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BACKGROUND: Uniportal thoracoscopic lateral basal segmentectomy is the most technically challenging anatomic segmentectomy,1-3 especially when it involves combined subsegmentectomy or sub-subsegmentectomy. Therefore, there are very few reports detailing its technical aspect. PATIENT AND METHOD: In this multimedia article, we describe a very complex uniportal thoracoscopic combined seg-sub-subsegmentectomy of RS9+10bii through the oblique fissure approach and the inferior pulmonary ligament approach, following a single-direction strategy4,5 to advance the procedure, utilizing the stem-branch method3,6 for segmental/subsegmental/sub-subsegmental structure tracking, and employing dual-display method, which comprises the intravenous ICG injection method and the inflation/deflation method, to identify intersegmental and inter-seg-sub-subsegmental planes. RESULTS: The operation lasted 169 min, with approximately 20 mL of blood loss. The patient experienced an active hemothorax and two spontaneous pneumothoraxes on postoperative days 1, 4, and 19, respectively, all of which resolved promptly after treatment. Histopathological examination of the specimen documented invasive non-mucinous adenocarcinoma with negative surgical margins and lymph nodes. The staging was determined as pT1bN0M0, stage IA2. During the 14-month follow-up period, there were no signs of tumor recurrence or metastasis observed. The FVC, FEV1, and FEV1%pred decreased by 11.9%, 12.5%, and 12.8%, respectively, at postoperative month 6. CONCLUSIONS: Complex basal segmentectomies, which necessitate combined subsegmental or sub-subsegmental resections, such as RS9+10bii, are feasible using the dual-display and combined approaches method. This method simplifies the steps of the very complex combined subsegmentectomy, averting the need for extensive lung resection. In addition, when performing these combined segmentectomies, precise anatomical dissection is crucial to prevent complications such as minor bronchopleural fistulas.
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PURPOSE: Toludesvenlafaxine is a recently developed antidepressant that belongs to the triple reuptake inhibitor class. Despite the in vitro evidence that toludesvenlafaxine inhibits the reuptake of serotonin (5-HT), norepinephrine (NE) and dopamine (DA), there is no in vivo evidence that toludesvenlafaxine binds to DAT and increases DA level, a mechanism thought to contribute to its favorable clinical performance. METHODS: Positron emission tomography/computed tomography (PET/CT) was used to examine the DAT binding capacity in healthy rats and human subjects and microdialysis was used to examine the striatal DA level in rats. [18F]FECNT and [11C]CFT were used as PET/CT radioactive tracer for rat and human studies, respectively. RESULTS: In rats, 9 mg/kg of toludesvenlafaxine hydrochloride (i.v.) followed by an infusion of 3 mg/kg via minipump led to the binding rate to striatum DAT at 3.7 - 32.41% and to hypothalamus DAT at 5.91 - 17.52% during the 45 min scanning period. 32 mg/kg oral administration with toludesvenlafaxine hydrochloride significantly increased the striatal DA level with the AUC0 - 180 min increased by 63.9%. In healthy volunteers, 160 mg daily toludesvenlafaxine hydrochloride sustained-release tablets for 4 days led to an average occupancy rates of DAT at 8.04% ± 7.75% and 8.09% ± 7.00%, respectively, in basal ganglion 6 h and 10 h postdose. CONCLUSION: These results represent the first to confirm the binding of toludesvenlafaxine to DAT in both rats and humans using PET/CT, and its elevation of brain DA level, which may help understand the unique pharmacological and functional effects of triple reuptake inhibitors such as toludesvenlafaxine. GOV IDENTIFIERS: NCT05905120. Registered 14 June 2023. (retrospectively registered).
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Succinato de Desvenlafaxina , Proteínas da Membrana Plasmática de Transporte de Dopamina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Ratos , Humanos , Animais , Masculino , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Adulto , Ligação Proteica , Ratos Sprague-Dawley , Feminino , Dopamina/metabolismoRESUMO
The novel heptanuclear cadmium borovanadate [Cd(en)3]{[Cd(H2O)(en)]6[B20V12O60(OH)2]}·8H2O (en = ethylenediamine) has been prepared under hydrothermal condition. It exhibits a 2D layered architecture that is built up from the [Cd(H2O)(en)]2+ coordination cations and new sandwich-type borovanadate anions [B20V12O60(OH)2]14- constructed by BO3, BO4, BO3(OH), and VO5 units. It features the first heptanuclear cadmium borovanadate containing the single valence of V4+ cations and unique B/V ratio (B/V = 20/12). Its thermal, magnetic, XPS, and optical properties have been systematically studied. The Eg (2.60 eV), EVB (1.69 eV), and ECB (-0.91 eV) were well determined by the UV-vis diffuse reflectance spectrum, UPS curve, and the formula ECB = EVB - Eg, respectively. The photocatalytic experiments revealed that the borovanadate could be selected as an effective and stable heterogeneous catalyst for the reduction of CO2 to CH4 by means of visible light (the amount for CH4 gas could reach 50.57 µmol·g-1·h-1 when the reaction time was 3 h). The recycling experiment and photocatalytic mechanism were also well investigated and established in detail.
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BACKGROUND: Most stroke patients suffer from an imbalance in blood supply, which causes severe brain damage leading to functional deficits in motor, sensory, swallowing, cognitive, emotional, and speech functions. Repetitive transcranial magnetic stimulation (rTMS) is thought to restore functions impaired during the stroke process and improve the quality of life of stroke patients. However, the efficacy of rTMS in treating post-stroke function impairment varies significantly. Therefore, we conducted a meta-analysis of the number of patients with effective rTMS in treating post-stroke dysfunction. METHODS: The PubMed, Embase, and Cochrane Library databases were searched. Screening and full-text review were performed by three investigators. Single-group rate meta-analysis was performed on the extracted data using a random variable model. Then subgroup analyses were performed at the levels of stroke acuity (acute, chronic, or subacute); post-stroke symptoms (including upper and lower limb motor function, dysphagia, depression, aphasia); rTMS stimulation site (affected side, unaffected side); and whether or not it was a combination therapy. RESULTS: We obtained 8955 search records, and finally 33 studies (2682 patients) were included in the meta-analysis. The overall analysis found that effective strength (ES) of rTMS was 0.53. In addition, we found that the ES of rTMS from acute/subacute/chronic post-stroke was 0.69, 0.45, and 0.52. We also found that the ES of rTMS using high-frequency stimulation was 0.56, while the ES of rTMS using low-frequency stimulation was 0.53. From post-stroke symptoms, we found that the ES of rTMS in sensory aspects, upper limb functional aspects, swallowing function, and aphasia was 0.50, 0.52, 0.51, and 0.54. And from the site of rTMS stimulation, we found that the ES of rTMS applied to the affected side was 0.51, while the ES applied to the unaffected side was 0.54. What's more, we found that the ES of rTMS applied alone was 0.53, while the ES of rTMS applied in conjunction with other therapeutic modalities was 0.53. CONCLUSIONS: By comparing the results of the data, we recommend rTMS as a treatment option for rehabilitation of functional impairment in patients after stroke. We also recommend that rehabilitation physicians or clinicians use combination therapy as one of the options for patients.
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Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral/métodosRESUMO
BACKGROUND: Eye examinations and eyeglasses acquisition are typically integrated into a cohesive procedure in China. We conducted a randomized controlled trial using incognito standardized patient (SP) approach to evaluate the impact of separating eyeglasses sales on the accuracy of final prescription. METHODS: 52 SPs were trained to provide standardized responses during eye examinations, and undergoing refraction by a senior ophthalmologist at a national-level clinical center. SPs subsequently received eye examinations at 226 private optical shops and public hospitals in Shaanxi, northwestern China. The visits were randomly assigned to either control group, where SPs would typically purchase eyeglasses after refraction, or treatment group, where SPs made an advance declaration not to purchase eyeglasses prior to refraction. The dioptric difference between the final prescriptions provided by local refractionists and expert in the better-seeing eye was determined using the Vector Diopteric Distance method, and the completeness of exams was assessed against national standards. Multiple regressions were conducted to estimate the impact of no eyeglasses sales on the accuracy of the final prescription of local refractionists, as well as the completeness of examinations. RESULTS: Among 226 eye exams (73 in public hospitals, 153 in private optical shops), 133 (58.8%) were randomized to control group and 93 (41.2%) to no eyeglasses sales group. The inaccuracy rate of final prescriptions provided by local refractionists (≥ 1.0 D, experts' final prescription as the reference) was 25.6% in control group, while 36.6% in no-sale group (P = 0.077). The likelihood of providing inaccurate final prescriptions was significantly higher in no-sale group compared to control group (OR = 1.607; 95% CI: 1.030 to 2.508; P = 0.037). This was particularly evident in private optical shops (OR = 2.433; 95% CI: 1.386 to 4.309; P = 0.002). In terms of process quality, the no-sale group performed significantly less subjective refraction (OR = 0.488; 95% CI: 0.253 to 0.940; P = 0.032) and less testing SP's own eyeglasses (OR = 0.424; 95% CI: 0.201 to 0.897; P = 0.025). The duration of eye exams was 3.917 min shorter (95% CI: -6.798 to -1.036; P = 0.008) in no-sale group. CONCLUSIONS: Separating eyeglasses sales from optical care could lead to worse quality of eye care. Policy makers should carefully consider the role of economic incentives in healthcare reform.
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Erros de Refração , Humanos , Erros de Refração/diagnóstico , Erros de Refração/terapia , Acuidade Visual , Óculos , Refração Ocular , ChinaRESUMO
The world is currently facing urgent climate and environmental issues, such as global warming, ecosystem collapse, and energy shortages. In this context, this study selected data from 2000 to 2021 and employed the Method of Moment Quantile Regression (MMQR) to thoroughly investigate the impact of renewable energy consumption, economic complexity, and geopolitical risks on the ecological footprint of the Group of Twenty (G20) countries. The results indicate that in countries with lower quantiles, renewable energy consumption significantly reduces the ecological footprint, whereas its effect is not prominent in countries with higher quantiles. Economic complexity has a negative impact on the ecological footprint, and this impact becomes stronger as the quantile of the ecological footprint rises. Additionally, economic complexity moderates the effect of renewable energy on the ecological footprint. Geopolitical risks facilitate the growth of the ecological footprint. Likewise, robustness tests such as DOLS, FMOLS, and quantile regression confirm these estimates in the same framework. This study has conducted a profound analysis of global environmental issues, offering innovative perspectives and recommendations for achieving goals related to sustainable energy utilization, mitigating climate change, and improving the ecological environment. The findings of this research will guide policymakers in G20 countries to adopt more effective environmental protection measures, thereby contributing to the construction of a sustainable future.
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Ecossistema , Resiliência Psicológica , Desenvolvimento Econômico , Dióxido de Carbono , Energia RenovávelRESUMO
Optimization and control of wastewater treatment process (WTP) can contribute to cost reduction and efficiency. A wastewater treatment process multi-objective optimization (WTPMO) framework is proposed in this paper to provide suggestions for decision-making in setting parameters of WTP. Firstly, the prediction models based on Extreme Gradient Boosting (XGB) with Bayesian optimization (BO) are developed for predicting effluent water quality (EQ) and energy consumption (EC) for different influent quality and process parameter settings. Then, the SHapley Additive exPlanations (SHAP) algorithm is used to complement the interpretability of machine learning to quantitatively evaluate the impact of different features on the predicted targets. Finally, the Non-dominated Sorting Genetic Algorithm II (NSGA-II) with the Technique for Ordering Preferences on Similarity of Ideal Solutions (TOPSIS) is introduced to solve and make decisions on the multi-objective optimization problem. The WTPMO applicability is validated on Benchmark Simulation Model 1 (BSM1). The results show that BOXGB achieves accurate prediction for EQ and EC with R2 values of 0.923 and 0.965, respectively, indicating that BO can effectively select the model hyperparameters in XGB. Based on SHAP supplemented the interpretability of the model to fully explain how the influent water quality and decision variables affect the EQ and EC of the WTP. In addition, the optimized process parameters are determined based on NSGA-II and TOPSIS, and the EC optimization rate is 1.552% while guaranteeing water quality compliance. Overall, this research can effectively achieve the optimization of WTP, ensure that the effluent water quality meets the standards while reducing energy consumption, assist Wastewater treatment plants (WWTPs) to achieve more intelligent and efficient operation and maintenance management, and provide strong support for environmental protection and sustainable development goals.
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Algoritmos , Teorema de Bayes , Aprendizado de Máquina , Eliminação de Resíduos Líquidos , Águas Residuárias , Qualidade da Água , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Modelos TeóricosRESUMO
Accurate air quality index (AQI) prediction is essential in environmental monitoring and management. Given that previous studies neglect the importance of uncertainty estimation and the necessity of constraining the output during prediction, we proposed a new hybrid model, namely TMSSICX, to forecast the AQI of multiple cities. Firstly, time-varying filtered based empirical mode decomposition (TVFEMD) was adopted to decompose the AQI sequence into multiple internal mode functions (IMF) components. Secondly, multi-scale fuzzy entropy (MFE) was applied to evaluate the complexity of each IMF component and clustered them into high and low-frequency portions. In addition, the high-frequency portion was secondarily decomposed by successive variational mode decomposition (SVMD) to reduce volatility. Then, six air pollutant concentrations, namely CO, SO2, PM2.5, PM10, O3, and NO2, were used as inputs. The secondary decomposition and preliminary portion were employed as the outputs for the bidirectional long short-term memory network optimized by the snake optimization algorithm (SOABiLSTM) and improved Catboost (ICatboost), respectively. Furthermore, extreme gradient boosting (XGBoost) was applied to ensemble each predicted sub-model to acquire the consequence. Ultimately, we introduced adaptive kernel density estimation (AKDE) for interval estimation. The empirical outcome indicated the TMSSICX model achieved the best performance among the other 23 models across all datasets. Moreover, implementing the XGBoost to ensemble each predicted sub-model led to an 8.73%, 8.94%, and 0.19% reduction in RMSE, compared to SVM. Additionally, by utilizing SHapley Additive exPlanations (SHAP) to assess the impact of the six pollutant concentrations on AQI, the results reveal that PM2.5 and PM10 had the most notable positive effects on the long-term trend of AQI. We hope this model can provide guidance for air quality management.
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Poluentes Atmosféricos , Poluição do Ar , Inteligência Artificial , Incerteza , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Material Particulado/análiseRESUMO
Background: Eosinophilic esophagitis (EoE) is a complex allergic condition frequently accompanied by various atopic comorbidities in children, which significantly affects their life qualities. Therefore, this study aimed to evaluate pivotal molecular markers that may facilitate the diagnosis of EoE in pediatric patients. Methods: Three available EoE-associated gene expression datasets in children: GSE184182, GSE 197702, GSE55794, along with GSE173895 were downloaded from the GEO database. Differentially expressed genes (DEGs) identified by "limma" were intersected with key module genes identified by weighted gene co-expression network analysis (WGCNA), and the shared genes went through functional enrichment analysis. The protein-protein interaction (PPI) network and the machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest (RF), and XGBoost were used to reveal candidate diagnostic markers for EoE. The receiver operating characteristic (ROC) curve showed the efficacy of differential diagnosis of this marker, along with online databases predicting its molecular regulatory network. Finally, we performed gene set enrichment analysis (GSEA) and assessed immune cell infiltration of EoE/control samples by using the CIBERSORT algorithm. The correlations between the key diagnostic biomarker and immune cells were also investigated. Results: The intersection of 936 DEGs and 1446 key module genes in EoE generated 567 genes, which were primarily enriched in immune regulation. Following the construction of the PPI network and filtration by machine learning, CXCR2 served as a potential diagnostic biomarker of pediatric EoE with a perfect diagnostic efficacy (AUC = ~1.00) in regional tissue/peripheral whole blood samples. Multiple infiltrated immune cells were observed to participate in disrupting the homeostasis of esophageal epithelium to varying degrees. Conclusion: The immune-correlated CXCR2 gene was proved to be a promising diagnostic indicator for EoE, and dysregulated regulatory T cells (Tregs)/neutrophils might play a crucial role in the pathogenesis of EoE in children.
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Purpose: Concrete epidemiological evidence has suggested the mutually-contributing effect respectively between nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and periodontitis (PD); however, their shared crosstalk mechanism remains an open issue. Method: The NAFLD, PD, and T2DM-related datasets were obtained from the NCBI GEO repository. Their common differentially expressed genes (DEGs) were identified and the functional enrichment analysis performed by the DAVID platform determined relevant biological processes and pathways. Then, the STRING database established a PPI network of such DEGs and topological analysis through Cytoscape 3.7.1 software along with the machine-learning analysis by the least absolute shrinkage and selection operator (LASSO) algorithm screened out hub characteristic genes. Their efficacy was validated by external datasets using the receiver operating characteristic (ROC) curve, and gene expression and location of the most robust one was determined using single-cell sequencing and immunohistochemical staining. Finally, the promising drugs were predicted through the CTD database, and the CB-DOCK 2 and Pymol platform mimicked molecular docking. Result: Intersection of differentially expressed genes from three datasets identified 25 shared DEGs of the three diseases, which were enriched in MHC II-mediated antigen presenting process. PPI network and LASSO machine-learning analysis determined 4 feature genes, of which the MS4A6A gene mainly expressed by macrophages was the hub gene and key immune cell type. Molecular docking simulation chosen fenretinide as the most promising medicant for MS4A6A+ macrophages. Conclusion: MS4A6A+ macrophages were suggested to be important immune-related mediators in the progression of NAFLD, PD, and T2DM pathologies.
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Fut2-mediated α1,2-fucosylation is important for gut homeostasis, including the intestinal stem cell (ISC). The stemness of ISC declines with age, and aging-associated ISC dysfunction is closely related to many age-related intestinal diseases. We previously found intestinal epithelial dysfunction in some aged Fut2 knockout mice. However, how Fut2-mediated α1,2-fucosylation affects ISC aging is still unknown. On this basis, the herein study aims to investigate the role of Fut2-mediated α1,2-fucosylation in ISC aging. Aging models in ISC-specific Fut2 knockout mice were established. ISCs were isolated for proteomics and N-glycoproteomics analysis. ISC functions and mitochondrial functions were examined in mice and organoids. Ulex europaeus agglutinin I chromatography and site-directed mutagenesis were used to validate the key target fucosylated proteins of Fut2. As a result, Fut2 knockout impaired ISC stemness and promoted aging marker expression in aged mice. Proteomics analysis indicated mitochondrial dysfunction in Fut2 knockout ISC. More injured mitochondria, elevated levels of reactive oxygen species, and decreased levels of adenosine 5'-triphosphate (ATP) in Fut2 knockout ISC were found. Moreover, respiratory chain complex impairment and mitophagy dysfunction in Fut2 knockout ISC were further noted. Finally, Fut2 was demonstrated to regulate mitochondrial functions mainly by regulating the α1,2-fucosylation of N-acyl sphingosine amidohydrolase 2 (Asah2) and Niemann-Pick type C intracellular cholesterol transporter 1 (Npc1). In conclusion, this study demonstrated the substantial role of Fut2 in regulating ISC functions during aging by affecting mitochondrial function. These findings provide novel insights into the molecular mechanisms of ISC aging and therapeutic strategies for age-related intestinal diseases.
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Loop dynamics redesign is an important strategy to manipulate protein function. Cellobiose 2-epimerase (CE) and other members of its superfamily are widely used for diverse industrial applications. The structural feature of the loops connecting barrel helices contributes greatly to the differences in their functional characteristics. Inspired by the in-silico mutation with molecular dynamics (MD) simulation analysis, we propose a strategy for identifying disulfide bond mutation candidates based on the prediction of protein flexibility and residue-residue interaction. The most beneficial mutant with the newly introduced disulfide bond would simultaneously improve both its thermostability and its reaction propensity to the targeting isomerization product. The ratio of the isomerization/epimerization catalytic rate was improved from 4:103 to 9:22. MD simulation and binding free energy calculations were applied to provide insights into molecular recognition upon mutations. The comparative analysis of enzyme/substrate binding modes indicates that the altered catalytic reaction pathway is due to less efficient binding of the native product. The key residue responsible for the observed phenotype was identified by energy decomposition and was further confirmed by the mutation experiment. The rational design of the key loop region might be a promising strategy to alter the catalytic behavior of all (α/α)6-barrel-like proteins.
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Bone defects, resulting from trauma, inflammation, tumors, and various other factors, affect both health and quality of life. Although autologous bone transplantation is the gold-standard treatment for bone defects, it has disadvantages such as donor site limitations, prolonged surgical durations, and potential complications, necessitating the development of alternative bone tissue engineering materials. In this study, we used 3D printing technology to fabricate porous titanium implants characterized by superior biocompatibility and mechanical properties. Sodium alginate (SA) and strontium ions (Sr2+) were integrated into mineralized collagen matrices (MCs) to develop strontium-functionalized alginate-mineralized collagen hydrogels (SAMs) with high mechanical strength and sustained metal ion release ability. SAMs were seamlessly incorporated into the porous structures of 3D-printed titanium scaffolds, establishing a novel organic-inorganic bioactive interface. This composite system exhibited high biocompatibility in vitro and increased the expression of genes important for osteogenic differentiation and angiogenesis. In a rabbit model of femoral defect, the titanium implants effectively promoted bone and vascular regeneration on their surface, highlighting their potential in facilitating bone-implant integration.
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Piezocatalysis is a direct method for converting mechanical vibration into chemical energy. Herein, NiTiO3 is used in the piezocatalytic hydrogen evolution field for the first time. The noncentral symmetry of NiTiO3 is enhanced by doping with large radius elements. It is demonstrated that when a metal element replaces the sites of nickel, it results in lattice distortion and a higher piezoelectric response. In particular, Cd-doped NiTiO3 exhibits the highest H2 generation rate (1.52 mmol g-1 h-1), which is 13 times that of original NiTiO3.
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Artificial metalloenzymes (ArMs) are constructed by anchoring organometallic catalysts to an evolvable protein scaffold. They present the advantages of both components and exhibit considerable potential for the in vivo catalysis of new-to-nature reactions. Herein, Escherichia coli surface-displayed Vitreoscilla hemoglobin (VHbSD-Co) that anchored the cobalt porphyrin cofactor instead of the original heme cofactor was used as an artificial thiourea oxidase (ATOase) to synthesize 5-imino-1,2,4-thiadiazoles. After two rounds of directed evolution using combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy, the evolved six-site mutation VHbSD-Co (6SM-VHbSD-Co) exhibited significant improvement in catalytic activity, with a broad substrate scope (31 examples) and high yields with whole cells. This study shows the potential of using VHb ArMs in new-to-nature reactions and demonstrates the applicability of E. coli surface-displayed methods to enhance catalytic properties through the substitution of porphyrin cofactors in hemoproteins in vivo.
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Smart responsive materials are capable of responding to external stimuli and, compared to traditional materials, can be effectively reused and reduce usage costs in applications. However, smart responsive materials often face challenges such as the inability to repair extensive damage, instability in long-term performance, and inapplicability in extreme environments. This study combines 2D diamond nanosheets with organic fluorinated molecules to prepare a smart nanofluid (fluorinated diamond nanosheets, F-DN) with self-healing and self-adhesion properties. This smart nanofluid can be used to design various coatings for different applications. For example, coatings prepared on textured steel plates using the drop-casting method have excellent superhydrophobic and high oleophobic properties; coatings on titanium alloy plates achieve low friction and wear in the presence of lubricating additives of F-DN in perfluoropolyether (PFPE). Most impressively, coatings on steel plates not only provide effective corrosion resistance but also have the ability to self-heal significant damage (approximately 2 mm in width), withstand extremely low temperatures (-64 °C), and resist long-term corrosion factors (immersion in 3.5 wt % NaCl solution for 35 days). Additionally, it can act as a "coating glue" to repair extensive damage to other corrosion-resistant organic coatings and recover their original protective properties. Therefore, the smart nanofluid developed in this study offers diverse applications and presents new materials system for the future development of smart responsive materials.