Miracle-dz/UniFAR-FTUs huggingface dataset:
Metformin Attenuates Inflammatory Responses and Enhances Antibody Production in an Acute Pneumonia Model of Streptococcus pneumoniae

Metformin may potentially reverse various age-related conditions; however, it is unclear whether metformin can also mitigate or delay the deterioration of immunological resilience that occurs in the context of infections that are commonly observed in older persons. We examined whether metformin promotes the preservation of immunological resilience in an acute S. pneumoniae (SPN) infection challenge in young adult mice. Mice were fed metformin (MET-alone) or standard chow (controls-alone) for 10 weeks prior to receiving intratracheal inoculation of SPN. A subset of each diet group received pneumococcal conjugate vaccine at week 6 (MET + PCV and control + PCV). Compared to controls-alone, MET-alone had significantly less infection-associated morbidity and attenuated inflammatory responses during acute SPN infection. Metformin lowered the expression of genes in the lungs related to inflammation as well as shorter lifespan in humans. This was accompanied by significantly lower levels of pro-inflammatory cytokines (e.g., IL6). MET + PCV vs. control + PCV manifested enhanced SPN anticapsular IgM and IgG levels. The levels of SPN IgM production negatively correlated with expression levels of genes linked to intestinal epithelial structure among MET + PCV vs. control + PCV groups. Correspondingly, the gut microbial composition of metformin-fed mice had a significantly higher abundance in the Verrucomicrobia, Akkermansia muciniphila, a species previously associated with beneficial effects on intestinal integrity and longevity. Together, these findings indicate metformin’s immunoprotective potential to protect against infection-associated declines in immunologic resilience.
Machine Learning and Its Applications for Protozoal Pathogens and Protozoal Infectious Diseases

In recent years, massive attention has been attracted to the development and application of machine learning (ML) in the field of infectious diseases, not only serving as a catalyst for academic studies but also as a key means of detecting pathogenic microorganisms, implementing public health surveillance, exploring host-pathogen interactions, discovering drug and vaccine candidates, and so forth. These applications also include the management of infectious diseases caused by protozoal pathogens, such as Plasmodium, Trypanosoma, Toxoplasma, Cryptosporidium, and Giardia, a class of fatal or life-threatening causative agents capable of infecting humans and a wide range of animals. With the reduction of computational cost, availability of effective ML algorithms, popularization of ML tools, and accumulation of high-throughput data, it is possible to implement the integration of ML applications into increasing scientific research related to protozoal infection. Here, we will present a brief overview of important concepts in ML serving as background knowledge, with a focus on basic workflows, popular algorithms (e.g., support vector machine, random forest, and neural networks), feature extraction and selection, and model evaluation metrics. We will then review current ML applications and major advances concerning protozoal pathogens and protozoal infectious diseases through combination with correlative biology expertise and provide forward-looking insights for perspectives and opportunities in future advances in ML techniques in this field.
The Anterior Piriform Cortex and Predator Odor Responses: Modulation by Inhibitory Circuits

Rodents acquire more information from the sense of smell than humans because they have a nearly fourfold greater variety of olfactory receptors. They use olfactory information not only for obtaining food, but also for detecting environmental dangers. Predator-derived odor compounds provoke instinctive fear and stress reactions in animals. Inbred lines of experimental animals react in an innate stereotypical manner to predators even without prior exposure. Predator odors have also been used in models of various neuropsychiatric disorders, including post-traumatic stress disorder following a life-threatening event. Although several brain regions have been reported to be involved in predator odor-induced stress responses, in this mini review, we focus on the functional role of inhibitory neural circuits, especially in the anterior piriform cortex (APC). We also discuss the changes in these neural circuits following innate reactions to odor exposure. Furthermore, based on the three types of modulation of the stress response observed by our group using the synthetic fox odorant 2,5-dihydro-2,4,5-trimethylthiazoline, we describe how the APC interacts with other brain regions to regulate the stress response. Finally, we discuss the potential therapeutic application of odors in the treatment of stress-related disorders. A clearer understanding of the odor–stress response is needed to allow targeted modulation of the monoaminergic system and of the intracerebral inhibitory networks. It would be improved the quality of life of those who have stress-related conditions.
Wireless systems that extend our senses

Wireless signals, such as Wi-Fi, are traditionally used for communications. In this thesis, we show that these signals can also be used as sensing tools that enable us to learn about our environment without physically reaching out to the various objects in it. Specifically, as these signals travel in the medium, they traverse occlusions like walls and bounce off different objects and humans before arriving at a receiver; hence, they carry information about the environment. This thesis presents algorithms and software-hardware systems that extract this information to deliver a variety of new sensing capabilities. We deliver four fundamental contributions: We present the first design that uses Wi-Fi signals to see through walls, enabling us to detect people behind walls by relying purely on the reflections of Wi-Fi signals off their bodies. Next, we demonstrate how we can use radio frequency (RF) reflections to track people’s 3D locations and gestures in indoor environments without requiring them to wear or carry any devices. Beyond localizing people, we introduce the first system that can recover human silhouettes through walls; the captured silhouettes enable us to track the 3D positions of human limbs and body parts and to distinguish between different people behind a wall. Finally, we show how smart environments can monitor their inhabitants breathing and heart rates by relying purely on how the human body modulates reflected RF signals. To deliver these contributions, we exploit physical properties of RF signals, work across software-hardware boundaries, and introduce new systems and new algorithms that require redesigning the entire computing stack, from the hardware to the applications. We implement and evaluate these systems demonstrating how they can enable many new real-world applications including baby monitoring, elderly fall detection, non-invasive vital sign tracking, gesture control, and human identification through walls. Thesis Supervisor: Dina Katabi Title: Professor of Electrical Engineering and Computer Science
Factors Influencing Delayed Treatment in Patients With Breast Cancer During COVID-19 Pandemic

Background The outbreak of coronavirus disease 2019 (COVID-19) has endangered human health and life. This pandemic has changed people's lifestyle and affected the regular delivery of standard cancer treatment. In the present study, we aimed to explore the influencing factors of delayed treatment in patients with breast cancer during COVID-19 pandemic. Methods This study was a cross-sectional investigation, and the subjects were patients who were discharged from the department of burn and plastic surgery after February 2020. All participants completed this study's online questionnaire based on the WeChat and Wenjuanxing platforms. Levels of anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS). Patients were divided into a delay group and non-delay group according to the occurrence of delayed treatment. Univariate analysis was performed by using the t test or chi-square test. A logistic regression model was employed to determine factors associated with delayed treatment. Results The present study included a total of 397 patients with breast cancer, among whom delayed treatment occurred in 76 patients, accounting for 19.1%. Scores on both the anxiety subscale and depression subscale in delay group were significantly higher than those in non-delay group. Compared with non-delay group, we found that patients in delay group usually had a higher level of education (P = 0.020), worse self-feeling (P = 0.030), poor compliance of medical order (P = 0.042), and a higher prevalence of anxiety (P = 0.004) and depression (P = 0.012). Traffic inconvenience was also an important relevant factor for delayed treatment (P = 0.001). The prevalence of recurrence in delay group was higher than that in non-delay group (P = 0.018). By using logistic multivariate regression analysis, the results revealed that level of education and traffic inconvenience were independent factors influencing delayed treatment in patients with breast cancer during COVID-19 pandemic. Conclusion The prevalence of delayed treatment in patients with breast cancer during COVID-19 pandemic is relatively high. Our findings reveal several influencing factors closely associated with delayed treatment, which is useful information that will be beneficial for patients to receive standardized therapy by taking targeted measures.
Age-Dependent Effects of Chronic Stress on Zebrafish Behavior and Regeneration

Stress can have a significant impact on many aspects of an organism’s physiology and behavior. However, the relationship between stress and regeneration, and how this relationship changes with age remains poorly understood. Here, we subjected young and old zebrafish to a chronic stress protocol and evaluated the impact of stress exposure on multiple measures of zebrafish behavior, specifically thigmotaxis (open field test) and scototaxis (light/dark preference test), and on regeneration ability after partial tail amputation. We found evidence that young and older adult fish are differentially impacted by stress. Only young fish showed a significant change in anxiety-like behaviors after being exposed to chronic stress, while their regeneration ability was not affected by the stress protocol. On the other hand, older fish regenerated their caudal fin significantly slower compared to young fish, but their behavior remained unaffected after being exposed to stress. We further investigated the expression of two candidate genes (nlgn1 and sam2) expressed in the central nervous system, and known to be associated with stress and anxiety-like behavior. The expression of stress-related gene candidate sam2 increased in the brain of older individuals exposed to stress. Our results suggest there is a close relationship between chronic stress, regeneration, and behavior in zebrafish (Danio rerio), and that the impact of stress is age-dependent.
Recent Differentiation of Aquatic Bacterial Communities in a Hydrological System in the Cuatro Ciénegas Basin, After a Natural Perturbation

Pozas Rojas is a hydrological system comprising nine isolated shallow ponds and a deep lagoon, which were temporally merged in 2010 by increased rainfall due to a tropical cyclone. In this work, we assess which components, biotic interactions, or environment filtering effects, drive the assembly of microbial communities after a natural perturbation. Arsenic, pH, and temperature are among the most significant environmental variables between each pond, clustering the samples in two main groups, whereas microbial composition is diverse and unique to each site, with no core at the operational taxonomic unit level and only 150 core genera when studied at the genus level. Los Hundidos lagoon has the most differentiated community, which is highly similar to the epipelagic Mediterranean Sea communities. On the other hand, the shallow ponds at the Pozas Rojas system resemble more to epicontinental hydrological systems, such as some cold rivers of the world and the phreatic mantle from Iowa. Overall, despite being a sole of water body 2 years prior to the sampling, interspecific interactions, rather than environmental selection, seem to play a more important role in Pozas Rojas, bolstered by founder effects on each poza and subsequent isolation of each water body.
Clinical and Cardiovascular Magnetic Resonance Predictors of Early and Long-Term Clinical Outcome in Acute Myocarditis

Introduction The natural history of acute myocarditis (AM) remains partially unknown and predictors of outcome are debated. We sought to assess the impact of various cardiac magnetic resonance (CMR) parameters on early and long-term prognosis in a population of patients with AM. Materials and Methods In a two-center longitudinal study, we included consecutive patients with diagnosis of AM based on CMR and without hemodynamic compromise. The primary endpoint was the occurrence of an event in the acute phase (≤15 days). Secondary endpoints were the occurrence of major adverse cardiac events (MACE) and recurrence of AM during follow-up. Results Three hundred and eighty-eight patients were included [mean age 38.5 years, 77.3% male, mean ejection fraction (EF):56%] of which 82% (317) presented with chest pain. CMR was performed 4 ± 2 days after index presentation. Overall, 38 patients (9.8%) had an event at the acute phase, 41 (10.6%) presented at least one MACE during follow-up (median 7.5 years, 6.6–8.9) and 30 (7.7%) experienced a recurrence of AM. By multivariate analysis, the independent predictors of initial complications were absence of chest pain (OR [95%CI] = 0.35 [0.15–0.82]), presence of syncope/pre-syncope (OR [95%CI] = 3.56 [1.26–10.02]), lower EF (OR [95%CI] = 0.94 [0.91–0.98] per%), myocardial extent of late gadolinium enhancement (LGE) (OR [95%CI] = 1.05 [1.002–1.100] per%) and absence of edema (OR [95%CI] = 0.44 [0.19–0.97]). Only age (HR [95%CI] = 1.021 [1.001–1.041] per year) and an initial alteration of EF (HR [95%CI] = 0.94 [0.91–0.97] per%) were associated with MACE during follow-up. Factors independently associated with AM recurrence were myocarditis prior to the index episodes (HR [95%CI] = 5.74 [1.72–19.22]) and viral syndrome at the index episode (HR [95%CI] = 4.21 [1.91–9.28]). Conclusion In routine consecutive hemodynamically stable patients with diagnosis of AM based on CMR, absence of edema, reduced EF, and extent of LGE were associated with early adverse outcome. Only age and EF were associated with long-term events.
Virological and Clinical Determinants of the Magnitude of Humoral Responses to SARS-CoV-2 in Mild-Symptomatic Individuals

Background Evidence on the determinants of the magnitude of humoral responses and neutralizing titers in individuals with mild COVID-19 is scarce. Methods In this cohort study of mild COVID-19 patients, we assessed viral load (VL) by RT-qPCR at two/three time points during acute infection, and anti-SARS-CoV-2 antibodies by ELISA and plasma neutralizing responses using a pseudovirus assay at day 60. Results Seventy-one individuals (65% female, median 42 years old) were recruited and grouped into high viral load (VL) >7.5 Log10 copies/mL (n=20), low, VL ≤7.5 Log10 copies/mL (n=22), or as Non-early seroconverters with a positive PCR (n=20), and healthy individuals with a negative PCR (n=9). Individuals with high or low VL showed similar titers of total neutralizing antibodies at day 60, irrespective of maximal VL or viral dynamics. Non-early seroconverters had lower antibody titers on day 60, albeit similar neutralizing activity as the groups with high or low VL. Longer symptom duration and older age were independently associated with increased humoral responses. Conclusions In mild SARS-CoV-2-infected individuals, the duration of symptoms and age (but not VL) contribute to higher humoral responses.
Gold Nanoclusters Potentially Facilitate Dentin Regeneration by Functioning Immunomodulation

It is presently difficult to achieve dental pulp vitality maintenance and regeneration in adult teeth. Dentin destruction results in the exposure of the dental pulp tissue to infectious oral environments, thereby triggering continuous severe pulp inflammation that impedes the self-regenerative capacity of the pulp. For these reasons, the regeneration of dentin bridges to block pulp tissue from the oral environment is an indispensable step. Nevertheless, this goal is difficult to achieve using present strategies, because the importance of immunoregulation in the pulp inflammatory microenvironment has been ignored. In our previous study, we found that the nanomaterial dihydrolipoic acid-functionalized gold nanoclusters (DHLA-AuNCs) efficiently regulated inflammatory responses in microglia (resident macrophages in the central nervous system), suggesting that DHLA-AuNCs may induce dentin bridge regeneration by regulating dental pulp macrophage responses. In the present study, we found that DHLA-AuNCs inhibited the M1 phenotype while promoting the M2 phenotype in macrophages in inflammatory conditions in vitro. This regulation of the inflammatory environment in dental pulp enhanced the differentiation of human dental pulp stromal cells (hDPC) toward odontoblasts, a beneficial effect on dentin regeneration. DHLA-AuNCs also had a direct role in the differentiation and mineralization of hDPC. These findings suggest that DHLA-AuNCs facilitate dentin regeneration through both efficient immunomodulation and direct induction of stromal cell differentiation/mineralization, providing a potential therapeutic nanomaterial for dentin bridge regeneration, effects that would be beneficial for dental pulp regeneration.
Integrated Proteomic and Metabolomic Analyses of Chicken Ovary Revealed the Crucial Role of Lipoprotein Lipase on Lipid Metabolism and Steroidogenesis During Sexual Maturity

During sexual maturation and ovulatory cycle in chickens, ovaries undergo dynamic morphological and functional changes. The aim of this study was to evaluate the integrated proteome and metabolome analyses of chicken ovaries to characterize the changes in protein and metabolite profiles during sexual maturity. The ovary of Rohman layers before (125 days of age) and after (139 days of age) sexual maturation were collected for proteome and metabolome sequencing. The results showed that a total of 680 differentially expressed proteins (DEPs) and 1,046 differential metabolites (DMs) were identified in the chicken ovary during sexual maturity. Among the DEPs, 595 proteins were up-regulated and 85 were down-regulated, whereas 519 metabolites were up-regulated and 527 were down-regulated. KEGG pathway enrichment analysis showed that DEPs were significantly enriched in glycerolipid metabolism, calcium signaling pathway, folate biosynthesis, fat digestion and absorption, NF-kB signaling pathway, and PPAR signaling pathway. However, DMs were significantly enriched in the metabolism pathways, PPAR signalling pathway, glycerolipid metabolism, ferroptosis, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids. The results of the integrated analyses of DEPs and DMs revealed that the PPAR signaling pathway and glycerolipid metabolism were the most significantly enriched pathways. Among the identified DEPs, lipoprotein lipase (LPL) was upregulated in sexually mature chicken ovaries and was significantly enriched in the glycerolipid metabolism pathway, which may partially explain the possible reasons for steroidogenesis and lipid reserves responsible for oocyte maturation and ovarian follicle development during sexual maturity in chickens. The results further revealed that LPL silencing decreased the content of lipid droplets (LDs), as well as the mRNA expression of lipid metabolism-related genes including; sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FASN); and steroidogenesis-related genes such as; cytochrome P450 11A1 (CYP11A1) and steroidogenic acute regulatory (StAR). The present study revealed that upregulation of LPL in the chicken ovary during sexual maturity promotes granulosa cell (GC) lipid metabolism and steroidogenesis. These findings provide a theoretical support for further studies to elucidate the mechanism of lipid metabolism to regulate the function of avian GCs during sexual maturity in chickens.
PreS/2-21-Guided siRNA Nanoparticles Target to Inhibit Hepatitis B Virus Infection and Replication

A viable therapy is needed to overcome the deadlock of the incurable chronic hepatitis B (CHB). The prolonged existence of covalently closed circular DNA (cccDNA) and integrated HBV DNA in the nucleus of hepatocytes is the root cause of CHB. As a result, it is critical to successfully suppress HBV DNA replication and eliminate cccDNA. RNA interference has been proven in recent research to silence the expression of target genes and thereby decrease HBV replication. However, siRNA is susceptible to be degraded by RNA enzymes in vivo, making it difficult to deliver successfully and lacking of tissue targeting. To exploit the advantages of siRNA technology while also overcoming its limitations, we designed a new strategy and prepared biomimetic nanoparticles that were directed by PreS/2-21 peptides and precisely loaded HBV siRNA. Experiments on these nanoparticles in vitro and in vivo revealed that they are tiny, stable, safe and highly targetable, with high inhibitory effects on HBV DNA, pgRNA, cccDNA, HBeAg and HBsAg. PreS/2-21-directed nanoparticles loaded with HBV gene therapy drugs are expected to be promising for the treatment of CHB.
COMMD2 Upregulation Mediated by an ncRNA Axis Correlates With an Unfavorable Prognosis and Tumor Immune Infiltration in Liver Hepatocellular Carcinoma

Liver hepatocellular carcinoma (LIHC) seriously endangers the health and quality of life of individuals worldwide. Increasing evidence has underscored that the copper metabolism MURR1 domain (COMMD) family plays important roles in tumorigenesis. However, the specific role, biological function, mechanism and prognostic value of COMMD2 and its correlation with immune cell infiltration in LIHC remain unknown. In this study, we first determined the expression and prognostic potential of COMMD2 in human tumors using The Cancer Genome Atlas (TCGA) data and identified COMMD2 as a potential oncogene in LIHC. High COMMD2 expression was associated with pathological tumor stage and metastasis. Subsequently, noncoding RNAs (ncRNAs) upregulating COMMD2 expression were identified by performing expression, correlation, and survival analyses in combination. The CRNDE/LINC00511/SNHG17/HCG18-miR-29c-3p axis was identified as the most likely ncRNA-associated pathway upstream of COMMD2 in LIHC. Next, the expression profiles of COMMD2 and ncRNAs were validated in LIHC tissues and adjacent normal tissues. Furthermore, COMMD2 was significantly positively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint molecule expression. Importantly, COMMD2 potentially influenced prognosis by regulating immune cell infiltration in LIHC. Finally, COMMD2 was knocked down in LIHC cell lines using siRNAs for functional assays in vitro, resulting in suppressed cell proliferation and migration. In summary, our findings showed that the ncRNA-mediated upregulation of COMMD2 was associated with an unfavorable prognosis correlated with immune cell infiltration in LIHC.