Gloeobacter rhodopsin (GR) is a cyanobacterial proton pump which can be potentially applied to optogenetics. We solved the crystal structure of GR and found that it has overall similarity to the ...homologous proton pump from Salinibacter ruber, xanthorhodopsin (XR). We identified distinct structural characteristics of GR's hydrogen bonding network in the transmembrane domain as well as the displacement of extracellular sides of the transmembrane helices relative to those of XR. Employing Raman spectroscopy and flash-photolysis, we found that GR in the crystals exists in a state which displays retinal conformation and photochemical cycle similar to the functional form observed in lipids. Based on the crystal structure of GR, we selected a site for spin labeling to determine GR's oligomerization state using double electron-electron resonance (DEER) spectroscopy and demonstrated the pH-dependent pentamer formation of GR. Determination of the structure of GR as well as its pentamerizing propensity enabled us to reveal the role of structural motifs (extended helices, 3-omega motif and flipped B-C loop) commonly found among light-driven bacterial pumps in oligomer formation. Here we propose a new concept to classify these pumps based on the relationship between their oligomerization propensities and these structural determinants.
Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the SFTS Virus (SFTSV), is a global health threat. SFTSV in Taiwan has only been reported in ruminants and wild animals. Thus, we aimed ...to investigate the infection statuses of dogs and cats, the animals with closer human interactions. Overall, the SFTSV RNA prevalence was 23% (170/735), with dogs showing a 25.9% (111/429) prevalence and cats at 19.3% (59/306) prevalence. Noticeably, the prevalence in stray animals (39.8% 77/193) was significantly higher than in domesticated ones (17.2%, 93/542). Among the four categories analyzed, the highest SFTSV prevalence was found in the stray dogs at 53.9% (120/193), significantly higher than the 24.2% prevalence noted in stray cats. In contrast, domesticated animals exhibited similar prevalence rates, with 17.1% for dogs and 17.2% for cats. It is noteworthy that in the domesticated animal groups, a significantly elevated prevalence (45%, 9/20) was observed among cats exhibiting thrombocytopenia compared to those platelet counts in the reference range (4.8%, 1/21). The high infection rate in stray animals, especially stray dogs, indicated that exposure to various outdoor environments influences the prevalence of infections. Given the higher human interaction with dogs and cats, there is a need for proactive measures to reduce the risk associated with the infection of SFTSV in both animals and humans.
Genotype I (GI) virus has replaced genotype III (GIII) virus as the dominant Japanese encephalitis virus (JEV) in the epidemic area of Asia. The mechanism underlying the genotype replacement remains ...unclear. Therefore, we focused our current study on investigating the roles of mosquito vector and amplifying host(s) in JEV genotype replacement by comparing the replication ability of GI and GIII viruses. GI and GIII viruses had similar infection rates and replicated to similar viral titers after blood meal feedings in Culex tritaeniorhynchus. However, GI virus yielded a higher viral titer in amplifying host-derived cells, especially at an elevated temperature, and produced an earlier and higher viremia in experimentally inoculated pigs, ducklings, and young chickens. Subsequently we identified the amplification advantage of viral genetic determinants from GI viruses by utilizing chimeric and recombinant JEVs (rJEVs). Compared to the recombinant GIII virus (rGIII virus), we observed that both the recombinant GI virus and the chimeric rJEVs encoding GI virus-derived NS1-3 genes supported higher replication ability in amplifying hosts. The replication advantage of the chimeric rJEVs was lost after introduction of a single substitution from a GIII viral mutation (NS2B-L99V, NS3-S78A, or NS3-D177E). In addition, the gain-of-function assay further elucidated that rGIII virus encoding GI virus NS2B-V99L/NS3-A78S/E177E substitutions re-gained the enhanced replication ability. Thus, we conclude that the replication advantage of GI virus in pigs and poultry is the result of three critical NS2B/NS3 substitutions. This may lead to more efficient transmission of GI virus than GIII virus in the amplifying host-mosquito cycle.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to examine the prevalence and associated factors of malnutrition in older community-dwellers and explore the interaction between associated factors.
A total of 474,467 older ...community-dwellers aged 65 or above were selected in Guangzhou, China. We used a two-step methodology to detect the associated factors of malnutrition and constructed logistic regression models to explore the influencing factors and interactive effects on three patterns of malnutrition.
The prevalence of malnutrition was 22.28%. Older adults with both hypertension and diabetes (RERI = 0.13), both meat or fish diet and hypertension (RERI = 0.79), and both meat or fish diet and diabetes (RERI = 0.81) had positive additive interaction effects on the risk of obesity, whereas those on a vegetarian diet with hypertension (RERI = -0.25) or diabetes (RERI = -0.19) had negative additive interaction effects. Moreover, the interactions of physical activity with a meat or fish diet (RERI = -0.84) or dyslipidemia (RERI = -0.09) could lower the risk of obesity.
Malnutrition was influenced by different health factors, and there were interactions between these influencing factors. Pertinent dietary instruction should be given according to different nutritional status indexes and the prevalence of metabolic diseases to avoid the occurrences of malnutrition among older adults.
Abstract
Background
Effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus long-acting insulins (LAIs) on preventing progressive chronic kidney outcomes is uncertain for type 2 ...diabetes (T2D) patients requiring intensive glycemic control. This study aimed to evaluate comparative effectiveness of GLP-1RA versus LAI therapies on progressive chronic kidney outcomes among patients having poor glycemic control and requiring these injectable glucose-lowering agents (GLAs).
Methods
7279 propensity-score-matched pairs of newly stable GLP-1RA and LAI users in 2013–2018 were identified from Taiwan’s National Health Insurance Research Database and followed until death or 12/31/2019 (intention-to-treat). Subdistributional hazard model was utilized to assess the comparative effectiveness on a composite renal outcome (i.e., renal insufficiency eGFR < 15 mL/min/1.73 m
2
, dialysis-dependent end-stage renal disease ESRD, or renal death) and its individual components. Sensitivity analyses with the as-treated scenario, PS weighting, high-dimensional PS techniques, using cardiovascular diseases (CVDs) as positive control outcomes, and interaction testing were performed.
Results
In primary analyses, subdistribution hazard ratios (95% CIs) for initiating GLP-1RAs versus LAIs for the composite renal outcome, renal insufficiency, dialysis-dependent ESRD, and renal death were 0.39 (0.30–0.51), 0.43 (0.32–0.57), 0.29 (0.20–0.43), and 0.28 (0.15–0.51), respectively. Sensitivity analysis results were consistent with the primary findings. CVD history and the medication possession ratio of prior oral GLAs possessed modification effects on GLP-1RA-associated kidney outcomes.
Conclusion
Using GLP-1RAs versus LAIs was associated with kidney benefits in T2D patients requiring intensive glycemic control and potentially at high risk of kidney progression. GLP-1RAs should be prioritized to patients with CVDs or adherence to prior oral GLAs to maximize kidney benefits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to assess the impact of diabetic retinopathy (DR) severity on the incidence of major adverse cardiac events (MACE) and end-stage renal disease (ESRD) in T1D patients. Patients ...diagnosed with T1D between 1999 and 2013 were identified from patient-level data of Taiwan's National Health Insurance Research database. A total of 1135 patients were included and classified into mild DR (n = 454), severe DR (n = 227), or non-DR (n = 454) by using propensity score matching. Multi-state model analyses, an extension of competing risk models with adjustment for transition-specific covariates for prediction of subsequent MACE and ESRD, were performed. MACE and ESRD risks were significantly higher in the severe DR patients; a 2.97-fold (1.73, 5.07) and 12.29-fold (6.50, 23.23) increase in the MACE risk among the severe DR patients compared to the mild DR and DR-free patients, respectively; and, a 5.91-fold (3.50, 9.99) and 82.31-fold (29.07, 233.04) greater ESRD risk of severe DR patients than that of the mild DR and DR-free groups, respectively (p < 0.001). Severity of DR was significantly associated with the late diabetes-related vascular events (i.e., MACE, ESRD) among T1D patients.
Background
Arbuscular mycorrhizal fungi (AMF) have been applied to promote the growth of different crop species, but knowledge about the impacts of symbiosis on foxtail millet at the physiological ...and molecular levels have remained limited. In this study, we compared the mycorrhization phenotypes of one cultivar and three different landraces and performed a comprehensive transcriptomic analysis to assess the effects of genetic variation on the responses to symbiosis.
Results
Our results showed that colonization by AMF did not enhance biomass accumulation but significantly increased grain production only in three lines. More than 2,000 genes were affected by AMF colonization in all lines. Most AM symbiosis-conserved genes were induced, but the induction levels varied between lines. Gene Ontology (GO) analysis showed that Biological Function terms related to nitrogen transport and assimilation were only enriched in TT8. Similarly, two of phosphate starvation-induced phosphate transporters were only simultaneously downregulated in TT8. In the other two lines, the enrichment of GO terms associated with cell wall reorganization and lignification was observed, though the effects were different.
Conclusion
This study reveals the impacts of genetic variation of millet lines on the responses to AM symbiosis and provides information regarding AMF application for millet production.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study assessed the effects of dipeptidyl peptidase‐4 inhibitors (DPP4is) vs. sulfonylureas (SUs) on composite renal, cardiovascular, and hospitalized hypoglycemia outcomes in type 2 diabetes ...(T2D) patients with advanced chronic kidney disease (CKD) who were underrepresented in previous clinical studies. The National Health Insurance Research Database was utilized. Patients with T2D and advanced CKD (stages 3b‐5) with stable use of DPP4is or SUs were identified during 2011–2015 and followed until death or December 31, 2016. The primary outcome was the composite renal outcome. Secondary outcomes included hospitalized heart failure (HHF), major adverse cardiovascular event (MACE), hospitalized hypoglycemia, and all‐cause death. Subdistribution hazard models were employed to assess treatment effects on clinical outcomes. A total of 1,204 matched pairs of DPP4i and SU users were analyzed. Compared with SUs, DPP4is had no significant difference in the risks of the composite renal outcome, HHF, and three‐point and four‐point MACE (hazard ratios (95% confidence intervals): 1.10 (0.93–1.31), 1.11 (0.95–1.30), 0.97 (0.79–1.19), and 1.08 (0.94–1.24), respectively), but reduced risks of hospitalized hypoglycemia (0.53 (0.43–0.64)) and all‐cause death (0.71 (0.53–0.96)). In conclusion, among patients with T2D and advanced CKD, the use of DPP4is vs. SUs was associated with comparable safety profiles on renal and cardiovascular outcomes, and reduced risks of hospitalized hypoglycemia and all‐cause death. DPP4is may be preferred for patients with T2D and advanced CKD, and the regular monitoring on cardiac function remains crucial among this population who are at a higher risk of HHF.
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