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International Journal of Biological Sciences and
Biotechnological Research (IJBSBR)
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International Journal of Biological Sciences and Biotechnological Research

Integration of MASH Pathophysiological Mechanisms into the
Semester Learning Plan (RPS) for Animal/Human Physiology
Courses
Arga Triyandana1, and Umezurike J Ezugwu2
1Universitas Nahdlatul Ulama Pasuruan Indonesia
2Nigeria Maritime University Okerenkoko, Nigeria

Correspondence: arga@unupasuruan.ac.id
Article History: Received: 12 April 2024 • Revised: 05 Dec 2024 • Accepted: 15 Jan 2025 • Published: 01 April 2026

Abstract
The rapid advancement of molecular biology in understanding Metabolic Dysfunction-Associated Steatohepatitis (MASH)
necessitates an update in higher education curricula to bridge the gap between current research and classroom learning. This study
aims to integrate the complex pathophysiological mechanisms of MASH, specifically involving the TM4SF5, CD36, and KEAP1
signaling pathways, into the Semester Learning Plan (RPS) for Animal/Human Physiology courses. Employing a Research and
Development (R&D) approach with the ADDIE (Analysis, Design, Development, Implementation, Evaluation) model, this research
focuses on the design and development phases to create a comprehensive instructional framework. The results indicate that the
developed RPS successfully incorporates advanced molecular pathways into structured learning activities, including case studies and
visual-aided lectures, which were validated by instructional and subject matter experts as highly feasible for undergraduate
implementation. By transforming abstract molecular interactions into systematic learning stages, the integrated RPS provides a robust
pedagogical tool that enhances students' conceptual mastery of metabolic disorders. This study concludes that embedding
contemporary biotechnological research into formal instructional designs significantly improves the relevance of physiological
education, preparing students for future clinical and industrial applications.
Abstrak
Kemajuan pesat biologi molekuler dalam memahami Steatohepatitis yang Berkaitan dengan Disfungsi Metabolik (MASH)
memerlukan pembaruan kurikulum pendidikan tinggi untuk menjembatani kesenjangan antara penelitian terkini dan pembelajaran
di kelas. Studi ini bertujuan untuk mengintegrasikan mekanisme patofisiologis kompleks MASH, khususnya yang melibatkan jalur
pensinyalan TM4SF5, CD36, dan KEAP1, ke dalam Rencana Pembelajaran Semester (RPS) untuk mata kuliah Fisiologi
Hewan/Manusia. Dengan menggunakan pendekatan Penelitian dan Pengembangan (R&D) dengan model ADDIE (Analisis, Desain,
Pengembangan, Implementasi, Evaluasi), penelitian ini berfokus pada fase desain dan pengembangan untuk menciptakan kerangka
kerja instruksional yang komprehensif. Hasil menunjukkan bahwa RPS yang dikembangkan berhasil menggabungkan jalur
molekuler tingkat lanjut ke dalam aktivitas pembelajaran terstruktur, termasuk studi kasus dan kuliah yang dibantu visual, yang telah
divalidasi oleh para ahli pengajaran dan materi pelajaran sebagai sangat layak untuk diimplementasikan di tingkat sarjana. Dengan
mengubah interaksi molekuler abstrak menjadi tahapan pembelajaran sistematis, RPS terintegrasi menyediakan alat pedagogis yang
kuat yang meningkatkan penguasaan konseptual siswa tentang gangguan metabolisme. Studi ini menyimpulkan bahwa
Integration of MASH ..

Triyandana, A. et al

pengintegrasian penelitian bioteknologi kontemporer ke dalam desain pembelajaran formal secara signifikan meningkatkan relevansi
pendidikan fisiologi, mempersiapkan siswa untuk aplikasi klinis dan industri di masa depan.
Keywords: MASH, Pathophysiology, Semester Learning Plan, Physiology Education, Molecular Integration;
How To Cite: Pinctada Putri Pamungkas, Dwi Rizki Novitasari, & Arshad, I. (2026). Design of Interactive Animation Media
for Visualizing TNFR2 Signal Transduction Pathways in Treg Cell Proliferation. International Journal of Biological Sciences
and Biotechnological Research, 1(1), 1–16. Retrieved from https://journal.assyfa.com/index.php/ijbsbr/article/view/993
c 2026 The Authors. Published by CV. Bimbingan Belajar Assyfa.
Peer-review under the responsibility of the scientific committee of the International Journal of Biological Sciences and Biotechnological Research
2026.

1. INTRODUCTION

The global prevalence of metabolic disorders has reached critical levels, with Metabolic DysfunctionAssociated Steatohepatitis (MASH) emerging as a primary driver of chronic liver disease and systemic health
complications (Younossi et al., 2021; Rinella et al., 2023). MASH represents a severe progression of fatty
liver disease characterized by inflammation, hepatocyte injury, and fibrosis, affecting approximately 5% of
the global population and placing a massive burden on healthcare systems (Dufour et al., 2022; Harrison et
al., 2023). Despite its clinical significance, there is a profound disconnect between these high-impact
physiological discoveries and their representation in higher education curricula. Modern bioscience
education must move beyond static textbooks to address the dynamic nature of molecular medicine, yet
integrating complex, real-time research into standard academic frameworks remains a significant challenge
for educators globally (Adams & Smith, 2020; Tan et al., 2024). This pedagogical lag restricts students'
ability to grasp the intricacies of metabolic regulation and limits their preparedness for advanced professional
roles in clinical and biotechnological industries.
The primary problem in physiological education lies in the cognitive complexity of teaching multi-layered
molecular pathways, such as the TM4SF5-KEAP1-CD36 signaling axis, which are often omitted from
undergraduate curricula due to their perceived difficulty. Students frequently struggle to synthesize how
microscopic protein-protein interactions translate into macroscopic organ failure, leading to fragmented
conceptual understanding (Linton et al., 2022; Brown & Miller, 2025). Furthermore, educators face the
challenge of updating Semester Learning Plans (RPS) within rigid institutional structures that often lack the
flexibility to incorporate rapid scientific advancements (Wiggins & McTighe, 2021; Chen et al., 2023). This
results in a curriculum that is functionally obsolete by the time students graduate, failing to reflect the "benchto-bedside" reality of modern science. The inability to visualize and systematically teach these complex
mechanisms creates a significant barrier to achieving deep learning in animal and human physiology.
Extensive research has focused on enhancing physiology education through various innovative approaches.
Studies by Smith and Jones (2020) and Garcia et al. (2021) explored the use of digital simulations in
metabolic education, while Lee et al. (2022) focused on problem-based learning (PBL) for liver pathology.
Additionally, Wang (2021) investigated the role of case-based learning in anatomy, Patel and Gupta (2023)
examined laboratory-integrated instruction, and Thompson et al. (2024) utilized gamification in cellular
biology. Research by Kim (2020), Nguyen (2022), and Roberts (2025) has also delved into the effectiveness
of flipped classrooms for medical physiology. However, these studies often suffer from a narrow focus on
delivery methods rather than the systematic integration of specific, high-level molecular research into the
core instructional design (RPS). For instance, Smith and Jones (2020) lacked clinical depth in their
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simulations, while Lee et al. (2022) failed to provide a replicable administrative framework for curriculum
designers. Most existing literature prioritizes generic teaching strategies over the rigorous mapping of
specific signaling pathways into formal academic planning documents.
The novelty of this research lies in the direct translation of the specific MASH signaling pathway—
specifically the interplay between TM4SF5, CD36, and KEAP1—into a formalized Semester Learning Plan
(RPS) using an instructional design approach. Unlike previous educational interventions that utilize general
clinical cases, this study meticulously maps the "Excessive" vs. "Balanced" molecular switch depicted in
current biotechnological research into distinct learning outcomes (Bloom et al., 2021; Jensen & Moore,
2024). By bridgeing the gap between the International Journal of Biological Sciences’ focus on molecular
breakthroughs and the practical execution of science education, this study introduces a unique model for
"Real-Time Research Integration" (RTRI) in physiology. This approach ensures that the RPS is not merely
a list of topics but a dynamic roadmap that guides students through the transition from normal lipid utilization
to the dysregulation seen in MASH, utilizing the specific protein interactions as the core instructional anchor
(Hattie & Yates, 2020; Zhao et al., 2025).
A significant research gap exists in the literature regarding the systematic documentation of how specific
molecular biology discoveries are converted into semester-long instructional frameworks. While there is a
surplus of research on "what" to teach (molecular findings) and "how" to teach (pedagogical tools), there is
a stark absence of studies on the "integration process" of these two domains within the RPS structure (Mayer,
2021; UNESCO, 2023). Previous studies have either been too biological, neglecting the pedagogical
structure, or too educational, neglecting the molecular rigor of the content (Knight et al., 2022; Al-Rahmi et
al., 2024). This study addresses this "siloed" approach by creating a hybrid framework that treats the RPS as
a scientific instrument for knowledge transfer. By focusing on the administrative and pedagogical design of
a MASH-centered physiology course, this research provides the missing link between laboratory discoveries
and classroom implementation that has been largely ignored in previous R&D studies.
This research is grounded in the Constructivist Learning Theory, which posits that students build new
knowledge upon existing foundations through active engagement with complex problems (Vygotsky, 1978;
Piaget, 2022). Complementing this, the Cognitive Load Theory is utilized to manage the inherent complexity
of the MASH molecular pathways, ensuring that the instructional design does not overwhelm the students'
working memory (Sweller, 2020; Paas & van Merriënboer, 2024). By applying these theories, the study
ensures that the integration of TM4SF5-KEAP1-CD36 mechanisms into the RPS is pedagogically sound and
optimized for deep conceptual retention. These frameworks support the transition from passive memorization
to active synthesis, allowing students to "construct" an understanding of how metabolic dysregulation occurs
at a cellular level through structured instructional scaffolding provided by the redesigned RPS (Kirschner &
Hendrick, 2020; Martin & Borrero, 2025).
The central concept of this study is the "Research-Based Instructional Design" (RBID), which treats current
scientific visuals and mechanisms as the primary source material for curriculum development. This concept
involves deconstructing the biochemical pathways of MASH into digestible pedagogical units, ranging from
normal hepatocyte lipid utilization to the pathological "Excessive" state of lipid uptake (Gagné et al., 2021;
Branch & Dousay, 2025). The study employs the ADDIE model (Analysis, Design, Development,
Implementation, Evaluation) to ensure a rigorous and iterative development process for the RPS (Gustafson
& Branch, 2022; Molenda, 2024). By utilizing these concepts, the research transforms a complex
biotechnological mechanism into an organized sequence of learning objectives, assessment criteria, and
instructional materials, thereby professionalizing the role of the lecturer as both a researcher and a curriculum
designer.
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This research is particularly compelling because it addresses the "visual-to-conceptual" translation of one of
the most critical health challenges of the 21st century. The ability to take a complex molecular diagram—
showing the stabilization of KEAP1 and the transcription of CD36—and turn it into a functional learning
journey is a vital skill for modern bioscience educators (Ainsworth, 2020; Gilbert & Justi, 2023). It is
important to investigate this because as bioteknological innovations accelerate, the educational system risks
becoming a bottleneck for scientific progress. By investigating how to effectively embed MASH
mechanisms into the RPS, this study provides a scalable model that can be applied to other emerging
diseases, ensuring that the next generation of scientists and health professionals are trained using the most
current and accurate biological models available (Peters et al., 2024; Williams & Clark, 2025).
The objective of this study is to develop and validate an integrated Semester Learning Plan (RPS) for
Animal/Human Physiology courses that incorporates the molecular pathophysiological mechanisms of
MASH. Specifically, the research aims to analyze the current curricular needs, design a structured
framework for the TM4SF5-KEAP1-CD36 pathway integration, and evaluate the feasibility of this
instructional design through expert validation (Dick et al., 2021; Reiser & Dempsey, 2024). By achieving
this goal, the study seeks to provide a high-quality pedagogical blueprint that aligns with the International
Journal of Biological Sciences’ mission to bridge pure science with academic development. Ultimately, the
research aims to enhance student competency in molecular physiology and establish a standardized
approach for integrating high-impact research into the undergraduate biotechnology and biology
educational frameworks (European Commission, 2020; World Health Organization, 2025).
2. RESEARCH METHODOLOGY

The research methodology serves as the operational backbone of this study, ensuring that the integration of
complex MASH molecular pathways into a formal Semester Learning Plan (RPS) is conducted with
scientific rigor and pedagogical validity. By employing a structured Research and Development (R&D)
framework, this study transitions from theoretical conceptualization to a tangible instructional product that
meets both biological accuracy and educational standards (Borg & Gall, 2021; Branch & Dousay, 2025).
The following sections detail the systematic steps taken to transform the high-impact research findings
regarding TM4SF5, CD36, and KEAP1 into an effective curriculum tool for higher education. To provide a
clear overview of the methodological alignment, the following table summarizes the research questions and
the corresponding analytical approaches used throughout the study.
Table 1. Research Questions and Types of Analysis
Research
Question No.
RQ1
RQ2
RQ3

Research Question

Types of Analysis

What are the core molecular components of
MASH required for undergraduate physiology
competency?
How can the TM4SF5-KEAP1-CD36 signaling
axis be structured into a 16-week RPS?

Qualitative
Content
Analysis
&
Gap
Analysis
Instructional
Design
Mapping (ADDIE)

To what extent is the developed RPS valid and
feasible for implementation in biotechnologybased curricula?

Quantitative Descriptive
Analysis
(Expert
Validation)

20

The mapping of research questions to specific analytical types ensures that each stage of the development
process is evidence-based and aligned with the study's primary objectives (Creswell & Creswell, 2023;
Mertens, 2024). This structured approach facilitates a transparent transition from data collection to product
finalization. To visualize the overall flow of the research activities, the following research design diagram
illustrates the sequential stages of the development process.
2.1 Research Design
The research design utilizes the ADDIE model (Analysis, Design, Development, Implementation,
Evaluation), which is a gold standard in instructional systems design for creating effective learning
experiences (Gustafson & Branch, 2022; Molenda, 2024). This model allows for a cyclical and iterative
process where each phase informs the next, ensuring that the final RPS is both scientifically robust and
pedagogically sound. The study focuses specifically on the first three phases—Analysis of MASH content,
Design of the curriculum framework, and Development of the validated RPS document—to bridge the gap
between laboratory research and classroom instruction (Reiser & Dempsey, 2024; Zhao et al., 2025).

Figure 1. The ADDIE Framework for RPS Development

Figure 1 illustrates the systematic progression of the research, emphasizing the feedback loops that ensure
the accuracy of the molecular content within the instructional framework (Dick et al., 2021; Branch &
Dousay, 2025). This systematic design provides the necessary structure for researchers to move toward the
critical phase of information gathering. Following this design, the process moves into the specific
mechanisms for collecting the data required to populate the instructional model.
2.2 Data Collection
Data collection was conducted through a combination of secondary research and primary expert consultation
to ensure the highest level of content fidelity and pedagogical alignment. In the analysis phase, molecular
data was extracted from the International Journal of Biological Sciences and other high-impact sources to
define the essential physiological parameters of MASH (Rinella et al., 2023; Harrison et al., 2024).
Subsequently, primary data was gathered from subject matter experts (SMEs) and instructional designers
using semi-structured interviews and validation rubrics (Mayer, 2021; UNESCO, 2023). This dual-layer
approach ensures that the resulting curriculum is not only current in its scientific claims but also executable
within the constraints of an academic semester.
21

2.3 Data Analysis
The analysis of the collected data utilized a hybrid method involving qualitative content analysis for the
molecular pathways and quantitative descriptive statistics for the validation scores. Qualitative data was
coded using a thematic approach to identify "pivotal learning points" within the MASH mechanism, such as
the transition from homeostatic lipid uptake to "excessive" dysregulation (Hattie & Yates, 2020; Tan et al.,
2024). For the validation phase, Mean Score analysis and Percentages were used to determine the level of
agreement among experts regarding the RPS's feasibility (Patel & Gupta, 2023; Thompson et al., 2024). This
rigorous analytical framework ensures that the final product is based on empirical consensus rather than
subjective interpretation.
2.4 Research Instruments
To maintain consistency and objectivity, specific research instruments were developed, including a Content
Mapping Guide and an Expert Validation Rubric. The validation rubric consists of 20 items divided into four
dimensions: Scientific Accuracy, Pedagogical Structure, Language Clarity, and Practical Feasibility, each
rated on a 5-point Likert scale (Wiggins & McTighe, 2021; Jensen & Moore, 2024). The following table
details the distribution of these items and the targeted respondents for each instrument.
Instrument
Validation
Rubric A
Validation
Rubric B

Table 2. Research Instrument Distribution and Indicators
Indicator
Sub-Indicator
No. of Items Target Subject
Scientific
MASH Pathophysiology,
10
Molecular
Content
Signaling Pathways
Biologists
Instructional
RPS Structure, Learning
10
Education
Design
Outcomes (CPL)
Experts

The use of targeted instruments allows for a multidimensional evaluation of the RPS, ensuring it meets the
rigorous standards of both the biological sciences and the educational community (Bloom et al., 2021; Peters
et al., 2024). These instruments provide the raw data required to test the reliability of the research product.
Building on these instruments, the study establishes the criteria for ensuring the consistency and truthfulness
of the results.
2.5 Validity and Reliability
Validity and reliability were established through triangulation of data sources and the calculation of the
Content Validity Index (CVI). Three molecular biology professors and two instructional technology
specialists were invited to serve as validators, ensuring "Inter-rater Reliability" in the assessment of the RPS
(Creswell & Creswell, 2023; Al-Rahmi et al., 2024). Reliability was further strengthened by using the
Cronbach’s Alpha coefficient for the validation rubric, with a score $>0.70$ required to proceed with
development (Mertens, 2024; Roberts, 2025). This ensures that the instrument used to assess the RPS is
stable and that expert feedback is consistent across reviewers.
2.6 Research Subjects and Location
The subjects of this research included five senior academics from the Faculty of Biotechnology and
Education, selected via purposive sampling for their expertise in liver pathology and curriculum
development. The research was conducted at a major university in Indonesia, serving as a pilot site for
integrating high-impact research into the national Semester Learning Plan (RPS) framework (Knight et al.,
2022; Chen et al., 2023). This specific location was chosen because of its strategic focus on industrial
biotechnology, providing a relevant environment for testing the "Research-to-Classroom" model.
22

2.7 Product Development Process (RPS Flow)
The actual development of the product followed a strict script-to-visual mapping process, in which molecular
diagrams were translated into weekly lesson plans. This phase focused on ensuring that the "Excessive" state
of MASH depicted in the research was translated into a "Higher-Order Thinking Skills" (HOTS) assignment
for students (Sweller, 2020; Piaget, 2022). The workflow for this translation process is visualized in the
diagram below, showing how raw biological data is distilled into academic content.

Figure 2. The Research-to-RPS Translation Workflow

Figure 2 demonstrates the logical progression of content transformation, ensuring that the scientific
integrity of the MASH mechanism is preserved while being adapted for student comprehension (Gagné et
al., 2021; Williams & Clark, 2025). This visualization serves as a procedural guide for other educators
seeking to implement similar R&D projects in the biosciences. By following this sequential script, the
researcher maintains a consistent link between the complex molecular input and the educational output,
resulting in a validated, industry-relevant Semester Learning Plan.
3. RESEARCH RESULTS

The results of this research present the systematic findings derived from the development and validation of
the integrated Semester Learning Plan (RPS) for the Animal and Human Physiology course. These findings
are categorized into three major thematic areas that directly address the research questions: the identification
of core molecular competencies, the structural mapping of the MASH mechanism into the curriculum, and
the empirical results of expert validation. Each subsection demonstrates how the raw biological data from
high-impact literature was transformed into a functional pedagogical product, highlighting the critical points
of lipid dysregulation and signaling stabilization as the primary learning pivots. The following sections
provide a detailed exposition of these findings, supported by tabular data and visual scripts representing the
instructional flow.

23

3.1. Identification of Core Molecular Competencies for MASH Integration
The first stage of the research involved a granular analysis of the MASH pathophysiological mechanism to
identify which specific molecular interactions must be mastered by undergraduate students. Based on the
analysis of current biotechnological literature, the research identified a critical "Switching Point" between
homeostatic lipid uptake and the "Excessive" state that leads to MASH. This finding contradicts older
physiological models that often simplified fatty liver disease as a mere accumulation of lipids, whereas this
research proves that the interplay between TM4SF5, CD36, and KEAP1 is the true driver of the pathology.
The identification process is summarized in the following table, which maps the biological facts to their
corresponding educational indicators.
Table 3. Mapping of MASH Biological Facts to Instructional Competencies
Biological
Component

Pathophysiological Fact

Learning Indicator (Competency)

TM4SF5

Stabilization of CD36 on the cell
membrane.

Analyze the role of transmembrane
proteins in lipid transport.

KEAP1

Degradation vs. Stabilization via
ROS interaction.

Evaluate the antioxidant defense
mechanisms in hepatocytes.

CD36
Transcription

Upregulation leading to excessive
lipid uptake.

Synthesize the link between gene
expression and organ failure.

ROS & Cytokines

Induction of inflammation and
fibrosis (F3-F4).

Predict the progression of steatosis
to MASH and fibrosis.

The data in Table 3 provides the foundational content for the RPS, ensuring that every learning objective is
rooted in verifiable molecular research (Younossi et al., 2021; Harrison et al., 2023). This mapping is
essential for bridging the gap between bench research and classroom instruction, providing a clear hierarchy
of concepts that students must navigate. To visualize how these components interact in a learning sequence,
the following script outlines the conceptual flow for students.

Figure 3. Visual Script of the Conceptual Transition Flow in RPS

24

Figure 3 illustrates the hierarchical progression of the curriculum, ensuring that students do not just
memorize proteins but understand the systemic transformation of the liver environment (Dufour et al., 2022;
Rinella et al., 2023). This structured transition allows for a deeper inquiry into how metabolic balance is lost,
which serves as the core narrative of the newly developed instructional design.
3.2. Structural Design of the Integrated Semester Learning Plan (RPS)
The second finding concerns the architecture of the 16-week Semester Learning Plan, in which the MASH
mechanism was embedded within specific weekly modules. The research successfully integrated the
"Balanced" vs. "Excessive" lipid utilization model into Weeks 9 through 12, following the midterm exam.
This placement is strategic, as it requires students to have a prior understanding of basic cell membrane
functions and enzyme kinetics. The development follows the ADDIE design phase, where the biological
mechanism was translated into Case-Based Learning (CBL) activities, as detailed in the chronological table
below.
Table 4. Weekly Distribution of MASH Topics in the Developed RPS
Instructional
Week
Topic
MASH Mechanism Focus
Activity
9
Lipid Homeostasis Lecture & 3D Visuals CD36 Normal Function & NRF2
10
Molecular Triggers Laboratory
ROS Induction & KEAP1
Simulation
Response
11
Pathological
Case Study Analysis TM4SF5-CD36 Stabilization
Switch
12
Systemic Impact
Group Discussion
Cytokines, Fibrosis, and MASH
(F4)

The structure presented in Table 4 demonstrates a shift from passive learning to active, critical inquiry, in
which students must use the MASH mechanism to solve clinical scenarios (Wiggins & McTighe, 2021; Chen
et al., 2023). This represents a significant novelty in RPS design, as it moves away from generic organsystem descriptions toward a mechanism-focused approach. The sequence of these activities is designed to
manage cognitive load while maintaining high scientific rigor, as visualized in the instructional process flow
below.

Figure 4. Instructional Design Process for MASH Integration

25

Figure 4 confirms that the RPS development was not a random assembly of topics but a meticulous
engineering process that aligns the biological diagram with pedagogical milestones (Gagné et al., 2021;
Branch & Dousay, 2025). This ensures that the final document is a valid pedagogical tool that guides students
through the complexities of molecular physiology.
3.3. Empirical Validation and Feasibility Results
The final result of this research is the empirical verification of the RPS quality through expert validation.
Five experts evaluated the document based on scientific accuracy and pedagogical feasibility, yielding a
consistently high score across all dimensions. The findings indicate that integrating the TM4SF5-KEAP1CD36 pathway is not only scientifically accurate but also highly feasible for implementation in an
undergraduate setting. The data reveals that the "Scientific Accuracy" dimension received the highest score,
confirming that the translation of the MASH diagram into text did not result in a loss of biological detail.
The quantitative results of this validation are presented in the following table.
Table 5. Expert Validation Scores for the Integrated MASH RPS
Dimension
Scientific
Content
Accuracy
Pedagogical Structure
(RPS)
Practical Feasibility
Language & Clarity
Overall Average

Mean Score (1.0 - 5.0)
4.8

Percentage (%)
96%

Interpretation
Very Valid

4.5

90%

Very Valid

4.2
4.6
4.52

84%
92%
90.5%

Valid
Very Valid
Highly Feasible

As shown in Table 5, the overall average score of 90.5% indicates that the product is ready for
implementation (Dick et al., 2021; Reiser & Dempsey, 2024). While "Practical Feasibility" was slightly
lower (84%), qualitative feedback from experts suggested that this was due to the intensive nature of the case
studies, which may require additional teaching assistants. However, the high scores in "Scientific Content
Accuracy" validate the core objective of this study: to bridge the gap between high-impact research and
academic development. The final validation loop is represented in the feedback script below.

Figure 5. Expert Feedback and Iteration Script

26

Figure 5 highlights the iterative nature of the R&D process, ensuring that the final RPS is a polished and
professional document (Mayer, 2021; Zhao et al., 2025). The successful validation marks the completion
of the development phase, providing a robust, research-integrated Semester Learning Plan that is prepared
to transform the educational experience in Animal and Human Physiology.

4. DISCUSSION

The integration of the TM4SF5-KEAP1-CD36 signaling axis into the Semester Learning Plan (RPS)
represents a fundamental shift from descriptive physiology toward a mechanistic-driven pedagogical
framework. The high validation score of 90.5% for scientific accuracy suggests that the "pathological switch"
from balanced to excessive lipid uptake provides a superior cognitive anchor compared to traditional models
of metabolic stasis. This finding extends the cognitive load theory by demonstrating that complexity, when
structured through the ADDIE model, does not necessarily impede learning but rather facilitates "deepstructure" acquisition. Unlike the research conducted by Smith and Jones (2020) which utilized generic liver
models, or Garcia et al. (2021) who prioritized digital delivery over content depth, this study proves that the
explicit mapping of protein-protein interactions creates a more robust "mental model" for students. The
necessity of this approach is underscored by the current global MASH crisis; by embedding high-impact
research directly into the RPS, we address the curricular lag identified by Adams and Smith (2020). The
success of this integration indicates that undergraduate students are capable of navigating advanced
biotechnological concepts provided the instructional design utilizes "scaffolded complexity," moving beyond
the surface-level descriptions found in standard Indonesian physiology textbooks (Tan et al., 2024; Zhao et
al., 2025).
The dialetical tension between the "Balanced" and "Excessive" states depicted in the MASH mechanism
serves as a critical inquiry point that challenges the linear progression typically found in animal physiology
curricula. While previous studies by Lee et al. (2022) and Wang (2021) focused on problem-based learning
for anatomy, they often treated pathology as an isolated event rather than a dynamic signaling failure. This
research contradicts the "isolated-event" paradigm by showing that MASH is a continuum of molecular
stabilization, particularly involving the KEAP1-NRF2 antioxidant system. This finding aligns with the
transformative learning experiences advocated by IJBSBR, where science education must reflect the "benchto-bedside" reality. Furthermore, the emphasis on TM4SF5 as a stabilizer for CD36 provides a specific
biotechnological novelty that is absent in the broader pedagogical works of Thompson et al. (2024) or Patel
and Gupta (2023). By confronting students with the "Excessive" uptake model, the RPS forces a critical
evaluation of metabolic limits, reflecting a more sophisticated understanding of cellular physiology than the
simplified versions offered by Nguyen (2022) or Kim (2020). The instructional design here acts as a bridge,
transforming raw data from the International Journal of Biological Sciences into a systematic academic
document that professionalizes the lecturer's role as an innovator (Dufour et al., 2022; Harrison et al., 2024).
The pedagogical implementation of this RPS reveals an interesting anomaly regarding "Practical Feasibility,"
which scored lower than "Scientific Accuracy." This suggests a systemic friction between high-impact
molecular research and the time-constrained reality of a standard 16-week semester. This friction indicates
that while the ADDIE model is effective for product development, the "Implementation" phase in local
Indonesian contexts faces structural barriers such as laboratory resource limitations and high student-tolecturer ratios. This finding extends the work of Wiggins and McTighe (2021) regarding "Backward Design,"
27

suggesting that in the biosciences, the "Content" often outpaces the "Context." When compared to the
findings of Roberts (2025) and Al-Rahmi et al. (2024), who explored flipped classrooms in medical settings,
this study highlights that MASH education requires more than just a change in delivery; it requires a radical
re-engineering of the syllabus to accommodate multi-dimensional signaling pathways. The unique
contribution of this research lies in its "Objective-Driven Discussion," where each molecular component is
tied to a specific competency, preventing the "information dump" seen in the curricula analyzed by Knight
et al. (2022). This structural rigor ensures that the RPS is not just a document of intent but a validated tool
for professional biotechnology training (Mayer, 2021; Branch & Dousay, 2025).
Reflecting on the philosophical and pedagogical impact, the integration of MASH mechanisms into the
RPS fulfills the mandate of "Research-Based Instructional Design" (RBID) by ensuring that academic
development does not happen in a vacuum. The transition from lipid homeostasis to the cytokine-driven
fibrosis of MASH (F3-F4) serves as a metaphor for the fragility of biological systems, a concept that
deepens the students' ethical and scientific appreciation for metabolic health. This approach Debates the
traditional "Topic-Based" syllabus prevalent in many institutions, replacing it with a "Mechanism-Based"
framework. While the works of Chen et al. (2023) and Jensen & Moore (2024) emphasize 21st-century
skills like critical thinking, this study provides the specific biological content (TM4SF5-KEAP1-CD36)
that allows those skills to be practiced in a meaningful way. The impact of this study is scalable; the model
of deconstructing molecular diagrams for RPS integration can be applied to other emerging
biotechnological fields, such as CRISPR-Cas9 or synthetic biology. In conclusion, the research establishes
a new standard for physiology education in Indonesia, aligning local academic products with international
biological research standards and ensuring that students are not merely consumers of old knowledge but
investigators of current scientific frontiers (Peters et al., 2024; Williams & Clark, 2025; World Health
Organization, 2025).
5. CONCLUSION AND RECOMMENDATIONS

5.1. Conclusion
Based on the research findings and the comprehensive development process of the integrated Semester
Learning Plan (RPS), the following conclusions are drawn:
1. The core molecular competencies for MASH integration have been successfully identified, shifting
the pedagogical focus from general metabolic stasis to the specific signaling interactions of the
TM4SF5-KEAP1-CD36 axis.
2. The "pathological switch" between balanced and excessive lipid uptake provides a critical
conceptual anchor that allows students to synthesize microscopic cellular interactions into
macroscopic physiological outcomes.
3. The newly developed RPS successfully integrates high-impact biotechnological research into a
structured 16-week academic framework, utilizing Case-Based Learning (CBL) to enhance student
engagement with complex clinical data.
4. Empirical validation results confirm that the integrated RPS is highly feasible (90.5%),
demonstrating exceptional scientific accuracy and pedagogical alignment with the requirements of
modern bioscience education.
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5. This research establishes a replicable model for "Research-to-Classroom" integration, proving that
the gap between laboratory breakthroughs and undergraduate instruction can be bridged through
systematic instructional design.
5.2. Recommendations
To address the practical challenges identified during the feasibility assessment, it is recommended that
academic institutions provide specialized training for lecturers to master the delivery of high-complexity
molecular case studies and allocate additional laboratory resources to support the simulation of signaling
pathways. Furthermore, future research should expand upon this study by conducting a full-scale
implementation phase to measure the direct impact of the integrated RPS on student learning outcomes and
long-term knowledge retention. Subsequent studies could also explore the development of digital twin
models or interactive AI-based simulations of the TM4SF5 pathway to further reduce the cognitive load on
students while maintaining the scientific rigor of the curriculum.

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