Synthesis of chiral sulfinate esters by asymmetric condensation.

Achiral sulfur functional groups, such as sulfonamide, sulfone, thiol and thioether, are common in drugs and natural products. By contrast, chiral sulfur functional groups are often neglected as pharmacophores1-3, although sulfoximine, with its unique physicochemical and pharmacokinetic properties4,5, has been recently incorporated into several clinical candidates. Thus, other sulfur stereogenic centres, such as sulfinate ester, sulfinamide, sulfonimidate ester and sulfonimidamide, have started to attract attention. The diversity and complexity of these sulfur stereogenic centres have the potential to expand the chemical space for drug discovery6-10. However, the installation of these structures enantioselectively into drug molecules is highly challenging. Here we report straightforward access to enantioenriched sulfinate esters via asymmetric condensation of prochiral sulfinates and alcohols using pentanidium as an organocatalyst. We successfully coupled a wide range of sulfinates and bioactive alcohols stereoselectively. The initial sulfinates can be prepared from existing sulfone and sulfonamide drugs, and the resulting sulfinate esters are versatile for transformations to diverse chiral sulfur pharmacophores. Through late-stage diversification11,12 of celecoxib and other drug derivatives, we demonstrate the viability of this unified approach towards sulfur stereogenic centres.

Therapeutic intervention in neuroinflammation for neovascular ocular diseases through targeting the cGAS-STING-necroptosis pathway.

The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.

Silencing of the T-type voltage-gated calcium channel α1 subunit by fungus-mediated RNAi altered the structure of F-actin and caused defective behaviors in Ditylenchus destructor.

BACKGROUND: T-type calcium channels, characterized as low-voltage activated (LVA) calcium channels, play crucial physiological roles across a wide range of tissues, including both the neuronal and nonneuronal systems. Using in situ hybridization and RNA interference (RNAi) techniques in vitro, we previously identified the tissue distribution and physiological function of the T-type calcium channel α1 subunit (DdCα1G) in the plant-parasitic nematode Ditylenchus destructor. METHODS AND RESULTS: To further characterize the functional role of DdCα1G, we employed a combination of immunohistochemistry and fungus-mediated RNAi and found that DdCα1G was clearly distributed in stylet-related tissue, oesophageal gland-related tissue, secretory-excretory duct-related tissue and male spicule-related tissue. Silencing DdCα1G led to impairments in the locomotion, feeding, reproductive ability and protein secretion of nematodes. To confirm the defects in behavior, we used phalloidin staining to examine muscle changes in DdCα1G-RNAi nematodes. Our observations demonstrated that defective behaviors are associated with related muscular atrophy. CONCLUSION: Our findings provide a deeper understanding of the physiological functions of T-type calcium channels in plant-parasitic nematodes. The T-type calcium channel can be considered a promising target for sustainable nematode management practices.

A specific RIP3+ subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism.

Retinal neovascularization is a leading cause of severe visual loss in humans, and molecular mechanisms of microglial activation-driven angiogenesis remain unknown. Using single-cell RNA sequencing, we identified a subpopulation of microglia named sMG2, which highly expressed necroptosis-related genes Rip3 and Mlkl. Genetic and pharmacological loss of function demonstrated that hypoxia-induced microglial activation committed to necroptosis through the RIP1/RIP3-mediated pathway. Specific deletion of Rip3 gene in microglia markedly decreased retinal neovascularization. Furthermore, hypoxia induced explosive release of abundant FGF2 in microglia through RIP3-mediated necroptosis. Importantly, blocking signaling components of the microglia necropotosis-FGF2 axis largely ablated retinal angiogenesis and combination therapy with simultaneously blocking VEGF produced synergistic antiangiogenic effects. Together, our data demonstrate that targeting the microglia necroptosis axis is an antiangiogenesis therapy for retinal neovascular diseases.

Epigallocatechin-3-Gallate Inhibits Atrial Fibrosis and Reduces the Occurrence and Maintenance of Atrial Fibrillation and its Possible Mechanisms.

BACKGROUND: Atrial fibrosis is one of the main causes of the onset and recurrence of atrial fibrillation (AF), for which there is no effective treatment. The aim of this study was to investigate the effect and mechanism of epigallocatechin-3-gallate (EGCG) on AF in rats. METHODS: The rat model of AF was established by rapid pacing induction after angiotensin-II (Ang-II) induced atrial fibrosis to verify the relationship between atrial fibrosis and the AF. The expression levels of TGF-ß/Smad3 pathway molecules and lysyl oxidase (LOX) in AF were detected. Subsequently, EGCG was used to intervene Ang-II-induced atrial fibrosis to explore the role of EGCG in the treatment of AF and its inhibitory mechanism on fibrosis. It was further verified that EGCG inhibited the production of collagen and the expression of LOX through the TGF-ß/Smad3 pathway at the cellular level. RESULTS: The results showed that the induction rate and maintenance time of AF in rats increased with the increase of the degree of atrial fibrosis. Meanwhile, the expressions of Col I, Col III, molecules related to TGF-ß/Smad3 pathway, and LOX increased significantly in the atrial tissues of rats in the Ang-II induced group. EGCG could reduce the occurrence and maintenance time of AF by inhibiting the degree of Ang-induced rat atrial fibrosis. Cell experiments confirmed that EGCG could reduce the synthesis of collagen and the expression of LOX in cardiac fibroblast induced by Ang-II. The possible mechanism is to down-regulate the expression of genes and proteins related to the TGF-ß/Smad3 pathway. CONCLUSION: EGCG could downregulate the expression levels of collagen and LOX by inhibiting the TGF-ß/Smad3 signaling pathway, alleviating Ang-II-induced atrial fibrosis, which in turn inhibited the occurrence and curtailed the duration of AF.

Ground-state intramolecular proton transfer inhibits the selective methylation on quinoline and pyridine derivatives.

Methylation is one of the crucial steps for drug discovery, organic synthesis, and catalysis. Despite being a versatile and well-known chemical reaction, its chemoselectivity has not been well addressed. In this paper, we reported a thorough experimental and computational investigation of the selective N-methylation of N-heterocyclic compounds, mainly quinolines and pyridines. These reactions were conducted in a base-free manner under ambient conditions using iodomethane as the methylating reagent, exhibited good chemoselectivity, and were tolerant of other amine, carboxyl, or hydroxyl functional groups without needing protection. To this end, 13 compounds were synthesized as a proof-of-concept and 7 crystal structures were obtained. However, the chemoselectivity failed in the presence of a thiol group. Detailed quantum chemical calculations provided insights into the N-methylation mechanism and its selectivity and demonstrated that the isomerization induced by ground-state intramolecular proton transfer (GSIPT) in the presence of a thiol group inhibits the N-methylation.

Disease burden and attributable risk factors of neonatal disorders and their specific causes in China from 1990 to 2019 and its prediction to 2024.

BACKGROUND: Neonatal health is a cornerstone for the healthy development of the next generation and a driving force for the progress of population and society in the future. Updated information on the burden of neonatal disorders (NDs) are of great importance for evidence-based health care planning in China, whereas such an estimate has been lacking at national level. This study aims to estimate the temporal trends and the attributable burdens of selected risk factors of NDs and their specific causes in China from 1990 to 2019, and to predict the possible trends between 2020 and 2024. METHODS: Data was explored from the Global Burden of Disease study (GBD) 2019. Six measures were used: incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Absolute numbers and age-standardized rates (with 95% uncertainty intervals) were calculated. The specific causes of NDs mainly included neonatal preterm birth (NPB), neonatal encephalopathy due to birth asphyxia and trauma (NE), neonatal sepsis and other neonatal infections (NS), and hemolytic disease and other neonatal jaundice (HD). An autoregressive integrated moving average (ARIMA) model was used to forecast disease burden from 2020 to 2024. RESULTS: There were notable decreasing trends in the number of deaths (84.3%), incidence (30.3%), DALYs (73.5%) and YLLs (84.3%), while increasing trends in the number of prevalence (102.3%) and YLDs (172.7%) from 1990 to 2019, respectively. The corresponding age-standardized rates changed by -74.9%, 0.1%, -65.8%, -74.9%, 86.8% and 155.1%, respectively. Four specific causes of NDs followed some similar and different patterns. The prediction results of the ARIMA model shown that all measures still maintained the original trends in the next five years. Low birth weight, short gestation, ambient particulate matter pollution and household air pollution from solid fuels were the four leading risk factors. CONCLUSION: The health burden due to NDs is declining and is likely to continue to decline in the future in China. Delaying the increasing burden of disability may be the next target of concern. Targeted prevention and control strategies for specific causes of NDs are urgently needed to reduce the disease burden.

Thermal Dynamic Self-Healing Supramolecular Dopant Towards Efficient and Stable Flexible Perovskite Solar Cells.

Flexible perovskite solar cells (FPSCs) have attracted great attention due to their advantageous traits such as low cost, portability, light-weight, etc. However, mechanical stability is still the weak point in their practical application. Herein, we prepared efficient FPSCs with remarkable mechanical stability by a dynamic thermal self-healing effect, which can be realized by the usage of a supramolecular adhesive. The supramolecular adhesive, which was obtained by random copolymerization of acrylamide and n-butyl acrylate, is amphiphilic, has a proper glass transition temperature and a high density of hydrogen-bond donors and receptors, providing the possibility of thermal dynamic repair of mechanical damage in FPSCs. The adhesive also greatly improves the leveling property of the precursor solution on the hydrophobic poly[bis(4-phenyl)(2,4,6-trimethylphenyl)]amine (PTAA) surface. PSCs containing this adhesive achieve more than a 20 % power conversion efficiency (PCE) on flexible substrates and a 21.99 % PCE on rigid substrates (certified PCE of 21.27 %), with improved electron mobility and reduced defect concentration.

IL-17 signaling induces iNOS+ microglia activation in retinal vascular diseases.

Activation of microglia and inflammation-mediated vascular damages are suggested to play a decisive role in the pathogenesis of various retinopathies. The inducible nitric oxide synthase (iNOS) was required for activated microglia-mediated injuries. However, the induction mechanism of microglia activation during retinal vascular diseases is still elusive. Here we showed that IL-17 induced microglia activation with high expression of iNOS and promoted the development of retinal vascular diseases. IL-17-dependent activation of the STAT3-iNOS pathway was essentially required for microglia activation, which promoted endothelial cell growth and accelerated vascular leakage and leukostasis via IL-6 in vitro and in vivo. Taken together, our data provide novel mechanistic insights on microglia activation-mediated retinopathy, unveil the specific role of IL-17 on microglia, and define novel therapeutic targets for treating retinal vascular diseases.

Multivariate Polycrystalline Metal-Organic Framework Membranes for CO2/CH4 Separation.

Membrane technology is attractive for natural gas separation (removing CO2, H2O, and hydrocarbons from CH4) because of membranes' low energy consumption and small environmental footprint. Compared to polymeric membranes, microporous inorganic membranes such as silicoaluminophosphate-34 (SAPO-34) membrane can retain their separation performance under conditions close to industrial requirements. However, moisture and hydrocarbons in natural gas can be strongly adsorbed in the pores of those membranes, thereby reducing the membrane separation performance. Herein, we report the fabrication of a polycrystalline MIL-160 membrane on an Al2O3 substrate by in situ hydrothermal synthesis. The MIL-160 membrane with a thickness of ca. 3 µm shows a remarkable molecular sieving effect in gas separation. Besides, the pore size and environment of the MIL-160 membrane can be precisely controlled using reticular chemistry by regulating the size and functionality of the ligand. Interestingly, the more polar fluorine-functionalized multivariate MIL-160/CAU-10-F membrane exhibits a 10.7% increase in selectivity for CO2/CH4 separation and a 31.2% increase in CO2 permeance compared to those of the MIL-160 membrane. In addition, hydrophobic MIL-160 membranes and MIL-160/CAU-10-F membranes are more resistant to water vapor and hydrocarbons than the hydrophilic SAPO-34 membranes.

Tetrazole-Functionalized Zirconium Metal-Organic Cages for Efficient C2 H2 /C2 H4 and C2 H2 /CO2 Separations.

Isoreticular functionalization is a well-elucidated strategy for pore environment tuning and the basis of gas separation performance in extended frameworks. The extension of this approach to discrete porous molecules such as metal-organic cages (MOCs) is conceptually straightforward but hindered by synthetic complications, especially stability concerns. We report the successful isoreticular functionalization of a zirconium MOC with tetrazole moiety by bottom-up synthesis. The title compound (ZrT-1-tetrazol) shows promising C2 H2 /CO2 and C2 H2 /C2 H4 separation performance, as demonstrated by adsorption isotherms, breakthrough experiments, and density functional theory calculations. The design analogy between MOFs and highly stable MOCs may guide the synthesis of novel porous materials for challenging separation applications.

Enantioselective Addition-Alkylation of α,ß-Unsaturated Carbonyls via Bisguanidinium Silicate Ion Pair Catalysis.

Silicon hydrides, alkynylsilanes, and alkoxylsilanes were activated by fluoride in the presence of bisguanidinium catalyst to form hypervalent silicate ion pairs. These activated silicates undergo 1,4-additions with chromones, coumarins, and α-cyanocinnamic esters generating enolsilicate intermediates, for a consequent stereoselective alkylation reaction. The reduction-alkylation reaction proceeded under mild conditions using polymethylhydrosiloxane, a cheap and environmentally friendly hydride source. The addition-alkylation reactions with alkynylsilanes and alkoxylsilanes resulted in the construction of two vicinal chiral carbon centers with excellent enantioselectivities and diastereoselectivities (up to 99% ee, >99:1 dr). Density functional theory calculations and experimental NMR studies revealed that penta-coordinated silicates are crucial intermediates.

Dietary approach to stop hypertension diet and risk of coronary artery disease: a meta-analysis of prospective cohort studies.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet can lower blood pressure, but its role in preventing coronary artery disease (CAD) remains in debate. Thus, we performed a meta-analysis of prospective cohort studies to address this issue. We carried out a systematical search in databases of PubMed and Embase to screen out eligible publications. Relative risks (RRs) of CAD in the included studies were summarised using random-effect meta-analysis. Dose-response association between DASH diet score and CAD risk was also evaluated. Seven prospective studies were finally included, with a total of 377,725 participants and 15,074 CAD cases. Compared to lower adherence, higher adherence to the DASH diet was associated a decreased risk of CAD (RR 0.82, 95% confidence interval [CI]: 0.78-0.87). Subgroup and sensitivity analyses supported the preventive effects of DASH diet against CAD, and there was no indication of publication bias. For a curvilinear dose-response pattern, the RRs (95% CIs) of CAD for the 4 knots (5th, 35th, 65th and 95th percentiles) of DASH diet score were 0.93 (0.89-0.98), 0.87 (0.80-0.95), 0.81 (0.72-0.90) and 0.74 (0.68-0.82), respectively. For a linear dose-response manner, each 4-point increase in the DASH diet score could reduce the risk of CAD by 5% (RR 0.95, 95% CI: 0.94-0.97). The results of our study indicate that higher adherence to the DASH diet confers a reduced risk of developing CAD.

Contractile heterogeneity in ventricular myocardium.

The transmural heterogeneity of the contractility in ventricular muscle has not been well-studied. Here, we investigated the calcium transient and sarcomere contraction/relaxation in the endocardial (Endo) and epicardial (Epi) myocytes. Endo and Epi myocytes were isolated from C57/BL6 mice by Langendorff perfusion. Ca2+ transient and sarcomere contraction/relaxation were recorded simultaneously at different stimulation frequencies using a dual excitation fluorescence photomultiplier system. We found that the Endo myocytes have higher baseline diastolic calcium, significantly larger calcium transient and stronger sarcomere shortening than Epi myocytes. However, both the rising and decline phases for calcium transient and sarcomere shortening were slower in Endo than in Epi myocytes. When simulation frequency was increased from 1 to 3 Hz, a greater percent increase in the diastole calcium level, Ca2+ transient and sarcomere shortening amplitude has been observed in the Endo myocytes. Accordingly, the frequency-dependent acceleration in the decay rate of calcium transient and sarcomere relaxation was more profound in the Endo than in Epi myocytes. Western blot analysis showed that CaMKII activity was significantly higher in Epi than in Endo myocardium before stimulation. However, this transmural heterogeneity was reversed by rapid pacing. CaMKII inhibition by KN93 diminished the frequency-dependent alterations of Ca2+ transient and sarcomere contraction. Our results suggest that the contractility of ventricular myocytes is heterogeneous. The Endo-myocardium is the major force generating layer in the heart, both at slow and fast heart rate, and the transmural heterogeneity of CaMKII activation plays an important role in the frequency-dependent alterations.

[Correlation of Heart Rate and Geographical Environmental Factors with Reference Values of Left Ventricular Ejection Fraction in Healthy Adult Males].

Objective To establish a model for obtaining the reference values of left ventricular ejection fraction(LVEF) in Chinese healthy adult males by exploring the relationships of these reference values with heart rate and geographical environment factors. Methods LVEF and heart rate reference values (X1) were collected from 3502 healthy adult males from 2006 to 2016. Correlation analysis and ridge regression were employed to extract dependent geographical environment factors and predict the LVEF reference values. The Kriging interpolation was applied to reveal the spatial distribution of the LVEF reference values. Results LVEF and heart rate (X1) were significantly correlated with five geographical environment factors. LVEF was negatively correlated with heart rate (X1),latitude (X3),and annual range of temperature (X9) and positively correlated with annual mean air temperature (X6),annual mean relative humidity (X7),and annual precipitation amount (X8). The reference values of LVEF had a negative correlation with heart rate. The ridge regression equation of LVEF reference values and geographical environment factors was as follows:Y=68.464-0.0949X3-0.0619X6-0.00128X7+0.00069X8-0.0199X9±3.329. The equation of LVEF reference values with heart rate and geographical environment factors was Y=75.923-0.1035X1-0.0958X3-0.0741X6+0.00094X7+0.00081X8-0.0211X9±3.288. Conclusion The LVEF reference values among Chinese healthy adult males decreased from south to north. They can be determined based on the regression models after the geographical factors of a certain region are obtained. The new model offers a geographic basis for the establishment of LVEF reference values.

Michael-Michael Addition Reactions Promoted by Secondary Amine-Thiourea: Stereocontrolled Construction of Barbiturate-Fused Tetrahydropyrano Scaffolds and Pyranocoumarins.

Bifunctional secondary amine-thiourea organocatalysts were successfully applied in the stereocontrolled synthesis of barbiturate-fused tetrahydropyrano scaffolds. Compared with typically used tertiary amine-thiourea organocatalysts, the developed catalysts exhibited excellent catalytic performance in the domino Michael-Michael reaction between N, N'-dimethylbarbituric acid and Morita-Baylis-Hillman acetates of nitroalkenes to yield pharmaceutically important heterocycles in good yields with excellent enantioselectivities. Moreover, this catalytic protocol can also be applied to synthesize biologically active pyranocoumarin compounds.

Base-Promoted Intermolecular Cyclization of Substituted 3-Aryl(Heteroaryl)-3-chloroacrylaldehydes and Tetrahydroisoquinolines: An Approach to Access Pyrrolo[2,1-a]isoquinolines.

We have developed a new base-promoted intermolecular cascade cyclization reaction of substituted 3-aryl(heteroaryl)-3-chloroacrylaldehydes and tetrahydroisoquinolines in one pot. The reaction provides a facile and practical synthesis of pyrrolo[2,1-a]isoquinolines. A number of pyrrolo[2,1-a]isoquinolines were synthesized in moderate to high yields (up to 97%).

Hydroxytyrosol improves mitochondrial function and reduces oxidative stress in the brain of db/db mice: role of AMP-activated protein kinase activation.

Hydroxytyrosol (HT) is a major polyphenolic compound found in olive oil with reported anti-cancer and anti-inflammatory activities. However, the neuroprotective effect of HT on type 2 diabetes remains unknown. In the present study, db/db mice and SH-SY-5Y neuroblastoma cells were used to evaluate the neuroprotective effects of HT. After 8 weeks of HT administration at doses of 10 and 50 mg/kg, expression levels of the mitochondrial respiratory chain complexes I/II/IV and the activity of complex I were significantly elevated in the brain of db/db mice. Likewise, targets of the antioxidative transcription factor nuclear factor erythroid 2 related factor 2 including p62 (sequestosome-1), haeme oxygenase 1 (HO-1), and superoxide dismutases 1 and 2 increased, and protein oxidation significantly decreased. HT treatment was also found to activate AMP-activated protein kinase (AMPK), sirtuin 1 and PPARγ coactivator-1α, which constitute an energy-sensing protein network known to regulate mitochondrial function and oxidative stress responses. Meanwhile, neuronal survival indicated by neuron marker expression levels including activity-regulated cytoskeleton-associated protein, N-methyl-d-aspartate receptor and nerve growth factor was significantly improved by HT administration. Additionally, in a high glucose-induced neuronal cell damage model, HT effectively increased mitochondrial complex IV and HO-1 expression through activating AMPK pathway, followed by the prevention of high glucose-induced production of reactive oxygen species and declines of cell viability and VO2 capacity. Our observations suggest that HT improves mitochondrial function and reduces oxidative stress potentially through activation of the AMPK pathway in the brain of db/db mice.

Separating the effects of internal friction and transition state energy to explain the slow, frustrated folding of spectrin domains.

The elongated three-helix bundle domains spectrin R16 and R17 fold some two to three orders of magnitude more slowly than their homologue R15. We have shown that this slow folding is due, at least in part, to roughness in the free-energy landscape of R16 and R17. We have proposed that this roughness is due to a frustrated search for the correct docking of partly preformed helices. However, this accounts for only a small part of the slowing of folding and unfolding. Five residues on the A helix of R15, when inserted together into R16 or R17, increase the folding rate constants, reduce landscape roughness, and alter the folding mechanism to one resembling R15. The effect of each of these mutations individually is investigated here. No one mutation causes the behavior seen for the five in combination. However, two mutations, E18F and K25V, significantly increase the folding and unfolding rates of both R16 and R17 but without a concomitant loss in landscape roughness. E18F has the greatest effect on the kinetics, and a Φ-value analysis of the C helix reveals that the folding mechanism is unchanged. For both E18F and K25V the removal of the charge and resultant transition state stabilization is the main origin of the faster folding. Consequently, the major cause of the unusually slow folding of R16 and R17 is the non-native burial of the two charged residues in the transition state. The slowing due to landscape roughness is only about fivefold.

Identification of 4 autophagy-related genes in heart failure by bioinformatics analysis and machine learning.

Introduction: Autophagy refers to the process of breaking down and recycling damaged or unnecessary components within a cell to maintain cellular homeostasis. Heart failure (HF) is a severe medical condition that poses a serious threat to the patient's life. Autophagy is known to play a pivotal role in the pathogenesis of HF. However, our understanding of the specific mechanisms involved remains incomplete. Here, we identify autophagy-related genes (ARGs) associated with HF, which we believe will contribute to further comprehending the pathogenesis of HF. Methods: By searching the GEO (Gene Expression Omnibus) database, we found the GSE57338 dataset, which was related to HF. ARGs were obtained from the HADb and HAMdb databases. Annotation of GO and enrichment analysis of KEGG pathway were carried out on the differentially expressed ARGs (AR-DEGs). We employed machine learning algorithms to conduct a thorough screening of significant genes and validated these genes by analyzing external dataset GSE76701 and conducting mouse models experimentation. At last, immune infiltration analysis was conducted, target drugs were screened and a TF regulatory network was constructed. Results: Through processing the dataset with R language, we obtained a total of 442 DEGs. Additionally, we retrieved 803 ARGs from the database. The intersection of these two sets resulted in 15 AR-DEGs. Upon performing functional enrichment analysis, it was discovered that these genes exhibited significant enrichment in domains related to "regulation of cell growth", "icosatetraenoic acid binding", and "IL-17 signaling pathway". After screening and verification, we ultimately identified 4 key genes. Finally, an analysis of immune infiltration illustrated significant discrepancies in 16 distinct types of immune cells between the HF and control group and up to 194 potential drugs and 16 TFs were identified based on the key genes. Discussion: In this study, TPCN1, MAP2K1, S100A9, and CD38 were considered as key autophagy-related genes in HF. With these relevant data, further exploration of the molecular mechanisms of autophagy in HF can be carried out.