Lightweight Electrolyte Design for Li/Sulfurized Polyacrylonitrile (SPAN) Batteries.

Sulfurized polyacrylonitrile (SPAN) recently emerges as a promising cathode for high-energy lithium (Li) metal batteries owing to its high capacity, extended cycle life, and liberty from costly transition metals. As the high capacities of both Li metal and SPAN lead to relatively small electrode weights, the weight and specific energy density of Li/SPAN batteries are particularly sensitive to electrolyte weight, highlighting the importance of minimizing electrolyte density. Besides, the large volume changes of Li metal anode and SPAN cathode require inorganic-rich interphases that can guarantee intactness and protectivity throughout long cycles. This work addresses these crucial aspects with an electrolyte design where lightweight dibutyl ether (DBE) is used as a diluent for concentrated lithium bis(fluorosulfonyl)imide (LiFSI)-triethyl phosphate (TEP) solution. The designed electrolyte (d = 1.04 g mL-1) is 40%-50% lighter than conventional localized high-concentration electrolytes (LHCEs), leading to 12%-20% extra energy density at the cell level. Besides, the use of DBE introduces substantial solvent-diluent affinity, resulting in a unique solvation structure with strengthened capability to form favorable anion-derived inorganic-rich interphases, minimize electrolyte consumption, and improve cell cyclability. The electrolyte also exhibits low volatility and offers good protection to both Li metal anode and SPAN cathode under thermal abuse.

Synergetic Dual-Additive Electrolyte Enables Highly Stable Performance in Sodium Metal Batteries.

Sodium (Na)-metal batteries (SMBs) are considered one of the most promising candidates for the large-scale energy storage market owing to their high theoretical capacity (1,166 mAh g-1) and the abundance of Na raw material. However, the limited stability of electrolytes still hindered the application of SMBs. Herein, sulfolane (Sul) and vinylene carbonate (VC) are identified as effective dual additives that can largely stabilize propylene carbonate (PC)-based electrolytes, prevent dendrite growth, and extend the cycle life of SMBs. The cycling stability of the Na/NaNi0.68Mn0.22Co0.1O2 (NaNMC) cell with this dual-additive electrolyte is remarkably enhanced, with a capacity retention of 94% and a Coulombic efficiency (CE) of 99.9% over 600 cycles at a 5 C (750 mA g-1) rate. The superior cycling performance of the cells can be attributed to the homogenous, dense, and thin hybrid solid electrolyte interphase consisting of F- and S-containing species on the surface of both the Na metal anode and the NaNMC cathode by adding dual additives. Such unique interphases can effectively facilitate Na-ion transport kinetics and avoid electrolyte depletion during repeated cycling at a very high rate of 5 C. This electrolyte design is believed to result in further improvements in the performance of SMBs.

[Diagnosis of combined ophthalmic and dermatological manifestations of HIV]. / Diagnostika sochetannykh oftal'mologicheskikh i dermatologicheskikh proyavlenii VICh-infektsii.

This article contains up-to-date information on the features of ophthalmological and dermatological manifestations of human immunodeficiency virus (HIV) infection based on the analysis of studies published in 2018-2022. The article also presents a description of a clinical case of HIV infection in a 54-year-old female patient with synchronous manifestation of eye symptoms in the form of retinal vasculitis of the optic nerve head and Kaposi's sarcoma localized on the skin of the face.

Direct in situ measurements of electrical properties of solid-electrolyte interphase on lithium metal anodes.

The solid-electrolyte interphase (SEI) critically governs the performance of rechargeable batteries. An ideal SEI is expected to be electrically insulative to prevent persistently parasitic reactions between the electrode and the electrolyte and ionically conductive to facilitate Faradaic reactions of the electrode. However, the true nature of the electrical properties of the SEI remains hitherto unclear due to the lack of a direct characterization method. Here we use in situ bias transmission electron microscopy to directly measure the electrical properties of SEIs formed on copper and lithium substrates. We reveal that SEIs show a voltage-dependent differential conductance. A higher rate of differential conductance induces a thicker SEI with an intricate topographic feature, leading to an inferior Coulombic efficiency and cycling stability in Li∣∣Cu and Li∣∣LiNi0.8Mn0.1Co0.1O2 cells. Our work provides insight into the targeted design of the SEI with desired characteristics towards better battery performance.

Early Failure of Lithium-Sulfur Batteries at Practical Conditions: Crosstalk between Sulfur Cathode and Lithium Anode.

Lithium-sulfur (Li-S) batteries are one of the most promising next-generation energy storage technologies due to their high theoretical energy and low cost. However, Li-S cells with practically high energy still suffer from a very limited cycle life with reasons which remain unclear. Here, through cell study under practical conditions, it is proved that an internal short circuit (ISC) is a root cause of early cell failure and is ascribed to the crosstalk between the S cathode and Li anode. The cathode topography affects S reactions through influencing the local resistance and electrolyte distribution, particularly under lean electrolyte conditions. The inhomogeneous reactions of S cathodes are easily mirrored by the Li anodes, resulting in exaggerated localized Li plating/stripping, Li filament formation, and eventually cell ISC. Manipulating cathode topography is proven effective to extend the cell cycle life under practical conditions. The findings of this work shed new light on the electrode design for extending cycle life of high-energy Li-S cells, which are also applicable for other rechargeable Li or metal batteries.

Deep Eutectic Solvent Based on Lithium Bis[(trifluoromethyl)sulfonyl] Imide (LiTFSI) and 2,2,2-Trifluoroacetamide (TFA) as a Promising Electrolyte for a High Voltage Lithium-Ion Battery with a LiMn2O4 Cathode.

To design safe and electrochemically stable electrolytes for lithium-ion batteries, this study describes the synthesis and the utilization of new deep eutectic solvents (DESs) based on the mixture of 2,2,2-trifluoroacetamide (TFA) with a lithium salt (LiTFSI, lithium bis[(trifluoromethane)sulfonyl]imide). These prepared DESs were characterized in terms of thermal properties, ionic conductivity, viscosity, and electrochemical properties. Based on the appearance of the product and DSC measurements, it appears that this system is liquid at room temperature for LiTFSI mole fraction ranging from 0.25 to 0.5. At χLiTFSI = 0.25, DESs exhibited favorable electrolyte properties, such as thermal stability (up to 148 °C), relatively low viscosity (42.2 mPa.s at 30 °C), high ionic conductivity (1.5 mS.cm-1 at 30 °C), and quite large electrochemical stability window up to 4.9-5.3 V. With these interesting properties, selected DES was diluted with slight amount of ethylene carbonate (EC). Different amounts of EC (x = 0-30 %wt) were used to form hybrid electrolytes for battery testing with high voltage LiMn2O4 cathode and Li anode. The addition of the EC solvent into DES expectedly aims at enhancing the battery cycling performance at room temperature due to reducing the viscosity. Preliminary results tests clearly show that LiTFSI-based DES can be successfully introduced as an electrolyte in the lithium-ion batteries cell with a LiMn2O4 cathode material. Among all of the studied electrolytes, DES (LiTFSI: TFA = 4:1 + 10 %wt EC) is the most promising. The EC-based system exhibited a good specific capacity of 102 mAh.g-1 at C/10 with the theoretical capacity of 148 mAh.g-1 and a good cycling behavior maintaining at 84% after 50 cycles.

Exploring how virtual primary care visits affect patient burden of treatment.

BACKGROUND: There is growing emphasis on the role of digital solutions in supporting chronic disease management. This has the potential to increase the burden patients experience in managing their health by offloading care from the health system to patients. This paper explores the effects of virtual visits on patient burden using an explicit framework measuring both the work patients do to care for their health and the challenges they experience that exacerbate burden. METHODS: This mixed methods study evaluates a large pilot implementation of virtual visits (video, audio, and asynchronous messaging with providers) in primary care in Ontario, Canada. Participants were recruited using convenience sampling from patients using a virtual visit platform to complete a semi-structured interview or a survey including a free-text response. We conducted 17 interviews and reviewed 427 free text responses related to explore patients' perceived value and burden of these visits. We used qualitative analyses to map patients' feedback on their experience to the framework on patient burden. MAIN FINDINGS: Virtual visits appear to reduce the work patients must do to manage their care by 1) improving access, convenience, and time needed for medical appointments, and 2) making it easier to access information and support for chronic disease management. Virtual visits also alleviate patients' perceived burden by improving continuity of care, experience of care, and providing some cost savings. CONCLUSIONS: Virtual visits reduced overall patient burden of treatment by decreasing the required patient effort of managing medical appointments and monitoring their health, and by minimizing challenges experienced when accessing care. For regions that want to improve patient experience of care, virtual visits are likely to be of benefit. There is need for further research on the generalizability of the findings herein, particularly for high-needs populations under-represented such as those of low socioeconomic status and those in rural and remote locations.

Exosomal Annexin II Promotes Angiogenesis and Breast Cancer Metastasis.

Tumor-derived exosomes are emerging mediators of tumorigenesis and tissue-specific metastasis. Proteomic profiling has identified Annexin II as one of the most highly expressed proteins in exosomes; however, studies focused on the biological role of exosomal Annexin II (exo-Anx II) are still lacking. In this study, mechanistic insight was sought regarding exo-Anx II and its function in angiogenesis and breast cancer metastasis. Multiple in vitro and in vivo techniques were used to study the role of exo-Anx II in angiogenesis. Using atomic force microscopy and Western blotting, exo-Anx II expression was characterized in normal and breast cancer cells. In addition, organ-specific metastatic breast cancer cells and animal models were used to define the role exo-Anx II in breast cancer metastasis. Results revealed that exo-Anx II expression is significantly higher in malignant cells than normal and premetastatic breast cancer cells. In vitro and in vivo studies demonstrated that exo-Anx II promotes tPA-dependent angiogenesis. Furthermore, in vivo analysis indicated that metastatic exosomes create a favorable microenvironment for metastasis, and exo-Anx II plays an important role in this process, as priming with Anx II-depleted exosomes reduces brain (∼4-fold) and lung (∼2-fold) metastasis. Upon delineating the mechanism, it was discovered that exo-Anx II causes macrophage-mediated activation of the p38MAPK, NF-κB, and STAT3 pathways and increased secretion of IL6 and TNFα. These data demonstrate an important role for exo-Anx II in breast cancer pathogenesis. IMPLICATIONS: Exosome-associated Annexin II plays an important role in angiogenesis and breast cancer metastasis, which can be exploited as a potential biomarker as well as a therapeutic target for diagnosis and treatment of metastatic breast cancer. Mol Cancer Res; 15(1); 93-105. ©2016 AACR.

Functional immunoglobulin E cross-reactivity between Pas n 1 of Bahia grass pollen and other group 1 grass pollen allergens.

BACKGROUND: Grass pollens are major triggers of allergic rhinitis and asthma, but the immunological relationships between pollen allergens of the subtropical Bahia grass, Paspalum notatum, and temperate grasses are unresolved. OBJECTIVE: To assess serum IgE cross-reactivity between subtropical P. notatum and temperate Lolium perenne (Ryegrass) pollen allergens. METHODS: Serum IgE reactivities of grass pollen-allergic patients with P. notatum, L. perenne and Cynodon dactylon (Bermuda grass) pollen extracts and their respective purified group 1 allergens, Pas n 1, Lol p 1 and Cyn d 1, were compared by immunoblotting, ELISA and basophil activation. RESULTS: In a cohort of 51 patients from a temperate region, a high frequency of IgE reactivity with each grass pollen was detected, but reactivity with L. perenne pollen was substantially greater than with P. notatum and C. dactylon pollen. Similarly, serum IgE reactivity with Lol p 1 was greater than with Pas n 1 or Cyn d 1. For seven of eight sera studied in detail, asymmetric serum IgE cross-reactivity was observed; L. perenne pollen inhibited IgE reactivity with P. notatum pollen but not the converse, and IgE reactivity with Pas n 1 was inhibited by Lol p 1 but IgE reactivity with Lol p 1 was not inhibited by Pas n 1 or Cyn d 1. Importantly, P. notatum pollen and Pas n 1 activated basophils in grass pollen-allergic patients from a temperate region, although stimulation was greater by pollen of L. perenne than P. notatum or C. dactylon, and by Lol p 1 than Pas n 1 or Cyn d 1. In contrast, a cohort of 47 patients from a subtropical region showed similar IgE reactivity with P. notatum and L. perenne pollen, and reciprocal cross-inhibition of IgE reactivity between L. perenne and P. notatum. CONCLUSIONS: Pollen allergens of the subtropical P. notatum, including Pas n 1, show clinically relevant IgE cross-reactivity with pollen allergens of L. perenne but also species-specific IgE reactivity.

Childhood melanoma: update and treatment.

Childhood melanoma is a rare but potentially fatal disease that is important to include in the differential diagnosis of any pigmented lesion in a child. The best prognosis is achieved with early diagnosis and definitive surgical excision. Adjuvant chemotherapy and immunotherapy are options for those with more advanced tumors. Melanoma in children must be treated as aggressively as in adults because childhood melanoma may be equally devastating.

The clinical appearance of clonal nevi (inverted type A nevi).

BACKGROUND: The term "clonal nevus" is used to describe a variant of melanocytic nevus that histologically exhibits a localized proliferation of pigmented epithelioid dermal melanocytes within an otherwise ordinary nevus (Ball NJ, Golitz LE. Melanocytic nevi with focal atypical epithelioid cell components: a review of seventy-three cases. J Am Acad Dermatol 1994; 30: 724-729). Reports to date have focused on the histologic appearance of these lesions. AIM: To characterize the clinical appearance of clonal nevi. METHODS: Clinical and histologic examinations were performed of a single clonal nevus from each of five patients (two men and three women; age range, 37-80 years). RESULTS: All nevi were round to oval in shape with smooth, well-defined borders. They were uniformly tan to light brown in color, except for a single blue-gray to blue-black focus of hyperpigmentation. The diameters of the nevi ranged from 2.5 to 10 mm. In individual nevi, the hyperpigmented focus was either centrally or eccentrically located and measured 1-2 mm in diameter. Histologically, these lesions showed banal melanocytes associated with a localized proliferation of melanocytes with abundant pigmented cytoplasm in the dermis, admixed with melanophages. CONCLUSIONS: The appearance of clonal nevi--tan with a focus of blue-gray to blue-black pigmentation--allows one to recognize the lesion clinically.

Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11beta-hydroxylase.

Pituitary homeobox 1 (Ptx1/Pitx1) is a homeodomain-containing transcription factor present throughout pituitary development. Ptx1/Pitx1 interacts with steroidogenic factor 1 (SF-1) in the regulation of pituitary gene expression. SF-1 also plays a critical role in the transcription of enzymes involved in adrenal steroidogenesis. Therefore, we analyzed the presence and role of Ptx1/Pitx1 in human adrenal cortex. Both Ptx1/Pitx1 and SF-1 mRNA were expressed in the human adrenal gland, and immuno-electron microscopy demonstrated the presence of Ptx1/Pitx1 protein in the nucleus of adrenocortical cells. Computer analysis revealed the presence of Ptx1/Pitx1 signal sequences within the promoter region of human 11beta hydroxylase ( hCYP11B1). To examine the role of Ptx1/Pitx1 in the regulation of the genes, we prepared reporter constructs using the 5'-flanking DNA of the hCYP11B1 gene and transfected them into Y-1 mouse adrenocortical cells, HeLa and CV-1 cells. Ptx1/Pitx1 stimulation of hCYP11B1 reporter activity (3-fold over basal) in Y-1 cells was equal to that observed with SF-1. The hCYP11B1 promoter activity in Y-1 cells was not synergistically increased by co-transfection with both Ptx1/Pitx1 and SF-1. Both basal and ACTH-stimulated hCYP11B1 reporter activities in Y-1 cells were increased by co-transfection with either Ptx1/Pitx1 or SF-1 expression vectors. In contrast, co-transfection with both Ptx1/Pitx1 and SF-1 synergistically increased hCYP11B1 promoter activity in HeLa and CV-1 cells (5-fold and 20-fold over basal, respectively). In conclusion, this study represents the first demonstration for a role of Ptx1/Pitx1 in the regulation of transcription of enzymes involved in adrenal steroidogenesis.

Numerous, small, darkly pigmented melanocytic nevi: the cheetah phenotype.

BACKGROUND: The presence of multiple atypical nevi or numerous melanocytic nevi increases the risk for the development of cutaneous melanoma. OBJECTIVE: We sought to describe a distinct clinical phenotype characterized by numerous (>100), small (< or =4 mm), darkly pigmented melanocytic nevi that are uniform in color. METHODS: Biopsy specimens from 6 patients (3 men and 3 women; age range, 44 to 81 years) with this clinical phenotype were reviewed and compared with a database of melanocytic lesions analyzed by the Yale Dermatopathology Laboratory (YDL) in the year 2000. RESULTS: Of the 6 patients, 4 had multiple primary melanomas develop (n = 2-4), ranging from in situ to 1.0 mm in depth. The other 2 patients each had 1 nevus with severe cytologic atypia. When compared with the YDL database, our patients were more likely to have the following pigmented lesions: junctional melanocytic nevi, junctional lentiginous nevi, junctional nevi with cytologic atypia, and simple lentigines (P <.001). CONCLUSIONS: The longitudinal evaluation of patients with this phenotype can be challenging because similar-appearing pigmented lesions (small and uniformly dark-brown to black) had a range of histologic diagnoses from simple lentigo to junctional lentiginous nevus to thin melanoma.

Construction of attenuated HIV-1 accessory gene immunization cassettes.

Delivery of genetic expression cassettes into animals can effectively induce both humoral and cellular immunity to the expressed gene product. Previously, we used this strategy to immunize against HIV-1 structural and enzymatic proteins in mice, non-human primates and in humans. In contrast, the use of the accessory genes including vif, vpr, vpu and nef as immunotherapeutic vaccine targets has not been well characterized. Our goal is to design an effective genetic HIV vaccine, which includes the accessory genes as part of a multi-component immunogen. In order to develop accessory genes as genetic vaccines, we have molecularly cloned and analysed the sequence variation and immunogenic potential present in these genes derived from viral isolates obtained from HIV-1 infected patients and laboratory isolates. Prototype genetic variants were selected and their ability to induce humoral and cellular immune responses was studied in animal models. We observed that attenuated accessory genes can effectively induce both humoral and cellular responses in mice and the resulting immune response is directly correlated with DNA concentrations delivered and the number of boosts. This strategy can be used generally to develop an effective, safe DNA vaccine for any pathogen.

HIV-1 viral protein R (Vpr) as a regulator of the target cell.

Among the putative 'accessory genes' of HIV-1, the 96 amino acid virion-associated Vpr gene product has been described to have several novel biological activities. These include cytoplasmic-to-nuclear translocation thus empowering HIV to infect and replicate in nondividing cells and to function to increase viral replication, particularly in monocytes. Along with these viral effects, we describe the dramatic biological changes induced by HIV-1 Vpr in the target cells of HIV infection including induction of changes in transcriptional patterns and complete inhibition of proliferation which collectively is termed differentiation. These changes occur in the absence of other viral gene products and suggest that Vpr mediates its proviral effects partially or perhaps solely through modulation of the state of the target cell rather than directly on the virus. The inhibition of proliferation in T-cell lines has been proposed by several groups to demonstrate that the inhibition of proliferation specifically arrests the cell cycle further supporting the notion that Vpr activity is directed at cellular targets. We have recently described a role for Vpr in modulating the glucocorticoid pathway, a pathway involved in the regulation of the state of the cell in cytoplasmic-to-nuclear translocation and in the modulation of host cell transcription. Importantly, certain antiglucocorticoids have been shown to modulate Vpr activity in vitro. These results demonstrate that the cell contains specific receptor(s) molecule(s) through which Vpr mediates its activity and that these molecules have implications for cell biology in general. These results collectively demonstrate that Vpr represents a unique target for anti-HIV drug development and has significance for HIV-1 disease progression.

Management of multiple drug-resistant malaria in Viet Nam.

Malaria is still the most common infectious cause of mortality and morbidity in Viet Nam as it is in many developing countries in the tropics. The presence of resistance to available antimalarials and compliance in the target population are factors that influence the choice of drugs and regimens. In order to develop an ideal treatment for malaria, we conducted several clinical trials in patients with the disease in different settings. The results of these trials suggest that a combination of single dose artemisinin (or its derivatives) and mefloquine is the most effective, safe and practical treatment for acute non-complicated malaria due to multidrug-resistant Plasmodium falciparum. Concerning severe and complicated malaria, parenteral or rectal multi-doses of artemisinin or analogues are recommended due to their rapid parasite clearance time and other possible anti-cytoadherence effects. With its rapid parasite clearance, very early treatment of uncomplicated cases with artemisinin (and derivatives), especially at a health post level may help to prevent the development of complications, consequently reducing the number of severe cases and the malaria mortality rate.

'Hertwig Effect' in plants: induced parthenogenesis through the use of irradiated pollen.

Studies of four combinations of Nicotiana involving four species, N. langsdorffii (N. l.), N. alata (N. a.), N. glutinosa (N. g.) and N. tabacum (N. t.), have shown that parthenogenetic haploid and diploid maternal individuals may arise with the use of male gametes (pollen) treated with high doses of ionising radiation in plants, similar to that found in animals ("Hertwig Effect'). At lower doses (10-20 Kr) rapidly diminishing numbers of seedlings were produced and many of these died soon after germination or before reaching maturity. In the intraspecific combination N. l. × N. l., viable seeds were produced only at the lower doses of 10 and 15 Kr. In the interspecific combination N. l. × N. a., at lower doses, all plants that came to bloom showed variable hybrid morphology. There were no plants resembling the female parent. In the combination N.t. × N.a., at lower doses there were rare surviving plants which were maternal dihaploid (1 plant out of 4 at 15 Kr) or tetraploid N. tabacum (all 5 plants at 20 Kr). All surviving plants at higher doses (50 and 100 Kr) were maternal tetraploids. In the combination N.t.×N.g., plants produced at lower than 20 Kr were almost all either aneuploid or triploid hybrids. Dihaploid, maternal N. tabacum plants appeared at 20 Kr and higher doses. After 50 Kr the large proportion of plants produced were maternal dihaploid or tetraploid N. tabacum.