Key points
In a cold environment, mammals increase their food intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently ...unknown.
Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation.
Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β‐oxidation or autophagy weakened the fasting‐induced cold resistance.
Repression of mechanistic target of rapamycin (mTOR) signalling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signalling may be involved in the fasting‐induced cold resistance in fish.
Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress.
In cold environments, most homeothermic animals increase their food intake to supply more energy to maintain body temperature, whereas most poikilothermic animals such as fishes decrease or even stop feeding under cold stress. However, the physiological value of fasting during cold resistance in poikilotherms has not been explained. Here, we show that moderate fasting largely enhanced cold resistance in fish. By using pharmacological (fenofibrate, mildronate, chloroquine and rapamycin) and nutritional approaches (fatty acids diets and amino acids diets) in wild‐type or specific gene knock‐out zebrafish models (carnitine palmitoyltransferase‐1b‐deficient strain, CPT1b−/−, or autophagy‐related protein 12‐deficient strain, ATG12−/−), we verified that fasting‐stimulated lipid catabolism and autophagy played essential roles in the improved cold resistance. Moreover, suppression of the mechanistic target of rapamycin (mTOR) pathway by using rapamycin mostly mimicked the beneficial effects of fasting in promoting cold resistance as either the physiological phenotype or transcriptomic pattern. However, these beneficial effects were largely reduced when the mTOR pathway was activated through high dietary leucine supplementation. We conclude that fasting helps fish to resist cold stress by modulating lipid catabolism and autophagy, which correlates with the mTOR signalling pathway. Therefore, fasting can act as a protective strategy of fish in resisting coldness.
Key points
In a cold environment, mammals increase their food intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently unknown.
Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation.
Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β‐oxidation or autophagy weakened the fasting‐induced cold resistance.
Repression of mechanistic target of rapamycin (mTOR) signalling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signalling may be involved in the fasting‐induced cold resistance in fish.
Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress.
In this study, using coconut fibers as raw material, activated carbon fibers were prepared
via
carbonization and KOH activation processes. The morphology, composition, specific surface area, pore ...structure and thermal stability of the resulting activated carbon fibers were systematically characterized. It was found that the activation process increases the specific surface area of carbon fibers to a greater extent
via
formation of a large number of micropores (0.7-1.8 nm) and a certain amount of slit-shaped mesopores (2-9 nm). The specific surface area and the pore volume of the activated carbon fibers reach 1556 m
2
g
−1
and 0.72 cm
3
g
−1
, respectively. The activation process can also decompose the tar deposits formed after the carbonization process by pyrolysis, making the surface of the activated carbon fibers smoother. To study the adsorption properties of the as-prepared activated carbon fibers, the adsorption capacities and adsorption kinetics of various organic dyes including methylene blue, Congo red and neutral red were investigated. The adsorption capacities of the dyes increased with the increasing initial dye concentrations, and varied greatly with the pH value of the system. In methylene blue and neutral red systems, the adsorption capacities reach the maximum at pH 9, and in the Congo red system, it reaches the maximum at pH 3. The adsorption capacities of the activated carbon fibers in methylene blue, Congo red and neutral red systems reached equilibrium at 150, 120, and 120 min, and the maximum adsorption capacities were 21.3, 22.1, and 20.7 mg g
−1
, respectively. The kinetics of the adsorption process was investigated using three models including pseudo-first-order, pseudo-second-order and intraparticle diffusion models. The results indicated that the dynamic adsorption processes of coconut-based activated carbon fibers to methylene blue, Congo red and neutral red were all in accordance with the second-order kinetic model, and the equations are as follows:
t
/
Q
t
= 0.1028 +
t
/21.3220,
t
/
Q
t
= 0.1128 +
t
/21.5982 and
t
/
Q
t
= 0.0210 +
t
/20.6612.
Activated carbon fibers with high micropore volume and large specific surface area were prepared from abundant and low-cost coconut fibers, which show excellent adsorption performances towards various dyes.
Metabolic associated fatty liver disease (MAFLD) is a new definition for liver disease associated with known metabolic dysfunction. Based on new diagnostic criteria, we aimed to investigate its ...prevalence and risk factors in Chinese population.
We conducted this study in a health examination population who underwent abdominal ultrasonography in China. The diagnosis of MAFLD was based on the new diagnostic criteria. The characteristics of the MAFLD population, as well as the associations between MAFLD and metabolic abnormalities, were explored. Mann-Whitney U test and chi-square test were performed to compare different variables. Binary logistic regression was used to determine the risk factors for MAFLD.
Among 139,170 subjects, the prevalence of MAFLD was 26.1% (males: 35.4%; females: 14.1%). The prevalence based on female menopausal status, that is, premenopausal, perimenopausal, and postmenopausal, was 6.1%, 16.8%, and 30.2%, respectively. In different BMI groups (underweight, normal, overweight and obese), the prevalence was 0.1%, 4.0%, 27.4% and 59.8%, respectively. The proportions of abnormal metabolic features in the MAFLD group were significantly higher than those in the non-MAFLD group, as was the proportion of elevated alanine aminotransferase (ALT) (42.5% vs. 11%, P < 0.001). In nonobese individuals with MAFLD, the proportions of abnormal metabolic features were also all significantly higher than those in nonobese individuals without MAFLD. The prevalence of metabolic syndrome (MS), dyslipidaemia, and hyperuricaemia, respectively, in the MAFLD group (53.2%, 80.0%, and 45.0%) was significantly higher than that in the non-MAFLD group (10.1%, 41.7%, and 16.8%). Logistic regression revealed that age, BMI, waist circumference, ALT, triglycerides, fasting glucose, uric acid and platelet count were associated with MAFLD.
MAFLD is prevalent in China and varies considerably among different age, sex, BMI, and female menopausal status groups. MAFLD is related to metabolic disorders, especially obesity, while metabolic disorders also play important roles in the occurrence of MAFLD in nonobese individuals. MAFLD patients exhibit a high prevalence of MS, dyslipidaemia, hyperuricaemia, and elevated liver enzymes. MAFLD tends to coexist with systemic metabolic disorders, and a deep inner relationship may exist between MAFLD and MS. Metabolic disorders should be considered to improve the management of MAFLD.
Conditioned pain modulation (CPM) is impaired in people with chronic pain such as knee osteoarthritis (KOA). The purpose of this randomized, controlled clinical trial was to investigate whether ...strong electroacupuncture (EA) was more effective on chronic pain by strengthening the CPM function than weak EA or sham EA in patients with KOA.
In this multicenter, three-arm parallel, single-blind randomized controlled trial, 301 patients with KOA were randomly assigned. Patients were randomized into three groups based on EA current intensity: strong EA (> 2 mA), weak EA (< 0.5 mA), and sham EA (non-acupoint). Treatments consisted of five sessions per week, for 2 weeks. Primary outcome measures were visual analog scale (VAS), CPM function, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
Three hundred one patients with KOA were randomly assigned, among which 271 (90.0%) completed the study (mean age 63.93 years old). One week of EA had a clinically important improvement in VAS and WOMAC but not in CPM function. After 2 weeks treatment, EA improved VAS, CPM, and WOMAC compared with baseline. Compared with sham EA, weak EA (3.8; 95% CI 3.45, 4.15; P < .01) and strong EA (13.54; 95% CI 13.23, 13.85; P < .01) were better in improving CPM function. Compared with weak EA, strong EA was better in enhancing CPM function (9.73; 95% CI 9.44, 10.02; P < .01), as well as in reducing VAS and total WOMAC score.
EA should be administered for at least 2 weeks to exert a clinically important effect on improving CPM function of KOA patients. Strong EA is better than weak or sham EA in alleviating pain intensity and inhibiting chronic pain.
This study was registered with the Chinese Clinical Trial Registry ( ChiCTR-ICR-14005411 ), registered on 31 October 2014.
Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis‐inducing agents have great potential as new antitumor candidates. Here, we report a IrIII complex (Ir1) ...containing a ferrocene‐modified diphosphine ligand that localizes in lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton‐like reaction, produce hydroxyl radicals, induce lipid peroxidation, down‐regulate glutathione peroxidase 4, and result in ferroptosis. RNA sequencing analysis shows that Ir1 can significantly affect pathways related to ferroptosis and cancer immunity. Accordingly, Ir1 can induce immunogenic cells death and suppress tumor growth in vitro, regulate T cell activity and immune microenvironments in vivo. In conclusion, we show the potential of small molecules with ferroptosis‐inducing capabilities for effective cancer immunotherapy.
Ferroptosis‐inducing agents have potential as antitumor candidates. A ferrocene‐modified IrIII complex with Fenton‐like catalytic activity is used to disturb the cellular redox balance, which leads to lipid peroxidation and ferroptosis of cancer cells. Ferroptosis induced by the IrIII complex causes immunogenic cell death (ICD) of cancer cell in vitro, which enhances cancer immune response in vivo.
Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and ...low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O'
,O
-(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1
-imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction. Our study showed that the MLP could deliver polo-like kinase 1 siRNA (siPLK1) into glioma cells and effectively enhance the cellular uptake of MLP/siPLK1 because of increased positive charges induced by hypoxia and low pH. Moreover, MLP/siPLK1 was shown to be very effective in inhibiting the growth of glioma cells both in vitro and in vivo. Therefore, the MLP is a promising siRNA delivery system for tumor therapy.
Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health
. Despite intense research efforts, how, when and where ...new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing
of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China
. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. ...Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular-LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.
Key points
The pparab subtype in zebrafish is much more highly expressed in tissues with high oxidative activity than pparaa.
The pparab deficiency in zebrafish reduces fatty acid β‐oxidation both in ...liver and muscle, illustrating its functional homology as a mammalian peroxisome proliferator‐activated receptor α (PPARα).
pparab deficiency promotes metabolic reprogramming by increasing glucose utilization and inhibiting amino acid breakdown.
The present study brings new insights into the comprehensive regulatory roles of PPARα in the cellular fuel selection and provides a valuable animal model for PPARα studies from a viewpoint of comparative physiology.
Dysfunction of lipid metabolism is involved in the pathogenesis of several chronic metabolic diseases. Peroxisome proliferator‐activated receptor α (PPARα) is essential for normal metabolic homeostasis and, in particular, for the regulation of fatty acid β‐oxidation (FAO). However, little is known about its regulation roles in systemic nutrient metabolism. To explore the underlying modulation role of PPARα in metabolic homeostasis, we generated a pparab‐knockout zebrafish (Danio rerio) model. The pparab mutants demonstrated lower expression of key enzymes involved in FAO, as well as lower mitochondrial and peroxisomal FAO in tissues, which was associated with lipid accumulation in liver and visceral mass. Conversely, glucose utilization was higher because they demonstrated lower blood glucose and tissue glycogen concentrations, as well as activation of the phosphoinositide 3‐kinase/AKT pathway. In addition, pparab‐deficient zebrafish demonstrated activation of AKT/mammalian target of rapamycin signalling and higher protein content, implying greater protein synthesis and/or lower amino acid breakdown. These data clearly revealed that pparab deletion reduces FAO but increases glucose utilization and protein deposition to maintain energy homeostasis. The present study provides new insights into the comprehensive regulatory role of PPARα in systemic energy metabolism in fish, and this pparab‐deficient zebrafish also constitutes a valuable model for investigating the functions of PPARα in mammals from comparative physiology aspects.
Key points
The pparab subtype in zebrafish is much more highly expressed in tissues with high oxidative activity than pparaa.
The pparab deficiency in zebrafish reduces fatty acid β‐oxidation both in liver and muscle, illustrating its functional homology as a mammalian peroxisome proliferator‐activated receptor α (PPARα).
pparab deficiency promotes metabolic reprogramming by increasing glucose utilization and inhibiting amino acid breakdown.
The present study brings new insights into the comprehensive regulatory roles of PPARα in the cellular fuel selection and provides a valuable animal model for PPARα studies from a viewpoint of comparative physiology.
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Magnesium (Mg) and its alloys have become a research frontier in biodegradable materials owing to their superior biocompatibility and excellent biomechanical compatibility. However, ...their high degradation rate in the physiological environment should be well tackled prior to clinical applications. This review summarizes the latest progress in the development of polymeric coatings on biodegradable Mg alloys over the last decade, regarding preparation strategies for polylactic acid (PLA), poly (latic-co-glycolic) acid (PLGA), polycaprolactone (PCL), polydopamine (PDA), chitosan (CS), collagen (Col) and their composite, and their performance in terms of corrosion resistance and biocompatibility. Feasible perspectives and developing directions of next generation of polymeric coatings with respect to biomedical Mg alloys are briefly discussed.
Magnesium (Mg) and its alloys have become a research frontier in biodegradable materials owing to their superior biocompatibility and suitable biomechanical compatibility. However, the principal drawback of Mg-based implants is their poor corrosion resistance in physiological environments. Hence, it is vital to mitigate the degradation/corrosion behavior of Mg alloys for safe biomedical deployments. This review summarizes the latest progress in development of polymeric coatings on biomedical Mg alloys regarding preparation strategy, corrosion resistance and biocompatibility, including polylactic acid (PLA), poly (latic-co-glycolic) acid (PLGA), polycaprolactone (PCL), chitosan (CS), polydopamine (PDA), collagen (Col) and their composite. In addition, functionalized polymer coatings with Mg alloys exhibits a promising prospect owing to their ability of degradation along with biocompatibility, self-healing, drug-delivery and osteoinduction.
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