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Atmospheric instability is one of the necessary conditions for the occurrence of severe convective weather, which is characterized by its intricacies. This paper first briefly reviews the air parcel theory and points out its limitations in application, for example, changes in pressure and vorticity of the environmental atmosphere inevitably caused by the strong upward motion of parcels in convective storms. Then, the concepts of static instability, symmetric instability, and other types of instability are reviewed. A special focus is given to summarizing the conditions for conditional instability, moist absolute instability, and conditional symmetric instability, as well as their relationship with the occurrence and development of convective storms, with some misunderstandings being clarified. The most effective method for determining conditional instability is to make a finite virtual displacement of the parcel and then use convective available potential energy (CAPE) for identification. However, the calculation of CAPE and convective inhibition is sensitive to the temperature and moisture of the parcel, and they should be computed and corrected using virtual temperature. The optimal CAPE value has better representativeness than that of the surface-based CAPE. In strong vertical wind shear and low CAPE environments, the acceleration effect of dynamic disturbance pressure gradient caused by rotation is crucial for the development of severe convective storms. Convective instability does not necessarily correspond to conditional instability. A straightforward method for distinguishing conditional symmetric instability is to use saturated equivalent geostrophic potential vorticity. We further summarize the mesoscale rainband characteristics caused by this type of instability.

Abstract Breast cancer (BC) is the most frequent malignant cancer diagnosis and is a primary factor for cancer deaths in women. The clinical subtypes of BC include estrogen receptor (ER) positive, progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER2) positive, and triple-negative BC (TNBC). Based on the stages and subtypes of BC, various treatment methods are available with variations in the rates of progression-free disease and overall survival of patients. However, the treatment of BC still faces challenges, particularly in terms of drug resistance and recurrence. The study of epigenetics has provided new ideas for treating BC. Targeting aberrant epigenetic factors with inhibitors represents a promising anticancer strategy. The KDM5 family includes four members, KDM5A, KDM5B, KDM5C, and KDMD, all of which are Jumonji C domain-containing histone H3K4me2/3 demethylases. KDM5 proteins have been extensively studied in BC, where they are involved in suppressing or promoting BC depending on their specific upstream and downstream pathways. Several KDM5 inhibitors have shown potent BC inhibitory activity in vitro and in vivo, but challenges still exist in developing KDM5 inhibitors. In this review, we introduce the subtypes of BC and their current therapeutic options, summarize KDM5 family context-specific functions in the pathobiology of BC, and discuss the outlook and pitfalls of KDM5 inhibitors in this disease.

Abstract Increasing evidence infers that some complex diseases are attributed to co-infection with multiple pathogens, such as shrimp white feces syndrome (WFS); however, there is a lack of experimental evidence to validate such causal link. This deficiency further impedes rational design of probiotics to elicit desired benefits to shrimp WFS resistance. Herein, we validated the causal roles of Vibrio fluvialis, V. coralliilyticus and V. tubiashii (in a ratio of 7:2:1) in shrimp WFS etiology, which fully satisfied Koch’s postulates. Correspondingly, we precisely designed four antagonistic strains: Ruegeria lacuscaerulensis, Nioella nitratireducens, Bacillus subtilis and Streptomyces euryhalinus in a ratio of 4:3:2:1, which efficiently guarded against WFS. Dietary supplementation of the probiotics stimulated beneficial gut populations, streptomycin, short chain fatty acids, taurine metabolism potentials, network stability, tight junction, and host selection, while reducing turnover rate and average variation degree of gut microbiota, thereby facilitating ecological and mechanical barriers against pathogens. Additionally, shrimp immune pathways, such as Fcγ R-mediated phagocytosis, Toll-like receptor and RIG-I-like receptor signaling pathways conferring immune barrier, were activated by probiotics supplementation. Collectively, we establish an updated framework for precisely validating co-infection with multiple pathogens and rationally designing antagonistic probiotics. Furthermore, our findings uncover the underlying beneficial mechanisms of designed probiotics from the probiotics–gut microbiome–host immunity axis.

Abstract RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid–protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure–activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy. Graphical Abstract

Lysine-specific demethylase 4 A (KDM4A, also named JMJD2A, KIA0677, or JHDM3A) is a demethylase that can remove methyl groups from histones H3K9me2/3, H3K36me2/3, and H1.4K26me2/me3. Accumulating evidence suggests that KDM4A is not only involved in body homeostasis (such as cell proliferation, migration and differentiation, and tissue development) but also associated with multiple human diseases, especially cancers. Recently, an increasing number of studies have shown that pharmacological inhibition of KDM4A significantly attenuates tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. Although there are several reviews on the roles of the KDM4 subfamily in cancer development and therapy, all of them only briefly introduce the roles of KDM4A in cancer without systematically summarizing the specific mechanisms of KDM4A in various physiological and pathological processes, especially in tumorigenesis, which greatly limits advances in the understanding of the roles of KDM4A in a variety of cancers, discovering targeted selective KDM4A inhibitors, and exploring the adaptive profiles of KDM4A antagonists. Herein, we present the structure and functions of KDM4A, simply outline the functions of KDM4A in homeostasis and non-cancer diseases, summarize the role of KDM4A and its distinct target genes in the development of a variety of cancers, systematically classify KDM4A inhibitors, summarize the difficulties encountered in the research of KDM4A and the discovery of related drugs, and provide the corresponding solutions, which would contribute to understanding the recent research trends on KDM4A and advancing the progression of KDM4A as a drug target in cancer therapy.

IntroductionAeromonas spp. are ubiquitous inhabitants of ecosystems, and many species are opportunistically pathogenic to humans and animals. Multidrug-resistant (MDR) Aeromonas species have been widely detected in hospitals, urban rivers, livestock, and aquatic animals.ResultsIn this study, we identified two Aeromonas isolates, namely Aeromonas veronii 0728Q8Av and Aeromonas caviae 1029Y16Ac, from coastal waters in Zhejiang, China. Both isolates exhibited typical biochemical characteristics and conferred MDR to 11 kinds of antibiotics, remaining susceptible to ceftazidime. Whole-genome sequencing revealed that both isolates harbored multiple antibiotic resistance genes (ARGs) and several mobile genetic elements (MGEs) on the chromosomes, each containing a resistance genomic island (GI), a typical class 1 integron, a transposon, and various insertion sequences (ISs). Most ARGs were situated within the multiple resistance GI, which contained a class 1 integron and a transposon in both Aeromonas isolates. Furthermore, a chromosomal mcr-3.16 gene was identified in A. veronii 0728Q8Av, while a chromosomal mcr-3.3 was found in A. caviae 1029Y16Ac. Both mcr-3 variants were not located within but were distanced from the multidrug resistance GI on the chromosome, flanking by multiple ISs. In addition, a mcr-3-like was found adjacent to mcr-3.16 to form a tandem mcr-3.16-mcr-3-like-dgkA structure; yet, Escherichia coli carrying the recombinants of mcr-3-like did not exhibit resistance to colistin. And an incomplete mcr-3-like was found adjacent to mcr-3.3 in A. caviae 1029Y16Ac, suggesting the possibility that mcr-3 variants originated from Aeromonas species. In vivo bacterial pathogenicity test indicated that A. veronii 0728Q8Av exhibited moderate pathogenicity towards infected ayu, while A. caviae 1029Y16Ac was non-virulent.DiscussionThus, both Aeromonas species deserve further attention regarding their antimicrobial resistance and pathogenicity.

The present study was conducted to evaluate the effect of dietary Silphium perfoliatum L. on growth performance, immunity, intestinal health, and resistance against Nocardia seriolae of largemouth bass. Four dietary concentrations of S. perfoliatum L. were prepared: 0% (SPL0), 1% (SPL1), 2.5% (SPL2.5), and 5% (SPL5). After 60 d feeding, a challenge test was conducted by injecting N. seriolae intraperitoneally. The results showed that supplementing the diets with S. perfoliatum L. could promote the weight gain rate, specific growth rate, and feed intake. Meantime, S. perfoliatum L. could also enhance the activity of immune-related enzymes and improve the expression of immune-related genes in the liver. Compared to the control group, S. perfoliatum L. improved intestinal morphology and reduced the abundance of harmful bacteria in intestinal microbiota. Importantly, supplementing the diets with S. perfoliatum L. protected largemouth bass from N. seriolae infection, resulting in a relative percent survival (RPS) of 24% (SPL1), 31.99% (SPL2.5), and 43.99% (SPL5). In conclusion, the present study showed that S. perfoliatum L. could boost growth performance, enhance immunity, promote intestinal health, and improve the ability of largemouth bass against N. seriolae infection.

Abstract Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN – a multi-view, weakly-supervised deep clustering method – which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer’s disease and brain endophenotypes associated with hypertension, from MRI and single nucleotide polymorphism data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-associated neuroimaging phenotypes.

Zinc finger Asp-His-His-Cys motif-containing (zDHHC) proteins, known for their palmitoyltransferase (PAT) activity, play crucial roles in diverse cellular processes, including immune regulation. However, their non-palmitoyltransferase immunomodulatory functions and involvement in teleost immune responses remain underexplored. In this study, we systematically characterized the zDHHC family in the large yellow croaker (Larimichthys crocea), identifying 22 members. Phylogenetic analysis unveiled that each of the 22 LczDHHCs formed distinct clusters with their orthologues from other teleost species. Furthermore, all LczDHHCs exhibited a highly conserved DHHC domain, as confirmed by tertiary structure prediction. Notably, LczDHHC23 exhibited the most pronounced upregulation following Pseudomonas plecoglossicida (P. plecoglossicida) infection of macrophage/monocyte cells (MO/MΦ). Silencing LczDHHC23 led to heightened pro-inflammatory cytokine expression and diminished anti-inflammatory cytokine levels in MO/MΦ during infection, indicating its anti-inflammatory role. Functionally, LczDHHC23 facilitated M2-type macrophage polarization, as evidenced by a significant skewing of MO/MΦ towards the pro-inflammatory M1 phenotype upon LczDHHC23 knockdown, along with the inhibition of MO/MΦ necroptosis induced by P. plecoglossicida infection. These findings highlight the non-PAT immunomodulatory function of LczDHHC23 in teleost immune regulation, broadening our understanding of zDHHC proteins in host-pathogen interactions, suggesting LczDHHC23 as a potential therapeutic target for immune modulation in aquatic species.

Licorice (Glycyrrhiza glabra) is a plant of the genus Glycyrrhiza in the family Fabaceae/Leguminosae and is a renowned natural herb with a long history of medicinal use dating back to ancient times. Glycyrrhizin (GLY), the main active component of licorice, serves as a widely utilized therapeutic agent in clinical practice. GLY exhibits diverse medicinal properties, including anti-inflammatory, antibacterial, antiviral, antitumor, immunomodulatory, intestinal environment maintenance, and liver protection effects. However, current research primarily emphasizes GLY’s antiviral activity, while providing limited insight into its antibacterial properties. GLY demonstrates a broad spectrum of antibacterial activity via inhibiting the growth of bacteria by targeting bacterial enzymes, impacting cell membrane formation, and altering membrane permeability. Moreover, GLY can also bolster host immunity by activating pertinent immune pathways, thereby enhancing pathogen clearance. This paper reviews GLY’s inhibitory mechanisms against various pathogenic bacteria-induced pathological changes, its role as a high-mobility group box 1 inhibitor in immune regulation, and its efficacy in combating diseases caused by pathogenic bacteria. Furthermore, combining GLY with other antibiotics reduces the minimum inhibitory concentration, potentially aiding in the clinical development of combination therapies against drug-resistant bacteria. Sources of information were searched using PubMed, Web of Science, Science Direct, and GreenMedical for the keywords “licorice”, “Glycyrrhizin”, “antibacterial”, “anti-inflammatory”, “HMGB1”, and combinations thereof, mainly from articles published from 1979 to 2024, with no language restrictions. Screening was carried out by one author and supplemented by others. Papers with experimental flaws in their experimental design and papers that did not meet expectations (antifungal papers, etc.) were excluded.

Enterocytozoon hepatopenaei (EHP) is a parasite in shrimp farming. EHP mainly parasitizes the hepatopancreas of shrimp, causing slow growth, which severely restricts the economic income of shrimp farmers. To explore the pathogenic mechanism of EHP, the host subcellular construction, molecular biological characteristics, and mitochondrial condition of Litopenaeus vannamei were identified using transmission electron microscopy (TEM), real-time qPCR, an enzyme assay, and flow cytometry. The results showed that EHP spores, approximately 1 μm in size, were located on the cytoplasm of the hepatopancreas. The number of mitochondria increased significantly, and mitochondria morphology showed a condensed state in the high-concentration EHP-infected shrimp by TEM observation. In addition, there were some changes in mitochondrial potential, but apoptosis was not significantly different in the infected shrimp. The qPCR results showed that the gene expression levels of hexokinase and pyruvate kinase related to energy metabolism were both upregulated in the diseased L. vannamei. Enzymatic activity showed hexokinase and lactate dehydrogenase were significantly increased in the shrimp infected with EHP, indicating EHP infection can increase the glycolysis process and decrease the oxidative phosphorylation process of L. vannamei. Previous transcriptomic data analysis results also support this conclusion.

Infection with the pathogenic bacterium Vibrio parahaemolyticus typically causes severe hepatopancreatic damage in Penaeus vannamei, often resulting in acute shrimp mortality. Therefore, protecting the shrimp’s hepatopancreas is crucial for enhancing their disease resistance. Previous research has demonstrated that the probiotic strain Lactobacillus plantarum Ep-M17 inhibits the growth of V. parahaemolyticus E1 in vitro. However, it remains uncertain whether Ep-M17 can provide protective benefits to the shrimp’s hepatopancreas. To address this knowledge gap, our present study investigated the histological changes, enzyme activity, gene transcription, and metabolite levels in the hepatopancreas of shrimp after a 4-week diet supplemented with Ep-M17. The results revealed that incorporating Ep-M17 into the shrimp’s diet alleviated the damage by V. parahaemolyticus E1 infection in hepatopancreatic cells. In addition, the inclusion of Ep-M17 notably boosted the effectiveness of immunodigestive enzymes such as SOD, AKP, and CAT. Furthermore, Ep-M17 stimulated gene transcription in crucial immune response-related signalling pathways like the mitogen-activated protein kinase signaling pathway and the antigen processing and presentation pathway. Moreover, the incorporation of Ep-M17 into shrimp diets increased the levels of β-alanine, and histidine in the hepatopancreas, enhancing anti-inflammatory capacity and improving the shrimp’s immune response. Overall, the results indicate that incorporating Ep-M17 into the diet can enhance shrimp disease resistance by bolstering both immune response and metabolic activity within the hepatopancreas. These results underscore the importance of probiotics in controlling aquatic animal diseases and highlight Ep-M17 as a promising dietary supplement for enhancing shrimp health and immunity in aquaculture.

The balance between ubiquitination and deubiquitination is instrumental in the regulation of protein stability and maintenance of cellular homeostasis. The deubiquitinating enzyme, ubiquitin-specific protease 36 (USP36), a member of the USP family, plays a crucial role in this dynamic equilibrium by hydrolyzing and removing ubiquitin chains from target proteins and facilitating their proteasome-dependent degradation. The multifaceted functions of USP36 have been implicated in various disease processes, including cancer, infections, and inflammation, via the modulation of numerous cellular events, including gene transcription regulation, cell cycle regulation, immune responses, signal transduction, tumor growth, and inflammatory processes. The objective of this review is to provide a comprehensive summary of the current state of research on the roles of USP36 in different pathological conditions. By synthesizing the findings from previous studies, we have aimed to increase our understanding of the mechanisms underlying these diseases and identify potential therapeutic targets for their treatment.

Glugea plecoglossi is an obligate intracellular microsporidium, which poses a significant threat to ayu (Plecoglossus altivelis). In vitro cultivation models are invaluable tools for investigating intracellular microorganisms, including G. plecoglossil. In this study, we attempted to in vitro cultivate G. plecoglossi using primary cultures derived from ayu monocytes/macrophages (MO/MΦ), a murine-derived macrophage cell line RAW264.7, and the epithelioma papulosum cyprini (EPC) cell line. The results demonstrated that MO/MΦ infected with spores exhibited a pronounced immune response which was presented by rapidly high expression levels of inflammatory cytokines, such as PaIL-1β, PaTNF-α, PaIL-10, and PaTGF-β, and detached within 96 h post-infection (hpi). Infected RAW264.7 cells remained capable of stable passage yet exhibited cellular deformation with a decrease in intracellular spores occurring around 8 days post-infection (dpi). In contrast, EPC cells promised a substantial parasite population, and the cytokine expression levels returned to normal by 8 dpi. In addition, G. plecoglossi spores recovered from EPC cells could infect young ayu, suggesting that EPC cells might be used as an in vitro cultivation system for G. plecoglossi.

It is challenging to manage schizophrenic catatonia and comorbid chronic intestinal pseudo-obstruction (CIPO). The pathology of catatonia is unclear. There are few reports or research on this issue. In this case, we present a middle-aged woman diagnosed with schizophrenia with catatonic features and comorbid CIPO. In the treatment process, modified electroconvulsive therapy (mECT) improved her stupor and CIPO partially. Lorazepam alleviated her stupor and CIPO completely. It is the first report describing complete remission with lorazepam in patient suffering from comorbid schizophrenic catatonia and CIPO, which may benefit the exploration of pathophysiology and treatment of comorbidity of schizophrenia with catatonia and CIPO.

Background Long-term use of antipsychotics or other dopamine antagonists can result in the extrapyramidal side effect of tardive dyskinesia (TD). Case presentation: An 18-year-old female patient experienced abnormal speech and behavior and because of an equivocal diagnosis, she was given daily doses of 300 mg of quetiapine and 60 mg of ziprasidone. She had used these medications for 2 years before the appearance of involuntary abnormal movements. These movements, which were classified as TD, steadily worsened and markedly interfered with her daily life. Following a trial-and-error course of therapy with vitamin E, vitamin B6, amantadine, valproic acid sodium, lorazepam, and diazepam, the drugs were gradually reduced and stopped, yet the aberrant movements persisted. Finally, the patient was given olanzapine, clonazepam, baclofen, and gabapentin. The Abnormal Involuntary Movement Scale was used to assess changes in the patient's condition. Her TD was efficiently managed through co-administration of olanzapine, clonazepam, baclofen, and gabapentin. Conclusions The possibility of TD inducing by antipsychotic use is a clinical concern, even though atypical antipsychotics decrease the incidence of extrapyramidal side effects, and it cannot be entirely excluded. This report provides useful insights into the management of TD and will help clinicians manage similar cases.

Zoonotic parasites pose significant health risks globally. In the present study, we combined a microfluidic chip with loop-mediated isothermal amplification (on-chip LAMP) to detect five zoonotic parasites: Toxoplasma gondii, Cryptosporidium parvum, Cryptosporidium hominis, Clonorchis sinensis, and Taenia solium. This method enabled the simultaneous parallel analysis of five genetic markers from a maximum of four samples per chip. The on-chip LAMP assay was conducted in a highly automated format via the addition (by pipetting) of each sample in a single operation. The reaction was performed in volumes as low as 5 μL at a temperature of 65°C for 60 min, achieving limits of detection ranging from 10−2 to 10−3 pg./μL of recombinant plasmid DNA. All the time-to-positive values were less than 40 min, and almost all the coefficients of variation were less than 10%, even when using limit of detection concentrations for multiple pathogens, indicating robust reproducibility among replicates. The clinical sensitivity and specificity for detecting 135 field samples were 98.08 and 97.59%, respectively, compared with traditional biological methods, indicating good applicability in the detection of field samples. This on-chip LAMP assay allows for low reagent consumption, ease of operation, and multiple analyses of samples and genetic targets, and is applicable for on-site detection and the routine monitoring of multiple zoonotic parasites.

Transferrin plays an important role in iron metabolism and has been reported to be involved in the immune response to environmental stress. In this study, the transferrin gene (LwTf) from Amur ide (Leuciscus waleckii) was cloned and characterized. The cDNA was observed to contain an open reading frame (ORF) of 1998bp and encode a 665-amino-acid-long protein that shares 73.04% identity with the transferrin from silver carp (Hypophthalmichthys molitrix). Amino acid alignment analysis showed that LwTf contained an initial peptide and two lobes (N- and C-lobes). Quantitative real-time PCR (qPCR) analyses showed that the expression levels of LwTf were abundant in the liver of the fish but were also significant in the brain and spleen, with lower expression observed in six other tissues. The temporal expression profiles were detected during the alkaline challenge experiment in alkali-water and freshwater populations of healthy adult Amur ide. LwTf expression was significantly upregulated in the main immune organs (spleen, kidney, and head kidney) of the freshwater Amur ide population compared to that in the alkali-water Amur ide population. Taken together, these results indicate that in Amur ide, LwTf might play an important role in the innate immune response to a high alkaline stress.

Human whole-brain functional connectivity networks have been shown to exhibit both local/quasilocal (e.g., a set of functional sub-circuits induced by node or edge attributes) and non-local (e.g., higher-order functional coordination patterns) properties. Nonetheless, the non-local properties of topological strata induced by local/quasilocal functional sub-circuits have yet to be addressed. To that end, we proposed a homological formalism that enables the quantification of higher-order characteristics of human brain functional sub-circuits. Our results indicate that each homological order uniquely unravels diverse, complementary properties of human brain functional sub-circuits. Noticeably, the H1 homological distance between rest and motor task was observed at both the whole-brain and sub-circuit consolidated levels, which suggested the self-similarity property of human brain functional connectivity unraveled by a homological kernel. Furthermore, at the whole-brain level, the rest–task differentiation was found to be most prominent between rest and different tasks at different homological orders: (i) Emotion task (H0), (ii) Motor task (H1), and (iii) Working memory task (H2). At the functional sub-circuit level, the rest–task functional dichotomy of the default mode network is found to be mostly prominent at the first and second homological scaffolds. Also at such scale, we found that the limbic network plays a significant role in homological reconfiguration across both the task and subject domains, which paves the way for subsequent investigations on the complex neuro-physiological role of such network. From a wider perspective, our formalism can be applied, beyond brain connectomics, to study the non-localized coordination patterns of localized structures stretching across complex network fibers.

Leukocyte cell-derived chemotaxin-2 (LECT2, also named ChM-II), initially identified as a chemokine mediating neutrophil migration, is a multifunctional secreted factor involved in diverse physiological and pathological processes. The high sequence similarity of LECT2 among different vertebrates makes it possible to explore its functions by using comparative biology. LECT2 is associated with many immune processes and immune-related diseases via its binding to cell surface receptors such as CD209a, Tie1, and Met in various cell types. In addition, the misfolding LECT2 leads to the amyloidosis of several crucial tissues (kidney, liver, and lung, etc.) by inducing the formation of insoluble fibrils. However, the mechanisms of LECT2-mediated diverse immune pathogenic conditions in various tissues remain to be fully elucidated due to the functional and signaling heterogeneity. Here, we provide a comprehensive summary of the structure, the “double-edged sword” function, and the extensive signaling pathways of LECT2 in immune diseases, as well as the potential applications of LECT2 in therapeutic interventions in preclinical or clinical trials. This review provides an integrated perspective on the current understanding of how LECT2 is associated with immune diseases, with the aim of facilitating the development of drugs or probes against LECT2 for the theranostics of immune-related diseases.

In this study, we developed a novel method for the detection of Vibrio alginolyticus, utilizing the specific recognition of an aptamer for V. alginolyticus and signal amplification via hybridization chain reaction (HCR) and horseradish-peroxidase-conjugated streptavidin. The proposed HCR-based multivalent aptamer (multi-Apt) amplifier allows for sensitive detection of V. alginolyticus in a linear range from 10 to 107 CFU/mL. The linear equation is y = 747.5x + 126.2, R2 = 0.986, and the limit of detection (LOD) is 3 CFU/mL. Seawater and freshwater samples were utilized in the spike recovery experiment, yieldng a recovery rates ranging from 94.3% to 108.8%. The relative standard deviation (RSD) for all samples is below 6.73%. Taken together, the proposed method has great potential for application in monitoring of V. alginolyticus in aquaculture environments.

Azoxystrobin (AZ) is one of the most widely used strobilurin fungicides in the world, and its residue has seriously endangered aquatic ecological security. Our previous data showed that AZ exposure may reduce the resistance of fish to rhabdovirus infection in aquatic environment. Here, we further reported a potential long-term adverse effect of AZ exposure on the antiviral and immunosuppressive recovery in fish, and observed that mitochondrial dynamic balance was disturbed by AZ in which excessive mitochondrial fission occurred in response to decreased ATP levels. When a recovery operation was performed in AZ-exposed cells and fish, infectivity of our model virus, spring viraemia of carp virus (SVCV), was significantly decreased in vitro (using the epithelioma papulosum cyprini [EPC] fish cell line) and in vivo (using zebrafish) in a time-dependent manner. Also, the expression of eight innate antiviral immune genes (IFNs, ISG15, MX1, RIG-I, IRF3, Nrf2 and HO-1) showed a similar change to SVCV replication between the longer exposure period and the expression recovery. Additionally, AZ facilitated horizontal transmission of SVCV in a static cohabitation challenge model, predicting the increase of the potential for the viral outbreak. Therefore, our data suggest that long-term effect of AZ on irreparable impairment in fish made AZ residue potentially greater for ecological risks.

Procambarus clarkii is an important economic aquaculture species worldwide. Infectious hypodermal and hematopoietic necrosis virus (IHHNV) infects numerous crustacean hosts, including P. clarkii. However, there have been few reports on the prevalence of IHHNV in P. clarkii. In this study, 200 farmed P. clarkii were collected from Anhui, Jiangsu, Zhejiang, Hunan, Hubei, and Sichuan provinces in China. PCR detection was employed per the protocol by the World Organization for Animal Health (WOAH) to identify and detect the presence of IHHNV. The positive rate of IHHNV in different provinces ranged from 16.7 to 56.7%, and the overall IHHNV-positive rate was 38.5%. IHHNV strains isolated in this study related closely to infectious IHHNV and split into two major distinct branches. Besides, the IHHNV strains shared a high homology (93.4–99.4%). These findings suggest that a high prevalence of IHHNV was established in farmed P. clarkii in the middle and lower reaches of the Yangtze River.

Abstract Background In rare cases, intrahepatic cholangiocarcinoma can present as a pyogenic liver abscess and are often misdiagnosed. This study aimed to analyze the imaging features of intrahepatic cholangiocarcinoma mimicking a pyogenic liver abscess. Methods The clinical data and imaging results of eight patients with pathologically confirmed intrahepatic cholangiocarcinoma mimicking a liver abscess were retrospectively collected. Results The mean age was 58 years with a range of 46–68 years. Fever and leukocytosis were present in six patients. All the eight lesions were a single mass. Air–liquid levels were present in two patients. Only one patient showed hepatic lobar atrophy and hepatic capsule retraction. The double target sign of liver abscess was not noticed in the CT/MRI images of all eight patients. The inner wall of the lesion was rough and irregular, with multiple dot/patchy and wall nodule enhancements. The abscess wall and the marginal parenchyma were supplied by the hepatic artery in four patients, and the intralesional arteries were rough and disrupted. Bile duct dilatation was seen adjacent to the lesion. In seven patients, diffusion-weighted images showed irregular patchy restricted diffusion in the marginal parenchyma of the necrotic area in addition to the prominent restricted diffusion in the necrotic area. Two patients with cholangiolithiasis showed patchy slight CT hypodensity, slight T1 hypointensity, slight T2 hyperintensity, and patchy delayed enhancement. Multiple lymph nodes enlargement in the hepatic hilar area and the retroperitoneal space were seen in five patients. Conclusion Intrahepatic cholangiocarcinoma mimicking a pyogenic liver abscess have unique imaging features and require careful image examination to avoid misdiagnosis.

Hepatocellular carcinoma (HCC) is a highly vascularized, inflammatory, and abnormally proliferating tumor. Monotherapy is often unable to effectively and comprehensively inhibit the progress of HCC. In present study, we selected ginsenoside Rg3, ganoderma lucidum polysaccharide (GLP), and oridonin as the combined therapy. These three plant monomers play important roles in anti-angiogenesis, immunological activation, and apoptosis promotion, respectively. However, the low solubility and poor bioavailability seriously hinder their clinical application. To resolve these problems, we constructed a new drug, Rg3, GLP, and oridonin self-microemulsifying drug delivery system (RGO-SMEDDS). We found that this drug effectively inhibits the progression of HCC by simultaneously targeting multiple signaling pathways. RGO-SMEDDS restored immune function by suppressing the production of immunosuppressive cytokine and M2-polarized macrophages, reduced angiogenesis by downregulation of vascular endothelial growth factor and its receptor, and retarded proliferation by inhibiting the epidermal growth factor receptor EGFR/AKT/epidermal growth factor receptor/protein kinase B/glycogen synthase kinase-3 (GSK3) signaling pathway. In addition, RGO-SMEDDS showed considerable safety in acute toxicity tests. Results from this study show that RGO-SMEDDS is a promising therapy for the treatment of HCC.

Diseases are a significant impediment to aquaculture’s sustainable and healthy growth. The aquaculture industry is suffering significant financial losses as a result of the worsening water quality and increasing frequency of aquatic disease outbreaks caused by the expansion of aquaculture. Drug control, immunoprophylaxis, ecologically integrated control, etc. are the principal control strategies for fish infections. For a long time, the prevention and control of aquatic diseases have mainly relied on the use of various antibiotics and chemical drugs. However, long-term use of chemical inputs not only increases pathogenic bacteria resistance but also damages the fish and aquaculture environments, resulting in drug residues in aquatic products, severely impeding the development of the aquaculture industry. The development and use of aquatic vaccines are the safest and most effective ways to prevent aquatic animal diseases and preserve the health and sustainability of aquaculture. To give references for the development and implementation of aquatic vaccines, this study reviews the development history, types, inoculation techniques, mechanisms of action, development prospects, and challenges encountered with aquatic vaccines.

ObjectiveCLCA1 is a secreted protein with protease activity, and its expression is associated with inflammatory airway diseases. This study aimed to investigate the role of CLCA1 and IL-13 in pediatric asthma.MethodsIn asthmatic and healthy children, the correlation between CLCA1 expression and blood IL-4, and IL-13 levels were investigated by serological analyses such as RT-qPCR and ELISA. The effects on the activity and apoptosis of bronchial epithelial cells following IL-13 stimulation were explored in vitro by the CCK-8 assay and flow cytometry, respectively. CLCA1 siRNA was used to knock down the expression level of bronchial epithelial cells and the effect of IL-13 stimulation on these cells was assessed by the CCK-8 assay and flow cytometry.ResultsCLCA1, IL-4, and IL-13 were highly expressed in the serum of children with asthma. CLCA1 expression was highly correlated to serum IL-13. IL-13 stimulation reduced the activity of bronchial epithelial cells in vitro and promoted apoptosis. Lastly, knockdown of CLCA1 rescued the IL-13-induced decrease in activity and apoptosis.ConclusionCLCA1 is highly expressed in children with asthma and mediates the contributory effect of IL-13 on the occurrence and development of pediatric asthma.

Breast cancer (BC) is a kind of malignant cancer in women, and it has become the most diagnosed cancer worldwide since 2020. Histone methylation is a common biological epigenetic modification mediating varieties of physiological and pathological processes. Lysine-specific demethylase 1 (LSD1), a first identified histone demethylase, mediates the removal of methyl groups from histones H3K4me1/2 and H3K9me1/2 and plays a crucial role in varieties of cancer progression. It is also specifically amplified in breast cancer and contributes to BC tumorigenesis and drug resistance via both demethylase and non-demethylase manners. This review will provide insight into the overview structure of LSD1, summarize its action mechanisms in BC, describe the therapeutic potential of LSD1 inhibitors in BC, and prospect the current opportunities and challenges of targeting LSD1 for BC therapy.

Torasemide, a pyridine-3-sulfonylurea derivative, is a high-efficiency loop diuretic. During the process development of torasemide, five process-related substances, which have been specified in the pharmacopeia, would be produced. In this study, all these related substances, including compounds A–E, were synthesized via simple procedures and subsequently characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectrometry. Particularly, a simple synthetic method for compound A has not been found in previous literature. It is worth noting that other related substances could be prepared from compound B in one or two steps. The availability of these related substances could allow for quality control in the process of torasemide.

BackgroundMacrophages play important roles in diabetes and sepsis-related intestinal injury. Accumulating evidence suggests that microRNAs (miRNAs) act as the fundamental link between macrophage polarization and tissue injury. However, the underlying mechanisms of miRNAs in regulating macrophage polarization–related intestinal injury under diabetes and sepsis conditions remain unclear.MethodsThe cecal ligation and puncture (CLP)–induced sepsis models were established in male wild-type (WT) and diabetic mice. Clodronate liposome was used to deplete macrophage. H&E staining, inflammatory cytokines [tumor necrosis factor–α (TNF-α), interleukin-1β (IL-1β), and IL-6], and intestinal mucosal barrier function markers [occludin, ZO-1, lipopolysaccharide (LPS), and intestinal fatty acid binding protein (iFABP)] were used to assess elevated intestinal damage. miRNA array, RNA-seq, and bioinformatic analysis were performed to detect the miRNA and messenger RNA (mRNA) expression and the potential regulation mechanism. In vitro, RAW264.7 cells were cultured in the absence or presence of high glucose and LPS, miR-3061 mimics, and Snail small interfering RNA stimulation, respectively, for further mechanism studies. Luciferase reporter assay was used to confirm the interplay between miRNA and its target genes.ResultsCompared with WT CLP mice, the diabetic CLP mice showed severe intestinal damage characterized by significant increases in Chui’s scores, expression of inflammatory cytokines (TNF-α, IL-1β, and IL-6), serum LPS and iFABP concentration, and significant reductions in tight junction protein occludin and ZO-1 levels. Macrophage depletion reversed the intestinal damage caused by CLP. The bioinformatic analysis revealed that miR-3061/Snail1 might be a potential regulation axis of macrophage polarization. Furthermore, high glucose and LPS stimulation increased M1 macrophage and reduced the levels of miR-3061, which was negatively associated with Snail1 in RAW264.7 cells. Mechanistic studies demonstrated that miR-3061 regulated macrophage polarization by targeting the Snail1 mRNA 3′‐untranslated region. Moreover, miR-3061 overexpression suppressed Snail1 expression and inhibited M1 macrophage and inflammatory cytokines.ConclusionThis study elucidated that diabetes exacerbated sepsis-induced intestinal injury by promoting M1 macrophage polarization and further demonstrated that the miR-3061/Sani1 axis may be the potential target of macrophage polarization.

Breast cancer (BC) is a common malignancy that mainly occurred in women and it has become the most diagnosed cancer annually since 2020. Berberine (BBR), an alkaloid extracted from the Berberidacea family, has been found with broad pharmacological bioactivities including anti-inflammatory, anti-diabetic, anti-hypertensive, anti-obesity, antidepressant, and anticancer effects. Mounting evidence shows that BBR is a safe and effective agent with good anticancer activity against BC. However, its detailed underlying mechanism in BC treatment remains unclear. Here, we will provide the evidence for BBR in BC therapy and summarize its potential mechanisms. This review briefly introduces the source, metabolism, and biological function of BBR and emphasizes the therapeutic effects of BBR against BC via directly interacting with effector proteins, transcriptional regulatory elements, miRNA, and several BBR-mediated signaling pathways. Moreover, the novel BBR-based therapeutic strategies against BC improve biocompatibility and water solubility, and the efficacies of BBR are also briefly discussed. Finally, the status of BBR in BC treatment and future research directions is also prospected.

Collective migration plays critical roles in developmental, physiological and pathological processes, and requires a dynamic actomyosin network for cell shape change, cell adhesion and cell-cell communication. The dynamic network of mitochondria in individual cells is regulated by mitochondrial fission and fusion, and is required for cellular processes including cell metabolism, apoptosis and cell division. But whether mitochondrial dynamics interplays with and regulates actomyosin dynamics during collective migration is not clear. Here, we demonstrate that proper regulation of mitochondrial dynamics is critical for collective migration of Drosophila border cells during oogenesis, and misregulation of fission or fusion results in reduction of ATP levels. Specifically, Drp1 is genetically required for border cell migration, and Drp1-mediated mitochondrial fission promotes formation of leading protrusion, likely through its regulation of ATP levels. Reduction of ATP levels by drug treatment also affects protrusion formation as well as actomyosin dynamics. Importantly, we find that RhoA/ROCK signaling, which is essential for actin and myosin dynamics during border cell migration, could exert its effect on mitochondrial fission through regulating Drp1’s recruitment to mitochondria. These findings suggest that RhoA/ROCK signaling may couple or coordinate actomyosin dynamics with mitochondrial dynamics to achieve optimal actomyosin function, leading to protrusive and migratory behavior.

Surface proteins are a type of proteins expressed on the surface of bacteria that play an important role in cell wall synthesis, maintenance of cell morphology, and signaling with the host. Our previous study showed that the probiotic Lactobacillus plantarum HC-2 improved the growth performance and immune response of Litopenaeus vannamei. To further investigate the probiotic mechanism, we determined the automatic aggregation ability of the bacteria and surface hydrophobicity of HC-2 after being treated with 5 M of lithium chloride (LiCl) and observed the morphology and adhesion of the bacteria to HCT116 cells. The results showed that with the removal of the HC-2 surface protein, the auto-aggregation ability and surface hydrophobicity of HC-2 decreased, and the crude mucus layer coated on the bacterial surface gradually dissociated. The adhesion rate of HC-2 to HCT116 cells decreased from 98.1 to 20.9%. Moreover, a total of 201 unique proteins were identified from the mixture of the surface proteins by mass spectrometry (MS). Several proteins are involved in transcription and translation, biosynthetic or metabolic process, cell cycle or division, cell wall synthesis, and emergency response. Meanwhile, a quantitative real-time PCR qPCR_ showed that HC-2 was mainly colonized in the midgut of shrimp, and the colonization numbers were 15 times higher than that in the foregut, while the colonization rate in the hindgut was lower. The adhesion activity measurement showed that the adhesion level of HC-2 to crude intestinal mucus of L. vannamei was higher than that of bovine serum albumin (BSA) and collagen, and the adhesion capacity of the bacterial cells decreased with the extension of LiCl-treatment time. Finally, we identified the elongation factor Tu, Type I glyceraldehyde-3-phosphate dehydrogenase, small heat shock protein, and 30S ribosomal protein from the surface proteins, which may be the adhesion proteins of HC-2 colonization in the shrimp intestine. The above results indicate that surface proteins play an important role in maintaining the cell structure stability and cell adhesion. Surface proteomics analysis contributes to describing potential protein-mediated probiotic-host interactions. The identification of some interacting proteins in this work may be beneficial to further understand the adhesion/colonization mechanism and probiotic properties of L. plantarum HC-2 in the shrimp intestine.

Abstract Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.

Abstract Background To evaluate different stages of liver fibrosis in cynomolgus monkeys by comparing magnetic resonance-perfusion weighted imaging (MR-PWI) quantitative and semi-quantitative parameters, and confirm the best detection indicators for diagnosis of liver fibrosis. Methods A liver fibrosis model of different stages (S0–S4) was established in cynomolgus monkeys. The changes in MR-PWI quantitative and semi-quantitative parameters with the progression of liver fibrosis were investigated. Results MR-PWI quantitative parameters gradually decreased with the progression of liver fibrosis. Hepatic arterial perfusion index (HPI) was found to increase with the progression of liver fibrosis and significant differences of HPI between each group were observed. There was a highly positive correlation between HPI and the stages of liver fibrosis. Receiver operating characteristic (ROC) curve analysis showed that HPI had the highest efficacy of the MR-PWI quantitative parameters for the diagnosis of liver fibrosis. The MR-PW semi-quantitative parameters gradually reduced with the progression of liver fibrosis, and the differences were statistically significant between stages S3–S4 and S0–S2. Time to peak (TPP) gradually extended and showed a positive correlation with the stages of liver fibrosis. TTP had the highest efficacy of the semi-quantitative parameters for diagnosis of liver fibrosis. Conclusions Both the MR-PWI quantitative and semi-quantitative parameters of the liver fibrosis model in cynomolgus monkeys varied at different stages of liver fibrosis, and HPI and TTP were the best detection indices for quantitative and semi-quantitative evaluation of liver fibrosis, respectively.

Cyprinid herpesvirus 2 (CyHV-2) is the etiological agent of herpesviral hematopoietic necrosis (HVHN) disease, which causes serious economic losses in the crucian carp culture industry. In this study, by displaying ORF132 on the surface of Saccharomyces cerevisiae cells (named EBY100/pYD1-ORF132), we evaluated the protective efficacy of oral administration against CyHV-2 infection. Intense innate and adaptive immune responses were evoked in both mucosal and systemic tissues after oral vaccination with EBY100/pYD1-ORF132. Importantly, oral vaccination provided significant protection for crucian carp post CyHV-2 infection, resulting in a relative percent survival (RPS) of 64%. In addition, oral administration suppressed the virus load and relieved histological damage in selected tissues. Our results indicated that surface-displayed ORF132 on S. cerevisiae could be used as potential oral vaccine against CyHV-2 infection.

An outbreak of white spot syndrome virus (WSSV) can hit shrimp culture with a devastating blow, and there are no suitable measures to prevent infection with the virus. In this study, the activity of active molecules from Chinese herbs against WSSV was evaluated and screened. Taxifolin had the highest rate (84%) of inhibition of the WSSV infection. The viral infectivity and genome copy number were reduced by 41% when WSSV virion was pretreated with taxifolin prior to shrimp infection. A continuous exchange of taxifolin significantly reduced the mortality of shrimp infected with WSSV. Due to the WSSV virion infectivity being affected by taxifolin, the horizontal transmission of the virus was blocked with an inhibition rate of up to 30%, which would further reduce the cost of a viral outbreak. Additionally, the viral genome copy number was also reduced by up to 63% in shrimp preincubated in taxifolin for 8 h. There may be a connection to the enhancement of innate immunity in shrimp that resulted in a 15% reduction in mortality for taxifolin-fed shrimp after the WSSV challenge. After dietary supplementation with taxifolin, the resistance of larvae to WSSV was improved, indicating that taxifolin may be a potential immunostimulant for shrimp to prevent WSD. Therefore, the results indicate that taxifolin has application potential for blocking a WSSV outbreak and reducing the loss of shrimp culture.

Microplastics (MPs) are normally defined as small plastic wastes with a size of 1 μm to 5 mm in diameter. This tiny plastic debris is abundant in aquatic systems and poses a great threat to aquatic biota. To date, toxicological assessment of MPs is predominantly dependent on metazoan animals, although their applications are sometimes limited due to the high cost, narrow ecological niche, or ethical considerations. In this regard, unicellular eukaryotes (i.e., protozoa) that are ubiquitously present in nature represent a promising alternative for evaluating the toxicity of MPs. In this study, we selected Paramecium bursaria (P. bursaria) as a representative of protozoa and further investigated behavioral and molecular changes in MPs-exposed P. bursaria. Our results showed that following MPs uptake, P. bursaria exhibited various changes, including anomalies in swimming patterns, reduction in moving speed, impairment of avoidance behavior, elevation of oxidative stress, and potential disturbance of endosymbiosis. These elicited changes in P. bursaria in response to MPs exposure were pronounced and measurable. Overall, this study demonstrated that P. bursaria could serve as a promising alternative for the toxicological assessment of MPs and may be further applied to evaluate the toxicity of other environmental contaminants.

Objective Endoplasmic reticulum stress (ERS) is present in chondrocytes of osteoarthritis, and the intensity of ERS is related to the degree of cartilage degeneration. In vitro intervention strategies can change the status of ERS and induce the inhibition of ERS‐related pathway. Therefore, this study is designed to explore the role and molecular mechanism of cartilage stem cells (ACSCs) of ERS in chondrocytes after hip replacement. Methods Human cartilage cell lines C28/I2 were cultured as the control group. The ERS inducer was added into C28/I2 as ERS group. The third ERS + stem cells group was formed by adding cartilage stem cells into ERS group, and further transfection of si‐PERK was defined as si‐PERK + ERS + stem cells group. Cell cycle and apoptosis in the four groups were determined by flow cytometry. The protein expression of GRP78, PERK, ATF4, TMEM119, CDK4, Cyclin D, and BMP6 in chondrocytes in the four groups were investigated by western blot, and the distribution of PERK, TMEM119, and BMP6 in chondrocytes were observed by immunofluorescence assay. In addition, the transcriptional levels of Bcl2, Bax, and Caspase 3 were also determined by RT‐PCR. Results In cell cycle assay, ERS increased the accumulation of cells in G0/G1 and G2/M, while cartilage stem cells weakened the effects. The apoptosis rates in control group, ERS, ERS + stem cells, si‐PERK + ERS + stem cells were 0%, 21.3%, 18.9%, and 15.9%, respectively, and the difference of apoptosis rate between the latter three groups and control group was statistically significant (P

The Drosophila transgenic technology and fluorescent protein fusions are powerful tools to analyze protein expression patterns, subcellular localization and protein dynamics. Recently, the Drosophila transgenic technology has been improved by the highly efficient phiC31 site-specific integration system. Many new and improved fluorescent proteins with desirable advantages have been developed. However, the phiC31 system and the newly developed fluorescent proteins have not been systematically applied in Drosophila transgenic vectors. Here, we have constructed a modular toolset of C-terminal fluorescent protein fusion vectors based on phiC31 site-specific integration system for the generation of transgenic Drosophila lines. These cloning vectors contain a variety of fluorescent tags, including blue, cyan, green or red fluorescent proteins, photoactivatable or photoswitchable fluorescent proteins, fluorescent timers, photosensitizers and bimolecular fluorescence complementation tags. These vectors provide a range of transcriptional regulation options including UAST, UASP, UASC, LexAop, QUAS, Ubi, αTub67C and αTub84B promoters, and two screening marker options including white and vermilion gene. The vectors have been tested in vivo and can produce fluorescent chimeric proteins that are functional.

Akin to their mammalian counterparts, teleost fish possess a complex assortment of highly specialized immune cells that are capable of unleashing potent innate immune responses to eradicate or mitigate incoming pathogens, and also differentiate into memory lymphocytes to provide long-term protection. Investigations into specific roles and functions of fish immune cells depend on the precise separation of each cell type. Commonly used techniques, for example, density gradient centrifugation, rely on immune cells to have differing sizes or densities and thus fail to separate between similar cell types (e.g. T and B lymphocytes). Furthermore, a continuously growing database of teleost genomic information has revealed an inventory of cellular markers, indicating the possible presence of immune cell subsets in teleost fish. This further complicates the interpretation of results if subsets of immune cells are not properly separated. Consequently, monoclonal antibodies (mAbs) against specific cellular markers are required to precisely identify and separate novel subsets of immune cells in fish. In the field of fish immunology, mAbs are largely generated using the hybridoma technology, resulting in the development of mAbs against specific cellular markers in different fish species. Nevertheless, this technology suffers from being labour-intensive, time-consuming and most importantly, the inevitable loss of diversities of antibodies during the fusion of antibody-expressing B lymphocytes and myeloma cells. In light of this, the focus of this review is to discuss the potential applications of fluorescence-activated cell sorting and droplet-based microfluidics, two emerging technologies capable of screening and identifying antigen-specific B lymphocytes in a high-throughput manner, in promoting the development of valuable reagents for fish immunology studies. Our main goal is to encourage the incorporation of alternative technologies into the field of fish immunology to promote the production of specific antibodies in a high-throughput and cost-effective way, which could better allow for the precise separation of fish immune cells and also facilitate the identification of novel immune cell subsets in teleost fish.

Intensive studies have evaluated abiotic factors in shaping host gut microbiota. In contrast, little is known on how and to what extent abiotic (geochemical variables) and biotic (i.e., surrounding microbes, younger shrimp, and age) factors assemble the gut microbiota over shrimp ontogeny. Considering the functional importance of gut microbiota in improving host fitness, this knowledge is fundamental to sustain a desirable gut microbiota for a healthy aquaculture. Here, we characterized the successional rules of both the shrimp gut and rearing water bacterial communities over the entire shrimp farming. Both the gut and rearing water bacterial communities exhibited the time decay of similarity relationship, with significantly lower temporal turnover rate for the gut microbiota, which were primarily governed by shrimp age (days postlarval inoculation) and water pH. Gut commensals were primary sourced (averaged 60.3%) from their younger host, rather than surrounding bacterioplankton (19.1%). A structural equation model revealed that water salinity, pH, total phosphorus, and dissolve oxygen directly governed bacterioplankton communities but not for the gut microbiota. In addition, shrimp gut microbiota did not simply mirror the rearing bacterioplankton communities. The gut microbiota tended to be governed by variable selection over shrimp ontogeny, while the rearing bacterioplankton community was shaped by homogeneous selection. However, the determinism of rare and stochasticity of abundant subcommunities were consistent between shrimp gut and rearing water. These findings highlight the importance of independently interpreting host-associated and free-living communities, as well as their rare and abundant subcommunities for a comprehensive understanding of the ecological processes that govern microbial successions.

The water vapor-related microphysical processes (WVRMPs) in cloud microphysics schemes are crucial to the formation and dissipation of clouds, which have a significant impact on the quantitative precipitation forecasting of numerical weather prediction models. In this study, a well physics-based parallel-split transition approach (PSTA) to compute the WVRMPs from the same temperature and humidity state is developed and compared with the original sequential-update transition approach (SUTA) in a double-moment cloud microphysics scheme. Case study and batch experiments were carried out to investigate their different impacts on the clouds and precipitation simulated by the Global/Regional Assimilation and Prediction System (GRAPES) regional 3 km high-resolution model of the China Meteorological Administration (CMA), named CMA-MESO. The results show that the PSTA experiment tends to simulate a narrower and more concentrated precipitation area with a higher-intensity center compared to those of the SUTA experiment, which is more consistent with the observations. In the cold region, the net transition rates of WVRMPs from the PSTA experiment with more ice-phase hydrometeors are higher than those from the SUTA experiment. While in the warm region, the condensation and evaporation rates with violent fluctuation simulated by the SUTA are significantly larger than those from the PSTA experiment, resulting in less precipitation. The batch experiments indicate that the equitable threat scores (ETSs) of 24-h precipitation simulated by the PSTA are just slightly better than those of the SUTA, yet its ETSs of 48-h precipitation have been systematically improved for all magnitude levels against the SUTA. It is demonstrated that more attention should be paid to the reasonable treatments of the WVRMPs in developing cloud microphysics schemes.

This study was conducted in order to identify the presence of four synthetic phenolic antioxidants (SPAs): propyl gallate (PG), tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) in various food stuffs that are commonly consumed in Malaysia. The identification method was optimized and validated before it was applied to the analyses of eighty three food samples which include chewing gum, chili sauce, cereal-based snack food, noodles, potato snack, cereal breakfast, oat, biscuit, cookie, coffee, junk food, seaweed, nut, chocolate, apple juice, orange juice and blackcurrant juice. Twenty nine food samples contained SPAs either singly or in combination. The chromatography conditions such as elution method, flow rate and wavelength were optimized. Good linearity ranges (1–300 mgL–1) were found for all the four phenolic antioxidants. RSD for repeatability and reproducibility ranged from 0.15–0.84% for both precision analyses. LOD and LOQ ranged from 0.02–0.67 and 0.06–2.03 mgL–1, respectively. Recoveries of the four SPAs ranged from 80.4 to 119.0% when selected food items spiked at 10, 50, and 100 mgL–1.

Small‐sized fingerprint sensors, due to the convenience of integration, are widely used in many applications, especially on smart phones. However, the friction ridge information decreases with the reduction of the collected fingerprint area, resulting in degraded recognition performance. Mosaicking fingerprint impressions has been proved to be effective in boosting the recognition accuracy. Nonetheless, the minutiae‐based mosaicking methods do not work well when there is no sufficient number of minutiae in the overlapping area while existing minutia‐free mosaicking methods are not robust to distortion and result in low mosaicking accuracy. In this study, a novel minutia‐free mosaicking algorithm used the coarse‐to‐fine approach is proposed to obtain a larger fingerprint impression from a couple of small‐sized fingerprint impressions. It consists of three stages: an orientation field‐based coarse alignment, a ridge matching‐based fine alignment, and a nonlinear deformation correction with block‐correspondence Thin Plate Spline model. Experimental results on the XDfinger database demonstrate that the proposed method outperforms the other six mosaicking methods in terms of reject‐to‐fuse rate, registration accuracy, and verification performance. Specifically, in the verification scenario, the equal error rate is reduced from 1.98% of a single impression to 0.41% of two impressions mosaicked by the authors' method.

Information transition and sharing is necessary for business process management and multi-source information may cause information conflict and reduce activity efficiency. This paper proposes a novel activity efficiency model in business process under conflict information. First, the evidence theory and Pignistic probability conversion are used to measure the conflict information by the difference sum of the probability conversion function based on the relations among the evidences. Second, the M/M/1 queuing system and the mapping between the conflict coefficient and service time are adopted to set up the single activity efficiency model, which is followed by the key activity efficiency models with respect to the four typical process structures, such as the Sequence structure, OR-Join structure, AND-Join structure and loop structure. Then, for a validation experiment, the road-rail intermodal transport business process is introduced and the container preparation activity of the operator sub-business process is demonstrated. As a result, the conflict information has a clear impact on the container preparation activity efficiency. Finally, it is concluded that the models here achieve to quantify the impact mechanism of conflict information on one activity efficiency, which indicates the activity service optimization direction from the view of information sharing.

Summary: During development, cells undergo multiple, distinct morphogenetic processes to form a tissue or organ, but how their temporal order and time interval are determined remain poorly understood. Here we show that the nuclear receptors E75 and DHR3 regulate the temporal order and time interval between the collective migration and lumen formation of a coherent group of cells named border cells during Drosophila oogenesis. We show that E75, in response to ecdysone signaling, antagonizes the activity of DHR3 during border cell migration, and DHR3 is necessary and sufficient for the subsequent lumen formation that is critical for micropyle morphogenesis. DHR3's lumen-inducing function is mainly mediated through βFtz-f1, another nuclear receptor and transcription factor. Furthermore, both DHR3 and βFtz-f1 are required for chitin secretion into the lumen, whereas DHR3 is sufficient for chitin secretion. Lastly, DHR3 and βFtz-f1 suppress JNK signaling in the border cells to downregulate cell adhesion during lumen formation.

Summary: During collective cell migration, front cells tend to extend a predominant leading protrusion, which is rarely present in cells at the side or rear positions. Using Drosophila border cells (BCs) as a model system of collective migration, we revealed the presence of a supracellular actomyosin network at the peripheral surface of BC clusters. We demonstrated that the Myosin II-mediated mechanical tension as exerted by this peripheral supracellular network not only mediated cell-cell communication between leading BC and non-leading BCs but also restrained formation of prominent protrusions at non-leading BCs. Further analysis revealed that a cytoplasmic dendritic actin network that depends on the function of Arp2/3 complex interacted with the actomyosin network. Together, our data suggest that the outward pushing or protrusive force as generated from Arp2/3-dependent actin polymerization and the inward restraining force as produced from the supracellular actomyosin network together determine the collective and polarized morphology of migratory BCs.