Phthalocyanines exhibit superior photoproperties that make them a surely attractive class of photosensitisers for photodynamic therapy of cancer. Several derivatives are at various phases of clinical ...trials, and efforts have been put continuously to improve their photodynamic efficacy. To this end, various strategies have been applied to develop advanced phthalocyanines with optimised photoproperties, dual therapeutic actions, tumour-targeting properties and/or specific activation at tumour sites. The advantageous properties and potential of phthalocyanines as advanced photosensitisers for photodynamic therapy of cancer are highlighted in this tutorial review.
Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in ...a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva.
This was a prospective diagnostic validity study comparing the detection rate of respiratory viruses between saliva and nasopharyngeal aspirate (NPA) among adult hospitalized patients using Xpert® Xpress Flu/RSV. The cost and time associated with the collection of saliva and nasopharyngeal specimens were also estimated.
Between July and October 2017, 214 patients were recruited. The overall agreement between saliva and NPA was 93.3% (196/210, κ 0.851, 95% CI 0.776–0.926). There was no significant difference in the detection rate of respiratory viruses between saliva and NPA (32.9% (69/210) versus 35.7% (75/210); p 0.146). The overall sensitivity and specificity were 90.8% (81.9%–96.2%) and 100% (97.3%–100%), respectively, for saliva, and were 96.1% (88.9%–99.2%) and 98.5% (94.7%–99.8%), respectively, for NPA. The time and cost associated with the collection of saliva were 2.26-fold and 2.59-fold lower, respectively, than those of NPA.
Saliva specimens have high sensitivity and specificity in the detection of respiratory viruses by an automated multiplex Clinical Laboratory Improvement Amendments-waived point-of-care molecular assay when compared with those of NPA. The use of saliva also reduces the time and cost associated with specimen collection.
The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or ...vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT
) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3-5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT
titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.
c-Met represents an important emerging therapeutic target in cancer. In this study, we demonstrate the mechanism by which c-Met tyrosine kinase inhibition inhibits tumor growth in a highly invasive ...Asian-prevalent head and neck cancer, nasopharyngeal cancer (NPC). c-Met tyrosine kinase inhibitors (TKIs; AM7 and c-Met TKI tool compound SU11274) downregulated c-Met phosphorylation, resulting in marked inhibition of NPC cell growth and invasion. Strikingly, inhibition of c-Met resulted in significant downregulation of TP53-induced Glycolysis and Apoptosis Regulator (TIGAR) and subsequent depletion of intracellular NADPH. Importantly, overexpression of TIGAR ameliorated the effects of c-Met kinase inhibition, confirming the importance of TIGAR downregulation in the growth inhibitory activity of c-Met TKI. The effects of c-Met inhibition on TIGAR and NADPH levels were observed with two different c-Met TKIs (AM7 and SU11274) and with multiple cell lines. As NADPH provides a crucial reducing power required for cell survival and proliferation, our findings reveal a novel mechanistic action of c-Met TKI, which may represent a key effect of c-Met kinase inhibition. Our data provide the first evidence linking c-Met, TIGAR and NADPH regulation in human cancer cells suggesting that inhibition of a tyrosine kinase/TIGAR/NADPH cascade may have therapeutic applicability in human cancers.
Biodegradable antimicrobial polymers are a promising solution for combating drug resistant microbes. When designing these materials, the balance between charge and hydrophobicity significantly ...affects the antimicrobial activity and selectivity toward microbes over mammalian cells. Furthermore, where the charge and hydrophobicity is located on the molecules has also proven to be significant. A series of antimicrobial homopolymer polycarbonates were synthesized, where the hydrophobic/hydrophilic balance was controlled by varying the spacer between the charged quaternary ammonium moiety and the polymer backbone (a "same-centered" structure where the hydrophobic moiety is directly attached to the charged moiety). These homopolymers were active against all microbes tested but depending on the spacer length some hemolytic activity was observed. To reduce the polymer hemolytic activity we systematically varied the polymer composition by copolymerizing the different monomers used in the "same center" homopolymers. By maintaining charge on each repeat unit but copolymerizing monomers having varied hydrophobic side chain lengths, polymers with high activity and selectivity were achieved. In addition, these macromolecules act via a membrane disruption mechanism, making them less likely to induce resistance.
Polymeric metal phthalocyanines have great potential as electrocatalysts, yet their incorporation on a current collector without losing the activity of metal centers remains a challenge. Herein, a ...new strategy for preparing a series of polymeric cobalt phthalocyanines containing S linkers (pCoPc‐1) or SO2 linkers (pCoPc‐2) and their tunable electrochemical properties are reported. The pCoPcs coated on various substrates show favorable electrocatalytic activities toward oxygen and hydrogen evolution reactions (OER and HER). Particularly, the pCoPc‐1 layer on Co3O4 nanosheet arrays exerts a cooperative effect enhancing both the OER and HER performances, and the subsequent phosphorization (P@pCoPc‐1/Co3O4|CC) significantly boosts the HER performance with enhanced hydrophilicity and conductivity. The high permeability and stability reinforcement of the pCoPc‐1 layer allow the phosphorization of underlying Co3O4 to CoP without degradation, which remarkably enhances OER and HER performances as manifested by low overpotentials of 320 and 120 mV at 10 mA cm−2, respectively. When engaged as a bifunctional electrocatalyst for the overall water splitting, the P@pCoPc‐1/Co3O4|CC requires a low cell voltage of 1.672 V at 10 mA cm−2, showing long‐term durability and mechanical robustness. This study demonstrates the collaborative catalytic role of polymeric macrocyclic compounds that offers versatile tunability and stability for various electrocatalytic reactions.
The polymeric cobalt phthalocyanines containing S linkers (pCoPc‐S) allow the partial phosphorization of underlying Co3O4 nanoarrays on carbon cloth to CoP (P@pCoPc‐S/Co3O4|CC), enabling remarkably enhanced catalytic performances toward oxygen and hydrogen evolution reactions. This improvement is ascribed to the modified electronic structure by S‐linker, enhanced hydrophilicity and conductivity, and cooperative catalytic effect due to the excellent permeability of the pCoPc‐S.
Healthcare workers (HCWs) use personal protective equipment (PPE) in Ebola virus disease (EVD) situations. However, preventing the contamination of HCWs and the environment during PPE removal ...crucially requires improved strategies. This study aimed to compare the efficacy of three PPE ensembles, namely, Hospital Authority (HA) Standard Ebola PPE set (PPE1), Dupont Tyvek Model, style 1422A (PPE2), and HA isolation gown for routine patient care and performing aerosol-generating procedures (PPE3) to prevent EVD transmission by measuring the degree of contamination of HCWs and the environment.
A total of 59 participants randomly performed PPE donning and doffing. The trial consisted of PPE donning, applying fluorescent solution on the PPE surface, PPE doffing of participants, and estimation of the degree of contamination as indicated by the number of fluorescent stains on the working clothes and environment. Protocol deviations during PPE donning and doffing were monitored.
PPE2 and PPE3 presented higher contamination risks than PPE1. Environmental contaminations such as those originating from rubbish bin covers, chairs, faucets, and sinks were detected. Procedure deviations were observed during PPE donning and doffing, with PPE1 presenting the lowest overall deviation rate (%) among the three PPE ensembles (
0.05).
Contamination of the subjects' working clothes and surrounding environment occurred frequently during PPE doffing. Procedure deviations were observed during PPE donning and doffing. Although PPE1 presented a lower contamination risk than PPE2 and PPE3 during doffing and protocol deviations, the design of PPE1 can still be further improved. Future directions should focus on designing a high-coverage-area PPE with simple ergonomic features and on evaluating the doffing procedure to minimise the risk of recontamination. Regular training for users should be emphasised to minimise protocol deviations, and in turn, guarantee the best protection to HCWs.
A novel coumarin–rhodamine conjugate was prepared, and its metal binding properties were studied by UV/Vis and fluorescence spectroscopy. The conjugate serves as a ratiometric and highly selective ...fluorescent sensor for Hg2+ ions. Its metal‐responsive spectral properties were utilized to construct a molecular keypad lock with four inputs and dual fluorescence outputs. The complexity of this molecular logic network can greatly enhance the security level of this device.
A coumarin–rhodamine conjugate serves as a ratiometric and highly selective fluorescent sensor for Hg2+ ions. Its metal‐responsive spectral properties were utilized to construct an advanced molecular keypad lock with a high security level.
An unsymmetrical bisferrocenyl silicon(IV) phthalocyanine has been prepared in which the disulfide and hydrazone linkers can be cleaved by dithiothreitol and acid, respectively. The separation of the ...ferrocenyl quenchers and the phthalocyanine core greatly enhances the fluorescence emission, singlet oxygen production, intracellular fluorescence intensity, and in vitro photocytotoxicity. The results have been compared with those for the two symmetrical analogues which contain either the disulfide or hydrazone linker and therefore can only be activated by one of these stimuli. For the dual activatable agent, the greatest enhancement can be attained under a slightly acidic environment (pH = 4.5-6.8) and in the presence of dithiothreitol (in millimolar range), which can roughly mimic the acidic and reducing environment of tumor tissues. This compound can also be activated in tumor-bearing nude mice. It exhibits an increase in fluorescence intensity in the tumor over the first 10 h after intratumoral injection and can effectively inhibit the growth of tumor upon illumination.
A facile approach to assemble catalase‐like photosensitizing nanozymes with a self‐oxygen‐supplying ability was developed. The process involved Fe3+‐driven self‐assembly of fluorenylmethyloxycarbonyl ...(Fmoc)‐protected amino acids. By adding a zinc(II) phthalocyanine‐based photosensitizer (ZnPc) and the hypoxia‐inducible factor 1 (HIF‐1) inhibitor acriflavine (ACF) during the Fe3+‐promoted self‐assembly of Fmoc‐protected cysteine (Fmoc‐Cys), the nanovesicles Fmoc‐Cys/Fe@Pc and Fmoc‐Cys/Fe@Pc/ACF were prepared, which could be disassembled intracellularly. The released Fe3+ could catalyze the transformation of H2O2 enriched in cancer cells to oxygen efficiently, thereby ameliorating the hypoxic condition and promoting the photosensitizing activity of the released ZnPc. With an additional therapeutic component, Fmoc‐Cys/Fe@Pc/ACF exhibited higher in vitro and in vivo photodynamic activities than Fmoc‐Cys/Fe@Pc, demonstrating the synergistic effect of ZnPc and ACF.
Fe3+ ions can promote the self‐assembly of Fmoc‐protected amino acids to form nanovesicles and catalyze the transformation of H2O2 enriched in cancer cells to oxygen, thereby ameliorating the hypoxic condition and promoting the photosensitizing activity of the encapsulated photosensitizer (ZnPc) in the nanovesicles. By entrapping an additional therapeutic agent (ACF), the nanovesicles can exhibit a synergistic effect for eradication of hypoxic cancer cells and tumors.
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