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.

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.

Mixed selling of different poultry species facilitates emergence of public-health-threating avian influenza viruses.

ABSTRACTLive poultry markets (LPMs) are regarded as hubs for avian influenza virus (AIV) transmission in poultry and are a major risk factor in human AIV infections. We performed an AIV surveillance study at a wholesale LPM, where different poultry species were sold in separate stalls, and nine retail LPMs, which received poultry from the wholesale LPM but where different poultry species were sold in one stall, in Guangdong province from 2017 to 2019. A higher AIV isolation rate was observed at the retail LPMs than the wholesale LPM. H9N2 was the dominant AIV subtype and was mainly present in chickens and quails. The genetic diversity of H9N2 viruses was greater at the retail LPMs, where a complex system of two-way transmission between different poultry species had formed. The isolated H9N2 viruses could be classed into four genotypes: G57 and the three novel genotypes, NG164, NG165, and NG166. The H9N2 AIVs isolated from chickens and quails at the wholesale LPM only belonged to the G57 and NG164 genotypes, respectively. However, the G57, NG164, and NG165 genotypes were identified in both chickens and quails at the retail LPMs. We found that the replication and transmission of the NG165 genotype were more adaptive to both poultry and mammalian models than those of its precursor genotype, NG164. Our findings revealed that mixed poultry selling at retail LPMs has increased the genetic diversity of AIVs, which might facilitate the emergence of novel viruses that threaten public health.

The Heteroepitaxy of Thick ß-Ga2O3 Film on Sapphire Substrate with a ß-(AlxGa1-x)2O3 Intermediate Buffer Layer.

A high aluminum (Al) content ß-(AlxGa1-x)2O3 film was synthesized on c-plane sapphire substrate using the gallium (Ga) diffusion method. The obtained ß-(AlxGa1-x)2O3 film had an average thickness of 750 nm and a surface roughness of 2.10 nm. Secondary ion mass spectrometry results indicated the homogenous distribution of Al components in the film. The Al compositions in the ß-(AlxGa1-x)2O3 film, as estimated by X-ray diffraction, were close to those estimated by X-ray photoelectron spectroscopy, at ~62% and ~61.5%, respectively. The bandgap of the ß-(AlxGa1-x)2O3 film, extracted from the O 1s core-level spectra, was approximately 6.0 ± 0.1 eV. After synthesizing the ß-(AlxGa1-x)2O3 film, a thick ß-Ga2O3 film was further deposited on sapphire substrate using carbothermal reduction and halide vapor phase epitaxy. The ß-Ga2O3 thick film, grown on a sapphire substrate with a ß-(AlxGa1-x)2O3 buffer layer, exhibited improved crystal orientation along the (-201) plane. Moreover, the scanning electron microscopy revealed that the surface quality of the ß-Ga2O3 thick film on sapphire substrate with a ß-(AlxGa1-x)2O3 intermediate buffer layer was significantly improved, with an obvious transition from grain island-like morphology to 2D continuous growth, and a reduction in surface roughness to less than 10 nm.

Product, building, and infrastructure material stocks dataset for 337 Chinese cities between 1978 and 2020.

Reliable city-level product, building, and infrastructure material stocks data are essential for understanding historical material use patterns, benchmarking material efficiency, and informing future recycling potentials. However, such urban material stocks data are often limited, due primarily to unavailable, inconsistent, or noncontinuous city-level statistics. Here, we provided such an Urban Product, Building, and Infrastructure Material Stocks (UPBIMS) dataset for China, a country that has undergone a remarkable urbanization process in the past decades, by collating different official statistics and applying various gap-filling methods. This dataset contains the stock of 24 materials contained in 10 types of products, buildings, and infrastructure in all 337 prefecture-level cities in China from 1978 to 2020. This quality controlled and unified dataset is the first of its kind with such a full coverage of all prefecture-level Chinese cities and can be used in a variety of applications, for example in urban geography, industrial ecology, circular economy, and climate change mitigation. Every piece of data is tagged with its source and the dataset will be periodically updated.

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.

Multi-color luminescence and anticounterfeiting application of upconversion nanoparticle.

Multi-color luminescence materials are important in the illumination, solid-state three-dimensional display, information storage, biological labelling and anticounterfeiting fields. Herein, we designed a novel core-shell structure upconversion nanoparticle (UCNP) material (NaYF4) with lanthanide ion doping to achieve multi-color luminescence under a single NIR excitation laser. Different from the typical single-sensitizer materials, the core-shell structure utilizes Nd3+, Yb3+, Tm3+ and Er3+ ions to obtain tuning of the color and brightness. The doping of Nd3+ ions enhances the weak color (red) light source to maintain the light color balance. Benefiting from the color adjustment of the sensitizers and the change of the core-shell coating, bright-white emission and flexible color emission from red to green, cyan and blue can be achieved via the diverse doped rare earth ions in a single UCNP under continuous-wave laser excitation (980 nm). Simultaneously, the emission color of the UCNPs can change with the intensity of the excitation light source and the wavelength. The bright-white emission can be used for lighting displays, and the flexible full-color emission can be applied in the anticounterfeiting and information storage fields.

Assessment of cobalt recycling potential and environmental impact in China from 1994 to 2020.

Cobalt recycling is important for solving environmental problems such as resource shortage and pollution emissions. This paper quantifies the positive significance of cobalt recycling on resource replenishment and pollution emission by using the substance flow analysis and life cycle analysis. The results show that the proportion of recycled cobalt supplied as cobalt raw material is 7.1%, which improves the supply structure of the resource. Meanwhile, the environmental impact of recycling cobalt using the combined treatment process is low. The environmental impact of mining cobalt from mines is about 4.03-41.53 times that of recycling cobalt from cobaltiferous waste materials. However, the overall cobalt recycling is not ideal. First, the cobalt recycling rate is growing slowly. From 1994 to 2020, 245,132 t of cobalt-containing final products entered waste management in China. However, only 79,593 t of cobalt have been recycled, with a recycling rate of 32.47%. Secondly, many recycling enterprises only carry out recycling for a certain type of cobaltiferous waste materials due to the non-uniform cobalt recycling process. Finally, China's cobalt recycling policy does not divide the recycling channels for cobalt waste and does not regulate the specific process. In the future, China should set up separate recycling systems for cobaltiferous waste materials according to different categories and consider adopting combined treatment processes. China can only promote the sustainable use of cobalt if it ensures stable and orderly cobalt recycling in terms of policy and technology.

Field efficacy of HVT-H9 vaccination after natural infection of H9N2 avian influenza virus in broilers.

H9N2 subtype avian influenza virus (AIV) has been persistently circulating in China. It causes huge economic losses to the poultry industry and poses a great threat to public health. Previously, we constructed a turkey herpesvirus live vector vaccine candidate strain expressing an H9 gene, HVT-H9. Results showed that immunisation with HVT-H9 could provide good immunity in specific pathogen free (SPF) chickens. In this study, field-bred Arbour Acres plus (AA+) broilers were additionally immunised with HVT-H9 at one day of age. Then, broilers were naturally infected with H9N2 AIV. During the endemic period, death occurred in flocks without HVT-H9 immunisation and the mortality rate increased rapidly, forming a clear death wave. However, HVT-H9 vaccination prevented broiler mortality. Etiological tests and serological tests showed that broilers were positive for H9N2 AIV. Collectively, HVT-H9 immunisation provided good immunity for broilers in the field by inhibiting H9N2 virus infection and transmission.

SRSF5-Mediated Alternative Splicing of M Gene is Essential for Influenza A Virus Replication: A Host-Directed Target Against Influenza Virus.

Splicing of influenza A virus (IAV) RNA is an essential process in the viral life cycle that involves the co-opting of host factors. Here, it is demonstrated that induction of host serine and arginine-rich splicing factor 5 (SRSF5) by IAV facilitated viral replication by enhancing viral M mRNA splicing. Mechanistically, SRSF5 with its RRM2 domain directly bounds M mRNA at conserved sites (M mRNA position 163, 709, and 712), and interacts with U1 small nuclear ribonucleoprotein (snRNP) to promote M mRNA splicing and M2 production. Mutations introduced to the three binding sites, without changing amino acid code, significantly attenuates virus replication and pathogenesis in vivo. Likewise, SRSF5 conditional knockout in the lung protects mice against lethal IAV challenge. Furthermore, anidulafungin, an approved antifungal drug, is identified as an inhibitor of SRSF5 that effectively blocks IAV replication in vitro and in vivo. In conclusion, SRSF5 as an activator of M mRNA splicing promotes IAV replication and is a host-derived antiviral target.

Simultaneous Improvement of Strength and Ductility of Dual-Phase Steel Processed by Multi-Step Cyclic Rolling and Intercritical Annealing.

In the present study, a multi-step (MS) cyclic rolling and intercritcal annealing process was proposed and applied for dual-phase (DP) steel. The MS process performed three times with 27% deformations and intercritical annealing, while the single-step (SS) process performed an 81% rolling, along with intercritical annealing. A microstructure with an average grain size of 3 µm and a martensite content of ~40% was obtained after MS treatment, which is similar to results obtained from the SS treatment. However, the distribution exhibits significant differences between the two different routes. A more homogenous distribution of ferrite-martensite was achieved after the multi-step compared with the single-step treatment. The yield strength of MS is slightly smaller than that of SS, while the ultimate tensile strength is better, which results in a decrease in yield ratio. Furthermore, the ductility was greatly improved after MS, which is mainly attributed to the uniform chain-like distribution of martensite.

Status and Challenges for Vaccination against Avian H9N2 Influenza Virus in China.

In China, H9N2 avian influenza virus (AIV) has become widely prevalent in poultry, causing huge economic losses after secondary infection with other pathogens. Importantly, H9N2 AIV continuously infects humans, and its six internal genes frequently reassort with other influenza viruses to generate novel influenza viruses that infect humans, threatening public health. Inactivated whole-virus vaccines have been used to control H9N2 AIV in China for more than 20 years, and they can alleviate clinical symptoms after immunization, greatly reducing economic losses. However, H9N2 AIVs can still be isolated from immunized chickens and have recently become the main epidemic subtype. A more effective vaccine prevention strategy might be able to address the current situation. Herein, we analyze the current status and vaccination strategy against H9N2 AIV and summarize the progress in vaccine development to provide insight for better H9N2 prevention and control.

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.

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.

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.

Carotid blowout syndrome caused by chronic infection: A case report.

BACKGROUND: Carotid blowout syndrome (CBS) refers to rupture of the extracranial carotid artery and its branches; as a severe complication, it usually occurs after surgery or radiotherapy for malignant tumours of the head and neck. We present a case of CBS caused by chronic infection of the external carotid artery (ECA). In this case, we did not find any evidence of head and neck tumours. CASE SUMMARY: A 42-year-old man was referred to the Emergency Department with a complaint of a lump found on the left side of his neck with pain and fever for 4 d. We diagnosed the condition as neck infection with abscess formation based on physical examination, routine blood examination, ultrasound examination and plain computed tomography (CT) and decided to perform emergency surgery. During the operation, 30 mL of grey and smelly pus was drained from the deep surface of the sternocleidomastoid muscle. The second day after the operation, the patient suddenly exhibited a large amount of haemoptysis and incision bleeding. The enhanced CT showed distal occlusion of the left ECA and irregular thickening of the broken ends of the artery encased in an uneven enhancement of soft tissue density. Infected ECA occlusion and rupture were considered. The patient was transferred to a vascular unit for transcatheter ECA embolization and recovered well. CONCLUSION: Surgeons need to pay attention to vascular lesions caused by chronic infection that may develop into acute CBS.

Battery technology and recycling alone will not save the electric mobility transition from future cobalt shortages.

In recent years, increasing attention has been given to the potential supply risks of critical battery materials, such as cobalt, for electric mobility transitions. While battery technology and recycling advancement are two widely acknowledged strategies for addressing such supply risks, the extent to which they will relieve global and regional cobalt demand-supply imbalance remains poorly understood. Here, we address this gap by simulating historical (1998-2019) and future (2020-2050) global cobalt cycles covering both traditional and emerging end uses with regional resolution (China, the U.S., Japan, the EU, and the rest of the world). We show that cobalt-free batteries and recycling progress can indeed significantly alleviate long-term cobalt supply risks. However, the cobalt supply shortage appears inevitable in the short- to medium-term (during 2028-2033), even under the most technologically optimistic scenario. Our results reveal varying cobalt supply security levels by region and indicate the urgency of boosting primary cobalt supply to ensure global e-mobility ambitions.

Research trend and dynamical development of focusing on the global critical metals: a bibliometric analysis during 1991-2020.

Critical metals are indispensable to a world seeking to transition away from carbon. Yet their extraction, processing, and application leave an unsustainable global environment and climate change footprint. To capture the development dynamics and research emphases of critical metals throughout their life cycle, this paper adopts bibliometrics to analyze the various stages of global critical metal flow in multiple dimensions to reveal the hot issues and future strategic trends. The research results indicate that the number of research papers on critical metals is annually rising, with remarkably rapid growth after 2010. Judging from the number of articles published by the authors and the citations, among the authors, Kawakita, Poettgen, Anwander, Inoue, and Dongmei Cui have a significant influence on critical metal research fields. The institutions with the most research on critical metals are universities, not research institutes. In addition, the focus has extended from a single discipline to the interdisciplinary development of multiple disciplines. Analysis of keywords shows that "rare metals" and "precious metals" are the most popular metals among the researched metals. The researched buzzwords of critical metals are disappearing, convergent, and merging over time. The research has focused on the mining and the whole life cycle process of extraction, treatment, and application. Based on the above characteristics, this paper tries to understand the dynamic development and evolution of global critical metals from multiple dimensions, resorting to giving a reference for follow-up-related research scholars.

Efficacy and safety of naotaifang capsules for hypertensive cerebral small vessel disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Background: Hypertensive cerebral small vessel disease (HT-CSVD) is a cerebrovascular clinical, imaging and pathological syndrome caused by hypertension (HT). The condition manifests with lesions in various vessels including intracranial small/arterioles, capillaries, and small/venules. Hypertensive cerebral small vessel disease has complex and diverse clinical manifestations. For instance, it can present as an acute stroke which progresses to cause cognitive decline, affective disorder, unstable gait, dysphagia, or abnormal urination. Moreover, hypertensive cerebral small vessel disease causes 25-30% of all cases of ischemic strokes and more than 50% of all cases of single or mixed dementias. The 1-year recurrence rate of stroke in cerebral small vessel disease patients with hypertension is 14%. In the early stage of development, the symptoms of hypertensive cerebral small vessel disease are concealed and often ignored by patients and even clinicians. Patients with an advanced hypertensive cerebral small vessel disease manifest with severe physical and mental dysfunction. Therefore, this condition has a substantial economic burden on affected families and society. Naotaifang (NTF) is potentially effective in improving microcirculation and neurofunction in patients with ischemic stroke. In this regard, this multicenter randomized controlled trial (RCT) aims to furtherly evaluate the efficacy and safety of naotaifang capsules on hypertensive cerebral small vessel disease. Methods: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 388 eligible subjects were recruited from the First Hospital of Hunan University of Chinese Medicine, Hunan Academy of Chinese Medicine Affiliated Hospital, the First Hospital of Shaoyang University, the First Traditional Chinese Medicine Hospital of Changde, and Jiangmen Wuyi Hospital of Traditional Chinese Medicine from July 2020 to April 2022. After a 4-week run-in period, all participants were divided into the intervention group (represented by Y-T, N-T) and control group (represented by Y-C, N-C); using a stratified block randomized method based on the presence or absence of brain damage symptoms in hypertensive cerebral small vessel disease (represented by Y and N). The Y-T and N-T groups were administered different doses of naotaifang capsules, whereas Y-C and N-C groups received placebo treatment. These four groups received the treatments for 6 months. The primary outcome included Fazekas scores and dilated Virchow-robin spaces (dVRS) grades on magnetic resonance imaging (MRI). The secondary outcomes included the number of lacunar infarctions (LI) and cerebral microbleeds (CMB) on magnetic resonance imaging, clinical blood pressure (BP) level, traditional Chinese medicine (TCM) syndrome scores, mini-mental state examination (MMSE) scale, and safety outcomes. Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds on magnetic resonance imaging were tested before enrollment and after 6 months of treatment. The clinical blood pressure level, traditional Chinese medicine syndrome scores, mini-mental state examination scale and safety outcomes were tested before enrollment, after 3-month, 6-month treatment and 12th-month follow-up respectively. Conclusion: The protocol will comfirm whether naotaifang capsules reduce Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds, clinical blood pressure, increase mini-mental state examination scores, traditional Chinese medicine syndrome scores of Qi deficiency and blood stasis (QDBS), and improve the quality of life of subjects. The consolidated evidence from this study will shed light on the benefits of Chinese herbs for hypertensive cerebral small vessel disease, such as nourishing qi, promoting blood circulation and removing blood stasis, and dredging collaterals. However, additional clinical trials with large samples and long intervention periods will be required for in-depth research. Clinical Trial registration: www.chictr.org.cn, identifier ChiCTR1900024524.

Recombinant HA1-ΔfliC enhances adherence to respiratory epithelial cells and promotes the superiorly protective immune responses against H9N2 influenza virus in chickens.

H9N2 subtype avian influenza virus (AIV) is an ongoing threat causing substantial loss to the poultry industry and thus necessitating the development of safe and effective vaccines against AIV. Given that inactivated vaccines are less effective in activating the mucosal immune system, we aimed to generate a vaccine that can actively engage the mucosal immunity which is the front line of the immune system. We generated a group of flagellin-based hemagglutinin globular head (HA1) fusion proteins and characterized their immunogenicity and efficacy. We found that Salmonella typhimurium flagellin (fliC) lacking the hypervariable domain (called herein as HA1-ΔfliC) was recognized by TLR5 and induced a moderate innate immune response compared to N-terminus of fliC (HA1-fliC) and C-terminus of fliC (fliC-HA1). The HA1-ΔfliC protein had increased adherence to the nasal cavity and trachea than HA1-fliC and fliC-HA1 and significantly increased the HA-specific sIgA titers. Our in vivo results revealed that chickens treated with HA1-ΔfliC had a significantly reduced level of viral loads in the cloaca and throat compared with chickens treated with inactivated vaccine. Overall, these results revealed that HA1-ΔfliC can protect chickens against H9N2 AIV by eliciting the efficient mucosal immune responses.