Ultrasound assessment of diaphragmatic dysfunction in non-critically ill patients: relevant indicators and update.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

Novel Bifunctional Conjugates Targeting PD-L1/PARP7 as Dual Immunotherapy for Potential Cancer Treatment.

Bifunctional conjugates targeting PD-L1/PARP7 were designed, synthesized, and evaluated for the first time. Compounds B3 and C6 showed potent activity against PD-1/PD-L1 interaction (IC50 = 0.426 and 0.342 µM, respectively) and PARP7 (IC50 = 2.50 and 7.05 nM, respectively). They also displayed excellent binding affinity with hPD-L1, approximately 100-200-fold better than that of hPD-1. Both compounds restored T-cell function, leading to the increase of IFN-γ secretion. In the coculture assay, B3 and C6 enhanced the killing activity of MDA-MB-231 cells by Jurkat T cells in a concentration-dependent manner. Furthermore, B3 and C6 displayed significant in vivo antitumor efficacy in a melanoma B16-F10 tumor mouse model, more than 5.3-fold better than BMS-1 (a PD-L1 inhibitor) and RBN-2397 (a PARP7i clinical candidate) at the dose of 25 mg/kg, without observable side effects. These results provide valuable insight and understanding for developing bifunctional conjugates for potential anticancer therapy.

Covalent Organic Framework-Based Materials for Advanced Lithium Metal Batteries.

Lithium metal batteries (LMBs), with high energy densities, are strong contenders for the next generation of energy storage systems. Nevertheless, the unregulated growth of lithium dendrites and the unstable solid electrolyte interphase (SEI) significantly hamper their cycling efficiency and raise serious safety concerns, rendering LMBs unfeasible for real-world implementation. Covalent organic frameworks (COFs) and their derivatives have emerged as multifunctional materials with significant potential for addressing the inherent problems of the anode electrode of the lithium metal. This potential stems from their abundant metal-affine functional groups, internal channels, and widely tunable architecture. The original COFs, their derivatives, and COF-based composites can effectively guide the uniform deposition of lithium ions by enhancing conductivity, transport efficiency, and mechanical strength, thereby mitigating the issue of lithium dendrite growth. This review provides a comprehensive analysis of COF-based and derived materials employed for mitigating the challenges posed by lithium dendrites in LMB. Additionally, we present prospects and recommendations for the design and engineering of materials and architectures that can render LMBs feasible for practical applications.

TRIM24 Cooperates with Ras Mutation to Drive Glioma Progression through snoRNA Recruitment of PHAX and DNA-PKcs.

The factors driving glioma progression remain poorly understood. Here, the epigenetic regulator TRIM24 is identified as a driver of glioma progression, where TRIM24 overexpression promotes HRasV12 anaplastic astrocytoma (AA) progression into epithelioid GBM (Ep-GBM)-like tumors. Co-transfection of TRIM24 with HRasV12 also induces Ep-GBM-like transformation of human neural stem cells (hNSCs) with tumor protein p53 gene (TP53) knockdown. Furthermore, TRIM24 is highly expressed in clinical Ep-GBM specimens. Using single-cell RNA-sequencing (scRNA-Seq), the authors show that TRIM24 overexpression impacts both intratumoral heterogeneity and the tumor microenvironment. Mechanically, HRasV12 activates phosphorylated adaptor for RNA export (PHAX) and upregulates U3 small nucleolar RNAs (U3 snoRNAs) to recruit Ku-dependent DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Overexpressed TRIM24 is also recruited by PHAX to U3 snoRNAs, thereby facilitating DNA-PKcs phosphorylation of TRIM24 at S767/768 residues. Phosphorylated TRIM24 induces epigenome and transcription factor network reprogramming and promotes Ep-GBM-like transformation. Targeting DNA-PKcs with the small molecule inhibitor NU7441 synergizes with temozolomide to reduce Ep-GBM tumorigenicity and prolong animal survival. These findings provide new insights into the epigenetic regulation of Ep-GBM-like transformation and suggest a potential therapeutic strategy for patients with Ep-GBM.

Oxygen evolution and its drivers in a stratified reservoir: A supply-side perspective for informing hypoxia alleviation strategies.

Hypoxia in stratified waters greatly threatens aquatic ecology and societal development owing to enhanced nutrient discharge and increasing global temperature. Current research predominantly alleviates hypoxia by reducing dissolved oxygen (DO) consumption or conducting hypolimnetic oxygenation, yet their implementation has encountered bottlenecks. Therefore, this study explores the potential of increasing the inherent DO supplies in stratified reservoirs to mitigate hypoxia. High-frequency in situ observations and massive modeling experiments are integrated to discern the DO supply mode and the dominant driver of DO evolution. Results indicate that periodic thermodynamic conditions determine the DO supply relationships between oxygen sources (inflow carriage, reaeration, and photosynthesis) for different water layers. Thermal stratification causes the hypolimnion to rely mostly on the inflow for DO supply, leading to a fragile budget prone to hypoxia. However, episodic hydrodynamic events (turnover, wind stir, density current, and flood) can promote DO supply and inhibit hypoxia. Temperature and DO regimes are primarily driven by outflow conditions, followed by inflow and meteorology conditions. Furthermore, hypolimnetic hypoxia can be regulated by altering inflow volume, outflow volume, and outlet elevation. These findings highlight the importance of longitudinal solute exchange in DO evolution in stratified reservoirs, providing a basis for alleviating hypoxia through cascade reservoir operations.

Role of miRNAs in neurovascular injury and repair.

MicroRNAs (miRNA) are endogenously produced small, non-coded, single-stranded RNAs. Due to their involvement in various cellular processes and cross-communication with extracellular components, miRNAs are often coined the "grand managers" of the cell. miRNAs are frequently involved in upregulation as well as downregulation of specific gene expression and thus, are often found to play a vital role in the pathogenesis of multiple diseases. Central nervous system (CNS) diseases prove fatal due to the intricate nature of both their development and the methods used for treatment. A considerable amount of ongoing research aims to delineate the complex relationships between miRNAs and different diseases, including each of the neurological disorders discussed in the present review. Ongoing research suggests that specific miRNAs can play either a pathologic or restorative and/or protective role in various CNS diseases. Understanding how these miRNAs are involved in various regulatory processes of CNS such as neuroinflammation, neurovasculature, immune response, blood-brain barrier (BBB) integrity and angiogenesis is of empirical importance for developing effective therapies. Here in this review, we summarized the current state of knowledge of miRNAs and their roles in CNS diseases along with a focus on their association with neuroinflammation, innate immunity, neurovascular function and BBB.

Sustainable All-Day Thermoelectric Power Generation From the Hot Sun and Cold Universe.

Energy conversion from the environment into electricity is the most direct and effective electricity source to sustainably power off-grid electronics, once the electricity requirement exceeds the capability of traditional centralized power supply systems. Normally photovoltaic cells have enabled distributed power generation during the day, but do not work at night. Thus, efficient electricity generation technologies for a sustainable all-day power supply with no necessity for energy storage remain a challenge. Herein, an innovative all-day power generation strategy is reported, which self-adaptively integrates the diurnal photothermal and nocturnal radiative cooling processes into the thermoelectric generator (TEG) via the spectrally dynamic modulated coating, to continuously harvest the energy from the hot sun and the cold universe for power generation. Synergistic with the optimized latent heat phase change material, the electricity generation performance of the TEG is dramatically enhanced, with a maximum power density exceeding 1000 mW m-2 during the daytime and up to 25 mW m-2 during the nighttime, corresponding to an improvement of 123.1% and 249.1%, compared with the conventional strategy. This work maximizes the utilization of ambient energy resources to provide an environmentally friendly and uninterrupted power generation strategy. This opens up new possibilities for sustained power generation both daytime and nighttime.

Wireless sequential dual light delivery for programmed PDT in vivo.

Using photodynamic therapy (PDT) to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light. Polymeric nanocarriers are widely used for photosensitizer delivery, while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy. Furthermore, the generated short-lived reactive oxygen spieces (ROS) can hardly diffuse out of nanocarriers, resulting in low PDT efficacy. Therefore, a smart nanocarrier system which can be degraded by light, followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy. A light-sensitive polymer nanocarrier encapsulating photosensitizer (RB-M) was synthesized. An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer. Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently. Optimal irradiation time, dose, and RB-M concentration were determined using an agent-based digital simulation method. In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose, which is a clinically significant event that enhances treatment safety.

KAP1 stabilizes MYCN mRNA and promotes neuroblastoma tumorigenicity by protecting the RNA m6A reader YTHDC1 protein degradation.

BACKGROUND: Neuroblastoma (NB) patients with amplified MYCN often face a grim prognosis and are resistant to existing therapies, yet MYCN protein is considered undruggable. KAP1 (also named TRIM28) plays a crucial role in multiple biological activities. This study aimed to investigate the relationship between KAP1 and MYCN in NB. METHODS: Transcriptome analyses and luciferase reporter assay identified that KAP1 was a downstream target of MYCN. The effects of KAP1 on cancer cell proliferation and colony formation were explored using the loss-of-function assays in vitro and in vivo. RNA stability detection was used to examine the influence of KAP1 on MYCN expression. The mechanisms of KAP1 to maintain MYCN mRNA stabilization were mainly investigated by mass spectrum, immunoprecipitation, RIP-qPCR, and western blotting. In addition, a xenograft mouse model was used to reveal the antitumor effect of STM2457 on NB. RESULTS: Here we identified KAP1 as a critical regulator of MYCN mRNA stability by protecting the RNA N6-methyladenosine (m6A) reader YTHDC1 protein degradation. KAP1 was highly expressed in clinical MYCN-amplified NB and was upregulated by MYCN. Reciprocally, KAP1 knockdown reduced MYCN mRNA stability and inhibited MYCN-amplified NB progression. Mechanistically, KAP1 regulated the stability of MYCN mRNA in an m6A-dependent manner. KAP1 formed a complex with YTHDC1 and RNA m6A writer METTL3 to regulate m6A-modified MYCN mRNA stability. KAP1 depletion decreased YTHDC1 protein stability and promoted MYCN mRNA degradation. Inhibiting MYCN mRNA m6A modification synergized with chemotherapy to restrain tumor progression in MYCN-amplified NB. CONCLUSIONS: Our research demonstrates that KAP1, transcriptionally activated by MYCN, forms a complex with YTHDC1 and METTL3, which in turn maintain the stabilization of MYCN mRNA in an m6A-dependent manner. Targeting m6A modification by STM2457, a small-molecule inhibitor of METTL3, could downregulate MYCN expression and attenuate tumor proliferation. This finding provides a new alternative putative therapeutic strategy for MYCN-amplified NB.

LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling.

BACKGROUND: Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). METHODS: LncRNA microarray assay was performed to document abundance changes of lncRNAs in paclitaxel (PTX)-resistant MDA-MB-231 BCSC (ALDH+) and non-BCSC (ALDH-). RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to determine the binding proteins of LINC00115. The clinical significance of the LINC00115 pathway was examined in TNBC metastatic lymph node tissues. The biological function of LINC00115 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA sequencing, mass spectrometry, and the CRISPR/Cas9-knockout system. The therapeutic potential of LINC00115 was examined through xenograft animal models. RESULTS: LINC00115 functions as a scaffold lncRNA to link SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3 at both K106 and K200 in drug-resistant BCSC. PLK3 methylation decreases PLK3 phosphorylation of HIF1α and thereby increases HIF1α stability. HIF1α, in turn, upregulates ALKBH5 to reduce m6A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1α are prognostic for clinical triple-negative breast cancers. CONCLUSIONS: Our findings uncover LINC00115 as a critical regulator of BCSC and highlight targeting LINC00115 and SETDB1 as a potential therapeutic strategy for chemotherapeutic resistant breast cancer.

Multifield-Modulated Spintronic Terahertz Emitter Based on a Vanadium Dioxide Phase Transition.

The efficient generation and active modulation of terahertz (THz) waves are strongly required for the development of various THz applications such as THz imaging/spectroscopy and THz communication. In addition, due to the increasing degree of integration for the THz optoelectronic devices, miniaturizing the complex THz system into a compact unit is also important and necessary. Today, integrating the THz source with the modulator to develop a powerful, easy-to-adjust, and scalable or on-chip THz emitter is still a challenge. As a new type of THz emitter, a spintronic THz emitter has attracted a great deal of attention due to its advantages of high efficiency, ultrawide band, low cost, and easy integration. In this study, we have proposed a multifield-modulated spintronic THz emitter based on the VO2/Ni/Pt multilayer film structure with a wide band region of 0-3 THz. Because of the pronounced phase transition of the integrated VO2 layer, the fabricated THz emitter can be efficiently modulated via thermal or electric stimuli with a modulation depth of about one order of magnitude; the modulation depths under thermal stimulation and electrical stimulation were 91.8% and 97.3%, respectively. It is believed that this multifield modulated spintronic THz emitter will provide various possibilities for the integration of next-generation on-chip THz sources and THz modulators.

Effect of glabridin combined with bakuchiol on UVB-induced skin damage and its underlying mechanism: An experimental study.

BACKGROUND: Research has demonstrated the anti-photoaging properties of glabridin and bakuchiol. METHODS: The impact of glabridin, glabridin + bakuchiol, and bakuchiol on the levels of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) in mice skin fibroblasts was observed. Furthermore, we investigated the potential roles of fibronectin (FN), interferon-γ (IFN-γ), interleukin-22 (IL-22), and transforming growth factor-ß (TGF-ß) in the tissues, and evaluated their impact on the enzymatic levels in the skin. In conjunction with transcriptomic analysis, metabolomic profiling, and network pharmacology, all samples underwent comprehensive metabolomic and principal component analysis. The Venny2.1 method was utilized to identify variances in shared metabolites between the treatment group and the UVB group, as well as between the UVB group and the control group. Subsequently, a cluster heat map was generated to forecast and analyze metabolic pathways and targets. RESULTS: The outcomes from the hematoxylin and eosin and toluidine blue staining revealed that glabridin and bakuchiol markedly decreased dermal thickness and suppressed mast cell infiltration in photoaged mice. Immunohistochemistry and Elisa analysis revealed that glabridin and bakuchiol effectively attenuated the levels of pro-inflammatory factors, including IL-1ß, tumor necrosis factor-α, IL-22, and IFN-γ. Furthermore, an increase in the levels of anti-inflammatory factors such as FN and TGF-ß was also observed. The determination of the contents of superoxide dismutase, hydroxypropyltransferase and malondialdehyde in mice dorsal skin revealed that glabridin and bakuchiol not only elevated the levels of superoxide dismutase and hydroxyproline, but also reduced malondialdehyde content. Due to the limited number of shared differential metabolites exclusively within Kyoto Encyclopedia of Genes and Genomes, comprehensive pathway enrichment analysis was not feasible. CONCLUSION: This study demonstrates that glabridin and bakuchiol effectively impede photoaging and alleviate skin inflammation in mice.

Design, Synthesis, and Structure-Activity Relationship of Novel Pyridazinone-Based PARP7/HDACs Dual Inhibitors for Elucidating the Relationship between Antitumor Immunity and HDACs Inhibition.

Histone deacetylases (HDACs) inhibitors such as vorinostat (SAHA) has been used to treat hematologic malignancies (rather than solid tumors) and have been found to suppress the JAK/STAT, a critical signal pathway for antitumor immunity, while PARP7 inhibitor RBN-2397 could activate the type I interferons (IFN-I) pathway, facilitating downstream effects such as STAT1 phosphorylation and immune activation. To elucidate whether simultaneous inhibition of these two targets could interfere with these two signal pathways, a series of pyridazinone-based PARP7/HDACs dual inhibitors have been designed, synthesized, and evaluated in vitro and in vivo experiments. Compound 9l was identified as a potent and balanced dual inhibitor for the first time, exhibiting excellent antitumor capabilities both in vitro and in vivo. This suggests that 9l can be used as a valuable tool molecule for investigating the relationship between anticancer immunity and HDAC inhibition.

Concurrent inhibition of pBADS99 synergistically improves MEK inhibitor efficacy in KRASG12D-mutant pancreatic ductal adenocarcinoma.

Therapeutic targeting of KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) has remained a significant challenge in clinical oncology. Direct targeting of KRAS has proven difficult, and inhibition of the KRAS effectors have shown limited success due to compensatory activation of survival pathways. Being a core downstream effector of the KRAS-driven p44/42 MAPK and PI3K/AKT pathways governing intrinsic apoptosis, BAD phosphorylation emerges as a promising therapeutic target. Herein, a positive association of the pBADS99/BAD ratio with higher disease stage and worse overall survival of PDAC was observed. Homology-directed repair of BAD to BADS99A or small molecule inhibition of BADS99 phosphorylation by NCK significantly reduced PDAC cell viability by promoting cell cycle arrest and apoptosis. NCK also abrogated the growth of preformed colonies of PDAC cells in 3D culture. Furthermore, high-throughput screening with an oncology drug library to identify potential combinations revealed a strong synergistic effect between NCK and MEK inhibitors in PDAC cells harboring either wild-type or mutant-KRAS. Mechanistically, both mutant-KRAS and MEK inhibition increased the phosphorylation of BADS99 in PDAC cells, an effect abrogated by NCK. Combined pBADS99-MEK inhibition demonstrated strong synergy in reducing cell viability, enhancing apoptosis, and achieving xenograft stasis in KRAS-mutant PDAC. In conclusion, the inhibition of BADS99 phosphorylation enhances the efficacy of MEK inhibition, and their combined inhibition represents a mechanistically based and potentially effective therapeutic strategy for the treatment of KRAS-mutant PDAC.

Prevention and Potential Treatment Strategies for Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.

Risk assessment of SARS-CoV-2 replicating and evolving in animals.

The retransmissions of SARS-CoV-2 from several mammals - primarily mink and white-tailed deer - to humans have raised concerns for the emergence of a new animal-derived SARS-CoV-2 variant to worsen the pandemic. Here, we discuss animal species that are susceptible to natural or experimental infection with SARS-CoV-2 and can transmit the virus to mates or humans. We describe cutting-edge techniques to assess the impact of a mutation in the viral spike (S) protein on its receptor and on antibody binding. Our review of spike sequences of animal-derived viruses identified nine unique amino acid exchanges in the receptor-binding domain (RBD) that are not present in any variant of concern (VOC). These mutations are present in SARS-CoV-2 found in companion animals such as dogs and cats, and they exhibit a higher frequency in SARS-CoV-2 found in mink and white-tailed deer, suggesting that sustained transmissions may contribute to maintaining novel mutations. Four of these exchanges, such as Leu452Met, could undermine acquired immune protection in humans while maintaining high affinity for the human angiotensin-converting enzyme 2 (ACE2) receptor. Finally, we discuss important avenues of future research into animal-derived viruses with public health risks.

Craniofacial Fibrous Dysplasia in Fronto-Orbital Region: A Single-Center Retrospective Study of 38 Cases.

OBJECTIVE: This study presents the clinical characteristics, imaging manifestations, and surgical experience in 38 patients diagnosed with craniofacial fibrous dysplasia in fronto-orbital region (foFD). METHODS: We retrospectively analyzed the clinical data from 38 patients who had surgery for foFD. The surgical procedure typically involved extensive tumor removal, followed by immediate reconstruction of the frontal bone and orbit using synthetic materials. Additionally, 9 patients underwent simultaneous microscopic decompression of the optic canal. RESULTS: Common clinical manifestations included progressive fronto-orbital bone deformity (35), proptosis (28), orbital dystopia (21), and visual impairment (9). The disease primarily affecting the frontal bone (38), the sphenoid bone (28), and the ethmoid bone (24). The optic canal was involved in 9 patients with functional impairment. Computed tomography scans in all 38 cases revealed satisfactory repair material positioning and complete resolution of frontal deformities. Among the 9 patients who underwent optic canal decompression, 7 experienced partial recovery of visual acuity after surgery. CONCLUSIONS: In the surgical treatment of foFD, it is crucial to achieve maximal bone resection and repair skull defects, while decompressing the optic canal can provide significant benefits for patients with decreased visual function preoperatively. The use of preformed artificial materials offers advantages in aesthetic restoration after lesion excision.

Hypoxia-inducible factor-1: Regulatory mechanisms and drug therapy in myocardial infarction.

Myocardial infarction (MI), an acute cardiovascular disease characterized by coronary artery blockage, inadequate blood supply, and subsequent ischemic necrosis of the myocardium, is one of the leading causes of death. The cellular, physiological, and pathological responses following MI are complex, involving multiple intertwined pathological mechanisms. Hypoxia-inducible factor-1 (HIF-1), a crucial regulator of hypoxia, plays a significant role in of the development of MI by modulating the behavior of various cells such as cardiomyocytes, endothelial cells, macrophages, and fibroblasts under hypoxic conditions. HIF-1 regulates various post-MI adaptive reactions to acute ischemia and hypoxia through various mechanisms. These mechanisms include angiogenesis, energy metabolism, oxidative stress, inflammatory response, and ventricular remodeling. With its crucial role in MI, HIF-1 is expected to significantly influence the treatment of MI. However, the drugs available for the treatment of MI targeting HIF-1 are currently limited, and most contain natural compounds. The development of precision-targeted drugs modulating HIF-1 has therapeutic potential for advancing MI treatment research and development. This study aimed to summarize the regulatory role of HIF-1 in the pathological responses of various cells following MI, the diverse mechanisms of action of HIF-1 in MI, and the potential drugs targeting HIF-1 for treating MI, thus providing the theoretical foundations for potential clinical therapeutic targets.