Shifting redox reaction equilibria on demand using an orthogonal redox cofactor.

Nature's two redox cofactors, nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), are held at different reduction potentials, driving catabolism and anabolism in opposite directions. In biomanufacturing, there is a need to flexibly control redox reaction direction decoupled from catabolism and anabolism. We established nicotinamide mononucleotide (NMN+) as a noncanonical cofactor orthogonal to NAD(P)+. Here we present the development of Nox Ortho, a reduced NMN+ (NMNH)-specific oxidase, that completes the toolkit to modulate NMNH:NMN+ ratio together with an NMN+-specific glucose dehydrogenase (GDH Ortho). The design principle discovered from Nox Ortho engineering and modeling is facilely translated onto six different enzymes to create NMN(H)-orthogonal biocatalysts with a consistent ~103-106-fold cofactor specificity switch from NAD(P)+ to NMN+. We assemble these enzymes to produce stereo-pure 2,3-butanediol in cell-free systems and in Escherichia coli, enabled by NMN(H)'s distinct redox ratio firmly set by its designated driving forces, decoupled from both NAD(H) and NADP(H).

Recombinant parainfluenza virus 5 expressing clade 2.3.4.4b H5 hemagglutinin protein confers broad protection against H5Ny influenza viruses.

The global circulation of clade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) in poultry and wild birds, increasing mammal infections, continues to pose a public health threat and may even form a pandemic. An efficacious vaccine against H5Ny HPAIVs is crucial for emergency use and pandemic preparedness. In this study, we developed a parainfluenza virus 5 (PIV5)-based vaccine candidate expressing hemagglutinin (HA) protein of clade 2.3.4.4b H5 HPAIV, termed rPIV5-H5, and evaluated its safety and efficacy in mice and ferrets. Our results demonstrated that intranasal immunization with a single dose of rPIV5-H5 could stimulate H5-specific antibody responses, moreover, a prime-boost regimen using rPIV5-H5 stimulated robust humoral, cellular, and mucosal immune responses in mice. Challenge study showed that rPIV5-H5 prime-boost regimen provided sterile immunity against lethal clade 2.3.4.4b H5N1 virus infection in mice and ferrets. Notably, rPIV5-H5 prime-boost regimen provided protection in mice against challenge with lethal doses of heterologous clades 2.2, 2.3.2, and 2.3.4 H5N1, and clade 2.3.4.4h H5N6 viruses. These results revealed that rPIV5-H5 can elicit protective immunity against a diverse clade of highly pathogenic H5Ny virus infection in mammals, highlighting the potential of rPIV5-H5 as a pan-H5 influenza vaccine candidate for emergency use.IMPORTANCEClade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) have been widely circulating in wild birds and domestic poultry all over the world, leading to infections in mammals, including humans. Here, we developed a recombinant PIV5-vectored vaccine candidate expressing the HA protein of clade 2.3.4.4b H5 virus. Intranasal immunization with rPIV5-H5 in mice induced airway mucosal IgA responses, high levels of antibodies, and robust T-cell responses. Importantly, rPIV5-H5 conferred complete protection in mice and ferrets against clade 2.3.4.4b H5N1 virus challenge, the protective immunity was extended against heterologous H5Ny viruses. Taken together, our data demonstrate that rPIV5-H5 is a promising vaccine candidate against diverse H5Ny influenza viruses in mammals.

Tubulin participates in establishing protoxylem vessel reinforcement patterns and hydraulic conductivity in maize.

Water transportation to developing tissues relies on the structure and function of plant xylem cells. Plant microtubules govern the direction of cellulose microfibrils and guide secondary cell wall formation and morphogenesis. However, the relevance of microtubule-determined xylem wall thickening patterns in plant hydraulic conductivity remains unclear. In the present study, we identified a maize (Zea mays) semi-dominant mutant, designated drought-overly-sensitive1 (ZmDos1), the upper leaves of which wilted even when exposed to well-watered conditions during growth; the wilting phenotype was aggravated by increased temperatures and decreased humidity. Protoxylem vessels in the stem and leaves of the mutant showed altered thickening patterns of the secondary cell wall (from annular to spiral), decreased inner diameters, and limited water transport efficiency. The causal mutation for this phenotype was found to be a G-to-A mutation in the maize gene α-tubulin4, resulting in a single amino acid substitution at position 196 (E196K). Ectopic expression of the mutant α-tubulin4 in Arabidopsis (Arabidopsis thaliana) changed the orientation of microtubule arrays, suggesting a determinant role of this gene in microtubule assembly and secondary cell wall thickening. Our findings suggest that the spiral wall thickenings triggered by the α-tubulin mutation are stretched during organ elongation, causing a smaller inner diameter of the protoxylem vessels and affecting water transport in maize. This study underscores the importance of tubulin-mediated protoxylem wall thickening in regulating plant hydraulics, improves our understanding of the relationships between protoxylem structural features and functions, and offers candidate genes for the genetic enhancement of maize.

Integrated gene co-expression network analysis and experimental validation revealed potential targets of human urine extract CDA-II in treating chronic myeloid leukemia.

BACKGROUND: Cell differentiation agent II (CDA-II) exhibits potent anti-proliferative and apoptosis-inducing properties against a variety of cancer cells. However, its mechanism of action in chronic myeloid leukemia (CML) remains unclear. METHODS: Cell counting Kit 8 (CCK-8) and flow cytometry were used to investigate the effects of CDA-II on the biological characteristics of K562 cells. Gene (mRNA and lncRNA) expression profiles were analyzed by bioinformatics to screen differentially expressed genes and to perform enrichment analysis. The Pearson correlation coefficients of lncRNAs and mRNAs were calculated using gene expression values, and a lncRNA/mRNA co-expression network was constructed. The MCODE and cytoHubba plugins were used to analyze the co-expression network. RESULTS: The Results, derived from CCK-8 and flow cytometry, indicated that CDA-II exerts dual effects on K562 cells: it inhibits their proliferation and induces apoptosis. From bioinformatics analysis, we identified 316 mRNAs and 32 lncRNAs. These mRNAs were predominantly related to the meiotic cell cycle, DNA methylation, transporter complex and peptidase regulator activity, complement and coagulation cascades, protein digestion and absorption, and cell adhesion molecule signaling pathways. The co-expression network comprised of 163 lncRNA/mRNA interaction pairs. Notably, our analysis results implicated clustered histone gene families and five lncRNAs in the biological effects of CDA-II on K562 cells. CONCLUSION: This study highlights the hub gene and lncRNA/mRNA co-expression network as crucial elements in the context of CDA-II treatment of CML. This insight not only enriches our understanding of CDA-II's mechanism of action but also might provide valuable clues for subsequent experimental studies of CDA-II, and potentially contribute to the discovery of new therapeutic targets for CML.

Dielectric Screening inside Carbon Nanotubes.

Dielectric screening plays a vital role in determining physical properties at the nanoscale and affects our ability to detect and characterize nanomaterials using optical techniques. We study how dielectric screening changes electromagnetic fields and many-body effects in nanostructures encapsulated inside carbon nanotubes. First, we show that metallic outer walls reduce the scattering intensity of the inner tube by 2 orders of magnitude compared to that of air-suspended inner tubes, in line with our local field calculations. Second, we find that the dielectric shift of the optical transition energies in the inner walls is greater when the outer tube is metallic than when it is semiconducting. The magnitude of the shift suggests that the excitons in small-diameter inner metallic tubes are thermally dissociated at room temperature if the outer tube is also metallic, and in essence, we observe band-to-band transitions in thin metallic double-walled nanotubes.

Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In in vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored adenosine triphosphate (ATP) synthesis. Among the transcriptome sequencing data, the difference of CXCL5 (C-X-C motif chemokine ligand 5) was the most significant. Both high copper and ADR exposure can cause upregulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.NEW & NOTEWORTHY Cuproptosis induced by excessive copper accumulation leads to podocyte cytoskeleton damage by promoting mitochondrial dysfunction, and CXCL5 acts as an upstream signal mediating the occurrence of cuproptosis.

Long noncoding RNA XIST: a novel independent prognostic biomarker for patients with ABC-DLBCL receiving R-CHOP treatment.

Approximately one-third of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) cases were unresponsive to standard first-line therapy; thus, identifying biomarkers to evaluate therapeutic efficacy and assessing the emergence of drug resistance is crucial. Through early-stage screening, long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) was found to be correlated with the R-CHOP treatment response. This study aimed to clarify the characteristics of XIST in ABC-DLBCL. The expression level of XIST in 161 patients with ABC-DLBCL receiving R-CHOP therapy was examined via RNA in situ hybridization, and the association between XIST expression and clinicopathological features, treatment response and prognosis was analyzed in the study cohort and validated in the Gene Expression Omnibus cohort. Cell biological experiments and bioinformatics analyses were conducted to reveal aberrant signaling. The proportion of complete response in patients with high XIST expression was lower than that in patients with low XIST expression (53.8% versus 77.1%) (P = 0.002). High XIST expression was remarkably associated with the characteristics of tumor progression and was an independent prognostic element for overall survival (P = 0.039) and progression-free survival (P = 0.027) in ABC-DLBCL. XIST was proven to be involved in m6A-related methylation and ATF6-associated autophagy. XIST knockdown repressed ABC-DLBCL cellular proliferation by regulating Raf/MEK/ERK signaling. High XIST expression was associated with ABC-DLBCL tumorigenesis and development and contributed to R-CHOP treatment resistance. XIST may be a promising signal to predict ABC-DLBCL prognosis.

Inhibition of STAT3 by S3I-201 suppress peritoneal fibroblast phenotype conversion and alleviate peritoneal fibrosis.

Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis.

Emerging role of N6-methyladenosine in the homeostasis of glucose metabolism.

N6-methyladenosine (m6A) is the most prevalent post-transcriptional internal RNA modification, which is involved in the regulation of diverse physiological processes. Dynamic and reversible m6A modification has been shown to regulate glucose metabolism, and dysregulation of m6A modification contributes to glucose metabolic disorders in multiple organs and tissues including the pancreas, liver, adipose tissue, skeletal muscle, kidney, blood vessels, and so forth. In this review, the role and molecular mechanism of m6A modification in the regulation of glucose metabolism were summarized, the potential therapeutic strategies that improve glucose metabolism by targeting m6A modifiers were outlined, and feasible directions of future research in this field were discussed as well, providing clues for translational research on combating metabolic diseases based on m6A modification in the future.

N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation.

BACKGROUND: Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. METHODS: Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. RESULTS: circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. CONCLUSIONS: Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

Mutation status of the KMT2 family associated with immune checkpoint inhibitors (ICIs) therapy and implicating diverse tumor microenvironments.

Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts (n = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival (P < 0.001, hazard ratio [HR] = 0.733 [95% confidence interval (CI): 0.632-0.850]), progression-free survival (P = 0.002, HR = 0.669 [95% CI: 0.518-0.864]), durable clinical benefit (P < 0.001, 54.1% vs. 32.6%), and objective response rate (P < 0.001, 40.6% vs. 22.0%). Through a comprehensive analysis of the tumor microenvironment across different KMT2 mutation statuses, we observed that tumors harboring the KMT2 mutation exhibited enhanced immunogenicity, increased infiltration of immune cells, and higher levels of immune cell cytotoxicity, suggesting a propensity towards a "hot tumor" phenotype. Therefore, our study indicates a potential association between KMT2 mutations and a more favorable response to ICI therapy and implicates different tumor microenvironments associated with ICI therapy response.

Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) complex, is a zoonotic disease that remains one of the leading causes of death worldwide. Latent tuberculosis infection reactivation is a challenging obstacle to eradicating TB globally. Understanding the gene regulatory network of Mtb during dormancy is important. This review discusses up-to-date information about TB gene regulatory networks during dormancy, focusing on the regulation of lipid and energy metabolism, dormancy survival regulator (DosR), White B-like (Wbl) family, Toxin-Antitoxin (TA) systems, sigma factors, and MprAB. We outline the progress in vaccine and drug development associated with Mtb dormancy.

Association of depressive symptoms and sleep disturbances with survival among US adult cancer survivors.

BACKGROUND: Depression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors. METHODS: This population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality. RESULTS: During the median follow-up of 69 months (interquartile range, 37-109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0-4), a PHQ-9 score (5-9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03-1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04-1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01-2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0-4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5-9 and no sleep disturbances were 1.72 (1.21-2.44) and 1.69 (1.10-2.61), respectively, and 2.61 (1.43-4.78) and 2.77 (1.27-6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16-3.27). CONCLUSIONS: Depressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).

Endoplasmic Reticulum-Targeting Self-Assembly Nanosheets Promote Autophagy and Regulate Immunosuppressive Tumor Microenvironment for Efficient Photodynamic Immunotherapy.

The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-TER-Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-TER-Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy.

Trinitarian Design of Gradient Artificial Interphase Enables Colossal Granular Li Deposits for Stable Li-Metal Batteries.

The cycling lifespan of Li-metal batteries is compromised by the unstable solid electrolyte interphase (SEI) and the continuous Li dendrites, restricting their practical implementations. Given these challenges, establishing an artificial SEI holds promise. Herein, a trinitarian gradient interphase is innovatively designed through composite coatings of magnesium fluoride (MgF2), N-hexadecyltrimethylammonium chloride (CTAC), and polyvinylidene fluoride-hexafluoropropylene copolymer (PVDF-HFP) on Li-metal anode (LMA). Specifically, the MgF2/CTAC/PVDF-HFP SEI spontaneously forms a lithium fluoride (LiF)-rich PVDF-HFP-based SEI, along with lithium-magnesium (Li-Mg) alloy substrate as lithiophilic electronic conductor and positively charged CTAC during plating. Noticeably, the Li-Mg alloy homogenizes the distribution of electric field and reduce the internal resistance, while the electronically insulated LiF/PVDF-HFP composite SEI offers fast ion-conducting and mechanical flexibility, accommodating the volumetric expansion and ensuring stable Li-ion flux. Additionally, CTAC at the dendritic tip is pivotal for mitigating dendrites through its electrostatic shield mechanism. Innovatively, this trinitarian synergistic mechanism, which facilitates colossal granular Li deposits, constructs a dendrite-free LMA, leading to stable cycling performances in practical Li||LFP, popular Li||NCM811, and promising Li||S full cells. This work demonstrates the design of multifunctional composite SEI for comprehensive Li protection, thereby inspiring further advancements in artificial SEI engineering for alkali-metal batteries.

Consistent community assembly but contingent species pool effects drive ß-diversity patterns of multiple microbial groups in desert biocrust systems.

One of the key goals of ecology is to understand how communities are assembled. The species co-existence theory suggests that community ß-diversity is influenced by species pool and community assembly processes, such as environmental filtering, dispersal events, ecological drift and biotic interactions. However, it remains unclear whether there are similar ß-diversity patterns among different soil microbial groups and whether all these mechanisms play significant roles in mediating ß-diversity patterns. By conducting a broad survey across Chinese deserts, we aimed to address these questions by investing biological soil crusts (biocrusts). Through amplicon-sequencing, we acquired ß-diversity data for multiple microbial groups, that is, soil total bacteria, diazotrophs, phoD-harbouring taxa, and fungi. Our results have shown varying distance decay rates of ß-diversity across microbial groups, with soil total bacteria showing a weaker distance-decay relationship than other groups. The impact of the species pool on community ß-diversity varied across microbial groups, with soil total bacteria and diazotrophs being significantly influenced. While the contributions of specific assembly processes to community ß-diversity patterns varied among different microbial groups, significant effects of local community assembly processes on ß-diversity patterns were consistently observed across all groups. Homogenous selection and dispersal limitation emerged as crucial processes for all groups. Precipitation and soil C:P were the key factors mediating ß-diversity for all groups. This study has substantially advanced our understanding of how the communities of multiple microbial groups are structured in desert biocrust systems.

Robustness of the modified multi-trench fiber design with two gaps.

We investigate the robustness of a modified multi-trench fiber (MTF) design with two gaps numerically. The excellent suppression of high-order modes is demonstrated over a wide range of the gap misalignment and the fundamental mode loss is barely affected even with the 5 dB/m scattering loss in gaps at the modified two-gap MTF for the first time. Therefore, the required fabrication accuracy decreases.

Design method for eliminating spectral line tilt in a multiple sub-pupil ultra-spectral imager (MSPUI).

A multiple sub-pupil ultra-spectral imaging system designed with a single spectrometer and detector can simultaneously detect multiple-channel spectra with ultra-high spectral resolution. However, due to using a prism in the system's front end, the nonlinear dispersion introduces spectral line tilt in the imaging spectra. This phenomenon can lead to bias in the final spectral data. To eliminate this issue, we propose a new design by introducing a second prism to correct this spectral tilt in the system. The angle of spectral line tilt generated by the nonlinear dispersion of the first prism is derived. It provides the theoretical basis for characterizing the second complementary prism. Finally, a UV multiple sub-pupil ultra-spectral imaging system is designed. The system employs two pupil separation prisms and one flat panel array to segment the pupil in three channels, each operating within spectral ranges of 180∼210 nm, 275∼305 nm, and 370∼400 nm, respectively. The spectral resolutions in all three channels are better than 0.1 nm. The corrected spectral line tilt is less than 1/3 of a pixel in the two channels with pupil separation prisms. At a Nyquist frequency of 30 lp/mm, the modulation transfer functions of all three channels are greater than 0.7, ensuring imaging quality. The design results indicate that the method proposed in this paper, utilizing complementary prisms, can effectively correct the spectral line tilt caused by the nonlinear dispersion of the pupil separation prisms. This design approach can be a reference for developing multiple sub-pupil ultra-spectral imaging systems.

Protease SfpB plays an important role in cell membrane stability and immune system evasion in Streptococcus agalactiae.

Bacteria possess the ability to develop diverse and ingenious strategies to outwit the host immune system, and proteases are one of the many weapons employed by bacteria. This study sought to identify S. agalactiae additional serine protease and determine its role in virulence. The S. agalactiae THN0901 genome features one S8 family serine peptidase B (SfpB), acting as a secreted and externally exposed entity. A S8 family serine peptidase mutant strain (ΔsfpB) and complement strain (CΔsfpB) were generated through homologous recombination. Compared to the wild-type strain THN0901, the absorption of EtBr dyes was significantly reduced (P < 0.01) in ΔsfpB, implying an altered cell membrane permeability. In addition, the ΔsfpB strain had a significantly lower survival rate in macrophages (P < 0.01) and a 61.85 % lower adhesion ability to the EPC cells (P < 0.01) compared to THN0901. In the in vivo colonization experiment using tilapia as a model, 210 fish were selected and injected with different bacterial strains at a concentration of 3 × 106 CFU/tail. At 6, 12, 24, 48, 72 and 96 h post-injection, three fish were randomly selected from each group and their brain, liver, spleen, and kidney tissues were isolated. Subsequently, it was demonstrated that the ΔsfpB strain exhibited a markedly diminished capacity for colonization in tilapia. Additionally, the cumulative mortality of ΔsfpB in fish after intraperitoneal injection was reduced by 19.92-23.85 %. In conclusion, the findings in this study have demonstrated that the SfpB plays a significant role in S. agalactiae cell membrane stability and immune evasion. The immune evasion is fundamental for the development and transmission of invasive diseases, the serine protease SfpB may be a promising candidate for the development of antimicrobial agents to reduce the transmission of S. agalactiae.

Gill lesions are the main cause of death in yellowfin seabream (Acanthopagrus latus) following infection with Amyloodinium ocellatum.

Amyloodiniosis, caused by the ectoparasite Amyloodinium ocellatum, affects the healthy development of mariculture. This study used a local infection method to identify the pathogenic target organ responsible for the death of infected fish. Comparing the relationship between the abundance of trophonts in gills and skin with the mortality of infected fish using local infection showed that severe gill infections cause the mortality of infected fish. At the 40 % survival rate of infected fish, the parasite abundance in the gill was 14,167 ± 4371. The gill filaments of the infected fish were structurally disordered, with pronounced lesions associated with the presence of trophonts, such as epithelial cell degeneration and massive lymphocytic infiltration. However, the skin showed no obvious pathological changes. The TUNEL assay showed a significant presence of apoptotic cells concentrated in the area of A. ocellatum infection. The trophonts on the gills developed faster than those parasitising the skin and fins. Microbiome analysis revealed that at the phylum level, Proteobacteria, Bacteroidota, and Firmicutes are abundant in the skin, while Verrucomicrobiota, Bacteroidota, and Proteobacteria are abundant in the gills of A. latus. Furthermore, A. ocellatum infection significantly reduced (p < 0.05) the richness and diversity of the gill microbial community of A. latus. Infection by A. ocellatum increased the relative abundance of several putative pathogenic bacteria (Flavobacterium and Nocardia) in the gill and skin of A. latus, possibly increasing the likelihood of disease in the host. In conclusion, these results evidenced that severe gill infections by A. ocellatum cause mortality in infected fish, which clarifies the direction for exploring the pathogenesis of amyloodiniosis.