The ability of an individual's immune system to mount a productive response against the tumor is critical for the success of immunotherapy. Clinical trials in multiple tumor types have revealed that the degree and way in which any one person's immune system mobilizes to eliminate tumor cells can vary widely, contributing to immunotherapeutic efficacy. Efforts to uncover biological factors contributing to response rates is a crucial area of ongoing research given the pressing clinical need to better stratify patients based on likelihood of response to a given therapy. While sex differences have long been observed in the field of immunobiology, the consideration of sex as a biological variable in the immunotherapeutic treatment of cancer patients has yet to be addressed or incorporated into patient care. Over the past decade, in part due to the National Institute of Health (NIH)‑mandated changes in how sex is handled as a biological variable, research has shifted markedly in how clinical and preclinical data are reported and interpreted. These changes have brought renewed attention to the ways sex shapes anti‑tumor immunity and responses to immunotherapy. In this review, we examine the expanding body of research demonstrating that male and female immune responses differ in their effectiveness against tumors and explore the implications of these differences for responses to immunotherapy.
The Type I-E CRISPR/Cas system in Salmonella enterica is increasingly hypothesized to function as a condition-dependent regulatory interface rather than exclusively as an adaptive immune module. Rooted in its evolutionary origins within mobile genetic elements such as casposons, this system reflects a functional transition toward influencing bacterial pathogenesis. A central hypothesis suggests that CRISPR components-specifically Cascade, Cas3, and Cas6-are integrated into core regulatory networks governing pathogenicity islands, biofilm formation, and oxidative stress adaptation. This regulatory control likely operates through a programmed deviation from the traditional immunity paradigm, where suboptimal PAM recognition or partial sequence complementarity allows Cascade to bind DNA without licensing Cas3 for lethal cleavage. Consequently, the machinery may facilitate transcriptional modulation through steric hindrance, acting as a natural CRISPR interference mechanism. Coordinated by global regulators like H-NS and LeuO in response to environmental cues such as pH fluctuations, this system effectively functions as a molecular rheostat. Collectively, these hypotheses offer a conceptual framework for novel translational strategies, including anti-CRISPR-based therapeutics and engineered evolutionary trap concepts.
A recent study in Nature identified the rice (Oryza sativa) nucleotide-binding site and leucine-rich repeat (NLR) receptor XA48, which recognized the ancient bacterial effector XopG and triggered immunity by promoting degradation of the negative regulators OsVOZ1/2. Population genomics revealed an asymmetric selection, with Xa48 retained in indica but lost in japonica due to a reproductive penalty. By stacking XA48-mediated effector-triggered immunity (ETI) with XA21-mediated pattern-triggered immunity (PTI) and introducing the compatible OsVOZ1S allele, broad-spectrum bacterial blight resistance from wild rice was reconstituted. This work provides a design strategy that helps break the growth-defence trade-off.
NK cells are classically defined by their rapid cytotoxicity against tumor cells and infected cells and by early inflammatory cytokine production. However, unconventional roles for NK cells as regulators of immunity and tissue homeostasis have recently been uncovered. Beyond their classical roles, NK cells can orchestrate leukocyte trafficking, curtail responses of other immune cells, remove protein aggregates, support pregnancy, and contribute to healthy tissue regeneration. We discuss the importance of these myriad functional activities of NK cells in infection, cancer, autoimmunity, atopic and allergic disease, pregnancy, tissue injury, and neurodegenerative diseases. The functional pleiotropy of NK cells provides new avenues of translational utility for these innate lymphocytes and represents an unexplored complexity in conventional clinical applications of NK cells against infection and cancer.
Vaccination is the most effective way to prevent infectious diseases and safeguard public health. Yet, most new vaccines fail in late clinical trials, and even established ones often underperform in populations apart from those in which they were initially tested. This can lead to reduced vaccine responsiveness, breakthrough infections, and prevent or delay herd immunity. While the causes of vaccine hyporesponsiveness remain difficult to identify, quantify, and therefore address, numerous reports indicate a predominant role of environmental factors. This has notably been demonstrated by a reduction in the immunogenicity and efficacy of various vaccines when transitioning from urban to rural human populations. Here, we tested whether and, if so, how the environment can cause vaccine hyporesponsiveness. We hypothesised that if the leading causes of vaccine hyporesponsiveness were environmental, then environmentally driven hyporesponsiveness would be exacerbated when individuals are under nutritional stress; specifically predicting that high-quality diet supplementation would increase vaccine responsiveness. Finally, we predicted that parasitic helminth infections, which are more common in rural populations, would degrade vaccine responsiveness, e.g., due to their ability to modulate host immunity, and that anthelmintic treatment could rescue vaccine responsiveness in infected individuals. To test these hypotheses, we coupled lab and field experiments with structural causal modelling, and quantified diphtheria toxoid-specific IgG1 optical density (OD) in paired conspecific cohorts of laboratory-reared and wild wood mice (Apodemus sylvaticus) given a single or two doses of diphtheria toxoid vaccine formulated with alum, with and without diet supplementation. We found that anti-toxoid IgG1 OD was ∼ 47 % lower in thewildwoodmice compared to the laboratory-reared population. We also demonstrated that, across both habitats (wild and lab), substantial variation in vaccine responsiveness was caused by diet. However, contrary to our predictions, this high-quality dietary supplementation resulted in lower vaccine responsiveness. Further, once the effects of habitat, diet, and sex were adjusted for, increasing helminth infection burdens negatively affected anti-toxoid IgG1 OD. Counterfactual predictions from our structural causal model suggested that targeting anthelmintic treatment at heavily infected individuals could have improved their anti-toxoid IgG1 OD responses by approximately 2 to 4-fold. Our results indicated that the wild environment and access to a high-quality diet played a dramatic role in shaping the immune system's response to immunisation. Further, we showed that laboratory settings, even when using a genetically diverse, non-traditional model, systematically yielded higher IgG1 OD than was observed in free-living conspecifics on the same protocol. We provide a causally explicit modelling approach to quantify how habitat, diet, and parasites jointly shape anti-diphtheria toxoid IgG1 levels in a focal population, and to prioritise adjunct interventions such as deworming where model assumptions hold.
Angiogenesis serves as a central hallmark of breast cancer progression by driving the formation of a dysfunctional vascular network that sustains tumor growth, enables metabolic adaptation, and facilitates metastasis. Hypoxia within the tumor microenvironment (TME) stabilizes hypoxia-inducible factor-1α (HIF-1α), that transcriptionally activates key pro-angiogenic mediators, including vascular endothelial growth factor (VEGF) and angiopoietins (ANGPT). Concurrently, stromal and immune constituents of the TME, particularly cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), potently augment angiogenesis through the secretion of cytokines, growth factors, and extracellular matrix-remodeling enzymes. These mediators promote endothelial cell activation, increase vascular permeability, and facilitate immune suppression. The VEGF/VEGFR signaling axis serves as a master regulator, orchestrating endothelial cell proliferation, migration, survival, and neovascularization. Although anti-angiogenic agents such as the VEGF-neutralizing monoclonal antibody bevacizumab have demonstrated clinical efficacy, responses are frequently transient owing to intrinsic and acquired resistance, intratumoral vascular heterogeneity, and compensatory activation of alternative angiogenic pathways. Consequently, contemporary therapeutic approaches prioritize rational combination regimens integrating anti-angiogenic agents with chemotherapy, immunotherapy, or radiotherapy to induce vascular normalization, enhance drug penetration, and potentiate antitumor immunity. Targeting the TME, including stromal and immune components, together with bioactive phytochemicals, possessing anti-angiogenic and immunomodulatory properties, has emerged as a promising strategy. This review integrates current knowledge on tumor-endothelial crosstalk, hypoxia- and inflammation-driven angiogenic signatures such as VEGF, miR-20a, and ANGPTL4, while evaluating emerging modalities, including microRNA-based interventions, nanoparticle delivery, and TME reprogramming to overcome resistance and enhance the precision and durability of anti-angiogenic therapies in breast cancer.
Endometritis is a prevalent uterine inflammatory disease that significantly compromises fertility; however, the host-microbial mechanisms governing disease susceptibility remain poorly defined. Although the gut microbiota is increasingly recognized as a central regulator of systemic and extraintestinal immunity, its role in uterine inflammation has received little attention. Here, we investigated whether gut microbiota dysbiosis modulates susceptibility to endometritis and sought to identify the microbial mediators underlying this relationship. Antibiotic-induced dysbiosis markedly exacerbated uterine inflammation and tissue injury in mice, whereas fecal microbiota transplantation (FMT) re-established microbial homeostasis and substantially ameliorated uterine pathology. 16S rRNA sequencing identified Bifidobacterium pseudolongum as a commensal species depleted during dysbiosis and restored following FMT. Monocolonization with B. pseudolongum conferred protection against dysbiosis-associated uterine inflammation, evidenced by diminished IL-1β, TNF-αand IL-10 production, reduced HMGB1 and HABP2 levels, restored epithelial tight junction protein expression-including ZO-1, Claudin-3, and Occludin, and attenuated neutrophil and macrophage infiltration. Beyond the dysbiosis model, B. pseudolongum demonstrated both prophylactic and therapeutic efficacy in murine models of Escherichia coli- and LPS-induced endometritis, suppressing inflammatory responses, limiting tissue damage, preserving epithelial barrier integrity, and reducing immune cell infiltration. In vitro assays showed that culture supernatants of B. pseudolongum inhibited E. coli growth under cell-free conditions, indicating a potential antimicrobial activity in vitro. Taken together, these findings support a gut-uterus immunological axis in which B. pseudolongum attenuates infection-driven uterine inflammation through the coordinated modulation of immune responses, epithelial barrier maintenance, and antimicrobial defense. Our study positions B. pseudolongum as a compelling microbiota-based candidate for the prevention and treatment of endometritis.
Human sapovirus (HuSaV) has long occupied a peripheral position in etiological research on acute gastroenteritis. However, in the context of widespread rotavirus vaccination, the pathogen spectrum of childhood diarrhoea has been reshaped; molecular diagnostics have continued to evolve; and evidence from birth cohorts and environmental surveillance has accumulated. Together, these developments have prompted a systematic reassessment of the public health significance of HuSaV in childhood diarrhoea, outbreaks in childcare facilities and schools, asymptomatic infection, and persistent infection in immunocompromised hosts. Here, we review key advances in HuSaV research across disease burden and epidemiological patterns, genome organization and evolution, natural history and immune responses, experimental models and host interactions, complex clinical phenotypes, and surveillance-to-public-health translation. We further propose priority directions for the next 5 years, including the establishment of standardized antigen panels and reference strain repositories, integration of serological and genotyping data within longitudinal cohorts, elucidation of viral receptor recognition, cell entry and immune-evasion mechanisms, and the development of closed-loop linkages between experimental-model research and population-level surveillance systems. Overall, HuSaV has evolved from a historically underestimated pathogen associated with acute gastroenteritis in infants and young children into a key enteric viral pathogen that requires dedicated surveillance, mechanistic investigation and translational intervention strategies in the post-rotavirus vaccine era. The research paradigm is likewise shifting from descriptive epidemiology towards an integrated framework that combines disease burden, host immunity, experimental systems and transmission surveillance.
Loss of major histocompatibility complex (MHC)-I is a hallmark of prostate cancer (PCa) immune evasion and immunotherapy failure. Here, we identify ZNF263 as a transcriptional repressor that silences MHC-I by recruiting nucleosome-remodeling and deacetylase (NuRD) to the STAT1 promoter, reducing STAT1 and MHC-I expression. Hypoxia enhances this repression through two ZNF263 modifications: phosphorylation-driven phase separation that strengthens NuRD interaction and O-GlcNAcylation at S662 that aids STAT1 promoter binding. O-GlcNAcylation also promotes interaction with protein kinase, DNA‑activated catalytic subunit (PRKDC), amplifying phosphorylation. Interferon‑gamma (IFN‑γ)‑induced MHC-I induction is augmented upon ZNF263 loss. In silico docking identified Viroptic as a Krüppel‑associated box (KRAB) pocket binder disrupting ZNF263-NuRD, derepressing STAT1, and potentiating IFN-γ antitumor immunity in vivo. High ZNF263 correlates with low MHC-I, scarce CD8+ T cells, and poor survival, providing rationale for targeting ZNF263 in PCa immunotherapy.
Evidence from multiple studies shows that the appendix may play a significant role in the pathogenesis of ulcerative colitis (UC). These findings have sparked interest in the possibility of appendicectomy as a potential adjunctive strategy in UC. This narrative review was conducted by synthesizing data from meta-analyses, immunological research, surgical case studies, population data reports, and prospective trials published since 2000. The evidence was appraised with a focus on appendicectomy and its clinical outcomes in UC, risks and limitations, as well as possible future directions. Observational studies show a reduced risk of colectomy and UC-related hospital admissions when appendicectomy is performed before UC diagnosis. On the other hand, appendicectomy post UC diagnosis in the presence of appendiceal inflammation has shown increased risk of colectomy. But if an appendicectomy is performed in the absence of inflammation, it might not correlate to the risk or reduce the risk of relapse and complications. Evidence also shows that patients with refractory UC may benefit from appendicectomy and may show longer periods of remission. However, some studies show appendicectomy might increase the colorectal cancer risk due to alterations in immunity and microbiota. While medical management remains the first line, appendicectomy may act as an adjunct surgical option in carefully selected cases before escalating to a colectomy. Large multicenter studies and randomized clinical trials are required to identify strategies for patient selection, potential complications, durability of response, and long-term outcomes. The appendix plays a major role in the pathogenesis of ulcerative colitis. Studies show appendicectomy could benefit selected patients with this disease and may be considered as an adjunct treatment to delay or avoid colectomy.
HEDIS Childhood Immunization Status (CIS) Combination 10 is a pediatric quality measure within a widely used health care performance framework; HEDIS is used by more than 90% of U.S. health plans, covering more than 190 million people in plans that report HEDIS quality results. Because HEDIS immunization measures support population-level monitoring and quality improvement, they are directly relevant to public health practice. However, aggregate reporting limits public health use by obscuring component-level drivers of noncompletion. To apply explainable machine learning as a public health informatics approach to identify vaccine components associated with CIS Combo 10 completion among U.S. children aged 24-35 months. We analyzed 2021-2023 National Immunization Survey-Child public-use files. The age-eligible cohort included 32,997 children; weighted modeling included 16,021 children. Survey-weighted logistic regression estimated national trends with 95% CIs, and Random Forest modeling with SHAP and cross-validation identified component-level predictors. CIS Combo 10 completion declined from 53.7% in 2021 to 44.6% in 2023; the survey-weighted regression model was statistically significant (annual OR 0.83, 95% CI 0.831-0.834; P<.001). Influenza and rotavirus had the largest mean absolute SHAP values. CIS Combo 10 completion declined substantially from 2021 to 2023. An explainable public health informatics approach identified influenza and rotavirus as actionable targets for immunization quality improvement.
Colorectal cancer (CRC) remains a global malignancy with high morbidity and mortality. Long-term uncontrolled intestinal inflammation drives CRC initiation and development. As a vital essential fatty acid and prostaglandin precursor, arachidonic acid (AA) participates in inflammatory and immune regulation, and its metabolic disorder is tightly linked to multiple inflammatory diseases and CRC. This study clarified the progress of research on AA metabolism and CRC through bibliometric analysis, and analyzed the clinical application prospects of COX inhibitors in CRC by integrating clinical trial data. For bibliometric analysis, data were retrieved from WOSCC (1990-2025) using specific search terms, preprocessed, and analyzed via R Studio and LDA topic model to clarify publication trends and research hotspots. Meanwhile, relevant clinical trials of COX inhibitors for CRC and its precancerous lesions were collected from the Trialtrove database for multidimensional analysis. This bibliometric analysis highlights the significant growth in research on AA metabolism in colorectal cancer, identifying key authors, countries, and research hotspots. The field has transitioned from a focus on COX-2 and PGE2 to a more integrated understanding that includes gut microbiota and immune modulation. For clinical trial analysis, among the 61 included trials, aspirin and celecoxib monotherapies were dominant, and combination regimens have drawn rising attention. Regarding trial status, less than one-third of trials were completed, while plenty remained active or terminated early. By synthesizing the results of bibliometric and clinical trial landscape studies, we summarized drugs targeting the AA pathway that inhibit inflammatory cancer transformation.
Adiponectin is a pleiotropic adipocytokine with anti-inflammatory, antioxidant, and insulin-sensitizing functions. Its regulatory role in glucose and lipid metabolism, endothelial homeostasis, and immune responses positions it as a key determinant of immunometabolic resilience. Dysregulated adiponectin signaling has been increasingly implicated in adverse COVID-19 outcomes, particularly among individuals with metabolic comorbidities. To synthesize mechanistic, preclinical, and translational evidence on adiponectin signaling in COVID-19 and evaluate its potential as a therapeutic and lifestyle-modulated target. A critical review of published literature on adiponectin biology, AdipoR1/R2 receptor signaling, AMPK and PPAR-α pathways, cytokine regulation, oxidative stress, and infection-induced metabolic reprogramming was conducted. COVID-19 is consistently associated with reduced circulating adiponectin, with the greatest declines observed in obesity, diabetes, and metabolic syndrome. Mechanistic and animal studies show that adiponectin activation attenuates hyperinflammation, oxidative stress, endothelial dysfunction, and multi-organ injury. These effects are mediated through AMPK activation, PPAR-α modulation, NF-κB suppression, and restoration of metabolic-immune balance. Adiponectin signaling represents a promising therapeutic target for mitigating COVID-19 severity, especially in metabolically vulnerable populations. Pharmacological agonists and lifestyle interventions that enhance adiponectin pathways warrant further translational investigation.
Heat stress is a critical environmental factor disrupting systemic homeostasis and impairing mental health, with increasing evidence linking prolonged thermal exposure to depression and related neuropsychological disorders. Chronic heat stress induces neuroendocrine dysregulation via hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, alongside oxidative stress, neuroinflammation, mitochondrial dysfunction, and altered neurotransmitter signaling, collectively elevating risks of mood disturbances, anxiety, cognitive decline, and sleep disorders. Emerging evidence highlights nutrition as a key modulator of heat stress-induced neuropathology. Adequate macronutrient intake supports energy balance and thermoregulation, while micronutrients such as B vitamins, vitamin D, magnesium, zinc, selenium, and iron are essential for neurotransmission, antioxidant defense, and immune function. Additionally, phytochemicals including polyphenols, flavonoids, and carotenoids exert neuroprotective, anti-inflammatory, and HPA-regulatory effects, partly through modulation of the gut-brain axis. This integrative approach offers promising non-pharmacological strategies to enhance resilience against heat-induced depression.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by autoantibody production and multi-organ involvement due to dysregulated immune responses. Ongoing research aims to understand the underlying mechanisms of this immune dysregulation, with particular interest in immune checkpoint molecules such as VISTA (encoded by the VSIR gene), which exerts context-dependent immunomodulatory effects. We analyzed a large-scale single-cell RNA-seq (scRNA-seq) dataset (GSE174188) comprising 261 samples (162 SLE cases, 99 controls) to investigate VSIR expression patterns across peripheral blood mononuclear cell (PBMC) subsets in SLE versus controls, using bioinformatics tools. Additionally, fresh PBMCs were isolated from SLE patients and healthy controls, and VSIR mRNA levels were quantified by RT-qPCR in treatment-naïve cases and those receiving Prednisolone, Hydroxychloroquine, or supplementary medications. Associations between VSIR expression and clinical/demographic parameters, including disease activity index, were also evaluated. scRNA-seq analysis revealed significantly upregulated VSIR expression in monocytes from SLE patients compared to healthy controls. In contrast, pseudobulk differential expression analysis of the entire PBMC population, corroborated by RT-qPCR on fresh samples, demonstrated downregulation of VSIR in SLE cases overall (log₂ fold change = -1.23). Notably, VSIR expression differed across treatment groups, with the lowest levels observed in treatment-naïve patients and higher levels in those receiving first-line therapies (prednisolone and hydroxychloroquine). Furthermore, VSIR expression exhibited a significant negative correlation with SLE disease activity index. This study demonstrates decreased VSIR expression in the whole PBMC population in SLE patients, suggesting a potential role in disease pathogenesis processes possibly through altered immune checkpoint regulation. Moreover, VSIR expression was associated with treatment status, with higher expression observed in patients receiving standard first-line therapies.
The present document aims to present a reflection derived from a narrative review on the evolution of complementary feeding (CF) recommendations worldwide and their application in Mexico. Based on the analysis of international guidelines and consensus statements, such as those published by European Society for Pediatric Gastroenterology, Hepatology and Nutrition, Latin American Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the World Health Organization, members of the Mexican Academy of Pediatrics review the main points of convergence and controversy related to the initiation, progression, and characteristics of CF during the first two years of life. The document highlights that this period is critical for growth, neurological development, immune maturation, and the establishment of healthy eating habits in the long term. Likewise, it emphasizes the relevance of the first 1000 days of life and the need to promote breastfeeding, dietary diversity, and the timely introduction of foods rich in essential nutrients. The review also addresses current topics such as the early introduction of allergenic foods, the role of different food textures, the prevention of obesity and allergies, as well as the importance of avoiding sugar-sweetened beverages, ultra-processed foods, and restrictive diets without specialized supervision. From the Mexican perspective, it is recognized that international recommendations must be contextualized according to the epidemiological, cultural, and social realities of the country. Finally, the Academia Mexicana de Pediatría proposes practical recommendations directed at healthcare professionals to promote responsive, safe, and evidence-based CF that contributes to the overall well-being of Mexican infants. El presente documento tiene como objetivo manifestar algunas reflexiones derivadas de una revisión narrativa sobre la evolución de las recomendaciones de la alimentación complementaria (AC) en el mundo y su práctica en México. A partir del análisis de consensos y guías internacionales, como las publicadas por la Sociedad Europea de Gastroenterología, Hepatología y Nutrición Pediátrica, la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica y la Organización Mundial de la Salud, miembros de la Academia Mexicana de Pediatría revisan los principales puntos de convergencia y controversia relacionados con el inicio, progresión y características de la AC durante los primeros dos años de vida. El documento destaca que este periodo es crítico para el crecimiento, desarrollo neurológico, maduración inmunitaria y establecimiento de hábitos alimentarios saludables a largo plazo. Asimismo, se enfatiza la relevancia de los primeros 1,000 días de vida y la necesidad de promover la lactancia materna, la diversidad alimentaria y la introducción oportuna de alimentos ricos en nutrimentos esenciales. La revisión también aborda temas actuales como la introducción temprana de alimentos alergénicos, el papel de las diferentes texturas, la prevención de obesidad y alergias, así como la importancia de evitar bebidas azucaradas, ultraprocesados y dietas restrictivas sin supervisión especializada. Desde la perspectiva mexicana, se reconoce que las recomendaciones internacionales deben contextualizarse según las realidades epidemiológicas, culturales y sociales del país. Finalmente, la Academia Mexicana de Pediatría propone recomendaciones prácticas dirigidas a profesionales de la salud, con el fin de favorecer una AC perceptiva, segura y basada en evidencia científica, que contribuya al bienestar integral de las y los lactantes mexicanos.
Immune checkpoint blockade has limited efficacy in microsatellite-stable colorectal cancer, where immune resistance may reflect stromal remodeling, tumor-intrinsic immune evasion, or both. Bulk classifications such as the Consensus Molecular Subtypes can mix these mechanisms into discrete labels. We developed two continuous indices computable from bulk data, a stromal myeloid fibrotic index (SMI) based on TGFβ signaling and an SPP1+ macrophage program, and a residualized immune evasion index (IEI_resid) combining CIN70 with reduced antigen presentation after adjustment for tumor purity and immune content. Across three cohorts (n = 1,243), SMI was associated with macrophage abundance, while IEI_resid was associated with lower antigen presentation scores. In CPTAC COAD, SMI aligned with extracellular matrix and stromal protein markers, whereas IEI_resid aligned with reduced antigen presentation proteins and a composite APM protein score. SMI and IEI_resid improved model fit beyond CMS and beyond ESTIMATE stromal and immune scores. Spatial transcriptomics in two independent tumors provided supportive evidence for compartment-level separation of stromal and epithelial programs and higher immune signal in stromal-dominant regions. These results provide a practical framework to model stromal remodeling and tumor-intrinsic antigen presentation features as partially separable dimensions in colorectal cancer.
Influenza vaccination coverage is suboptimal nationwide. To evaluate the effectiveness of centralized text message recall for influenza vaccination among children conducted by the New York City Department of Health and Mental Hygiene. A randomized assignment of 149 860 children, split between the intervention and control groups. Pediatric patients drawn from the Citywide Immunization Registry in New York City. Children aged 15 months to 18 years who did not receive an influenza vaccine in the 2016-2017 season and as of the study date in the 2017-2018 season. The Citywide Immunization Registry sent a generic Short Message Service (SMS) text message to the parents or guardians of the children: "The Health Department recommends that your child/children receive an annual flu shot. Call your doctor today!" Risk ratios of the proportions of children who received an influenza vaccine in the intervention and control groups within 28 days after the text message was sent. On October 25-26, 2017, 74 553 parents or guardians were sent a text message and 74 526 served as the control group. Of text messages sent, 73% were delivered successfully. Within 28 days of the intervention, 4.7% of children aged 15 months to 4 years in the text message group received an influenza vaccine compared with 4.3% in the control group, a statistically significant 9.5% relative increase in vaccination uptake (RR: 1.095, 95% CI: 1.001-1.199). Centralized text messages had a small positive effect on influenza vaccination among younger children. This approach may contribute to improving influenza vaccination in the pediatric population.
The red palm weevil, Rhynchophorus ferrugineus (Olivier), is one of the most destructive palm pests worldwide. Despite its tropical origin, this species tolerates moderately low temperatures and has an expansion potential that may be enhanced by global warming. However, the molecular mechanisms underlying cold stress remain poorly understood. This study provides a transcriptomic analysis of its larval response to cold stress. Using RNA-Seq on larvae exposed for 7 d to a sublethal low (5 °C) or control (23 °C) temperature, we identified 701 differentially expressed unigenes (580 protein-coding genes, 81 long noncoding RNAs [lncRNAs], and 40 with transposable elements [TEs]), of which 448 were upregulated and 253 downregulated under cold exposure. Functional enrichment revealed strong repression of cell cycle, along with the induction of stress-responsive pathways, including small heat shock proteins, detoxification enzymes (CYPs, UDP-glucuronosyltransferase), immune effectors (antimicrobial peptides, lectins, peptidoglycan-recognition proteins), and genes involved in cuticle remodeling. A subset of differentially expressed lncRNAs and TE-linked genes was associated with immune and chaperone responses, suggesting multilayered transcriptional regulation. These results indicate that R. ferrugineus larvae respond to low temperature by downregulating non-essential, energy-intensive programs while activating molecular chaperones, detoxification and immune defenses, and reinforcing structural barriers. This pattern, probably underestimated by the stronger starvation stress of controls, is consistent with an integrated strategy involving metabolic depression and enhanced cryoprotection. Our results represent a fundamental step that will guide data-driven studies to determine whether the cold-response mechanisms identified here are fully deployed in R. ferrugineus, as well as for future research on novel pest control strategies.
Multiple sclerosis (MS), an immune-mediated inflammatory demyelinating disorder of the central nervous system (CNS), is driven by microglia as key orchestrators of neuroinflammation. This study assessed the preventive potential of temporin-GHaR6R (GHaR6R), an antimicrobial peptide derived from Hylarana guentheri skin, using the experimental autoimmune encephalomyelitis (EAE) murine model of MS. Preventive administration of GHaR6R significantly reduced EAE incidence and alleviated clinical severity, while histopathological analyses (HE and LFB staining) revealed attenuated inflammatory cell infiltration and demyelination in the spinal cord. Mechanistically, GHaR6R suppressed M1 microglial polarization, thereby limiting excessive neuroinflammatory activation. In vitro, GHaR6R inhibited TNF-α and IL-6 secretion, reduced mitochondrial ROS production, preserved mitochondrial membrane potential in LPS-activated BV2 microglia, and promoted the shift from M1 to M2 microglial polarization. Consistent with these findings, GHaR6R downregulated mitochondrial fission protein Drp-1 while upregulating the fusion mediators MFN1 and MFN2 in both EAE-affected spinal cords and LPS-stimulated BV2 cells. Immunofluorescence analysis showed increased colocalization of Iba-1 with MFN1/2, indicating enhanced mitochondrial fusion in microglia. Taken together, these results demonstrate that GHaR6R ameliorates EAE progression by modulating microglial mitochondrial dynamics, mitigating neuroinflammation, and inhibiting M1 polarization, highlighting its potential as an early prophylactic intervention for MS.