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Preliminary data from the CDC “v-safe after vaccination health checker” surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System did not show any obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. More data are needed to better inform maternal, pregnancy, and infant outcomes.

Pancreatic β cell dysfunction contributes to the pathogenesis of type 2 diabetes. MiR-21 has been shown to be induced in the islets of glucose intolerant patients and type 2 diabetic mice. However, the role of miR-21 in the regulation of pancreatic β cell function remains largely elusive. In the current study, we identify the pathway by which miR-21 regulates glucose-stimulated insulin secretion utilizing mice lacking miR-21 in their β cells ( miR-21β KO). We find that miR-21β KO mice develop glucose intolerance due to impaired glucose-stimulated insulin secretion. Mechanistic studies reveal that miR-21 enhances glucose uptake and subsequently promotes insulin secretion by up-regulating Glut2 expression in a miR-21-Pdcd4-AP-1 dependent pathway. Over-expression of Glut2 in knockout islets results in rescue of the impaired glucose-stimulated insulin secretion. Furthermore, we demonstrate that delivery of miR-21 into the pancreas of type 2 diabetic db/db male mice is able to promote Glut2 expression and reduce blood glucose level. Taking together, our results reveal that miR-21 in islet β cell promotes insulin secretion and support a role for miR-21 in the regulation of pancreatic β cell function in type 2 diabetes. The microRNA miR-21 is induced in the islets of patients with glucose intolerance and diabetic mice. Here the authors report that deletion of miR-21 in pancreatic β-cells impairs glucose-stimulated insulin secretion via reduced glucose uptake, while a miR-21 agomir reduces blood glucose leves in diabetic male mice.

Psoriasis is a chronic inflammatory autoimmune skin disease characterized by erythematous plaques covered with silvery-white scales, often accompanied by systemic complications such as psoriatic arthritis and cardiovascular diseases. The disease and its systemic complications substantially impair quality of life, compromise socioeconomic status, and threaten patient safety. The occurrence and progression of this disease are related to the IL-23/IL-17 axis and involve the aberrant activation and interactions of multiple immune cells, along with genetic predispositions and environmental triggers. Although current therapeutic approaches, including topical agents, systemic medications, biologic agents targeting key cytokines, and Janus Kinase inhibitors, can control symptoms and delay disease progression, a complete cure has not been achieved. Furthermore, these strategies face challenges relating to the cost, safety, efficacy and precision of targeting. This review summarizes recent advances in mechanistic research, highlighting the interplay among microorganisms, innate and adaptive immunity in psoriasis. We also evaluate a range of emerging therapies, including biologics, small-molecule inhibitors, Chimeric antigen receptor T-cell cell therapy, RNA interference-based strategies, and alternative medicine. Specifically, we focus on their novel mechanisms, efficacy challenges, safety profiles, and targeting accuracy. Finally, we assess their potential in personalized treatment, aiming to achieve long-term remission, and propose the future prospects of precision medicine in psoriasis management.

The integrity of the corneal epithelium is essential for the maintenance of the physiological function of the cornea. Studies have found that inflammation greatly delays corneal wound healing. NF-κB c-Rel is preferentially expressed by immune cells and promotes the expression of inflammatory cytokines. In the current study, we sought to investigate whether c-Rel could be used as a potential therapeutic target for treating a corneal injury. Our studies reveal that expressions of c-Rel and its inflammatory targets are significantly increased in the cornea of mice with corneal injury. In addition, we find that c-Rel-deficient mice exhibit accelerated corneal wound healing and reduced expression of inflammatory cytokines. Further studies show that topical treatment on the corneal surface using nano-polymers or exosomes loaded with c-Rel-specific siRNA (siRel) can effectively accelerate regular and diabetic corneal wound healing. More importantly, we find that exosomes, as carriers of siRel, showed better efficacy than nano-polymers in treating corneal injury. We further demonstrate that exosomes secreted by mesenchymal stem cells can efficiently transfer siRNA into macrophages and dendritic cells but not T cells. Taken together, these results indicate that blocking c-Rel may represent an attracting strategy for the treatment of both regular and diabetic corneal injury.

Fruit acidity is an essential factor affecting blueberry organoleptic quality. The organic acid content in blueberry fruit mainly contributes to fruit acidity. This study aims to evaluate the effect of exogenous salicylic acid (SA), the principal metabolite of aspirin, on the organoleptic quality and organic acid metabolism in rabbiteye blueberry ( Vaccinium virgatum Ait, ‘Powderblue’) during cold storage (4 °C). Results showed that SA-treated fruit reduced fruit decay and weight loss delayed fruit softening, and decline of total soluble solids (TSS). TA and total organic acid amounts stayed the same during the late storage period in SA-treated fruit. Four kinds of organic acid components, malic acid, quinic acid, citric acid, and succinic acid, were at higher levels in fruit treated by SA as compared to control. SA enhanced the activities of PEPC, NAD-MDH, and CS to promote the synthesis of malic acid and citric acid. Meanwhile, the activities of NADP-ME, ACL, and ACO, which participated in the degradation of malic acid and citric acid, were inhibited by SA. qPCR results also showed that the expression of VcPEPC , VcNAD-MDH , and VcCS genes were upregulated. In contrast, SA downregulated the expression of VcNADP-ME , VcACL , and VcACO genes. In conclusion, SA could regulate the key genes and enzymes that participated in organic acids metabolism to maintain the freshness of blueberry during cold storage, therefore minimizing the economic loss.

The nasal mucosa forms a critical barrier against the invasion of respiratory pathogens. Composed of a heterogeneous assortment of cell types, the nasal mucosa relies on the unique characteristics and complex intercellular dynamics of these cells to maintain their structural integrity and functional efficacy. In this study, single-cell RNA sequencing (scRNA-seq) of porcine nasal mucosa was performed, and nineteen distinct nasal cell types, including nine epithelial cell types, five stromal cell types, and five immune cell types, were identified. The distribution patterns of three representative types of epithelial cells (basal cells, goblet cells, and ciliated cells) were subsequently detected by immunofluorescence. We conducted a comparative analysis of these data with published human single-cell data, revealing consistent differentiation trajectories among porcine and human nasal epithelial cells. Specifically, basal cells serve as the initial stage in the differentiation process of nasal epithelial cells, which then epithelial cells. This research not only enhances our understanding of the composition and transcriptional signature of porcine nasal mucosal cells but also offers a theoretical foundation for developing alternative models for human respiratory diseases.

Two coronavirus disease 2019 (COVID-19) vaccines are currently authorized for use in the United States. The Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine on December 11, 2020, and for the Moderna COVID-19 vaccine on December 18, 2020; each is administered as a 2-dose series. The Advisory Committee on Immunization Practices issued interim recommendations for Pfizer-BioNTech and Moderna COVID-19 vaccines on December 12, 2020 (1), and December 19, 2020 (2), respectively; initial doses were recommended for health care personnel and long-term care facility (LTCF) residents (3). Safety monitoring for these vaccines has been the most intense and comprehensive in U.S. history, using the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system, and v-safe,* an active surveillance system, during the initial implementation phases of the COVID-19 national vaccination program (4). CDC conducted descriptive analyses of safety data from the first month of vaccination (December 14, 2020-January 13, 2021). During this period, 13,794,904 vaccine doses were administered, and VAERS received and processed 6,994 reports of adverse events after vaccination, including 6,354 (90.8%) that were classified as nonserious and 640 (9.2%) as serious. The symptoms most frequently reported to VAERS were headache (22.4%), fatigue (16.5%), and dizziness (16.5%). A total of 113 deaths were reported to VAERS, including 78 (65%) among LTCF residents; available information from death certificates, autopsy reports, medical records, and clinical descriptions from VAERS reports and health care providers did not suggest any causal relationship between COVID-19 vaccination and death. Rare cases of anaphylaxis after receipt of both vaccines were reported (4.5 reported cases per million doses administered). Among persons who received Pfizer-BioNTech vaccine, reactions reported to the v-safe system were more frequent after receipt of the second dose than after the first. The initial postauthorization safety profiles of the two COVID-19 vaccines in current use did not indicate evidence of unexpected serious adverse events. These data provide reassurance and helpful information regarding what health care providers and vaccine recipients might expect after vaccination.

Macrophages play important roles in the regulation of the innate and adaptive immune responses. Classically activated macrophages and alternatively activated macrophages are the two major forms of macrophages and have opposing functionalities. Tumor necrosis factor-α-induced protein 8-2 is expressed primarily by immune cells and negatively regulates type 1 innate and adaptive immune responses to maintain immune tolerance. While previous studies indicate that TIPE2 promotes M2 but inhibits M1 macrophage differentiation, the underlying molecular mechanism by which TIPE2 promotes M2 macrophage differentiation remains unclear. Our current study shows that TIPE2-deficient bone-marrow cells are defective in IL-4 induced M2 macrophage differentiation in vitro. Mechanistic studies revealed that TIPE2 promotes phosphoinositide metabolism and the activation of the down-stream AKT signaling pathway, which in turn leads to the expression of markers specific for M2 macrophages. In addition, our results showed that Tipe2-deficiency does not affect the activation of the JAK-STAT6 signaling pathway that also plays an important role during M2 macrophage differentiation. Taken together, these results indicate that TIPE2 promotes M2 macrophage differentiation through the activation of PI3K-AKT signaling pathway, and may play an important role during the resolution of inflammation, parasite control, as well as tissue repair.

Stem cells have self-renewal ability and multi-directional differentiation potential. They have tissue repair capabilities and are essential for maintaining the tissue homeostasis. The depletion of stem cells is closely related to the occurrence of body aging and aging-related diseases. Therefore, revealing the molecular mechanisms of stem cell aging will set new directions for the therapeutic application of stem cells, the study of aging mechanisms, and the prevention and treatment of aging-related diseases. This review comprehensively describes the molecular mechanisms related to stem cell aging and provides the basis for further investigations aimed at developing new anti-stem cell aging strategies and promoting the clinical application of stem cells.

Objectives/Goals: The World Trade Center (WTC) Health Program (Program), a limited federal healthcare program for eligible people exposed to the terrorist attacks on September 11, 2001, expanded telemedicine services during the COVID-19 pandemic. We analyzed service use trends from 2020–2021 to describe how the program implemented telemedicine services. Methods/Study Population: We estimated use rates of telemedicine-eligible services and telemedicine services by all included program members and by subgroups of members defined by member type (responder or survivor) and selected characteristics for the study period 2020–2021. We described the use trends of total telemedicine-eligible visits, telemedicine visits, and in-person visits, respectively, by quarter. We calculated the quarterly rates of telemedicine use per 1000 living members. We used a multivariable logistic regression to examine associations between member characteristics and telemedicine use rates. Results/Anticipated Results: About 75% of telemedicine visits were related to mental health services. In the second quarter of 2020 (April–June), telemedicine use rate (367 visits/1000 members) increased, exceeding in-person service rate (152 visits/1000 members) by 1.4 fold. Telemedicine use rate decreased gradually in the rest of the study period but still represented 38% of total visits by the end of 2021. Regression models showed differences in telemedicine use rates by member type and by demographic characteristics. Survivor members (vs. responder members), those self-identified as non-Hispanic Other races (vs. non-Hispanic White), those with preferred non-English language (vs. preferred English), and those not living in the New York metropolitan area (vs. living in the New York metropolitan area) were less likely to use telemedicine. Discussion/Significance of Impact: The expansion of telemedicine service provided members uninterrupted access to necessary health services during the COVID-19 pandemic. It underscored the importance of extensive partner collaboration, the capacity to rapidly develop necessary technical guidance, and the flexibility to timely address frequent regulatory guidance updates.