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BACKGROUND: CD74 is ectopically expressed in many tumors and can regulate tumor immunity. However, there are many gaps in the study of the prognostic value of CD74 expression and immune infiltration in hepatocellular carcinoma (HCC). METHODS: An online tumor database was searched to obtain data on gene/protein expression. Immune infiltration analysis was performed using the Tumor Immune Estimation Resource and Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer databases. Single-cell data were obtained from the Tissue-specific Gene Expression and Regulation, Single-cell Transcriptomes of Tumor Immune Microenvironment and Tumor Immune Single-cell Hub 2 databases. RESULTS: CD74 was highly expressed in HCC patients. HCC patients with high CD74 expression who consumed alcohol or were negative for hepatitis virus had a better prognosis than patients with low CD74 expression. CD74 was mainly enriched in immune response regulation pathways. Both copy number variations in CD74 and CD74 expression patterns affected the infiltration levels of immune cells. Interestingly, CD74 regulated the differentiation of myeloid cells. CD74 in macrophages and dendritic cells (DCs) forms complex networks with malignant cells and hepatic progenitor cell (HPC)-like cells, respectively. High CD74 expression in HPC-like cells and malignant cells significantly decreased the fraction of C-type lectin domain family 9 A (CLEC9A)-cDC1+ DCs and IL-1B+ macrophages, respectively. Their crosstalk subsequently shaped the tumor microenvironment of HCC, possibly through the CD74-MIF axis. Importantly, patients with high CD74 expression presented higher immune scores and achieved good outcomes after receiving immunotherapy. CONCLUSION: High CD74 expression is associated with the abundance of a variety of immune cell types, mediating interactions among tumor and immune cells and shaping the malignant behavior of HCC. In summary, CD74 may be a hallmark for determining the prognosis and immune cell infiltration levels of HCC patients.
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Antígenos de Diferenciación de Linfocitos B , Carcinoma Hepatocelular , Antígenos de Histocompatibilidad Clase II , Inmunoterapia , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/etiología , Microambiente Tumoral/inmunología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/etiología , Antígenos de Diferenciación de Linfocitos B/metabolismo , Antígenos de Diferenciación de Linfocitos B/genética , Inmunoterapia/métodos , Antígenos de Histocompatibilidad Clase II/metabolismo , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Pronóstico , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor , Biología Computacional/métodosRESUMEN
Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.
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The composition of skeletal muscle fiber types affects the quality of livestock meat and human athletic performance and health. L-arginine (Arg), a semi-essential amino acid, has been observed to promote the formation of slow-twitch muscle fibers in animal models. However, the precise molecular mechanisms are still unclear. This study investigates the role of Arg in skeletal muscle fiber composition and mitochondrial function through the mTOR signaling pathway. In vivo, 4-week C56BL/6J male mice were divided into three treatment groups and fed a basal diet supplemented with different concentrations of Arg in their drinking water. The trial lasted 7 weeks. The results show that Arg supplementation significantly improved endurance exercise performance, along with increased SDH enzyme activity and upregulated expression of the MyHC I, MyHC IIA, PGC-1α, and NRF1 genes in the gastrocnemius (GAS) and quadriceps (QUA) muscles compared to the control group. In addition, Arg activated the mTOR signaling pathway in the skeletal muscle of mice. In vitro experiments using cultured C2C12 myotubes demonstrated that Arg elevated the expression of slow-fiber genes (MyHC I and Tnnt1) as well as mitochondrial genes (PGC-1α, TFAM, MEF2C, and NRF1), whereas the effects of Arg were inhibited by the mTOR inhibitor rapamycin. In conclusion, these findings suggest that Arg modulates skeletal muscle fiber type towards slow-twitch fibers and enhances mitochondrial functions by upregulating gene expression through the mTOR signaling pathway.
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Arginina , Fibras Musculares Esqueléticas , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/efectos de los fármacos , Ratones , Arginina/metabolismo , Arginina/farmacología , Masculino , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Ratones Endogámicos C57BL , Fibras Musculares de Contracción Lenta/metabolismo , Fibras Musculares de Contracción Lenta/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Línea CelularRESUMEN
BACKGROUND: Cotton is globally important crop. Verticillium wilt (VW), caused by Verticillium dahliae, is the most destructive disease in cotton, reducing yield and fiber quality by over 50% of cotton acreage. Breeding resistant cotton cultivars has proven to be an efficient strategy for improving the resistance of cotton to V. dahliae. However, the lack of understanding of the genetic basis of VW resistance may hinder the progress in deploying elite cultivars with proven resistance. RESULTS: We planted the VW-resistant Gossypium hirsutum cultivar Zhongzhimian No.2 (ZZM2) in an artificial greenhouse and disease nursery. ZZM2 cotton was subsequently subjected to transcriptome sequencing after Vd991 inoculation (6, 12, 24, 48, and 72 h post-inoculation). Several differentially expressed genes (DEGs) were identified in response to V. dahliae infection, mainly involved in resistance processes, such as flavonoid and terpenoid quinone biosynthesis, plant hormone signaling, MAPK signaling, phenylpropanoid biosynthesis, and pyruvate metabolism. Compared to the susceptible cultivar Junmian No.1 (J1), oxidoreductase activity and reactive oxygen species (ROS) production were significantly increased in ZZM2. Furthermore, gene silencing of cytochrome c oxidase subunit 1 (COX1), which is involved in the oxidation-reduction process in ZZM2, compromised its resistance to V. dahliae, suggesting that COX1 contributes to VW resistance in ZZM2. CONCLUSIONS: Our data demonstrate that the G. hirsutum cultivar ZZM2 responds to V. dahliae inoculation through resistance-related processes, especially the oxidation-reduction process. This enhances our understanding of the mechanisms regulating the ZZM2 defense against VW.
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Resistencia a la Enfermedad , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Gossypium , Enfermedades de las Plantas , Gossypium/genética , Gossypium/microbiología , Gossypium/inmunología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/inmunología , Resistencia a la Enfermedad/genética , Ascomicetos/fisiología , Regulación de la Expresión Génica de las Plantas , Transcriptoma , VerticilliumRESUMEN
The pervasive employment of antibiotics has engendered the advent of drug-resistant bacteria, imperiling the well-being and health of both humans and animals. Infections precipitated by such multi-resistant bacteria, especially those induced by methicillin-resistant Staphylococcus aureus (MRSA), pervade hospital settings, constituting a grave menace to patient vitality. Antimicrobial peptides (AMPs) have garnered considerable attention as a potent countermeasure against multidrug resistant bacteria. In preceding research endeavors, an insect-derived antimicrobial peptide is identified that, while possessing antimicrobial attributes, manifested suboptimal efficacy against drug-resistant Gram-positive bacteria. To ameliorate this issue, this work enhances the antimicrobial capabilities of the initial ß-hairpin AMPs by substituting the structural sequence of the original AMPs with variant lengths of hydrophobic amino acid-hydrophilic amino acid repeat units. Throughout this endeavor, this work has identified a number of peptides that possess highly effective antibacterial characteristics against a wide range of bacteria. Additionally, some of these peptides have the ability to self-assemble into nanofibers, which then build networks in a distinctive manner to capture bacteria. Consequently, they represent prospective antibiotic alternatives for addressing wound infections engendered by drug-resistant bacteria.
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Antibacterianos , Nanofibras , Infección de Heridas , Nanofibras/química , Antibacterianos/farmacología , Antibacterianos/química , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Pruebas de Sensibilidad Microbiana , Animales , Péptidos/química , Péptidos/farmacologíaRESUMEN
Excessive discharge of nitrogen-containing chemical products into the natural water environment leads to the serious environmental problem of nitrate-nitrogen pollution, threatening the ecological balance and human health. In this study, we propose an efficient denitrification electrochemical method utilizing iron-doped zeolite imidazolium framework derived defective nitrogen-doped carbon (d-FeNC) catalysts. The d-FeNC catalyst exhibited 97 % nitrate removal efficiency and 94 % total nitrogen (TN) removal, and the reaction rate constant was increased from 0.73 h-1 of the Fe-undoped electrocatalyst (d-NC) to 1.11 h-1. The successful synthesis of d-FeNC with carbon defect sites and encapsulated Fe was confirmed by in-depth characterization. In situ electron paramagnetic resonance (EPR) analysis in conjunction with cyclic voltammetry (CV) tests confirmed the carbon substrates with defect enhanced the trapping of atomic hydrogen (H*) on the catalyst surface. Density functional theory (DFT) calculations clarified the doping of Fe facilitated the adsorption of nitrate, resulting in contact of H* with nitrate on the catalyst surface. In the synergy of the defective state organic framework and metal Fe, H* and nitrate realized a collision process. The electrochemical denitrification system achieved an excellent nitrate removal capacity of 7587 mgN·g-1cat in high-concentration nitrate solution and showed excellent stability under various conditions. Overall, this study underscores the potential of defective iron-doped carbon catalysts for efficient electrocatalytic denitrification, providing a promising approach for sustainable wastewater treatment.
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Objective To analyze the diagnostic values of H2FPEF and HFA-PEFF scores for heart failure with preserved ejection fraction (HFpEF) and HFpEF complicated with atrial fibrillation (HFpEF-AF) in Chinese patients and explore the related factors. Methods A cross-sectional study was conducted.A total of 835 consecutive HFpEF patients treated in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from 2009 to 2020 were selected and assigned to a HFpEF-AF group (n=267) and a HFpEF group (n=568) according to the presence of AF or not.HFA-PEFF and H2FPEF scores were used for retrospective diagnosis and the diagnostic consistency of the two scores was assessed.One hundred and thirty-six healthy volunteers with age and sex matching the patients during the same period were selected as healthy controls.The receiver operating characteristic (ROC) curves were established for H2FPEF and HFA-PEFF scores in diagnosing HFpEF-AF and HFpEF,on the basis of which the diagnostic performance of the two scores was evaluated. Results There was no difference in the HFA-PEFF score between the two groups (P=0.070).However,the HFpEF-AF group had higher mean H2FPEF score and higher proportion of patients with the score no less than 6 than the HFpEF group (P<0.001).According to the ROC curves,HFA-PEFF and H2FPEF scores demonstrated high performance in diagnosing all HFpEF patients,with the area under the curve (AUC) of 0.892 and 0.922 and the optimal cut-offs of 4 and 4,respectively.The HFA-PEFF score showed similar performance in diagnosing HFpEF and HFpEF-AF,with the AUC of 0.899 and 0.911,respectively.The H2FPEF score had higher performance in diagnosing HFpEF-AF (AUC of approximately 1.000) and low performance in diagnosing HFpEF (AUC of 0.885). Conclusions The HFA-PEFF score is applicable in the diagnosis of both HFpEF and HFpEF-AF.The H2FPEF score may underestimate HFpEF in Chinese patients,and its applicability in the Chinese patients with HFpEF alone remains to be investigated.
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Fibrilación Atrial , Insuficiencia Cardíaca , Volumen Sistólico , Humanos , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/complicaciones , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Estudios Transversales , Masculino , Femenino , Anciano , Estudios Retrospectivos , Curva ROC , Persona de Mediana Edad , Pueblo Asiatico , Pueblos del Este de AsiaRESUMEN
Although the pathogenesis of rheumatoid arthritis (RA) remains unclear, an increasing number of studies have confirmed that pyroptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is an important factor affecting the progression of RA. Periplogenin (PPN) is a natural cardiac glycoside; reportedly, it exerts anti-inflammatory and analgesic effects in diseases by inhibiting cell growth and migration. This study aimed to determine the effect of PPN on the growth, migration, and invasion of RA-FLS and the potential mechanism of pyroptosis regulation. We discovered that PPN could inhibit the migration and invasion abilities of RA-FLS and block their growth cycle, down-regulate the secretion and activation of NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18, and reduce the number of pyroptosis. In summary, PPN inhibited pyroptosis, reduced the release of inflammatory factors, and improved RA-FLS inflammation by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.
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Artritis Reumatoide , Fibroblastos , Piroptosis , Transducción de Señal , Sinoviocitos , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Caspasa 1/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/efectos de los fármacos , Gasderminas , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Piroptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sinoviocitos/efectos de los fármacos , Sinoviocitos/metabolismo , Sinoviocitos/patologíaRESUMEN
Deoxynivalenol (DON) is a prevalent toxin causing severe liver damage through hepatocellular oxidative stress. However, the underlying mechanisms and effective therapeutic approaches remain unknown. Here, the unique role of the xenobiotic metabolism factor pregnane X receptor (PXR) in mediating DON-induced hepatocellular oxidative stress is investigated. Treatment with the PXR agonist 3-indole-propionic acid (IPA) alleviates DON-induced oxidative stress and liver injury both in vitro and in vivo. Mechanistically, it is discovered for the first time that PXR agonist IPA directly transactivates the m6A demethylase FTO expression, leading to site-specific demethylation and decreased abundance of YTHDC1-bound Malat1 lncRNA at single-nucleotide resolution. The diminished m6A modification of Malat1 lncRNA reduces its stability and augments antioxidant pathways governed by NRF2, consequently mitigating DON-induced liver injury. Furthermore, Malat1 knockout mice exhibit decreased DON-induced liver injury, emphasizing the role of Malat1 lncRNA in oxidative stress. Collectively, the findings establish that PXR-mediated m6A-dependent Malat1 lncRNA expression determines hepatocyte oxidative stress via m6A demethylase FTO, providing valuable insights into the potential mechanisms underlying DON-induced liver injury and offers potential therapeutic strategies for its treatment.
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Desmetilación , Ratones Noqueados , Estrés Oxidativo , Receptor X de Pregnano , ARN Largo no Codificante , Tricotecenos , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Ratones , Tricotecenos/toxicidad , Receptor X de Pregnano/metabolismo , Receptor X de Pregnano/genética , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos C57BL , Hígado/metabolismo , Hígado/efectos de los fármacos , HumanosRESUMEN
The decomposition of ammonia-N to environmental-friendly N2 remains a fundamental problem for water treatment. We proposed a way to selectively and efficiently oxidize ammonia to N2 through an integrated photoeletrocatalysischlorine reactions (PECCl) system based on a bifunctional TiO2 nanotube photoanode. The ·OH and HClO can be simultaneously generated on the TiO2 nanotube photoanode in this system, which can in situ form ClO· for efficient ammonia removal. Compared with electrochemicalchlorine (EC-Cl), photocatalysischlorine (PC-Cl) and photoelectrocatalysis (PEC) systems, the PEC-Cl system exhibited much higher electrocatalytic activity due to the synergetic effect of photoelectrocatalyst and electrocatalyst in bifunctional TiO2 nanotube electrode. The removal efficiency of ammonia-N and total-N reached 100.0 % and 93.3 % at 0.3 V (vs Ag/AgCl) in the PEC-Cl system. Moreover, the system was efficient under various pH conditions. The reactions between ClO-/ClO· and the N-containing intermediates contributed to the high performance of the system, which expanded the reactions from the electrode surface to the electrolyte. Furthermore, radical scavenging and free chlorine determination experiments confirmed that ClO· and free chlorine were the main active species that enabled the ammonia oxidation. This study presents new understanding on the role of active species for ammonia removal in wastewater.
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Staphylococcus aureus (S. aureus) is a common pathogenic bacterium in animal husbandry that can cause diseases such as mastitis, skin infections, arthritis, and other ailments. The formation of biofilms threatens and exacerbates S. aureus infection by allowing the bacteria to adhere to pathological areas and livestock product surfaces, thus triggering animal health crises and safety issues with livestock products. To solve this problem, in this review, we provide a brief overview of the harm caused by S. aureus and its biofilms on livestock and animal byproducts (meat and dairy products). We also describe the ways in which S. aureus spreads in animals and the threats it poses to the livestock industry. The processes and molecular mechanisms involved in biofilm formation are then explained. Finally, we discuss strategies for the removal and eradication of S. aureus and biofilms in animal husbandry, including the use of antimicrobial peptides, plant extracts, nanoparticles, phages, and antibodies. These strategies to reduce the spread of S. aureus in animal husbandry help maintain livestock health and improve productivity to ensure the ecologically sustainable development of animal husbandry and the safety of livestock products.
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Cell senescence has been implicated in the pathology of Parkinson's disease (PD). Both abnormal α-synuclein aggregation and iron deposition are suggested to be the triggers, facilitators, and aggravators during the development of PD. In this study, we investigated the involvement of α-synuclein and iron in the process of cell senescence in a mouse model of PD. In order to overexpress α-syn-A53T in the substantia nigra pars compacta (SNpc), human α-syn-A53T was microinjected into both sides of the SNpc in mice. We found that overexpression of α-syn-A53T for one week induced significant pro-inflammatory senescence-associated secretory phenotype (SASP), increased cell senescence-related proteins (ß-gal, p16, p21, H2A.X and γ-H2A.X), mitochondrial dysfunction accompanied by dysregulation of iron-related proteins (L-ferritin, H-ferritin, DMT1, IRP1 and IRP2) in the SNpc. In contrast, significant loss of nigral dopaminergic neurons and motor dysfunction were only observed after overexpression of α-syn-A53T for 4 weeks. In PC12 cells stably overexpressing α-syn-A53T, iron overload (ferric ammonium citrate, FAC, 100 µM) not only increased the level of reactive oxygen species (ROS), p16 and p21, but also exacerbated the processes of oxidative stress and cell senescence signalling induced by α-syn-A53T overexpression. Interestingly, reducing the iron level with deferoxamine (DFO) or knockdown of transferrin receptor 1 (TfR1) significantly improved both the phenotypes and dysregulated proteins of cell senescence induced by α-syn-A53T overexpression. All these evidence highlights the toxic interaction between iron and α-synuclein inducing cell senescence, which precedes nigral dopaminergic neuronal loss in PD. Further investigation on cell senescence may yield new therapeutic agents for the prevention or treatment of PD.
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Enfermedad de Parkinson , Ratas , Ratones , Animales , Humanos , Enfermedad de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Neuronas Dopaminérgicas/metabolismo , Hierro/metabolismo , Sustancia Negra/metabolismo , Sustancia Negra/patología , Dopamina/metabolismo , Senescencia Celular , Modelos Animales de EnfermedadRESUMEN
Gut microbiota disturbance and systemic inflammation have been implicated in the degeneration of dopaminergic neurons in Parkinson's disease (PD). How the alteration of gut microbiota results in neuropathological events in PD remains elusive. In this study, we explored whether and how environmental insults caused early neuropathological events in the substantia nigra (SN) of a PD mouse model. Aged (12-month-old) mice were orally administered rotenone (6.25 mg·kg-1·d-1) 5 days per week for 2 months. We demonstrated that oral administration of rotenone to ageing mice was sufficient to establish a PD mouse model and that microglial activation and iron deposition selectively appeared in the SN of the mice prior to loss of motor coordination and dopaminergic neurons, and these events could be fully blocked by microglial elimination with a PLX5622-formulated diet. 16 S rDNA sequencing analysis showed that the gut microbiota in rotenone-treated mice was altered, and mice receiving faecal microbial transplantation (FMT) from ageing mice treated with rotenone for 2 months exhibited the same pathology in the SN. We demonstrated that C-X-C motif chemokine ligand-1 (CXCL1) was an essential molecule, as intravenous injection of CXCL1 mimicked almost all the pathology in serum and SN induced by oral rotenone and FMT. Using metabolomics and transcriptomics analyses, we identified the PPAR pathway as a key pathway involved in rotenone-induced neuronal damage. Inhibition of the PPARγ pathway was consistent in the above models, whereas its activation by linoleic acid (60 mg·kg-1·d-1, i.g. for 1 week) could block these pathological events in mice intravenously injected with CXCL1. Altogether, these results reveal that the altered gut microbiota resulted in neuroinflammation and iron deposition occurring early in the SN of ageing mice with oral administration of rotenone, much earlier than motor symptoms and dopaminergic neuron loss. We found that CXCL1 plays a crucial role in this process, possibly via PPARγ signalling inhibition. This study may pave the way for understanding the "brain-gut-microbiota" molecular regulatory networks in PD pathogenesis. The aged C57BL/6 male mice with rotenone intragastric administration showed altered gut microbiota, which caused systemic inflammation, PPARγ signalling inhibition and neuroinflammation, brain iron deposition and ferroptosis, and eventually dopaminergic neurodegeneration in PD.
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Microbioma Gastrointestinal , Enfermedad de Parkinson , Ratones , Animales , Masculino , Rotenona/toxicidad , Enfermedades Neuroinflamatorias , PPAR gamma , Ratones Endogámicos C57BL , Enfermedad de Parkinson/patología , Sustancia Negra/patología , Neuronas Dopaminérgicas/patología , Inflamación/patología , Hierro , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Malunion of tibial pilon fracture, especially with a large cartilage loss of the tibial plafond, is a tough clinical conundrum. This study describes a joint-preserving technique that mainly involves corrective intraarticular osteotomy and osteoperiosteal iliac autograft transplantation for treating these generally considered unreconstructable tibial plafond. METHODS: Sixteen patients with an average age of 33.6 years who were treated with this joint-preserving method between 2013 and 2020 were retrospectively analyzed. Ankle distraction was applied in all patients. Additional osteochondral autograft transplantation for talus was performed in 4 patients and supramalleolar osteotomy in 2 patients. The visual analog scale (VAS) score, the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, the 36-Item Short Form Health Survey (SF-36) score, and the ankle range of motion (ROM) were used for outcome analysis. Radiographic assessment was conducted, and the complications were recorded. RESULTS: At a mean follow-up of 41.1 months, the mean VAS, AOFAS, and SF-36 scores improved from 6.3, 47.6, and 38.0 to 1.7, 84.4, and 70.8, respectively (P < .001 for each). The ankle ROM improved from 27.5 to 32.2 degrees (P = .023). The mean area of ilium blocks was 3.5 cm2, and the mean external fixation time was 94.1 days. Radiographs showed that good osteointegration was found in all patients and no significant progression of osteoarthritis in 15 patients. The major complications included poor incision healing in 2 patients and severe ankle stiffness in 2 patients, with one of them developing considerable varus-type osteoarthritis but reporting no pain. No deep infection, nonunion, or malunion occurred, and no secondary arthrodesis was performed during the final follow-up. CONCLUSION: Osteoperiosteal iliac autograft transplantation might be an alternative surgical option for reconstructing unreconstructable malunited pilon fractures with a large cartilage loss of the tibial plafond in young patients. LEVEL OF EVIDENCE: Level IV, case series.
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Fracturas de Tobillo , Osteoartritis , Fracturas de la Tibia , Humanos , Adulto , Estudios Retrospectivos , Autoinjertos , Ilion , Tibia/cirugía , Fracturas de la Tibia/cirugía , Fracturas de la Tibia/complicaciones , Fracturas de Tobillo/complicaciones , Articulación del Tobillo/cirugía , Osteoartritis/cirugía , Resultado del TratamientoRESUMEN
Thirty new tricyclicmatrinic derivatives were successively synthesized and evaluated for their inhibitory activity on the accumulation of triglycerides (TG) in AML12 cells, using 12 N-m-trifluoromethylbenzenesulfonyl matrine (1) as the hit compound. Among the analogues, compound 7n possessing 11-trimethylbutylamine quaternary exerted the highest in vitro TG-lowering potency, as well as a good safety profile. 7n significantly attenuated the hepatic injury and steatosis, and ameliorated dyslipidemia and dysglycemia in the mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet. Primary mechanism study revealed that upregulation of peroxisome proliferator-activated receptors α (PPARα)-carnitine palmitoyltransferase 1A (CPT1A) pathway mediated the efficacy of 7n. Our study provides powerful information for developing this kind of compound into a new class of anti-NAFLD candidates, and compound 7n is worthy of further investigation as an ideal lead compound.
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Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Matrinas , Triglicéridos/metabolismo , Hígado/metabolismo , PPAR alfa/metabolismo , Ratones Endogámicos C57BLRESUMEN
The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.
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COVID-19 , Microbiota , Neumonía , Humanos , COVID-19/genética , COVID-19/metabolismo , SARS-CoV-2/genética , Respiración Artificial , Pulmón , Neumonía/metabolismo , BacteriasRESUMEN
Quantification of behaviors in macaques provides crucial support for various scientific disciplines, including pharmacology, neuroscience, and ethology. Despite recent advancements in the analysis of macaque behavior, research on multi-label behavior detection in socially housed macaques, including consideration of interactions among them, remains scarce. Given the lack of relevant approaches and datasets, we developed the Behavior-Aware Relation Network (BARN) for multi-label behavior detection of socially housed macaques. Our approach models the relationship of behavioral similarity between macaques, guided by a behavior-aware module and novel behavior classifier, which is suitable for multi-label classification. We also constructed a behavior dataset of rhesus macaques using ordinary RGB cameras mounted outside their cages. The dataset included 65â¯913 labels for 19 behaviors and 60â¯367 proposals, including identities and locations of the macaques. Experimental results showed that BARN significantly improved the baseline SlowFast network and outperformed existing relation networks. In conclusion, we successfully achieved multi-label behavior detection of socially housed macaques with both economic efficiency and high accuracy.
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Conducta Animal , Animales , Macaca mulattaRESUMEN
Introduction: Laparoscopic minimally invasive surgery has been widely used in the diagnosis and treatment of gynaecological diseases. Aim: To investigate the effect of dexmedetomidine on perioperative haemodynamics and cognitive function in elderly gynaecological patients who underwent laparoscopic surgery. Material and methods: Clinical baseline characteristics, haemodynamic parameters, renin activity, norepinephrine level, cognitive function, pain level, and sedation were compared between the 2 groups. Results: At T4 (10 min after extubation) and T5 (1 h after extubation), significant differences were found in systolic blood pressure, diastolic blood pressure, and heart rate between the 2 groups (p < 0.05); renin activity and norepinephrine level were much lower in the dexmedetomidine group than in the control group at T3 (10 min before extubation) and T4 (p < 0.05). One day before surgery, there were no significant differences in Mini-mental state examination (MMSE), visual analogue scale (VAS), and Ramsay scores between the 2 groups (p > 0.05), but the MMSE score 1 day after surgery and the Ramsay score at 12 h after surgery in the dexmedetomidine group were much higher than that in the control group (p < 0.05). Notably, at 2, 4, 12, 24, and 48 h after surgery, the VAS score in the dexmedetomidine group was significantly lower than that in the control group (p < 0.05). Conclusions: Dexmedetomidine has a better clinical effect in improving perioperative haemodynamics and early cognitive function in elderly gynaecological patients who received laparoscopic surgery.
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Heavy computational load inhibits the application of groundwater contaminant numerical model to groundwater pollution source identification, remediation design, and uncertainty analysis, since a large number of model runs are required for these applications. Machine learning-based surrogate models are an effective approach to enhance the efficiency of the numerical models, and have recently attracted considerable attention in the field of groundwater contaminant modeling. Here, we review 120 research articles on machine learning-based surrogate models for groundwater contaminant modeling that were published between 1994 and 2022. We outline the state of the art method, identify the most significant research challenges, and suggest potential future directions. The six major applications of machine learning-based surrogate models are groundwater pollution source identification, groundwater remediation design, coastal aquifer management, uncertainty analysis of groundwater, groundwater monitoring network design, and groundwater transport parameters inversion. Together, these account for more than 90% of the studies we review. Latin hypercube sampling (LHS) is the most widely used sampling method, and artificial neural networks (ANNs) and Kriging are the two most widely used methods for constructing surrogate model. No method is universally superior, the advantages and disadvantages of different methods, as well as the applicability of these methods for different application purposes of groundwater contaminant modeling were analyzed. Some recommendations on the method selection for various application fields are given based on the reviews and experiences. Based on our review of the state-of-the-art, we suggest several future research directions to enhance the feasibility of the machine learning-based surrogate models of groundwater contaminant modeling: the alleviation of the curse of dimensionality, enhancing transferability, practical applications for real case studies, multi-source dada fusion, and real-time monitoring and prediction.
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Agua Subterránea , Modelos Teóricos , Aprendizaje Automático , Contaminación Ambiental , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: The extracellular space between the cell wall and plasma membrane is a battlefield in plant-pathogen interactions. Within this space, the pathogen employs its secretome to attack the host in a variety of ways, including immunity manipulation. However, the role of the plant secretome is rarely studied for its role in disease resistance. RESULTS: Here, we examined the secretome of Verticillium wilt-resistant Gossypium hirsutum cultivar Zhongzhimian No.2 (ZZM2, encoding 95,327 predicted coding sequences) to determine its role in disease resistance against the wilt causal agent, Verticillium dahliae. Bioinformatics-driven analyses showed that the ZZM2 genome encodes 2085 secreted proteins and that these display disequilibrium in their distribution among the chromosomes. The cotton secretome displayed differences in the abundance of certain amino acid residues as compared to the remaining encoded proteins due to the localization of these putative proteins in the extracellular space. The secretome analysis revealed conservation for an allotetraploid genome, which nevertheless exhibited variation among orthologs and comparable unique genes between the two sub-genomes. Secretome annotation strongly suggested its involvement in extracellular stress responses (hydrolase activity, oxidoreductase activity, and extracellular region, etc.), thus contributing to resistance against the V. dahliae infection. Furthermore, the defense response genes (immunity marker NbHIN1, salicylic acid marker NbPR1, and jasmonic acid marker NbLOX4) were activated to varying degrees when Nicotina benthamiana leaves were agro-infiltrated with 28 randomly selected members, suggesting that the secretome plays an important role in the immunity response. Finally, gene silencing assays of 11 members from 13 selected candidates in ZZM2 displayed higher susceptibility to V. dahliae, suggesting that the secretome members confer the Verticillium wilt resistance in cotton. CONCLUSIONS: Our data demonstrate that the cotton secretome plays an important role in Verticillium wilt resistance, facilitating the development of the resistance gene markers and increasing the understanding of the mechanisms regulating disease resistance.