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The cytokine interleukin-6 (IL-6) plays a crucial role in autoimmune and inflammatory diseases. Understanding the precise mechanism of IL-6 interaction at the amino acid level is essential to develop IL-6-inhibiting compounds. In this study, we employed computer-guided drug design tools to predict the key residues that are involved in the interaction between IL-6 and its receptor IL-6R. Subsequently, we generated IL-6 mutants and evaluated their binding affinity to IL-6R and the IL-6R - gp130 complex, as well as monitoring their biological activities. Our findings revealed that the R167A mutant exhibited increased affinity for IL-6R, leading to enhanced binding to IL-6R - gp130 complex and subsequently elevated intracellular phosphorylation of STAT3 in effector cells. On the other hand, although E171A reduced its affinity for IL-6R, it displayed stronger binding to the IL-6R - gp130 complex, thereby enhancing its biological activity. Furthermore, we identified the importance of R178 and R181 for the precise recognition of IL-6 by IL-6R. Mutants R181A/V failed to bind to IL-6R, while maintaining an affinity for the IL-6 - gp130 complex. Additionally, deletion of the D helix resulted in complete loss of IL-6 binding affinity for IL-6R. Overall, this study provides valuable insights into the binding mechanism of IL-6 and establishes a solid foundation for future design of novel IL-6 inhibitors.
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Interleucina-6 , Simulação de Acoplamento Molecular , Ligação Proteica , Receptores de Interleucina-6 , Interleucina-6/metabolismo , Interleucina-6/genética , Humanos , Receptores de Interleucina-6/metabolismo , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/química , Receptor gp130 de Citocina/metabolismo , Receptor gp130 de Citocina/genética , Receptor gp130 de Citocina/química , Mutagênese Sítio-Dirigida , Sítios de Ligação , Fator de Transcrição STAT3/metabolismo , Fosforilação , MutaçãoRESUMO
The microscopic structure of the material's solid-liquid interface significantly influences its physicochemical properties. Peak force infrared microscopy (PFIR) is a powerful technique for analyzing these interfaces at the nanoscale, revealing crucial structure-activity relationships. PFIR is recognized for its explicit photothermal signal generation mechanism but tends to overlook other photoinduced forces, which can disturb the obtained infrared spectra, thereby reducing spectral signal-to-noise ratio (SNR) and sensitivity. We have developed a multiphysics-coupled theoretical model to assess the magnitudes of various photoinduced forces in PFIR experiments and have found that the magnitude of the photoacoustic force is comparable to that of the photothermal expansion force in a liquid environment. Our calculations show that through simple modulation of the pulse waveform it is possible to effectively suppress the photoacoustic interference, thereby improving the SNR and sensitivity of PFIR. This work aims to alert researchers to the potential for strong photoacoustic interference in liquid-phase PFIR measurements and enhance the performance of PFIR by clarifying the photoinduced forces entangled in the signals.
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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.
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Antivirais , Vírus da Influenza A Subtipo H1N1 , Peptídeos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Humanos , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/síntese química , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Células Madin Darby de Rim Canino , Cães , Relação Dose-Resposta a Droga , Animais , Estrutura Molecular , Sequência de AminoácidosRESUMO
Isobavachin (IBA) is a dihydroflavonoid compound with various pharmacological effects. However, further investigation into the hepatotoxicity of IBA is necessary. This study aims to identify the hepatotoxic effects of IBA and explore its potential mechanisms. The study assessed the impact of IBA on the viability of AML12, HepG2, LO2, rat, and mouse primary hepatocytes using MTT and LDH assays. Autophagy was detected in AML12 cells after IBA treatment using electron microscopy, MDC, and Ad-mCherry-GFP-LC3B fluorescence. The effect of IBA on autophagy-related proteins was examined using Western blot. The results showed that IBA had dose-dependent inhibitory effects on five cells, induced autophagy in AML12 cells, and promoted autophagic flux. The study found that IBA treatment inhibited phosphorylation of PI3K, Akt, and mTOR, while increasing phosphorylation levels of AMPK and ULK1. Treatment with both AMPK and PI3K inhibitors reversed the expression of AMPK and PI3K-Akt-mTOR signaling pathway proteins. These results suggest that IBA may have hepatocytotoxic effects but can also prevent IBA hepatotoxicity by inhibiting the AMPK and PI3K/Akt/mTOR signaling pathways. This provides a theoretical basis for preventing and treating IBA hepatotoxicity in clinical settings.
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BACKGROUND AIMS: Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding (CSPEB) is common. Contemporary estimates of risk are lacking. We aimed to identify risk factors for and outcomes following CSPEB. METHODS: We analyzed multi-center prospective ERCP data between 2018-2023 with 30-day follow-up. The primary outcome was CSPEB, defined as hematemesis, melena, or hematochezia resulting in: hemoglobin drop ≥20 g/L or transfusion and/or endoscopy to evaluate suspected bleeding, and/or unplanned healthcare visitation and/or prolongation of existing admission. Firth logistic regression was employed. P-values <0.05 were significant, with odds ratios (ORs) and 95% confidence intervals reported. RESULTS: CSPEB occurred following 129 (1.5%) of 8,517 ERCPs (mean onset 3.2 days), with 110 of 4,849 events (2.3%) occurring following higher-risk interventions (sphincterotomy, sphincteroplasty, pre-cut sphincterotomy, and/or needle-knife access). CSPEB patients required endoscopy and transfusion in 86.0% and 53.5% of cases, respectively, with three cases (2.3%) being fatal. P2Y12 inhibitors were held for a median of 4 days (IQR 4) prior to higher-risk ERCP. Following higher-risk interventions, P2Y12 inhibitors (OR 3.33, 1.26-7.74), warfarin (OR 8.54, 3.32-19.81), dabigatran (OR 13.40, 2.06-59.96), rivaroxaban (OR 7.42, 3.43-15.24) and apixaban (OR 4.16, 1.99-8.20) were associated with CSPEB. Significant intraprocedural bleeding post sphincterotomy (OR 2.32, 1.06-4.60), but not post sphincteroplasty, was also associated. Concomitant cardiorespiratory events occurred more frequently within 30 days following CSPEB (OR 12.71, 4.75-32.54). CONCLUSIONS: Risks of antiplatelet-related CSPEB may be underestimated by endoscopists based on observations of suboptimal holding before higher-risk ERCP. Appropriate periprocedural antithrombotic management is essential and could represent novel quality initiative targets.
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Alzheimer's disease (AD) is a leading cause of cognitive impairment worldwide. Overweight and obesity are strongly associated with comorbidities, such as hypertension, diabetes, and insulin resistance (IR), which contribute substantially to the development of AD and subsequent morbidity and mortality. Adipose tissue (AT) is a highly dynamic organ composed of a diverse array of cell types, which can be classified based on their anatomic localization or cellular composition. The expansion and remodeling of AT in the context of obesity involves immunometabolic and functional shifts steered by the intertwined actions of multiple immune cells and cytokine signaling within AT, which contribute to the development of metabolic disorders, IR, and systemic markers of chronic low-grade inflammation. Chronic low-grade inflammation, a prolonged, low-dose stimulation by specific immunogens that can progress from localized sites and affect multiple organs throughout the body, leads to neurodystrophy, increased apoptosis, and disruption of homeostasis, manifesting as brain atrophy and AD-related pathology. In this review, we sought to elucidate the mechanisms by which AT contributes to the onset and progression of AD in obesity through the mediation of chronic low-grade inflammation, particularly focusing on the roles of adipokines and AT-resident immune cells.
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Tecido Adiposo , Doença de Alzheimer , Inflamação , Obesidade , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/etiologia , Obesidade/metabolismo , Obesidade/imunologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Tecido Adiposo/imunologia , Inflamação/metabolismo , Inflamação/patologia , Animais , Adipocinas/metabolismoRESUMO
KANNO is a new human blood group that was recently discovered. The KANNO antigen shares the PRNP gene with the prion protein and the prion protein E219K polymorphism determines the presence or absence of the KANNO antigen and the development of anti-KANNO alloantibodies. These alloantibodies specifically react with prion proteins, which serve as substrates for conversion into pathological isoforms in some prion diseases and may serve as effective targets for resisting prion infection. These findings establish a potential link between the KANNO blood group and human prion disease via the prion protein E219K polymorphism. We reviewed the interesting correlation between the human PRNP gene's E219K polymorphism and the prion proteins it expresses, as well as human red blood cell antigens. Based on the immune serological principles of human blood cells, the prion protein E219K polymorphism may serve as a foundation for earlier molecular diagnosis and future drug development for prion diseases.
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An increasing number of epidemiological studies have explored the relationship between the risk of gastric cancer and specific dietary patterns, but the findings remain inconclusive. We, therefore, performed this comprehensive systematic review and meta-analysis to analyze the available evidence regarding the associations between a priori and a posteriori dietary patterns and the risk of gastric cancer. A systematic search of six electronic databases, including PubMed, Web of Science, EBSCO, Scopus, China National Knowledge Infrastructure (CNKI), and Wanfang Data, was carried out to retrieve the relevant articles published up to March 2024. Thirty-six studies (10 cohort and 26 case-control studies) with a total of 2â 181â 762 participants were included in the final analyses. Combining 15 effect sizes extracted from 12 articles, we observed a reduced risk of gastric cancer in the highest versus the lowest categories of the Mediterranean diet [relative risk (RR), 0.72; 95% confidence interval (CI), 0.61-0.85; Pâ <â 0.001]. Combining 11 effect sizes from 10 articles (involving 694â 240 participants), we found that the highest Dietary Inflammatory Index scores were significantly associated with an increased risk of gastric cancer (RR, 1.32; 95% CI, 1.11-1.57; Pâ <â 0.001). A reduced risk of gastric cancer was shown for the highest compared with the lowest categories of healthy dietary pattern (RR, 0.78; 95% CI, 0.67-0.91; Pâ =â 0.002). Conversely, the highest adherence to the Western dietary pattern was associated with an increased risk of gastric cancer (RR, 1.33; 95% CI, 1.19-1.49; Pâ <â 0.001). Our study demonstrated that the Mediterranean diet and a healthy dietary pattern were associated with a decreased risk of gastric cancer. Conversely, the Dietary Inflammatory Index and Western dietary pattern were associated with an increased risk of gastric cancer.
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The extraordinary adaptability and dispersal abilities have allowed Hyphantria cunea to expand its range, posing a great threat to urban landscapes and natural ecosystems. Searching for safe, efficient, and low-cost control methods may provide new strategies for pest management in H. cunea spread areas. In this study, based on the attraction of insects by preferred hosts, it was found that the response rates of virgin H. cunea female adults to Salix matsudana, Juglans mandshurica and Ulmus pumila were 89.17%, 97.92% and 93.98%, respectively. It was further found that this significant preference was mainly related to the volatiles m-xylene, o-xylene, dodecane and tetradecane found in the three species. Even though all four compounds at 10 µL/mL and 100 µL/mL had significant attractive effects on the virgin H. cunea female adults, m-xylene and dodecane at 100 µL/mL elicited significant EAG responses and tending behaviors by stimulating the olfactory receptor neurons (ORN A) of females, with response rates of 83.13% and 84.17%, while also having significant attractive effects on virgin male adults with rates of 65.74% and 67.51%. Therefore, both m-xylene and dodecane which at concentrations of 100 µL/mL had strong attractions to adults, could be used as the first choice of attractants for both sexes of H. cunea. This has important practical significance in reducing the frequency of H. cunea generations, limiting their population, controlling their spread range, and improving the efficiency of pest management in epidemic areas.
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Compostos Orgânicos Voláteis , Animais , Feminino , Masculino , Compostos Orgânicos Voláteis/farmacologia , JuglansRESUMO
The emerging field of nanoscale infrared (nano-IR) offers label-free molecular contrast, yet its imaging speed is limited by point-by-point traverse acquisition of a three-dimensional (3D) data cube. Here, we develop a spatial-spectral network (SS-Net), a miniaturized deep-learning model, together with compressive sampling to accelerate the nano-IR imaging. The compressive sampling is performed in both the spatial and spectral domains to accelerate the imaging process. The SS-Net is trained to learn the mapping from small nano-IR image patches to the corresponding spectra. With this elaborated mapping strategy, the training can be finished quickly within several minutes using the subsampled data, eliminating the need for a large-labeled dataset of common deep learning methods. We also designed an efficient loss function, which incorporates the image and spectral similarity to enhance the training. We first validate the SS-Net on an open stimulated Raman-scattering dataset; the results exhibit the potential of 10-fold imaging speed improvement with state-of-the-art performance. We then demonstrate the versatility of this approach on atomic force microscopy infrared (AFM-IR) microscopy with 7-fold imaging speed improvement, even on nanoscale Fourier transform infrared (nano-FTIR) microscopy with up to 261.6 folds faster imaging speed. We further showcase the generalization of this method on AFM-force volume-based multiparametric nanoimaging. This method establishes a paradigm for rapid nano-IR imaging, opening new possibilities for cutting-edge research in materials, photonics, and beyond.
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It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of five Yucatan and two Panepinto minipigs to verify obstructive sleep apnea (OSA), eight and four ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D deformational changes of the circumscribed regions were measured simultaneously with electromyographic activity of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in three nonobese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions, respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of deformational changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The distance changes between the dorsal surface of tongue base and soft palate during inspiration increased in normal but decreased in obese OSA minipigs.
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Obesidade , Palato Mole , Apneia Obstrutiva do Sono , Porco Miniatura , Língua , Animais , Suínos , Apneia Obstrutiva do Sono/fisiopatologia , Língua/fisiopatologia , Palato Mole/fisiopatologia , Obesidade/fisiopatologia , Obesidade/complicações , Obesidade/patologia , Fenômenos Biomecânicos , Eletromiografia , Respiração , MasculinoRESUMO
BACKGROUND: The six-helix bundle (6-HB) is a core structure formed during the membrane fusion process of viruses with the Class I envelope proteins. Peptide inhibitors, including the marketed Enfuvirtide, blocking the membrane fusion to exert inhibitory activity were designed based on the heptads repeat interactions in 6-HB. However, the drawbacks of Enfuvirtide, such as drug resistance and short half-life in vivo, have been confirmed in clinical applications. Therefore, novel design strategies are pivotal in the development of next-generation peptide-based fusion inhibitors. OBJECTIVE: The de novo design of α-helical peptides against MERS-CoV and IAVs has successfully expedited the development of fusion inhibitors. The reported sequences were completely nonhomologous with natural peptides, which can provide some inspirations for the antiviral design against other pathogenic viruses with class I fusion proteins. Here, we design a series of artificial C-peptides based on the similar mechanism of 6-HB formation and general rules of heptads repeat interaction. METHODS: The inhibitory activity of peptides against HIV-1 was assessed by HIV-1 Env-mediated cell-cell fusion assays. Interaction between artificial C-peptides and target peptides was evaluated by circular dichroism, polyacrylamide gel electrophoresis, size-exclusion chromatography, and sedimentation velocity analysis. Molecular docking studies were performed by using Schrödinger molecular modelling software. RESULTS: The best-performing artificial C-peptide, 1SR, was highly active against HIV-1 env-mediated cell-cell fusion. 1SR binds to the gp41 NHR region, assembling polymer to prevent endogenous 6-HB formation. CONCLUSION: We have found an artificial C-lipopeptide lead compound with inhibitory activity against HIV-1. Also, this paper enriched both N- and C-teminal heptads repeat interaction rules in 6-HB and provided an effective idea for next-generation peptide-based fusion inhibitors against HIV-1.
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The preparation of polymer gels via cross-linking of four-arm star-shaped poly(ethylene glycol) (Tetra-PEG) precursors is an attractive strategy to prepare networks with relatively well-defined topologies. Typically, Tetra-PEG gels are obtained by cross-linking heterocomplementary reactive Tetra-PEG precursors. This study, in contrast, explores the cross-linking of self-reactive, thiol-end functional Tetra-PEG macromers to form disulfide-cross-linked gels. The structure of the disulfide-cross-linked Tetra-PEG gels was studied with multiple-quantum NMR (MQ-NMR) spectroscopy and small-angle neutron scattering (SANS) experiments. In line with earlier simulation studies, these experiments showed a strong dependence of the relative fractions of the different network connectivities on the concentration of the thiol-end functional Tetra-PEG macromer that was used for the synthesis of the networks. Disulfide-cross-linked Tetra-PEG gels prepared at macromer concentrations below the overlap concentration (c = 0.66c*) primarily feature defect connectivity motifs, such as primary loops and dangling ends. For networks prepared at macromer concentrations above the overlap concentration, the fraction of single-link connectivities was found to be similar to that in amide-cross-linked Tetra-PEG gels obtained by heterocomplementary cross-linking of N-hydroxysuccinimide ester and amine functional Tetra-PEG macromers. Since disulfide bonds are susceptible to reductive cleavage, these disulfide-cross-linked gels are of interest, e.g., as reduction-sensitive hydrogels for a variety of biomedical applications.
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PURPOSE: This study aimed to investigate the underlying factors driving the onset of myopia, specifically the role of the ciliary muscle's contraction in the elongation of the axial length of the eye. METHODS: The retrospective study was conducted utilizing data from three ophthalmic centers in Shanghai and Beijing. Both Chinese and Caucasian children were involved. The axial length of the subjects' eyes was measured in both relaxed and contracted state of the ciliary muscle. A comprehensive mechanical model was also developed to observe the influence of ciliary muscle contraction on the axial length. RESULTS: This study included a sample of 198 right eyes of 198 myopic children. Of these, 97 were male and 101 were female, 126 were of Chinese ethnicity and 72 were Caucasian. The age of onset for myopia ranged from 5.9 to 16.9 years old. The axial length of the eye decreased 0.028 ± 0.007mm following dilation, indicating relaxation of the ciliary muscle (t paired student = 15.16, p = 6.72 x 10-35). In contrast, ciliary muscle contraction resulted in an increase in axial length. Considering proportionality, a significant 90.4% (179 eyes) exhibited a reduced axial length, while a minor 9.6% (19 eyes) demonstrated an increase post-mydriasis. Finite element modeling demonstrated that muscle contraction caused a tension force that transmits towards the posterior pole of the eye, causing it to extend posteriorly. CONCLUSION: The contraction of the ciliary muscle leads to an extension of the axial length. This could potentially be the initiating factor for myopia.
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Miopia , Criança , Humanos , Masculino , Feminino , Pré-Escolar , Adolescente , Estudos Retrospectivos , China , Miopia/etiologia , Corpo Ciliar , Músculo Liso , Comprimento Axial do OlhoRESUMO
Background: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) can lead to significant morbidity and mortality. We aimed to develop an accurate post-ERCP pancreatitis risk prediction model using easily obtainable variables. Methods: Using prospective multi-center ERCP data, we performed logistic regression using stepwise selection on several patient-, procedure-, and endoscopist-related factors that were determined a priori. The final model was based on a combination of the Bayesian information criterion and Akaike's information criterion performance, balancing the inclusion of clinically relevant variables and model parsimony. All available data were used for model development, with subsequent internal validation performed on bootstrapped data using 10-fold cross-validation. Results: Data from 3021 ERCPs were used to inform models. There were 151 cases of post-ERCP pancreatitis (5.0% incidence). Variables included in the final model included female sex, pancreatic duct cannulation, native papilla status, pre-cut sphincterotomy, increasing cannulation time, presence of biliary stricture, patient age, and placement of a pancreatic duct stent. The final model was discriminating, with a receiver operating characteristic curve statistic of 0.79, and well-calibrated, with a predicted risk-to-observed risk ratio of 1.003. Conclusions: We successfully developed and internally validated a promising post-ERCP pancreatitis clinical prediction model using easily obtainable variables that are known at baseline or observed during the ERCP procedure. The model achieved an area under the curve of 0.79. External validation is planned as additional data becomes available.
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Purpose: We aimed to explore the effects of percutaneous coronary intervention (PCI) on the ophthalmic artery (OA) hemodynamics in patients with acute coronary syndrome (ACS). Methods: A total of 73 participants (Group0: healthy controls, Group1: Patients with ACS underwent PCI < 3 months, Group2: Patients with ACS underwent PCI ≥ 3 months) were enrolled. Computed tomographic angiography images were used to construct three-dimensional models of participants' OAs. Numerical simulations based on computational fluid dynamics were used to acquire hemodynamic parameters. Results: The angle between the OA and internal carotid artery in Group2 was significantly larger compared with Group0 and Group1 (P = 0.003 and P = 0.044). Hemodynamic simulation showed a significantly slower OA blood velocity in Group1 than in the control (P < 0.001) and Group2 (P = 0.033). Lower wall shear stress was found in Group1 than that in control (P = 0.040). Patients after PCI had a higher wall pressure than healthy controls (P = 0.012 and P = 0.004). Mass flow ratios were decreased in Group1 and Group2 (P = 0.021 and P = 0.002). The hemodynamic parameters of OA were correlated with several clinical indicators. Conclusions: The OA blood flow velocity of patients with ACS after PCI initially slowed down, which increased the risk of plaque formation, and then showed an increasing trend. There was a correlation between OA hemodynamic parameters and clinical indexes related to cardiac stress. Ischemia-reperfusion injury and changes in blood flow status after PCI may affect OA morphology and hemodynamics, leading to ocular lesions. Trial registration: ChiCTR2100050428.
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Acquired Immune Deficiency Syndrome (AIDS) is a devastating infectious disease caused by the Human Immunodeficiency Virus type 1 (HIV-1). Enfuvirtide(T20) is the first HIV-1 fusion inhibitor for marketing, which plays an important role in AIDS treatment. However, in the clinical application process, T20 has several drawbacks, such as a high level of development of drug resistance, a short half-life in vivo, and rapid renal clearance, which severely limits the clinical application. Therefore, the development of novel fusion inhibitors to address T20 shortcomings has long been the research hotspot. Short peptides have a long half-life through modification and a high barrier to drug resistance, which is expected to solve the current fusion inhibitors dilemma. In this paper, we summarized six emerging R&D strategies for short peptide-based fusion inhibitors against HIV-1. We hope that this review will provide fresh insights into the development of novel fusion inhibitors, as well as ideas for other viral fusion inhibitor discoveries based on the common membrane fusion 6-HB core structure.
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BACKGROUND: Compared to adult scoliosis, correcting scoliosis in children often presents greater challenges. This is attributed to two key factors. Firstly, it involves accounting for the growth potential of children. Secondly, the thinner pedicles in children can complicate screw insertion, particularly when dealing with existing deformities. The utilization of intraoperative navigation technology offers a modest improvement in the precision of screw placement but does come with the drawback of increased radiation exposure. The aim of this study is to investigate and assess the accuracy of manually inserting pedicle screws in the thoracic and lumbar spine to rectify deformities in children with early-onset congenital scoliosis. METHODS: In this retrospective study, 26 hospitalized patients diagnosed with early-onset congenital scoliosis between December 2014 and December 2019 were selected. The cohort comprised 16 boys and 10 girls, aged between 2 and 10 years, with an average age of 4.68 ± 2.42 years. Pedicle screw fixation was applied in the segment spanning from T1 to L5. Pedicle screws were inserted manually, guided by the positioning of the C-arm and anatomical markers. The assessment of pedicle screw placement was based on the distance of penetration into the medial, lateral, or anterior bone cortex of the vertebral body, including the pedicle, categorized into three grades: Grade 1 (placement <2 mm), Grade 2 (placement between 2-4 mm), and Grade 3 (placement >4 mm). Grade 1 indicates accurate pedicle screw placement, while Grades 2 and 3 signify abnormal pedicle screw placement. Complications related to pedicle screw insertion were also recorded, both during and after the surgical procedure. RESULTS: A total of 173 pedicle screws were inserted in this study, with an average of 6.65 screws per patient. Accurate screw placement was achieved in 143 cases (82.7%), while 30 pedicle screws were found to be abnormal. Among the abnormal screws, 24 were categorized as Grade 2 (13.9%), and 6 as Grade 3 (3.5%). Grade 2 abnormalities were distributed across 20 thoracic vertebrae and 4 lumbar vertebrae, while Grade 3 abnormalities affected 5 thoracic vertebrae and 1 lumbar vertebra. When comparing the lumbar and thoracic vertebral regions, a significant difference in the rate of abnormal screw placement was observed (χ2 = 5.801, p < 0.05). The rate of abnormal screw placement was higher in the thoracic vertebral region with abnormal vertebral bodies than in the lumbar vertebral regions. Furthermore, a statistically significant difference in the rate of abnormal screw placement was found between the concave and convex sides (χ2 = 23.047, p < 0.05). The concave side of the abnormal vertebral body had a higher rate of abnormal screw placement (55.6%, 15/27) compared to the convex side (20.1%, 7/34), and this difference was statistically significant (p < 0.05). Throughout the intraoperative and postoperative follow-up period, spanning from 12 to 56 months, only one patient experienced issues with wound healing, and no complications related to pedicle screw placement occurred, such as hemopneumothorax, pedicle fracture, nerve root injury, aortic injury, screw loosening, pullout or breakage, or spinal cord injury. CONCLUSIONS: In children under 10 years of age with early-onset congenital scoliosis, the freehand placement of thoracic and lumbar pedicle screws demonstrates a high level of accuracy. Moreover, complications associated with pedicle screw insertion are infrequent following surgery. It is advisable to exercise caution when placing pedicle screws in thoracic vertebral bodies and morphologically abnormal vertebral bodies, with particular attention to the concave side when screw placement is required in these regions.
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Parafusos Pediculares , Escoliose , Masculino , Adulto , Criança , Feminino , Humanos , Pré-Escolar , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Escoliose/congênito , Estudos Retrospectivos , Vértebras Torácicas/cirurgia , DorsoRESUMO
Plant health is intricately linked to crop quality, food security and agricultural productivity. Obtaining accurate plant health information is of paramount importance in the realm of precision agriculture. Wearable sensors offer an exceptional avenue for investigating plant health status and fundamental plant science, as they enable real-time and continuous in-situ monitoring of physiological biomarkers. However, a comprehensive overview that integrates and critically assesses wearable plant sensors across various facets, including their fundamental elements, classification, design, sensing mechanism, fabrication, characterization and application, remains elusive. In this study, we provide a meticulous description and systematic synthesis of recent research progress in wearable sensor properties, technology and their application in monitoring plant health information. This work endeavours to serve as a guiding resource for the utilization of wearable plant sensors, empowering the advancement of plant health within the precision agriculture paradigm.
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Agricultura , Dispositivos Eletrônicos Vestíveis , Agricultura/métodos , Produtos Agrícolas , Técnicas Biossensoriais/instrumentaçãoRESUMO
Fufang Xiling Jiedu capsule (FXJC), a traditional Chinese medicine that evolved from "Yinqiao Powder", is widely used for the treatment of cold and influenza. However, due to a lack of in vivo metabolism research, the chemical components responsible for the therapeutic effects still remain unclear. Hence, this study aimed to describe the metabolic profiles of the FXJC in rat plasma, urine, and feces. A combined data mining strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was employed and 201 xenobiotics, including 117 prototype components and 84 metabolites were detected. Phenolic acids, flavonoids, triterpenes, and lignans were prominent ingredients absorbed in vivo, and the major metabolic pathways of the detected metabolites were glucuronidation, sulfation, methylation, and oxidation. This is the first systematic study on the metabolism of the FXJC in vivo, providing valuable information for future studies on the efficacy, toxicity, and mechanism of the FXJC.