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BACKGROUND: Perioperative management to maintain intraoperative haemodynamic stability is crucial during surgical treatment of pheochromocytomas and paragangliomas (PPGLs). Although approximately 70% of PPGLs carry pathogenic variants (PVs) in susceptibility genes, whether intraoperative haemodynamic instability (IHI) is associated with genetic background remains unclear. This study aimed to analyse IHI in patients with PPGL due to PVs in different genes. MATERIALS AND METHODS: This retrospective study recruited 756 patients with abdominal PPGL from two tertiary care centres. Clinical information including sex, age, catecholamine-associated signs and symptoms (CAS), tumour location and size, biochemistry, and perioperative characteristics were collected. Genetic mutations were investigated using next-generation sequencing. RESULTS: Among the 671 patients included in the analysis, 61.8% (415/671) had IHI. IHI was significantly associated with genetic background in patients with PPGL. Most (80.9%, 89/110) patients with PPGL due to PVs in HRAS suffered IHI. In contrast, only half (31/62) of patients with PPGL due to PVs in VHL had IHI. In the multivariate regression analysis, compared to those with negative genetic testing results, patients with PPGL due to PVs in HRAS (OR 3.82, 95% CI 2.187-6.679, P<0.001), the other cluster 2 genes (OR 1.95, 95% CI 1.287-2. 569, P< 0.05), and cluster 1 genes other than VHL (OR 2.35, 95% CI 1.338-4.111, P<0.05) were independent risk factors for IHI, while PVs in VHL was not independent risk factor (OR 1.09, 95% CI 0.605-1.953, P>=0.05). In addition, age at diagnosis of primary tumour, presenting of CAS, and tumour size were identified as independent factors for IHI. The nomogram illustrated that genetic background as sharing the largest contribution to IHI, followed by tumour size, age, and presenting of CAS. CONCLUSION: IHI is associated with the genetic background in patients with PPGL. The perioperative management of patients with PPGL can be personalized according to their genetic backgrounds, tumour size, age, and presenting of CAS.
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Human complement factor H (CFH) plays a central role in regulating activated C3b to protect host cells. CFH contain 20 short complement regulator (SCR) domains and eight N-glycosylation sites. The N-terminal SCR domains mediate C3b degradation while the C-terminal CFH domains bind to host cell surfaces to protect these. Our earlier study of Pichia-generated CFH fragments indicated a self-association site at SCR-17/18 that comprises a dimerization site for human factor H. Two N-linked glycans are located on SCR-17 and SCR-18. Here, when we expressed SCR-17/18 without glycans in an E. coli system, analytical ultracentrifugation showed that no dimers were now formed. To investigate this novel finding, full-length CFH and its C-terminal fragments were purified from human plasma and Pichia pastoris respectively, and their glycans were enzymatically removed using PNGase F. Using size-exclusion chromatography, mass spectrometry, and analytical ultracentrifugation, SCR-17/18 from Pichia showed notably less dimer formation without its glycans, confirming that the glycans are necessary for the formation of SCR-17/18 dimers. By surface plasmon resonance, affinity analyses interaction showed decreased binding of deglycosylated full-length CFH to immobilised C3b, showing that CFH glycosylation enhances the key CFH regulation of C3b. We conclude that our study revealed a significant new aspect of CFH regulation based on its glycosylation and its resulting dimerisation.
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Background: Haemaphysalis flava is a notorious parasite for humans and animals worldwide. The organs of H. flava are bathed in hemolymph, which is a freely circulating fluid. Nutrients, immune factors, and waste can be transported to any part of the body via hemolymph. The main soluble components in hemolymph are proteins. However, knowledge of the H. flava proteome is limited. Methods: The hemolymph was collected from fully engorged H. flava ticks by leg amputation. Hemolymph proteins were examined by both blue native polyacrylamide gel electrophoresis (BN-PAGE) and sodium dodecyl sulfate PAGE (SDS-PAGE). Proteins extracted from the gels were further identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Two bands (380 and 520 kDa) were separated from tick hemolymph by BN-PAGE and were further separated into four bands (105, 120, 130, and 360 kDa) by SDS-PAGE. LC-MS/MS revealed that seven tick proteins and 13 host proteins were present in the four bands. These tick proteins mainly belonged to the vitellogenin (Vg) family and the α-macroglobulin family members. In silico structural analysis showed that these Vg family members all had common conserved domains, including the N-terminus lipid binding domain (LPD-N), the C-terminus von Willebrand type D domain (vWD), and the domain of unknown function (DUF). Additionally, two of the Vg family proteins were determined to belong to the carrier protein (CP) by analyzing the unique N-terminal amino acid sequences and the cleaving sites. Conclusion: These findings suggest that the Vg family proteins and α-macroglobulin are the primary constituents of the hemolymph in the form of protein complexes. Our results provide a valuable resource for further functional investigations of H. flava hemolymph effectors and may be useful in tick management.
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The development of core-shelled heterostructures with the unique morphology can improve the electrochemical properties of hybrid supercapacitors (HSC). Here, CuCo2S4 nanowire arrays (NWAs) are vertically grown on nickel foam (NF) utilizing hydrothermal synthesis. Then, CoMo-LDH nanosheets are uniformly deposited on the CuCo2S4 NWAs by electrodeposition to obtain the CoMo-LDH@CuCo2S4 NWAs/NF electrode. Due to the superior conductivity of CuCo2S4 (core) and good redox activity of CoMo-LDH (shell), the electrode shows excellent electrochemical properties. The electrode's specific capacity is 1271.4 C g-1 at 1 A g-1, and after 10, 000 cycles, its capacity retention ratio is 92.2 % at 10 A g-1. At a power density of 983.9 W kg-1, the CoMo-LDH@CuCo2S4 NWAs/NF//AC/NF device has an energy density of 52.2 Wh kg-1. This indicates that CoMo-LDH@CuCo2S4/NF has a great potential for supercapacitors.
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Iron deficiency (ID) is common in patients with acute myocardial infarction (AMI). It is unknown whether patients with AMI combined with ID will benefit from iron supplementation therapy. This study aimed to assess the relationship between iron therapy and mortality in AMI patients. Retrospective analysis was performed in subjects screened from the Medical Information Mart in Intensive Care-IV database. The data were obtained from ICU patients admitted to Beth Israel Deaconess Medical Center between 2008 and 2019. The patients were divided into two groups according to iron treatment exposure. Propensity score matching (PSM) was performed in the original cohort at a 1:1 ratio. Univariate and multivariate analyses were performed to adjust for confounding factors. The primary outcome was 28-day mortality. A total of 426 patients were included in this study. After 1:1 PSM, 208 patients were analyzed. Iron treatment was associated with a lower risk of 28-day mortality (9 deaths (8.65%) in the iron treatment group vs. 21 deaths (20.19%) in the non-iron treatment group; HR = 0.39; 95% CI = 0.17-0.89; p = 0.025) and in-hospital mortality (4 deaths (3.85%) in the iron treatment group vs. 12 deaths (11.54%) in the non-iron treatment group; OR, 0.15; 95% CI, 0.03-0.74; p = 0.029). Iron treatment was associated with reduced 28-day mortality in patients with AMI combined with ID. Iron treatment had no significant effect on the length of hospitalization or the length of ICU stay. Prospective studies are needed to verify this conclusion.
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In order to achieve rapid and effective identification of Hebei yam, a qualitative discrimination model was constructed based on near infrared (NIR), mid infrared (MIR), and microscopic Raman spectra in combination with individual spectra and multispectral data fusion strategies. The results showed that the gray wolf optimizer-support vector machine (GWO-SVM) model constructed by mid-level fusion using the three feature spectra performed the best in distinguishing the geographic origin of the yam, with a prediction accuracy of 100.00% in both the training set and the test set, and an F1 score of 1.00. The results indicated that due to spectral complementarity, NIR, MIR and Raman combined with feature-level fusion can be used as a powerful, non-destructive, fast and feasible tool for geographic origin classification and brand protection of Hebei yam. This work is expected to be a potential method for origin identification analysis and quality monitoring in the food and pharmaceutical industries.
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D-glucaric acid is an important organic acid with numerous applications in therapy, food, and materials, contributing significantly to its substantial market value. The biosynthesis of D-glucaric acid (GA) from renewable sources such as glucose has garnered significant attention due to its potential for sustainable and cost-effective production. This review summarizes the current understanding of the cell factories for GA production in different chassis strains, from static to dynamic control strategies for regulating their metabolic networks. We highlight recent advances in the optimization of D-glucaric acid biosynthesis, including metabolic dynamic control, alternative feedstocks, metabolic compartments, and so on. Additionally, we compare the differences between different chassis strains and discuss the challenges that each chassis strain must overcome to achieve highly efficient GA productions. In this review, the processes of engineering a desirable cell factory for highly efficient GA production are just like an epitome of metabolic engineering of strains for chemical biosynthesis, inferring general trends for industrial chassis strain developments.
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Ácido Glucárico , Engenharia Metabólica , Redes e Vias Metabólicas , Engenharia Metabólica/métodos , Ácido Glucárico/metabolismo , Redes e Vias Metabólicas/genética , Glucose/metabolismo , Microbiologia Industrial/métodosRESUMO
Mining activities disrupt the natural oxidative balance underground, increasing the oxidation of metal sulfides like pyrite. This process leads to the formation of highly acidic mine drainage (AMD) with elevated concentrations of iron (Fe) and sulfate (SO42-). However, generic plugging and backfilling methods, when applied without considering the specific post-mining oxidative environments of different metal mines, often yields minimal results. To clarify the distribution of the underground redox environment after mining of a metal mine in Dexing, China, fifteen water samples from flood and dry periods, as well as fifteen borehole samples, were collected for hydrogeological and chemical analysis. For the first time, the study proposed that the redox zone could be identified and delineated through vertical analysis of water storage media, mineral composition, and hydrochemical characteristics. A hydrogeochemical cause model was constructed, revealing that AMD formation primarily occurs in oxidative and transition zones. Based on the redox zone characteristics of the study area, actual engineering sealing was performed on the oxidation and transition zones of cavity No. 23. As a result, the pH increased from 2.5 before remediation to 4.5, indicating a reduction in acidity. The concentrations of SO42- and Fe significantly decreased, reducing from 1360.0 mg/L and 147.0 mg/L before treatment to 726.0 mg/L and 23.6 mg/L after treatment; the total decrease amounting to 46.6 % and 84.0 %, respectively. The concentrations of Mn and Cu similarly, decreased by 10.7 % and 15.6 %, respectively. This study provides a novel approach and valuable reference for the refined identification and classification of redox zones after metal mine exploitation, as well as for the targeted plugging and treatment of cavities that produce AMD.
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Detecting chromosome structural abnormalities in medical genetics is essential for diagnosing genetic disorders and understanding their implications for an individual's health. However, existing computational methods are formulated as a binary-class classification problem trained only on representations of positive/negative chromosome pairs. This paper introduces an innovative framework for detecting chromosome abnormalities with banding resolution, capable of precisely identifying and masking the specific abnormal regions. We highlight a pixel-level abnormal mapping strategy guided by banding features. This approach integrates data from both the original image and banding characteristics, enhancing the interpretability of prediction results for cytogeneticists. Furthermore, we have implemented an ensemble approach that pairs a discriminator with a conditional random field heatmap generator. This combination significantly reduces the false positive rate in abnormality screening. We benchmarked our proposed framework with state-of-the-art (SOTA) methods in abnormal screening and structural abnormal region segmentation. Our results show cutting-edge effectiveness and greatly reduce the high false positive rate. It also shows superior performance in sensitivity and segmentation accuracy. Being able to identify abnormal regions consistently shows that our model has demonstrated significant clinical utility with high model interpretability. BRChromNet is open-sourced and available at https://github.com/frankchen121212/BR-ChromNet.
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While cycloaddition reactions of bicyclobutanes (BCBs) have emerged as a potent method for synthesizing (hetero-)bicyclo[n.1.1]alkanes (usually n ≤ 3), their utilization in the synthesis of bicyclo[4.1.1]octane derivatives (BCOs) is still underdeveloped. Here, a palladium-catalyzed formal (4 + 3) reaction of BCBs with 1,4-O/C dipole precursors for the synthesis of oxa-BCOs is described. Unlike previous catalytic polar (3 + X) cycloadditions of BCBs, which are typically achieved through the activation of BCB substrates, the current reaction represents a novel strategy for realizing the cycloaddition of BCBs through the activation of the "X" cycloaddition partner. Moreover, the obtained functionalized oxa-BCOs products can be readily modified through various synthetic transformations.
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Fiber-shaped electrochemical capacitors (FSECs) have garnered substantial attention to emerging portable, flexible, and wearable electronic devices. However, achieving high electronic and ionic conductivity in fiber electrodes while maintaining a large specific surface area is still a challenge for enhancing the capacitance and rapid response of FSECs. Here, we present an electric-field-assisted cold-wall plasma-enhanced chemical vapor (EFCW-PECVD) method for direct growth of vertical graphene (VG) on fiber electrodes, which is incorporated in the FSECs. The customized reactor mainly consists of two radio frequency coils: one for plasma generation and the other for substrate heating. Precise temperature control can be achieved by adjusting the conductive plates and the applied power. With induction heating, only the substrate is heated to above 500 °C within just 5 min, maintaining a low temperature in the gas phase for the growth of VG with a high quality. Using this method, VG was easily grown on metallic fibers. The VG-coated titanium fibers for FSECs exhibit an ultrahigh rate performance and quick ion transport, enabling the conversion of an alternating current signal to a direct current signal and demonstrating outstanding filtering capabilities.
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Hexagonal boron nitride (hBN) has emerged as a promising protection layer for dielectric integration in the next-generation large-scale integrated electronics. Although numerous efforts have been devoted to growing single-crystal hBN film, wafer-scale ultraflat hBN has still not been achieved. Here, we report the epitaxial growth of 4 in. ultraflat single-crystal hBN on Cu0.8Ni0.2(111)/sapphire wafers. The strong coupling between hBN and Cu0.8Ni0.2(111) suppresses the formation of wrinkles and ensures the seamless stitching of parallelly aligned hBN domains, resulting in an ultraflat single-crystal hBN film on a wafer scale. Using the ultraflat hBN as a protective layer, we integrate the wafer-scale ultrathin high-κ dielectrics onto two-dimensional (2D) materials with a damage-free interface. The obtained hBN/HfO2 composite dielectric exhibits an ultralow current leakage (2.36 × 10-6 A cm-2) and an ultrathin equivalent oxide thickness of 0.52 nm, which meets the targets of the International Roadmap for Devices and Systems. Our findings pave the way to the synthesis of ultraflat 2D materials and integration of future 2D electronics.
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BACKGROUND: With the fast pace of modern life, people have less time for meals, but few studies have examined the association between the habit of fast eating and metabolic diseases. OBJECTIVE: Combining the results of the current study and the prior ones, we aimed to investigate the possible relationship between fast eating and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This is a sub-analysis of a multicenter cross-sectional study of 1965 participants investigated the association between fast eating and MASLD in Chinese. Fast eating was defined as meal time less than five minutes and participants were divided into three categories based on their self-reported frequency of fast eating: ≤1 time/month, ≤1 time/week and ≥2 times/week. We further conducted a literature search for available studies published before November, 2023 as well as a meta-analysis to investigate the association between fast eating and MASLD. RESULTS: The proportion of MASLD was 59.3%, 50.5%, and 46.2% in participants with fast eating ≥2 times/week, ≤1 time/week and ≤1 time/month, respectively (P for trend <0.001). The frequency of fast eating was independently associated with risk of MASLD after multiple adjustment for sex, age, demographics, smoking and drinking status, BMI and clinical metabolic parameters (OR, 1.29; 95%CI, 1.09-1.53). Participants who ate fast frequently (≥2 times/week) had 81% higher risk of MASLD (P = 0.011). A meta-analysis of five eligible studies confirmed that frequent fast eating was associated with increased risk of MASLD (pooled OR, 1.22; 95%CI, 1.07-1.39). CONCLUSIONS: Frequent fast eating was associated with an increased risk of MASLD.
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Comportamento Alimentar , Humanos , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Fatores de Tempo , China/epidemiologia , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Refeições , Fígado Gorduroso/epidemiologiaRESUMO
Background: Despite the potential demonstrated by targeted plasma metabolite modulators in halting the progression of chronic kidney disease (CKD), a lingering uncertainty persists concerning the causal relationship between distinct plasma metabolites and the onset and progression of CKD. Methods: A genome-wide association study was conducted on 1,091 metabolites and 309 metabolite ratios derived from a cohort of 8,299 unrelated individuals of European descent. Employing a bidirectional two-sample Mendelian randomization (MR) analysis in conjunction with colocalization analysis, we systematically investigated the associations between these metabolites and three phenotypes: CKD, creatinine-estimated glomerular filtration rate (creatinine-eGFR), and urine albumin creatinine ratio (UACR). In the MR analysis, the primary analytical approach employed was inverse variance weighting (IVW), and sensitivity analysis was executed utilizing the MR-Egger method and MR-pleiotropy residual sum and outlier (MR-PRESSO). Heterogeneity was carefully evaluated through Cochrane's Q test. To ensure the robustness of our MR results, the leave-one-out method was implemented, and the strength of causal relationships was subjected to scrutiny via Bonferroni correction. Results: Our thorough MR analysis involving 1,400 plasma metabolites and three clinical phenotypes yielded a discerning identification of 21 plasma metabolites significantly associated with diverse outcomes. Specifically, in the forward MR analysis, 6 plasma metabolites were determined to be causally associated with CKD, 16 with creatinine-eGFR, and 7 with UACR. Substantiated by robust evidence from colocalization analysis, 6 plasma metabolites shared causal variants with CKD, 16 with creatinine-eGFR, and 7 with UACR. In the reverse analysis, a diminished creatinine-eGFR was linked to elevated levels of nine plasma metabolites. Notably, no discernible associations were observed between other plasma metabolites and CKD, creatinine-eGFR, and UACR. Importantly, our analysis detected no evidence of horizontal pleiotropy. Conclusion: This study elucidates specific plasma metabolites causally associated with CKD and renal functions, providing potential targets for intervention. These findings contribute to an enriched understanding of the genetic underpinnings of CKD and renal functions, paving the way for precision medicine applications and therapeutic strategies aimed at impeding disease progression.
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Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular , Análise da Randomização Mendeliana , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo , Feminino , Masculino , Creatinina/sangue , Polimorfismo de Nucleotídeo Único , Biomarcadores/sangue , Estudos de Coortes , Rim/metabolismo , Pessoa de Meia-IdadeRESUMO
Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the precise mechanisms by which individual stem cells exit the marrow are not understood. This study identified cell-extrinsic and molecular determinants of a mobilizable pool of blood-forming stem cells. We found that a subset of HSCs displays macrophage-associated markers on their cell surface. Although fully functional, these HSCs are selectively niche-retained as opposed to stem cells lacking macrophage markers, which exit the BM upon forced mobilization. Macrophage markers on HSCs could be acquired through direct transfer by trogocytosis, regulated by receptor tyrosine-protein kinase C-Kit (CD117), from BM-resident macrophages in mouse and human settings. Our study provides proof of concept that adult stem cells utilize trogocytosis to rapidly establish and activate function-modulating molecular mechanisms.
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Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Proteínas Proto-Oncogênicas c-kit , Trogocitose , Animais , Humanos , Camundongos , Células-Tronco Adultas/fisiologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Nicho de Células-Tronco , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Antígenos de DiferenciaçãoRESUMO
OBJECTIVE: This scoping review and meta-analysis aimed to map the evidence regarding prognostic factors in Chinese patients with immunoglobulin light chain (AL) amyloidosis and to identify current research gaps. METHODS: We searched EMBASE, PubMed, and CNKI databases from their inception to 15 September 2021. All studies investigated the association between any prognostic factor and target outcomes, including overall survival (OS), progression-free survival (PFS), and end-stage renal disease (ESRD) in Chinese patients with AL amyloidosis. RESULTS: This scoping review included 52 studies, of which 44 with 6,432 patients contributed to the multivariate prognostic analysis. Multivariate analysis identified a total of 106 factors that correlated with OS, 16 factors with PFS, and 18 factors with ESRD. Five prognostic factors were significantly associated with PFS, and 11 prognostic factors were significantly associated with ESRD. Meta-analysis was only available for prognostic factors without heterogeneous cutoff values, for which hazard ratios (HRs) and their 95% confidence intervals (CIs) were reported. Meta-analysis showed that bone marrow plasma cells (BMCs) (HR: 1.96, 95% CI: 1.21-3.19, p < 0.05) and interventricular septal thickness (IVST) (HR: 1.23, 95% CI: 1.10-1.38, p < 0.05) were independently associated with OS. CONCLUSION: The significant prognostic factors associated with OS, PFS, and ESRD in Chinese patients with AL amyloidosis were related to plasma cell tumor load, biological characteristics, cardiac involvement, renal involvement, population characteristics, and treatment. Further studies should explore additional prognostic factors in patients with AL amyloidosis to develop prognostic models.
The significant prognostic factors associated with OS, PFS, and ESRD in Chinese patients with AL amyloidosis were related to plasma cell tumor load, biological characteristics, cardiac involvement, renal involvement, population characteristics, and treatment.Meta-analysis showed there was a significant association between BMCs or interventricular septal thickness and OS.
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Amiloidose de Cadeia Leve de Imunoglobulina , Falência Renal Crônica , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Prognóstico , China/epidemiologia , Falência Renal Crônica/mortalidade , Cadeias Leves de Imunoglobulina/sangue , Intervalo Livre de Progressão , População do Leste AsiáticoRESUMO
This study proposes a novel anaerobic digestion (AD) strategy combining recyclable photoactivated nanomaterials with illumination to enhance electronic transfer for anaerobic microorganisms. Results showed that 7000 Lux illumination increased methane production yield and rate. Incorporating Fe3O4 into graphite carbon nitride (g-C3N4) created a recyclable Fe3O4/g-C3N4 (FG) nanocomposite with improved light absorption, conductivity, redox properties, and methane promotion. The highest methane yield from corn straw was achieved with 7000 Lux and 1.5 g/L FG nanocomposite, 22.6% higher than the dark control. The AD system exhibited increased adenosine triphosphate content, improved redox performance, reduced electron transfer resistance, and higher photocurrent intensity. These improvements bolstered the microorganisms and key genes involved in hydrolysis and acidification, which in turn optimized the acetoclastic pathway. Furthermore, this strategy promoted microorganisms associated with direct interspecies electron transfer, fostering a favorable environment for methanogenic activities, paving the way for future anaerobic reactor developments.
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Grafite , Metano , Nanocompostos , Zea mays , Metano/metabolismo , Zea mays/química , Nanocompostos/química , Anaerobiose , Grafite/química , Luz , Compostos de Nitrogênio , Oxirredução , Resíduos , Reatores Biológicos , NitrilasRESUMO
Background: Anomalous pulmonary venous connection with malposition of septum primum (MSP) is a rare pediatric cardiovascular malformation. Although reports in the literature are scarce, accurate pre-operative imaging diagnosis is crucial for selecting the appropriate clinical intervention and determining the prognosis for affected children. Case description: In both case reports, the cardiovascular malformations were incidental findings. In the second case, an enlarged cardiac silhouette was observed on chest x-ray due to pneumonia, which was subsequently confirmed by ultrasound. Combined with computed tomography angiography examination, the diagnosis of MSP-type anomalous pulmonary venous connection was established. Conclusions: Comprehensive imaging examinations are essential in reducing misdiagnosis and achieving an accurate diagnosis of MSP-type anomalous pulmonary venous connection. The typical imaging findings for MSP-type anomalous pulmonary venous connection include absence or hypoplasia of the superior limbic band of the septum secundum, leftward displacement of the septum primum, and partial or total pulmonary vein drainage into the anatomical right atrium.
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Influenza viruses are susceptible to seasonal influenza, which has repeatedly caused global pandemics and jeopardized human health. Vaccines are only used as preventive medicine due to the extreme mutability of influenza viruses, and antiviral medication is the most significant clinical treatment to reduce influenza morbidity and mortality. Nevertheless, the clinical application of anti-influenza virus agents is characterized by the narrow therapeutic time window, the susceptibility to drug resistance, and relatively limited effect on severe influenza. Therefore, it is of great significance to develop novel anti-influenza virus drugs to fulfill the urgent clinical needs. Influenza viruses enter host cells through the hemagglutinin (HA) mediated membrane fusion process, and fusion inhibitors function antivirally by blocking hemagglutinin deformation, promising better therapeutic efficacy and resolving drug resistance, with targets different from marketed medicines. Previous studies have shown that unnatural peptides derived from Human Immunodeficiency Virus Type 1 (HIV-1) membrane fusion proteins exhibit anti-HIV-1 activity. Based on the similarity of the membrane fusion protein deformation process between HIV-1 and H1N1, we selected sequences derived from the gp41 subunit in the HIV-1 fusion protein, and then constructed N-trimer spatial structure through inter-helical isopeptide bond modification, to design the novel anti-H1N1 fusion inhibitors. The results showed that the novel peptides could block 6-HB formation during H1N1 membrane fusion procedure, and thus possessed significant anti-H1N1 activity, comparable to the positive control oseltamivir. Our study demonstrates the design viability of peptide fusion inhibitors based on similar membrane fusion processes among viruses, and furthermore provides an important idea for the novel anti-H1N1 inhibitors development.