Search

Identification of innovative therapeutic targets for the treatment of cognitive impairment in Parkinson’s disease (PD) is urgently needed. Hydrogen sulfide (H2S) plays an important role in cognitive function. Therefore, this work is aimed at investigating whether H2S attenuates the cognitive impairment in PD and the underlying mechanisms. In the rotenone- (ROT-) established PD rat model, NaHS (a donor of H2S) attenuated the cognitive impairment and promoted microglia polarization from M1 towards M2 in the hippocampus of PD rats. NaHS also dramatically upregulated the Warburg effect in the hippocampus of PD rats. 2-Deoxyglucose (2-DG, an inhibitor of the Warburg effect) abolished NaHS-upregulated Warburg effect in the hippocampus of PD rats. Moreover, the inhibited hippocampal Warburg effect by 2-DG abrogated H2S-excited the enhancement of hippocampal microglia M2 polarization and the improvement of cognitive function in ROT-exposed rats. Our data demonstrated that H2S inhibits the cognitive dysfunction in PD via promoting microglia M2 polarization by enhancement of hippocampal Warburg effect.

Motor neuron diseases involve degeneration of motor neurons in the brain (upper motor neurons), brain stem, and spinal cord (lower motor neurons). Symptoms vary depending on the degree of upper and lower neuron involvement, but progressive painless weakness is the predominant complaint. Motor neuron disease includes numerous specific disorders, including amyotrophic lateral sclerosis, spinal muscular atrophy, spinal bulbar muscular atrophy, and other inherited and acquired conditions. Abnormalities on nerve conduction studies, repetitive nerve stimulation, needle electromyography, and other electrodiagnostic techniques help to distinguish these disorders from each other, and from other disorders with progressive weakness.

Formaldehyde (FA) causes neurotoxicity and contributes to the occurrence of neurodegenerative diseases. However, the mechanism of FA-induced neurotoxicity has not been fully elucidated. Ferritinophagy, an autophagy process of ferritin mediated by the nuclear receptor coactivator 4 (NCOA4), is a potential mechanism of neurotoxicity. In this study, we explored whether ferritinophagy is associated with the neurotoxicity of FA. Our results showed that FA (50, 100, 200 μM; 24 h) exposure upregulated ferritinophagy in the mouse hippocampal neuronal HT22 cells, which was evidenced by the upregulated autophagic flux, the increased colocalizations of NCOA4 with ferritin heavy chain (FTH1) and NCOA4 with microtubule-associated protein 1 light chain-3B (LC3B), the augmented expression of NCOA4, and the reduced content of FTH1. We also found that FA (0.1, 1, and 10 μmol, i.c.v., 7d) administration boosted ferritinophagy in the hippocampus of Sprague-Dawley (SD) rats, which was demonstrated by the accumulated autophagosomes, the increased expressions of LC3II/I and NCOA4, and the decreased contents of p62 and FTH1 in the hippocampus. Further, we confirmed that inhibition of ferritinophagy by silencing the expression of NCOA4 decreased FA-induced toxic damage in HT22 cells. These results indicated that FA induces neurotoxicity by promoting ferritinophagy. Our findings suggest a potential mechanism insight into the FA-induced neurotoxicity, which in turn provides a new thought for the treatment of FA-related neurodegenerative diseases.

This study proposed a nonenzymatic sensor for lactic acid detection based on copper doped zinc oxide (CZO) modified by graphitic carbon nitride (g-C3N4) and iron–platinum nanoparticles (FePt NPs). The silver paste electrodes of the sensor were prepared using screen printing technology, and the CZO sensing film was deposited using radio frequency (R.F.) sputtering system. The g-C3N4 nanosheet solution was prepared through liquid exfoliating of the g-C3N4 in water. The sensing film was modified by adding different contents of the FePt NPs in g-C3N4 solution. The various concentrations of the FePt NPs were 0.03, 0.1, and 0.3 wt%. The ${V}$ – ${T}$ measurement system was applied to investigate the sensing characteristics of the lactic acid sensors based on CZO sensing film modified by g-C3N4 and FePt NPs. The surface morphology of the sensor was analyzed by scanning electron microscope (SEM), X-ray diffraction (XRD), and dynamic light scattering (DLS). In this work, the 0.1 wt% FePt NPs-g-C3N4 lactic acid sensor has the best sensitivity, linearity, response time, and the limit of detection (LOD).

This study proposed a potentiometric non-enzymatic electrochemical sensor for glucose detection based on copper doped zinc oxide (CZO) as a sensing film. In this article, a metal oxide film was used, which was able to react catalytically with glucose. The wires of the sensor were prepared by screen printing technology, and the CZO thin film was deposited on the sensor by the radio frequency (R. F.) sputtering system. In order to make the non-enzymatic sensor more stable, Nafion layer was added to the working electrodes. The characteristics of the sensor were measured using a voltage time (V-T) measurement system. Average sensitivity and linearity of the Nafion/CZO glucose sensor was tested in glucose concentrations ranging from 2 mM - 14 mM. After experiment, it was confirmed that the sensor had good performance. Experiments confirmed that the Nafion/CZO sensor exhibited characteristics including: good selectivity for glucose, average sensitivity of 6.45 mV/mM, a linearity of 0.998, a response time of 20 sec, and a limit of detection (LOD) of 0.51 mM. The device has a low relative standard deviation (RSD) and would be suitable for further development and eventual use in biomedical applications.

The saturated hydraulic conductivity of soils is a critical concept employed in basic calculation in the geotechnical engineering field. The Kozeny–Carman equation, as a well-known relationship between hydraulic conductivity and the properties of soils, is considered to apply to sands but not to clays. To solve this problem, a new formula was established based on Hagen–Poiseuille's law. To explain the influence on the seepage channel surface caused by the interaction of soil particles and partially viscous fluid, the surface area ratio was introduced. A modified framework for determining the hydraulic radius was also proposed. Next, the relationship between the effective void ratio and the total void ratio was established for deriving the correlation of hydraulic conductivity and total void ratio. The improved equation was validated using abundant experimental results from clays, silts, and sands. According to the results, the accuracies of the proposed model with two fitted multipliers for clays, silts, and sands are 94.6, 96.6, and 100%, respectively, but with only one fitted parameter, the accuracies are 97.1, 91.5, and 100%, respectively. The proposed model can be considered to have a satisfactory capability to predict hydraulic conductivity for a wide variety of soils, ranging from clays to sands. HIGHLIGHTS An improved model of the soil particle-water system was proposed.; The surface area ratio δ is introduced.; We establish an improved method for estimating the effective void ratio.; The relationship between LL and As for clay was established.; The correlation between the parameters C and the specific surface area of soils was established.

A non-enzymatic copper-doped zinc oxide glucose sensor, which is covered with silver nanowires (AgNWs) and modified with Nafion, can be employed to measure glucose with a concentration of 2–14 mM. In this study, X-ray photoelectron spectroscopy (XPS) was used to analyze the film of the working electrodes, and the AgNWs on the electrode surface were analyzed by a field-emission scanning electron microscope (FE-SEM). Also, the AgNW/CZO structure was investigated through the use of an atomic force microscope (AFM) and an ultraviolet/visible (UV/Vis) spectrophotometer. Finally, we used electrochemical impedance spectroscopy (EIS) and the voltage–time (V–T) measurement system to measure the sensing characteristics of the thin film. The potentiometric non-enzymatic glucose sensor has the average sensitivity of 10.31 mV/mM, and the linearity is 0.997. Also, the sensor has the response time with 15 s, and the interference experiment proved that it has good anti-interference and excellent repeatability (relative standard deviation (RSD) = 3%). Besides, the sensor still maintains a certain degree of average sensitivity at high temperatures, and it has the limit of detection (LOD) with 0.272 mM.

From our other works, we have developed urea biosensor based on graphene oxide/nickel oxide sensing film modified either by Au nanoparticles or ${\gamma }$ -Fe2O3 nanoparticles. In this study, we have further developed back-end calibration circuit to reduce the drift effect and hysteresis effect of the two types of the urea biosensors. The back-end calibration circuit is composed of non-inverting amplifiers, error amplifiers, P-MOSFET transmission transistor, feedback networks, output voltage capacitors and resistor dividers. After applying the back-end calibration circuit, the drift rate of urea biosensor modified by Au NPs is reduced from 3.06 mV/hr to 0.28 mV/hr, which is 90.85% reduction. The drift rate of urea biosensor modified by ${\gamma }$ -Fe2O3 NPs is reduced from 3.92 mV/hr to 0.57 mV/hr, which is 85.46% reduction. Through the back-end calibration circuit to reduce the hysteresis effect, the hysteresis voltage for the forward cycle and reverse cycle of the urea biosensor modified by Au NPs are reduced by 26% and 30%, respectively. The hysteresis voltage for the forward cycle and reverse cycle of the urea biosensor modified by ${\gamma }$ -Fe2O3 NPs are reduced by 23% and 28%, respectively.

Introduction We have previously demonstrated the antagonistic role of hydrogen sulfide (H2S) in the cognitive dysfunction of streptozotocin (STZ)-induced diabetic rats. It has been confirmed that the impaired hippocampal autophagic flux has a key role in the pathogenesis of cognitive impairment and that ornithine decarboxylase (ODC)/spermidine (Spd) pathway plays an important role in the formation of memory by promoting autophagic flux. Objectives To investigate the roles of hippocampal ODC/Spd pathway and autophagic flux in H2S-attenuated cognitive impairment in STZ-induced diabetic rats. Methods Cognitive function is judged by the novel objective recognition task (NOR), the Y-maze, and the Morris water maze (MWM) tests. The ODC/Spd pathway in hippocampus was evaluated using the expression of ODC detected by western blot and the level of Spd assayed by GC-MS. Autophagic flux was assessed using the expressions of Beclin-1, LC3II/I, and P62 detected by western blot, and the number of autophagosomes observed by transmission electron microscope. Results Sodium hydrosulfide (NaHS, a donor of H2S) markedly improved the autophagic flux in the hippocampus of STZ-exposed rats, as evidenced by a decrease in the number of autophagosomes as wells as downregulations in the expressions of LC3-II, Beclin-1, and P62 in the hippocampus of cotreatment with NaHS and STZ rats. NaHS also up-regulated the expression of ODC and the level of Spd in the hippocampus of STZ-induced diabetic rats. Furthermore, inhibited hippocampal ODC/Spd pathway by difluoromethylornithine (DFMO) markedly reversed the protections of NaHS against the hippocampal autophagic flux impairment as well as the cognitive dysfunction in STZ-exposed rats. Conclusion These findings indicated that improving hippocampal autophagic flux plays a key role in H2S-attenuated cognitive impairment in STZ-induced diabetic rats, as results of up-regulating hippocampal ODC/Spd pathway.

In this work, we used radio frequency (RF) system and screen printing technology to fabricate urea biosensor based on urease-maghemite nanoparticles ( $\gamma $ -Fe2O3 NPs)/graphene oxide (GO)/nickel oxide (NiO) sensing membrane on silver conductive wire printed polyethylene terephthalate (PET) substrate. The ${V}$ – ${T}$ measurement system was used to investigate the sensing characteristics of urea biosensors based on GO/NiO sensing membrane modified by $\gamma $ -Fe2O3 NPs. The sensing membrane was modified by adding different contents of $\gamma $ -Fe2O3 NPs. The concentration of $\gamma $ -Fe2O3 NPs was 1 mg/mL. When the volume ratio of urease/ $\gamma $ -Fe2O3 NPs was 1/1, it had the best sensitivity. The average sensitivity, the linearity, and the limit of detection of (LOD) of the best urea biosensor in this work were 52.36 mV/decade ± 0.22 mV/decade, 0.996, and $7.91~{\mu }\text{M}$ , respectively. The effect of temperature on the urea biosensor was investigated from 25 °C to 65 °C. The stability of urea biosensors was evaluated by the effect of hysteresis and long-term storage stability. After 29 days, the average sensitivity remained 80.62% of the initial value. Compared with other urea biosensors, our urea biosensor based on urease- $\gamma $ -Fe2O3 NPs/GO/NiO sensing membrane has better average sensitivity.

Most landslides induced by reservoir impoundment and rainfall in the Three Gorges Reservoir area of China are usually characterized by bedding-plane shear zones. This paper presents an experimental study of the interaction between water and shear-zone materials. A series of tests, including wetting-drying cycles and soaking tests, were carried out. The results show that the fluid-solid interaction not only reduces the shear strength of shear-zone soil but also accelerates the disintegration process of clastic rock from shear zone. After the fluid-solid interaction at different pH values, the clastic rock samples produce the most clay minerals in acidic solution. Similarly, the clay minerals of shear-zone soil samples increase dramatically after 45 days of soaking in acidic environment. According to the tests, it is found that the shear-zone soil in eluvium may originate from the weathered clastic rock near the shear zones under long-term fluid-solid interaction.

Homocysteine (Hcy) accelerates neuronal senescence and induces age-related neurodegenerative diseases. Silence signal regulating factor 1 (SIRT1) prolongs lifespan and takes neuroprotective effects. We have previously demonstrated that hydrogen sulfide (H2S) prevents Hcy-induced apoptosis of neuronal cells and has neuroprotective effect. In the present work, we aimed to investigate whether H2S protects HT22 cells against Hcy-induced neuronal senescence and whether SIRT1 mediates this role of H2S. We found that Hcy induced cellular senescence in HT22 cells, as determined by β-galactosidase staining, expressions of P16INK4a, P21CIPL, and trypan blue Staining, which are the markers of cellular senescence. However, sodium hydrosulfide (NaHS, the donor of H2S) significantly reversed Hcy-induced cellular senescence. Interestingly, NaHS not only up-regulated the expression of SIRT1 in HT22 cells but also reversed Hcy-downregulated the expression of SIRT1 in HT22 cells. Furthermore, we found that pretreatment with Sirtinol (an inhibitor of SIRT1) markedly reversed the protection of NaHS against Hcy-induced HT22 cells senescence and apoptosis. Our findings illustrated that H2S protects HT22 cells against Hcy-induced senescence by up-regulating SIRT1.

Most deep-seated landslides are characterized by large volumes with deep shear surfaces. They are sensitive to hydrological forcing, especially in climate change scenarios. This paper studies the role of soil–water interaction in affecting the motion of a deep-seated landslide near the southeast coast of China, where seasonal rainfall combined with annual typhoons caused the instability of a previous stable slope. A comprehensive investigation consisting of field monitoring and experiments of soil–water interaction is carried out. The monitoring data show that the landslide exhibits alternate dormant and active stages, corresponding to rainy and dry seasons, respectively. The enduring precipitations predominate the landslide motion, while intensive rainfall brought by typhoon events leads to transient deformation. In addition, wet treatment of intact and reconstituted soils is adopted to mimic the interaction between rainwater and landslide material. The results obtained from in-situ and laboratory direct shear tests indicate that the soil–water interaction is time-dependent. The long-term interaction gives rise to significant strength reduction of soils, thereby regulating the movement of the landslide.

Objective. This study aims to clinically investigate and compare the therapeutic effects and treatment cycle between traditional direct bonding and OrthGuide computer-aided indirect bonding in orthodontic treatment. Methods. Forty patients treated at the Department of Orthodontics, Beijing Rytime Dental Hospital between July 1, 2016, and December 31, 2019, were included. The patients were divided into a control group ( n = 20 , traditional direct bonding) and a test group ( n = 20 , OrthGuide computer-aided indirect bonding). The American Board of Orthodontics (ABO) measurement was performed on patients using Uceph cephalometric analysis software to compare intragroup and intergroup differences, and the treatment cycles of all patients were recorded. Results. After treatment, U1-NA (mm), ∠U1-SN (°), LL-EP (mm), and UL-EP (mm) in the control group were significantly lower than before treatment, and there was no significant difference in other ABO measurement indexes, while the test group showed no marked difference in all ABO measurements between pre- and posttreatment. Further, intergroup comparison showed no significant difference in ABO measurements in pre- and posttreatment between the two groups. The test group had a shorter treatment cycle than the control group, with an average treatment cycle of 21.20 ± 7.14 months in the control group and 17.17 ± 4.16 months in the test group. Conclusion. There was no significant difference in the therapeutic effects between the direct and indirect bonding techniques. However, OrthGuide computer-assisted indirect bonding demonstrated a significantly shorter treatment cycle and might be more efficient than traditional direct bonding.

Sense mutations in several conserved modifiable sites of histone H3 have been found to be strongly correlated with multiple tissue-specific clinical cancers. These clinical site mutants acquire a distinctively new epigenetic role and mediate cancer evolution. In this study, we mimicked histone H3 at the 56th lysine (H3K56) mutant incorporation in mouse embryonic stem cells (mESCs) by lentivirus-mediated ectopic expression and analyzed the effects on replication and epigenetic regulation. The data show that two types of H3K56 mutants, namely H3 lysine 56-to-methionine (H3K56M) and H3 lysine 56-to-alanine (H3K56A), promote replication by recruiting more minichromosome maintenance complex component 3 and checkpoint kinase 1 onto chromatin compared with wild-type histone H3 and other site substitution mutants. Under this condition, the frequency of genomic copy number gain in H3K56M and H3K56A cells globally increases, especially in the Mycl1 region, a known molecular marker frequently occurring in multiple malignant cancers. Additionally, we found the disruption of H3K56 acetylation distribution in the copy-gain regions, which indicates a probable epigenetic mechanism of H3K56M and H3K56A. We then identified that H3K56M and H3K56A can trigger a potential adaptation to transcription; genes involved in the mitogen-activated protein kinase pathway are partially upregulated, whereas genes associated with intrinsic apoptotic function show obvious downregulation. The final outcome of ectopic H3K56M and H3K56A incorporation in mESCs is an enhanced ability to form carcinomas. This work indicates that H3K56 site conservation and proper modification play important roles in harmonizing the function of the replication machinery in mESCs.

The complete mitochondrial genome of a soldier beetle, Cantharis plagiata (Coleoptera, Canthridae), was sequenced. The mitogenome is a double-stranded circular molecule, and the obtained sequence had 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA subunits, and an AT-rich region, as in other insects. Total length of this mitogenome is 16,315 bp and the composition of each base is A (41.4%), T (37.5%), C (12.7%), G (8.4%), respectively. The phylogenetic tree analysis using 25 species of Elateroidea showed that C. plagiata is closest to C. pellucida, which confirms its systematic status in Cantharidae.

Potentiometric biosensors based on flexible arrayed silver paste electrode and copper-doped zinc oxide sensing film modified by iron-platinum nanoparticles (FePt NPs) are designed and manufactured to detect lactate in human. The sensing film is made of copper-doped zinc oxide (CZO) by a radio frequency (RF) sputtering system, and then modified by iron-platinum nanoparticles (FePt NPs). The surface morphology of copper-doped zinc oxide (CZO) is analyzed by scanning electron microscope (SEM). FePt NPs are analyzed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The average sensitivity, response time, and interference effect of the lactate biosensors are analyzed by voltage-time (V-T) measurement system. The electrochemical impedance is analyzed by electrochemical impedance spectroscopy (EIS). The average sensitivity and linearity over the concentration range 0.2–5 mM are 25.32 mV/mM and 0.977 mV/mM, respectively. The response time of the lactate biosensor is 16 s, with excellent selectivity.

Notch signaling and epigenetic factors are known to play critical roles in regulating tissue homeostasis in most multicellular organisms, but how Notch signaling coordinates with epigenetic modulators to control differentiation remains poorly understood. Here, we identify heterochromatin protein 1c (HP1c) as an essential epigenetic regulator of gut homeostasis in Drosophila. Specifically, we observe that HP1c loss-of-function phenotypes resemble those observed after Notch signaling perturbation and that HP1c interacts genetically with components of the Notch pathway. HP1c represses the transcription of Notch target genes by directly interacting with Suppressor of Hairless (Su(H)), the key transcription factor of Notch signaling. Moreover, phenotypes caused by depletion of HP1c in Drosophila can be rescued by expressing human HP1γ, suggesting that HP1γ functions similar to HP1c in Drosophila. Taken together, our findings reveal an essential role of HP1c in normal development and gut homeostasis by suppressing Notch signaling.

In recent years, glucose biosensors play an important role in diabetes detection. This paper describes a potentiometric non-enzymatic glucose biosensor. The sensor is modified by silver nanowires (Ag NWs) which are fabricated by the polyol method. Using the voltage-time (V-T) system and electrochemical impedance spectroscopy (EIS), the sensing characteristics of the sensor are analyzed and the impact of silver nanowires (Ag NWs) on the performance of the sensor are investigated.

The mechanisms underlying formaldehyde (FA)-induced neurotoxicity have not yet been fully clarified. Ferroptosis is a novel regulatory cell death and the Warburg effect is involved in regulating neural function. In this study, we investigated whether FA-induced neurotoxicity is implicated in neuronal ferroptosis and determined whether the Warburg effect mediates FA-induced neuronal ferroptosis. We found that FA (0.1, 0.5 and 1.0 mM, 6 h) induced cell death in HT22 cells (a cell line of mouse hippocampal neuron), as evidenced by a decrease in cell viability and an increase in cell mortality; enhanced oxidative stress, as evidenced by a decrease in glutathione (GSH) and increases in malondialdehyde (MDA), 4-Hydroxynonenal (4-HNE), as well as reactive oxygen species (ROS); increased the iron content; and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells. Meanwhile, we found that FA (0.1, 1, 10 μmol) decreased the cross-sectional of mitochondria, increased the level of lipid ROS and iron content in primary hippocampal cells. We showed that FA (0.1, 0.5 and 1.0 mM, 6 h) upregulated the Warburg effect in HT22 cells, as evidenced by up-regulations of pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK-1), and lactate dehydrogenase (LDHA) proteins; down-regulation of pyruvate dehydrogenase (PDH); and an increase in lactate production. Also, we found that FA (0.1, 1, 10 μmol, 7 d) upregulated the Warburg effect in hippocampal tissue, as evidenced by up-regulations of PKM2, PDK-1, and LDHA proteins; down-regulation of PDH. Furthermore, the inhibition of the Warburg effect by dichloroacetate (DCA) protected HT22 cells against FA-induced ferroptosis and cell death. Collectively, these data indicated that FA induces ferroptosis in hippocampal neuronal cells by upregulation of the Warburg effect.

Diabetes-associated cognitive dysfunction (DACD) characterized by hippocampal injury increases the risk of major cerebrovascular events and death. Endoplasmic reticulum (ER) stress and synaptic dysfunction play vital roles in the pathological process. At present, no specific treatment exists for the prevention and/or the therapy of DACD. We have recently reported that hydrogen sulfide (H