David M. Irwin

Most nonmammalian tetrapods exhibit more than three phalanges in their posterior digits (III–V), whereas mammals are restricted to no more than three. So far, the molecular mechanism underlying this evolutionary reduction and the functions of Lhx2 and Lhx9 in digit development remain unclear. Here we show divergent evolution of Lhx2 and Lhx9 expression patterns in embryonic limbs across tetrapods. We further demonstrate that although ectopic overexpression of each gene in chick embryos delayed limb skeletal development, only Lhx9 reduced the phalanx number in the posterior digits. Transcriptomic analysis showed that Lhx2 regulates pathways for chondrocyte and osteoblast differentiation, and Lhx9 preferentially influences skeletal segmentation via the bone morphogenetic protein (BMP) pathway. The unique function and differential expression of Lhx9 in the limb buds between mammals and nonmammalian tetrapods suggest it may have acquired a role in suppressing phalanx number, driving the evolutionary reduction of phalanx number in mammals.

Objective: Skin is a complex tissue whose health is modulated by multiple factors. Exposure to the environment causes damage to skin cells and skin tissue. Identification of factors that can improve skin cell function potentially can prevent or reverse skin aging. Fibroblast growth factors (FGFs) induce growth of skin cells and regulate multiple genes important for skin function. However, FGFs cannot penetrate skin and thus cannot be used as therapeutic factors. Methods: Here we tested three proline-containing tripeptides for their ability to induce skin cell growth, change gene expression within these cells, and protect cells from harmful agents. We also tested the ability of one peptide to penetrate skin, a prerequisite to influence skin cells in vivo. Results: We identified three short proline-containing tripeptides that increase both fibroblast and keratinocyte cell growth, increase the abundance of COL1A1 (collagen type 1) and AQP3 (aquaporin 3) mRNA transcripts and decrease IL6 (interleukin-6) transcripts, all features of improved skin health. These tripeptides, when used as a pretreatment, prevent an increase in the abundance of MMP1 (matrix metalloprotease 1), a biomarker of skin damage when these cells are treated with an aging compound. Finally, we show that one of these tripeptides can penetrate skin. Conclusions: Proline-containing tripeptides have properties that indicate they can be used to reduce or reverse skin damage.

Tumors pose an enormous burden to human health due to their high incidence and mortality rates, constituting a major global public health concern. Tumor immunotherapy is a revolutionary treatment for patients with complicated conditions or for those who have not responded well to conventional treatment. Vaccine technology effectively prevents infectious diseases, and tumor vaccines have been recently demonstrated to have significant potential as a tumor therapy. Antigens for tumor vaccines can be derived from several different types of tumor cell materials, including entire cells, cell lysates, cell vesicles, and cell membranes. The selection and optimization of antigens are critical for vaccine effectiveness, as they should trigger a precise immune system defensive response against a specific pathogen (or cells) without producing overwhelming negative side effects. They should precisely trigger the immune system's defensive responses against specific pathogens or cells without producing overwhelming negative side effects. Supported by a robust theoretical basis and substantial preclinical evidence, tumor cell‐derived vaccines hold considerable potential for future research and clinical translation. This review introduces the current state of tumor cell‐derived vaccines, discusses their limitations, and explores future pathways to their advancement. Tumor cell‐derived vaccines may emerge as a novel strategy for the treatment of cancer, allowing patients to have more effective treatment options.

SARS-CoV and MERS-CoV are two coronaviruses that have received significant attention due to their high pathogenicity and mortality rates in human populations. In this study, we compared their evolutionary dynamics to provide a One Health perspective on their differences in terms of the results of disease control. The phylogenetic network of SARS-CoVs showed that human isolates gathered into a “super-spreader” cluster and were distinct from civet isolates. In contrast, dromedary camel- and human-isolated MERS-CoVs were clustered together. Thus, most clades of MERS-CoV can infect humans, and MERS-CoVs seem to more easily spill over the animal-to-human interface. Additionally, the civet can be easily controlled, while the intermediate host (dromedary camels) of MERS-CoV is an important livestock species, so it is impossible to eliminate all animals. This further leads to difficulties in disease control in MERS. Although MERS-CoVs are endemic to dromedary camels in both the Middle East and Africa, human infections are mainly linked to the Middle East. The nucleotide sequences of the MERS-CoV receptor gen (dipeptidyl peptidase 4 (DPP4)) from 30 Egyptians, 36 Sudanese, and 34 Saudi Arabians showed little difference. These findings suggest that the observed disparities in MERS prevalence between populations in the Middle East and Africa may be more strongly attributed to inadequate disease surveillance and the limited camel-to-human transmission of clade C MERS-CoV in Africa, rather than variations in DPP4 gene.

SARS-CoV and MERS-CoV are two coronaviruses that received great attention due to their high pathogenicity and mortality rates in human populations. In this study, we compared their evolutionary dynamics to provide a One Health perspective of their different results of disease control. The phylogenetic network of SARS-CoVs showed that human isolates gathered into a “super-spreader” cluster, and were distinct from civet isolates. In contrast, dromedary camel- and human-isolated MERS-CoVs were clustered together. Thus, most clades of MERS-CoV can infect humans, and MERS-CoVs seem easier to spill over from animal-to-human interface. Additionally, the civet can be easily controlled, while the intermediate host (dromedary camels) of MERS-CoV is important livestock, so it is impossible to eliminate all animals. This further leads to difficulties in disease control of MERS. Although MERS-CoVs are endemic to dromedary camels in both the Middle East and Africa, human infections are mainly linked to the Middle East. The nucleotide sequences of the MERS-CoV receptor gene--dipeptidyl peptidase 4 (DPP4) from 30 Egyptians, 36 Sudanese, and 34 Saudi Arabians showed little difference. These findings suggest that the observed disparities in MERS prevalence between populations in the Middle East and Africa may be attributed more to inadequate disease surveillance and the limited camel-to-human transmission of clade C MERS-CoV in Africa, rather than variations in DPP4 gene.

The interdigital webs of aquatic tetrapods are a key structure evolved for adaptation, which are formed by inhibiting interdigital cell death (ICD). Diverse interdigital morphologies have independently evolved among species, and the regulatory mechanisms responsible for their development are still not fully understood. The Chinese soft-shell turtle (Pelodiscus sinensis) serves as a good research model that exhibits transitional traits from webless to fully webbed. In this study, we collected eight samples of interdigital webs from the fore- and hindlimbs of turtles at embryonic stage 19 (TK19) for RNA sequencing (RNA-seq) analysis. We identified 608 differentially expressed genes (DEGs). Whole-mount in situ hybridization (WISH) and real-time quantitative PCR (RT-qPCR) of representative genes confirmed the accuracy of the transcriptomic results. These findings not only provide new perspectives and data to support comparative studies of adaptive convergent evolution in aquatic animals but also enhance our understanding of the mechanisms underlying tetrapod limb morphogenesis. Furthermore, these results provide potential molecular targets for research on the plasticity of programmed cell death or senescence.