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BACKGROUND: Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids for mammals. Maternal BCAAs during pregnancy have been associated with newborn development. Meanwhile, BCAAs have been tightly linked with insulin resistance and diabetes in recent years. Diabetes in pregnancy is a common metabolic disorder. The current study aims to assess the circulating BCAA levels in pregnant women with diabetes and their relationship with neonatal development. METHODS: The serum concentrations of BCAAs and their corresponding branched-chain α-keto acids (BCKAs) catabolites in 33 pregnant women with normal glucose tolerance, 16 pregnant women with type 2 diabetes before pregnancy (PDGM), and 15 pregnant women with gestational diabetes mellitus (GDM) were determined using a liquid chromatography system coupled to a mass spectrometer. The data were tested for normal distribution and homogeneity of variance before statistical analysis. Correlations were computed with the Pearson correlation coefficient. RESULTS: The maternal serum BCAAs and BCKAs levels during late pregnancy were higher in women with PGDM than those in healthy women. Meanwhile, the circulating BCAAs and BCKAs showed no significant changes in women with GDM compared with those in healthy pregnant women. Furthermore, the circulating BCAA and BCKA levels in women with PGDM were positively correlated with the weight of the newborn. The circulating leucine level in women with GDM was positively correlated with the weight of the newborn. BCAA and BCKA levels in healthy pregnant women showed no correlation with newborn weight. CONCLUSIONS: The serum BCAAs in pregnant women with diabetes, which was elevated in PGDM but not GDM, were positively correlated with newborn weight. These findings highlight potential approaches for early identification of high-risk individuals and interventions to reduce the risk of adverse pregnancy outcomes.
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Aminoácidos de Cadena Ramificada , Peso al Nacer , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Humanos , Femenino , Embarazo , Diabetes Gestacional/sangre , Recién Nacido , Aminoácidos de Cadena Ramificada/sangre , Adulto , Diabetes Mellitus Tipo 2/sangre , Embarazo en Diabéticas/sangreRESUMEN
Flupyradifurone (FPF) has been reported to have a potential risk to terrestrial and aquatic ecosystems. In the present study, the effects of chronic FPF exposure on bees were systematically investigated at the individual behavioral, tissue, cell, enzyme activity, and the gene expression levels. Chronic exposure (14 d) to FPF led to reduced survival (12 mg/L), body weight gain (4 and 12 mg/L), and food utilization efficiency (4 and 12 mg/L). Additionally, FPF exposure (12 mg/L) impaired sucrose sensitivity and memory of bees. Morphological analysis revealed significant cellular and subcellular changes in brain neurons and midgut epithelial cells, including mitochondrial damage, nuclear disintegration, and apoptosis. FPF exposure (4 and 12 mg/L) led to oxidative stress, as evidenced by increased lipid peroxidation and alterations in antioxidant enzyme activity. Notably, gene expression analysis indicated significant dysregulation of apoptosis, immune, detoxification, sucrose responsiveness and memory-related genes, suggesting the involvement of different pathways in FPF-induced toxicity. The multiple stresses and potential mechanisms described here provide a basis for determining the intrinsic toxicity of FPF.
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Estrés Oxidativo , Animales , Abejas/efectos de los fármacos , Abejas/fisiología , Estrés Oxidativo/efectos de los fármacos , Estrés Fisiológico , 4-Butirolactona/toxicidad , 4-Butirolactona/análogos & derivadosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Berberine (BBR) is the main active component from Coptidis rhizome, a well-known Chinese herbal medicine used for metabolic diseases, especially diabetes for thousands of years. BBR has been reported to cure various metabolic disorders, such as nonalcoholic fatty liver disease (NAFLD). However, the direct proteomic targets and underlying molecular mechanism of BBR against NAFLD remain less understood. AIM OF THE STUDY: To investigate the direct target and corresponding molecular mechanism of BBR on NAFLD is the aim of the current study. MATERIALS AND METHODS: High-fat diet (HFD)-fed mice and oleic acid (OA) stimulated HepG2 cells were utilized to verify the beneficial impacts of BBR on glycolipid metabolism profiles. The click chemistry in proteomics, DARTS, CETSA, SPR and fluorescence co-localization analysis were conducted to identify the targets of BBR for NAFLD. RNA-seq and shRNA/siRNA were used to investigate the downstream pathways of the target. RESULTS: BBR improved hepatic steatosis, ameliorated insulin resistance, and reduced TG levels in the NAFLD models. Importantly, Aldo-keto reductase 1B10 (AKR1B10) was first proved as the target of BBR for NAFLD. The gene expression of AKR1B10 increased significantly in the NAFLD patients' liver tissue. We further demonstrated that HFD and OA increased AKR1B10 expression in the C57BL/6 mice's liver and HepG2 cells, respectively, whereas BBR decreased the expression and activities of AKR1B10. Moreover, the knockdown of AKR1B10 by applying shRNA/siRNA profoundly impacted the beneficial effects on the pathogenesis of NAFLD by BBR. Meanwhile, the changes in various proteins (ACC1, CPT-1, GLUT2, etc.) are responsible for hepatic lipogenesis, fatty acid oxidation, glucose uptake, etc. by BBR were reversed by the knockdown of AKR1B10. Additionally, RNA-seq was used to identify the downstream pathway of AKR1B10 by examining the gene expression of liver tissues from HFD-fed mice. Our findings revealed that BBR markedly increased the protein levels of PPARα while downregulating the expression of PPARγ. However, various proteins of PPAR signaling pathways remained unaffected post the knockdown of AKR1B10. CONCLUSIONS: BBR alleviated NAFLD via mediating PPAR signaling pathways through targeting AKR1B10. This study proved that AKR1B10 is a novel target of BBR for NAFLD treatment and helps to find new targets for the treatment of NAFLD by using active natural compounds isolated from traditional herbal medicines as the probe.
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Aldo-Ceto Reductasas , Berberina , Dieta Alta en Grasa , Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Humanos , Berberina/farmacología , Berberina/uso terapéutico , Células Hep G2 , Masculino , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos/efectos de los fármacos , Ratones , Aldo-Ceto Reductasas/metabolismo , Aldo-Ceto Reductasas/genética , Aldehído Reductasa/metabolismo , Aldehído Reductasa/genética , Glucosa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Resistencia a la InsulinaRESUMEN
Health of honey bees is threatened by a variety of stressors, including pesticides and parasites. Here, we investigated effects of acetamiprid, Varroa destructor, and Nosema ceranae, which act either alone or in combination. Our results suggested that interaction between the three factors was additive, with survival risk increasing as the number of stressors increased. Although exposure to 150 µg/L acetamiprid alone did not negatively impact honey bee survival, it caused severe damage to midgut tissue. Among the three stressors, V. destructor posed the greatest threat to honey bee survival, and N. ceranae exacerbated intestinal damage and increased thickness of the midgut wall. Transcriptomic analysis indicated that different combinations of stressors elicited specific gene expression responses in honey bees, and genes involved in energy metabolism, immunity, and detoxification were altered in response to multiple stressor combinations. Additionally, genes associated with Toll and Imd signalling, tyrosine metabolism, and phototransduction pathway were significantly suppressed in response to different combinations of multiple stressors. This study enhances our understanding of the adaptation mechanisms to multiple stressors and aids in development of suitable protective measures for honey bees. ENVIRONMENTAL IMPLICATION: We believe our study is environmentally relevant for the following reasons: This study investigates combined effects of pesticide, Varroa destructor, and Nosema ceranae. These stressors are known to pose a threat to long-term survival of honey bees (Apis mellifera) and stability of the ecosystems. The research provides valuable insights into the adaptive mechanisms of honey bees in response to multiple stressors and developing effective conservation strategies. Further research can identify traits that promote honey bee survival in the face of future challenges from multiple stressors to maintain the overall stability of environment.
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Neonicotinoides , Nosema , Varroidae , Animales , Abejas/efectos de los fármacos , Nosema/efectos de los fármacos , Neonicotinoides/toxicidad , Varroidae/efectos de los fármacos , Insecticidas/toxicidadRESUMEN
The significance of gut microbiota in regulating animal immune response to viral infection is increasingly recognized. However, how chronic bee paralysis virus (CBPV) exploits host immune to disturb microbiota for its proliferation remains elusive. Through histopathological examination, we discovered that the hindgut harbored the highest level of CBPV, and displayed visible signs of damages. The metagenomic analysis showed that a notable reduction in the levels of Snodgrassella alvi and Lactobacillus apis, and a significant increase in the abundance of the opportunistic pathogens such as Enterobacter hormaechei and Enterobacter cloacae following CBPV infection. Subsequent co-inoculation experiments showed that these opportunistic pathogens facilitated the CBPV proliferation, leading to accelerated mortality in bees and exacerbation of bloated abdomen symptoms after CBPV infection. The expression level of antimicrobial peptide (AMP) was found to be significantly up-regulated by over 1000 times in response to CBPV infection, as demonstrated by subsequent transcriptome and quantitative real-time PCR investigations. In particular, through correlation analysis and a bacteriostatic test revealed that the AMPs did not exhibit any inhibitory effect against the two opportunistic pathogens. However, they did demonstrate inhibitory activity against S. alvi and L. apis. Our findings provide different evidence that the virus infection may stimulate and utilize the host's AMPs to eradicate probiotic species and facilitate the proliferation of opportunistic bacteria. This process weakens the intestinal barrier and ultimately resulting in the typical bloated abdomen.
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Microbioma Gastrointestinal , Virus de Insectos , Virus ARN , Virosis , Virus , Abejas , Animales , Virus ARN/fisiología , Péptidos Antimicrobianos , Virus de Insectos/fisiología , ParálisisRESUMEN
Antibiotics can cure diseases caused by bacterial infections, but their widespread use can have some side effects, such as probiotic reduction. There is an urgent need for such agents that can not only alleviate the damage caused by antibiotics, but also maintain the balance of the gut microbiota. In this study, we first characterized the nanocrystalline cellulose (NCC) extracted from plant jute (Corchorus olitorius L.) leaves. Next, we evaluated the protective effect of jute NCC and cellulose on human model gut bacteria (Lacticaseibacillus rhamnosus and Escherichia coli) under antibiotic stress by measuring bacterial growth and colony forming units. We found that NCC is more effective than cellulose in adsorbing antibiotics and defending the gut bacteria E. coli. Interestingly, the low-dose jute NCC clearly maintained the balance of key gut bacteria like Snodgrassella alvi and Lactobacillus Firm-4 in bees treated with tetracycline and reduced the toxicity caused by antibiotics. It also showed a more significant protective effect on human gut bacteria, especially L. rhamnosus, than cellulose. This study first demonstrated that low-dose NCC performed satisfactorily as a specific probiotic to mitigate the adverse effects of antibiotics on gut bacteria.
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Natural plant nanocrystalline cellulose (NCC), exhibiting a number of exceptional performance characteristics, is widely used in food fields. However, little is known about the relationship between NCC and the antiviral effect in animals. Here, we tested the function of NCC in antiviral methods utilizing honey bees as the model organism employing Israeli acute paralysis virus (IAPV), a typical RNA virus of honey bees. In both the lab and the field, we fed the IAPV-infected bees various doses of jute NCC (JNCC) under carefully controlled conditions. We found that JNCC can reduce IAPV proliferation and improve gut health. The metagenome profiling suggested that IAPV infection significantly decreased the abundance of gut core bacteria, while JNCC therapy considerably increased the abundance of the gut core bacteria Snodgrassella alvi and Lactobacillus Firm-4. Subsequent metabolome analysis further revealed that JNCC promoted the biosynthesis of fatty acids and unsaturated fatty acids, accelerated the purine metabolism, and then increased the expression of antimicrobial peptides (AMPs) and the genes involved in the Wnt and apoptosis signaling pathways against IAPV infection. Our results highlighted that JNCC could be considered as a prospective candidate agent against a viral infection.
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Corchorus , Dicistroviridae , Microbioma Gastrointestinal , Abejas , Animales , Celulosa/farmacología , Corchorus/genética , Antivirales/farmacologíaRESUMEN
We numerically investigate a tunable plasmon-induced transparency based on bulk Dirac semimetal (BDS) metamaterial in the terahertz band. In the unit cell, the prominent transparent peak appears to be due to the interference between the cut wires (CWs) and split-ring resonators (SRRs). An active modulation via near-field coupling is obtained by varying the Fermi level of the BDS. Introducing photoactive silicon, it will be found that once the intensity of the pump light is adjusted, a tunable transparent peak will appear. Furthermore, by shifting the coupling distance between CWs and SRRs, the depth of the transparent peak will change accordingly. Finally, we place the structure in environments with different refractive indices, which will exhibit excellent sensitivity and facilitate the application of biochemical sensors. This simple and easy-to-fabricate metamaterial structure will have excellent potential applications in modulation, filters, and detection.
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Under realistic environmental conditions, bees are often exposed to multiple stressors, especially Varroa destructor and pesticides. In this study, the effects of exposure to NOAEC of chlorothalonil during the larval stage, in the presence or absence of V. destructor, was examined in terms of survival, morphological and transcriptional changes. The interaction between chlorothalonil and V. destructor on the survival of honey bee was additive. V. destructor are the dominant factor in the interaction for survival and transcriptome alternation. The downregulation of the genes related to tissue growth and caste differentiation may directly link to the mortality of honey bees. Either chlorothalonil or V. destructor induces the irregular morphology of trophocytes and oenocytes in the fat body. In addition to irregular shapes, oenocytes in V. destructor alone and double-stressor treatment group showed altered nuclei and vacuoles in the cytoplasm. The interaction of V. destructor and chlorothalonil at the larval stage have potential adverse effects on the subsequent adult bees, with up-regulation of genes involved in lipid metabolism and detoxification/defense in fat body tissue. Our findings provide a comprehensive understanding of combinatorial effects between biotic and abiotic stressors on one of the most important pollinators, honey bees.
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Plaguicidas , Varroidae , Abejas , Animales , Varroidae/metabolismo , Larva , Nitrilos/toxicidad , Nitrilos/metabolismo , Plaguicidas/metabolismoRESUMEN
Domesticated honeybees and wild bees are some of the most important beneficial insects for human and environmental health, but infectious diseases pose a serious risk to these pollinators, particularly following the emergence of the ectoparasitic mite Varroa destructor as a viral vector. The acquisition of this novel viral vector from the Asian honeybee Apis ceranae has fundamentally changed viral epidemiology in its new host, the western honeybee A. mellifera. While the recently discovered Lake Sinai Viruses (LSV) have been associated with weak honeybee colonies, they have not been associated with vector-borne transmission. By combining a large-scale multi-year survey of LSV in Chinese A. mellifera and A. cerana honeybee colonies with globally available LSV-sequence data, we investigate the global epidemiology of this virus. We find that globally distributed LSV is a highly diverse multi-strain virus, which is predominantly associated with the western honeybee A. mellifera. In contrast to the vector-borne deformed wing virus, LSV is not an emerging disease. Instead, demographic reconstruction and strong global and local population structure indicates that it is a highly variable multi-strain virus in a stable association with its main host, the western honeybee. Prevalence patterns in China suggest a potential role for migratory beekeeping in the spread of this pathogen, demonstrating the potential for disease transmission with the man-made transport of beneficial insects.
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Abejas , Virus ARN , Varroidae , Animales , Humanos , Abejas/parasitología , Abejas/virología , China/epidemiología , Virus ARN/genética , Varroidae/virología , VirusRESUMEN
The Dicistroviridae is a virus family that includes many insect pathogens. These viruses contain a positive-sense RNA genome that is replicated by the virally encoded RNA-dependent RNA polymerase (RdRP) also named 3Dpol. Compared with the Picornaviridae RdRPs such as poliovirus (PV) 3Dpol, the Dicistroviridae representative Israeli acute paralysis virus (IAPV) 3Dpol has an additional N-terminal extension (NE) region that is about 40-residue in length. To date, both the structure and catalytic mechanism of the Dicistroviridae RdRP have remain elusive. Here we reported crystal structures of two truncated forms of IAPV 3Dpol, namely Δ85 and Δ40, both missing the NE region, and the 3Dpol protein in these structures exhibited three conformational states. The palm and thumb domains of these IAPV 3Dpol structures are largely consistent with those of the PV 3Dpol structures. However, in all structures, the RdRP fingers domain is partially disordered, while different conformations of RdRP substructures and interactions between them are also present. In particular, a large-scale conformational change occurred in the motif B-middle finger region in one protein chain of the Δ40 structure, while a previously documented alternative conformation of motif A was observed in all IAPV structures. These experimental data on one hand show intrinsic conformational variances of RdRP substructures, and on the other hand suggest possible contribution of the NE region in proper RdRP folding in IAPV.
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Picornaviridae , ARN Polimerasa Dependiente del ARN , ARN Polimerasa Dependiente del ARN/metabolismo , Picornaviridae/genética , ARNRESUMEN
Background: Chlorothalonil and acetamiprid are chemical pesticides commonly used in agricultural production and have been shown to have negative effects on bee's fitness. Despite many studies have revealed that honey bee (Apis mellifera L.) larvae are posting a high risk on exposure to pesticides, but the toxicology information of chlorothalonil and acetamiprid on bee larvae remain limited. Results: The no observed adverse effect concentration (NOAEC) of chlorothalonil and acetamiprid for honey bee larvae were 4 µg/mL and 2 µg/mL, respectively. Except for CarE, the enzymic activities of GST and P450 were not influenced by chlorothalonil at NOAEC, while chronic exposure to acetamiprid slightly increased the activities of the three tested enzymes at NOAEC. Further, the exposed larvae showed significantly higher expression of genes involved in a series of different toxicologically relevant process following, including caste development (Tor (GB44905), InR-2 (GB55425), Hr4 (GB47037), Ac3 (GB11637) and ILP-2 (GB10174)), immune system response (abaecin (GB18323), defensin-1 (GB19392), toll-X4 (GB50418)), and oxidative stress response (P450, GSH, GST, CarE). Conclusion: Our results suggest that the exposure to chlorothalonil and acetamiprid, even at concentrations below the NOAEC, showed potentially effects on bee larvae's fitness, and more important synergistic and behavioral effects that can affect larvae fitness should be explored in the further.
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The catalytic bis-allylation of alkynes is an important but challenging protocol to construct all-carbon tetra-substituted alkenes. Particularly, the catalytic unsymmetrical bis-allylation of alkynes remains as an underexplored task to date. We herein report an unprecedented unsymmetrical bis-allylation by simultaneously utilizing electrophilic trifluoromethyl alkene and nucleophilic allylboronate as the allylic reagents. With the aid of robust Ni0 /NHC catalysis, valuable skipped trienes can be obtained in high regio- and stereo-selectivities under mild conditions. Mechanistic studies indicate that the reaction may proceed through a ß-fluorine elimination of a nickelacycle followed by a transmetalation step with allylboronate. The present method exhibits a good tolerance of various functional groups. Besides, the skipped triene products can undergo an array of elaborate transformations, which highlights the potential applications of this strategy.
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Optical biosensor, which perceptively captures the variety of refractive index (RI) of the surrounding environment, has great potential applications in detecting property changes and types of analytes. However, the disequilibrium of light-matter interaction in different polarizations lead to the polarization-dependence and low sensitivity. Here, we propose a polarization-independent and ultrasensitive biosensor by introducing a one-dimensional topological photonic crystal (1D TPhC), where two N-period 1D photonic crystals (PhC1 and PhC2) with different topological invariants are designed for compressing the interaction region of the optical fields, and enhancing the interaction between the light and analyte. Since the strong light-matter interaction caused by the band-inversion is polarization-independent, the biosensor can obtain superior sensing performance both for TE and TM polarization modes. The sensitivity and Figure of Merit (FOM) of the designed biosensor are 1.5677×106 RIU-1 (1.3497 × 106 RIU-1) and 7.8387×1010 RIU-1deg-1 (4.4990×1010 RIU-1deg-1) for TM (TE) polarization mode, which performs two orders of magnitude enhancement compared with the reported biosensors. With the protection of the topological edge state, this biosensor has high tolerance to the thickness deviations and refractive index (RI) variations of the component materials, which can reduce the requirements on fabrication and working environment. It is anticipated that the proposed biosensor possesses excellent sensing performances, may have great potentials in environmental monitoring, medical detection, etc.
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Técnicas Biosensibles , Fotones , Óptica y Fotónica , RefractometríaRESUMEN
Antibiotics are omnipresent in the environment due to their widespread use, and they have wide-ranging negative impacts on organisms. Virus resistance differs substantially between domesticated Apis mellifera and wild Apis cerana, although both are commonly raised in China. Here, we investigated whether antibiotics can increase the sensitivity of honey bees to viral infection using the Israeli acute paralysis virus (IAPV) and tetracycline as representative virus and antibiotic. Although IAPV multiplied to lower levels in A. cerana than A. mellifera, resulting in decreased mortality (P < 0.01), there was no significant difference in immune responses to viral infection between the two species. Adult worker bees (A. cerana and A. mellifera) were treated with or without tetracycline to demonstrate the prominent role of gut microbiota against viral infection, and found Lactobacillus played a vital antiviral role in A. cerana. In A. cerana but not A. mellifera, tetracycline treatment reduced clearly bee survival and increased susceptibility to IAPV infection (P < 0.01). Our findings revealed that long-term antibiotic treatment in A. mellifera had altered the native gut microbiome and promoted the sensitivity to viral infection. We highlight the effects of antibiotics exposure on resistance to microbial and viral infection.
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Antibacterianos , Virosis , Abejas , Animales , Antibacterianos/toxicidad , Antivirales , Tetraciclinas , BacteriasRESUMEN
Butafulvene is a constitutional isomer of benzene, comprising a cyclobutene skeleton bearing two exocyclic conjugated methylene units. As a result of the intrinsic high strain energy and anti-aromaticity, the preparation of butafulvene compounds has been a fundamental issue for the development of butafulvene chemistry. Here an efficient palladium-catalysed coupling protocol involving propargylic compounds has been developed, providing a solid and versatile strategy for the rapid assembly of symmetric butafulvene derivatives. Based on mechanistic studies, two complementary mechanisms, both involving palladium catalysis, have been confirmed. With the mechanism unveiled, the synthesis of non-symmetric butafulvenes has also been achieved. Advantages of this strategy include tolerance to a wide range of propargylic molecules, mild reaction conditions, simple catalytic systems and easy scalability. The synthetic potential of the products as platform molecules for cyclobutene derivatives has also been demonstrated.
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Benceno , Paladio , Catálisis , Paladio/químicaRESUMEN
Black queen cell virus (BQCV) is a severe threat to the honeybee (Apis mellifera) worldwide. Although several BQCV strains have been reported in China, the molecular basis for BQCV pathogenicity has not been well understood. Thus, a reverse genetic system of BQCV is required for studying viral replication and its pathogenic mechanism. Here, the complete genome sequence of BQCV was obtained from honeybees using reverse transcription PCR (RT-PCR), namely a BQCV China-GS1 strain (KY741959). Then, a phylogenetic tree was built to analyse the genetic relationships among BQCV strains from different regions. Our results showed that the BQCV China-GS1 contained two ORFs, consistent with the known reference strains, except for the BQCV China-JL1 strain (KP119603). Furthermore, the infectious clone of BQCV was constructed based on BQCV China-GS1 using a low copy vector pACYC177 and gene recombination. Due to the lack of culture cells for bee viruses, we infected the healthy bees with infectious clone of BQCV, and the rescued BQCV resulted in the recovery of recombinant virus, which induced higher mortality than those of the control group. Immune response after inoculated with BQCV further confirmed that the infectious clone of BQCV caused the cellular and humoral immune response of honeybee (A. mellifera). In conclusion, the full nucleotide sequence of BQCV China-GS1 strain was determined, and the infectious clone of BQCV was constructed in this study. These data will improve the understanding of pathogenesis and the host immune responses to viral infection.
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Dicistroviridae , Virus ARN , Virus , Animales , Abejas , Dicistroviridae/genética , Sistemas de Lectura Abierta , Filogenia , Virus ARN/genética , Virus/genéticaRESUMEN
A hardware-friendly bisection neural network (BNN) topology is proposed in this work for approximately implementing massive pieces of complex functions in arbitrary on-chip configurations. Instead of the conventional reconfigurable fully connected neural network (FC-NN) circuit topology, the proposed hardware-friendly topology performs NN behaviors in a bisection structure, in which each neuron includes two constant synapse connections for both inputs and outputs. Compared with the FC-NN one, the reconfiguration of the BNN circuit topology eliminates the remarkable amount of dummy synapse connections in hardware. As the main target application, this work aims at building a general-purpose BNN circuit topology that offers a great amount of NN regressions. To achieve this target, we prove that the NN behaviors of the FC-NN circuit topologies can be migrated to the BNN circuit topologies equivalently. We introduce two approaches including the refining training algorithm and the inverted-pyramidal strategy to further reduce the number of neurons and synapses. Finally, we conduct the inaccuracy tolerance analysis to suggest the guideline for ultra-efficient hardware implementations. Compared with the state-of-the-art FC-NN circuit topology-based TrueNorth baseline, the proposed design can achieve 17.8-22.2 × hardware reduction and less than 1% inaccuracy.
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Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. Berberine (BBR) is an effective therapeutic agent in alleviating NAFLD. Berberrubine (BRB) is one of the main active metabolites of BBR, which shows significant anti-obesity and antihypoglycemic effects. However, whether BRB is responsible for the in vivo therapeutic effect and the underlying mechanism of BRB on NAFLD have not been elucidated. In this study, the ability of BRB to ameliorate NAFLD, together with its molecular mechanism, was investigated. The results showed that BRB treatments could significantly improve hepatic steatosis and insulin resistance in high-fat diet (HFD)-fed mice and oleic acid (OA)-treated HepG2 cells. Meanwhile, BBR and BRB treatment similarly prevented lipid accumulation by regulating the protein expression of ATGL, GK, PPARα, CPT-1, ACC1, FAS, and CD36. In addition, compared with BBR, BRB could maintain glucose homeostasis via GLUT2, GSK3ß, and G6Pase in HFD-fed mice. Furthermore, the components of the gut microbiota in mice were analyzed by 16S rRNA gene sequencing. BBR and BRB treatment could greatly modify the structure and composition of gut microbiota. At the genus level, BBR and BRB treatment decreased Lactobacillus and Romboutsia, while BBR increased beneficial bacteria, such as Akkermansia and Bacteroides, and BRB increased beneficial bacteria, such as Ileibacterium and Mucispirillum. Altogether, both BRB and BBR were active in alleviating NAFLD in vivo and BRB might be used as a functional material to treat NAFLD clinically.