Search Results (2,756)

Adult hematopoietic stem cells (HSCs) and bone marrow (BM) mesenchymal stem/stromal cells (MSCs) are essential for lifelong hematopoiesis, skeletal homeostasis, immune competence, and tissue regeneration. The use of electronic cigarettes (E-cigs) among women of reproductive age continues to rise, raising concerns about potential adverse developmental effects; however, the long-term consequences of maternal E-cig vaping on offspring BM stem cell function and hematopoietic homeostasis remain incompletely understood. Here, using a rat model of maternal E-cig exposure (containing nicotine) during gestation, combined with longitudinal in vivo analyses and complementary ex vivo studies of human cells, we show that prenatal E-cig exposure is associated with persistent alterations in offspring BM stem cell function and lineage commitment. Gestational E-cig exposure was associated with expansion of the CD11b/c⁺ myeloid-enriched compartment, increased CD90⁺ stromal cells, and impaired osteogenic differentiation in rat offspring. Complementary experiments using primary human cells showed that nicotine exposure was associated with reduced T-cell proliferation and impaired cytotoxic activity in a proof-of-principle co-culture assay. Mechanistically, transcriptomic profiling followed by Gene Ontology and pathway enrichment analyses identified alterations in molecular programs associated with KLF4–Notch1 signaling, mitochondrial biogenesis, inflammation, and stem cell regulation in the BM of E-cig-exposed rat offspring. Changes in CCL11, FTO, and RUNX2 were additionally associated with an inflammatory and aging-related molecular phenotype that persisted from early life into adulthood, although these findings do not establish a causal CCL11–FTO–RUNX2 signaling axis or direct cellular senescence. Collectively, our study provides a phenotypic and mechanistic framework for understanding how maternal E-cig exposure may influence long-term offspring hematopoietic, skeletal, and immune health while highlighting the need for further studies to establish causal molecular mechanisms and determine their relevance to maternal E-cig use in humans. Full article

Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer deaths worldwide. Mutations of the RAS and BRAF genes and the location of the primary tumor determine the choice of systemic therapy. Panitumumab—a fully human anti-EGFR monoclonal antibody—is well-established in the treatment of patients with wild-type RAS and BRAF and left-sided tumor localization. The aim of this review is to summarize the role and potential of targeted therapies for colorectal cancer with monoclonal antibodies such as panitumumab or cetuximab, to provide current evidence on the position of panitumumab in the treatment of mCRC, and to discuss biomarkers and qualification strategies for targeted therapy, including the role of ctDNA in disease monitoring and rechallenge. The work is based on a narrative review of literature from the PubMed, Scopus, Web of Science and Google Scholar databases, including publications available until May 2026. The efficacy of panitumumab was confirmed in phase III studies: first-line (PRIME: prolongation of OS by 5.6 months) and second-line treatment. A key condition for eligibility is complete RAS and BRAF genotyping, assessment of MSI/dMMR status, HER2 amplification, and tumor location. ctDNA analysis enables monitoring of tumor clonal evolution and qualification for rechallenge—the CHRONOS study showed 30% objective responses with liquid biopsy-based selection. Associations with BRAF/MEK and KRAS G12C inhibitors and modulation of the immune microenvironment via the CCL5/CCR5 axis remain promising directions. Panitumumab occupies an important position in the treatment of patients with mCRC, but increasingly precise molecular stratification and dynamic monitoring of disease with ctDNA are becoming the basis for the effective and rational use of the drug. Unlike reviews that selectively focus on individual aspects of anti-EGFR therapy, the following work integrates all aspects: from molecular biology and biomarkers used to qualify patients to clinical data on panitumumab and new strategies in the fight against mCRC. Further development of next-generation sequencing methods and standardization of ctDNA panels will be crucial for the widespread deployment of targeted therapies in everyday clinical practice. The role of panitumumab is well established in appropriately selected patients with RAS wild-type, particularly left-sided, metastatic colorectal cancer (mCRC). Combining panitumumab with immune checkpoint inhibitors warrants further investigation, particularly in patients with MSS/pMMR mCRC. The observed activity of panitumumab in combination with nivolumab and ipilimumab provides a rationale for further clinical evaluation and monitoring. Full article

The purpose of the present study was to investigate how periodontitis and diabetes mellitus (DM) are associated with Alzheimer’s disease (AD) through microRNA (miRNA) using AD model mice. The experimental period was 8 weeks. Twenty-four male knock-in mice (B6-AppNL-G-F/NL-G-F/J) were divided into four groups: control group fed a normal diet (C), DM group fed a high-fat/sucrose diet (DM), periodontitis (P) group, and DM + periodontitis (DM+P) group. Memory performance was compared using the Y-maze test. Next-generation sequencing was performed on brain samples, and fold changes in miRNA expression were calculated by comparing the DM+P and C groups. Integrated miRNA–mRNA analysis identified putative miRNA-targeted mRNAs, and protein expression of the top candidate gene was assessed. Memory function in the DM+P group was significantly lower than in the C group. Among the seven mRNAs identified by the integrated analysis, Neurod1 showed the greatest decrease in expression, and it was predicted to be regulated by miR-693-3p. Neurod1 protein expression in the hippocampus was significantly lower in the DM+P group than the C group. Our results suggest that the combined exposure to periodontitis and DM was associated with AD-like pathological changes and identified the miR-693-3p/Neurod1 pair as a candidate regulatory axis. Full article

Hair follicle stem cells (HFSCs) are critical for hair follicle (HF) morphogenesis and cyclic hair regeneration. Periostin (POSTN), an extracellular matrix protein involved in tissue development and skin cell regulation, remains poorly characterized in HFSCs. In this study, we constructed CRISPR/Cas9 vectors targeting POSTN and validated their editing efficiency in primary HFSCs. POSTN editing significantly suppressed cell proliferation and promoted apoptosis. Transcriptomic analysis identified 988 differentially expressed genes (DEGs) enriched in immune responses and MAPK, PI3K–Akt, and cAMP pathways. Metabolomic analysis revealed 98 differential metabolites (DMs) associated with nucleotide metabolism and FoxO, AMPK, and cAMP pathways. Integrated multi-omics analysis showed extensive correlations between DEGs and DMs, and highlighted the cAMP pathway as the core regulatory axis. Western blot (WB) validation confirmed that POSTN editing reduced PKA and CREB phosphorylation, indicating inhibition of the cAMP/PKA/CREB signaling. These findings demonstrate that POSTN regulates HFSCs’ proliferation and apoptosis partially via the cAMP/PKA/CREB pathway, providing novel insights into the functional regulation of HFSCs. Full article

(1) Background: Perfluorodecanoic acid (PFDA), a persistent perfluoroalkyl obesogen, promotes adipogenesis, yet whether its effects can be pharmacologically opposed remains unknown. (2) Methods: We examined the interaction between PFDA (50, 75 μM) and the dietary polyphenol curcumin (20, 30 μM) throughout the 8-day 3T3-L1 preadipocyte differentiation protocol, using cell-viability (WST-1) assays with a two-factor interaction analysis, Oil Red O lipid quantification and mRNA profiling of Pparg, Cebpa, Srebf1, and Fasn. (3) Results: PFDA alone increased lipid accumulation and upregulated Pparg, Cebpa, and Fasn, whereas Srebf1 was induced only weakly and only at the higher dose, a pattern compatible with preferential engagement of the PPARγ/C/EBPα program over the SREBP-1c lipogenic pathway at the mRNA level, although the transcripts were not formally compared and no protein-level data were obtained. At two sub-cytotoxic concentrations, curcumin preserved potent antiadipogenic activity, reducing lipid accumulation by up to 67.3% and reversing PFDA-induced gene upregulation. At the viability endpoint the two compounds acted independently: curcumin significantly reduced viability and PFDA significantly increased it, with no statistically detectable interaction between them (two-way ANOVA, interaction p = 0.85). (4) Conclusions: This dissociation shows that a chemical interaction defined at one biological endpoint does not predict its outcome at another, a principle with broad implications for mixture toxicology—and it establishes curcumin as a candidate dietary intervention that intercepts an obesogen’s transcriptional program against environmentally driven metabolic disruption. Full article

Osteoarthritis (OA) is increasingly recognized as a mechanically driven whole-joint disease in which abnormal mechanotransduction initiates a cascade of mitochondrial dysfunction, chronic inflammation, and progressive cartilage degeneration. Among the mechanosensitive molecules identified to date, Piezo1 has emerged as a key mechanosensitive regulator linking pathological mechanical loading to intracellular calcium signaling and downstream cellular responses. Growing evidence indicates that persistent Piezo1 activation promotes mitochondrial calcium overload, excessive reactive oxygen species production, ATP depletion, mitochondrial membrane depolarization, and impaired mitophagy, ultimately amplifying chondrocyte dysfunction and extracellular matrix degradation. In parallel, mitochondrial damage triggers immunometabolic reprogramming through activation of the cGAS–STING pathway and the NLRP3 inflammasome. It also promotes pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, and interleukin-6. Together, these responses may contribute to a self-perpetuating cycle of inflammation and tissue destruction. This review provides a comprehensive synthesis of recent advances regarding the role of Piezo1 in OA, focusing on the mechanistic links between mechanotransduction, mitochondrial dysfunction, mitophagy, and immunometabolic dysregulation. We further discuss the contribution of mitochondrial quality-control pathways, including PINK1/Parkin-, BNIP3-, and FUNDC1-mediated mitophagy, as well as alterations in mitochondrial dynamics involving DRP1, MFN1, MFN2, and OPA1. Emerging experimental models are discussed as valuable tools for accelerating therapeutic discovery. Finally, we critically evaluate current therapeutic strategies targeting the Piezo1–mitochondria axis, including mechanosensitive channel modulation, mitochondrial protection, mitophagy enhancement, gene therapy, biomaterial-assisted delivery, and nanomedicine. Collectively, current evidence supports the Piezo1–mitochondria–immune axis as an important mechanistic framework contributing to OA pathogenesis and as a potential therapeutic target. Integrating mechanobiology, mitochondrial medicine, and precision-engineered experimental models may facilitate the development of next-generation disease-modifying therapies capable of slowing or preventing osteoarthritis progression. Full article

Background: High-altitude hypobaric hypoxia (HH) is a major environmental stressor that impairs cognitive function, yet effective and widely available therapeutics remain limited. Although Rhodiola rosea has shown neuroprotective effects, its resource scarcity restricts large-scale application. Cistanche tubulosa (Schrenk) Wight, a traditional Chinese functional food, has been increasingly used in health supplements due to its anti-fatigue, anti-dementia, and memory-enhancing properties, suggesting potential benefits against hypoxia-induced cognitive impairment. Objective: This study aimed to investigate the effects of C. tubulosa ethanol extract (CTE) on hippocampal tissue and gut microbiota upon chronic HH exposure using SPF male Sprague–Dawley (SD) rats. Methods: A total of 60 male SD rats were randomly assigned to six experimental groups (n = 10 per group): normoxic control, untreated HH model, positive control (R. rosea), and low-, medium-, high-dose CTE treatment groups. Behavioral tests (Morris water maze), hippocampal histopathology, serum and hippocampal oxidative stress markers (SOD, GSH-Px, MDA), expression of PI3K/Akt/mTOR-HIF-1α signaling pathway proteins (by immunohistochemistry), and gut microbiota composition (by 16S rRNA sequencing) were evaluated. Results: The results demonstrated that CTE significantly improved cognitive function, enhanced SOD and GSH activities, and reduced MDA levels in both hippocampus and serum. CTE also modulated the expression of PI3K/Akt/mTOR-HIF-1α pathway proteins in the hippocampus. Furthermore, CTE altered gut microbial diversity and abundance, increasing the proportion of beneficial bacteria, which may further influence hippocampal function via the gut–brain axis. Conclusion: These findings provide scientific evidence for the application of C. tubulosa as a potential health supplement for high-altitude adaptation and lay a foundation for subsequent research. Full article

(1) Background: methicillin‑resistant Staphylococcus aureus (MRSA) is a zoonotic pathogen, and its hemolysins serve as key virulence factors. Functional membrane microdomains (FMMs) are protein-enriching platforms and regulate diverse physiological functions by recruiting and assembling various proteins. However, whether and how FMMs regulate the hemolytic ability of MRSA remains unclear. This study aimed to investigate FMM-mediated regulation of MRSA hemolysins and the underlying mechanisms. (2) Methods: Homologous recombination was employed to generate FMM-disrupted (N315ΔfloA) and complemented (N315ΔfloA::floA) strains from the MRSA N315 wild-type strain (N315 WT). The three strains were compared with respect to hemolytic activity, transcript levels of key virulence and regulatory genes, and in vivo virulence. (3) Results: Disruption of FMMs significantly enhanced hemolytic activity compared with N315 WT and complemented strains. Meanwhile, FMM disruption repressed the two-component system genes (vraS and vraR), while activating the agr operon (agrB, agrD, agrC and agrA) and its effector molecule RNAIII, leading to upregulation of hemolysin genes (hla, hlb, hld). In vivo, N315ΔfloA infection markedly increased mortality in G. mellonella larvae and BALB/c mice, with significantly elevated pro-inflammatory factors (TNF-α, IL-6, and IL-1β) in mouse plasma. All these phenotypes were effectively reversed in N315ΔfloA::floA. (4) Conclusions: Disruption of FMMs potentiates both hemolytic activity and overall virulence in MRSA, with the potential underlying mechanism involving the VraS/R-Agr regulatory axis that drives transcriptional upregulation of hemolysin-encoding genes. Full article

Background: Homeobox transcription factors regulate developmental programs, cellular plasticity, and tumor progression, yet the role of H2.0-like homeobox (HLX) in prostate cancer (PCa) remains poorly defined. We investigated the clinical significance of HLX and its relationship to the pro-metastatic transcription factor TBX2. Methods: Transcriptomic and clinical datasets from TCGA, MET500, and SU2C/PCF cohorts were analyzed to assess HLX expression, clinicopathologic associations, and its relationship with TBX2. Functional studies in human PCa cell lines included TBX2 gain- and loss-of-function, HLX knockdown, chromatin immunoprecipitation (ChIP), and expression analyses. Shared HLX- and TBX2-associated pathways were evaluated by Reactome enrichment analysis, and Hallmark Gene Set Enrichment Analysis compared castration-resistant prostate cancer (CRPC) bone metastases with high versus low HLX expression (GSE77930; n = 5/group). In vivo relevance was assessed in an orthotopic TBX2 dominant-negative PCa xenograft model. Results: Human PCa datasets showed that HLX expression was elevated in PCa versus normal prostate tissue and associated with higher Gleason grade, lymph node involvement, aggressive molecular subtypes, and shorter disease-free survival. HLX expression also positively correlated with TBX2 across human PCa cohorts. HLX- and TBX2-associated transcriptional programs converged on extracellular matrix organization, cell adhesion, NOTCH, and VEGF-MAPK signaling pathways. Furthermore, HLX-high CRPC bone metastases were enriched for epithelial–mesenchymal transition, NOTCH, TGF-β, inflammatory, angiogenic, hypoxic, and KRAS signaling pathways. Mechanistic studies showed that HLX knockdown suppressed extracellular matrix-associated genes and key NOTCH pathway components. ChIP demonstrated direct TBX2 binding to the HLX promoter, and genetic modulation of TBX2 expression established HLX as a downstream target of TBX2. Consistent with these findings, reduced HLX expression in orthotopic TBX2 dominant-negative xenografts was associated with loss of metastatic progression. Conclusions: HLX is a candidate biomarker of aggressive PCa and a direct transcriptional target of TBX2. These findings identify a previously unrecognized TBX2–HLX regulatory axis associated with metastatic transcriptional programs and aggressive disease in advanced PCa. Full article

Triple-negative breast cancer (TNBC) is characterized by marked immune microenvironment heterogeneity and variable chemotherapy response, yet the epithelial transcriptional programs governing cytotoxic immune activation remain poorly understood. We performed an exploratory, integrative analysis using single-cell RNA sequencing of 31,962 cells from eight TNBC patients operationally stratified into Good and Bad Prognosis groups based on pathological lymphoid infiltration, a discovery grouping subsequently validated against pathological complete response (pCR) in three independent bulk RNA-seq cohorts. This analysis identified four epithelial transcriptional states. The G5 DNA damage subpopulation—predominantly restricted to Good Prognosis tumors (29.2% vs. 0%)—and the G4 Metabolism subpopulation—2.4-fold enriched in Bad Prognosis—were the primary prognostic signatures. Machine learning validation using nested leave-one-cohort-out (LOCO) cross-validation across 614 samples demonstrated that G4 + G5 raw genes with random forest yielded the largest observed mean AUC of 0.653, though these results are exploratory and do not establish a validated clinical classifier. CellChat ligand–receptor interaction analysis revealed that G5 DNA-damage epithelial cells are the dominant immune activators in Good Prognosis TNBC, predominantly engaging CD8 cytotoxic T cells through MHC-I antigen presentation via HLA-A/B/C/E/F → CD8A/CD8B interactions, the highest-probability signaling pathway identified. Spatial transcriptomics independently validated significantly higher DNA damage and CD8 T-cell scores in Good Prognosis tissue. Together, these exploratory findings suggest a framework in which tumor-intrinsic DNA damage signaling is associated with MHC-I antigen presentation upregulation and CD8 cytotoxic T-cell engagement, supporting further investigation of this axis and its potential implications for combining DNA-damaging chemotherapy with immune checkpoint blockade in TNBC. Full article

Background: Berberine, an isoquinoline alkaloid present in Berberis spp., Coptis chinensis and Hydrastis canadensis, is among the most widely consumed metabolic-health supplements, popularized as “nature’s Ozempic”. Concurrent, often undisclosed use with prescription drugs is common in older adults, yet berberine is far from inert. Objective: To synthesize the evidence on berberine as a perpetrator of supplement–drug interactions, propose a four-axis mechanistic taxonomy, with product quality treated separately as a modifier of exposure rather than as a mechanism, and derive a clinically actionable risk-stratification framework. Methods: Structured narrative review, prepared per the SANRA quality criteria; PubMed/MEDLINE, Scopus, Web of Science and Embase were searched up to May 2026. Results: Despite very low systemic exposure (oral bioavailability 0.68% in rats; low ng/mL plasma concentrations in humans), high luminal, enterocytic and hepatic concentrations generate interaction liability, documented in humans for a few pairs and mechanistic for most, along four mechanistic axes: inhibition, and transcriptional induction, of CYP3A4, with CYP2D6/CYP2C9 inhibition that is quasi-irreversible through a metabolite-intermediate complex; transporter modulation (P-glycoprotein, OCT1/OCT2, and MATE1); pharmacodynamic additivity (hypoglycemia, hypotension, and QT prolongation); and microbiome- and gut-barrier-mediated effects, the last of these being a candidate axis rather than a demonstrated one. Product-quality variability is treated separately, as a modifier of exposure. The clinical anchor is increased cyclosporine exposure in renal-transplant recipients (AUC +34.5%; trough 29.3% above control). These elements are integrated into a three-tier risk-stratification framework that combines perpetrator potency, victim-drug vulnerability, and patient vulnerability, with each tier being linked to a defined pharmacy action. Conclusions: In patients on multiple medications, and particularly when berberine is co-administered with drugs of narrow therapeutic index, it should be managed as an active pharmacological perpetrator rather than as an inert supplement. Unstandardized product quality and an unsettled European regulatory framework, under which national limits differ by more than an order of magnitude, further widen the uncertainty around the dose actually delivered. Berberine use should therefore be elicited routinely at medication reconciliation and stratified by mechanism, by victim-drug vulnerability, and by patient risk, with particular attention to metabolic self-medication in the GLP-1 era. Full article

Background: Climate change-driven heat stress (HS) poses a growing threat to pregnancy outcomes; however, the mechanisms linking maternal HS to fetal growth restriction (FGR) remain incompletely understood, and effective nutritional interventions are lacking. The gut–placenta axis critically governs maternal–fetal health, but its role in mediating HS-related FGR has yet to be elucidated. Methods: A murine model of gestational HS (38.5 °C, 2.5 h daily from E0.5 to E12.5) was established to investigate the protective effects of chlorogenic acid (CGA) on HS-induced FGR. Placental efficiency, oxidative status, barrier integrity, and intestinal permeability were assessed. Gut microbiota composition was profiled by 16S rRNA sequencing, while tight junction protein expression in the placenta and intestine was evaluated by Western blot. Additionally, antibiotic-induced microbiota reduction and fecal microbiota transplantation (FMT) were performed to explore the role of gut microbiota in alleviating HS. Results: HS exposure significantly reduced fetal weight without altering litter size, accompanied by reduced placental efficiency and proportion of the labyrinth zone relative to the total placental area. HS triggered oxidative stress and downregulated tight junction proteins (Claudin-1, Occludin) in both the placenta and intestine, indicating compromised barrier integrity. CGA treatment robustly reversed these abnormalities and restored placental structure. In the gut, CGA prevented HS-induced intestinal barrier dysfunction and selectively reshaped the microbiota, enhancing the Firmicutes/Bacteroidetes ratio and promoting beneficial Lactobacillus lineages. Notably, under antibiotic-induced microbial reduction, FMT from CGA-treated donors effectively alleviated HS-induced fetal growth restriction. Conclusions: In summary, our study suggests that gestational HS exposure may trigger FGR through the gut–placenta axis. CGA effectively reverses FGR by restoring placental efficiency and placental barrier integrity, while alleviating maternal gut dysbiosis and intestinal barrier impairment. FMT experiments further confirm that the gut microbiota may play a key role in this protection. Collectively, these findings suggest that targeting the gut–placenta axis with CGA may offer a practical nutritional strategy to mitigate HS-triggered adverse pregnancy outcomes. Full article

Cisplatin is an effective chemotherapeutic agent whose clinical use is limited by dose-dependent off-target toxicities, particularly hepatic and cardiac injury. The present study investigated the protective efficacy of rutin-mediated selenium nanoparticles (RUT-SeNPs) against cisplatin-induced hepato-cardiotoxicity in rats and compared their effects against those of free rutin and sodium selenite. RUT-SeNPs were characterized using dynamic light scattering, zeta potential analysis, transmission electron microscopy, X-ray diffraction, and UV–visible spectroscopy. Thirty-five male rats were randomly assigned to five groups: control (CON), cisplatin (CIS), CIS + Rutin, CIS + selenium, and CIS + RUT-SeNPs. Cisplatin administration caused marked hepatic and cardiac injury, as evidenced by altered liver-function indices, elevated cardiac injury biomarkers, oxidative stress, inflammatory activation, endoplasmic reticulum stress, and apoptosis. These effects were associated with increased lipid peroxidation, depletion of endogenous antioxidants, KEAP1 upregulation, Nrf2 suppression, activation of the TLR4/MAPK/NF-κB inflammatory axis, elevated TNF-α, IL-6, and COX-2 levels, and increased mRNA expression of the ER stress-related genes PERK, ATF4, ATF6, and CHOP. Cisplatin also promoted mitochondrial apoptosis, as indicated by increased Bax expression and cytochrome c release together with reduced Bcl-2 levels. Although rutin and sodium selenite partially mitigated these alterations, RUT-SeNPs produced the most pronounced protective effects by restoring redox homeostasis, suppressing inflammatory signaling, reducing the elevated expression of ER stress-related genes, and limiting mitochondrial apoptotic activation. These molecular improvements were accompanied by substantial preservation of the hepatic and cardiac histoarchitecture. Collectively, these results indicate that RUT-SeNPs may represent a promising nanoformulation for reducing cisplatin-induced hepato-cardiac toxicity through coordinated modulation of oxidative stress, inflammation, endoplasmic reticulum stress, and apoptosis. Full article

Direct-acting antivirals (DAAs) cure most chronic hepatitis C virus (HCV) infections, yet whether the gut microbiota returns toward a healthy state after viral clearance remains uncertain. We systematically reviewed DAA-era adult HCV studies using sequencing-based fecal microbiota assessment (PROSPERO CRD420261374682). Longitudinal alpha-diversity change was pooled by REML random-effects meta-analysis with Hartung–Knapp adjustment, and compositional/functional findings were synthesized narratively. Seven studies met qualitative criteria and five longitudinal reports were extractable. Because participant overlap between two Thai reports could not be excluded, the primary conservative non-overlap analysis of four reports (180 paired observations) gave Hedges’ g = 0.13 (95% CI −0.53 to 0.80; I² ≈ 89%); the five-report sensitivity estimate was directionally positive but imprecise (g = 0.35, 95% CI −0.38 to 1.07). Recovery concentrated in richness (Chao1), whereas evenness-weighted diversity (Shannon, Hill) barely moved; beneficial taxa such as Faecalibacterium and Blautia increased after SVR. These findings are consistent with uneven, richness-led microbial recovery, but the overall certainty of the pooled evidence is very low (GRADE); functional and clinical recovery remain insufficiently characterized and undemonstrated. Full article

The results of a numerical modeling of the laminar water flow and mixed conductive–convective heat transfer in highly elongated heatsink with continuous rectangular microchannels, and a width-to-length ratio of 625 (i.e., 0.2 mm to 125 mm), are presented, along with two methods of fluid entry (along and perpendicular to the base of the heatsink) for a wide range of surface heat flux density q from 30 to 2000 kW/m² and water volume flow rate from 10 to 50 L/h (${Re}_D=26-128$). It has been demonstrated that: (1) The elongated microchannel maintains its effectiveness in heat removal by water, even under conditions of high q-value; however, in the terminal sections the temperature can approach the maximum permissible operating level for high-loaded silicon electronic components (~95–100 °C). (2) For microchannel heatsinks, the direction of the incoming flow is not of significant influence, since the microchannel structure, even with a height of 2.5 mm, exhibits substantial diffusivity and the flow in the inlet area rapidly turns along the heat distribution base; this flow further possesses the same characteristics as in the case of the input flow parallel to the axis of the microchannels. The developed model allows for the optimization of geometric, kinematic and thermal parameters of highly efficient microchannel devices, depending on the expected operating conditions. Full article