Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1-b][1,3,4]Thiadiazole Moiety.

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200 µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.

Nanoscale Metal-Organic Frameworks-Mediated Degradation of Mutant p53 Proteins and Activation of cGAS-STING Pathway for Enhanced Cancer Immunotherapy.

Activating cGAS-STING pathway has great potential to achieve effective antitumor immunotherapy. However, mutant p53 (mutp53), a commonly observed genetic alteration in over 50% of human cancer, will impede the therapeutic performance of the cGAS-STING pathway. Herein, multifunctional ZIF-8@MnO2 nanoparticles are constructed to degrade mutp53 and facilitate the cGAS-STING pathway. The synthesized ZIF-8@MnO2 can release Zn2+ and Mn2+ in cancer cells to induce oxidative stress and cytoplasmic leakage of fragmented mitochondrial double-stranded DNAs (dsDNAs). Importantly, the released Zn2+ induces variable degradation of multifarious p53 mutants through proteasome ubiquitination, which can alleviate the inhibitory effects of mutp53 on the cGAS-STING pathway. In addition, the released Mn2+ further increases the sensitivity of cGAS to dsDNAs as immunostimulatory signals. Both in vitro and in vivo results demonstrate that ZIF-8@MnO2 effectively promotes the cGAS-STING pathway and synergizes with PD-L1 checkpoint blockades, leading to remarkable regression of local tumors as well as distant metastases of breast cancer. This study proposes an inorganic metal ion-based nanoplatform to enhance the cGAS-STING-mediated antitumor immunotherapy, especially to those tumors with mutp53 expression.

Portable evaluation of obstructive sleep apnea in adults: A systematic review.

Obstructive sleep apnea (OSA) is a significant healthcare burden affecting approximately one billion people worldwide. The prevalence of OSA is rising with the ongoing obesity epidemic, a key risk factor for its development. While in-laboratory polysomnography (PSG) is the gold standard for diagnosing OSA, it has significant drawbacks that prevent widespread use. Portable devices with different levels of monitoring are available to allow remote assessment for OSA. To better inform clinical practice and research, this comprehensive systematic review evaluated diagnostic performances, study cost and patients' experience of different levels of portable sleep studies (type 2, 3, and 4), as well as wearable devices and non-contact systems, in adults. Despite varying study designs and devices used, portable diagnostic tests are found to be sufficient for initial screening of patients at risk of OSA. Future studies are needed to evaluate cost effectiveness with the incorporation of portable diagnostic tests into the diagnostic pathway for OSA, as well as their application in patients with chronic respiratory diseases and other comorbidities that may affect test performance.

"Digital Dividend" or "Digital Divide": What Role Does the Internet Play in the Health Inequalities among Chinese Residents?

With the vigorous development of the medical industry in China, residents' health has been significantly improved. However, along with the income gap, urban-rural gap, and healthcare resource gap caused by economic development, health inequality has become a fundamental barrier to the promotion of residents' health. The popularity of the Internet has helped close the gap to some extent, but it also has drawbacks. Using data from the China Family Panel Studies (CFPS) from 2014 to 2018, we evaluated the effects of Internet usage on health disparities among residents using fixed effect models, mediation effect models, and other methodologies. The findings indicate that Internet usage can help to minimize health inequality since it lowers income inequality, promotes health consciousness, and reduces depression. Furthermore, Internet usage plays a greater role on the health improvement of the middle-aged, the elderly, urban residents, and females. Although the Internet has brought "digital dividends" in general, the Internet usage rates among different groups also reveal that there is a clear "digital gap" among rural residents, elderly groups, and low-income groups. These results have significant implications for promoting healthcare equality.

A systematic review: Cost-effectiveness of continuous glucose monitoring compared to self-monitoring of blood glucose in type 1 diabetes.

Continuous glucose monitoring (CGM) is rapidly becoming a vital tool in the management of type 1 diabetes. Its use has been shown to improve glycaemic management and reduce the risk of hypoglycaemic events. The cost of CGM remains a barrier to its widespread application. We aimed to identify and synthesize evidence about the cost-effectiveness of utilizing CGM in patients with type 1 diabetes. Studies were identified from MEDLINE, Embase and Cochrane Library from January 2010 to February 2022. Those that assessed the cost-effectiveness of CGM compared to self-monitored blood glucose (SMBG) in patients with type 1 diabetes and reported lifetime incremental cost-effectiveness ratio (ICER) were included. Studies on critically ill or pregnant patients were excluded. Nineteen studies were identified. Most studies compared continuous subcutaneous insulin infusion and SMBG to a sensor-augmented pump (SAP). The estimated ICER range was [$18,734-$99,941] and the quality-adjusted life year (QALY) gain range was [0.76-2.99]. Use in patients with suboptimal management or greater hypoglycaemic risk revealed more homogenous results and lower ICERs. Limited studies assessed CGM in the context of multiple daily injections (MDI) (n = 4), MDI and SMBG versus SAP (n = 2) and three studies included hybrid closed-loop systems. Most studies (n = 17) concluded that CGM is a cost-effective tool. This systematic review suggests that CGM appears to be a cost-effective tool for individuals with type 1 diabetes. Cost-effectiveness is driven by reducing short- and long-term complications. Use in patients with suboptimal management or at risk of severe hypoglycaemia is most cost-effective.

The Impact of Social Pension Schemes on the Mental Health of the Chinese Elderly: A Mediating Effect Perspective of Two-Way Intergenerational Support.

With the rapid decline in China's fertility rate, the acceleration of aging, the continuous miniaturization and nucleation of China's family structure, and the deterioration of the elderly's living conditions and mental states, the elderly's mental health has emerged as a major public health issue and a major social problem. Pensions are the elderly's primary source of income, and they can help them meet their basic needs while also promoting family harmony and improving their mental health. Based on the data of the 2012, 2016, and 2018 Chinese Family Panel Studies (CFPS), we empirically examined the impact of pensions on the elderly's mental health by using the fixed effects model, mediating effect model, and so on. The results show that receiving pension benefits can significantly reduce the level of depression and improve the mental health of the elderly. Receiving pension benefits causes reverse intergenerational economic transfer, which reduces the effect of pensions on the elderly's mental health to some extent, but the life care and mental comfort provided by children increases when the elderly share pensions with their children. Overall, receiving pension benefits improves the mental health of the elderly. In addition, the effect of pensions on the elderly with different characteristics is heterogeneous. The older elderly, women, the elderly living with their children, and the elderly in rural areas all benefit more from receiving pension benefits. Moreover, the worse the mental health of the elderly is, the stronger the influence of pensions on their mental health is. Our discussion has important policy implications.

Machine Learning Based on a Multiparametric and Multiregional Radiomics Signature Predicts Radiotherapeutic Response in Patients with Glioblastoma.

METHODS: The MRI images, genetic data, and clinical data of 152 patients with GBM were analyzed. 122 patients from the TCIA dataset (training set: n = 82; validation set: n = 40) and 30 patients from local hospitals were used as an independent test dataset. Radiomics features were extracted from multiple regions of multiparameter MRI. Kaplan-Meier survival analysis was used to verify the ability of the imaging signature to predict the response of GBM patients to radiotherapy before an operation. Multivariate Cox regression including radiomics signature and preoperative clinical risk factors was used to further improve the ability to predict the overall survival (OS) of individual GBM patients, which was presented in the form of a nomogram. RESULTS: The radiomics signature was built by eight selected features. The C-index of the radiomics signature in the TCIA and independent test cohorts was 0.703 (P < 0.001) and 0.757 (P = 0.001), respectively. Multivariate Cox regression analysis confirmed that the radiomics signature (HR: 0.290, P < 0.001), age (HR: 1.023, P = 0.01), and KPS (HR: 0.968, P < 0.001) were independent risk factors for OS in GBM patients before surgery. When the radiomics signature and preoperative clinical risk factors were combined, the radiomics nomogram further improved the performance of OS prediction in individual patients (C-index = 0.764 and 0.758 in the TCIA and test cohorts, respectively). CONCLUSION: This study developed a radiomics signature that can predict the response of individual GBM patients to radiotherapy and may be a new supplement for precise GBM radiotherapy.

Adoption of Biologically Effective Dose of the Non-Target Lung Volume to Predict Symptomatic Radiation Pneumonitis After Stereotactic Body Radiation Therapy With Variable Fractionations for Lung Cancer.

Background: This study aims to establish lung biologically effective dose (BED)-based uniform dosimetric constraints for minimizing the risk of symptomatic radiation pneumonitis (SRP) from stereotactic body radiation therapy (SBRT) using variable fractionations in patients with lung tumors. Materials and Methods: A total of 102 patients with primary or oligometastatic lung tumors treated with SBRT in our institution were enrolled into this study. The associations between the clinical and dosimetric parameters and the incidences of SRP were analyzed using univariate and multivariate Cox regression hazard models. The receiver operating characteristic (ROC) curve was generated to evaluate the predictive performance of lung BED on the SRP risk compared with the physical dose. Results: SRP occurred in 11 patients (10.8%). In univariate analysis, the mean lung dose (p = 0.002), V5 (p = 0.005), V20 (p < 0.001), and the percentage of non-target normal lung volume receiving more than a BED of 5-170 Gy (VBED5-170, p < 0.05) were associated with SRP. Multivariate logistic regression analysis showed that there existed a significant statistical correlation between SRP and VBED70 (p < 0.001), which performed better than V5 or V20 on the ROC curves, resulting in an optimal cut-off value of lung VBED70 of 2.22%. Conclusions: This retrospective study indicated that non-target lung BED may better predict SRP from patients with SBRT-treated lung cancer. Limiting the lung VBED70 below 2.22% may be favorable to reduce the incidence of SRP, which warranted further prospective validation.

Preoperative Platelet-to-Lymphocyte Ratio Is Not Associated With Postoperative Atrial Fibrillation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after coronary artery bypass grafting (CABG) and is associated with increased short-term and long-term mortality. While the precise etiology of POAF remains unclear, inflammation is a known contributing factor. Preliminary studies have suggested that an elevated preoperative platelet-to-lymphocyte ratio (PLR), an inexpensive and readily available novel inflammatory biomarker, may be associated with increased incidence of POAF after CABG. This study sought to further investigate this hypothesis. METHODS: The study cohort included all patients undergoing isolated CABG, with no prior history of arrhythmia, who were operated on between August 1, 2010, and December 31, 2018, at a major Australian tertiary center (n = 1457). Patients were divided into low (<86) or high (≥86) PLR groups based on an optimal cutoff derived from receiver-operating characteristic curve analysis. The incidence of POAF was then compared. Categorical variables were analyzed using the chi-square test and continuous variables using logistic regression. RESULTS: Of 1457 patients, 495 (34.0%) developed POAF. There was no statistically significant difference in the incidence of POAF between patients in the high-PLR and low-PLR groups (34.8% vs 31.0%; P = .22). Using multivariable logistic regression analysis, high PLR was not independently associated with POAF (odds ratio, 1.04; P = .78). CONCLUSIONS: Elevated preoperative PLR is not independently associated with POAF in patients undergoing isolated CABG. The findings of this study differ from those of 2 previous smaller studies.

Biochar-related studies from 1999 to 2018: a bibliometrics-based review.

Biochar has been paid great attentions during the last two decades, because of its resources potentials and environmental benefits. A bibliometric analysis was applied to assess the publications regarding the keyword biochar from the Web of Science database during the period of 1999 to 2018. A total of 8629 publications were obtained with a rapid increase of annual citations and number of papers. The research topics were diversified, which were mainly divided into "Environmental Sciences and Ecology," "Agriculture," and "Engineering." Bioresource Technology was the journal which published most of the relevant papers. China ranked first in the number of published papers, followed by the USA, Australia, UK, and Germany. Especially, China established close collaboration with the USA in joint publication. Analysis of the keywords indicated that biochar production, comparative sorption, soil-applied black carbon, and soil management were the main research hotspots of biochar. The burst detection reflected that the innovation of biochar production and the new application field of biochar was the future research trends. These results can provide insight into the research progress regarding biochar.

Investigation on Cutting Performance of Micro-Textured Cutting Tools.

This paper explores the influence of micro textures on cutting performance of polycrystalline cubic boron nitride (PCBN) tools from two aspects, that is, tool wear and machined surface roughness. By designing micro-hole textures with different forms and scales on the rake face of tools when PCBN tools turn hardened steel GCr15, and combining finite element analysis (FEA) technology and cutting experiments, the cutting performance of micro-textured tools is simulated and analyzed. This paper analyses the influence of micro textures on tool wear and machined surface roughness by analyzing cutting force, Mises stress and maximum shear stress of tool surface. Results of finite element analysis (FEA) and cutting experiments show that the reasonable micro-hole textures can significantly alleviate tool wear and improve machined surface quality when compared with the non-textured tools. Besides, the size of micro-hole textures on the rake face play an important role in reducing the cutting force and tool wear. This is mainly because micro-hole textures can reduce cutting force and improve tool surface stress. Finally, by designing reasonable micro-hole textures on the rake face, the problems of bad roughness of machined workpiece and severe tool wear of PCBN tools in cutting GCr15 material are solved. Consequently, the paper shows that micro-hole textures have a positive effect on improving the cutting performance of tool.

Dual-Energy Computed Tomography-Based Iodine Quantitation for Response Evaluation of Lung Cancers to Chemoradiotherapy/Radiotherapy: A Comparison With Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography-Based Positron Emission Tomography/Computed Tomography Response Evaluation Criterion in Solid Tumors.

OBJECTIVE: The objective of this study was to investigate the correlation between dual-energy computed tomography (DECT)-based iodine quantitation and fluorine-18 fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging for response evaluation of lung cancers to treatment. METHODS: In this prospective study, a total of 32 pairs of DECT and F-FDG PET/CT imaging acquired consecutively from 13 patients with primary or metastatic lung cancers receiving either radiotherapy alone or chemoradiotherapy were analyzed. Imaging examinations were performed before, immediately, and no later than 6 months after treatment for response evaluation. Iodine-related parameters including the total iodine uptake (TIU) and vital volume (VIV) from DECT and metabolic metrics such as the standardized uptake value normalized to lean body mass (SULpeak), metabolic tumor volume (MTV), and the total lesion glycolysis (TLG) from F-FDG-PET/CT were generated and measured by semiautomatic approaches. Dual-energy CT and PET/CT metrics were calculated and followed up with comparison with response evaluation criteria in solid tumors (RECIST). RESULTS: Analysis of pretreatment imaging data revealed a strong correlation between DECT metrics (RECIST, TIU, and VIV) and F-FDG PET/CT metrics (MTV, TLG) with coefficients of R ranging from 0.86 to 0.90 (P < 0.01). With the delivery of treatment, all measured DECT and PET/CT metrics significantly decreased whereas the descending amplitude in RECIST was significantly smaller than that of the remaining parameters (P < 0.05). During follow-up examinations, both metrics followed a similar changing pattern. Overall, strong consistency was found between RECIST, TIU, VIV and SULpeak, MTV, TLG (R covers 0.78-0.96, P < 0.05). CONCLUSIONS: Semiautomatic iodine-related quantitation in DECT correlated well with metabolism-based measurements in F-FDG PET/CT, suggesting that DECT-based iodine quantitation might be a feasible substitute for assessment of lung cancer response to chemoradiotherapy/radiotherapy with comparison with F-FDG PET/CT.

[Quantitative Imaging Assessment of Tumor Response to Chemoradiation 
in Lung Cancer].

Precision medicine demands accurate assessment of tumor response to therapies with the purpose of timely optimization or adjustment of the given treatment regimens. Chemoradiation remains the standard of care in advanced lung cancers and imaging-based noninvasive response evaluation could improve therapeutic efficacy and reduce treatment-related severe side effects. In this review, we overviewed the applications and pitfalls of major imaging modalities in response evaluation in lung cancer from a quantitative perspective. The development of radiomics will provide more precise information for treatment predicting, evaluation and prognosis.