Search

To reduce energy consumption, a new pulping process called A-D-E-RC (acidification/desalination/electrolysis/recycle-cooking) was developed by a research group in Guangxi University of China. The present work focuses on the step of recycle cooking (RC) to further investigate the technical feasibility of A-D-E-RC methods. Golden bamboo grass was considered as fiber source material for pulp, and it was cooked with the acidic treating of wastewater from black liquor. Then, the pulp obtained from each cooking was made into paper to test the changes in its physical properties. As a result, the pulp yield increased from 43.9% to 50.2%, after re-using acidified black liquor, and the paper's tear index and tensile index were improved. Therefore, this study demonstrated the feasibility of recycle cooking (RC) fiber materials for pulp applied the acidic treating wastewater from black liquor, and thereby, it further identifies the technical feasibility of A-D-E-RC pulping methods.

The increasing consumption of paper products has led to a shortage of paper fiber raw materials. It is necessary to develop new plant materials to alleviate the shortage of fiber suitable for papermaking. In this study, the fast-growing plant golden bamboo grass (Arundo donax), which is cultivated and planted in Guangxi province of China, was used as a new material for pulping. The average pulp yield by cyclic-cooking method averaged 48.6%, being 4.1% greater than the pulp yield by the ordinary caustic soda method. Much of the increased yield was attributable to the reprecipitation of lignin onto the fibers. The paper properties of the pulp prepared by cycle-cooked method did not decrease significantly, compared with the pulp prepared by the usual single-cooked method. Therefore, the pulp met the requirements of national standards of many kinds of papers. However, the pulp was not suitable for bleaching, due to its high consumption of oxidizing agents to reach the required brightness. Therefore, this research demonstrates that the fast-growing plant, Arundo donax is a good raw material for pulp, and the innovative method of cycle-cooking method can significantly improve the pulp yield.

This study investigated the dynamic recrystallization (DRX) mechanism and hot-deformation behavior of the solution-treated Mg-0.5Bi-0.5Sn-0.5Mn (BTM000) alloy during hot compression at temperatures ranging from 175 to 225 °C with a strain rate of 0.001–1 s−1. Processing maps and constitutive equation were used for a detailed analysis. The results showed a strong correlation with a coefficient of 0.987669, indicating the accuracy of proposed method in predicting the hot deformation behavior. The average activation energy (Q) was found to be 139.10 kJ/mol, and the stress component (n) was calculated to be 7.96, suggesting that cross-slip is the primary deformation mechanism. Based on the processing maps, the most suitable processing conditions were found to be within the range of 210–290 °C with a strain rate of 0.37–1 s−1. At a low strain rate of 0.001 s−1, the dominant deformation mechanism observed was pyramidal slip. However, at higher temperatures (175–325 °C) and a strain rate of 1 s−1, a transformation from basal slip to a combination of basal slip and pyramidal slip was observed. Under low-temperature and low-strain-rate conditions (175 °C/0.001 s−1), continuous dynamic recrystallization (CDRX) was the dominant mechanism. In contrast, under other deformation conditions (175 °C/1 s−1, 325 °C/0.001 s−1, 325 °C/1 s−1), a synergistic effect between discontinuous dynamic recrystallization (DDRX) and CDRX was evident. Through quasi-situ kernel average misorientation (KAM) characterization, it was observed that the local storage energy associated with CDRX was significantly lower compared to the combination of CDRX and DDRX, indicating a higher likelihood of CDRX occurrence.

In this study, the role of microstructure in tailoring the mechanical properties and corrosion behaviors of as-rolled dilute Mg–Bi binary alloys (MB-x, where x = 0.2 and 0.8 wt%) without/with Mg3Bi2 nanoprecipitates along the grain boundaries was systemically explored. The MB-0.8 alloy with Mg3Bi2 phases exhibited superior strength, ductility, and anticorrosion synergy (with a tensile yield stress of 235 MPa, ultimate tensile strength of 285 MPa, elongation of 10.3%, and Pi-168h of 0.105 mm/y). Strength–ductility synergy was achieved owing to the grain boundary strengthening and activation of prismatic and/or pyramidal slip systems. The transformation of the corrosion mode inhibited the corrosion of the MB-0.8 alloy. Therefore, our approach provides an effective strategy for developing Mg alloys that exhibit superior characteristics.

The addition of Sn improves the properties of Mg–Bi-based alloys, and can potentially overcome the high-temperature limitations of magnesium (Mg) alloys. However, high-Sn alloying leads to stress concentration during hot extrusion. Hence, in this study, the dynamic recrystallization (DRX) mechanism and hot-deformation behavior of a novel precipitate-free Mg–0.25Bi–0.25Sn alloy during hot compression conducted at 250–400 °C with strain rate of 0.001–1 s−1 were examined in detail by constructing processing maps and deriving constitutive equation. The obtained correlation coefficient was 0.99113, indicating that the proposed method can adequately predict the hot deformation behavior of the studied alloy. The calculated average activation energy was 143.0336 kJ/mol. According to the processing maps, the ideal processing areas corresponded to the conditions of 300–400 °C/0.001 s−1/1 s−1 and 400 °C/0.1 s−1. In addition, a transformation of prismatic slip to pyramidal II slip was observed at 350 °C, and the continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX) processes occurred during hot compression. The classification of the dominant DRX mechanisms was based on the Zener–Hollomon parameter (Z). Under high-Z deformation conditions, CDRX and DDRX occurred simultaneously; however, CDRX was the predominant process. Under medium-Z deformation conditions, DDRX was the only DRX process. Under low-Z deformation conditions, DDRX dominated over the DRX mechanism and was partially accompanied by CDRX.

The joint storage and reciprocal retrieval of learnt associated signals are presumably encoded by associative memory cells. In the accumulation and enrichment of memory contents in lifespan, a signal often becomes a core signal associatively shared for other signals. One specific group of associative memory neurons that encode this core signal likely interconnects multiple groups of associative memory neurons that encode these other signals for their joint storage and reciprocal retrieval. We have examined this hypothesis in a mouse model of associative learning by pairing the whisker tactile signal sequentially with the olfactory signal, the gustatory signal, and the tail-heating signal. Mice experienced this associative learning show the whisker fluctuation induced by olfactory, gustatory, and tail-heating signals, or the other way around, that is, memories to multi-modal associated signals featured by their reciprocal retrievals. Barrel cortical neurons in these mice become able to encode olfactory, gustatory, and tail-heating signals alongside the whisker signal. Barrel cortical neurons interconnect piriform, S1-Tr, and gustatory cortical neurons. With the barrel cortex as the hub, the indirect activation occurs among piriform, gustatory, and S1-Tr cortices for the second-order associative memory. These associative memory neurons recruited to encode multi-modal signals in the barrel cortex for associative memory are downregulated by neuroligin-3 knockdown. Thus, associative memory neurons can be recruited as the core cellular substrate to memorize multiple associated signals for the first-order and the second-order of associative memories by neuroligin-3-mediated synapse formation, which constitutes neuronal substrates of cognitive activities in the field of memoriology.

Acute lung injury (ALI) is a serious inflammatory disease with high morbidity and mortality. Rosavin is an anti-inflammatory and antioxidant phenylpropanoid and glucoside, which is isolated from Rhodiola rosea L. However, its potential molecular mechanisms and whether it has protective effects against lipopolysaccharide (LPS)-induced ALI remain to be elucidated. To assess the in vitro anti-inflammatory effects and anti-lung injury activity of rosavin, RAW264.7 and A549 cells were stimulated using 1 μg/mL LPS. Rosavin attenuated LPS-induced activation of the TLR-4/NF-κB signaling pathway in RAW264.7 cells and inhibited LPS-induced release of inflammatory factors in A549 cells. A mouse model of acute lung injury was constructed by intraperitoneal injection of 5 mg/kg LPS to observe the therapeutic effect of rosavin. Transcriptomics analysis and Western blot assays were utilized to verify the molecular mechanism, rosavin (20, 40, and 80 mg/kg) dose-dependently ameliorated histopathological alterations, reduced the levels of inflammatory factors, and inhibited the TLR-4/NF-κB/MAPK signaling pathway and apoptosis activation. Rosavin is a promising therapeutic candidate for acute lung injury by inhibiting the TLR-4/NF-κB/MAPK pathway.

Memory traces are believed to be broadly allocated in cerebral cortices and the hippocampus. Mutual synapse innervations among these brain areas are presumably formed in associative memory. In the present study, we have used neuronal tracing by pAAV-carried fluorescent proteins and neuroligin-3 mRNA knockdown by shRNAs to examine the role of neuroligin-3-mediated synapse formation in the interconnection between primary associative memory cells in the sensory cortices and secondary associative memory cells in the hippocampus during the acquisition and memory of associated signals. Our studies show that mutual synapse innervations between the barrel cortex and the hippocampal CA3 region emerge and are upregulated after the memories of associated whisker and odor signals come into view. These synapse interconnections are downregulated by a knockdown of neuroligin-3-mediated synapse linkages. New synapse interconnections and the strengthening of these interconnections appear to endorse the belief in an interaction between the hippocampus and sensory cortices for memory consolidation.

Memories associated to signals have been proven to rely on the recruitment of associative memory neurons that are featured by mutual synapse innervations among cross-modal cortices. Whether the consolidation of associative memory is endorsed by the upregulation of associative memory neurons in an intramodal cortex remains to be examined. The function and interconnection of associative memory neurons were investigated by in vivo electrophysiology and adeno-associated virus-mediated neural tracing in those mice that experienced associative learning by pairing the whisker tactile signal and the olfactory signal. Our results show that odorant-induced whisker motion as a type of associative memory is coupled with the enhancement of whisking-induced whisker motion. In addition to some barrel cortical neurons encoding both whisker and olfactory signals, i.e., their recruitment as associative memory neurons, the synapse interconnection and spike-encoding capacity of associative memory neurons within the barrel cortex are upregulated. These upregulated alternations were partially observed in the activity-induced sensitization. In summary, associative memory is mechanistically based on the recruitment of associative memory neurons and the upregulation of their interactions in intramodal cortices.

Four compounds (1, 5, 7, and 8) were first isolated from the genus Belamcanda Adans. nom. conserv., and six known compounds (2–4, 6, 9, and 10) were isolated from the rhizome of Belamcanda chinensis (L.) DC. Their structures were confirmed by spectroscopic data. Herein, compounds 1–10 were rhapontigenin, trans-resveratrol, 5,7,4′-trihydroxy-6,3′,5′-trimethoxy-isoflavone, irisflorentin, 6-hydroxybiochannin A, iridin S, pinoresinol, 31-norsysloartanol, isoiridogermanal, and iristectorene B, respectively. All compounds were evaluated for their antiproliferative effects against five tumor cell lines (BT549, 4T1, MCF7, MDA-MB-231, and MDA-MB-468). Among them, compound 9 (an iridal-type triterpenoid) showed the highest activity against 4T1 and MDA-MB-468 cells. Further studies displayed that compound 9 inhibited cell metastasis, induced cells cycle arrest in the G1 phase, exhibited significant mitochondrial damage in 4T1 and MDA-MB-468 cells including excess reactive oxygen species, decreased mitochondrial membrane potential, and induced 4T1 and MDA-MB-468 cell apoptosis for the first time. In summary, these findings demonstrate that compound 9 exerts promising potential for triple-negative breast cancer treatment and deserves further evaluation.

Salvianolic acid A (SAA) is one of the major components in Salvia miltiorrhiza Bge., with various pharmacological activities, and is likely to be a promising agent for the treatment of kidney diseases. The purpose of this study was to explore the protective effect and mechanisms of SAA on kidney disease. In this study, the improvement effects of SAA (10, 20, 40 mg/kg, i.g.) on kidney injury rats were investigated by detecting the levels of KIM-1, NGAL in serum and UP in the urine of AKI model rats established with gentamicin, as well as the levels of SCr and UREA in serum and IL-6, IL-12, MDA and T-SOD in the kidneys of CKD model rats established with 5/6 nephrectomy. HE and Masson staining were used to observe the histopathological changes in the kidney. Network pharmacology and Western blotting were used to explore the mechanism of SAA in improving kidney injury. The results showed that SAA improved kidney function in kidney injury rats by reducing the kidney index and pathological injury by HE and Masson staining, reducing the levels of KIM-1, NGAL and UP in AKI rats and UREA, SCr and UP in CKD rats, as well as exerting anti-inflammatory and anti-oxidative stress effects by inhibiting the release of IL-6 and IL-12, reducing MDA and increasing T-SOD. Western blotting results showed that SAA significantly reduced the phosphorylation levels of ERK1/2, p38, JNK and smad2/3, and the expression of TLR-4 and smad7. In conclusion, SAA plays a significant role in improving kidney injury in rats and the mechanism may be achieved by regulating the MAPKs and TGF-β1/smads signaling pathways.

The clinical application of gentamicin may lead to acute kidney injury (AKI), and the nephrotoxicity of gentamicin is related to the pathological mechanism of several oxidative and inflammatory cytokines. Plant-derived essential oils have good anti-inflammatory and antioxidant properties. This study aimed to clarify the protective effect of Amomum tsao-ko essential oils (AOs) on gentamicin-induced AKI in rats and its possible mechanism. The rat AKI model was induced by intraperitoneal injection of gentamicin. After 14 days of oral AO treatment, the renal function and pathological changes of the kidney tissues were evaluated, and the level of kidney tissue oxidative stress was detected. The content of inflammatory cytokines was measured by ELISA. The expression of ERK1/2, JNK1/2, p38, NF-κB, caspase-3, and Bax/Bcl-2 proteins were estimated by Western blot analysis. The results showed that taking AO reduced the contents of serum urea and creatinine in AKI rats and improve the pathological changes and oxidative stress of the kidney tissue in rats. At the same time, AO reduced inflammation and apoptosis during AKI by regulating the MAPK pathway. The data show that AO has a protective effect on the kidneys and may be a potential drug for treating kidney injury.

Under chronic stress, the appearance of depression-like behaviors may be related to the decline of the brain's reward circuit function which caused by long-term lack of reward. However, the effect of reward treatment on depressive-like behaviors induced by chronic stress and its molecular mechanism in the brain remain poorly understood. Here, accompanying with companion was used to imitate a reward to study the effect of reward on depression-like behaviors induced by chronic unpredicted mild stress (CUMS), and high-throughput sequencing was used to analyze the miRNA and mRNA profiles in ventral tegmental area (VTA) harvested from depression-like and resilient behaviors mice. We observed that CUMS-induced depression-like behaviors were ameliorated by accompanying with companion in mice, and 202 differentially expressed genes (DEGs) were found to be associated with depression-like behaviors, 27 DEGs associated with resilience, 159 DEGs associated with accompanying with companion. Importantly, we also obtained 228 differentially expressed miRNAs that associated with accompanying with companion. Furthermore, the miRNA-mRNA network associated with companion was established in ventral tegmental area, based on the miRNA and mRNA profiles. Altogether, our results uncover a new way to ameliorate depression-like behavior, as well as many potential drug targets to prevent or treat depression.

Alpha-functionalized organic acids are building blocks of many bioactive compounds. Here, the authors developed a toolbox-like, modular set of enzymes that reset chiral groups, turning achiral glycine and simple aldehydes into stereodefined α-keto acids, α-hydroxy acids, and α-amino acids.

Soil-borne pathogen Phytophthora sojae is an oomycete that causes devastating damage to soybean yield. To mine original resistant genes in soybean is an effective and environmentally-friend approach controlling the disease. In this study, soybean proteins were extracted from the first trifoliolates infected by predominant P. sojae race 1 and analyzed by two-dimensional gel electrophoresis. Nineteen differently-expressed protein spots were detected, and 10 of them were further applied for Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry Assay. One protein containing a dirigent (DIR) domain was identified and belonged to the DIR-b/d family. Therefore, it was named as GmDRR1 (Glycine max Disease Resistance Response 1). Then, GmDRR1 gene was pathologically confirmed to be involved in the resistant to P. sojae in soybean. GmDRR1-GFP (green fluorescent protein) fusion proteins localized in the cell membrane. qRT-PCR results showed GmDRR1 gene expressed differently in P. sojae resistant- and susceptible-soybean cultivars. By the promoter analysis, we found a haplotype H8 was existing in most resistant soybean varieties, while a haplotype H77 was existing in most susceptible soybean varieties. The H77 haplotype had seven SNPs (C to A, G to C, C to A, T to A, T to C, T to C, and T to A) and two single nucleotide insertions. The results supported that the expression difference of GmDRR1 genes between P. sojae resistant- and susceptible-soybean cultivars might depend on the GmDRR1 promoter SNPs. The results suggested that GmDRR1 was a dirigent protein involved in soybean resistant to P. sojae and paved a novel way for investigation of the molecular regulatory mechanism of the defense response to P. sojae in soybean.

Clerodendrum is a genus of ca. 500 species in the family Lamiaceae and widely distributed throughout the whole world. Up to now, many species of this genus have been described in various indigenous systems of medicine and are used in preparation of folklore medicines for the treatment of various life-threatening diseases, and more than eleven species of the Clerodendrum genus have been very well studied for their chemical constituents and biological activities, and 283 compounds, including monoterpene and its derivatives, sesquiterpene, diterpenoids, triterpenoids, flavonoid and flavonoid glycosides, phenylethanoid glycosides, steroids and steroid glycosides, cyclohexylethanoids, anthraquinones, cyanogenic glycosides, and others have been isolated and identified. Pharmacological studies have shown that these compounds and extracts from the Clerodendrum genus have extensive activities, such as anti-inflammatory and anti-nociceptive, anti-oxidant, anti-hypertensive, anticancer, antimicrobial, anti-diarrheal, hepatoprotective, hypoglycemic and hypolipidemic, memory enhancing and neuroprotective, and other activities. In this review, we attempt to highlight over phytochemical progress and list the phytoconstituents isolated from the genus Clerodendrum reported so far. The biological activities of this genus are also covered.

The immature epicarps of Juglans mandshurica and Juglans regia have been used as folk medicine for the treatment of cancer in China. Other parts of the J.mandshurica plant, including leaves, branches, barks, and stems, have reported antitumor activities. We previously found that various diarylheptanoids and phenolic compounds isolated from J. mandshurica epicarps show significant antitumor activities. However, there are no reports of quantitative analysis of diarylheptanoids and phenolic compounds of J. mandshurica. In this study, a validated quantitative method, based on ultraperformance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry, was employed to determine the contents of eight diarylheptanoids and seven phenolic compounds in the epicarps of J. mandshurica during different growth periods, in different parts of the plant, and in the epicarps of two Juglans species. The most successful J. mandshurica epicarp harvesting time fell between Day 12 and Day 27. The leaves of J. mandshurica showed potential for medical use as they had the highest content of the 15 compounds (3.399 ± 0.013 mg/g). We showed for the first time that the total content of diarylheptanoids in J. mandshurica is higher than that in J. regia, though, conversely, J. regia has higher contents of phenolic compounds. The method developed in this study is practical and simple and can be applied for quantitative analysis for evaluating the intrinsic quality of J. mandshurica.

The acquisition of associated signals is commonly seen in life. The integrative storage of these exogenous and endogenous signals is essential for cognition, emotion and behaviors. In terms of basic units of memory traces or engrams, associative memory cells are recruited in the brain during learning, cognition and emotional reactions. The recruitment and refinement of associative memory cells facilitate the retrieval of memory-relevant events and the learning of reorganized unitary signals that have been acquired. The recruitment of associative memory cells is fulfilled by generating mutual synapse innervations among them in coactivated brain regions. Their axons innervate downstream neurons convergently and divergently to recruit secondary associative memory cells. Mutual synapse innervations among associative memory cells confer the integrative storage and reciprocal retrieval of associated signals. Their convergent synapse innervations to secondary associative memory cells endorse integrative cognition. Their divergent innervations to secondary associative memory cells grant multiple applications of associated signals. Associative memory cells in memory traces are defined to be nerve cells that are able to encode multiple learned signals and receive synapse innervations carrying these signals. An impairment in the recruitment and refinement of associative memory cells will lead to the memory deficit associated with neurological diseases and psychological disorders. This review presents a comprehensive diagram for the recruitment and refinement of associative memory cells for memory-relevant events in a lifetime.

Crataegi folium have been used as medicinal and food materials worldwide due to its pharmacological activities. Although the leaves of Crataegus songorica (CS), Crataegus altaica (CA) and Crataegus kansuensis (CK) have rich resources in Xinjiang, China, they can not provide insights into edible and medicinal aspects. Few reports are available on the qualitative and quantitative analysis of flavonoids compounds of their leaves. Therefore, it is necessary to develop efficient methods to determine qualitative and quantitative flavonoids compounds in leaves of CS, CA and CK. In the study, 28 unique compounds were identified in CS versus CK by qualitative analysis. The validated quantitative method was employed to determine the content of eight flavonoids of the leaves of CS, CA and CK within 6 min. The total content of eight flavonoids was 7.8–15.1 mg/g, 0.1–9.1 mg/g and 4.8–10.7 mg/g in the leaves of CS, CA and CK respectively. Besides, the best harvesting periods of the three species were from 17th to 26th September for CS, from 30th September to 15th October for CA and CK. The validated and time-saving method was successfully implemented for the analysis of the content of eight flavonoids compounds in CS, CA and CK for the first time.

The acquisition, integration and storage of exogenous associated signals are termed as associative learning and memory. The consequences and processes of associative thinking and logical reasoning based on these stored exogenous signals can be memorized as endogenous signals, which are essential for decision making, intention, and planning. Associative memory cells recruited in these primary and secondary associative memories are presumably the foundation for the brain to fulfill cognition events and emotional reactions in life, though the plasticity of synaptic connectivity and neuronal activity has been believed to be involved in learning and memory. Current reports indicate that associative memory cells are recruited by their mutual synapse innervations among co-activated brain regions to fulfill the integration, storage and retrieval of associated signals. The activation of these associative memory cells initiates information recall in the mind, and the successful activation of their downstream neurons endorses memory presentations through behaviors and emotion reactions. In this review, we aim to draw a comprehensive diagram for associative memory cells, working principle and modulation, as well as propose their roles in cognition, emotion and behaviors.

Associative learning is a common way for information acquisition, and the integrative storage of multiple associated signals is essential for associative thinking and logical reasoning. In terms of the cellular mechanism for associative memory, our studies by behavioral task and cellular imaging demonstrate that paired whisker and odor stimulations lead to odorant-induced whisker motion and associative memory cell recruitment in the barrel cortex (BC), which is driven presumably by synapse innervation from co-activated sensory cortices. To confirm these associative memory cells and synapse innervations essential for associative memory and to examine their potential mechanisms, we studied a causal relationship between epigenetic process and memory cell/synapse recruitment by manipulating miRNAs and observing the changes from the recruitments of associative memory cells and synapse innervations to associative memory. Anti-miRNA-324 and anti-miRNA-133a in the BC significantly downregulate new synapse innervation, associative memory cell recruitment and odorant-induced whisker motion, where Tau-tubulin kinase-1 expression is increased. Therefore, the upregulated miRNA-324 in associative learning knocks down Ttbk1-mediated Tau phosphorylation and microtubule depolymerization, which drives the balance between polymerization and depolymerization toward the axon prolongation and spine stabilization to initiate new synapse innervations and to recruit associative memory cells.

This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury.

Functional plasticity at cortical synapses and neurons is presumably associated with learning and memory. Additionally, coordinated refinement between glutamatergic and GABAergic neurons occurs in associative memory. If these assumptions are present, neuronal plasticity strength and learning efficiency should be correlated. We have examined whether neuronal plasticity strength and learning efficiency are quantitatively correlated in a mouse model of associative learning. Paired whisker and odor stimulations in mice induce odorant-induced whisker motions. The fully establishment of this associative memory appears fast and slow, which are termed as high learning efficiency and low learning efficiency, respectively. In the study of cellular mechanisms underlying this differential learning efficiency, we have compared the strength of neuronal plasticity in the barrel cortices that store associative signals from the mice with high vs. low learning efficiencies. Our results indicate that the levels of learning efficiency are linearly correlated with the upregulated strengths of excitatory synaptic transmission on glutamatergic neurons and their excitability, as well as the downregulated strengths of GABAergic neurons' excitability, their excitatory synaptic inputs and inhibitory synaptic outputs in layers II~III of barrel cortices. The correlations between learning efficiency in associative memory formation and coordinated plasticity at cortical glutamatergic and GABAergic neurons support the notion that the plasticity of associative memory cells is a basis for memory strength.

Associative memory is essential for cognition, in which associative memory cells and their plasticity presumably play important roles. The mechanism underlying associative memory extinction vs. maintenance remains unclear, which we have studied in a mouse model of cross-modal associative learning. Paired whisker and olfaction stimulations lead to a full establishment of odorant-induced whisker motion in training day 10, which almost disappears if paired stimulations are not given in a week, and then recovers after paired stimulation for an additional day. In mice that show associative memory, extinction and recovery, we have analyzed the dynamical plasticity of glutamatergic neurons in layers II–III of the barrel cortex and layers IV–V of the motor cortex. Compared with control mice, the rate of evoked spikes as well as the amplitude and frequency of excitatory postsynaptic currents increase, whereas the amplitude and frequency of inhibitory postsynaptic currents (IPSC) decrease at training day 10 in associative memory mice. Without paired training for a week, these plastic changes are persistent in the barrel cortex and decayed in the motor cortex. If paired training is given for an additional day to revoke associative memory, neuronal plasticity recovers in the motor cortex. Our study indicates persistent neuronal plasticity in the barrel cortex for cross-modal memory maintenance as well as the dynamical change of neuronal plasticity in the motor cortex for memory retrieval and extinction. In other words, the sensory cortices are essential for long-term memory while the behavior-related cortices with the inability of memory retrieval are correlated to memory extinction.

Associative learning and memory are common activities in life, and their cellular infrastructures constitute the basis of cognitive processes. Although neuronal plasticity emerges after memory formation, basic units and their working principles for the storage and retrieval of associated signals remain to be revealed. Current reports indicate that associative memory cells, through their mutual synapse innervations among the co-activated sensory cortices, are recruited to fulfill the integration, storage and retrieval of multiple associated signals, and serve associative thinking and logical reasoning. In this review, we aim to summarize associative memory cells in their formation, features and functional impacts.

Associative learning and memory are common activities in life, and their cellular infrastructures constitute the basis of cognitive processes. Although neuronal plasticity emerges after memory formation, basic units and their working principles for the storage and retrieval of associated signals remain to be revealed. Current reports indicate that associative memory cells, through their mutual synapse innervations among the co-activated sensory cortices, are recruited to fulfill the integration, storage and retrieval of multiple associated signals, and serve associative thinking and logical reasoning. In this review, we aim to summarize associative memory cells in their formation, features and functional impacts.

Human brain function undergoes complex transformations across the lifespan. We employed resting-state functional MRI and graph-theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole-brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years. Brain networks were constructed by computing Pearson's correlations in blood-oxygenation-level-dependent temporal fluctuations among 1024 parcellation units followed by graph-based network analyses. We observed that the human brain functional connectome exhibited highly preserved non-random modular and rich club organization over the entire age range studied. Further quantitative analyses revealed linear decreases in modularity and inverted-U shaped trajectories of local efficiency and rich club architecture. Regionally heterogeneous age effects were mainly located in several hubs (e.g., default network, dorsal attention regions). Finally, we observed inverse trajectories of long- and short-distance functional connections, indicating that the reorganization of connectivity concentrates and distributes the brain's functional networks. Our results demonstrate topological changes in the whole-brain functional connectome across nearly the entire human lifespan, providing insights into the neural substrates underlying individual variations in behavior and cognition. These results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age-related neuropsychiatric disorders.

Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveals the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory.

Major depression is a prevalent mood disorder. Chronic stress is presumably main etiology that leads to the neuron and synapse atrophies in the limbic system. However, the intermediate molecules from stresses to neuronal atrophy remain elusive, which we have studied in the medial prefrontal cortices from depression mice.The mice were treated by the chronic unpredictable mild stress (CUMS) until they expressed depression-like behaviors confirmed by the tests of sucrose preference, forced swimming and Y-maze. High-throughput sequencings of microRNA and mRNA in the medial prefrontal cortices were performed in CUMS-induced depression mice versus control mice to demonstrate the molecular profiles of major depression. In the medial prefrontal cortices of depression-like mice, the levels of mRNAs that translated the proteins for the GABAergic synapses, dopaminergic synapses, myelination, synaptic vesicle cycle and neuronal growth were downregulated. miRNAs of regulating these mRNAs are upregulated.The deteriorations of GABAergic and dopaminergic synapses as well as axonal growth are associated with CUMS-induced depression.

Stressful life leads to mood disorders. Chronic mild stress is presumably major etiology for depression, and acute severe stress leads to anxiety. These stressful situations may impair hypothalamus-pituitary-adrenal axis and in turn induce synapse dysfunction. However, it remains elusive how the stress hormones mess up subcellular compartments and interactions between excitatory and inhibitory neurons, which we have investigated in mouse amygdala, a structure related to emotional states.Dexamethasone was chronically given by intraperitoneal injection once a day for one week or was acutely washed into the brain slices. The neuronal spikes and synaptic transmission were recorded by whole-cell patching in amygdala neurons of brain slices. The chronic or acute administration of dexamethasone downregulates glutamate release as well as upregulates GABA release and GABAergic neuron spiking. The chronic administration of dexamethasone also enhances the responsiveness of GABA receptors.The upregulation of GABAergic neurons and the downregulation of glutamatergic neurons by glucocorticoid impair their balance in the amygdala, which leads to emotional disorders during stress.

Neural plasticity is associated with memory formation. The coordinated refinement and interaction between cortical glutamatergic and GABAergic neurons remain elusive in associative memory, which we examine in a mouse model of associative learning. In the mice that show odorant-induced whisker motion after pairing whisker and odor stimulations, the barrel cortical glutamatergic and GABAergic neurons are recruited to encode the newly learnt odor signal alongside the innate whisker signal. These glutamatergic neurons are functionally upregulated, and GABAergic neurons are refined in a homeostatic manner. The mutual innervations between these glutamatergic and GABAergic neurons are upregulated. The analyses by high throughput sequencing show that certain microRNAs related to regulating synapses and neurons are involved in this cross-modal reflex. Thus, the coactivation of the sensory cortices through epigenetic processes recruits their glutamatergic and GABAergic neurons to be the associative memory cells as well as drive their coordinated refinements toward the optimal state for the storage of the associated signals.

In this research, three categories of phenylpropanoid glycosides (PPGs) were designed and synthesized with PPGs isolated from Rhodiola rosea L. as lead compounds. Their inhibitory abilities toward acetylcholinesterase (AChE) and xanthine oxidase (XOD) were also tested. Some of the synthetic PPGs exhibited excellent enzyme inhibitory abilities.

Periostracum cicadae, the cast-off shell of the cicada Cryptotympana pustulata Fabricius, is used in traditional Chinese medicine for its diaphoretic, anticonvulsive, sedative, antipyretic, and antiallergic effects. However, the exact pathogenesis of immunoglobulin A nephropathy (IgAN) remains unclear, thereby hindering investigations to identify novel therapeutic agents. A rat IgAN model was established by administration of bovine serum albumin, lipopolysaccharide, and carbon tetrachloride, which simultaneously established blood stasis and a heat syndrome model. The animals were sacrificed to detect changes in protein levels in urine and blood. Immunofluorescence was performed to assess IgA deposition in the glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematology and eosin, periodic acid-Schiff, TUNEL (TdT-mediated dUTP Nick-End Labeling), and immunohistochemical staining were performed to evaluate histopathological changes in kidney tissues. Additionally, target-related proteins were measured by Western blotting. Periostracum cicadae resulted in a reduction in blood and urine protein levels. Serum TNF-α, IL-1β, and IL-6 levels significantly decreased in the periostracum cicadae-treated groups compared to the IgAN group. Furthermore, a reduction in MCP-1 (Monocyte Chemotactic Protein-1), TLR4 ((Toll-Like Receptor 4)), and IgA expression levels and a dose-dependent increase in caspase 3 expression were observed in response to periostracum cicadae treatment. TGF-β1(Transforming Growth Factor-β) levels decreased, whereas that of Fas increased in the kidney tissues of the periostracum cicadae-treated groups. The findings of the present study indicate that periostracum cicadae induces apoptosis and improves kidney inflammation and fibrosis in IgA nephropathy rat models.

A series of fluorescent sensors based on 8-hydroxyquinoline dansylate as core and dendritic PAMAM as shell were synthesized. Their fluorescence characteristic and fluorescent sensing behavior toward metal ions were studied in water/methanol (1: 1, v/v). The sensors exhibit good selectivity and sensitivity for Fe3+ ion and to some extent for Cr3+ ion. The third generation dendrimer has the better sensitivity than the first and second generations.

This study investigated the volatile flavor compounds and antioxidant properties of the essential oil of chrysanthemums that was extracted from the fresh flowers of 10 taxa of Chrysanthemum morifolium from three species; namely Dendranthema morifolium (Ramat.) Yellow, Dendranthema morifolium (Ramat.) Red, Dendranthema morifolium (Ramat.) Pink, Dendranthema morifolium (Ramat.) White, Pericallis hybrid Blue, Pericallis hybrid Pink, Pericallis hybrid Purple, Bellis perennis Pink, Bellis perennis Yellow, and Bellis perennis White. The antioxidant capacity of the essential oil was assayed by spectrophotometric analysis. The volatile flavor compounds from the fresh flowers were collected using dynamic headspace collection, analyzed using auto thermal desorber–gas chromatography/mass spectrometry, and identified with quantification using the external standard method. The antioxidant activities of Chrysanthemum morifolium were evaluated by DPPH and FRAP assays, and the results showed that the antioxidant activity of each sample was not the same. The different varieties of fresh Chrysanthemum morifolium flowers were distinguished and classified by fingerprint similarity evaluation, principle component analysis (PCA), and cluster analysis. The results showed that the floral volatile component profiles were significantly different among the different Chrysanthemum morifolium varieties. A total of 36 volatile flavor compounds were identified with eight functional groups: hydrocarbons, terpenoids, aromatic compounds, alcohols, ketones, ethers, aldehydes, and esters. Moreover, the variability among Chrysanthemum morifolium in basis to the data, and the first three principal components (PC1, PC2, and PC3) accounted for 96.509% of the total variance (55.802%, 30.599%, and 10.108%, respectively). PCA indicated that there were marked differences among Chrysanthemum morifolium varieties. The cluster analysis confirmed the results of the PCA analysis. In conclusion, the results of this study provide a basis for breeding Chrysanthemum cultivars with desirable floral scents, and they further support the view that some plants are promising sources of natural antioxidants.

BackgroundAcidosis impairs cognitions and behaviors presumably by acidification-induced changes in neuronal metabolism. Cortical GABAergic neurons are vulnerable to pathological factors and their injury leads to brain dysfunction. How acidosis induces GABAergic neuron injury remains elusive. As the glia cells and neurons interact each other, we intend to examine the role of the astrocytes in acidosis-induced GABAergic neuron injury.ResultsExperiments were done at GABAergic cells and astrocytes in mouse cortical slices. To identify astrocytic involvement in acidosis-induced impairment, we induced the acidification in single GABAergic neuron by infusing proton intracellularly or in both neurons and astrocytes by using proton extracellularly. Compared the effects of intracellular acidification and extracellular acidification on GABAergic neurons, we found that their active intrinsic properties and synaptic outputs appeared more severely impaired in extracellular acidosis than intracellular acidosis. Meanwhile, extracellular acidosis deteriorated glutamate transporter currents on the astrocytes and upregulated excitatory synaptic transmission on the GABAergic neurons. Moreover, the antagonists of glutamate NMDA-/AMPA-receptors partially reverse extracellular acidosis-induced injury in the GABAergic neurons.ConclusionOur studies suggest that acidosis leads to the dysfunction of cortical GABAergic neurons by astrocyte-mediated excitotoxicity, in addition to their metabolic changes as indicated previously.

Rhodiola rosea L. (RRL) possesses a wide range of pharmacological properties, including lung-protective activity, and has been utilized in folk medicine for several 100 years. However, the lung-protective mechanism remains unclear. This study investigated the possible lung-protective activity mechanism of RRL in a pulmonary fibrosis (PF) rat model. Lung fibrotic injury was induced in Sprague–Dawley rats by single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg). The rats were administered 125, 250, or 500 mg/kg of a 95% ethanol extract of RRL for 28 days. The animals were killed to detect changes in body weight, serum levels of glutathione (GSH) and total superoxide dismutase (T-SOD), as well as lung tissue hydroxyproline (HYP) content. Tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining were performed to observe the histopathological changes in lung tissues. Additionally, target-related proteins were measured by Western blotting. RRL alleviated the loss of body weight induced by instilling BLM in PF rats, particularly at the 500 mg/kg per day dose. RRL reduced HYP (p < 0.01) and increased GSH and T-SOD contents. BALF levels of TNF-α, TGF-β1, and IL-6 decreased significantly in the RRL-treated groups. Expression levels of matrix metalloproteinase-9 (MMP-9) and α-smooth muscle actin decreased significantly in a dose-dependent manner in response to RRL. Moreover, the levels of TGF-β1 and tissue inhibitor of metalloproteinase-1 in lung tissues also decreased in the RRL-treated groups. RRL alleviated BLM-induced PF in rats. Our results reveal that the protective effects of RRL against fibrotic lung injury in rats are correlated with its anti-inflammatory, antioxidative, and anti-fibrotic properties. MMP-9 may play important roles in BLM-induced PF.

BackgroundCross-modal plasticity is characterized as the hypersensitivity of remaining modalities after a sensory function is lost in rodents, which ensures their awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain unclear. We aim to study the role of different types of neurons in cross-modal plasticity.Methodology/principal findingsIn addition to behavioral tasks in mice, whole-cell recordings at the excitatory and inhibitory neurons, and their two-photon imaging, were conducted in piriform cortex. We produced a mouse model of cross-modal sensory plasticity that olfactory function was upregulated by trimming whiskers to deprive their sensory inputs. In the meantime of olfactory hypersensitivity, pyramidal neurons and excitatory synapses were functionally upregulated, as well as GABAergic cells and inhibitory synapses were downregulated in piriform cortex from the mice of cross-modal sensory plasticity, compared with controls. A crosswire connection between barrel cortex and piriform cortex was established in cross-modal plasticity.Conclusion/significanceAn upregulation of pyramidal neurons and a downregulation of GABAergic neurons strengthen the activities of neuronal networks in piriform cortex, which may be responsible for olfactory hypersensitivity after a loss of whisker tactile input. This finding provides the clues for developing therapeutic strategies to promote sensory recovery and substitution.

BackgroundThe neurons and synapses work coordinately to program the brain codes of controlling cognition and behaviors. Spike patterns at the presynaptic neurons regulate synaptic transmission. The quantitative regulations of synapse dynamics in spike encoding at the postsynaptic neurons remain unclear.Methodology/principal findingsWith dual whole-cell recordings at synapse-paired cells in mouse cortical slices, we have investigated the regulation of synapse dynamics to neuronal spike encoding at cerebral circuits assembled by pyramidal neurons and GABAergic ones. Our studies at unitary synapses show that postsynaptic responses are constant over time, such as glutamate receptor-channel currents at GABAergic neurons and glutamate transport currents at astrocytes, indicating quantal glutamate release. In terms of its physiological impact, our results demonstrate that the signals integrated from quantal glutamatergic synapses drive spike encoding at GABAergic neurons reliably, which in turn precisely set spike encoding at pyramidal neurons through feedback inhibition.Conclusion/significanceOur studies provide the evidences for the quantal glutamate release to drive the spike encodings precisely in cortical circuits, which may be essential for programming the reliable codes in the brain to manage well-organized behaviors.

Graph-based computational network analysis has proven a powerful tool to quantitatively characterize functional architectures of the brain. However, the test-retest (TRT) reliability of graph metrics of functional networks has not been systematically examined. Here, we investigated TRT reliability of topological metrics of functional brain networks derived from resting-state functional magnetic resonance imaging data. Specifically, we evaluated both short-term (5 months apart) TRT reliability for 12 global and 6 local nodal network metrics. We found that reliability of global network metrics was overall low, threshold-sensitive and dependent on several factors of scanning time interval (TI, long-term>short-term), network membership (NM, networks excluding negative correlations>networks including negative correlations) and network type (NT, binarized networks>weighted networks). The dependence was modulated by another factor of node definition (ND) strategy. The local nodal reliability exhibited large variability across nodal metrics and a spatially heterogeneous distribution. Nodal degree was the most reliable metric and varied the least across the factors above. Hub regions in association and limbic/paralimbic cortices showed moderate TRT reliability. Importantly, nodal reliability was robust to above-mentioned four factors. Simulation analysis revealed that global network metrics were extremely sensitive (but varying degrees) to noise in functional connectivity and weighted networks generated numerically more reliable results in compared with binarized networks. For nodal network metrics, they showed high resistance to noise in functional connectivity and no NT related differences were found in the resistance. These findings provide important implications on how to choose reliable analytical schemes and network metrics of interest.

BackgroundAction potentials are the essential unit of neuronal encoding. Somatic sequential spikes in the central nervous system appear various in amplitudes. To be effective neuronal codes, these spikes should be propagated to axonal terminals where they activate the synapses and drive postsynaptic neurons. It remains unclear whether these effective neuronal codes are based on spike timing orders and/or amplitudes.Methodology/principal findingsWe investigated this fundamental issue by simultaneously recording the axon versus soma of identical neurons and presynaptic vs. postsynaptic neurons in the cortical slices. The axons enable somatic spikes in low amplitude be enlarged, which activate synaptic transmission in consistent patterns. This facilitation in the propagation of sequential spikes through the axons is mechanistically founded by the short refractory periods, large currents and high opening probability of axonal voltage-gated sodium channels.Conclusion/significanceAn amplification of somatic incomplete spikes into axonal complete ones makes sequential spikes to activate consistent synaptic transmission. Therefore, neuronal encoding is likely based on spike timing order, instead of graded analogues.

BACKGROUND: Loss of a sensory function is often followed by the hypersensitivity of other modalities in mammals, which secures them well-awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain to be documented. METHODOLOGY/PRINCIPAL FINDINGS: Multidisciplinary approaches, such as electrophysiology, behavioral task and immunohistochemistry, were used to examine the involvement of specific types of neurons in cross-modal plasticity. We have established a mouse model that olfactory deficit leads to a whisking upregulation, and studied how GABAergic neurons are involved in this cross-modal plasticity. In the meantime of inducing whisker tactile hypersensitivity, the olfactory injury recruits more GABAergic neurons and their fine processes in the barrel cortex, as well as upregulates their capacity of encoding action potentials. The hyperpolarization driven by inhibitory inputs strengthens the encoding ability of their target cells. CONCLUSION/SIGNIFICANCE: The upregulation of GABAergic neurons and the functional enhancement of neuronal networks may play an important role in cross-modal sensory plasticity. This finding provides the clues for developing therapeutic approaches to help sensory recovery and substitution.

Periostracum Cicadae is the cast-off shell of the cicada Cryptotympana pustulata Fabricius, it is a widely used animal based traditional folk medicine, it is found to have many effects including antipyretic, antiallergic and antioxidant activities. In this study, ten N-acetyldopamine dimers, named Cicadamide C1–C10 (compounds 1–10), were isolated from Periostracum Cicadae. One-dimensional NMR, twodimensional NMR, mass spectrometry, CD spectroscopy, and chemical evidence were performed to further determine their structures. In the results, ten N-acetyldopamine dimers were isolated and their structures were elucidated. This study provides a basic reference for further biological effects study on Periostracum Cicadae. [ABSTRACT FROM AUTHOR]