Evaluation of the shear stability of aerobic granular sludge from a pilot-scale membrane bioreactor: Establishment of a quantitative method.

This work established a quantitative method to access the shear stability of aerobic granular sludge (AGS) and validated its feasibility by using the mature AGS from a pilot-scale (50 tons/day) membrane bioreactor (MBR) for treating real municipal wastewater. The results showed that the changing rate (ΔS) of the peak area (S) of granule size distribution (GSD) exhibited an exponential relationship (R2≥0.76) with the shear time (y=a-b·cx), which was a suitable indicative index to reflect the shear stability of different AGS samples. The limiting granule size (LGS) was defined and proposed to characterize the equilibrium size for AGS after being sheared for a period of time, whose value in terms of Dv50 showed high correlation (R2=0.92) with the parameter a. The free Ca2+ (28.44-34.21 mg/L) in the influent specifically interacted with polysaccharides (PS) in the granule's extracellular polymeric substance (EPS) as a nucleation site, thereby inducing the formation of Ca precipitation to enhance its Young's modulus, while Ca2+ primarily interacted with PS in soluble metabolic product (SMP) during the initial granulation process. Furthermore, the Young's modulus significantly affected the parameter a related to shear stability (R2=0.99). Since the parameter a was more closely related (R2=1.00) to ΔS than that of the parameter b or c, the excellent correlation (R2=0.99) between the parameter a and the wet density further verified the feasibility of this method.

Relationship between indexed surgery and postcardiotomy extracorporeal life support outcomes.

OBJECTIVES: Veno-arterial extracorporeal life support (V-A ECLS) is increasingly being utilized for postcardiotomy shock (PCS), though data describing the relationship between type of indexed operation and outcomes are limited. This study compared V-A ECLS outcomes across four major cardiovascular surgical procedures. METHODS: This was a single-center retrospective study of patients who required V-A ECLS for PCS between 2015 and 2022. Patients were stratified by the type of indexed operation, which included aortic surgery (AoS), coronary artery bypass grafting (CABG), valve surgery (Valve), and combined CABG and valve surgery (CABG + Valve). Factors associated with postoperative outcomes were assessed using logistic regression. RESULTS: Among 149 PCS patients who received V-A ECLS, there were 35 AoS patients (23.5%), 29 (19.5%) CABG patients, 59 (39.6%) Valve patients, and 26 (17.4%) CABG + Valve patients. Cardiopulmonary bypass times were longest in the AoS group (p < 0.01). Regarding causes of PCS, AoS patients had a greater incidence of ventricular failure, while the CABG group had a higher incidence of ventricular arrhythmia (p = 0.04). Left ventricular venting was most frequently utilized in the Valve group (p = 0.07). In-hospital mortality was worst among CABG + Valve patients (p < 0.01), and the incidence of acute kidney injury was highest in the AoS group (p = 0.03). In multivariable logistic regression, CABG + Valve surgery (odds ratio (OR) 4.20, 95% confidence interval 1.30-13.6, p = 0.02) and lactate level at ECLS initiation (OR, 1.17; 95% CI, 1.06-1.29; p < 0.01) were independently associated with mortality. CONCLUSIONS: We demonstrate that indications, management, and outcomes of V-A ECLS for PCS vary by type of indexed cardiovascular surgery.

Study on membrane fouling mechanisms and mitigation strategies in a pilot-scale anaerobic membrane bioreactor (P-AnMBR) treating digestate.

Anaerobic Membrane Bioreactor (AnMBR) are employed for solid-liquid separation in wastewater treatment, enhancing process efficiency of digestion systems treating digestate. However, membrane fouling remains a primary challenge. This study operated a pilot-scale AnMBR (P-AnMBR) to treat high-concentration organic digestate, investigating system performance and fouling mechanisms. P-AnMBR operation reduced acid-producing bacteria and increased methane-producing bacteria on the membrane, preventing acid accumulation and ensuring stable operation. The P-AnMBR effectively removed COD and VFA, achieving removal rates of 82.3 % and 92.0 %, respectively. Higher retention of organic nitrogen and lower retention of ammonia nitrogen were observed. The membrane fouling consisted of organic substances (20.3 %), predominantly polysaccharides, and inorganic substances (79.7 %), primarily Mg ions (10.1 %) and Ca ions (4.5 %). To reduce the increased transmembrane pressure (TMP) caused by fouling (a 10.6-fold increase in filtration resistance), backwash frequency experiment was conducted. It revealed a 30-min backwash frequency minimized membrane flux decline, facilitating recovery to higher flux levels. The water produced amounted to 70.3 m³ over 52 days. The research provided theoretical guidance and practical support for engineering applications, offering practical insights for scaling up P-AnMBR.

Advanced electrochemical membrane technologies for near-complete resource recovery and zero-discharge of urine: Performance optimization and evaluation.

The depletion of nutrient sources in fertilizers demands a paradigm shift in the treatment of nutrient-rich wastewater, such as urine, to enable efficient resource recovery and high-value conversion. This study presented an integrated bipolar membrane electrodialysis (BMED) and hollow fiber membrane (HFM) system for near-complete resource recovery and zero-discharge from urine treatment. Computational simulations and experimental validations demonstrated that a higher voltage (20 V) significantly enhanced energy utilization, while an optimal flow rate of 0.4 L/min effectively mitigated the negative effects of concentration polarization and electro-osmosis on system performance. Within 40 min, the process separated 90.13% of the salts in urine, with an energy consumption of only 8.45 kWh/kgbase. Utilizing a multi-chamber structure for selective separation, the system achieved recovery efficiencies of 89% for nitrogen, 96% for phosphorus, and 95% for potassium from fresh urine, converting them into high-value products such as 85 mM acid, 69.5 mM base, and liquid fertilizer. According to techno-economic analysis, the cost of treating urine using this system at the lab-scale was $6.29/kg of products (including acid, base, and (NH4)2SO4), which was significantly lower than the $20.44/kg cost for the precipitation method to produce struvite. Excluding fixed costs, a net profit of $18.24/m3 was achieved through the recovery of valuable products from urine using this system. The pilot-scale assessment showed that the net benefit amounts to $19.90/m3 of urine, demonstrating significant economic feasibility. This study presents an effective approach for the near-complete resource recovery and zero-discharge treatment of urine, offering a practical solution for sustainable nutrient recycling and wastewater management.

Stratified structure of membrane clogs observed in full scale cross-flow tubular ultrafiltration (UF) system: Fouling characterization and a proposed two-stage formation mechanism.

Membrane fouling remains a significant challenge in wastewater treatment, hindering both efficiency and lifespan. This study reports a distinct phenomenon of stratified membrane clogging observed in a full-scale cross-flow tubular ultrafiltration (UF) system treating sludge anaerobic digestion (AD) reject water. The distinct stratified structure, comprising inner and outer layers within the cake layer, has not been previously described. This research involved characterizing the filtration performance, analyzing membrane clog composition, and proposing a two-stage formation mechanism for the stratified clogs. It was revealed that higher inorganic and lower organic content in the outer layer compared to the inner layer. Acid and alkali treatments demonstrated the effectiveness of combined cleaning strategies. A mathematical model was developed to determine the critical conditions for stratified clog formation, influenced by membrane flux and cross-flow velocity (CFV). It is proposed that outer layer forms through long-term selective deposition, while the inner layer results from short-term dewatering within limited tubular space. High CFV (>2.5 m/s) prevents inner layer formation. Critical conditions for stratification occur at a flux of 18 L/m2/h with a CFV of 0.1 m/s or 65 L/m2/h with a CFV of 0.35 m/s. This study contributes a novel understanding of stratified membrane clogging, proposing a two-stage formation mechanism and identifying critical conditions, which provides insights for effective fouling control strategies and maintenance of operational efficiency for membrane systems.

Maintaining quality of postharvest green pepper fruit using melatonin by regulating membrane lipid metabolism and enhancing antioxidant capacity.

Green pepper quality often deteriorates during storage because of membrane lipid damage and oxidative stress. This study investigated the effects of exogenous melatonin (MT) on green pepper storage quality, membrane lipids, and antioxidant metabolism. The results showed that MT increased the activities of superoxide dismutase, catalase, ascorbate peroxidase, peroxidase, monodehydroascorbate reductase, and dehydroascorbate reductase in green peppers compared to the control group. It upregulated expression of multiple enzymes; reduced accumulation of reactive oxygen species such as dehydroascorbic acid, H2O2, and O2.-; and maintained high ascorbic acid, glutathione, coenzyme II, and nicotinamide adenine dinucleotide while reducing oxidized glutathione levels. In addition, MT decreased lipoxygenase and phospholipase D activities, downregulated ReLOX and RePLD expression, and delayed the degradation of phosphatidylcholine, phosphatidylethanolamine, and oleic, linoleic, and linolenic acids in green peppers. These results suggest that MT helps to improve the chilling injury and quality of green peppers and extends shelf life.

Effect of an evidence-based early rehabilitation program on adult patients with venovenous extracorporeal membrane oxygenation: A cohort study.

OBJECTIVES: To assess the efficacy of early rehabilitation program for VV-ECMO patients and observe the influence on the respiratory and skeletal muscles. DESIGN: A cohort study. SETTING: The study was conducted with VVECMO patients in a comprehensive ICU with 32 beds. MAIN OUTCOME MEASURES: Ultrasound measurements were performed on each patients on day 1, 4, 7, 10, and 14, including diaphragmatic excursion (DE), diaphragmatic thickening fraction (DTF), intercostal muscle thickening fraction (ICMTF), thickness of the rectus femoris (RF), thickness of vastus intermedius (VI), and rectus femoris cross-sectional area (RF-CSA). Data on basic characteristics, results of ultrasound measurements, patients outcomes and adverse events were collected. RESULTS: 22 patients received usual rehabilitation measures were set as the control group and 23 patients underwent early rehabilitation program were set as the study group. There were no differences in diaphragmatic excursion, diaphragmatic thickening fraction, intercostal muscle thickening fraction, thickness of rectus femoris, thickness of vastus intermedius, rectus femoris cross-sectional area between two groups on day 1 after VV-ECMO treatment (P > 0.05). The variation of diaphragmatic thickening fraction and intercostal muscle thickening fraction decreased on the day 7 and 14 after treatment (P < 0.05). The variation of vastus intermedius thickness and rectus femoris cross-sectional area in the study group was less compared with those in the control group on day 4, 7, 10 and 14. The ECMO duration in the study group was shorter than that in the control group (12.00 [10.00-16.25] days vs. 8.00 [6.00-12.25] days, P = 0.002), but there was no difference in the duration of mechanical ventilation. CONCLUSION: Early rehabilitation program can ameliorate muscle atrophy. We recommend implementation of our rehabilitation program in VV-ECMO patients. This program can improve skeletal muscle atrophy and dysfunction in patients with VV-ECMO effectively and perhaps improve quality of life for patients in the future. IMPLICATIONS FOR CLINICAL PRACTICE: Early rehabilitation program put higher demands bedside nurses. It requires them to observe conditions of VVECMO patients closely, assess the feasibility of rehabilitation promptly, and monitor for any adverse reactions. Ultrasound measurement is a noninvasive and useful tool to assess muscle atrophy in ICU patients. Early rehabilitation program can improve skeletal muscle atrophy and dysfunction in patients with VV-ECMO effectively.

Comparative analysis of oxygenator dysfunction in polymethylpentene oxygenators: A pilot study.

INTRODUCTION: Polymethylpentene (PMP) oxygenators serve as the primary oxygenator type utilized for ECMO. With the number of PMP oxygenators available, it has become increasingly important to determine differences among each oxygenator type that can lead to varying metrics of oxygenator dysfunction. METHODS: This study was a retrospective, single-center analysis of adult patients supported on ECMO between December 2020 to December 2021 with varying PMP oxygenators including the Medtronic Nautilus Smart (Minneapolis, MA), the Eurosets AMG PMP (Medolla, Italy) and Getinge Quadrox-iD and the Getinge Cardiohelp HLS Module Advanced System (Gothenberg, Sweden). RESULTS: A total of 19 patients were included in our study. 10 patients (52.6%) were supported with a Medtronic Nautilus Smart oxygenator, 5 patients (26.3%) were supported with an Eurosets AMG PMP Oxygenator, and 4 patients (21.1%) were supported with either a Getinge Quadrox-iD oxygenator or Getinge Cardiohelp HLS system. Patients supported with Eurosets AMG PMP oxygenators experienced higher resistance and lower post-oxygenator PaO2 in comparison to other cohorts (p < .02 and < .002 respectively). There was no difference in measured oxygen transfer between cohorts (p = .667). Two patients, both supported by Eurosets AMG PMP, experienced oxygenator failure (p = .094). CONCLUSION: Radial flow oxygenators are prone to higher resistance and lower post-oxygenator PaO2when compared to transverse flow oxygenators. Future larger multicenter studies are required to fully discern the differences between flow-varying polymethylpentene oxygenators and their appropriate cutoffs for oxygenator dysfunction.

Prostate-Specific Membrane Antigen PET/CT-Guided, Metastasis-Directed Radiotherapy for Oligometastatic Castration-Resistant Prostate Cancer.

Systemic treatments for metastatic castration-resistant prostate cancer (mCRPC) include androgen deprivation therapy, androgen receptor pathway inhibitors, chemotherapy, and radiopharmaceuticals, all of which have associated toxicity. Prostate-specific membrane antigen (PSMA) PET/CT allows for higher sensitivity in detecting metastatic disease than is possible with conventional imaging. We hypothesized that PSMA PET/CT-guided, metastasis-directed radiotherapy may offer durable disease control with low toxicity rates in patients with mCRPC who have a limited number of metastases. Methods: We retrospectively screened 5 prospective PSMA PET/CT studies for patients with mCRPC who had up to 5 sites of oligorecurrent or oligoprogressive disease on PSMA PET/CT and subsequently received definitive-intent, metastasis-directed radiotherapy to all new or progressing sites with concurrent androgen deprivation therapy. Progression-free survival, freedom from new lines of systemic therapy, and overall survival (OS) were calculated from the start of metastasis-directed radiotherapy using Kaplan-Meier analysis. Biochemical response was defined as at least a 50% decrease in prostate-specific antigen 6 mo after the start of treatment. Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 5. Results: Twenty-four patients met the inclusion criteria with a median follow-up of 33.8 mo (interquartile range, 27.6-45.1 mo). Between October 2017 and April 2023, 11 patients (45.8%) had 1 treated site, 10 patients (41.7%) had 2, and 3 patients (12.5%) had 3. Five sites were prostate or prostate bed, 15 were nodal, 19 were osseous, and 1 was visceral. Seventeen patients (70.8%) continued their preexisting systemic therapy, whereas 7 (29.2%) started a new systemic therapy. Median progression-free survival was 16.4 mo (95% CI, 9.8-23.0 mo). The biochemical response rate was 66.7%. Median freedom from a new line of systemic therapy was 29.0 mo (95% CI, 7.6-50.4 mo). Median OS was not reached. The 2- and 4-y OS rates were 91.1% (95% CI, 79.3%-100%) and 68.8% (95% CI, 45.1%-92.5%), respectively. Grade 2 and grade 3 or higher toxicity rates were 4.2% and 0%, respectively. Conclusion: PSMA PET/CT-guided, metastasis-directed radiotherapy appears to offer durable disease control with low toxicity rates for oligometastatic castration-resistant prostate cancer. Further prospective studies are needed to compare metastasis-directed radiotherapy with systemic therapy versus systemic therapy alone and PSMA PET/CT-guided versus conventional imaging-guided radiotherapy.

Subcellular expression of CD30 in cutaneous mastocytosis-An important factor for targeted treatment.

BACKGROUND: The subcellular distribution of CD30 on mast cells and the presence of eosinophils in cutaneous mastocytosis require further investigation, especially as the cell surface expression of CD30 is critical for the therapeutic response of systemic mastocytosis to brentuximab vedotin. OBJECTIVE: Investigation of 147 biopsy specimens from 143 patients with cutaneous mastocytosis for mast cell density and distribution, frequency of CD30 expression, CD30 staining patterns, and presence and distribution of eosinophils. Correlation with clinical patterns. METHODS: Retrospective multicenter immunohistochemical study of CD30 expression, eosinophils and basic clinical data in cutaneous mastocytosis. RESULTS: CD30 expression was found in all samples (cut-off: ≥1%), whereby the staining was predominantly cytoplasmic in 99% of the samples. Additional membrane staining was detected in 62% of the samples. Surface expression of CD30 was more common in biopsy specimens with a high mast cell burden and in biopsy specimens with a higher CD30 expression rate. Eosinophils were admixed in 58% of the samples. Females and older patients showed a trend of a lower mast cell burden. LIMITATIONS: Retrospective study on formalin-fixed and paraffin-embedded tissue without functional analysis. CONCLUSION: Most cases of cutaneous mastocytosis show cell surface expression of CD30 expression and is, therefore, in principle, accessible for therapy with antibodies against CD30, provided the overall situation of the patient warrants.

Targeting endocytosis to sensitize cancer cells to programmed cell death.

Evading programmed cell death (PCD) is a hallmark of cancer that allows tumor cells to survive and proliferate unchecked. Endocytosis, the process by which cells internalize extracellular materials, has emerged as a key regulator of cell death pathways in cancer. Many tumor types exhibit dysregulated endocytic dynamics that fuel their metabolic demands, promote resistance to cytotoxic therapies, and facilitate immune evasion. This review examines the roles of endocytosis in apoptotic resistance and immune escape mechanisms utilized by cancer cells. We highlight how inhibiting endocytosis can sensitize malignant cells to therapeutic agents and restore susceptibility to PCD. Strategies to modulate endocytosis for enhanced cancer treatment are discussed, including targeting endocytic regulatory proteins, altering membrane biophysical properties, and inhibiting Rho-associated kinases. While promising, challenges remain regarding the specificity and selectivity of endocytosis-targeting agents. Nonetheless, harnessing endocytic pathways represents an attractive approach to overcome apoptotic resistance and could yield more effective therapies by rendering cancer cells vulnerable to PCD. Understanding the interplay between endocytosis and PCD regulation is crucial for developing novel anticancer strategies that selectively induce tumor cell death.

Scenedesmus sp. as a phycoremediation agent for heavy metal removal from landfill leachate in a comparative study: batch, continuous, and membrane bioreactor (MBR).

Improper disposal of municipal solid waste led to the release of heavy metals into the environment through leachate accumulation, causing a range of health and environmental problems. Phycoremediation, using microalgae to remove heavy metals from contaminated water, was investigated as a promising alternative to traditional remediation methods. This study explored the potential of Scenedesmus sp. as a phycoremediation agent for heavy metal removal from landfill leachate. The study was conducted in batch, continuous, and membrane bioreactor (MBR). In the batch system, Scenedesmus sp. was added to the leachate and incubated for 15 days before the biomass was separated from the suspension. In the continuous system, Scenedesmus sp. was cultured in a flow-through system, and the leachate was continuously fed into the system with flow rates measured at 120, 150, and 180 mL/h for 27 days. The MBR system was similar to the continuous system, but it incorporated a membrane filtration step to remove suspended solids from the treated water. The peristaltic pump was calibrated to operate at five different flow rates: 0.24 L/h, 0.30 L/h, 0.36 L/h, 0.42 L/h, and 0.48 L/h for the MBR system and ran for 24 h. The results showed that Scenedesmus sp. was effective in removing heavy metals such as lead (Pb), cobalt (Co), chromium (Cr), nickel (Ni), and zinc (Zn) from landfill leachate in all three systems. The highest removal efficiency was observed for Ni, with a removal of 0.083 mg/L in the MBR and 0.068 mg/L in batch mode. The lowest removal efficiency was observed for Zn, with a removal of 0.032 mg/L in the MBR, 0.027 mg/L in continuous mode, and 0.022 mg/L in batch mode. The findings depicted that the adsorption capacity varied among the studied metal ions, with the highest capacity observed for Ni (II) and the lowest for Zn (II), reflecting differences in metal speciation, surface charge interactions, and affinity for the adsorbent material. These factors influenced the adsorption process and resulted in varying adsorption capacities for different metal ions. The study also evaluated the biomass growth of Scenedesmus sp. and found that it was significantly influenced by the initial metal concentration in the leachate. The results of this study suggest that Scenedesmus sp. can be used as an effective phycoremediation agent for removing heavy metals from landfill leachate.

Nanosecond pulse electric field treatment initiates mitochondrial apoptosis pathway by inducing mitochondrial morphological changes in myocardial cells.

BACKGROUND: As an emerging myocardial ablation technique, the mechanism of nanosecond pulse electric field (nsPEF) ablation is currently less studied. Mitochondria are one of the important membrane structure organelles in cells, participating in numerous life activities within the cell. This study aimed to explore the morphological changes of mitochondria in living cells following nsPEF treatment. METHODS: Myocardial cells were treated with a self-made solid-state LTD high-voltage nanosecond pulse generator with a pulse width of 100 ns for 80 times. The changes in mitochondrial membrane potential and cell apoptosis in rat myocardial cells after nsPEFs were investigated using JC-1 assay kit, apoptosis double staining assay kit, and mitochondrial fluorescence probe. RESULTS: The results showed that after nsPEF treatment, the mitochondrial membrane potential decreased, apoptosis increased, and the average mitochondrial area decreased from 0.48 µm2 in live myocardial cells to 0.16 µm2. The average circumference ranges from 3.17 µm dropped to 1.60 µm. The shape factor decreased from 1.92 to 1.41. The aspect ratio has decreased from 2.16 to 1.59. nsPEF treatment induces changes in the morphology of myocardial cell mitochondria. CONCLUSIONS: Based on the results of mitochondrial membrane potential and apoptosis, it can be inferred that under this equipment and parameter conditions, nsPEF treatment first causes changes in mitochondrial morphology, and then initiates the mitochondrial apoptosis pathway, which may provide experimental basis for investigating the potential mechanism of nsPEF ablation of myocardial cells.

Revealing the Structural Intricacies of Biomembrane-Interfaced Emulsions with Small- and Ultra-Small-Angle Neutron Scattering.

Utilizing cell membranes from diverse cell types for biointerfacing has demonstrated significant advantages in enhancing colloidal stability and incorporating biological properties, tailored specifically for various biomedical applications. However, the structures of these materials, particularly emulsions interfaced with red blood cell (RBC) or platelet (PLT) membranes, remain an underexplored area. This study systematically employs small- and ultra-small-angle neutron scattering (SANS and USANS) with contrast variation to investigate the structure of emulsions containing perfluorohexane within RBC (RBC/PFH) and PLT membranes (PLT/PFH). The findings reveal that the scattering length density of RBC and PLT membranes is 1.5 × 10-6 Å-2, similar to 30% (w/w) deuterium oxide. Using this solvent as a cell membrane-matching medium, estimated droplet diameters are 770 nm (RBC/PFH) and 1.5 µm (PLT/PFH), based on polydispersed sphere model fitting. Intriguingly, calculated patterns and invariant analysis reveal native droplet architectures featuring entirely liquid PFH cores, differing significantly from the observed bubble-droplet core system in electron microscopy. This highlights the advantage of SANS and USANS in differentiating genuine colloidal structures in complex dispersions. In summary, this work underscores the pivotal role of SANS and USANS in characterizing biointerfaced colloids and in uncovering novel colloidal structures with significant potential for biomedical applications and clinical translation.

Cytosolic serpins act in a cytoprotective feedback loop that limits ESX-1-dependent death of Mycobacterium marinum-infected macrophages.

Serine protease inhibitors (serpins) constitute the largest family of protease inhibitors expressed in humans, but their role in infection remains largely unexplored. In infected macrophages, the mycobacterial ESX-1 type VII secretion system permeabilizes internal host membranes and causes leakage into the cytosol of host DNA, which induces type I interferon (IFN) production via the cyclic GMP-AMP synthase (cGAS) and stimulator of IFN genes (STING) surveillance pathway, and promotes infection in vivo. Using the Mycobacterium marinum infection model, we show that ESX-1-mediated type I IFN signaling in macrophages selectively induces the expression of serpina3f and serpina3g, two cytosolic serpins of the clade A3. The membranolytic activity of ESX-1 also caused leakage of cathepsin B into the cytosol where it promoted cell death, suggesting that the induction of type I IFN comes at the cost of lysosomal rupture and toxicity. However, the production of cytosolic serpins suppressed the protease activity of cathepsin B in this compartment and thus limited cell death, a function that was associated with increased bacterial growth in infected mice. These results suggest that cytosolic serpins act in a type I IFN-dependent cytoprotective feedback loop to counteract the inevitable toxic effect of ESX-1-mediated host membrane rupture. IMPORTANCE: The ESX-1 type VII secretion system is a key virulence determinant of pathogenic mycobacteria. The ability to permeabilize host cell membranes is critical for several ESX-1-dependent virulence traits, including phagosomal escape and induction of the type I interferon (IFN) response. We find that it comes at the cost of lysosomal leakage and subsequent host cell death. However, our results suggest that ESX-1-mediated type I IFN signaling selectively upregulates serpina3f and serpina3g and that these cytosolic serpins limit cell death caused by cathepsin B that has leaked into the cytosol, a function that is associated with increased bacterial growth in vivo. The ability to rupture host membranes is widespread among bacterial pathogens, and it will be of interest to evaluate the role of cytosolic serpins and this type I IFN-dependent cytoprotective feedback loop in the context of human infection.

Molecular insights reveal how the glycolipids in cell membrane mitigates nanomaterial's invasion.

Nanomaterial-cellular membrane interaction is crucial for the cytotoxicity of such materials in theoretical investigations. However, previous research often used cellular membrane models with one or few lipid types, which deviates significantly from realistic membrane compositions. Here, employing molecular dynamics (MD) simulations, we investigate the impact of a typical nanomaterial, boron nitride (BN), on a cellular membrane model based on the realistic small intestinal epithelial cell (SIEC) membrane. This membrane contains a complex composition, including abundant glycolipids. Our MD simulations reveal that BN nanosheet can partially insert into the SIEC membrane, maintaining a stable binding conformation without causing obvious structural changes. Dynamic analyses suggest that van der Waals (vdW) interactions drive the binding process between BN and the SIEC membrane. Further simulation of the interaction between BN nanosheet and deglycosylated SIEC membrane confirms that BN nanosheet cause significant structural damage to deglycosylated SIEC membranes, completely inserting into the membrane, extracting lipids, and burying some lipid hydrophilic heads within the membrane interior. Quantitative analyses of mean squared displacements (MSD) of membranes, membrane thicknesses, area per lipid, and order parameters indicate that BN nanosheet causes more substantial damage to deglycosylated SIEC membrane than to intact SIEC membrane. This comparison suggests the molecular mechanism involved in mitigating BN invasion by SIEC membrane that the polysaccharide heads of glycolipids in the SIEC membrane form a significant steric hindrance on membrane surface, not only hindering the insertion of BN, but also resisting the lipid extraction by BN. Free energy calculations further support this conclusion. Overall, our MD simulations not only shed new light into the reduced impact of BN nanosheet on the realistic SIEC membrane but also highlight the importance of glycolipids in protecting cell membranes from nanomaterial invasion, contributing to a deeper understanding of nanomaterial-realistic cell membrane interactions.

Rapid photothermal assay for ultrasensitive point-of-care detection of tumor markers based on a filter membrane.

An ultrasensitive photothermal assay was designed for point-of-care testing (POCT) of tumor markers based on a filter membrane. Firstly, Cu2-xSe was successfully encapsulated in liposome spheres with biotin on the surface and connected to carcinoembryonic antigen (CEA) aptamer with 3'end modified biotin by streptavidin. Secondly, the CEA antibody was successfully modified on the surface of the nitrocellulose membrane through simple incubation. Finally, the assay process was completed using a disposable syringe, and the temperature was recorded using a handheld infrared temperature detector. In the range 0-50 ng mL-1, the temperature change of the nitrocellulose membrane has a strong linear relationship with CEA concentration, and the detection limit is 0.097 ng mL-1. It is worth noting that the entire testing process can be easily performed in 10 min, much shorter than traditional clinical methods. In addition, this method was successfully applied to the quantitative determination of CEA levels in human serum samples with a recovery of 96.2-103.3%. This rapid assay can be performed by "one suction and one push" through a disposable syringe, which is simple to operate, and the excellent sensitivity reveals the great potential of the proposed strategy in the POCT of tumor biomarkers.

Helicobacter pylori Outer Membrane Vesicles: Biogenesis, Composition, and Biological Functions.

Helicobacter pylori has been recognized not only as a causative agent of a spectrum of gastroduodenal diseases including chronic gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer, but also as the culprit in several extra-gastric diseases. However, the association of H. pylori infection with extra-gastric diseases remains elusive, prompting a reevaluation of the role of H. pylori-derived outer membrane vesicles (OMVs). Like other gram-negative bacteria, H. pylori constitutively sheds biologically active OMVs for long-distance delivery of bacterial virulence factors in a concentrated and protected form, averting the need of direct bacterial contact with distant host cells to induce extra-gastric diseases associated with this gastric pathogen. Additionally, H. pylori-derived OMVs contribute to bacterial survival and chronic gastric pathogenesis. Moreover, the immunogenic activity, non-replicable nature, and anti-bacterial adhesion effect of H. pylori OMVs make them a desirable vaccine candidate against infection. The immunogenic potency and safety concerns of the OMV contents are challenges in the development of H. pylori OMV-based vaccines. In this review, we discuss recent advances regarding H. pylori OMVs, focusing on new insights into their biogenesis mechanisms and biological functions.

Comparative study on corneal epithelium healing: effects of crosslinked hyaluronic acid and amniotic membrane extract eye drops in rats.

Introduction: Corneal ulcers are common lesions in both human and veterinary medicine. However, only a few studies have evaluated the efficacy of cross-linked hyaluronic acid (X-HA) eye drops on corneal wound healing. To our knowledge, this is the first study to demonstrate and compare the efficacy of amniotic membrane extract eye drops (AMEED) and X-HA for corneal wound healing in rats. Material and methods: A total of 15 male Wistar rats (30 eyes) were used in this study. Then, 10 eyes were treated with X-HA, AMEED, or 0.9% saline. After general and topical anesthesia, a superficial corneal ulcer was created using a corneal trephine. The defect was further polished with a diamond burr. Three groups of 10 eyes each were treated with either one drop of 0.75% X-HA or AMEED or 0.9% saline (control), administered every 12 h for a duration of 72 h. The median epithelial defect area (MEDA), expressed as a percentage of the total corneal surface, was measured at 0, 12, 24, 36, 48, and 72 h. Re-epithelization time scores were also evaluated. The Kruskal-Wallis test was used to compare median times for re-epithelization and histopathologic scores between groups, while the Friedman test (for paired data) was employed to compare results from the serial analysis of MEDA and vascularization scores between groups. Results: MEDA was not significantly different between X-HA and AMEED. However, MEDA was significantly smaller in the X-HA group compared to the control group at 36 h (2.73 interquartile range (IQR) 5.52% x 9.95 IQR 9.10%, P=0.024) and 48 h (0.00 IQR 0.26% x 6.30 IQR 8.54%, P=0.030). The overall time for re-epithelization was significantly lower in the X-HA group (3.00 IQR 3.00) compared to the AMEED (6.5 IQR 3.00) and control (7.00 IQR 1.00) groups (P=0.035). Vascularization, hydropic degeneration, and epithelial-stromal separation were significantly less observed in samples in the X-HA-treated compared to samples in the AMEED- and saline-treated groups. Significantly more corneal epithelium cells were labeled for caspase3 in samples from the AMEED- and saline-treated groups compared to those from the X-HA-treated group. Discussion: Topical X-HA has been shown to accelerate corneal epithelial healing. AMEED did not decrease corneal re-epithelialization time. X-HA may also potentially be used as an adjunct therapy for treating corneal ulcers in clinical situations.

Determining expression changes of ANO7 and SLC38A4 membrane transporters in colorectal cancer.

Membrane transporters are proteins responsible for facilitating the movement of molecules within biological membranes. They play a vital role in maintaining cellular homeostasis by regulating the transport of nutrients, ions, and other molecules into and out of cells. Our aim is to identify biomarkers in colorectal cancer using membrane transporter proteins. We utilized COAD TCGA data for this purpose. Subsequently, we conducted differential gene analysis and feature selection using membrane transporter proteins. Furthermore, we identified two potential genes, including ANO7 and SLC38A4. To validate the expression profiles of ANO7 and SLC38A4, key genes in this context, RT-qPCR was employed on colorectal cancer samples and adjacent normal tissues. Additionally, utilizing GEPIA2, Kaplan-Meier survival analysis, and cBioPortal, we assessed the status of these genes in various cancers, examining their methylation and mutation patterns. In conclusion, we suggest that ANO7 and SLC38A4 serve as prognostic biomarkers in colorectal cancer.