Fully automated measurement of femoral neck axis line in anatomical coordinate system using CT images.

The femoral neck is the most vulnerable site for fractures within the hip joint. Due to its complex three-dimensional structure and special blood supply mechanism, the treatment of femoral neck fractures is difficult and the healing probability is low. Using computers to accurately and automatically locate the femoral neck axis can detect the density of femoral neck, the neck-shaft angle and the anteversion angle, which effectively assists in the prevention and treatment of femoral neck fractures. Additionally, the traditional femoral neck axis positioning schemes have limitations in accuracy, automation and assistance to bone density measurement. Therefore, this paper proposes a new fully automatic femoral neck axis positioning method. First, the coronal plane's three-dimensional reconstruction highlights the details of the target bone, and then designs a coarse localization module based on multi-scale template matching to obtain the rough range of the femoral neck axis. Then, a detailed localization module based on the femoral neck virtual slices is used to obtain the contour centers and accurately locates the three-dimensional femoral neck axis. This method has been validated in comparison with the manual measurement method. Experimental results revealed that the extracted femoral neck axis in this study can achieve automation, ensure accuracy, and avoid subjective effects effectively and has the potential value to be applied in the prevention and treatment of femoral neck fractures.

The influence of EEG channels and features significance on automatic detection of epileptic waves in MECT.

Modified Electric Convulsive Therapy (MECT) is an efficacious physical therapy in treating mental disorders. The occurrence of epilepsy is a crucial benchmark for evaluating therapeutic effectiveness. However, the medical field still lacks relevant research on automatically detecting epileptic waves in MECT. Therefore, this article proposes a novel automatic detection method of epileptic waves in MECT. In this article, EEG local features (time, frequency, and time-frequency domains) and global features (Pearson correlation coefficient) are combined for epileptic wave detection with SVM (Support Vector Machine). We researched the system with 15 EEG detection channels. The dataset under investigation contains EEG data from 22 patients who received MECT and presented with epileptic seizures. The results revealed that LA (Logarithm of Activity) feature exhibits the best classification significance. When epileptic waves appear, there is a decrease in the power ratio of delta waves and an increase in the power ratio of theta waves. Additionally, the complexity of EEG decreases while the correlation between EEG channels increases. The Cz, F4, and P3 channels exhibit the highest classification significance among all EEG channels. Furthermore, based on the channel classification significance, the EEG detection channels number can be reduced to 8. Similarly, based on the feature classification significance, the local feature number can be reduced from 9 to 3. These conclusions can improve detection efficiency and reduce the cost for MECT. Moreover, the method we proposed can effectively detect epileptic waves in MECT. This work can provide physicians with a reference for evaluating the effectiveness of MECT.

Antimicrobial dichloroisocyanurate-salts for controlled release of chlorine.

Sodium dichloroisocyanurate (Na-DCC), a disinfectant known for rapid decomposition in water, loses its effectiveness with complete release of free available chlorine (FAC) in under an hour. To overcome this, a series of chlorine rich transition metal complexes/tetrabutylammonium (TBA) salts of DCC, including 2Na[Cu(DCC)4], 2Na[Fe(DCC)4], 2Na[Co(DCC)4]·6H2O, 2Na[Ni(DCC)4]·6H2O, and TBA[DCC]·4H2O have been developed for extended chlorine release studies. The DCC-salts are synthesized based on the metathesis reaction process and are characterized using IR, NMR, CHN analyses, TGA,DSC, and Lovi bond colorimeter. The DCC-salts displayed poor water solubility and low decomposition chlorine release profile compared to Na-DCC. The water solubility of DCC-salts was reduced by a factor of 5.37 to 2500 compared to Na-DCC. The decomposition release of FAC from DCC-salts has been studied over time in comparison to Na-DCC in distilled water using a Lovi-bond colorimeter. DCC-salts displayed controlled FAC release profiles that varied from 1-13 days depending on the type of metal/TBA unit in them, whereas the parent Na-DCC displayed complete FAC release in about 0.91 h. For a proof of concept, the controlled release of metal from one of the DCC-metal complex salts, i.e., copper from the Cu-DCC is also investigated with a function of time in distilled water at RT. The 100% release of copper from Cu-DCC was identified over a period of 10 days. In addition, the applicability of DCC-salts as excellent antiviral agents against the bacteriophage T4 and antibacterial agents against Erwinia, Pseudomonas aeruginosa PA014 (Gram-negative), and Staphylococcus epidermidis (Gram-positive) compared to Na-DCC has been demonstrated.

Dipeptide-polysaccharides hydrogels through co-assembly.

Self-assembling dipeptide hydrogels are attracting attention in food, materials, and biomedicine. However, there are still limitations such as weak hydrogel properties. Herein, we introduced two types of polysaccharides (Arabic gum and citrus pectin) into an alkyl-chain modified dipeptide (C13-tryptophan-tyrosine (C13-WY)) to generate co-assembled C13-WY-arabic gum and C13-WY-pectin hydrogels. The co-assembled hydrogels exhibited enhanced mechanical properties and stability. The G' value of C13-WY-arabic gum and C13-WY-pectin hydrogels was 3 and 10 times larger than that of C13-WY hydrogel, respectively. The addition of Arabic gum and citrus pectin led to the co-assembly and molecular rearrangement. Moreover, co-assembled hydrogels showed more ß-sheet structure and hydrogen bonds. Importantly, the self-/co-assembled hydrogels showed low cytotoxicity. We utilized these hydrogels for the encapsulation of docetaxel and they showed a high embedding rate and slow-release. Our findings provide a novel strategy for the development of stable supramolecular peptide hydrogels with good biocompatibility through simple co-assembly.

Research progress in tigliane-type macrocyclic diterpenoids / 中国中药杂志

Tigliane type macrocyclic diterpenoids with special structures and diverse bioactivities are mainly extracted from plants of Euphorbiaceae and Thymelaeaceae. According to the different functional groups, they can be classified into types of phorbol esters, C-4 deoxyphorbol esters, C-12 deoxyphorbol esters, C-16 or C-17 substituted phorbol esters and others. Most of them present promising antiviral activities and cytotoxic activities and are expected to be developed as candidates for anti-AIDS, anti-tuberculosis, and anti-tumor clinical trials, demonstrating great potential for the application in healthcare. This paper reviews 115 novel tigliane-type diterpenoids discovered since 2013 and summarize their chemical structures and bioactivities, aiming to lay a foundation for further development and utilization of these compounds and provide new ideas for the development of clinical drugs.

Thermal conditions and active substance stability affect the isomerization and degradation of lycopene.

This study evaluated the effects of thermal treatment conditions (100-120 °C, 0-5 h) and active substance stability on the isomerization and degradation of lycopene in the "Sanhong" pummelo (C. grandis cv. Sanhongmiyou) matrix. The results revealed that the degradation of (all-E)-lycopene and total lycopene in pummelo could be well fit by the first-order kinetic model under thermal treatment. The total Z-lycopene ratio was maintained at nearly 40 % (120 °C, 4 h). The behavior of lycopene was related to the degradation of active substances, such as the degradation of ascorbic acid and polysaccharides. The stability of polysaccharides was temperature-dependent, and with the increasing temperature (100-120 °C), a significant negative correlation was observed between the content of Z-isomers and polysaccharides. The enhancement of lycopene isomerization was attributed to the degradation of polysaccharides under thermal treatment. These findings facilitate the functional development and efficient utilization of lycopene in fruit processing.

Sequence-Selected C13-Dipeptide Self-Assembled Hydrogels for Encapsulation of Lemon Essential Oil with Antibacterial Activity.

Supramolecular self-assembling peptide hydrogels are attracting attention. The switching of even one amino acid may lead to differences in structure and functions of peptide hydrogels. Herein, we investigate the effect of substitution of a single amino acid residue on the gelation properties of C13-dipeptide hydrogels. We show that four C13-R1Y (C13-VY, C13-FY, C13-WY, and C13-YY) can form hydrogels with drastically tunable rigidity (the G' values were 5.74, 0.16, 27.74, and 67.90 KPa, respectively). Moreover, C13-WY and C13-YY hydrogels with high stability and excellent mechanical properties formed ß-sheet nanofiber cross-linked networks. Furthermore, we applied four hydrogels into encapsulation of lemon essential oil (LEO). The peptide hydrogels had a high encapsulation rate and slowly released the LEO. Importantly, the LEO-loaded hydrogels showed enhanced antibacterial activity than free LEO. Our results clearly demonstrate the significance of side-chain interactions in determining hydrogel properties and their potential application in encapsulation for nutrition agents and hydrophobic drugs.

A Comparative Study on Relieving Exercise-Induced Fatigue by Inhalation of Different Citrus Essential Oils.

Citrus essential oils (CEOs) possess physiological functions due to diverse aroma components. However, evidence for the effects of CEOs on exercise performance and exercise-induced fatigue is limited. The CEOs with discrepancies in components may exert different effects on the amelioration of exercise-induced fatigue. In this study, sweet orange (Citrus sinensis L.) essential oil (SEO), lemon (Citrus limon Osbeck) essential oil (LEO), and bergamot (Citrus bergamia Risso and Poit) essential oil (BEO) were chosen to explore the effect on amelioration of exercise-induced fatigue. Our results demonstrated that SEO and LEO increased the swimming time by 276% and 46.5%, while BEO did not. Moreover, the three CEOs exerted varying effects on mitigating exercise-induced fatigue via inhibiting oxidative stress, protecting muscle injury, and promoting glucose-dependent energy supply. Accordingly, BEO showed the best efficiency. Moreover, the GC-MS and Pearson correlation analysis of BEO showed that the contents of the major components, such as (±)-limonene (32.9%), linalyl butyrate (17.8%), and linalool (7.7%), were significantly positively correlated with relieving exercise-induced fatigue.

Comparative Evaluation on the Bioaccessibility of Citrus Fruit Carotenoids In Vitro Based on Different Intake Patterns.

The intake pattern has a great impact on the bioaccessibility of carotenoids from citrus fruit. Here, we compared the bioaccessibility of carotenoids from fresh citrus fruit (FC), fresh citrus juice (FCJ), and not-from-concentrate citrus juice (NCJ) and analyzed the influencing factors. The results demonstrated that particle size, viscosity, and some active components of the samples during digestion are potential factors affecting the bioaccessibility of carotenoids. The total carotenoid bioaccessibility of NCJ (31.45 ± 2.58%) was significantly higher than that of FC (8.11 ± 0.43%) and FCJ (12.43 ± 0.49%). This work demonstrates that NCJ is an appropriate intake pattern to improve the bioaccessibility of carotenoids from citrus fruit. The findings also suggest that adjustment of food intake patterns is an effective way to improve the digestion and absorption of nutrients.

Understanding the Adhesion Mechanism of Hydroxyapatite-Binding Peptide.

Understanding the interactions between the protein collagen and hydroxyapatite is of high importance for understanding biomineralization and bone formation. Here, we undertook a reductionist approach and studied the interactions between a short peptide and hydroxyapatite. The peptide was selected from a phage-display library for its high affinity to hydroxyapatite. To study its interactions with hydroxyapatite, we performed an alanine scan to determine the contribution of each residue. The interactions of the different peptide derivatives were studied using a quartz crystal microbalance with dissipation monitoring and with single-molecule force spectroscopy by atomic force microscopy. Our results suggest that the peptide binds via electrostatic interactions between cationic moieties of the peptide and the negatively charged groups on the crystal surface. Furthermore, our findings show that cationic residues have a crucial role in binding. Using molecular dynamics simulations, we show that the peptide structure is a contributing factor to the adhesion mechanism. These results suggest that even small conformational changes can have a significant effect on peptide adhesion. We suggest that a bent structure of the peptide allows it to strongly bind hydroxyapatite. The results presented in this study improve our understanding of peptide adhesion to hydroxyapatite. On top of physical interactions between the peptide and the surface, peptide structure contributes to adhesion. Unveiling these processes contributes to our understanding of more complex biological systems. Furthermore, it may help in the design of de novo peptides to be used as functional groups for modifying the surface of hydroxyapatite.

Liuwei Dihuangtang Alleviates Myelin Injury in vHIP and Depression-like Behavior of Diabetes Mellitus Combined with Comorbid Depression Rats via AMPK/Akt/GSK3β/Nrf2 Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Liuwei Dihuangtang on depression-like behavior of diabetes mellitus combined with comorbid depression （DD） rats， so as to explore its action mechanism. MethodFifty male SD rats of SPF grade were fed with high fat diet and injected with low-dose streptozotocin （STZ） via tail vein for inducing diabetes. Afterwards， the diabetic rats were exposed to chronic unpredictable mild stress （CUMS） for 28 d. The successfully modeled DD rats were randomly divided into five groups： model group， fluoxetine （10 mg·kg-1·d-1） group， and low-， medium-， and high-dose （3.375， 6.75， 13.5 g·kg-1·d-1） Liuwei Dihuangtang groups， with 10 in each group. Another 10 rats were classified into the normal control group and treated with intragastric administration of normal saline for four weeks. The tail suspension test and open field test were conducted to evaluate the depressive-like phenotype of rats. The contents of malondialdehyde （MDA）， reactive oxygen species （ROS）， 8-hydroxy-2 deoxyguanosine （8-OHdG）， superoxide dismutase （SOD）， and glutathione （GSH） in ventral hippocampus （vHIP） were measured by enzyme-linked immunosorbent assay （ELISA）， and the myelin basic protein （MBP） expression in vHIP by immunofluorescence assay. The expression levels of MBP， myelin protein lipoprotein （PLP）， myelin oligodendrocyte glycoprotein （MOG）， phosphorylated adenosine 5'-monophosphate-activated protein kinase （p-AMPK）/AMPK， phosphorylated protein kinase B （p-Akt）/Akt， phosphorylated glycogen synthase kinase 3β （p-GSK3β）/GSK3β， and nuclear factor erythroid-2 related factor 2（Nrf2） were determined by Western blotting. ResultCompared with the normal control group， the model group exhibited significantly prolonged immobility in the tail suspension test （P<0.01） and shortened residence at the central area in the open field test （P<0.01）. The immobility time in the medium- and high-dose Liuwei Dihuangtang groups declined to different degrees as compared with that of the model group （P<0.01）， while the residence time at the central area was significantly increased （P<0.05， P<0.01）. Compared with the normal control group， the model group displayed down-regulated MBP， PLP， and MOG protein expression in vHIP （P<0.01）. Compared with the model group， Liuwei Dihuangtang at the low dose up-regulated the expression of MBP （P<0.05）， but did not obviously affect the expression of MOG and PLP. Fluoxetine and Liuwei Dihuangtang at the medium and high doses up-regulated the expression of MBP， PLP， and MOG （P<0.05， P<0.01）. Comparison with the normal control group revealed that the MBP fluorescence intensity in vHIP of the model group was significantly weakened （P<0.01）. After the intervention， the MBP fluorescence intensities in the medium- and high-dose Liuwei Dihuangtang groups and fluoxetine group were enhanced in contrast to that of the model group （P<0.05， P<0.01）. SOD and GSH in the model group were lower than those in the normal control group （P<0.01）， whereas the MDA， ROS， and 8-OHdG expression levels were higher （P<0.01）. Compared with the model group， Liuwei Dihuangtang at the medium and high doses and fluoxetine all down-regulated the expression levels of MDA， ROS， and 8-OHdG （P<0.05，P<0.01）， while up-regulated SOD and GSH expression （P<0.05，P<0.01）. The expression levels of p-AMPK， p-Akt， and Nrf2 in the model group were down-regulated as compared with those in the control group， and the expression of p-GSK3β was up-regulated （P <0.01）. As demonstrated by comparison with the model group， the protein expression of p-AMPK in the low-dose Liuwei Dihuangtang group was elevated （P<0.05）， while p-Akt and Nrf2 were slightly increased， exhibiting no statistical significant difference. However， the protein expression levels of p-AMPK， p-Akt， and Nrf2 in the medium- and high-dose Liuwei Dihuangtang groups and fluoxetine group were up-regulated， while those of p-GSK3β were down-regulated （P<0.05，P<0.01）. ConclusionLiuwei Dihuangtang improves the depressive-like behavior of DD rats， which may be related to its activation of the AMPK/Akt/GSK3β/NRF2 pathway， regulation of the oxidative stress in vHIP， and enhancement of myelin repair.

Modified Shuyuwan Mediated Mitochondrial Autophagy Improve APP/PS1 Mice Oxidative Stress Injury and Ability of Learning and Memory / 中国实验方剂学杂志

ObjectiveTo explore the effects and related mechanisms of modified Shuyuwan on the decline of learning and memory in Alzheimer's disease （AD） mice. MethodForty 5-month-old SPF APP/PS1 mice were randomly divided into model group， Donepezil group， modified Shuyuwan group， modified Shuyuwan+ chloroquine （CQ） group， 10 mice in each group， the same background wild type C57BL/6J ten mice were set as the normal group. Among them， the modified Shuyuwan group was given the modified Shuyuwan decoction （10 g·kg-1）， the Donepezil group was given the Donepezil hydrochloride solution （0.45 mg·kg-1）， the modified Shuyuwan + CQ group was CQ （10 mg·kg-1） was injected intraperitoneally on the basis of the modified Shuyuwan group， and the normal group and the model group were given the same amount of normal saline intragastrically， once a day， for a total of 35 days. After the administration， Morris water maze experiment and new object recognition experiment to detect the spatial memory ability of mice. TdT-mediated dUTP Nick-End Labeling（TUNEL） staining to detect the apoptosis level of mouse hippocampal CA1 neurons， biochemical detection of reactive oxygen species （ROS） and superoxide in mouse hippocampal neurons dismutase （SOD） levels. transmission electron microscopy to observe the ultrastructure of neuronal mitochondria in the CA1 region of mouse hippocampus. Western blot to detect mouse hippocampal mitochondrial autophagy adaptor protein （p62） and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）， PTEN-induced kinase 1 （PINK1）， E3 Ubiquitin Ligase（Parkin）protein expression level. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） detection of mouse hippocampal mitochondrial forkhead transcription factor O1 （FoxO1）， PINK1， Parkin mRNA expression level. ResultCompared with the normal group， the escape latency of the model group mice increased significantly， the number of crossing platforms and the retention time in the target quadrant decreased significantly， the relative resolution index decreased significantly， and the ability to recognize new objects was weakened （P<0.05）， neurons in the hippocampus CA1 area decreased. The number of dead cells increased significantly （P<0.05）， the level of ROS was significantly increased （P<0.01）， and the level of SOD was significantly decreased （P<0.01）， the morphology of hippocampal mitochondria was severely damaged， the expression of p62 and LC3Ⅱ proteins increased （P<0.01）， Parkin protein expression decreased （P<0.05）， and PINK1 protein expression increased （P<0.05）， FoxO1， PINK1， Parkin mRNA expressions all decreased （P<0.05）. Compared with the model group， the mice's escape latency was significantly shortened after the intervention of the modified Shuyuwan， the number of crossing platforms and the proportion of residence time in the target quadrant increased significantly， the relative resolution index increased significantly， and the ability to identify new objects was enhanced （P<0.05）. Apoptotic cells were significantly reduced （P<0.05）. ROS levels were significantly reduced （P<0.01）， and SOD levels were significantly increased （P<0.05， P<0.01）， mitochondrial morphology and various structures were significantly improved， p62， LC3Ⅱ protein expression decrease （P<0.05，P<0.01）， PINK1， Parkin protein expression increased （P<0.01）. FoxO1， PINK1， Parkin mRNA expression increased （P<0.05， P<0.01）. Compared with the modified Shuyuwan group， the evasion latency of mice in the modified Shuyuwan + CQ group increased significantly， the number of crossing platforms and the proportion of residence time in the target quadrant decreased， and the relative resolution index decreased （P<0.05）， the SOD level was significantly reduced （P<0.01）. The damage of mitochondrial morphology and structure increased again， the expression of p62 and LC3Ⅱ protein increased （P<0.05， P<0.01）， and the expression of PINK1 and Parkin decreased significantly（P<0.05， P<0.01）. FoxO1， PINK1， and Parkin mRNA expression was significantly reduced （P<0.05， P<0.01）. ConclusionModified Shuyuwan can effectively improve the oxidative stress damage and learning and memory ability of AD mice. The mechanism may be related to up-regulating the expression of FoxO1， PINK1， and Parkin factors， promoting mitochondrial autophagy， reducing oxidative stress， and protecting neuronal damage.

Liuwei Dihuangtang Alleviates Myelin Injury in Anterior Cingulate Cortex and Depression-like Behaviors of Rats with Diabetes Mellitus and Depression via Promoting Autophagy and Regulating Microglial Phenotype / 中国实验方剂学杂志

ObjectiveTo observe the effect of Liuwei Dihuangtang （LWDHT） on depression-like behaviors of rats with diabetes mellitus and depression （DD） and explore its mechanism. MethodThe diabetes mellitus （DM） model was induced by the high-fat diet and tail vein injection of low-dose streptozotocin （STZ） in 50 male Sprague-Dawley rats of SPF grade. Then the DD model was induced by chronic unpredictable mild stress （CUMS） for 28 days in DM rats. Fifty DD rats were randomly divided into model group， fluoxetine group （10 mg·kg-1·d-1）， and low-， medium-， and high-dose LWDHT groups （3.375， 6.75， 13.5 g·kg-1·d-1）， with 10 rats in each group. Another 10 healthy rats were assigned into a control group and received normal saline by gavage. After four weeks of drug intervention， the forced swimming assay was carried out to assess the depression-like behaviors of rats. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in the anterior cingulate cortex （ACC） were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence was used to detect the expression of myelin basic protein （MBP） in ACC and the co-localization of ionized calcium-binding adapter molecule 1 （Iba1） with intracellular microtubule-associated protein 1 light chain 3 （LC3）. The protein expression levels of MBP， myelin proteolipid protein （PLP）， myelin oligodendrocyte glycoprotein （MOG）， Beclin-1， LC3， p62， and microglia （MG） phenotypic protein-related inducible nitric oxide synthase （iNOS）， and arginase 1 （Arg1） were detected by Western blot. ResultCompared with the control group， the model group showed shortened swimming time and prolonged immobility time （P<0.01）. Compared with the model group， the medium- and high-dose LWDHT groups showed reduced immobility time （P<0.05， P<0.01）. Compared with the control group， the model group showed decreased protein expression of MBP， PLP， and MOG in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated protein expression of MBP， PLP， and MOG （P<0.05， P<0.01）. Compared with the control group， the model group showed decreased MBP fluorescence intensity in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed increased MBP fluorescence intensity in the ACC region （P<0.05， P<0.01）. Compared with the control group， the model group showed increased expression of iNOS （P<0.01） and slightly increased Arg1 protein expression. Compared with the model group， the medium- and high-dose LWDHT groups and the fluoxetine group showed down-regulated iNOS expression and up-regulated Arg1 protein expression （P<0.05， P<0.01）， but there was no significant difference between the fluoxetine group and the medium-，high-dose LWDHT groups. Compared with the control group， the model group showed increased expression levels of proinflammatory factors IL-1β and TNF-α in the ACC region （P<0.01） and slightly increased expression levels of anti-inflammatory factors IL-4 and IL-10. Compared with the model group， the fluoxetine group， and the medium- and high-dose LWDHT groups showed down-regulated expression of IL-1β and TNF-α （P<0.05， P<0.01） and up-regulated expression of IL-4 and IL-10 （P<0.05， P<0.01）. Compared with the control group， the model group showed reduced expression levels of Beclin-1 and LC3Ⅱ （P<0.01） and increased expression level of p62 （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated Beclin-1 and LC3Ⅱ expression （P<0.01） and down-regulated p62 expression （P<0.01）. Compared with the control group， the model group showed decreased LC3+Iba1+ cells in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed increased LC3+Iba1+ cells （P<0.05， P<0.01）. ConclusionLWDHT can alleviate the depression-like behaviors in DD rats presumedly by promoting MG autophagy， regulating MG phenotypic changes， and increasing MG clearance of myelin sheath fragments. Meanwhile， MG phenotypic transformation also inhibits ACC inflammation in DD rats， improves the local microenvironment of oligodendrocyte proliferation and differentiation， and ultimately promotes the repair and remyelination of damaged myelin sheath.

Antiviral Activity of Peptide-Based Assemblies.

The COVID-19 pandemic highlighted the importance of developing surfaces and coatings with antiviral activity. Here, we present, for the first time, peptide-based assemblies that can kill viruses. The minimal inhibitory concentration (MIC) of the assemblies is in the range tens of micrograms per milliliter. This value is 2 orders of magnitude smaller than the MIC of metal nanoparticles. When applied on a surface, by drop casting, the peptide spherical assemblies adhere to the surface and form an antiviral coating against both RNA- and DNA-based viruses including coronavirus. Our results show that the coating reduced the number of T4 bacteriophages (DNA-based virus) by 3 log, compared with an untreated surface and 6 log, when compared with a stock solution. Importantly, we showed that this coating completely inactivated canine coronavirus (RNA-based virus). This peptide-based coating can be useful wherever sterile surfaces are needed to reduce the risk of viral transmission.

Antiviral Polymers Based on N-Halamine Polyurea.

N-halamines are a commonly applied class of antimicrobial agents used for a variety of applications relating to human health. Here, we present the modulation of the common polymers polyurea and polyguanidine with the N-halamine technology. The N-H bonds in either polymer were converted to N-Cl or N-Br bonds capable of releasing Cl+ or Br+ cations to aqueous media as antiviral agents. Controlled release of the oxidizing agents was monitored for a period of 4 weeks. Antiviral activity was evaluated against the T4 bacteriophage as well as against the highly stable plant virus belonging to the Tobamovirus genus, tomato brown rugose fruit virus. The incorporation of the N-halamine technology on commonly used polymers has effectively introduced antiviral functionality for a wide variety of potential applications.

Effect of Modified Shuyuwan on Neuroinflammation in APP/PS1 Dementia Mice Based on Nlrp3/ASC/Caspase-1 Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of modified Shuyuwan in amyloid precursor protein/ presenilin 1 （APP/PS1） dementia mice on cognitive and memory impairment and to explore its mechanism. Method:The 40 APP/PS1 mice were divided into model group （given Physiological saline）， low and high-dose modified Shuyuwan （14，64 g·kg^-1）group， and donepezil group （1 mg·kg^-1） and 10 wild mice were set as the blank control group （given Physiological saline）. All of the mice were administered intragastrically for 35 days. The memory and space exploration ability of mice was detected by Morris water maze， the morphology of mouse hippocampal neurons were observed by Nissl staining. The deposition of <italic>β </italic>amyloid 1-42（A<italic>β</italic>_1-42） in mouse hippocampus was detected by immunohistochemistry， and the expression of ionized calcium-binding adapter molecule 1（Iba1）， a marker of hippocampal microglia （MG） and Nitric oxide synthase（iNOS）， a marker of actived MG， were detected by immunofluorescence. The protein expression of NLR family pyrin domain containing 3（Nlrp3）， Apoptosis-associated speck-like protein containing a Caspase-recruitment domain （ASC）， cysteine protease-1（Caspase-1）and interleukin-1 beta （IL-1<italic>β</italic>） were detected by Western blot， and the expression of IL-1<italic>β</italic>， tumor necrosis factor-<italic>α</italic>（TNF-<italic>α</italic>）and interleukin-18 （IL-18） mRNA were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the blank control group， the memory and space exploration ability of the model group were significantly reduced （<italic>P</italic><0.05）， the number of hippocampal neurons decreased， the deposition of A<italic>β</italic>_1-42 increased， the markers of actived MG Iba1，iNOS increased， the protein expression of Nlrp3， ASC， Caspase-1， IL-1<italic>β</italic> increased significantly （<italic>P</italic><0.05）， and the mRNA expression of IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> increased significantly （<italic>P</italic><0.05）. Compared with model group， the Chinese medicine group can improve the APP/PS1 mice's space exploration ability and memory ability （<italic>P</italic><0.05）， increase the number of hippocampal neurons， reduce A<italic>β</italic>_1-42 deposition， reduce the activation of MG， and reduce the protein expression of Nlrp3， ASC， Caspase-1 and IL-1<italic>β</italic> （<italic>P</italic><0.05）， and reduced the expression of IL-1<italic>β</italic> mRNA （<italic>P</italic><0.05）. Conclusion:Modified Shuyuwan can reduce the expression of IL-1<italic>β</italic> and other inflammatory factors in the hippocampus of APP/PS1 mice by inhibiting the Nlrp3/ASC/Caspase-1 pathway， and relieve nerve inflammation and pathological injury of AD.

Xiaoyaosan Promotes Myelin Regeneration and Alleviates Depressive Symptoms in Vascular Dementia Mice with Depression via Promoting Microglia Polarization / 中国实验方剂学杂志

Objective:To investigate the effect of Xiaoyaosan on depressive behavioral phenotype in mice with vascular dementia （VaD） mice and its possible mechanism. Method:Sixty three-month-old male C57/BL6 mice were divided into the normal control group， model group， positive control group， as well as low-， medium-， and high-dose Xiaoyaosan groups. Mice in all groups except for the normal control group underwent bilateral carotid artery stenosis. Two weeks later， they were subjected to chronic restraint stress， 6 h per day， for inducing VaD complicated with depression. Mice in the low-， medium-， and high-dose Xiaoyaosan groups were treatment with intragastric administration of Xiaoyaosan decoction （5， 10， 20 g·kg^-1）， the ones in the positive control group with fluoxetine （10 mg·kg^-1）， and those in the normal control group and model group with an equal volume of normal saline for four weeks， during which the restraint stress was maintained. The depressive behavioral phenotype of mice was observed in sugar water preference test and tail suspension test. The fluorescence expression of myelin basic protein （MBP） in ventral hippocampus （vHIP） was detected by fluorescence immunoassay. The ultrastructure of myelin sheath in vHIP was observed by transmission electron microscopy. The protein expression levels of MBP， myelin oligodendrocyte glycoprotein （MOG）， myelin-associated glycoprotein （MAG）， triggering receptor expressed on myeloid cells-2 （TREM2）， inducible nitric oxide synthase （iNOS）， arginase 1 （Arg1）， interleukin-I<italic>β</italic> （IL-1<italic>β</italic>）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） were assayed by Western blot. Result:As revealed by behavioral test， compared with the normal control group， the model group exhibited prolonged immobility time and decreased percentage of sugar water preference （<italic>P</italic><0.01）. Compared with the model group， Xiaoyaosan significantly shortened the immobility time of mice （<italic>P</italic><0.05） and increased the percentage of sugar water preference （<italic>P</italic><0.01）. Western blot results showed that the protein expression levels of MBP， MOG， and MAG in vHIP of the model group were remarkably decreased as compared with those of the normal control group （<italic>P</italic><0.01）. The protein expression levels of MBP， MOG， and MAG in vHIP of the low-dose Xiaoyaosan group were increased in contrast to those in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the protein expression of iNOS was decreased （<italic>P</italic><0.01）. The protein expression levels of MBP， MOG， MAG， TREM2， Arg1， IL-4， and IL-10 in the medium- and high-dose Xiaoyaosan groups were up-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）， whereas those of iNOS， IL-1<italic>β</italic>， and TNF-<italic>α</italic> were down-regulated （<italic>P</italic><0.01）. The immunofluorescence findings demonstrated that the mean fluorescence intensity of MBP in the model group declined in comparison with that in the normal control group （<italic>P</italic><0.01）， while the mean fluorescence intensities of MBP in the low-， medium-， and high-dose Xiaoyaosan groups were enhanced to different degrees （<italic>P</italic><0.01）. It was observed under the transmission electron microscope that the myelin structure of the model group was loosened and the dense layer was separated and irregularly arranged. Xiaoyaosan improved the structural integrity of myelin sheath and the looseness of lamellar structure. Conclusion:Xiaoyaosan ameliorates the depressive behavioral phenotype of VaD mice， which may be related to the up-regulation of TREM2， the induction of M2 polarization of microglia cells， the enhancement of their anti-inflammatory and phagocytic abilities， and the promotion of damaged myelin sheath regeneration.

Coassembly of C13-Dipeptides: Gelations from Solutions and Precipitations.

C13-dipeptides that did not gel on their own were found to form hydrogels when combined with mixtures (coassembly). At pH = 4.6, by mixing negatively charged C13-WD (C13-WD2- and/or C13-WD-) with C13-KW or C13-YK, where the side chain of K carried positive charge, two composite hydrogels with different mechanical properties were formed. The gels exhibited various fiber structures that would account for their individual functionalities. According to molecular dynamics computer simulations, the composite systems formed spherical micelles through hydrophobic interactions that further aggregate to form gels through electrostatic interactions. The electrostatic repulsions between C13-WD molecules were interfered by insertions of C13-KW or C13-YK molecules, which result in gel formation in the composite systems. The results of computer simulations well explained the experimental observations, which provided new insights into the design and selection strategies for peptide gelators.

A Comprehensive Study on Self-Assembly and Gelation of C13-Dipeptides-From Design Strategies to Functionalities.

Computational and experimental methods were applied to investigate the self-assembly and gelation of C13-dipeptides. A modified aggregation propensity (APS) was introduced to correlate the effects of side chains of amino acids on the tendency to aggregate. From the experimental results, the ranges of 0.156 < APS < 0.250 seemed to be a proper region for the C13-dipeptides to form hydrogels, while other molecules with higher or lower APS were insoluble or dissociated. As observed from molecular dynamics simulations, the C13-dipeptides first formed small aggregates through hydrophobic interactions and then rearranged through electrostatic attractions and hydrogen bonds for self-assembly. The C13-dipeptides tended to be antiparallel packed, as shown by hydrogen bonding analyses. Experimental observations and analyses on the structures of C13-dipeptide hydrogels matched the computational conclusions very well. From the five selected gelators, i.e., C13-GW, C13-VY, and C13-WT, strong π-π stacking was observed. For C13-WS, strong hydrogen bonding was found, and in C13-WY, both strong π-π interactions and hydrogen bonds were found. It takes around 90 min or longer for C13-dipeptides to form hydrogels, and those formed by C13-WY and C13-WS had weak water holding capacities, which might be due to strong intermolecular hydrogen bonding. From rheological studies, the C13-dipeptides formed strong chemical gels that were stabilized by strong interactions between the molecular aggregates. These gelators exhibit the potentials to be environmentally friendly substitutes for the common functionalized peptide gelators.

Effects of different ionic strengths on the physicochemical properties of plant and animal proteins-stabilized emulsions fabricated using ultrasound emulsification.

In this study, high intensity ultrasound (HIU) was used to produce food protein stabilized emulsions under different ionic strengths (0, 25, 50, 100, 200 and 300 mM NaCl). Five plant and animal food proteins, whey protein isolate (WPI), soy protein isolate (SPI), bovine gelatin, peanut protein isolate (PPI) and corn zein were selected as protein emulsifiers. PPI and zein could not form emulsions using ultrasound emulsification at all ionic strengths (from 0 to 300 mM NaCl). However, ultrasound could induce stable emulsions using SPI, WPI and gelatin as emulsifiers. Moreover, different ionic strengths and protein types influenced the physicochemical properties of HIU induced emulsions obviously. It was found that the droplet sizes of gelatin emulsions were lower than those of SPI and WPI emulsions at salt concentrations of 300 mM NaCl. Furthermore, gelatin emulsions had better stability against environmental stresses (salt and temperature) than that of SPI and WPI emulsions. Moreover, the adsorbed protein (%) at the oil/water interface of SPI emulsions was higher than those of WPI and gelatin emulsions. However, the adsorbed protein amount of all proteins stabilized emulsions increased significantly after salt addition. The absolute ζ-potential values decreased with the increase of salt concentrations. The microrheology results indicated that the SPI emulsions formed a gel-like structure at high salt concentrations (>50 mM NaCl) as SPI emulsions exhibited higher elasticity than WPI and gelatin emulsions. In conclusion, the ultrasound as a green emulsification technique could be used to fabricate emulsions stabilized by plant and animal proteins.