Photodynamic therapy (PDT) is a promising and minimally invasive method for the treatment of superficial diseases, and photosensitizers with high phototoxicity indices (defined as ...(IC50dark)/(IC50irradiation)) are essential for the development of ideal photosensitizing properties for this technology. Herein, we report a series of photocytotoxic copper(II) complexes Cu(RQYMP)(dppn) (RQYMP=N,N,O‐tridentate Schiff‐base derivatives, dppn=benzoidipyrido3,2‐a;2′,3′‐cphenazine), the structures of which have been confirmed by mass spectrometry and FTIR spectroscopy. X‐ray crystallography revealed that the CuN4O core of the Cu(cumylQYMP)(dppn)(ClO4) complex (3) has a distorted square‐pyramidal geometry. Phototoxicity indices of 329 against human squamous cell carcinoma (SCC15) and 296 against basal cell carcinoma (BCC) cell lines have been determined with Cu(3‐OMeQYMP)(dppn)(ClO4) (4). This can be attributed to the formation of reactive oxygen species, cell apoptosis, and caspase‐3 activation, indicating high potential of complex 4 as a photosensitizer candidate in PDT. Thus, copper complexes bearing suitable Schiff‐base ligands with a dppn co‐ligand may be considered for the design of efficient metal‐based anticancer agents for PDT.
Copper complexes for PDT: Photocytotoxic copper(II) complexes Cu(RQYMP)(dppn) (RQYMP=N,N,O‐tridentate Schiff‐base derivatives, dppn=benzoidipyrido3,2‐a;2′,3′‐cphenazine) show high phototoxicity indices against SCC15 and BCC cancer cells owing to the generation of reactive oxygen species and caspase‐3‐mediated cell apoptosis.
Batteries are the core component of electric vehicles (EVs) and energy storage systems (ESSs), being crucial technologies contributing to carbon neutrality, energy security, power system reliability, ...economic efficiency, etc. The effective operation of batteries requires precise knowledge of the state of health (SOH) of the battery. A lack of proper knowledge of SOH may lead to the improper use of severely aged batteries, which may result in degraded system performance or even a risk of failure. This makes it important to accurately estimate battery SOH using only operational data, and this is the main topic of this study. In this study, we propose a novel method for online SOH estimation for batteries featuring simple online computation and robustness against measurement anomalies while avoiding the need for full cycle discharging and charging operation data. Our proposed method is based on incremental capacity analysis (ICA) to extract battery aging feature parameters and regression using simple piecewise linear interpolation. Our proposed method is compared with back-propagation neural network (BPNN) regression, a popular method for SOH estimation, in case studies involving actual data from battery aging experiments under realistic discharging and temperature conditions. In terms of accuracy, our method is on par with BPNN results (about 5% maximum relative error), while the simplicity of our method leads to better computation efficiency and robustness against data anomalies.
Osteosarcoma is the most common primary malignant bone tumor, particularly among children and adolescents, and the prognosis of osteosarcoma patients remains poor. The NADPH oxidase 2 (NOX2) has been ...found over-expressed in several human cancers, and closely associated with poor prognosis. Meanwhile the role of NOX2 in osteosarcoma patients has not been reported. This study aimed to investigate the clinicopathological and prognostic significance of NOX2 in osteosarcoma patients.
Immunohistochemistry (IHC), western blot (WB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of NOX2 in 55 primary osteosarcoma specimens and in 20 non-neoplastic bone tissue specimens. The correlations between NOX2 expression and clinicopathological parameters were analysed by using the χ2 test or Fisher's exact test. Disease free survival and overall survival of osteosarcoma patients were assessed by using the Kaplan-Meier method and Cox proportional hazards model.
NOX2 was over-expressed significantly in osteosarcoma compared with that in non-neoplastic bone tissue, and correlated with progression free survival (P < 0.001) and overall survival (P < 0.001). The over-expression of NOX2 was associated with tumor size (P < 0.001), tumor location (P < 0.001). The Cox analysed shown that the over-expression of NOX2 was predicted to be worse PFS (hazard ratio (HR) = 4.10, P = 0.004) and OS (hazard ratio (HR) = 3.50, P = 0.010) time in osteosarcoma patients.
The results of our study suggest that the over-expression of NOX2 is related to adverse clinical outcome, and can be viewed as an independent prognostic marker in osteosarcoma. Further research is required to verify the predictive value of NOX2 in osteosarcoma patients.
There is increasing evidence that deep sequencing-based T cell repertoire can sever as a biomarker of immune response in cancer patients; however, the characteristics of T cell repertoire including ...diversity and similarity, as well as its prognostic significance in patients with cervical cancer (CC) remain unknown. In this study, we applied a high throughput T cell receptor (TCR) sequencing method to characterize the T cell repertoires of peripheral blood samples from 25 CC patients, 30 cervical intraepithelial neoplasia (CIN) patients and 20 healthy women for understanding the immune alterations during the cervix carcinogenesis. In addition, we also explored the signatures of TCR repertoires in the cervical tumor tissues and paired sentinel lymph nodes from 16 CC patients and their potential value in predicting the prognosis of patients. Our results revealed that the diversity of circulating TCR repertoire gradually decreased during the cervix carcinogenesis and progression, but the circulating TCR repertoires in CC patients were more similar to CIN patients than healthy women. Interestingly, several clonotypes uniquely detected in CC patients tended to share similar CDR3 motifs, which differed from those observed in CIN patients. In addition, the TCR repertoire diversity in sentinel lymphatic nodes from CC patients was higher than in tumor tissues. More importantly, less clonotypes in TCR repertoire of sentinel lymphatic node was associated with the poor prognosis of the patients. Overall, our findings suggested that TCR repertoire might be a potential indicator of immune monitoring and a biomarker for predicting the prognosis of CC patients. Although functional studies of T cell populations are clearly required, this study have expanded our understanding of T cell immunity during the development of CC and provided an experimental basis for further studies on its pathogenesis and immunotherapy.
The T-cell immune responses in nasopharyngeal carcinoma patients have been extensively investigated recently for designing adoptive immunotherapy or immune checkpoint blockade therapy. However, the ...distribution characteristics of T cells associated with NPC pathogenesis are largely unknown. We performed deep sequencing for TCR repertoire profiling on matched tumor/adjacent normal tissue from 15 NPC patients and peripheral blood from 39 NPC patients, 39 patients with other nasopharyngeal diseases, and 33 healthy controls. We found that a lower diversity of TCR repertoire in tumors than paired tissues or a low similarity between the paired tissues was associated with a poor prognosis in NPC. A more diverse TCR repertoire was identified in the peripheral blood of NPC patients relative to the controls; this was related to a significant decrease in the proportion of high-frequency TCR clones in NPC. Higher diversity in peripheral blood of NPC patients was associated with a worse prognosis. Due to the peculiarity of the Vβ gene usage patterns in the peripheral blood of NPC patients, 15 Vβ genes were selected to distinguish NPC patients from controls by the least absolute shrinkage and selection operator analysis. We identified 11 clonotypes shared by tumors and peripheral blood samples from different NPC patients, defined as “NPC-associated” that might have value in adoptive immunotherapy. In conclusion, we here report the systematic and overall characteristics of the TCR repertoire in tumors, adjacent normal tissues, and peripheral blood of NPC patients. The data obtained may be relevant to future clinical studies in the setting of immunotherapy for NPC patients.
Chiral 3-substituted benzoxaboroles were designed as carbapenemase inhibitors and efficiently synthesised
via
asymmetric Morita-Baylis-Hillman reaction. Some of the benzoxaboroles were potent ...inhibitors of clinically relevant carbapenemases and restored the activity of meropenem in bacteria harbouring these enzymes. Crystallographic analyses validate the proposed mechanism of binding to carbapenemases,
i.e.
in a manner relating to their antibiotic substrates. The results illustrate how combining a structure-based design approach with asymmetric catalysis can efficiently lead to potent β-lactamase inhibitors and provide a starting point to develop drugs combatting carbapenemases.
An organocatalytic MBH cascade reaction was developed to construct new 3-(α-acrylic acid) benzoxaboroles, designed to mimic 'anchoring' pharmacophore features of carbapenems, with the aim of helping overcome carbapenemase resistance.
Biological cells in vivo typically reside in a dynamic flowing microenvironment with extensive biomechanical and biochemical cues varying in time and space. These dynamic biomechanical and ...biochemical signals together act to regulate cellular behaviors and functions. Microfluidic technology is an important experimental platform for mimicking extracellular flowing microenvironment in vitro. However, most existing microfluidic chips for generating dynamic shear stress and biochemical signals require expensive, large peripheral pumps and external control systems, unsuitable for being placed inside cell incubators to conduct cell biology experiments. This study has developed a microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow. Further, based on the lumped‐parameter and distributed‐parameter models of multiscale fluid dynamics, the oscillatory flow field and the concentration field of biochemical factors has been simulated at the cell culture region within the designed microfluidic chip. Using the constructed experimental system, the feasibility of the designed microfluidic chip has been validated by simulating biochemical factors with red dye. The simulation results demonstrate that dynamic shear stress and biochemical signals with adjustable period and amplitude can be generated at the cell culture chamber within the microfluidic chip. The amplitudes of dynamic shear stress and biochemical signals is proportional to the pressure difference and inversely proportional to the flow resistance, while their periods are correlated positively with the flow capacity and the flow resistance. The experimental results reveal the feasibility of the designed microfluidic chip. Conclusively, the proposed microfluidic generator based on autonomously oscillatory flow can generate dynamic shear stress and biochemical signals without peripheral pumps and external control systems. In addition to reducing the experimental cost, due to the tiny volume, it is beneficial to be integrated into cell incubators for cell biology experiments. Thus, the proposed microfluidic chip provides a novel experimental platform for cell biology investigations.
Potential clinical application values of certain cytokines and chemokines that participate in the process of tumor growth, invasion, and metastasis have been reported. However, there still lack of ...biomarkers for a great many of malignancy. This study identified cytokines or chemokines involved in the occurrence and development of nasopharyngeal carcinoma (NPC), which might be a biomarker for noninvasive early diagnosis.
The plasma levels of 19 cytokines and chemokines were detected by the luminex liquid array-based multiplexed immunoassays in 39 NPC patients before and after treatment by definitive intensity-modulated radiotherapy (IMRT).
Plasma levels of almost all of the 19 cytokines and chemokines in NPC patients were higher than healthy controls, while only IFN-γ, IL-1b IL-6, MCP-1, TNF-α, FKN, IL-12P70, IL-2, IL-5 and IP-10 showed significant differences. However, expression levels of most of the 19 cytokines and chemokines decreased after therapy, especially IFN-γ, IL-10, IL-1b, IL-6, IL-8, MCP-1, TNF-α, VEGF, IL-17A, IL-2, IL-5 and MIP-1b, have a dramatic decline. Taking together, plasma levels of IFN-γ, IL-1b, IL-6, MCP-1, TNF-α, IL-2 and IL-5 are significantly increased in NPC patients and dramatically decreased after treatment, suggesting these cytokines and chemokines might play important roles in the progress of NPC. More interestingly, the expression level of MPC-1 is significantly associated with clinical stage.
MCP-1 might involve in the genesis and development process of NPC, which might serve as a noninvasive biomarker for early diagnosis.
Subjective cognitive decline (SCD) may be the first symptomatic manifestation of Alzheimer's disease, but information on its health correlates is still sparse in Chinese older adults. This study ...aimed to estimate SCD symptoms and its association with socio-demographic characteristics, common chronic diseases among southern Chinese older adults.
Participants aged 60 years and older from 7 communities and 2 nursing homes in Guangzhou were recruited and interviewed with standardized assessment tools. Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure poor sleep quality, depression symptoms and anxiety symptoms. The SCD symptoms were measured by SCD questionnaire 9 (SCD-Q9) which ranged from 0 to 9 points, with a higher score indicating increased severity of the SCD. Participants were divided into low score group (SCD-Q9 score ≤ 3) and higher score group (SCD-Q9 score > 3). Chi-square tests and multivariate logistic regression analysis were used for exploring the influences of different characteristics of socio-demographic and lifestyle factors on SCD symptoms. Univariate and multivariate logistic regression analysis were applied to explore the association between SCD symptoms with common chronic diseases.
A total of 688 participants were included in our analysis with a mean age of 73.79 (SD = 8.28, range: 60-101), while 62.4% of the participants were females. The mean score of the SCD-Q9 was 3.81 ± 2.42 in the whole sample. A total of 286 participants (41.6%) were defined as the low score group (≤3 points), while 402 participants (58.4%) were the high score group (> 3 points). Multivariate logistic regression analysis revealed that female (OR = 1.99, 95%CI: 1.35-2.93), primary or lower education level (OR = 2.58, 95%CI: 1.38-4.83), nursing home (OR = 1.90, 95%CI: 1.18-3.05), napping habits (OR = 1.59, 95%CI: 1.06-2.40), urolithiasis (OR = 2.72, 95%CI: 1.15-6.40), gout (OR = 2.12, 95%CI: 1.14-3.93), poor sleep quality (OR = 1.93, 95%CI: 1.38-2.71), depression symptoms (OR = 3.01, 95%CI: 1.70-5.34) and anxiety symptoms (OR = 3.11, 95%CI: 1.29-7.46) were independent positive related to high SCD-Q9 score. On the other hand, tea-drinking habits (OR = 0.64, 95%CI: 0.45-0.92), current smoking (OR = 0.46, 95%CI: 0.24-0.90) were independent negative related to high SCD-Q9 score.
Worse SCD symptoms were closely related to common chronic diseases and socio-demographic characteristics. Disease managers should pay more attention to those factors to early intervention and management for SCD symptoms among southern Chinese older adults.
In present study, we develop a new segregation index having both geometrical and physical significances, on the basis of segregation profile of granular bed. We carry out a DEM simulation to validate ...this index and analyze the segregation of binary mixture. The DEM analysis reveals that the segregation profile of granular bed subjected to vibration is in general in a reverse “N” mode, which tends to narrow and weaken as vibration continues. At a proper vibration amplitude, the reverse “N” pattern diminishes progressively and the overall segregation profile evolves into a three-line-segment pattern which stands for the ideal state of full segregation. A comparison analysis indicates that the new index proposed in this study is able to give a more proper estimation of segregation phenomenon for binary mixtures, as compared with other indices from the literature.
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•A segregation index GPSI of both geometrical and physical meanings has been proposed.•The segregation profile of granular bed in vibration is in a reverse "N" pattern.•The new index gives a segregation description close to the true situation.
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