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Objectives: With rising rates of maxillofacial fracture, postoperative infection following rigid internal fixation is an important issue that requires immediate resolution. It is important to explore an alternative antibacterial method apart from conventional antibiotics. A controlled experiment was conducted to evaluate the effectiveness of a caerin 1.9 peptide–coated titanium plate in reducing mandibular infection in New Zealand (NZ) rabbits, aiming to minimise the risk of post–metallic implantation infection. Methods: Twenty-two NZ rabbits were randomly divided into 3 groups. The experiment group received caerin 1.9 peptide–coated titanium plates and mixed oral bacteria exposure. The control group received normal titanium plates with mixed oral bacteria exposure. The untreated group served as a control to prove that bacteria in the mouth can cause infection. Weight, temperature, hepatic function, and C-reactive protein levels were measured. Wound and bone conditions were evaluated. Further analysis included local infection, anatomic conditions, histology, and bacterial load. Results: No significant differences were found in temperature, weight, blood alanine aminotransferase, and C-reactive protein levels amongst the 3 groups. The experiment group showed the lowest amount of bacterial RNA in wounds. Additionally, the experiment group had higher peripheral lymphocyte counts compared to the control group and lower neutrophil counts on the third and seventh day postoperatively. Histologic analysis revealed lower levels of inflammatory cell infiltration, bleeding, and areas of necrosis in the experimental group compared with the controls. Conclusions: A caerin 1.9–coated titanium plate is able to inhibit bacterial growth in a NZ rabbit mandibular mixed bacteria infection model and is worth further investigation.

Abstract Background Cancer immunotherapy, particularly immune checkpoint inhibitors (ICBs) such as anti-PD-1 antibodies, has revolutionised cancer treatment, although response rates vary among patients. Previous studies have demonstrated that caerin 1.1 and 1.9, host-defence peptides from the Australian tree frog, enhance the effectiveness of anti-PD-1 and therapeutic vaccines in a murine TC-1 model by activating tumour-associated macrophages intratumorally. Methods We employed a murine B16 melanoma model to investigate the therapeutic potential of caerin 1.1 and 1.9 in combination with anti-CD47 and a therapeutic vaccine (triple therapy, TT). Tumour growth of caerin-injected primary tumours and distant metastatic tumours was assessed, and survival analysis conducted. Single-cell RNA sequencing (scRNAseq) of CD45+ cells isolated from distant tumours was performed to elucidate changes in the tumour microenvironment induced by TT. Results The TT treatment significantly reduced tumour volumes on the treated side compared to untreated and control groups, with notable effects observed by Day 21. Survival analysis indicated extended survival in mice receiving TT, both on the treated and distant sides. scRNAseq revealed a notable expansion of conventional type 1 dendritic cells (cDC1s) and CD4+CD8+ T cells in the TT group. Tumour-associated macrophages in the TT group shifted toward a more immune-responsive M1 phenotype, with enhanced communication observed between cDC1s and CD8+ and CD4+CD25+ T cells. Additionally, TT downregulated M2-like macrophage marker genes, particularly in MHCIIhi and tissue-resident macrophages, suppressing Cd68 and Arg1 expression across all macrophage types. Differential gene expression analysis highlighted pathway alterations, including upregulation of oxidative phosphorylation and MYC target V1 in Arg1hi macrophages, and activation of pro-inflammatory pathways in MHCIIhi and tissue-resident macrophages. Conclusion Our findings suggest that caerin 1.1 and 1.9, combined with immunotherapy, effectively modulate the tumour microenvironment in primary and secondary tumours, leading to reduced tumour growth and enhanced systemic immunity. Further investigation into these mechanisms could pave the way for improved combination therapies in advanced melanoma treatment.

Cancer remains a major global health challenge. Immunotherapy has revolutionized the management of cancer, yet only a limited number of patients respond to such treatments. This is largely attributed to the immunosuppressive tumor microenvironment, which diminishes the effectiveness of immunotherapy. Recent studies have underscored the potential of naturally derived caerin 1 peptides, particularly caerin 1.1 and caerin 1.9, which exhibit strong antitumor effects and enhance the efficacy of immunotherapies in animal models. This review encapsulates the current research aimed at augmenting the effectiveness of immunotherapy, focusing on the role of caerin 1.1 and caerin 1.9 in boosting immunotherapeutic outcomes, elucidating possible mechanisms, and discussing their limitations and challenges.

Abstract Thanks to high performance above room temperature, antimonide laser diodes have shown great potential for broad application in the mid-infrared spectral region. However, the laser`s performance noticeably deteriorates due to the reduction of carrier confinement with increased emission wavelength. In this paper, a novel active region with higher carrier confinements both of electron and hole, by the usage of an indirect bandgap material of Al0.5GaAs0.04Sb as the quantum barrier, was put up to address the poor carrier confinement of GaSb-based type-I multi-quantum-well (MQW) diode lasers emission wavelength above 2.5 µm. The carrier confinement and the differential gain in the designed active region are enhanced as a result of the first proposed usage of an indirect-gap semiconductor as the quantum barrier with larger band offsets in conduction and valence bands, leading to high internal quantum efficiency and low threshold current density of our lasers. More importantly, the watt-level output optical power is obtained at a low injection current compared to the state of the art. Our work demonstrates a direct and cost-effective solution to address the poor carrier confinement of the GaSb-based MQW lasers, thereby achieving high-power mid-infrared lasers.

Saponins are a diverse class of secondary metabolites that are often reported to exhibit a variety of pharmacological applications. While research into the elucidation and application of plant and class Holothuroidea-derived saponins (i.e., sea cucumbers) is extensive, the class Asteroidea-derived saponins (i.e., seastars) have been largely overlooked and primarily limited to elucidation. This review provides a comprehensive overview of the cytotoxic activities of asteroid-derived saponins against various cell cultures, for instance, mammalian erythrocytes, multiple microbial strains and cancer cell lines, including melanoma, breast, colon, and lung cancers. Highlighting the distinct structural variations in these saponins, this review examines their selective cytotoxicity and potency, with many demonstrating IC50 values in the low micromolar range. Specific compounds, such as asterosaponins and polyhydroxylated saponins, exhibit noteworthy effects, particularly against melanoma and lung carcinoma cells, while triterpenoid saponins were found to be highly cytotoxic to both erythrocytes and fungal cells. This review also addresses gaps in the research area, including the need for additional in vitro antimicrobial studies, in vivo studies, and further exploration of their mechanisms of action. By consolidating recent findings, we have shed light on the therapeutic potential of asteroid-derived steroidal saponins in developing novel antimicrobial and anticancer agents.

This paper is concerned with the following first-order Hamiltonian system $ \begin{equation} \nonumber \dot{z} = \mathscr{J}H_{z}(t, z), \end{equation} $ where the Hamiltonian function $ H(t, z) = \frac{1}{2}Lz\cdot z+A(\epsilon t)G(|z|) $ and $ \epsilon > 0 $ is a small parameter. Under some natural conditions, we obtain a new existence result for ground state homoclinic orbits by applying variational methods. Moreover, the concentration behavior and exponential decay of these ground state homoclinic orbits are also investigated.

In the imaging process of Complementary Metal Oxide Semiconductor (CMOS) image sensor, noise is inevitably introduced at various stages. This effect is particularly serious when detecting weak signals, such as ultraviolet light. Through theoretical analysis of CMOS noise, we deduce that the main noise under illumination is non-uniformity noise by averaging the images to eliminate granular noise. Existing image denoising methods rely on simulated noise, which perform poorly when applied to real detectors. To address this issue, we establish a novel CMOS image dataset. Initially, we obtain the non-uniformity noise blocks from the CMOS imaging system designed in this paper. Then, we utilize a GAN network to augment the noise data. Next, we randomly combine these noise blocks with high-quality images from the DF2K dataset to form paired image datasets. In recent years, the development of various deep learning algorithms has significantly improved the effectiveness of image noise reduction compared to traditional algorithms. This paper combines convolutional neural network and proposes the MSR-Net denoising algorithm, which is based on the U-Net network and incorporates the Res2Net module as its main network structure. It provides features with different scale receptive fields and enhances image details. Additionally, to more accurately reflect the visual perceptual effects of the images, we propose a novel image evaluation metric, Uniform pixel outliers (UPO), making the image evaluation more adequate. Experiments were conducted on our proposed image dataset, results indicate that compared with similar noise reduction algorithms, this method performs better in both qualitative and quantitative aspects, effectively suppressing noise dominated by non-uniform noise.

Objective: To explore the value of ear morphological inspection in identifying the nine constitutions of traditional Chinese medicine (TCM) by analyzing the correlation between these two research objects. Methods: A cross-sectional research design was employed. The participants' ear morphology was determined using the Ear Morphology Inspection Information Evaluation Form, while constitution was assessed using the Constitution in Chinese Medicine Questionnaire. Data were statistically analyzed, and one-way and multi-factor logistic regression analyses were conducted. Results: Among 888 participants, 270 (30.41%) had a balanced constitution, and 618 (69.59%) had different biased constitution types. The analysis revealed that thick auricles (P

Abstract Background About 20% of breast cancers in humans are basal-like, a subtype that is often triple-negative and difficult to treat. An effective translational model for basal-like breast cancer is currently lacking and urgently needed. To determine whether spontaneous mammary tumors in pet dogs could meet this need, we subtyped canine mammary tumors and evaluated the dog–human molecular homology at the subtype level. Methods We subtyped 236 canine mammary tumors from 3 studies by applying various subtyping strategies on their RNA-seq data. We then performed PAM50 classification with canine tumors alone, as well as with canine tumors combined with human breast tumors. We identified feature genes for human BLBC and luminal A subtypes via machine learning and used these genes to repeat canine-alone and cross-species tumor classifications. We investigated differential gene expression, signature gene set enrichment, expression association, mutational landscape, and other features for dog–human subtype comparison. Results Our independent genome-wide subtyping consistently identified two molecularly distinct subtypes among the canine tumors. One subtype is mostly basal-like and clusters with human BLBC in cross-species PAM50 and feature gene classifications, while the other subtype does not cluster with any human breast cancer subtype. Furthermore, the canine basal-like subtype recaptures key molecular features (e.g., cell cycle gene upregulation, TP53 mutation) and gene expression patterns that characterize human BLBC. It is enriched in histological subtypes that match human breast cancer, unlike the other canine subtype. However, about 33% of canine basal-like tumors are estrogen receptor negative (ER−) and progesterone receptor positive (PR+), which is rare in human breast cancer. Further analysis reveals that these ER−PR+ canine tumors harbor additional basal-like features, including upregulation of genes of interferon-γ response and of the Wnt-pluripotency pathway. Interestingly, we observed an association of PGR expression with gene silencing in all canine tumors and with the expression of T cell exhaustion markers (e.g., PDCD1) in ER−PR+ canine tumors. Conclusions We identify a canine mammary tumor subtype that molecularly resembles human BLBC overall and thus could serve as a vital translational model of this devastating breast cancer subtype. Our study also sheds light on the dog–human difference in the mammary tumor histology and the hormonal cycle.

Power scaling in conventional broad-area (BA) lasers often leads to the operation of higher-order lateral modes, resulting in a multiple-lobe far-field profile with large divergence. Here, we report an advanced sawtooth waveguide (ASW) structure integrated onto a wide ridge waveguide. It strategically enhances the loss difference between higher-order modes and the fundamental mode, thereby facilitating high-power narrow-beam emission. Both optical simulations and experimental results illustrate the significant increase in additional scattering loss of the higher-order modes. The optimized ASW lasers achieve an impressive output power of 1.1 W at 4.6 A at room temperature, accompanied by a minimal full width at half maximum lateral divergence angle of 4.91°. Notably, the far-field divergence is reduced from 19.61° to 11.39° at the saturation current, showcasing a remarkable 42% improvement compared to conventional BA lasers. Moreover, the current dependence of divergence has been effectively improved by 38%, further confirming the consistent and effective lateral mode control capability offered by our design.

ABSTRACT Caerin 1 is a family of host defense peptides with antimicrobial properties originally isolated from the Australian tree frog. Both caerin 1.1 and caerin 1.9 have been demonstrated to inhibit infections caused by multiple antibiotic-resistant bacteria, both in vitro and in vivo. In this current study, we conducted a comparison of the minimum inhibitory concentrations of caerin 1.1 and caerin 1.9 (referred to as caerin 1.1/1.9) with commonly used antibiotics against various bacteria, including Staphylococcus aureus, Copper-Green Pseudomonas aeruginosa, Acinetobacter baumannii, and Streptococcus haemolyticus. Our findings reveal that caerin 1.1/1.9 not only prevent the formation of biofilms by A. baumannii but also exhibit a therapeutic effect on established biofilms. Furthermore, our study demonstrates that caerin 1.1/1.9 significantly inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) strains in a murine skin infection model. A quantitative proteomic analysis conducted as part of our study indicates that caerin 1.1/1.9 primarily activate oxidative phosphorylation pathways, along with several pathways associated with tissue repair and growth. These findings were observed in comparison to untreated tissues that were infected with MRSA in mice. In summary, our research outcomes suggest that caerin 1.1/1.9 exhibit the potential to serve as promising drug candidates for treating complicated antibiotic-resistant bacterial infections in humans. IMPORTANCE Caerin 1.1 and caerin 1.9, natural antimicrobial peptides derived from tree frogs, have demonstrated the ability to inhibit the growth of antibiotic-resistant bacteria, comparable to certain widely used antibiotics. Additionally, these peptides exhibit the capacity to prevent or treat biofilms formed by bacteria in conjunction with bodily components. The mechanisms underlying their antibacterial effects were investigated through a mouse model of bacterial skin infection, utilizing proteomic analysis as a technological approach.

Abstract The nervous system of the Asteroidea (starfish or seastar) consists of radial nerve cords (RNCs) that interconnect with a ring nerve. Despite its relative simplicity, it facilitates the movement of multiple arms and numerous tube feet, as well as regeneration of damaged limbs. Here, we investigated the RNC ultrastructure and its molecular components within the of Pacific crown-of-thorns starfish (COTS; Acanthaster sp.), a well-known coral predator that in high-density outbreaks has major ecological impacts on coral reefs. We describe the presence of an array of unique small bulbous bulbs (40–100 μm diameter) that project from the ectoneural region of the adult RNC. Each comprise large secretory-like cells and prominent cilia. In contrast, juvenile COTS and its congener Acanthaster brevispinus lack these features, both of which are non-corallivorous. Proteomic analysis of the RNC (and isolated neural bulbs) provides the first comprehensive echinoderm protein database for neural tissue, including numerous secreted proteins associated with signalling, transport and defence. The neural bulbs contained several neuropeptides (e.g., bombyxin-type, starfish myorelaxant peptide, secretogranin 7B2-like, Ap15a-like, and ApNp35) and Deleted in Malignant Brain Tumor 1-like proteins. In summary, this study provides a new insight into the novel traits of COTS, a major pest on coral reefs, and a proteomics resource that can be used to develop (bio)control strategies and understand molecular mechanisms of regeneration.

Abstract Background Cervical cancer (CC) is the 3rd most common cancer in women and the 4th leading cause of deaths in gynaecological malignancies, yet the exact progression of CC is inconclusive, mainly due to the high complexity of the changing tumour microenvironment (TME) at different stages of tumorigenesis. Importantly, a detailed comparative single-nucleus transcriptomic analysis of tumour microenvironment (TME) of CC patients at different stages is lacking. Methods In this study, a total of 42,928 and 29,200 nuclei isolated from the tumour tissues of stage-I and II CC patients and subjected to single-nucleus RNA sequencing (snRNA-seq) analysis. The cell heterogeneity and functions were comparatively investigated using bioinformatic tools. In addition, label-free quantitative mass spectrometry based proteomic analysis was carried out. The proteome profiles of stage-I and II CC patients were compared, and an integrative analysis with the snRNA-seq was performed. Results Compared with the stage-I CC (CCI) patients, the immune response relevant signalling pathways were largely suppressed in various immune cells of the stage-II CC (CCII) patients, yet the signalling associated with cell and tissue development was enriched, as well as metabolism for energy production suggested by the upregulation of genes associated with mitochondria. This was consistent with the quantitative proteomic analysis that showed the dominance of proteins promoting cell growth and intercellular matrix development in the TME of CCII group. The interferon-α and γ responses appeared the most activated pathways in many cell populations of the CCI patients. Several collagens, such as COL12A1, COL5A1, COL4A1 and COL4A2, were found significantly upregulated in the CCII group, suggesting their roles in diagnosing CC progression. A novel transcript AC244205.1 was detected as the most upregulated gene in CCII patients, and its possible mechanistic role in CC may be investigated further. Conclusions Our study provides important resources for decoding the progression of CC and set the foundation for developing novel approaches for diagnosing CC and tackling the immunosuppressive TME.

Abstract GaSb-based single-transverse-mode narrow ridge waveguide (RW) lasers with high power and simultaneous good beam quality have broad application prospects in the mid-infrared wavelength region. Yet its design and formation have not been investigated systematically, while the beam characteristics that affect their suitability for specific applications remain rarely analyzed and optimized. The present work addresses these issues by theoretically establishing a waveguide parameter domain that generalizes the overall possible combinations of ridge widths and etch depths that support single-transverse-mode operation for GaSb-based RW lasers. These results are applied to develop two distinct and representative waveguide designs derived from two proposed major optimization routes of model gain expansion and index-guiding enhancement. The designs were evaluated experimentally based on prototype 1-mm cavity-length RW lasers in the 1950 nm wavelength range, which were fabricated with waveguides having perpendicular ridge and smooth side-walls realized through optimized dry etching conditions. The model gain expanded RW laser design with a relatively shallow-etched (i.e., 1.55 $$\upmu$$ μ m) and wide ridge (i.e., 7 $$\upmu$$ μ m) yielded the highest single-transverse-mode power to date of 258 mW with a narrow lateral divergence angle of 11.1 $$^\circ$$ ∘ full width at half maximum at 800 mA under room-temperature continuous-wave operation, which offers promising prospects in pumping and coupling applications. Meanwhile, the index-guiding enhanced RW laser design with a relatively deeply etched (i.e., 2.05 $$\upmu$$ μ m) and narrow ridge (i.e., 4 $$\upmu$$ μ m) provided a highly stable and nearly astigmatism-free fundamental mode emission with an excellent beam quality of M $$^2$$ 2 factor around 1.5 over the entire operating current range, which is preferable for seeding external cavity applications and complex optical systems.

Objective: To initially explore traditional Chinese medicine patterns in a bleomycin-induced pulmonary fibrosis mouse model. Methods: Thirty-six C57BL/6 mice were divided by the random number table method (with 12 rats per group) into three groups: a blank group, a model group, and a number 2 Feibi recipe (FBR-2) group. The pulmonary fibrosis mouse model was established by intratracheal instillation of bleomycin. The FBR-2 group was treated with FBR-2 for 4 weeks. Symptoms in the mice such as mental behavior, food/water intake, body weight, body temperature, respiratory rate, and tongue image were observed. The samples were collected on the 14th day and 28th day after modeling, and lung tissues were visually assessed and microscopically evaluated by staining with hematoxylin-eosin and Masson. The expression levels of hydroxyproline, interleukin (IL)-33, IL-37, tissue plasminogen activator, and plasminogen activator inhibitor-1 were determined by enzyme-linked immunosorbent assay. Results: Mice in the model group were poor in spirit, less active, slow in response, showed reduced food/water intake, body temperature, and body weight, increased respiratory rate, and their tongue color had changed from light red to dark red. However, treatment with FBR-2 significantly improved these symptoms. Extensive inflammatory cell infiltration and collagen fiber deposition were observed in the lung tissues of the model group. Compared with the blank group, the levels of hydroxyproline, IL-33, and plasminogen activator inhibitor-1 in the model group significantly increased (all P

Background The crown-of-thorns starfish (COTS; Acanthaster species) is a slow-moving corallivore protected by an extensive array of long, sharp toxic spines. Envenomation can result in nausea, numbness, vomiting, joint aches and sometimes paralysis. Small molecule saponins and the plancitoxin proteins have been implicated in COTS toxicity. Methods Brine shrimp lethality assays were used to confirm the secretion of spine toxin biomolecules. Histological analysis, followed by spine-derived proteomics helped to explain the source and identity of proteins, while quantitative RNA-sequencing and phylogeny confirmed target gene expression and relative conservation, respectively. Results We demonstrate the lethality of COTS spine secreted biomolecules on brine shrimp, including significant toxicity using aboral spine semi-purifications of >10 kDa (p > 0.05, 9.82 µg/ml), supporting the presence of secreted proteins as toxins. Ultrastructure observations of the COTS aboral spine showed the presence of pores that could facilitate the distribution of secreted proteins. Subsequent purification and mass spectrometry analysis of spine-derived proteins identified numerous secretory proteins, including plancitoxins, as well as those with relatively high gene expression in spines, including phospholipase A2, protease inhibitor 16-like protein, ependymin-related proteins and those uncharacterized. Some secretory proteins (e.g., vitellogenin and deleted in malignant brain tumor protein 1) were not highly expressed in spine tissue, yet the spine may serve as a storage or release site. This study contributes to our understanding of the COTS through functional, ultrastructural and proteomic analysis of aboral spines.

Abstract Schistosomiasis is a medically significant disease caused by helminth parasites of the genus Schistosoma. The schistosome life cycle requires chemically mediated interactions with an intermediate (aquatic snail) and definitive (human) host. Blocking parasite development within the snail stage requires improved understanding of the interactions between the snail host and the Schistosoma water-borne free-living form (miracidium). Innovations in snail genomics and aquatic chemical communication provide an ideal opportunity to explore snail-parasite coevolution at the molecular level. Rhodopsin G protein-coupled receptors (GPCRs) are of particular interest in studying how trematode parasites navigate towards their snail hosts. The potential role of GPCRs in parasites makes them candidate targets for new antihelminthics that disrupt the intermediate host life-cycle stages, thus preventing subsequent human infections. A genomic-bioinformatic approach was used to identify GPCR orthologs between the snail Biomphalaria glabrata and miracidia of its obligate parasite Schistosoma mansoni. We show that 8 S. mansoni rhodopsin GPCRs expressed within the miracidial stage share overall amino acid similarity with 8 different B. glabrata rhodopsin GPCRs, particularly within transmembrane domains, suggesting conserved structural features. These GPCRs include an orphan peptide receptor as well as several with strong sequence homologies with rhabdomeric opsin receptors, a serotonin receptor, a sulfakinin (SK) receptor, an allatostatin-A (buccalin) receptor and an FMRFamide receptor. Buccalin and FMRFa peptides were identified in water conditioned by B. glabrata, and we show synthetic buccalin and FMRFa can stimulate significant rates of change of direction and turn-back responses in S. mansoni miracidia. Ortholog GPCRs were identified in S. mansoni miracidia and B. glabrata. These GPCRs may detect similar ligands, including snail-derived odorants that could facilitate miracidial host finding. These results lay the foundation for future research elucidating the mechanisms by which GPCRs mediate host finding which can lead to the potential development of novel anti-schistosome interventions.

Teneurin C-terminal associated peptide (TCAP) is an ancient bioactive peptide that is highly conserved in metazoans. TCAP administration reduces cellular and behavioural stress in vertebrate and urochordate models, yet despite numerous studies in higher animals, there is limited knowledge of its role in invertebrates. In particular, there are no studies on TCAP’s effects on the heart of any metazoan, which is a critical organ in the stress response. We used the Sydney rock oyster (SRO) as an invertebrate model to investigate a potential role for sroTCAP in regulating cardiac activity, including during stress. sroTCAP is localized to the neural innervation network of the SRO heart, and suggested binding with various heart proteins related to metabolism and stress, including SOD, GAPDH and metabotropic glutamate receptor. Intramuscular injection of sroTCAP (10 pmol) significantly altered the expression of heart genes that are known to regulate remodelling processes under different conditions, and modulated several gene families responsible for stress mitigation. sroTCAP (1 and 10 pmol) was shown to cause transient bradycardia (heart rate was reduced by up to 63% and for up to 40 min post-administration), indicative of an unstressed state. In summary, this study has established a role for a TCAP in the regulation of cardiac activity through modulation of physiological and molecular components associated with energy conservation, stress and adaptation. This represents a novel function for TCAP and may have implications for higher-order metazoans.

Abstract In this paper we study the existence and multiplicity of solutions for the following nonlinear Choquard equation: − Δ u + V ( x ) u = [ | x | − μ ∗ | u | p ] | u | p − 2 u , x ∈ R N , $$\begin{aligned} -\Delta u+V(x)u=\bigl[ \vert x \vert ^{-\mu }\ast \vert u \vert ^{p}\bigr] \vert u \vert ^{p-2}u,\quad x \in \mathbb{R}^{N}, \end{aligned}$$ where N ≥ 3 $N\geq 3$ , 0 < μ < N $0

Schistosomiasis, caused by infection with Schistosoma digenetic trematodes, is one of the deadliest neglected tropical diseases in the world. The Schistosoma lifecycle involves the miracidial infection of an intermediate freshwater snail host, such as Biomphalaria glabrata. Dispersing snail host-derived Schistosoma miracidia attractants has been considered a method of minimising intermediate host infections and, by extension, human schistosomiasis. The attractiveness of B. glabrata to miracidia is known to be reduced following infection; however, the relationship between duration of infection and attractiveness is unclear. Excretory-secretory proteins (ESPs) most abundant in attractive snail conditioned water (SCW) are key candidates to function as miracidia attractants. This study analysed SCW from B. glabrata that were naïve (uninfected) and at different time-points post-miracidia exposure (PME; 16h, 1-week, 2-weeks and 3-weeks PME) to identify candidate ESPs mediating Schistosoma mansoni miracidia behaviour change, including aggregation and chemoklinokinesis behaviour (random motion, including slowdown and increased turning rate and magnitude). Miracidia behaviour change was only observed post-addition of naïve and 3W-PME SCW, with other treatments inducing significantly weaker behaviour changes. Therefore, ESPs were considered attractant candidates if they were shared between naïve and 3W-PME SCW (or exclusive to the former), contained a predicted N-terminal signal peptide and displayed low identity (

Insects of different orders produce elaborate structures to protect their eggs from the many threats they may face from the environment and natural enemies. In the weevil genus Gonipterus, their dark, hardened egg capsule is possibly generated by a mixture of the insects' excrement and glandular substances. To test this hypothesis, this study focused on the elucidation of protein components present in the egg capsule cover and interrogated them through comparative analysis and gene expression to help infer potential functions. First, female Gonipterus sp. n. 2 reproductive and alimentary tissues were isolated to establish a reference transcriptome-derived protein database. Then, proteins from weevil frass (excrement) and egg capsule cover were identified through mass spectrometry proteomics. We found that certain egg capsule cover proteins were both exclusive and shared between frass and egg capsule cover, including those of plant origin (e.g. photosystem II protein) and others secreted by the weevil, primarily from reproductive tissue. Among them, a mucin/spidroin-like protein and novel proteins with repetitive units that likely play a structural role were identified. We have confirmed the dual origin of the egg capsule cover substance as a blend of the insects’ frass and secretions. Novel proteins secreted by the weevils are key candidates for holding the egg case cover together.

Genomic studies of canine tumours have been done for individual cancer types or dog breeds. Here the authors analyse canine tumour genomics data across multiple breeds and cancer types, finding that mutational burden is associated with TP53 mutations and that Golden Retrievers are enriched for particular signatures.

Abstract Background Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. While many patients survive, a portion of PTC cases display high aggressiveness and even develop into refractory differentiated thyroid carcinoma. This may be alleviated by developing a novel model to predict the risk of recurrence. Ferroptosis is an iron-dependent form of regulated cell death (RCD) driven by lethal accumulation of lipid peroxides, is regulated by a set of genes and shows a variety of metabolic changes. To elucidate whether ferroptosis occurs in PTC, we analyse the gene expression profiles of the disease and established a new model for the correlation. Methods The thyroid carcinoma (THCA) datasets were downloaded from The Cancer Genome Atlas (TCGA), UCSC Xena and MisgDB, and included 502 tumour samples and 56 normal samples. A total of 60 ferroptosis related genes were summarised from MisgDB database. Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) were used to analyse pathways potentially involving PTC subtypes. Single sample GSEA (ssGSEA) algorithm was used to analyse the proportion of 28 types of immune cells in the tumour immune infiltration microenvironment in THCA and the hclust algorithm was used to conduct immune typing according to the proportion of immune cells. Spearman correlation analysis was performed on the ferroptosis gene expression and the correlation between immune infiltrating cells proportion. We established the WGCNA to identify genes modules that are highly correlated with the microenvironment of immune invasion. DEseq2 algorithm was further used for differential analysis of sequencing data to analyse the functions and pathways potentially involving hub genes. GO and KEGG enrichment analysis was performed using Clusterprofiler to explore the clinical efficacy of hub genes. Univariate Cox analysis was performed for hub genes combined with clinical prognostic data, and the results was included for lasso regression and constructed the risk regression model. ROC curve and survival curve were used for evaluating the model. Univariate Cox analysis and multivariate Cox analysis were performed in combination with the clinical data of THCA and the risk score value, the clinical efficacy of the model was further evaluated. Results We identify two subtypes in PTC based on the expression of ferroptosis related genes, with the proportion of cluster 1 significantly higher than cluster 2 in ferroptosis signature genes that are positively associated. The mutations of Braf and Nras are detected as the major mutations of cluster 1 and 2, respectively. Subsequent analyses of TME immune cells infiltration indicated cluster 1 is remarkably richer than cluster 2. The risk score of THCA is in good performance evaluated by ROC curve and survival curve, in conjunction with univariate Cox analysis and multivariate Cox analysis results based on the clinical data shows that the risk score of the proposed model could be used as an independent prognostic indicator to predict the prognosis of patients with papillary thyroid cancer. Conclusions Our study finds seven crucial genes, including Ac008063.2, Apoe, Bcl3, Acap3, Alox5ap, Atxn2l and B2m, and regulation of apoptosis by parathyroid hormone-related proteins significantly associated with ferroptosis and immune cells in PTC, and we construct the risk score model which can be used as an independent prognostic index to predict the prognosis of patients with PTC.

ObjectiveTo investigate the effect of the 131I-labeled high-affinity peptides Caerin 1.1 and Caerin 1.9 for the treatment of A549 human NSCLC cells.Methods① 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and plate clone formation assays were performed to confirm the in vitro anti-tumor activity of Caerin 1.1 and Caerin 1.9. ② Chloramine-T was used to label Caerin 1.1 and Caerin 1.9 with 131I, and the Cell Counting Kit 8 assay was performed to analyze the inhibitory effect of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9 on the proliferation of NSCLC cells. An A549 NSCLC nude mouse model was established to investigate the in vivo anti-tumor activity of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9.Results① Caerin 1.1 and Caerin 1.9 inhibited the proliferation of NSCLC cells in vitro in a concentration-dependent manner. The half-maximal inhibitory concentration was 16.26 µg/ml and 17.46 µg/ml, respectively, with no significant intergroup difference (P>0.05). ② 131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 were equally effective and were superior to their unlabeled versions in their ability to inhibit the proliferation and growth of NSCLC cells (P>0.05).Conclusions131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 inhibit the proliferation and growth of NSCLC cells and may become potential treatments for NSCLC.

Teneurin C-terminal associated peptide (TCAP) is an ancient bioactive peptide that is highly conserved in metazoans. TCAP administration reduces cellular and behavioral stress in vertebrate and urochordate models. There is little information for invertebrates regarding the existence or function of a TCAP. This study used the Sydney rock oyster (SRO) as a molluscan model to characterize an invertebrate TCAP, from molecular gene analysis to its physiological effects associated with hemocyte phagocytosis. We report a single teneurin gene (and 4 teneurin splice variants), which encodes a precursor with TCAP that shares a vertebrate-like motif, and is similar to that of other molluscan classes (gastropod, cephalopod), arthropods and echinoderms. TCAP was identified in all SRO tissues using western blotting at 1-2 different molecular weights (~22 kDa and ~37kDa), supporting precursor cleavage variation. In SRO hemolymph, TCAP was spatially localized to the cytosol of hemocytes, and with particularly high density immunoreactivity in granules. Based on ‘pull-down’ assays, the SRO TCAP binds to GAPDH, suggesting that TCAP may protect cells from apoptosis under oxidative stress. Compared to sham injection, the intramuscular administration of TCAP (5 pmol) into oysters modulated their immune system by significantly reducing hemocyte phagocytosis under stress conditions (low salinity and high temperature). TCAP administration also significantly reduced hemocyte reactive oxygen species production at ambient conditions and after 48 h stress, compared to sham injection. Transcriptomic hemocyte analysis of stressed oysters administered with TCAP demonstrated significant changes in expression of genes associated with key metabolic, protective and immune functions. In summary, this study established a role for TCAP in oysters through modulation of physiological and molecular functions associated with energy conservation, stress and cellular defense.

A great deal of research undertaken in child language development, neurolinguistics and various branches of functional and cognitive linguistics has shown that a main source of language development is the spoken input to which learners are exposed. Despite the fact that for most adult L2 learners, the greatest exposure to the L2 is the input they experience in the classroom, we still know very little of the linguistic quality of L2 classroom input and its links to L2 development. The study reported in this paper is a partial response to this gap. Drawing on research from L1 classrooms linking the linguistic quality of teacher questions to the linguistic quality of student responses and grounded in the shared theoretical and methodological framework of conversation analysis and interactional linguistics, our study examines the linguistic designs of L2 teacher questions and the links between them and the L2 student responses they engender.

Interleukin 10 (IL-10) belongs to IL-10 family cytokines that are critical for maintaining the integrity of epithelial tissues, protecting pathogenic infection, and preventing excessive immune responses to damage self. Temporal IL-10 signaling blockade enhances vaccine-induced tumor regression by CD8 + T cells. IL-10, especially pegylated IL-10, mediates tumor regression by expanding tumor-infiltrating CD8 + T cells. Moreover, targeting IL-10 enhances immune checkpoint inhibitor mediated tumor regression. In the current paper, we will review recent advances in this area and discuss the complexity of IL-10 manipulation for cancer therapy.

We propose a novel graded AlGaAsSb layer growth method to achieve a super-linear interface by precisely controlling the cell temperature and valve position. Atomically smooth surface and lattice-matched epitaxy was confirmed by AFM and the HRXRD characterization of the graded AlGaAsSb layer sample. With the inserted graded layer between the cladding and waveguide layers, high-power, high-efficiency GaSb-based laser emitters and laser bars were confirmed. The linearly graded interface layer smooths the potential barrier peak between the cladding and waveguide layers, which resulted in a low turn-on voltage of 0.65 V and an ultra-low series resistance of 0.144 Ω. A maximum continuous-wave output power of 1.8 W was obtained with a high power conversion efficiency of 28% at 1.1 A and 12% at 8 A. A facet-coated laser bar was also fabricated with a record-high CW output power of 18 W. A high internal quantum efficiency of 83 was maintained at 40 °C, implying improved carrier injection efficiency, which benefits from the built-in electric field of the composition-graded AlGaAsSb layer.

Facial appearance reveals clues about personality. Studies have found that facial width-to-height ratio (fWHR) correlates with some personality traits, and mandibular morphology as a potential facial feature that might have correlation with personality traits. Therefore, a face recognition study was carried out to explore the personality traits’ correlation to both fWHR and bilateral mandibular line angles. Specifically, face images of 904 college students in China were collected and measured, with the personality traits evaluated using the 16 Personality Factor Questionnaire. Analyses revealed that the average bilateral mandibular line angle of the male were significantly more extensive than that of the female, while the fWHR of the female was significantly more extensive than that of the male. We found facial features (fWHR and average bilateral mandibular line angle) were correlated with 16PF in the canonical correlation analysis and the loadings of bilateral mandibular line angles were greater than that of fWHR. The fWHR was significantly negatively correlated with the scores of sensitivity and self-reliance in male but none of the factors related to fWHR in female. The bilateral mandibular line angles were significantly negatively correlated with the scores of social boldness in male, and were significantly negatively correlated with the scores of vigilance and apprehension in female. Over all, the correlations between fWHR, average bilateral mandibular line angle and certain 16PF factors in male and female tend to be different, suggesting that such correlations might vary with gender. In the future, mandibular morphology could be selected as a potential indicator in facial perception. The limitations of this study were the participants were limited to 18–30 years of age and the mandibular morphology was not measured with anthropometry, which could be further improved in future studies.

The relative lack of marine venom pharmaceuticals can be anecdotally attributed to difficulties in working with venomous marine animals, including how to maintain venom bioactivity during extraction and purification. The primary aim of this systematic literature review was to examine the key factors for consideration when extracting and purifying jellyfish venom toxins to maximise their effectiveness in bioassays towards the characterisation of a single toxin.An up-to-date database of 119 peer-reviewed research articles was established for all purified and semi-purified venoms across all jellyfish, including their level of purification, LD50, and the types of experimental toxicity bioassay used (e.g., whole animal and cell lines). We report that, of the toxins successfully purified across all jellyfish, the class Cubozoa (i.e., Chironex fleckeri and Carybdea rastoni) was most highly represented, followed by Scyphozoa and Hydrozoa. We outline the best practices for maintaining jellyfish venom bioactivity, including strict thermal management, using the “autolysis” extraction method and two-step liquid chromatography purification involving size exclusion chromatography. To date, the box jellyfish C. fleckeri has been the most effective jellyfish venom model with the most referenced extraction methods and the most isolated toxins, including CfTX-A/B. In summary, this review can be used as a resource for the efficient extraction, purification, and identification of jellyfish venom toxins.

The red seaweed Asparagopsis taxiformis is a promising ruminant feed additive with anti-methanogenic properties that could contribute to global climate change solutions. Genomics has provided a strong foundation for in-depth molecular investigations, including proteomics. Here, we investigated the proteome of A. taxiformis (Lineage 6) in both sporophyte and gametophyte stages, using soluble and insoluble extraction methods. We identified 741 unique non-redundant proteins using a genome-derived database and 2007 using a transcriptome-derived database, which included numerous proteins predicted to be of fungal origin. We further investigated the genome-derived proteins to focus on seaweed-specific proteins. Ontology analysis indicated a relatively large proportion of ion-binding proteins (i.e., iron, zinc, manganese, potassium and copper), which may play a role in seaweed heavy metal tolerance. In addition, we identified 58 stress-related proteins (e.g., heat shock and vanadium-dependent haloperoxidases) and 44 photosynthesis-related proteins (e.g., phycobilisomes, photosystem I, photosystem II and ATPase), which were in general more abundantly identified from female gametophytes. Forty proteins were predicted to be secreted, including ten rhodophyte collagen-alpha-like proteins (RCAPs), which displayed overall high gene expression levels. These findings provide a comprehensive overview of expressed proteins in A. taxiformis, highlighting the potential for targeted protein extraction and functional characterisation for future biodiscovery.

The OI135.6 nm radiation intensity and the associated change with solar activity are very complex, and this is particularly the case during November 2020. In this paper, we investigated the OI135.6 nm radiation intensity in the low-latitude ionosphere during a quiet geomagnetic period. The Ionospheric Photometer (IPM) instrument onboard the FY-3(D) meteorological satellite was employed to measure the OI135.6 nm night airglow at 02:00 LT (local time) and its response to the solar activity. The results showed there is a statistically significant correlation between the intensity of the equatorial ionospheric anomaly (EIA) and solar activity after midnight. The EIA at 02:00 LT and before midnight shared the same climatological characteristics—strong in equinoxes and weak in solstices. In November 2020, when the F10.7 flux significantly increased, the OI135.6 nm radiation intensity in the EIA region recorded a 100–200% increase compared to the previous month, which was much higher than in the same period in the preceding two years. A similar phenomenon was observed at the same time by the Global-scale Observations of Limb and Disk (GOLD), which makes continuous observations of ionospheric structure variation in global patterns. Data analysis suggests that the EIA at 02:00 LT was due to the attenuation of the EIA before midnight after the disappearance of the eastward electric field. The magnetic latitude of the EIA crest (hereafter denoted by θmlF2) indicates a range-and-seasonal rule of hemispherical asymmetry: closer to the geomagnetic equator in equinoxes and farther away from the geomagnetic equator in solstices. Further studies are needed.

Symmetric narrow waveguide structure has been developed and fabricated to achieve low beam divergence and improved coupling performance of the 1.95 μm GaSb-based single-transverse-mode diode lasers. The near-field expansion effect of the narrowed 150 nm vertical waveguide design leads to a reduced fast-axis beam divergence of 44.2° full width at half maximum (FWHM) as well as 62% single-mode fiber (SMF) coupling efficiency, which has 55% relative promotion compared to the 40% efficiency of the conventional 270 nm waveguide design with 60.4° FWHM. The highest SMF coupling power of 113 mW was obtained by the 210 nm narrow waveguide lasers with lower internal optical loss at a 55% coupling efficiency, which performed balanced optimal performance with a narrowed divergence of 53.4° and a relatively high optical power of 206 mW. The high coupling efficiency and power will provide more promising prospects for the GaSb-based single-transverse-mode lasers in the widespread fiber-based and external-cavity applications.

The development of topical cream drugs that increase the immune activation of tumour-infiltrating lymphocytes against tumour and chronic viral infection-associated lesions is of great immunotherapeutic significance. This study demonstrates that the topical application of a temperature-sensitive gel containing caerin 1.1 and 1.9 peptides reduces nearly 50% of the tumour weight of HPV16 E6/E7-transformed TC-1 tumour-bearing mice via improving the tumour microenvironment. Confocal microscopy confirms the time-dependent penetration of caerin 1.9 through the epidermal layer of the ear skin structure of mice. Single-cell transcriptomic analysis shows that the caerin 1.1/1.9 gel expands the populations with high immune activation level and largely stimulates the pro-inflammatory activity of NK and dendritic cells. Closely associated with INFα response, Cebpb seems to play a key role in altering the function of all Arg1hi macrophages in the caerin group. In addition, the caerin gel treatment recruits almost two-fold more activated CD8+ T cells to the TME, relative to the untreated tumour, which shows a synergistic effect derived from the regulation of S1pr1, Ccr7, Ms4a4b and Gimap family expression. The TMT10plex-labelling proteomic quantification further demonstrates the activation of interferon-alpha/beta secretion and response to cytokine stimulus by the caerin gel, while the protein contents of several key regulators were elevated by more than 30%, such as Cd5l, Gzma, Ifit1, Irf9 and Stat1. Computational integration of the proteome with the single-cell transcriptome consistently suggested greater activation of NK and T cells with the topical application of caerin peptide gel.

ABSTRACT The host defense peptide caerin 1.9 was originally isolated from skin secretions of an Australian tree frog and inhibits the growth of a wide range of bacteria in vitro. In this study, we demonstrated that caerin 1.9 shows high bioactivity against several bacteria strains, such as Staphylococcus aureus, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus haemolyticus in vitro. Importantly, unlike the antibiotic Tazocin, caerin 1.9 does not induce bacterial resistance after 30 rounds of in vitro culture. Moreover, caerin 1.1, another peptide of the caerin family, has an additive antibacterial effect when used together with caerin 1.9. Furthermore, caerin 1.1 and 1.9 prepared in the form of a temperature-sensitive gel inhibit MRSA growth in a skin bacterial infection model of two murine strains. These results indicate that caerin 1.1 and 1.9 peptides could be considered an alternative for conventional antibiotics. IMPORTANCE Antibiotic-resistant bacteria cause severe problems in the clinic. We show in our paper that two short peptides isolated from an Australian frog and prepared in the form of a gel are able to inhibit the growth of antibiotic-resistant bacteria in mice, and, unlike antibiotics, these peptides do not lead to the development of peptide-resistant bacteria strains.

Wild abalone (Family Haliotidae) populations have been severely affected by commercial fishing, poaching, anthropogenic pollution, environment and climate changes. These issues have stimulated an increase in aquaculture production; however production growth has been slow due to a lack of genetic knowledge and resources. We have sequenced a draft genome for the commercially important temperate Australian ‘greenlip’ abalone (Haliotis laevigata, Donovan 1808) and generated 11 tissue transcriptomes from a female adult abalone. Phylogenetic analysis of the greenlip abalone with reference to the Pacific abalone (Haliotis discus hannai) indicates that these abalone species diverged approximately 71 million years ago. This study presents an in-depth analysis into the features of reproductive dysfunction, where we provide the putative biochemical messenger components (neuropeptides) that may regulate reproduction including gonad maturation and spawning. Indeed, we isolate the egg-laying hormone neuropeptide and under trial conditions induce spawning at 80% efficiency. Altogether, we provide a solid platform for further studies aimed at stimulating advances in abalone aquaculture production. The H. laevigata genome and resources are made available to the public on the abalone ‘omics website, http://abalonedb.org.

Abstract Background Schistosomiasis is a harmful neglected tropical disease caused by infection with Schistosoma spp., such as Schistosoma mansoni. Schistosoma must transition within a molluscan host to survive. Chemical analyses of schistosome-molluscan interactions indicate that host identification involves chemosensation, including naïve host preference. Proteomic technique advances enable sophisticated comparative analyses between infected and naïve snail host proteins. This study aimed to compare resistant, susceptible and naïve Biomphalaria glabrata snail-conditioned water (SCW) to identify potential attractants and deterrents. Methods Behavioural bioassays were performed on S. mansoni miracidia to compare the effects of susceptible, F1 resistant and naïve B. glabrata SCW. The F1 resistant and susceptible B. glabrata SCW excretory–secretory proteins (ESPs) were fractionated using SDS-PAGE, identified with LC-MS/MS and compared to naïve snail ESPs. Protein-protein interaction (PPI) analyses based on published studies (including experiments, co-expression, text-mining and gene fusion) identified S. mansoni and B. glabrata protein interaction. Data are available via ProteomeXchange with identifier PXD015129. Results A total of 291, 410 and 597 ESPs were detected in the susceptible, F1 resistant and naïve SCW, respectively. Less overlap in ESPs was identified between susceptible and naïve snails than F1 resistant and naïve snails. F1 resistant B. glabrata ESPs were predominately associated with anti-pathogen activity and detoxification, such as leukocyte elastase and peroxiredoxin. Susceptible B. glabrata several proteins correlated with immunity and anti-inflammation, such as glutathione S-transferase and zinc metalloproteinase, and S. mansoni sporocyst presence. PPI analyses found that uncharacterised S. mansoni protein Smp_142140.1 potentially interacts with numerous B. glabrata proteins. Conclusions This study identified ESPs released by F1 resistant, susceptible and naïve B. glabrata to explain S. mansoni miracidia interplay. Susceptible B. glabrata ESPs shed light on potential S. mansoni miracidia deterrents. Further targeted research on specific ESPs identified in this study could help inhibit B. glabrata and S. mansoni interactions and stop human schistosomiasis.

Abstract Background Therapeutic vaccines against cervical cancer remain ineffective. Previously, we demonstrated that blocking the signalling of a cytokine, interleukin 10, at the time of immunisation elicited significantly higher numbers of antigen specific T cells and inhibited tumour growth in mice. Results In the current paper, we demonstrate, in a HPV16 E6/E7 transformed TC-1 tumour mouse model, that despite increased antigen specific T cell numbers, blocking IL-10 signalling at the time of immunisation does not increase the survival time of the TC-1 tumour bearing mice compared to mice receiving the same immunisation with no IL-10 signalling blockade. Moreover, the function of tumour infiltrating T cells isolated 3 weeks post TC-1 transplantation is more suppressed than those isolated 2 weeks after tumour inoculation. We demonstrate that synthesized caerin peptides, derived from amphibian skin secretions, 1) were able to inhibit TC-1 tumour growth both in vitro and in vivo; 2) are environmentally stable; and 3) promote the secretion of pro-inflammatory interlukine-6 by TC-1 cells. Notably caerin peptides were able to increase the survival time of TC-1 tumour bearing mice after therapeutic vaccination with a HPV16E7 peptide-based vaccine containing IL-10 inhibitor, via recruiting increased levels of T cells to the tumour site. Conclusion Caerin peptides increase the efficacy of a therapeutic vaccine by recruiting more T cells to the tumour site.

Objective: To explore the correlations between five-pattern personality scores and autonomic nervous response indicators in Chinese female college students, to provide a foundation for further exploration of the modern physiological basis of these personality types. Methods: Subjects were asked to fill in “The Five-Pattern Personality Inventory” (revised edition 2008). Taiyang, Shaoyang, yin-yang balance, Taiyin, and Shaoyin personalities were scored. The galvanic skin response and heart rate, and the low frequency (LF), high frequency (HF), and LF/HF ratio of heart rate variability were collected using a 16-channel physiological recorder (BIOPAC MP150). Relationship between the five-pattern personality scores and autonomic nervous response indicators was analyzed using bivariate correlation. Results: The five-pattern personality scores of the subjects were compared with national averages. The Taiyang and Shaoyang personality scores of the subjects were significantly lower than the overall national average, the national female average, and the national female average in the 18–29-year-old age group (all P

Objective: To investigate the diversity of experiences of sadness emotion and physiological responses among female college students with high neuroticism (HN) and low neuroticism (LN) during the late luteal phase (LLP) and early follicular phase (EFP). Methods: Forty-two participants were classified as the HN group and 41 as the LN group based on their neuroticism score (Eysenck Personality Questionnaire Short Scale for Chinese). Participants watched sadness-inducing experimental films during the LLP and EFP. Results: The HN group showed similar sadness intensities in both phases. The LN group showed higher sadness intensity in the LLP than the EFP. The LN group's sadness scale assessments were lower than the HN group in both phases. The blood volume pulse in the HN group fell in both the LLP and EFP (both P .05). Between-group comparisons showed heart rate was significantly lower in the HN group than the LN group during EFP (P = .009), but there were no statistically significant differences in subjective experience and physiological data during LLP. The HN group had stronger sadness feelings and greater sadness arousal than the LN group during EFP. There were significant associations between menstrual cycle-related changes in sadness ratings and changes in physiological outcomes. Conclusion: Women with HN have less fluctuation in sadness than those with LN during the menstrual cycle, but experience strong sadness feelings in the LLP. Women with HN show stronger physiological responses in the EFP than those with LN, and have the highest responses in the LLP. Keywords: Neuroticism, Menstruation, Sadness, Emotional responses

Elucidating the infectivity of Schistosoma mansoni, one of the main etiological agents of human schistosomiasis, requires an improved understanding of the behavioural mechanisms of cercariae, the non-feeding mammalian infective stage. This study investigated the presence and effect of cercariae-derived putative neuropeptides on cercarial behaviour when applied externally. Cercariae were peptidomically analysed and 11 neuropeptide precursor proteins, all of which were specific to the Schistosoma genus and most of which highly expressed in the cercarial stage, were identified in cercariae for the first time. Protein–protein interaction analysis predicted the interaction of various neuropeptide precursors (e.g., Sm-npp-30, Sm-npp-33, Sm-npp-35) with cercarial structural proteins (e.g., myosin heavy chain and titin). In total, nine putative neuropeptides, selected based on their high hydrophobicity and small size (~1 kilodalton), were tested on cercariae (3 mg/mL) in acute exposure (1 min) and prolonged exposure (360 min) behavioural bioassays. The peptides AAYMDLPW-NH2, NRKIDQSFYSYY-NH2, FLLALPSP-OH, and NYLWDTRL-NH2 stimulated acute increases in cercarial spinning, stopping, and directional change during active states. However, only NRKIDQSFYSYY-NH2 caused the same behavioural changes at a lower concentration (0.1 mg/mL). After prolonged exposure, AAYMDLPW-NH2 and NYLWDTRL-NH2 caused increasing passive behaviour and NRKIDQSFYSYY-NH2 caused increasing body-first and head-pulling movements. These findings characterise behaviour-altering novel putative neuropeptides, which may inform future biocontrol innovations to prevent human schistosomiasis.

Abstract Objectives Developing a vaccine formula that alters the tumor‐infiltrating lymphocytes to be more immune active against a tumor is key to the improvement of clinical responses to immunotherapy. Here, we demonstrate that, in conjunction with E7 antigen‐specific immunotherapy, and IL‐10 and PD‐1 blockade, intratumoral administration of caerin 1.1/1.9 peptides improves TC‐1 tumor microenvironment (TME) to be more immune active than injection of a control peptide. Methods We compared the survival time of vaccinated TC‐1 tumor‐bearing mice with PD‐1 and IL‐10 blockade, in combination with a further injection of caerin 1.1/1.9 or control peptides. The tumor‐infiltrating haematopoietic cells were examined by flow cytometry. Single‐cell transcriptomics and proteomics were used to quantify changes in cellular activity across different cell types within the TME. Results The injection of caerin 1.1/1.9 increased the efficacy of vaccinated TC‐1 tumor‐bearing mice with anti‐PD‐1 treatment and largely expanded the populations of macrophages and NK cells with higher immune activation level, while reducing immunosuppressive macrophages. More activated CD8+ T cells were induced with higher populations of memory and effector‐memory CD8+ T subsets. Computational integration of the proteome with the single‐cell transcriptome supported activation of Stat1‐modulated apoptosis and significant reduction in immune‐suppressive B‐cell function following caerin 1.1 and 1.9 treatment. Conclusions Caerin 1.1/1.9‐containing treatment results in improved antitumor responses. Harnessing the novel candidate genes preferentially enriched in the immune active cell populations may allow further exploration of distinct macrophages, T cells and their functions in TC‐1 tumors.

The Common or Brown Garden Snail, Cornu aspersum, is an invasive land snail that has successfully colonized a diverse range of global environments. Like other invasive land snails, it is a significant pest of a variety of agricultural crops, including citrus, grapes and canola. Cornu aspersum secretes a mucus trail when mobile that facilitates locomotion. The involvement of the trail in conspecific chemical communication has also been postulated. Our study found that anterior tentacle contact with conspecific mucus elicited a significant increase in heart rate from 46.9 to 51 beats per minute. In order to gain a better understanding of the constituents of the trail mucus and the role it may play in snail communication, the protein and volatile components of mucus trails were investigated. Using two different protein extraction methods, mass spectrometry analysis yielded 175 different proteins, 29 of which had no significant similarity to any entries in the non-redundant protein sequence database. Of the mucus proteins, 22 contain features consistent with secreted proteins, including a perlucin-like protein. The eight most abundant volatiles detected using gas chromatography were recorded (including propanoic acid and limonene) and their potential role as putative pheromones are discussed. In summary, this study has provided an avenue for further research pertaining to the role of trail mucus in snail communication and provides a useful repository for land snail trail mucus components. This may be utilized for further research regarding snail attraction and dispersal, which may be applied in the fields of agriculture, ecology and human health.

Summary: Madin-Darby canine kidney II (MDCKII) cells are widely used to study epithelial morphogenesis. To better understand this process, we performed time course RNA-seq analysis of MDCKII 3D cystogenesis, along with polarized 2D cells for comparison. Our study reveals a biphasic change in the transcriptome that occurs after the first cell cycle and coincides with lumen establishment. This change appears to be linked to translocation of β-catenin, supported by analyses with AVL9- and DENND5A-knockdown clones, and regulation by HNF1B, supported by ATAC-seq study. These findings indicate a qualitative change model for transcriptome remodeling during epithelial morphogenesis, leading to cell proliferation decrease and cell polarity establishment. Furthermore, our study reveals that active mitochondria are retained and chromatin accessibility decreases in 3D cysts but not in 2D polarized cells. This indicates that 3D culture is a better model than 2D culture for studying epithelial morphogenesis.

Host defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as human cancerous cell proliferation both in vitro and in vivo. However, the mechanism underlying their anti-proliferative activities against HPV18+ cervical cancer HeLa cells remains unknown. This study comparatively investigated the anti-proliferation on HeLa cells by caerin 1.1, 1.9, and their mixture, followed by confocal microscopy examination to assess the cellular intake of the peptides. Tandem mass tag labeling proteomics was employed to reveal the proteins that were significantly regulated by the peptide treatment in cells and cell growth environment, to elucidate the signaling pathways that were modulated. Western blot was performed to confirm the modulation of the pathways. Both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect compared to untreated and control peptide. They entered the cells with different magnitudes. Intensive protein-protein interaction was detected among significantly upregulated proteins. Translation, folding and localization of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptotic signaling was suggested as a result of tumor necrosis factor-α (TNF-α) pathway activation, indicated by the dose-dependent elevated levels of caspase 3 and caspase 9. The epidermal growth factor receptor and androgen receptor pathways appeared inhibited by the peptides. Moreover, the activation of T-cell receptor derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of HeLa cells. Our results indicate that caerin 1.1 and 1.9 mediate apoptotic signals of HeLa cells and may subsequently enhances adaptive T cell immune responses.

Assassin bugs use their salivary venoms for various purposes, including defense, prey paralyzation, and extra-oral digestion, but the mechanisms underlying the functional complexity of the venom remain largely unclear. Since venom glands are composed of several chambers, it is suggested that individual chambers may be specialized to produce chemically distinct venoms to exert different functions. The current study assesses this hypothesis by performing toxicity assays and transcriptomic and proteomic analysis on components from three major venom gland chambers including the anterior main gland (AMG), the posterior main gland (PMG), and the accessory gland (AG) of the assassin bug Platymeris biguttatus. Proteotranscriptomic analysis reveals that AMG and PMG extracts are rich in hemolytic proteins and serine proteases, respectively, whereas transferrin and apolipophorin are dominant in the AG. Toxicity assays reveal that secretions from different gland chambers have distinct effects on the prey, with that from AG compromising prey mobility, that from PMG causing prey death and liquifying the corpse, and that from AMG showing no significant physiological effects. Our study reveals a functional cooperation among venom gland chambers of assassin bugs and provides new insights into physiological adaptations to venom-based predation and defense in venomous predatory bugs.

Genital warts are one of the most common sexually transmitted diseases worldwide. The disease is a result of infection with low-risk types of human papillomaviruses, mostly type 6 and 11. Current therapies for genital warts are mainly ablative, or alternatively topical application of imiquimod cream and sinecatechin (polyphenon E) ointment to the warts. However, low patient compliance and high recurrence rate are significant problems for the treatment of genital warts by imiquimod and ablative therapies. We summarise recent literature in this area and propose combining imiquimod with other therapies to increase the efficacy of imiquimod.

Objective: Research on the biological mechanisms by which the liver controls dispersion and regulates emotion usually focuses on psychological stress. This study investigated the biological mechanisms underlying the liver's regulation of emotion using the Trier Social Stress Test (TSST). Differences in subjective stress, subjective emotion, and physiological responses were examined between healthy women (Group A) and depressed women with liver qi stagnation syndrome (Group B). Method: Subjects were 72 women who met the inclusion criteria after physical examination. The EPQ-RSC, BAI, and BDI-21 were used to assess personality and emotion. Subjects completed a 5-point scale to measure subjective stress. Heart rate and heart rate variability were measured. To measure changes in activity of the locus coeruleus–norepinephrine (LC-NE)/autonomic nervous system and the HPA axis, saliva samples were collected at the end of the rest and preparation periods, and 5 time pionts after the TSST task. The PAD Emotion Scale was completed at 4 time points before and after the TSST task. Saliva cortisol was tested. These indexes were compared between the two groups. Results: There were 33 subjects in Group A and 39 subjects in Group B. Subjects in Group B had lower levels of stress, pleasure, and dominance, but higher arousal (after the task: P