcomes were as follows: 1 patient was diagnosed as intraductal papillary mucinous neoplasm (IPMN) and 1 patient was diagnosed as pancreatic neuroendocrine tumors (PNET) (Grade 1), 8 patients with pancreatic ductal adenocarcinoma (PDAC). 1 patient with pancreatic neuroendocrine carcinoma (PNEC) died because of tumor recurrence and metastasis during the follow-up period, the median (Min-Max) survival time was 12 (8-26) months. 5 patients with PDAC and 1 patient with malignant IPMN were currently in the follow-up period. CONCLUSION: It is safe and feasible to perform RPD with vascular resection and reconstruction. The patient's condition should be fully evaluated before surgery to select the most appropriate treatment.

Prediction of response after chemoradiation for esophageal cancer using a combination of dosimetry and CT radiomics.

PURPOSE: To investigate the treatment response prediction feasibility and accuracy of an integrated model combining computed tomography (CT) radiomic features and dosimetric parameters for patients with esophageal cancer (EC) who underwent concurrent chemoradiation (CRT) using machine learning. METHODS: The radiomic features and dosimetric parameters of 94 EC patients were extracted and modeled using Support Vector Classification (SVM) and Extreme Gradient Boosting algorithm (XGBoost). The 94-sample dataset was randomly divided into a 70-sample training subset and a 24-sample independent test set while keeping the class proportions intact via stratification. A receiver operating characteristic (ROC) curve was used to assess the performance of models using radiomic features alone and using combined radiomic features and dosimetric parameters. RESULTS: A total of 42 radiomic features and 18 dosimetric parameters plus the patients' characteristic parameters were extracted for these 94 cases (58 responders and 36 non-responders). XGBoost plus principal component analysis (PCA) achieved an accuracy and area under the curve of 0.708 and 0.541, respectively, for models with radiomic features combined with dosimetric parameters, and 0.689 and 0.479, respectively, for radiomic features alone. Image features of GlobalMean X.333.1, Coarseness, Skewness, and GlobalStd contributed most to the model. The dosimetric parameters of gross tumor volume (GTV) homogeneity index (HI), Cord Dmax, Prescription dose, Heart-Dmean, and Heart-V50 also had a strong contribution to the model. CONCLUSIONS: The model with radiomic features combined with dosimetric parameters is promising and outperforms that with radiomic features alone in predicting the treatment response of patients with EC who underwent CRT. KEY POINTS: • The model with radiomic features combined with dosimetric parameters is promising in predicting the treatment response of patients with EC who underwent CRT. • The model with radiomic features combined with dosimetric parameters (prediction accuracy of 0.708 and AUC of 0.689) outperforms that with radiomic features alone (best prediction accuracy of 0.625 and AUC of 0.412). • The image features of GlobalMean X.333.1, Coarseness, Skewness, and GlobalStd contributed most to the treatment response prediction model. The dosimetric parameters of GTV HI, Cord Dmax, Prescription dose, Heart-Dmean, and Heart-V50 also had a strong contribution to the model.

Regulation of angiopoietin-like protein 8 expression under different nutritional and metabolic status.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with increasing prevalence worldwide. Angiopoietin-like protein 8 (ANGPTL8), a member of the angiopoietin-like protein family, is involved in glucose metabolism, lipid metabolism, and energy homeostasis and believed to be associated with T2DM. Expression levels of ANGPTL8 are often significantly altered in metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus. Studies have shown that ANGPTL8, together with other members of this protein family, such as angiopoietin-like protein 3 (ANGPTL3) and angiopoietin-like protein 4 (ANGPTL4), regulates the activity of lipoprotein lipase (LPL), thereby participating in the regulation of triglyceride related lipoproteins (TRLs). In addition, members of the angiopoietin-like protein family are varyingly expressed among different tissues and respond differently under diverse nutritional and metabolic status. These findings may provide new options for the diagnosis and treatment of diabetes, metabolic syndromes and other diseases. In this review, the interaction between ANGPTL8 and ANGPTL3 or ANGPTL4, and the differential expression of ANGPTL8 responding to different nutritional and metabolic status during the regulation of LPL activity were reviewed.

The Plastidial Glyceraldehyde-3-Phosphate Dehydrogenase Is Critical for Abiotic Stress Response in Wheat.

Plastidial glyceraldehyde-3-phosphate dehydrogenase (GAPDH, GAPCp) are ubiquitous proteins that play pivotal roles in plant metabolism and are involved in stress response. However, the mechanism of GAPCp's function in plant stress resistance process remains unclear. Here we isolated, identified, and characterized the TaGAPCp1 gene from Chinese Spring wheat for further investigation. Subcellular localization assay indicated that the TaGAPCp1 protein was localized in the plastid of tobacco (Nicotiana tobacum) protoplast. In addition, quantitative real-time PCR (qRT-PCR) unraveled that the expression of TaGAPCp1 (GenBank: MF477938.1) was evidently induced by osmotic stress and abscisic acid (ABA). This experiment also screened its interaction protein, cytochrome b6-f complex iron sulfite subunit (Cyt b6f), from the wheat cDNA library using TaGAPCp1 protein as a bait via the yeast two-hybrid system (Y2H) and the interaction between Cyt b6f and TaGAPCp1 was verified by bimolecular fluorescence complementation assay (BiFC). Moreover, H2O2 could also be used as a signal molecule to participate in the process of Cyt b6f response to abiotic stress. Subsequently, we found that the chlorophyll content in OE-TaGAPCp1 plants was significantly higher than that in wild type (WT) plants. In conclusion, our data revealed that TaGAPCp1 plays an important role in abiotic stress response in wheat and this stress resistance process may be completed by H2O2-mediated ABA signaling pathway.

MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells.

The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/ß-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, ß-catenin, E-cadherin, N-cadherin, Snail, GSK-3ß, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/ß-catenin pathway to protect the ß-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/ß-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/ß-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells.

Treatment outcome comparisons between exons 19 and 21 EGFR mutations for non-small-cell lung cancer patients with malignant pleural effusion after first-line and second-line tyrosine kinase inhibitors.

Recent studies demonstrated a significantly increased frequency of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC) patients with malignant pleural effusions (MPEs). The purpose of this study is to investigate the effect of first-line and second-line EGFR-tyrosine kinase inhibitors (TKIs) in the treatment of NSCLC with MPEs harboring exon 19 deletion and L858R mutation. From 2010 to 2015, 203 NSCLC patients with MPEs harboring EGFR mutation treated with EGFR-TKIs were reviewed. The efficacy were evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. The objective response rate (ORR) and disease control rate (DCR) for patients treated with first-line and second-line EGFR-TKIs were 21.9%, 91.4% and 14.7%, 85.3%, respectively. The overall median PFS and OS of enrolled NSCLC patients with MPE were 9.3 months (95% CI, 8.4-10.2 months), 20.9 months (95% CI, 18.9-22.9 months) after first-line TKIs, and 7.6 months (95% CI, 6.6-8.6 months), 15.3 months (95% CI, 13.6-15.9 months) after second-line TKIs. The exon 19 deletion arm had a longer median PFS (9.4 vs 7.1 months, p=0.003) and OS (16.8 vs 13.8 months, p=0.003) compared with the L858R mutation arm after second-line TKIs. In a conclusion, EGFR genotype was an independent predictor of PFS and OS. No significant side effects differences between the two mutation groups was observed for first or second-line EGFR-TKIs. This study demonstrated that EGFR mutations are significant predictors for advanced NSCLC patients with MPE receiving second-line EGFR-TKIs treatment.