Effect of the Surfactant Type on the Demulsification of the W/O Crude Oil Emulsion Produced by Surfactant-Polymer Flooding.

At present, there are many works on the influences of partially hydrolyzed polyacrylamide (HPAM) and surfactant on the stability and treatment of O/W emulsion produced by surfactant-polymer (SP) flooding. However, there are few related reports on the effects of HPAM and surfactant on the demulsification of W/O crude oil emulsion produced by SP flooding. Especially, there is no report on the effect of the surfactant type. In this paper, sodium dodecyl sulfate (SDS), octylphenol polyoxyethylene ether (OP-10), and alkyl C16-18 hydroxypropyl sulfobetaine (HSB1618) were selected as representatives of the anionic surfactant, nonionic surfactant, and zwitterionic surfactant, respectively. Demulsification experiments and interface behavior experiments were conducted to investigate their influences on the demulsification performance of a demulsifier D1. The results showed that the order of the negative effect of the surfactant type on dehydration speed and the dehydration rate of D1 was HPAM + OP-10 > HPAM + HSB1618 > HPAM + SDS. There is no difference in the effect of three surfactants on the conformation adjustment of D1 at the W/O interface, but the properties of the composite W/O interface formed by them and D1 were different. The coalescence time was longest when there were HPAM and OP-10 in water, while the lg(G 1'/G demulsifier')/lgG 1' was the smallest, which led to the most difficult demulsification of W/O emulsion. This work can guide surfactant selection during SP flooding from the perspective of produced fluid treatment.

Sucrose Stearates Stabilized Oil-in-Water Emulsions: Gastrointestinal Fate, Cell Cytotoxicity and Proinflammatory Effects after Simulated Gastrointestinal Digestion.

Different structural composition ratios of sucrose stearates with hydrophilic-hydrophobic balance (HLB) values ranging from 1 to 16 on lipolysis in emulsion were investigated using a simulated gastrointestinal tract (GIT). Results showed a direct correlation between the HLB values of sucrose stearates and the lipolysis rate of emulsions, and a lower HLB value led to diminished lipolysis in the GIT simulation model. Mechanism study indicated that poor emulsifying capacity of sucrose stearates and lipolysis of sucrose stearates with lower HLB value inhibited the digestive behavior of oil. In addition, monoester was mainly hydrolyzed in the gastric phase, whereas sucrose polyesters caused lipolysis in the intestinal phase using an in vitro digestive model and HPLC analysis, further suppressing lipid digestion. Furthermore, a decrease in cell cytotoxicity and proinflammatory effects on Caco-2 and Raw264.7 were observed post-digestion, respectively. This work offers important insights into the effects of the degree of esterification of sucrose stearate on lipid digestion behavior in oil-in-water emulsions.

Carbon, nitrogen, and phosphorus metabolic relationships and reaction mechanisms in SBBR processes in the plateau habitat.

In this study, two laboratory-scale SBBR reactors were established in a plateau habitat. Using high flux sequencing, the SBBR process was compared by natural sediment and autotrophic sludge to characterize the functional modules and functional genes of carbon, nitrogen, and phosphorus metabolism under different working conditions and to analyze the reaction mechanism. The results showed that all the functional modules of carbon metabolism and nitrogen metabolism were found in the SBBR process, except for methane metabolism, which occurred at 25 °C in tank 2, the functional modules related to methane metabolism are enhanced at all working conditions. Except for methane metabolism, all functional genes in tank 2 are inhibited by different working conditions, whereas tank 1 shows a slight enhancement. The different working conditions in nitrogen metabolism demonstrate inhibition of functional modules and functional genes in both tanks. Oxidative phosphorylation was missing five functional modules, except for M00153, where only two genes, K00424 and K22501, are missing, all of the required genes are missing in the other four functional modules. Overall the different conditions demonstrated some inhibition in both reaction tanks of the SBBR process. It is preferable to use self-cultivated sludge for membrane acclimation when operating the SBBR process in a plateau habitat. The findings of this study can be used to further research microbial carbon, nitrogen, and phosphorus metabolism mechanisms in SBBR processes in plateau habitats.

Semiparametric multivariate joint model for skewed-longitudinal and survival data: A Bayesian approach.

Joint models and statistical inference for longitudinal and survival data have been an active area of statistical research and have mostly coupled a longitudinal biomarker-based mixed-effects model with normal distribution and an event time-based survival model. In practice, however, the following issues may standout: (i) Normality of model error in longitudinal models is a routine assumption, but it may be unrealistically violating data features of subject variations. (ii) Data collected are often featured by the mixed types of multiple longitudinal outcomes which are significantly correlated, ignoring their correlation may lead to biased estimation. Additionally, a parametric model specification may be inflexible to capture the complicated patterns of longitudinal data. (iii) Missing observations in the longitudinal data are often encountered; the missing measures are likely to be informative (nonignorable) and ignoring this phenomenon may result in inaccurate inference. Multilevel item response theory (MLIRT) models have been increasingly used to analyze the multiple longitudinal data of mixed types (ie, continuous and categorical) in clinical studies. In this article, we develop an MLIRT-based semiparametric joint model with skew-t distribution that consists of an extended MLIRT model for the mixed types of multiple longitudinal data and a Cox proportional hazards model, linked through random-effects. A Bayesian approach is employed for joint modeling. Simulation studies are conducted to assess performance of the proposed models and method. A real example from primary biliary cirrhosis clinical study is analyzed to estimate parameters in the joint model and also evaluate sensitivity of parameter estimates for various plausible nonignorable missing data mechanisms.

Highly anisotropic and elastic cellulosic scaffold guiding cell orientation and osteogenic differentiation via topological and mechanical cues.

Inspired by the similarity of anisotropic channels in wood to the canals of bone, the elastic wood-derived (EW) scaffolds with anisotropic channels were prepared via simple delignification treatment of natural wood (NW). We hypothesize that the degree of delignification will lead to differences in mechanical properties of scaffolds, which in turn directly affect the behaviors and fate of stem cells. The delignification process did not destroy the anisotropic channel structure of the scaffolds, but endowed the scaffolds with good elasticity and rapid stress relaxation. Interestingly, the micron-scale anisotropic channels of the scaffolds can highly promote the polarization of cells along the direction of channels. We also found that the alkaline phosphatase of EW scaffold can reach to about 13.1 U/gprot, which was about double that of NW scaffold. Moreover, the longer the delignification time, the better the osteogenic activity of the EW scaffolds. We further hypothesize that the osteogenic activity of scaffolds is related to the stress relaxation properties. The immunofluorescence staining showed that when the stress relaxation time of scaffold was shortened to about 10 s, the nuclear ratio of YAP of scaffold increased to 0.22, which well supports our hypothesis.

Body mass index and carpal tunnel syndrome: A case-control study.

To investigate the electrophysiological characteristics of carpal tunnel syndrome (CTS) and to evaluate the relationship between electrophysiological indexes and body mass index (BMI). In the analysis of 153 hospitalized patients with CTS, the median motor conduction velocity, motor conduction amplitude, motor conduction latency, sensor conduction velocity, sensor conduction amplitude and median sensory latency were analyzed. BMI was calculated. Total 171 healthy individuals were selected as control group. According to Guidelines for Prevention and Control of Overweight and Obesity in Chinese Adults, patients were divided into groups A, B and C. Patients with BMI (kg/m2) <24 were classified into group A; those with 24 ≤ BMI < 28 were regarded as overweight and classified into group B; and those with BMI ≥ 28 were regarded as obese and classified into group C. The BMI of CTS patients was significantly higher than that of healthy individuals (P < .05). For the sensory nerve, with the increase of BMI, the incubation period was gradually prolonged and the conduction velocity gradually decreases (P < .05). In terms of motor latency, with an increase in BMI, the latency showed a trend of first decreasing and then increasing, while the conduction velocity showed a trend of first increasing and then decreasing (P < .05). Electrophysiological examination plays an important supporting role in the diagnosis of CTS. BMI is positively correlated with the degree of CTS injury to a certain extent. Weight loss can effectively prevent the occurrence of CTS and slow the progression of nerve damage in CTS patients.

Susceptibility Analysis of Glacier Debris Flow Based on Remote Sensing Imagery and Deep Learning: A Case Study along the G318 Linzhi Section.

Glacial debris flow is a common natural disaster, and its frequency has been increasing in recent years due to the continuous retreat of glaciers caused by global warming. To reduce the damage caused by glacial debris flows to human and physical properties, glacier susceptibility assessment analysis is needed. Most research efforts consider the effect of existing glacier area and ignore the effect of glacier ablation volume change. In this paper, we consider the impact of glacier ablation volume change to investigate the susceptibility of glacial debris flow. The susceptibility to mudslide was evaluated by taking the glacial mudslide-prone ditch of G318 Linzhi section of Sichuan-Tibet Highway as the research object. First, by using a simple band ratio method with manual correction, we produced a glacial mudslide remote sensing image dataset, and second, we proposed a deep-learning-based approach using a weight-optimized glacial mudslide semantic segmentation model for accurately and automatically mapping the boundaries of complex glacial mudslide-covered remote sensing images. Then, we calculated the ablation volume by the change in glacier elevation and ablation area from 2015 to 2020. Finally, glacial debris flow susceptibility was evaluated based on the entropy weight method and Topsis method with glacial melt volume in different watersheds as the main factor. The research results of this paper show that most of the evaluation indices of the model are above 90%, indicating that the model is reasonable for glacier boundary extraction, and remote sensing images and deep learning techniques can effectively assess the glacial debris flow susceptibility and provide support for future glacial debris flow disaster prevention.

Comparative efficacy and safety of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes: A network meta-analysis.

INTRODUCTION: This study aimed to evaluate the clinical efficacy and safety of 4 weekly formulations of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on glycemic control, including glycemic control, by using a network meta-analysis (NMA). METHODS: PubMed, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched from inception until June 10, 2022. Randomized clinical trials (RCTs) enrolling participants with diabetes mellitus type 2 and a follow-up of at least 12 weeks were included, for which 4 eligible GLP-1RAs Exenatide, Dulaglutide, Semaglutide, Loxenatide were compared with either each other or placebo. The primary outcome is the change of hemoglobin A1c level. Secondary outcomes including additional glycemic control indicators and adverse events (AE). Frequentist random-effect NMA were conducted for effect comparison. This meta-analysis was registered on PROSPERO, CRD42022342241. RESULTS: The NMA synthesized evidence from 12 studies covering 6213 patients and 10 GLP-1RA regimens. A pairwise comparison of glycosylated hemoglobin type A1C (HbA1c) lowering effects showed that once-weekly GLP-1 receptor agonists were significantly better than placebo, and their glucose-lowering intensity was Semaglutide 2.0mg, Semaglutide 1.0mg, Dulaglutide 4.5mg, and Semaglutide 0.5mg, Dulaglutide 3.0mg, PEX168 200ug, Dulaglutide 1.5mg, PEX168 100ug and Dulaglutide 0.75mg. The GLP-1RA regimen has a comparable safety profile for hypoglycemia. And with the exception of PEX168, all other long-acting GLP-1RA drugs had lower rates of diarrhea, nausea and vomiting than placebo. CONCLUSION: Regimens of GLP-1RAs had differential glycemic control. The efficacy and safety of Semaglutide 2.0mg in comprehensively lowering blood sugar showed the best performance.

The Effect of Multiple Factors on Working Memory Capacities: Aging, Task Difficulty, and Training.

GOAL: Working memory (WM) is a memory system with a limited capacity that can process and store information temporarily in the performing of cognitive tasks. Despite WM is known to be influenced by age, the difficulty of tasks and trained or not from behavior studies, little is known about their relationships from the aspect of the brain functional network. Our goal was to explore the factor of aging-related changes of WM with brain functional networks. METHODS: In this study, 25 healthy elderly and 23 healthy young volunteers were recruited for electroencephalogram (EEG) recording during the visual WM task with four difficulty levels (1-4 backs). In each back, we repeat the experiment with four sessions, and we add training sections between session one and session two as well as between session two and session three. However, we remove any training section between session three and session four in order to evaluate the impact of forgetting on WM in different age groups. After the experiment, we utilized graph theoretical analysis to characterize the brain functional network in three frequency bands (alpha, beta, and theta). RESULTS: From the well-designed experiment, we found that physiological aging influences brain network connectivity and makes the functional brain network less differentiated. Moreover, there is an inverse relationship between alpha activity and WM load for the elderly group, which is absent in the young group. At the same time, theta band activity will be correlated with behavioral performance for the elderly group with WM training between sessions, which is also absent in the young group. To further study the influence of difficulty of tasks and training on the WM, we distinguish the tasks with quantified topological characteristics, and the classification results manifest that the training is more effective for the young group. Finally, through the establishment of a brain map before and after training, we find that the right parietal lobe plays an important role in the training of WM for the elderly group whereas the beta band plays an important role in WM for both the elderly group and the young group. CONCLUSION: Taken together, our findings clarify the underlying mechanism of WM under different frequency bands in terms of physiological aging, the influence of training, and task difficulty. SIGNIFICANCE: the working memory capacities can be uncovered in terms of the combination of three-way ANOVA and EEG-based graph theoretical analysis.

Highly Elastic and Anisotropic Wood-Derived Composite Scaffold with Antibacterial and Angiogenic Activities for Bone Repair.

Scaffold-based tissue engineering is a promising strategy to address the rapidly growing demand for bone implants, but developing scaffolds with bone extracellular matrix-like structures, suitable mechanical properties, and multiple biological activities remains a huge challenge. Here, it is aimed to develop a wood-derived composite scaffold with an anisotropic porous structure, high elasticity, and good antibacterial, osteogenic, and angiogenic activities. First, natural wood is treated with an alkaline solution to obtain a wood-derived scaffold with an oriented cellulose skeleton and high elasticity, which can not only simulate collagen fiber skeleton in bone tissue but also greatly improve the convenience of clinical implantation. Subsequently, chitosan quaternary ammonium salt (CQS) and dimethyloxalylglycine (DMOG) are further modified on the wood-derived elastic scaffold through a polydopamine layer. Among them, CQS endows the scaffold with good antibacterial activity, while DMOG significantly improves the scaffold's osteogenic and angiogenic activities. Interestingly, the mechanical characteristics of the scaffolds and the modified DMOG can synergistically enhance the expression of yes-associated protein/transcriptional co-activator with PDZ binding motif signaling pathway, thereby effectively promoting osteogenic differentiation. Therefore, this wood-derived composite scaffold is expected to have potential application in the treatment of bone defects.

Quantile-Adaptive Sufficient Variable Screening by Controlling False Discovery.

Sufficient variable screening rapidly reduces dimensionality with high probability in ultra-high dimensional modeling. To rapidly screen out the null predictors, a quantile-adaptive sufficient variable screening framework is developed by controlling the false discovery. Without any specification of an actual model, we first introduce a compound testing procedure based on the conditionally imputing marginal rank correlation at different quantile levels of response to select active predictors in high dimensionality. The testing statistic can capture sufficient dependence through two paths: one is to control false discovery adaptively and the other is to control the false discovery rate by giving a prespecified threshold. It is computationally efficient and easy to implement. We establish the theoretical properties under mild conditions. Numerical studies including simulation studies and real data analysis contain supporting evidence that the proposal performs reasonably well in practical settings.

Photocurable liquid crystal hydrogels with different chargeability and tunable viscoelasticity based on chitin whiskers.

We develop a kind of photocurable liquid crystal hydrogels with bone extracellular matrix (ECM)-like liquid crystal state and viscoelasticity, as well as different chargeability. First, positively charged chitin whiskers (CHWs) and negatively charged maleic anhydride chitin whiskers (mCHWs) were prepared, which further self-assemble to form chiral nematic liquid crystals under ultrasonic treatment, respectively. Subsequently, poly (ethylene glycol) diacrylate (PEGDA) and photo initiator were added, and then two kinds of liquid crystal hydrogels with bone ECM-like viscoelasticity and different chargeability were prepared under ultraviolet (UV) irradiation. Benefiting from the bone ECM-like liquid crystal state and viscoelasticity, the prepared liquid crystal hydrogels exhibit remarkable cell affinity and osteogenic ability. Moreover, the liquid crystal hydrogel with negatively charged mCHWs is more favorable for cell adhesion, spreading and osteogenic differentiation than that with positively charged CHWs. This work provides a promising strategy to prepare the hydrogels with bone ECM-like liquid crystal properties and viscoelasticity for bone repair.

Pannier is a key regulator of embryogenesis, pupal development and female reproduction in the insect pest Bactrocera dorsalis.

BACKGROUND: Most arthropods are famous for their large reproductive capacity, with the ovary playing a vital role in the process. The study of the regulatory mechanisms of ovarian development may have the potential for a reproduction-based pest management strategy. GATA-binding transcription factors (GATAs) as important regulatory factors mediate many physiological processes, including development, immunity, insecticide resistance and reproduction. The Pannier (pnr), a member of GATA family, was confirmed to be involved in ovarian development of Bactrocera dorsalis in our previous study. However, the direct evidence of pnr regulating the fly ovarian development is still lacking. RESULTS: We used CRISPR/Cas9 to create Bdpnr loss-of-function mutations. Homozygous Bdpnr-/- mutants were nonviable, with most individuals dying during embryogenesis, some surviving to the larval stages, and the remaining few dying during pupation. In contrast, heterozygous individuals reached the adult stage, but ovarian development was disrupted, with concomitant decreases in egg laying and hatching rates. We also found that two genes encoding vitellogenin proteins (BdVg1 and BdVg2) and the vitellogenin receptor (BdVgR) were significantly down-regulated in heterozygous mutants compared to wild-type controls. CONCLUSION: These results indicate that Bdpnr is required for embryonic and post-embryonic development, including the formation of ovaries. Bdpnr could therefore be considered as a molecular target for tephritid fly pest control. © 2022 Society of Chemical Industry.

Drug-Loaded and Anisotropic Wood-Derived Hydrogel Periosteum with Super Antibacterial, Anti-Inflammatory, and Osteogenic Activities.

Current artificial periostea mainly focus on osteogenic activity but overlook structural and mechanical anisotropy, as well as the importance of antibacterial and anti-inflammatory properties. Here, inspired by the anisotropic structure of wood, the delignified wood (named white wood, WW) with a porous and highly oriented cellulose fiber skeleton was obtained, which was further filled with polyvinyl alcohol (PVA) hydrogel loaded with curcumin (Cur) and phytic acid (PA). The prepared wood-derived hydrogel composite membranes can not only exhibit an obvious anisotropic structure and good mechanical properties but also sustainably release loaded drugs to obtain long-term biological activities. Creatively, PA can effectively improve the bioavailability of Cur; more importantly, Cur and PA play an obvious synergistic effect in antibacterial, anti-inflammatory, and osteogenic activities. Compared with the wood-derived hydrogel composite membranes without drug loading, as well as loaded with Cur or PA only, these loaded with Cur and PA are significantly more conducive to inhibiting the growth of bacteria and inflammatory response and facilitating the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells. This kind of anisotropic wood-derived hydrogel composite membrane with fantastic antibacterial, anti-inflammatory, and osteogenic activities is expected to be ideal artificial periostea.

Translation and validation of the Chinese ABCD risk questionnaire to evaluate adults' awareness and knowledge of the risks of cardiovascular diseases.

BACKGROUND: Assessment of health beliefs and risk perception is a critical means to prevent coronary heart disease, but there are few such studies on assessment in the Chinese population. Given the demonstrated value and widespread use of the Attitudes and Beliefs about Cardiovascular Disease Risk Questionnaire (ABCD), this study was designed to translate it into Chinese, and to evaluate its reliability and validity in a Chinese population. METHODS: The Chinese version of the ABCD was created using the Beaton translation model, which included forward and backward translation. The reliability and construct validity of the Chinese ABCD were examined in a sample of 353 adults who participated in the public welfare projects of the Chinese National Center for Cardiovascular Diseases in Guilin city, Guangxi. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to examine the factor structure of the Chinse ABCD. The internal consistency of the questionnaire was assessed using Cronbach's α and corrected item-total correlations. RESULTS: We deleted item 7 in the knowledge dimension of the Chinese ABCD and added two items about smoking and sleep knowledge, while retaining 25 of the original items, so that it finally included 27 items. The correlations were .20-.90; the correlations between each item and the total score of the ABCD were .34-.86; and the item-level Content Validity Index (I-CVI) was .86-1.00. The results of the EFA showed that all items were close to .40, and the cumulative variance contribution rate was 63.88%. The model fit was acceptable (χ2 = 698.79, df = 243, χ2/df = 2.87, P < 0.001, SRMR = 0.06, RMSEA = 0.05, CFI = 0.96, and TLI = 0.94) according to the CFA. The Cronbach' s α of the entire questionnaire was .86, and the α of each of dimension was .65, .90, .88, and .78. The split-half reliability of the entire the ABCD was .67, and the test-retest reliability was .97 (P < 0.05). The questionnaire had good reliability and validity and was associated with sociodemographic and health-related characteristics (smoking and Body Mass Index). CONCLUSION: The Chinese version of the ABCD has good reliability and validity, and provides a reliable assessment tool for measuring public health beliefs about the risk of cardiovascular disease, promoting the primary prevention of coronary heart disease.

Multivariate piecewise joint models with random change-points for skewed-longitudinal and survival data.

Methodological development and application of joint models for longitudinal and time-to-event data have mostly coupled a single longitudinal outcome-based linear mixed-effects model with normal distribution and Cox proportional hazards model. In practice, however, (i) profile of subject's longitudinal response may follow a `broken-stick nonlinear' (piecewise) trajectory. Such multiple phases are an important indicator to help quantify treatment effect, disease diagnosis and clinical decision-making. (ii) Normality in longitudinal models is a routine assumption, but it may be unrealistically obscuring important features of subject variations. (iii) Data collected are often featured by multivariate longitudinal outcomes which are significantly correlated, ignoring their correlation may lead to biased estimation. (iv) It is of importance to investigate how multivariate longitudinal outcomes are associated with event time of interest. In the article, driven by a motivating example, we propose Bayesian multivariate piecewise joint models with a skewed distribution and random change-points for longitudinal measures with an attempt to cope with correlated multivariate longitudinal data, adjust departures from normality, mediate accuracy from longitudinal trajectories with random change-point and tailor linkage in specifying a time-to-event process. A real example is analyzed to demonstrate methodology and simulation studies are conducted to evaluate performance of the proposed models and method.

Bayesian Joint Modeling of Multivariate Longitudinal and Survival Data With an Application to Diabetes Study.

Joint models of longitudinal and time-to-event data have received a lot of attention in epidemiological and clinical research under a linear mixed-effects model with the normal assumption for a single longitudinal outcome and Cox proportional hazards model. However, those model-based analyses may not provide robust inference when longitudinal measurements exhibit skewness and/or heavy tails. In addition, the data collected are often featured by multivariate longitudinal outcomes which are significantly correlated, and ignoring their correlation may lead to biased estimation. Under the umbrella of Bayesian inference, this article introduces multivariate joint (MVJ) models with a skewed distribution for multiple longitudinal exposures in an attempt to cope with correlated multiple longitudinal outcomes, adjust departures from normality, and tailor linkage in specifying a time-to-event process. We develop a Bayesian joint modeling approach to MVJ models that couples a multivariate linear mixed-effects (MLME) model with the skew-normal (SN) distribution and a Cox proportional hazards model. Our proposed models and method are evaluated by simulation studies and are applied to a real example from a diabetes study.

PFKP alleviates glucose starvation-induced metabolic stress in lung cancer cells via AMPK-ACC2 dependent fatty acid oxidation.

Cancer cells adopt metabolic reprogramming to promote cell survival under metabolic stress. A key regulator of cell metabolism is AMP-activated protein kinase (AMPK) which promotes catabolism while suppresses anabolism. However, the underlying mechanism of AMPK in handling metabolic stress in cancer remains to be fully understood. In this study, by performing a proteomics screening of AMPK-interacting proteins in non-small-cell lung cancer (NSCLC) cells, we discovered the platelet isoform of phosphofructokinase 1 (PFKP), a rate-limiting enzyme in glycolysis. Moreover, PFKP was found to be highly expressed in NSCLC patients associated with poor survival. We demonstrated that the interaction of PFKP and AMPK was greatly enhanced upon glucose starvation, a process regulated by PFKP-associated metabolites. Notably, the PFKP-AMPK interaction promoted mitochondrial recruitment of AMPK which subsequently phosphorylated acetyl-CoA carboxylase 2 (ACC2) to enhance long-chain fatty acid oxidation, a process helping maintenance of the energy and redox homeostasis and eventually promoting cancer cell survival under glucose starvation. Collectively, we revealed a critical non-glycolysis-related function of PFKP in regulating long-chain fatty acid oxidation via AMPK to alleviate glucose starvation-induced metabolic stress in NSCLC cells.

WIPI2 positively regulates mitophagy by promoting mitochondrial recruitment of VCP.

The mammalian Atg18 ortholog WIPI2 is a key regulator of LC3 lipidation to promote autophagosome biogenesis during nonselective macroautophagy, while its functions in selective autophagy such as mitophagy remain largely unexplored. In this study, we explored the role of WIPI2 in PINK1-PRKN/parkin-mediated mitophagy. First, we found that WIPI2 is recruited to damaged mitochondria upon mitophagy induction. Second, loss of WIPI2 impedes mitochondrial damaging agents-induced mitophagy. Third, at molecular level, WIPI2 binds to and promotes AAA-ATPase VCP/p97 (valosin containing protein) to damaged mitochondria; and WIPI2 depletion blunts the recruitment of VCP to damaged mitochondria, leading to reduction in degradation of outer mitochondrial membrane (OMM) proteins and mitophagy. Finally, WIPI2 is implicated in cell fate decision as cells deficient in WIPI2 are largely resistant to cell death induced by mitochondrial damage. In summary, our study reveals a critical regulatory role of WIPI2 in mitochondrial recruitment of VCP to promote OMM protein degradation and eventual mitophagy.Abbreviations: ATG, autophagy related; CALCOCO2/NDP52, calcium binding and coiled-coil domain 2; CCCP, carbonyl cyanide chlorophenylhydrazone; CYCS, cytochrome c, somatic; HSPD1/HSP60, heat shock protein family D (Hsp60) member 1; IMM, inner mitochondrial membrane; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; NPLOC4, NPL4 homolog, ubiquitin recognition factor; OMM, outer mitochondrial membrane; OPTN, optineurin; PtdIns3P, phosphatidylinositol-3-phosphate; PINK1, PTEN induced kinase 1; PRKN/Parkin, parkin RBR E3 ubiquitin protein ligase; UBXN6/UBXD1, UBX domain protein 6; UFD1, ubiquitin recognition factor in ER associated degradation 1; VCP/p97, valosin containing protein; WIPI2, WD repeat domain, phosphoinositide interacting 2.

Proton Magnetic Resonance Spectroscopy for Diagnosis of Non-Motor Symptoms in Parkinson's Disease.

Background: The current diagnosis of Parkinson's disease (PD) is mainly based on the typical clinical manifestations. However, 60% dopaminergic neurons have died when the typical clinical manifestations occur. Predictive neurobiomarkers may help identify those PD patients having non-motor disorders or in different stage and achieving the aim of early diagnosis. Up to date, few if any neuroimaging techniques have been described useful for non-movement disorders diagnosis in PD patients. Here, we investigated the alteration of metabolites in PD patients in different stage of PD and non-motor symptoms including sleep, gastrointestinal and cognitive dysfunction, by using the 1H-MRS. Methods: A total of 48 subjects were included between 2017 and 2019: 37 PD (15 men, age 47-82 years) and 11 healthy people (8 men, age 49-74 years). All participants underwent MRI and multi-voxel 1H-MRS examination within 3 days in admission. Six kinds of metabolites, such as creatine (Cr), N-acetyl aspartate/creatine (NAA/Cr), N-acetyl aspartate/choline (NAA/Cho), choline/creatine (Cho/Cr), lipid/creatine (LL/Cr), and myo-Inositol/creatine ratio (mI/Cr) were tested among the PD group and the control groups. Statistical analyses and correlation analyses were performed by using SPSS. The p < 0.05 was considered statistically significant. Results: Compared late PD group with a control group or early group, higher Cr ratio and lower NAA/Cr ratio were observed in the late PD group (p < 0.05). The mI/Cr in the late PD group was also lower than that in the early PD group (p < 0.05). Regarding the relationship between metabolites and NMS, Cho/Cr was higher in the sleep disorder group, whereas mI/Cr was lower in the gastrointestinal dysfunction group in comparison with the non-symptom groups. Moreover, Cr, Cho/Cr, mI/Cr, and LL/Cr were identified to have higher concentrations in the cognitive group in thalamus. Conclusions: Proton magnetic resonance spectroscopy is an advanced tool to quantify the metabolic changes in PD. Three biomarkers (Cr, NAA/Cr, and mI/Cr) were detected in the late stage of PD, suggesting that these markers might be potential to imply the progression of PD. In addition, subgroups analysis showed that MRS of thalamus is a sensitive region for the detection of cognitive decline in PD, and the alteration of neurochemicals (involving Cr, Cho, mI, and LL) may be promising biomarkers to predict cognitive decline in PD.