TFAP2A-activated ITGB4 promotes lung adenocarcinoma progression and inhibits CD4+/CD8+ T-cell infiltrations by targeting NF-κB signaling pathway.

Background: Immune-associated genes play vital roles in the tumorigenesis, progression and immunotherapy responses of malignant tumors. This study aimed to comprehensively evaluate the role and mechanism of novel immune-associated gene integrin ß4 (ITGB4) in the progression and immune microenvironment of lung adenocarcinoma (LUAD). Methods: There were 770 immune-associated genes curated from NanoString PanCancer Immune Profiling Panel. Differentially expressed immune-related genes were initially screened using transcriptome data from 57 paired LUAD samples in The Cancer Genome Atlas (TCGA) and 15 paired LUAD samples in GSE31210, and were further validated in 19 paired LUAD samples from our institution. Log-rank test was adopted to identify LUAD prognosis associated genes. Among the identified differentially expressed genes, ITGB4 was ultimately chosen for further analysis. Subsequently, the functionality and mechanisms of ITGB4 were investigated in two LUAD cell lines, A549 and PC9, which exhibited relatively high expression levels of ITGB4. Following this, the impact of ITGB4 on the proliferation and metastasis of LUAD in vivo was evaluated using nude mice. Additionally, its effect on T cell infiltration was studied using immunocompetent C57BL/6J mice. Results: ITGB4 was found to be significantly up-regulated in LUAD and associated with an unfavorable prognosis. Functionally, ITGB4 could promote LUAD cell proliferation, migration and invasion. Consistently, in vivo experiments demonstrated that ITGB4 knockdown suppressed LUAD tumor growth and metastasis. Additionally, ITGB4 could suppress CD4+ and CD8+ T-cell infiltrations in LUAD cells. Mechanistically, ITGB4 could activate the NF-κB signaling pathway by interacting with IκBα. Furthermore, TFAP2A could directly bind to the ITGB4 promoter and transcriptionally activate ITGB4 in LUAD cells. In addition, laminin-5, a ligand of ITGB4, was found to promote LUAD progression by activating the ITGB4 signaling. Conclusions: ITGB4 was transcriptionally activated by TFAP2A, and could promote LUAD progression and inhibit CD4+/CD8+ T-cell infiltrations by activating the NF-κB signaling pathway. ITGB4 may serve as a potential immunotherapeutic target of LUAD.

A Novel Upside-Down Thermal Annealing Method Toward High-Quality Active Layers Enables Organic Solar Cells with Efficiency Approaching 20.

The emerging non-fullerene acceptors with low voltage losses have pushed the power conversion efficiency of organic solar cells (OSCs) to ≈20% with auxiliary morphology optimization. Thermal annealing (TA), as the most widely adopted post-treatment method, has been playing an essential role in realizing the potential of various material systems. However, the procedure of TA, i.e., the way that TA is performed, is almost identical among thousands of OSC papers since ≈30 years ago other than changes in temperature and annealing time. Herein, a reverse thermal annealing (RTA) technique is developed, which can enhance the dielectric constant of active layer film, thereby producing a smaller Coulomb capture radius (14.93 nm), meanwhile, forming a moderate nano-scale phase aggregation and a more favorable face-on molecular stacking orientation. Thus, this method can reduce the decline in open circuit voltage of the conventional TA method by achieving decreased radiative (0.334 eV) and non-radiative (0.215 eV) recombination loss. The power conversion efficiency of the RTA PM6:L8-BO-X device increases to 19.91% (certified 19.42%) compared to the TA device (18.98%). It is shown that this method exhibits a superb universality in 4 other material systems, revealing its dramatic potential to be employed in a wide range of OSCs.

Breakthroughs in AI and multi-omics for cancer drug discovery: A review.

Cancer is one of the biggest medical challenges we face today. It is characterized by abnormal, uncontrolled growth of cells that can spread to different parts of the body. Cancer is extremely complex, with genetic variations and the ability to adapt and evolve. This means we must continuously pursue innovative approaches to developing new cancer drugs. While traditional drug discovery methods have led to important breakthroughs, they also have significant limitations that make it difficult to efficiently create new, cost-effective cancer therapies. Integrating computational tools into the cancer drug discovery process is a major step forward. By harnessing computing power, we can overcome some of the inherent barriers of traditional methods. This review examines the range of computational techniques now being used, such as molecular docking, QSAR models, virtual screening, and pharmacophore modeling. It looks at recent advances in areas like machine learning and molecular simulations. The review also discusses the current challenges with these technologies and envisions future directions, underscoring how transformative these computational tools can be for creating targeted, new cancer treatments.

Genetic analysis of preaxial polydactyly: identification of novel variants and the role of ZRS duplications in a Chinese cohort of 102 cases.

Preaxial polydactyly (PPD) is a congenital limb malformation, previously reported to be caused primarily by variants in the ZRS and upstream preZRS regions. This study investigated genetic variations associated with PPD, focusing on point variants and copy number variations (CNVs) in the ZRS and preZRS regions. Comprehensive genetic analyses were conducted on 102 patients with PPD, including detailed clinical examinations and Sanger sequencing of the ZRS and preZRS regions. Additionally, real-time quantitative PCR (qPCR) was used to detect CNVs in the ZRS region. The evolutionary conservation and population frequencies of identified variants were also evaluated. Six point variants were identified, among which four are likely pathogenic novel variants: 93G > T (g.156584477G > T), 106G > A (g.156584464G > A), 278G > A (g.156584292G > A), and 409A > C (g.156585378A > C). Additionally, qPCR analysis revealed that 66.67% of patients exhibited ZRS duplications. Notably, these duplications were also present in cases with newly identified potential pathogenic point variants. These findings suggest the possible interaction of point variants in ZRS and preZRS through a common pathogenic mechanism, leading jointly to PPD. The findings expand the variant spectrum associated with non-syndromic polydactyly and highlight that, despite different classifications, anterior polydactyly caused by variants in ZRS and nearby regions may share common pathogenic mechanisms. The incorporation of various variant types in genetic screening can effectively enhance the rate of pathogenic variant detection and contribute to the cost-effectiveness of genetic testing for limb developmental defects, thereby promoting healthy births.

Regulating Intermolecular Interactions and Film Formation Kinetics for Record Efficiency in Difluorobenzothiadizole-based Organic Solar Cells.

The difluorobenzothiadizole (ffBT) unit is one of the most classic electron-accepting building blocks used to construct D-A copolymers for applications in organic solar cells (OSCs). Historically, ffBT-based polymers have achieved record power conversion efficiencies (PCEs) in fullerene-based OSCs owing to their strong temperature-dependent aggregation (TDA) characteristics. However, their excessive miscibility and rapid aggregation kinetics during film formation have hindered their performance with state-of-the-art non-fullerene acceptors (NFAs). Herein, we synthesized two ffBT-based copolymers, PffBT-2T and PffBT-4T, incorporating different π-bridges to modulate intermolecular interactions and aggregation tendencies. Experimental and theoretical studies revealed that PffBT-4T exhibits reduced electrostatic potential differences and miscibility with L8-BO compared to PffBT-2T. This facilitates improved phase separation in the active layer, leading to enhanced molecular packing and optimized morphology. Moreover, PffBT-4T demonstrated a prolonged nucleation and crystal growth process, leading to enhanced molecular packing and optimized morphology. Consequently, PffBT-4T-based devices achieved a remarkable PCE of 17.5%, setting a new record for ffBT-based photovoltaic polymers. Our findings underscore the importance of conjugate backbone modulation in controlling aggregation behavior and film formation kinetics, providing valuable insights for the design of high-performance polymer donors in organic photovoltaics.

Operation room nursing based on humanized nursing mode combined with nitric oxide on rehabilitation effect after lung surgery.

BACKGROUND: With advancements in the diagnosis and treatment of lung diseases, lung segment surgery has become increasingly common. Postoperative rehabilitation is critical for patient recovery, yet challenges such as complications and adverse outcomes persist. Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications. AIM: To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery, focusing on pulmonary function, recovery speed, and overall treatment costs. METHODS: A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group (n = 39) receiving a routine nursing program and an experimental group (n = 40) receiving additional humanized nursing interventions and atomized inhalation of nitric oxide. Key indicators were compared between the two groups alongside an analysis of treatment costs. RESULTS: The experimental group demonstrated significant improvements in pulmonary function, reduced average recovery time, and lower total treatment costs compared to the control group. Moreover, the quality of life in the experimental group was significantly better in the 3 months post-surgery, indicating a more effective rehabilitation process. CONCLUSION: The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes, accelerates recovery, and reduces economic burden. This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.

Negative energy balance affects perinatal ewe performance, rumen morphology, rumen flora structure, and placental function.

This study investigated the effects of negative energy balance (NEB) on perinatal ewes, with a focus on changes in growth performance, serum biochemical parameters, rumen fermentation, ruminal bacteria composition, placental phenotype-related indicators, and expression levels of genes related to placental function. Twenty ewes at 130 days of gestation were randomly allocated to either the positive energy balance (PEB) or NEB groups. In the experiment, ewes in the PEB group were fed the same amount as their intake during the pre-feeding baseline period, while ewes in the NEB group were restricted to 70% of their individual baseline feed intake. The experiment was conducted until 42 days postpartum, and five double-lamb ewes per group were selected for slaughter. The results demonstrated that NEB led to a significant decrease in body weight, carcass weight, and the birth and weaning weights of lambs (P < 0.05). Additionally, NEB caused alterations in serum biochemical parameters, such as increased non-esterified fatty acids and ß-hydroxybutyrate levels and decreased cholesterol and albumin levels (P < 0.05). Rumen fermentation and epithelial parameters were also affected, with a reduction in the concentrations of acetic acid, butyric acid, total acid and a decrease in the length of the rumen papilla (P < 0.05). Moreover, NEB induced changes in the structure and composition of ruminal bacteria, with significant differences in α-diversity indices and rumen microbial community composition (P < 0.05). Gene expression in rumen papilla and ewe placenta was also affected, impacting genes associated with glucose and amino acid transport, proliferation, apoptosis, and angiogenesis (P < 0.05). These findings screened the key microbiota in the rumen of ewes following NEB and highlighted the critical genes associated with rumen function. Furthermore, this study revealed the impact of NEB on placental function in ewes, providing a foundation for investigating how nutrition in ewes influences reproductive performance. This research demonstrates how nutrition regulates reproductive performance by considering the combined perspectives of rumen microbiota and placental function.

Acidification state and interannual variability in marginal sea: A case study of the Bohai and the Yellow Seas surface waters in April 2023.

The acidification of the marginal seawater was a more intricate process than the ocean. Although some studies have been done on seasonal acidification in the bottom water of Chinese marginal seas, research on surface water acidification has still been insufficient. We analyzed the acidification properties and controlling factors in the Bohai Sea (BS) and Yellow Sea (YS) surface water during April 2023. The observation showed that the average surface water pH of the BS, North Yellow Sea (NYS), and South Yellow Sea (SYS) were 8.09 ± 0.06, 8.13 ± 0.05, and 8.15 ± 0.05. Phytoplankton significantly impacted pH and Ωarag, while riverine inputs and biological activity played a vital role in controlling DIC and TA. The Yellow River significantly impacted the BS. The North Yellow Sea Cold Water Mass had a limited impact on acidification, while the South Yellow Sea Cold Water Mass significantly affected the SYS. Regarding seasonal fluctuations, Ωarag was significantly higher in summer than in other seasons. DIC and TA showed different patterns in both the BS and YS, with a minimal fluctuation in pH. Over the last two decades, the pH in the BS showed a slight annual decline, and the rate of change was (-1.45 ± 2.19) × 10-5 yr-1. In contrast, the NYS and SYS have slightly risen, with rates of change of (2.39 ± 1.24) × 10-5 and (1.23 ± 0.76) × 10-5 yr-1. We believed that surface water acidification in the BS and YS did not follow the expected trend of significant acidification observed in open oceanic regions. Instead, the acidification process in these marginal seas was dominated by local factors such as riverine inputs, biological activity, and cold water masses, resulting in minimal pH changes over the last two decades.

Plasma Insulin Predicts Early Amyloid-ß Pathology Changes in Alzheimer's Disease.

Background: Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD), sharing similar pathophysiological traits like impaired insulin signaling. Objective: To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology. Methods: A total of 304 participants were included in the Alzheimer's Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages. Results: In the non-demented group, amyloid-ß (Aß)+ participants (e.g., as reflected by CSF Aß42) exhibited significantly lower plasma insulin levels compared to non-demented Aß-participants (p < 0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF Aß42 and pTau181 levels) when compared to the A-T- group within the non-dementia group (p = 0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF Aß42 levels (p < 0.001) across all participants. This association was particularly significant in the Aß-group (p = 0.002) and among non-demented individuals (p < 0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF Aß42 (p = 0.006), whereas baseline CSF Aß42 did not show a similar correlation with changes in plasma insulin over time. Conclusions: These findings suggest an association between plasma insulin and early Aß pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early Aß pathology.

Sex differences in the relationship between depression and Alzheimer's disease-mechanisms, genetics, and therapeutic opportunities.

Depression and Alzheimer's disease (AD) are prevalent neuropsychiatric disorders with intriguing epidemiological overlaps. Their interrelation has recently garnered widespread attention. Empirical evidence indicates that depressive disorders significantly contribute to AD risk, and approximately a quarter of AD patients have comorbid major depressive disorder, which underscores the bidirectional link between AD and depression. A growing body of evidence substantiates pervasive sex differences in both AD and depression: both conditions exhibit a higher incidence among women than among men. However, the available literature on this topic is somewhat fragmented, with no comprehensive review that delineates sex disparities in the depression-AD correlation. In this review, we bridge these gaps by summarizing recent progress in understanding sex-based differences in mechanisms, genetics, and therapeutic prospects for depression and AD. Additionally, we outline key challenges in the field, holding potential for improving treatment precision and efficacy tailored to male and female patients' distinct needs.

Effect of apheresis plasma donation on plasma uric acid levels, the lipid profile, and major plasma proteins in plasma donors in China: A multicenter, prospective cohort study.

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

Semi-supervised learning in diagnosis of infant hip dysplasia towards multisource ultrasound images.

Background: Automated diagnosis of infant hip dysplasia is heavily affected by the individual differences among infants and ultrasound machines. Methods: Hip sonographic images of 493 infants from various ultrasound machines were collected in the Department of Orthopedics in Yangzhou Maternal and Child Health Care Service Centre. Herein, we propose a semi-supervised learning method based on a feature pyramid network (FPN) and a contrastive learning scheme based on a Siamese architecture. A large amount of unlabeled data of ultrasound images was used via the Siamese network in the pre-training step, and then a small amount of annotated data for anatomical structures was adopted to train the model for landmark identification and standard plane recognition. The method was evaluated on our collected dataset. Results: The method achieved a mean Dice similarity coefficient (DSC) of 0.7873 and a mean Hausdorff distance (HD) of 5.0102 in landmark identification, compared to the model without contrastive learning, which had a mean DSC of 0.7734 and a mean HD of 6.1586. The accuracy, precision, and recall of standard plane recognition were 95.4%, 91.64%, and 94.86%, respectively. The corresponding area under the curve (AUC) was 0.982. Conclusions: This study proposes a semi-supervised deep learning method following Graf's principle, which can better utilize a large volume of ultrasound images from various devices and infants. This method can identify the landmarks of infant hips more accurately than manual operators, thereby improving the efficiency of diagnosis of infant hip dysplasia.

The key pathways for drought tolerance in Cerasus humilis were unveiled through transcriptome analysis.

Drought stress exerts a significant impact on the growth, development, and yield of fruit trees. Cerasus humilis is an endemic drought-resistant fruit tree in northern China. To elucidate the underlying mechanism of drought resistance in C. humilis, comprehensive physiological measurements and transcriptome analysis were conducted on the leaves of C. humilis subjected to 15- or 22-days of drought stress. We identified multiple GO terms and KEGG pathways associated with the drought stress response by performing GO and KEGG analysis on DEGs. Furthermore, through the prediction of transcription factors (TFs) and analysis of their expression levels, we observed differential expression patterns among most members of stress-responsive TF families as the duration of drought stress increased. WGCNA analysis was performed on the transcriptome to identify gene cluster modules that exhibited a strong correlation with the durations of drought. Subsequently, these modules underwent GO and KEGG enrichment analyses. The study revealed that the TF-mediated lignin biosynthesis pathway, along with the plant hormone signal transduction pathway, played a prominent role in responding to drought stress of C. humilis. Gene profiling analysis, qRT-PCR, and determination of phytohormone and lignin contents further supported this hypothesis. The hierarchical gene regulatory network was finally constructed based on DEGs from the aforementioned key enriched pathways to predict the gene regulatory mechanisms in response to stress for C. humilis. The findings from this study provide valuable insights into how C. humilis copes with drought stress while analyzing crucial gene pathways associated with its resistance from a TF perspective. This research is significant for the genetic breeding of economic forests.

CAIDE Score, Alzheimer's Disease Pathology, and Cognition in Cognitively Normal Adults: The CABLE Study.

Background: Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score serves as a credible predictor of an individual's risk of dementia. However, studies on the link of the CAIDE score to Alzheimer's disease (AD) pathology are scarce. Objective: To explore the links of CAIDE score to cerebrospinal fluid (CSF) biomarkers of AD as well as to cognitive performance. Methods: In the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, we recruited 600 cognitively normal participants. Correlations between the CAIDE score and CSF biomarkers of AD as well as cognitive performance were probed through multiple linear regression models. Whether the correlation between CAIDE score and cognitive performance was mediated by AD pathology was researched by means of mediation analyses. Results: Linear regression analyses illustrated that CAIDE score was positively associated with tau-related biomarkers, including pTau (p < 0.001), tTau (p < 0.001), as well as tTau/Aß42 (p = 0.008), while it was in negative association with cognitive scores, consisting of MMSE score (p < 0.001) as well as MoCA score (p < 0.001). The correlation from CAIDE score to cognitive scores was in part mediated by tau pathology, with a mediation rate varying from 3.2% to 13.2%. Conclusions: A higher CAIDE score, as demonstrated in our study, was linked to more severe tau pathology and poorer cognitive performance, and tau pathology mediated the link of CAIDE score to cognitive performance. Increased dementia risk will lead to cognitive decline through aggravating neurodegeneration.

Physical frailty, genetic predisposition, and incident dementia: a large prospective cohort study.

Physical frailty and genetic factors are both risk factors for increased dementia; nevertheless, the joint effect remains unclear. This study aimed to investigated the long-term relationship between physical frailty, genetic risk, and dementia incidence. A total of 274,194 participants from the UK Biobank were included. We applied Cox proportional hazards regression models to estimate the association between physical frailty and genetic and dementia risks. Among the participants (146,574 females [53.45%]; mean age, 57.24 years), 3,353 (1.22%) new-onset dementia events were recorded. Compared to non-frailty, the hazard ratio (HR) for dementia incidence in prefrailty and frailty was 1.396 (95% confidence interval [CI], 1.294-1.506, P < 0.001) and 2.304 (95% CI, 2.030-2.616, P < 0.001), respectively. Compared to non-frailty and low polygenic risk score (PRS), the HR for dementia risk was 3.908 (95% CI, 3.051-5.006, P < 0.001) for frailty and high PRS. Furthermore, among the participants, slow walking speed (HR, 1.817; 95% CI, 1.640-2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545-1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502-1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479-1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328-1.615, P < 0.001) were independently associated with dementia risk compared to non-frailty. Particularly, precise modulation for different dementia genetic risk populations can also be identified due to differences in dementia risk resulting from the constitutive pattern of frailty in different genetic risk populations. In conclusion, both physical frailty and high genetic risk are significantly associated with higher dementia risk. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, especially in those at high genetic risk.

Identification and functional marker development of SbPLSH1 conferring purple leaf sheath in sorghum.

KEY MESSAGE: We identified a SbPLSH1gene conferring purple leaf sheath in sorghum (sorghumbicolor(L.) Moench)and developed a functional markerfor it. The purple leaf sheath of sorghum, a trait mostly related to anthocyanin deposition, is a visually distinguishable morphological marker widely used to evaluate the purity of crop hybrids. We aimed to dissect the genetic mechanism for leaf sheath color to mine the genes regulating this trait. In this study, two F2 populations were constructed by crossing a purple leaf sheath inbred line (Gaoliangzhe) with two green leaf sheath inbred lines (BTx623 and Silimei). Based on the results of bulked-segregant analysis sequencing, bulk-segregant RNA sequencing, and map-based cloning, SbPLSH1 (Sobic.006G175700), which encodes a bHLH transcription factor on chromosome 6, was identified as the candidate gene for purple leaf sheath in sorghum. Genetic analysis demonstrated that overexpression of SbPLSH1 in Arabidopsis resulted in anthocyanin deposition and purple petiole, while two single-nucleotide polymorphism (SNP) variants on the exon 6 resulted in loss of function. Further haplotype analysis revealed that there were two missense mutations and one cis-acting element mutation in SbPLSH1, which are closely associated with leaf sheath color in sorghum. Based on the variations, a functional marker (LSC4-2) for marker-assisted selection was developed, which has a broad-spectrum capability of distinguishing leaf sheath color in natural variants. In summary, this study lays a foundation for analyzing the genetic mechanism for sorghum leaf sheath color.

A Review of Bioactive Compound Effects from Primary Legume Protein Sources in Human and Animal Health.

The global demand for sustainable and nutritious food sources has catalyzed interest in legumes, known for their rich repertoire of health-promoting compounds. This review delves into the diverse array of bioactive peptides, protein subunits, isoflavones, antinutritional factors, and saponins found in the primary legume protein sources-soybeans, peas, chickpeas, and mung beans. The current state of research on these compounds is critically evaluated, with an emphasis on the potential health benefits, ranging from antioxidant and anticancer properties to the management of chronic diseases such as diabetes and hypertension. The extensively studied soybean is highlighted and the relatively unexplored potential of other legumes is also included, pointing to a significant, underutilized resource for developing health-enhancing foods. The review advocates for future interdisciplinary research to further unravel the mechanisms of action of these bioactive compounds and to explore their synergistic effects. The ultimate goal is to leverage the full spectrum of benefits offered by legumes, not only to advance human health but also to contribute to the sustainability of food systems. By providing a comprehensive overview of the nutraceutical potential of legumes, this manuscript sets a foundation for future investigations aimed at optimizing the use of legumes in the global pursuit of health and nutritional security.