PRMT4 interacts with NCOA4 to inhibit ferritinophagy in cisplatin-induced acute kidney injury.

Cisplatin-induced acute kidney injury (AKI) is commonly seen in the clinical practice, and ferroptosis, a type of non-apoptotic cell death, plays a pivotal role in it. Previous studies suggested that protein arginine methyltransferase 4 (PRMT4) was incorporated in various bioprocesses, but its role in renal injuries has not been investigated. Our present study showed that PRMT4 was highly expressed in renal proximal tubular cells, and it was downregulated in cisplatin-induced AKI. Besides, genetic disruption of PRMT4 exacerbated, while its overexpression attenuated, cisplatin-induced redox injuries in renal proximal epithelia. Mechanistically, our work showed that PRMT4 interacted with NCOA4 to inhibit ferritinophagy, a type of selective autophagy favoring lipid peroxidation to accelerate ferroptosis. Taken together, our study demonstrated that PRMT4 interacted with NCOA4 to attenuate ferroptosis in cisplatin-induced AKI, suggesting that PRMT4 might present as a new therapeutic target for cisplatin-related nephropathy.

Habitat Suitability and Determinants for Anatidae in Multi-Watershed Composite Wetlands in Anhui, China.

Habitat suitability analysis is essential in habitat and species conservation. Anatidae are known for their migratory behaviour, high population density, and wide distribution range. Understanding their habitat utilzation and influencing factors is crucial in targeted conservation and management. In this study, we collected Anatidae diversity data, including the number of species, through field surveys from October 2021 to March 2022 and thirty habitat variables through an online database in Anhui Province, China. By using MaxEnt, we simulated the habitat suitability of twenty-one Anatidae species, revealing potential distribution sites in Anhui Province. Generalized linear mixed models (GLMM) were employed to identify factors affecting the distribution of geese and ducks. The results showed that high-suitability habitats were predominantly located in the large lakes of the Yangtze River floodplain. The GLMM analysis showed significant correlations between Anatidae richness and altitude, distribution of farmland, and human footprint. In addition, ducks were more sensitive to the human interference factor than geese. In summary, the lakes in the Yangtze River floodplain emerged as the most important Anatidae habitats in Anhui Province due to their abundant wetland resources, flat terrain, and high distribution of farmlands. These findings provide a scientific basis for the development of relevant conservation strategies and measures, aiding in wildlife epidemic monitoring, prevention, and control.

Assessment of Waterbird Habitat Importance and Identification of Conservation Gaps in Anhui Province.

Wetlands are among the most important habitats of highly wetland-dependent waterbirds but are subject to ongoing habitat loss and degradation owing to intensified anthropogenic activities. The scarcity of human and natural resources makes effective habitat protection an important concern. Here, we aimed to investigate waterbird habitat protection methods for Anhui Province, China, a critical stopover and wintering area on the East Asian-Australasian Flyway that features rich wetland resources subject to significant habitat loss and degradation. We evaluated the status and importance of 306 wintering waterbird habitats and identified the key environmental influences and current protection gaps using the entropy weights method and generalized additive modeling. We found 73 important habitats for waterbirds in Anhui Province, which were classified into levels of importance (descending from I to V) according to the natural discontinuity method. Level I and Level II habitats were mainly located in the Yangtze River floodplain and Level IV habitats in the Huaihe River floodplain. The gap analysis showed that 42 important waterbird habitats had protection gaps, accounting for 57.53% of the total area. Waterbird habitat importance was significantly correlated with elevation, normalized vegetation index, lake area, and lake circumference but not with distance from roads or population density. The results of this study provide scientific information for waterbird habitat conservation planning, which is crucial for maintaining wetland ecosystem functions.

Risedronate-functionalized manganese-hydroxyapatite amorphous particles: A potent adjuvant for subunit vaccines and cancer immunotherapy.

The cGAS-STING pathway and the Mevalonate Pathway are druggable targets for vaccine adjuvant discovery. Manganese (Mn) and bisphosphonates are known to exert adjuvant effects by targeting these two pathways, respectively. This study found the synergistic potential of the two pathways in enhancing immune response. Risedronate (Ris) significantly amplified the Mn adjuvant early antibody response by 166-fold and fortified its cellular immunity. However, direct combination of Mn2+ and Ris resulted in increased adjuvant toxicity (40% mouse mortality). By the combination of doping property of hydroxyapatite (HA) and its high affinity for Ris, we designed Ris-functionalized Mn-HA micro-nanoparticles as an organic-inorganic hybrid adjuvant, named MnHARis. MnHARis alleviated adjuvant toxicity (100% vs. 60% survival rate) and exhibited good long-term stability. When formulated with the varicella-zoster virus glycoprotein E (gE) antigen, MnHARis triggered a 274.3-fold increase in IgG titers and a 61.3-fold surge in neutralization titers while maintaining a better long-term humoral immunity compared to the aluminum adjuvant. Its efficacy spanned other antigens, including ovalbumin, HPV18 VLP, and SARS-CoV-2 spike protein. Notably, the cellular immunity elicited by the group of gE + MnHARis was comparable to the renowned Shingrix®. Moreover, intratumoral co-administration with an anti-trophoblast cell surface antigen 2 nanobody revealed synergistic antitumor capabilities. These findings underscore the potential of MnHARis as a potent adjuvant for augmenting vaccine immune responses and improving cancer immunotherapy outcomes.

Circ ubiquitin-like-containing plant homeodomain and RING finger domains protein 1 increases the stability of G9a and ubiquitin-like-containing plant homeodomain and RING finger domains protein 1 messenger RNA through recruiting eukaryotic translation initiation factor 4A3, transcriptionally inhibiting PDZ and homeobox protein domain protein 1, and promotes the metastasis of hepatocellular carcinoma.

BACKGROUND AND AIM: Circular ubiquitin-like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1-G9a-ubiquitin-like, containing PHD and ring finger domains 1 (UHRF1) mRNA-eukaryotic translation initiation factor 4A3 (EIF4A3)-PDZ and LIM domain 1 (PDLIM1) network in HCC. METHODS: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial-mesenchymal transition (EMT)-related proteins, and Hippo-Yap pathway components was determined by quantitative polymerase chain reaction (Q-PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit-8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull-down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co-immunoprecipitation was performed to examine the binding between UHRF1 and G9a. RESULTS: Circular ubiquitin-like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription. CONCLUSION: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo-Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1-G9a-UHRF1 mRNA-EIF4A3-PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment.

Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD.

Continual evolution of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural infection or vaccination. The rapid nature of these changes has incited a need for the development of superior broad nAbs (bnAbs) and/or the rational design of an antibody cocktail that can protect against the mutated virus strain. Here, we report two angiotensin-converting enzyme 2 competing nAbs-8H12 and 3E2-with synergistic neutralization but evaded by some Omicron subvariants. Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing. Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5. Together, these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

Rational design of a cross-type HPV vaccine through immunodominance shift guided by a cross-neutralizing antibody.

In vaccine development, broadly or cross-type neutralizing antibodies (bnAbs or cnAbs) are frequently targeted to enhance protection. Utilizing immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization strategies. However, the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly elucidated. In this study, we discovered a cross-type neutralizing monoclonal antibody, 13H5, against human papillomavirus 6 (HPV6) and HPV11. This nAb exhibited a marked preference for HPV6, demonstrating superior binding activity to virus-like particles (VLPs) and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum (90% vs. 31%). Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex, we delineated the epitope as spanning four segments of amino acids (Phe42-Ala47, Gly172-Asp173, Glu255-Val275, and Val337-Tyr351) on the L1 surface loops. Further interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and L1. Substituting Ser341 with alanine, which is the residue type present in HPV11 L1, almost completely abolished binding activity to 13H5. By swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1 (Ser341, Thr338, and Thr339), we engineered chimeric HPV11-6HI VLPs. Remarkably, the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human primates. This approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

Impact of Season on Intestinal Bacterial Communities and Pathogenic Diversity in Two Captive Duck Species.

Vertebrates and their gut bacteria interact in complex and mutually beneficial ways. The intestinal microbial composition is influenced by several external influences. In addition to food, the abiotic elements of the environment, such as temperature, humidity, and seasonal fluctuation are also important determinants. Fecal samples were collected from two captive duck species, Baikal teal (Sibirionetta formosa) and common teal (Anas crecca) across four seasons (summer, autumn, winter, and spring). These ducks were consistently fed the same diet throughout the entire experiment. High throughput sequencing (Illumina Mi-seq) was employed to analyze the V4-V5 region of the 16sRNA gene. The dominant phyla in all seasons were Proteobacteria and Firmicutes. Interestingly, the alpha diversity was higher in winter for both species. The NMDS, PCoA, and ANOSIM analysis showed the distinct clustering of bacterial composition between different seasons, while no significant differences were discovered between duck species within the same season. In addition, LefSe analysis demonstrated specific biomarkers in different seasons, with the highest number revealed in winter. The co-occurrence network analysis also showed that during winter, the network illustrated a more intricate structure with the greatest number of nodes and edges. However, this study identified ten potentially pathogenic bacterial species, which showed significantly enhanced diversity and abundance throughout the summer. Overall, our results revealed that season mainly regulated the intestinal bacterial community composition and pathogenic bacteria of captive ducks under the instant diet. This study provides an important new understanding of the seasonal variations in captive wild ducks' intestinal bacterial community structure. The information available here may be essential data for preventing and controlling infections caused by pathogenic bacteria in captive waterbirds.

CHIP protects against septic acute kidney injury by inhibiting NLRP3-mediated pyroptosis.

Septic acute kidney injury (S-AKI), the most common type of acute kidney injury (AKI), is intimately related to pyroptosis and oxidative stress in its pathogenesis. Carboxy-terminus of Hsc70-interacting protein (CHIP), a U-box E3 ligase, modulates oxidative stress by degrading its targeted proteins. The role of CHIP in S-AKI and its relevance with pyroptosis have not been investigated. In this study, we showed that CHIP was downregulated in renal proximal tubular cells in lipopolysaccharide (LPS)-induced S-AKI. Besides, the extent of redox injuries in S-AKI was attenuated by CHIP overexpression or activation but accentuated by CHIP gene disruption. Mechanistically, our work demonstrated that CHIP interacted with and ubiquitinated NLRP3 to promote its proteasomal degradation, leading to the inhibition of NLRP3/ACS inflammasome-mediated pyroptosis. In summary, this study revealed that CHIP ubiquitinated NLRP3 to alleviate pyroptosis in septic renal injuries, suggesting that CHIP might be a potential therapeutic target for S-AKI.

Gut Fungal Communities Are Influenced by Seasonality in Captive Baikal Teal (Sibirionetta formosa) and Common Teal (Anas crecca).

Understanding the dynamics of avian gut fungal communities and potentially pathogenic species across different seasons is crucial for assessing their health and ecological interactions. In this study, high-throughput sequencing was employed to examine the changes in gut fungal communities and the presence of potential pathogens between different seasons in captive Baikal teal and common teal. Between the summer and autumn seasons, both duck species showed significant differences in fungal diversity and community composition. A higher fungal diversity in both species was exhibited in the summer than in the autumn. Ascomycota and Basidiomycota were the two most common phyla, with a greater proportion of Ascomycota than Basidiomycota in both duck species in the summer. Interestingly, our study also identified animal pathogens and plant saprotrophs in the gut fungal communities. Seasonal variation had an effect on the diversity and abundance of both animal pathogens and saprotrophs. Specifically, during the summer season, the diversity and relative abundance were higher compared to the autumn season. In addition, there were differences between duck species in terms of animal pathogens, while no significant differences were observed in saprotrophs. Overall, the communities of the gut fungi, animal pathogens, and saprotrophs were found to be influenced by seasonal changes rather than host species. Therefore, seasonal variations might dominate over host genetics in shaping the gut microbiota of captive Baikal teal and common teal. This study underscores the importance of incorporating an understanding of seasonal dynamics and potential pathogens within the gut microbiota of captive ducks. Such considerations have the potential to drive progress in the development of sustainable and economically viable farming practices.

WBP2 restrains the lysosomal degradation of GPX4 to inhibit ferroptosis in cisplatin-induced acute kidney injury.

Cisplatin is one of the major causes of acute kidney injury (AKI) in clinical practice, and ferroptosis is an essential form of cell death in cisplatin-induced AKI (CP-AKI). WW domain binding protein-2 (WBP2), a molecular chaperon, is involved in the progression of various malignancies, but its role in renal injuries has not been investigated. Our present study employed bioinformatics analysis to identify WBP2 as a potential modulator of AKI and ferroptosis. Preliminary laboratory investigations showed that WBP2, highly expressed in renal proximal tubular cells, was downregulated in CP-AKI. Further studies demonstrated that WBP2 decelerated ferroptosis to alleviate CP-AKI. Mechanistically, WBP2 interacted with glutathione peroxidase 4 (GPX4, a key detoxicating enzyme for ferroptosis) via its PPXY1 motif to inhibit ferroptosis. Furthermore, the in-depth investigations revealed that WBP2 competed with heat shock cognate protein 70 (HSC70) for the binding with the KEFRQ-like motifs of GPX4, leading to the deceleration of chaperon-mediated autophagy of GPX4. All in all, this study indicated the beneficial effect of WBP2 in CP-AKI and its relevance with ferroptosis, thus providing a novel insight into the modulation of ferroptosis in cisplatin-related nephropathy.

Morphological characteristics influence the spatial mixing patterns of shorebirds at Shengjin Lake.

The coexistence of species with similar ecological niches is one of the core interests of community ecology research. However, how functional feeding traits, including bill size and leg length, determine the niche of mixed flocks of shorebird species has seldomly been studied, as well as, microhabitat variables affect the spatial patterns of availability and the quality of patches for wintering. From October 2016 to March 2017 at Shengjin Lake, Anhui Province, China, we recorded 226 scan samples from the different microhabitats and 93 focal animal videos of four common shorebird species: common greenshank, spotted redshank, Kentish plover, and little ringed plover. We found that the species participating in the mixed groups were different in each microhabitat. The results of the overlap index for microhabitats and foraging techniques between the species were consistent with the morphological characteristics of these species. Kentish and little ringed plovers had the highest Pianka's niche overlap index values of 0.95 and 0.98 for microhabitats and foraging techniques, respectively, whereas common greenshank and spotted redshank had values of 0.78 and 0.89, respectively. Common greenshank and spotted redshank used four foraging techniques: a single probe (PR), multiple probes (MPR), a single peck (PE), and multiple pecks (MPE). Kentish and little ringed plovers only used PE and MPE. The mean bill size, mean leg length, and mean foraging frequency were significantly associated with water depth. The mean bill size and mean leg length were both significantly correlated with the mean foraging frequency of shorebirds. The vegetated area was the most important variable for grouping among shorebirds. We concluded that the four species showed differences in their preferred microhabitats and foraging patterns. Interspecific morphological differences, including bill and leg lengths, resulted in niche differentiation. Thus, effective resource allocation by regional species was realized, and a dynamic balance was achieved by the mixed foraging species. The information on foraging behavior and habitat requirements could be useful in the management of water levels in natural areas and conservation of a diversity of wintering shorebirds.

Truncated glycoprotein E of varicella-zoster virus is an ideal immunogen for Escherichia coli-based vaccine design.

Varicella-zoster virus (VZV) is a highly infectious agent responsible for both varicella and herpes zoster disease. Despite high efficacy, there remain safety and accessibility concerns with the licensed vaccines. Here, we sought to produce a VZV gE immunogen using an E. coli expression system. We found that the soluble expression and yield of gE protein could be enhanced via C-terminal truncations to the protein, thereby facilitating a robust and scalable purification process for the purpose of vaccine manufacturing. The lead truncated gE (aa 31-358), hereafter referred to as tgE, was a homogenous monomer in solution and showed excellent antigenicity. Finally, we assessed and compared the immunogenicity of tgE with commercial vOka LAV and Shingrix vaccine. We found that aluminum-adjuvanted tgE was immunogenic as compared with vOka LAV. When adjuvanted with AS01B, a two-dose immunization of tgE showed comparable or better potency in antibody responses and cell-mediated immunity with those of the Shingrix vaccine at the same dosage, especially in terms of the proportion of IFN-γ-expressing CD4+ T cells. In conclusion, this method of E. coli-mediate tgE expression offers a cost-effective and scalable strategy to generate an ideal VZV gE immunogen for the development of both varicella and zoster vaccines.

Distribution patterns and drivers of nonendemic and endemic glires species in China.

Spatial patterns and determinants of species richness in complex geographical regions are important subjects of current biogeography and biodiversity conservation research. Glires are small herbivorous mammal species with limited migratory ability that may serve as an indicator of biodiversity and ecosystems. Herein, we aimed to evaluate how multiple ecological hypotheses could explain the species richness patterns of glires in China. Initially, we constructed a mapping grid cell operating units of 80 × 80 km2 which covered China's land mass and mapped the distribution ranges of the 237 glires species that had recorded. The glires taxa were separated into three response variables based on their distribution: (a) all species, (b) nonendemic species, and (c) endemic species. The species richness patterns of the response variables were evaluated using four predictor sets: (a) hydrothermal characteristics, (b) climatic seasonality, (c) habitat heterogeneity, and (d) human factors. We performed regression tree analysis, multiple linear regression analysis, and variation partitioning analyses to determine the effects of predictors on spatial species patterns. The results showed that the distribution pattern of species richness was the highest in the Hengduan Mountains and surrounding areas in southwest China. However, only a few endemic species adapted to high-latitude environments. It was found that there are differences about the determinants between nonendemic and endemic species. Habitat heterogeneity was the most influential determinant for the distribution patterns of nonendemic species richness. Climatic seasonality was the best predictor to determine the richness distribution pattern of endemic species, whereas this was least affected by human factors. Furthermore, it should be noted that hydrothermal characteristics were not strong predictors of richness patterns for all or nonendemic species, which may be due to the fact that there are also more species in some areas with less precipitation or energy. Therefore, glires are likely to persist in areas with characteristics of high habitat heterogeneity and stable climate.

Critical Residues Involved in the Coassembly of L1 and L2 Capsid Proteins of Human Papillomavirus 16.

Human papillomaviruses (HPV) are small DNA viruses associated with cervical cancer, warts, and other epithelial tumors. Structural studies have shown that the HPV capsid consists of 360 copies of the major capsid protein, L1, arranged as 72 pentamers in a T=7 icosahedral lattice, coassembling with substoichiometric amounts of the minor capsid protein, L2. However, the residues involved in the coassembly of L1 and L2 remain undefined due to the lack of structure information. Here, we investigated the solvent accessibility surfaces (SASs) of the central cavity residues of the HPV16 L1 pentamer in the crystal structure because those internal exposed residues might mediate the association with L2. Twenty residues in L1 protein were selected to be analyzed, with four residues in the lumen of the L1 pentamer identified as important: F256, R315, Q317, and T340. Mutations to these four residues reduced the PsV (pseudovirus) infection capacity in 293FT cells, and mutations to R315, Q317, and T340 substantially perturb L2 from coassembling into L1 capsid. Compared with wild-type (WT) PsVs, these mutant PsVs also have a reduced ability to become internalized into host cells. Finally, we identified a stretch of negatively charged residues on L2 (amino acids [aa] 337 to 340 [EEIE]), mutations to which completely abrogate L2 assembly into L1 capsid and subsequently impair the endocytosis and infectivity of HPV16 PsVs. These findings shed light on the elusive coassembly between HPV L1 and L2. IMPORTANCE Over 200 types of HPV have been isolated, with several high-risk types correlated with the occurrence of cervical cancer. The HPV major capsid protein, L1, assembles into a T=7 icosahedral viral shell, and associates with the minor capsid protein, L2, which plays a critical role in the HPV life cycle. Despite the important role of the L2 protein, its structure and coassembly with L1 remain elusive. In this study, we analyzed the amino acid residues at the proposed interface between L1 and L2. Certain mutations at these sites decreased the amount of L2 protein assembled into the capsid, which, in turn, led to a decrease in viral infectivity. Knowledge about these residues and the coassembly of L1 and L2 could help to expand our understanding of HPV biology and aid in the development of countermeasures against a wide range of HPV types by targeting the L2 protein.

Omics-guided bacterial engineering of Escherichia coli ER2566 for recombinant protein expression.

The goal of bacterial engineering is to rewire metabolic pathways to generate high-value molecules for various applications. However, the production of recombinant proteins is constrained by the complexity of the connections between cellular physiology and recombinant protein synthesis. Here, we used a rational and highly efficient approach to improve bacterial engineering. Based on the complete genome and annotation information of the Escherichia coli ER2566 strain, we compared the transcriptomic profiles of the strain under leaky expression and low temperature-induced stress. Combining the gene ontology (GO) enrichment terms and differentially expressed genes (DEGs) with higher expression, we selected and knocked out 36 genes to determine the potential impact of these genes on protein production. Deletion of bluF, cydA, mngR, and udp led to a significant decrease in soluble recombinant protein production. Moreover, at low-temperature induction, 4 DEGs (gntK, flgH, flgK, flgL) were associated with enhanced expression of the recombinant protein. Knocking out several motility-related DEGs (ER2666-ΔflgH-ΔflgL-ΔflgK) simultaneously improved the protein yield by 1.5-fold at 24 °C induction, and the recombinant strain had the potential to be applied in the expression studies of different exogenous proteins, aiming to improve the yields of soluble form to varying degrees in comparison to the ER2566 strain. Totally, this study focused on the anabolic and stress-responsive hub genes of the adaptation of E. coli to recombinant protein overexpression on the transcriptome level and constructs a series of engineering strains increasing the soluble protein yield of recombinant proteins which lays a solid foundation for the engineering of bacterial strains for recombinant technological advances. KEY POINTS: • Comparative transcriptome analysis shows host responses with altered induction stress. • Deletion of bluF, cydA, mngR, and udp genes was identified to significantly decrease the soluble recombinant protein productions. • Synchronal knockout of flagellar genes in E. coli can enhance recombinant protein yield up to ~ 1.5-fold at 24 °C induction. • Non-model bacterial strains can be re-engineered for recombinant protein expression.

Electroencephalography Signatures for Hepatic Encephalopathy in Cirrhosis Patients Treated with Proton Pump Inhibitors: An Exploratory Pilot Study.

(1) Background: Hepatic encephalopathy (HE) is a common complication in cirrhosis patients, and recently, clinical evidence indicates that a higher risk of HE is associated with the usage of proton pump inhibitors. However, the cortical mechanism underlying this neurological disorder of HE remains unknown. (2) Methods: We review the medical recordings of 260 patients diagnosed with liver cirrhosis between January 2021 and March 2022 in one tertiary hospital. Logistic regression analyses were performed to identify the risk factor of HE development. To examine the relationship between cortical dynamics and the administration of proton pump inhibitors, resting-state electroencephalograms (EEGs) were conducted in cirrhosis patients who were treated with proton pump inhibitors. (3) Results: About 28.5% (74 out of 260) of participants developed secondary HE in this study. The logistics regression model indicated that multiple risk factors were associated with the incidence of secondary HE, including proton pump inhibitors usage, white blood cell and neutrophil counts, hemoglobin, prothrombin time activity, and blood urea nitrogen. A total of twelve cirrhosis patients who were scheduled to use proton pump inhibitors consented to performing electroencephalogram recordings upon admission, and eight of twelve participants were diagnosed with HE. Spectral analysis revealed that the decrease in alpha oscillation activities was potentially associated with the development of HE. (4) Conclusions: Our data support the susceptibility of secondary HE in cirrhosis patients treated by proton pump inhibitors. One potential cortical mechanism underlying the neurological disease is the suppression of alpha oscillations in the brain.

Characterization of an Escherichia coli-derived triple-type chimeric vaccine against human papillomavirus types 39, 68 and 70.

In vaccinology, a potent immunogen has two prerequisite attributes-antigenicity and immunogenicity. We have rational designed a triple-type HPV vaccine against HPV58, -33 and -52 covered in Gardasil 9 based on the sequence homology and similar surface loop structure of L1 protein, which is related to cross-type antigenicity. Here, we design another triple-type vaccine against non-vaccine types HPV39, -68 and -70 by immunogenicity optimization considering type specific immunodominant epitopes located in separate region for different types. First, we optimized the expression of wild-type HPV39, -68 and -70 L1-only virus-like particles (VLPs) in E. coli through N-terminal truncation of HPV L1 proteins and non-fusion soluble expression. Second, based on genetic relationships and an L1 homologous loop-swapping rationale, we constructed several triple-type chimeric VLPs for HPV39, -68 and -70, and obtained the lead candidate named H39-68FG-70DE by the immunogenicity optimization using reactivity profile of a panel type-specific monoclonal antibodies. Through comprehensive characterization using various biochemical, VLP-based analyses and immune assays, we show that H39-68FG-70DE assumes similar particulate properties as that of its parental VLPs, along with comparable neutralization immunogenicity for all three HPV types. Overall, this study shows the promise and translatability of an HPV39/68/70 triple-type vaccine, and the possibility of expanding the type-coverage of current HPV vaccines. Our study further expanded the essential criteria on the rational design of a cross-type vaccine, i.e. separate sites with inter-type similar sequence and structure as well as type-specific immunodominant epitope to be clustered together.

Identification of RPS7 as the Biomarker of Ferroptosis in Acute Kidney Injury.

Objective: This paper aims to explore novel ferroptosis-related biomarkers for acute kidney injury (AKI). Methods: Various bioinformatic methods, such as differential expression analysis, functional annotation analysis, machine learning, and chemical-gene network analysis, were used in this study. Furthermore, the expression and proferroptotic role of RPS7 were validated with further bioinformatics analysis and biochemical experiments. Results: GSE30718 dataset and GSE139061 dataset were used, and the differentially expressed genes (DEGs) were screened. The DEGs were overlapped with ferroptosis-related genes and genes associated with AKI, which led to the identification of four candidate genes. Machine learning and ROC curve analysis were conducted, and RPS7 and TRIB3 were selected for diagnostic model analysis and functional analysis. Finally, the upregulation of RSP7 in cisplatin-induced AKI was validated in cisplatin-induced AKI, and its proferroptotic role was confirmed in cisplatin-treated proximal tubular cells. Conclusion: Our results indicated that RPS7 might present as a novel ferroptosis-related biomarker for AKI, and it derived ferroptosis to accentuate cisplatin-induced AKI.

Genetic engineering of baculovirus-insect cell system to improve protein production.

The Baculovirus Expression Vector System (BEVS), a mature foreign protein expression platform, has been available for decades, and has been effectively used in vaccine production, gene therapy, and a host of other applications. To date, eleven BEVS-derived products have been approved for use, including four human vaccines [Cervarix against cervical cancer caused by human papillomavirus (HPV), Flublok and Flublok Quadrivalent against seasonal influenza, Nuvaxovid/Covovax against COVID-19], two human therapeutics [Provenge against prostate cancer and Glybera against hereditary lipoprotein lipase deficiency (LPLD)] and five veterinary vaccines (Porcilis Pesti, BAYOVAC CSF E2, Circumvent PCV, Ingelvac CircoFLEX and Porcilis PCV). The BEVS has many advantages, including high safety, ease of operation and adaptable for serum-free culture. It also produces properly folded proteins with correct post-translational modifications, and can accommodate multi-gene- or large gene insertions. However, there remain some challenges with this system, including unstable expression and reduced levels of protein glycosylation. As the demand for biotechnology increases, there has been a concomitant effort into optimizing yield, stability and protein glycosylation through genetic engineering and the manipulation of baculovirus vector and host cells. In this review, we summarize the strategies and technological advances of BEVS in recent years and explore how this will be used to inform the further development and application of this system.