Mal Groups Research Articles

Ultrasound‐activated in situ click chemistry to trigger autophagosome tracking for enhanced autophagy blockade and synergistic cancer therapy

AbstractThe blockade of cytoprotective autophagy has been demonstrated to effectively enhance the efficacy of sonodynamic therapy (SDT). However, the limited recognition of antiautophagy agents for autophagosomes impedes the clinical application of autophagy inhibition. To efficiently deliver hydroxychloroquine (HCQ), an autophagy inhibitor, to autophagosomes, we utilized a strategy based on in situ click chemistry between sulfhydryl (‐SH) and maleimide (Mal) groups to trigger autophagosomes tracking and suppress tumor growth synergistically. A cascade nanoreactor was synthesized by encapsulating Mal‐modified HCQ (MHCQ) into a manganese porphyrin‐based metal‐organic framework with sonosensitizer properties, followed by poly(ethylene glycol)ylated liposomal membrane coating. After ultrasound irradiation, SDT‐induced apoptotic cells released damaged proteins with free ‐SH groups, which MHCQ rapidly captured in situ via a Mal‐thiol click reaction. When autophagosomes actively wrapped damaged proteins for detoxification, they simultaneously internalized HCQ anchored on proteins. In this scenario, antiautophagy drugs could actively track intracellular autophagosomes instead of undergoing passive diffusion in the cytosol. The interaction between HCQ and autophagic vesicles was greatly enhanced, which strengthened the blocking efficiency of autophagy and resulted in complete cell death. Overall, this study with smart design provides a promising strategy for improving intracellular targeted delivery to autophagosomes, thereby enhancing antitumor therapy.

Dual-targeted nano-encapsulation of neonatal porcine islet-like cell clusters with triiodothyronine-loaded bifunctional polymersomes

There is growing evidence that neonatal porcine islet-like cell clusters (NPCCs) isolated from piglets can be used to treat type 1 diabetes in humans. However, graft rejection is a common complication in humans owing to the prevalence of xenoantigens in porcine. Therefore, researchers have investigated various islet encapsulation techniques that could protect against these antigens. To this end, this study presents a robust nano-encapsulation method based on bifunctional polymersomes (PSomes), in which N-hydroxysuccinimide (NHS) and maleimide (Mal) groups conjugated to the PSomes terminal interact with the amine and thiol groups on the surface of NPCCs to induce dual targeting via two covalent bonds. The findings indicate that the ratio of NHS to Mal on PSomes is optimal for dual targeting. Moreover, triiodothyronine (T3) is known to promotes pancreatic islet maturation and differentiation of endocrine cells into beta cells. T3 encapsulated in PSomes is shown to increase the glucose sensitivity of NPCCs and enhance insulin secretion from NPCCs. Furthermore, improvements in the nano-encapsulation efficiency and insulin-secreting capability of NPCCs through dual targeting via dual-Psomes are demonstrated. In conclusion, the proposed nano-encapsulation technique could pave the way for significant advances in islet nano-encapsulation and the imprevement of NPCC immaturity via T3 release.

Hsp90 participates in the necroptosis of mouse neural cells induced by aluminum through the RIP1/RIP3/MLKL pathway

Objective: To investigate whether heat shock protein 90 (HSP90) participates in the necroptosis of C57BL/6 mouse neurons and spatial memory impairment induced by Aluminum maltol [Al (mal) (3)] through RIP1/RIP3/MLKL pathway. Methods: In March 2022, Thirty-two C57 mice were randomly divided into control group, Low dose group, a medium dose group, and a high-dose group, with 8 mice in each group, and injected intraperitoneally with physiological saline, 20, 40, and 80, respectivelyμmol/kgAl (mal) (3) was administered, it was injected 5 days a week and discontinued 2 days for 60 days. Morris water maze test was used to test the spatial learning and memory ability of mice. Nissl staining was used to observe the pathological changes of brain tissue. The protein expression levels of RIP1, RIP3, MLKL and HSP90 in hippocampus were determined by Western blotting. Results: In the water maze experiment, compared with the control group, the number of mice crossing the platform decreased in each dose group, the difference was statistically significant (H=9.50, P=0.023), and the number of mice crossing the platform was statistically significant among each dose group (P <0.05). Compared with the control group, the number of hippocampal nerve cells in each dose group decreased, the arrangement was disordered, and the Nissellite bodies decreased. Western blotting results showed that compared with the control group, the expression level of RIP1 protein in the hippocampus of mice in high-dose group was higher, and the difference was statistically significant (P <0.05). The expression levels of RIP3, MLKL and HSP90 in hippocampal tissue of mice in medium and high dose groups were increased, and the differences were statistically significant (P<0.05). After siRNA intervention decreased the expression of HSP90 protein, the expressions of HSP90, RIP1, RIP3 and MLKL in Al (mal) (3) groups were increased, and the differences were statistically significant (P<0.05) . Conclusion: Through RIP1/RIP3/MLKL pathway, HSP90 is involved in neuronal programmed necrosis and spatial memory impairment induced by maltol aluminum in C57 mice.

Cascade enzymatic preparation of carboxymethyl chitosan-based multifunctional hydrogels for promoting cutaneous wound healing

Designing wound dressings with inherent multifunctional therapeutic effects is desirable for clinical applications. Herein, a series of multifunctional carboxymethyl chitosan (CMCS)-based hydrogels were fabricated by the facile urate oxidase (UOX)-horseradish peroxidase (HRP) cascade enzymatic crosslinking system. For the first time, the cascade enzymatic crosslinking system was not only used for preparing hydrogel wound dressings but also for accelerating wound healing due to the activity retention of the self-compartmental enzymes. A CMCS derivative (HCMCS-mF) synthesized by successively grafting 4-hydroxybenzaldehyde (H) and 5-methylfurfural (mF) on CMCS and a quaternary ammonium crosslinker (QMal) with terminal grafting maleimide (Mal) groups were combined with enzymatic system for the facile preparation of hydrogels. The mild Diels-Alder (DA) crosslinking reaction between mF and Mal groups constructed the first network of hydrogels. The cascade UOX-HRP system mediated the oxidative crosslinking of phenols thus forming the second gel network. Self-entrapped UOX maintained its enzymatic activity and could continuously catalyze the oxidation of uric acid, generating therapeutic allantoin. These porous, degradable, mechanically stable hydrogels with excellent antioxidant performance and enhanced antibacterial capacity could effectively accelerate skin wound repair by simultaneously reducing oxidative stress, relieving inflammation, promoting collagen deposition and upregulating the expression level of CD31.

Exploiting maleimide-functionalized hyaluronan hydrogels to test cellular responses to physical and biochemical stimuli

Current in vitro three-dimensional (3D) models of liver tissue have been limited by the inability to study the effects of specific extracellular matrix (ECM) components on cell phenotypes. This is in part due to limitations in the availability of chemical modifications appropriate for this purpose. For example, hyaluronic acid (HA), which is a natural ECM component within the liver, lacks key ECM motifs (e.g. arginine–glycine–aspartic acid (RGD) peptides) that support cell adhesion. However, the addition of maleimide (Mal) groups to HA could facilitate the conjugation of ECM biomimetic peptides with thiol-containing end groups. In this study, we characterized a new crosslinkable hydrogel (i.e. HA-Mal) that yielded a simplified ECM-mimicking microenvironment supportive of 3D liver cell culture. We then performed a series of experiments to assess the impact of physical and biochemical signaling in the form of RGD peptide incorporation and transforming growth factor ß (TGF-ß) supplementation, respectively, on hepatic functionality. Hepatic stellate cells (i.e. LX-2) exhibited increased cell–matrix interactions in the form of cell spreading and elongation within HA-Mal matrices containing RGD peptides, enabling physical adhesions, whereas hepatocyte-like cells (HepG2) had reduced albumin and urea production. We further exposed the encapsulated cells to soluble TGF-ß to elicit a fibrosis-like state. In the presence of TGF-ß biochemical signals, LX-2 cells became activated and HepG2 functionality significantly decreased in both RGD-containing and RGD-free hydrogels. Altogether, in this study we have developed a hydrogel biomaterial platform that allows for discrete manipulation of specific ECM motifs within the hydrogel to better understand the roles of cell–matrix interactions on cell phenotype and overall liver functionality.

Therapeutic Efficacy and the Impact of the "Dose" Effect of Acupuncture to Treat Sciatica: A Randomized Controlled Pilot Study.

PurposeTo investigate the required sample size for and feasibility of a full-scale randomized controlled trial examining the impact of the “dose” effect of acupuncture in treating sciatica.Patients and methodsFifty-seven patients with sciatica, aged 35–70 years, were recruited and screened. Thirty-one participants were randomly assigned to receive “low-dose” manual acupuncture (MAL) (n= 15) or “high-dose” manual acupuncture (MAH) (n=16). The acupuncture treatment was administered twice weekly for 4 weeks. The primary outcome was the visual analog scale (VAS) score at baseline and after 4 weeks of acupuncture treatment. Secondary outcomes included the Roland Disability Questionnaire for Sciatica (RDQS), the Sciatica Bothersomeness Index (SBI), and the World Health Organization Quality of Life in the Brief Edition (WHOQOL-BREF) scores at baseline and after 4 weeks of acupuncture treatment.ResultsThirty patients completed the study. For all patients, acupuncture achieved significant improvement in the VAS (5.48±2.0, p<0.001), RDQS (3.18±2.83, p=0.004), and SBI (2.85±3.23, p=0.008) scores, but not in the WHOQOL-BREF scores. In the between-group analysis, the assessed scales showed no significant differences between the MAL and MAH groups. However, based on the level of chronicity, the MAH group demonstrated greater improvement in the outcomes and a significant benefit in the physical subscale of the WHOQOL-BREF (p<0.05).ConclusionResults of this pilot study indicate that acupuncture is safe and may effectively relieve symptoms and disability in patients with non-acute sciatica. MAL was as effective as MAH in treating sciatica. A subsequent trial with a larger sample size (estimated at n=96) is required to confirm whether patients with a high level of chronicity would benefit from MAH treatment.Trial registrationNCT03489681.

The effects of royal jelly on oxidative stress and toxicity in tissues induced by malathion, an organophosphate insecticide

Royal jelly is a bee product frequently used in pharmaceutical, food and cosmetic industries due to its biological activities. The present study aimed to determine the effects of royal jelly on malathion-induced toxicity and biochemical changes. The rats that were used as experimental animals in the study were divided into 6 groups. Control group rats were administered nothing, while carrier chemicals (1% DMSO) were administered to sham group rats. Malathion group (MAL) rats were injected with 0.8 g/kg malathion in DMSO subcutaneously. Saline solution that included 100 mg/kg royal jelly was administered with gavage to the rats in the royal jelly group (RJ). 100 mg/kg royal jelly was administered to RJ+MAL group rats via gavage 1 hour before the injection of 0.8 g/kg malathion. 100 mg/kg royal jelly was administered to MAL+RJ group rats via gavage 1 hour after the injection of 0.8 g/kg malathion. After the experimental process (24 hours), blood samples were taken from the rats in each group under anesthesia (ketamine+xylazine). MDA, NO, GSH, GPx (glutathione peroxidase), CAT, SOD and AChE activities were determined in blood, liver, kidney and brain tissues. It was found that erythrocyte, liver, kidney and brain MDA (malondialdehyde) concentrations in MAL groups were statistically significantly higher when compared to the other groups (p&lt;0.05). It was observed that GSH (glutathione) concentrations increased in the brain, while they decreased in erythrocyte, liver and kidney in the MAL group when compared to the control and sham groups. CAT (catalase) concentration significantly decreased in erythrocyte, liver, kidney and brain tissues in the MAL group when compared to the control and sham groups (p&lt;0.05). SOD (superoxide dismutase) concentration in the MAL group decreased significantly (p&lt;0.05) when compared to other groups, while SOD concentration increased significantly in the therapy and prevention groups (p&lt;0.05) when compared to the others. It was found that serum acetylcholinesterase (AChE) concentration was significantly lower in the MAL group when compared to sham and control groups (p&lt;0.05). Thus, it was concluded that malathion led to lipid peroxidation and oxidative stress in MDA and NO (nitric oxide) levels and toxicity in AChE activities. It was also determined that royal jelly could be effective against oxidative damage and toxicity. The findings suggested that the antioxidant effect of royal jelly could support the treatment of malathion, which is one of the insecticides that contain organophosphate and could lead to oxidative stress. It is considered that the prophylactic characteristics of royal jelly was more effective on malathion toxicity when compared to therapatic properties.

A Pilot Study of Neurocognitive Function and Brain Structures in Adolescents With Alcohol Use Disorders: Does Maltreatment History Matter?

Neurocognitive and brain structural differences are associated with adolescent onset alcohol use disorders (AUDs). Maltreatment histories may contribute to current results. To examine these issues, healthy adolescents (n = 31), adolescents without maltreatment and AUD (AUD - MAL, n = 28), and adolescents with AUDs with maltreatment (AUD + MAL, n = 17) underwent comprehensive neurocognitive assessments and MRI structural scans. Controls performed significantly better than the two AUD groups in math and language. The AUD + MAL group performed significantly lower in sustained attention compared to the AUD - MAL and control groups and lower in reading compared to controls. The AUD + MAL group had larger left pars triangularis, a region of the inferior frontal gyrus, compared to the AUD-MAL and control groups, and smaller anterior corpus callosum volumes versus the AUD - MAL group. There were no group differences in other prefrontal cortex, amygdala, hippocampus, and parahippocampal volumes. The AUD + MAL group showed an inverse correlation between hippocampal volumes and age. AUD variables were associated with lower performance in fine-motor and executive function. Cannabis use variables were associated with lower performance in fine-motor, language, visual-spatial, memory, and executive function. Parahippocampal volumes positively correlated with abstinence. The preliminary results suggest adolescent AUD studies should consider examinations of maltreatment history, comorbid substance use disorders, and recovery during abstinence in their analyses.

Control of Probe Density at DNA Biosensor Surfaces Using Poly(l-lysine) with Appended Reactive Groups.

Biosensors and materials for biomedical applications generally require chemical functionalization to bestow their surfaces with desired properties, such as specific molecular recognition and antifouling properties. The use of modified poly(l-lysine) (PLL) polymers with appended oligo(ethylene glycol) (OEG) and thiol-reactive maleimide (Mal) moieties (PLL-OEG-Mal) offers control over the presentation of functional groups. These reactive groups can readily be conjugated to, for example, probes for DNA detection. Here we demonstrate the reliable conjugation of thiol-functionalized peptide nucleic acid (PNA) probes onto predeposited layers of PLL-OEG-Mal and the control over their surface density in the preceding synthetic step of the PLL modification with Mal groups. By monitoring the quartz crystal microbalance (QCM) frequency shifts of the binding of complementary DNA versus the density of Mal moieties grafted to the PLL, a linear relationship between probe density and PLL grafting density was found. Cyclic voltammetry experiments using Methylene Blue-functionalized DNA were performed to establish the absolute probe density values at the biosensor surfaces. These data provided a density of 1.2 × 1012 probes per cm2 per % of grafted Mal, thus confirming the validity of the density control in the synthetic PLL modification step without the need of further surface characterization.

Friday, September 28, 2018 10:30 AM–12:00 PM abstracts: deformity: technical factors: 172. Is achieving optimal spinopelvic parameters necessary to obtain substantial clinical benefit? Analysis of patients who underwent circumferential mis or hybrid surgery with open posterior instrumentation

BACKGROUND CONTEXT It has been proposed that achieving optimal spinopelvic alignment is needed to attain significant clinical improvement. PURPOSE The purpose of this study was to determine whether obtaining optimal spinopelvic alignment was necessary to achieve a minimal clinically important difference (MCID) or substantial clinical benefit (SCB). STUDY DESIGN/SETTING Multicenter retrospective review. PATIENT SAMPLE A total of 153 patients who underwent less invasive surgery for adult spinal deformity (ASD). OUTCOME MEASURES Oswestry Disability Index. METHODS Inclusion criteria were age ≥18 years, and one of the following: coronal Cobb>20°, SVA>5cm, PT>20°, PI-LL>10°. Patients were treated with circumferential MIS or hybrid surgery and had 2-year minimum follow-up. Based on optimal spinopelvic parameters (PI-LL±10°, PT RESULTS There were 74 AL and 149 MAL patients. Age and BMI were similar between groups. Although baseline SVA was similar, PI-LL (9.9° vs. 17.7°, p=0.002) and PT (19° vs. 24.7°, p=0.001) significantly differed between AL and MAL groups, respectively. As expected postoperatively, the AL and MAL groups differed significantly in PI-LL (−0.9° vs. 13.1°, p 0.05) or SCB (40.5% vs. 46.3%, p>0.05), respectively. On multivariate analysis controlling for surgical and preop demographic differences, achieving optimal spinopelvic parameters was not associated with achieving MCID (OR 0.645, 0.31–1.33, 95%CI) or SCB (OR 0.644, 0.31–1.35, 95%CI) ODI. CONCLUSIONS Achieving optimal spinopelvic parameters does not appear to be a predictor for achieving MCID or SCB. Since spinopelvic parameters are correlated with clinical outcomes, our findings suggest that the presently accepted optimal spinopelvic parameters may require modification.

Qualitative Analysis of Modified Hand Test

Qualitative analysis of modified Hand Test was carried out on 500 participants further bifurcated into 350 normal, 50 maladjusted, 50 neurotic and 50 psychotic participants. Their ages ranged from 11 years to 90 years with mean age of 34.44 SD (17.34). The qualitative analysis based up on seventeen categories which includes ambivalent, automatic phrase, cylindrical, denial, emotion, gross, hiding, immature, impotent, inanimate, movement, oral, and perplexity, sensual, sexual and original. Original Purposive sampling technique was used. Modified Hand test with four new adapted stimulus was administered in accordance with described instructions by its author. Testing the limit procedure was applied only for psychotic group. Post-test inquiry was held to clarify certain responses. The results of the study depicted interesting features which differentiates four groups. E.g. normal group did not produce any sexual, hiding, repetition responses. More number of repetitive responses were found in mal adjective and neurotic groups. Certain new areas were also explored like introjections produced by psychotic group. Need for altruism by doctors sub group of normal population. Direction by teachers. Interesting results are expected with other different sample and are likely to provide insight in order to understand human behavior in tradition of idiosyncratic approach.

Effects of antiepileptic drugs on the serum folate and vitamin B12 in various epileptic patients.

Epilepsy is a common neurodegenerative disease with an increasing morbidity. Clinical treatment of epilepsy includes symptomatic treatment, etiological treatment, surgery and prevention. The aim of the present study was to determine the effects of antiepileptic drugs (AEDs) on serum folate and vitamin B12 in various epileptic patients, and to examine the correlation between these effects and secondary cerebrovascular events. A total of 68 epileptic patients, diagnosed between May 2012 and May 2014, were included in the present study. The study included 8 cases of autonomic seizures, 10 cases of absence seizures, 13 cases of complex partial seizures, 28 cases of generalized tonic-clonic seizures, and 9 cases of simple partial seizures. The patients received appropriate AED treatment according to the characteristics of epileptic seizure and the treatment guidance. The differences in the serum levels of folate and vitamin B12 in these patients, and the differences in the secondary cerebrovascular events in these patients after 1 year follow-up were analyzed. The difference in the AEDs used by various epileptic patients was statistically significant (P<0.05). The proportion of AED monotherapy in the autonomic seizure group and petit mal group was highest, and the proportion of two AED in combination with the psychomotor seizure, grand mal and simple partial seizure groups was highest. The serum levels of folate and vitamin B12 in these patients following treatment were significantly lower than those prior to treatment (P<0.05). The differences in the serum levels of folate and vitamin B12 in these groups following treatment were not statistically significant (P>0.05). The difference in the incidence of cerebrovascular events in these groups at follow up was not statistically significant (P>0.05). The multifactorial logistic regression analysis revealed that the serum levels of folate and vitamin B12 were the independent risk factors for epilepsy with secondary cerebrovascular events [folate: odds ratio (OR)=0.536, P=0.039; vitamin: OR=0.382, P=0.041]. In conclusion, various AEDs may decrease the serum levels of folate and vitamin B12 and affect the secondary cerebrovascular events in various epileptic patients. Thus, regular supplementation of folate and vitamin B12 may be an option.

Comparison of Levofloxacin- and Moxifloxacin-Based Triple Therapies with Standard Treatment in Eradication of Helicobacter Pylori as First-Line Therapy

Aim: It is recommended that treatments that include clarithromycin should be avoided in eradication of Helicobacter pylori (HP) in cases where clarithromycin resistance is higher than 20%. We aimed to compare levofloxacin- and moxifloxacin-based triple therapies with standard treatment and with each other in eradication of helicobacter pylori as first-line therapy. Materials and Methods: Patients were randomized prospectively as three groups. There were 102 patients in the levofloxacin group, 101 patients in the moxifloxacin group, and 103 patients in the standard treatment group. The patients received levofloxacin 500 mg daily, amoxicillin 1 g b.i.d. and lansoprazole 30 mg b.i.d. for ten days (LAL) in the levofloxacin group; moxifloxacin 400 mg daily, amoxicillin 1 g b.i.d. and lansoprazole 30 mg b.i.d. (MAL) in the moxifloxacin group; and clarithromycin 500 mg b.i.d., amoxicillin 1 g b.i.d. and lansoprazole 30 mg b.i.d. (CAL) in the standard treatment group. At post-treatment week 6, HP was checked by using stool antigen test. Results: In the eradication of Helicobacter pylori, the success rate as determined by per protocol (PP) analysis was 92% in the LAL group, 91.8% in the MAL group, and 82.4% in the CAL group. A statistically significant difference was found in the LAL and MAL groups compared to the CAL group (p < 0.05). There was no difference between the LAL and MAL groups. Conclusions: It was determined that levofloxacin- and moxifloxacin-based triple therapies were more effective than the standard treatment in first-line setting in the eradication of Helicobacter pylori. In addition, no difference was found between levofloxacin- and moxifloxacin-based triple therapies. Currently observed high efficacy may be evaluated in treatment. Although quinolon resistance is not considered a major problem, it appears to be a factor that may reduce treatment success over a period of time.

A Mild and Efficient Approach to Functional Single-Chain Polymeric Nanoparticles via Photoinduced Diels–Alder Ligation

We present a new ambient temperature synthetic approach for the preparation of single-chain polymeric nanoparticles (SCNPs) under mild conditions using a UV-light-triggered Diels–Alder (DA) reaction for the intramolecular cross-linking of single polymer chains. Well-defined random copolymers with varying contents of styrene (S) and 4-chloromethylstyrene (CMS) were synthesized employing a nitroxide-mediated radical polymerization (NMP) initiator functionalized with a terminal alkyne moiety. Postpolymerization modification with 4-hydroxy-2,5-dimethylbenzophenone (DMBP) and an N-maleimide (Mal) derivative led to the functional linear precursor copolymers. The intramolecular cross-linking was performed by activating the DMBP groups via irradiation with UV light of 320 nm for 30 min in diluted solution (cPolymer = 0.017 mg mL–1). The ensuing DA reaction between the activated DMBP and the Mal groups resulted in well-defined single-chain polymeric nanoparticles. To control the size of the SCNPs, random copolymers with varying CMS contents (i.e., different functional group densities (FGD)) were employed for the single-chain collapse. Additionally, monotethered nanoparticles were prepared via the copper-catalyzed azide–alkyne cycloaddition between the alkyne bearing copolymer with the highest FGD and an azide-terminated poly(ethylene glycol) (PEG) prior to UV-induced cross-linking. The formation of SCNPs was followed by size exclusion chromatography (SEC), nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM).

Bright far-red/near-infrared fluorescent conjugated polymer nanoparticles for targeted imaging of HER2-positive cancer cells

We report the design and synthesis of a far-red/near-infrared (FR/NIR) fluorescent conjugated polymer, PFDBT-POSS, bearing poly{[9,9-di(hexyl)fluorene]-alt-co-[4,7-bis(thiophen-2-yl)-2,1,3-benzothiazole]} (PFDBT) as the backbone and bulky polyhedral oligomeric silsesquioxane (POSS) as side chains. PFDBT-POSS based nanoparticles (NPs) with maleimide (Mal) groups on the surface are prepared by encapsulating the polymer using DSPE-PEG2000 and DSPE-PEG2000-Mal as matrix. The obtained PFDBT-POSS-Mal NPs show a maximum absorption at ∼536 nm and a FR/NIR emission centred at ∼687 nm. It has a quantum yield (QY) of 13.6% in water, which is 6-fold higher than that of PFDBT-Mal NPs (QY = 2%), indicating that incorporation of POSS segments as pendants can efficiently suppress fluorescence quenching. The presence of Mal functional groups allows for efficient bioconjugation with anti-HER2 affibody by click reaction. The resultant PFDBT-POSS-Affibody serves as a reliable fluorescent probe with low cytotoxicity and high photostability in targeted detection and cellular imaging of HER2-overexpressed cancer cells using SKBR-3 as an example. Of particular interest is that the absorption maximum of PFDBT-POSS-Mal NPs overlaps well with the commercial 543 nm laser line, which ensures the most efficient utilization of the light harvesting property of the probe to generate bright fluorescence signals. This study provides an efficient strategy to design bright FR/NIR fluorescent CP NPs with long wavelength absorption and emission for biological applications.

The response of the crab Paralithodes Camtschaticus (Tilesius, 1815) to geomagnetic storms

There are a number of environmental factors for whose perception Nature has not provided living organisms with special receptors. The most important one is the geomagnetic field. If animals had magne� toreceptors, they could use them as a compass to ori� ent in Earth’s magnetic field. Therefore, many researchers have long been trying to discover the abil� ity to perceive the geomagnetic field in different ani� mal groups and in humans with the use of a variety of techniques [5, 8]. However, these studies are notable for the lack of reasonable assumptions on the mecha� nisms of action of magnetic fields on animalsThe dis� covery of electroreception in some fish species gave the opportunity to prove, with the help of rigorous meth� ods of sensory physiology, the ability of animals to per� ceive Earth’s electric and magnetic fields [4]. How� ever, electroreceptors were found in a small group of fish. The finding of biogenic magnetite in many ani� mals allowed a new insight into the problem of magne� toreception [3]. For this reason, a hypothesis on the possible use of biogenic magnetite by animals for geo� magnetic orientation is attractive among biologists [1, 2]. The finding of the ability of certain sensory structures to perceive magnetic fields is also important for sen� sory physiology, because this is evidence for a new type of receptors (magnetoreceptors) that may help to explain orientation and migration behaviors. How� ever, these sensory formations have not been found in animals thus far. Invertebrates, including crabs, lack electrorecep� tors, although, in the course of evolution and vital activity, they are exposed to variations in Earth’s mag� netic field. Therefore, our study was aimed at evaluat� ing the possibility of perception of the geomagnetic field and its variations by invertebrates as exemplified by crabs. We used a special experimental setup to study the locomotor activity of crabs under the action of the geomagnetic field. The setup contained a kinematic block, a transducer of direct current to modulated

Aluminium-Maltolate-induced Impairment of Learning, Memory and Hippocampal Long-term Potentiation in Rats

Recently, aluminium (Al) has been proposed to be one of the environmental factors responsible for cause Alzheimer's disease (AD). However, the relationship between Al and AD is controversial. To investigate the effects of subchronic Aluminium-maltolate (Al (mal)(3)) exposure on the behavioral, electrophysiological functions. Forty Sprague-Dawley (SD) rats were randomly distributed into five groups. Over two months, rats in the saline group received daily intraperitoneal (i.p.) injections 0.9% saline, rats in the maltolate group received 7.56 mg/kg maltolate, and rats in the 0.27, 0.54, 1.08 mg/kg Al (mal)(3) groups received i.p. administrations of these three doses, respectively. Neural behavior was assessed in Morris water maze. Long-term potentiation (LTP) in hippocampus was recorded. Al content in the neocortex was determined using a graphite furnace atomic absorption spectrophotometer. Our studies indicate that subchronic Al (mal)(3) exposure significantly impaired spatial learning and memory abilities, suppressed the LTP in the CA1 hippocampal area, and elevated Al levels in cerebral cortex in a dose-dependent fashion. In conclusion, low doses of Al (mal)(3) can still lead to dramatic Al accumulation in the brain, severely impair learning and memory capacities, and hippocampal LTP.

Morphological evaluation of cranial and maxillary shape differences of the brachymorphic mouse with spontaneous malocclusion using three‐dimensional micro‐computed tomography

The aim of this study was to determine whether significant cranial and maxillary deformity exists in BALB/c-bm/bm (brachymorphism) mouse with spontaneous malocclusion using three-dimensional (3D) images. Thirty female mice were divided into the following three groups: control group (BALB/c mice, n = 10), Norm group (BALB/c-bm/bm mice with normal occlusion, n = 10), and Mal group (BALB/c-bm/bm mice with malocclusion, n = 10). Nine points in the skull were selected, and transverse and antero-posterior distances were measured using three-dimensional images of micro-computed tomography (CT). Moreover, 3D images were superimposed at the median plane to visualize the skull shape asymmetry. The transverse distances at the posterior cranial and maxillary region and the antero-posterior distances in the Norm and Mal groups were significantly shorter than those in the control group. The nasal septum of the Mal group was significantly shorter than that of the Norm group. Morphological measurements and superimposed 3D images showed that lateral deviation occurred at the anterior cranial and maxillary region in the Mal group. The 3D micro-CT images revealed that the antero-posterior length and posterior transverse width at the cranium and maxilla in BALB/c-bm/bm mice were significantly smaller than those in BALB/c mice. It was quantitatively and morphologically clear that BALB/c-bm/bm mice show a spontaneous transverse crossbite owing to lateral deviation of the maxilla and nasal bone.

Three-dimensional craniomaxillary characteristics of the mouse with spontaneous malocclusion using micro-computed tomography

The aim of this study was to clarify the morphological characteristics of craniomaxillary deviations in BALB/c-bm/bm mice with a spontaneous malocclusion (incisal transverse crossbite) using three-dimensional (3D) morphological measurements. Sixty female mice aged 13 and 25 weeks were divided into the following groups: control (BALB/c-+/+ mice, n = 20), norm (BALB/c-bm/bm mice with a normal occlusion, n = 20), and mal (BALB/c-bm/bm mice with a malocclusion, n = 20). Various points in the skull were selected and the distances between two points were measured using 3D micro-computed tomography (CT) images. Statistically significant differences in measurement values among the three groups were evaluated by one-way analysis of variance with a probability level of P < 0.05 considered statistically significant. At both ages, the lengths of almost all measurements in the norm and mal groups were significantly shorter than those in the control group. Comparison between the shifted and non-shifted sides in the mal group showed that significant lateral deviation at the maxilla and nasal bone had occurred. Using 3D micro-CT images, the results of this study quantitatively showed that the craniomaxillary complex of BALB/c-bm/bm mice was significantly smaller than that of BALB/c-+/+ mice and that BALB/c-bm/bm mice have a spontaneous transverse crossbite due to lateral deviation of the maxilla and nasal bone.

Endemic Ecuadorian glassfrog Cochranella mache is Critically Endangered because of habitat loss

Amphibians are one of the most threatened ani- mal groups. In the Family Centrolenidae c. 50% of the spe- cies are declining and threatened with extinction. One of these is the glassfrog Cochranella mache, endemic to seasonal evergreen forests of the West Ecuadorian region and restricted to highly fragmented forest of , 100 km 2 in the Cordillera Mache-Chindul, north-western coastal Ec- uador, at 100-640 m. We surveyed this region to elucidate the distribution and conservation status of C. mache. We located it in three new localities and also found a museum specimen from a further new locality. We recommend that the species should be categorized as Critically Endangered because of the continuous and progressive destruction of its increasingly fragmented habitat. Recent surveys of glassfrog species sympatric with C. mache showed low relative abundances compared to surveys in the 1970s and 1980s. Because of the relationship between forest and local climate we suggest that gradual declines of lowland glassfrog pop- ulations may be caused by local climate changes produced by forest destruction. In situ conservation is required to halt and mitigate these impacts. Further research on the effects of habitat loss, fragmentation, and associated climate changes on Neotropical amphibians is required.