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"Zhu, Quan"
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Spatial Morphological Characteristics and Evolution of Traditional Villages in the Mountainous Area of Southwest Zhejiang
National-level traditional villages in Liandu District and Qingyuan County, Lishui City, in the southwestern mountainous area of Zhejiang Province serve as research objects in our exploration of the external representation and deep spatial structure changes in traditional village spatial forms from a synchronic and diachronic perspective. We use morphological indices, space syntax, city image surveys, and other analysis methods to reveal the formation and evolution of these forms. We find that: (1) Traditional village boundaries in the mountainous area of southwest Zhejiang are mainly clusters and bands, which are restricted by geographical conditions and tend to expand in the direction of rivers and roads. (2) The original spatial forms of settlements effectively organize the travel activities of local residents and external visitors, while the corresponding two fabric centers basically coincide. However, with the continuous evolution of settlements and the intervention of modern construction projects, the centers have shifted slightly. (3) Factors such as the natural environment, clan consanguinity, and economic and technological conditions jointly act on spatial forms manifesting as “stability maintenance” and “sudden change” games; thus, the forms show overlapping and integration across multiple temporal and spatial points.
Journal Article
Immunization with Toxoplasma gondii GRA17 Deletion Mutant Induces Partial Protection and Survival in Challenged Mice
Toxoplasmosis remains a world-threatening disease largely because of the lack of a fully effective vaccine. Here, we created a Δ
mutant by disrupting the virulence factor
using CRISPR-Cas9 method. Then, we tested whether Δ
tachyzoites can be used as a live-attenuated vaccine against acute, chronic, and congenital
infection in mice. Immune response evoked by Δ
immunization suggested a sequential Th1 and Th2 T cell response, indicated by high levels of Th1 and a mixed Th1/Th2 cytokines at 28 and 70 days after immunization, respectively. Δ
-mediated immunity fully protected mice against lethal infection with wild-type (wt) RH strain, heterologous challenge with PYS, and TgC7 strains of the Chinese ToxoDB#9 genotype, and
Pru strain. Although parasite cysts were detected in 8 out of 10 immunized mice, cyst burden in the brain was significantly reduced (
< 0.05) in immunized mice (53 ± 15 cysts/brain) compared to non-immunized mice (4,296 ± 687 cysts/brain). In respect to congenital infection, the litter size, survival rate, and body weight (BW) of pups born to Δ
-immunized dams were not different compared to pups born to naïve control dams (
= 0.24). However, a marked reduction in the litter size (
< 0.001), survival rate, and BW (
< 0.01) of pups born to non-immunized and infected dams was detected. Also, immunized dams infected with type II Pru strain had significantly (
< 0.001) less cyst burden in the brain compared with non-immunized and infected dams. These findings show that immunization with Δ
strain evokes cell-mediated and neutralizing antibody responses and confers some degree of protection against challenge with homologous and heterologous virulent
strains.
Journal Article
Case Report: Polymyxin E-associated reversible leukopenia
With the increasing challenge of antibiotic resistance, polymyxin E is considered a last-line treatment option for infections caused by highly resistant bacteria. However, its use may lead to various adverse reactions, such as nephrotoxicity, neurotoxicity, and allergic reactions.
This study describes a case of polymyxin E-associated leukopenia in a 50-year-old female treated for
infection. During polymyxin E therapy, the patient developed leukopenia, with white blood cell (WBC) counts declining from 5.65×10
/L to 0.91×10
/L. The condition resolved progressively after the cessation of polymyxin E. The Naranjo scale yielded a score of 7 for polymyxin E-associated leukopenia, while other medications scored ≤0. The WHO-Uppsala Monitoring Centre (WHO-UMC) causality classification system categorized the relationship as 'probable.'
These findings suggest that polymyxin E likely induces leukopenia, emphasizing the need for rigorous WBC monitoring during treatment and prompt discontinuation when hematologic abnormalities emerge to minimize patient health risks.
Journal Article
Diagnosis of toxoplasmosis and typing of Toxoplasma gondii
Toxoplasmosis, caused by the obligate intracellular protozoan
Toxoplasma gondii
, is an important zoonosis with medical and veterinary importance worldwide. The disease is mainly contracted by ingesting undercooked or raw meat containing viable tissue cysts, or by ingesting food or water contaminated with oocysts. The diagnosis and genetic characterization of
T. gondii
infection is crucial for the surveillance, prevention and control of toxoplasmosis. Traditional approaches for the diagnosis of toxoplasmosis include etiological, immunological and imaging techniques. Diagnosis of toxoplasmosis has been improved by the emergence of molecular technologies to amplify parasite nucleic acids. Among these, polymerase chain reaction (PCR)-based molecular techniques have been useful for the genetic characterization of
T. gondii
. Serotyping methods based on polymorphic polypeptides have the potential to become the choice for typing
T. gondii
in humans and animals. In this review, we summarize conventional non-DNA-based diagnostic methods, and the DNA-based molecular techniques for the diagnosis and genetic characterization of
T. gondii
. These techniques have provided foundations for further development of more effective and accurate detection of
T. gondii
infection. These advances will contribute to an improved understanding of the epidemiology, prevention and control of toxoplasmosis.
Journal Article
Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging haemorrhagic fever that was first described in rural areas of China. The causative agent, SFTS virus (SFTSV), is a novel phlebovirus in the Bunyaviridae family. Since the first report in 2010, SFTS has been found in 11 provinces of China, with about 2500 reported cases, and an average case-fatality rate of 7·3%. The disease was also reported in Japan and Korea in 2012; Heartland virus, another phlebovirus genetically closely related to SFTSV, was isolated from two patients in the USA. The disease has become a substantial risk to public health, not only in China, but also in other parts of the world. The virus could undergo rapid evolution by gene mutation, reassortment, and homologous recombination in tick vectors and vertebrate reservoir hosts. No specific treatment of SFTS is available, and avoiding tick bites is an important measure to prevent the infection and transmission of SFTSV. This Review provides information on the molecular characteristics and ecology of this emerging tick-borne virus and describes the epidemiology, clinical signs, pathogenesis, diagnosis, treatment, and prevention of human infection with SFTSV.
Journal Article
Toxocariasis: a silent threat with a progressive public health impact
Background
Toxocariasis is a neglected parasitic zoonosis that afflicts millions of the pediatric and adolescent populations worldwide, especially in impoverished communities. This disease is caused by infection with the larvae of
Toxocara canis
and
T. cati
, the most ubiquitous intestinal nematode parasite in dogs and cats, respectively. In this article, recent advances in the epidemiology, clinical presentation, diagnosis and pharmacotherapies that have been used in the treatment of toxocariasis are reviewed.
Main text
Over the past two decades, we have come far in our understanding of the biology and epidemiology of toxocariasis. However, lack of laboratory infrastructure in some countries, lack of uniform case definitions and limited surveillance infrastructure are some of the challenges that hindered the estimation of global disease burden. Toxocariasis encompasses four clinical forms: visceral, ocular, covert and neural. Incorrect or misdiagnosis of any of these disabling conditions can result in severe health consequences and considerable medical care spending. Fortunately, multiple diagnostic modalities are available, which if effectively used together with the administration of appropriate pharmacologic therapies, can minimize any unnecessary patient morbidity.
Conclusions
Although progress has been made in the management of toxocariasis patients, there remains much work to be done. Implementation of new technologies and better understanding of the pathogenesis of toxocariasis can identify new diagnostic biomarkers, which may help in increasing diagnostic accuracy. Also, further clinical research breakthroughs are needed to develop better ways to effectively control and prevent this serious disease.
Journal Article
Prevalence of the emerging novel Alongshan virus infection in sheep and cattle in Inner Mongolia, northeastern China
Background
Alongshan virus (ALSV) is a novel discovered segmented flavivirus associated with human febrile illness in northeastern China.
Ixodes persulcatus
is considered as a candidate vector of ALSV in the endemic regions. However, the role of domesticated animals in the circulation and transmission of ALSV have not been investigated. To evaluate the prevalence of ALSV infections in domesticated animals, viral RNA and viral specific antibodies were detected in sheep and cattle in Hulunbuir of northeastern Inner Mongolia. The findings contribute to the understanding of the ecology and transmission of ALSV among different natural hosts.
Methods
A total of 480 animal serum samples were collected in Hulunbuir of northeastern China in May, 2017. Viral specific antibodies were tested by indirect enzyme-linked immunosorbent assay (ELISA) with a purified
E. coli
recombinant capsid protein (VP2) of ALSV (strain H3) and further detected by viral neutralization test (VNT). RNA in serum samples were extracted and detected for ALSV sequence by quantitative real-time RT-PCR. ALSV RNA positive samples were used for virus isolation.
Results
ALSV-specific antibodies were detected in 9.2% (22/240) of examined sheep and 4.6% (11/240) of examined cattle by ELISA, while lower serological positivity with 4.2% (10/240) for sheep and 1.7% (4/240) for cattle was confirmed by VNT. In contrast, the prevalence of ALSV RNA was much higher, ranging from 26.3% (63/240) in sheep to 27.5% (66/240) in cattle. The partial S1 (NS5-like) and S3 (NS3-like) segments of ALSVs in sheep and cattle shared high identities of more than 98% to the human and tick isolates in the studied regions.
Conclusions
These results suggest that the natural infection of ALSV can be found in sheep and cattle in the endemic regions.
Journal Article
The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence
Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T . gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite’s daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T . gondii .
Journal Article
The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony
Sexual development in
Toxoplasma gondii
is a multistep process that culminates in the production of oocysts, constituting approximately 50% of human infections. However, the molecular mechanisms governing sexual commitment in this parasite remain poorly understood. Here, we demonstrate that the transcription factors AP2XI-2 and AP2XII-1 act as negative regulators, suppressing merozoite-primed pre-sexual commitment during asexual development. Depletion of AP2XI-2 in type II Pru strain induces merogony and production of mature merozoites in an alkaline medium but not in a neutral medium. In contrast, AP2XII-1-depleted Pru strain undergoes several rounds of merogony and produces merozoites in a neutral medium, with more pronounced effects observed under alkaline conditions. Additionally, we identified two additional AP2XI-2-interacting proteins involved in repressing merozoite programming. These findings underscore the intricate regulation of pre-sexual commitment by a network of factors and suggest that AP2XI-2 or AP2XII-1-depleted Pru parasites can serve as a model for studying merogony in vitro.
Wang et al. discovered that AP2XI-2 and AP2XII-1 negatively regulate merozoite-primed pre-sexual commitment in Toxoplasma gondii, and parasites depleted of either AP2XI-2 or AP2XII-1 can serve as a valuable in vitro model for studying merogony.
Journal Article