Replacing Red and Processed Meat With Mushrooms Linked to a Lower Risk of Early Death (Food)

Replacing a daily serving of red or processed meat with one serving of mushrooms lowers the risk of dying from any cause, according to a study published in Nutrition Journal.

Researchers compared mushroom intake with all-cause and cause-specific mortality data from participants of the Third National Health and Nutrition Examination Survey (NHANES III) extant data (1988–1994). Those who consumed more mushrooms had a lower risk for all-cause mortality when compared to those who did not eat mushrooms.

Results also showed replacing 1 daily serving of red or processed meats with mushrooms was associated with a lower risk of death. A possible mechanism for the reduced risk includes the antioxidant properties of ergothioneine and glutathione, compounds associated with high mushroom intake.

These findings support a previous meta-analysis that showed a protective effect of these same antioxidants against breast cancer.


References

  1. Ba DM, Gao X, Muscat J, et al. Association of mushroom consumption with all-cause and cause-specific mortality among American adults: prospective cohort study findings from NHANES III. Nutr J. 2021;20(1):38-49. doi: 10.1186/s12937-021-00691-8
  2. Ba DM, Ssentongo P, Beelman RB, Muscat J, Gao X, Richie JP. Higher mushroom consumption is associated with lower risk of cancer: a systematic review and meta-analysis of observational studies. Adv Nutr. 2021;nmab015-nmab029. doi: 10.1093/advances/nmab015

Provided by Physicians Committee for Responsible Medicine

An In Vitro Model of the Gut-Liver-Brain Axis for Studying Neurodegenerative Diseases (Neuroscience)

Study in a Sentence: Researchers modelled the interactions between three different organ systems with relevance to neurodegenerative disease pathology, the gut, liver, and brain, by connecting microphysiological systems (MPS) containing patient-derived cells from these organs. 

Healthy for Humans: The causes and mechanisms of neurodegenerative diseases like Parkinson’s disease are not well understood, although environmental and genetic factors have been implicated, and recently a role for the gut microbiome has been hypothesized. 

Redefining Research: To better understand the interactions between the gut, liver, and brain (the gut-liver-brain axis) in the context of Parkinson’s disease, an MPS containing patient-derived cerebral cells that express a known Parkinson’s disease causing genetic variant were connected with gut and liver MPSs. The interactions between these model organ systems enhance the ability of the cerebral MPS to mimic real Parkinson’s disease states and provide a promising nonanimal in vitro platform to study neurodegenerative disease mechanisms.

Featured image credit: gettyimages


Reference

Trapecar M, Wogram E, Svoboda D, et al. Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases. Science Advances. 2021;7(5):eabd1707. doi.org/10.1126/sciadv.abd1707.


Provided by Physicians Committee for Responsible Medicine

Scientists Develop Fast Antibiotic Susceptibility Test for Antibiotic Resistance Analysis of Clinical Urine and Blood Samples (Medicine)

WHO experts estimated that the annual number of deaths caused by antibiotic resistance will increase from the current 700,000 to 10 million by 2050, which could cost the global economy 100 trillion dollars. One major cause behind the ever-increasing emergence and spread of antibiotic-resistant bacteria is the misuse and overuse of antibiotics in treating bacteria-infected patients. At present, the conventional phenotypic antibiotic susceptibility test (AST) for pathogenic bacteria typically takes 3-7 days to obtain analysis results of pathogen identification and antibiotic sensitivity of patient samples. To determine an efficacious antibiotic for an infecting pathogen and reduce the need for broad-spectrum antibiotics, it is vital to rapidly identify the antibiotic susceptibility profile of the pathogen.  

Recently, SONG Yizhi’s research team from the Suzhou Institute of Biomedical Engineering and Technology of the Chinese Academy of Sciences (CAS), WANG Minggui’s research team from the Huashan Hospital affiliated to Fudan University, in collaboration with HUANG Wei’s research team from the University of Oxford, developed a fast Raman-assisted antibiotic susceptibility test (FRAST) utilizing single cell Raman spectroscopy coupled with heavy water (D2O) labeling, which applies to blood and urine samples. Under optimal conditions, the sample-to-report time of FRAST could be reduced to three hours for urine samples and 21 hours for sepsis samples. 

Fig. 1. Turnaround time (TAT) required for implementing the conventional AST and FRAST for blood and urine samples. (Image by SIBET)

FRAST is based on the combination of Raman spectroscopy and D2O labeling, and its principle is that metabolically active bacteria in the presence of D2O will take in deuterium from D2O via nicotinamide adenine dinucleotide phosphate (NADPH) and add D into biomolecules to form carbon-deuterium (C-D) bonds. The cells containing C-D bonds show a distinguishable Raman band shifted from C-H vibration, and the band can be served as a distinct biomarker for the metabolic activity of a single cell. Under the effect of antibiotics, the susceptible bacteria do not show this band due to antibiotic inhibition of the metabolic activity. 

For urinary samples, the bacteria were collected by centrifugation, and then were observed under a confocal Raman microscope to capture the Raman fingerprints, which can reflect the number of bacteria in the samples. After that, the collected fingerprints were matched with the database of Gram-negative and Gram-positive bacteria by machine learning models to identify whether the bacteria are Gram-positive or negative, so as to determine an appropriate susceptibility plate. Then, the urine samples were added to the plate and incubated for 1 hour before adding D2O.

After being exposed to D2O for 1 hour, the samples were centrifuged and washed to collect Raman spectra. The minimum inhibitory concentration (MIC) was then calculated according to the intensity of C-D peak after applying antibiotics. For sepsis samples, they were cultivated in aerobic blood bottles in a blood cultivation system until it flagged positive, then the same method was adopted to collect Raman spectra and calculate the MIC value. 

Fig. 2. The flow chart of FRAST procedures for clinical urine and blood samples. (Image by SIBET)

This pilot work carried out around 3,200 experiments and acquired about 64,000 single-cell Raman spectra. A large amount of data has provided a comprehensive and large-scale evaluation of the Raman deuterium-labeling AST assay. As a result, the FRAST and the gold standard (the broth microdilution method or automated susceptibility testing system) showed high consistency.

Compared with other Raman-DIP-based studies on pathogens’ susceptibility to antibiotics, this study proved for the first time that the combination of single cell Raman spectroscopy and D2O labeling can be used to analyze the drug resistance of pathogens in urine or blood samples. Besides, integrating with the Raman-based approach for Gram stain classification makes FRAST a relatively independent and complete test method.

Therefore, clinicians can rapidly identify antibiotic susceptibility of pathogens without other assistance. Different from the molecular diagnosis of drug resistance developed in recent years, FRAST is based on the phenotype of the bacteria treated with antibiotics, and there will be no misjudgment on antibiotic susceptibility due to unknown drug resistance mechanisms or gene expression regulation.

The research has been published in an article entitled “Development of a Fast Raman-Assisted Antibiotic Susceptibility Test (FRAST) for the Antibiotic Resistance Analysis of Clinical Urine and Blood Samples” on Analytical Chemistry. This research was supported by the National Key R&D Program of China, the Scientific Instrument Developing Project of CAS, etc. 

Featured image: Gram stain classification of pathogenic bacteria was accurately predicted by FRAST. (Image by SIBET) 


Reference: Xiaofei Yi, Yizhi Song, Xiaogang Xu, Di Peng, Jingkai Wang, Xingwang Qie, Kaicheng Lin, Miao Yu, Mingfeng Ge, Yun Wang, Dayi Zhang, Qiwen Yang, Minggui Wang, and Wei E. Huang, “Development of a Fast Raman-Assisted Antibiotic Susceptibility Test (FRAST) for the Antibiotic Resistance Analysis of Clinical Urine and Blood Samples”, Anal. Chem. 2021, 93, 12, 5098–5106.
https://doi.org/10.1021/acs.analchem.0c04709


Provided by Chinese Academy of Sciences

SAC Phosphoinositide Phosphatases Modulate Auxin-Mediated Plant Development (Botany)

Plant hormone auxin plays critical roles in controlling almost every aspect of plant growth and development, such as phototropic and gravitropic responses. It has fascinated plant biologists since its discovery in 1930s. One of the features about this small molecule is the polar auxin transport and polarity of its transporters. However, the mechanisms have not been well understood.  

Recently, scientist from the Institute of Botany of the Chinese Academy of Sciences (CAS), together with collaborators, identified new players in modulating polarity of auxin transporters.  

They found that three suppressor of actin (SAC) domain and transmembrane domain containing phosphoinositide phosphatases control the homeostasis of phosphoinositides, PtdIns4P and PtdIns(4,5)P2, in the model plant Arabidopsis thaliana.  

The double and triple mutants of the three SAC genes displayed severe developmental defects or lethality, with dramatic increase of PtdIns4P and PtdIns(4,5)P2 contents. The auxin peaks and polarity of auxin transporters were disrupted, likely due to the delay of recycling of the transporter proteins in the mutant plant cells.  

“These findings revealed new genes and related mechanisms modulating the polarity of auxin transporters, and the conserved functions of the SAC phosphoinositide phosphatases with transmembrane domain in eukaryotes,” said Prof. CHENG Youfa, correspondence author of the study. 

This study has been published online in the journal New Phytologist.  

Featured image: Wild type (WT) vs. sac mutant cells. PtdIns4P and PtdIns(4,5)P2 accumulation and disruption of auxin transporter protein cycling and polar localization in the SAC mutant cell. (Image by IBCAS)


Reference: Song, L., Wang, Y., Guo, Z., Lam, S.M., Shui, G. and Cheng, Y. (2021), NCP2/RHD4/SAC7, SAC6 and SAC8 phosphoinositide phosphatases are required for PtdIns4P and PtdIns(4,5)P2 homeostasis and Arabidopsis development. New Phytologist. Accepted Author Manuscript. https://doi.org/10.1111/nph.17402


Provided by Chinese Academy of Sciences

Phytochrome Proteins Promote Heat Stress-induced Leaf Senescence (Botany)

The frequency and intensity of extreme high temperature weather increase accompanying global warming. Correspondingly, heat stress induced leaf premature senescence has greatly affected plant growth and development. Nevertheless, the molecular mechanisms of leaf senescence induced by heat stress is still lacking of systematic understanding.  

A research group led by Prof. WANG Lei from the Institute of Botany of the Chinese Academy of Sciences (IBCAS) has recently found that the Phytochrome Interacting Factors (PIFs), which are crucial integrators of light and temperature signals in Arabidopsis thaliana, can promote heat stress-induced leaf senescence.  

The researchers firstly examined the sensitivity of rosette leaves of both mutants and overexpression lines of PIFs in response to heat stress. They found that PIFs mutants displayed a significantly delayed heat stress-induced leaf senescence phenotype, whereas the elevated PIFs levels in transgenic lines could accelerate heat stress-induced leaf senescence.

Transcriptome analysis combined with previous ChIP-seq data revealed that NAC019, SAG113, IAA29CBF2 and BRI1 were the potential targets of PIF4 and PIF5 proteins to mediate heat-induced leaf senescence.  

Meanwhile, they found that PIF4 and PIF5 proteins were gradually accumulated during the recovery after heat shock treatment, and the transcript levels of NAC019 and SAG113, who can facilitate leaf senescence, were also gradually accumulated, but the transcript level of leaf senescence inhibitor IAA29 was continuously decreased, suggesting that they might be the key target genes of PIF4 and PIF5 to regulate heat-induced leaf senescence.  

Furthermore, they showed that light/dark signals and circadian clock played important roles in heat stress-induced leaf senescence. Interestingly, Arabidopsis thaliana was more tolerant to heat stress-induced leaf senescence in the daytime under LD conditions (12h light/12h dark). Intriguingly, the heat induced leaves senescence was even faster on subjective day and slower on subjective night under continuous light condition.  

“The study thus establishes a molecular framework for deciphering the underlying mechanisms of PIF4 and PIF5 in mediating heat stress-induced leaf senescence, and provides a candidate target for generating heat resistant crops to better cope with climate warming,” said Prof. WANG Lei, correspondence author of the study.  

These findings were published online in Journal of Experimental Botany

Featured image: A proposed working model for PIF4 and PIF5 mediated heat stress induced senescence in Arabidopsis. (Image by IBCAS)


Reference: Na Li, Cunpei Bo, Yuanyuan Zhang, Lei Wang, PIF4 and PIF5 Proteins Promote Heat Stress Induced Leaf Senescence in Arabidopsis, Journal of Experimental Botany, 2021;, erab158, https://doi.org/10.1093/jxb/erab158


Provided by Chinese Academy of Sciences

New Immune Evasion Mechanism Achieved by FTO-mediated Regulation of Glycolytic Metabolism (Biology)

CD8+ T cells are the key immune cells to recognize and eliminate tumor cells, but their functions are usually inhibited by the immunosuppressive tumor microenvironment. Previous studies have shown that tumor cells utilize diverse epigenetic mechanisms to evade T cell-mediated immune surveillance.

As a dynamic and reversible modification of the epitranscriptome, m6A modification affects the RNA stability and translation processes, playing an important role in the occurrence and progress of tumors. However, how m6A modifications participate in regulating the tumor immune microenvironment and regulating T cell-mediated immune surveillance is still unclear.

In a study published in Cell Metabolism, a team led by Prof. HAN Dali from Beijing Institute of Genomics of the Chinese Academy of Sciences (China National Center for Bioinformation), Prof. XU Michelle Meng from Tsinghua University, and Prof. YANG Caiguang from Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, revealed that the m6A demethylase FTO could enhance the glycolytic metabolism of tumor cells through epitranscriptomic regulation, thereby inhibiting T cell activation and promoting immune evasion.

The researchers found that knocking down the m6A demethylase FTO in various solid tumors can inhibit tumor growth in mice and increase the proportion of tumor-infiltrating antigen-specific CD8+ T cells, and showed that knocking down FTO in tumors leads to faster activation of CD8+ T cells, promoting their antitumor capability.

Through integrated analysis of multidimensional omics sequencing data, including RNA-seq, MeRIP-seq (m6A-seq), ATAC-seq, ChIP-seq, they found that FTO can specifically remove the m6A modification on mRNA transcripts of multiple bZIP family transcription factors, thus facilitating their mRNA stability. These bZIP family transcription factors can promote the expression of glycolytic genes and enhance the glycolytic activity of tumor cells, which in turn inhibits the activation of CD8+ T cells.

Besides, the researchers used the small molecule inhibitor Dac51 that targets FTO to further verify the mechanism of FTO in regulating glycolysis metabolism and escaping immune surveillance.

They conducted PD-L1 blockade and Dac51 treatment in tumor-bearing mice model, and found that both can effectively inhibit tumor growth in mice, while the combination of PD-L1 and Dac51 can greatly improve the therapeutic effect. Also, they found that Dac51 treatment can also effectively enhance the antitumor immune response of T cells in patient-derived organoid model, suggesting the possibility of Dac51 in clinical applications.

This study uncovers that RNA epitranscriptome can be operating as an additional layer of genetic regulation for immune evasion, which would facilitate the discovery of a new class of potentially vulnerable epitranscriptomic immunotherapy targets.


Reference: Yi Liu, Guanghao Liang, Hongjiao Xu et al., “Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance”, Cell Metabolism, 2021 DOI: https://doi.org/10.1016/j.cmet.2021.04.001


Provided by Chinese Academy of Sciences

Research Reveals Cis-acting Regulatory of Lotus (Botany)

Lotus (Nelumbo nucifera) can be divided into two ecotypes with different characteristics adapting to various climatic regions, termed as tropical lotus with whip-like, long and thin rhizome and temperate lotus with enlarged and starch-enriched rhizome, respectively. The rhizome derived from underground stems expansion in temperate lotus is a vital phenotypic innovation during the evolutionary process. 

In previous studies, some key genes and pathways affecting lotus enlargement have been identified by transcriptomics. However, it is unclear how genetic changes, particularly cis-regulatory variations, can cause expression divergence of key genes that subsequently contribute to the phenotypic variations of lotus.  

To understand how cis-acting variations between the two lotus ecotypes promote phenotypic differentiation and adaptive evolution, researchers from the Wuhan Botanical Garden of the Chinese Academy of Sciences (CAS) used allele-specific expression (ASE) analysis relying on whole-genome resequencing and transcriptome sequencing data from parents (ZhouOu ♂, DongHe♀) and F1 hybrids with three tissues (flowers, leaves and rhizomes) to study cis-acting regulatory mechanism.  

They found that cis-acting elements (promoters) from tropical lotus were more active than those from temperate lotus, because genes of tissues in F1s showed strong consistent ASE biased towards the tropical line. Compared to genes with allelic expression bias, genes with unbiased expression in offspring evolved more slowly in their promoter regions.  

The researchers further uncovered that cis-acting regulation has vital effects on genes in metabolic and phytohormone-related pathways in the rhizome which participates in adaptive phenotypic differentiation between two lotus ecotypes.  

Overall, this study reveals that cis-regulatory changes between the two parents can have a profound impact on ecotypic differentiation, particularly rhizome enlargement.   

Results were published in an article in Plant Molecular Biology entitled “Biased allelic expression in tissues of F1 hybrids between tropical and temperate lotus (Nelumbo nucifera)“.    

This research was supported by grants from the National Natural Science Foundation of China, the Youth Innovation Promotion Association of CAS, the Strategic Priority Research Program of CAS, the Bureau of Landscaping and Forestry of Wuhan Municipality, among others. 

Featured image: The plant materials and schema of ASE analyses (Image by GAO Zhiyan) 

Reference: Gao, Z., Li, H., Yang, X. et al. Biased allelic expression in tissues of F1 hybrids between tropical and temperate lotus (Nelumbo nuicfera). Plant Mol Biol 106, 207–220 (2021). https://doi.org/10.1007/s11103-021-01138-8


Provided by Chinese Academy of Sciences

Self-powered Flexible Neural Stimulator Designed for Bidirectional Modulation of Neural Plasticity (Neuroscience)

Recently, Dr. ZHAN Yang’s team and Dr. LI Guanglin’s team from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, in collaboration with the team from the University of Electronic Science and Technology of China, designed a self-powered flexible wearable neural stimulator to achieve bidirectional modulation of neural plasticity.

The study was published in Nano Energy on March 19.

Modulating neural plasticity is an effective means to treat diseases such as Alzheimer’s disease, drug addiction and stroke.

At present, common commercial neural stimulators usually require batteries or sockets to maintain power supply. The bulky system framework and inflexible component design limit the comprehensive application of the equipment.

In this study, the designed neural stimulator can induce the formation of long-term potentiation or depression through generating high-frequency and low-frequency pulses in two modes, thus achieving the bidirectional adjustment of neural plasticity.

It integrates an elastic self-powered nanogenerator, a signal modulation unit and a nerve stimulation electrode. Features of small size, lightweight, elasticity and portability allow it to convert the mechanical energy generated during exercise into a nerve stimulation signal and modulate the synaptic plasticity.

The researchers connected the device to the mouse brain, and found that the signal modulation module transmitted the collected energy into a dual-mode stimulation signal, which induced the formation of long-term potentiation and depression of the hippocampus without external energy supply.

The designed neural stimulator provides new ideas for the treatment of neurological diseases based on synaptic plasticity and bidirectional brain-computer interaction.

The study was supported by the National Key Research and Development Program, the National Natural Science Foundation of China, the Shenzhen-Hong Kong Institute of Brain Science, and the Sichuan Science and Technology Program.

Featured image: Self-powered flexible neural stimulator achieves bidirectional modulation of neural plasticity (Image by SIAT)


Reference: Tianming Zhao, Yechao Han, Liuni Qin, Hongye Guan, Lili Xing, Xiaojian Li, Xinyu Xue, Guanglin Li, Yang Zhan, Bidirectional modulation of neural plasticity by self-powered neural stimulation, Nano Energy, Volume 85, 2021, 106006, ISSN 2211-2855, https://doi.org/10.1016/j.nanoen.2021.106006. (https://www.sciencedirect.com/science/article/pii/S2211285521002640)


Provided by Chinese Academy of Sciences

Study Reveals Protective Effects of β-hydroxy-β-methylbutyrate Supplementation on Liver Injury (Medicine)

As a key metabolic organ and a major site for detoxification in the body, the liver plays an important role in protecting body from bacteria and their toxic products, such as lipopolysaccharide (LPS).

β-Hydroxy-β-methylbutyrate (HMB) is a derivative of leucine and metabolized in the liver from the keto acid of leucine. Although most of the endogenous HMB is generated in the liver, how HMB supplementation affects subjects with liver disease remains unclear.

Recently, a team of researchers from China Agricultural University and the Institute of Subtropical Agriculture (ISA) of the Chinese Academy of Sciences revealed the role of HMB supplementation in liver injury.

Their findings were published in Oxidative Medicine and Cellular Longevity on April 2.Using a lipopolysaccharide (LPS)-challenged piglet model, the researchers found that HMB supplementation ameliorated liver histomorphological abnormalities and restored the elevation of serum activities of aspartate aminotransferase and alkaline phosphatase (useful biochemical indicator of liver injury) induced by LPS challenge.

The results suggest that HMB exerted beneficial effects on the inhibition of liver injury. Upon further investigation, they found that the mechanism might be associated with improved hepatic energy metabolism via regulating AMP-activated protein kinase signaling pathway and reduced liver inflammation via modulating toll-like receptor 4 and nucleotide-binding oligomerization domain protein signaling pathways.

These findings may help developing new interventions to ameliorate liver injury and dysfunction in animals and humans with exposure to endotoxin.

Featured image: Histological examination of the liver samples of piglets injected with lipopolysaccharide (LPS) or saline. Sections were obtained with haematoxylin and eosin (×200). CON: control; HMB: β-hydroxy-β-methylbutyrate. © Duan et al.


Reference: Yehui Duan, Bo Song, Changbing Zheng, Yinzhao Zhong, Qiuping Guo, Jie Zheng, Yulong Yin, Jianjun Li, Fengna Li, “Dietary Beta-Hydroxy Beta-Methyl Butyrate Supplementation Alleviates Liver Injury in Lipopolysaccharide-Challenged Piglets”, Oxidative Medicine and Cellular Longevity, vol. 2021, Article ID 5546843, 9 pages, 2021. https://doi.org/10.1155/2021/5546843


Provided by Chinese Academy of Sciences