The review, led by Cunchao Zhao and colleagues, introduces a framework the authors call ESAR, short for Extraction–Structure–Activity Relationship. The central idea is deceptively simple: extraction conditions determine molecular structure, and molecular structure determines biological function. Yet the authors contend that decades of mushroom polysaccharide research have treated these three dimensions separately, with extraction specialists optimizing yields, chemists cataloging compositions, and pharmacologists screening activities, all without cross-linking the data needed to reveal causal, predictive relationships. The result, they argue, is a field that has remained largely descriptive rather than mechanistic.

To build the framework, the team searched Web of Science and Google Scholar for English-language studies published between 2020 and 2025, retrieving roughly 1,800 records. After screening and deduplication, about 206 studies were retained for qualitative synthesis, with inclusion contingent on analytical validation by at least two orthogonal techniques such as nuclear magnetic resonance spectroscopy, FTIR, gas chromatography–mass spectrometry, or size-exclusion chromatography coupled with multi-angle light scattering. The synthesis maps how processing variables, including pH, temperature, ionic strength, solvent type, and extraction time, feed into structural outputs such as monosaccharide composition, glycosidic linkages, molecular weight, and higher-order conformation, and how those outputs in turn govern biological effects.

The structural stakes are considerable. Most mushroom polysaccharides are dominated by glucose, mannose, and galactose, with rarer sugars such as fucose, rhamnose, arabinose, and xylose modulating heterogeneity. Mild hot-water extraction tends to enrich glucose-heavy beta-glucans, which primarily drive immune activation through the Dectin-1 receptor, whereas alkaline or enzyme-assisted routes recover more mannans and other heteropolymers that often correlate with antioxidant activity. Excess heat or acid can selectively strip away deoxy sugars or depolymerize the chains entirely. In one cited example, monosaccharide composition remained stable at 79 degrees Celsius for three hours, but extraction above 100 degrees Celsius produced clear compositional shifts and a marked loss of beta-glucan branching.

Molecular weight emerges as another dialable quality attribute, and the review is emphatic that the popular assumption that smaller is always better does not hold. Low-molecular-weight fragments penetrate cells more efficiently and can trigger reactive-oxygen-dependent apoptosis in cancer cells, while high-molecular-weight polymers achieve multivalent receptor clustering that supercharges immune signaling. Lentinan from shiitake, extracted with hot water, retains a triple-helical beta-glucan structure in the 4 to 60 kilodalton range that engages Dectin-1 and complement receptor 3 to stimulate cytokine release. Yet alkaline extraction of Phellinus linteus mycelia yielded a polysaccharide of roughly 343 kilodaltons with potent anti-proliferative and hepatoprotective effects, and a 336-kilodalton polysaccharide from Lentinus velutinus killed HeLa and HepG2 cancer cells while sparing normal cells. Mid-range polymers between roughly 20 and 40 kilodaltons, such as fractions from Helvella leucopus and Hypsizygus ulmarius, consistently combine solubility with receptor accessibility.

To make such comparisons meaningful across methods as different as hot water, deep eutectic solvents, ultrasound, microwave, and subcritical water, the authors introduce a standardized hardness index that quantifies extraction severity. Thermal treatments are scored in degree-hours, chemical treatments in molarity-hours, and physical intensification in watt-hours or megapascal-hours. The index reveals, for example, that subcritical water at 140 to 180 degrees Celsius drives auto-hydrolysis that slashes molecular weight to around 2 kilodaltons, while ionic liquids disrupt hydrogen bonding and swell cell walls to release intact 500-kilodalton beta-glucans. A table mapping dozens of species, from Ganoderma lucidum to Poria cocos, links each extraction condition to the resulting structure and activity, providing what amounts to a recipe book for tailoring polysaccharides to specific applications.

Conformation adds a further layer of control. Triple-helical conformations, generally preserved by hot-water or enzyme-assisted extraction, strengthen multivalent binding to immune receptors and are consistently associated with potent immunomodulation, activating signaling cascades through NF-kappaB and MAPK pathways. Ultrasound and microwave treatment can uncoil those helices, exposing side chains that sometimes strengthen radical scavenging but weaken Dectin-1 recognition. Chemical modification tells the same story in reverse: DMSO and alkali transform lentinan’s triple helix into single chains and reduce its activity, but incorporating selenium nanoparticles restores helicity and enhances antitumor efficacy, while sulfonation partially recovers function through charged-group interactions with immune receptors.

The framework’s predictive power is most striking in the immunology and metabolism chapters. Beta-(1,3)-glucans with beta-(1,6) branches from shiitake, reishi, and Dictyophora indusiata show the strongest macrophage and cytokine activation, whereas linear alpha-(1,4) or beta-(1,4) polysaccharides from some Pleurotus and Auricularia species yield milder antioxidant or prebiotic effects. In diabetes models, branched beta-glucans of moderate molecular weight enhance glucose uptake through GLUT4 translocation and PI3K/Akt activation, while gut microbiota studies show Morchella polysaccharides promoting beneficial Lactobacillus populations and Auricularia hydrolysates improving GLP-1 secretion. In obesity models, Pleurotus eryngii polysaccharides reduced fat deposition by upregulating LDL receptors, and Tremella fuciformis polysaccharides suppressed adipogenic transcription factors including PPAR-gamma and C/EBP-alpha.

Notably, the review challenges the assumption that purification always improves performance. Crude polysaccharides from Lepista nuda outperformed purified isolates in antioxidant assays, and complete deproteinization of lentinan extracts reduced interleukin-2 induction, pointing to synergistic contributions from co-extracted proteins and phenolics. The authors also flag persistent weaknesses in the literature: receptor activation is usually inferred rather than measured directly, helix preservation is rarely confirmed by circular dichroism or SAXS, and inconsistent calibration and assay protocols make cross-study comparison unreliable. Conflicting trends in antioxidant activity, with some studies favoring low-molecular-weight fractions and others high-molecular-weight ones, likely reflect these methodological inconsistencies rather than genuine biology.

The translational outlook is nonetheless substantial. Lentinan, schizophyllan, and the polysaccharopeptides PSK and PSP have already advanced to clinical use or evaluation as cancer adjuvants in Japan and China, and a meta-analysis of 52 randomized trials found lentinan combined with cisplatin improved outcomes in malignant pleural effusion. Beyond medicine, extraction-tailored polysaccharides are stabilizing emulsions, fortifying gluten-free baked goods, extending the shelf life of biodegradable curcumin-doped packaging films, and boosting probiotic viability in yogurt. The authors close with a playbook for the field: report processing parameters precisely, pair orthogonal structural analytics with mechanism-anchored bioassays on matched fractions, deliberately target molecular-weight sweet spots, and validate through adequately powered human studies. If adopted, they argue, ESAR could transform scattered correlations into predictive design rules, turning mushroom polysaccharide development from a search for active extracts into the engineering of process-defined polymer architectures for targeted therapeutic and nutritional ends.

Subject of Research: Process-programmed relationships between extraction methods, molecular structure, and bioactivity of edible and medicinal mushroom polysaccharides.

Article Title: Process-Programmed Extraction–Structure–Activity Relationships (ESAR) in edible and medicinal mushroom polysaccharides: a mechanistic and application-oriented framework

Article References: Zhao, C., Aaqil, M., He, R., Kamil, M., Zheng, J., Guo, Y., Zhang, Z., Nawaz, T., Zhang, F., You, L., & Tian, Y. (2026). Process-Programmed Extraction–Structure–Activity Relationships (ESAR) in edible and medicinal mushroom polysaccharides: a mechanistic and application-oriented framework. Journal of Advanced Research, 87, 1045-1077. https://doi.org/10.1016/j.jare.2025.12.040

Image Credits: AI Generated

DOI: 10.1016/j.jare.2025.12.040

Keywords: mushroom polysaccharides, extraction methods, structure–activity relationships, beta-glucans, immunomodulation, antitumor activity, antioxidant, molecular weight, triple helix, gut microbiota, antidiabetic, functional foods

The study, published in Discover Global Society, analyzed 294 scholarly publications indexed in the Scopus database between 2000 and 2025, all focused on UBIE research connected to Brazil, Russia, India, China, and South Africa. Using two widely respected bibliometric tools, VOSviewer and Biblioshiny, author Ravi Shankar Rai of C-DAC Noida charted publication trends, citation networks, keyword patterns, author productivity, and bibliographic coupling across the corpus. The results reveal a field that barely existed at the turn of the millennium but has since become a mature and rapidly expanding research program, with important lessons for scientists, university leaders, and policymakers alike.

The temporal trends alone tell a striking story. Between 2000 and 2012, fewer than five papers on university-based innovation ecosystems connected to BRICS countries appeared each year, signaling that the topic was still in its conceptual infancy. The decisive inflection point arrived in 2013 and 2014, coinciding with a surge of policy interest in knowledge-based development across the BRICS economies and a proliferation of Triple Helix-themed conferences and special journal issues. After steady growth through 2019, the field dipped during the pandemic years of 2019 to 2021, then rebounded sharply, reaching 39 papers in 2023 and 45 articles in 2024. That late surge, the study notes, coincides with the rising popularity of newer theoretical frameworks and a broader push toward open innovation and stakeholder engagement.

The disciplinary makeup of the literature is equally revealing. Social sciences account for roughly 28 percent of the papers, reflecting a focus on governance, policymaking, and institutions, while business, management, and accounting contribute about 26.8 percent, centered on entrepreneurial universities and commercialization. Economics, econometrics, and finance represent 11 percent, and smaller but growing shares come from decision sciences, environmental science, and computer science—the latter signaling the emergence of digital innovation as a research theme. Notably, engineering contributes only 4.2 percent and energy a mere 2.4 percent, suggesting that the applied technological dimensions of university-driven innovation remain understudied, particularly within BRICS countries where such questions carry enormous strategic weight.

Behind these aggregate patterns stand a relatively small set of influential scholars. Almeida M., Cai Y., Fischer B., and Schaeffer P.R. each authored six papers in the corpus, shaping the field’s agenda on institutional structures and policy processes, while Etzkowitz H. and Fischer B.B. published five each. The institutional diversity represented—universities spanning Brazil, South Korea, China, Finland, India, and South Africa—underscores the international character of the research, even as the concentration of productivity among a handful of institutions raises questions about who effectively sets the field’s intellectual direction.

Citation analysis adds a crucial layer of nuance. Etzkowitz’s 2004 article on the evolution of the entrepreneurial university stands as the most globally cited work, with 500 citations, reflecting the enduring power of the Triple Helix model of university–industry–government interaction. Yet its low local citation ratio suggests the field draws on the Triple Helix more in a citational than a critically engaged way. Meanwhile, Cheng and colleagues’ 2019 study of a Chinese nanotech innovation cluster recorded the highest intra-field influence, a hallmark of an emerging research stream that has not yet penetrated wider citation networks. Normalized citation metrics point to recent empirical work, such as Li’s 2020 study, gaining traction quickly within the community.

Perhaps the most policy-relevant finding concerns the gap between publication volume and citation impact at the country level. China leads the corpus in total citations with 1,071, followed by Brazil with 647—consistent with their roles as the bloc’s largest producers of academic output. But when citations are measured per article, a very different hierarchy emerges. Finland averages 70.2 citations per paper, nearly five times China’s 14.3, while Chile (65.5) and South Korea (59.2) also far outperform the BRICS group. India, despite its substantial research base, averages just 6.9 citations per article. The contrast suggests two distinct strategies: scale-driven output in China and Brazil versus smaller-volume, high-impact research in Finland, Chile, and Korea—a distinction with real implications for how nations should evaluate the returns on their innovation investments.

The co-citation analysis, which maps which scholars are cited together, exposes the field’s intellectual architecture in four main clusters: a dominant core around Etzkowitz and the Triple Helix; a cluster focused on regional innovation policy in Asia, especially China; a group studying university entrepreneurship and commercialization; and a cluster concerned with regional economic development. Strikingly, the architects of the Quadruple and Quintuple Helix frameworks—models that add civil society and environmental sustainability to the classic three-actor model—are nearly absent from the network’s key nodes. For a field studying innovation in societies marked by deep inequality and urgent environmental challenges, the study argues, this omission is both a theoretical weakness and a practical blind spot.

Keyword analysis reinforces the same diagnosis. The term ‘triple helix’ appears 81 times, ‘innovation’ 71 times, and ‘China’ 61 times, confirming both the framework’s dominance and the concentration of geographic attention. The notion of the ‘entrepreneurial university’ appears 17 times, marking a conceptual shift toward universities as active agents of economic development. Yet terms related to social equity, inclusive innovation, and sustainable development are conspicuously rare—an omission the study identifies as a significant conceptual gap given the socio-economic realities of BRICS nations.

The study also looks forward. The 2024–2025 expansion of BRICS to include Indonesia, Egypt, Ethiopia, Iran, and the UAE introduces a wave of new institutional and cultural contexts that existing UBIE scholarship, built around the original five members, has not yet absorbed. The author calls for comparative research on Quadruple and Quintuple Helix approaches, systematic examination of equity and inclusiveness within university innovation ecosystems, longitudinal studies tracking how ecosystems respond to political and economic shifts, and deeper investigation of digital technologies and artificial intelligence as forces reshaping university–industry–government collaboration. For policymakers, the message is equally clear: building successful innovation ecosystems requires more than increased research funding. It demands institutional arrangements that let universities act as genuine innovation partners, and attention to who actually benefits from the knowledge universities create.

Subject of Research: Bibliometric analysis of university-based innovation ecosystem research in BRICS countries from 2000 to 2025

Article Title: A bibliometric analysis of university based innovation ecosystem research in BRICS countries from 2000 to 2025

Article References: Rai, R. S. (2026). A bibliometric analysis of university based innovation ecosystem research in BRICS countries from 2000 to 2025. Discover Global Society, 4(1), Article 235. https://doi.org/10.1007/s44282-026-00491-7

Image Credits: AI Generated

DOI: 10.1007/s44282-026-00491-7

Keywords: university-based innovation ecosystems, BRICS, bibliometric analysis, Triple Helix, Quadruple Helix, entrepreneurial university, innovation policy, higher education, university–industry collaboration, Scopus, emerging economies, knowledge-based development