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AIM: To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD). METHODS: A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n=15) or rituximab (Group RTX, n=18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes. RESULTS: Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (P0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections. CONCLUSION: The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Abstract Background Gyrodactylus is a lineage of monogenean flatworm ectoparasites exhibiting many features that make them a suitable model to study the host-parasite coevolutionary dynamics. Previous coevolutionary studies of this lineage mainly relied on low-power datasets (a small number of samples and a single molecular marker) and (now) outdated algorithms. Methods To investigate the coevolutionary relationship of gyrodactylids and their fish hosts in high resolution, we used complete mitogenomes (including two newly sequenced Gyrodactylus species), a large number of species in the single-gene dataset, and four different coevolutionary algorithms. Results The overall coevolutionary fit between the parasites and hosts was consistently significant. Multiple indicators confirmed that gyrodactylids are generally highly host-specific parasites, but several species could parasitize either multiple (more than 5) or phylogenetically distant fish hosts. The molecular dating results indicated that gyrodactylids tend to evolve towards high host specificity. Speciation by host switch was identified as a more important speciation mode than co-speciation. Assuming that the ancestral host belonged to Cypriniformes, we inferred four major host switch events to non-Cypriniformes hosts (mostly Salmoniformes), all of which occurred deep in the evolutionary history. Despite their relative rarity, these events had strong macroevolutionary consequences for gyrodactylid diversity. For example, in our dataset, 57.28% of all studied gyrodactylids parasitized only non-Cypriniformes hosts, which implies that the evolutionary history of more than half of all included lineages could be traced back to these major host switch events. The geographical co-occurrence of fishes and gyrodactylids determined the host use by these gyrodactylids, and geography accounted for most of the phylogenetic signal in host use. Conclusions Our findings suggest that the coevolution of Gyrodactylus flatworms and their hosts is largely driven by geography, phylogeny, and host switches. Graphical Abstract

This research sought to examine how the physicochemical characteristics of soy globulins and different processing techniques influence the gel properties of soy yogurt. The goal was to improve these gel properties and rectify any texture issues in soy yogurt, ultimately aiming to produce premium-quality plant-based soy yogurt. In this research study, the investigation focused on examining the impact of 7S/11S, homogenization pressure, and glycation modified with glucose on the gel properties of soy yogurt. A plant-based soy yogurt with superior gel and texture properties was successfully developed using a 7S/11S globulin-glucose conjugate at a 1:3 ratio and a homogenization pressure of 110 MPa. Compared to soy yogurt supplemented with pectin or gelatin, this yogurt demonstrated enhanced characteristics. These findings provide valuable insights into advancing plant protein gels and serve as a reference for cultivating new soybean varieties by soybean breeding experts.

Abstract Anaerobic parasitic ciliates are a specialized group of ciliates that are adapted to anoxic and oxygen-depleted habitats. Among them, Balantidium polyvacuolum, which inhabits the hindgut of Xenocyprinae fishes, has received very limited scientific attention, so the molecular mechanism of its adaptation to the digestive tract microenvironment is still unclear. In this study, transmission electron microscopy (TEM) and single-cell transcriptome analysis were used to uncover the metabolism of B. polyvacuolum. Starch granules, endosymbiotic bacteria, and multiple specialized mitochondrion-related organelles (MROs) of various shapes were observed. The MROs may have completely lost the electron transport chain (ETC) complexes I, III, IV, and V and only retained succinate dehydrogenase subunit A (SDHA) of complex II. The tricarboxylic acid (TCA) cycle was also incomplete. It can be inferred that the hypoxic intestinal environment has led to the specialization of the mitochondria in B. polyvacuolum. Moreover, carbohydrate-active enzymes (CAZymes), including carbohydrate esterases, enzymes with a carbohydrate-binding module, glycoside hydrolases, and glycosyltransferases, were identified, which may constitute evidence that B. polyvacuolum is able to digest carbohydrates and starch. These findings can improve our knowledge of the energy metabolism and adaptive mechanisms of B. polyvacuolum.

Abstract The evidence that parasitic animals exhibit elevated mitogenomic evolutionary rates is inconsistent and limited to Arthropoda. Similarly, the evidence that mitogenomic evolution is faster in species with low locomotory capacity is limited to a handful of animal lineages. We hypothesised that these two variables are associated and that locomotory capacity is a major underlying factor driving the elevated rates in parasites. Here, we study the evolutionary rates of mitogenomes of 10,906 bilaterian species classified according to their locomotory capacity and parasitic/free-living life history. In Bilateria, evolutionary rates were by far the highest in endoparasites, much lower in ectoparasites with reduced locomotory capacity and free-living lineages with low locomotory capacity, followed by parasitoids, ectoparasites with high locomotory capacity, and finally micropredatory and free-living lineages. The life history categorisation (parasitism) explained ≈45%, locomotory capacity categorisation explained ≈39%, and together they explained ≈56% of the total variability in evolutionary rates of mitochondrial protein-coding genes in Bilateria. Our findings suggest that these two variables play major roles in calibrating the mitogenomic molecular clock in bilaterian animals.

Abstract The COVID-19 pandemic has had a widespread impact on a global scale, and the evolution of considerable dominants has already taken place. Some variants contained certain key mutations located on the receptor binding domain (RBD) of spike protein, such as E484K and N501Y. It is increasingly worrying that these variants could impair the efficacy of current vaccines or therapies. Therefore, analyzing and predicting the high-risk mutations of SARS-CoV-2 spike glycoprotein is crucial to design future vaccines against the different variants. In this work, we proposed an in silico approach, immune-escaping score (IES), to predict high-risk immune-escaping hot spots on the receptor-binding domain (RBD), implemented through integrated delta binding free energy measured by computational mutagenesis of spike-antibody complexes and mutation frequency calculated from viral genome sequencing data. We identified 23 potentially immune-escaping mutations on the RBD by using IES, nine of which occurred in omicron variants (R346K, K417N, N440K, L452Q, L452R, S477N, T478K, F490S, and N501Y), despite our dataset being curated before the omicron first appeared. The highest immune-escaping score (IES = 1) was found for E484K, which agrees with recent studies stating that the mutation significantly reduced the efficacy of neutralization antibodies. Furthermore, our predicted delta binding free energy and IES show a high correlation with high-throughput deep mutational scanning data (Pearson’s r = 0.70) and experimentally measured neutralization titers data (mean Pearson’s r = −0.80). In summary, our work presents a new method to identify the potentially immune-escaping mutations on the RBD and provides valuable insights into future COVID-19 vaccine design.

The liver fluke disease caused by Clonorchis sinensis is one of the most serious food-borne parasitic diseases in China. Many freshwater fish and shrimps can be infected with C. sinensis metacercariae as the second intermediate hosts in endemic regions. Owing to the lack of infected humans and the good administration of pet dogs and cats in cities of non-endemic regions, few fish are expected to be infected with C. sinensis metacercariae in urban lakes. To determine the infection of C. sinensis metacercariae in freshwater fish and shrimps in urban lakes, a total of 18 fish species and one shrimp species were investigated in the East Lake of Wuhan City. Metacercariae were isolated by artificial digestive juice and identified using morphology and rDNA-ITS2 sequences. Five species of fish, Pseudorasbora parva, Ctenogobius giurinus, Squalidus argentatus, Hemiculter leuciclus, and Rhodeus spp., were infected with C. sinensis metacercariae. The overall prevalence of C. sinensis was 32.5%. The highest prevalence was found in P. parva with 57.9%, while S. argentatus exhibited the highest mean abundance (13.9). Apart from the C. sinensis metacercariae, four species of other trematode metacercariae were also identified across twelve fish species in total. Owing to the consumption of undercooked fish and feeding cats with small fish caught by anglers, there is a potential risk that the small fish infected with C. sinensis metacercariae may act as an infection source to spread liver fluke. Given the complete life cycle of C. sinensis, stray cats and rats were inferred to act as the important final hosts of C. sinensis in urban lakes in non-endemic areas.

Abstract Background Chilodonella uncinata is an aerobic ciliate capable of switching between being free-living and parasitic on fish fins and gills, causing tissue damage and host mortality. It is widely used as a model organism for genetic studies, but its mitochondrial metabolism has never been studied. Therefore, we aimed to describe the morphological features and metabolic characteristics of its mitochondria. Methods Fluorescence staining and transmission electron microscopy (TEM) were used to observe the morphology of mitochondria. Single-cell transcriptome data of C. uncinata were annotated by the Clusters of Orthologous Genes (COG) database. Meanwhile, the metabolic pathways were constructed based on the transcriptomes. The phylogenetic analysis was also made based on the sequenced cytochrome c oxidase subunit 1 (COX1) gene. Results Mitochondria were stained red using Mito-tracker Red staining and were stained slightly blue by DAPI dye. The cristae and double membrane structures of the mitochondria were observed by TEM. Besides, many lipid droplets were evenly distributed around the macronucleus. A total of 2594 unigenes were assigned to 23 functional classifications of COG. Mitochondrial metabolic pathways were depicted. The mitochondria contained enzymes for the complete tricarboxylic acid (TCA) cycle, fatty acid metabolism, amino acid metabolism, and cytochrome-based electron transport chain (ETC), but only partial enzymes involved in the iron-sulfur clusters (ISCs). Conclusions Our results showed that C. uncinata possess typical mitochondria. Stored lipid droplets inside mitochondria may be the energy storage of C. uncinata that helps its transmission from a free-living to a parasitic lifestyle. These findings also have improved our knowledge of the mitochondrial metabolism of C. uncinata and increased the volume of molecular data for future studies of this facultative parasite. Graphical Abstract

Abstract Background Within the class Enoplea, the earliest-branching lineages in the phylum Nematoda, the relatively highly conserved ancestral mitochondrial architecture of Trichinellida is in stark contrast to the rapidly evolving architecture of Dorylaimida and Mermithida. To better understand the evolution of mitogenomic architecture in this lineage, we sequenced the mitogenome of a fish parasite Pseudocapillaria tomentosa (Trichinellida: Capillariidae) and compared it to all available enoplean mitogenomes. Results P. tomentosa exhibited highly reduced noncoding regions (the largest was 98 bp), and a unique base composition among the Enoplea. We attributed the latter to the inverted GC skew (0.08) in comparison to the ancestral skew in Trichinellidae (-0.43 to -0.37). Capillariidae, Trichuridae and Longidoridae (Dorylaimida) generally exhibited low negative or low positive skews (-0.1 to 0.1), whereas Mermithidae exhibited fully inverted low skews (0 to 0.05). This is indicative of inversions in the strand replication order or otherwise disrupted replication mechanism in the lineages with reduced/inverted skews. Among the Trichinellida, Trichinellidae and Trichuridae have almost perfectly conserved architecture, whereas Capillariidae exhibit multiple rearrangements of tRNA genes. In contrast, Mermithidae (Mermithida) and Longidoridae (Dorylaimida) exhibit almost no similarity to the ancestral architecture. Conclusions Longidoridae exhibited more rearranged mitogenomic architecture than the hypervariable Mermithidae. Similar to the Chromadorea, the evolution of mitochondrial architecture in enoplean nematodes exhibits a strong discontinuity: lineages possessing a mostly conserved architecture over tens of millions of years are interspersed with lineages exhibiting architectural hypervariability. As Longidoridae also have some of the smallest metazoan mitochondrial genomes, they contradict the prediction that compact mitogenomes should be structurally stable. Lineages exhibiting inverted skews appear to represent the intermediate phase between the Trichinellidae (ancestral) and fully derived skews in Chromadorean mitogenomes (GC skews = 0.18 to 0.64). Multiple lines of evidence (CAT-GTR analysis in our study, a majority of previous mitogenomic results, and skew disruption scenarios) support the Dorylaimia split into two sister-clades: Dorylaimida + Mermithida and Trichinellida. However, skew inversions produce strong base composition biases, which can hamper phylogenetic and other evolutionary studies, so enoplean mitogenomes have to be used with utmost care in evolutionary studies.

Foxtail millet (Setaria italica), a short-day plant, is one of the important crops for food security encountering climate change, particularly in regions where it is a staple food. Under the short-day condition in Taiwan, the heading dates (HDs) of foxtail millet accessions varied by genotypes and ambient temperature (AT). The allelic polymorphisms in flowering time (FT)–related genes were associated with HD variations. AT, in the range of 13°C–30°C that was based on field studies at three different latitudes in Taiwan and observations in the phytotron at four different AT regimes, was positively correlated with growth rate, and high AT promoted HD. To elucidate the molecular mechanism of foxtail millet HD, the expression of 14 key FT-related genes in four accessions at different ATs was assessed. We found that the expression levels of SiPRR95, SiPRR1, SiPRR59, SiGhd7-2, SiPHYB, and SiGhd7 were negatively correlated with AT, whereas the expression levels of SiEhd1, SiFT11, and SiCO4 were positively correlated with AT. Furthermore, the expression levels of SiGhd7-2, SiEhd1, SiFT, and SiFT11 were significantly associated with HD. A coexpression regulatory network was identified that shown genes involved in the circadian clock, light and temperature signaling, and regulation of flowering, but not those involved in photoperiod pathway, interacted and were influenced by AT. The results reveal how gene × temperature and gene × gene interactions affect the HD in foxtail millet and could serve as a foundation for breeding foxtail millet cultivars for shift production to increase yield in response to global warming.

Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.

Abstract Phylogenetic analysis has entered the genomics (multilocus) era. For less experienced researchers, conquering the large number of software programs required for a multilocus‐based phylogenetic reconstruction can be somewhat daunting and time‐consuming. PhyloSuite, a software with a user‐friendly GUI, was designed to make this process more accessible by integrating multiple software programs needed for multilocus and single‐gene phylogenies and further streamlining the whole process. In this protocol, we aim to explain how to conduct each step of the phylogenetic pipeline and tree‐based analyses in PhyloSuite. We also present a new version of PhyloSuite (v1.2.3), wherein we fixed some bugs, made some optimizations, and introduced some new functions, including a number of tree‐based analyses, such as signal‐to‐noise calculation, saturation analysis, spurious species identification, and etc. The step‐by‐step protocol includes background information (i.e., what the step does), reasons (i.e., why do the step), and operations (i.e., how to do it). This protocol will help researchers quick‐start their way through the multilocus phylogenetic analysis, especially those interested in conducting organelle‐based analyses.

Abstract Background During the coronavirus disease 2019 (COVID-19) containment, primary health care (PHC) facilities inChina played an important role in providing both healthcare and public care services to community populations. The tasks of COVID-19 containment facilitated by PHC facilities were different among different regions and during different periods of COVID-19 pandemic. We sought to investigate the gaps on task participation, explore existing problems and provide corresponding solutions. Methods Semi-structured face-to-face interviews with COVID-19 prevention and control management teams of PHC facilities were conducted. Purposive stratified sampling was used and 32 team members of 22 PHC facilities were selected from Wuhan (as high-risk city), Shanghai (as medium-risk city) and Zunyi (as low-risk city). Framework analysis was employed to analyze the transcribed recordings. Results The main tasks of PHC facilities during the early period of the pandemic included assisting in contact tracing and epidemiological investigation, screening of populations at high-risk at travel centers/internals, house-by-house, or pre-examination/triage within PHC facilities; at-home/ centralized quarantine management; the work of fever sentinel clinics. Further analyses revealed the existing problems and suggestions for improvement or resolutions. Regular medical supply reserves were recommended because of the medical supply shortage during the pre-outbreak period. Temporarily converted quarantine wards and centralized quarantine centers could be used to deal with pressures on patients’ treatment and management of the febrile patients. Only after strict evaluation of nucleic acid testing (NAT) results and housing conditions, decision on quarantine at-home or centralized quarantine centers could be made. Settings of fever sentinel clinics at PHC facilities allowed fever patients with no COVID-19 infection risks for treatment without being transferred to fever clinics of the designed secondary hospitals. Psychological intervention was sometimes in need and really helped in addressing individuals’ mental pressures. Conclusions During the COVID-19 containment, PHC facilities in China were responsible for different tasks and several problems were encountered in the working process. Accordingly, specific and feasible suggestions were put forward for different problems. Our findings are highly beneficial for healthcare teams and governments in handling similar situations.

Objectives: The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. Methods: Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. Result: A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. Conclusions: Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD. [ABSTRACT FROM AUTHOR]

BackgroundAcquired immunodeficiency syndrome (AIDS) is a global pandemic caused by human immunodeficiency virus (HIV), which is transmitted through human behaviors, such as sexual intercourse, intravenous drug injection, and blood transfusion. Rare studies have focused on the evaluation of the effects of culture, society, and HIV-related policies in adjusting people's HIV-related behaviors, i.e., ways of HIV transmission.MethodsBy taking the new HIV infections in Hubei Province each year from 1995 to 2020 as the sample, our study used the Hierarchical Age-Period-Cohort (HAPC) model to analyze the effects of age, period, and cohort on the trends of ways of HIV transmission.ResultsFrom 1995 to 2020, the number of new HIV infections in Hubei presented a general upward trend. A total of 34,636 HIV infections were reported during this period. According to the statistics of the new HIV infections in Hubei Province between 1995 and 2020, there is a negative correlation between age (−0.099, p < 0.001), squared age (−0.002, p < 0.001), and the rate of blood transmission. While there is a positive correlation between age (0.143, p < 0.001), squared age (0.002, p < 0.001), and the rate of HIV infection through sexual transmission. The significant period and cohort effects on ways of HIV transmission were also observed in the Chinese population.ConclusionSexual and blood transmission are the two main ways of HIV infection in China and Hubei. The trend of blood transmission is in accordance with the wave of blood trade in the early 1990s in China. The trend of sexual transmission indicates an increasing need to promote safer sexual behavior among the older population and later generations and design more tailored, innovative, and diverse HIV prevention strategies, especially for the high-risk groups.

This study aimed at exploring the impact of post-epidemic era on teachers’ behavioral intention of distance education. In this study, purposive sampling method was used to enroll 390 teachers in colleges and universities, high schools and vocational schools, and junior high and elementary schools to be the research subjects for the questionnaire survey. A total of 360 questionnaires were collected for statistics, and AMOS 23.0 statistical software was used to analyze the correlation between variables. Meanwhile, a structural equation model was used to analyze and verify the impact of the technology acceptance model, information system success model, and diffusion of innovations theory. According to the results, the system quality of distance teaching platforms certainly affected perceived usefulness, and perceived usefulness affected teachers’ attitudes toward using distance teaching systems. In addition, perceived ease of use had an impact on perceived usefulness, and trialability had an impact on teachers’ attitudes toward using distance teaching systems. Finally, teachers’ attitude toward using a distance teaching system also affected their behavioral intention. According to the results, suggestions were made in this study to teachers and students for distance teaching. Additionally, the main contribution of this study lies in providing specific strategies for further distance teaching through empirical results in combination with on-site teaching.

This paper aims to explore the change of learning mode of college students from physical courses to online courses due to the impact of the COVID-19 pandemic. The questionnaire survey method is used to conduct research on the behavior intentions of college students in online teaching under the pandemic. A total of 600 questionnaires are distributed, and 530 questionnaires are collected, for a recovery rate of 88%. A total of 493 supported questionnaires are received, for an effective recovery rate of 93%. Descriptive statistics of data analysis are used to analyze the distribution of background variables of college students, and a structural equation model is used to analyze and verify the impact of external variables (trust, convenience, perceived critical mass) on the technology acceptance model (perceived usefulness, perceived ease of use, attitude, and behavior intention). The results found no significant impact of the trust of college students in online teaching on the perceived usefulness, and significant impact of trust on the perceived ease of use. There is significant impact of convenience on perceived usefulness, and no significant impact of convenience on perceived ease of use. There is no significant impact of perceived critical mass on perceived usefulness, and significant impact of perceived critical mass on perceived ease of use. There is significant impact of perceived ease of use on perceived usefulness, and significant impact of perceived usefulness on attitude. There is significant impact of perceived ease of use on attitude, and significant impact of attitude on behavior intention. Based on the research results, practical suggestions and research suggestions are proposed in this research, which can be used as a reference for college students to use online courses for learning.

Primary cutaneous lymphomas are rare non-Hodgkin lymphomas consisting of heterogeneous disease entities. Photodynamic therapy (PDT) utilizing photosensitizers irradiated with a specific wavelength of light in the presence of oxygen exerts promising anti-tumor effects on non-melanoma skin cancer, yet its application in primary cutaneous lymphomas remains less recognized. Despite many in vitro data showing PDT could effectively kill lymphoma cells, clinical evidence of PDT against primary cutaneous lymphomas is limited. Recently, a phase 3 “FLASH” randomized clinical trial demonstrated the efficacy of topical hypericin PDT for early-stage cutaneous T-cell lymphoma. An update on recent advances of photodynamic therapy in primary cutaneous lymphomas is provided.