A double-tuned 1 H/31 P coil for rabbit heart metabolism detection at 3 T.

Magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) employing proton nuclear resonance has emerged as a pivotal modality in clinical diagnostics and fundamental research. Nonetheless, the scope of MRI/MRS extends beyond protons, encompassing nonproton nuclei that offer enhanced metabolic insights. A notable example is phosphorus-31 (31 P) MRS, which provides valuable information on energy metabolites within the skeletal muscle and cardiac tissues of individuals affected by diabetes. This study introduces a novel double-tuned coil tailored for 1 H and 31 P frequencies, specifically designed for investigating cardiac metabolism in rabbits. The proposed coil design incorporates a butterfly-like coil for 31 P transmission, a four-channel array for 31 P reception, and an eight-channel array for 1 H reception, all strategically arranged on a body-conformal elliptic cylinder. To assess the performance of the double-tuned coil, a comprehensive evaluation encompassing simulations and experimental investigations was conducted. The simulation results demonstrated that the proposed 31 P transmit design achieved acceptable homogeneity and exhibited comparable transmit efficiency on par with a band-pass birdcage coil. In vivo experiments further substantiated the coil's efficacy, revealing that the rabbit with experimentally induced diabetes exhibited a lower phosphocreatine/adenosine triphosphate ratio compared with its normal counterpart. These findings emphasize the potential of the proposed coil design as a promising tool for investigating the therapeutic effects of novel diabetes drugs within the context of animal experimentation. Its capability to provide detailed metabolic information establishes it as an indispensable asset within this realm of research.

A 16-channel loop array for in vivo macaque whole-brain imaging at 7 T.

Combining multimodal approaches with functional magnetic resonance imaging (fMRI) has catapulted the research on brain circuitries of non-human primates (NHPs) into a new era. However, many studies are constrained by a lack of appropriate RF coils. In this study, a single loop transmit and 16-channel receive array coil was constructed for brain imaging of macaques at 7 Tesla (7 T). The 16 receive channels were mounted on a 3D-printed helmet-shaped form closely fitting the macaque head, with fourteen openings arranged for multimodal devices around the cortical regions. Coil performance was evaluated by quantifying and comparing signal-to-noise ratio (SNR) maps, noise correlations, g-factor maps and flip-angle maps with a 28-channel commercial knee coil. The in vivo results suggested that the macaque coil has higher SNR in cortical regions and better acceleration ability in parallel imaging, which may benefit revealing mesoscale organizations in the brain.

Trend in incidence of stroke in Jindong District from 2016 to 2022 / 预防医学

Objective@#To investigate the trends in incidence of stroke in Jindong District, Jinhua City, Zhejiang Province from 2016 to 2022, so as to provide to the evidence for improving the stroke control strategy.@*Methods@#The incidence of stroke in Jindong District from 2016 to 2022 was collected through the Zhejiang Chronic Disease Monitoring Information System, and standardized by the data of the Chinese National Population Census in 2010. The gender-, age- and subtype-specific incidence of stroke was calculated, and the trends in stroke incidence were investigated with average annual percent change (AAPC).@*Results@#A total of 9 159 stroke cases were reported in Jindong District from 2016 to 2022, with crude incidence of 386.52/105 and standardized incidence of 276.75/105. The crude incidence of stroke appeared a tendency towards a rise (AAPC=3.704%, 95%CI: 0.792%-6.700%, P<0.05), while the standardized incidence showed no significant changing patterns (P>0.05). The crude incidence of stroke was significantly higher among men than among women (438.69/105 vs. 334.66/105; χ2=14.028, P<0.05), and the standardized incidence of stroke was significantly higher among men than among women (316.58/105 vs. 237.31/105; χ2=6.985, P<0.05). The crude incidence of stroke appeared a tendency towards a rise with age（χ2=5 290.180, P<0.05), and the crude incidence of stroke appeared a tendency towards a decline with age among residents at ages of 45 to 64 years (AAPC=-9.135%, 95%CI: -15.003% to -2.861%, P<0.05), while no significant changing patterns were found in the crude incidence of stroke among residents at other age groups (P>0.05). The crude incidence of ischemic stroke was significantly higher than that of hemorrhagic stroke (306.08/105 vs. 76.89/105; χ2=137.184, P<0.05).@*Conclusions@#The incidence of stroke appeared a tendency towards a rise in Jindong District from 2016 to 2022, with ischemic stroke as the predominant subtype. Male and middle-aged and elderly populations should be given a high priority for stroke control.

Diffusion along perivascular spaces as marker for impairment of glymphatic system in Parkinson's disease.

The brain glymphatic system is involved in the clearance of misfolding α-synuclein, the impaired glymphatic system may contribute to the progression of Parkinson's disease (PD). We aimed to analyze the diffusion tensor image along the perivascular space (DTI-ALPS) and perivascular space (PVS) burden to reveal the relationship between the glymphatic system and PD. A cross-sectional study using a 7 T MRI of 76 PD patients and 48 controls was performed to evaluate the brain's glymphatic system. The DTI-ALPS and PVS burden in basal ganglia were calculated. Correlation analyses were conducted between DTI-ALPS, PVS burden and clinical features. We detected lower DTI-ALPS in the PD subgroup relative to controls, and the differences were more pronounced in patients with Hoehn & Yahr stage greater than two. The decreased DTI-ALPS was only evident in the left hemisphere in patients in the early stage but involved both hemispheres in more advanced PD patients. Decreased DTI-ALPS were also correlated with longer disease duration, higher Unified Parkinson's Disease Rating Scale motor score (UPDRS III) and UPDRS total scores, as well as higher levodopa equivalent daily dose. Moreover, the decreased DTI-ALPS correlated with increased PVS burden, and both indexes correlated with PD disease severity. This study demonstrated decreased DTI-ALPS in PD, which might initiate from the left hemisphere and progressively involve right hemisphere with the disease progression. Decreased DTI-ALPS index correlated with increased PVS burden, indicating that both metrics could provide supporting evidence of an impaired glymphatic system. MRI evaluation of the PVS burden and diffusion along PVS are potential imaging biomarkers for PD for disease progression.

Improvement of extraction from Hericium erinaceus on the gut-brain axis in AD-like mice.

In this study, results showed the extractions of Hericium erinaceus can ameliorate the learning and memory abilities significantly, reduce the swelling of brain tissues, neuronal apoptosis, and down-regulate the expression of Alzheimer's disease intracellular markers including Tau and Aß1-42. 16S rRNA sequencing of gut microbiota indicated that the extractions maintained the diversity and stability of the microbial community, rebalanced the ratio of Firmicutes/Proteobacteria, increased the abundance of some probiotics such as Lactobacillus and Akkermansia, and reduced some pathogenic bacteria and opportunistic pathogenic bacteria such as Enterobacteriaceae. In addition, Akkermanisa, Blautia, Oscillospira, Dehalobacterium, Ackermansia, Allobaculum and Coprococcus were up-regulated, and these bacteria have the effect of anti-intestinal inflammation.Some genera with inhibitory effects on inflammation, such as Desulfovibrio, Alistipes and Rikenellaceae, were down-regulated. Deep studies showed that multi-target compounds from Hericium erinaceus could target the gut microbiota, regulate the metabolism, inflammation, immunity and insulin to slow the progression of Alzheimer's disease. The results suggested that extractions from Hericium erinaceus could be formulated as dietary supplement or/and drug treatments against Alzheimer's disease. However, these pharmacologically active ingredients and mode of action require clinical studies.

Circular RNA NF1-419 Inhibits Proliferation and Induces Apoptosis by Regulating Lipid Metabolism in Astroglioma Cells.

BACKGROUND: Astroglioma is the most common primary tumor of the central nervous system. Currently, there is no effective treatment for astroglioma. In the present study, the extract (L3) from Ganoderma Lucidum (G. lucidum) was found to inhibit the growth of astroglioma U87 cells and change the expression of circular RNAs (circRNAs). One of these, including the circular NF1-419 (circNF1-419), was of interest because NF1 gene is a classic tumor suppressor gene. OBJECTIVES: The functional role of circ-NF1-419 in the inhibition of astroglioma cells remains unknown. This study focuses on the role of circNF1-419 in functional abnormalities of U87 astroglioma cells and aims to elaborate on its regulatory mechanism. METHODS: The circNF1-419 overexpressing U87 (U87-NF1-419) cells were constructed. We generated U87-NF1-419 to evaluate the role of circNF1-419 on cell cycle, apoptosis, proliferation, tumor growth and metabolic regulation. Finally, we used docking screening to identify compounds in G. lucidum extracts that target circ-419. RESULTS: U87-NF1-419 can promote cell apoptosis and regulate lipid metabolism through glycerophospholipid metabolism and retrograde endocannabinoid signaling. Further examinations revealed that the expression of metabolic regulators, such as L-type voltage-operated calcium channels (L-VOCC), phospholipase C-ß3 (PLCß3), Mucin1, cationic amino acid transporter 4 (CAT4), cationic amino acid transporter 1 (CAT1) and a kinase (PRKA) anchor protein 4 (AKAP4) was inhibited, while phosphatidylserine synthase 1 (PTDSS1) was enhanced in U87-NF1-419 cells. In vivo experiments showed that circNF1-419 inhibits tumor growth in BALB/C nude mice, and enhanced AKAP4 and PTDSS1 in tumor tissues. The virtual docking screening results supported that ganosporeric acid A, ganodermatriol, ganoderic acid B and α-D-Arabinofuranosyladenine in L3 could activate circNF1-419 in astroglioma treatment. CONCLUSION: This study indicated that circNF1-419 could be a therapeutic target for the clinical treatment of astroglioma. L3 from Ganoderma Lucidum (G. lucidum) could inhibit astroglioma growth by activating circNF1-419.

Immune activation of characteristic gut mycobiota Kazachstania pintolopesii on IL-23/IL-17R signaling in ankylosing spondylitis.

It is very important to understand the communication and interaction mechanisms between the host and its resident microorganisms on host physiology and for precise diagnosis and treatment. Although intestinal fungi and bacteria dysbiosis is increasingly linked to ankylosing spondylitis (AS), their mechanisms of action have been rarely illustrated. In this paper, fecal samples from 10 AS monkeys and 10 healthy controls were collected to systematically characterize the gut mycobiota and microbiota in AS monkeys by 16S rRNA and ITS2 DNA sequencing. Our results showed the gut fungi of Kazachstania pintolopesii, Saccharomycetaceae, Kazachstania, and Saccharomyceteles. Saccharomycetes were specially enriched in AS, and the microbiota of AS monkeys was characterized by an increased abundance of Clostridia, Clostridiales, Ruminococcaceae, and Prevotella 2, using Line Discriminant Analysis Effect Size. Compared to healthy controls, decreased ITS2/16S biodiversity ratios and altered bacterial-fungal interkingdom networks were observed in AS monkeys. Oral administration of K. pintolopesii activates IL-17RA pathway and induce inflammatory reaction in the colonic tissue of C57BL/6 mice, as well as multiple AS phenotypes, including fungal and bacterial dysbiosis, immune responses of NK cells, platelets, T cells, leukocytes, B-cell activation, rheumatoid arthritis, and inflammatory bowel disease. We also found the secreted products of K. pintolopesii could activate the IL-17RA pathway, which induces PANoptosis in macrophage RAW264.7 cells. Much worse, the PANoptosis products could promote the proliferation and morphological changes of K. pintolopesii, which resulted in much more K. pintolopesii and a severe inflammatory reaction. Interestingly, the inflammatory factor TNF-α can promote the morphological transformation of Candida albicans and K. pintolopesii, which is worthy of further study. The characteristic fungi in all these findings implied that fungal and bacterial dysbiosis have a close link to AS and that their communication and interaction indeed play an important role in autoimmune responses, and K. pintolopesii could be a potential marker microorganism in AS, although its specific mechanism is not fully elucidated.

Genetic diversity and main functional composition of Lingzhi strains from main producing areas in China.

In this study, we used genotyping by sequencing (GBS) to examine the genetic diversity of 22 strains of Lingzhi and the quality differences in 15 fruit bodies of Lingzhi from different Chinese regions. The phylogenetic trees of 22 strains were constructed based on ITS (Internal transcribed spacer) and SNP (single nucleotide polymorphism). Moisture, ash, water-soluble extracts, alcohol-soluble extracts, polysaccharides, and triterpenoids from 15 fruit bodies of Lingzhi were detected and analyzed based on Chinese Pharmacopoeia and the US Pharmacopoeia references. Moreover, the monosaccharide composition of polysaccharides was studied using PMP-HPLC, and the effect of polysaccharides on the proliferation rate of splenocytes was investigated in vitro. The identification results of these strains by the phylogenetic trees which were constructed based on ITS sequences and SNPs showed that most of the strains applied in the main producing areas of Lingzhi in China were accurate except for a few inaccurate strains. The moisture, ash, water and alcohol soluble extractive, polysaccharide and triterpenoid content of all samples were meet the requirements of the Chinese Pharmacopoeia, while the polysaccharide and triterpenoid content of less than half of the samples meet the requirements of the U.S. Pharmacopoeia. The polysaccharide extracted from these samples have different effects on the proliferation rate of spleen cells. To sum up, this is the first study that reported on the differences in Lingzhi strains from the main producing areas in China. The quality of some fruit bodies did not meet the pharmacopeia requirements, and wrong strains were used in some production areas; thus, strains should be given special attention before legal processing.

Long-Term Administration of Triterpenoids From Ganoderma lucidum Mitigates Age-Associated Brain Physiological Decline via Regulating Sphingolipid Metabolism and Enhancing Autophagy in Mice.

With the advent of the aging society, how to grow old healthily has become an important issue for the whole of society. Effective intervention strategies for healthy aging are most desired, due to the complexity and diversity of genetic information, it is a pressing concern to find a single drug or treatment to improve longevity. In this study, long-term administration of triterpenoids of Ganoderma lucidum (TGL) can mitigate brain physiological decline in normal aging mice. In addition, the age-associated pathological features, including cataract formation, hair loss, and skin relaxation, brown adipose tissue accumulation, the ß-galactosidase staining degree of kidney, the iron death of spleen, and liver functions exhibit improvement. We used the APP/PS1 mice and 3 × Tg-AD mice model of Alzheimer's Disease (AD) to further verify the improvement of brain function by TGL and found that Ganoderic acid A might be the effective constituent of TGL for anti-aging of the brain in the 3 × Tg-AD mice. A potential mechanism of action may involve the regulation of sphingolipid metabolism, prolonging of telomere length, and enhance autophagy, which allows for the removal of pathological metabolites.

A diet high in sugar and fat influences neurotransmitter metabolism and then affects brain function by altering the gut microbiota.

Gut microbiota (GM) metabolites can modulate the physiology of the host brain through the gut-brain axis. We wished to discover connections between the GM, neurotransmitters, and brain function using direct and indirect methods. A diet with increased amounts of sugar and fat (high-sugar and high-fat (HSHF) diet) was employed to disturb the host GM. Then, we monitored the effect on pathology, neurotransmitter metabolism, transcription, and brain circularRNAs (circRNAs) profiles in mice. Administration of a HSHF diet-induced dysbacteriosis, damaged the intestinal tract, changed the neurotransmitter metabolism in the intestine and brain, and then caused changes in brain function and circRNA profiles. The GM byproduct trimethylamine-n-oxide could degrade some circRNAs. The basal level of the GM decided the conversion rate of choline to trimethylamine-n-oxide. A change in the abundance of a single bacterial strain could influence neurotransmitter secretion. These findings suggest that a new link between metabolism, brain circRNAs, and GM. Our data could enlarge the "microbiome-transcriptome" linkage library and provide more information on the gut-brain axis. Hence, our findings could provide more information on the interplay between the gut and brain to aid the identification of potential therapeutic markers and mechanistic solutions to complex problems encountered in studies of pathology, toxicology, diet, and nutrition development.

Maternal high sugar and fat diet benefits offspring brain function via targeting on the gut-brain axis.

A recent study showed that a gestational high fat diet protects 3xTg-AD offspring from memory impairments, synaptic dysfunction, and brain pathology. However, it is unknown whether this diet exerts the same effects on normal mice or on other functions, and if so, how. In the present study, mother mice were pre-fed a high sugar and high fat (HSHF) diet for 1 month and then fertilized; the HSHF diet was continued until birth and then mother mice were returned to a standard diet. The gut microbiota, and intestinal and brain functions of the offspring were dynamically monitored at 7, 14, 28, and 56 days old until 16 months of age. Results showed that the HSHF diet significantly affected the gut microbiota structure of the offspring, especially during the early life stage. In addition, in the HSHF diet offspring, there were influenced on various types of neurons, including cholinergic and GABAergic neurons, on autophagy levels in the brain, and on inflammation levels in the intestinal tract. When the offspring grew older (16 months), we found that some genes of benefit against nervous system disease were activated, such as Lhx8, GPR88, RGS9, CD4, DRD2, RXRG, and Syt6, and the expression of cholinergic and GABAergic neurons biomarker protein increased. Although the inflammation levels in the nervous and peripheral systems showed no obvious differences, the AFP level of individuals on the HSHF diet was much higher than those on the standard diet, suggesting that more accurate and/or personalized nutrition is needed. Taken together, the results show that a maternal HSHF diet benefits the offspring by reducing the risk of nervous diseases, which might depend on LHX8 activation to modulate cholinergic and GABAergic neurons via the gut-brain axis, but still need much more deep studies.

Protective effect of Ganoderma lucidum spore extract in trimethylamine-N-oxide-induced cardiac dysfunction in rats.

Previous research has shown that the extracts from the Ganoderma lucidum spore (GS) have potentially cardioprotective effects, but there is still abundant room for development in determining its mechanism. In this study, the rat model of cardiac dysfunction was established by intraperitoneal injection of trimethylamine-N-oxide (TMAO), and the extracts of GS (oil, lipophilic components, and polysaccharides) were given intragastrically at a dose of 50 mg/kg/day to screen the pharmacological active components of GS. After 50 days of treatments, we found that the extraction from GS reduced the levels of total cholesterol, triglyceride, and low-density lipoprotein; increased the levels of high-density lipoprotein; and reduced the levels of serum TMAO when compared to the model group (P < 0.05); especially the GS polysaccharides (DT) and GS lipophilic components (XF) exhibited decreases in serum TMAO compared to TMAO-induced control. The results of 16S rRNA sequencing showed that GS could change the gut microbiota, increasing the abundance of Firmicutes and Proteobacteria in the DT-treated group and XF-treated group, while reducing the abundance of Actinobacteria and Tenericutes. Quantitative proteomics analysis showed that GS extracts (DT and XF) could regulate the expression of some related proteins, such as Ucp1 (XF-TMAO/M-TMAO ratio is 2.76), Mpz (8.52), Fasn (2.39), Nefl (1.85), Mtnd5 (0.83), Mtnd2 (0.36), S100a8 (0.69), S100a9 (0.70), and Bdh1 (0.72). The results showed that XF can maintain the metabolic balance and function of the heart by regulating the expression of some proteins related to cardiovascular disease, and DT can reduce the risk of cardiovascular diseases by targeting gut microbiota.

Auxiliary antitumor effects of fungal proteins from Hericium erinaceus by target on the gut microbiota.

Cancer represents a major disease burden worldwide. Despite continuous advances obtained in medical therapies recently, resistance to standard drugs and adverse effects still represent important causes of therapeutic failure. There is growing evidence that the gut microbiota can affect the response to chemo- and immunotherapeutic drugs by modulating efficacy and/or toxicity, and diet is the most important factor affecting the gut microbiota. In this study, we assessed the auxiliary antitumor effects of immunomodulatory fungal proteins from Hericium erinaceus (HEP) administered with the chemotherapy drug 5-Fluorouracil (5-Fu), and we attempted to identify new potential prebiotic bacteria for auxiliary antitumor treatment. There were 1,455 proteins identified from H. erinaceus. In a xenografted mouse model of cancer, HEP with 5-Fu significantly suppressed tumor growth, inhibited inflammatory markers such as interferon (IFN)-γ, interleukin (IL)-1ß, IL-2, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS), and regulated the expression of Akt, CCDN1, CKD4, FOXM1, MMP7, MYC, PPAR-α, and PPAR-γ. 16S rRNA sequencing showed that HEP ameliorated the dysbacteriosis induced by 5-Fu, as it inhibited certain aerobic and microaerobic bacteria including Parabacteroides, Flavobacteriaceae, Christensenellaceae, Anoxybacillus, Aggregatibacter, Comamonadaceae, Planococcaceae, Desulfovibrionaceae, Sporosarcina, Staphylococcus, Aerococcaceae, and Bilophila in the xenografted mice, and increase some probiotic bacteria such as Bifidobacterium, Gemellales, Blautia, Sutterella, Anaerostipes, Roseburia, Lachnobacterium, Lactobacillus, and Desulfovibrio. This demonstrates that HEP could promote the antitumor efficacy of 5-Fu by improving the microbiota composition, the immune inflammatory response, and homeostasis.

Alcohol Extracts From Ganoderma lucidum Delay the Progress of Alzheimer's Disease by Regulating DNA Methylation in Rodents.

Age-related changes in methylation are involved in the occurrence and development of tumors, autoimmune disease, and nervous system disorders, including Alzheimer's disease (AD), in elderly individuals; hence, modulation of these methylation changes may be an effective strategy to delay the progression of AD pathology. In this study, the AD model rats were used to screen the main active extracts from the mushroom, Ganoderma lucidum, for anti-aging properties, and their effects on DNA methylation were evaluated. The results of evaluation of rats treated with 100 mg/kg/day of D-galactose to induce accelerated aging showed that alcohol extracts of G. lucidum contained the main active anti-aging extract. The effects on DNA methylation of these G. lucidum extracts were then evaluated using SAMP8 and APP/PS1 AD model mice by whole genome bisulfite sequencing, and some methylation regulators including Histone H3, DNMT3A, and DNMT3B in brain tissues were up-regulated after treatment with alcohol extracts from G. lucidum. Molecular docking analysis was carried out to screen for molecules regulated by specific components, including ganoderic acid Mk, ganoderic acid C6, and lucidone A, which may be active ingredients of G. lucidum, including the methylation regulators of Histone H3, MYT, DNMT3A, and DNMT3B. Auxiliary tests also demonstrated that G. lucidum alcohol extracts could improve learning and memory function, ameliorate neuronal apoptosis and brain atrophy, and down-regulate the expression of the AD intracellular marker, Aß1-42. We concluded that alcohol extracts from G. lucidum, including ganoderic acid and lucidone A, are the main extracts involved in delaying AD progression.

Prebiotic Effect of Fructooligosaccharides from Morinda officinalis on Alzheimer's Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis.

Gut microbiota influences the central nervous system disorders such as Alzheimer's disease (AD). The prebiotics and probiotics can improve the host cognition. A previous study demonstrated that fructooligosaccharides from Morinda officinalis (OMO) exert effective memory improvements in AD-like animals, thereby considered as potential prebiotics; however, the underlying mechanism still remains enigma. Thus, the present study investigated whether OMO is effective in alleviating AD by targeting the microbiota-gut-brain axis. OMO was administered in rats with AD-like symptoms (D-galactose- and Aß1-42-induced deficient rats). Significant and systematic deterioration in AD-like animals were identified, including learning and memory abilities, histological changes, production of cytokines, and microbial community shifts. Behavioral experiments demonstrated that OMO administration can ameliorate the learning and memory abilities in both AD-like animals significantly. AD parameters showed that OMO administration cannot only improve oxidative stress and inflammation disorder, but also regulate the synthesis and secretion of neurotransmitter. Histological changes indicated that OMO administration ameliorates the swelling of brain tissues, neuronal apoptosis, and down-regulation of the expression of AD intracellular markers (Tau and Aß1-42). 16S rRNA sequencing of gut microbiota indicated that OMO administration maintains the diversity and stability of the microbial community. In addition, OMO regulated the composition and metabolism of gut microbiota in inflammatory bowel disease (IBD) mice model treated by overdosed antibiotics and thus showed the prebiotic potential. Moreover, gut microbiota plays a major role in neurodevelopment, leading to alterations in gene expression in critical brain and intestinal regions, thereby resulting in perturbation to the programming of normal cognitive behaviors. Taken together, our findings suggest that the therapeutic effect of the traditional medicine, M. officinalis, on various neurological diseases such as AD, is at least partially contributed by its naturally occurring chemical constituent, OMO, via modulating the interaction between gut ecology and brain physiology.