Dynamic spatial progression of isolated lithium during battery operations.

The increasing demand for next-generation energy storage systems necessitates the development of high-performance lithium batteries1-3. Unfortunately, current Li anodes exhibit rapid capacity decay and a short cycle life4-6, owing to the continuous generation of solid electrolyte interface7,8 and isolated Li (i-Li)9-11. The formation of i-Li during the nonuniform dissolution of Li dendrites12 leads to a substantial capacity loss in lithium batteries under most testing conditions13. Because i-Li loses electrical connection with the current collector, it has been considered electrochemically inactive or 'dead' in batteries14,15. Contradicting this commonly accepted presumption, here we show that i-Li is highly responsive to battery operations, owing to its dynamic polarization to the electric field in the electrolyte. Simultaneous Li deposition and dissolution occurs on two ends of the i-Li, leading to its spatial progression toward the cathode (anode) during charge (discharge). Revealed by our simulation results, the progression rate of i-Li is mainly affected by its length, orientation and the applied current density. Moreover, we successfully demonstrate the recovery of i-Li in Cu-Li cells with >100% Coulombic efficiency and realize LiNi0.5Mn0.3Co0.2O2 (NMC)-Li full cells with extended cycle life.

Efficient Delivery of Biological Cargos into Primary Cells by Electrodeposited Nanoneedles via Cell-Cycle-Dependent Endocytosis.

Nanoneedles are a useful tool for delivering exogenous biomolecules to cells. Although therapeutic applications have been explored, the mechanism regarding how cells interact with nanoneedles remains poorly studied. Here, we present a new approach for the generation of nanoneedles, validated their usefulness in cargo delivery, and studied the underlying genetic modulators during delivery. We fabricated arrays of nanoneedles based on electrodeposition and quantified its efficacy of delivery using fluorescently labeled proteins and siRNAs. Notably, we revealed that our nanoneedles caused the disruption of cell membranes, enhanced the expression of cell-cell junction proteins, and downregulated the expression of transcriptional factors of NFκB pathways. This perturbation trapped most of the cells in G2 phase, in which the cells have the highest endocytosis activities. Taken together, this system provides a new model for the study of interactions between cells and high-aspect-ratio materials.

Suspension electrolyte with modified Li+ solvation environment for lithium metal batteries.

Designing a stable solid-electrolyte interphase on a Li anode is imperative to developing reliable Li metal batteries. Herein, we report a suspension electrolyte design that modifies the Li+ solvation environment in liquid electrolytes and creates inorganic-rich solid-electrolyte interphases on Li. Li2O nanoparticles suspended in liquid electrolytes were investigated as a proof of concept. Through theoretical and empirical analyses of Li2O suspension electrolytes, the roles played by Li2O in the liquid electrolyte and solid-electrolyte interphases of the Li anode are elucidated. Also, the suspension electrolyte design is applied in conventional and state-of-the-art high-performance electrolytes to demonstrate its applicability. Based on electrochemical analyses, improved Coulombic efficiency (up to ~99.7%), reduced Li nucleation overpotential, stabilized Li interphases and prolonged cycle life of anode-free cells (~70 cycles at 80% of initial capacity) were achieved with the suspension electrolytes. We expect this design principle and our findings to be expanded into developing electrolytes and solid-electrolyte interphases for Li metal batteries.

Underpotential lithium plating on graphite anodes caused by temperature heterogeneity.

Rechargeability and operational safety of commercial lithium (Li)-ion batteries demand further improvement. Plating of metallic Li on graphite anodes is a critical reason for Li-ion battery capacity decay and short circuit. It is generally believed that Li plating is caused by the slow kinetics of graphite intercalation, but in this paper, we demonstrate that thermodynamics also serves a crucial role. We show that a nonuniform temperature distribution within the battery can make local plating of Li above 0 V vs. Li0/Li+ (room temperature) thermodynamically favorable. This phenomenon is caused by temperature-dependent shifts of the equilibrium potential of Li0/Li+ Supported by simulation results, we confirm the likelihood of this failure mechanism during commercial Li-ion battery operation, including both slow and fast charging conditions. This work furthers the understanding of nonuniform Li plating and will inspire future studies to prolong the cycling lifetime of Li-ion batteries.

Nanoparticle Amplification Labeling for High-Performance Magnetic Cell Sorting.

Magnetic cell sorting is an enabling tool for the isolation of specific cellular subpopulations for downstream applications and requires the cells to be labeled by a sufficient number of magnetic nanoparticles to leverage magnetophoresis for efficient separation. This requirement makes it challenging to target weakly expressed biomarkers. Here, we developed a new approach that selectively and efficiently amplifies the magnetic labeling on cells through sequentially connected antibodies and nanoparticles delivered to the surface or interior of the cell. Using this approach, we achieved amplification up to 100-fold for surface and intracellular markers. We also demonstrated the utility of this assay for enabling high-performance magnetic cell sorting when it is applied to the analysis of rare tumor cells for cancer diagnosis and the purification of transfected CAR T cells for immunotherapy. The data presented demonstrate a useful tool for the stratification of rare cell subpopulations.

Capillary-Assisted Molecular Pendulum Bioanalysis.

The development of robust biosensing strategies that can be easily implemented in everyday life remains a challenge for the future of modern biosensor research. While several reagentless approaches have attempted to address this challenge, they often achieve user-friendliness through sacrificing sensitivity or universality. While acceptable for certain applications, these trade-offs hinder the widespread adoption of reagentless biosensing technologies. Here, we report a novel approach to reagentless biosensing that achieves high sensitivity, rapid detection, and universality using the SARS-CoV-2 virus as a model target. Universality is achieved by using nanoscale molecular pendulums, which enables reagentless electrochemical biosensing through a variable antibody recognition element. Enhanced sensitivity and rapid detection are accomplished by incorporating the coffee-ring phenomenon into the sensing scheme, allowing for target preconcentration on a ring-shaped electrode. Using this approach, we obtained limits of detection of 1 fg/mL and 20 copies/mL for the SARS-CoV-2 nucleoproteins and viral particles, respectively. In addition, clinical sample analysis showed excellent agreement with Ct values from PCR-positive SARS-CoV-2 patients.

Correlating Li-Ion Solvation Structures and Electrode Potential Temperature Coefficients.

Temperature coefficients (TCs) for either electrochemical cell voltages or potentials of individual electrodes have been widely utilized to study the thermal safety and cathode/anode phase changes of lithium (Li)-ion batteries. However, the fundamental significance of single electrode potential TCs is little known. In this work, we discover that the Li-ion desolvation process during Li deposition/intercalation is accompanied by considerable entropy change, which significantly contributes to the measured Li/Li+ electrode potential TCs. To explore this phenomenon, we compare the Li/Li+ electrode potential TCs in a series of electrolyte formulations, where the interaction between Li-ion and solvent molecules occurs at varying strength as a function of both solvent and anion species as well as salt concentrations. As a result, we establish correlations between electrode potential TCs and Li-ion solvation structures and further verify them by ab initio molecular dynamics simulations. We show that measurements of Li/Li+ electrode potential TCs provide valuable knowledge regarding the Li-ion solvation environments and could serve as a screening tool when designing future electrolytes for Li-ion/Li metal batteries.

Potentiometric Measurement to Probe Solvation Energy and Its Correlation to Lithium Battery Cyclability.

The electrolyte plays a critical role in lithium-ion batteries, as it impacts almost every facet of a battery's performance. However, our understanding of the electrolyte, especially solvation of Li+, lags behind its significance. In this work, we introduce a potentiometric technique to probe the relative solvation energy of Li+ in battery electrolytes. By measuring open circuit potential in a cell with symmetric electrodes and asymmetric electrolytes, we quantitatively characterize the effects of concentration, anions, and solvents on solvation energy across varied electrolytes. Using the technique, we establish a correlation between cell potential (Ecell) and cyclability of high-performance electrolytes for lithium metal anodes, where we find that solvents with more negative cell potentials and positive solvation energies-those weakly binding to Li+-lead to improved cycling stability. Cryogenic electron microscopy reveals that weaker solvation leads to an anion-derived solid-electrolyte interphase that stabilizes cycling. Using the potentiometric measurement for characterizing electrolytes, we establish a correlation that can guide the engineering of effective electrolytes for the lithium metal anode.

Detection of SARS-CoV-2 Viral Particles Using Direct, Reagent-Free Electrochemical Sensing.

The development of new methods for direct viral detection using streamlined and ideally reagent-free assays is a timely and important, but challenging, problem. The challenge of combatting the COVID-19 pandemic has been exacerbated by the lack of rapid and effective methods to identify viral pathogens like SARS-CoV-2 on-demand. Existing gold standard nucleic acid-based approaches require enzymatic amplification to achieve clinically relevant levels of sensitivity and are not typically used outside of a laboratory setting. Here, we report reagent-free viral sensing that directly reads out the presence of viral particles in 5 minutes using only a sensor-modified electrode chip. The approach relies on a class of electrode-tethered sensors bearing an analyte-binding antibody displayed on a negatively charged DNA linker that also features a tethered redox probe. When a positive potential is applied, the sensor is transported to the electrode surface. Using chronoamperometry, the presence of viral particles and proteins can be detected as these species increase the hydrodynamic drag on the sensor. This report is the first virus-detecting assay that uses the kinetic response of a probe/virus complex to analyze the complexation state of the antibody. We demonstrate the performance of this sensing approach as a means to detect, within 5 min, the presence of the SARS-CoV-2 virus and its associated spike protein in test samples and in unprocessed patient saliva.

Health-related quality of life, functional decline, and long-term mortality in older patients following hospitalisation due to COVID-19.

BACKGROUND: Older people are particularly vulnerable to severe COVID-19. Little is known about long-term consequences of COVID-19 on health-related quality of life (HR-QoL) and functional status in older people, and the impact of age in this context. We aimed to study age-related change in health-related quality of life, functional decline and mortality among older patients 6 months following hospitalisation due to COVID-19. METHODS: This was a cohort study including patients aged 60 years and older admitted to four general hospitals in South-Eastern Norway due to COVID-19, from March 1 up until July 1, 2020. Patients who were still alive were invited to attend a six-month follow-up. Change in HR-QoL and functional status compared to before the COVID-19 hospitalisation were assessed using the EuroQol 5-dimensional-5 levels questionnaire (EQ. 5D-5L). A change in visual analogue scale (VAS) score of 7 or more was considered clinically relevant. RESULTS: Out of 216 patients aged 60 years and older that were admitted to hospital due to COVID-19 during the study period, 171 were still alive 180 days after hospital admission, and 106 patients (62%) attended the six-month follow-up. Mean age was 74.3 years, 27 patients (26%) had experienced severe COVID-19. Fifty-seven participants (54%) reported a decrease in the EQ. 5D-5L VAS score after 6 months, with no significant difference between persons aged 75 years and older compared to younger. Seventy participants (66%) reported a negative change in any of the dimensions of the EQ. 5D-5L, with impaired ability to perform activities of daily life (35%), reduced mobility (33%) and having more pain or discomfort (33%) being the most commonly reported changes. Forty-six participants (43%) reported a negative change in cognitive function compared to before the COVID-19 hospitalisation. Six-month mortality was 21%, and increased with increasing age. CONCLUSIONS: More than half of the patients reported a negative change in HR-QoL 6 months following hospitalisation due to COVID-19, and one out of three experienced a persistently impaired mobility and ability to carry out activities of daily living. The results suggest awareness of long-term functional decline in older COVID-19 patients.

Designing a Nanoscale Three-phase Electrochemical Pathway to Promote Pt-catalyzed Formaldehyde Oxidation.

Gas-phase heterogeneous catalysis is a process spatially constrained on the two-dimensional surface of a solid catalyst. Here, we introduce a new toolkit to open up the third dimension. We discovered that the activity of a solid catalyst can be dramatically promoted by covering its surface with a nanoscale-thin layer of liquid electrolyte while maintaining efficient delivery of gas reactants, a strategy we call three-phase catalysis. Introducing the liquid electrolyte converts the original surface catalytic reaction into an electrochemical pathway with mass transfer facilitated by free ions in a three-dimensional space. We chose the oxidation of formaldehyde as a model reaction and observed a 25000-times enhancement in the turnover frequency of Pt in three-phase catalysis as compared to conventional heterogeneous catalysis. We envision three-phase catalysis as a new dimension for catalyst design and anticipate its applications in more chemical reactions from pollution control to the petrochemical industry.

Fluorescent Droplet Cytometry for On-Cell Phenotype Tracking.

Profiling the heterogeneous phenotypes of live cancer cells is a key capability that requires single-cell analysis. However, acquiring information at the single-cell level for live cancer cells is challenging when small collections of cells are being targeted. Here, we report single-cell analysis for low abundance cells enabled by fluorescent droplet cytometry (FDC), an approach that uses a biomarker-specific enzymatic fluorescent assay carried out using a droplet microfluidic platform. FDC utilizes DNA-functionalized antibodies in droplets to achieve specific on-cell target detection and enables characterization and profiling of live cancer cells with single-cell resolution based on their surface phenotype. Using this approach, we achieve live-cell phenotypic profiling of multiple surface markers acquired with small (<40 cells) collections of cells.

Amino acid metabolism, lipid metabolism, and oxidative stress are associated with post-stroke depression: a metabonomics study.

BACKGROUND: Post-stroke depression (PSD) is a mood disorder characterized by depression and anhedonia caused by stroke. Metabolomics identified metabolites associated with PSD, but previous studies are based on gas chromatography (GC)/mass spectrometry (MS). This study aimed to perform a liquid chromatography (LC)-MS-based metabolomics study of the plasma metabolite profiles between patients with PSD and controls. METHODS: This was a prospective study of patients with stroke enrolled between July and December 2017 at the Second Affiliated Hospital of Nanchang University. Patients were grouped as Hamilton Depression Rating Scale > 7 (PSD) or < 7 (controls). Metabonomics profiling of plasma sampled was conducted by LC-MS. By combining multivariable and univariable statistical analyses, significant differential metabolites between the two groups were screened. The threshold for significant differences was VIP ≥1 and P < 0.05. Log2FC is the logarithm of the mean ratio between the two groups. RESULTS: There were no significant difference with respect to age, NIHSS score, and MMSE between the two groups (all P > 0.05). There were six differential metabolites between the PSD and stroke groups, of which three metabolites were increased and three were decreased. Compared with the control group, p-chlorophenylalanine (Log2FC = 1.37, P = 0.03), phenylacetyl glutamine (Log2FC = 0.21, P = 0.048), and DHA (Log2FC = 0.77, P = 0.01) levels were higher in the PSD group, while betaine (trimethylglycine) (Log2FC = - 0.79, P = 0.04), palmitic acid (Log2FC = - 0.51, P = 0.001), and MHPG-SO4 (Log2FC = - 2.37, P = 0.045) were decreased. CONCLUSION: Plasma metabolomics showed that amino acid metabolism (phenylacetyl glutamine, p-chlorophenylalanine, trimethylglycine), lipid metabolism (DHA, palmitic acid, trimethylglycine), and oxidative stress (DHA, palmitic acid, trimethylglycine) were associated with PSD. These results could help to reveal the pathophysiological mechanism of PSD and eventually identify treatment targets.

Wrinkled Graphene Cages as Hosts for High-Capacity Li Metal Anodes Shown by Cryogenic Electron Microscopy.

Lithium (Li) metal has long been considered the "holy grail" of battery anode chemistry but is plagued by low efficiency and poor safety due to its high chemical reactivity and large volume fluctuation, respectively. Here we introduce a new host of wrinkled graphene cage (WGC) for Li metal. Different from recently reported amorphous carbon spheres, WGC show highly improved mechanical stability, better Li ion conductivity, and excellent solid electrolyte interphase (SEI) for continuous robust Li metal protection. At low areal capacities, Li metal is preferentially deposited inside the graphene cage. Cryogenic electron microscopy characterization shows that a uniform and stable SEI forms on the WGC surface that can shield the Li metal from direct exposure to electrolyte. With increased areal capacities, Li metal is plated densely and homogeneously into the outer pore spaces between graphene cages with no dendrite growth or volume change. As a result, a high Coulombic efficiency (CE) of ∼98.0% was achieved under 0.5 mA/cm2 and 1-10 mAh/cm2 in commercial carbonate electrolytes, and a CE of 99.1% was realized with high-concentration electrolytes under 0.5 mA/cm2 and 3 mAh/cm2. Full cells using WGC electrodes with prestored Li paired with Li iron phosphate showed greatly improved cycle lifetime. With 10 mAh/cm2 Li metal deposition, the WGC/Li composite anode was able to provide a high specific capacity of ∼2785 mAh/g. With its roll-to-roll compatible fabrication procedure, WGC serves as a highly promising material for the practical realization of Li metal anodes in next-generation high energy density secondary batteries.

Evolution of the Solid-Electrolyte Interphase on Carbonaceous Anodes Visualized by Atomic-Resolution Cryogenic Electron Microscopy.

The stability of modern lithium-ion batteries depends critically on an effective solid-electrolyte interphase (SEI), a passivation layer that forms on the carbonaceous negative electrode as a result of electrolyte reduction. However, a nanoscopic understanding of how the SEI evolves with battery aging remains limited due to the difficulty in characterizing the structural and chemical properties of this sensitive interphase. In this work, we image the SEI on carbon black negative electrodes using cryogenic transmission electron microscopy (cryo-TEM) and track its evolution during cycling. We find that a thin, primarily amorphous SEI nucleates on the first cycle, which further evolves into one of two distinct SEI morphologies upon further cycling: (1) a compact SEI, with a high concentration of inorganic components that effectively passivates the negative electrode; and (2) an extended SEI spanning hundreds of nanometers. This extended SEI grows on particles that lack a compact SEI and consists primarily of alkyl carbonates. The diversity in observed SEI morphologies suggests that SEI growth is a highly heterogeneous process. The simultaneous emergence of these distinct SEI morphologies highlights the necessity of effective passivation by the SEI, as large-scale extended SEI growths negatively impact lithium-ion transport, contribute to capacity loss, and may accelerate battery failure.

Can screening tools for potentially inappropriate prescriptions in older adults prevent serious adverse drug events?

PURPOSE: The purpose of the study is to identify and explore risk factors of serious adverse drug events (SADE) and SADE-related admissions in acutely hospitalized multimorbid older adults and assess whether these could have been prevented by adherence to the prescription tools Screening Tool of Older Persons' Prescriptions (STOPP) and The Norwegian General Practice (NORGEP) criteria. METHODS: Cross-sectional study of acutely admitted patients to a medical department in a Norwegian regional hospital. Eligible patients were community-dwelling, receiving home care services, and aged 75+, with ≥ 3 chronic diseases. Medications and information regarding the admission were retrieved from the referral letter and medical records, while an expert panel identified SADE using the Common Terminology Criteria for Adverse Events and SADE-related admissions. RESULTS: We included 232 patients. Mean (SD) age was 86 (5.7) years, 137 (59%) were female, 121 (52%) used 5-9 drugs whereas 65 (28%) used ≥ 10. We identified SADEs in 72 (31%) of the patients, and in 49 (68%) of these cases, the SADE was considered to cause the hospital admission. A low body mass index (BMI) and a high Cumulative Illness Rating Scale-Geriatrics (CIRS-G) score were independent risk factors for SADEs. Among the SADEs identified, 32 (44%) and 11 (15%) were preventable by adherence to STOPP and NORGEP, respectively. CONCLUSIONS: We found a high prevalence of SADE leading to hospitalization. Risk factors for SADE were high CIRS-G and low BMI. STOPP identified more SADEs than NORGEP, but adherence to the prescription tools could only to a limited degree prevent SADEs in this patient group.

Delirium and cognitive impairment among older patients in Norwegian emergency departments. / Delirium og kognitiv svikt blant eldre i norske akuttmottak.

BACKGROUND: Delirium is common and underdiagnosed among patients in hospitals, and is associated with complications, increased mortality, onset of dementia and need for nursing home care. Cognitive impairment from other causes is also common among hospitalised elderly people and is a key risk factor for delirium. Since no relevant prevalence studies have been undertaken in Norwegian hospitals, we investigated the prevalence of delirium among elderly patients in Norwegian emergency departments on World Delirium Awareness Day, 14 March 2018. MATERIAL AND METHOD: We included patients ≥ 75 years who arrived in ten Norwegian emergency departments between 08:00 and 22:00 on that day. We identified delirium and cognitive impairment using the '4AT' screening tool and registered the patients' age and gender and the hospital and department to which they were admitted (internal medicine, surgery, orthopaedics, 'other'). RESULTS: Of 118 included patients, 20 (17 per cent) showed signs of delirium and 36 (30 per cent) showed signs of other forms of cognitive impairment. All hospitals and all categories of departments received patients with signs of delirium and cognitive impairment. INTERPRETATION: Delirium and other forms of cognitive impairment are both common among elderly patients in Norwegian emergency departments. Our results indicate that all hospital departments who treat elderly patients frequently observe these issues. All departments should therefore have routines to identify and deal with patients who suffer from delirium and cognitive impairment.

The Human Tau Interactome: Binding to the Ribonucleoproteome, and Impaired Binding of the Proline-to-Leucine Mutant at Position 301 (P301L) to Chaperones and the Proteasome.

The tau protein is central to the etiology of several neurodegenerative diseases, including Alzheimer's disease, a subset of frontotemporal dementias, progressive supranuclear palsy and dementia following traumatic brain injury, yet the proteins it interacts with have not been studied using a systematic discovery approach. Here we employed mild in vivo crosslinking, isobaric labeling, and tandem mass spectrometry to characterize molecular interactions of human tau in a neuroblastoma cell model. The study revealed a robust association of tau with the ribonucleoproteome, including major protein complexes involved in RNA processing and translation, and documented binding of tau to several heat shock proteins, the proteasome and microtubule-associated proteins. Follow-up experiments determined the relative contribution of cellular RNA to the tau interactome and mapped interactions to N- or C-terminal tau domains. We further document that expression of P301L mutant tau disrupts interactions of the C-terminal half of tau with heat shock proteins and the proteasome. The data are consistent with a model whereby a higher propensity of P301L mutant tau to aggregate may reflect a perturbation of its chaperone-assisted stabilization and proteasome-dependent degradation. Finally, using a global proteomics approach, we show that heterologous expression of a tau construct that lacks the C-terminal domain, including the microtubule binding domain, does not cause a discernible shift of the proteome except for a significant direct correlation of steady-state levels of tau and cystatin B.

Clinical impact of potentially inappropriate medications during hospitalization of acutely ill older patients with multimorbidity.

OBJECTIVE: To identify potentially inappropriate medications (PIMs), to compare drug changes between geriatric and other medical wards, and to investigate the clinical impact of PIMs in acutely hospitalized older adults. SETTING AND SUBJECTS: Retrospective study of 232 home-dwelling, multimorbid older adults (aged ≥75 years) acutely admitted to Vestfold Hospital Trust, Norway. MAIN OUTCOME MEASURES: PIMs were identified by Norwegian general practice (NORGEP) criteria and Beers' 2012 criteria. Clinical correlates were laboratory measures, functional and mental status, physical frailty, and length of stay. RESULTS: Mean (SD) age was 86 (5.7) years, and length of stay was 6.5 (4.8) days. During the stay, the mean number of drugs used regularly changed from 7.8 (3.6) to 7.9 (3.6) (p = 0.22), and drugs used pro re nata (prn) changed from 1.4 (1.6) to 2.0 (1.7) (p < 0.001). The prevalence of any PIM changed from 39.2% to 37.9% (p = 0.076), while anticholinergics and benzodiazepines were reduced significantly (p ≤ 0.02). The geriatric ward reduced drug dosages (p < 0.001) and discontinued PIMs (p < 0.001) significantly more often than other medical wards. No relations between number of PIMS and clinical outcomes were identified, but the concomitant use of ≥3 psychotropic/opioid drugs was associated with reduced hand-grip strength (p ≤ 0.012). CONCLUSION: Hospitalization did not change polypharmacy or PIMs. Drug treatment was more appropriate on the geriatric than other medical wards. No clinical impact of PIMs was observed, but prescribers should be vigilant about concomitant prescription of ≥3 psychotropics/opioids. KEY POINTS: Acute hospitalization of older patients with multimorbidity did not increase polypharmacy or potentially inappropriate medications. Prescription of anticholinergics and benzodiazepines was significantly reduced. The geriatric ward reduced drug dosages and discontinued potentially inappropriate medications more frequently than the other medical wards.