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Recombinant adeno-associated virus (rAAV) vector gene delivery systems have demonstrated great promise in clinical trials but continue to face durability and dose-related challenges. Unlike rAAV gene therapy, integrating gene addition approaches can provide curative expression in mitotically active cells and pediatric populations. We explored a novel in vivo delivery approach based on an engineered transposase, Sleeping Beauty (SB100X), delivered as an mRNA within a lipid nanoparticle (LNP), in combination with an rAAV-delivered transposable transgene. This combinatorial approach achieved correction of ornithine transcarbamylase deficiency in the neonatal Spfash mouse model following a single delivery to dividing hepatocytes in the newborn liver. Correction remained stable into adulthood, while a conventional rAAV approach resulted in a return to the disease state. In non-human primates, integration by transposition, mediated by this technology, improved gene expression 10-fold over conventional rAAV-mediated gene transfer while requiring 5-fold less vector. Additionally, integration site analysis confirmed a random profile while specifically targeting TA dinucleotides across the genome. Together, these findings demonstrate that transposable elements can improve rAAV-delivered therapies by lowering the vector dose requirement and associated toxicity while expanding target cell types.
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Biochar application may mitigate N2O emissions and increase crop yield, yet little is known about microbial dynamics variation. To investigate the potential of increasing yield and reducing emissions of biochar in tropical areas and the dynamic mechanism of related microorganisms, a pot experiment was conducted to investigate the biochar application on pepper yield, N2O emissions, and dynamic variation of related microorganisms. Three treatments were applied:2% biochar amendment (B), conventional fertilization (CON), and no nitrogen (CK). The results showed that the yield of the CON treatment was higher than that of the CK treatment. Compared with that of the CON treatment, biochar amendment significantly increased the yield of pepper by 18.0% (P<0.05), and biochar amendment could increase the content of NH+4-N and NO-3-N in soil in most periods of pepper growth. Compared with that in the CON treatment, the B treatment significantly reduced cumulative N2O emissions by 18.3% (P<0.05). Ammonia oxidizing archaea (AOA)-amoA and ammonia oxidizing bacteria (AOB)-amoA were very significantly negatively correlated with N2O flux (P<0.01). N2O flux was significantly negatively correlated with nosZ gene abundance (P<0.05). This indicated that N2O emission may have mainly resulted from the denitrification process. In the early stage of pepper growth, biochar significantly reduced N2O emissions by reducing the value of (nirK+nirS)/nosZ, whereas in the late stage of pepper growth, the value of (nirK+nirS)/nosZ of the B treatment was higher than that of the CON treatment, resulting in higher N2O flux in the B treatment. Therefore, biochar amendment could not only increase vegetable production in tropical areas but also reduce N2O emissions, which can be used as a new strategy to improve soil fertility in Hainan Province and other tropical areas.
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Amoníaco , Verduras , Archaea , SueloRESUMEN
Opioid use disorder (OUD) is a chronic disease characterized by compulsive opioid taking and seeking, affecting millions of people worldwide. The high relapse rate is one of the biggest challenges in treating opioid addiction. However, the cellular and molecular mechanisms underlying relapse to opioid seeking are still unclear. Recent studies have shown that DNA damage and repair processes are implicated in a broad spectrum of neurodegenerative diseases as well as in substance use disorders. In the present study, we hypothesized that DNA damage is related to relapse to heroin seeking. To test our hypothesis, we aim to examine the overall DNA damage level in prefrontal cortex (PFC) and nucleus accumbens (NAc) after heroin exposure, as well as whether manipulating DNA damage levels can alter heroin seeking. First, we observed increased DNA damage in postmortem PFC and NAc tissues from OUD individuals compared to healthy controls. Next, we found significantly increased levels of DNA damage in the dorsomedial PFC (dmPFC) and NAc from mice that underwent heroin self-administration. Moreover, increased accumulation of DNA damage persisted after prolonged abstinence in mouse dmPFC, but not in NAc. This persistent DNA damage was ameliorated by the treatment of reactive oxygen species (ROS) scavenger N-acetylcysteine, along with attenuated heroin-seeking behavior. Furthermore, intra-PFC infusions of topotecan and etoposide during abstinence, which trigger DNA single-strand breaks and double-strand breaks respectively, potentiated heroin-seeking behavior. These findings provide direct evidence that OUD is associated with the accumulation of DNA damage in the brain (especially in the PFC), which may lead to opioid relapse.
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Analgésicos Opioides , Heroína , Ratones , Animales , Heroína/farmacología , Núcleo Accumbens , Corteza Prefrontal , Recurrencia , AutoadministraciónRESUMEN
BACKGROUND: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder with an enormous socioeconomic burden. Opioid overdose deaths have reached an epidemic level, especially for fentanyl. One of the biggest challenges to treat OUD is the relapse to drug seeking after prolonged abstinence. Abnormalities in insulin-like growth factor-1 (IGF-1) have been reported in various neurological and psychiatric disorders, including OUD. However, whether IGF-1 and its downstream signaling pathways are associated with relapse to fentanyl seeking remains unclear. METHODS: Mice were subjected to daily 2-hour fentanyl (10 µg/mL, 27 µL/infusion) oral self-administration training for 14 days, followed by 14-day fentanyl cessation. Expression levels of IGF-1/IGF-1 receptor and downstream signaling pathways in the dorsomedial prefrontal cortex (dmPFC) were detected. Then, IGF-1 was bilaterally microinjected into the dmPFC from fentanyl cessation day 9 to day 13. Fentanyl-seeking behavior and excitatory synaptic transmission of pyramidal neurons in PFC were evaluated. RESULTS: We found that 14-day cessation from fentanyl oral self-administration caused significant downregulation of IGF-1 and IGF-1 receptor phosphorylation in the dmPFC. These changes were accompanied by inhibition of the downstream Akt and S6 signaling pathway. In addition, local administration of IGF-1 in the dmPFC attenuated context-induced fentanyl-seeking behavior. Furthermore, electrophysiology and immunohistochemistry analyses showed that IGF-1 blocked fentanyl-induced reduction of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptors-mediated excitatory synaptic transmission as well as synaptic expression of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and N-methyl-D-aspartate receptor subunits. CONCLUSIONS: These results suggest that IGF-1 in the PFC plays a pivotal role in regulating fentanyl seeking after prolonged cessation from fentanyl oral self-administration.
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Fentanilo , Trastornos Relacionados con Opioides , Ratas , Ratones , Animales , Fentanilo/farmacología , Fentanilo/metabolismo , Ratas Sprague-Dawley , Factor I del Crecimiento Similar a la Insulina/metabolismo , Receptor IGF Tipo 1/metabolismo , Microinyecciones , Corteza Prefrontal/metabolismo , Comportamiento de Búsqueda de Drogas/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , RecurrenciaRESUMEN
Intentional replantation involves a combination of periodontics, endodontics, prosthodontics and oral surgery. Crown-root fracture management is still complicated nowadays. A fracture line extending longitudinally to the subgingival area and intruding bioogical width could affect infection control, gingival health and crown restoration. In the present study, we present two cases. Case 1 involved a 23-year-old man who presented at our hospital with crown-root fracture of the maxillary left central incisor. A radiographic image of the tooth revealed a fracture line under the alveolar crest. The fractured tooth was treated with intentional replantation with 180-degree rotation, root canal treatment and veneer restoration. The patient was followed up for 60 months. The replanted tooth functioned well, and no symptoms of resorption or ankylosis were observed by radiographic examination. Case 2 involved a 20-year-old woman who was referred to our hospital for crown-root fracture of her maxillary teeth. A radiographic examination revealed complicated crown-root fracture of the maxillary right lateral incisor and both maxillary central incisors. The central incisors were treated with intentional replantation with 180-degree rotation. At the 48-month follow-up, the fractured teeth were found to have regained normal function based on clinical and radiographic examination. Limited case reports are available on a long-term follow-up of intentional replantation with 180-degree rotation. These two cases, particularly case 2, presented optimal healing after 4 years with unideal crown-root ratios. This case report suggests that this old method of preserving teeth with crown-root fractures can be used as a last resort to save teeth owing to its timesaving and microinvasive procedure.
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Anquilosis del Diente , Fracturas de los Dientes , Reimplante Dental , Femenino , Humanos , Masculino , Adulto Joven , Coronas , Tratamiento del Conducto Radicular/métodos , Rotación , Corona del Diente/cirugía , Fracturas de los Dientes/diagnóstico por imagen , Fracturas de los Dientes/cirugía , Reimplante Dental/métodos , Raíz del Diente/diagnóstico por imagen , Raíz del Diente/cirugíaAsunto(s)
Brucella , Brucelosis , Brucelosis/diagnóstico , Cromatografía de Afinidad , Oro Coloide , HumanosRESUMEN
Insulin-like growth factor 1 (IGF1) influences synaptic function in addition to its role in brain development and aging. Although the expression levels of IGF1 and IGF1 receptor (IGF1R) peak during development and decline with age, the adult brain has abundant IGF1 or IGF1R expression. Studies reveal that IGF1 regulates the synaptic transmission in neurons from young animals. However, the action of IGF1 on neurons in the adult brain is still unclear. Here, we used prefrontal cortical (PFC) slices from adult mice (â¼8 weeks old) to characterize the role of IGF1 on excitatory synaptic transmission in pyramidal neurons and the underlying molecular mechanisms. We first validated IGF1R expression in pyramidal neurons using translating ribosomal affinity purification assay. Then, using whole-cell patch-clamp recording, we found that IGF1 attenuated the amplitude of evoked excitatory postsynaptic current (EPSC) without affecting the frequency and amplitude of miniature EPSC. Furthermore, this decrease in excitatory neurotransmission was blocked by pharmacological inhibition of IGF1R or conditional knockdown of IGF1R in PFC pyramidal neurons. In addition, we determined that IGF1-induced decrease of EPSC amplitude was due to postsynaptic effect (internalization of a-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptors [AMPAR]) rather than presynaptic glutamate release. Finally, we found that inhibition of metabotropic glutamate receptor subtype-1 (mGluR1) abolished IGF1-induced attenuation of evoked EPSC amplitude and decrease of AMPAR expression at synaptic membrane, suggesting mGluR1-mediated endocytosis of AMPAR was involved. Taken together, these data provide the first evidence that IGF1 regulates excitatory synaptic transmission in adult PFC via the interaction between IGF1R-dependent signaling pathway and mGluR1-mediated AMPAR endocytosis.
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Factor I del Crecimiento Similar a la Insulina , Corteza Prefrontal , Células Piramidales , Transmisión Sináptica , Animales , Factor I del Crecimiento Similar a la Insulina/farmacología , Ratones , Corteza Prefrontal/citología , Células Piramidales/fisiologíaRESUMEN
Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.
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Guías de Práctica Clínica como Asunto , HumanosRESUMEN
In this study, glycated soy ß-conglycinin (ß-CG) stabilized curcumin (Cur) composites were fabricated by a unique reversible self-assembly character of ß-conglycinin-dextran conjugates (ß-CG-DEX). Intrinsic fluorescence and far-UV CD spectra revealed that glycation did not affect the self-assembly property of ß-CG in the pH-shifting treatment. The structure of ß-CG-DEX could be unfolded at pH 12.0 and reassembled during acidification (from pH 12.0 to 7.0). Meanwhile, ß-CG-DEX-3d, which was incubated at 60 °C for 3 days, exhibited a high loading capacity (123.4 mg/g) for curcumin, which far exceeds that (74.90 mg/g) of ß-CG-Cur. Moreover, the reassembled ß-CG-DEX-3d-Cur showed eminent antioxidant activity of approximately 1.5 times higher than that of free curcumin. During the simulated gastrointestinal condition, compared with ß-CG-Cur, ß-CG-DEX-3d-Cur nanoparticles showed a more stable and sustained release of curcumin. Thus, ß-CG-DEX has immense potential to become a new delivery carrier for hydrophobic food components by means of a self-assembly strategy.
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Curcumina , Nanopartículas , Antígenos de Plantas , Antioxidantes/química , Curcumina/química , Preparaciones de Acción Retardada , Dextranos/química , Portadores de Fármacos/química , Globulinas , Nanopartículas/química , Tamaño de la Partícula , Polifenoles , Proteínas de Almacenamiento de Semillas , Proteínas de SojaRESUMEN
Chronic social isolation stress during adolescence induces susceptibility for neuropsychiatric disorders. Here we show that 5-week post-weaning isolation stress induces sex-specific behavioral abnormalities and neuronal activity changes in the prefrontal cortex (PFC), basal lateral amygdala (BLA), and ventral tegmental area (VTA). Chemogenetic manipulation, optogenetic recording, and in vivo calcium imaging identify that the PFC to BLA pathway is causally linked to heightened aggression in stressed males, and the PFC to VTA pathway is causally linked to social withdrawal in stressed females. Isolation stress induces genome-wide transcriptional alterations in a region-specific manner. Particularly, the upregulated genes in BLA of stressed males are under the control of activated transcription factor CREB, and CREB inhibition in BLA normalizes gene expression and reverses aggressive behaviors. On the other hand, neuropeptide Hcrt (Hypocretin/Orexin) is among the top-ranking downregulated genes in VTA of stressed females, and Orexin-A treatment rescues social withdrawal. These results have revealed molecular mechanisms and potential therapeutic targets for stress-related mental illness.
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Neuropéptidos , Aislamiento Social , Estrés Psicológico , Complejo Nuclear Basolateral/metabolismo , Femenino , Humanos , Masculino , Neuropéptidos/metabolismo , Corteza Prefrontal/metabolismo , Estrés Psicológico/metabolismo , Área Tegmental Ventral/metabolismoRESUMEN
Background: Hereditary spastic paraplegia (HSP) is a rare group of genetically heterogeneous, neurodegenerative disorders. The aim of this study was to identify pathological candidate genes and variants in a large pedigree cohort of 11 purely HSP patients in Yunnan Province. Methods: Whole-exome sequencing (WES) was applied to 2 HSP patients and 1 control patient to screen out the candidate gene variants. Then, filtration and verification of these pathological variants were performed by Sanger sequencing. Results: After the raw data were filtered, two genes with novel variations (SPAST: c.1510 C>T, p.Gln504X, RefSeq.NM_199436; DNAJC16: c.718 C>T, p.Q240X, Ref Seq NM_015291) were identified. The accession numbers of the genes in the ClinVar database were SCV001573094 and SCV001573804, respectively. One gene with a reported single nucleotide polymorphism (CPT1C: rs150853576) was filtered as a candidate variant. Using Sanger sequencing, the novel SPAST gene (protein: Spastin) variant leading to a predicted premature termination and an 18% deletion of the SPAST/spastic paraplegia type 4 (SPG4) protein was confirmed to exist only in affected individuals. The candidate CPT1C and DNAJC16 variants were verified in almost all HSP patients, with one exception. Conclusions: Considering that the clinical symptoms and time of onset of HSP are highly heterogeneous, the SPAST as a genotype-phenotype cosegregated variant might be the causative gene of this pedigree, and the other two variants might present cumulative risks to the occurrence and progression of HSP. These three candidate genes with or without novel variants may be potential contributors to disease onset, and therefore useful diagnostic and therapeutic biomarkers. Further research is required to confirm the functions of these genes.
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Renal artery thrombosis can cause acute occlusion of unilateral or bilateral renal arteries,and kidney failure would be induced if it is not diagnosed and treated in time.Therefore,rapid and correct treatment is especially important for renal artery thrombosis.Due to the lack of specificity of clinical manifestations,this disease in commonly misdiagnosed or missed and thus has a low early diagnosis rate.Here we report a case of acute renal artery thrombosis to improve the diagnosis and treatment.
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Obstrucción de la Arteria Renal , Trombosis , Enfermedad Aguda , Errores Diagnósticos/efectos adversos , Humanos , Arteria Renal , Obstrucción de la Arteria Renal/diagnóstico , Trombosis/diagnóstico , Trombosis/etiologíaRESUMEN
Large-scale genetic studies have revealed that the most prominent genes disrupted in autism are chromatin regulators mediating histone methylation/demethylation, suggesting the central role of epigenetic dysfunction in this disorder. Here, we show that histone lysine 4 dimethylation (H3K4me2), a histone mark linked to gene activation, is significantly decreased in the prefrontal cortex (PFC) of autistic human patients and mutant mice with the deficiency of top-ranking autism risk factor Shank3 or Cul3. A brief treatment of the autism models with highly potent and selective inhibitors of the H3K4me2 demethylase LSD1 (KDM1A) leads to the robust rescue of core symptoms of autism, including social deficits and repetitive behaviors. Concomitantly, LSD1 inhibition restores NMDA receptor function in PFC and AMPA receptor-mediated currents in striatum of Shank3-deficient mice. Genome-wide RNAseq and ChIPseq reveal that treatment of Shank3-deficient mice with the LSD1 inhibitor restores the expression and H3K4me2 occupancy of downregulated genes enriched in synaptic signaling and developmental processes. The immediate early gene tightly linked to neuronal plasticity, Egr1, is on the top list of rescued genes. The diminished transcription of Egr1 is recapitulated in PFC of autistic human patients. Overexpression of Egr1 in PFC of Shank3-deficient mice ameliorates social preference deficits. These results have for the first time revealed an important role of H3K4me2 abnormality in ASD pathophysiology, and the therapeutic potential of targeting H3K4me2 demethylase LSD1 or the downstream molecule Egr1 for ASD.
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Trastorno Autístico , Histonas , Humanos , Ratones , Animales , Histonas/metabolismo , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Cromatina , Modelos Animales de Enfermedad , Proteínas de Microfilamentos/genética , Proteínas del Tejido Nervioso/metabolismoRESUMEN
OBJECTIVES: To investigate the value of morphological feature and signal intensity ratio (SIR) derived from conventional magnetic resonance imaging (MRI) in distinguishing primary central nervous system lymphoma (PCNSL) from atypical glioblastoma (aGBM). METHODS: Pathology-confirmed PCNSLs (n = 93) or aGBMs (n = 48) from three institutions were retrospectively enrolled and divided into training cohort (n = 98) and test cohort (n = 43). Morphological features and SIRs were compared between PCNSL and aGBM. Using linear discriminant analysis, multiple models were constructed with SIRs and morphological features alone or jointly, and the diagnostic performances were evaluated via receiver operating characteristic (ROC) analysis. Areas under the curves (AUCs) and accuracies (ACCs) of the models were compared with the radiologists' assessment. RESULTS: Incision sign, T2 pseudonecrosis sign, reef sign and peritumoral leukomalacia sign were associated with PCNSL (training and overall cohorts, P < 0.05). Increased T1 ratio, decreased T2 ratio and T2/T1 ratio were predictive of PCNSL (all P < 0.05). ROC analysis showed that combination of morphological features and SIRs achieved the best diagnostic performance for differentiation of PCNSL and aGBM with AUC/ACC of 0.899/0.929 for the training cohort, AUC/ACC of 0.794/0.837 for the test cohort and AUC/ACC of 0.869/0.901 for the overall cohort, respectively. Based on the overall cohort, two radiologists could distinguish PCNSL from aGBM with AUC/ACC of 0.732/0.724 for radiologist A and AUC/ACC of 0.811/0.829 for radiologist B. CONCLUSION: MRI morphological features can help differentiate PCNSL from aGBM. When combined with SIRs, the diagnostic performance was better than that of radiologists' assessment.
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Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been probed in cerebral ischemia, while the regulatory mechanism of ZFAS1 in focal cerebral ischemia (FCI) via binding to microRNA (miR)-144-5p remains rarely explored. This study aims to decipher the function of ZFAS1 on FCI via sponging miR-144-5p to modulate fibroblast growth factor 7 (FGF7). The focal cerebral ischemia rat model was established by occlusion of the middle cerebral artery (MCAO) Lentivirus vectors altering ZFAS1, miR-144-5p or FGF7 expression were injected into rats before MCAO. Then, ZFAS1, miR-144-5p, and FGF7 levels were detected, the inflammatory factor level, oxidative stress level, angiogenesis, neurological function injury and neuronal apoptosis were assessed. The binding relations among ZFAS1, miR-144-5p and FGF7 were validated. ZFAS1 and FGF7 expression was elevated, while miR-144-5p expression was reduced in FCI rats. Decreased ZFAS1 or FGF7 or enriched miR-144-5p repressed the inflammatory response, oxidative stress, neuronal apoptosis, while it improved angiogenesis, and neurological function recovery; while up-regulated ZFAS1 exerted opposite effects. The augmented miR-144-5p or silenced FGF7 reversed the effects of enriched ZFAS1. ZFAS1 sponged miR-144-5p that targeted FGF7. Inhibition of lncRNA ZFAS1 improves functional recovery and angiogenesis after FCI via miR-144-5p/FGF7 axis. This study provides novel therapeutic targets for FCI treatment.
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Isquemia Encefálica/psicología , Factor 7 de Crecimiento de Fibroblastos/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Animales , Isquemia Encefálica/etiología , Isquemia Encefálica/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Masculino , Estrés Oxidativo , RatasRESUMEN
RATIONALE: Adverse psychosocial factors during early childhood or adolescence compromise neural structure and brain function, inducing susceptibility for many psychiatric disorders such as substance use disorder. Nevertheless, the mechanisms underlying early life stress-induced addiction vulnerability is still unclear, especially for opioids. OBJECTIVES: To address this, we used a mouse heroin self-administration model to examine how chronic early social isolation (ESI) stress (5 weeks, beginning at weaning) affects the behavioral and neural responses to heroin during adulthood. RESULTS: We found that ESI stress did not alter the acquisition for sucrose or heroin self-administration, nor change the motivation for sucrose on a progressive ratio schedule. However, ESI stress induced an upward shift of heroin dose-response curve in female mice and increased motivation and seeking for heroin in both sexes. Furthermore, we examined the neuronal activity (measured by c-Fos expression) within the key brain regions of the mesocorticolimbic system, including the prelimbic cortex (PrL), infralimbic cortex (IL), nucleus accumbens (NAc) core and shell, caudate putamen, and ventral tegmental area (VTA). We found that ESI stress dampened c-Fos expression in the PrL, IL, and VTA after 14-day forced abstinence, while augmented the neuronal responses to heroin-predictive context and cue in the IL and NAc core. Moreover, ESI stress disrupted the association between c-Fos expression and attempted infusions during heroin-seeking test in the PrL. CONCLUSIONS: These data indicate that ESI stress leads to increased seeking and motivation for heroin, and this may be associated with distinct changes in neuronal activities in different subregions of the mesocorticolimbic system.
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Heroína , Núcleo Accumbens , Adulto , Animales , Preescolar , Femenino , Humanos , Masculino , Ratones , Núcleo Accumbens/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Autoadministración , Aislamiento Social , Sacarosa , Área Tegmental Ventral/metabolismoRESUMEN
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has shown promising results in improving the survival of ovarian cancer patients. Although the safety profiles of CRS-HIPEC exist, more attention should be paid to gastrointestinal complications, as the procedure involves a considerable proportion of bowel resection and anastomosis. AIM: To identify the risk factors for delayed gastric emptying in ovarian cancer treated with CRS-HIPEC. METHODS: A cross-sectional study was conducted. According to the inclusion and exclusion criteria, we retrospectively analyzed 77 patients admitted between March 2014 and April 2018 with advanced and recurrent ovarian cancer treated with CRS-HIPEC in Beijing Shijitan Hospital of Capital Medical University. Risk factors for delayed gastric emptying were analyzed using univariate analysis. All of the statistically significant variables in the univariate analysis were entered into the multivariable logistic regression model to determine factors independently associated with delayed gastric emptying. RESULTS: Among the 77 included patients, 36.4% (28/77) had delayed gastric emptying after CRS-HIPEC. The median age and body mass index of all patients were 59 years and 22.83 kg/m2, respectively. Preoperative chemotherapy was administered in 55 patients (71%). Sixty-two patients (81%) had a history of at least one previous pelvic surgery. The median operation time and intraoperative hemorrhage volume were 630 min and 600 mL, respectively. Omentectomy was performed in 32 cases of primary ovarian cancer and 24 cases of recurrence. The median peritoneal cancer index was 16. The risk factors for delayed gastric emptying from the univariate analysis were body mass index < 23 kg/m2 (X 2 = 5.059, P = 0.025), history of pelvic surgery (X 2 = 4.498, P = 0.034), history of chemotherapy (X 2 = 4.334, P = 0.037), operation time ≥ 7 h (X 2 = 4.827, P = 0.047), and intraoperative hemorrhage ≥ 800 mL (X 2 = 7.112, P = 0.008). Multivariable analysis revealed that age ≥ 70 years (HR = 7.127; 95%CI 1.122-45.264; P = 0.037) and intraoperative hemorrhage ≥ 800 mL (HR = 3.416; 95%CI 1.067-10.939; P = 0.039) were independently associated with postoperative delayed gastric emptying after CRS-HIPEC. CONCLUSION: Postoperative gastrointestinal management, including prolonged nasogastric intubation, should be promoted for patients over 70 years or those with intraoperative bleeding exceeding 800 mL.
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Based on the rice-vegetable crop rotation model, in-situ measurements of nitrous oxide (N2O) and methane (CH4) emissions were conducted in double-cropping rice fields in Hainan to determine the impact of coconut chaff biochar on greenhouse gas emissions. The experiment involved four treatments:conventional farming fertilization (CON), nitrogen fertilizer combined with 20 t ·hm-2 biochar (B1), nitrogen fertilizer combined with 40 t ·hm-2 biochar (B2), and no nitrogen fertilizer, as the control (CK). The N2O and CH4 emissions were measured using static chamber-gas chromatography during the two paddy seasons, and the global warming potential (GWP) and greenhouse gas intensity (GHGI) were also estimated. The results show that N2O emission dynamics during the early rice season are closely related to the mineral nitrogen content of the soil. The N2O is emitted at the rice seedling and tillering stages after fertilization. The cumulative N2O emission during the early rice season was 0.18-0.76 kg ·hm-2. Compared with the CON treatment, the biochar treatments reduced N2O by 18%-43%, and the B2 treatment resulted in a significant reduction. The addition of biochar may promote the reduction of N2O at the early rice seedling stage and increase N2O emissions by improving the soil NO3--N content at the early rice tillering stage. During the late rice season, N2O is emitted during the heading and maturity stages, and the cumulative N2O emission was 0.17-0.34 kg ·hm-2. The B1 treatment reduced emissions by 37%, and B2 increased emission by only 3%, which is not a significant difference. The peak of CH4 emissions from rice fields appeared in the late phase of the early rice season and prophase of the late rice season. The cumulative emission of CH4 in the early rice season was 3.11-14.87 kg ·hm-2. Compared with CON, the CK treatment increased emission by 39%. The biochar treatment may increase soil aeration and limit the ability of CH4 production in the early rice season, as B1 and B2 treatments reduced CH4 emissions by 28% and 71%. The cumulative CH4 emission in late rice season was 53.1-146.3 kg ·hm-2, and the emission dynamics were significantly positively correlated with NH4+-N content. CK and B1 treatments increased CH4 emissions by 52% and 99%, respectively compared with CON, and the B2 treatment significantly increased CH4 emissions by 176%. Compared with CON, the B1 and B2 treatments increased the yield by 12.0% and 14.3% when applied in the early rice season and by 7.6% and 0.4% when applied in the late rice season, respectively. Due to the increased methane emissions in the late rice season, biochar amendment increased the GWP of the double-cropping rice field, in which the high amount of biochar reached a significant level; different amounts of biochar had no significant effect on the GHGI of the double-cropping rice field. Thus, the application of coconut chaff biochar for the reduction of greenhouse gas emission, from rice fields in hot areas, requires further research.
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Óxido Nitroso , Oryza , Agricultura , Carbón Orgánico , China , Cocos , Fertilizantes/análisis , Metano/análisis , Óxido Nitroso/análisis , SueloRESUMEN
Alternating dry and wet conditions affect the main processes of N2O production, such as nitrification and denitrification. Such conditions are very common in tropical rice-growing areas, such as Hainan. As a type of soil amendment, biochar is widely used to improve physical and chemical properties of soil and to reduce soil greenhouse gas emissions. However, there is a lack of existing in-depth research on the emission reductions of biochar when used in tropical soils that undergo frequently alternating dry and wet conditions. In this experiment, typical paddy soil from northern Hainan was used as the test soil, and corn stalk biochar, carbonized under anaerobic conditions at 400â, was used as the test biochar. This experiment explored the effects of adding biochar on soil greenhouse gas emissions and microbial-related functional genes under different water management conditions. The experiment comprised a 30 d culture, kept in the dark at 25â, and a total of six treatments:alternating dry-wet conditions without adding biochar (AWD1), alternating dry-wet conditions with 2% biochar (AWD2), alternating dry-wet conditions with 4% biochar (AWD3), continuous flooding without adding biochar (CF1), continuous flooding with 2% biochar (CF2), and continuous flooding with 4% biochar (CF3). The results showed that:â the addition of biochar under different moisture conditions can reduce N2O emissions in acidic paddy soil (P<0.05, the same below), as the total N2O emissions with the AWD3 treatment were 0.43 mg ·kg-1, which indicates an approximate reduction of 68%, relative to the AWD1 treatment; â¡ Corn stalk biochar can significantly increase the soil pH under different water management conditions. Compared to the no-biochar treatment, the soil pH increased by 0.5 units on average after cultivation with the addition of biochar, and as the soil NH4+-N content increased, it led to a decrease in Eh. ⢠Corn stalk biochar significantly reduces the abundance of ammonia oxidizing bacteria and significantly increases the nosZ gene abundance. However, it decreases the ratio of (nirK+nirS)/nosZ, inhibits the nitrification process, and promotes the reduction of N2O in the denitrification process. Thereby, the addition of corn stalk biochar can reduce N2O emissions. These results show that alternating dry-wet conditions, combined with the addition of corn stalk biochar, are beneficial for reducing N2O emissions in paddy soil, which may have further application in the reduction of agricultural greenhouse gas emissions in northern Hainan.
Asunto(s)
Óxido Nitroso , Suelo , Carbón Orgánico , Óxido Nitroso/análisis , Microbiología del Suelo , Agua , Abastecimiento de AguaRESUMEN
Large-scale genetic screening has identified KMT5B (SUV420H1), which encodes a histone H4 K20 di- and tri-methyltransferase highly expressed in prefrontal cortex (PFC), as a top-ranking high-risk gene for autism. However, the biological function of KMT5B in the brain is poorly characterized, and how KMT5B deficiency is linked to autism remains largely unknown. Here we knocked down Kmt5b in PFC and examined behavioral and electrophysiological changes, as well as underlying molecular mechanisms. Mice with Kmt5b deficiency in PFC display social deficits, a core symptom of autism, without the alteration of other behaviors. Kmt5b deficiency also produces deficits in PFC glutamatergic synaptic transmission, which is accompanied by the reduced synaptic expression of glutamate receptor subunits and associated proteins. Kmt5b deficiency-induced reduction of H4K20me2 impairs 53BP1-mediated DNA repair, leading to the elevation of p53 expression and its target gene Ddit4 (Redd1), which is implicated in synaptic impairment. RNA-sequencing data indicate that Kmt5b deficiency results in the upregulation of genes enriched in cellular stress response and ubiquitin-dependent protein degradation. Collectively, this study has revealed the functional role of Kmt5b in the PFC, and suggests that Kmt5b deficiency could cause autistic phenotypes by inducing synaptic dysfunction and transcriptional aberration.