EGFR degraders in non-small-cell lung cancer: Breakthrough and unresolved issue.

The epidermal growth factor receptor (EGFR) has been well validated as a therapeutic target for anticancer drug discovery. Osimertinib has become the first globally accessible third-generation EGFR inhibitor, representing one of the most advanced developments in non-small-cell lung cancer (NSCLC) therapy. However, a tertiary Cys797 to Ser797 (C797S) point mutation has hampered osimertinib treatment in patients with advanced EGFR-mutated NSCLC. Several classes of fourth-generation EGFR inhibitors were consequently discovered with the aim of overcoming the EGFRC797S mutation-mediated resistance. However, no clinical efficacy data of the fourth-generation EGFR inhibitors were reported to date, and EGFRC797S mutation-mediated resistance remains an "unmet clinical need." Proteolysis-targeting chimeric molecules (PROTACs) obtained from EGFR-TKIs have been developed to target drug resistance EGFR in NSCLC. Some PROTACs are from nature products. These degraders compared with EGFR inhibitors showed better efficiency in their cellular potency, inhibition, and toxicity profiles. In this review, we first introduce the structural properties of EGFR, the resistance, and mutations of EGFR, and then mainly focus on the recent advances of EGFR-targeting degraders along with its advantages and outstanding challenges.

Hierarchical joint analysis of marginal summary statistics-Part I: Multipopulation fine mapping and credible set construction.

Recent advancement in genome-wide association studies (GWAS) comes from not only increasingly larger sample sizes but also the shift in focus towards underrepresented populations. Multipopulation GWAS increase power to detect novel risk variants and improve fine-mapping resolution by leveraging evidence and differences in linkage disequilibrium (LD) from diverse populations. Here, we expand upon our previous approach for single-population fine-mapping through Joint Analysis of Marginal SNP Effects (JAM) to a multipopulation analysis (mJAM). Under the assumption that true causal variants are common across studies, we implement a hierarchical model framework that conditions on multiple SNPs while explicitly incorporating the different LD structures across populations. The mJAM framework can be used to first select index variants using the mJAM likelihood with different feature selection approaches. In addition, we present a novel approach leveraging the ideas of mediation to construct credible sets for these index variants. Construction of such credible sets can be performed given any existing index variants. We illustrate the implementation of the mJAM likelihood through two implementations: mJAM-SuSiE (a Bayesian approach) and mJAM-Forward selection. Through simulation studies based on realistic effect sizes and levels of LD, we demonstrated that mJAM performs well for constructing concise credible sets that include the underlying causal variants. In real data examples taken from the most recent multipopulation prostate cancer GWAS, we showed several practical advantages of mJAM over other existing multipopulation methods.

The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study.

BACKGROUND: Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate. RESULTS: ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year. CONCLUSIONS: ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components. TRIAL REGISTRATION: registered with Chictr.org.cn (ChiCTR2100051405).

Factors influencing delayed high-dose methotrexate excretion and its correlation with adverse reactions after treatment in children with malignant hematological tumors.

Background: High-dose methotrexate (HDMTX) is crucial in treating pediatric malignant hematological tumors. However, its use is often complicated by delayed excretion and associated adverse reactions, which can significantly affect treatment outcomes and patient safety. Identifying risk factors is essential for safer, more effective therapy. This study aimed to investigate the influencing factors for delayed excretion and their correlation with adverse reactions in children with malignant hematological tumors after receiving HDMTX chemotherapy. Methods: From April to October 2021, the clinical information of children who had undergone HDMTX chemotherapy and had their blood tested for drug concentration was gathered by the Department of Hematology and Oncology at Shanghai Children's Medical Center. Via univariate and multivariate logistic regression, the factors affecting the delayed excretion of HDMTX were examined, and the relationship between delayed excretion and unfavorable effects in children was determined. Results: This study included 99 patients comprising 199 courses of HDMTX. The occurrence rate of HDMTX delayed excretion was 20.1%. Age ≥9 years and a 24-hour methotrexate (MTX) concentration of 64 µmol/L were independent risk factors for delayed MTX excretion according to multivariate logistic regression analysis (P<0.05). Negative side effects, such as fever, infection, mucositis, gastrointestinal response, and decreased platelet count in children with delayed excretion were statistically significant when compared to those of children with normal excretion. White blood cell reduction, hemoglobin levels below 65 g/L, MTX excretion delay, and concomitant etoposide treatment were all independent risk factors for infection in children. Conclusions: To estimate the risk of delayed MTX excretion during HDMTX therapy, patient laboratory data should be scrutinized, especially for patients ≥9 years or those with a 24-hour MTX concentration of greater than 64 µmol/L.

Vegetative cell wall protein OsGP1 regulates cell wall mediated soda saline-alkali stress in rice.

Plant growth and development are inhibited by the high levels of ions and pH due to soda saline-alkali soil, and the cell wall serves as a crucial barrier against external stresses in plant cells. Proteins in the cell wall play important roles in plant cell growth, morphogenesis, pathogen infection and environmental response. In the current study, the full-length coding sequence of the vegetative cell wall protein gene OsGP1 was characterized from Lj11 (Oryza sativa longjing11), it contained 660 bp nucleotides encoding 219 amino acids. Protein-protein interaction network analysis revealed possible interaction between CESA1, TUBB8, and OsJ_01535 proteins, which are related to plant growth and cell wall synthesis. OsGP1 was found to be localized in the cell membrane and cell wall. Furthermore, overexpression of OsGP1 leads to increase in plant height and fresh weight, showing enhanced resistance to saline-alkali stress. The ROS (reactive oxygen species) scavengers were regulated by OsGP1 protein, peroxidase and superoxide dismutase activities were significantly higher, while malondialdehyde was lower in the overexpression line under stress. These results suggest that OsGP1 improves saline-alkali stress tolerance of rice possibly through cell wall-mediated intracellular environmental homeostasis.

Ruthenium-Catalyzed C-H Arylation of Aromatic Acids with ortho-Haloaniline To Access Phenanthridinones.

Phenanthridinone is a significant moiety in pharmaceutical and material science; thus, it is highly desirable to develop an efficient and robust method to construct phenanthridinone from readily available starting materials. Herein, we report a Ru-catalyzed C-H arylation of aromatic carboxylic acids with ortho-haloanilines, followed by intramolecular dehydration to afford phenanthridinones in high yields.

1,2,3-Thiadiazole as a Modifiable and Scalable Directing Group for ortho-C-H Functionalization.

In the last few decades, directed C-H bond functionalization has had enormous applicability in academia and industry. The development of a novel, readily accessible, and scalable directing group with modifiable ability is highly desirable in C-H functionalization. Herein, we report the 1,2,3-thiadiazole as a modifiable directing group for C-H amidation and alkynylation with dioxazolones, p-toluenesulfonyl azide, and bromoalkynes in high yield. The densely functionalized 1,2,3-thiadiazole products are modified into thioamide, multisubstituted furan, γ-thiapyrone, thiazole, and various alkynyl sulfides through simple and one-step reactions. The competition experiments reveal that the directing ability of 1,2,3-thiadiazole is slightly weaker than pyridine and bidentate amide but stronger than the widely used carboxylate.

Association between adequate dietary protein and all-cause and cardiovascular mortality in patients with selective glomerular hypofiltration syndrome.

Aims: To determine the impact of dietary protein intake and protein sources on all-cause and cardiovascular mortality of selective glomerular hypofiltration syndrome (SGHS) patients. Methods: This study recruited participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. Cox proportional hazard models and competing risk models were employed to investigate the effects of dietary protein intake and protein sources on all-cause and cardiovascular mortality in SGHS patients. Additionally, Cox regression models utilizing restricted cubic splines (RCS) were used to explore potential non-linear associations. Results: Over a median follow-up period of 204 months, 20.71% (449/2168) participants died, with 5.40% (117/2168) experiencing cardiovascular mortality. In the fully adjusted model, participants with the highest dietary protein intake (Q4, ≥107.13 g d-1) exhibited a 40% reduced risk of all-cause mortality (HR: 0.60, 95% CI: 0.39 to 0.94) and an 88% reduced risk of cardiovascular mortality (HR: 0.12, 95% CI: 0.04 to 0.35) compared to those with the lowest dietary protein intake (Q1, < 57.93 g d-1). Notably, non-red meat protein sources were found to reduce the risk of all-cause and cardiovascular mortality, whereas no significant association was observed with red meat consumption. Conclusion: Adequate dietary protein intake has been linked to a decreased risk of all-cause and cardiovascular mortality in individuals with selective glomerular hypofiltration syndromes. This protective effect seems to be primarily associated with protein obtained from non-red meat sources.

Ametoctradin resistance risk and its resistance-related point mutation in PsCytb of Phytophthora sojae confirmed using ectopic overexpression.

Ametoctradin is mainly used to treat plant oomycetes diseases, but the mechanism and resistance risk of ametoctradin in Phytophthora sojae remain unknown. This study determined the ametoctradin sensitivity of 106 P. sojae isolates and found that the frequency distribution of the median effective concentration (EC50) of ametoctradin was unimodal with a mean value of 0.1743 ± 0.0901 µg/mL. Furthermore, ametoctradin-resistant mutants had a substantially lower fitness index compared with that of wild-type isolates. Although ametoctradin did not show cross-resistance to other fungicides, negative cross-resistance to amisulbrom was found. In comparison to sensitive isolates, the control efficacy of ametoctradin to resistant mutants was lower, implying a low to moderate ametoctradin resistance risk in P. sojae. All ametoctradin-resistant mutants contained a S33L point mutation in PsCytb. A system with overexpression of PsCytb in the nucleus was established. When we ectopically overexpressed S33L-harboring PsCytb, P. sojae developed ametoctradin resistance. We hypothesized that the observed negative resistance between ametoctradin and amisulbrom could be attributed to conformational changes in the binding cavity of PsCytb at residues 33 and 220.

Single-cell sequencing reveals increased LAMB3-positive basal keratinocytes and ZNF90-positive fibroblasts in autologous cultured epithelium.

Autologous cultured epithelium grafting (ACEG) presents a promising treatment for refractory vitiligo, yet concerns regarding infections and immunological reactions hinder its surgical use due to serum and feeder dependencies. Addressing this, we culture autologous epithelium under serum- and feeder-free (SFF) conditions, comparing its safety and efficacy with serum- and feeder-dependent (SFD) conditions in stable vitiligo patients, and we discover no significant differences in repigmentation between the SFF and SFD grafts. Single-cell RNA transcriptomics on SFF- and SFD-cultured epithelium alongside healthy skin reveal increased populations of LAMB3+ basal keratinocytes and ZNF90+ fibroblasts in the SFF sheets. Functional analyses showcase active cellular metabolism in LAMB3+ basal keratinocytes, vital in extracellular matrix homeostasis, while ZNF90+ fibroblasts demonstrate increased differentiation, essential in collagen formation for cell adhesion. Importantly, these cell populations in SFF sheets exhibit enhanced interactions with melanocytes compared to SFD sheets. Further, knockdown experiments of LAMB3 in keratinocytes and ZNF90 in fibroblasts lead to a downregulation in melanocyte ligand-receptor-related genes. Overall, SFF sheets demonstrate comparable efficacy to SFD sheets, offering superior safety. LAMB3+ basal keratinocytes and ZNF90+ fibroblasts act as potential drivers behind repigmentation in ACEG under SFF conditions. This study provides translational insights into ACEG repigmentation and potential therapeutic targets for vitiligo.

Enhanced quality of hESC-derived melanocytes through modified concentration of endothelin-1.

The study investigated the effectiveness of EDN1 and EDN3 cytokines in the differentiation of melanocytes from hESCs. The findings showed that 100 nM EDN1 was more effective in promoting hESC to CD117+/TYR+ melanoblasts compared to 100 nM EDN3. Additionally, maintaining melanoblasts is beneficial for preserving the ability to proliferate. The study found that 10 nM EDN1 helped maintain the proliferation of melanoblasts without over maturing them into melanocytes in the late stage of differentiation. Thus, using 100 nM EDN1 in the initial stage and 10 nM EDN1 in the late stage proved to be an efficient and cost-effective method for obtaining hESC-derived melanocytes. The preliminary results suggest that EDN1 promotes melanoblast formation during the initial differentiation stage through its binding to both the EDNRB receptor and EDNRA receptor. This study provides a valuable tool for studying the development of human melanocytes and modelling the biology of disease.

SCAR: Single-cell and Spatially-resolved Cancer Resources.

Advances in sequencing and imaging technologies offer a unique opportunity to unravel cell heterogeneity and develop new immunotherapy strategies for cancer research. There is an urgent need for a resource that effectively integrates a vast amount of transcriptomic profiling data to comprehensively explore cancer tissue heterogeneity and the tumor microenvironment. In this context, we developed the Single-cell and Spatially-resolved Cancer Resources (SCAR) database, a combined tumor spatial and single-cell transcriptomic platform, which is freely accessible at http://8.142.154.29/SCAR2023 or http://scaratlas.com. SCAR contains spatial transcriptomic data from 21 tumor tissues and single-cell transcriptomic data from 11 301 352 cells encompassing 395 cancer subtypes and covering a wide variety of tissues, organoids, and cell lines. This resource offers diverse functional modules to address key cancer research questions at multiple levels, including the screening of tumor cell types, metabolic features, cell communication and gene expression patterns within the tumor microenvironment. Moreover, SCAR enables the analysis of biomarker expression patterns and cell developmental trajectories. SCAR also provides a comprehensive analysis of multi-dimensional datasets based on 34 state-of-the-art omics techniques, serving as an essential tool for in-depth mining and understanding of cell heterogeneity and spatial location. The implications of this resource extend to both cancer biology research and cancer immunotherapy development.

SCAN: Spatiotemporal Cloud Atlas for Neural cells.

The nervous system is one of the most complicated and enigmatic systems within the animal kingdom. Recently, the emergence and development of spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) technologies have provided an unprecedented ability to systematically decipher the cellular heterogeneity and spatial locations of the nervous system from multiple unbiased aspects. However, efficiently integrating, presenting and analyzing massive multiomic data remains a huge challenge. Here, we manually collected and comprehensively analyzed high-quality scRNA-seq and ST data from the nervous system, covering 10 679 684 cells. In addition, multi-omic datasets from more than 900 species were included for extensive data mining from an evolutionary perspective. Furthermore, over 100 neurological diseases (e.g. Alzheimer's disease, Parkinson's disease, Down syndrome) were systematically analyzed for high-throughput screening of putative biomarkers. Differential expression patterns across developmental time points, cell types and ST spots were discerned and subsequently subjected to extensive interpretation. To provide researchers with efficient data exploration, we created a new database with interactive interfaces and integrated functions called the Spatiotemporal Cloud Atlas for Neural cells (SCAN), freely accessible at http://47.98.139.124:8799 or http://scanatlas.net. SCAN will benefit the neuroscience research community to better exploit the spatiotemporal atlas of the neural system and promote the development of diagnostic strategies for various neurological disorders.

Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

A systematic review of the accuracy of digital surgical guides for dental implantation.

PURPOSE: This review aimed to reveal the influence of implant guides on surgical accuracy with regard to supporting types, manufacturing methods and design (including fixation screws and sleeves). METHODS: A literature search related to accuracy of surgical guides for dental implantation was performed in Web of Science and PubMed. Studies with in vivo or in vitro deviation data published in recent 5 years (2018-2022) were included and assessed by Newcastle-Ottawa Scale with regard to risk of bias and reliability degree of clinical studies. Accuracy-related deviation data were summarized as forest plots and normal distributions. RESULTS: Forty-one articles were included with high degree of credibility. Data showed that implant surgery accuracy can be achieved with mean distance deviation < 2 mm (most < 1 mm) and angular deviation < 8° (most < 5°). CONCLUSIONS: Bilateral tooth-supported guides exhibited highest in vitro accuracy and similar in vivo accuracy to unilateral tooth-supported guides; mucosa-supported guides exhibit lowest in vivo accuracy, while its in vitro data showed low credibility due to mechanical complexity of living mucosa tissue. Milling exhibited higher in vivo accuracy of guides than 3d-printing, though further data support was needed. Design of fixation screws and sleeves of implant guides affected the surgical accuracy and might remain a research focus in near future. However, lack of universal evaluation standards for implantation accuracy remained a major problem in this field. The influence of implant guides on surgical accuracy revealed in this review might shed light on future development of dental implantology.

Association between missing teeth number and all-cause and cardiovascular mortality: NHANES 1999-2004 and 2009-2014.

BACKGROUND: The association between tooth loss and all-cause and cardiovascular mortality requires further investigation. METHODS: This study included 17993 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999-2004 and 2009-2014. Weighted multivariable Cox proportional hazard models were used to assess the association between tooth loss and all-cause and cardiovascular mortality. Restricted cubic splines (RCS) were incorporated in the models to explore potential nonlinear relationships. RESULTS: Over a median follow-up of 116 months, 2152 participants died, including 625 cardiovascular deaths. Compared to participants without missing teeth, participants with 11-19 missing teeth had the highest risk of all-cause mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.43-2.51), while participants with 6-10 missing teeth had the highest risk of cardiovascular mortality (HR 2.51, 95% CI 1.68-3.76). RCS analyses revealed nonlinear associations between number of missing teeth and all-cause (p < 0.001) and cardiovascular (p = 0.001) mortality. With < 10 missing teeth, each additional missing tooth increased all-cause and cardiovascular mortality by 6% (HR 1.06, 95% CI 1.03-1.09) and 9% (HR 1.09, 95% CI 1.03-1.15), respectively. However, when the number of missing teeth was ≥10, the risk of mortality did not continue to increase with more missing teeth. A significant interaction was found between tooth loss and age (p < 0.001 for both outcomes). CONCLUSION: We observed an inverted L-shaped association between tooth loss and mortality, wherein risks increased with more missing teeth until 10, but did not continue increasing thereafter. The association was stronger in adults < 65 years old.

Innovative Solid Slippery Coating: Uniting Mechanical Durability, Optical Transparency, Anti-Icing, and Anti-Graffiti Traits.

Slippery coatings, such as the slippery liquid-infused porous surface (SLIPS), have gained significant attention for their potential applications in anti-icing and anti-fouling. However, they lack durability when subjected to mechanical impact. In this study, we have developed a robust slippery coating by blending polyurethane acrylate (PUA) with methyltriethoxysilane (MTES) and perfluoropolyether (PFPE) in the solvent of butyl acetate. The resulting mixture is homogeneous and allows for uniform coating on various substrates using a drop coating process followed by drying at 160 °C for 3 h. The cured coating exhibits excellent water repellency (contact angle of ~108° and sliding angle of ~8°), high transparency (average visible transmittance of ~90%), exceptional adherence to the substrate (5B rating according to ASTMD 3359), and remarkable hardness (4H on the pencil hardness scale). Moreover, the coating is quite flexible and can be folded without affecting its wettability. The robustness of the coating is evident in its ability to maintain a sliding angle below 25° even when subjected to abrasion, water jetting, high temperature, and UV irradiation. Due to its excellent nonwetting properties, the coating can be employed in anti-icing, anti-graffiti, and anti-sticking applications. It effectively reduces ice adhesion on aluminum substrates from approximately 217 kPa to 12 kPa. Even after 20 cycles of icing and de-icing, there is only a slight increase in ice adhesion, stabilizing at 40 kPa. The coating can resist graffiti for up to 400 cycles of writing with an oily marker pen and erasing with a tissue. Additionally, the coating allows for easy removal of 3M tape thereon without leaving any residue.

Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study.

BACKGROUND AND AIMS: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden. METHODS: This study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk. RESULTS: A total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59-3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21-2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002-1.006, P < 0.001) . CONCLUSION: Elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. WHAT IS ALREADY KNOWN ON THIS TOPIC?: Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear. WHAT THIS STUDY ADDS?: Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY?: Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD.

Role of Polysaccharides from Marine Seaweed as Feed Additives for Methane Mitigation in Ruminants: A Critical Review.

Given the increasing concerns regarding greenhouse gas emissions associated with livestock production, the need to discover effective strategies to mitigate methane production in ruminants is clear. Marine algal polysaccharides have emerged as a promising research avenue because of their abundance and sustainability. Polysaccharides, such as alginate, laminaran, and fucoidan, which are extracted from marine seaweeds, have demonstrated the potential to reduce methane emissions by influencing the microbial populations in the rumen. This comprehensive review extensively examines the available literature and considers the effectiveness, challenges, and prospects of using marine seaweed polysaccharides as feed additives. The findings emphasise that marine algal polysaccharides can modulate rumen fermentation, promote the growth of beneficial microorganisms, and inhibit methanogenic archaea, ultimately leading to decreases in methane emissions. However, we must understand the long-term effects and address the obstacles to practical implementation. Further research is warranted to optimise dosage levels, evaluate potential effects on animal health, and assess economic feasibility. This critical review provides insights for researchers, policymakers, and industry stakeholders dedicated to advancing sustainable livestock production and methane mitigation.