An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors.

Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX) and interleukin-1α as responsible for HSC maintenance in vitro. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs. Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents. These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations

Pulmonary and systemic responses of highly pure and well-dispersed single-wall carbon nanotubes after intratracheal instillation in rats

The present study was conducted to assess the pulmonary and systemic responses in rats after intratracheal instillation of highly pure, well-dispersed, and well-characterized SWCNTs. Exposure to SWCNTs up to 2mg/kg did not produce mortality, changes in clinical signs, or body weights during the observation period. Dose-dependent changes were observed in the lung weight, BALF inflammatory cells, and biochemical parameters such as LDH value, protein content, IL-1β and IL-6 activity, and histopathology. In the 0.04 mg/kg SWCNT-exposed group, almost no changes were observed during the observation period. In the 0.2 mg/kg SWCNT-exposed group, pulmonary inflammatory responses were observed after instillation. In the 1 mg/kg and 2 mg/kg SWCNT-exposed group, acute lung inflammation and subsequent granuloma accompanied by increased lung weights were observed. Furthermore, the histopathological findings in the lungs of rats exposed to SWCNTs showed inflammatory responses related with the vital reaction to the foreign substance that was instilled intratracheally, and there were no fibrosis, atypical lesion, or tumor-related findings even at the highest dose (2 mg/kg) of SWCNT-exposed groups up to 6 months after instillation. For all groups, histopathological changes due to the instillation exposure of SWCNTs were observed only in the lungs and lung-associated lymph nodes and not in the other tissues examined (i.e. the liver, kidney, spleen, and cerebrum)

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Binaphthyl–Bipyridyl Cyclic Dyads as a Chiroptical Switch

A series of chiral cyclic dyads, axially chiral binaphthyls linked to a 3,3′-bipyridyl, was synthesized. The dyad <b>2</b> bearing methoxy groups exhibited ON/OFF properties in circularly polarized luminescence (CPL), yielding a |<i>g</i>_lum| of 1.6 × 10^–3 or 0 without any change in fluorescence. This type of CPL switch is unprecedented. Regioisomer <b>4</b> exhibited a <i>dextro</i>/<i>levo</i> rotation switching ability in [α]_D. X-ray structures as well as experimental and theoretical analyses suggested that the switching properties depended on conformational changes

Binaphthyl–Bipyridyl Cyclic Dyads as a Chiroptical Switch

A series of chiral cyclic dyads, axially chiral binaphthyls linked to a 3,3′-bipyridyl, was synthesized. The dyad <b>2</b> bearing methoxy groups exhibited ON/OFF properties in circularly polarized luminescence (CPL), yielding a |<i>g</i>_lum| of 1.6 × 10^–3 or 0 without any change in fluorescence. This type of CPL switch is unprecedented. Regioisomer <b>4</b> exhibited a <i>dextro</i>/<i>levo</i> rotation switching ability in [α]_D. X-ray structures as well as experimental and theoretical analyses suggested that the switching properties depended on conformational changes

Binaphthyl–Bipyridyl Cyclic Dyads as a Chiroptical Switch

A series of chiral cyclic dyads, axially chiral binaphthyls linked to a 3,3′-bipyridyl, was synthesized. The dyad <b>2</b> bearing methoxy groups exhibited ON/OFF properties in circularly polarized luminescence (CPL), yielding a |<i>g</i>_lum| of 1.6 × 10^–3 or 0 without any change in fluorescence. This type of CPL switch is unprecedented. Regioisomer <b>4</b> exhibited a <i>dextro</i>/<i>levo</i> rotation switching ability in [α]_D. X-ray structures as well as experimental and theoretical analyses suggested that the switching properties depended on conformational changes

Binaphthyl–Bipyridyl Cyclic Dyads as a Chiroptical Switch

A series of chiral cyclic dyads, axially chiral binaphthyls linked to a 3,3′-bipyridyl, was synthesized. The dyad <b>2</b> bearing methoxy groups exhibited ON/OFF properties in circularly polarized luminescence (CPL), yielding a |<i>g</i>_lum| of 1.6 × 10^–3 or 0 without any change in fluorescence. This type of CPL switch is unprecedented. Regioisomer <b>4</b> exhibited a <i>dextro</i>/<i>levo</i> rotation switching ability in [α]_D. X-ray structures as well as experimental and theoretical analyses suggested that the switching properties depended on conformational changes

Binaphthyl–Bipyridyl Cyclic Dyads as a Chiroptical Switch

A series of chiral cyclic dyads, axially chiral binaphthyls linked to a 3,3′-bipyridyl, was synthesized. The dyad <b>2</b> bearing methoxy groups exhibited ON/OFF properties in circularly polarized luminescence (CPL), yielding a |<i>g</i>_lum| of 1.6 × 10^–3 or 0 without any change in fluorescence. This type of CPL switch is unprecedented. Regioisomer <b>4</b> exhibited a <i>dextro</i>/<i>levo</i> rotation switching ability in [α]_D. X-ray structures as well as experimental and theoretical analyses suggested that the switching properties depended on conformational changes