Sustaining Surface Lithiophilicity of Ultrathin Li-Alloy Coating Layers on Current Collector for Zero-Excess Li-Metal Batteries.

Zero-excess Li-metal batteries (ZE-LMBs) have emerged as the ultimate battery platform, offering an exceptionally high energy density. However, the absence of Li-hosting materials results in uncontrolled dendritic Li deposition on the Cu current collector, leading to chronic loss of Li inventory and severe electrolyte decomposition, limiting its full utilization upon cycling. This study presents the application of ultrathin (≈50 nm) coatings comprising six metallic layers (Cu, Ag, Au, Pt, W, and Fe) on Cu substrates in order to provide insights into the design of Li-depositing current collectors for stable ZE-LMB operation. In contrast to non-alloy Cu, W, and Fe coatings, Ag, Au, and Pt coatings can enhance surface lithiophilicity, effectively suppressing Li dendrite growth, thereby improving Li reversibility. Considering the distinct Li-alloying behaviors, particularly solid-solution and/or intermetallic phase formation, Pt-coated Cu current collectors maintain surface lithiophilicity over repeated Li plating/stripping cycles by preserving the original coating layer, thereby attaining better cycling performance of ZE-LMBs. This highlights the importance of selecting suitable Li-alloy metals to sustain surface lithiophilicity throughout cycling to regulate dendrite-less Li plating and improve the electrochemical stability of ZE-LMBs.

Integrative analysis of microRNA-mediated mitochondrial dysfunction in hippocampal neural progenitor cell death in relation with Alzheimer's disease

Adult hippocampal neurogenesis plays a pivotal role in maintaining cognitive brain function; however, this process diminishes with age, particularly in patients with neurodegenerative disorders. While small, non-coding microRNAs (miRNAs) are crucial for hippocampal neural stem (HCN) cell maintenance, their involvement in neurodegenerative disorders remains unclear. This study aims to elucidate the mechanisms through which miRNAs regulate HCN cell death and their potential involvement in neurodegenerative disorder. We performed a comprehensive microarray-based analysis to investigate changes in miRNA expression in insulin-deprived HCN cells, as an in vitro model for cognitive impairment. Remarkably, miR-150-3p, miR-323-5p, and miR-370-3p which increased significantly over time following insulin withdrawal, induced pronounced mitochondrial fission and dysfunction, ultimately leading to HCN cell death. Notably, these miRNAs collectively target the mitochondrial fusion protein OPA1, with miR-150-3p also targeting MFN2. Furthermore, data-driven analyses involving human subjects within the hippocampus and brain revealed significant reductions of OPA1 and MFN2 in the Alzheimer's disease (AD) patients. Our results indicate that miR-150-3p, miR-323-5p, and miR-370-3p contribute to deficits in hippocampal neurogenesis by modulating mitochondrial dynamics. Our findings provide a novel insight into the intricate connection between miRNAs and mitochondrial dynamics, shedding light on their potential involvement in conditions characterized by deficits in hippocampal neurogenesis, such as AD.

Modified Technique of Chemoport Placement in Severely Obese Patient for Administration of Chemotherapy.

A common site of chemoport implantation is the anterior chest wall. However, it is difficult to needle chemoport and to maintain needles in severely obese patients. Because the skin is thick, it is difficult to find the port and the needle easily comes off. We describe a different safe and easy to replicate method of chemoport placement in a severely obese patient. We placed the chemopot directly above the sternum. It is particularly more useful for very obese patients. This technique is safe and an easy to replicate method of chemoport placement.

Predictors of Persistent Post-Surgical Pain Following Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management. METHODS: We searched MEDLINE, EMBASE, CINAHL, AMED, SPORTDiscus, and PsycINFO for observational studies that explored the association between risk factors and persistent pain (≥3 months) after total knee replacement. We pooled estimates of association for all independent variables reported by >1 study. RESULTS: Thirty studies (26,517 patients) reported the association of 151 independent variables with persistent pain after knee replacement. High certainty evidence demonstrated an increased risk of persistent pain with pain catastrophizing (absolute risk increase [ARI] 23%, 95% confidence interval [CI] 12 to 35), younger age (ARI for every 10-year decrement from age 80, 4%, 95% CI 2 to 6), and moderate-to-severe acute post-operative pain (ARI 30%, 95% CI 20 to 39). Moderate certainty evidence suggested an association with female sex (ARI 7%, 95% CI 3 to 11) and higher pre-operative pain (ARI 35%, 95% CI 7 to 58). Studies did not adjust for both peri-operative pain severity and pain catastrophizing, which are unlikely to be independent. High to moderate certainty evidence demonstrated no association with pre-operative range of motion, body mass index, bilateral or unilateral knee replacement, and American Society of Anesthesiologists score. CONCLUSIONS: Rigorously conducted observational studies are required to establish the relative importance of higher levels of peri-operative pain and pain catastrophizing with persistent pain after knee replacement surgery.

Night-time gastric acid suppression by tegoprazan compared to vonoprazan or esomeprazole.

AIMS: Nocturnal acid breakthrough has been considered an unmet need of proton-pump inhibitors. Tegoprazan, a novel potassium-competitive acid blocker, is expected to show improved properties for this unmet need. This study was aimed to compare night-time acid suppression by tegoprazan with that by vonoprazan or esomeprazole, and to explore the effect of CYP2C19 phenotypes on acid-suppressive effects. METHODS: A randomized, open-label, 3-period, 6-sequence crossover study was conducted. A single oral dose of tegoprazan 50 mg, vonoprazan 20 mg or esomeprazole 40 mg was administered at night in each period. Continuous intragastric pH was monitored at baseline and after each dosing. RESULTS: Sixteen healthy subjects (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, 5 poor metabolizers) completed the study. After a single dose of tegoprazan, intragastric pH increased more rapidly to over 4 at approximately 1 hour compared to the other treatments, and elevated intragastric pH was maintained stably at night. Tegoprazan exhibited night-time acid suppression for slightly but not significantly longer than vonoprazan, and greater than esomeprazole; % time at pH ≥ 4 at night was 66.0%, 60.5% and 36.1% for tegoprazan, vonoprazan and esomeprazole, respectively. Night-time acid suppression by tegoprazan and vonoprazan was not dependent on CYP2C19 phenotypes, while that by esomeprazole tended to be influenced by CYP2C19 phenotypes. CONCLUSION: Tegoprazan produced more rapid, potent and well sustained night-time acid suppression vs. vonoprazan or esomeprazole when administered at night. Furthermore, tegoprazan showed no CYP2C19 phenotype dependency in acid suppression. It suggests the potential of tegoprazan, especially in preventing nocturnal acid breakthrough.

Potentiation of long-acting ß2-agonist and glucocorticoid responses in human airway epithelial cells by modulation of intracellular cAMP.

INTRODUCTION: Over 300 million people in the world live with asthma, resulting in 500,000 annual global deaths with future increases expected. It is estimated that around 50-80% of asthma exacerbations are due to viral infections. Currently, a combination of long-acting beta agonists (LABA) for bronchodilation and glucocorticoids (GCS) to control lung inflammation represent the dominant strategy for the management of asthma, however, it is still sub-optimal in 35-50% of moderate-severe asthmatics resulting in persistent lung inflammation, impairment of lung function, and risk of mortality. Mechanistically, LABA/GCS combination therapy results in synergistic efficacy mediated by intracellular cyclic adenosine monophosphate (cAMP). HYPOTHESIS: Increasing intracellular cAMP during LABA/GCS combination therapy via inhibiting phosphodiesterase 4 (PDE4) and/or blocking the export of cAMP by ATP Binding Cassette Transporter C4 (ABCC4), will potentiate anti-inflammatory responses of mainstay LABA/GCS therapy. METHODS: Expression and localization experiments were performed using in situ hybridization and immunohistochemistry in human lung tissue from healthy subjects, while confirmatory transcript and protein expression analyses were performed in primary human airway epithelial cells and cell lines. Intervention experiments were performed on the human airway epithelial cell line, HBEC-6KT, by pre-treatment with combinations of LABA/GCS with PDE4 and/or ABCC4 inhibitors followed by Poly I:C or imiquimod challenge as a model for viral stimuli. Cytokine readouts for IL-6, IL-8, CXCL10/IP-10, and CCL5/RANTES were quantified by ELISA. RESULTS: Using archived human lung and human airway epithelial cells, ABCC4 gene and protein expression were confirmed in vitro and in situ. LABA/GCS attenuation of Poly I:C or imiquimod-induced IL-6 and IL-8 were potentiated with ABCC4 and PDE4 inhibition, which was greater when ABCC4 and PDE4 inhibition was combined. Modulation of cAMP levels had no impact on LABA/GCS modulation of Poly I:C-induced CXCL10/IP-10 or CCL5/RANTES. CONCLUSION: Modulation of intracellular cAMP levels by PDE4 or ABCC4 inhibition potentiates LABA/GCS efficacy in human airway epithelial cells challenged with viral stimuli. The data suggest further exploration of the value of adding cAMP modulators to mainstay LABA/GCS therapy in asthma for potentiated anti-inflammatory efficacy.

Adhesive-Based Fabrication Technique for Culture of Lung Airway Epithelial Cells with Applications in Cell Patterning and Microfluidics.

This work describes a versatile and cost-effective cell culture method for micropatterning and growing adherent cells on porous membranes using pressure-sensitive double-sided adhesives. This technique also allows cell culture using conventional methods and their easy integration into microfluidic chip devices. Adhesives can be used to form different patterns of cultured cells, which can be used for cell proliferation and wound-healing models. To demonstrate the viability of our system, we evaluate the toxicity effect of five different adhesives on two distinct airway epithelial cell lines and show functional applications for cell patterning and microfluidic cell culture chip fabrication. We developed a sandwiched microfluidic device that enabled us to culture cells in a submerged condition and transformed it into a dynamic platform when required. The viability of cells and their inflammatory responses to IL-1ß stimulation were investigated. Our technique is applicable for conventional culturing of cells, widely available in biomedical research labs, while enabling the introduction of perfusion for an advanced dynamic cell culture model when needed.

Application of Random Mutagenesis and Synthetic FadR Promoter for de novo Production of ω-Hydroxy Fatty Acid in Yarrowia lipolytica.

As a means to develop oleaginous biorefinery, Yarrowia lipolytica was utilized to produce ω-hydroxy palmitic acid from glucose using evolutionary metabolic engineering and synthetic FadR promoters for cytochrome P450 (CYP) expression. First, a base strain was constructed to produce free fatty acids (FFAs) from glucose using metabolic engineering strategies. Subsequently, through ethyl methanesulfonate (EMS)-induced random mutagenesis and fluorescence-activated cell sorting (FACS) screening, improved FFA overproducers were screened. Additionally, synthetic promoters containing bacterial FadR binding sequences for CYP expression were designed to respond to the surge of the concentration of FFAs to activate the ω-hydroxylating pathway, resulting in increased transcriptional activity by 14 times from the third day of culture compared to the first day. Then, endogenous alk5 was screened and expressed using the synthetic FadR promoter in the developed strain for the production of ω-hydroxy palmitic acid. By implementing the synthetic FadR promoter, cell growth and production phases could be efficiently decoupled. Finally, in batch fermentation, we demonstrated de novo production of 160 mg/L of ω-hydroxy palmitic acid using FmeN3-TR1-alk5 in nitrogen-limited media. This study presents an excellent example of the production of ω-hydroxy fatty acids using synthetic promoters with bacterial transcriptional regulator (i.e., FadR) binding sequences in oleaginous yeasts.

Interactions between ABCC4/MRP4 and ABCC7/CFTR in human airway epithelial cells in lung health and disease.

ATP binding cassette (ABC) transporters are present in all three domains of life - Archaea, Bacteria, and Eukarya. The conserved nature is a testament to the importance of these transporters in regulating endogenous and exogenous substrates required for life to exist. In humans, 49 ABC transporters have been identified to date with broad expression in different lung cell types with multiple transporter family members contributing to lung health and disease. The ABC transporter most commonly known to be linked to lung pathology is ABCC7, also known as cystic fibrosis transmembrane conductance regulator - CFTR. Closely related to the CFTR genomic sequence is ABCC4/multi-drug resistance protein-4. Genomic proximity is shared with physical proximity, with ABCC4 and CFTR physically coupled in cell membrane microenvironments of epithelial cells to orchestrate functional consequences of cyclic-adenosine monophosphate (cAMP)-dependent second messenger signaling and extracellular transport of endogenous and exogenous substrates. The present concise review summarizes the emerging data defining a role of the (ABCC7/CFTR)-ABCC4 macromolecular complex in human airway epithelial cells as a physiologically important pathway capable of impacting endogenous and exogenous mediator transport and ion transport in both lung health and disease.

Cu(In,Ga)Se2 Solar Cells Integrated with Subwavelength Structured Cover Glass Fabricated by One-Step Self-Masked Etching.

We report an anti-reflective cover glass for Cu(In,Ga)Se2 (CIGS) thin film solar cells. Subwavelength structures (SWSs) were fabricated on top of a cover glass using one-step self-masked etching. The etching method resulted in dense whiskers with high aspect ratio. The produced structure exhibited excellent anti-reflective properties over a broad wavelength range, from the ultraviolet to the near infrared. Compared to a flat-surface glass, the average transmittance of the glass integrated with the SWSs improved from 92.4% to 95.2%. When the cover glass integrated with the SWSs was mounted onto the top of a CIGS device, the short-circuit current and the efficiency of the solar cell were enhanced by 4.38 and 6%, respectively, compared with a CIGS solar cell without cover glass.

Association between media attention and presentation of vaccination information on Canadian chiropractors' websites: a prospective mixed-methods cohort study.

BACKGROUND: Historically, some chiropractors have been critical of vaccination, and this has been the subject of recent media attention in Canada. We explored the association between media attention and public dissemination of vaccination information on Canadian chiropractors' websites. METHODS: In 2016, we identified all Canadian chiropractors' websites that provided information on vaccination by extracting details from the regulatory college website for each province using the search engine on their "find a chiropractor" page. We assessed the quality of information using the Web Resource Rating Tool (scores range from 0% [worst] to 100% [best]), determined whether vaccination was portrayed in a positive, neutral or negative manner, and conducted thematic analysis of vaccination content. We revisited all identified websites in 2019 to explore for changes to posted vaccination material. RESULTS: In July 2016, of 3733 chiropractic websites identified, 94 unique websites provided information on vaccination: 59 (63%) gave negative messaging, 19 (20%) were neutral and 16 (17%) were positive. The quality of vaccination content on the websites was generally poor, with a median Web Resource Rating Tool score of 19%. We identified 4 main themes: there are alternatives to vaccination, vaccines are harmful, evidence regarding vaccination and health policy regarding vaccination. From 2012 to 2016, there was 1 Canadian newspaper story concerning antivaccination statements by chiropractors, whereas 51 news articles were published on this topic between 2017 and 2019. In April 2019, 45 (48%) of the 94 websites we had identified in 2016 had removed all vaccination content or had been discontinued. INTERPRETATION: In 2016, a minority of Canadian chiropractors provided vaccination information on their websites, the majority of which portrayed vaccination negatively. After substantial national media attention, about half of all vaccination material on chiropractors' websites was removed within several years.

An Active and Soft Hydrogel Actuator to Stimulate Live Cell Clusters by Self-folding.

The hydrogels are widely used in various applications, and their successful uses depend on controlling the mechanical properties. In this study, we present an advanced strategy to develop hydrogel actuator designed to stimulate live cell clusters by self-folding. The hydrogel actuator consisting of two layers with different expansion ratios were fabricated to have various curvatures in self-folding. The expansion ratio of the hydrogel tuned with the molecular weight and concentration of gel-forming polymers, and temperature-sensitive molecules in a controlled manner. As a result, the hydrogel actuator could stimulate live cell clusters by compression and tension repeatedly, in response to temperature. The cell clusters were compressed in the 0.7-fold decreases of the radius of curvature with 1.0 mm in room temperature, as compared to that of 1.4 mm in 37 °C. Interestingly, the vascular endothelial growth factor (VEGF) and insulin-like growth factor-binding protein-2 (IGFBP-2) in MCF-7 tumor cells exposed by mechanical stimulation was expressed more than in those without stimulation. Overall, this new strategy to prepare the active and soft hydrogel actuator would be actively used in tissue engineering, drug delivery, and micro-scale actuators.

Luminescent down-shifting CsPbBr3 perovskite nanocrystals for flexible Cu(In,Ga)Se2 solar cells.

To overcome the parasitic absorption of ultraviolet (UV) light in the transparent conductive oxide (TCO) layer of flexible Cu(In,Ga)Se2 (CIGS) thin film solar cells, a CsPbBr3 perovskite nanocrystal based luminescent down-shifting (LDS) layer was integrated on CIGS solar cells fabricated on a stainless steel foil. The CsPbBr3 perovskite nanocrystal absorbs solar irradiation at wavelengths shorter than 520 nm and emits photons at a wavelength of 532 nm. These down-shifted photons pass the TCO layer without parasitic absorption and are absorbed in the CIGS absorber layer where they generate photocurrent. By minimizing the parasitic absorption in the TCO layer, the external quantum efficiency (EQE) of the CIGS solar cell with the CsPbBr3 perovskite nanocrystal layer is highly improved in the UV wavelength range between 300 and 390 nm. Additionally, in the wavelength range between 500 and 1100 nm, the EQE is improved since the surface reflectance of the CIGS device with the CsPbBr3 perovskite LDS layer was reduced. This is because the CsPbBr3 perovskite nanocrystal layer, which has an effective refractive index of 1.82 at a wavelength of 800 nm, reduces the large refractive index mismatch between air (nair = 1.00) and the TCO layer (nZnO = 1.96 at a wavelength of 800 nm). Both the short circuit current density and power conversion efficiency of the flexible CIGS solar cell integrated with the CsPbBr3 perovskite are improved by 4.5% compared with the conventional CIGS solar cell without the CsPbBr3 perovskite LDS layer.

Enhanced Light Harvesting in Photovoltaic Devices Using an Edge-Located One-Dimensional Grating Polydimethylsiloxane Membrane.

In streamlined multipurpose applications for light management and protection, encapsulants are merged with photonic crystal structures into solar modules. We present an edge-located 1D grating, attachable polymer on the top of a photovoltaic module to provide a strategy for capturing solar light and improving cell efficiency. Large-area solar arrays suffer from space utilization problems due to nonactive area. The introduction of periodically patterned gratings with specific geometric range is highly preferred to redirect the light toward photovoltaic active areas. To realize optimized broadband light diffraction for solar devices, the theoretical analysis of one-dimensional line patterned diffraction gratings was performed through wave-optic-based simulation. Based on the experimental results, the replica molding-based patterning method was adopted to fabricate the grating polymer for low-cost thin-film production. Also, we demonstrated enhanced light collection by grating patterned encapsulants with improved current density in comparison to the performance of a flat surface.

The impact of cigarette smoke exposure, COPD, or asthma status on ABC transporter gene expression in human airway epithelial cells.

ABC transporters are conserved in prokaryotes and eukaryotes, with humans expressing 48 transporters divided into 7 classes (ABCA, ABCB, ABCC, ABCD, ABDE, ABCF, and ABCG). Throughout the human body, ABC transporters regulate cAMP levels, chloride secretion, lipid transport, and anti-oxidant responses. We used a bioinformatic approach complemented with in vitro experimental methods for validation of the 48 known human ABC transporters in airway epithelial cells using bronchial epithelial cell gene expression datasets available in NCBI GEO from well-characterized patient populations of healthy subjects and individuals that smoke cigarettes, or have been diagnosed with COPD or asthma, with validation performed in Calu-3 airway epithelial cells. Gene expression data demonstrate that ABC transporters are variably expressed in epithelial cells from different airway generations, regulated by cigarette smoke exposure (ABCA13, ABCB6, ABCC1, and ABCC3), and differentially expressed in individuals with COPD and asthma (ABCA13, ABCC1, ABCC2, ABCC9). An in vitro cell culture model of cigarette smoke exposure was able to recapitulate select observed in situ changes. Our work highlights select ABC transporter candidates of interest and a relevant in vitro model that will enable a deeper understanding of the contribution of ABC transporters in the respiratory mucosa in lung health and disease.

Stereoselective construction of sterically hindered oxaspirocycles via chiral bidentate directing group-mediated C(sp3)-O bond formation.

The systematic investigation of chiral bidentate auxiliaries has resulted in the discovery of a chiral 2,2-dimethyl-1-(pyridin-2-yl)propan-1-amine-derived directing group that enables stereoselective palladium(ii)-catalyzed intramolecular C(sp3)-O bond formation. This new chiral directing group exhibited high reactivity in the activation of methylene C(sp3)-H bonds with excellent levels of stereoselectivity (a diastereomeric ratio of up to 39 : 1), which allowed the construction of a wide range of oxaspirocycles. Mechanistic investigations were also conducted to elucidate the reaction mechanism and understand the origin of the diastereoselectivity. DFT calculations suggest that only modest levels of diastereoselectivity are accomplished at the rate-determining C-H metalation-deprotonation step and the d.r. is further enriched at the reductive elimination step.

Investigation of Hole-Transporting Poly(triarylamine) on Aggregation and Charge Transport for Hysteresisless Scalable Planar Perovskite Solar Cells.

Organometallic halide perovskite solar cells (PSCs) have unique photovoltaic properties for use in next-generation solar energy harvesting systems. The highest efficiency of PSCs reached 22.1% on a laboratory scale of <0.1 cm2 device area. Thus, scaling up is the next step toward commercialization, but the difficulty in controlling the quality of large-area perovskite thin films remains a fundamental challenge. It has also been frequently reported that the J- V hysteresis is intensified in PSCs with areas larger than 1 cm2. In this study, we have fabricated a large-area perovskite layer using PbICl films, providing an intrinsic porous layer and enhancing the uniformity of the perovskite layer at areas larger than 1 cm2. Furthermore, we have investigated the polymeric properties of the prevalent hole-transporting material poly(triarylamine) (PTAA) with its photovoltaic performance. Two types of PTAAs, poly[bis(4-phenyl)(2,4-dimethylphenyl)amine] and poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine], were compared. A series of PTAAs with different molecular weights ( Mw) and polydispersity indices were studied, as the molecular weight of the PTAA is a key factor in determining the electrical properties and photovoltaic performance of the system. The fabricated PSCs with an aperture area of 1 cm2 based on a high-molecular-weight PTAA achieved a power conversion efficiency of 16.47% with negligible hysteresis and excellent reproducibility.

Ultrawide Spectral Response of CIGS Solar Cells Integrated with Luminescent Down-Shifting Quantum Dots.

Conventional Cu(In1-x,Gax)Se2 (CIGS) solar cells exhibit poor spectral response due to parasitic light absorption in the window and buffer layers at the short wavelength range between 300 and 520 nm. In this study, the CdSe/CdZnS core/shell quantum dots (QDs) acting as a luminescent down-shifting (LDS) layer were inserted between the MgF2 antireflection coating and the window layer of the CIGS solar cell to improve light harvesting in the short wavelength range. The LDS layer absorbs photons in the short wavelength range and re-emits photons in the 609 nm range, which are transmitted through the window and buffer layer and absorbed in the CIGS layer. The average external quantum efficiency in the parasitic light absorption region (300-520 nm) was enhanced by 51%. The resulting short circuit current density of 34.04 mA/cm2 and power conversion efficiency of 14.29% of the CIGS solar cell with the CdSe/CdZnS QDs were improved by 4.35 and 3.85%, respectively, compared with those of the conventional solar cells without QDs.

Rh(iii)-catalyzed 7-azaindole synthesis via C-H activation/annulative coupling of aminopyridines with alkynes.

An efficient Rh(iii)-catalyzed 7-azaindole synthesis was developed via C-H activation/annulative coupling of aminopyridines with alkynes. The reaction was highly regioselective and tolerated various functional groups, permitting the construction of various 7-azaindoles.