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.
Li‐rich cathode materials have attracted increasing attention because of their high reversible discharge capacity (>250 mA h g−1), which originates from transition metal (TM) ion redox reactions and ...unconventional oxygen anion redox reactions. However, many issues need to be addressed before their practical applications, such as their low kinetic properties and inefficient voltage fading. The development of cutting‐edge technologies has led to cognitive advances in theory and offer potential solutions to these problems. Herein, a recent in‐depth understanding of the mechanisms and the frontier electrochemical research progress of Li‐rich cathodes are reviewed. In addition, recent advances associated with various strategies to promote the performance and the development of modification methods are discussed. In particular, excluding Li‐rich Mn‐based (LRM) cathodes, other branches of the Li‐rich cathode materials are also summarized. The consistent pursuit is to obtain energy storage devices with high capacity, reliable practicability, and absolute safety. The recent literature and ongoing efforts in this area are also described, which will create more opportunities and new ideas for the future development of Li‐rich cathode materials.
The practical applications of Li‐rich cathode materials, especially Li‐rich Mn‐based (LRM) cathodes, are hindered by their inherent shortcomings. In this case, the recent understanding of complex reaction mechanisms, the novel modification methods, and the corresponding development trends are comprehensively reviewed. Additionally, other branches and the future opportunities of the Li‐rich cathode materials are also summarized.
Abstract
A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 ...antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months,
p
= 0.0011; 53.3% vs 13.3%,
p
= 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (
p
= 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (
p
< 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (
p
= 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.
Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory ...syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID‐19). Here, we conducted a prospective, multicenter, open‐label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID‐19. We consecutively recruited 130 COVID‐19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID‐19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID‐19 patients at different disease stages.
Dietary usage of microencapsulated oils has been proved to promote growth and gut health in land animals, however, these beneficial effects have not been intensively investigated in aquatic animals. ...The present study hypothesized that dietary microencapsulated oils could alleviate negative effects caused by high-fat diet (HFD) in fish, thus we fed juvenile Nile tilapia with HFD (15% fat) by using normal or microencapsulated oils as lipid sources for 8 weeks. To compare the effects between different microencapsulated oils with different fatty acid composition, two oil mixtures (PL: 60% palm oil +40% linseed oil; FL: 60% fish oil +40% linseed oil) were used. After feeding trial, the growth, body composition, fatty acid composition, resistance to pathogenic bacteria challenge, activities of immune enzymes, expressions of inflammation genes, intestinal structure and microbiota were measured, respectively. The results indicated that microencapsulated oils didn’t affect fish growth, body composition, and muscle fatty acid composition, but improved the intestinal activities of lysozyme (LZM) and resistance against Aeromonas hydrophila. Further tests showed that microencapsulated oils not only improved the structure of intestine, but also increased the number of beneficial bacteria (Bacillus and Paenibacillus) and decreased the number of harmful bacteria (Pseudoalteromonas and Roseovarius) in the intestine. Those beneficial effects are more significant between normal PL oil and microencapsulated PL oil, but no significant difference in FL oil groups. Taken together, these results suggested that microencapsulated oil might enhance immune activities in the Nile tilapia fed with HFD by improving intestinal structure and microflora. Moreover, the beneficial effects of the microencapsulated oil are correlated to the oil composition. To the best of our knowledge, this is the first study illustrating the beneficial effects of dietary microencapsulated oil in the fish fed with HFD.
•Microencapsulated oil could help to alleviate adverse effects caused by high-fat diet in tilapia.•Microencapsulated oil could enhance immune activities in tilapia through improving intestinal structure and microflora.•The beneficial effects of the microencapsulated oil are correlated to the oil composition.•This study could provide fundamental basis for microencapsulated oil usage in aquafeed formation.
Fish cannot use carbohydrate efficiently and instead utilize protein for energy supply, thus limiting dietary protein storage. Protein deposition is dependent on protein turnover balance, which ...correlates tightly with cellular energy homeostasis. Mitochondrial fatty acid β-oxidation (FAO) plays a crucial role in energy metabolism. However, the effect of remodeled energy homeostasis caused by inhibited mitochondrial FAO on protein deposition in fish has not been intensively studied.
This study aimed to identify the regulatory role of mitochondrial FAO in energy homeostasis maintenance and protein deposition by studying lipid, glucose, and protein metabolism in fish.
Carnitine-depleted male Nile tilapia (initial weight: 4.29 ± 0.12 g; 3 mo old) were established by feeding them with mildronate diets (1000 mg/kg/d) for 6 wk. Zebrafish deficient in the carnitine palmitoyltransferase 1b gene (cpt1b) were produced by using CRISPR/Cas9 gene-editing technology, and their males (154 ± 3.52 mg; 3 mo old) were used for experiments. Normal Nile tilapia and wildtype zebrafish were used as controls. We assessed nutrient metabolism and energy homeostasis–related biochemical and molecular parameters, and performed 14C-labeled nutrient tracking and transcriptomic analyses.
The mitochondrial FAO decreased by 33.1–88.9% (liver) and 55.6–68.8% (muscle) in carnitine-depleted Nile tilapia and cpt1b -deficient zebrafish compared with their controls (P < 0.05). Notably, glucose oxidation and muscle protein deposition increased by 20.5–24.4% and 6.40–8.54%, respectively, in the 2 fish models compared with their corresponding controls (P < 0.05). Accordingly, the adenosine 5'-monophosphate–activated protein kinase/protein kinase B–mechanistic target of rapamycin (AMPK/AKT-mTOR) signaling was significantly activated in the 2 fish models with inhibited mitochondrial FAO (P < 0.05).
These data show that inhibited mitochondrial FAO in fish induces energy homeostasis remodeling and enhances glucose utilization and protein deposition. Therefore, fish with inhibited mitochondrial FAO could have high potential to utilize carbohydrate. Our results demonstrate a potentially new approach for increasing protein deposition through energy homeostasis regulation in cultured animals.
Hydrogel-based devices are widely used as flexible electronics, biosensors, soft robots, and intelligent human-machine interfaces. In these applications, high stretchability, low hysteresis, and ...anti-fatigue fracture are essential but can be rarely met in the same hydrogels simultaneously. Here, we demonstrate a hydrogel design using tandem-repeat proteins as the cross-linkers and random coiled polymers as the percolating network. Such a design allows the polyprotein cross-linkers only to experience considerable forces at the fracture zone and unfold to prevent crack propagation. Thus, we are able to decouple the hysteresis-toughness correlation and create hydrogels of high stretchability (~1100%), low hysteresis (< 5%), and high fracture toughness (~900 J m
). Moreover, the hydrogels show a high fatigue threshold of ~126 J m
and can undergo 5000 load-unload cycles up to 500% strain without noticeable mechanical changes. Our study provides a general route to decouple network elasticity and local mechanical response in synthetic hydrogels.
Environmental selection and dispersal limitation are two of the primary processes structuring biotic communities in ecosystems, but little is known about these processes in shaping soil microbial ...communities during secondary forest succession. We examined the communities of ectomycorrhizal (EM) fungi in young, intermediate and old forests in a Chinese subtropical ecosystem, using 454 pyrosequencing. The EM fungal community consisted of 393 operational taxonomic units (OTUs), belonging to 21 EM fungal lineages, in which three EM fungal lineages and 11 EM fungal OTUs showed significantly biased occurrence among the young, intermediate and old forests. The EM fungal community was structured by environmental selection and dispersal limitation in old forest, but only by environmental selection in young, intermediate, and whole forests. Furthermore, the EM fungal community was affected by different factors in the different forest successional stages, and the importance of these factors in structuring EM fungal community dramatically decreased along the secondary forest succession series. This study suggests that different assembly mechanisms operate on the EM fungal community at different stages in secondary subtropical forest succession.
Biomimetic assembly of high-quality nanosheets into nacre-like structures can produce macroscopic films with favorable mechanical and optical performances due to the intrinsic properties and high ...level of ordering of the nanoscale building blocks. Natural ground mica is abundant and exhibits great application potential. However, large size and low aspect ratio greatly limit its biomimetic assembly. Moreover, exfoliation of ground mica into high-quality nanosheets remains a significant challenge. Here, we report that large-scale exfoliation of ground mica into mono- or few-layered mica nanosheets with a production rate of ~1.0 g h
can be successfully achieved. The mica nanosheets are then assembled into strong biomimetic polymeric mica film that inherits the high electric insulation, excellent visible transmittance, and unique ultraviolet-shielding properties of natural mica. Its overall performance is superior to that of natural sheet mica and other biomimetic films, making the polymeric mica film a suitable substrate for flexible and transparent devices.
Long non-coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the role and molecular mechanism of lncRNA XIST in gastric cancer is still unknown.
Real-time PCR ...analysis was performed to measure the expression levels of lncRNA XIST in gastric cancer tissues and cell lines, the correlation between lncRNA XIST expression and clinicopathological characteristics and prognosis was analyzed in gastric cancer patients. The biological function of lncRNA XIST on gastric cancer cells were determined both in vitro and in vivo. The regulating relationship between lncRNA XIST and miR-101 was investigated in gastric cancer cells.
lncRNA XIST was significantly up-regulated in gastric cancer tissues and cell lines. Overexpression of lncRNA XIST was markedly associated with larger tumor size, lymph node invasion, distant metastasis and TNM stage in gastric cancer patients. Functionally, knockdown of lncRNA XIST exerted tumor-suppressive effects by inhibiting cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Furthermore, an inverse relationship between lncRNA XIST and miR-101 was found. Polycomb group protein enhancer of zeste homolog 2 (EZH2), a direct target of miR-101, could mediated the biological effects that lncRNA XIST exerted.
lncRNA XIST is up-regulated and is associated with aggressive tumor phenotypes and patient survival in gastric cancer, and the newly identified lncRNA XIST/miR-101/EZH2 axis could be a potential biomarkers or therapeutic targets for gastric cancer patients.
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