To assess long-term outcomes for seven biological disease-modifying antirheumatic drugs (bDMARD
) and one Janus kinase (JAK)-inhibitor in rheumatoid arthrit
.
We retrospectively analyzed data from ...801 rheumatoid arthritis patients visiting our rheumatology clinic between 2003 and 2017. We determined drug survival rates, drug discontinuation, and switching rates in these patients.
Among the drugs administered to naïve subjects, the drug-survival rate was highest for tocilizumab, at 77.8% after 6 years, whereas the rates for golimumab, etanercept, abatacept, infliximab, and adalimumab, were 61.5%, 48.9%, 41.6%, 34.5%, and 34.4%, respectively. Switching drugs led to decreased survival rates. The discontinuation rates for all drugs due to adverse events and poor efficacy increased rapidly in the first 2 years and the first 6 months, respectively.
This report is a long-term analysis of a large cohort of rheumatoid arthritis patients from a single rheumatology clinic in Japan. We conclude that to maximize the survival rate of antirheumatic drugs, it is important to maintain their effectiveness over long periods of time by appropriate drug choices and optimizing dosage before switching drugs.
An ultrapure deep-blue multi-resonance-induced thermally activated delayed fluorescence material (DOB2-DABNA-A) is designed and synthesized. Benefiting from a fully resonating extended helical ...π-conjugated system, this compound has a small ΔE
value of 3.6 meV and sufficient spin-orbit coupling to exhibit a high-rate constant for reverse intersystem crossing (k
= 1.1 × 10
s
). Furthermore, an organic light-emitting diode employing DOB2-DABNA-A as an emitter is fabricated; it exhibits ultrapure deep-blue emission at 452 nm with a small full width at half maximum of 24 nm, corresponding to Commission Internationale de l'Éclairage (CIE) coordinates of (0.145, 0.049). The high k
value reduces the efficiency roll-off, resulting in a high external quantum efficiency (EQE) of 21.6% at 1000 cd m
.
BN-embedded nonacene, tridecacene, and heptadecacene frameworks were constructed using one-shot quadruple, sextuple, and octuple borylation reactions, respectively. The key to success is the ...judicious choice of borylating reagents and long-chain alkyl-substituted carbazolyl groups as boron-trapping groups, which suppressed the decrease in HOMO energy and insolubilization associated with borylation. Based on the product yields, each electrophilic C–H borylation proceeded in >99% yield, which is the best efficiency reported so far for C–H borylation reactions. Owing to the multiple resonance effects of boron and nitrogen, the prepared acenes exhibited ultra-narrowband green thermally activated delayed fluorescence with full-width at half-maximum of 12–16 nm; moreover, their k RISC values were in the order of 105 s–1. We fabricated an organic light-emitting diode by employing the nonacene as an emitter, which exhibited high external quantum efficiency (EQE) of 28.7%. The device also showed a minimum efficiency roll-off with an EQE of 25.8% at 1000 cd m–2.
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•Incorporating double excitation contributions into conventional time-dependent density functional theory (TDDFT) improves the energy of excited singlet states for multiresonant ...molecular systems.•As a result, energy gaps between singlet and triplet excited states become closer to experimental observation.•By this strategy, double hybrid TDDFT (DH-TDDFT), inverted energy gap situations can be treated in the framework of TDDFT as well.•DH-TDDFT methods may be promising as a cost-effective prediction tool.
Singlet–triplet energy gaps (ΔEST) for multiresonant molecular systems are investigated within time-dependent density functional theory (TDDFT), using conventional linear response TDDFT (LR-TDDFT) and double hybrid TDDFT (DH-TDDFT) schemes. LR-TDDFT methods systematically overestimate ΔEST; on the other hand, by explicitly taking double excitation characters into consideration, DH-TDDFT considerably improves the gap problem. Further theoretical analysis shows that DH-TDDFT calculations also work for the description of negative gap situations, which LR-TDDFT intrinsically fails. The present findings demonstrate the applicability of TDDFT-based methods for predicting ΔEST as a relatively low-cost computational approach, encouraging us to develop new exchange-correlation functionals suited for DH-TDDFT calculations.
In Asian developing countries, undeveloped and ineffective sewer systems are causing surface water pollution by a lot of contaminants, especially pharmaceuticals and personal care products (PPCPs). ...Therefore, the risks for freshwater fauna need to be assessed. The present study aimed at: i) elucidating the contamination status; ii) evaluating the bioaccumulation; and iii) assessing the potential risks of PPCP residues in surface water and freshwater fish from three Asian countries. We measured 43 PPCPs in the plasma of several fish species as well as ambient water samples collected from India (Chennai and Bengaluru), Indonesia (Jakarta and Tangerang), and Vietnam (Hanoi and Hoa Binh). In addition, the validity of the existing fish blood–water partitioning model based solely on the lipophilicity of chemicals is assessed for ionizable and readily metabolizable PPCPs. When comparing bioaccumulation factors calculated from the PPCP concentrations measured in the fish and water (BAFmeasured) with bioconcentration factors predicted from their pH-dependent octanol–water partition coefficient (BCFpredicted), close values (within an order of magnitude) were observed for 58–91 % of the detected compounds. Nevertheless, up to 110 times higher plasma BAFmeasured than the BCFpredicted were found for the antihistamine chlorpheniramine in tilapia but not in other fish species. The plasma BAFmeasured values of the compound were significantly different in the three fish species (tilapia > carp > catfish), possibly due to species-specific differences in toxicokinetics (e.g., plasma protein binding and hepatic metabolism). Results of potential risk evaluation based on the PPCP concentrations measured in the fish plasma suggested that chlorpheniramine, triclosan, haloperidol, triclocarban, diclofenac, and diphenhydramine can pose potential adverse effects on wild fish. Results of potential risk evaluation based on the PPCP concentrations measured in the surface water indicated high ecological risks of carbamazepine, sulfamethoxazole, erythromycin, and triclosan on Asian freshwater ecosystems.
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•Chlorpheniramine and triclosan showed species-specific bioaccumulation factors.•Protein binding may cause high bioaccumulation of chlorpheniramine in tilapia plasma.•High levels of parabens indicated inflows of untreated wastewater into urban rivers.•Carbamazepine, sulfamethoxazole, erythromycin, and triclosan reached high risk levels.
The selenium (Se)-containing imidazole compound selenoneine (2-selenyl-
N
α
,
N
α
,
N
α
-trimethyl-
l
-histidine) is a strong scavenger of reactive oxygen species (ROS) in the blood and tissues of ...fish. Intravenous injection of selenoneine into yellowtail has been shown to delay changes in meat color and prevent met-myoglobin formation in red muscle. In this study, to determine whether selenoneine can improve stress tolerance and meat quality in fish, we examined the biological antioxidant functions of selenoneine in fish in vivo. Juvenile amberjack (
Seriola dumerili
) were cultured and fed a diet containing selenoneine for 9 weeks. Total Se and selenoneine concentrations increased in amberjack blood and muscles during the study period. We also measured the oxidative–redox potential (ORP) in fish muscle using an ORP electrode and found that muscle ORP and ROS levels were closely correlated with the Se concentration in blood and muscles. We conclude that dietary administration of selenoneine led to its accumulation in amberjack blood and muscles, resulting in reduced ORP and ROS levels in the muscles.
White spot syndrome virus (WSSV) has been one of the most devastating pathogens affecting the global shrimp industry since its initial outbreaks in Asia in the early 1990s. In this study, we ...recovered 13 complete metagenome-assembled genomes (MAGs) of Japanese WSSV isolates and 30 draft WSSV MAGs recovered from publicly available sequencing data, to investigate the genomic evolution of WSSV. Phylogenetic analysis revealed two major phylotypes, designated phylotypes I and II. Bayesian divergence time estimates placed the divergence time of the two phylotypes between 1970 and the early 1980s, with an estimated substitution rate of 1.1 × 10
–5
substitutions per site per year, implying the existence of pre-pandemic genetic diversity of WSSV in Asia. Based on this scenario, phylotype I was responsible for the 1990s pandemic and spread worldwide, whereas phylotype II was localized in Asia and infiltrated Australia. Two cross-phylotype recombinant lineages were identified, which demonstrate the role of genomic recombination in generating the genetic diversity of WSSV. These results provide important insights into the evolution of WSSV and may help uncover the ultimate origins of this devastating pathogen.
To fulfill ultra-high-definition display, efficient and bright green organic light-emitting diodes with Commission Internationale de l'Éclairage y-coordinate ≥ 0.7 are required. Although there are ...some preceding reports of highly efficient devices based on pure-green multi-resonance emitters, the efficiency rolloff and device stabilities for those pure-green devices are still unsatisfactory. Herein, we report the rational design of two pure-green multi-resonance emitters for achieving highly stable and efficient pure-green devices with CIE
s that are close to the NTSC and BT. 2020 standards. In this study, our thermally activated delayed fluorescence OLEDs based on two pure-green multi-resonance emitters result in CIE
up to 0.74. In hyperfluorescent device architecture, the CIE
s further meet the x-coordinate requirements, i.e., NTSC (0.21) and BT. 2020 (0.17), while keeping their CIE
s ~ 0.7. Most importantly, hyperfluorescent devices display the high maximum external quantum efficiencies of over 25% and maximum luminance of over 10
cd m
with suppressed rolloffs (external quantum efficiency of ~20% at 10
cd m
) and long device stabilities with LT
s of ~ 600 h.
A pseudotuberculosis pathogen, Photobacterium damselae subsp. piscicida (Pdp), has caused enormous economic damage to yellowtail aquaculture in Japan. The Ivy gene has been discovered in plasmid of ...Pdp, and it has been proposed that it may help bacteria evade lysozyme-mediated lysis during interaction with an animal host. However, the lysozyme-inhibiting activity of Pdp-derived Ivy (Ivy-Pdp) is unknown, and it is unclear whether it acts as a virulence factor for host biophylaxis. In this study, the inhibitory effect of Ivy-Pdp on lysozyme was evaluated by expressing and purifying the recombinant Ivy-Pdp protein (rIvy-Pdp). The rIvy-Pdp protein inhibited hen egg white lysozyme activity in an rIvy-Pdp-concentration-dependent manner, and its inhibitory effect was similar under different temperature and pH conditions. The serum and skin mucus of the yellowtail (which is the host species of Pdp), Japanese flounder, and Nile tilapia showed bacteriolytic activity. In contrast, the addition of rIvy-Pdp inhibited the lytic activity in the serum of these fish species. In particular, it significantly inhibited lytic activity in the serum and skin mucus of Nile tilapia. On the basis of these results, we suggest that Ivy-Pdp is a temperature- and pH-stable lysozyme inhibitor. Additionally, Ivy-Pdp inhibited the lytic activity of lysozyme, which is involved in host biophylaxis. In summary, we inferred that Ivy-Pdp is an important factor that diminishes the sterilization ability of C-type lysozyme when Pdp infects the host.
•Ivy-Pdp highly preserved the CKPHDC motif, as with Ivy derived from known pathogenic bacteria.•Ivy-Pdp inhibited HEWL lytic activity, regardless of temperature and pH.•Ivy-Pdp inhibited lytic activity of yellowtail and Nile tilapia serum.
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