A 12‐week feeding trial was conducted to evaluate the effects of dietary phosphorus on growth performance, whole‐body composition, liver phosphorus metabolism enzyme and digestive enzyme activities ...of coho salmon (Oncorhynchus kisutch) alevins. Six experimental diets were formulated with graded phosphorus levels of 0.3%, 0.59%, 0.73%, 0.85%, 1.05% and 1.19% respectively. Each diet was fed to triplicate groups of fish (0.36 ± 0.01 g), which were randomly assigned to 18 tanks (water volume 240‐L), with each stocked initially with 50 fish. The specific growth rate (SGR), whole‐body and vertebrae phosphorus contents, lipase and amylase were significantly improved with dietary phosphorus level increased from 0.3% to 0.85% (p < .05). The feed conversion rate, alkaline phosphatase and creatine kinase activities were significantly decreased with dietary phosphorus level increased from 0.3% to 0.73% (p < .05). The hepatosomatic index, intestosomatic index, condition factor and whole‐body moisture, crude protein, crude lipid and ash were not affected by dietary treatments (p > .05). More accurate information on dietary phosphorus requirement was obtained by cubic curve regression analysis of SGR, whole‐body and vertebrae phosphorus contents, which indicated that phosphorus dietary requirement levels for coho salmon alevins were 0.95%, 1.06% and 1.11% respectively.
2,4,6-trinitrotoluene (TNT) has been reported to cause numerous adverse effects. However, the detailed molecular mechanisms underlying TNT-induced liver toxicity need to be elucidated. In this study, ...we used HepG2 (p53wt) and Hep3B (p53null) cell lines to investigate the cytotoxic effects of TNT. At first, we found that TNT significantly decreased cell viability and induced DNA damage. Thereafter, through transcriptomic analysis, we observed that the diverse biological functions affected included mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Mitochondrial dysfunction was evidenced by the loss of mitochondrial membrane potential, increased expression of cleaved-caspase-9&-3 and increased caspase-3/7 activity, indicating that apoptosis had occurred. In addition, the expressions of some ER stress-related proteins had increased. Next, we investigated the role of reactive oxygen species (ROS) in TNT-induced cellular toxicity. The levels of DNA damage, mitochondrial dysfunction, ER stress and apoptosis were alleviated when the cells were pretreated with N-acetyl-cysteine (NAC). These results indicated that TNT caused the ROS dependent apoptosis via ER stress and mitochondrial dysfunction. Finally, the cells transfected with CHOP siRNA significantly reversed the TNT-induced apoptosis, which indicated that ER stress led to apoptosis. Overall, we examined TNT-induced apoptosis via ROS dependent mitochondrial dysfunction and ER stress in HepG2 and Hep3B cells.
•Functional ACM-based composites facilitate the photocatalytic process in both aqueous/gaseous condition.•Abundant surface properties of ACM provide the high capability of adsorption, the ...distribution of photocatalysts, and the transfer of photo-generated electrons.•Surface activating and interlayered modification on ACM benefit combination of the photocatalysts and the support.•Compared with type 1:1 ACM, type 2:1 ACM exhibits more flexible structure that provides more space for photocatalysts loading.
Aluminosilicate clay mineral (ACM) is a kind of typical raw materials that used widely in manufacturing industry owing to the abundant reserve and low-cost exploring. In past two decades, in-depth understanding on unique layered structure and abundant surface properties endows ACM in the emerging research and application fields. In field of solar-chemical energy conversion, ACM has been widely used to support various semiconductor photocatalysts, forming the composites and achieving efficient conversion of reactants under sunlight irradiation. To date, classic ACM such as kaolinite and montmorillonite, loaded with semiconductor photocatalysts has been widely applied in photocatalysis. This review summaries the recent works on ACM-based composites in photocatalysis. Focusing on the properties of surface and layered structure, we elucidate the different features in the composition with various functional photocatalysts on two typical kinds of ACM, i.e., type 1:1 and type 2:1. Not only large surface area and active surface hydroxyl group assist the substrate adsorption, but also the layered structure provides more space to enlarge the application of ACM-based photocatalysts. Besides, we overview the modifications on ACM from both external surface and the inter-layer space that make the formation of composites more efficiently and boost the photo-chemical process. This review could inspire more upcoming design and synthesis for ACM-based photocatalysts, leading this kind of economic and eco-friendly materials for more practical application in the future.
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We report a case in which real‐time remote interrogation and reprogramming of the parameters of a dual‐chamber pacemaker was performed during the COVID‐19 pandemic. The described case demonstrated ...the safety and effectiveness of CIED remote programming based on the 5G cloud technology support platform (5G‐CTP), and showed that the application of real‐time remote programming would help in reducing the risk of cross‐infection between doctors and patients.
Epilepsy, a common neurological disorder, is featured with recurrent seizures. Its underlying pathological mechanisms remain elusive. Here, we provide evidence for loss of neogenin (NEO1), a ...coreceptor for multiple ligands, including netrins and bone morphological proteins, in the development of epilepsy. NEO1 is reduced in hippocampi from patients with epilepsy based on transcriptome and proteomic analyses.
knocking out (KO) in mouse brains displays elevated epileptiform spikes and seizure susceptibility. These phenotypes were undetectable in mice, with selectively depleted NEO1 in excitatory (NeuroD6-Cre
) or inhibitory (parvalbumin
) neurons, but present in mice with specific hippocampal astrocytic
KO. Additionally, neurons in hippocampal dentate gyrus, a vulnerable region in epilepsy, in mice with astrocyte-specific
KO show reductions in inhibitory synaptic vesicles and the frequency of miniature inhibitory postsynaptic current(mIPSC), but increase of the duration of miniature excitatory postsynaptic current and tonic NMDA receptor currents, suggesting impairments in both GABAergic transmission and extracellular glutamate clearance. Further proteomic and cell biological analyses of cell-surface proteins identified GLAST, a glutamate-aspartate transporter that is marked reduced in
KO astrocytes and the hippocampus. NEO1 interacts with GLAST and promotes GLAST surface distribution in astrocytes. Expressing NEO1 or GLAST in
KO astrocytes in the hippocampus abolishes the epileptic phenotype. Taken together, these results uncover an unrecognized pathway of NEO1-GLAST in hippocampal GFAP
astrocytes, which is critical for GLAST surface distribution and function, and GABAergic transmission, unveiling NEO1 as a valuable therapeutic target to protect the brain from epilepsy.
Autophagosome–lysosome pathway (ALP) insufficiency has been suggested to play a critical role in the pathogenesis of cardiac hypertrophy. However, the mechanisms underlying ALP insufficiency remain ...largely unknown, and strategies to specifically manipulate ALP insufficiency for treating cardiac hypertrophy are lacking. Transcription factor EB (TFEB), as a master regulator of ALP, regulates the generation and function of autophagosomes and lysosomes. We found that TFEB was significantly decreased, whereas autophagosome markers were increased in phenylephrine (PE)-induced and transverse aortic constriction–induced cardiomyocyte hypertrophy and failing hearts from patients with dilated cardiomyopathy. Knocking down TFEB induced ALP insufficiency, as indicated by increased autophagosome markers, decreased light chain 3II flux, and cardiomyocyte hypertrophy manifested through increased levels of atrial natriuretic peptide and β-myosin heavy chain and enlarged cell size. The effects of TFEB knockdown were abolished by promoting autophagy. TFEB overexpression improved autophagic flux and attenuated PE-stimulated cardiomyocyte hypertrophy and transverse aortic constriction–induced hypertrophic remodeling, fibrosis, and cardiac dysfunction. Curcumin analog compound C1, a specific TFEB activator, similarly attenuated PE-induced ALP insufficiency and cardiomyocyte hypertrophy. TFEB knockdown increased the accumulation of GATA4, a transcription factor for several genes causing cardiac hypertrophy by blocking autophagic degradation of GATA4, whereas knocking down GATA4 attenuated TFEB downregulation–induced cardiomyocyte hypertrophy. Both TFEB overexpression and C1 promoted GATA4 autophagic degradation and alleviated PE-induced cardiomyocyte hypertrophy. In conclusion, TFEB downregulation plays a vital role in the development of pressure overload–induced cardiac hypertrophy by causing ALP insufficiency and blocking autophagic degradation. Activation of TFEB represents a potential therapeutic strategy for treating cardiac hypertrophy.
Traditional security inks relying on fluorescent/phosphorescent molecules are facing increasing risks of forgery or tampering due to their simple readout scheme (i.e., UV-light irradiation) and the ...advancement of counterfeiting technologies. In this work, a multidimensional data-encryption method based on non-fluorescent polymers via a "lock-key" mechanism is developed. The non-fluorescent invisible polymer inks serve as the "lock" for data-encryption, while the anti-rigidochromic fluorophores that can distinctively light up the polymer inks with programed emissions are "keys" for decryption. The emission of decrypted data is prescribed by polymer chemical structure, molecular weight, topology, copolymer sequence, and phase structure, and shows distinct intensity, wavelength, and chirality compared with the intrinsic emission of fluorophores. Therefore, the data is triply encrypted and naturally gains a high-security level, e.g., only one out of 20 000 keys can access the only correct readout from 40 000 000 possible outputs in a three-polymers-based data-encryption matrix. Note that fluorophores lacking anti-rigidochrimism cannot selectively light up the inks and fail in data-decryption. Further, the diverse topologies, less well-defined structures, and random-coiled shapes of polymers make it impossible for them to be imitated. This work offers a new design for security inks and boosts data security levels beyond the reach of conventional fluorescent inks.
We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were ...more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.
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•We build the genomic and transcriptomic landscape of 465 primary TNBCs•Chinese TNBC cases demonstrate more PIK3CA mutations and LAR subtype•Transcriptomic data classify TNBCs into four subtypes•Multi-omics profiling identifies potential targets within specific TNBC subtypes
Jiang et al. characterize primary Chinese triple-negative breast cancer (TNBC) and classify it into four subtypes. They find that these TNBCs have more frequent PIK3CA mutations and chromosome 22q11 copy-number gains than non-Asian TNBCs and that the LAR subtype has more ERBB2 somatic mutations and CDKN2A loss.
This study aimed to assess and compare procalcitonin (PCT) and C-reactive protein (CRP) levels between COVID-19 and non-COVID-19 sepsis patients. Additionally, we evaluated the diagnostic efficiency ...of PCT and CRP in distinguishing between Gram-positive (GP) and Gram-negative (GN) bacterial infections. Moreover, we explored the associations of PCT with specific pathogens in this context.
The study included 121 consecutive sepsis patients who underwent blood culture testing during the COVID-19 epidemic. PCT and CRP were measured, and reverse transcriptase-polymerase chain reaction (RT-PCR) was employed for the detection of COVID-19 nucleic acid. The Mann-Whitney U-test was used to compare PCT and CRP between the COVID-19 and non-COVID-19 groups. Receiver operating characteristic (ROC) curves were generated to compare PCT and CRP levels in the GN group versus the GP group for assessing the diagnostic efficiency. The kruskal-Wallis H test was applied to assess the impact of specific pathogen groups on PCT concentrations.
A total of 121 sepsis patients were categorized into a COVID-19 group (n = 25) and a non-COVID-19 group (n = 96). No significant differences in age and gender were observed between the COVID-19 and non-COVID-19 groups. The comparison of biomarkers between these groups showed no statistically significant differences. The optimal cut-off values for PCT and CRP in differentiating between GP and GN infections were 1.03 ng/mL and 34.02 mg/L, respectively. The area under the ROC curve was 0.689 (95% confidence interval (CI) 0.591-0.786) for PCT and 0.611 (95% CI 0.505-0.717) for CRP. The diagnostic accuracy was 69.42% for PCT and 58.69% for CRP. The study found a significant difference in PCT levels among specific groups of pathogens (P < 0.001), with the highest levels observed in Escherichia coli infections. The frequency of Staphylococcus spp. positive results was significantly higher (36.0%) in COVID-19 compared to non-COVID-19 sepsis patients (P = 0.047).
Sepsis patients with COVID-19 revealed a significantly higher culture positivity for staphylococcus spp. than the non-COVID-19 group. Both PCT and CRP showed moderate diagnostic efficiency in differentiating between GP and GN bacterial infections. PCT showed potential utility in identifying E. coli infections compared to other pathogens.
Aims/Introduction
The predictive value of admission hyperglycemia in the long‐term prognosis of acute myocardial infarction patients is still controversial. We aimed to investigate this value based ...on the diabetes status.
Materials and Methods
We carried out a multicenter, retrospective study of 1,288 acute myocardial infarction patients enrolled in 11 hospitals between March 2014 and June 2019 in Chengdu, China. The patients were classified into those with diabetes and those without diabetes, each was further divided into: hyperglycemia and non‐hyperglycemia subgroups, according to the optimal cut‐off value of the blood glucose to predict all‐cause mortality during follow up. The end‐points were all‐cause death and major adverse cardiovascular and cerebrovascular events, including all‐cause death, non‐fatal myocardial infarction, vessel revascularization and non‐fatal stroke.
Results
In the follow‐up period of 15 months, we observed 210 (16.3%), 6 (0.5%), 57 (4.4%) and 34 (2.6%) cases of death, non‐fatal myocardial infarction, revascularization and non‐fatal stroke, respectively. The optimal cut‐off values of admission blood glucose for patients with diabetes and patients without diabetes to predict all‐cause mortality during follow up were 14.80 and 6.77 mmol/L, respectively. We divided patients with diabetes (n = 331) into hyperglycemia (n = 92) and non‐hyperglycemia (n = 239), and patients without diabetes (n = 897) into hyperglycemia (n = 425) and non‐hyperglycemia (n = 472). The cumulative rates of all‐cause death and major adverse cardiovascular and cerebrovascular events among the patients in each hyperglycemia group was higher than that in the corresponding non‐hyperglycemia group (P < 0.001). In patients without diabetes, admission hyperglycemia was an independent predictor of all‐cause mortality and major adverse cardiovascular and cerebrovascular events.
Conclusion
Admission hyperglycemia was an independent predictor for long‐term prognosis in acute myocardial infarction patients without diabetes.
The prognostic value of admission hyperglycemia on long‐term prognosis remains elusive, especially in acute myocardial infarction patients with diabetes. Regarding acute myocardial infarction patients, there has been no accurate threshold of admission hyperglycemia to predict mortality. Therefore, in our study, we used different cut‐off values in patients with and without diabetes to discuss their predictive value in the long‐term prognosis of acute myocardial infarction patients.
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