The recent outbreak of COVID-19 has been rapidly spreading on a global scale. To date, there is no specific vaccine against the causative virus, SARS-CoV-2, nor is there an effective medicine for treating COVID-19, thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19. By extracting and analyzing all available published clinical data, we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19. Specifically, preexisting chronic conditions such as hypertension, cardiovascular disease, chronic kidney disease, and diabetes are strongly associated with an increased risk of developing severe COVID-19; surprisingly, however, we found no correlation between chronic liver disease and increased disease severity. In addition, we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality. Given the high risk of comorbidity and the high mortality rate associated with tissue damage, organ function should be monitored closely in patients diagnosed with COVID-19, and this approach should be included when establishing new guidelines for managing these high-risk patients. Moreover, additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe, potentially fatal complications, and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease. Taken together, these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.

No abstract

The complex drug delivery barrier in the eye reduces the bioavailability of many drugs, resulting in poor therapeutic effects. It is necessary to investigate new drugs through appropriate delivery routes and vehicles. Nanotechnology has utilized various nano-carriers to develop potential ocular drug delivery techniques that interact with the ocular mucosa, prolong the retention time of drugs in the eye, and increase permeability. Additionally, nano-carriers such as liposomes, nanoparticles, nano-suspensions, nano-micelles, and nano-emulsions have grown in popularity as an effective theranostic application to combat different microbial superbugs. In this review, we summarize the nano-carrier based drug delivery system developments over the last decade, particularly review the biology, methodology, approaches, and clinical applications of nano-carrier based drug delivery system in the field of ocular therapeutics. Furthermore, this review addresses upcoming challenges, and provides an outlook on potential future trends of nano-carrier-based drug delivery approaches in ophthalmology, and hopes to eventually provide successful applications for treating ocular diseases.

The design and development of self-calibrating ratiometric luminescent sensors for the fast, accurate, and sensitive discrimination and determination of pollutants in wastewater is highly desirable for public and environmental health. Herein, a 3D porous Tb(III)-based metal−organic framework (MOF), {[Tb-(HL)(H 2 O) 2 ]•x(solv)} n (1), was facilely synthesized using a ureafunctionalized tetracarboxylate ligand, 5,5′-(((1,4-phenylenebis-(azanediyl))bis(carbonyl))bis(azanediyl))diisophthalic acid (H 4 L). The activated framework showed a good water stability in both aqueous solutions at a wide pH range of 2−14 and simulated antibiotic wastewaters. Interestingly, this Tb-MOF exhibited dual luminescence owing to the partial energy transfer from the antenna H 4 L to Tb 3+ . More importantly, activated 1 (1a) that was dispersed in water showed a fast, accurate, and highly sensitive discrimination ability toward antibiotics with a good recyclability, discriminating three different classes of antibiotics from each other via the quenching or enhancement of the luminescence and tuning the emission intensity ratio between the H 4 L ligand and the Tb 3+ center for the first time. Simultaneously, 1a is a ratiometric luminescent sensor for the rapid, accurate, and quantitative discrimination of D 2 O from H 2 O. Furthermore, this complex was successfully used for the effective determination of antibiotics and D 2 O in real water samples. This work indicates that 1a represents the first ever MOF material for the discriminative sensing of antibiotics and D 2 O in H 2 O and promotes the practical application of Ln-MOF-based ratiometric luminescent sensors in monitoring water quality and avoiding any major leak situation.

There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10−15) and TMEM43/XPC (rs1043943; p = 3.59 × 10−8), were identified in a case–control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10−15) and BMPER (rs17169634; p = 1.45 × 10−10) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex‐stratified analyses identified sex‐specific longevity genes. Notably, sex‐differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not‐longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.

Objective: The association of occupational noise-induced hearing loss (NIHL) with noise energy was well documented, but the relationship between occupational noise and noise temporal structure is rarely reported. The objective of this study was to investigate the principal characteristics of the relationship between occupational NIHL and the temporal structure of noise. Methods: Audiometric and shift-long noise exposure data were collected from 3102 Chinese manufacturing workers from six typical industries through a cross-sectional survey. In data analysis, A-weighted 8-h equivalent SPL ( L Aeq.8h ), peak SPL, and cumulative noise exposure (CNE) were used as noise energy indicators, while kurtosis (β) was used as the indicator of noise temporal structure. Two NIHL were defined: (1) high-frequency noise-induced hearing loss (HFNIHL) and (2) noise-induced permanent threshold shift at test frequencies of 3, 4, and 6 kHz (noise-induced permanent threshold shift [NIPTS 346 ]). The noise characteristics of different types of work and the relationship between these characteristics and the prevalence of NIHL were analyzed. Results: The noise waveform shape, with a specific noise kurtosis, was unique to each type of work. Approximately 27.92% of manufacturing workers suffered from HFNIHL, with a mean NIPTS 346 of 24.16 ± 14.13 dB HL. The Spearman correlation analysis showed that the kurtosis value was significantly correlated with the difference of peak SPL minus its L Aeq.8h across different types of work ( p < 0.01). For a kurtosis-adjusted CNE, the linear regression equation between HFNIHL% and CNE for complex noise almost overlapped with Gaussian noise. Binary logistic regression analysis showed that L Aeq.8h , kurtosis, and exposure duration were the key factors influencing HFNIHL% ( p < 0.01). The notching extent in NIPTS at 4 kHz became deeper with the increase in L Aeq.8h and kurtosis. HFNIHL% increased most rapidly during the first 10 years of exposure. HFNIHL% with β ≥ 10 was significantly higher than that with β < 10 ( p < 0.05), and it increased with increasing kurtosis across different CNE or L Aeq.8h levels. When L Aeq.8h was 80 to 85 dB(A), the HFNIHL% at β ≥ 100 was significantly higher than that at 10 ≤ β < 100 or β < 10 ( p < 0.05 and p < 0.01, respectively). Conclusions: In the evaluation of hearing loss caused by complex noise, not only noise energy but also the temporal structure of noise must be considered. Kurtosis of noise is an indirect metric that is sensitive ...

The wide application of multi-walled carbon nanotubes (MWCNT) has raised serious concerns about their safety on human health and the environment. However, the potential harmful effects of MWCNT remain unclear and contradictory. To clarify the potentially toxic effects of MWCNT and to elucidate the associated underlying mechanisms, the effects of MWCNT on human lung adenocarcinoma A549 cells were examined at both the cellular and the protein level. Cytotoxicity and genotoxicity were examined, followed by a proteomic analysis (2-DE coupled with LC-MS/MS) of the cellular response to MWCNT. Our results demonstrate that MWCNT induces cytotoxicity in A549 cells only at relatively high concentrations and longer exposure time. Within a relatively low dosage range (30 µg/ml) and short time period (24 h), MWCNT treatment does not induce significant cytotoxicity, cell cycle changes, apoptosis, or DNA damage. However, at these low doses and times, MWCNT treatment causes significant changes in protein expression. A total of 106 proteins show altered expression at various time points and dosages, and of these, 52 proteins were further identified by MS. Identified proteins are involved in several cellular processes including proliferation, stress, and cellular skeleton organization. In particular, MWCNT treatment causes increases in actin expression. This increase has the potential to contribute to increased migration capacity and may be mediated by reactive oxygen species (ROS).

Three Cd(II) iso-frameworks {[Cd(BIPA)(IPA)]·DMF} (1), {[Cd(BIPA)(HIPA)]·DMF} (2), and {[Cd(BIPA)(NIPA)]·2HO} (3) were synthesized from the self-assembly of the BIPA ligand (BIPA = bis(4-(1 H-imidazol-1-yl)phenyl)amine) and different carboxylic ligands (HIPA = isophthalic acid, HHIPA = 5-hydroxyisophthalic acid, HNIPA = 5-nitroisophthalic acid) with Cd(II), which have amino groups, amino and phenolic hydroxyl groups, and amino and nitro groups, respectively. Both 1 and 2 exhibit CO uptakes of more than 20 wt %, indicating that amino and phenolic hydroxyl functionalized groups are beneficial to CO adsorption. Their applications and mechanisms in detecting metal ions were researched. The results exhibit that 1 and 2 are dual-responsive photoluminescent sensors for Hg and Pb ions with low detection concentration and high quenching constant. Besides, like most MOFs, 3 can detect a trace quantity of Fe and Cu.