Biological Programs Research Articles

Penn Academy for Skin Health (PASH): An Experiential Pipeline Program in Skin Biology and Dermatology for High-School Students

Penn Academy for Skin Health (PASH): An Experiential Pipeline Program in Skin Biology and Dermatology for High-School Students

The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood

BackgroundTelomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old.MethodsThis research involved 895 mother–child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath’s epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones.ResultsThe linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), − 13.22 (− 23.21 to − 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), − 14.13 (− 21.59 to − 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (P = 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (P = 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than − 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than − 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than − 1.35, followed by a plateau between − 1.35 and − 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than − 0.67.ConclusionsIn this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth.

Lifetime Violence and Perinatal Sleep Quality: A Scoping Review

Abstract Introduction In-utero experience of violence through maternal experience of intimate partner violence (IPV) is a risk factor for adverse pregnancy outcomes via ‘biological programming,’ whose effect can be mediated by sleep. We conducted a scoping review to synthesize the current evidence of the association between experiences of violence and sleep in women. Methods Between August and October 2023, we conducted a search in four databases (PubMed, APA PsycInfo, Embase, and Web of Science) for peer-reviewed articles, using 11 inclusion and exclusion criteria. Any study published in English in peer-reviewed journals that conducted original research on the association between exposure to violence (lifetime IPV, IPV during the previous year, during and 1 year after pregnancy, as well as adverse childhood experiences) and poor sleep outcomes (sleep disturbances, insomnia, poor sleep quality, and longer time to fall asleep) in the perinatal population were included. Results The synthesis of the 12 included studies revealed a positive association between exposure to violence and poor sleep, and between adverse childhood experiences and sleep disturbances or poor sleep during pregnancy. Moreover, IPV in the postpartum period was associated with poor sleep. Conclusion Most of the evidence synthesized comprises data from high-income countries, resulting in lack of cultural context. However, it is evident that the experience of violence throughout life is a risk for poor perinatal sleep quality. Thus, there is a growing need to study this association, especially in resource-limited settings, where data on sleep health is largely absent, inform pregnancy care and maternal and child health policies.

An integrated engineering worldview of synthetic biology education through the lens of webinar based pedagogy.

Synthetic biology is an interdisciplinary field that brings together engineering and biology concepts alongside the arts and social sciences to develop solutions to pressing problems in our world. The education of students entering this field has relied on a diverse set of pedagogical methods to accomplish this goal. One non-profit group, iGEM-the International Genetically Engineered Machine competition, has been a driver of students' awareness of synthetic biology for the last 20 years giving many young researchers their first experience in the field of synthetic biology. Dissemination of synthetic biology concepts by iGEM has occurred through several programs including a webinar series started during the 2020 COVID pandemic. The iGEM webinar series successfully engaged students by taking inspiration from synthetic biology programs in Europe, North America, and Asia that had themselves evolved alongside iGEM. The webinar designers modeled the content after their experiences in iGEM as well as their academic courses, pedagogy, and mentoring experiences. This series has produced globally accessible pedagogy for both technical synthetic biology knowledge and the communication skills necessary to build and communicate synthetic biology projects. The hope is that this series functions as a lasting blueprint that can be used by future educators in synthetic biology and other disciplines to reduce barriers that students face when attempting to enter cutting edge fields.

A point mutation in VIG1 boosts development and chilling tolerance in rice

The rice paddy-direct seeding system has been widely adopted due to its low cost and convenience, whereas its application is mainly constrained by low seedling vigor, cold sensitivity, eventually resulting in reduced grain yield. Here, we show vig1a and vig1b, two allelic mutants of OsbZIP01, that both demonstrate greatly enhanced seedling vigor and chilling tolerance but differ in final grain production. The vig1a phenotype can be obtained via simultaneous mutation of the genes OsbZIP01 and OsbZIP18, or by selectively manipulating the basic region of OsbZIP01. Destroying the leucine zipper region of OsbZIP01 in vig1a turns vig1a to be vig1b. Further analysis reveals that OsbZIP01 and OsbZIP18 function cooperatively in diverse crucial biological programs that determine seedling establishment, chilling tolerance, and grain yield through their interactions. These findings provide a strategy toward simultaneously improving seedling vigor, chilling tolerance, and grain yield for rice production.

Postdoctoral Research Fellowships in Biology Program (NSF)

Postdoctoral Research Fellowships in Biology Program (NSF)

Carbon in soil macroaggregates under coffee agroforestry systems: Modeling the effect of edaphic fauna and residue input

Crop diversification tends to favor the soil fauna community, soil aggregation, and consequently soil organic carbon (SOC) stock. Understanding the association between these attributes can help in understanding the dynamics of physical protection of soil organic matter. In this context, our study aimed to answer: (1) how does the edaphic macrofauna community and soil carbon and aggregate classes respond to two types of coffee agroforestry systems (coffee with Grevillea robusta and coffee with banana) and how these responses differ from native ecosystem; (2) how and to what extent are soil aggregation regulated by the complex structural interactions of plant residue input, SOC, and the soil faunal community? The work was conducted in the municipality of Planalto, state of Bahia, Brazil. Three systems were evaluated: agroforestry system of Coffee arabica L. with Grevillea robusta (CG); agroforestry system of Coffee arabica with Musa spp. (CB); and native forest (NF). Four plots were delimited in each system, in which dry fractionation of the soil was performed to obtain aggregates of classes >6, 6–4, 4–2 and < 2 mm. The macrofauna was sampled using the Tropical Soil Biology and Fertility Program method. The labile and total carbon of the soil and aggregates were determined and the carbon management indices were calculated. The CG and CB presented a greater amount of larger size aggregates (> 6, 6–4 and 4–2 mm) than the NF. The CB system provided more favorable conditions for the soil macrofauna. Despite this, both coffee agroforestry systems favored the occurrence of Oligochaeta. The CG was more favorable to maintain labile fractions of organic matter than the CB. The edaphic fauna show a close relationship with the formation of carbon aggregates and stabilization which was directly influenced by continuous input of plant residues in diverse coffee growing systems.

Exploring Advances in Reproduction and Stem Cell Biology: Highlights from The 24th and 19th International Congresses in Iran.

The 24th and 19th International Congresses on Reproduction and Stem Cell Biology in the Islamic Republic of Iran brought together experts and researchers worldwide to explore the latest advancements in these fields. Different topics were discussed, including such as reproductive health, infertility treatments, stem cell research, and regenerative medicine. This report provides a summary of the congress's key findings by emphasizing pioneer research and technologies that can influence the future of reproduction and stem cell biology programs. The presence of keynote speakers such as Professor Nicolas Rivron, Mohammad Ebrahim Parsanezhad, Ashraf Moini, Abbas Aflatoonian, Hadi Shafiee, Anna Brini, Omid Camron Farokhzad, and Jeffrey Schweitzer added value to the event, which had over 1100 participants from around the world. While foreign speakers were from various countries Iranian speakers mainly came from Tabriz, Isfahan, Shiraz, Babol, and Tehran that all discussed cutting-edge science and successful disease treatments. To ensure a more comprehensive representation, it is suggested that a wider geographic distribution of national and foreign speakers should be considered in future plan.

Analysis on Work Status of Bachelor of Science in Biology Graduates for Curriculum Development: A Tracer Study

The research aims to assess the employment status of Bachelor of Science in Biology graduates to guide the curriculum enhancement that can meet the industry demands. Using a tracer study approach, the data was gathered from graduates. The results indicate that numerous graduates are working in sectors connected to BS Biology. The research identifies important areas for enhancement in the curriculum, such as improved hands-on experience and cross-disciplinary classes. The graduates emphasized the significance of abilities like research, laboratory methods, and critical reasoning which are essential in their careers. The study reveals that most graduates from the BS in Biology program have successfully secured employment by heeding their feedback and most of them secure full-time positions. The majority of the respondents completed their studies in 2023, with over half of them were male, 90.32% were unmarried, some are still in school, and nearly half of the respondents earn between Php10,001 - Php20,000 monthly. Around half of them held professional, technical, or supervisory roles. In addition, most graduates believed that their degree programs had equipped them with the necessary knowledge and skills to succeed in their desired professions. Moreover, the current job of the participants is fairly satisfying for the survey respondents. Recommendations from the study involve incorporating additional practical learning opportunities, cultivating relationships with professionals in the field, and consistently revising the curriculum to keep pace with evolving scientific discoveries. Thus, this research offers valuable information for schools looking to improve their biology programs, thereby better preparing the students for future careers.

Unravelling the genetic basis and regulation networks related to fibre quality improvement using chromosome segment substitution lines in cotton.

The elucidation of genetic architecture and molecular regulatory networks underlying complex traits remains a significant challenge in life science, largely due to the substantial background effects that arise from epistasis and gene-environment interactions. The chromosome segment substitution line (CSSL) is an ideal material for genetic and molecular dissection of complex traits due to its near-isogenic properties; yet a comprehensive analysis, from the basic identification of substitution segments to advanced regulatory network, is still insufficient. Here, we developed two cotton CSSL populations on the Gossypium hirsutum background, representing wide adaptation and high lint yield, with introgression from G. barbadense, representing superior fibre quality. We sequenced 99 CSSLs that demonstrated significant differences from G. hirsutum in fibre, and characterized 836 dynamic fibre transcriptomes in three crucial developmental stages. We developed a workflow for precise resolution of chromosomal substitution segments; the genome sequencing revealed substitutions collectively representing 87.25% of the G.barbadense genome. Together, the genomic and transcriptomic survey identified 18 novel fibre-quality-related quantitative trait loci with high genetic contributions and the comprehensive landscape of fibre development regulation. Furthermore, analysis determined unique cis-expression patterns in CSSLs to be the driving force for fibre quality alteration; building upon this, the co-expression regulatory network revealed biological relationships among the noted pathways and accurately described the molecular interactions of GhHOX3, GhRDL1 and GhEXPA1 during fibre elongation, along with reliable predictions for their interactions with GhTBA8A5. Our study will enhance more strategic employment of CSSL in crop molecular biology and breeding programmes.

Peningkatan Literasi Biodiversitas Menggunakan Model Kebun Botani di Madiun

The improvement of literacy on biodiversity growing in the residential areas can support the attitude of society to sustain the ecology, even improving the life quality based on local potentials. However, there are limited live-learning facilities available for biodiversity education. Hence, a community service was carried out by the Study Program of Biology and Study Program of Food Technology, Faculty of Agricultural Technology, Widya Mandala Surabaya Catholic University, Indonesia. Its objective was to improve literacy on biodiversity of the societal partners through knowledge enrichment and awareness of biodiversification potentials which grow in their residential areas. The societal partners are alumni, high school students (St. Bonaventura and the 6th State High School, Madiun), and Pemberdayaan Kesejahteraan Keluarga (PKK) group “Asman Toga” from Rejomulyo village, Madiun; totally 45 participants. The activities included (a) building a botanical garden named Arbor Vitae”, (b)focused group discussion (FGD), and (c) workshop. Currently, it finished a clearing land and planting more than 50 species for foods and nutraceutical/medicinal sources as well as ecological services. The “Arbor Vitae” had been embedded into university institution by appointing a management in charged. Meanwhile, the improvement of literacy was measured from pre- and post-test during FGD which indicated a significant increase in partners’ literacy by 45.44%; after screening 18 respondents completely filled the tests. The test statements grouped into four indicators of literacy on biodiversity. Moreover, the workshop was complementarily improving the partners’ skill with technology of telang flower jelly drink, purslane medical simplisia, and water clarification using moringa seeds.

Paternal influence on pregnancy: Setting the precedence

According to sociologist, Sylvia patriarchy is “a system of social structures and practices in which men dominate, oppress, and exploit women.” Derived from the Greek word patriarkhēs, patriarchy means “the rule of the father.” American sociologist Allan Johnson further mentions that patriarchy is a kind of society in which even though men and women participate, but is male-privileged, maledominated, male-identified, and male-centered. Apart from the sociologist’s point of view of society, it seems that developmental programs in biology also have a patriarchal trend. At least, that’s what is reported from several studies recently. Lopez-Tello et al., reported a paternal insulinlike growth factor 2 (Igf2)-related selective trafficking of maternal resources toward the fetus for its development. Metabolic demands for the fetus are enhanced during pregnancy. It is, therefore, observed that there is a relatively greater shunting of metabolic fuels toward the fetus to increase nutrient availability, more than it is perhaps allowed by the maternal system. The placenta assists in this shuttle by promoting insulin resistance, which leads to glucose intolerance in the mother. This glucose is now made available to the fetal compartments. The paternal Igf2 gene undergoes genomic imprinting, and only the copy inherited from the father is active. Paternally active Igf2 expressed in placental endocrine cells directs the maternal lipids and carbohydrates toward the fetus, an excellent example of paternal manipulation of maternal physiology and metabolic patriarchy. Further, studies have shown that fathers fed with a high-fat diet reduce the pregnancy success rate because of the reduction of their sperm motility. Excess intake of processed food, highsugar diets, or fructose has consequences on offspring’s cardiovascular and metabolic diseases. Males fed a low protein diet in mice results in glucose intolerance, metabolic and cardiovascular dysfunctions, and altered patterns of bone mineralization in pups. We, therefore, can conclude a robust paternal influence on pregnancy and fetal outcome. Pregnancy was once thought of as an exclusively maternal affair. Increasing research in this arena seems to have smashed that stereotype with paternal influence seems to play a significant role in shaping the birth process. It is high time that Sylvia patriarchal understanding is redefined with the paternal share of responsibility beyond just dominance and an authoritarian role.

Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.

Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in two B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis.

Understanding the movement and dispersal patterns of released Fopius arisanus (Hymenoptera: Braconidae) parasitoids in a papaya orchard.

Implementation of augmentative biological control requires estimates of parasitoid dispersal from the release point to determine appropriate release density, spacing, and timing. This study evaluated the movement patterns of Fopius arisanus Sonan (Hymenoptera: Braconidae) parasitoids, which have historically been used to control invasive tephritid fruit flies. The wasps were released from the central point, and dispersal was monitored over time using parasitism in sentinel fruit and trap captures at 40 points radiating out from the center (15-240 m). The releases were conducted 4 times during June, July, September, and November 2006. The data showed that there were large declines in dispersal by distance. Parasitism was greatest closest to the release point, within 30 m. Parasitism was also greatest within the first 24 h of the release. After 1 wk, parasitism decreased from 41% to 1.5% within 30 m. These data correlated strongly with trap capture data, which also showed that parasitoid movement favored the SE region of our release site, roughly corresponding to the overall prevailing winds. Wind speed, relative humidity, and temperature all affected parasitoid movement during our trial, indicating the complex environmental factors that can affect release success. This is the first report of dispersal metrics for F. arisanus. Our findings are in agreement with other similar studies on braconid movement generally and suggest that frequent, high-density releases are most effective since the dispersal of F. arisanus is limited and retention in the environment is low. We discuss our results in the context of international augmentative biological control release programs.

Charting the Etanercept Journey: Tracing Cost Dynamics in Poland's Off-Patent Market from Reference Drug Rivalry to Biosimilar Monopoly.

To evaluate the pricing of etanercept (ETN) reference and biosimilar drugs in a changing competitive to monopolized market. We conducted a comprehensive, retrospective analysis of ETN market competition, specifically changes in tender price based on shifts in market monopoly, including the effects on cost evolution, in the off-patent market in Poland. We included a total of 473 tenders for ETN purchase in dedicated biologic drug reimbursement programs, covering both pre-filled syringes and automatic injectors. This study covers the timeframe from November 2017 to December 2023, throughout which we evaluated a unique setting of ETN market re-monopolization from the perspective of payer, hospital and patient benefits resulting from changing cost calculations. Between 2017 and 2022, Erelzi was recorded as having the largest total tender volume (59%), with a mean price [per ETN daily defined dose (DDD)] of €7.28, followed by Enbrel (31%, €8.34) and Benepali (10%, €9.45), respectively. Over the last 6 months of waning market competition, the mean price for winning bids was estimated at €5.69. After market re-monopolization by an ETN biosimilar, the mean price of winning bids increased to €8.09, and continued to increase (€9.71) in the last 6 months of available follow-up. In contrast to the competitive era, no significant relationship between tender volume and winning price was recorded after re-monopolization. In the most recent tenders, mean ETN prices increased up to €15.82, nearly tripling the lowest prices of the competitive market period. In the early re-monopolization market, mean annual treatment cost per patient is estimated at over €3800, which exceeds therapy costs in the prior competitive market years, and is expected to increase to over €6200 based on the most recent tenders. On a healthcare system level, this corresponds to over €3.42 million excess costs due to market monopoly. Higher ETN prices resulted in downstream failure of regulatory incentives to promote affordable biologics. Due to higher pricing, hospitals lost over an estimated €2.52 million, with possible risk of treatment restrictions. For the same reason, the public payer achieved comparable savings, allowing for partial coverage of higher reimbursement expenses. This nation-level scenario of market re-monopolization by a biosimilar drug confirms net loss and excess costs for the healthcare payer, as can be expected from economic theory. The upwards drug repricing and restriction of treatment availability occurs much more rapidly than the decrement in a period of market competition.

Technologies for Studying and Teaching Human Anatomy: Implications in Academic Education.

The teaching of human anatomy (HA) constitutes one of the fundamental pillars of the curriculum in biological and healthcare-related programs. Therefore, it is imperative that the methodology and didactics employed in this discipline equip students in the best possible way. The traditional method of teaching HA involves lectures and practical classes with previously dissected cadaveric specimens and dissection activities. Concurrently, the present era is witnessing the emergence and popularization of new digital technologies connected to the internet, among which we can highlight smartphones, quick response codes, and virtual reality devices, along with the dissemination of complementary imaging methods, such as radiography, ultrasonography, magnetic resonance imaging, and computerized tomography. From this perspective, the objective of this review is to analyze how each of these new tools integrates into the academic context, in order to diversify the teaching of HA and contribute to better understanding of the HA content during academic training, as well as the clinical applications.

Analysis of Intelligent Teaching Ability of Pre-service Biology Teachers Based on TPACK Theory

The level of Technological Pedagogical Content Knowledge (TPACK) of modern intelligent-based teaching directly affects the teaching ability of pre-service teachers. In this study, all the students majoring in biological sciences in the College of Life Sciences of X Normal University were selected as the research objects. The existing TPACK level of pre-service biological teachers was investigated by means of literature research and questionnaire survey, and the factors that might influence the TPACK level of pre-service biological teachers were analyzed. The results showed that the overall TPACK level of pre-service biology teachers was in the middle level, and the TK level was the lowest, followed by the TPCK level. The seniors were higher than the freshmen in all dimensions of TPACK, and there were significant differences in each dimension. Seniors were higher than juniors in all dimensions of TPACK, and there were significant differences between them in CK and TPK, while there were no significant differences in other dimensions. Comparing the juniors and seniors as a whole with the freshmen and sophomores students as a whole, it was found that the former was higher than the latter in seven dimensions, and the differences in each dimension were extremely significant. This indicates that the establishment of the biological talent training program had a significant promoting effect on the improvement of pre-service teachers' TPACK level. This provides an important theoretical basis for the training of TPACK level of pre-service biology teachers in this school.

Preoperative neoadjuvant targeted therapy remodels intra-tumoral heterogeneity of clear-cell renal cell carcinoma and ferroptosis inhibition induces resistance progression

Neoadjuvant tyrosine kinase inhibitor (TKI) therapy is an important treatment option for advanced renal cell carcinoma (RCC). Many RCC patients may fail to respond or be resistant to TKI therapy. We aimed to explore the key mechanisms of neoadjuvant therapy résistance. We obtained tumor samples from matched pre-treatment biopsy and post-treatment surgical samples and performed single-cell RNA sequencing. Sunitinib-resistant ccRCC cell lines were established. Ferroptosis was detected by ferrous ion and lipid peroxidation levels. Tumor growth and resistance to Sunitinib was validated in vitro and vivo. Immunohistochemistry was used to validate the levels key genes and lipid peroxidation. Multi-center cohorts were included, including TCGA, ICGC, Checkmate-025 and IMmotion151 clinical trial. Survival analysis was performed to identify the associated clinical and genomic variables. Intratumoral heterogeneity was first described in the whole neoadjuvant management. The signature of endothelial cells was correlated with drug sensitivity and progression-free survival. Ferroptosis was shown to be the key biological program in malignant cell resistance. We observed tissue lipid peroxidation was negatively correlated with IL6 and tumor response. TKI-resistant cell line was established. SLC7A11 knockdown promoted cell growth and lipid peroxidation, increased the ferroptosis level, and suppressed the growth of tumor xenografts significantly (P < 0.01). IL6 could reverse the ferroptosis and malignant behavior caused by SLC7A11 (−) via JAK2/STAT3 pathway, which was rescued by the ferroptosis inducer Erastin. Our data indicate that ferroptosis is a novel strategy for advanced RCC treatment, which activated by IL6, providing a new idea for resistance to TKIs.

A facile halogen assisted intramolecular cyclization of (E)‐3‐(substituted benzylidene)‐1‐(substituted phenyl)pyrrolidine‐2,5‐dione

AbstractA straightforward method for producing pyrrolo‐chromenes involved the utilization of a Wittig reaction, where maleimides reacted with ortho‐hydroxy benzaldehyde. This reaction yields ortho‐hydroxy benzylidine succinimides, which subsequently undergo molecular bromine‐induced intramolecular cyclization, resulting in (E)‐3‐(substituted benzylidine)‐1‐(substituted phenyl) pyrrolidine‐2,5‐dione derivatives (6g‐n). The traditional reaction methods demonstrates efficient performance when carried out in a DMF solvent. This approach proves to be user‐friendly and provides numerous benefits, including reduced reaction duration, increased product yields, and milder operating conditions. The compounds synthesized in this study will be integrated into our biological screening program and any discoveries pertaining to their biological properties will be further investigated and subsequently documented.

Harold C. Slavkin: A Transformative Leader of Our Times

Harold (Hal) C. Slavkin, DDS, the 22nd president of the American Association for Dental, Oral, and Craniofacial Research (1993 to 1994), died on December 22, 2023. During a career that spanned almost 6 decades, Hal distinguished himself as an international authority on craniofacial biology and an advocate for oral health equity. He served as dean of the University of Southern California’s dental school, founded the school’s Center for Craniofacial Molecular Biology, created the nation’s first PhD program in craniofacial biology, and served as the sixth director of the National Institute of Dental and Craniofacial Research. Hal’s studies of the molecular and cellular underpinnings of craniofacial malformations prepared him to champion translational research later in his career, when his work with patient advocates revealed the importance of applying new discoveries to clinical practice. A visionary thinker, skilled administrator, progressive educator, compelling communicator, researcher, scholar, and mentor, Hal was known as a Renaissance leader. He rejoiced in fostering collaborative synergies among people and organizations. Throughout his life, family was his central grounding force. He and his wife, Lois, advanced a wide range of social and community initiatives and took great pride in their children, grandchildren, and great-grandchildren. We remember Hal for his indelible spirit, unflappable enthusiasm for science, fierce advocacy for social justice, and infectious zest for life. Here, we outline his multidimensional accomplishments through the lenses of academia, government, and nonprofit organizations. Although it is with heavy hearts that we bid goodbye to this remarkable man, our spirits are lightened by the many gifts he left behind.