Recombinant parainfluenza virus 5 expressing clade 2.3.4.4b H5 hemagglutinin protein confers broad protection against H5Ny influenza viruses.

The global circulation of clade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) in poultry and wild birds, increasing mammal infections, continues to pose a public health threat and may even form a pandemic. An efficacious vaccine against H5Ny HPAIVs is crucial for emergency use and pandemic preparedness. In this study, we developed a parainfluenza virus 5 (PIV5)-based vaccine candidate expressing hemagglutinin (HA) protein of clade 2.3.4.4b H5 HPAIV, termed rPIV5-H5, and evaluated its safety and efficacy in mice and ferrets. Our results demonstrated that intranasal immunization with a single dose of rPIV5-H5 could stimulate H5-specific antibody responses, moreover, a prime-boost regimen using rPIV5-H5 stimulated robust humoral, cellular, and mucosal immune responses in mice. Challenge study showed that rPIV5-H5 prime-boost regimen provided sterile immunity against lethal clade 2.3.4.4b H5N1 virus infection in mice and ferrets. Notably, rPIV5-H5 prime-boost regimen provided protection in mice against challenge with lethal doses of heterologous clades 2.2, 2.3.2, and 2.3.4 H5N1, and clade 2.3.4.4h H5N6 viruses. These results revealed that rPIV5-H5 can elicit protective immunity against a diverse clade of highly pathogenic H5Ny virus infection in mammals, highlighting the potential of rPIV5-H5 as a pan-H5 influenza vaccine candidate for emergency use.IMPORTANCEClade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) have been widely circulating in wild birds and domestic poultry all over the world, leading to infections in mammals, including humans. Here, we developed a recombinant PIV5-vectored vaccine candidate expressing the HA protein of clade 2.3.4.4b H5 virus. Intranasal immunization with rPIV5-H5 in mice induced airway mucosal IgA responses, high levels of antibodies, and robust T-cell responses. Importantly, rPIV5-H5 conferred complete protection in mice and ferrets against clade 2.3.4.4b H5N1 virus challenge, the protective immunity was extended against heterologous H5Ny viruses. Taken together, our data demonstrate that rPIV5-H5 is a promising vaccine candidate against diverse H5Ny influenza viruses in mammals.

Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals.

Avian influenza virus (AIV) can evolve multiple strategies to combat host antiviral defenses and establish efficient infectivity in mammals, including humans. H9N2 AIV and its reassortants (such as H5N6 and H7N9 viruses) pose an increasing threat to human health; however, the mechanisms involved in their increased virulence remain poorly understood. We previously reported that the M1 mutation T37A has become predominant among chicken H9N2 isolates in China. Here, we report that, since 2010, this mutation has also been found in the majority of human isolates of H9N2 AIV and its emerging reassortants. The T37A mutation of M1 protein enhances the replication of H9N2 AIVs in mice and in human cells. Interestingly, having A37 instead of T37 increases the M1 protein stability and resistance to proteasomal degradation. Moreover, T37 of the H9N2 M1 protein is phosphorylated by protein kinase G (PKG), and this phosphorylation induces the rapid degradation of M1 and reduces viral replication. Similar effects are also observed in the novel H5N6 virus. Additionally, ubiquitination at K187 contributes to M1-37T degradation and decreased replication of the virus harboring T37 in the M1 protein. The prevailing AIVs thereby evolve a phospho-resistant mutation in the M1 protein to avoid viral protein degradation by host factors, which is advantageous in terms of replication in mammalian hosts.

Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection.

Pigs are considered as important hosts or "mixing vessels" for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.

Cucurbitacin IIb Extracted from Hemsleya penxianensis Induces Cell Cycle Arrest and Apoptosis in Bladder Cancer Cells by Regulating Cell Cycle Checkpoints and Mitochondrial Apoptotic Pathway.

Cucurbitacin IIb (CuIIb) extracted from Hemsleya penxianensis has been demonstrated anticancer activity in many malignancies, however, its effect against bladder cancer cells and the molecular mechanism remains unclear. Accordingly, in the present study, we evaluated the effect and further the underlying mechanism of CuIIb on bladder cancer cells. Cell viability and clonogenicity were examined to evaluate growth suppressive effect of CuIIb, alongside mechanism exploration was conducted based on RNA sequencing (RNA-seq). The results showed that CuIIb exposure inhibited the growth of T24 and UM-UC-3 bladder cancer cells as indicated by its obvious suppression on cell viability and clonogenicity. Mechanistic studies by RNA-seq and quantifying analysis of RNA-seq data by TMNP indicated cell cycle modulated by cell cycle checkpoints and apoptosis mediated by PI3K/Akt pathway might account for the anticancer activity of CuIIb. Consistently, results of flow cytometry and AO/EB staining demonstrated that the growth-suppressive effect of CuIIb was mediated by cell cycle arrest in G2/M phase and robust induction of cell apoptosis, which was further confirmed by immunoblotting and mitochondrial membrane potential (ΔΨm) analysis. Collectively, the results presented herein indicated that CuIIb exhibited anticancer activity on bladder cancer which may be a potential candidate for improving bladder cancer outcomes.

Tracking Three Decades of Global Neodymium Stocks and Flows with a Trade-Linked Multiregional Material Flow Analysis.

Neodymium (Nd), an essential type of rare earth element, has attracted increasing attention in recent years due to its significant role in emerging technologies and its globally imbalanced demand and supply. Understanding the global and regional Nd stocks and flows would thus be important for understanding and mitigating potential supply risks. In this work, we applied a trade-linked multiregional material flow analysis to map the global and regional neodymium cycles from 1990 to 2020. We reveal increasingly complex trade patterns of Nd-containing products and a clearly dominant but slightly weakening role of China in the global Nd trade (for both raw materials and semi- and final products) along the life cycle in the last 30 years. A total of 880 kt Nd was mined accumulatively and flowed into the global socioeconomic system, mainly as NdFeB permanent magnets (79%) in semi-products and conventional vehicles and home appliances (together 48%) in final products. Approximately 64% (i.e., 563 kt Nd) of all the mined Nd globally were not recycled, indicating a largely untapped potential of recycling in securing Nd supply and an urgency to overcome the present technological and non-technical challenges. The global Nd cycle in the past three decades is characterized by different but complementary roles of different regions along the global Nd value chain: China dominates in the provision of raw materials and semi- and final products, Japan focuses on the manufacturing of magnets and electronics, and the United States and European Union show advantages in the vehicle industry. Anticipating increasing demand of Nd in emerging energy and transport technologies in the future, more coordinated efforts among different regions and increased recycling are urgently needed for ensuring both regional and global Nd supply and demand balance and a common green future.

Comprehensive Engineering Frequency Domain Analysis and Vibration Suppression of Flexible Aircraft Based on Active Disturbance Rejection Controller.

The crash of an aircraft with an almost vertical attitude in Wuzhou, Guangxi, China, on 21 March 2022, has caused a robust discussion in the civil aviation community. We propose an active disturbance rejection controller (ADRC) for suppressing aeroelastic vibrations of a flexible aircraft at the simulation level. The ADRC has a relatively simple structure and it has been proved in several fields to provide better control than the classical proportional-integral-derivative (PID) control theory and is easier to translate from theory to practice compared with other modern control theories. In this paper, the vibration model of the flexible aircraft was built, based on the first elastic vibration mode of the aircraft. In addition, the principle of ADRC is explained in detail, a second-order ADRC was designed to control the vibration model, and the system's closed-loop frequency domain characteristics, tracking effect and sensitivity were comprehensively analyzed. The estimation error of the extended state observer (ESO) and the anti-disturbance effect were analyzed, while the robustness of the closed-loop system was verified using the Monte Carlo method, which was used for the first time in this field. Simulation results showed that the ADRC suppressed aircraft elastic vibration better than PID controllers and that the closed-loop system was robust in the face of dynamic parameters.

Cold adaptation in drylands: transcriptomic insights into cold-stressed Nostoc flagelliforme and characterization of a hypothetical gene with cold and nitrogen stress tolerance.

Environmental stressors, especially low temperature, are very common on the earth's dryland systems. Terrestrial cyanobacteria have evolved with cold adaptability in addition to extreme dryness and high irradiation resistance. The dryland soil surface-dwelling species, Nostoc flagelliforme, serves as a potential model organism to gain insights into cyanobacterial cold adaptation. In this study, we performed transcriptomic analysis of N. flagelliforme samples in response to low temperature. The results revealed that the biological processes, such as terpenoid biosynthetic process, oxidoreductase activity, carbohydrate metabolism, biosynthesis of secondary metabolites, lipid and nitrogen metabolism, were significantly and dynamically changed during the cold stress. It was noteworthy that the transcription of the denitrification pathway for ammonia accumulation was enhanced, implying an importance for nitrogen utilization in stress resistance. In addition, characterization of a cold-responsive hypothetical gene csrnf1 found that it could greatly improve the cold-resistant performance of cells when it was heterologously expressed in transgenic Nostoc sp. PCC 7120. It was also found that csrnf1 transgenic strain exhibited resistance to nitrogen-deficient environmental stress. Considering that dryland cyanobacteria have to cope with low temperature on infertile soils, this study would enrich our understanding on the importance of multifunction of the genes for environmental cold adaptation in drylands.

Truncation of PA-X Contributes to Virulence and Transmission of H3N8 and H3N2 Canine Influenza Viruses in Dogs.

Equine-origin H3N8 and avian-origin H3N2 canine influenza viruses (CIVs) prevalent in dogs are thought to pose a public health threat arising from intimate contact between dogs and humans. However, our understanding of CIV virulence is still limited. Influenza A virus PA-X is a fusion protein encoded in part by a +1 frameshifted open reading frame (X-ORF) in segment 3. The X-ORF can be translated in full-length (61-amino-acid) or truncated (41-amino-acid) form. Genetic analysis indicated that the X-ORFs of equine H3N8 and avian H3N2 influenza viruses encoded 61 amino acids but were truncated after introduction into dogs. To determine the effect of PA-X truncation on the biological characteristics of CIVs, we constructed four recombinant viruses on H3N8 and H3N2 CIV backgrounds bearing truncated or full-length PA-Xs. We observed that truncation of PA-X increased growth of both H3N8 and H3N2 CIVs in MDCK cells and suppressed expression from cotransfected plasmids in MDCK cells. Furthermore, truncation of PA-X enhanced viral pathogenicity in dogs, as shown by aggravated clinical symptoms and histopathological changes, increased viral replication in the respiratory system, and prolonged virus shedding. Additionally, CIVs with truncated PA-Xs were transmitted more efficiently in dogs. Global gene expression profiling of the lungs of infected dogs revealed that differentially expressed genes were mainly associated with inflammatory responses, which might contribute to the pathogenicity of PA-X-truncated CIVs. Our findings revealed that truncation of PA-X might be important for the adaptation of influenza viruses to dogs.IMPORTANCE Epidemics of equine-origin H3N8 and avian-origin H3N2 influenza viruses in canine populations are examples of successful cross-species transmission of influenza A viruses. Genetic analysis showed that the PA-X genes of equine H3N8 or avian H3N2 influenza viruses were full-length, with X-ORFs encoding 61 amino acids; however, those of equine-origin H3N8 or avian-origin H3N2 CIVs were truncated, suggesting that PA-X truncation occurred after transmission to dogs. In this study, we extended the PA-X genes of H3N8 and H3N2 CIVs and compared the biological characteristics of CIVs bearing different lengths of PA-X. We demonstrated that for both H3N8 and H3N2 viruses, truncation of PA-X increased virus yields in MDCK cells and enhanced viral replication, pathogenicity, and transmission in dogs. These results might reflect enhanced suppression of host gene expression and upregulation of genes related to inflammatory responses. Collectively, our data partially explain the conservation of truncated PA-X in CIVs.

Isolation, X-ray crystal structure of the new diterpene and identification of others lignans and flavonoids from the fresh needles of Pinus massoniana.

Three new compounds, namely massonside C (1), massonianoside F (2), and 3, 8-dimethyl- herbacetin-7-O-ß-D-glucopyranoside (3), together with five known compounds (4-8), were isolated from the fresh needles of Pinus massoniana. Their structures were established by 1D, 2D NMR, HRMS and comparison with the literature data. The absolute configuration of 1 was confirmed by a combination of X-ray single crystal analysis. All isolated compounds were evaluated for the protective effect of human umbilical vein endothelial cells against oxidative damage.

Effect of kallikrein on microcirculation of rats with pancreatic ischemia reperfusion injury (IRI).

The common pathway for pancreatitis onset is pancreatic ischemia reperfusion injury (IRI), which plays an especially significant role in the evolution process from acute edematous pancreatitis (AP) towards severe acute pancreatitis (SAP). This study explored the effect of Kallikrein (PK) on pancreatic ischemia reperfusion injury (IRI). Male Wistar rats were taken as study objects, and a SAP -IRI combined model was established through retrograde infusion of 5% sodium taurocholate in biliopancreatic duct combining 30 min splenic artery clipping; drug intervention was carried out by pumping PK into rat caudal vein. Pancreatic microcirculation blood flow, pancreatic micro vascular permeability, hemorheological change and levels of adherence factors CD18 and CD54 were determined respectively. PK can obviously improve pancreatic microcirculation blood flow volume and velocity of IRI rats and expand arteriole; expand diameter of pancreatic blood capillary so that perfusion state tends to be stable; decrease pancreatic micro vascular permeability, reduce rat whole blood viscosity, erythrocyte deformation index and rigidity index; SAP-IRI combination reduces expression levels of white cell adhesion factor CD18 and vascular endothelial cell adhesion cell CD54 in rats. In conclusion, PK is an effective method of improving SAP pancreatic IRI microcirculation.

Prevailing I292V PB2 mutation in avian influenza H9N2 virus increases viral polymerase function and attenuates IFN-ß induction in human cells.

Adaptation of PB2 protein is important for the establishment of avian influenza viruses in mammalian hosts. Here, we identify I292V as the prevalent mutation in PB2 of circulating avian H9N2 and pandemic H1N1 viruses. The same dominant PB2 mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses. In human cells, PB2-292V in H9N2 virus has the combined ability of conferring higher viral polymerase activity and stronger attenuation of IFN-ß induction than that of its predecessor PB2-292I. IFN-ß attenuation is accompanied by higher binding affinity of PB2-292V for host mitochondrial antiviral signalling protein, an important intermediary protein in the induction of IFN-ß. In the mouse in vivo model, PB2-292V mutation increases H9N2 virus replication with ensuing increase in disease severity. Collectively, PB2-292V is a new mammalian adaptive marker that promotes H9N2 virus replication in mammalian hosts with the potential to improve transmission from birds to humans.

Detection of nitroaromatics in aqueous media based on luminescence resonance energy transfer using upconversion nanoparticles as energy donors.

Upconversion nanoparticle (UCNP)-based luminescence resonance energy transfer (LRET) systems are a powerful tool widely used to detect organic molecules or metal ions because of their simplicity and high sensitivity. The sandwich structure NaYF4:Er3+,Yb3+@NaYF4@NH2 UCNPs, as a highly selective and sensitive aqueous probe for detecting nitroaromatics, has been designed and prepared by a cothermolysis method and modified with polyetherimide to acquire amine groups on the surface of the core/shell UCNPs. The detection principle of nitroaromatics is based on LRET, which forms the Meisnheimer complex between the electron-deficient cyclobenzene of nitroaromatics and the electron-rich amino group on the surface of the sandwich structure UCNPs. As a consequence, nitroaromatics can be brought into close proximity to the sandwich structure UCNPs. With the increase of nitroaromatics (2,4,6-trinitrophenol and 2,4,6-trinitrotoluene) concentrations, the sandwich structure NaYF4:Er3+,Yb3+@NaYF4@NH2 UCNPs display a dramatic luminescent quenching effect at 407 nm and 540 nm under 980 nm excitation. The luminescent quenching intensity of the sandwich structure UCNPs is linearly correlated to the concentration of the nitroaromatics. The detection limit of 2,4,6-trinitrophenol (TNP) and 2,4,6-trinitrotoluene (TNT) are 0.78 and 0.77 ng ml-1, respectively. Therefore, the sandwich structure of NaYF4:Er3+,Yb3+@NaYF4@NH2 UCNPs can act as a valuable probe to detect nitroaromatics in public safety and security conditions.

Product and Metal Stocks Accumulation of China's Megacities: Patterns, Drivers, and Implications.

The rapid urbanization in China since the 1970s has led to an exponential growth of metal stocks (MS) in use in cities. A retrospect on the quantity, quality, and patterns of these MS is a prerequisite for projecting future metal demand, identifying urban mining potentials of metals, and informing sustainable urbanization strategies. Here, we deployed a bottom-up stock accounting method to estimate stocks of iron, copper, and aluminum embodied in 51 categories of products and infrastructure across 10 Chinese megacities from 1980 to 2016. We found that the MS in Chinese megacities had reached a level of 2.6-6.3 t/cap (on average 3.7 t/cap for iron, 58 kg/cap for copper, and 151 kg/cap for aluminum) in 2016, which still remained behind the level of western cities or potential saturation level on the country level (e.g., approximately 13 t/cap for iron). Economic development was identified as the most powerful driver for MS growth based on an IPAT decomposition analysis, indicating further increase in MS as China's urbanization and economic growth continues in the next decades. The latecomer cities should therefore explore a wide range of strategies, from urban planning to economy structure to regulations, for a transition toward more "metal-efficient" urbanization pathways.

[Preventive and therapeutic effects of Keluoxin Capsules on early diabetic retinopathy in db/db mice].

The aim of this paper was to investigate the preventive effects of Keluoxin Capsules(KLX) on diabetic retinopathy in db/db mice. One hundred male db/db diabetic mice(45-55 g, 8 weeks) were randomly divided into 5 groups(model, KLX low dose, KLX middle dose, KLX high dose, Dobesilate) and 20 male C57 BL/KsJdb~(+/+) were taken as control group. Body weight and fasting blood-glucose were detected every week. Mice were administrated with saline(control and model group), KLX(780, 1 560, 3 120 mg·kg~(-1)·d~(-1), ig), Dobesilate(195 mg·kg~(-1)·d~(-1), ig) for 20 weeks, respectively. At the end of the administration, optical coherence tomography, fundus fluorescein angiography and electroretinogram of the retina were measured. The eyeball was extirpated and retina was isolated to make paraffin section, followed by HE staining and glial fibrillary acidic protein(GFAP) immunohistochemistry. The results indicated that KLX has no obvious effect on body weight and fasting blood level in db/db mice. However, KLX could significantly regulate the thickness of retinal ganglion layer and inner plexiform layer. KLX was able to remarkably reduce the quantity of diabetic microvessel. Meanwhile, KLX could notably improve retinal function. Moreover, KLX could observably modulate the cell arrangement and edema in each layer. There was no markable difference in retina according to the immunochemistry assay. In the present study, KLX exert marked preventive effects on diabetic retinopathy in db/db mice, which provided an experimental evidence for clinical use.

Highly Pathogenic Avian Influenza H5N6 Viruses Exhibit Enhanced Affinity for Human Type Sialic Acid Receptor and In-Contact Transmission in Model Ferrets.

UNLABELLED: Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SAα2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans. IMPORTANCE: Extended epizootics and panzootics of H5N1 viruses have led to the emergence of the novel 2.3.4.4 clade of H5 virus subtypes, including H5N2, H5N6, and H5N8 reassortants. Avian H5N6 viruses from this clade have caused three fatalities out of six severe human infections in China since the first case in 2014. However, the biological properties of this subtype, especially the pathogenicity and transmission in mammals, are not known. Here, we found that natural avian H5N6 viruses have acquired a high affinity for human-type virus receptor. Compared to the parental clade 2.3.4 H5N1 virus, emergent H5N6 isolates showed less severe pathogenicity in mice and ferrets but acquired efficient in-contact transmission in ferrets. These findings suggest that the threat of avian H5N6 viruses to humans should not be ignored.

Testis expressed 19 is a novel cancer-testis antigen expressed in bladder cancer.

Bladder cancer exhibits high mortality as a result of limited therapeutic options and a high recurrence rate. Accordingly, novel treatments such as immunotherapy have emerged as promising therapeutic modalities to prolong overall patient survival and effect a disease cure, which has renewed enthusiasm for the identification of tumor-specific target antigens. Cancer-testis (CT) antigens are recognized as ideal targets for immunotherapy because of their expression features and high immunogenicity profiles. Here, we investigate the expression pattern of a novel CT antigen, testis-expressed 19 (TEX19), in patients with bladder carcinoma and among multiple human tissues. Six bladder cancer cell lines (T24, UM-UC-3, J82, 5637, SW780, and RT4) were also analyzed for TEX19 expression. Our results reveal that TEX19 expression in normal tissue is restricted to human testis. In addition, TEX19 mRNA expression was detected in 60 % (24/40) bladder cancer samples, whereas 58.20 % (110/189) were positive for TEXT19 protein expression. Compared to low-grade tumors, TEX19 exhibited increased expression in high-grade tumors, from 53.69 to 77.14 %, respectively (P = 0.011). TEX19 was also expressed in all six bladder cancer cell lines. Together, our findings suggest that TEX19 represents a novel CT gene and might play a role in the progression of bladder cancer and that this gene therefore provides a potential target for immunotherapy treatment strategies against bladder cancer.

Characterization of a novel H3N2 influenza virus isolated from domestic ducks in China.

Cases of human infection with a novel H7N9 avian influenza virus (AIV) were first reported in March 2013, which caused 115 deaths within a single year. Beyond that, other subtypes of H7 AIV were isolated from poultry in eastern China during the same period, including H7N7 and H7N2 AIV. In the present study, a subtype H3N2 AIV was isolated from ducks from Anhui Province, China. Sequence and phylogenetic analyses revealed that seven gene segments of this virus showed the highest sequence homology with that of the H7 subtype influenza virus, which is presumed to be the reassortants of the H3 and H7 subtypes AIV. The present study also reconfirmed that the reassortment between the H7 subtype and waterfowl-originating AIVs universally occurred in waterfowl. Animal inoculation tests showed that the virus has low pathogenicity in chickens; however, it could be replicated in the lungs of mice. The emergence of this H3N2 isolate emphasizes the importance of enhancing the surveillance of waterfowl-originating AIVs, the identification of novel reassortant strains, and characterization of their biological properties.

[Effects of stocking density and exchanging water frequency on growth and inner quality of Whitmania pigra].

The effects of stocking density and exchanging water frequency on growth, digestive enzyme activity, anti-oxidative enzyme and inner quality of Whitmania pigra Whitman were evaluated with corresponding measures. The results showed that the eventual biomass, specific growth rate, gained weight rate, activities of amylase, lipase, protease, SOD, CAT, and ALP correlated positively with stocking density and negatively with exchanging water frequency (P<0.05). Exchanging water frequency had negative correlation with ammonia nitrogen, nitrite, and hydrogen sulfide while revealed positive correlation with dissolved oxygen in the water. Stocking density and exchanging water frequency showed no significant effects on the contents of moisture, total ash, and acid-insoluble ash. It suggested that the optimum stocking density was 7.5 million per hectare and the appropriate exchanging water interval was 72 h.

Compound danshen tablet ameliorated aß25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins.

BACKGROUND: Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer's disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aß25-35-induced cognitive impairment in mice. METHODS: Mice were randomly divided into 5 groups: the control group (sham operated), the Aß25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aß25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aß25-35 to establish the mice model of Alzheimer's disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA. RESULTS: The results showed that Aß25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aß25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice. CONCLUSION: These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines and neurotrophins.

Genetic and Biological Characteristics of Duck-Origin H4N6 Avian Influenza Virus Isolated in China in 2022.

The interaction between migratory birds and domestic waterfowl facilitates viral co-infections, leading to viral reassortment and the emergence of novel viruses. In 2022, samples were collected from duck farms around Poyang Lake in Jiangxi Province, China, which is located within the East Asia-Australasia flyway. Three strains of H4N6 avian influenza virus (AIV) were isolated. Genetic and phylogenetic analyses showed that the isolated H4N6 avian influenza viruses (AIVs) belonged to new genotypes, G23 and G24. All isolated strains demonstrated dual receptor binding properties. Additionally, the isolated strains were able to replicate efficiently not only in avian cells but also in mammalian cells. Furthermore, the H4N6 AIV isolates could infect chickens, with viral replication detected in the lungs and extrapulmonary organs, and could transmit within chicken flocks through contact, with viral shedding detected only in oropharyngeal swabs from chickens in the contact group. Notably, the H4N6 AIV could infect mice without prior adaptation and replicate in the lungs with high viral titers, suggesting that it is a potential threat to humans. In conclusion, this study provides valuable insight into the characteristics of H4N6 strains currently circulating in China.