Unprotected Organic Cations─The Dilemma of Highly Li-Concentrated Ionic Liquid Electrolytes.

Highly Li-concentrated electrolytes have been widely studied to harness their uniquely varying bulk and interface properties that arise from their distinctive physicochemical properties and coordination structures. Similar strategies have been applied in the realm of ionic liquid electrolytes to exploit their improved functionalities. Despite these prospects, the impact of organic cation behavior on interfacial processes remains largely underexplored compared to the widely studied anion behavior. The present study demonstrates that the weakened interactions between cations and anions engender "unprotected" organic cations in highly Li-concentrated ionic liquid electrolytes, leading to the decomposition of electrolytes during the initial charge. This decomposition behavior is manifested by the substantial irreversible capacities and inferior initial Coulombic efficiencies observed during the initial charging of graphite negative electrodes, resulting in considerable electrolyte consumption and diminished energy densities in full-cell configurations. The innate cation behavior is ascertained by examining the coordination environment of ionic liquid electrolytes with varied Li concentrations, where intricate ionic interactions between organic cations and anions are unveiled. In addition, anionic species with high Lewis basicity were introduced to reinforce the ionic interactions involving organic cations and improve the initial Coulombic efficiency. This study verifies the role of unprotected organic cations while highlighting the significance of the coordination environment in the performance of ionic liquid electrolytes.

Fluoride Ion in Alcohols: Isopropanol vs Hexafluoroisopropanol.

The utility of alcohol as a hydrogen bonding donor is considered a providential avenue for moderating the high basicity and reactivity of the fluoride ion, typically used with large cations. However, the practicality of alcohol-fluoride systems in reactions is hampered by the limited understanding of the pertinent interactions between the OH group and F-. Therefore, this study comparatively investigates the thermal, structural, and physical properties of the CsF-2-propanol and CsF-1,1,1,3,3,3-hexafluoro-2-propanol systems to explicate the effects of the fluoroalkyl group on the interaction of alcohols and F-. The two systems exhibit vastly different phase diagrams despite the similar saturated concentrations. A combination of spectroscopic analyses, alcohol activity coefficient measurements, and theoretical calculations reveal the fluorinated alcohol system harbors the stronger OH···F- interactions between the two systems. The diffusion coefficient and ionic conductivity measurements attribute the present results to disparate states of ion association in the two systems.

Challenges for Field-Effect-Transistor-Based Graphene Biosensors.

Owing to its outstanding physical properties, graphene has attracted attention as a promising biosensor material. Field-effect-transistor (FET)-based biosensors are particularly promising because of their high sensitivity that is achieved through the high carrier mobility of graphene. However, graphene-FET biosensors have not yet reached widespread practical applications owing to several problems. In this review, the authors focus on graphene-FET biosensors and discuss their advantages, the challenges to their development, and the solutions to the challenges. The problem of Debye screening, in which the surface charges of the detection target are shielded and undetectable, can be solved by using small-molecule receptors and their deformations and by using enzyme reaction products. To address the complexity of sample components and the detection mechanisms of graphene-FET biosensors, the authors outline measures against nonspecific adsorption and the remaining problems related to the detection mechanism itself. The authors also introduce a solution with which the molecular species that can reach the sensor surfaces are limited. Finally, the authors present multifaceted approaches to the sensor surfaces that provide much information to corroborate the results of electrical measurements. The measures and solutions introduced bring us closer to the practical realization of stable biosensors utilizing the superior characteristics of graphene.

Trigger of the Highly Resistive Layer Formation at the Cathode-Electrolyte Interface in All-Solid-State Lithium Batteries Using a Garnet-Type Lithium-Ion Conductor.

Interfacial materials design is critical in the development of all-solid-state lithium batteries. We must develop an electrode-electrolyte interface with low resistance and effectively utilize the energy stored in the battery system. Here, we investigated the highly resistive layer formation process at the interface of a layered cathode: LiCoO2, and a garnet-type solid-state electrolyte: Li6.4La3Zr1.4Ta0.6O12, during the cosintering process using in situ/ex situ high-temperature X-ray diffraction. The onset temperature of the reaction between a lithium-deficient LixCoO2 and Li6.4La3Zr1.4Ta0.6O12 is 60 °C, while a stoichiometric LiCoO2 does not show any reaction up to 900 °C. The chemical potential gap of lithium first triggers the lithium migration from the garnet phase to the LixCoO2 below 200 °C. The lithium-extracted garnet gradually decomposes around 200 °C and mostly disappears at 500 °C. Since the interdiffusion of the transition metal is not observed below 500 °C, the early-stage reaction product is the decomposed lithium-deficient garnet phase. Electrochemical impedance spectroscopy results showed that the highly resistive layer is formed even below 200 °C. The present work offers that the origin of the highly resistive layer formation is triggered by lithium migration at the solid-solid interface and decomposition of the lithium-deficient garnet phase. We must prevent spontaneous lithium migration at the cathode-electrolyte interface to avoid a highly resistive layer formation. Our results show that the lithium chemical potential gap should be the critical parameter for designing an ideal solid-solid interface for all-solid-state battery applications.

Systematic Study of Aluminum Corrosion in Ionic Liquid Electrolytes for Sodium-Ion Batteries: Impact of Temperature and Concentration.

The development of sodium-ion batteries utilizing sulfonylamide-based electrolytes is significantly encumbered by the corrosion of the Al current collector, resulting in capacity loss and poor cycling stability. While ionic liquid electrolytes have been reported to suppress Al corrosion, a recent study found that pitting corrosion occurs even when ionic liquids are employed. This study investigates the effects of temperature and Na salt concentration on the Al corrosion behavior in different sulfonylamide-based ionic liquid electrolytes for sodium-ion batteries. In the present work, cyclic voltammetry measurements and scanning electron microscopy showed that severe Al corrosion occurred in ionic liquids at high temperatures and low salt concentrations. X-ray photoelectron spectroscopy was employed to identify the different elemental components and verify the thickness of the passivation layer formed under varied salt concentrations and temperatures. The differences in the corrosion behaviors observed under the various conditions are ascribed to the ratio of free [FSA]- to Na+-coordinating [FSA]- in the electrolyte and the stability of the newly formed passivation layer. This work aims at augmenting the understanding of Al corrosion behavior in ionic liquid electrolytes to develop advanced batteries.

Mechanism of Reductive Fluorination by PTFE-Decomposition Fluorocarbon Gases for WO3.

Reductive fluorination, which entails the substitution of O2- from oxide compounds with F- from fluoropolymers, is considered a practical approach for preparing transition-metal oxyfluorides. However, the current understanding of the fundamental reaction paths remains limited due to the analytical complexities posed by high-temperature reactions in glassware. Therefore, to expand this knowledgebase, this study investigates the reaction mechanisms behind the reductive fluorination of WO3 using polytetrafluoroethylene (PTFE) in an Ni reactor. Here, we explore varied reaction conditions (temperature, duration, and F/W ratio) to suppress the formation of carbon byproducts, minimize the dissipation of fluorine-containing tungsten (VI) compounds, and achieve a high fluorine content. The gas-solid reaction paths are analyzed using infrared spectroscopy, which revealed tetrafluoroethylene (C2F4), hexafluoropropene (C3F6), and iso-octafluoroisobutene (i-C4F8) to be the reactive components in the PTFE-decomposition gas during the reactions with WO3 at 500 °C. CO2 and CO are further identified as gaseous byproducts of the reaction evincing that the reaction is prompted by difluorocarbene (:CF2) formed after the cleavage of C═C bonds in i-C4F8, C3F6, and C2F4 upon contact with the WO3 surface. The solid-solid reaction path is established through a reaction between WO3 and WO3-xFx where solid-state diffusion of O2- and F- is discerned at 500 °C.

Stimulation of interferon-ß responses by aberrant SARS-CoV-2 small viral RNAs acting as retinoic acid-inducible gene-I agonists.

Patients with severe COVID-19 exhibit a cytokine storm characterized by greatly elevated levels of cytokines. Despite this, the interferon (IFN) response is delayed, contributing to disease progression. Here, we report that SARS-CoV-2 excessively generates small viral RNAs (svRNAs) encoding exact 5' ends of positive-sense genes in human cells in vitro and ex vivo, whereas endemic human coronaviruses (OC43 and 229E) produce significantly fewer similar svRNAs. SARS-CoV-2 5' end svRNAs are RIG-I agonists and induce the IFN-ß response in the later stages of infection. The first 60-nt ends bearing duplex structures and 5'-triphosphates are responsible for immune-stimulation. We propose that RIG-I activation by accumulated SARS-CoV-2 5' end svRNAs may contribute to later drive over-exuberant IFN production. Additionally, the differences in the amounts of svRNAs produced and the corresponding IFN response among CoV strains suggest that lower svRNA production during replication may correlate with the weaker immune response seen in less pathogenic CoVs.

Biosensing with Surface-Charge-Modulated Graphene Field-Effect Transistors beyond Nonlinear Electrolytic Screening.

In field-effect transistor (FET) biosensors, charge screening in electrolyte solutions limits the sensitivity, thereby restricting the applicability of FET sensors. This is particularly pronounced in graphene FET (GFET) biosensors, where the bare graphene surface possesses a strongly negative charge, which impedes the high sensitivity of GFETs owing to nonlinear electrolytic screening at the interfaces between graphene and liquid. In this study, we counteracted the negative surface charge of graphene by decorating positively charged compounds and demonstrated the sensing of C-reactive protein (CRP) with surface-charge-modulated GFETs (SCM-GFETs). We integrated multiple SCM-GFETs with anti-CRP antibodies and nonfunctionalized GFETs into a chip and measured differentials to eliminate background changes to improve measurement reliability. The FET response corresponded to the fluorescence images, which visualized the specific adsorption of CRP. The estimated dissociation constant was consistent with previously reported values; this supports the conclusion that the results are attributed to specific adsorption. Conversely, the signal in GFETs without decoration was obscured by noise because of nonlinear electrolytic screening, further emphasizing the significance of surface-charge modulation. The limit of detection of the system was determined to be 2.9 nM. This value has the potential to be improved through further optimization of the surface charges to align with specific applications. Our devices effectively circumvent nonlinear electrolytic screening, opening the door for further advancements in GFET biosensor technology.

ACE2 N-glycosylation modulates interactions with SARS-CoV-2 spike protein in a site-specific manner.

SARS-CoV-2 has evolved continuously and accumulated spike mutations with each variant having a different binding for the cellular ACE2 receptor. It is not known whether the interactions between such mutated spikes and ACE2 glycans are conserved among different variant lineages. Here, we focused on three ACE2 glycosylation sites (53, 90 and 322) that are geometrically close to spike binding sites and investigated the effect of their glycosylation pattern on spike affinity. These glycosylation deletions caused distinct site-specific changes in interactions with the spike and acted cooperatively. Of note, the particular interaction profiles were conserved between the SARS-CoV-2 parental virus and the variants of concern (VOCs) Delta and Omicron. Our study provides insights for a better understanding of the importance of ACE2 glycosylation on ACE2/SARS-CoV-2 spike interaction and guidance for further optimization of soluble ACE2 for therapeutic use.

Ionic strength-sensitive and pH-insensitive interactions between C-reactive protein (CRP) and an anti-CRP antibody.

C-reactive protein (CRP) is an important biomarker of infection and inflammation, as CRP is one of the most prominent acute-phase proteins. CRP is usually detected using anti-CRP antibodies (Abs), where the intermolecular interactions between CRP and the anti-CRP Ab are largely affected by the pH and ionic strength of environmental solutions. Therefore, it is important to understand the environmental effects of CRP-anti-CRP Ab interactions when designing highly sensitive biosensors. Here, we investigated the efficiency of fluorescently labeled CRP-anti-CRP monoclonal antibody (mAb) interactions at different pHs and ionic strengths. Our results indicate that the affinity was insensitive to pH changes in the range of 5.9 to 8.1, while it was significantly sensitive to ionic strength changes. The binding affinity decreased by 55% at an ionic strength of 1.6 mM, when compared to that under a physiological condition (~150 mM). Based on the isoelectric focusing results, both the labeled CRP and anti-CRP mAb were negatively charged in the studied pH range, which rendered the system insensitive to pH changes, but sensitive to ionic strength changes. The decreased ionic strength led to a significant enhancement of the repulsive force between CRP and the anti-CRP mAb. Although the versality of the findings is not fully studied yet, the results provide insights into designing highly sensitive CRP sensors, especially field-effect transistor-based sensors.

In Situ Orthorhombic to Amorphous Phase Transition of Nb2O5 and Its Temperature Effect on Pseudocapacitive Behavior.

Niobium pentoxide (Nb2O5) represents an exquisite class of negative electrode materials with unique pseudocapacitive kinetics that engender superior power and energy densities for advanced electrical energy storage devices. Practical energy devices are expected to maintain stable performance under real-world conditions such as temperature fluctuations. However, the intercalation pseudocapacitive behavior of Nb2O5 at elevated temperatures remains unexplored because of the scarcity of suitable electrolytes. Thus, in this study, we investigate the effect of temperature on the pseudocapacitive behavior of submicron-sized Nb2O5 in a wide potential window of 0.01-2.3 V. Furthermore, ex situ X-ray diffraction and X-ray photoelectron spectroscopy reveal the amorphization of Nb2O5 accompanied by the formation of NbO via a conversion reaction during the initial cycle. Subsequent cycles yield enhanced performance attributed to a series of reversible NbV, IV/NbIII redox reactions in the amorphous LixNb2O5 phase. Through cyclic voltammetry and symmetric cell electrochemical impedance spectroscopy, temperature elevation is noted to increase the pseudocapacitive contribution of the Nb2O5 electrode, resulting in a high rate capability of 131 mAh g-1 at 20,000 mA g-1 at 90 °C. The electrode further exhibits long-term cycling over 2000 cycles and high Coulombic efficiency ascribed to the formation of a robust, [FSA]--originated solid-electrolyte interphase during cycling.

Octaphyrin(1.0.1.0.1.0.1.0) as an Organic Electrode for Li and Na Rechargeable Batteries.

Organic electrode materials for rechargeable batteries have come into the spotlight due to their structural tunability and diversity. In this study, it is found that bisnickel(II) meso-mesityloctaphyrin(1.0.1.0.1.0.1.0) (Oct) is exhibiting multiple oxidation states with extended π-conjugation pathways to afford an active electrode material in Li and Na-organic batteries and secure interactions with Li+ (or Na+ ) and anions enabling efficient dual ionic charge/discharge behaviors. Cyclic voltammograms of the Oct electrode elucidate constantly reversible redox processes in both Li and Na organic batteries and pseudocapacitive behaviors at high currents. Subsequent absorption transformations in CV-UV/VIS/NIR spectroscopic analysis and TD-DFT calculations upon the different redox states of Oct conclusively indicate that six electrons are involved in redox-interconversions per unit cycle with corresponding absorption transformations, which also assessed with charge-and-discharge cell capacities. Significant contributions of the pseudocapacitive processes over the diffusion-controlled processes proceeding in Li- and Na-Oct cells induced fast charge/discharge performance and long-term cyclability.

Strategies for Harnessing High Rate and Cycle Performance from Graphite Electrodes in Potassium-Ion Batteries.

Potassium-ion batteries (PIBs) have been lauded as the next-generation energy storage systems on account of their high voltage capabilities and low costs and the high abundance of potassium resources. However, the practical utility of PIBs has been heavily encumbered by severe K metal dendrite formation, safety issues, and insufficient electrochemical performance during operations─indeed critical issues that underpin the need for functional electrolytes with high thermal stability, robust solid-electrolyte interphase (SEI)-forming capabilities, and high electrochemical performance. In a bid to establish a knowledge framework for harnessing high rate capabilities and long cycle life from graphite negative electrodes, this study presents the physical properties and electrochemical behavior of a high K+ concentration inorganic ionic liquid (IL) electrolyte, K[FSA]-Cs[FSA] (FSA- = bis(fluorosulfonyl)amide) (54:46 in mol), at an intermediate temperature of 70 °C. This IL electrolyte demonstrates an ionic conductivity of 2.54 mS cm-1 and a wide electrochemical window of 5.82 V. Charge-discharge tests performed on a graphite negative electrode manifest a high discharge capacity of 278 mAh g-1 (0.5 C) at 70 °C, a high rate capability (106 mAh g-1 at 100 C), and a long cyclability (98.7% after 450 cycles). Stable interfacial properties observed by electrochemical impedance spectroscopy during cycling are attributed to the formation of sulfide-rich all-inorganic SEI, which was examined through X-ray photoelectron spectroscopy. The performance of the IL is collated with that of an N-methyl-N-propylpyrrolidinium-based organic IL to provide insight into the synergism between the highly concentrated K+ electrolyte at intermediate temperatures and the all-inorganic SEI during electrochemical operations of the graphite negative electrode.

Efficacy of bath-psoralen and ultraviolet A therapy for mycosis fungoides - retrospective analysis of 62 cases.

Photochemotherapy with psoralen and ultraviolet A (PUVA) is widely used for refractory skin diseases. Bathwater delivery of 8-methoxypsoralen (8-MOPS) with subsequent UVA irradiation (bath-PUVA) or oral administration of 8-MOPS with UVA is used to treat mycosis fungoides. We retrospectively analyzed 62 patients with mycosis fungoides (8 stage IA, 30 stage IB, 5 stage IIB, 18 stage IIIA, and 1 stage IVA2) treated with bath-PUVA at the Dermatology Clinic of Nagoya City University Hospital from November 2004 to December 2013. A complete response was achieved in 37 (59.7%) patients, a partial response was achieved in 16 (25.8%), and stable disease was achieved in 6 (9.7%). Progressive disease was observed in 3 (4.8%) patients. Almost all patients in stage IA/IB achieved a complete response. Of the 5 stage IIB patients, 2 achieved a partial response, 1 achieved stable disease, and 2 had progressive disease. The serum concentrations of soluble interleukin-2 receptor and lactate dehydrogenase decreased significantly following treatment with bath-PUVA (p < 0.001). We examined the risk factors of patients whose stage progressed despite PUVA treatment. A multivariate Cox regression analysis of risk factors associated with stage progression yielded a hazard ratio of 28.5 for stage IIb. Treatment with bath-PUVA is highly effective in the early stages of mycosis fungoides, and partially effective in advanced stages.

Drift Suppression of Solution-Gated Graphene Field-Effect Transistors by Cation Doping for Sensing Platforms.

Solution-gated graphene field-effect transistors (SG-GFETs) provide an ideal platform for sensing biomolecules owing to their high electron/hole mobilities and 2D nature. However, the transfer curve often drifts in an electrolyte solution during measurements, making it difficult to accurately estimate the analyte concentration. One possible reason for this drift is that p-doping of GFETs is gradually countered by cations in the solution, because the cations can permeate into the polymer residue and/or between graphene and SiO2 substrates. Therefore, we propose doping sufficient cations to counter p-doping of GFETs prior to the measurements. For the pre-treatment, GFETs were immersed in a 15 mM sodium chloride aqueous solution for 25 h. The pretreated GFETs showed that the charge neutrality point (CNP) drifted by less than 3 mV during 1 h of measurement in a phosphate buffer, while the non-treated GFETs showed that the CNP was severely drifted by approximately 50 mV, demonstrating a 96% reduction of the drift by the pre-treatment. X-ray photoelectron spectroscopy analysis revealed the accumulation of sodium ions in the GFETs through pre-treatment. Our method is useful for suppressing drift, thus allowing accurate estimation of the target analyte concentration.

Recent advances in sulfur tetrafluoride chemistry: syntheses, structures, and applications.

Sulfur and fluorine occupy crucial positions in main group chemistry because these two elements form a variety of compounds with versatile bond modalities and unique functionalities. Among sulfur-fluorine compounds, the importance of SF4 and its derivatives is recognized in the literature. The amphoteric nature of SF4 results in its rich Lewis acidic and basic reactivities; the reactions with F- acceptors and donors yield [SF3]+ and [SF5]- salts, respectively. Lewis basic molecules can also form adducts with SF4via various interaction motifs. The deoxofluorinating properties of SF4 have been used by organic chemists to selectively introduce fluorine atoms in specific substrates, extending also to industrial applications. Although the properties and reactivity of SF4 have been studied since its first synthesis, the recent progress in the SF4-related chemistry is striking, involving various fields of chemistry. In this Frontier article, recent advances, mainly the last ten years, in syntheses and structures of SF4-related compounds including its cationic and anionic derivatives and adducts with Lewis bases are concisely reviewed. Their uses in fundamental and applied inorganic chemistries are also described.

Mixed alkali-ion transport and storage in atomic-disordered honeycomb layered NaKNi2TeO6.

Honeycomb layered oxides constitute an emerging class of materials that show interesting physicochemical and electrochemical properties. However, the development of these materials is still limited. Here, we report the combined use of alkali atoms (Na and K) to produce a mixed-alkali honeycomb layered oxide material, namely, NaKNi2TeO6. Via transmission electron microscopy measurements, we reveal the local atomic structural disorders characterised by aperiodic stacking and incoherency in the alternating arrangement of Na and K atoms. We also investigate the possibility of mixed electrochemical transport and storage of Na+ and K+ ions in NaKNi2TeO6. In particular, we report an average discharge cell voltage of about 4 V and a specific capacity of around 80 mAh g-1 at low specific currents (i.e., < 10 mA g-1) when a NaKNi2TeO6-based positive electrode is combined with a room-temperature NaK liquid alloy negative electrode using an ionic liquid-based electrolyte solution. These results represent a step towards the use of tailored cathode active materials for "dendrite-free" electrochemical energy storage systems exploiting room-temperature liquid alkali metal alloy materials.

Double mutations in the H9N2 avian influenza virus PB2 gene act cooperatively to increase viral host adaptation and replication for human infections.

Avian H9N2 influenza viruses in East Asia are genetically diversified and multiple genotypes (A-W) have been established in poultry. Genotype S strains are currently the most prevalent strains, have caused many human infections and pose a public health threat. In this study, human adaptation mutations in the PB2 polymerase in genotype S strains were identified by database screening. Several PB2 double mutations were identified that acted cooperatively to produce higher genotype S virus polymerase activity and replication in human cells than in avian cells and to increase viral growth and virulence in mice. These mutations were chronologically and phylogenetically clustered in a new group within genotype S viruses. Most of the relevant human virus isolates carry the PB2-A588V mutation together with another PB2 mutation (i.e. K526R, E627V or E627K), indicating a host adaptation advantage for these double mutations. The prevalence of PB2 double mutations in human H9N2 virus isolates has also been found in genetically related human H7N9 and H10N8 viruses. These results suggested that PB2 double mutations in viruses in the field acted cooperatively to increase human adaptation of the currently prevalent H9N2 genotype S strains. This may have contributed to the recent surge of H9N2 infections and may be applicable to the human adaptation of several other avian influenza viruses. Our study provides a better understanding of the human adaptation pathways of genetically related H9N2, H7N9 and H10N8 viruses in nature.

Stable Cycle Performance of a Phosphorus Negative Electrode in Lithium-Ion Batteries Derived from Ionic Liquid Electrolytes.

Although high-capacity negative electrode materials are seen as a propitious strategy for improving the performance of lithium-ion batteries (LIBs), their advancement is curbed by issues such as pulverization during the charge/discharge process and the formation of an unstable solid electrolyte interphase (SEI). In particular, electrolytes play a vital role in determining the properties of an SEI layer. Thus, in this study, we investigate the performance of a red phosphorus/acetylene black composite (P/AB) prepared by high-energy ball milling as a negative electrode material for LIBs using organic and ionic liquid (IL) electrolytes. Galvanostatic tests performed on half cells demonstrate high discharge capacities in the 1386-1700 mAh (g-P/AB)-1 range along with high Coulombic efficiencies of 85.3-88.2% in the first cycle, irrespective of the electrolyte used. Upon cycling, the Li[FSA]-[C2C1im][FSA] (FSA- = bis(fluorosulfonyl)amide and C2C1im+ = 1-ethyl-3-methylimidazolium) IL electrolyte (2:8 in mol) demonstrates a high capacity retention of 78.8% after 350 cycles, whereas significant capacity fading is observed in the Li[PF6] and Li[FSA] organic electrolytes. Electrochemical impedance spectroscopy conducted with cycling revealed lower interfacial resistance in the IL electrolyte than in the organic electrolytes. Scanning electron microscopy and X-ray photoelectron spectroscopy after cycling in different electrolytes evinced that the IL electrolyte facilitates the formation of a robust SEI layer comprising multiple layers of sulfur species resulting from FSA- decomposition. A P/AB|LiFePO4 full cell using the IL electrolyte showed superior capacity retention than organic electrolytes and a high energy density under ambient conditions. This work not only illuminates the improved performance of a phosphorous-based negative electrode alongside ionic liquid electrolytes but also displays a viable strategy for the development of high-performance LIBs, especially for large-scale applications.

Clear cell injury associated with reduced expression of carbonic anhydrase II in eccrine glands consistently occurs in patients with acquired idiopathic generalized anhidrosis.

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. It has been believed that AIGA patients usually present no significant morphological alterations in the secretory portion of eccrine glands consisting of clear, dark and myoepithelial cells. However, we have recently revealed morphological damage of eccrine glands in AIGA patients by immunohistochemistry. Moreover, inhibitory side-effects against carbonic anhydrase II (CA II) by the antiepileptic reagent topiramate have been reported to cause heat intolerance mimicking AIGA. To determine the precise morphological changes and CA II expression in eccrine glands of AIGA patients, electron microscopic observation and immunohistochemistry were applied to skin of both anhidrotic (non-sweating) and normohidrotic (sweating-preserved) sites, taken from each patient clinically diagnosed with AIGA. We found consistent clear cell injury in eccrine glands in anhidrotic skin samples of AIGA patients. Electron micrographs demonstrated edematous, swollen and destructive damage in clear cells of eccrine glands from non-sweating areas of almost all AIGA patients. Immunohistochemically, clear cells showed reduced CA II expression that was heterogeneously distributed in non-sweating skin. Some areas showed almost complete loss of CA II expression in spite of preserved dark cells, and others showed mild or moderate loss of it. Selective destruction of clear cells resulting in heterogenous atrophy in AIGA patients may be important to elucidate its etiology.