Micropatterned Polymer Nanoarrays with Distinct Superwettability for a Highly Efficient Sweat Collection and Sensing Patch.

Wearable sweat sensor offers a promising means for noninvasive real-time health monitoring, but the efficient collection and accurate analysis of sweat remains challenging. One of the obstacles is to precisely modulate the surface wettability of the microfluidics to achieve efficient sweat collection. Here a facile initiated chemical vapor deposition (iCVD) method is presented to grow and pattern polymer nanocone arrays with distinct superwettability on polydimethylsiloxane microfluidics, which facilitate highly efficient sweat transportation and collection. The nanoarray is synthesized by manipulating monomer supersaturation during iCVD to induce controlled nucleation and preferential vertical growth of fluorinated polymer. Subsequent selective vapor deposition of a conformal hydrogel nanolayer results in superhydrophilic nanoarray floor and walls within the microchannel that provide a large capillary force and a superhydrophobic ceiling that drastically reduces flow friction, enabling rapid sweat transport along varied flow directions. A carbon/hydrogel/enzyme nanocomposite electrode is then fabricated by sequential deposition of highly porous carbon nanoparticles and hydrogel nanocoating to achieve sensitive and stable sweat detection. Further encapsulation of the assembled sweatsensing patch with superhydrophobic nanoarray imparts self-cleaning and water-proof capability. Finally, the sweat sensing patch demonstrates selective and sensitive glucose and lactate detection during the on-body test.

Deep learning-based classification and spatial prognosis risk score on whole-slide images of lung adenocarcinoma.

AIMS: Classification of histological patterns in lung adenocarcinoma (LUAD) is critical for clinical decision-making, especially in the early stage. However, the inter- and intraobserver subjectivity of pathologists make the quantification of histological patterns varied and inconsistent. Moreover, the spatial information of histological patterns is not evident to the naked eye of pathologists. METHODS AND RESULTS: We establish the LUAD-subtype deep learning model (LSDLM) with optimal ResNet34 followed by a four-layer Neural Network classifier, based on 40 000 well-annotated path-level tiles. The LSDLM shows robust performance for the identification of histopathological subtypes on the whole-slide level, with an area under the curve (AUC) value of 0.93, 0.96 and 0.85 across one internal and two external validation data sets. The LSDLM is capable of accurately distinguishing different LUAD subtypes through confusion matrices, albeit with a bias for high-risk subtypes. It possesses mixed histology pattern recognition on a par with senior pathologists. Combining the LSDLM-based risk score with the spatial K score (K-RS) shows great capacity for stratifying patients. Furthermore, we found the corresponding gene-level signature (AI-SRSS) to be an independent risk factor correlated with prognosis. CONCLUSIONS: Leveraging state-of-the-art deep learning models, the LSDLM shows capacity to assist pathologists in classifying histological patterns and prognosis stratification of LUAD patients.

Physiological Functions of FBW7 in Metabolism.

FBW7 is the recognition subunit of the SCF (Skp1-Cullin1-F-box proteins) E3 ubiquitin ligase complex, and it determines the specificity of the SCF substrate. SCFFBW7 is a recognized tumor suppressor because of its ability to degrade many proto-oncogenic substrates. Recent studies have shown that FBW7 plays a key role in metabolism by targeting the degradation of critical regulators involved in cellular metabolism in a ubiquitin-dependent manner. Here, we review recent studies, which highlight the important role of FBW7 in metabolism.

PKA/ATGL signaling pathway is involved in ER stress-mediated lipolysis in adipocytes of grass carp (Ctenopharyngodon idella).

The relationship between endoplasmic reticulum stress (ER stress) and lipolysis in mammals has been widely studied, but it is relatively scarce in fish. The present study used grass carp Ctenopharyngodon idella as a model to investigate the effect of ER stress on lipolysis in adipocytes of fish. We found that ER stress evoked by tunicamycin (TM) treatment significantly induced lipolysis in adipocytes. Subsequently, in order to further investigate whether protein kinase A (PKA) is involved in ER stress-induced lipolysis, we treated adipocytes with PKA activator forskolin and inhibitor H89. The results showed that the mechanism was related to the activation of PKA, especially the catalytic subunit PRKACBa. Notably, we also found that PKA regulates lipolysis by targeting mRNA level and protein and enzyme activities of adipotriglyceride lipase (ATGL). Taken together, our findings suggest that PKA/ATGL signaling pathway is involved in ER stress-mediated lipolysis of grass carp adipocytes. It provides a theoretical basis for further study on the mechanism of lipolysis in fish and other vertebrates.

Endoplasmic reticulum stress is involved in lipid accumulation induced by oleic acid in adipocytes of grass carp (Ctenopharyngodon idella): focusing on the transcriptional level.

It has been extensively claimed that endoplasmic reticulum stress (ER stress) is related to lipid accumulation in mammals, but little is known in fish. This study aims at elucidating the role of ER stress in mediating lipid accumulation induced by monounsaturated oleic acid (OA) with a focus on the transcriptional level. We treated the adipocytes of grass carp with 200 µM and 400 µM OA, respectively, while the control group was treated with 2% bovine serum albumin (BSA). The results showed that cell viability was significantly improved, while 400 µM OA treatment promoted neutral lipid accumulation along with stimulating ER stress more obviously. Although lipolysis and fatty acid ß-oxidation were activated simultaneously, the primary effect of OA seems to be promotion of lipid accumulation. To further explore whether ER stress affects lipid accumulation, 4-phenyl butyric acid (4-PBA), an effective inhibitor of ER stress, was used to pretreat the cells for 4 h. Unsurprisingly, it was found that the mRNA expressions of genes linked with ER stress were decreased. Intracellular triglyceride (TG) content was also decreased, which was in accordance with the mRNA expressions of adipogenic and lipogenic transcription factors as well as their target genes. Collectively, our data shows that ER stress may take part in OA-induced lipid accumulation in adipocytes via activating adipogenesis and lipogenesis. Based on this, strategies for protecting ER could be used to alleviate excessive accumulation of lipid in grass carp adipose tissue.

Yield-Adjusted Operation for Convolution Filter Denoising.

A perfect denoising for measurement shall remove noise, while keeping signal truth, so it is a dual-objective optimization of the signal yield and the noise residue. The frequency difference between the noise and signal is the basis of band-limited filter denoising. The root cause for the sharp peak denoise distortion is the insufficient spectrum sampling because of the scattered frequency distribution, which makes it hard to achieve dual-objective optimization. Thus, this article proposes a four-step operation of the signal yield adjustment for beyond the band-limited system. The first step is identifying the signal and noise levels in raw data, then adjusting the sampling density of high-signal level areas and enriching it by linear interpolation, then smoothing the reshaped profile, which is friendly to the filter, and finally, restoring the deformed one to its original form. An executable script function has fully achieved the whole operation. Some actual sharp spectra (Raman, NMR, laser-induced breakdown spectroscopy, and X-ray diffraction) make a comparison between the way with the Savitzky-Golay (SG) method and wavelet (multi-scale) denoising. The results show that all the effects are better than those of the SG filter, all estimations of the yield of signals are more than 99%, and the residue of noise is less than 10%. With multi-scale denoising, this operation is more targeted and gets more rational spectrum profiles─noise reduction without spectrum distortion.

Nuclear factor-κB subunit p65 is involved in lipopolysaccharide-induced lipid accumulation via regulating DGAT1b in Ctenopharyngodon idellus kidney cells.

Lipopolysaccharide (LPS) can promote the accumulation of triglycerides (TGs) in CIK (Ctenopharyngodon idellus kidney) cells, but the underlying mechanism is unclear. In this study, two genes involved TG synthesis, DGAT1a and DGAT1b, were isolated and characterized from grass carp Ctenopharyngodon idella, which encode peptides of 498 and 501 amino acids, respectively. Phylogenetic and synteny analyses indicated that DGAT1a and DGAT1b could have originated from the teleost-specific genome duplication event. Analysis of the exon-intron structures clarified that genomic structures of all DGAT1 proteins are conserved in vertebrates. DGAT1a mRNA was highly expressed in gut, adipose tissue and heart, while DGAT1b mRNA was highly expressed in liver and kidney. After LPS treatment, only expression of DGAT1b was up-regulated and knockdown of DGAT1b reduced the content of TG, suggesting that DGAT1b is involved in LPS-induced lipid accumulation. To explore the mechanism underlying the transcriptional regulation of DGAT1b in response to LPS, we cloned DGAT1b promoter sequence. Its promoter sequence consists of IRF7, RelA (p65) and RelB binding elements. Dual luciferase assay and q-PCR suggested that the promoter of DGAT1b can be activated by the overexpression of p65, but cannot be triggered by IRF7 and RelB. Mutational analysis shows that the potential p65 binding sites may locate in the region -111/-100 bp of the DGAT1b promoter. These results indicated that DGAT1b is the target gene of NF-κB p65. Finally, inhibiting p65 effectively decreased LPS-induced lipid accumulation. Taken together, we demonstrate that NF-κB p65 takes part in the lipid accumulation by regulating DGAT1b-induced TG synthesis in LPS signalling in CIK cells. The finding that NF-κB p65 links LPS signalling and TG synthesis adds to our growing appreciation of the interplay between immunity and lipid metabolism in fish.

Perilipin 1-3 in grass carp Ctenopharyngodon idella: molecular characterization, gene structure, tissue distribution, and mRNA expression in DHA-induced lipid droplet formation in adipocytes.

Perilipin family is the main structural proteins of lipid droplet (LD) that is intracellular neutral lipid store ponds, and regulates LD assembly and formation, and is crucial for lipid metabolism. Here three paralogs of perilipin family were characterized from grass carp and their complete coding sequences (CDS) were obtained, including perilipin1, perilipin2, and perilipin3, coding peptides of 492, 454, and 419 amino acids, respectively. The alignment of the homology of grass carp perilipin deduced amino acid sequences with other teleost species showed that the homology with mammalian was less than 55%. PAT (perilipin) domain in mammalian was also predicted in grass carp perilipin 1-3 proteins. Genomic organization analysis revealed that grass carp perilipin1 contained 6 coding exons, while both perilipin2 and perilipin3 consisted of 7 coding exons. The mRNA encoding three paralogs were expressed in a wide range of tissues; perilipin1-3 were primarily expressed in adipose tissue and liver; besides, perilipin3 was also highly expressed in the heart. In vitro, 200 µM DHA increased the proportion of smaller lipid droplets effectively in fully differentiated adipocytes of grass carp. The mRNA expression of perilipin1, perilipin2, and perilipin3 was significantly increased in the adipocytes treated with DHA (P < 0.05, P < 0.01). The same responses of different paralogs in the adipocytes during DHA treatment suggest that they might play synergistic roles in the formation of LDs.

Two faces of PPARα/NFκB signaling pathway in inflammatory responses to adipocytes lipolysis in grass carp Ctenopharyngodon idella.

Adipose tissue plays an important role in energy reservation, also be considered as vital immunological organ in animals. Adipocytes are the basic unit of adipose tissue, while little is known about the relationship between lipid metabolism and inflammatory response in fish adipocytes so far. In this study, forskolin was used to induce adipocyte lipolysis, and 5 µM forskolin and 30 µM forskolin both triggered lipolysis by increasing ATGL expression. Consequently, 30 µM Forskolin instead of 5 µM Forskolin induced the expression of NF-κB and its target pro-inflammatory cytokine genes including MCP-1, IL-6 and TNF-α. Further study found that low grade rate of lipolysis activated PPARα gene, and its inhibitory effect on the mRNA expression of NF-κB and its target genes inhibited the adipocyte inflammation. On the contrary, high grade rate of lipolysis increased the expression levels of NF-κB and its target genes, while their expression were attenuated by inhibition of reactive oxygen species (ROS) using α-tocopherol, suggesting that ROS generated due to the PPARα-mediated oxidation of released fatty acids from lipolysis may contribute to adipocyte inflammation. These results indicated that PPARα has dose effect in inflammatory responses to adipocyte lipolysis in grass carp. Taken together, grass carp adipocytes have immune activity. The inflammatory response is linked to the grade rate of adipocyte lipolysis in grass carp adipocytes, and excessive adipocyte lipolysis may promote a dynamic immune response in adipose tissue. This is the first study showing the regulatory effects of lipolysis on immune functions in fish adipocytes.

Fumigaclavine C attenuates adipogenesis in 3T3-L1 adipocytes and ameliorates lipid accumulation in high-fat diet-induced obese mice.

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

Screening and identification of immunoactive peptide mimotopes for the enhanced serodiagnosis of tuberculosis.

Although serological detection is a practical strategy for early detection and diagnosis of tuberculosis (TB), inconsistent and imprecise estimates of sensitivity and specificity block its development and application for clinic. New or alternative serological antigens with improved accuracy are urgently needed. A phage-displayed random peptide library was employed to screen for immunoactive peptides using specific immunoglobulin G (IgG) of TB patients as target molecules. With two screening strategies, 20 single phages displaying different sequences were obtained and no sequence homology was found among these phages. From the results of phage-ELISA, H12, TB6, TB15, and TB18 phages showed higher affinity to IgGs from TB patients(S/N ≥2.1) and were identified as the positive clones. Significant differences in the detection values of sera from 47 TB patients and 37 healthy individuals were found for these four phage clones. According to the reactivity of 284 human sera to synthetic H12, TB6, TB15, and TB18 peptides as determined by ELISA, TB15 showed significantly higher areas under the curve (AUC) and sensitivity than other peptides, providing a lead molecule for the development of new serology diagnostic strategies for TB.

Alkylation of terminal alkynes with transient σ-alkylpalladium(II) complexes: a carboalkynylation route to alkyl-substituted alkynes.

A mild and general alkylation of terminal alkynes with transient σ-alkylpalladium(II) complexes for assembling alkyl-substituted alkynes is described. This method represents a new way to the use of transient σ-alkylpalladium(II) complexes in organic synthesis through 1,2-carboalkynylation of alkenes.

Rhodium-catalyzed synthesis of isoquinolines and indenes from benzylidenehydrazones and internal alkynes.

A new route is presented for the selective assembly of isoquinolines and indenes by rhodium-catalyzed tandem cyclization of benzylidenehydrazones with internal alkynes. This method involves the selective cleavage of the N-N bond and the C═N bonds and is dependent on the substituents of the benzylidenehydrazone.

Development and Validation of a Bayesian Network-Based Model for Predicting Coronary Heart Disease Risk From Electronic Health Records.

BACKGROUND: Traditional risk evaluation models have been applied to guide public health and clinical practice in various studies. However, the application of existing methods to data sets with missing and censored data, as is often the case in electronic health records, requires additional considerations. We aimed to develop and validate a predictive model that exhibits high performance with data sets that contain missing and censored data. METHODS AND RESULTS: This is a retrospective cohort study of coronary heart disease at Weihai Municipal Hospital on unique patients aged 18 to 96 years between 2013 and 2021. A total of 169 692 participants formed our study population, of which 10 895 participants were diagnosed with coronary heart disease. Models were built for the risk of coronary heart disease based on demographic, laboratory, and medical history variables. All complete samples were assigned to the training set (n=110 325), whereas the remaining samples were assigned to the validation set (n=59 367). The area under the receiver operating characteristic curve value was 0.800 (95% CI, 0.794-0.805), and the C statistic was 0.796 (95% CI, 0.791-0.801) in the derivation cohort, and the corresponding values were 0.837 (95% CI, 0.821-0.853) and 0.838 (95% CI, 0.822-0.854) in the validation cohort. The calibration curve demonstrated its good calibration ability, and decision curve analysis showed its clinical usefulness. CONCLUSIONS: Our proposed risk prediction model has demonstrated significant effectiveness in handling the complexities of electronic health record data, which often involve extensive missing data and censoring. This approach may offer potential assistance in the use of electronic health records to enhance patient outcomes.

Study on the Degradation Effect of Carbonaceous Shale under the Coupling Effect of Chemical Erosion and High Temperature.

The southwest region of China has abundant groundwater and high-temperature geothermal energy. Carbonaceous shale, as one of the typical surrounding rocks in this region, often suffers from deterioration effects due to the coupled action of groundwater chemical erosion and high temperature, which affects the long-term stability of tunnel engineering. In order to investigate the deterioration effects of carbonaceous shale under the coupled action of chemical erosion and high temperature, carbonaceous shale from a tunnel of Lixiang Railway in Yunnan Province was taken as the research object. The microstructure and mineral composition of the samples before and after chemical erosion were obtained with a scanning electron microscope-energy dispersive spectrometer and an X-ray diffraction test. Then, triaxial compression tests were conducted on the samples under different time points and different temperature effects of chemical erosion, and the stress-strain curves and the deterioration laws under a single factor were obtained. An improved numerical simulation method based on the parallel bond model was developed, which can account for the coupled effects of chemical erosion and high temperature on the rock. By simulating the triaxial compression test of carbonaceous shale, the deterioration law of carbonaceous shale under the coupled action was discussed. The results show that chemical erosion has a significant deterioration effect on the triaxial compressive strength of carbonaceous shale, and the degree of deterioration is related to the erosion time. In the first 30 days of erosion, the triaxial compressive strength of carbonaceous shale decreased by 11.38%, which was the largest deterioration range. With the increase in erosion time, the deterioration rate gradually decreased; temperature had a significant threshold effect on the strength of carbonaceous shale, and a clear turning point appeared at about 200 °C. By simulating the deterioration effects of carbonaceous shale under the coupled action of chemical erosion and high temperature, it was found that the longer the duration of chemical erosion, the stronger the temperature sensitivity of carbonaceous shale, and the more serious the loss of compressive strength during the heating process. When the temperature was low, the strength of carbonaceous shale changed little, and some samples even showed an increase in strength; when the temperature was high, the strength of carbonaceous shale decreased significantly, showing deterioration characteristics. The numerical simulation method was compared and verified with the indoor test results, and it was found that the numerical calculation had a good agreement with the test results.

Palladium-catalyzed methylation of alkynyl C(sp)-H bonds with dimethyl sulfonium ylides.

A novel palladium-catalyzed methylation protocol for the synthesis of methyl-functionalized internal alkynes has been established. This methylation method is achieved through a C(sp)-C(sp(3)) bond formation process and represents a new synthetic application of sulfonium ylides.

Epidemiology of lean/non-obese nonalcoholic fatty liver disease in China: A systematic review and meta-analysis.

OBJECTIVES: To assess the prevalence and metabolic characteristics of lean/non-obese (L/NO) nonalcoholic fatty liver disease (NAFLD) in China. METHODS: The databses, inlcuding PubMed, Web of Science, EMBASE, as well as Cochrane databases, were retrieved for eligible studies. The prevalence together with clinical features of L/NO-NAFLD in China were analyzed using a random/fixed effects model. Lean or nonobese participants were characterized by the cut-offs of body mass index used in original studies. Heterogeneity was identified using meta-regression and subgroup analyses. RESULTS: We included 25 studies for the final analysis comprising 229091 L/NO Chinese adults and 22641 diagnosed with NAFLD, with the NAFLD prevalence of 8.98% (95% confidence interval [CI]: [5.55-13.13] for L-NAFLD Chinese participants and 13.77% (95% CI: [11.13-16.63]) for NO-NAFLD Chinese participants. This prevalence gradually increased during the past few years. The community and health checkup populations presented similar prevalence (14.19% vs. 13.55%). Meanwhile, L/NO patients with NAFLD showed lower blood pressure (128.86/80.48 vs. 136.09/84.98 mmHg), waist circumference (80.63 vs. 92.73 cm), fasting blood glucose (5.53 vs. 5.69 mmol/L), uric acid (339.14 vs. 365.46 µmol/L), triglyceride levels (1.63 vs. 1.94 mmol/L), alanine transaminase (30.28 vs. 33.12 IU/L), and γ-glutamyl transferase (29.9 vs. 43.68 IU/L), but higher levels of high-density lipoprotein cholesterol (1.33 vs. 1.26 mmol/L) compared to overweight/obese (OW/O) patients with NAFLD. CONCLUSION: Prevalence of NAFLD was slightly lower among the L/NO-NAFLD Chinese population than the global level but has obviously increased recently. In addition, the metabolic profile of L/NO-NAFLD patients was generally better compared to OW/O-NAFLD patients.PROSPERO Reg. No.: CRD42022327240.

DHA induces adipocyte lipolysis through endoplasmic reticulum stress and the cAMP/PKA signaling pathway in grass carp (Ctenopharyngodon idella).

Docosahexaenoic acid (DHA) is a biologically active fatty acid that reduces the accumulation of lipids. However, the molecular mechanism underlying this process, particularly in fish, is not well understood. Recent studies show that endoplasmic reticulum (ER) stress triggers the activation of the unfolded protein response, which has been revealed to play an essential role in lipid metabolism. In this study, we explored the effect of DHA on ER stress and investigated the potential molecular mechanisms underlying DHA-induced adipocyte lipolysis in grass carp (Ctenopharyngodon idella) both in vivo and in vitro. We found that DHA remarkably reduced the triglyceride content, increased the secretion of glycerol, promoted lipolysis in adipocytes and evoked ER stress, whereas inhibiting ER stress using 4-phenyl butyric acid (4-PBA) inhibited the effects of DHA (P < 0.05). These results implied that ER stress potentially participates in DHA-induced adipocyte lipolysis. Additionally, STF-083010, a specific inositol-requiring enzyme 1α (IRE1α)-inhibitor, attenuated the effects of DHA on lipolysis, demonstrating that IRE1α and X-box binding protein 1 potentially participate in DHA-induced lipolysis. DHA also activated the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway by increasing the level of cAMP and activating the PKA enzyme (P < 0.05). Nevertheless, H89, a PKA inhibitor, weakened DHA-induced lipolysis by inhibiting the cAMP/PKA signaling pathway. Furthermore, inhibiting ER stress using 4-PBA also inhibited lipolysis and alleviated DHA-induced activation of the cAMP/PKA signaling pathway, suggesting that ER stress may participate in DHA-induced lipolysis through the activation of the cAMP/PKA signaling pathway. Our data illustrate that DHA supplementation can be a promising nutritional strategy for ameliorating lipid accumulation in grass carp. The present study elucidated the molecular mechanism for DHA-induced lipolysis in grass carp adipocytes and emphasized the importance of ER stress and the cAMP/PKA pathway in DHA-induced lipolysis. These results deepen our understanding of ameliorating lipids deposition in freshwater fish by targeting DHA.

The endoplasmic reticulum stress and B cell lymphoma-2 related ovarian killer participate in docosahexaenoic acid-induced adipocyte apoptosis in grass carp (Ctenopharyngodon idellus).

Docosahexaenoic acid (DHA) lessens adipose tissue lipid deposition partly by inducing adipocyte apoptosis in grass carp, but the underlying mechanism remains unclear. Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) is the novel pathway for inducing apoptosis. This study aimed to explore the potential role of ER stress in DHA-induced apoptosis in grass carp (Ctenopharyngodon idellus) adipocytes. DHA induced apoptosis by deforming the nuclear envelope, condensing the chromatin, and increasing the expression of apoptosis-related proteins and genes in vivo and in vitro (P < 0.05). However, the ER stress inhibitor, 4-phenylbutyric acid (4-PBA), effectively suppressed DHA-induced apoptosis (P < 0.05), indicating that ER stress mediates DHA-induced adipocyte apoptosis. Furthermore, we observed that 200 µM DHA significantly up-regulates the transcripts of B cell lymphoma-2 (BCL-2) related ovarian killer (BOK) in vitro (P < 0.05). BOK is a pro-apoptotic protein in the BCL-2 family, which governs the mitochondria apoptosis pathway. Hence, we hypothesized that BOK might be an important linker between ER stress and apoptosis. We cloned and identified two grass carp BOK genes, BOKa and BOKb, which encode peptides of 213 and 216 amino acids, respectively. BOKa primarily localizes in ER and mitochondria in the cytoplasm, while BOKb localizes in the nucleus and cytoplasm of grass carp adipocytes. Moreover, 200 µM DHA treatment up-regulated the mRNA expression of BOKa and BOKb, whereas 4-PBA suppressed the DHA-induced expressions. These results raised the possibility that BOK participates in DHA-induced adipocyte apoptosis through ER stress signaling, in line with its localization in ER and mitochondria. Two UPR branches, the inositol-requiring enzyme 1 (IRE1α) and activating transcription factor 6 (ATF6) signaling pathways, are possibly important in DHA-induced adipocyte apoptosis, unlike protein kinase RNA-activated-like ER kinase. The study also emphasized the roles of BOKa and BOKb in IRE1α- and ATF6-mediated apoptosis. This work is the first to elucidate the importance of the ER stress-BOK pathway during adipocyte apoptosis in teleost.

Cultivated fish accumulates excessive inedible fats in the abdominal cavity, thus wasting energy and causing metabolic disease. This study showed that docosahexaenoic acid (DHA) induces apoptosis in grass carp adipocytes through endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Therefore, DHA possibly alleviates lipid accumulation partly by reducing the number of adipocytes. Furthermore, transcriptome analysis demonstrated that B cell lymphoma-2-related ovarian killer (BOK) is probably an important linker between ER stress and apoptosis. We first cloned and identified the grass carp BOK genes, BOKa and BOKb. Next, we preliminarily confirmed that BOKa and BOKb participate in DHA-induced apoptosis mainly through activating transcription factor 6 and inositol-requiring enzyme 1 α signaling pathways, the branches of UPR. This study provides a theoretical foundation for the lipid-reduction role of DHA in teleost.

Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI.

The purpose of this study was to explore the value of resting-state magnetic resonance imaging (MRI) based on the brain extraction tool (BET) algorithm in evaluating the cranial nerve function of patients with delirium in intensive care unit (ICU). A total of 100 patients with delirium in hospital were studied, and 20 healthy volunteers were used as control. All the subjects were examined by MRI, and the images were analyzed by the BET algorithm, and the convolution neural network (CNN) algorithm was introduced for comparison. The application effects of the two algorithms were analyzed, and the differences of brain nerve function between delirium patients and normal people were explored. The results showed that the root mean square error, high frequency error norm, and structural similarity of the BET algorithm were 70.4%, 71.5%, and 0.92, respectively, which were significantly higher than those of the CNN algorithm (P < 0.05). Compared with normal people, the ReHo values of pontine, hippocampus (right), cerebellum (left), midbrain, and basal ganglia in delirium patients were significantly higher. ReHo values of frontal gyrus, middle frontal gyrus, left inferior frontal gyrus, parietal lobe, and temporal lobe and anisotropy scores (FA) of cerebellums (left), frontal lobe, temporal lobe (left), corpus callosum, and hippocampus (left) decreased significantly. The average diffusivity (MD) of medial frontal lobe, superior temporal gyrus (right), the first half of cingulate gyrus, bilateral insula, and caudate nucleus (left) increased significantly (P < 0.05). MRI based on the deep learning algorithm can effectively improve the image quality, which is valuable in evaluating the brain nerve function of delirium patients. Abnormal brain structure damage and abnormal function can be used to help diagnose delirium.