Ultrasensitive Self-Driven Terahertz Photodetectors Based on Low-Energy Type-II Dirac Fermions and Related Van der Waals Heterojunctions.

The exotic electronic properties of topological semimetals (TSs) have opened new pathways for innovative photonic and optoelectronic devices, especially in the highly pursuit terahertz (THz) band. However, in most cases Dirac fermions lay far above or below the Fermi level, thus hindering their successful exploitation for the low-energy photonics. Here, low-energy type-II Dirac fermions in kitkaite (NiTeSe) for ultrasensitive THz detection through metal-topological semimetal-metal heterostructures are exploited. Furthermore, a heterostructure combining two Dirac materials, namely, graphene and NiTeSe, is implemented for a novel photodetector exhibiting a responsivity as high as 1.22 A W-1 , with a response time of 0.6 µs, a noise-equivalent power of 18 pW Hz-0.5 , with outstanding stability in the ambient conditions. This work brings to fruition of Dirac fermiology in THz technology, enabling self-powered, low-power, room-temperature, and ultrafast THz detection.

Development of Joint Activity Angle Measurement and Cloud Data Storage System.

In this study, we developed a range of motion sensing system (ROMSS) to simulate the function of the elbow joint, with errors less than 0.76 degrees and 0.87 degrees in static and dynamic verification by the swinging and angle recognition modules, respectively. In the simulation process, the É£ correlation coefficient of the Pearson difference between the ROMSS and the universal goniometer was 0.90, the standard deviations of the general goniometer measurements were between ±2 degrees and ±2.6 degrees, and the standard deviations between the ROMSS measurements were between ±0.5 degrees and ±1.6 degrees. With the ROMSS, a cloud database was also established; the data measured by the sensor could be uploaded to the cloud database in real-time to provide timely patient information for healthcare professionals. We also developed a mobile app for smartphones to enable patients and healthcare providers to easily trace the data in real-time. Historical data sets with joint activity angles could be retrieved to observe the progress or effectiveness of disease recovery so the quality of care could be properly assessed and maintained.

Tumor suppressor miR-424-5p abrogates ferroptosis in ovarian cancer through targeting ACSL4.

Ovarian cancer is the most lethal gynecological cancer. In spite of recent advances, clinical outcomes remain poor, urgently needing novel therapeutic approaches. Growing evidence indicates that microRNAs play crucial roles in ovarian carcinogenesis and progression and that ferroptosis serves as a novel tumor suppressor. However, the molecular mechanisms of miRNA-mediated ferroptosis regulation in ovarian cancer are still largely unknown. In the present study, we show that miR-424-5p negatively regulates ferroptosis by directly targeting ACSL4 in ovarian cancer cells. Upregulation of miR-424-5p suppressed ACSL4 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Meanwhile, knockdown of miR-424-5p increased the sensitivity of ovarian cancer cells to erastin and RSL3. Furthermore, ACSL4 was upregulated in ovarian cancer tissues, and high ACSL4 expression predicted worse prognosis and sensitized ovarian cancer cells to erastin- and RSL3-induced ferroptosis. Importantly, decreases in lipid peroxides and ferroptotic cell death mediated by miR-424-5p could be abrogated by ACSL4 overexpression. Taken together, our findings demonstrate that miR-424-5p regulates ferroptosis by targeting ACSL4 in ovarian cancer cells and suggest a potential therapeutic approach for ovarian cancer.

Rhizospheric pore-water content predicts the biochar-attenuated accumulation, translocation, and toxicity of cadmium to lettuce.

Metal bioavailability controls its behaviors in soil-plant system, especially involved in biochar amendment. This study compared a rhizospheric pore-water extraction against a BCR sequential extraction method to understand cadmium (Cd) bioavailability in two typical Chinese soils. Soils were spiked with five levels of Cd (CdCl2) and remediated with 3% corn-straw derived biochar. After 60 days of lettuce growth, Cd accumulation and enzyme activities in tissues were analyzed. Results showed that biochar increased soil properties (pH, CEC and SOM) compared to un-amended soils, but decreased contents of bioavailable Cd in soil pore-water (Cdpore-water) and BCR extracted Cd (CdFi+Fii). Contents of Cdpore-water were lower in yellow-brown soils than that in red soils. Pearson analysis showed that bioavailable Cd is negatively correlated with soil pH and CEC (p < 0.05). Cd accumulation in lettuce roots and leaves both were decreased by biochar addition, and the established linear equations proved that soil Cdpore-water is the best predictor for Cd accumulation in lettuce roots (r2 = 0.964) and in leaves (r2 = 0.953), followed by CdFi+Fii. Transfer factor (TF) values of Cd from roots to leaves were lower than 1, and slightly better correlated with soil Cdpore-water (r = -0.674, p < 0.01) than CdFi+Fii (r = -0.615, p < 0.01). Aggregated boosted tree (ABT) analyses indicated that soil properties together with Cdpore-water contribute more than 50% to root enzyme activities. Collectively, soil Cdpore-water is a promising predictor of Cd bioavailability, accumulation and toxicity in soil-plant system with biochar addition.

High transparent mid-infrared silicon "window" decorated with amorphous photonic structures fabricated by facile phase separation.

High transparency in the infrared (IR) region is desirable for most common IR materials and devices, due to their high interfacial reflectance, resulting from the high refractive indices of constituent substances. Herein, a new strategy, with using phase-separated polystyrene (PS)/polymethylmethacrylate (PMMA) blends as masks, is proposed to fabricate subwavelength structures for Si with significantly enhanced mid-IR transmission. Maximum transmittance approaching to 70% and 90% are achieved with single and double- side structured Si respectively. The fabricated subwavelength structures are short-range ordered amorphous photonic structures (APSs). By using different spin-coating speeds and molar ratios of PS to PMMA and by adjusting the etching duration time, tunable enhanced transmission are also obtained. The good performance of high transmission is confirmed by mid-IR thermal imaging experiments. Furthermore, the enhanced transmission is effective over a wide range of incident angles up to 50° and well maintained at high temperatures up to 600 °C.

PHD/HIF-1 upregulates CA12 to protect against degenerative disc disease: a human sample, in vitro and ex vivo study.

Intervertebral disc degeneration is a major cause of low back pain. The nucleus pulposus (NP) is an important intervertebral disc component. Recent studies have shown that carbonic anhydrase 12 (CA12) is a novel NP marker. However, the mechanism by which CA12 is regulated and its physiological function are unclear. In our study, CA12, hypoxia-inducible factor 1α (HIF-1α) and HIF-2α expression levels were examined in 81 human degenerated NP samples using real-time RT-PCR, immunohistochemistry and western blot. Rat NP cells were cultured in a hypoxic environment, and hypoxia-induced CA12 expression was examined. Rat NP cells were treated with HIF-1α siRNA or the prolyl hydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) to evaluate the role of PHD/HIF-1 in regulating CA12 expression. Rat NP cells were treated with CA12 siRNA to determine the function of CA12. A rat ex vivo model was established to confirm that PHD, HIF-1, and CA12 have important roles in disc degeneration. We found that CA12 was significantly downregulated in degenerated human NP samples at the mRNA and protein levels. CA12 expression sharply increased by ~30-fold in response to hypoxia. The expression of HIF-1α, but not HIF-2α, also decreased in degenerated human NP samples and was positively correlated with CA12 expression. HIF-1α knockdown under hypoxia reduced the CA12 mRNA and protein expression levels. DMOG treatment increased HIF-1α and CA12 expression. CA12 knockdown significantly inhibited anabolic protein expression, whereas catabolic enzymes remained unchanged. The ex vivo experiments supported our in vitro studies of the role of PHD/HIF-1/CA12. In conclusion, CA12 is downregulated in degenerated NPs, and its expression may be regulated by the PHD/HIF-1 axis. Decreased CA12 expression may lead to decreased extracellular matrix synthesis, which contributes to degenerative disc disease progression.

Colorful solar selective absorber integrated with different colored units.

Solar selective absorbers are the core part for solar thermal technologies such as solar water heaters, concentrated solar power, solar thermoelectric generators and solar thermophotovoltaics. Colorful solar selective absorber can provide new freedom and flexibility beyond energy performance, which will lead to wider utilization of solar technologies. In this work, we present a monolithic integration of colored solar absorber array with different colors on a single substrate based on a multilayered structure of Cu/TiN(x)O(y)/TiO(2)/Si(3)N(4)/SiO(2). A colored solar absorber array with 16 color units is demonstrated experimentally by using combinatorial deposition technique via changing the thickness of SiO(2) layer. The solar absorptivity and thermal emissivity of all the color units is higher than 92% and lower than 5.5%, respectively. The colored solar selective absorber array can have colorful appearance and designable patterns while keeping high energy performance at the same time. It is a new candidate for a number of solar applications, especially for architecture integration and military camouflage.

Ethnic Differences in Preterm Birth Risks for Pregnant Women with Thyroid Dysfunction or Autoimmunity: A Meta-analysis.

OBJECTIVE: Abnormal maternal thyroid function is associated with preterm birth. However, this association stays dubious in relevant individual studies for ethnic difference reasons and lack of direct supporting data. This study aimed to evaluate the relationship between preterm birth and thyroid dysfunction or autoimmunity based on ethnic differences. METHODS: Relevant studies were identified through searches of MEDLINE, Excerpta Medica, Wan Fang, China Biological Medicine disc, and China National Knowledge Infrastructure from inception to June 15, 2016. Original articles in which an incidence or prevalence of thyroid dysfunction or autoimmunity before second trimester of pregnancy could be extracted were included. RESULTS: Thirty-two unique studies were included for the final meta-analysis. Patients involved were divided into two groups: Group 1 (G1) and Group 2 (G2) comprising of Asian and Caucasian populations, respectively. Positive thyroid antibodies were associated with the occurrence of preterm birth in both G1 [odds ratio (OR): 3.62, 95% confidence interval (CI): 2.83-4.65] and G2 (OR: 1.35, 95% CI: 1.17-1.56); hypothyroidism, only in G2 (OR: 1.20, CI: 1.09-1.33); and subclinical hypothyroidism or hypothyroxinemia, in neither group. CONCLUSION: Thyroid autoimmunity may be a more favorable factor leading to preterm birth among pregnant women of different ethnicities, compared with thyroid dysfunction.

Corrigendum: Role of non-coding RNA in the pathophysiology and treatment of intrauterine adhesion.

[This corrects the article DOI: 10.3389/fgene.2022.948628.].

Predictive modeling of perioperative blood transfusion in lumbar posterior interbody fusion using machine learning.

Background: Accurate estimation of perioperative blood transfusion risk in lumbar posterior interbody fusion is essential to reduce the number, cost, and complications associated with blood transfusions. Machine learning algorithms have the potential to outperform traditional prediction methods in predicting perioperative blood transfusion. This study aimed to construct a machine learning-based perioperative transfusion risk prediction model for lumbar posterior interbody fusion in order to improve the efficacy of surgical decision-making. Methods: We retrospectively collected clinical data on 1905 patients who underwent lumbar posterior interbody fusion surgery at the Second Hospital of Shanxi Medical University between January 2021 and March 2023. All the data was randomly divided into a training set and a validation set, and the "feature_importances" method provided by eXtreme Gradient Boosting (XGBoost) algorithm was applied to select statistically significant features on the training set to establish five machine learning prediction models. The optimal model was identified by utilizing the area under the curve (AUC) and the probability calibration curve on the validation set. Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME) were employed for interpretable analysis of the optimal model. Results: In the postoperative outcomes of patients, the number of hospital days in the transfusion group was longer than that in the non-transfusion group. Additionally, the transfusion group experienced higher total hospital costs, 90-day readmission rates, and complication rates within 90 days after surgery than the non-transfusion group. A total of 9 features were selected for the models. The XGBoost model performed best with an AUC value of 0.958. The SHAP values showed that intraoperative blood loss, intraoperative fluid infusion, and number of fused segments were the top 3 most important features affecting perioperative blood transfusion in lumbar posterior interbody fusion. The LIME algorithm was used to interpret the individualized prediction. Conclusion: Surgery, ASA class, levels fused, total intraoperative blood loss, operative time, and preoperative Hb are viable predictors of perioperative blood transfusion in lumbar posterior interbody fusion. The XGBoost model has demonstrated superior predictive efficacy compared to the traditional logistic regression model, making it a more effective decision-making tool for perioperative blood transfusion.

Terahertz Nonlinear Hall Rectifiers Based on Spin-Polarized Topological Electronic States in 1T-CoTe2.

The zero-magnetic-field nonlinear Hall effect (NLHE) refers to the second-order transverse current induced by an applied alternating electric field; it indicates the topological properties of inversion-symmetry-breaking crystals. Despite several studies on the NLHE induced by the Berry-curvature dipole in Weyl semimetals, the direct current conversion by rectification is limited to very low driving frequencies and cryogenic temperatures. The nonlinear photoresponse generated by the NLHE at room temperature can be useful for numerous applications in communication, sensing, and photodetection across a high bandwidth. In this study, observations of the second-order NLHE in type-II Dirac semimetal CoTe2 under time-reversal symmetry are reported. This is determined by the disorder-induced extrinsic contribution on the broken-inversion-symmetry surface and room-temperature terahertz rectification without the need for semiconductor junctions or bias voltage. It is shown that remarkable photoresponsivity over 0.1 A W-1 , a response time of approximately 710 ns, and a mean noise equivalent power of 1 pW Hz-1/2 can be achieved at room temperature. The results open a new pathway for low-energy photon harvesting via nonlinear rectification induced by the NLHE in strongly spin-orbit-coupled and inversion-symmetry-breaking systems, promising a considerable impact in the field of infrared/terahertz photonics.

A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aß42-induced cytotoxicity and increasing microglial phagocytosis.

Alzheimer's disease (AD) is characterized by progressive memory loss due to extracellular senile plaques and intracellular neurofibrillary tangles. The toxic ß-amyloid (Aß) aggregates that form in AD can induce the overproduction of reactive oxygen species (ROS), nitric oxide (NO), and proinflammatory cytokines. These Aß aggregates likely play a pivotal role in the onset and progression of AD. Reducing Aß generation, inhibiting Aß toxicity, and improving Aß clearance are promising therapeutic strategies for AD. The present paper is the first to reveal a heptapeptide (XD4) isolated from a Ph.D.-C7C library through phage display that significantly inhibited Aß cytotoxicity, increased the microglial phagocytosis of Aß, decreased the Aß-induced generation of ROS and NO, and attenuated the disequilibrium of calcium homeostasis in vitro. Remarkably, XD4 also attenuated memory deficits in ß-amyloid precursor protein/presenilin 1 (APPswe/PS1dE9) transgenic mice, and reduced amyloid plaque burden and Aß40/42 levels. The results of the present study indicate that this peptide, which specifically targets Aß, may be a promising new therapy for patients exhibiting cognitive impairment and increased Aß burden.

Role of noncoding RNA in the pathophysiology and treatment of intrauterine adhesion.

Intrauterine adhesion (IUA) is one of the most common diseases of the reproductive system in women. It is often accompanied by serious clinical problems that damage reproductive function, such as menstrual disorder, infertility, or recurrent abortion. The clinical effect of routine treatment is not ideal, and the postoperative recurrence rate is still very high. Therefore, exploring the pathological mechanism of IUA and finding new strategies for the effective prevention and treatment of IUA are needed. The main pathological mechanism of IUA is endometrial fibrosis and scar formation. Noncoding RNA (ncRNA) plays an important role in the fibrosis process, which is one of the latest research advances in the pathophysiology of IUA. Moreover, the exosomal miRNAs derived from mesenchymal stem cells can be used to improve IUA. This paper reviewed the role of ncRNAs in IUA pathogenesis, summarized the core pathways of endometrial fibrosis regulated by ncRNAs, and finally introduced the potential of ncRNAs as a therapeutic target.

Design of Multifunctional Janus Metasurface Based on Subwavelength Grating.

In this paper, a Janus metasurface is designed by breaking the structural symmetry based on the polarization selection property of subwavelength grating. The structure comprises three layers: a top layer having a metallic nanostructure, a dielectric spacer, and a bottom layer having subwavelength grating. For a forward incidence, the metal-insulator-metal (MIM) structure operates as a gap plasmonic cavity if the linearly polarized (LP) component is parallel to the grating wires. It also acts as a high-efficiency dual-layer grating polarizer for the orthogonal LP component. For the backward incidence, the high reflectance of the grating blocks the function of the gap plasmonic cavity, leading to its pure functioning as a polarizer. A bifunctional Janus metasurface for 45 degrees beam deflector and polarizer, with a transmission of 0.87 and extinction ratio of 3840, is designed at 1.55 µm and is investigated to prove the validity of the proposed strategy. Moreover, the proposed metasurface can be cascaded to achieve more flexible functions since these functions are independent in terms of operational mechanism and structural parameters. A trifunctional Janus metasurface that acts as a focusing lens, as a reflector, and as a polarizer is designed based on this strategy. The proposed metasurface and the design strategy provide convenience and flexibility in the design of multifunctional, miniaturized, and integrated optical components for polarization-related analysis and for detection systems.

Efficacy and safety of massage therapy for chronic atrophic gastritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic atrophic gastritis (CAG) is an established precursor of gastric carcinoma with high prevalence worldwide. It is a typical complex gastro-intestinal disease with multiple influence factors, of which exact mechanisms remain unelucidated. Therefore, an ideal strategy to relieve CAG is urgently needed. In recent years, massage therapy has been increasingly accepted by CAG patients due to its lower costs, fewer unwanted side effects and safety for clinical use. In this systematic review, we aim to evaluate the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating chronic atrophic gastritis: Wanfang and Pubmed Database, China National Knowledge Infrastructure Database, Cochrane Central register of controlled trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to September 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULT: This proposed study will evaluate the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. The outcomes will include changes in CAG relief and adverse effect. CONCLUSION: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.

Simultaneous Immobilization of Soil Cd(II) and As(V) by Fe-Modified Biochar.

Remediation of soil heavy metal by biochar has been extensively studied. However, few studies focused on the role of biochar on the co-immobilization of cadmium (Cd(II)) and arsenate (As(V)) and related soil nutrient availability. Remediation tests were conducted with three types of pristine and ferric trichloride (FeCl3) modified biochar (rice, wheat, and corn straw biochar) in Cd-As co-contaminated soil, with application rates of 1, 5, and 10% (w/w) and the incubation of 1, 7, 10, and 15 days. Using TCLP (Toxicity Characteristic Leaching Procedure) method, 10% of FeCl3 modified corn-straw derived biochar (FCB) had the highest immobilization efficiency of Cd(II) (63.21%) and As(V) (95.10%) after 10 days of the incubation. Iron-modified biochar immobilized higher fractions of water-soluble (F1) and surface-absorbed (F2) metal fractions than pristine biochar. For FCB amendment, Cd was mostly presented in the organic matter (OM) and sulfides associated (F4) and residual (F5) fractions (88.52%), as was found in the Fe-Al (oxides and hydroxides) (F3), F4, and F5 fractions (75.87%). FCB amendment increased soil pH values and available iron contents (p < 0.05), while no changes in soil available phosphorus content (p > 0.05). This study showed that FCB application reduces the environmental mobility of metals in Cd-As contaminated soil, while it also increases soil pH and available nutrient mobility, improving soil environmental quality and reducing remediation costs.

[Study on the effect of hydraulic delivery vertebroplasty on vertebral morphology and bone cement diffusion].

OBJECTIVE: To evaluate the effect of different bone cement injection methods during percutaneous vertebroplasty(PVP) on vertebral morphology and cement diffusion. METHODS: The clinical data of 52 patients with single-segment osteoporotic vertebral compression fracture treated from January 2016 to December 2017 were retrospectively analyzed. The patients were divided into hydraumatic group (28 cases) and pusher group (24 cases) according to bone cement injection method during PVP. By comparing visual analogue scale(VAS), height of anterior vertebral body, compression ratio, kyphosis angle before and after operation and analyzing filling ratio of bone cement in the first 1/3, median line and back 1/3 of the vertebral body in lateral X-rays and the conditions of bone cement diffusion in AP X-rays were to evaluate the effect of different bone cement injection methods on vertebral morphology and cement diffusion. RESULTS: Postoperative VAS was obviously improved in all patients and hydraumatic group was better than pusher group(P<0.05). Postoperative height of anterior vertebral body, compression ratio and kyphosis angle obviously restored in all patients while there was no significant difference between two groups(P>0.05). There was no significant difference in filling ratio of bone cement in the first 1/3 and median line of the vertebral body by lateral X-ray films between two groups(P>0.05), but in the back 1/3 of the vertebral body filling ratio of bone cement in hydraumatic group was better than in pusher group(P<0.05). The distribution of bone cement from AP X-ray films were more significant in hydraumatic group(P<0.05). CONCLUSIONS: Hydraulic delivery vertebroplasty (HDVP) has better clinical efficacy and it can guarantee sufficient distribution of bone cement into the fractured vertebra and preferably restore the morphology of vertebral body, which is worthy of clinical application.

An indoleamine 2, 3-dioxygenase siRNA nanoparticle-coated and Trp2-displayed recombinant yeast vaccine inhibits melanoma tumor growth in mice.

Therapeutic vaccine is a promising approach in cancer therapy. But tumor-associated antigen peptides have weak immunogenicity and cancer patients are often characterized by immunosuppression and tolerance, leading to less efficiency of immunotherapy. We here successfully developed indoleamine 2, 3-dioxygenase (IDO) siRNA nanoparticle-coated and tyrosinase-related protein 2 (Trp2)-displayed recombinant Saccharomyces cerevisiae (YCP). YCPs had positive charges with a diameter of approximately 5µm, resulting in selective phagocytosis by APC cells. YCP-delivered siRNA and Trp2 successfully escaped from phagosomes, efficiently inhibited IDO expression in DCs, promoted the immune reaction of T cell against Trp2, increased the secretion of proinflammatory cytokines such as IFN-γ,TNF-α, and IL-6, and decreased the generation of regulatory T cells. Moreover, YCPs significantly inhibited melanoma tumor growth by alleviating immune tolerance and promoting Trp2-specific CD8+ T cell immune response. These results suggest that Saccharomyces cerevisiae as a combined immunotherapeutic platform to simultaneously delivery IDO-siRNA and Trp2 epitope peptide is a promising vaccine system for melanoma treatment.

Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau.P301S mouse model of Alzheimer's disease and frontotemporal dementia.

BACKGROUND: Truncated mis-disordered tau protein plays an important role in the pathogenesis of Alzheimer's disease (AD) and frontotemporal dementia (FTD). Tau294-305, an epitope in the truncated tau, is essential for pathological tau-tau interaction and aggregation. A tau294-305-targeted approach may have beneficial effects in the treatment of AD and FTD. METHODS: In this study, we genetically fused tau294-305 epitope to the hepatitis B virus core protein (HBc) major immunodominant region (MIR) (with the resultant protein termed T294-HBc), and we subcutaneously immunized a Tau.P301S transgenic mouse model of FTD and AD with T294-HBc four times. The levels and characteristics of antibodies induced by T294-HBc were determined by enzyme-linked immunosorbent assay. The effect of T294-HBc on the cognitive deficits of Tau.P301S mice was tested using the Morris water maze test, novel object recognition, and a Y-maze test. Western blot analysis and IHC were applied to measure the effect of T294-HBc on tau pathologies and neuroinflammation in the mouse brains. RESULTS: The results showed that T294-HBc self-assembled into HBc chimeric virus-like particles (VLPs) with tau294-305 displayed on the surface and that it induced high antibody titers specifically against the mis-disordered truncated tau. Further investigation showed that these antibodies simultaneously bound to microtubule-binding regions 1-4 (MTBR1-4) [tau263-274, tau294-305, tau325-336, tau357-368 and tau294-305(P301S)]. Moreover, T294-HBc VLP vaccination significantly ameliorated memory and cognitive decline; reduced the levels of AT8-positive tau, truncated tau monomer, and oligomer; attenuated microgliosis and astrogliosis; and rescued synaptic deficits in Tau.P301S transgenic mice. CONCLUSIONS: T294-HBc VLP vaccine elicited strong immune response and alleviated cognitive deficits and neuropathology progression in Tau.P301S mice, indicating that the T294-HBc VLP vaccine has promising therapeutic potential for the treatment of AD and FTD.

Fruitless Wolfberry-Sprout Extract Rescued Cognitive Deficits and Attenuated Neuropathology in Alzheimer's Disease Transgenic Mice.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aß leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reducing Aß levels and inhibiting Aß-induced neurotoxicity are feasible therapeutic strategies for AD treatment. Wolfberry has been traditionally used as a natural antioxidant and anti-aging product. However, whether wolfberry species has therapeutic potential on AD remains unknown. METHOD: The effects of fruitless wolfberry-sprout extract (FWE) on Aß fibrillation and fibril disaggregation was measured by thioflavin T fluorescence and transmission electron microscope imaging; Aß oligomer level was determined by dot-blot; Cell viability and apoptosis was assessed by MTT and TUNEL assay. The levels of Aß40/42, oxidative stress biomarkers and inflammatory cytokines were detected by corresponding kits. 8-month-old male APP/PS1 mice and their age-matched WT littermates were treated with FWE or vehicle by oral administration (gavage) once a day for 4 weeks. Then the cognitive performance was determined using object recognition test and Y-maze test. The Aß burden and gliosis was evaluated by immunostaining and immunoblotting, respectively. RESULTS: FWE significantly inhibited Aß fibrillation and disaggregated the formed Aß fibrils, lowered Aß oligomer level and Aß-induced neuro-cytotoxicity, and attenuated oxidative stress in vitro. Oral administration of FWE remarkably improved cognitive function, reduced Aß burden, decreased gliosis and inflammatory cytokines release, and ameliorated oxidative stress in the brains of APP/PS1 mice. CONCLUSION: These findings indicate that FWE is a promising natural agent for AD treatment.