Life Sciences[JOURNAL]
Sun
200 papers
Immune interventions in stroke: current progress and perspectives.
Guo C, Guan D, Liu Q … +1 more , Han Z
Sci China Life Sci · 2026 May · PMID 42228253 · Publisher ↗
Acute ischemic stroke (AIS) is a devastating cerebrovascular disorder associated with high morbidity, mortality, and long-term disability, where neuroinflammation serves as a central pathogenic driver mediating secondary...
Acute ischemic stroke (AIS) is a devastating cerebrovascular disorder associated with high morbidity, mortality, and long-term disability, where neuroinflammation serves as a central pathogenic driver mediating secondary brain injury and functional impairment. This comprehensive review synthesizes the latest advances in neuroimmune interventions for AIS over the past decade, drawing on systematic literature retrieval from PubMed, Web of Science, Embase, and Ovid Medicine. We first delineate the dual pro-inflammatory and anti-inflammatory mechanisms of key immune cells-including microglia, astrocytes, T cells, B cells, natural killer (NK) cells, monocytes, and neutrophils-in the ischemic brain. Specifically, we highlight their dynamic phenotypic polarization, intercellular crosstalk, and regulatory roles in shaping the post-ischemic immune microenvironment, which provides a theoretical basis for targeted immune interventions. Subsequently, we systematically summarize the clinical research progress on promising therapeutic strategies, encompassing traditional and novel agents such as tirofiban, methylprednisolone, natalizumab, fingolimod combined with alteplase, edaravone dexborneol, butylphthalide, JAK/STAT pathway inhibitors, ApTOLL, anakinra, and tocilizumab, as well as cell transplantation therapies. For each intervention, we analyze its efficacy, safety, underlying immune-modulatory mechanisms, and current clinical trial status. Finally, we discuss the existing challenges in clinical translation-such as suboptimal targeting efficiency, individual variability in treatment response, and unresolved safety concerns-and prospect future directions for precision immune therapy in AIS. This review offers a comprehensive and up-to-date overview of the neuroimmune landscape in AIS, providing valuable insights for researchers and clinicians engaged in stroke treatment and drug development.
Corrigendum to "Trigonelline mitigates bleomycin-induced pulmonary inflammation and fibrosis: Insight into NLRP3 inflammasome and SPHK1/S1P/hippo signaling modulation" [life sciences 336 (2024) 122272].
Zeyada MS, Eraky SM, El-Shishtawy MM
Life Sci · 2026 Sep · PMID 42225531 · Publisher ↗
Abstract loading — click title to view on PubMed.
Single-cell transcriptomics and multimodal molecular profiling revealed the oncogenesis and tumor microenvironment of cardiac myxoma.
Yu X, Shi Y, Xie M … +9 more , Deng K, Fu Z, Hao S, Pei Y, Liang Z, Guo L, Li J, Zhang J, Han X
Sci China Life Sci · 2026 May · PMID 42223569 · Publisher ↗
This study investigates the distinct cellular composition of cardiac myxoma (CM), the pathways underlying its origin, and the mechanisms driving the development of diverse tumor morphologies. A comprehensive single-cell...
This study investigates the distinct cellular composition of cardiac myxoma (CM), the pathways underlying its origin, and the mechanisms driving the development of diverse tumor morphologies. A comprehensive single-cell RNA sequencing (scRNA-seq) analysis was performed on five CM tissue samples and five normal atrial septum samples, encompassing the construction of a CM cell atlas, cell differentiation trajectory reconstruction, cell-cell interaction prediction, identification of cluster-specific transcription factor regulons, and assessment of tumor cell heterogeneity. Validation of scRNA-seq results was conducted through hematoxylin-eosin staining, multiplex immunofluorescence, cellular experiments, and a public database. This study profiled a total of 86,741 cells and identified 13 distinct cell sub-populations based on gene expression. Mesenchymal cells predominated in CM tissues, with high expression of calretinin. Findings from scRNA-seq analysis demonstrated that cardiac endothelial cells undergo endothelial-to-mesenchymal transition (EndoMT), giving rise to mesenchymal-like CM cells. Moreover, hematoxylin-eosin staining and multiplex immunofluorescence revealed variations in the subtypes and functions of tumor-associated fibroblasts and mural cells across different CM morphologies (lobulated and villous). This study demonstrated that CM cells exhibit mesenchymal-like characteristics and their origin is linked to the EndoMT of cardiac endothelial cells. The subtypes of tumor-associated fibroblasts and mural cells contribute to the morphological diversity of CM.
Docosahexaenoic acid alleviates Ornidazole toxicity related to spermatogenic dysfunction by modulating PPARγ-dependent ER-mitochondrial uncoupling.
Li C, Zhao S, Shi C … +19 more , Sun S, He Z, Xu Y, Zheng L, Tang T, Qiu S, Liang K, Zhang H, Zou Z, Feng Y, Zang M, Dong J, Ma J, Ma R, Fu C, Ge X, Wang Y, Jing J, Yao B
Sci China Life Sci · 2026 May · PMID 42223568 · Publisher ↗
Male infertility has been increasing globally, raising concerns for reproductive health. Ornidazole (ORN) emerges as a novel environmental pollutant and compromises male fertility. However, the protective role and underl...
Male infertility has been increasing globally, raising concerns for reproductive health. Ornidazole (ORN) emerges as a novel environmental pollutant and compromises male fertility. However, the protective role and underlying mechanisms of docosahexaenoic acid (DHA) against ORN-induced testicular damage remain unexplored. Our clinical data showed that elevated serum ORN levels were negatively correlated with sperm quality. In vivo, ORN exposure led to impaired spermatogenesis, including meiotic disorders. Specifically, ORN impaired redox balance and reduced the expression of mitochondrial respiratory chain proteins (Ndufs1 and SdhB) in spermatocytes. Supplementation with docosahexaenoic acid significantly restored the quantity of DDX4-positive germ cells and SYCP3-positive spermatocytes and facilitated the progression from zygotene to pachytene stage. Mechanistically, DHA restored mitochondrial function and ROS levels by stimulating peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Moreover, DHA reduced the expression of mitochondria-associated endoplasmic reticulum membranes (MAMs)-tethered voltage-dependent anion channel 1 (VDAC1), restoring MAMs balance and mitochondrial calcium homeostasis in a PPARγ-dependent manner. The DHA/PPARγ/VDAC1 axis in spermatocytes functions as a critical metabolic switch for regulating MAMs and ensuring mitochondrial homeostasis during meiosis. DHA is a promising therapeutic metabolite for oligoasthenozoospermia induced by environmental pollution.
Noncoding navigators of vascular smooth muscle cells: lncRNAs at the interface of vascular plasticity and therapeutic intervention.
Saha S, Mohanta S, Ain R
Life Sci · 2026 Sep · PMID 42219081 · Publisher ↗
Vascular smooth muscle cell (VSMC) plasticity underlies both adaptive and maladaptive vascular remodelling in cardiovascular disease. Contractile VSMCs maintain vascular tone and structural integrity, whereas pathologica...
Vascular smooth muscle cell (VSMC) plasticity underlies both adaptive and maladaptive vascular remodelling in cardiovascular disease. Contractile VSMCs maintain vascular tone and structural integrity, whereas pathological stimuli, such as inflammation, oxidative stress, hyperglycaemia, and mechanical injury induce phenotypic switching toward synthetic, proliferative, and osteogenic states. Emerging evidence implicates long non-coding RNAs (lncRNAs) as central regulators of these phenotypic transitions. Nuclear lncRNAs, including ANRIL, modulate chromatin architecture and recruit histone-modifying complexes to drive proliferation and repress contractile gene expression, while CARMN stabilizes SRF-Myocardin transcriptional complexes to preserve contractile identity. Cytoplasmic lncRNAs, such as SMILR, HIF1A-AS2, and PVT1, act as competing endogenous RNAs to sequester microRNAs, reinforcing pro-proliferative and pro-migratory programs. In disease contexts, dysregulated lncRNAs contribute to atherosclerosis, pulmonary arterial hypertension (PAH), restenosis, and vascular calcification. For example, MEG3, CASC2, MALAT1 and NEAT1 orchestrate hyperproliferation and apoptosis resistance in pulmonary artery smooth muscle cells, driving PAH progression, whereas H19, DANCR, and GAS5 regulate WNT/β-catenin, BMP, and NOTCH pathways to mediate VSMC osteogenic trans-differentiation in diabetes and chronic kidney disease. Translationally, circulating lncRNAs such as SMILR and ANRIL serve as potential biomarkers of vascular pathology, and preclinical studies targeting CARMN, MALAT1, and CASC2 demonstrate efficacy in modulating pathological remodelling. Collectively, lncRNAs integrate transcriptional, epigenetic, and post-transcriptional networks to govern VSMC phenotype and represent promising therapeutic targets for precision vascular medicine.
Empagliflozin restores electrocontractile function in cardiomyocytes following tebuconazole exposure.
Dos Santos Martins F, Resende ALB, de Sousa Marques IL … +6 more , Teles AS, Meireles MHV, de Almeida DL, Bleicher L, Santos-Miranda A, Joviano-Santos JV
Life Sci · 2026 Sep · PMID 42217566 · Publisher ↗
AIMS: Tebuconazole (TEB) is a fungicide that has been increasingly associated with cardiovascular effects. The Sodium-Glucose Cotransporter-2 Inhibitors, as Empagliflozin (EMPA), have emerged as a therapeutic class with...
AIMS: Tebuconazole (TEB) is a fungicide that has been increasingly associated with cardiovascular effects. The Sodium-Glucose Cotransporter-2 Inhibitors, as Empagliflozin (EMPA), have emerged as a therapeutic class with direct, independent, cardioprotective properties that extend beyond glycemic control. However, the mechanisms underlying these protective actions remain incompletely understood, particularly regarding whether EMPA can mitigate cardiotoxicity triggered by toxicants, as TEB. This study aimed to evaluate the potential action of EMPA during TEB exposure. MATERIALS AND METHODS: Cardiomyocytes from rats were isolated and divided as: control (vehicle), TEB, and TEB + EMPA (acute exposure). Contractility, action potential, calcium dynamics, and oxidative mechanisms were analyzed. Also, experimental structures of human and rat cardiac channels (Nav1.5, Cav1.2, and Kv4.2) were retrieved and used for high-exhaustiveness whole-protein docking of TEB and EMPA structures. KEY FINDINGS: EMPA prevented the increase in cell contraction induced by TEB. Moreover, EMPA inhibited TEB-induced depolarization of the resting membrane potential and action potential prolongation. TEB markedly impaired calcium handling in cardiomyocytes, rising transient amplitude and changing kinetics, whereas EMPA attenuated these disturbances. The alterations were not associated with oxidative mechanisms. Docking analyses revealed convergent and state-dependent binding patterns of TEB and EMPA across the ion channels. In conclusion, EMPA exposure mitigated TEB-induced cardiomyocyte impairments. There was a degree of superposition between the poses found for TEB and EMPA, which suggests that, even in different channels and in channels sites and respective states, they may compete for the same binding sites. SIGNIFICANCE: These findings highlight new pharmacological possibilities for EMPA, in pesticide-related cardiotoxicity.
Lacticaseibacillus parahuelsenbergensis THGS-36 alleviates acne-like inflammation and lipogenesis in sebocytes via CREB signaling.
Zheng Q, Yi GS, Bae CI … +5 more , Kim S, Nguyen TTM, Kim JW, Kim MJ, Yi TH
Life Sci · 2026 Sep · PMID 42214612 · Publisher ↗
Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit and is associated with Cutibacterium acnes overgrowth, excessive sebum production, and persistent inflammatory responses. This study evaluated th...
Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit and is associated with Cutibacterium acnes overgrowth, excessive sebum production, and persistent inflammatory responses. This study evaluated the anti-acne potential of the cell-free supernatant (CFS) from Lacticaseibacillus parahuelsenbergensis THGS-36 and investigated its host-modulatory effects in sebocytes with a focus on CREB-associated signaling. THGS-36 CFS exhibited dose-dependent antibacterial activity against C. acnes strains KACC 11946 and KACC 19884, with identical minimum inhibitory concentration and minimum bactericidal concentration values of 1.25 mg/mL, and inhibited biofilm formation beginning at a sub-inhibitory concentration. In human sebocytes, 50 μg/mL THGS-36 CFS reduced C. acnes adhesion by 17.2% and significantly suppressed C. acnes CFS-induced secretion of IL-1β, IL-6, IL-8, and TNF-α, concomitant with reduced expression of TLR2 and NFKBIA, as well as decreased phosphorylation of IκBα and p65, indicating attenuation of NF-κB signaling. Under IGF-1 stimulation, THGS-36 CFS decreased lipid accumulation and downregulated lipogenesis-associated transcripts, including SREBF1, FASN, and PPARG. Mechanistically, the anti-inflammatory and anti-lipogenic effects of THGS-36 CFS were associated with stimulus-dependent modulation of CREB phosphorylation. Whole-genome sequencing supported the safety profile of THGS-36 by revealing no detectable virulence- or antibiotic resistance-associated determinants and identifying putative class II bacteriocin gene clusters. Collectively, THGS-36 CFS exerts multi-target anti-acne activity by inhibiting C. acnes growth and biofilm formation while attenuating sebocyte inflammation and lipogenesis, supporting its potential as a safe adjuvant or alternative strategy for acne treatment.
Circadian rhythm disruption aggravates periodontitis via orchestrating TREM2+ macrophage-mediated bone resorption.
Wu P, Wang Y, Chu S … +4 more , Duan Z, Li X, Feng Q, Wang Y
Life Sci · 2026 Sep · PMID 42214611 · Publisher ↗
Circadian rhythm disruption (CRD) potently exacerbates periodontitis, yet how environmental circadian misalignment is sensed and transduced into localized inflammatory bone loss remains poorly understood. Using single-ce...
Circadian rhythm disruption (CRD) potently exacerbates periodontitis, yet how environmental circadian misalignment is sensed and transduced into localized inflammatory bone loss remains poorly understood. Using single-cell RNA sequencing of gingival tissues from a CRD-exacerbated mouse model, we identified a distinct macrophage subpopulation selectively expanded under CRD conditions and enriched along the osteoclastogenic trajectory. This subpopulation is characterized by high expression of Triggering Receptor Expressed on Myeloid cells 2 (TREM2). The CRD-driven accumulation of TREM2 macrophages positively correlated with the severity of alveolar bone destruction and increased osteoclast activity, alongside downregulation of the core circadian regulators BMAL1 within the periodontal microenvironment. TREM2 displays robust circadian oscillations in vitro, and CUT&Tag sequencing demonstrates that BMAL1 rhythmically binds the Trem2 promoter, establishing a clock-TREM2 regulatory axis. CRD disrupts this time-gated mechanism, leading to sustained TREM2 overexpression that pre-activates macrophages and drives excessive bone resorption. Local TREM2 inhibition alleviates gingival inflammation and reduces bone loss. Under RANKL stimulation, Bmal1 knockdown elevates TREM2 and the osteoclast master regulator NFATc1 across all circadian phases, indicating that inflammation-induced BMAL1 reduction relieves the circadian restriction on TREM2 expression. Collectively, these findings show that CRD disrupts BMAL1-mediated circadian gating of TREM2, and that restoring BMAL1 rhythmicity or directly inhibiting TREM2 may represent a therapeutic strategy to mitigate periodontitis exacerbated by circadian disruption.
Nitroxyl relieves acute kidney injury by suppressing SLC31A1-mediated cuproptosis in renal tubular epithelial cells.
Fu X, Chen BX, Wang J … +11 more , Yang L, Li J, Xu AJ, Wei M, Feng YY, Xing HY, Fan B, Lin SB, Zhu XX, Bai N, Cao C
Life Sci · 2026 Sep · PMID 42214610 · Publisher ↗
CONTEXT: Cuproptosis, a copper-dependent form of programmed cell death, has been implicated in the pathogenesis of acute kidney injury (AKI). Nitroxyl (HNO), the one-electron reduced and protonated form of nitric oxide (...
CONTEXT: Cuproptosis, a copper-dependent form of programmed cell death, has been implicated in the pathogenesis of acute kidney injury (AKI). Nitroxyl (HNO), the one-electron reduced and protonated form of nitric oxide (NO), is an emerging regulator of cellular function. However, the role of HNO in modulating cuproptosis during AKI remains largely unexplored. OBJECTIVE: This study aims to investigate the effect of HNO on cuproptosis in a murine model of renal ischemia-reperfusion (IR) injury. MATERIALS AND METHODS: An in vitro hypoxia/reoxygenation (HR) model using human kidney-2 (HK-2) cells and an in vivo renal IR injury mouse model were employed to determine the role of HNO in renal function. RESULTS: Here, we showed that baseline HNO fluorescence in HK-2 cells was enhanced by the HNO donor Angeli's salt (AS) and by the combined treatment with the hydrogen sulfide (HS) donor NaHS and the nitric oxide (NO) donor SNP. In contrast, HR exposure significantly reduced HNO fluorescence. AS administration mitigated oxidative stress, decreased cell apoptosis, and reduced inflammation, along with an overall improvement in renal function in mice with renal IR injury. Pretreatment with AS significantly reduced HR-induced cell vitality injury, apoptosis, reactive oxygen species (ROS) formation, and mitochondrial dysfunction in HK-2 cells. HNO reduced cuproptosis by downregulating the protein expression of ferredoxin 1 (FDX1) and lipoyl synthase (LIAS), and suppressing copper accumulation. The copper ion carrier Elesclomol abolished the renal benefits of HNO. Mechanistic studies showed that HNO promoted the lysosomal localization and degradation of the copper transporter solute carrier family 31 member 1 (SLC31A1), thereby alleviating cuproptosis in renal tubular epithelial cells. Importantly, overexpression of SLC31A1 prevented the effects of HNO on cellular injury and cuproptosis. DISCUSSION AND CONCLUSION: In summary, the present study demonstrated that HNO promotes the autophagy-lysosomal degradation of SLC31A1, which in turn inhibits cuproptosis and effectively alleviates AKI. These results provide experimental support for the potential of HNO as a promising agent for AKI.
Treadmill exercise attenuates neuroinflammation in APP/PS1 mice via gut microbiota remodeling: Evidence from fecal microbiota transplantation.
Yuan S, Lin L, Liu J … +7 more , Lin Q, Wang S, Wu J, Xu D, Liu Y, Lee JY, Qiu L
Life Sci · 2026 Sep · PMID 42214609 · Publisher ↗
Alzheimer's disease is associated with gut microbiota dysbiosis, intestinal barrier dysfunction, lipopolysaccharide (LPS) translocation, and neuroinflammation. However, it is unclear whether exercise-induced gut microbio...
Alzheimer's disease is associated with gut microbiota dysbiosis, intestinal barrier dysfunction, lipopolysaccharide (LPS) translocation, and neuroinflammation. However, it is unclear whether exercise-induced gut microbiota remodeling causally contributes to the neuroprotective effects of exercise in AD. Herein, APP/PS1 mice underwent 12 weeks of treadmill exercise, and fecal microbiota transplantation (FMT) was used to determine whether exercise-related benefits could be transferred to the recipient mice. Behavioral performance was assessed using the Morris water maze and open-field test. Gut microbial profiles were analyzed by 16S rDNA sequencing. Intestinal barrier integrity was evaluated using histology, AB-PAS staining, and tight-junction protein expression, while plasma and brain LPS levels were measured by enzyme-linked immunosorbent assay. Neuroinflammation was examined with immunofluorescence and Western blotting. It was found that treadmill exercise improved spatial learning, memory, and anxiety-like behavior in APP/PS1 mice. These benefits were partly reproduced in recipients of microbiota from exercised donors. Exercise also restored gut microbial diversity and composition, increased the abundance of taxa including Dubosiella and UBA1819, alleviated colonic injury, enhanced mucus secretion, upregulated ZO-1, Occludin, and Claudin-1, and reduced plasma and brain LPS levels. In parallel, exercise and FMT from exercised donors decreased brain TLR4 expression, attenuated microglial and astrocytic activation, and suppressed TLR4/NF-κB signaling and downstream inflammatory cytokines. These findings indicate that treadmill exercise alleviates neuroinflammation in APP/PS1 mice, at least in part, through gut microbiota remodeling, improved intestinal barrier integrity, and reduced LPS-driven inflammatory signaling.
Regenerative potential of muse cells in ROS-mediated cardiac injury: An in vitro oxygen-glucose deprivation/reoxygenation model.
Sallam A, Ibrahim Aly HS, El-Habachi NM … +3 more , Elkafrawy H, Awaad A, Mehanna RA
Life Sci · 2026 Sep · PMID 42214608 · Publisher ↗
AIMS: Myocardial Ischemia-reperfusion injury produces excessive reactive oxygen species, leading to myocardial cell death and debilitated cardiac function. The regenerative properties of cardiac stem/progenitor cells, pa...
AIMS: Myocardial Ischemia-reperfusion injury produces excessive reactive oxygen species, leading to myocardial cell death and debilitated cardiac function. The regenerative properties of cardiac stem/progenitor cells, particularly the Sca-1 population, remain narrow under ischemia-reperfusion injury conditions. Multilineage stress-enduring cells known as Muse cells, a distinguished subpopulation of SSEA-3 mesenchymal stromal cells (MSCs), have shown promise in tissue repair due to their stress-enduring, non-tumorigenic, and pluripotent-like properties. This study questioned the regenerative potential of Muse cells in rescuing Sca-1 cardiac stem cells exposed in vitro to oxygen-glucose deprivation/reoxygenation injury. MATERIALS AND METHODS: Muse cells were first isolated from human adipose mesenchymal stromal cells using Magnetic-activated cell sorting for SSEA-3 cells. Co-culture experiments were conducted to assess the impacts of Muse cells on Sca-1 cardiac stem cells proliferation, apoptosis, oxidative stress. Spontaneous Cardiac differentiation of Muse cells was assessed using expression of cardiac markers (GATA-4, Myosin light chain 2, Connexin-43, Troponin C1, and Myosin heavy chain 6. KEY FINDINGS: Muse cell co-culture with cells exposed to oxygen-glucose deprivation/reoxygenation injury significantly improved the survival and proliferation of Sca-1 cardiac stem cells, while reducing apoptosis and oxidative stress compared to untreated cells. Additionally, Muse cells enhanced spontaneous cardiac differentiation, as indicated by the upregulation of assessed cardiac markers. SIGNIFICANCE: Muse cells exert protective and supportive effects on cardiac stem cells under ischemic-like conditions and may represent a promising adjunct therapy to enhance endogenous cardiac repair. However, further studies are required to confirm functional cardiomyocyte differentiation and clinical applicability. CLINICAL TRIALS: Not available.
Airway sensory neurobiology and TRP channels in chronic cough: mechanisms, cough hypersensitivity, and therapeutic translation.
Yang X, Duan X
Life Sci · 2026 Sep · PMID 42214607 · Publisher ↗
AIMS: Chronic cough is increasingly viewed as a heterogeneous clinical syndrome associated with cough hypersensitivity, not simply a symptom defined by duration. This review examines key mechanisms in chronic cough, the...
AIMS: Chronic cough is increasingly viewed as a heterogeneous clinical syndrome associated with cough hypersensitivity, not simply a symptom defined by duration. This review examines key mechanisms in chronic cough, the reasons why mechanistic insights have translated poorly into therapy, and future directions involving patient stratification and biomarkers. MATERIALS AND METHODS: We reviewed and summarized mechanistic, preclinical, and translational studies on TRPA1, TRPV1, TRPV4, and TRPM8 channels, focusing on peripheral and central mechanisms and on how these findings relate to clinical development. KEY FINDINGS: TRP channels are multimodal sensors in airway sensory nerves and epithelial cells. They respond to irritants, temperature changes, mechanical stress, osmotic stimuli, and inflammatory mediators. Their activation can drive cation influx, neuronal depolarization, neuropeptide release, and ATP-P2X3 signaling, thereby increasing cough reflex sensitivity and neurogenic inflammation. The translational evidence differs across TRP subtypes. TRPV1 has relatively strong support from mechanistic studies and human cough challenge work, whereas TRPA1 is biologically plausible but still has limited human evidence. Evidence for TRPV4 and TRPM8 is more sparse, with TRPV4 mainly linked to ATP-purinergic signaling and TRPM8 less clearly defined in chronic cough. To date, TRP-channel antagonists have produced limited and inconsistent reductions in spontaneous cough frequency. SIGNIFICANCE: These findings suggest that blocking peripheral TRP channels alone may not be enough to control cough hypersensitivity. Future studies should connect patient selection with biomarkers and clinically relevant endpoints.
The RFX6 mechanism spine: A unified model linking transcriptional coordination to endocrine resilience and diabetes pathogenesis.
Mohammed AK, Saeed R, Khalique A … +2 more , Solanki P, Taneera J
Life Sci · 2026 Sep · PMID 42214606 · Publisher ↗
Glucose homeostasis requires coordinated insulin, glucagon, and incretin secretion across pancreatic and gastrointestinal endocrine systems. Despite heterogeneous genetic and environmental triggers, diabetes converges on...
Glucose homeostasis requires coordinated insulin, glucagon, and incretin secretion across pancreatic and gastrointestinal endocrine systems. Despite heterogeneous genetic and environmental triggers, diabetes converges on β-cell dysfunction and disrupted inter-endocrine coordination. Regulatory Factor X6 (RFX6) is essential for endocrine development and remains expressed in adult islets and enteroendocrine cells; however, its functions have largely been studied in isolated contexts. Here, we integrate developmental, epigenomic, physiological, and genetic evidence into a hypothesis-generating framework in which RFX6 functions as a dosage-sensitive endocrine regulator. RFX6-associated programs are linked to glucose sensing, membrane excitability, insulin secretion, redox stability, and gut-islet signaling. Available genetic and functional evidence supports a model in which graded reduction in RFX6 activity correlates with a spectrum of phenotypes: biallelic loss-of-function variants cause syndromic neonatal diabetes (Mitchell-Riley syndrome), heterozygous variants are associated to impaired insulin secretion in RFX6-MODY, and common regulatory variants near the RFX6 locus contribute to susceptibility to polygenic type 2 diabetes. We propose a five-tier "Mechanism Spine" linking chromatin regulation to endocrine physiology and clinical phenotype while emphasizing that its translational implications remain preliminary.
Corrigendum to moxonidine ameliorates cardiac injury in rats with metabolic syndrome by regulating autophagy [Life Sci. 312 (2023)/121,210].
El-Sayed SS, Rezq S, Alsemeh AE … +1 more , Mahmoud MF
Life Sci · 2026 Sep · PMID 42209369 · Publisher ↗
Abstract loading — click title to view on PubMed.
Transfer RNA-derived small RNA-Gly activates the ACPH/GRHL1 axis to facilitate liver cell regeneration in acute-on chronic liver failure.
Yu M, Xu W, Chen G … +7 more , Lei Y, Si H, Liu J, Wen N, Chong Y, Jie Y, Zhao Q
Sci China Life Sci · 2026 May · PMID 42207451 · Publisher ↗
Transfer RNA (tRNA)-derived small RNAs (tsRNAs) represent a novel class of small non-coding RNAs. Our previous study showed that tsRNA exhibits differential expression patterns in patients with acute-on-chronic liver fai...
Transfer RNA (tRNA)-derived small RNAs (tsRNAs) represent a novel class of small non-coding RNAs. Our previous study showed that tsRNA exhibits differential expression patterns in patients with acute-on-chronic liver failure (ACLF), suggesting its potential as a biomarker for ACLF. Nevertheless, the precise role and underlying molecular mechanisms of tsRNA in ACLF remain largely unknown. Using small tsRNA sequencing, the present study revealed that tsRNA-Gly levels were significantly reduced in both plasma exosomes and liver tissues from patients with ACLF. Functionally, robust overexpression of tsRNA-Gly remarkably enhanced liver cell regeneration, while its downregulation inhibited this process. Mechanistically, tsRNA-Gly directly binds to the N-terminal motif domain of acylpeptide hydrolase (ACPH), a non-canonical RNA-binding protein, via a specific recognition sequence (+17-+24). This interaction stabilizes ACPH by suppressing its ubiquitin-proteasome-mediated degradation, thereby increasing its intracellular abundance. The stabilized ACPH forms a functional complex with tsRNA-Gly to activate grainy head-like 1 (GRHL1), driving its nuclear translocation and transcriptional upregulation of Cyclin D1 (CCND1) via direct promoter binding. In summary, our findings demonstrate that tsRNA-Gly serves as a critical regulator of liver regeneration through the ACPH/GRHL1/CCND1 axis. This novel discovery not only enriches our understanding of the molecular mechanisms underlying tsRNA function but also offers new insights into the role of tsRNAs in the pathogenesis of ACLF.
The janus-faced extracellular matrix remodeling in acute lung injury: a gatekeeper of macrophage localization and phenotype.
Xie F, Sun Y, Wei X … +7 more , Zhang W, Luo W, Huang J, Fang S, Zhang X, Qiu H, Chao J
Sci China Life Sci · 2026 May · PMID 42192081 · Publisher ↗
Although the extracellular matrix (ECM) is a highly dynamic partner of the immune system, its immunoregulatory role during the early phase of sepsis-induced acute lung injury (ALI) remains poorly defined. Using a murine...
Although the extracellular matrix (ECM) is a highly dynamic partner of the immune system, its immunoregulatory role during the early phase of sepsis-induced acute lung injury (ALI) remains poorly defined. Using a murine cecal ligation and puncture (CLP) model, we observed dynamic ECM remodeling characterized by rapid collagen loss within 24 h, followed by a pathological fibroproliferation phase. Proteomic profiling of the degraded ECM demonstrated its immunoregulatory potential. In vitro studies revealed that annexin A1 (ANXA1), an upregulated ECM component, promoted anti-inflammatory macrophage polarization via the formyl-peptide receptor 2/lipoxin A4 (FPR2/ALX)-dependent 5'-adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway. However, under pathological conditions, collagen loss markedly reduces the number of key binding sites for integrin β1 (Itgb1), thereby disrupting macrophage-ECM adhesion and resulting in macrophage detachment; upon entering the inflammatory microenvironment, these cells acquire a proinflammatory phenotype, exacerbating pulmonary inflammation. Capitalizing on the collagen biosynthetic function of ascorbic acid (AA), we investigated its capacity to restore macrophage-ECM adhesion therapeutically. In vitro, treatment of fibroblasts with AA on decellularized CLP-ECM increased collagen deposition and improved macrophage adhesion. In vivo, intratracheal instillation of AA (20 mg/kg) enhanced collagen biosynthesis, which promoted ECM restoration, sustained interstitial macrophage retention, suppressed proinflammatory cytokine production, and ultimately resolved lung injury. Our study reveals that ECM degradation is an early immunoregulatory event and suggests a therapeutic approach for ECM repair via airway-targeted AA delivery in ALI.
Creation of intermuscular bone-free genetic mutants in grass carp and multiomics reveals molecular regulatory basis.
Liu JQ, Nie CH, Wang ZY … +6 more , Yu Y, Zhang DY, Wang J, Qian XQ, Wan SM, Gao ZX
Sci China Life Sci · 2026 Jul · PMID 42189391 · Publisher ↗
Grass carp (Ctenopharyngodon idellus) is an economically important fish, produced at the highest level among all freshwater aquaculture fish in the world, yet the significant number of intermuscular bones (IBs) present i...
Grass carp (Ctenopharyngodon idellus) is an economically important fish, produced at the highest level among all freshwater aquaculture fish in the world, yet the significant number of intermuscular bones (IBs) present in the fillets severely limits its consumption and processing options. To address this limitation, we first investigated the developmental characteristics of IBs in grass carp. Our results revealed that the key period for IB ossification from myosepta occurred between 15 and 40 days post-hatching (dph). Through gene editing of runx2b, the key gene for IB development, we successfully constructed an F population with runx2b mutations, and the F generation was created through breeding of female and male founders. Subsequently, individuals that completely lacked IBs were screened out from F generation, and then F generations completely lacked IBs were bred. Micro-CT showed that the loss of IBs caused by the runx2b mutation did not affect the formation or mineral density of other main skeletal elements (P>0.05) or the proportion of fat or muscle volume (P>0.05). Nutritional characteristic profiling further revealed no significant differences between the runx2b mutant grass carp without IBs and the wild-type grass carp with IBs in terms of moisture, crude protein, crude fat, amino acids, fatty acids, total sugars, collagen, or other nutrients (P>0.05). An integrated analysis of transcriptomic, proteomic, and metabolomic data provided important information regarding the genetic regulation of nutritional indicators of muscle in grass carp without IBs. Changes in the expression of genes related to Ca signaling and movement indicated that the adaptation of grass carp without IBs leads to increased muscle contraction. These data provide an essential reference for the quality assessment of fish lacking IBs and indicate that this new strain of grass carp has great potential for improving its seeds and processing industry.
IVSA-based siRNA targeted delivery system as a universal strategy for the treatment of EGFR-positive cancer.
Guo H, Zhang X, Bai X … +9 more , Su Y, Yuan R, Guo X, Zhou Z, Hu X, Yan C, Chen X, Zhang CY, Fu Z
Sci China Life Sci · 2026 May · PMID 42189390 · Publisher ↗
Achieving precise antitumour drug delivery to tumour sites and selectively inhibiting oncogene function remain core challenges in cancer treatment. While small interfering RNAs (siRNAs) are a powerful means of achieving...
Achieving precise antitumour drug delivery to tumour sites and selectively inhibiting oncogene function remain core challenges in cancer treatment. While small interfering RNAs (siRNAs) are a powerful means of achieving these goals, their clinical application is limited by delivery barriers, particularly in extrahepatic tissues. Based on the in vivo self-assembled (IVSA) siRNA delivery system, we developed a targeted therapeutic approach for EGFR-positive tumours in this study. We designed an IVSA genetic circuit that can reprogram the liver to produce and self-assemble EGFR siRNAs into small extracellular vesicles (sEVs) tagged with an EGFR-targeting peptide (GE11). The siRNA-encapsulating sEVs can be transported via the blood circulation and guided to EGFR-positive tumour cells by a targeting peptide for tumour therapy. In EGFR-driven NSCLC models, the IVSA siRNA dramatically reduced tumour size and suppressed EGFR expression more effectively than traditional treatments such as gefitinib or osimertinib. We evaluated the efficacy of this system in orthotopic gastric and breast cancer models to further show its therapeutic value for other EGFR-positive tumours. In these models, the IVSA siRNA resulted in significant tumour suppression and enhanced survival outcomes. These findings underscore the versatility and potency of the IVSA platform as a universal therapeutic approach for EGFR-targeted siRNA delivery, providing a promising new avenue for treating a range of EGFR-positive cancers.
Efficient combined use of electroacupuncture with ordered collagen scaffolds enhances the therapeutic efficacy of human spinal cord-derived neural progenitor cells therapy in spinal cord injury rats.
Zou Y, Xue W, Guo B … +16 more , Li L, Zhao Y, Wu X, Xiao Z, Zhang Q, Ma D, Zhao X, Chen B, Shen H, Xu W, Zhang H, Yin Y, Shi Y, Cui Y, Gu R, Dai J
Sci China Life Sci · 2026 May · PMID 42189389 · Publisher ↗
Most spinal cord injury (SCI) patients experience severe morbidity and permanent disability. Currently, effective clinical treatments remain limited. Beyond direct nerve damage, spinal cord lesions result in atrophy of l...
Most spinal cord injury (SCI) patients experience severe morbidity and permanent disability. Currently, effective clinical treatments remain limited. Beyond direct nerve damage, spinal cord lesions result in atrophy of lower limb muscles, thereby impeding motor function recovery. Our therapeutic approach for repairing complete SCI combines traditional Chinese electroacupuncture stimulation of the Jiaji (EX-B2) and Zusanli (ST36) acupoints with the transplantation of human spinal cord-derived neural progenitor cells (hsc-NPCs) delivered on an ordered collagen scaffold. Results indicated that electroacupuncture was applied both to enhance the efficacy of hsc-NPCs therapy for nerve regeneration at the lesion site and to prevent muscle atrophy, contributing to motor function recovery. This innovative approach integrates Eastern and Western medical perspectives to pursue breakthroughs in SCI treatment.
Food processing-derived carbon dots disrupt male fertility via the gut-testis axis.
Chen P, Ma M, Li Y … +7 more , Chen X, Xu Z, Guo J, Hu X, Lv L, Guo J, Liu G
Sci China Life Sci · 2026 May · PMID 42189388 · Publisher ↗
Carbon dots (CDs) are unintentionally formed during thermal processing of food and are emerging environmental pollutants that may pose health risks. We investigated the reproductive toxicity of food-derived CDs via the g...
Carbon dots (CDs) are unintentionally formed during thermal processing of food and are emerging environmental pollutants that may pose health risks. We investigated the reproductive toxicity of food-derived CDs via the gut-testicular axis by exposing male mice to environmentally relevant doses (25 and 100 mg kg d) for 15 weeks. Multi-omics analysis (including metagenomics, transcriptomics, and metabolomics) revealed that CDs significantly altered the gut microbiota composition, reducing beneficial bacteria (Akkermansia muciniphila, P<0.01) while increasing pathogenic bacteria (Desulfovibrionaceae, P<0.001). Functional analysis revealed upregulation of the lipopolysaccharide (LPS) biosynthesis pathway (P<0.001) and reduced levels of barrier-protective tryptophan metabolites. Time-series studies established a mechanistic sequence: microbiota disruption (days 1-3), intestinal barrier dysfunction (days 3-5), blood-testis barrier damage (days 5-7), testicular inflammation, and reproductive dysfunction. Dose-dependent testicular toxicity included reduced testosterone synthesis (P<0.001), impaired spermatogonial stem cell maintenance due to downregulation of PLZF, and impaired fertility. Testicular transcriptomics analysis revealed activation of the IL-17 signaling pathway and inhibition of steroidogenesis. This study provides comprehensive evidence that CD induces male reproductive toxicity through microbiota-dependent mechanisms, emphasizing the environmental health implications of dietary nanoparticle exposure.
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