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1.
Rev Cardiovasc Med ; 25(8): 274, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39228477

RESUMEN

Background: The impact of cardiac arrest (CA) at admission on the prognosis of patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains a subject of debate. Methods: We conducted a retrospective study at West China Hospital from 2018 to 2021, enrolling 247 patients with AMI complicated by CS (AMI-CS). Patients were categorized into CA and non-CA groups based on their admission status. Univariate and multivariate Cox regression analyses were performed, with 30-day and 1-year mortality as the primary endpoints. Kaplan-Meier plots were constructed, and concordance (C)-indices of the Global Registry of Acute Coronary Event (GRACE) score, Intra-aortic Balloon Pump in Cardiogenic Shock (IABP-SHOCK) II score, and IABP-SHOCK II score with CA were calculated. Results: Among the enrolled patients, 39 experienced CA and received cardiopulmonary resuscitation at admission. The 30-day and 1-year mortality rates were 40.9% and 47.0%, respectively. Neither univariate nor multivariate Cox regression analyses identified CA as a significant risk factor for 30-day and 1-year mortality. In C-statistics, the GRACE score exhibited a moderate effect (C-indices were 0.69 and 0.67, respectively), while the IABP-SHOCK II score had a better predictive performance (C-indices were 0.79 and 0.76, respectively) for the 30-day and 1-year mortality. Furthermore, CA did not enhance the predictive value of the IABP-SHOCK II score for 30-day (p = 0.864) and 1-year mortality (p = 0.888). Conclusions: Cardiac arrest at admission did not influence the survival of patients with AMI-CS. Active resuscitation should be prioritized for patients with AMI-CS, regardless of the presence of cardiac arrest.

2.
Nanomedicine (Lond) ; : 1-15, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225143

RESUMEN

Aim: To assess mesenchymal stem cells (MSCs) as carriers for HIF-1α siRNA-loaded nanoparticles (NPs) for targeted therapy of experimental choroidal neovascularization (CNV).Materials & methods: A poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid NP was designed. The transfection efficacy of MSCs with the hybrid NPs was assessed. Mice were intravenously injected with MSCs after laser photocoagulation and CNV was assessed at 7 days post-injection.Results & conclusion: The transfection efficiency of hybrid NPs into MSCs was 72.7%. HIF-1α mRNA expression in 661w cells co-cultured with MSC-hybrid-siRNA NPs was significantly lower. Intravenous delivery of MSC-hybrid-siRNA NPs greatly reduced CNV area and length. Intravenous injection of MSC-hybrid-siRNA NPs achieved therapeutic efficacy in reducing CNV area. The MSC-mediated homing enabled targeted inhibition of ocular angiogenesis.


[Box: see text].

3.
IEEE Trans Biomed Eng ; PP2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39208051

RESUMEN

OBJECTIVE: The artificial pancreas (AP) has shown promising potential in achieving closed-loop glucose control for individuals with type 1 diabetes mellitus (T1DM). However, designing an effective control policy for the AP remains challenging due to the complex physiological processes, delayed insulin response, and inaccurate glucose measurements. While model predictive control (MPC) offers safety and stability through the dynamic model and safety constraints, it lacks individualization and is adversely affected by unannounced meals. Conversely, deep reinforcement learning (DRL) provides personalized and adaptive strategies but faces challenges with distribution shifts and substantial data requirements. METHODS: We propose a hybrid control policy for the artificial pancreas (HyCPAP) to address the above challenges. HyCPAP combines an MPC policy with an ensemble DRL policy, leveraging the strengths of both policies while compensating for their respective limitations. To facilitate faster deployment of AP systems in real-world settings, we further incorporate meta-learning techniques into HyCPAP, leveraging previous experience and patient-shared knowledge to enable fast adaptation to new patients with limited available data. RESULTS: We conduct extensive experiments using the FDA-accepted UVA/Padova T1DM simulator across three scenarios. Our approaches achieve the highest percentage of time spent in the desired euglycemic range and the lowest occurrences of hypoglycemia. CONCLUSION: The results clearly demonstrate the superiority of our methods for closed-loop glucose management in individuals with T1DM. SIGNIFICANCE: The study presents novel control policies for AP systems, affirming the great potential of proposed methods for efficient closed-loop glucose control.

4.
Surgery ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39181724

RESUMEN

BACKGROUND: A single metric does not sufficiently capture the multidimensional and complex perioperative nature of treatment for patients with gastric cancer. There is a newly developed composite indicator, called textbook outcome, that reflects the "ideal" surgical outcome. However, limited evidence exists for the long-term prognosis of textbook outcome in patients with gastric cancer. Thus, this study was aimed at assessing the association between textbook outcome and long-term oncologic prognosis after gastrectomy. METHODS: In total, 2,658 consecutive patients who underwent gastrectomy between January 2004 and December 2017 were included. The primary endpoint was 5-year conditional survival (if the patient survived the first 30 days after surgery). Textbook outcome was defined as retrieved ≥15 lymph nodes, pR0 resection, complete-potentially curative resection during operation, hospitalization ≤21 days, no reinterventions, no severe postoperative complications, no hospital readmission ≤30 days after discharge, no unplanned intensive care unit treatment, and no 30-day postoperative mortality. Multivariable analysis was performed to evaluate the adjusted predictors of textbook outcome. A Cox regression analysis was used to analyze the relationship between achieving textbook outcome parameters and long-term oncologic prognosis. RESULTS: A total of 1,770 (66.6%) of the 2,658 patients achieved all textbook outcome metrics in this study. The textbook outcome group displayed a greater 5-year conditional overall survival than the nontextbook outcome group (64.7% vs 40.2%, P < .001). The 5-year conditional disease-free survival of the patients with textbook outcomes was strongly superior to that of the patients without textbook outcomes (63.1% vs 37.6%, P < .001). Textbook outcome was independently associated with longer 5-year conditional overall survival and disease-free survival (hazard ratio 0.494 [0.439-0.557] and hazard ratio 0.487 [0.433-0.547], respectively). CONCLUSIONS: Attaining textbook outcome is strongly related to an improved long-term oncologic prognosis for patients with gastric cancer, underscoring the need for continued efforts to enhance surgical care quality.

5.
Cell ; 187(19): 5393-5412.e30, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39121857

RESUMEN

Negative psychological states impact immunity by altering the gut microbiome. However, the relationship between brain states and microbiome composition remains unclear. We show that Brunner's glands in the duodenum couple stress-sensitive brain circuits to bacterial homeostasis. Brunner's glands mediated the enrichment of gut Lactobacillus species in response to vagus nerve stimulation. Cell-specific ablation of the glands markedly suppressed Lactobacilli counts and heightened vulnerability to infection. In the forebrain, we mapped a vagally mediated, polysynaptic circuit connecting the central nucleus of the amygdala to Brunner's glands. Chronic stress suppressed central amygdala activity and phenocopied the effects of gland lesions. Conversely, excitation of either the central amygdala or parasympathetic vagal neurons activated Brunner's glands and reversed the effects of stress on the gut microbiome and immunity. The findings revealed a tractable brain-body mechanism linking psychological states to host defense.


Asunto(s)
Duodeno , Microbioma Gastrointestinal , Estrés Psicológico , Nervio Vago , Animales , Ratones , Duodeno/microbiología , Nervio Vago/fisiología , Masculino , Ratones Endogámicos C57BL , Amígdala del Cerebelo/fisiología , Lactobacillus/fisiología , Neuronas/metabolismo
6.
Bioresour Bioprocess ; 11(1): 66, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980516

RESUMEN

Earthworm cultivation can effectively promote the resource utilization of agricultural waste. The efficient utilization of agricultural waste by earthworms mainly depends on the microbial communities in the guts. This study used silkworm excrement and cow manure as substrates for earthworm cultivation and investigated the associated bacterial communities during earthworms' growth. The survival rate of earthworms remained above 89% after 21 days of feeding with the two substrates. Proteobacteria, Actinobacteria, and Firmicutes constituted the predominant bacterial communities in earthworm growth, accounting for over 81% of the relative abundance in both guts and vermicompost. The bacteria richness and diversity in the foregut and midgut of earthworm were lower than those in the hindgut. The prediction function of intestinal bacterial communities of earthworms cultured with two substrates mainly involved biosynthesis, decomposition and energy production.

7.
Comput Struct Biotechnol J ; 23: 2746-2753, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39050785

RESUMEN

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

8.
Int J Biol Macromol ; 276(Pt 1): 133873, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39013505

RESUMEN

In this study, based on the self-assembly strategy, we fused CipA with carbonyl reductase LXCARS154Y derived from Leifsonia xyli by gene coding, and successfully performed the carrier-free immobilization of LXCARS154Y. The immobilized enzyme was then characterized using scanning electron microscope (SEM), dynamic light scattering (DLS) and fourier transform infrared spectroscopy (FTIR). Compared with the free enzyme, the immobilized LXCARS154Y exhibited a 2.3-fold improvement in the catalytic efficiency kcat/km for the synthesis of a chiral pharmaceutical intermediate (R)-3,5-bis(trifluoromethyl)phenyl ethanol ((R)-BTPE) by reducing 3,5-bis(trifluoromethyl)acetophenone (BTAP). Moreover, the immobilized enzyme showed the enhanced stability while maintaining over 61 % relative activity after 18 cycles of batch reaction. Further, when CipA-fused carbonyl reductase was employed for (R)-BTPE production in a continuous flow reaction, almost complete yield (97.0 %) was achieved within 7 h at 2 M (512.3 g/L) of BTAP concentration, with a space-time yield of 1717.1 g·L-1·d-1. Notably, we observed the retention of cofactor NADH by CipA-based enzyme aggregates, resulting in a higher total turnover number (TTN) of 4815 to facilitate this bioreductive process. This research developed a concise strategy for efficient preparation of chiral intermediate with cofactor self-sufficiency via continuous flow biocatalysis, and the relevant mechanism was also explored.


Asunto(s)
Oxidorreductasas de Alcohol , Enzimas Inmovilizadas , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Oxidorreductasas de Alcohol/química , Oxidorreductasas de Alcohol/metabolismo , Oxidorreductasas de Alcohol/genética , Reactores Biológicos , Cinética , Alcoholes/química , Biocatálisis , Coenzimas/química , Coenzimas/metabolismo , Estereoisomerismo
9.
Int Immunopharmacol ; 139: 112602, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39033660

RESUMEN

Chronic pain has emerged as a significant public health issue, seriously affecting patients' quality of life and psychological well-being, with a lack of effective pharmacological treatments. Numerous studies have indicated that macrophages play a crucial role in inflammatory pain, and targeting neuro-immune interactions for drug development may represent a promising direction for pain management. Chilobrachys jingzhao (C. jingzhao) is used as a folk medicine of the Li nationality with the efficacy of eliminating swelling, detoxicating, and relieving pain, and the related products are widely used in the market. However, the chemical constituents of C. jingzhao have not been reported, and the pharmacodynamic substance and the precise functional mechanism are unrevealed. Here we isolated a cyclic dipeptide, cyclo(L-Pro-L-Trp) (CPT) from C. jingzhao for the first time. CPT remarkably alleviated formalin-induced inflammatory pain and significantly inhibited inflammatory responses. In vivo, CPT attenuated neutrophil infiltration and plantar tissue edema and suppressed the mRNA expression of pro-inflammatory molecules. In vitro, CPT suppressed inflammation triggered by lipopolysaccharide (LPS) in both RAW 264.7 and iBMDM cells, reducing expressions of inducible nitric oxide synthase (iNOS), superoxide, and pro-inflammatory molecules. A mechanistic study revealed that CPT exerted an anti-inflammatory activity by blocking the mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, as well as alleviating the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). Our results elucidated the pharmacodynamic material basis of C. jingzhao, and CPT can be a promising lead for alleviating inflammation and inflammatory pain.


Asunto(s)
Antiinflamatorios , Formaldehído , Inflamación , FN-kappa B , Transducción de Señal , Factor 6 Asociado a Receptor de TNF , Animales , FN-kappa B/metabolismo , Ratones , Factor 6 Asociado a Receptor de TNF/metabolismo , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Masculino , Transducción de Señal/efectos de los fármacos , Inflamación/tratamiento farmacológico , Células RAW 264.7 , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/uso terapéutico , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Analgésicos/uso terapéutico , Analgésicos/farmacología , Humanos , Edema/tratamiento farmacológico , Edema/inducido químicamente , Edema/inmunología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología
10.
Acta Pharmacol Sin ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030309

RESUMEN

Recombinant human type 5 adenovirus (H101) is an oncolytic virus used to treat nasopharyngeal carcinoma. Owing to the deletion of the E1B-55kD and E3 regions, H101 is believed to selectively inhibit nasopharyngeal carcinoma. Whether H101 inhibits other type of tumors via different mechanisms remains unclear. In this study we investigated the effects of H101 on melanomas. We established B16F10 melanoma xenograft mouse model, and treated the mice with H101 (1 × 108 TCID50) via intratumoral injection for five consecutive days. We found that H101 treatment significantly inhibited B16F10 melanoma growth in the mice. H101 treatment significantly increased the infiltration of CD8+ T cells and reduced the proportion of M2-type macrophages. We demonstrated that H101 exhibited low cytotoxicity against B16F10 cells, but the endothelial cells were more sensitive to H101 treatment. H101 induced endothelial cell pyroptosis in a caspase-1/GSDMD-dependent manner. Furthermore, we showed that the combination of H101 with the immune checkpoint inhibitor PD-L1 antibody (10 mg/kg, i.p., every three days for three times) exerted synergic suppression on B16F10 tumor growth in the mice. This study demonstrates that, in addition to oncolysis, H101 inhibits melanoma growth by promoting anti-tumor immunity and inducing pyroptosis of vascular endothelial cells.

11.
Environ Res ; 261: 119530, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39004391

RESUMEN

With stringent regulations of internal combustion engine on reducing CO2 emission, ammonia has been used as an alternative fuel. Investigating how engine-related performance is affected by partial ammonia replacement of diesel fuel is essential for understanding the combustion. Therefore, in this study, a three-dimensional numerical simulation model is developed for the burning of two fuels of diesel and ammonia based on relevant parameters (i.e., compression ratio, load, ammonia energy fraction, etc.) in a lab-made diesel engine. The consequences of load and compression proportion on combustion and pollutant emissions are investigated for ammonia energy fractions between 50% and 90%. When the ammonia portion rises, the increased ammonia equivalent ratio causes ammonia to move away from the dilute combustion boundary and accelerates the combustion rate of ammonia. An increase in compression ratio significantly increases the specified thermal performance and combustion efficacy. When the compression ratio is 16, as the ammonia energy fractions increases, due to the increase in the proportion of ammonia, that is, the proportion of nitrogen atoms increases, more NOx is generated during the combustion process. When the ammonia substitution rate is 90%, as the compression ratio increases, the cylinder pressure and temperature increase. The combustion efficiency of ammonia increases, generating more NOx and NOx emissions can reach 0.66 mg/m3. At a compression ratio of 18, the NOx emissions can reach 1.59 mg/m3. However, under medium and low load conditions, as the ammonia fraction increases, the total energy of fuel decreases, and the combustion efficiency of ammonia decreases, resulting in a decrease in the heat released during combustion and a decrease in NOx emissions. When the ammonia substitution rate is 90% and the load is 25%, NOx emissions reach 0.1 mg/m3. This research provides theoretical suggestions for the profitable and use ammonia fuel in internal combustion engines in a clean manner.


Asunto(s)
Contaminantes Atmosféricos , Amoníaco , Gasolina , Óxidos de Nitrógeno , Emisiones de Vehículos , Amoníaco/análisis , Gasolina/análisis , Óxidos de Nitrógeno/análisis , Contaminantes Atmosféricos/análisis , Emisiones de Vehículos/análisis
12.
Nat Commun ; 15(1): 6288, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060236

RESUMEN

Host defense peptide (HDP)-mimicking polymers are promising therapeutic alternatives to antibiotics and have large-scale untapped potential. Artificial intelligence (AI) exhibits promising performance on large-scale chemical-content design, however, existing AI methods face difficulties on scarcity data in each family of HDP-mimicking polymers (<102), much smaller than public polymer datasets (>105), and multi-constraints on properties and structures when exploring high-dimensional polymer space. Herein, we develop a universal AI-guided few-shot inverse design framework by designing multi-modal representations to enrich polymer information for predictions and creating a graph grammar distillation for chemical space restriction to improve the efficiency of multi-constrained polymer generation with reinforcement learning. Exampled with HDP-mimicking ß-amino acid polymers, we successfully simulate predictions of over 105 polymers and identify 83 optimal polymers. Furthermore, we synthesize an optimal polymer DM0.8iPen0.2 and find that this polymer exhibits broad-spectrum and potent antibacterial activity against multiple clinically isolated antibiotic-resistant pathogens, validating the effectiveness of AI-guided design strategy.


Asunto(s)
Antibacterianos , Inteligencia Artificial , Polímeros , Polímeros/química , Polímeros/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Bacterias/efectos de los fármacos , Diseño de Fármacos
13.
Mol Genet Genomic Med ; 12(6): e2481, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38867642

RESUMEN

PURPOSE: To characterize the phenotype and genotype of a Chinese family with autosomal-dominant retinitis pigmentosa (RP) accompanied by iris coloboma. METHODS: The proband, a 34-year-old male, was examined with his family by using fundus photography, optical coherence tomography (OCT), autofluorescence, and full-field electroretinography (ffERG). Genetic analyses were conducted through whole-exome sequencing (WES) to screen for variations. RESULTS: Three members of this Chinese family were shown to be bilateral iris coloboma. The male proband and his mother exhibited typical RP feature. The proband's late grandfather had been documented manifestation of iris coloboma. The mode of inheritance was confirmed to be autosomal dominance. Through linkage analysis and WES, a heterozygous variation in the miR-204 gene (n.37C>T), a noncoding RNA gene, was identified in these three members. CONCLUSIONS: In this third independent and the first Asian family, the existence of a miR-204 variant associated with RP accompanied by iris coloboma was confirmed. Our findings reinforce the significance of miR-204 as an important factor influencing visual function in the retina. When phenotypes like RP accompanied by iris coloboma in an autosomal-dominant pattern, including in Chinese patients, miR-204 aberrations should be considered.


Asunto(s)
Coloboma , MicroARNs , Linaje , Retinitis Pigmentosa , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Coloboma/genética , Coloboma/patología , Pueblos del Este de Asia , Iris/anomalías , Iris/patología , MicroARNs/genética , Fenotipo , Retinitis Pigmentosa/genética
14.
bioRxiv ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38853855

RESUMEN

Psychological states can regulate intestinal mucosal immunity by altering the gut microbiome. However, the link between the brain and microbiome composition remains elusive. We show that Brunner's glands in the duodenal submucosa couple brain activity to intestinal bacterial homeostasis. Brunner's glands mediated the enrichment of gut probiotic species in response to stimulation of abdominal vagal fibers. Cell-specific ablation of the glands triggered transmissible dysbiosis associated with an immunodeficiency syndrome that led to mortality upon gut infection with pathogens. The syndrome could be largely prevented by oral or intra-intestinal administration of probiotics. In the forebrain, we identified a vagally-mediated, polysynaptic circuit connecting the glands of Brunner to the central nucleus of the amygdala. Intra-vital imaging revealed that excitation of central amygdala neurons activated Brunner's glands and promoted the growth of probiotic populations. Our findings unveil a vagal-glandular neuroimmune circuitry that may be targeted for the modulation of the gut microbiome. The glands of Brunner may be the critical cells that regulate the levels of Lactobacilli species in the intestine.

15.
EMBO Rep ; 25(7): 3040-3063, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38849673

RESUMEN

Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney causes ciliary elongation and cystogenesis, and cell-based proximity labeling proteomics and fluorescence microscopy show alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20, and polycystin-2 (PC2) are reduced in the cilia of DLG1-deficient cells compared to control cells. This phenotype is recapitulated in vivo and rescuable by re-expression of wild-type DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggest that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.


Asunto(s)
Proteínas Portadoras , Cilios , Homólogo 1 de la Proteína Discs Large , Canales Catiónicos TRPP , Animales , Cilios/metabolismo , Canales Catiónicos TRPP/metabolismo , Canales Catiónicos TRPP/genética , Ratones , Homólogo 1 de la Proteína Discs Large/metabolismo , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Humanos , Transporte de Proteínas , Ratones Noqueados , Riñón/metabolismo , Células Epiteliales/metabolismo , Unión Proteica , Reflujo Vesicoureteral/metabolismo , Reflujo Vesicoureteral/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Anomalías Urogenitales
16.
Surg Endosc ; 38(8): 4476-4484, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38902410

RESUMEN

BACKGROUND: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer. METHODS: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691). CONCLUSION: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery.


Asunto(s)
Gastrectomía , Laparoscopía , Tempo Operativo , Puntaje de Propensión , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Gastrectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Laparoscopía/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Estudios de Factibilidad , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
17.
Elife ; 122024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38921957

RESUMEN

Accurate prediction of the structurally diverse complementarity determining region heavy chain 3 (CDR-H3) loop structure remains a primary and long-standing challenge for antibody modeling. Here, we present the H3-OPT toolkit for predicting the 3D structures of monoclonal antibodies and nanobodies. H3-OPT combines the strengths of AlphaFold2 with a pre-trained protein language model and provides a 2.24 Å average RMSDCα between predicted and experimentally determined CDR-H3 loops, thus outperforming other current computational methods in our non-redundant high-quality dataset. The model was validated by experimentally solving three structures of anti-VEGF nanobodies predicted by H3-OPT. We examined the potential applications of H3-OPT through analyzing antibody surface properties and antibody-antigen interactions. This structural prediction tool can be used to optimize antibody-antigen binding and engineer therapeutic antibodies with biophysical properties for specialized drug administration route.


Asunto(s)
Regiones Determinantes de Complementariedad , Aprendizaje Profundo , Regiones Determinantes de Complementariedad/química , Regiones Determinantes de Complementariedad/inmunología , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Modelos Moleculares , Conformación Proteica , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/inmunología , Humanos
18.
J Clin Immunol ; 44(7): 155, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38922539

RESUMEN

PURPOSE: Moesin (MSN) deficiency is a recently reported combined immunodeficiency, and few cases have been reported to date. We describe a Chinese patient with a novel mutation causing MSN deficiency and a novel phenotype. METHODS: Clinical and immunological data were collected. Whole-exome sequencing was performed to identify gene mutations. MSN protein expression and T cell proliferation and activation were determined by flow cytometry. Cell migration was confirmed with a Transwell assay. Autoantibody levels were analyzed using antigen microarrays. RESULTS: The patient was a 10-year-old boy who presented with recurrent fever, oral ulcers and dermatomyositis-like symptoms, such as periorbital edema, facial swelling, elevated creatine kinase levels, and abnormal electromyography and muscle biopsy results. Epstein-Barr virus (EBV) DNA was detected in the serum, cells and tissues of this patient. He further developed nasal-type NK/T-cell lymphoma. A novel hemizygous mutation (c.68 A > G, p.N23S) in the MSN gene was found. The immunological phenotype of this patient included persistent decreases in T and B lymphocyte counts but normal immunoglobulin IgG levels. The patient had attenuated MSN protein expression and impaired T-cell proliferation and migration. The proportions of Tfh cells and CD21low B cells in the patient were higher than those in the controls. Moreover, 82 IgG and 102 IgM autoantibodies were more abundant in the patient than in the healthy controls. CONCLUSIONS: The novel mutation N23S is pathogenic and leads to a severe clinical phenotype. EBV infection, tumor, and dermatomyositis-like autoimmune symptoms may be associated with MSN deficiency, further expanding the understanding of the disease.


Asunto(s)
Dermatomiositis , Infecciones por Virus de Epstein-Barr , Proteínas de Microfilamentos , Mutación , Humanos , Masculino , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Dermatomiositis/genética , Dermatomiositis/diagnóstico , Dermatomiositis/inmunología , Niño , Proteínas de Microfilamentos/genética , Mutación/genética , Herpesvirus Humano 4 , Secuenciación del Exoma , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/diagnóstico , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Fenotipo , Linfocitos T/inmunología
19.
Nat Commun ; 15(1): 4493, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802342

RESUMEN

Abscisic acid (ABA) plays a crucial role in promoting plant stress resistance and seed dormancy. However, how ABA regulates rice quality remains unclear. This study identifies a key transcription factor SLR1-like2 (SLRL2), which mediates the ABA-regulated amylose content (AC) of rice. Mechanistically, SLRL2 interacts with NF-YB1 to co-regulate Wx, a determinant of AC and rice quality. In contrast to SLR1, SLRL2 is ABA inducible but insensitive to GA. In addition, SLRL2 exhibits DNA-binding activity and directly regulates the expression of Wx, bHLH144 and MFT2. SLRL2 competes with NF-YC12 for interaction with NF-YB1. NF-YB1 also directly represses SLRL2 transcription. Genetic validation supports that SLRL2 functions downstream of NF-YB1 and bHLH144 in regulating rice AC. Thus, an NF-YB1-SLRL2-bHLH144 regulatory module is successfully revealed. Furthermore, SLRL2 regulates rice dormancy by modulating the expression of MFT2. In conclusion, this study revealed an ABA-responsive regulatory cascade that functions in both rice quality and seed dormancy.


Asunto(s)
Ácido Abscísico , Regulación de la Expresión Génica de las Plantas , Oryza , Latencia en las Plantas , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Ácido Abscísico/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Latencia en las Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Factor de Unión a CCAAT/metabolismo , Factor de Unión a CCAAT/genética , Semillas/metabolismo , Semillas/crecimiento & desarrollo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Amilosa/metabolismo , Grano Comestible/metabolismo , Grano Comestible/genética , Plantas Modificadas Genéticamente
20.
Heliyon ; 10(10): e31062, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38803894

RESUMEN

Common complications following laparoscopic appendectomy include wound infection, bleeding, intra-abdominal abscess, small bowel obstruction, stump leakage, and stump appendicitis. Here, we presented a case reporting detailing a rare complication following laparoscopic appendectomy: the development of a metastatic neck abscess induced by Klebsiella pneumoniae(K. pneumoniae). A 49-year-old male underwent emergency laparoscopic surgery with prophylactic antibiotic administration for acute appendicitis. Subsequently, he experienced persistent neck pain and fever postoperatively, prompting further investigation. Pus and blood cultures revealed K. pneumoniae, with magnetic resonance imaging confirming the presence of a neck abscess. Antibiotic therapy was adjusted, and surgical drainage of the abscess was performed after multidisciplinary consultation. The patient was discharged without complications. While rare, metastatic abscesses following appendectomy warrant consideration, particularly in K. pneumoniae infections. Comprehensive clinical assessment, imaging, and laboratory evaluation are crucial for timely diagnosis and management of such complications.

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