Acute High-Output Heart Failure with Pulmonary Hypertension and Severe Liver Injury Caused by Amlodipine Poisoning: A Case Report.

Acute high-output heart failure (HOHF) with pulmonary hypertension and liver injury caused by amlodipine poisoning is very rare. We report a 52-year-old woman who suffered from severe shock after an overdose of amlodipine. Hemodynamic monitoring showed that while her left ventricular systolic function and cardiac output were elevated, her systemic vascular resistance decreased significantly. At the same time, the size of her right heart, her central venous pressure, and the oxygen saturation of her central venous circulation all increased abnormally. The patient's circulatory function and right ventricular dysfunction gradually improved after large doses of vasopressors and detoxification measures. However, her bilirubin and transaminase levels increased significantly on hospital day 6, with a CT scan showing patchy, low-density areas in her liver along with ascites. After liver protective treatment and plasma exchange, the patient's liver function gradually recovered. A CT scan 4 months later showed all her liver abnormalities, including ascites, had resolved. The common etiologies of HOHF were excluded in this case, and significantly reduced systemic vascular resistance caused by amlodipine overdose was thought to be the primary pathophysiological basis of HOHF. The significant increase in venous return and pulmonary blood flow is considered to be the main mechanism of right ventricular dysfunction and pulmonary hypertension. Hypoxic hepatitis caused by a combination of hepatic congestion and distributive shock may be the most important factors causing liver injury in this patient. Whether amlodipine has other mechanisms leading to HOHF and pulmonary hypertension needs to be further studied. Considering the significant increase of right heart preload, aggressive fluid resuscitation should be done very cautiously in patients with HOHF and shock secondary to amlodipine overdose.

It Takes Two to Tangle: Microneedle Patches Co-delivering Monoclonal Antibodies and Engineered Antimicrobial Peptides Effectively Eradicate Wound Biofilms.

Wound biofilms pose a great clinical challenge. Herein, this work reports a dissolvable microneedle patch for dual delivery of monoclonal antibodies anti-PBP2a and engineers antimicrobial peptides W379. In vitro antibacterial efficacy testing with microneedle patches containing a combination of 250 ng mL-1 W379 and 250 ng mL-1 anti-BPB2a decreases the bacterial count from ≈3.31 × 107 CFU mL-1 to 1.28 × 102 CFU mL-1 within 2 h without eliciting evident cytotoxicity. Ex vivo testing indicates W379 and anti-PBP2a co-loaded microneedle patch displayed a remarkable reduction of bacterial load by ≈7.18 log CFU after administered only once within 48 h. The bacterial count is significantly diminished compared to the treatment by either W379 or anti-PBP2a-loaded alone microneedle patches. When administered twice within 48 h, no bacteria are identified. Further in vivo study also reveals that after two treatments of W379 and anti-PBP2a co-loaded PVP microneedle patches within 48 h, the bacterial colonies are undetectable in a type II diabetic mouse wound biofilm model. Taken together, W379 and anti-PBP2a co-loaded PVP microneedle patches hold great promise in treating wound biofilms.

An Epileptic EEG Detection Method Based on Data Augmentation and Lightweight Neural Network.

OBJECTIVE: Epilepsy, an enduring neurological disorder, afflicts approximately 65 million individuals globally, significantly impacting their physical and mental wellbeing. Traditional epilepsy detection methods are labor-intensive, leading to inefficiencies. Although deep learning techniques for brain signal detection have gained traction in recent years, their clinical application advancement is hindered by the significant requirement for high-quality data and computational resources during training. METHODS & RESULTS: The neural network training initially involved merging two datasets of different data quality, namely Bonn University datasets and CHB-MIT datasets, to bolster its generalization capabilities. To tackle the issues of dataset size and class imbalance, we employed small window segmentation and Synthetic Minority Over-sampling Technique (SMOTE). algorithms to augment and equalize the data. A streamlined neural network architecture was then proposed, drastically reducing the model's training parameters. Notably, a model trained with a mere 9,371 parameters yielded impressive results. The three-classification task on the combined dataset delivered an accuracy of 98.52%, sensitivity of 97.99%, specificity of 99.35%, and precision of 98.44%. CONCLUSION: The experimental findings of this study underscore the superiority of the proposed method over existing approaches in both model size reduction and accuracy enhancement. As a result, it is more apt for deployment in low-cost, low computational hardware devices, including wearable technology, and various clinical applications. Clinical and Translational Impact Statement- This study is a Pre-Clinical Research. The lightweight neural network is easily deployed on hardware device for real-time epileptic EEG detection.

Zearalenone promotes porcine ESCs apoptosis by enhancing Drp1-mediated mitochondrial fragmentation and activating the JNK pathway.

Zearalenone (ZEA) is widely present in food and feed, and pigs are susceptible to its effects. This study explored the underlying function of ZEA-induced apoptosis in porcine endometrial stromal cells (ESCs) through activation of the JNK signaling pathway and mitochondrial division. This study utilized ESCs to explore the impact of exposure to ZEA. A mitochondrial division inhibitor (Mdivi) was also included as a reference. The results indicated a gradual decrease in cell viability with increasing ZEA concentration. In addition, ZEA can modify the growth status of porcine ESCs, disrupt their ultrastructure, and lead to apoptosis of porcine ESCs via the mitochondrial division pathway and JNK signaling pathway. In summary, our study found the critical targets of ZEA infected with pig ESCs, which provided a conceptual foundation to prevent and control ZEA.

Lesion location and serum levels of homocysteine are associated with early-onset post-stroke depression in acute ischemic stroke.

INTRODUCTION: It is well known that post-stroke depression (PSD) is a psychiatric complication after stroke which leads to worse functional outcome and poorer quality of life. Some risk factors including gender, stroke severity, lesion location, homocysteine (HCY), and so on are associated with PSD. This study aims to further explore the possible relationship between serum levels of HCY and early-onset PSD and the predictive value of HCY combined with stroke characteristics for early-onset PSD. METHODS: Two hundred forty-five patients with acute ischemic stroke who met the criteria were included in this study from March 2015 to March 2017. PSD was diagnosed at 2 weeks after stroke. The severity of depressive symptoms was evaluated with the Hamilton depression scale 17 items (HAMD-17), and patients with HAMD scores ≥7 were included in the PSD group. The demographic data, clinical characteristics, serum levels of HCY, and detailed radiological variables (e.g., lesion location and quantity of the brain infarct) were also examined. RESULTS: In total, 97 (39.6%) patients of the 245 patients were diagnosed with depression. The univariate analyses suggested that patients in PSD group had a higher NIHSS score, modified Rankin Scale score, and HCY levels than patients in non-PSD group (p < .001). The patients with PSD had higher proportion of multiple-site acute infarcts and frontal lobe lesion (p < .05). In multivariate logistic regression analysis, NIHSS score at admission, serum levels of HCY, and multiple-site lesions were independently related to early-onset PSD. Based on receiver operating characteristic curves analysis, the combination of HCY, NIHSS scores, multiple-site lesions, and lesion location revealed a highest area under the curve of 0.807 (95% confidence interval [CI]: 0.748-0.865, p < .001). Furthermore, there was a significantly increased risk of early-onset PSD associated with serum levels of HCY ≥16.98 µmol/L (odds ratio [OR] = 10.976, 95% CI: 5.585-21.573, p < .001). CONCLUSIONS: Our study indicated that higher NIHSS score, elevated serum levels of HCY, and multiple-site lesions may be independent risk factors of early-onset PSD. The combination of HCY, NIHSS scores, multiple-site lesions, and lesion location may provide greater predictive value than HCY alone for early-onset PSD. Early intervention for elevated serum levels of HCY may be a potential target for the intervention and prevention of PSD.

Combination of Zearalenone and Deoxynivalenol Induces Apoptosis by Mitochondrial Pathway in Piglet Sertoli Cells: Role of Endoplasmic Reticulum Stress.

Zearalenone (ZEA) and deoxynivalenol (DON) are widely found in various feeds, which harms livestock's reproductive health. Both mitochondria and endoplasmic reticulum (ER) can regulate cell apoptosis. This study aimed to explore the regulatory mechanism of endoplasmic reticulum stress (ERS) on ZEA- combined with DON-induced mitochondrial pathway apoptosis in piglet Sertoli cells (SCs). The results showed that ZEA + DON damaged the ultrastructure of the cells, induced apoptosis, decreased mitochondrial membrane potential, promoted the expression of cytochrome c (CytC), and decreased the cell survival rate. Furthermore, ZEA + DON increased the relative mRNA and protein expression of Bid, Caspase-3, Drp1, and P53, while that of Bcl-2 and Mfn2 declined. ZEA + DON was added after pretreatment with 4-phenylbutyric acid (4-PBA). The results showed that 4-PBA could alleviate the toxicity of ZEA + DON toward SCs. Compared with the ZEA + DON group, 4-PBA improved the cell survival rate, decreased the apoptosis rate, inhibited CytC expression, and increased mitochondrial membrane potential, and the damage to the cell ultrastructure was alleviated. Moreover, after pretreatment with 4-PBA, the relative mRNA and protein expression of Bid, Caspase-3, Drp1, and P53 were downregulated, while the relative mRNA and protein expression of Bcl-2 and Mfn2 were upregulated. It can be concluded that ERS plays an important part in the apoptosis of SCs co-infected with ZEA-DON through the mitochondrial apoptosis pathway, and intervention in this process can provide a new way to alleviate the reproductive toxicity of mycotoxins.

Identification of prognostic melatonin-related lncRNA signature in tumor immune microenvironment and drug resistance for breast cancer.

BACKGROUND: Melatonin is a neurohormone involved in diverse physiological processes, including regulation of circadian rhythm, oncogenesis and immune function. More attention are focused on the molecular events surrounding the occurrence of abnormally expressed lncRNAs leading to breast cancer. The purpose of this study was to evaluate the role of melatonin-related lncRNAs in the clinical management of BRCA patients and their immune responses. METHODS: The transcriptome data and clinical data of BRCA patients were acquired from TCGA database. A total of 1103 patients were randomly assigned to either training set or validation set. A melatonin-related lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis, immune microenvironment and drug resistance analysis associated to melatonin-related lncRNAs were performed by utilizing GO&KEGG, ESTIMATE and TIDE analysis. A nomogram based on the signature score and clinical characteristics was established, which was calibrated to increase prediction probability of 1-year, 3-year and 5-year survival for BRCA patients. RESULTS: BRCA patients were divided into two signature groups based on a 17-melatonin-related lncRNA signature. High-signature patients had worse prognosis than low-signature patients (p < 0.001). Univariate and multivariate Cox regression analysis proved that the signature score was an independent prognostic factor for BRCA patients. Functional analysis indicated that high-signature BRCA involved in regulation of processing and maturation of mRNA and misfolded protein response. Remarkably, immune microenvironment analysis showed that the proportion of tumor-infiltrating M2 macrophage and the expression of CTLA4 were significantly higher in high-signature BRCA. The calibration curves for the probability of invasive BRCA showed optimal agreement between the probability as predicted by the nomogram and the actual probability. CONCLUSIONS: A novel melatonin-related lncRNA signature was considered as an independent prognostic indicator for BRCA patients. Melatonin-related lncRNAs were potentially associated with tumor immune microenvironment and might be therapeutic targets for BRCA patients.

Inhibition of Mitochondrial Fission Alleviates Zearalenone-Induced Mitochondria-Associated Endoplasmic Reticulum Membrane Dysfunction in Piglet Sertoli Cells.

This study aimed to investigate the effects of zearalenone (ZEA) on piglet Sertoli cell (SC)-mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) based on mitochondrial fission, and to explore the molecular mechanism of ZEA-induced cell damage. After the SCs were exposed to the ZEA, the cell viability decreased, the Ca2+ levels increased, and the MAM showed structural damage. Moreover, glucose-regulated protein 75 (Grp75) and mitochondrial Rho-GTPase 1 (Miro1) were upregulated at the mRNA and protein levels. However, phosphofurin acidic cluster protein 2 (PACS2), mitofusin2 (Mfn2), voltage-dependent anion channel 1 (VDAC1), and inositol 1,4,5-trisphosphate receptor (IP3R) were downregulated at the mRNA and protein levels. A pretreatment with mitochondrial division inhibitor 1 (Mdivi-1) decreased the ZEA-induced cytotoxicity toward the SCs. In the ZEA + Mdivi-1 group, the cell viability increased, the Ca2+ levels decreased, the MAM damage was repaired, and the expression levels of Grp75 and Miro1 decreased, while those of PACS2, Mfn2, VDAC1, and IP3R increased compared with those in the ZEA-only group. Thus, ZEA causes MAM dysfunction in piglet SCs through mitochondrial fission, and mitochondria can regulate the ER via MAM.

Study on Pyrolysis of Shale Gas Oil-Based Drilling Cuttings: Kinetics, Process Parameters, and Product Yield.

The main reaction range (350-550 °C) of oil-based drilling cutting (OBDC) pyrolysis was studied by a thermogravimetric analyzer and a vacuum tube furnace. The average activation energies calculated by four model-free methods were 185.5 kJ/mol (FM), 184.16 kJ/mol (FWO), 166.17 kJ/mol (KAS), and 176.03 kJ/mol (Starink). The reaction mechanism was predicted by the Criado (Z-master plot) method. It is found that a high heating rate is helpful to predict the reaction mechanism, but it cannot be described by a single reaction model. Under the conditions of target temperature higher than 350 °C, residence time higher than 50 min, laying thickness less than 20 mm, and heating rate lower than 15 °C, the residual oil content is lower than 0.3% and the recovery rate of mineral oil is higher than 98.43%. Solid phase products accounted for more than 70%, reached the maximum 17.04% at 450 °C, and then decreased to 15.87% at 500 °C. Aromatic hydrocarbons, as coking precursors, are transformed from a low ring to a high ring. Recycled mineral oil can reconfigure oil-based mud (OBM). The research results can provide a theoretical basis for process optimization.

Zearalenone induces mitochondria-associated endoplasmic reticulum membranes dysfunction in piglet Sertoli cells based on endoplasmic reticulum stress.

Zearalenone (ZEA) is an estrogen-like mycotoxin, which mainly led to reproductive toxicity. The study aimed to investigate the molecular mechanism of ZEA-induced dysfunction of mitochondria-associated endoplasmic reticulum membranes (MAM) in piglet Sertoli cells (SCs) via the endoplasmic reticulum stress (ERS) pathway. In this study, SCs were used as a research object that was exposed to ZEA, and ERS inhibitor 4-Phenylbutyrate acid (4-PBA) was used as a reference. The results showed that ZEA damaged cell viability and increased Ca2+ levels; damaged the structure of MAM; up-regulated the relative mRNA and protein expression of glucose-regulated protein 75 (Grp75) and mitochondrial Rho-GTPase 1 (Miro1), while inositol 1,4,5-trisphosphate receptor (IP3R), voltage-dependent anion channel 1 (VDAC1), mitofusin2 (Mfn2) and phosphofurin acidic cluster protein 2 (PACS2) were down-regulated. After a 3 h 4-PBA-pretreatment, ZEA was added for mixed culture. The results of 4-PBA pretreatment showed that inhibition of ERS reduced the cytotoxicity of ZEA against piglet SCs. Compared with the ZEA group, inhibition of ERS increased cell viability and decreased Ca2+ levels; restored the structural damage of MAM; down-regulated the relative mRNA and protein expression of Grp75 and Miro1; and up-regulated the relative mRNA and protein expression of IP3R, VDAC1, Mfn2, and PACS2. In conclusion, ZEA can induce MAM dysfunction in piglet SCs via the ERS pathway, whereas ER can regulate mitochondria through MAM.

Structure of the Newcastle Disease Virus L protein in complex with tetrameric phosphoprotein.

Newcastle disease virus (NDV) belongs to Paramyxoviridae, which contains lethal human and animal pathogens. NDV RNA genome is replicated and transcribed by a multifunctional 250 kDa RNA-dependent RNA polymerase (L protein). To date, high-resolution structure of NDV L protein complexed with P protein remains to be elucidated, limiting our understanding of the molecular mechanisms of Paramyxoviridae replication/transcription. Here, we used cryo-EM and enzymatic assays to investigate the structure-function relationship of L-P complex. We found that C-terminal of CD-MTase-CTD module of the atomic-resolution L-P complex conformationally rearranges, and the priming/intrusion loops are likely in RNA elongation conformations different from previous structures. The P protein adopts a unique tetrameric organization and interacts with L protein. Our findings indicate that NDV L-P complex represents elongation state distinct from previous structures. Our work greatly advances the understanding of Paramyxoviridae RNA synthesis, revealing how initiation/elongation alternates, providing clues for identifying therapeutic targets against Paramyxoviridae.

Efficacy and Safety of a Booster Vaccination with Two Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: Results of a Double-Blind, Randomized, Placebo-Controlled, Phase 3 Trial in Abu Dhabi.

IMPORTANCE: The protective efficacy of COVID-19 vaccinations has declined over time such that booster doses are required. OBJECTIVE: To evaluate the efficacy and adverse events of booster doses of two inactivated COVID-19 vaccines. DESIGN: This is a double-blind, randomized, placebo-controlled phase 3 trial aiming to evaluate the protective efficacy, safety, and immunogenicity of inactivated SARS-CoV-2 vaccine (Vero cells) after inoculation with booster doses of inactivated COVID-19 vaccine. SETTING: Healthy volunteers were recruited in an earlier phase 3 trial of two doses of inactivated vaccine. The participants in Abu Dhabi maintained the blind state of the trial and received a booster dose of vaccine or placebo at least six months after the primary immunization. PARTICIPANTS: Adults aged 18 and older with no history of SARS-CoV, SARS-CoV-2, or Middle East respiratory syndrome infection (via onsite inquiry) were screened for eligibility. INTERVENTIONS: A total of 9370 volunteers were screened and randomly allocated, of which 61 voluntarily withdrew from the screening stage without booster inoculation; 9309 received the booster vaccination, with 3083 in the WIV04 group, 3150 in the HB02 group, and 3076 in the alum-only group. Further, 5µg and 4µg of inactivated SARS-CoV-2 virion was adsorbed into aluminum hydroxide in a 0.5 mL aqueous suspension for WIV04 and HB02 vaccines. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 from 14 days after the booster vaccine in the per-protocol population. A safety analysis was performed in the intention-to-treat population. RESULTS: Symptomatic COVID-19 was identified in 36 participants in the WIV04 group (9.9 [95% CI, 7.2-13.8] per 1000 person-years), 28 in the HB02 group (7.6 [95% CI, 5.2-11.0] per 1000 person-years), and 193 in the alum-only group (55.2 [95% CI, 47.9-63.5] per 1000 person-years), resulting in a vaccine efficacy of 82.0% (95% CI, 74.2-87.8%) for WIV04 and 86.3% (95% CI, 79.6-91.1%) for HB02. One severe case of COVID-19 occurred in the alum-only group, and none occurred in the vaccine groups. Adverse reactions within seven days after vaccination occurred in 29.4% to 34.3% of participants in the three groups. Serious adverse events were rare and not related to vaccines (WIV04: 17 [0.5%]; HB02: 11 [0.4%]; alum only: 40 [1.3%]). CONCLUSIONS AND RELEVANCE: This study evaluated the safety of the booster dose, which was well tolerated by participants. Booster doses given over six months after the completion of primary immunization can help to provide more-effective protection against COVID-19 in healthy people 18 years of age or older. At the same time, the anti-SARS-CoV-2 antibodies produced by the two groups of experimental vaccines exhibited extensive cross-neutralization against representative SARS-CoV-2 variants. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT04510207).

Toxicity of transition metal nanoparticles: A review of different experimental models in the gastrointestinal tract.

The development of nanotechnology is becoming a major trend nowadays. Nanoparticles (NPs) have been widely used in fields including food, biomedicine, and cosmetics, endowing NPs more opportunities to enter the human body. It is well-known that the gut microbiome plays a key role in human health, and the exposure of intestines to NPs is unavoidable. Accordingly, the toxicity of NPs has attracted more attention than before. This review mainly highlights recent advances in the evaluation of NPs' toxicity in the gastrointestinal system from the existing cell-based experimental models, such as the original mono-culture models, co-culture models, three-dimensional (3D) culture models, and the models established on microfluidic chips, to those in vivo experiments, such as mice models, Caenorhabditis elegans models, zebrafish models, human volunteers, as well as computer-simulated toxicity models. Owing to these models, especially those more biomimetic models, the outcome of the toxicity of NPs acting in the gastrointestinal tract can get results closer to what happened inside the real human microenvironment.

The microstructural abnormalities of cingulum was related to patients with mild cognitive impairment: a diffusion kurtosis imaging study.

OBJECTIVE: Our study aimed to investigate the correlations between microstructural changes of cingulum and patients with mild cognitive impairment (MCI) by diffusion kurtosis imaging (DKI) technique. METHOD: A total of 104 patients with cerebral small vessel diseases (cSVD) were retrospectively enrolled in this study. According to Montreal Cognitive Assessment Scale (MoCA) scores, these patients were divided into MCI group (n = 59) and non-MCI group (n = 45). The general clinical data was collected and analyzed. The regions of interests (ROIs) were selected for investigation in cingulum. The values of DKI parameters were measured in each ROI and compared between the two groups, the correlations between DKI parameters and MoCA scores were examined. RESULTS: Compared to non-MCI group, MCI patients had more severe white matter hyperintensities (WMHs) (P = 0.038) and lower MoCA scores (P < 0.01). MCI patients showed significantly decreased fractional anisotropy (FA), axial kurtosis (AK), mean kurtosis (MK), radial kurtosis (RK), and kurtosis fractional anisotropy (KFA) in the left cingulum in the cingulated cortex (CgC) region (all P < 0.0125). In the left CgC region, FA, AK, MK, RK, and KFA were positively correlated with MoCA scores (r = 0.348, 0.409, 0.310, 0.441, 0.422, all P < 0.001). Meanwhile, FA, AK, MK, RK, and KFA were also positively correlated with MoCA scores (r = 0.338, 0.352, 0.289, 0.380, 0.370, all P < 0.001) in the right CgC region. CONCLUSION: DKI technique could be used to explore the microstructural changes of cingulum in MCI patients and DKI-derived parameters might be feasible to evaluate MCI patients.

Study on Self-Humidification in PEMFC with Crossed Flow Channels and an Ultra-Thin Membrane.

In this study, a 3D model of a proton exchange membrane fuel cell (PEMFC) with crossed channels and an ultra-thin membrane is developed to investigate the feasibility of self-humidification; experiments utilizing a PEMFC stack with identical configurations are conducted to validate the simulation results and further investigate the effects of various operating conditions (OCs) on self-humidification. The results indicate that the crossed flow channel leads to enhanced uniformity of water distribution, resulting in improved cell performance under low/no humidification conditions. External humidifiers for the anode can be removed since the performance difference is negligible (≤3%) between RHa = 0% and 100%. Self-humidification can be achieved in the stack at 90 °C or below with an appropriate back pressure among 100-200 kPa. As the current density increases, there is a gradual convergence and crossing of the voltage at low RH with that at high RH, and the crossover points are observed at 60-80 °C with suitable pressure when successful self-humidification is achieved. Below the current density of the point, the stack's performance is inferior at lower RH due to membrane unsaturation, and conversely, the performance is inferior at higher RH due to flooding; this current density decreases with higher pressure and lower temperature.

The Fingerprint Identification of Asphalt Aging Based on 1H-NMR and Chemometrics Analysis.

In this study, the chemical structure of asphalt aging was analyzed and identified based on 1H-NMR quantitative technology and chemometrics analysis. The characteristic full component information of 30 samples before and after aging from 5 different oil sources was measured by 1H-NMR, and the results were converted into a data matrix. This study used PCA, HAC, OPLS-DA, and Fisher discriminant analysis to evaluate the change rules of the chemical composition of asphalt from different oil sources after aging. The results showed that the 1H-NMR spectra of 30 asphalt samples were very similar, and hydrogen could be divided into 4 categories according to the chemical shift: HA, Hα, Hß, and Hγ. The shapes of 1H-NMR of asphalt samples from different oil sources showed slight differences, while the shapes of the 1H-NMR spectra of asphalt samples with different aging degrees from the same oil source was basically the same. The results of PCA and HAC analysis showed that the samples of the same asphalt and asphalt with similar oil sources before and after aging were still in the same category, and the spatial distance was very close, while the spatial distance of asphalts from different oil sources was very different. The Fisher discriminant function established by PCA and HAC can be used to distinguish asphalt samples from different oil sources with an accuracy of up to 100%.

Two-Dimensional Simulation of the Freezing Characteristics in PEMFCs during Cold Start Considering Ice Crystallization Kinetics.

Cold start is one of the major issues that hinders the commercialization of polymer electrolyte membrane fuel cells (PEMFCs). In this study, a 2D transient multi-physics model is developed to simulate the cold start processes in a PEMFC. The phase change between water vapor, liquid water, and ice in the catalyst layers (CLs), micro porous layer (MPLs), and gas diffusion layers (GDLs) is also investigated, particularly the effect of ice crystallization kinetics when supercooled liquid water changes into ice. The factors affecting the different operating conditions and structural features of the membrane electrode assembly (MEA) are investigated. The results show that when the start temperature is -20 °C or higher, ice formation is delayed and the formation rate is decreased, and supercooled liquid water permeates from the CL into the MPL. For an MEA with relatively high hydrophobicity, the water permeation rate is high. These results can enable a PEMFC to start at subzero temperatures. The effect of ice crystallization kinetics is negligible when the fuel cell is started at -30 °C or below.

CYP4F2-Catalyzed Metabolism of Arachidonic Acid Promotes Stromal Cell-Mediated Immunosuppression in Non-Small Cell Lung Cancer.

SIGNIFICANCE: The identification of a role for CYP4F2-dependent metabolism in driving immune evasion in non-small cell lung cancer reveals a strategy to improve the efficacy of immunotherapy by inhibiting CYP4F2. See related article by Van Ginderachter, p. 3882.

Vaccination with Omicron Inactivated Vaccine in Pre-vaccinated Mice Protects against SARS-CoV-2 Prototype and Omicron Variants.

In response to the fast-waning immune response and the great threat of the Omicron variant of concern (VOC) to the public, we report the pilot-scale production of an inactivated Omicron vaccine candidate that induces high levels of neutralizing antibody titers to protect against the Omicron virus. Here, we demonstrate that the inactivated Omicron vaccine is safe and effective in recalling immune responses to the HB02, Omicron, and Delta viruses after one or two doses of BBIBP-CorV. In addition, the efficient productivity and good genetic stability of the manufactured inactivated vaccine is proved. These results support the further evaluation of the Omicron vaccine in a clinical trial.

Structural Insight into Terminal Galactose Recognition by Two Non-HBGA Binding GI.3 Noroviruses.

Human noroviruses (huNoVs) cause epidemic acute gastroenteritis using histo-blood group antigens (HBGAs) as host receptors or attachment factors to initiate an infection. While most huNoVs have been shown to bind HBGAs, some known clinical isolates, such as GI.3 DSV and VA115, do not recognize any HBGAs and thus the molecular mechanism behind their infections remains elusive. In this study, we provided both phenotypic and structural evidence to show that huNoV DSV and VA115 recognize a group of glycans with terminal galactoses as ligands. First, through glycan array we found that both DSV and VA115 protruding (P) domain proteins bound two oligosaccharides that share common terminal galactoses. Then, by determination of the crystal structures of DSV/VA115 P proteins in complex with Galα1-3Galß1-4Glc and/or NA2 N-Glycan, respectively, we showed that the terminal galactose is the main saccharide recognized by the two viral proteins. Our data demonstrated that GI huNoVs can interact with non-HBGA glycans through their conserved galactose binding site, shedding light on the mechanism of huNoV adaptation through recognizing new glycan receptors to facilitate their widespread nature in human population. These findings are also of significance in strategy development for huNoV control and prevention, as well as development of antiviral drugs. IMPORTANCE Human noroviruses (huNoVs) are the most important viral pathogens causing epidemic acute gastroenteritis worldwide. Previous studies indicated that histo-blood group antigens (HBGAs) are critical host-susceptibility factors affecting huNoV host susceptibility, host range, and probably prevalence. However, certain huNoVs, such as GI.3 DSV and VA115, do not recognize any HBGAs. This implies that other unknown host factors might exist and the molecular mechanism underlying their host receptor recognition or attachment remains elusive. In this study, we found that purified capsid protruding domain proteins from two GI.3 huNoVs specifically bind two glycans that contain a common terminal galactose. We solved the crystal structures of the complexes at atomic resolution and validated the vital amino acids involved in glycan recognition. Our findings elucidate the mechanism of GI.3 huNoV-non-HBGA glycan interaction, which explains why GI.3 virus strains could not bind human HBGAs, paving a way to the prevention and treatment of huNoV-associated diseases.