Different Risk of Tuberculosis and Efficacy of Isoniazid Prophylaxis in Rheumatoid Arthritis Patients with Biologic Therapy: A Nationwide Retrospective Cohort Study in Taiwan

Increasing evidence indicates an increased risk of tuberculosis (TB) for rheumatoid arthritis (RA) patients receiving biologic therapy, and the effectiveness of isoniazid prophylaxis (INHP) in TB prevention. We aimed to examine 1) the incidence rate (IR) and risk factors for TB among RA patients receiving different therapies; 2) INHP effectiveness for TB prevention; 3) mortality rates after TB diagnosis in patients receiving different therapies. This retrospective study was conducted using a nationwide database: 168,720 non-RA subjects and a total of 42,180 RA patients including 36,162 csDMARDs-exposed, 3,577 etanercept-exposed, 1,678 adalimumab-exposed and 763 rituximab-exposed patients. TB risk was 2.7-fold higher in RA cohort compared with non-RA group, with an adjusted hazard ratio (aHR) of 2.58. Advanced age, male, the use of corticosteroids≧5mg/day, and the presence of diabetes mellitus (DM), chronic obstructive pulmonary disease and chronic kidney disease were risk factors for developing TB. Using csDMARDs-exposed group as reference, aHR of TB was the highest with adalimumab treatment (1.52), followed by etanercept (1.16), and the lowest with rituximab (0.08). INHP could effectively reduce TB risk in biologics-exposed patients. Mortality rates after TB diagnosis were higher in RA patients, particularly the elderly and those with DM, with lower rates in adalimumab-exposed patients compared with csDMARDs-exposed patients. In conclusion, TB risk was increased in patients receiving TNF-α inhibitors, but the risk associated with rituximab therapy was relatively low. With the effectiveness of INHP shown in the prevention of biologics-associated TB, stricter implementation of INHP should be beneficial. The mortality from biologics–associated TB may be efficiently reduced through increased awareness.     

Cytosolic HMGB1 Mediates Autophagy Activation in an Emulsified Isoflurane Anesthesia Cell Model

Neurochemical Research - Inhalation anesthetic isoflurane may cause an increased risk of cognitive impairment. Previous studies have indicated that this cognitive decline is associated with...     

Chewing lice from high‐altitude and migrating birds in Yunnan,China, with descriptions of two new species of Guimaraesiella

In total, 366 birds representing 55 species in 24 families and eight orders, were examined for chewing lice (Phthiraptera: Amblycera, Ischnocera) in two high‐altitude localities in Yunnan Province, China. In Ailaoshan, almost all of the birds examined were resident passeriforms, of which 36% were parasitized by chewing lice. In Jinshanyakou, most birds were on migration, and included both passerine and non‐passerine birds. Of the passerine birds caught in Jinshanyakou, only one bird (0.7%) was parasitized by chewing lice. The prevalence of Myrsidea and Brueelia‐complex lice on birds caught in Ailaoshan was higher than in previous reports. Of the chewing lice identifiable to species level, three represent new records for China: Actornithophilus hoplopteri (Mjöberg, 1910), Maculinirmus ljosalfar Gustafsson & Bush, 2017 and Quadraceps sinensis Timmermann, 1954. In total, 17 new host records are included, of which we describe two as new species in the Brueelia‐complex: Guimaraesiella (Cicchinella) ailaoshanensis sp. nov. ex Schoeniparus dubius dubius (Hume, 1874) and G. (C.) montisodalis sp. nov. ex Fulvetta manipurensis tonkinensis Delacour & Jabouille, 1930. This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:9FC3D8EE‐2CED‐4DBE‐A1DB‐471B71260D27 .     

A cross-talk between epithelium and endothelium mediates human alveolar–capillary injury during SARS-CoV-2 infection

COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.Subject terms: Mechanisms of disease, Viral infection     

A Putative Calcium-Permeable Cyclic Nucleotide-Gated Channel, CNGC18, Regulates Polarized Pollen Tube Growth

A tip-focused Ca^2＋ gradient is tightly coupled to polarized pollen tube growth, and tip-localized influxes of extracellular Ca^2＋ are required for this process. However the molecular identity and regulation of the potential Ca^2＋ channels remains elusive. The present study has implicated CNGC18 （cyclic nucleotide-gated channel 18） in polarized pollen tube growth, because its overexpression induced wider and shorter pollen tubes. Moreover, CNGC18 overexpression induced depolarization of pollen tube growth was suppressed by lower extracellular calcium （[Ca^2＋]ex）. CNGC18-yellow fluorescence protein （YFP） was preferentially localized to the apparent post-Golgi vesicles and the plasma membrane （PM） in the apex of pollen tubes. The PM localization was affected by tip-localized ROP1 signaling. Expression of wild type ROP1 or an active form of ROP1 enhanced CNGC18-YFP localization to the apical region of the PM, whereas expression of RopGAP1 （a ROP1 deactivator） blocked the PM localization. These results support a role for PM-Iocalized CNGC18 in the regulation of polarized pollen tube growth through its potential function in the modulation of calcium influxes.     

Significant longevity-extending effects of EGCG on Caenorhabditis elegans under stress

Epigallocatechin gallate (EGCG), a main active ingredient of green tea, is believed to be beneficial in association with anticarcinogenesis, antiobesity, and blood pressure reduction. Here we report that EGCG extended Caenorhabditis elegans longevity under stress. Under heat stress (35°C), EGCG improved the mean longevity by 13.1% at 0.1 μg/ml, 8.0% at 1.0 μg/ml, and 11.8% at 10.0 μg/ml. Under oxidative stress, EGCG could improve the mean longevity of C. elegans by 172.9% at 0.1 μg/ml, 177.7% at 1.0 μg/ml, and 88.5% at 10.0 μg/ml. However, EGCG could not extend the life span of C. elegans under normal culture conditions. Further studies demonstrated that the significant longevity-extending effects of EGCG on C. elegans could be attributed to its in vitro and in vivo free radical-scavenging effects and its up-regulating effects on stress-resistance-related proteins, including superoxide dismutase-3 (SOD-3) and heat shock protein-16.2 (HSP-16.2), in transgenic C. elegans with SOD-3∷green fluorescent protein (GFP) and HSP-16.2∷GFP expression. Quantitative real-time PCR results showed that the up-regulation of aging-associated genes such as daf-16, sod-3, and skn-1 could also contribute to the stress resistance attributed to EGCG. As the death rate of a population is closely related to the mortality caused by external stress, it could be concluded that the survival-enhancing effects of EGCG on C. elegans under stress are very important for antiaging research.     

Identification of a stretch-activated monovalent cation channel from teleost urinary bladder cells.

The urinary bladder of euryhaline teleost is an important osmoregulatory organ which absorbs Na+, Cl-, and water from urine. Using patch clamp technique, single stretch-activated channels, which were permeable to K+ and Na+ (PNa/PK approximately 0.75) and had conductances of 55 and 116 pS, were studied. In excised, inside-out patches which were voltage-clamped in the physiological range of membrane potential, the single-channel open probability (Po) was low (approximately 0.02), and increased to a maximum of 0.9 with applied pipette suction. Single-channel conductance also increased with suction. The channels showed adaptation to applied suction and relaxed to a steady-state activity about 20 seconds after application of suction. The Po increased up to 0.9 with strong membrane depolarization (Vm = 0 to +80 mV); however, there was little dependence of Po on membrane potential in the physiological range. The kinetic data suggest that there is one conducting state and at least two non-conducting states of the channel. The open-time constant increased with suction but remained unchanged with membrane potential (Vm = -70 to +60 mV). The mean closed-time of the channel decreased with suction and membrane depolarization. These results demonstrate the presence of a non-selective monovalent cation channel which may be involved in cell volume regulation in the goby urinary bladder. Additionally, this channel may function as an enhancer of Na+ influx and K+ efflux across the bladder cell as part of transepithelial ion transport if it is located in apical membrane.