[Establishment of an Engineered Bacterial Membrane Biomimetic Nanodrug Delivery System and Its Role in the Treatment of Glioma]. / å·¥ç¨‹åŒ–ç»†èŒè†œä»¿ç”Ÿçº³ç±³è¯ç‰©é€’é€ç³»ç»Ÿçš„å»ºç«‹åŠåœ¨è„‘èƒ¶è´¨ç˜¤æ²»ç–—ä¸­çš„ä½œç”¨ç ”ç©¶.

Objective: To develop engineered bacterial membrane biomimetic nanoparticles, Angiopep-2 E. coli membrane (ANG-2 EM)@PDA-PEI-CpG (ANG-2 EM@PPC), for efficient targeted drug delivery in the treatment of glioma, and to provide theoretical and technical support for targeted glioma therapy. Methods: The expression of inaX-N-angiopep-2 engineered bacteria was constructed in the laboratory, and ANG-2 EM was obtained through lysozyme treatment and ultrafiltration centrifugation. ANG-2 EM@PPC was prepared by ultrasonication of bacterial membranes. Western blotting, agarose gel electrophoresis, and transmission electron microscopy (TEM) were used to verify the preparation. Particle size and Zeta potential were measured to investigate the stability of ANG-2 EM@PPC. Regarding cell experiments, CCK-8 assay was performed to determine the effect of ANG-2 EM@PPC on the survival rate of neutrophils. A flow chamber model was designed and constructed, and the uptake efficiency of neutrophils was measured by flow cytometry to investigate the hitchhiking efficiency of ANG 2 EM@PPC on neutrophils in inflammatory environment. Neutrophil death patterns were characterized by fluorescence microscopy, and flow cytometry and Western blotting were performed to examine neutrophil apoptotic bodies and the proportion of apoptotic bodies produced. Regarding animal experiments, a mouse model of in situ glioma was established and the inflammatory environment of tumor tissue was verified. The tumor model mice were divided into three groups, including DiR group, EM@PPC group, and ANG-2 EM@PPC group (all n=3), which were injected with DiR, ANG-2 EM@PDA-PEI-CpG, and EM@PDA-PEI-CpG via the tail vein, respectively (all at 10 mg/kg). Fluorescence images of organs and the brain were used to examine the distribution of the three formulations in vivo and in the brain. The tumor model mice were further divided into PBS group, PDA group, PC group, PPC group, EM@PPC group, and ANG-2 EM@PPC group (all n=4), which were injected with PBS, PDA, PC, PPC, EM@PPC, and ANG-2 EM@PPC injected via the tail vein, respectively (all at 10 mg/kg). Imaging was performed in vivo to observe tumor regression, and the survival rate and body mass of mice were measured to evaluate in vivo pharmacodynamics. TUNEL staining (brain tissue) and HE staining (brain, heart, liver, spleen, lung and kidney tissues) were performed to evaluate the therapeutic effect. Results: The results of TEM showed successful preparation of engineered bacterial membrane biomimetic nanoparticles, with PPC exhibiting a distinct shell-core structure and a shell thickness of about 8.2 nm. Due to the coating of ANG-2 EM, the shell thickness of ANG-2 EM@PPC increased to about 9.6 nm, with a clear bacterial membrane layer on the surface. Stability was maintained for at least one week. ANG-2 EM@PPC had no significant effect on the activity of neutrophils according to the findings from the CCK-8 assay. Flow cytometry showed that ANG-2 EM@PPC uptake is enhanced in activated neutrophils and hitchhiking on neutrophils was more efficient in the stationary state than that in the flowing condition. Compared with the EM@PPC group, the neutrophil hitchhiking ability of the ANG-2 EM@PPC group was enhanced (uptake efficiency 24.9% vs. 31.1%). Fluorescence microscopy showed that ANG-2 EM@PPC changed the death pathway of neutrophils from neutrophil extracellular traps-osis (NETosis) to apoptosis. Western blot confirmed the production of neutrophil apoptotic bodies, and flow cytometry showed that the production rate was as high as 77.7%. Animal experiments showed that there was no significant difference in the distribution of engineered bacterial membrane biomimetic nanoparticles in the organs (heart, liver, spleen, lungs, and kidney) in the DiR group, the EM@PPC gropu, and the ANG-2 EM@PPC group (P>0.05), but there was higher distribution in the brain tissue in EM@PPC and ANG-2 EM@PPC groups compared to the DiR group (P<0.05). Engineered bacterial membrane biomimetic nanoparticles crossed the blood-brain barrier (BBB), and exhibited high affinity to and internalization by neutrophils located in brain tumors. Compared with PBS, PDA, PC, and PPC groups, the survival rate and body mass of mice in the EM@PPC group were improved, tumor fluorescence intensity was weakened, and apoptotic cells were increased. These trends were even more prominent in the ANG-2 EM@PPC group. No abnormality was found in the HE staining of any group. Conclusion: An ANG-2 EM@PPC nanodelivery system with inflammation response characteristics was successfully prepared, capable of crossing BBB and targeting the tumor inflammatory microenvironment to improve the anti-glioma efficacy. This study provides a new drug delivery strategy for glioma treatment and offers a new idea for targeted drug delivery in the non-invasive inflammatory microenvironments in other central nervous system diseases.

Extracellular vesicle-mediated secretion of chlorophyll biosynthetic intermediates in the cyanobacterium Leptolyngbya boryana.

Extracellular vesicles (EVs) are derived from the outer membrane (OM) in Gram-negative bacteria and have diverse physiological functions. EV-mediated secretion of monovinyl protochlorophyllide (MV-Pchlide), the chlorophyll a (Chl) biosynthetic intermediate, was previously reported in a mutant lacking dark-operative Pchlide reductase in the cyanobacterium Leptolyngbya boryana. This study showed a detailed characterization of EVs from the wild-type (WT) of L. boryana grown under photoautotrophic and dark heterotrophic conditions, focusing on the accumulation of Chl intermediates. WT L. boryana cells produce two types of EVs, low-density EVs (L-EVs) and high-density EVs (H-EVs), both under light and dark conditions. L-EVs and H-EVs showed distinct morphological features and protein compositions. L-EVs from cells grown under both light and dark conditions commonly contained carotenoids, ketomyxol glycoside, and zeaxanthin, as major pigments. Based on the protein compositions of EVs and other cellular membrane fractions, L-EVs and H-EVs are probably derived from low-density OM and high-density OM interacting with cell walls, respectively. Fluorescence detection of pigments was applied to EVs, and the two Chl intermediates, protoporphyrin IX and protoporphyrin IX monomethyl ester, were commonly detected in both L-EVs from light- and dark-grown cells, whereas L-EVs from dark-grown cells contained additional MV-Pchlide, MV-protopheophorbide, and pheophorbide. The pigment ratios of L-EVs to the total culture medium of the Chl intermediates were much higher than those of carotenoids, suggesting an active transport of the Chl intermediates from the thylakoid membrane to L-EVs. Cyanobacterial EVs may play a novel role in alleviating the accumulation of Chl intermediates in cells. (248 words).

Preparation and characterization of structural and antifouling properties of chitosan/polyethylene oxide membranes.

It aims to prepare the chitosan (CS) and polyethylene oxide (PEO) hydrogel membranes with different CS/PEO blend ratios (100:0, 95:5, 90:10, 80:20 and 70:30) via solvent casting. The physicochemical properties of these membranes were investigated using various characterization techniques: Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive X-ray (EDX), contact angle, and tensile testing. The interaction of PEO and chitosan was investigated by DSC in terms of freezing bound, freezing free, and non-freezing PEO fraction. The cross-sectional surface morphology of membranes displayed a smoother surface with increasing PEO content up to 20 %, beyond which nonhomogeneity on the surface was visible. The antifouling behavior of membranes was investigated by bacterial adherence study, which showed an enhanced antifouling nature of membranes with the increase in the PEO content. The peeling strength of the membranes was measured using a 90° angle peeling test, and it was found that 20 % and more PEO content promotes easy removal from the gelatin slab. In addition to this, live/ dead assay of the CS was performed to visualize the presence of live and dead bacteria on the surface. The CS/PEO blend with 20 % PEO content has properties makes it suitable for use as a protective layer on wound dressings to prevent bacterial growth. It's use in wound dressings has the potential to reduce the pain during the time of dressing removal and improve patient outcomes. The present investigation leads to the development of a CS hydrogel matrix which exhibits very interesting interaction with the PEO moiety along with its innovative feature of antifouling and antimicrobial nature.

Unveiling the human fetal-maternal interface during the first trimester: biophysical knowledge and gaps.

The intricate interplay between the developing placenta and fetal-maternal interactions is critical for pregnancy outcomes. Despite advancements, gaps persist in understanding biomechanics, transport processes, and blood circulation parameters, all of which are crucial for safe pregnancies. Moreover, the complexity of fetal-maternal interactions led to conflicting data and methodological variations. This review presents a comprehensive overview of current knowledge on fetal-maternal interface structures, with a particular focus on the first trimester. More in detail, the embryological development, structural characteristics, and physiological functions of placental chorionic plate and villi, fetal membranes and umbilical cord are discussed. Furthermore, a description of the main structures and features of maternal and fetal fluid dynamic exchanges is provided. However, ethical constraints and technological limitations pose still challenges to studying early placental development directly, which calls for sophisticated in vitro, microfluidic organotypic models for advancing our understanding. For this, knowledge about key in vivo parameters are necessary for their design. In this scenario, the integration of data from later gestational stages and mathematical/computational simulations have proven to be useful tools. Notwithstanding, further research into cellular and molecular mechanisms at the fetal-maternal interface is essential for enhancing prenatal care and improving maternal and fetal health outcomes.

Unraveling the complex interplay between Mitochondria-Associated Membranes (MAMs) and cardiovascular Inflammation: Molecular mechanisms and therapeutic implications.

Cardiovascular diseases (CVDs) represent a significant public health concern because of their associations with inflammation, oxidative stress, and abnormal remodeling of the heart and blood vessels. In this review, we discuss the intricate interplay between mitochondria-associated membranes (MAMs) and cardiovascular inflammation, highlighting their role in key cellular processes such as calcium homeostasis, lipid metabolism, oxidative stress management, and ERS. We explored how these functions impact the pathogenesis and progression of various CVDs, including myocardial ischemia-reperfusion injury, atherosclerosis, diabetic cardiomyopathy, cardiovascular aging, heart failure, and pulmonary hypertension. Additionally, we examined current therapeutic strategies targeting MAM-related pathways and proteins, emphasizing the potential of MAMs as therapeutic targets. Our review aims to provide new insights into the mechanisms of cardiovascular inflammation and propose novel therapeutic approaches to improve cardiovascular health outcomes.

Interventions to Mitigate Pregnancy-Related Mortality and Morbidity in Black Birthing People: A Systematic Review.

OBJECTIVE: To conduct a systematic review of interventions to improve perinatal outcomes to mitigate pregnancy-related mortality and morbidity in Black birthing people. DATA SOURCES: We searched five databases from 2000 through the final search date of April 5, 2023: Cumulative Index of Nursing and Allied Health Literature Plus with Full Text (EBSCOhost), Embase (Elsevier), PubMed, and Scopus (Elsevier) and ClinicalTrials.gov. STUDY ELIGIBILITY CRITERIA: Only quantitative studies were eligible including observational and randomized controlled trials. All participants in selected studies must identify as Black or study results must be stratified by race that includes Black birthing people. The study must 1) measure a perinatal outcome of interest 2) occur in the United States and 3) be written in the English language. Studies were excluded if they were published prior to 2000, not published in the English language, or did not meet the criteria above. STUDY APPRAISAL AND SYNTHESIS METHODS: A data extraction template identified intervention type and perinatal outcome. Perinatal outcomes included but were not limited to: cardiovascular disorders, mortality, or preterm delivery. Interventions included: community programs, educational enhancement, individual counseling, medical intervention, or policy. Risk of bias was assessed using the Mixed Method Appraisal Tool. Three investigators assessed studies individually and group consensus was used for a final decision. RESULTS: From 4,302 unique studies, 41 studies met inclusion criteria. Community programs such as the Supplemental Program for Women, Infants, and Children (WIC) and Healthy Start (n=17, 41.5%) were the most common interventions studied. Individual counseling closely followed (n=15, 36.6%). Medical interventions were not among the more commonly used intervention types (n=9, 21.9%). Most articles focused on preterm delivery (n=28, 68.3%). Few articles studied cardiovascular disorders (n=4, 9.8%) or hemorrhage (n=3, 7.3%). No articles studied pregnancy-related morbidity. CONCLUSIONS: Despite current conversations on Black maternal mortality, there is currently limited literature examining interventions addressing perinatal morbidity and mortality in Black birthing people in the United States. These interventions do not address how to mitigate perinatal outcomes of interest. Patient-centered outcomes research is warranted to better understand as well as to resolve inequities related to Black maternal health. VIDEO ABSTRACT.

Sustainable synthesis pathways: Bacterial nanocellulose from lignocellulosic biomass for circular economy initiatives.

The hydrothermal pretreatment process stands out as a pivotal step in breaking down the hemicellulosic fraction of lignocellulosic biomasses, such as sugarcane bagasse and eucalyptus sawdust. This pretreatment step is crucial for preparing these materials for subsequent processes, particularly in food applications. This technique aims to disintegrate plant wall components like cellulose, hemicellulose, and lignin, and facilitating access in later phases such as enzymatic hydrolysis, and ultimately making fermentable sugars available. In this study, sugarcane bagasse and eucalyptus sawdust biomass underwent hydrothermal pretreatment at specific conditions, yielding two key components: dry biomass and hemicellulose liquor. The primary focus was to assess the impact of hydrothermal pretreatment followed by enzymatic hydrolysis, using the Celic Ctec III enzyme cocktail, to obtain fermentable sugars. These sugars were then transformed into membranes via strain Gluconacetobacter xylinus bacterial biosynthesis. Notably, the addition of a nitrogen source significantly boosted production to 14.76 g/ in hydrolyzed sugarcane bagasse, underscoring its vital role in bacterial metabolism. Conversely, in hydrolyzed eucalyptus, nitrogen source inclusion unexpectedly decreased yield, highlighting the intricate interactions in fermentation media and the pivotal influence of nitrogen supplementation. Characterization of membranes obtained in synthetic and hydrolyzed media through techniques such as FEG-SEM, FTIR, and TGA, followed by mass balance assessment, gauged their viability on an industrial scale. This comprehensive study aimed not only to understand the effects of pretreatment and enzymatic hydrolysis but to also evaluate the applicability and sustainability of the process on a large scale, providing crucial insights into its feasibility and efficiency in practical food-related scenarios, utilizing nanocellulose bacterial (BNC) as a key component.

Structural and physical-chemical properties of milk fat globules fractionated by a series of silicon carbide membranes.

Driven by the acknowledged health and functional properties of milk fat globules (MFGs), there is a growing interest to develop gentle methodologies for separation of fat from milk. In this study, separation of fat from raw milk and fractionation in streams containing MFGs of different size was achieved using a series of two silicon carbide ceramic membranes. A first step consisting of a 1.4 µm membrane aimed to concentrate the bulk of the fat, i.e. the larger MFGs (D[4,3] âˆ¼ 4 µm) followed by a 0.5 µm fractionation aimed to concentrate the residual milk fat in the permeate, i.e. fraction with the smaller MFGs (D[4,3] âˆ¼ 1.8-2.4 µm. The fat separation performance showed a yield of 92 % for the 1.4 µm membrane and 97 % for the 0.5 µm membrane. Both fat enriched retentates showed, by the confocal laser scanning microscopy, intact MFGs with limited damage in the MFG membrane. The fatty acid profile analysis and SAXS showed minor differences in fat acid composition and the crystallization behavior was related to differences in the fat content. The 0.5 µm permeate containing the smallest MFGs however showed larger aggregates and a trinomial particle size distribution, due to probably pore pressure induced coalescences. The series of silicon carbide membranes showed potential to concentrate some of MFGM proteins such as Periodic Schiff base 3/4 and cluster of differentiation 36 especially in the 0.5 µm retentates. A shift in casein to whey protein ratio from 80:20 (milk) to 50:50 was obtained in the final 0.5 µm permeate, which opens new opportunities for product development.

Nanoscale Mechanical Manipulation of Ultrathin SiN Membranes Enabling Infrared Near-Field Microscopy of Liquid-Immersed samples.

Scattering scanning near-field optical microscopy (s-SNOM) is a powerful technique for mid-infrared spectroscopy at nanometer length scales. By investigating objects in aqueous environments through ultrathin membranes, s-SNOM has recently been extended toward label-free nanoscopy of the dynamics of living cells and nanoparticles, assessing both the optical and the mechanical interactions between the tip, the membrane and the liquid suspension underneath. Here, the study reports that the tapping AFM tip induces a reversible nanometric deformation of the membrane manifested as either an indentation or protrusion. This mechanism depends on the driving force of the tapping cantilever, which is exploited to minimize topographical deformations of the membrane to improve optical measurements. Furthermore, it is shown that the tapping phase delay between driving signal and tip oscillation is a highly sensitive observable to study the mechanics of adhering objects, exhibiting highest contrast at low tapping amplitudes where the membrane remains nearly flat. Mechanical responses are correlated with simultaneously recorded spectroscopy data to reveal the thickness of nanometric water layers between membrane and adhering objects. Besides a general applicability of depth profiling, the technique holds great promise for studying mechano-active biopolymers and living cells, biomaterials that exhibit complex behaviors when under a mechanical load.

Preclinical evaluation of mucogingival defect treatment using piscine membranes: An in vivo assessment of wound healing.

Periodontitis is a bacteria-induced chronic inflammatory disease characterized by degradation of the supporting tissue and bone in the oral cavity. Treatment modalities seek to facilitate periodontal rehabilitation while simultaneously preventing further gingival tissue recession and potentially bone atrophy. The aim of this study was to compare two differently sourced membranes, a resorbable piscine collagen membrane and a porcine-derived collagen membrane, in the repair of soft tissue defects utilizing a preclinical canine model. This in vivo component consisted of 10 beagles which were subjected to bilateral maxillary canine mucogingival flap defects, as well as bilateral soft tissue defects (or pouches) with no periodontal ligament damage in the mandibular canines. Defects received either a piscine-derived dermal membrane, (Kerecis® Oral, Ísafjörður, Iceland) or porcine-derived dermal membrane (Geistlich Mucograft®, Wolhusen, Switzerland) in a randomized fashion (to avoid site bias) and were allowed to heal for 30, 60, or 90 days. Statistical evaluation of tissue thickness was performed using general linear mixed model analysis of variance and least significant difference (LSD) post hoc analyses with fixed factors of time and membrane. Semi-quantitative analysis employed for inflammation assessment was evaluated using a chi-squared test along with a heteroscedastic t-test and values were reported as mean and corresponding 95% confidence intervals. In both the mucogingival flap defects and soft tissue gingival pouches, no appreciable qualitative differences were observed in tissue healing between the membranes. Furthermore, no statistical differences were observed in the thickness measurements between piscine- and porcine-derived membranes in the mucogingival flap defects (1.05 mm [±0.17] and 1.29 mm [±0.17], respectively [p = .06]) or soft tissue pouches (1.36 mm [±0.14] and 1.47 mm [±0.14], respectively [p = .27]), collapsed over time. Independent of membrane source (i.e., piscine or porcine), similar inflammatory responses were observed in both the maxilla and mandible at the three time points (p = .88 and p = .79, respectively). Histologic and histomorphometric evaluation results indicated that both membranes yielded equivalent tissue responses, remodeling dynamics and healing patterns for the mucogingival flap as well as the soft tissue gingival pouch defect models.

HIV-1 and methamphetamine co-treatment in primary human astrocytes: TAARgeting ER/UPR dysfunction.

Objectives: Human immunodeficiency virus 1 (HIV-1) can invade the central nervous system (CNS) early during infection and persist in the CNS for life despite effective antiretroviral treatment. Infection and activation of residential glial cells lead to low viral replication and chronic inflammation, which damage neurons contributing to a spectrum of HIV-associated neurocognitive disorders (HAND). Substance use, including methamphetamine (METH), can increase one's risk and severity of HAND. Here, we investigate HIV-1/METH co-treatment in a key neurosupportive glial cell, astrocytes. Specifically, mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) signaling pathways, such as calcium and the unfolded protein response (UPR), are key mechanisms underlying HAND pathology and arise as potential targets to combat astrocyte dysfunction. Methods: Primary human astrocytes were transduced with a pseudotyped HIV-1 model and exposed to low-dose METH for seven days. We assessed changes in astrocyte HIV-1 infection, inflammation, mitochondrial antioxidant and dynamic protein expression, respiratory acitivity, mitochondrial calcium flux, and UPR/MAM mediator expression. We then tested a selective antagonist for METH-binding receptor, trace amine-associated receptor 1 (TAAR1) as a potetnial upstream regulator of METH-induced calcium flux and UPR/MAM mediator expression. Results: Chronic METH exposure increased astrocyte HIV-1 infection. Moreover, HIV-1/METH co-treatment suppressed astrocyte antioxidant and metabolic capacity while increasing mitochondrial calcium load and protein expression of UPR messengers and MAM mediators. Notably, HIV-1 increases astrocyte TAAR1 expression, thus, could be a critical regulator of HIV-1/METH co-treatment in astrocytes. Indeed, selective antagonism of TAAR1 significantly inhibited cytosolic calcium flux and induction of UPR/MAM protein expression. Conclusion: Altogether, our findings demonstrate HIV-1/METH-induced ER-mitochondrial dysfunction in astrocytes, whereas TAAR1 may be an upstream regulator for HIV-1/METH-mediated astrocyte dysfunction.

Design, synthesis and structure-activity relationship (SAR) studies of an unusual class of non-cationic fatty amine-tripeptide conjugates as novel synthetic antimicrobial agents.

Cationic ultrashort lipopeptides (USLPs) are promising antimicrobial candidates to combat multidrug-resistant bacteria. Using DICAMs, a newly synthesized family of tripeptides with net charges from -2 to +1 and a fatty amine conjugated to the C-terminus, we demonstrate that anionic and neutral zwitterionic USLPs can possess potent antimicrobial and membrane-disrupting activities against prevalent human pathogens such as Streptococcus pneumoniae and Streptococcus pyogenes. The strongest antimicrobials completely halt bacterial growth at low micromolar concentrations, reduce bacterial survival by several orders of magnitude, and may kill planktonic cells and biofilms. All of them comprise either an anionic or neutral zwitterionic peptide attached to a long fatty amine (16-18 carbon atoms) and show a preference for anionic lipid membranes enriched in phosphatidylglycerol (PG), which excludes electrostatic interactions as the main driving force for DICAM action. Hence, the hydrophobic contacts provided by the long aliphatic chains of their fatty amines are needed for DICAM's membrane insertion, while negative-charge shielding by salt counterions would reduce electrostatic repulsions. Additionally, we show that other components of the bacterial envelope, including the capsular polysaccharide, can influence the microbicidal activity of DICAMs. Several promising candidates with good-to-tolerable therapeutic ratios are identified as potential agents against S. pneumoniae and S. pyogenes. Structural characteristics that determine the preference for a specific pathogen or decrease DICAM toxicity have also been investigated.

Use of vaginal dinoprostone for women with term prelabor rupture of membranes and an unfavorable cervix within 6 h versus within 6-24 h.

BACKGROUND: Most guidelines propose inducing labor within 24 h following term (37 or more weeks of gestation) prelabor rupture of membranes (PROM). However, the exact timing for initiating induction within the 24 h period remains unknown. This study aims to comparatively assess the efficacy and safety of the use of vaginal dinoprostone within 6 h versus within 6-24 h for singleton pregnancies with PROM and an unfavorable cervix (Bishop score < 6). METHODS: This was a retrospective cohort study including singleton pregnancies with PROM and an unfavorable cervix (Bishop score < 6) in which labor was induced using vaginal dinoprostone. Women were divided into two groups according to the timing of the use of induction (within 6 h versus within 6-24 h after PROM). Baseline maternal data, maternal and neonatal outcomes were recorded for statistical analysis. RESULTS: 450 women were included, 146 (32.4%) of whom were induced within 6 h of PROM and 304 (67.6%) were induced within 6-24 h. Cesarean delivery rate (15.8% versus 29.3%, p = 0.002) and nonreassuring fetal heart rate tracing (4.8% versus 10.5%, p = 0.043) in group with vaginal dinoprostone within 6 h were significantly lower than those in group with vaginal dinoprostone within 6-24 h. There was no significant differences in terms of duration from IOL to vaginal delivery. CONCLUSION: Induction of labor within 6 h with vaginal dinoprostone after PROM for singleton pregnancies with an unfavorable cervix (Bishop score < 6) significantly associated with less cesarean section, less nonreassuring fetal heart rate tracing, compared to induction of labor within 6-24 h after PROM.

The correlation between mitochondria-associated endoplasmic reticulum membranes (MAMs) and Ca2+ transport in the pathogenesis of diseases.

Mitochondria and the endoplasmic reticulum (ER) are vital organelles that influence various cellular physiological and pathological processes. Recent evidence shows that about 5%-20% of the mitochondrial outer membrane is capable of forming a highly dynamic physical connection with the ER, maintained at a distance of 10-30 nm. These interconnections, known as MAMs, represent a relatively conserved structure in eukaryotic cells, acting as a critical platform for material exchange between mitochondria and the ER to maintain various aspects of cellular homeostasis. Particularly, ER-mediated Ca2+ release and recycling are intricately associated with the structure and functionality of MAMs. Thus, MAMs are integral in intracellular Ca2+ transport and the maintenance of Ca2+ homeostasis, playing an essential role in various cellular activities including metabolic regulation, signal transduction, autophagy, and apoptosis. The disruption of MAMs observed in certain pathologies such as cardiovascular and neurodegenerative diseases as well as cancers leads to a disturbance in Ca2+ homeostasis. This imbalance potentially aggravates pathological alterations and disease progression. Consequently, a thorough understanding of the link between MAM-mediated Ca2+ transport and these diseases could unveil new perspectives and therapeutic strategies. This review focuses on the changes in MAMs function during disease progression and their implications in relation to MAM-associated Ca2+ transport.

Development of pectin/chitosan-based electrospun biomimetic nanofiber membranes loaded with dihydromyricetin inclusion complexes for wound healing application.

Accidents and surgical procedures inevitably lead to wounds, presenting clinical challenges such as inflammation and microbial infections that impede the wound-healing process. This study aimed to address these challenges by developing a series of novel wound dressings known as electrospun biomimetic nanofiber membranes. These membranes were prepared using electrostatic spinning technique, incorporating hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes. The prepared electrospun biomimetic nanofiber membranes exhibited randomly arranged fiber morphology with average fiber diameters ranging from 200 to 400 nm, resembling the collagen fibers in the native skin. These membranes demonstrated excellent biocompatibility, hemocompatibility, surface hydrophilicity, and wettability, while also releasing dihydromyricetin in a sustained manner. In vitro testing revealed that these membranes, loaded with hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes, displayed higher antioxidant potential and inhibitory effects against Staphylococcus aureus and Escherichia coli. Furthermore, these membranes significantly reduced the M1 phenotypic transition in RAW264.7 cells, even when stimulated by lipopolysaccharides, effectively restoring M2 polarization, thereby shortening the inflammatory period. Additionally, the in vivo wound healing effects of these membranes were validated. In conclusion, this study introduces a promising nanofiber membrane with diverse biological properties that holds promise for addressing various crucial aspects of the wound-healing process.

Rejection of PFAS and priority co-contaminants in semiconductor fabrication wastewater by nanofiltration membranes.

Use of high-pressure membranes is an effective means for removal of per-and polyfluoroalkyl substances (PFAS) that is less sensitive than adsorption processes to variable water quality and specific PFAS structure. This study evaluated the use of nanofiltration (NF) membranes for the removal of PFAS and industry relevant co-contaminants in semiconductor fabrication (fab) wastewater. Initial experiments using a flat sheet filtration cell determined that the NF90 (tight NF) membrane provided superior performance compared to the NF270 (loose NF) membrane, with NF90 rejection values exceeding 97 % for all PFAS evaluated, including the ultrashort trifluoromethane sulfonic acid (TFMS). Cationic fab co-contaminants diaryliodonium (DIA), triphenylsulfonium (TPS), and tetramethylammonium hydroxide (TMAH) were not as highly rejected as anionic PFAS likely due to electrostatic effects. A spiral wound NF90 module was then used in a pilot system to treat a lab solution containing PFAS and co-contaminants and fab wastewater effluent. Treatment of the fab wastewater, containing high concentrations of perfluorocarboxylic acids (PFCAs), including trifluoroacetic acid (TFA: 96,413 ng/L), perfluoropropanoic acid (PFPrA: 11,796 ng/L), and perfluorobutanoic acid (PFBA: 504 ng/L), resulted in ≥92 % rejection of all PFAS while achieving 90 % water recovery in a semi-batch configuration. These findings demonstrate nanofiltration as a promising technology option for incorporation in treatment trains targeting PFAS removal from wastewater matrices.

A Light-Powered In Vitro Synthetic Enzymatic Biosystem for the Synthesis of 3-Hydroxypropionic Acid via CO2 Fixation.

3-Hydroxypropionic acid (3-HP) is a highly sought-after platform chemical serving as a precursor to a variety of high value-added chemical products. In this study, we designed and constructed a novel light-powered in vitro synthetic enzymatic biosystem comprising acetyl-CoA ligase, acetyl-CoA carboxylase, malonyl-CoA reductase, and phosphotransferase to efficiently produce 3-HP through CO2 fixation from acetate, a cost-effective and readily available substrate. The system employed natural thylakoid membranes (TMs) for the regeneration of adenosine triphosphate and nicotinamide adenine dinucleotide phosphate. Comprehensive investigations were conducted on the effects of buffer solutions, substrate concentrations, enzyme loading levels, and TMs loading levels to optimize the yield of 3-HP. Following optimization, a production of 0.46 mM 3-HP was achieved within 6 h from an initial 0.5 mM acetate, with a yield nearing 92%. This work underscores the simplicity of 3-HP production via an in vitro biomanufacturing platform and highlights the potential for incorporating TMs as a sustainable and environmentally friendly approach in biomanufacturing processes.

Bioinspired Microgel-Loaded Smart Membrane Filtration with the Thermo- and Ion-Dual Responsive Water Gate for Selective Lead(II) Separation.

Lead (Pb2+) is a ubiquitous pollutant. Membrane filtration represents one of the most common water treatment methods, but nanofiltration and ultrafiltration require high transmembrane pressure, while microfiltration has larger pore sizes than ions, making them unfavorable for direct ion removal at low cost. Selective and direct separation of Pb2+ via membrane filtration at high efficiency without sacrificing the flux of clean water still remains challenging. Herein, inspired by the Pb2+-tolerable oleander that enriches and prevents Pb2+ in roots from permeating the plant body, a smart Pb2+-adsorptive filtration membrane with a temperature- and ion-tunable water gate was prepared by loading dual-responsive poly(N-isopropylacrylamido-co-acrylamido-benzo-18-crown-6) (PNB-5-20) microgels onto a commercial membrane. The PNB-5-20 microgel exhibits pronounced temperature-responsive swelling/deswelling (hydrodynamic diameter, 650-330 nm) with a volume phase transition temperature (VPTT) at ∼33 °C. Moreover, the microgel shows a high Pb2+-adsorption capacity (qmax, 85.4 mg/g) and good selectivity (distribution coefficient Kd ∼ 1000 mL/g) thanks to its complexation with the crown ether, as well as good Pb2+ responsiveness, having the VPTT positively shifted to 40 °C in the presence of Pb2+ with enhanced swelling behaviors. Functionalized with PNB-5-20, the smart membrane integrates Pb2+ detection, adsorption, and tunable water drainage in a single device. The membrane selectively recognizes Pb2+ in the polluted water with the gates in membrane pores switching from "open" to "closed", intercepting and adsorbing Pb2+ with water permeation reduced. Once purified, the gates can be "re-opened" by increasing the temperature. Construction of such an intelligent membrane filtration device with a tunable water gate and excellent Pb2+ recognition and adsorption performance will greatly simplify the remediation of Pb2+-polluted water.

The Evolution of Microfluidic-Based Drug-Loading Techniques for Cells and Their Derivatives.

Conventional drug delivery techniques face challenges related to targeting and adverse reactions. Recent years have witnessed significant advancements in nanoparticle-based drug carriers. Nevertheless, concerns persist regarding their safety and insufficient metabolism. Employing cells and their derivatives, such as cell membranes and extracellular vesicles (EVs), as drug carriers effectively addresses the challenges associated with nanoparticle carriers. However, an essential hurdle remains in efficiently loading drugs into these carriers. With the advancement of microfluidic technology and its advantages in precise manipulation at the micro- and nanoscales, as well as minimal sample loss, it has found extensive application in the loading of drugs using cells and their derivatives, thereby fostering the development of drug-loading techniques. This paper outlines the characteristics and benefits of utilizing cells and their derivatives as drug carriers and provides an overview of current drug-loading techniques, particularly those rooted in microfluidic technology. The significant potential for microfluidic technology in targeted disease therapy through drug delivery systems employing cells and their derivatives, is foreseen.

Optimizing Archaeal Lipid Biosynthesis in Escherichia coli.

Membrane lipid chemistry is remarkably different in archaea compared with bacteria and eukaryotes. In the evolutionary context, this is also termed the lipid divide and is reflected by distinct biosynthetic pathways. Contemporary organisms have almost without exception only one type of membrane lipid. During early membrane evolution, mixed membrane stages likely occurred, and it was hypothesized that the instability of such mixtures was the driving force for the lipid divide. To examine the compatibility between archaeal and bacterial lipids, the bacterium Escherichia coli has been engineered to contain both types of lipids with varying success. Only limited production of archaeal lipid archaetidylethanolamine was achieved. Here, we substantially increased its production in E. coli by overexpression of an archaeal phosphatidylserine synthase needed for ethanolamine headgroup attachment. Furthermore, we introduced a synthetic isoprenoid utilization pathway to increase the supply of isopentenyl-diphosphate and dimethylallyl diphosphate. This improved archaeal lipid production substantially. The archaeal phospholipids also served as a substrate for the E. coli cardiolipin synthase, resulting in archaeal and novel hybrid archaeal/bacterial cardiolipin species not seen in living organisms before. Growth of the E. coli strain with the mixed membrane shows an enhanced sensitivity to the inhibitor of fatty acid biosynthesis, cerulenin, indicating a critical dependence of the engineered E. coli strain on its native phospholipids.