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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of this lineage mainly relied on low-power datasets (a small number of samples and a single molecular marker) and (now) outdated algorithms.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.

AIM: To observe the improvement of ocular hemodynamics before and after intraocular pressure(IOP)intervention in patients with non-arteritic anterior ischemic optic neuropathy(NAION).METHODS: Retrospective case series. Totally 92 patients(92 eyes)with NAION were admitted to the Department of Ophthalmology, Xi'an Fourth Hospital from July 2012 to September 2018. Forty-six patients received only basic treatment without IOP lowering treatment as the conventional treatment group. The other 46 patients were treated with brinzolamide eye drops combined with brimonidine eye drops to lower IOP on the basis of conventional treatment, as the IOP intervention group. Before and after treatment, the blood flow rate of the ophthalmic artery and central retinal artery were measured by color Doppler ultrasound. The IOP, best corrected visual acuity(BCVA), mean visual field defect(MD), retinal nerve fiber layer thickness(RNFLT), ophthalmic artery and central retinal artery peak systolic blood velocity(PSV), end-diastolic blood velocity(EDV), pulse index(PI)and resistance index(RI)were compared.RESULTS: Before treatment, there were no significant differences in IOP, BCVA(LogMAR), MD, RNFLT, PSV, EDV, PI and RI between the two groups(P>0.05). After 14d of treatment, IOP, BCVA(LogMAR), MD and RNFLT of the two groups were significantly improved compared with those before treatment(P

Abstract Background Accumulating evidence indicates that miRNAs are involved in multiple cellular functions and participate in various cancer development and progression, including breast cancer. Methods We aimed to investigate the role of miR-381-3p in breast cancer. The expression level of miR-381-3p and EMT transcription factors was examined by quantitative real-time PCR (qRT-PCR). The effects of miR-381-3p on breast cancer proliferation and invasion were determined by Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays. The regulation of miR-381-3p on its targets was determined by dual-luciferase analysis, qRT-PCR, and western blot. Results We found that the expression of miR-381-3p was significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-381-3p inhibited breast cancer proliferation and invasion, whereas knockdown of miR-381-3p promoted cell proliferation and invasion in MDA-MB-231 and SKBR3 cells. Mechanistically, overexpression of miR-381-3p inhibited breast cancer epithelial–mesenchymal transition (EMT). Both Sox4 and Twist1 were confirmed as targets of miR-381-3p. Moreover, transforming growth factor-β (TGF-β) could reverse the effects of miR-381-3p on breast cancer progression. Conclusions Our observation suggests that miR-381-3p inhibits breast cancer progression and EMT by regulating the TGF-β signaling via targeting Sox4 and Twist1.

Abstract Testing black hole’s charged property is a fascinating topic in modified gravity and black hole astrophysics. In the first Gravitational-Wave Transient Catalog (GWTC-1), ten binary black hole merger events have been formally reported, and these gravitational wave signals have significantly enhanced our understanding of the black hole. In this paper, we try to constrain the amount of electric charge with the parameterized post-Einsteinian framework by treating the electric charge as a small perturbation in a Bayesian way. We find that the current limits in our work are consistent with the result of Fisher information matrix method in previous works. We also develop a waveform model considering a leading order charge effect for binary black hole inspiral.

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.