Novel antiviral discoveries for Japanese encephalitis virus infections through reporter virus-based high-throughput screening.

Japanese encephalitis (JE) caused by JE virus (JEV), remains a global public health concern. Currently, there is no specific antiviral drug approved for the treatment of JE. While vaccines are available for prevention, they may not cover all at-risk populations. This underscores the urgent need for prophylaxis and potent anti-JEV drugs. In this context, a high-content JEV reporter system expressing Nanoluciferase (Nluc) was developed and utilized for a high-throughput screening (HTS) of a commercial antiviral library to identify potential JEV drug candidates. Remarkably, this screening process led to the discovery of five drugs with outstanding antiviral activity. Further mechanism of action analysis revealed that cepharanthine, an old clinically approved drug, directly inhibited virus replication by blocking GTP binding to the JEV RNA-dependent RNA polymerase. Additionally, treatment with cepharanthine in mice models alleviated JEV infection. These findings warrant further investigation into the potential anti-JEV activity of cepharanthine as a new therapeutic approach for the treatment of JEV infection. The HTS method employed here proves to be an accurate and convenient approach that facilitates the rapid development of antiviral drugs.

Selective Oxidation of Alcohol to Valuable Aldehydes Using Water as a Promoter in a Photoelectrochemical Cell.

Artificial photoelectrochemistry (PEC) has emerged as a promising and efficient technology for the sustainable conversion of solar energy into chemicals. In this study, we present a refined PEC process that enables the highly selective and stable production of piperonal and other valuable aldehydes through the oxidation of the corresponding alcohols. By employing Fe2O3 or TiO2 as the photoanode material and 2,2,6,6-tetramethylpiperidinooxy (TEMPO) as a redox mediator in an H2O/acetonitrile solution, we achieve 100% selectivity and a >95% Faradaic efficiency for piperonal production from piperonyl alcohol (PA) oxidation. Remarkably, we reveal the enhancing effect on the PA oxidation reactivity of appropriate-amount water in the solvent as it plays a crucial role in inhibiting the photoelectron-hole recombination efficiency and facilitating charge transfer. Mechanistic analysis suggests that TEMPO-mediated PA oxidation involves the formation of •O2- radicals by the reduction of oxygen on the cathode, resulting in water as the sole byproduct. Furthermore, our PEC oxidation system exhibits applications on the 100%-selective production of various conjugated aldehydes, including 4-anisaldehyde, cuminaldehyde, and the vitamin B6 derivative. By implementing a TiO2//Fe2O3 dual-photoanode system, we achieve an enhanced piperonal production rate of 31.2 µmol h-1 cm-2 at 1.0 V vs Ag/Ag+ and demonstrate its stability over a 102 h cyclic test, ensuring near-quantitative yield. This research illuminates the potential of the PEC strategy as a generally applicable method for the efficient production of high-value aldehydes.

CfIRF8-like interacts with the TBK1/IKKε family protein and regulates host antiviral innate immunity.

The interferon regulatory factor (IRF) family, a class of transcription factors with key functions, are important in host innate immune defense and stress response. However, further research is required to determine the functions of IRFs in invertebrates. In this study, the coding sequence of an IRF gene was obtained from the Zhikong scallop (Chlamys farreri) and named CfIRF8-like. The open reading frame of CfIRF8-like was 1371 bp long and encoded 456 amino acids. Protein domain prediction revealed a typical IRF domain in the N-terminus of the CfIRF8-like protein and a typical IRF3 domain in the C-terminus. Multiple sequence alignment confirmed the conservation of the amino acid sequences of these two functional protein domains. Phylogenetic analysis showed that CfIRF8-like clustered with mollusk IRF8 proteins and then clustered with vertebrate IRF3, IRF4, and IRF5 subfamily proteins. Quantitative real-time PCR detected CfIRF8-like mRNA in all tested scallop tissues, with the highest expression in the gills. Simultaneously, the expression of CfIRF8-like transcripts in gills was significantly induced by polyinosinic-polycytidylic acid challenge. The results of protein interaction experiments showed that CfIRF8-like could directly bind the TBK1/IKKε family protein of scallop (CfIKK2) via its N-terminal IRF domain, revealing the presence of an ancient functional TBK1/IKKε-IRF signaling axis in scallops. Finally, dual-luciferase reporter assay results showed that the overexpression of CfIRF8-like in human embryonic kidney 293T cells could specifically activate the interferon ß promoter of mammals and the interferon-stimulated response element promoter in dose-dependent manners. The findings of this preliminary analysis of the signal transduction and immune functions of scallop CfIRF8-like protein lay a foundation for an in-depth understanding of the innate immune function of invertebrate IRFs and the development of comparative immunology. The experimental results also provide theoretical support for the breeding of scallop disease-resistant strains.

Counteracting health risks by Modulating Homeostatic Signaling.

Homeostasis was initially conceptualized by Bernard and Cannon around a century ago as a steady state of physiological parameters that vary within a certain range, such as blood pH, body temperature, and heart rate [1,2]. The underlying mechanisms that maintain homeostasis are explained by negative feedbacks that are executed by the neuronal, endocrine, and immune systems. At the cellular level, homeostasis, such as that of redox and energy steady state, also exists and is regulated by various cell signaling pathways. The induction of homeostatic mechanism is critical for human to adapt to various disruptive insults (stressors); while on the other hand, adaptation occurs at the expense of other physiological processes and thus runs the risk of collateral damages, particularly under conditions of chronic stress. Conceivably, anti-stress protection can be achieved by stressor-mimicking medicinals that elicit adaptive responses prior to an insult and thereby serve as health risk countermeasures; and in situations where maladaptation may occur, downregulating medicinals could be used to suppress the responses and prevent subsequent pathogenesis. Both strategies are preemptive interventions particularly suited for individuals who carry certain lifestyle, environmental, or genetic risk factors. In this article, we will define and characterize a new modality of prophylactic intervention that forestalls diseases via modulating homeostatic signaling. Moreover, we will provide evidence from the literature that support this concept and distinguish it from other homeostasis-related interventions such as adaptogen, hormesis, and xenohormesis.

Regulation of Tyrosinase Gene Expression by Retinoic Acid Pathway in the Pacific Oyster Crassostrea gigas.

Retinoic acid (RA) plays important roles in various biological processes in animals. RA signaling is mediated by two types of nuclear receptors, namely retinoic acid receptor (RAR) and retinoid x receptor (RXR), which regulate gene expression by binding to retinoic acid response elements (RAREs) in the promoters of target genes. Here, we explored the effect of all-trans retinoic acid (ATRA) on the Pacific oyster Crassostera gigas at the transcriptome level. A total of 586 differentially expressed genes (DEGs) were identified in C. gigas upon ATRA treatment, with 309 upregulated and 277 downregulated genes. Bioinformatic analysis revealed that ATRA affects the development, metabolism, reproduction, and immunity of C. gigas. Four tyrosinase genes, including Tyr-6 (LOC105331209), Tyr-9 (LOC105346503), Tyr-20 (LOC105330910), and Tyr-12 (LOC105320007), were upregulated by ATRA according to the transcriptome data and these results were verified by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. In addition, increased expression of Tyr (a melanin-related TYR gene in C. gigas) and Tyr-2 were detected after ATRA treatment. The yeast one-hybrid assay revealed the DNA-binding activity of the RA receptors CgRAR and CgRXR, and the interaction of CgRAR with RARE present in the Tyr-2 promoter. These results provide evidence for the further studies on the role of ATRA and the mechanism of RA receptors in mollusks.

Preparation of Battery-Grade FePO4·2H2O Using the Stripping Solution Generated from Resource Recycling of Bauxite Residue.

A novel process for the high-value-use of iron from bauxite residue was proposed in this work. The process was trying to use the iron-containing stripping solution generated during resource recycling of bauxite residue to produce battery-grade FePO4·2H2O product. Thermodynamics calculation indicates that Fe and P in the stripping solution mainly existed in the form of FeHPO4+, and the theoretical pH for the conversion reaction from FePO4·2H2O to Fe(OH)3 was 1.72. The optimal condition for the synthesis of FePO4·2H2O using the stripping solution was determined as: reaction pH of 0.8, reaction temperature of 90°C, Fe/P ratio of 1, and reaction time of 24 h. XRD result showed that the synthesized FePO4·2H2O was well-crystallized and perfectly matched with the characteristic peaks of FePO4·2H2O. Moreover, all the parameters of the synthesized iron phosphate meet the quality requirements of battery precursor.

Increased substantia nigra echogenicity correlated with visual hallucinations in Parkinson's disease: a Chinese population-based study.

As a noninvasive technique, transcranial sonography (TCS) of substantia nigra (SN) has gradually showed its effectiveness not only in diagnosis but also in understanding clinical features of Parkinson's Disease (PD). This study aimed to further evaluate TCS for clinical diagnosis of PD, and to explore the association between sonographic manifestations and visual hallucinations (VH). A total of 226 subjects including 141 PD patients and 85 controls were recruited. All participants received TCS. A series of rating scales to evaluate motor and non-motor symptoms were performed in PD patients. Results showed that 172 subjects were successfully assessed by TCS. The area of SN was greater in PD patients than that in controls (P < 0.001). As receiver-operating characteristic (ROC) curve analysis showed, the best cutoff value for the larger SN echogenicity size was 23.5 mm2 (sensitivity 70.3%, specificity 77.0%). Patients with VH had larger SN area (P = 0.019), as well as higher Non-Motor Symptoms Scale (NMSS) scores (P = 0.018). Moreover, binary logistic regression analysis indicated that SN hyperechogenicity (odds ratio = 4.227, P = 0.012) and NMSS scores (odds ratio = 0.027, P = 0.042) could be the independent predictors for VH. In conclusion, TCS can be used as an auxiliary diagnostic tool for Parkinson's disease. Increased SN echogenicity is correlated with VH in Parkinson's disease, possibly because the brain stem is involved in the mechanism in the onset of VH. Further studies are needed to confirm these findings.

Construction of Natural-Product-Like Cyclophane-Braced Peptide Macrocycles via sp3 C-H Arylation.

Cyclic peptides have provided one of the most important platforms for exploration of biorelevant chemical space between small molecules and biologics. However, in comparison with the design and synthesis of small molecules, chemists' ability to fine-tune the three-dimensional structures and properties of cyclic peptides lag far behind. Intrigued by cyclophane peptide natural products, we wondered whether the rigid, planar, and hydrophobic cyclophane motif could provide a new design element for the synthesis of cyclic peptides with well-behaved 3D structures. Herein, we report a generally applicable method for synthesis of natural-product-like cyclophane-braced peptide macrocycles via Pd-catalyzed intramolecular C(sp3)-H arylation with aryl iodides at the remote γ position of various N-terminal aliphatic amino acid units using a simple picolinamide directing group. Products of high structural and stereochemical complexity were quickly assembled from easily accessible peptide precursors prepared by standard solid phase peptide synthesis. Many of these peptide macrocycles show highly ordered structures as revealed by X-ray crystallography. Remarkably, the PA-directed C(sp3)-H cyclization reaction of unprotected peptide substrates carrying various free polar side chains proceeded with high efficiency and selectivity in aqueous media. This demonstrates not only the synthetic utility of Pd-catalyzed C(sp3)-H functionalization reactions, but also offers a valuable new orthogonal reactivity for peptide chemistry.

Low Thermal Expansion Modulated by Off-Stoichiometric Effect in Nonstoichiometric Laves Phase Hf0.87Ta0.13Fe2+x Compounds.

Materials with a low coefficient of thermal expansion (CTE) are extremely demanded in many fields, varying from microelectronics to space technology. Here we report a novel method to achieve low CTE, which differs essentially from the conventional way that uses additives with negative thermal expansion (NTE) to compensate for the positive CTE of the matrix. The stoichiometric Hf0.87Ta0.13Fe2+x (x = 0) shows a giant NTE, which is gradually suppressed with increasing x and finally changed to near-zero thermal expansion (ZTE) at x ≈ 0.4. The excess Fe was suggested to form anti-site defects by occupying the 4f sites. As revealed by electron spin resonance (ESR) spectra, the weakened NTE is closely related to a slower ferromagnetic (FM) ordering process than observed at x = 0. In addition, the CTE can be further tuned by introducing an extra α-Fe phase to achieve a low CTE (e.g., 3.3 ppm/K for x = 1.0) with markedly enhanced mechanical properties, beneficial to applications.

A new age-related cutoff of medial temporal atrophy scale on MRI improving the diagnostic accuracy of neurodegeneration due to Alzheimer's disease in a Chinese population.

BACKGROUND: Visual rating scales are still the most popular tools in assessing atrophy degrees of whole brain and lobes. However, the false negative rate of the previous cutoff score of visual rating scales was relatively high for detecting dementia of Alzheimer's type (DAT). This study aimed to evaluate the diagnostic value of new cutoffs of visual rating scales on magnetic resonance imaging for discriminating DAT in a Chinese population. METHODS: Out of 585 enrolled subjects, 296 participants were included and diagnosed as normal cognition (NC)(n = 87), 138 diagnosed as amnestic mild cognitive impairment (aMCI), and 71 as dementia of Alzheimer's type (DAT). Receiver operating characteristic (ROC) curve analyses were used to calculate the diagnostic value of visual rating sales (including medial temporal atrophy (MTA), posterior atrophy rating scale (PA),global cortical atrophy scale (GCA) and medial temporal-lobe atrophy index (MTAi))for detecting NC from DAT . RESULTS: Scores of MTA correlated to age and Mini-mental state examination score. When used to detect DAT from NC, the MTA showed highest diagnostic value than other scales, and when the cutoff score of 1.5 of MTA scale, it obtained an optimal sensitivity (84.5%) and specificity (79.1%) respectively, with a 15.5% of false negative rate. Cutoff scores and diagnostic values were calculated stratified by age. For the age ranges 50-64, 65-74, 75-84 years, the following cut-offs of MTA should be used, ≥1.0(sensitivity and specificity were 92.3 and 68.4%), ≥1.5(sensitivity and specificity were 90.4 and 85.2%), ≥ 2.0(sensitivity and specificity were 70.8 and 82.3%) respectively. All of the scales showed relatively lower diagnostic values for discriminating aMCI from NC. CONCLUSIONS: The new age-based MTA cutoff showed better diagnostic accuracy for detecting DAT than previous standard, the list of practical cut-offs proposed here might be useful in clinical practice.

Adding Chinese herbal medicine to conventional therapy brings cognitive benefits to patients with Alzheimer's disease: a retrospective analysis.

BACKGROUND: Conventional therapy (CT) such as donepezil and memantine are well-known short-term treatments for the symptoms of Alzheimer's disease (AD). The efficacy of them, however, drops below baseline level after 9 months. In China, herbal therapy as a complementary therapy is very popular. Should conventional therapy combined with herbal therapy (CT + H) make add-on benefit? METHODS: In this retrospective cohort study, 344 outpatients diagnosed as probable dementia due to AD were collected, with the treatment of either CT + H or CT alone in clinical settings. All the patients were examined with coronary MRI scan. Cognitive functions were obtained by mini-mental state examination (MMSE) every 3 months with the longest follow-up of 24 months. RESULTS: Most of the patients were initially diagnosed with mild (MMSE = 21-26, n = 177) and moderate (MMSE = 10-20, n = 137) dementia. At 18 months, CT+ H patients scored on average 1.76 (P = 0.002) better than CT patients, and at 24 months, patients scored on average 2.52 (P < 0.001) better. At 24 months, the patients with improved cognitive function (△MMSE ≥ 0) in CT + H was more than CT alone (33.33% vs 7.69%, P = 0.020). Interestingly, patients with mild AD received the most robust benefit from CT + H therapy. The deterioration of the cognitive function was largely prevented at 24 months (ΔMMSE = -0.06), a significant improvement from CT alone (ΔMMSE = -2.66, P = 0.005). CONCLUSIONS: Compared to CT alone, CT + H significantly benefited AD patients. A symptomatic effect of CT + H was more pronounced with time. Cognitive decline was substantially decelerated in patients with moderate severity, while the cognitive function was largely stabilized in patients with mild severity over two years. These results imply that Chinese herbal medicines may provide an alternative and additive treatment for AD.

Palladium-catalyzed ß-C(sp(3))-H arylation of phthaloyl alanine with hindered aryl iodides: synthesis of complex ß-aryl α-amino acids.

An efficient protocol for palladium-catalyzed ß-C(sp(3))-H arylation of aliphatic carboxamides equipped with a 2-(2-pyridyl) ethylamine (PE) auxiliary was developed. The PE auxiliary is uniquely effective at facilitating the arylation of primary C(sp(3))-H bonds with sterically hindered aryl iodides. A variety of aryl iodides bearing alkoxyl, carbonyl, nitro and halogen groups on the ortho position can react with the PE-coupled phthaloyl alanine substrate in moderate to excellent yield. These reactions offer a useful solution for preparing complex ß-aryl α-amino acid products from readily accessible starting materials.

Herbal formula GAPT prevents beta amyloid deposition induced Ca(2+)/Calmodulin-dependent protein kinase II and Ca(2+)/Calmodulin-dependent protein phosphatase 2B imbalance in APPV717I mice.

BACKGROUND: Synaptic dysfunction is one of the pathological characteristics of Alzheimer's disease (AD), which is directly related to the progressive decline of cognitive function. CaMKII and CaN have been found to play important roles in memory processes and synaptic transmission. So present study aimed to elucidate relationships between CaMKII, CaN and cognitive decline in APPV717I mice, and to reveal whether the cognitive improving effects of GAPT is conducted through rebalance CaMKII and CaN. METHODS: Three-month-old-male APPV717I mice were randomly divided into ten groups (n = 12 per group) and received intragastrically administrated vehicle, donepezil or different doses of herbal formula GAPT for 8 or 4 months. Three-month-old male C57BL/6 J mice was set as vehicle control. RESULTS: Immunohistochemistry analysis showed that there were CaMKII expression decrease in the CA1 region of APPV717I transgenic mice, while the CaMKII expression of donepezil or GAPT treated transgenic mice were all increased. And there were CaN expression increase in the brain cortex of APPV717I transgenic mice, while there were decrease of CaN expression in donepezil or GAPT treated transgenic group. Western blot analysis showed the similar expression pattern without significant difference. CONCLUSION: GAPT extract have showed effectiveness in activating the expression of CaMKII and inhibiting the expression of CaN either before or after the formation of amyloid plaques in the brain of APPV717I transgenic mice, which may in certain way alleviated neuron synaptic dysfunction in AD.

The Chinese version of story recall: a useful screening tool for mild cognitive impairment and Alzheimer's disease in the elderly.

BACKGROUND: Decline in verbal episodic memory is a core feature of amnestic mild cognitive impairment (aMCI). The delayed story recall (DSR) test from the Adult Memory and Information Processing Battery (AMIPB) discriminates MCI from normal aging and predicts its conversion to Alzheimer's dementia. However, there is no study that validates the Chinese version of the DSR and reports cut-off scores in the Chinese population. METHODS: A total of 631 subjects were screened in the memory clinics of Dongzhimen Hospital, Beijing University of Chinese Medicine, China. 249 were considered to have normal cognition (NC), 134 met diagnostic criteria for MCI according to the MCI Working Group of the European Consortium on Alzheimer's Disease, and 97 met criteria for probable Alzheimer's disease (AD) according to the NINCDS/ADRDA criteria, 14 exhibited vascular dementia (VaD), and 50 had a diagnosis of another type of dementia. Receiver operating characteristic (ROC) curve analyses were used to calculate the story recall cutoff score for detecting MCI and AD. Normative data in the NC group were obtained as a function of age and education. RESULTS: In this Chinese sample, the normative mean DSR score was 28.10 ± 8.54 in the 50-64 year-old group, 26.22 ± 8.38 in the 65-74 year-old group, and 24.42 ± 8.38 in the 75-85 year-old group. DSR performance was influenced by age and education. The DSR test had high sensitivity (0.899) and specificity (0.799) in the detection of MCI from NC using a cut-off score of 15.5. When the cutoff score was 10.5, the DSR test obtained optimal sensitivity (0.980) and specificity (0.938) in the discrimination of AD from NC. Cutoff scores and diagnostic values were calculated stratified by age and education. CONCLUSIONS: The Chinese version of the DSR can be used as a screening tool to detect MCI and AD with high sensitivity and specificity, and it could be used to identify people at high risk of cognitive impairment.

Clean and efficient synthesis of LiFePO4 cathode material using titanium white waste and calcium dihydrogen phosphate.

Large amounts of titanium white waste are generated in the production of titanium dioxide using sulphate method, which in turn can be used to prepare LiFePO4 cathode material, thereby reducing environmental risks and achieving resource recovery. However, a key challenge lies in the elimination of impurities. In this work, a cost-efficient and straightforward approach based on phase transformation during hydrothermal treatment was proposed to utilize titanium white waste with calcium dihydrogen phosphate for the preparation of LiFePO4 cathode material. The content of Fe in the leachate was enriched to 81.5 g/L after purification, while 99.9 % of Ti and 98.36 % of Al and were successfully removed. In the subsequent process for Fe/P mother liquor preparation, the losses of Fe and P were only 5.82 % and 2.81 %, respectively. The Fe and P contents of the synthesized FePO4 product were 29.47 % and 17.08 %, respectively, and the Fe/P molar ratio was 0.986. Crystal phase of the product matched well with standard iron phosphate, and the lamellar microstructure of FePO4 was uniform with the particle size ranging from 3 to 5 µm. Moreover, the contents of impurities in the product were far below the standard. The initial discharge of LiFePO4 synthesized by the iron phosphate was 160.6 mAh.g-1 at 0.1C and maintained good reversible capacity after 100 cycles. This work may provide new strategy for preparing LiFePO4 cathode material from industrial solid waste.

A highly effective ferritin-based divalent nanoparticle vaccine shields Syrian hamsters against lethal Nipah virus.

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.

A combination extract of Renshen (Panax Ginseng), Yinyanghuo (Herba Epimedii Brevicornus), Yuanzhi (Radix Palygalae) and Jianghuang (Rhizoma Curcumae Longae) decreases glycogen synthase kinase 3beta expression in brain cortex of APPV7171 transgenic mice.

OBJECTIVE: To investigate the neuroprotective mechanism of combination extract of Renshen (Panax Ginseng), Yinyanghuo (Herba Epimedii Brevicornus), Yuanzhi (Radix Palygalae) and Jianghuang (Rhizoma Curcumae Longae) (GEPT) in treating Alzheimer's disease on the target of glycogen synthase kinase 3beta (GSK-3beta). METHODS: Three-month-old APPV7171 transgenic mice were randomly divided into ten groups (n = 12 per group) and intragastrically administrated vehicle or medicines: APP group was given 0.5% CMC, donepezil group was given donepezil (APP + D group) (0.92 mg/kg(-1) x day(-1)), and GEPT groups were given small dose of GEPT (APP+Gs group) (0.075 g/ kg(-1) x day(-1)), medium dose (APP+Gm group) (0.15 g/ kg(-1) day(-1)), and large dose (APP+GI group) (0.30 g/ kg(-1) x day(-1)) for 4 or 8 months, respectively. Three-month-old C57BL/6J mice as vehicle controls (n=12) were given 0.5% CMC for 4 or 8 months as well. The GSK-3beta expression in the cortex of 7- and 11-month-old APPV7171 transgenic mice with and without GEPT or donepezil treatment and normal C57BL/6J mice were measured via Western blotting and Immunohistochemistry. RESULTS: Immunohistochemistry analysis showed significant increase of GSK-3beta in the cerebral cortex of 7-month-old APP group (compare to control group P = 0.003), while the GSK-3beta expression of donepezil or GEPT group were all significantly decreased (Donepezil vs APP: P = 0.041; GI vs APP: P = 0.049; Gm vs APP: P = 0.029; Gh vs APP: P = 0.036). Western blot analysis showed similar results. The densitometric measures of GSK-3beta in APP mice increased significantly as compared with the control group (P = 0.008). And the GSK-3beta expression in donepezil and GEPT groups were all decreased. There was significant difference between Gh group or donepezil group and the control group (P = 0.05). Similar findings were shown in the 11-month-old mice in each group, except for greater decrease of GSK-3beta in the GEPT group. CONCLUSION: GEPT can effectively decrease the level of GSK-3beta expression in the brain cortex of APPV7171 transgenic mice, and such effect is more significant in 11-month-old mice. This partially explains the neuroprotecting mechanism of GEPT in preventing and treating of AD.

Recovery of iron and aluminum from iron-rich bauxite residue by an integrated phase reconstruction approach.

The comprehensive recovery of iron and aluminum from iron-rich bauxite residue (IRBR) is of critical importance both in terms of resource utilization and environment protection, which, however, is challenging due to the intertwined phases between Iron and aluminum. In this study, an integrated phase reconstruction approach, consisting of alkali roasting, two-stage column leaching, and carbonation decomposition, was proposed for Fe/Al recovery from IRBR. The results demonstrated that aluminum and sodium were fused into soluble substances such as sodium aluminate (Na7Al3O8, NaAlO2, and Na2O (Al2O3)11) in the alkali roasting process, allowing for the separation of Al and Fe in the subsequent leaching process. Following water/FeCl3 solution leaching, the removal efficiency of aluminum reached 84.66%, and Fe content in the residue could be enriched to 55.56%. Fe can be recycled as iron concentrate, and Al in the leaching solution with 75.95 g/L can be recovered in the form of Al(OH)3 through carbonation decomposition. This work provides an alternative strategy for the recovery of resources from IRBR, with potential implications for the sustainable development of the aluminum industry.

Identification and characterization of gonadotropin-releasing hormone (GnRH) in Zhikong scallop Chlamys farreri during gonadal development.

Gonadotropin-releasing hormone (GnRH) controls synthesis of sex steroid hormones through hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. But in mollusks, research on neuroendocrine control of gonadal function, such as the function of GnRH during gonadal development is limited. In this study, we investigated the morphology and structure of the nerve ganglia of Zhikong scallop Chlamys farreri by physiological and histological observations. We also cloned the ORF and studied the expression patterns of GnRH in the scallop. Tissue expression analysis showed that GnRH was highly expressed in parietovisceral ganglion (PVG). The in situ hybridization result further confirmed that GnRH mRNA only distributed in some good-sized neurons in the posterior lobe (PL) and some pint-sized neurons in the lateral lobe (LL). In addition, by examining the expression of GnRH during gonadal development in ganglia, we found GnRH displayed higher expression in the female scallops, and showed significant high expression at the growing stage of female scallops in PVG. This study would contribute to gaining insight into the mechanism underlying reproduction regulation by GnRH in the scallop and help to provide a better understanding of reproductive neuroendocrine in mollusks.

Evolution of Immune Evasion and Host Range Expansion by the SARS-CoV-2 B.1.1.529 (Omicron) Variant.

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has rapidly become the dominant strain, with an unprecedented number of mutations within its spike gene. However, it remains unknown whether these variants have alterations in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies and entry inhibitors. In this study, we found that Omicron spike has evolved to escape neutralization by three-dose inactivated-vaccine-elicited immunity but remains sensitive to an angiotensin-converting enzyme 2 (ACE2) decoy receptor. Moreover, Omicron spike could use human ACE2 with a slightly increased efficiency while gaining a significantly increased binding affinity for a mouse ACE2 ortholog, which exhibits limited binding with wild-type (WT) spike. Furthermore, Omicron could infect wild-type C57BL/6 mice and cause histopathological changes in the lungs. Collectively, our results reveal that evasion of neutralization by vaccine-elicited antibodies and enhanced human and mouse ACE2 receptor engagement may contribute to the expanded host range and rapid spread of the Omicron variant. IMPORTANCE The recently emerged SARS-CoV-2 Omicron variant with numerous mutations in the spike protein has rapidly become the dominant strain, thereby raising concerns about the effectiveness of vaccines. Here, we found that the Omicron variant exhibits a reduced sensitivity to serum neutralizing activity induced by a three-dose inactivated vaccine but remains sensitive to entry inhibitors or an ACE2-Ig decoy receptor. Compared with the ancestor strain isolated in early 2020, the spike protein of Omicron utilizes the human ACE2 receptor with enhanced efficiency while gaining the ability to utilize mouse ACE2 for cell entry. Moreover, Omicron could infect wild-type mice and cause pathological changes in the lungs. These results reveal that antibody evasion, enhanced human ACE2 utilization, and an expanded host range may contribute to its rapid spread.