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Reduction of carbon dioxide (CO2) by renewable electricity to produce multicarbon chemicals, such as ethylene (C2H4), continues to be a challenge because of insufficient Faradaic efficiency, low production rates, and complex mechanistic pathways. Here, we report that the rate-determining steps (RDS) on common copper (Cu) surfaces diverge in CO2 electroreduction, leading to distinct catalytic performances. Through a combination of experimental and computational studies, we reveal that CâC bond-making is the RDS on Cu(100), whereas the protonation of *CO with adsorbed water becomes rate-limiting on Cu(111) with a higher energy barrier. On an oxide-derived Cu(100)-dominant Cu catalyst, we reach a high C2H4 Faradaic efficiency of 72%, partial current density of 359 mA cm-2, and long-term stability exceeding 100 h at 500 mA cm-2, greatly outperforming its Cu(111)-rich counterpart. We further demonstrate constant C2H4 selectivity of >60% over 70 h in a membrane electrode assembly electrolyzer with a full-cell energy efficiency of 23.4%.
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The combination of the chiral concept and inorganic nanostructures holds great potential for significantly impacting catalytic processes and products. However, the synthesis of inorganic nanomaterials with engineered chiroptical activity and identical structure and size presents a substantial challenge, impeding exploration of the relationship between chirality (optical activity) and catalytic efficiency. Here, we present a facile wet-chemical synthesis for achieving intrinsic and tunable chiroptical activity within colloidal copper oxide nanostructures. These nanostructures exhibit strong spin-polarization selectivity compared with their achiral counterparts. More importantly, the ability to engineer chiroptical activity within the same type of chiral nanostructures allows for the manipulation of spin-dependent catalysis, facilitating a study of the connection between the chiroptical magnitude (asymmetric factor) and catalytic performance in inorganic nanostructures. Specifically, using these materials as model catalysts in a proof-of-concept catalytic reaction, we reveal a linear correlation between the asymmetric factor of chiral nanomaterials and the efficiency of the catalytic reaction. This work paves the way for the development of chiral inorganic nanosystems and their application in catalysis through chiroptical engineering.
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A precise radiotherapy plan is crucial to ensure accurate segmentation of glioblastomas (GBMs) for radiation therapy. However, the traditional manual segmentation process is labor-intensive and heavily reliant on the experience of radiation oncologists. In this retrospective study, a novel auto-segmentation method is proposed to address these problems. To assess the method's applicability across diverse scenarios, we conducted its development and evaluation using a cohort of 148 eligible patients drawn from four multicenter datasets and retrospective data collection including noncontrast CT, multisequence MRI scans, and corresponding medical records. All patients were diagnosed with histologically confirmed high-grade glioma (HGG). A deep learning-based method (PKMI-Net) for automatically segmenting gross tumor volume (GTV) and clinical target volumes (CTV1 and CTV2) of GBMs was proposed by leveraging prior knowledge from multimodal imaging. The proposed PKMI-Net demonstrated high accuracy in segmenting, respectively, GTV, CTV1, and CTV2 in an 11-patient test set, achieving Dice similarity coefficients (DSC) of 0.94, 0.95, and 0.92; 95% Hausdorff distances (HD95) of 2.07, 1.18, and 3.95 mm; average surface distances (ASD) of 0.69, 0.39, and 1.17 mm; and relative volume differences (RVD) of 5.50%, 9.68%, and 3.97%. Moreover, the vast majority of GTV, CTV1, and CTV2 produced by PKMI-Net are clinically acceptable and require no revision for clinical practice. In our multicenter evaluation, the PKMI-Net exhibited consistent and robust generalizability across the various datasets, demonstrating its effectiveness in automatically segmenting GBMs. The proposed method using prior knowledge in multimodal imaging can improve the contouring accuracy of GBMs, which holds the potential to improve the quality and efficiency of GBMs' radiotherapy.
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Hereditary spastic paraplegias (HSPs) comprise a large group of inherited neurologic disorders affecting the longest corticospinal axons (SPG1-86 plus others), with shared manifestations of lower extremity spasticity and gait impairment. Common autosomal dominant HSPs are caused by mutations in genes encoding the microtubule-severing ATPase spastin (SPAST; SPG4), the membrane-bound GTPase atlastin-1 (ATL1; SPG3A) and the reticulon-like, microtubule-binding protein REEP1 (REEP1; SPG31). These proteins bind one another and function in shaping the tubular endoplasmic reticulum (ER) network. Typically, mouse models of HSPs have mild, later onset phenotypes, possibly reflecting far shorter lengths of their corticospinal axons relative to humans. Here, we have generated a robust, double mutant mouse model of HSP in which atlastin-1 is genetically modified with a K80A knock-in (KI) missense change that abolishes its GTPase activity, whereas its binding partner Reep1 is knocked out. Atl1KI/KI/Reep1-/- mice exhibit early onset and rapidly progressive declines in several motor function tests. Also, ER in mutant corticospinal axons dramatically expands transversely and periodically in a mutation dosage-dependent manner to create a ladder-like appearance, on the basis of reconstructions of focused ion beam-scanning electron microscopy datasets using machine learning-based auto-segmentation. In lockstep with changes in ER morphology, axonal mitochondria are fragmented and proportions of hypophosphorylated neurofilament H and M subunits are dramatically increased in Atl1KI/KI/Reep1-/- spinal cord. Co-occurrence of these findings links ER morphology changes to alterations in mitochondrial morphology and cytoskeletal organization. Atl1KI/KI/Reep1-/- mice represent an early onset rodent HSP model with robust behavioral and cellular readouts for testing novel therapies.
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Modelos Animales de Enfermedad , Proteínas de la Membrana , Proteínas de Transporte de Membrana , Paraplejía Espástica Hereditaria , Animales , Axones/metabolismo , Retículo Endoplásmico/genética , Retículo Endoplásmico/metabolismo , GTP Fosfohidrolasas/genética , Humanos , Proteínas de la Membrana/genética , Proteínas de Transporte de Membrana/genética , Ratones , Ratones Noqueados , Mutación , Paraplejía Espástica Hereditaria/genética , Espastina/genéticaRESUMEN
PURPOSE: This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors. PATIENTS AND METHODS: Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control. The primary objective was to assess dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and dose recommended for dose expansion (DRDE). Secondary objectives included pharmacokinetics and efficacy. RESULTS: Forty-eight patients were enrolled (dose escalation, nâ =â 40; dose expansion, nâ =â 8). MTD was not reached; DRDE was 12 mg daily. DLTs were palmar-plantar erythrodysesthesia syndrome (8 mg, nâ =â 1) and hypertension (15 mg, nâ =â 2). The most common treatment-related adverse event was hypertension (50.0%). In 43 response-evaluable patients, 13 (30.2%) achieved partial response (PR; nâ =â 7) or stable disease (SD)â ≥â 24 weeks (nâ =â 6), including 4/11 (36.4%) with FGFR2 mutations/fusions and cholangiocarcinoma (PR nâ =â 3; SDâ ≥â 24 weeks nâ =â 1), 3/3 (100.0%) with hormone receptor (HR)-positive/HER2-negative breast cancer (PR nâ =â 2; SDâ ≥â 24 weeks nâ =â 1), 2/5 (40.0%) with triple-negative breast cancer (TNBC; PR nâ =â 1; SDâ ≥â 24 weeks nâ =â 1), and 1/1 (100.0%) with castrate-resistant prostate cancer (CRPC; PR). Four of 12 patients (33.3%; HR-positive/HER2-negative breast cancer, TNBC, prostate cancer, and cholangiocarcinoma) treated at DRDE had PRs. Tinengotinib's half-life was 28-34 hours. CONCLUSIONS: Tinengotinib was well tolerated with favorable pharmacokinetic characteristics. Preliminary findings indicated potential clinical benefit in FGFR inhibitor-refractory cholangiocarcinoma, HER2-negative breast cancer (including TNBC), and CRPC. Continued evaluation of tinengotinib is warranted in phase II trials.
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Antineoplásicos , Colangiocarcinoma , Hipertensión , Neoplasias , Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Mama Triple Negativas , Masculino , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Teorema de Bayes , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Antineoplásicos/efectos adversos , Colangiocarcinoma/tratamiento farmacológico , Hipertensión/inducido químicamente , Dosis Máxima ToleradaRESUMEN
Deep learning has broad applications in imaging through scattering media. Polarization, as a distinctive characteristic of light, exhibits superior stability compared to light intensity within scattering media. Consequently, the de-scattering network trained using polarization is expected to achieve enhanced performance and generalization. For getting optimal outcomes in diverse scattering conditions, it makes sense to train expert networks tailored for each corresponding condition. Nonetheless, it is often unfeasible to acquire the corresponding data for every possible condition. And, due to the uniqueness of polarization, different polarization information representation methods have different sensitivity to different environments. As another of the most direct approaches, a generalist network can be trained with a range of polarization data from various scattering situations, however, it requires a larger network to capture the diversity of the data and a larger training set to prevent overfitting. Here, in order to achieve flexible adaptation to diverse environmental conditions and facilitate the selection of optimal polarization characteristics, we introduce a dynamic learning framework. This framework dynamically adjusts the weights assigned to different polarization components, thus effectively accommodating a wide range of scattering conditions. The proposed architecture incorporates a Gating Network (GTN) that efficiently integrates multiple polarization features and dynamically determines the suitable polarization information for various scenarios. Experimental result demonstrates that the network exhibits robust generalization capabilities across continuous scattering conditions.
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AIM: Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury. METHODS AND RESULTS: Mass spectrometry-based, non-targeted metabolomic approach was used to profile coronary sinus blood from diabetic and non-diabetic Bama-mini pigs at 0.5-h post coronary artery ligation. Six metabolites had a |log2 (Fold Change)|> 1.3. Among them, the most changed is arachidonic acid (AA), levels of which were 32 times lower in diabetic pigs than in non-diabetic pigs. The AA-derived products, PGI2 and 6-keto-PGF1α, were also significantly reduced. AA treatment of cultured cardiomyocytes protected against cell death by 30% at 48 h of high glucose and oxygen deprivation, which coincided with increased mitophagic activity (as indicated by increased LC3II/LC3I, decreased p62 and increased parkin & PINK1), improved mitochondrial renewal (upregulation of Drp1 and FIS1), reduced ROS generation and increased ATP production. These cardioprotective effects were abolished by PINK1(a crucial mitophagy protein) knockdown or the autophagy inhibitor 3-Methyladenine. The protective effect of AA was also inhibited by indomethacin and Cay10441, a prostacyclin receptor antagonist. Furthermore, diabetic Sprague Dawley rats were subjected to coronary ligation for 40 min and AA treatment (10 mg/day per animal gavaged) decreased myocardial infarct size, cell apoptosis index, inflammatory cytokines and improved heart function. Scanning electron microscopy showed more intact mitochondria in the border zone of infarcted myocardium in AA treated rats. Lastly, diabetic patients after myocardial infarction had lower plasma levels of AA and 6-keto-PGF1α and reduced cardiac ejection fraction, compared with non-diabetic patients after myocardial infarction. Plasma AA level was inversely correlated with fasting blood glucose. CONCLUSIONS: AA protects against diabetic ischemic myocardial damage by promoting mitochondrial autophagy and renewal, which is related to AA derived PGI2 signaling. AA may represent a new strategy to treat diabetic myocardial ischemic injury.
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Diabetes Mellitus , Infarto del Miocardio , Humanos , Ratas , Animales , Porcinos , Ratas Sprague-Dawley , Ácido Araquidónico/farmacología , Porcinos Enanos/metabolismo , Infarto del Miocardio/metabolismo , Proteínas Quinasas/metabolismo , ApoptosisRESUMEN
OBJECTIVE: This study aimed to reveal the urinary and serum metabolic pattern of endometrial cancer (EC) and establish diagnostic models to identify EC from controls, high-risk from low-risk EC, and type II from type I EC. METHOD: This study included 146 EC patients (comprising 79 low-risk and 67 high-risk patients, including 124 type I and 22 type II) and 59 controls. The serum and urine samples were analyzed using ultraperformance liquid chromatography mass spectrometry. Analysis was used to elucidate the distinct metabolites and altered metabolic pathways. Receiver operating characteristic (ROC) analyses were employed to discover and validate the potential biomarker models. RESULTS: Serum and urine metabolomes displayed significant differences between EC and controls, with metabolites related to amino acid and nicotinamide metabolisms. The serum and urine panels distinguished these two groups with Area Under the Curve (AUC) of 0.821 and 0.902, respectively. The panel consisting of serum and urine metabolites demonstrated the best predictive ability (AUC = 0.953 and 0.976 in discovering and validation group). In comparing high-risk and low risk EC, differential metabolites were enriched in purine and glutamine metabolism. The AUC values for serum and urine panels were 0.818, and 0.843, respectively. The combined panel exhibited better predictive accuracy (0.881 in discovering group and 0.936 in external validation). In the comparison between type I and type II group, altered folic acid metabolism was identified. The serum, urine and combined panels discriminated these two groups with the AUC of 0.829, 0.913 and 0.922, respectively. CONCLUSION: The combined urine and serum metabolome effectively revealed the metabolic patterns in EC patients, offering valuable diagnostic models for EC diagnosis and classification.
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Neoplasias Endometriales , Metabolómica , Femenino , Humanos , Metabolómica/métodos , Cromatografía Líquida con Espectrometría de Masas , Metaboloma , Neoplasias Endometriales/diagnóstico , Biomarcadores/orinaRESUMEN
Topological photonic crystals (PCs) provide an effective method for controlling how light propagates and concentrates through their topological states. However, it remains unclear whether topological states can be obtained by combining two different two-dimensional (2D) PCs with topological non-trivial states. In this Letter, two types of 2D Penrose-square (P-S) PCs are proposed. These PCs can generate topological edge states (TESs) and topological corner states (TCSs) within the low-frequency part of the bandgap. Moreover, by combining these two non-trivial PCs, a total of two groups of TESs and four groups of TCSs can be generated in both the high-frequency and low-frequency parts of the common bandgap. To the best of our knowledge, the two proposed P-S PCs offer a new platform for investigating topological photonics and related devices, providing novel approaches and perspectives for generating topological states in 2D PCs.
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We report on an optical amplification and energy threshold of the two most prominent emission lines, 391.4 and 427.8â nm, of the cavity-less lasing of nitrogen ions pumped by femtosecond laser pulses. It was found that the two transitions both show optical amplification under a low gas pressure condition, while the 391.4â nm emission is barely amplified under high gas pressure. Moreover, the 427.8â nm emission presents a significant lower pump laser energy threshold and a larger gain factor than the 391.4â nm emission. Numerical simulations based on a three-state coupling model suggest that the smaller ionization Franck-Condon factor from the ground state of N2 to the vibrational level ν = 1 in X 2 Σ g+ state of N2 + favors the formation of population inversion corresponding to the 427.8â nm emission. Meanwhile, the competition between the strong field ionization and excitation induced by the pumping laser requires higher laser intensity to acquire the population inversion for the 391.4â nm radiation, leading to a corresponding larger energy threshold.
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We successfully demonstrated an intelligent adaptive beam alignment scheme using a reinforcement learning (RL) algorithm integrated with an 8 × 8 photonic array antenna operating in the 40â GHz millimeter wave (MMW) band. In our proposed scheme, the three key elements of RL: state, action, and reward, are represented as the phase values in the photonic array antenna, phase changes with specified steps, and an obtained error vector magnitude (EVM) value, respectively. Furthermore, thanks to the Q-table, the RL agent can effectively choose the most suitable action based on its prior experiences. As a result, the proposed scheme autonomously achieves the best EVM performance by determining the optimal phase. In this Letter, we verify the capability of the proposed scheme in single- and multiple-user scenarios and experimentally demonstrate the performance of beam alignment to the user's location optimized by the RL algorithm. The achieved results always meet the signal quality requirement specified by the 3rd Generation Partnership Project (3GPP) criterion for 64-QAM orthogonal frequency division multiplexing (OFDM).
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BACKGROUND: Bladder cancer is the second most common genitourinary malignancy worldwide. The death rate of bladder cancer has increased every year. However, the molecular mechanism of bladder cancer is not sufficiently studied. Deubiquitinating enzymes (DUBs) play an important role in carcinogenesis. Several studies have demonstrated that USP5 associated with malignancy and pathological progression in hepatocellular carcinoma, colorectal and non-small cell lung cancer. However, the role of USP5 in bladder cancer need to be explored. METHODS: The USP5 expression was analysed using the web server GEPIA. To explore USP5 function in bladder cancer, we constructed USP5-knockout cell lines in T24 cells. A FLAG-USP5 (WT USP5) plasmid and a plasmid FLAG-USP5 C335A (catalytic-inactive mutant) used to overexpress USP5 in EJ cells. CCK8, colony formation, transwell and scratch assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP5 and c-Jun. Cycloheximide (CHX) chase assays were performed to establish the effect of USP5 on c-Jun stability. Xenograft mouse model was used to study the role of USP5 in bladder cancer. RESULTS: USP5 expression is increased in bladder cancer patients. Genetic ablation of USP5 markedly inhibited bladder cancer cell proliferation, viability, and migration both in vitro and in vivo. RNA-seq and luciferase pathway screening showed that USP5 activated JNK signalling, and we identified the interaction between USP5 and c-Jun. USP5 was found to activate c-Jun by inhibiting its ubiquitination. CONCLUSIONS: Our results show that high USP5 expression promotes bladder cancer progression by stabilizing c-Jun and that USP5 is a potential therapeutic target in bladder cancer.
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AIMS: The dawn phenomenon (DP) is an abnormal early morning blood glucose rise without nocturnal hypoglycaemia, which can be more easily and precisely assessed with continuous glucose monitoring (CGM). This prospective study aimed to explore the association between DP and the risk of all-cause mortality in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 5542 adult inpatients with type 2 diabetes in a single centre were analysed. The magnitude of DP (ΔG) was defined as the increment in the CGM-determined glucose value from nocturnal nadir (after 24:00) to prebreakfast. Participants were stratified into four groups by ΔG: ≤1.11, 1.12-3.33, 3.34-5.55, and >5.55 mmol/L. Cox proportional hazard regression models were used to evaluate the impact of DP on all-cause mortality risk. RESULTS: During a median follow-up of 9.4 years, 1083 deaths were identified. The restricted cubic spline revealed a nonlinear (p for nonlinearity = 0.002) relationship between ΔG and the risk of all-cause mortality. A multivariate-adjusted Cox regression model including glycated haemoglobin A1c (HbA1c) showed that ΔG > 5.55 mmol/L was associated with 30% (95% CI, 1.01-1.66) higher risk of all-cause mortality, as compared with ΔG 1.12-3.33 mmol/L. CONCLUSIONS: Higher ΔG is significantly related to an increased risk of all-cause mortality in type 2 diabetes, suggesting that severe DP should be given more attention as a part of glucose management to reduce the risk of long-term adverse outcomes.
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Glucemia , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Femenino , Masculino , Persona de Mediana Edad , Glucemia/análisis , Estudios de Seguimiento , Estudios Prospectivos , Factores de Riesgo , Pronóstico , Anciano , Hemoglobina Glucada/análisis , Automonitorización de la Glucosa Sanguínea , Causas de Muerte , Biomarcadores/análisis , Biomarcadores/sangre , Ritmo Circadiano/fisiología , Hipoglucemia/mortalidad , Tasa de Supervivencia , AdultoRESUMEN
A highly stereoselective strategy for 1,2-cis-xylopyranoside bond formation was established via a preactivation-based, additive-modulated trichloroacetimidate glycosidation strategy. The current protocol is mild, practical, and successful with various xylopyranosyl donors and glycosyl acceptors, including acceptors that are reported to be less reactive due to steric hindrance. The utility of this method was demonstrated with the facile assembly of matriglycan constituent tetra- and hexasaccharides.
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Activation of O-glycosyl trihaloacetimidate glycosyl donors with AuCl3 as a catalyst and pivalonitrile (tBuCN) as a ligand led to excellent glycosidation results in terms of yield and anomeric selectivity. In this way, various ß-d-gluco- and ß-d-galactopyranosides were obtained conveniently and efficiently. Experimental studies and density functional theory (DFT) calculations, in order to elucidate the reaction course, support formation of the tBuCN-AuCl2-OR(H)+ AuCl4- complex as a decisive intermediate in the glycosidation event. Proton transfer from this acceptor complex to the imidate nitrogen leads to donor activation. In this way, guided by the C-2 configuration of the glycosyl donor, the alignment of the acceptor complex enforces the stereoselective ß-glycoside formation in an intramolecular fashion, thus promoting also a fast reaction course. The high stereocontrol of this novel 'Lewis acid-nitrile cooperative effect' is independent of the glycosyl donor anomeric configuration and without the support of neighboring group or remote group participation. The power of the methodology is shown by a successful glycoalkaloid solamargine synthesis.
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BACKGROUND: Early and appropriate antibiotic treatment improves the clinical outcome of patients with sepsis. There is an urgent need for rapid identification (ID) and antimicrobial susceptibility testing (AST) of bacteria that cause bloodstream infection (BSI). Rapid ID and AST can be achieved by short-term incubation on solid medium of positive blood cultures using MALDI-TOF mass spectrometry (MS) and the BD M50 system. The purpose of this study is to evaluate the performance of rapid method compared to traditional method. METHODS: A total of 124 mono-microbial samples were collected. Positive blood culture samples were short-term incubated on blood agar plates and chocolate agar plates for 5 â¼ 7 h, and the rapid ID and AST were achieved through Zybio EXS2000 MS and BD M50 System, respectively. RESULTS: Compared with the traditional 24 h culture for ID, this rapid method can shorten the cultivation time to 5 â¼ 7 h. Accurate organism ID was achieved in 90.6% of Gram-positive bacteria (GP), 98.5% of Gram-negative bacteria (GN), and 100% of fungi. The AST resulted in the 98.5% essential agreement (EA) and 97.1% category agreements (CA) in NMIC-413, 99.4% EA and 98.9% CA in PMIC-92, 100% both EA and CA in SMIC-2. Besides, this method can be used for 67.2% (264/393) of culture bottles during routine work. The mean turn-around time (TAT) for obtaining final results by conventional method is approximately 72.6 ± 10.5 h, which is nearly 24 h longer than the rapid method. CONCLUSIONS: The newly described method is expected to provide faster and reliable ID and AST results, making it an important tool for rapid management of blood cultures (BCs). In addition, this rapid method can be used to process most positive blood cultures, enabling patients to receive rapid and effective treatment.
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Bacterias , Pruebas de Sensibilidad Microbiana , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Antibacterianos/farmacología , Hongos/efectos de los fármacos , Hongos/aislamiento & purificación , Cultivo de Sangre/métodos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Factores de Tiempo , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Sepsis/microbiología , Sepsis/tratamiento farmacológico , Sepsis/diagnósticoRESUMEN
The endoplasmic reticulum (ER) consists of tubules that are shaped by the reticulons and DP1/Yop1p, but how the tubules form an interconnected network is unknown. Here, we show that mammalian atlastins, which are dynamin-like, integral membrane GTPases, interact with the tubule-shaping proteins. The atlastins localize to the tubular ER and are required for proper network formation in vivo and in vitro. Depletion of the atlastins or overexpression of dominant-negative forms inhibits tubule interconnections. The Sey1p GTPase in S. cerevisiae is likely a functional ortholog of the atlastins; it shares the same signature motifs and membrane topology and interacts genetically and physically with the tubule-shaping proteins. Cells simultaneously lacking Sey1p and a tubule-shaping protein have ER morphology defects. These results indicate that formation of the tubular ER network depends on conserved dynamin-like GTPases. Since atlastin-1 mutations cause a common form of hereditary spastic paraplegia, we suggest ER-shaping defects as a neuropathogenic mechanism.
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Dinamina I/metabolismo , Retículo Endoplásmico/metabolismo , GTP Fosfohidrolasas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animales , Dinaminas/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMEN
Topological rainbows (TRs) possess the potential to separate and localize topological photonic states across different frequencies. However, previous works on TRs have been confined to a single-frequency band. Furthermore, the achievement of multiband TRs within a single structure is still a significant challenge. In this paper, a composed structure waveguide is designed based on Penrose-triangle photonic crystals. By adjusting the size of scatterers and introducing non-Hermitian terms, we successfully realize dual-band TRs. This achievement will not only enhance the uniformity of the electric field intensity distribution but also provide the potential to introduce a new avenue for the development of robust photonic devices dedicated to processing vast amounts of data information.
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Conducting a comprehensive molecular-level evaluation of a photoacid generator (PAG) and its subsequent impact on lithography performance can facilitate the rational design of a promising 193 nm photoresist tailored to specific requirements. In this study, we integrated spectroscopy and computational techniques to meticulously investigate the pivotal factors of three prototypical PAG anions, p-toluenesulfonate (pTS-), 2-(trifluoromethyl)benzene-1-sulfonate (TFMBS-), and triflate (TF-), in the lithography process. Our findings reveal a significant redshift in the absorption spectra caused by specific PAG anions, attributed to their involvement in electronic transition processes, thereby enhancing the transparency of the standard PAG cation, triphenylsulfonium (TPS+), particularly at â¼193 nm. Furthermore, the electronic stability of PAG anions can be enhanced by solvent effects with varying degrees of strength. We observed the lowest vertical detachment energy of 6.6 eV of pTS- in PGMEA solution based on the polarizable continuum model, which prevents anion loss at 193 nm lithography. In addition, our findings indicate gas-phase proton affinity values of 316.4 kcal/mol for pTS-, 308.1 kcal/mol for TFMBS-, and 303.2 kcal/mol for TF-, which suggest the increasing acidity strength, yet even the weakest acid pTS- is still stronger than strong acid HBr. The photolysis of TPS+-based PAG, TPS+·pTS-, generated an excited state leading to homolysis bond cleavage with the lowest reaction energy of 83 kcal/mol. Overall, the PAG anion pTS- displayed moderate acidity, possessed the lowest photolysis reaction energy, and demonstrated an appropriate redshift. These properties collectively render it a promising candidate for an effective acid producer.
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BACKGROUND: This case involves a 28-year-old pregnant woman (39w+2) who was admitted to obstetrics due to abdominal tightness and bacteremia with Gardnerella vaginalis which developed after caesarean section and vaginal myomectomy. METHODS: A blood culture was performed, and the bacteria were identified through mass spectrometry. RESULTS: Mass spectrometry data indicated that the infection bacteria were Gardnerella vaginalis. The patient's temperature returned to normal after oral ampicillin in combination with clindamycin. CONCLUSIONS: Gardnerella vaginalis bacteremia is very rare in clinical practice, and the combination of ampicillin and clindamycin has a good therapeutic effect. This study may provide a reference for the diagnosis and treatment of Gardnerella vaginalis bacteremia.