Biology and Life Sciences

Abstract: Spatial proteomics has become an important approach for studying the molelccular composition of tissues while preserving their spatial context. Among the available technologies, tryptic peptide MALDI imaging enables fast, multiplexed, label-free, and antibody-independent protein analysis directly from tissue sections. However, confident peptide identification remains one of the major challenges of current MALDI imaging workflows, as most experiments are limited to MS1 acquisition and therefore lack in situ peptide fragmentation and amino acid sequence information. Consequently, peptide identification often relies on complementary (LC-)MS/MS analyses, which do not always enable unambiguous peptide assignment.Recent advances in trapped ion mobility spectrometry (TIMS) and parallel accumulation-serial fragmentation (PASEF) enable multiplexed, in situ, targeted peptide fragmentation during MALDI imaging experiments. By combining an exploratory TIMS-MS1 survey with targeted precursor selection and imaging parallel reaction monitoring (iprm)-PASEF acquisition, reliable peptide identification can be achieved in MALDI imaging.In this chapter, we describe a detailed protocol for targeted tryptic peptide MS/MS-based MALDI imaging using iprm-PASEF on the timsTOF fleX mass spectrometer. The workflow consists of tissue preparation with in situ protein digestion, followed by exploratory MALDI TIMS-MS1 imaging, precursor list generation, iprm-PASEF acquisition, and subsequent peptide identification. In addition, practical considerations for instrumental setup, precursor selection, and data analysis are discussed to facilitate implementation of the workflow for spatial proteomics applications.

Abstract: Proprotein convertase subtilisin/kexin type 6 (PCSK6) is a proteolytic enzyme that acts on a broad spectrum of substrates, including growth factors, extracellular proteases, adhesion molecules, protease activated receptor 1, the prorenin receptor, and Corin. As a consequence of its broad spectrum substrate activity, PCSK6 is implicated in a wide range of pathophysiological processes like cardiovascular disease, neurological disorders, arthritis and cancer. Of special interest, PCSK6 has recently been shown to be highly expressed in patients with idiopathic pulmonary fibrosis (IPF) and PCSK6 was associated with reduced survival, providing the first evidence linking PCSK6 to pulmonary fibrosis. In this review, we summarize the molecular biology of PCSK6, including its structural features and major substrates, and outline its pathophysiological roles across various diseases. Furthermore, we propose and discuss the potential involvement of PCSK6 in pulmonary fibrosis to guide future research.

Abstract: Bioactive polysaccharides such as fucoidan, β-glucans, and medicinal plant polysaccharides contain functional groups that can interact with drug molecules, and some of them also retain their own biological activities. Through reversible noncovalent interactions, these polysaccharides can associate with small-molecule drugs and form supramolecular nanocomplexes. This review discusses hydrogen bonding, hydrophobic association, electrostatic complexation, π–π stacking, and the cooperation among these interactions. The effects of pH, ionic strength, concentration, and solvent composition on assembly behavior are also considered. Nanoprecipitation/solvent exchange, polyelectrolyte complexation, direct aqueous self-assembly, and microfluidic-assisted assembly are compared in terms of nanostructure formation, process control, and reproducibility. Evidence from molecular, colloidal, solid-state, and computational characterization is considered together to clarify the relationship between structure, assembly, and performance. Reported benefits include improved drug dispersibility, colloidal stability, release control, bioavailability, cellular uptake, biodistribution, and safety. In some systems, the polysaccharide component may also contribute to therapeutic effects in tumors, inflammatory diseases, infected wounds, and local regenerative matrices. Quantitative mechanism studies, polysaccharide standardization, biocompatibility assessment, process scale-up, and long-term safety evaluation remain necessary for the further development of these drug delivery systems.

Abstract: Background and Objectives: To elucidate the material basis and molecular mechanisms of the Rehmanniae Radix–Sophorae Flos (RR-SF) herb pair for psoriasis treatment, and to verify causal effects of core targets from a genetic perspective, constructing an integrated “component–target–pathway–causality” evidence chain. Materials and Methods:A four-level strategy was employed: (1) UPLC-Q-TOF/MS identified chemical constituents of the RR-SF co-decoction; (2) network pharmacology screened active compounds (OB ≥ 30%, DL ≥ 0.10), predicted targets, constructed drug–compound–target–pathway and PPI networks, and performed GO/KEGG enrichment; (3) drug-target Mendelian randomization (MR) used eQTLs of 7 core targets as exposure and psoriasis GWAS as outcome, with IVW as primary method and MR-Egger, Cochran’s Q, leave-one-out, and Steiger tests for sensitivity analysis; (4) AutoDock Vina molecular docking verified binding between active compounds and core targets. Results: 109 constituents were identified, dominated by flavonoids (32), iridoids (26), and phenylethanoid glycosides (12). Network pharmacology yielded 14 active compounds and 159 shared targets, with SRC, MAPK3, RXRA, HSP90AA1, CTNNB1, AKT1, and MAPK1 as core hubs. Key pathways included IL-17, MAPK, Th17 differentiation, VEGF, PI3K-Akt, and NF-κB. MR confirmed causal associations: MAPK1 (OR = 2.58, 95% CI 1.49–4.46, P = 7.5 × 10⁻⁴, risk), HSP90AA1 (OR = 0.42, 95% CI 0.24–0.74, P = 2.6 × 10⁻³, protective), and SRC (OR = 2.00, 95% CI 1.04–3.87, P = 0.039). MAPK1 and HSP90AA1 remained significant after Bonferroni correction. Molecular docking identified quercetin–HSP90AA1 (−9.3 kcal/mol) and aeginetic acid–RXRA (−9.1 kcal/mol) as strongest interactions. Conclusions: RR-SF exerts anti-psoriatic effects via a multi-component–multi-target–multi-pathway mode. MR validated causality of core targets, and molecular docking identified quercetin–HSP90AA1 and aeginetic acid–RXRA as key intervention strategies, providing multi-dimensional evidence for precision psoriasis treatment.

Abstract: More than 180 chemically distinct RNA modifications – the epitranscriptome – have now been reported across all kingdoms of life and all forms of RNA. Given the emerging evidence for critical roles played by RNA modifications in many diseases, it is imperative to identify the function of all RNA modifications in the nearly 250,000 types of RNA in human cells – the human RNome. Here we take a step toward this goal by reviewing the literature to date and assembling a catalog of all established or putative human RNA modifications. While the identities and locations of many human RNA modifications are well established, emerging technologies are revealing new ones as well as old ones in unexpected locations, with low abundance and poorly characterized structures hampering their validation. To this end, we introduce an analytical validation framework that scores each reported human RNA modification for chemical identity and transcriptomic localization and then assigns it to one of three confidence tiers: Authenticated, Provisional, or Putative. Applying this framework, we critically re-examine the primary literature underlying 24 recently reported additions to the human epitranscriptome, evaluating the mass spectrometric, spectroscopic, and sequencing-based evidence supporting each as well as discussing their emerging biological roles and disease associations. We further extend this scoring system to modifications previously summarized in reviews and databases but not yet subjected to this level of scrutiny, compiling a comprehensive, tier-ranked inventory of the human epitranscriptome as of July 2026. Together, this catalog and framework provide a benchmark for evaluating future epitranscriptome discoveries, mapping the human RNome, and for derisking the translation of validated modifications as diagnostic and therapeutic targets.

Abstract: Canine distemper virus (CDV) is a multi-host morbillivirus of domestic dogs and wild carnivores, and early molecular detection is important for treatment, isolation, and wildlife surveillance. However, the most informative ante-mortem specimen type for RT-qPCR screening remains context dependent. This pilot study compared CDV RNA detection and viral load across paired sample matrices from nine dogs and screened archived blood/serum samples from four tigers and one clouded leopard. CDV RNA was extracted using a commercial viral nucleic-acid kit and amplified using a one-step RT-qPCR assay. Five of nine dogs were CDV-positive. Among positive dogs, conjunctival swabs detected CDV RNA in 5/5 animals (100%), followed by nasal swabs (4/5), rectal swabs (3/5), whole blood (2/5), and urine (1/5). Viral load ranged from 9.55 to 213,796.21 RNA copies/μL. Exact Cochran’s Q and Friedman tests did not reach statistical significance, but Kendall’s W suggested a moderate sample-type effect. These results support conjunctival swabs as the most consistent specimen in this dataset, with nasal and rectal swabs as useful complementary matrices.

Abstract: Mitochondrial genomes (mitogenomes) are no longer considered as entities simply engaged in cellular bioenergetics, but rather as dynamic, multifaceted synchronized systems assimilating genome architecture, evolutionary processes and organismal physiology. In the present review, the contemporary understanding of mitogenome organization, its diversity, evolution and associated functions across the eukaryotic life have been summarized in connection with mitonuclear co-evolution and briefly to some connection with human health. The manuscript comprehensively discusses the conserved and lineage-specific characteristic features of mitogenome architecture, including its genetic content, topology and regulatory elements governing its precise replication and transcription. Additionally, the review also explores the role of evolutionary dynamics, with emphasis on mutation-rate heterogeneity, recombination dynamics, gene rearrangements and the interacting roles of mutation, natural selection and genetic drift in shaping mitochondrial genome diversity and evolutionary trajectories. The comparative approaches highlight extensive diversity in mitogenome structural organization and its composition closely associated with life-history strategies such as metabolic rate, longevity and reproductive peculiarity. Moreover, at the functional level, variability potential of a mitogenome significantly influences oxidative phosphorylation efficiency, reactive oxygen species generation and orchestration of cellular signalling cascades. Fundamental to these processes is the existence of coordinated mitonuclear interrelationships, wherein co-evolution between mitochondrial and nuclear-encoded genes safeguards bioenergetic functional integrity, and while its inconsistencies could lead to reduced cellular fitness and disease progression. In humans, mutations in mitochondrial DNA (mtDNA) and heteroplasmy are significantly contribute to the development of primary mitochondrial disorders; they are being progressively implicated in other complex disease etiologies, including neurodegeneration, metabolic syndromes and cancer. Furthermore, the paper summarizes the phylogenetic utility of mitogenomes in the genomic era, accentuating the need to employ integrative approaches that could combine mitochondrial and nuclear data. Lastly, the role of emerging technological platforms, including long-read sequencing and multi-omics, which are expected to transform the current scenario of mitogenome research are being discussed. Altogether, the manuscript positioning the mitogenomes as indispensable entities bridging the gaps between evolutionary histories, physiological function and personalized precision medicine.

Abstract: The blood–brain barrier (BBB) is a coordinated multicellular interface in which intercellular communication shapes responses to injury and metabolic stress. However, the contributions of individual cell types to collective stress adaptation remain poorly understood. Here, we examined molecular and metabolic responses of 2D BBB models comprising endothelial cells, astrocytes, and pericytes exposed to hypoxia or sublethal HgCl₂ toxicity. An integrated platform combining gene and protein expression profiling, label-free vibrational spectroscopic imaging, and machine-learning-based analysis was used to assess stress-induced changes in cell-cycle regulation and metabolism across monoculture and co-culture configurations. Hypoxia broadly suppressed G1/S and G2/M regulators, inducing cell-cycle arrest with limited cell death, consistent with an adaptive response. HgCl₂ caused heterogeneous, model-dependent changes in viability and proliferative capacity. Spectroscopic phenotyping showed that co-cultured cells acquired molecular profiles characteristic of pericytes, indicating a dominant pericyte-driven influence on the cellular community. Fluorescence imaging further revealed intercellular mitochondrial transfer at cell–cell contact sites. These findings identify pericytes as key contributors to stress resistance and BBB cell survival. The developed spectroscopic–molecular platform provides a label-free framework for monitoring cellular communication and stress responses in multicellular BBB models.

Abstract: Contemporary photosynthesis relies on the dissipation of visible solar photon energy through chlorophyll. Chlorophyll biosynthesis in modern organisms is a complex pathway involving more than 14 enzymatic steps. Near the origin of life, however, complex enzymes could not have existed, so primordial photosynthesis must have been a simpler, more direct process, but still based on photon dissipation. We have argued that life began around the early Archean through the molecular dissipative structuring of UV-C chromophores (now known as the fundamental molecules of life) under the thermodynamic imperative of dissipating Earth’s surface solar UV-C photons into heat. Here, employing the Granick hypothesis (linking biosynthetic order to evolutionary history), we chart a plausible non-enzymatic route for the UV-C dissipative structuring of chlorophyll. Starting from a likely common Archean precursor, glutamic acid, we show how dissipative structuring under UV-C light could have led to molecules en route to chlorophyll with ever-greater photon absorption cross sections and bandwidths, moving towards the absorption of visible wavelengths of higher photon intensities. Such a process demonstrates all the hallmarks of molecular dissipative structuring and may have been at the foundations of the complex biosynthetic pathway of visible photosynthesis appearing around 3.7 Ga.

Abstract: Inflammatory cytokines are well-established drivers of organ-specific pathology, yet the seasonal patterning of their activity and its clinical implications remain poorly understood. IL-1, IL-6, and NF-B have traditionally been studied in isolation from seasonal biological rhythms, and current biomedical frameworks lack a unifying model integrating cytokine dominance, seasonal rhythmicity, and organ-specific disease progression. Recent advances in mapping Yellow Emperor’s Inner Canon (YEIC) conceptual constructs onto these molecular signaling pathways have created a translational foundation that makes such a cross-framework analysis feasible. This analysis proposes a unified inflammatory framework linking cytokine dominance to predictable seasonal cycles of tissue involvement and disease progression. This study is a systematic analysis. Classical descriptions of Bi syndrome from YEIC were translated into contemporary biomedical terminology using an established molecular mapping framework (Cold/IL-1, Dampness/IL-6, Wind/NF-B, Evil/LPS). For each season-tissue pair and organ progression pathway described in the YEIC, supporting evidence was systematically identified from peer-reviewed literature retrieved from PubMed, covering seasonal disease epidemiology, cytokine mechanisms, and clinical disease progression. Cytokine predominance mapped systematically onto distinct seasonal cycles of tissue involvement: bone (winter), tendons (spring), vasculature (summer), muscle (late summer), and skin (autumn). Unresolved inflammation progressed predictably to paired visceral injuries, including acute kidney injury, hepatitis, heart failure, splenomegaly, and asthma, respectively. The relative dominance of each mediator determined distinct joint manifestations: NF-B predominance corresponded to migratory arthritis, IL-1 predominance to gout, and IL-6 predominance to localized pain. This seasonal and organ-specific pattern was found to be precisely anticipated by the YEIC. These findings challenge the prevailing view that seasonal inflammatory conditions are etiologically unrelated, proposing instead a unified framework that accurately predicts their seasonal distribution and organ-specific progression. The YEIC, reinterpreted through a molecular lens, demonstrates a sophisticated physiological model with implications extending well beyond traditional Chinese medicine, offering clinically actionable insights into the seasonal epidemiology and unified pathophysiology of inflammatory disease.

Abstract: Cancer remains a major global health concern, driving the search for safe and effective bioactive compounds from natural sources. Jujube peel red pigment (JP), an anthocyanin-rich extract, has shown preliminary bioactivity, yet its antitumor potential and delivery challenges remain underexplored. This study systematically evaluated the in vitro antitumor activity of JP and developed a thermosensitive hydrogel-based local delivery system (JP-H) to overcome its rapid diffusion and poor retention. JP exhibited selective cytotoxicity against HeLa cervical cancer and B16 melanoma cells, with no obvious toxicity to normal L929 and RAW264.7 cells. Mechanistically, JP induced mitochondrial-dependent apoptosis via upregulating Bax and cleaved Caspase-9/-3, while downregulating Bcl-2, and concurrently triggered G1/S phase arrest through modulation of CCND1, CDK2, CDK4, PCNA, MYC, and TP53. To enable localized delivery, JP was incorporated into an injectable chitosan/gelatin/F127 thermosensitive hydrogel (JP-H), which exhibited rapid sol-gel transition at physiological temperature, shear-thinning behavior, and a porous microstructure. JP-H not only sustained JP release but also significantly enhanced antibacterial activity against E. coli and S. aureus compared to free JP. Furthermore, JP-H markedly inhibited HeLa cell migration and induced superior apoptotic/necrotic cell death in co-culture assays, outperforming free JP. Collectively, this work establishes JP as a multi-target antitumor agent and demonstrates JP-H as a promising local therapeutic platform combining sustained delivery, antibacterial protection, and enhanced anticancer efficacy for cervical cancer treatment.

Abstract: Network pharmacology has become a central paradigm in modern drug discovery, replacing the reductionist "one drug, one target" view with a systems-level understanding of how compounds engage networks of proteins that are linked to disease. Despite its impact, a typical network-pharmacology study remains fragmented and technically demanding: researchers must query several independent databases, install and reconcile multiple standalone tools for target collection, network construction, hub-gene ranking and pathway enrichment, and then manually bridge the results into structure-based follow-up such as molecular docking. This fragmentation is a persistent barrier, particularly for experimental and non-specialist users. Here we present the network-pharmacology module of Drug Design Studio (DDS) 2.0, a unified, user-friendly platform that automates the entire workflow — disease-target retrieval, compound-target prediction, shared-target identification, protein–protein interaction (PPI) network construction, hub-gene ranking and gene ontology/pathway enrichment — within a single guided interface, removing the burden of assembling disparate packages. Crucially, DDS 2.0 links the resulting hub genes directly to the docking and virtual-screening engine introduced in the previous DDS release: representative experimental structures are selected automatically and streamed into a docking-ready workspace, including for covalent binders. We validate the module by reproducing a published curcumin–triple-negative-breast-cancer (TNBC) study, confirming that DDS recovers the key targets, hubs and pathways. DDS 2.0 thus delivers an integrated route from systems-level analysis to structure-based drug design. DDS 2.0 is freely and publicly accessible via (http://soliman.ukzn.ac.za/DDS2.aspx). Comprehensive user documentation is built directly into DDS and can be accessed at any time from the Documentation panel.

Abstract: Background/Objectives: Oxidative stress and chronic inflammation are critical pathophysiological drivers of over 100 degenerative diseases and malignancies. Beta-Sitosterol (BS) and pteropodine (PT) are plant-derived bioactive compounds implicated in fatty acid metabolism and tissue homeostasis. This study aimed to evaluate the immunomodulatory capacity, selective cytotoxicity, acute anti-inflammatory effects, and antimutagenic potential of BS and PT using complementary in vivo and in vitro models.Methods: Male and female BALB/c mice were orally treated with BS (100–200 mg/kg) or PT (25–50 mg/kg). Humoral immunity against thymus-dependent antigens was assessed via a modified Jerne/Cunningham hemolytic plaque assay (SRBC immunization). Acute inflammation was evaluated using a TPA-induced mouse ear edema model. In vitro selective cytotoxicity was determined by exposing human hepatocellular carcinoma cells (HepG2) and normal human liver cells (Chang liver) to both compounds, evaluating cell adhesion and morphology. Results: Both BS and PT significantly enhanced the humoral immune response by increasing plaque-forming cells (IgM-producing B-lymphocytes) and elevated peripheral lymphocyte counts in BALB/c mice. Topically, both compounds effectively reduced TPA-induced acute ear edema. Furthermore, BS exhibited potent selective cytotoxicity, inducing complete cell detachment (CT100) and apoptotic morphological changes in HepG2 cancer cells, while leaving normal Chang liver cells unaffected (CT0). Conclusions: Pteropodine and beta-sitosterol exert significant immunomodulatory, anti-inflammatory, and antioxidant activities in vivo, alongside a remarkable tumor-selective cytotoxic profile in vitro, representing promising natural scaffolds for multi-target chemopreventive therapies.

Abstract: IMGT^®, the international information system^® (https://www.imgt.org) (IMGT) was created in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS) at Montpellier, France, to deal with and to manage the huge diversity of the immuno-globulins (IG) or antibodies and T cell receptors (TR), which are the antigen receptors (AR) of the adaptive immune response (AIR) of the jawed vertebrates. The founding of IMGT^® marked the advent of immunoinformatics, a new science which emerged at the interface between immunogenetics and bioinformatics. The biocuration of the IMGT data (IG and TR sequences, genes and structures) and the implementation of the IMGT system (7 databases, 17 tools, 25,000 Web resources pages) are based on the IMGT Sci-entific chart rules (keywords, labels, nomenclature, numbering…) generated from the IMGT-ONTOLOGY axioms and concepts. The IMGT nomenclature (IMGT-NC) and the IMGT unique numbering, the two pillars of immunoinformatics, have been used to de-fine 335 engineered variants for effector properties and formats of therapeutic antibodies (including chimerisotypes) and TR, fusion proteins for immune applications (FPIA) and composite proteins for clinical applications (CPCA). IMGT engineered var-iants names from the World Health Organization (WHO) International Nonproprietary Name (INN) programme descriptions contribute to the common language for immunoinformatics and artificial intelligence (AI).

Abstract: Durable therapeutic response depends not only on suppressing a disease-associated pathway, but also on changing the cellular dynamics that permit pathological or drug-tolerant states to persist and re-emerge. We distinguish transient activity modulation from kinetic remodeling, defined as a change in the drift, noise, flux, stability or transition structure governing cell-state accessibility. Using MAPK signaling as a model system, we organize remodeling into five idealized modes and link each to measurable signatures, including altered occupancy, switching, hysteresis and post-withdrawal recovery. This framework provides an experimental basis for identifying interventions that produce durable state control rather than temporary pathway inhibition.

Abstract: Eukaryotic genomes are organized into chromatin, a highly compact structure in which DNA is packaged into nucleosomes. Nucleosome formation, where DNA is wrapped around histone proteins, is essential for genome stability. This compaction protects DNA from damage and regulates accessibility of genes. Nucleosomes must be disassembled and reassembled during DNA replication and repair. These processes require precise regulation of histone folding, transfer, and deposition by a diverse network of histone chaperones. Chromatin assembly factor 1 (CAF-1) is a conserved histone chaperone that specifically deposits newly synthesized histones during replication-coupled and repair-coupled nucleosome assembly. The sliding clamp proliferating cell nuclear antigen (PCNA) serves as a regulatory scaffold during these processes by recruiting CAF-1 and many other proteins to sites of DNA replication and repair. Recent structural and biochemical studies have revealed increasingly complex mechanisms underlying PCNA-mediated CAF-1 recruitment, involving multiple protein interaction motifs, DNA-binding domains, and regulatory mechanisms that ensure efficient nucleosome assembly. This review summarizes current advances in understanding the molecular mechanisms by which human and yeast CAF-1 complexes are recruited to sites of DNA synthesis and how CAF-1 function is coordinated with other histone chaperones during replication and repair. These studies have provided important insights into how cells coordinate DNA metabolism with epigenome maintenance to preserve genome integrity.

Abstract: A hard protein corona was engineered onto tannic acid modified magnetic nanoparticles (SAMN@TA), a magnetic and luminescent core-shell nano-carrier, using Bovine Serum Amine Oxidase (BSAO), an enzyme catalysing the oxidation of polyamines and producing the corresponding aldehydes and hydrogen peroxide. The absorption and intracellular bioactivity of the self-assembled multimodal SAMN@TA@BSAO were investigated on an intestinal barrier model built with human colorectal adenocarcinoma (Caco-2) cells. The tailored BSAO corona possessed fouling resistance and, at the same time, was able to activate the clathrin-mediated endocytosis (CME) mechanism. Despite its size and intrinsic complexity, the nano-vehicle was effectively transported across the cell layer, safely transiting across the cell cytoplasm and reaching the lumen. As a function of intracellular polyamine concentration, the system biological activity induced intracellular oxidative stress, leading to the activation of Keap1/Nrf2 oxidative protection pathway. The SAMN@TA@BSAO effect was well described by a dose response curve with an EC50 of around 30 µg mL-1 and a programmable killing efficiency (> 50.0%), recalling the feasibility of a low molecular weight drug administration. The present study contributes to the nascent knowledge on engineering protein corona as a key to rationally design nanomaterials for biomedical applications.

Abstract: Regardless of whether consciousness is viewed as integrated information, a sensory input, a quantum process involving “brain microtubules”, a generative mental model, or else, its origins unavoidably lie in genetic coding, transcriptional variations, and protein synthesis. If the deepest mystery in biology, the genetic code, is solvable through basic biochemistry and evolution, consciousness, as its byproduct, must be governed by the same natural laws. Just as the genetic code, consciousness required specific evolutionary pressures to emerge, develop, and sustain its primary function. It is therefore only logical to suggest that the nature of consciousness is defined by the same molecular mechanisms that control all essential life processes in multicellular organisms – the code, its expression and its translation. Accordingly, this view posits that consciousness originates from the unique genomic signatures within neurons and the brain’s electrochemical circuity is a secondary result rather than the primary cause.

Abstract: Non-alcoholic fatty liver disease (NAFLD) specifically includes the stage of simple fatty liver and the stage of hepatitis. Recent research found mesenchymal stem cell therapy for NAFLD. Mesenchymal stem cells regulate metabolic pathways and energy transport pathways in disease models, reducing the synthesis and utilisation of glucose and fatty acids and restoring the homeostasis of the internal microenvironment. For areas with more severe damage, umbilical cord mesenchymal stem cells (UCMSC) are used for regenerative repair with classic Wnt pathway. The text explores the therapeutic effects of UCMSCs on hepatitis and the surrounding environment from a multifunctional perspective. Mesenchymal stem cells release exosomes in a paracrine manner into the damaged areas of the liver, promoting the differentiation and development of hepatic progenitor cells into hepatocytes, reducing differentiation into cholangiocytes, while assisting hepatic progenitor cells in resisting the progression of inflammation and fibrosis, and promoting the normal function of adaptive immune responses.

Abstract:

Water deficit severely limits rice productivity. The elite Dian (D1)-type hybrid japonica rice 'Dianheyou 615 (ZH1)' exhibits exceptional drought adaptation in high-altitude rainfed uplands of the Yungui Plateau, yet the underlying molecular mechanisms remain unknown. We compared phenotypic and transcriptomic responses of ZH1 and six other japonica cultivars under well-watered and water-deficit conditions. Water-deficit stress significantly impaired agronomic traits across all cultivars; however, ZH1 uniquely maintained relatively stable flag leaf morphology, seed-setting rate, and displayed distinctive stomatal traits, in stark contrast to its parental lines and other cultivars. Transcriptomic profiling at the jointing-to-booting stage defined a core drought response module of 174 conserved genes across all cultivars. Critically, by intersecting 1,097 ZH1-specific genes with drought-responsive elements, we pinpointed 15 core, cultivar-specific regulatory genes. These candidates are enriched in functions related to cuticle formation, carbohydrate metabolism, and stress signaling; among them, a DREB transcription factor (LOC4347618) is a prime candidate. qRT-PCR validated their expression. This conserved-to-cultivar-specific regulatory framework and the identified genes provide valuable resources for molecular breeding of water-saving, high-yield rice cultivars.