Biology subjects

Hang, C.

Publications and source records attributed to Hang, C..

4 recordsLinked to original sources

bioRxiv2026

Linoleic Acid-Lyso PG Axis promoting lipid droplet-mitochondria tethering by stabilizing Noncanonically Mitochondrial PPAR β/δ to Ameliorate Microglial Dysfunction in subarachnoid hemorrhage

Background Microglial lipid handling and mitochondrial failure contribute to brain injury after subarachnoid hemorrhage (SAH), but the lipid signals coupling these processes remain unclear. We investigated whether linoleic acid (LA) restores microglial homeostasis through lysophosphatidylglycerol 16:0 (LPG[16:0]) and peroxisome proliferator-activated receptor-{delta} (PPAR{delta}). Methods Cerebrospinal fluid metabolomics included 30 patients with aneurysmal SAH and 10 control participants. Mechanisms were examined in a blood-injection mouse model and hemoglobin-exposed primary mouse microglia using targeted lipidomics, RNA sequencing, mitochondrial and phagocytosis assays, pharmacological perturbation, fractionation, coimmunoprecipitation, thermal shift analysis, and structural modeling. Behavioral outcomes were evaluated by open-field, Y-maze, and Morris water-maze testing. Results; CSF LA was higher in SAH and discriminated the groups within this cohort (area under the curve, 0.9967 [95% CI, 0.9859-1.000]; P<0.001). LA attenuated inflammatory activation and restored phagocytosis, mitochondrial membrane potential, respiration, and ATP production in hemoglobin-exposed microglia. LA restored PLA2G15-associated LPG(16:0), which phenocopied these effects. Transcriptomic and inhibitor analyses identified PPAR{delta} as a downstream effector. LPG(16:0) increased PPAR{delta} stability, and fractionation and protease protection identified a PPAR{delta} pool on the cytosolic face of the outer mitochondrial membrane. PPAR{delta} associated with PLIN2 and CPT1A, promoted lipid droplet-mitochondria apposition, and supported fatty acid oxidation. In mice, LA reduced neuroinflammatory injury and partially improved anxiety-related behavior and spatial memory.

neuroscience↗

bioRxiv2026

Endothelial Baf60c in BPD-Associated Pulmonary Hypertension

BACKGROUNDBronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) complicates prematurity and carries substantial morbidity in extremely preterm infants. Pulmonary microvascular endothelial cell (PMVEC) dysfunction promotes capillary rarefaction and vascular remodeling, but epigenetic mechanisms after neonatal hyperoxia are poorly defined. Baf60c (SMARCD3), a SWI/SNF subunit supporting vascular homeostasis, and Smarcc2 (BAF170), a PBAF scaffold subunit linked to proliferative signaling, have not been studied together in BPD-PH. METHODSNeonatal C57BL/6 mice were exposed to 85% oxygen for 14 days. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy, lung weight index, and pulmonary histopathology were assessed; PMVEC proliferation, migration, and invasion were measured. Transcriptome sequencing with GO/KEGG analyses, siRNA knockdown, LY294002 inhibition, coimmunoprecipitation, and Western blotting mapped the Baf60c-Smarcc2-PI3K-Akt-mTOR axis. A Tie1-driven, lung-tropic adeno-associated virus delivered by superficial facial vein injection at postnatal day 1 enabled PMVEC-specific Baf60c overexpression. RESULTSHyperoxia increased RVSP, right ventricular hypertrophy, and lung weight index, impaired alveolarization, reduced capillary density, and promoted arteriolar remodeling. PMVEC function was impaired, with PI3K-Akt pathway enrichment and suppressed signaling. Hyperoxia decreased Baf60c and increased Smarcc2. Baf60c knockdown upregulated Smarcc2, suppressed PI3K-Akt-mTOR, and phenocopied hyperoxia; Smarcc2 knockdown had opposite effects. Baf60c bound Smarcc2 but not PI3K. PMVEC-specific Baf60c overexpression attenuated pulmonary hypertension and right ventricular hypertrophy and partially improved alveolar and microvascular injury. CONCLUSIONSHyperoxia-induced BPD-PH is associated with reduced Baf60c, increased Smarcc2, and suppressed PI3K-Akt-mTOR signaling in PMVECs. Baf60c may indirectly regulate this pathway through Smarcc2. Endothelial Baf60c is a potential therapeutic target in BPD-PH. Novelty and RelevanceO_ST_ABSWhat Is New?C_ST_ABSA neonatal hyperoxia BPD-PH model was characterized with adverse hemodynamic and pulmonary vascular endpoints together with PMVEC functional impairment. Hyperoxia downregulates Baf60c, upregulates Smarcc2, and suppresses PI3K-Akt-mTOR signaling in PMVECs. Baf60c interacts with Smarcc2 without direct PI3K binding. PMVEC-specific Baf60c overexpression via superficial facial vein AAV delivery ameliorates pulmonary hypertension. What Is Relevant?BPD-PH is a developmental pulmonary hypertension phenotype in which pulmonary vascular resistance and right ventricular load are measurable with RVSP and Fulton index, consistent with Group 3 PH biology. SWI/SNF-mediated chromatin remodeling in pulmonary endothelium may link neonatal oxygen injury to impaired angiogenic endothelial function. Clinical/Pathophysiological Implications?Endothelial Baf60c deficiency may contribute to pulmonary vascular rarefaction after neonatal hyperoxia. Restoring endothelial Baf60c may improve pulmonary hemodynamics in BPD-PH, although structural lung injury may be only partially reversible.

physiology↗

bioRxiv2023

Integrated genomics provides insights for the evolution of the polyphosphate accumulation trait of Ca. Accumulibacter

Candidatus Accumulibacter plays a major role in enhanced biological phosphorus removal (EBPR), but the key genomic elements in metagenome assembled genomes enabling their phosphorus cycling ability remain unclear. Pangenome analyses were performed to systematically compare the genomic makeup of Ca. Accumulibacter and non-Ca. Accumulibacter members within the Rhodocyclaceae family. Metatranscriptomic analyses of an enrichment culture of Ca. Accumulibacter clade IIC strain SCUT-2 were performed to investigate gene transcription characteristics in a typical anaerobic-aerobic cycle. Two hundred ninety-eight core genes were shown to be obtained by Ca. Accumulibacter at their least common ancestor. One hundred twenty-four of them were acquired via horizontal gene transfer (HGT) based on best-match analysis against the NCBI database. Fourty-four laterally derived genes were actively transcribed in a typical EBPR cycle, including the polyphosphate kinase 2 (PPK2) gene. Genes in the phosphate regulon (Pho) were poorly transcribed. Via a systematical analysis of the occurrences of these genes in closely related Dechloromonas-polyphosphate accumulating organisms (PAOs) and Propionivibrio-non-PAOs, a Pho dysregulation hypothesis is proposed to explain the mechanism of EBPR. It states that the PhoU acquired by HGT fails in regulating the high-affinity phosphate transport (Pst) system. To avoid phosphate poisoning, the laterally acquired PPK2 is employed to condense excess phosphate into polyphosphate. Alternatively, genes encoding PhoU and PPK2 are obtained from different donor bacteria, leading to unmatched phosphate concentration thresholds for their activation/inactivation. PPK2 tends to reduce the intracellular phosphate to concentration levels perceived by PhoU as low-phosphate states. PhoU is not activated to turn off the Pst system, resulting in continuous phosphate uptake. In conclusion, based on integrated genomic analyses, the HGT of phoU and ppk2 and the resultant Pho dysregulation may have triggered the development and evolution of the P cycling trait in Ca. Accumulibacter.

bioinformatics↗

bioRxiv2020

Electronic blood vessel

Advances in bioelectronics have great potential to address unsolvable biomedical problems in the cardiovascular system. By using poly(L-lactide-co-{varepsilon}-caprolactone) (PLC) that encapsulates the liquid metal to make flexible and bio-degradable electrical circuitry, we develop an electronic blood vessel that can integrate flexible electronics with three layers of blood vessel cells, to mimic and go beyond the natural blood vessel. It can improve the endothelization process through electrical stimulation and can enable controlled gene delivery into specific part of the blood vessel via electroporation. The electronic blood vessel has excellent biocompatibility in the vascular system and shows great patency three months post-implantation in a rabbit model. The electronic blood vessel would be an ideal platform to enable diagnostics and treatments in the cardiovascular system and can greatly empower personalized medicine by creating a direct link of vascular tissue-machine interface.

bioengineering↗