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Understanding and monitoring life history traits is often important in endangered species conservation. Populations of the endangered mussel Cumberlandian combshell Epioblasma brevidens have continued to decline in the Powell River, USA. Understanding and modeling mussel growth is critical for effective reintroduction of this endangered species. In this study, 2 yr old E. brevidens that were produced in our laboratory were released to the Powell River in 2009 to augment this declining population. A mark-recapture monitoring approach using passive integrated transponder (PIT) tags was used to assess the survival and growth of the released mussels. Hierarchical Bayesian growth models incorporating individual growth variations, periodic growth and growth cessations, along with multiple release occasions were developed and compared to the classic von Bertalanffy growth model. Our results showed that the hierarchical model that incorporated individual growth variation gave the best estimates of model parameters, yielding the lowest deviance information criterion value. Mussels exhibited different growth rates (K), including 0.015, 0.026, 0.110 and 0.050 (moñ1), corresponding to the duration of laboratory culture (ages 2, 3 and 4 yr old) and a growth cessation (GC) for 5.98 mo, respectively. The other parameters of asymptotic length (L∞) and age at zero length (t0) were 51.36 mm and -0.648 mo. The flexible structure of Bayesian hierarchical models allowed us to examine growth characteristics of E. brevidens in a changing environment to better understand the details of its growth and lifespan, thus providing useful data for conservation management.

Jing Zhao,* Jiuxiang He,* Xiaoyan Ding, Yuxin Zhou, Minchi Liu, Xiaozhong Chen, Wenxuan Quan, Dong Hua, Jun Tong, Jintao Li College of Basic Medicine, Army Medical University, Chongqing, 400038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jintao Li, College of Basic Medicine, Army Medical University, Gaotanyan Street, No. 30, Shapingba District, Chongqing, 400038, People’s Republic of China, Tel +1-86-23-68771389, Fax +1-86-23-68771391, Email ljtqms@tmmu.edu.cnBackground: The global prevalence of Dengue virus (DENV) infection poses a significant health risk, urging the need for effective vaccinations. Peptide vaccines, known for their capacity to induce comprehensive immunity against multiple virus serotypes, offer promise due to their stability, safety, and design flexibility. Spherical nucleic acid (SNA), particularly those with gold nanoparticle cores, present an attractive avenue for enhancing peptide vaccine efficacy due to their modularity and immunomodulatory properties.Methods: The spherical nucleic acid-TBB (SNA-TBB), a novel nanovaccine construct, was fabricated through the co-functionalization process of SNA with epitope peptide, targeting all four serotypes of the DENV. This innovative approach aims to enhance immunogenicity and provide broad-spectrum protection against DENV infections. The physicochemical properties of SNA-TBB were characterized using dynamic light scattering, zeta potential measurement, and transmission electron microscopy. In vitro assessments included endocytosis studies, cytotoxicity evaluation, bone marrow-dendritic cells (BMDCs) maturation and activation analysis, cytokine detection, RNA sequencing, and transcript level analysis in BMDCs. In vivo immunization studies in mice involved evaluating IgG antibody titers, serum protection against DENV infection and safety assessment of nanovaccines.Results: SNA-TBB demonstrated successful synthesis, enhanced endocytosis, and favorable physicochemical properties. In vitro assessments revealed no cytotoxicity and promoted BMDCs maturation. Cytokine analyses exhibited heightened IL-12p70, TNF-α, and IL-1β levels. Transcriptomic analysis highlighted genes linked to BMDCs maturation and immune responses. In vivo studies immunization with SNA-TBB resulted in elevated antigen-specific IgG antibody levels and conferred protection against DENV infection in neonatal mice. Evaluation of in vivo safety showed no signs of adverse effects in vital organs.Conclusion: The study demonstrates the successful development of SNA-TBB as a promising nanovaccine platform against DENV infection and highlights the potential of SNA-based peptide vaccines as a strategy for developing safe and effective antiviral immunotherapy.Keywords: nanovaccine, dengue virus, spherical nucleic acid, immunogenicity, peptide antigen

Xuan Wang, Dongyu Hua, Xiaole Tang, Shan Li, Rao Sun, Zheng Xie, Zhiqiang Zhou, Yilin Zhao, Jintao Wang, Shiyong Li, Ailin Luo Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of ChinaCorrespondence: Shiyong Li; Ailin Luo Email shiyongli@hust.edu.cn; alluo@tjh.tjmu.edu.cnAbstract: Postoperative neurocognitive disorder (PND) increases the length of hospital stay, mortality, and risk of long-term cognitive impairment. Perioperative sleep disturbance is prevalent and commonly ignored and may increase the risk of PND. However, the role of perioperative sleep disturbances in PND remains unclear. Nocturnal sleep plays an indispensable role in learning, memory, and maintenance of cerebral microenvironmental homeostasis. Hospitalized sleep disturbances also increase the incidence of postoperative delirium and cognitive dysfunction. This review summarizes the role of perioperative sleep disturbances in PND and elucidates the potential mechanisms underlying sleep-deprivation-mediated PND. Activated neuroinflammation and oxidative stress; impaired function of the blood-brain barrier and glymphatic pathway; decreased hippocampal brain-derived neurotrophic factor, adult neurogenesis, and sirtuin1 expression; and accumulated amyloid-beta proteins are associated with PND in individuals with perioperative sleep disorders. These findings suggest that the improvement of perioperative sleep might reduce the incidence of postoperative delirium and postoperative cognitive dysfunction. Future studies should further investigate the role of perioperative sleep disturbance in PND.Keywords: perioperative sleep disturbance, cognitive impairment, postoperative delirium, postoperative cognitive dysfunction, neuroinflammation

An effective bibliometric analysis based on the Science Citation Index (SCI) published by the Institute of Scientific Information (ISI) was carried out to identify the trend of ecological research between 1992 and 2022. This study put emphases on the high-frequency keywords and their relationships to reveal the hotspots and developing trends of ecological research fields. The results show that the hotpots of ecology has changed a lot during the last 30 years, but some topics occupied an important position in ecological research consistently. Especially, "Biodiversity" and "Climate change" have been obtained more and more attention, so their ranks also have been changed greatly. We also found that the most frequently used keywords are more varied than before and that keywords have become more closely related to each other. Another interesting and amazing result shows that the keywords related to anthropogenic increased sharply. Finally, keywords analysis was an effective approach for mapping ecological research. We guess that anthropogenic keywords may be a potential guide for future research. [ABSTRACT FROM AUTHOR]

Zhen Zhang,1,2 Hanqing Qian,1 Jie Huang,1 Huizi Sha,1 Hang Zhang,1 Lixia Yu,1 Baorui Liu,1 Dong Hua,3 Xiaoping Qian1 1Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Integrated Traditional Chinese Medicine and Western Medicine Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China Background: Red blood cell membrane-coated nanoparticle (RBCm-NP) platform, which consist of natural RBCm and synthetic polymeric core, can extend circulation time in vivo with an improved biocompatibility and stability of this biomimetic nanocarrier. To achieve better bioavailability of antitumor drugs that were loaded in RBCm-NPs, the functionalization of coated RBCm with specific targeting ability is essential. Bispecific recombinant protein anti-EGFR-iRGD, containing both tumor penetrating peptide (internalizing RGD peptide) and EGFR single-domain antibody (sdAb), seems to be an optimal targeting ligand for RBCm-NPs in the treatment of multiple tumors, especially colorectal cancer with high EGFR expression. Materials and methods: We modified the anti-EGFR-iRGD recombinant protein on the surface of RBCm-NPs by lipid insertion method to construct iE–RBCm–PLGA NPs and confirmed the presentation of active tumor-targeting ability in colorectal cancer models with high EGFR expression when compared with RBCm–PLGA NPs. In addition, potential anti- tumor drug gambogic acid (GA) was loaded into the NPs to endow the antitumor efficiency of iE–RBCm–GA/PLGA NPs. It was simultaneously evaluated whether GA can reach better biocompatibility benefiting from the improved antitumor efficiency of iE–RBCm–GA/PLGA NPs in colorectal cancer models. Results: We successfully modified anti-EGFR-iRGD proteins on the surface of biomimetic NPs with integrated and stable “shell–core” structure. iE–RBCm–PLGA NPs showed its improved targeting ability in vitro (multicellular spheroids [MCS]) and in vivo (nude mice bearing tumors). Besides, no matter on short-term cell apoptosis at tumor site (terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) and long-term tumor inhibition, iE–RBCm–GA/PLGA NPs achieved better antitumor efficacy than free GA in spite of the similar effects of cytotoxicity and apoptosis to GA in vitro. Conclusion: We expect that the bispecific biomimetic nanocarrier can extend the clinical application of many other potential antitumor drugs similar to GA and become a novel drug carrier in the colorectal cancer treatment. Keywords: biomimetic nanocarrier, anti-EGFR-iRGD recombinant protein, gambogic acid, targeting ability, antitumor efficiency, colorectal cancer

This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation than healthy controls (HCs), as measured with positron emission tomography using [18F]DPA-714, a second-generation radioligand for the translocator protein (TSPO). Fifteen women with FM and 10 HCs underwent neuroimaging. Distribution volume (VT) was calculated for in 28 regions of interest (ROIs) using Logan graphical analysis and compared between groups using multiple linear regressions. Group (FM vs HC) was the main predictor of interest and TSPO binding status (high- vs mixed-affinity) was added as a covariate. The FM group had higher VT in the right postcentral gyrus (b = 0.477, P = 0.033), right occipital gray matter (GM; b = 0.438, P = 0.039), and the right temporal GM (b = 0.466, P = 0.042). The FM group also had lower VT than HCs in the left isthmus of the cingulate gyrus (b = -0.553, P = 0.014). In the subgroup of high-affinity binders, the FM group had higher VT in the bilateral precuneus, postcentral gyrus, parietal GM, occipital GM, and supramarginal gyrus. Group differences in the right parietal GM were associated with decreased quality of life, higher pain severity and interference, and cognitive problems. In support of our hypothesis, we found increased radioligand binding (VT) in the FM group compared with HCs in several brain regions regardless of participants' TSPO binding status. The ROIs overlapped with prior reports of increased TSPO binding in FM. Overall, increasing evidence supports the hypothesis that FM involves microglia-mediated neuroinflammation in the brain. [ABSTRACT FROM AUTHOR]

Dan Hua,1 Weiling Kong,2 Xuemin Zheng,2 Zhixing Zhou,2 Bing Yu,2 Yazhou Li,2 Yuli Wang,2 Xue Yang,2 Changxiao Liu,2 Lida Tang,2 Ying Li,3 Min Gong21School of Pharmacy, Tianjin Medical University, 2Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, 3Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaAbstract: Self-assembling peptides are capable of forming a complex containing a cavity where cytotoxic agents can be wrapped in a self-assembling manner. These complexes are beneficial for improving the pharmacological properties and pharmacokinetics of cytotoxic agents, such as doxorubicin and paclitaxel. In the present study, this self-assembling feature was successfully integrated into a hexapeptide with matrix metalloproteinase (MMP)-2 specific targeting activity, producing a supramolecule possessing controlled drug release characteristics. The MMP-2 specific substrate fragment, PVGLIG, makes this supramolecule disassociate in the presence of MMP-2, and this system is considered to be a powerful tool for the treatment of tumors with high expression of MMP-2 or tumor metastasis. Our findings show that this modified self-assembling peptide with the PVGLIG fragment was able to significantly enhance specificity against HT1080 cells, a tumor cell line with high expression of MMP-2. In addition, residence time of the complex in blood was prolonged since paclitaxel was wrapped into the supramolecule. Our results suggest that the modified MMP-2 specific substrate, SAMTA7, could act as a controlled and sustained drug carrier for treatment of tumors with high expression of MMP-2 and for tumor metastasis.Keywords: matrix metalloproteinase, self-assembly, drug targeting system, paclitaxel

Rapid and accurate detection of pathogenic microorganism is critical for food safety. Salmonella is one of the common causes of food poisoning. In the present work, polyclonal antibody against the recombinant PagN protein was prepared, and coupled with carboxylated magnetic beads to form immunomagnetic beads (IMBs) for capturing Salmonella, which was then combined with qPCR technology which used the specific primers of invA gene to accurately quantify the number of colonies, thus establishing the IMBs-qPCR method for detection of Salmonella. 0.2 mg IMBs could specifically concentrate Salmonella, with the stable capturing efficiency of 80%, corresponding to the concentrations of 10² - 105 CFU/mL. The minimum detection limit concentration was 101 CFU/mL. The method was applied for detection and enumeration of Salmonella in pork and milk samples, and the capture efficiency of 77.38 and 80.92% were obtained. In summary, the IMBs-qPCR method established herein could effectively detect Salmonella with good specificity and sensitivity. The whole detection time was less than 9 h, which laid a foundation for development of a rapid detection kit for foodborne pathogens. [ABSTRACT FROM AUTHOR]

Significant proteolysis may occur during milk synthesis and secretion, as evidenced by the presence of protease-protease inhibitor complex containing the activated form of the type 2 transmembrane serine protease matriptase and the transmembrane Kunitz-type serine protease inhibitor HAI-1. In order to identify other proteolysis events that may occur during lactation, human milk was analyzed for species containing HAI-1 and HAI-2 which is closely related to HAI-1. In addition to the previously demonstrated matriptase-HAI-1 complex, HAI-1 was also detected in complex with prostasin, a glycosylphosphatidylinositol (GPI)-anchored serine protease. HAI-2 was also detected in complexes, the majority of which appear to be part of higher-order complexes, which do not bind to ionic exchange columns or immunoaffinity columns, suggesting that HAI-2 and its target proteases may be incorporated into special protein structures during lactation. The small proportion HAI-2 species that could be purified contain matriptase or prostasin. Human mammary epithelial cells are the likely cellular sources for these HAI-1 and HAI-2 complexes with matriptase and prostasin given that these protease-inhibitor complexes with the exception of prostasin-HAI-2 complex were detected in milk-derived mammary epithelial cells. The presence of these protease-inhibitor complexes in human milk provides in vivo evidence that the proteolytic activity of matriptase and prostasin are significantly elevated at least during lactation, and possibly contribute to the process of lactation, and that they are under tight control by HAI-1 and HAI-2.

The membrane-associated serine proteases matriptase and prostasin are believed to function in close partnership. Their zymogen activation has been reported to be tightly coupled, either as a matriptase-initiated proteolytic cascade or through a mutually dependent mechanism involving the formation of a reciprocal zymogen activation complex. Here we show that this putative relationship may not apply in the context of human matriptase and prostasin. First, the tightly coupled proteolytic cascade between matriptase and prostasin might not occur when modest matriptase activation is induced by sphingosine 1-phospahte in human mammary epithelial cells. Second, prostasin is not required and/or involved in matriptase autoactivation because matriptase can undergo zymogen activation in cells that do not endogenously express prostasin. Third, matriptase is not required for and/or involved in prostasin activation, since activated prostasin can be detected in cells expressing no endogenous matriptase. Finally, matriptase and prostasin both undergo zymogen activation through an apparently un-coupled mechanism in cells endogenously expressing both proteases, such as in Caco-2 cells. In these human enterocytes, matriptase is detected primarily in the zymogen form and prostasin predominantly as the activated form, either in complexes with protease inhibitors or as the free active form. The negligible levels of prostasin zymogen with high levels of matriptase zymogen suggests that the reciprocal zymogen activation complex is likely not the mechanism for matriptase zymogen activation. Furthermore, high level prostasin activation still occurs in Caco-2 variants with reduced or absent matriptase expression, indicating that matriptase is not required and/or involved in prostasin zymogen activation. Collectively, these data suggest that any functional relationship between natural endogenous human matriptase and prostasin does not occur at the level of zymogen activation.