A Three-in-One Hybrid Strategy for High-Performance Semiconducting Polymers Processed from Anisole.

The development of semiconducting polymers with good processability in green solvents and competitive electrical performance is essential for realizing sustainable large-scale manufacturing and commercialization of organic electronics. A major obstacle is the processability-performance dichotomy that is dictated by the lack of ideal building blocks with balanced polarity, solubility, electronic structures, and molecular conformation. Herein, through the integration of donor, quinoid and acceptor units, an unprecedented building block, namely TQBT, is introduced for constructing a serial of conjugated polymers. The TQBT, distinct in non-symmetric structure and high dipole moment, imparts enhanced solubility in anisole-a green solvent-to the polymer TQBT-T. Furthermore, PTQBT-T possess a highly rigid and planar backbone owing to the nearly coplanar geometry and quinoidal nature of TQBT, resulting in strong aggregation in solution and localized aggregates in film. Remarkably, PTQBT-T films spuncast from anisole exhibit a hole mobility of 2.30 cm2 V-1 s-1, which is record high for green solvent-processable semiconducting polymers via spin-coating, together with commendable operational and storage stability. The hybrid building block emerges as a pioneering electroactive unit, shedding light on future design strategies in high-performance semiconducting polymers compatible with green processing and marking a significant stride towards ecofriendly organic electronics.

Self-Healable Multifunctional Fibers via Thermal Drawing.

The development of soft electronics and soft fiber devices has significantly advanced flexible and wearable technology. However, they still face the risk of damage when exposed to sharp objects in real-life applications. Taking inspiration from nature, self-healable materials that can restore their physical properties after external damage offer a solution to this problem. Nevertheless, large-scale production of self-healable fibers is currently constrained. To address this limitation, this study leverages the thermal drawing technique to create elastic and stretchable self-healable thermoplastic polyurethane (STPU) fibers, enabling cost-effective mass production of such functional fibers. Furthermore, despite substantial research into the mechanisms of self-healable materials, quantifying their healing speed and time poses a persistent challenge. Thus, transmission spectra are employed as a monitoring tool to observe the real-time self-healing process, facilitating an in-depth investigation into the healing kinetics and efficiency. The versatility of the fabricated self-healable fiber extends to its ability to be doped with a wide range of functional materials, including dye molecules and magnetic microparticles, which enables modular assembly to develop distributed strain sensors and soft actuators. These achievements highlight the potential applications of self-healable fibers that seamlessly integrate with daily lives and open up new possibilities in various industries.

Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

The Synergistic Effect of Additives for Formamidinium-Based Inverted Dion-Jacobson 2D Perovskite Solar Cells with Enhanced Photovoltaic Performance.

Two-dimensional (2D) perovskite solar cells (PSCs) have attracted rapid growing attention due to their excellent environmental and operational stability. As an important type of 2D perovskite, Dion-Jacobson (DJ) 2D perovskites exhibit better structural integrity and more stable optoelectronic properties than those of Ruddlesden-Popper (RP) ones because of the elimination of weak van der Waals interactions. Random phase distribution, phase impurity, and weak crystallinity, however, can lead to severe nonradiative recombination losses in 2D perovskites and inferior device stability. Herein, formamidinium chloride (FACl) and lead chloride (PbCl2) are selected as additives to fabricate efficient and stable DJ 2D PSCs. The synergistic effect of additives could efficiently induce crystallization and suppress the low-n phase perovskites. The obtained 2D perovskites exhibit extended charge lifetime and enhanced charge transfer. The corresponding PSC device delivers an efficiency of 16.63% with a significantly improved open-circuit voltage (VOC) of 1.18 V and a fill factor (FF) of 81.65% than the control one. This PCE ranks the highest for inverted FA-based 2D DJ PSCs. Moreover, this device has exhibited exceptional long-term stability, which retains more than 95% of the initial efficiencies at about 50% relative humidity for 600 h.

Demographic and socioeconomic determinants of access to care: A subgroup disparity analysis using new equity-focused measurements.

Disparities in healthcare access and utilization associated with demographic and socioeconomic status hinder advancement of health equity. Thus, we designed a novel equity-focused approach to quantify variations of healthcare access/utilization from the expectation in national target populations. We additionally applied survey-weighted logistic regression models, to identify factors associated with usage of a particular type of health care. To facilitate generation of analysis datasets, we built an National Health and Nutrition Examination Survey (NHANES) knowledge graph to help automate source-level dynamic analyses across different survey years and subjects' characteristics. We performed a cross-sectional subgroup disparity analysis of 2013-2018 NHANES on U.S. adults for receipt of diabetes treatments and vaccines against Hepatitis A (HAV), Hepatitis B (HBV), and Human Papilloma (HPV). Results show that in populations with hemoglobin A1c level ≥6%, patients with non-private insurance were less likely to receive newer and more beneficial antidiabetic medications; being Asian further exacerbated these disparities. For widely used drugs such as insulin, Asians experienced insignificant disparities in odds of prescription compared to White patients but received highly inadequate treatments with regard to their distribution in U.S. diabetic population. Vaccination rates were associated with some demographic/socioeconomic factors but not the others at different degrees for different diseases. For instance, while equity scores increase with rising education levels for HBV, they decrease with rising wealth levels for HPV. Among women vaccinated against HPV, minorities and poor communities usually received Cervarix while non-Hispanic White and higher-income groups received the more comprehensive Gardasil vaccine. Our study identified and quantified the impact of determinants of healthcare utilization for antidiabetic medications and vaccinations. Our new methods for semantics-aware disparity analysis of NHANES data could be readily generalized to other public health goals to support more rapid identification of disparities and development of policies, thus advancing health equity.

Relationship between quantitative epicardial adipose tissue based on coronary computed tomography angiography and coronary slow flow.

BACKGROUND: The purpose of this study was to explore the relationship between quantitative epicardial adipose tissue (EAT) based on coronary computed tomography angiography (CCTA) and coronary slow flow (CSF). METHODS: A total of 85 patients with < 40% coronary stenosis on diagnostic coronary angiography were included in this retrospective study between January 2020 and December 2021. A semi-automatic method was developed for EAT quantification on CCTA images. According to the thrombolysis in myocardial infarction flow grade, the patients were divided into CSF group (n = 39) and normal coronary flow group (n = 46). Multivariate logistic regression was used to explore the relationship between EAT and CSF. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of EAT in CSF. RESULTS: EAT volume in the CSF group was significantly higher than that of the normal coronary flow group (128.83± 21.59 mL vs. 101.87± 18.56 mL, P < 0.001). There was no significant difference in epicardial fat attenuation index between the two groups (P > 0.05). Multivariate logistic regression analysis showed that EAT volume was independently related to CSF [odds ratio (OR) = 4.82, 95% confidence interval (CI): 3.06-7.27, P < 0.001]. The area under ROC curve for EAT volume in identifying CSF was 0.86 (95% CI: 0.77-0.95). The optimal cutoff value of 118.46 mL yielded a sensitivity of 0.80 and a specificity of 0.94. CONCLUSIONS: Increased EAT volume based on CCTA is strongly associated with CSF. This preliminary finding paves the way for future and larger studies aimed to definitively recognize the diagnostic value of EAT in CSF.

MSA-YOLOv5: Multi-scale attention-based YOLOv5 for automatic detection of acute ischemic stroke from multi-modality MRI images.

BACKGROUND AND OBJECTIVE: Acute ischemic stroke (AIS) is a common neurological disorder characterized by the sudden onset of cerebral ischemia, leading to functional impairments. Swift and precise detection of AIS lesions is crucial for stroke diagnosis and treatment but poses a significant challenge. This study aims to leverage multimodal fusion technology to combine complementary information from various modalities, thereby enhancing the detection performance of AIS target detection models. METHODS: In this retrospective study of AIS, we collected data from 316 AIS patients and created a multi-modality magnetic resonance imaging (MRI) dataset. We propose a Multi-Scale Attention-based YOLOv5 (MSA-YOLOv5), targeting challenges such as small lesion size and blurred borders at low resolutions. Specifically, we augment YOLOv5 with a prediction head to detect objects at various scales. Next, we replace the original prediction head with a Multi-Scale Swin Transformer Prediction Head (MS-STPH), which reduces computational complexity to linear levels and enhances the ability to detect small lesions. We incorporate a Second-Order channel attention (SOCA) module to adaptively rescale channel features by employing second-order feature statistics for more discriminative representations. Finally, we further validate the effectiveness of our method using the ISLES 2022 dataset. RESULTS: On our in-house AIS dataset, MSA-YOLOv5 achieves a 79.0% mAP0.5, substantially surpassing other single-stage models. Compared to two-stage models, it maintains a comparable performance level while significantly reducing the number of parameters and resolution. On the ISLES 2022 dataset, MSA-YOLOv5 attains an 80.0% mAP0.5, outperforming other network models by a considerable margin. MS-STPH and SOCA modules can significantly increase mAP0.5 by 2.7% and 1.9%, respectively. Visualization interpretability results show that the proposed MSA-YOLOv5 restricts high attention in the small regions of AIS lesions. CONCLUSIONS: The proposed MSA-YOLOv5 is capable of automatically and effectively detecting acute ischemic stroke lesions in multimodal images, particularly for small lesions and artifacts. Our enhanced model reduces the number of parameters while improving detection accuracy. This model can potentially assist radiologists in providing more accurate diagnosis, and enable clinicians to develop better treatment plans.

Disease Burden Evaluation of Injury and Poisoning in China from 2009 to 2019.

Background: We aimed to analyze the differences and changing trends of mortality of Injury and Poisoning (IP) between urban and rural areas and gender in China to find out the influencing factors and to propose improvement measures. Methods: IP mortality, population, economy, medical and health information data came from the official web-site of the National Bureau of Statistics, and basic data on education level came from the Chinese Ministry of Education. Then the differences of the mortality of IP were compared between different areas and gender in China from 2009 to 2019, and the relationships between the mortality changes of IP and education level, GDP per capita, the numbers of practicing physicians, health institutions and urbanization rate were also explored by establishing a ridge regression model. Results: The mortality of IP in rural areas was significantly higher than that of urban areas, and in male was higher than that of female (both P<0.001). Primary school graduates, GDP per capita, the number of practicing physicians, health institutions and urbanization rate had strong correlations (rmin=-0.622) with the mortality of IP. Ridge regression model showed that there was a quantitative relationship between primary school graduates, GDP per capita, the number of practising physicians, health institutions, urbanization rate and the mortality of IP in China. Conclusion: As the difference of working nature, economic development imbalance, psychological and gender, the mortality of IP was significantly different, so the state should take more effective measures to develop the urban and rural areas balanced, and reduce the IP risk in some particular occupations.

Semantically enabling clinical decision support recommendations.

BACKGROUND: Clinical decision support systems have been widely deployed to guide healthcare decisions on patient diagnosis, treatment choices, and patient management through evidence-based recommendations. These recommendations are typically derived from clinical practice guidelines created by clinical specialties or healthcare organizations. Although there have been many different technical approaches to encoding guideline recommendations into decision support systems, much of the previous work has not focused on enabling system generated recommendations through the formalization of changes in a guideline, the provenance of a recommendation, and applicability of the evidence. Prior work indicates that healthcare providers may not find that guideline-derived recommendations always meet their needs for reasons such as lack of relevance, transparency, time pressure, and applicability to their clinical practice. RESULTS: We introduce several semantic techniques that model diseases based on clinical practice guidelines, provenance of the guidelines, and the study cohorts they are based on to enhance the capabilities of clinical decision support systems. We have explored ways to enable clinical decision support systems with semantic technologies that can represent and link to details in related items from the scientific literature and quickly adapt to changing information from the guidelines, identifying gaps, and supporting personalized explanations. Previous semantics-driven clinical decision systems have limited support in all these aspects, and we present the ontologies and semantic web based software tools in three distinct areas that are unified using a standard set of ontologies and a custom-built knowledge graph framework: (i) guideline modeling to characterize diseases, (ii) guideline provenance to attach evidence to treatment decisions from authoritative sources, and (iii) study cohort modeling to identify relevant research publications for complicated patients. CONCLUSIONS: We have enhanced existing, evidence-based knowledge by developing ontologies and software that enables clinicians to conveniently access updates to and provenance of guidelines, as well as gather additional information from research studies applicable to their patients' unique circumstances. Our software solutions leverage many well-used existing biomedical ontologies and build upon decades of knowledge representation and reasoning work, leading to explainable results.

Study on the dynamic metabolic characteristic of main active ingredients in Danggui Buxue Decoction by liquid chromatography-tandem mass spectrometry based on in situ sequential metabolism strategy.

Danggui Buxue Decoction is a classic formula for replenishing qi and nourishing blood. Despite its widespread use, its dynamic metabolism involved remains unclear. Based on the sequential metabolism strategy, blood samples from different metabolic sites were obtained via in situ closed intestine ring integrated with a jugular venous continuous blood supply technique. An ultra-high-performance liquid chromatography-linear triple quadruple-Orbitrap-tandem mass spectrometry method was developed for the identification of prototypes and metabolites in rat plasma. The dynamic absorption and metabolic landscape of flavonoids, saponins, and phthalides were characterized. Flavonoids could be deglycosylated, deacetylated, demethylated, dehydroxylated, and glucuronicated in the gut and then absorbed for further metabolism. Jejunum is an important metabolic site for saponins biotransformation. Saponins that are substituted by Acetyl groups tend to lose their acetyl groups and convert to Astragaloside IV in the jejunum. Phthalides could be hydroxylated and glucuronidated in the gut and then absorbed for further metabolism. Seven components serve as crucial joints in the metabolic network and are potential candidates for the quality control of Danggui Buxue Decoction. The sequential metabolism strategy described in this study could be useful for characterizing the metabolic pathways of Chinese medicine and natural products in the digestive system.

Exceptional Electron-Rich Heteroaromatic Pentacycle for Ultralow Band Gap Conjugated Polymers and Photothermal Therapy.

Stable redox-active conjugated molecules with exceptional electron-donating abilities are key components for the design and synthesis of ultralow band gap conjugated polymers. While hallmark electron-rich examples such as pentacene derivatives have been thoroughly explored, their poor air stability has hampered their broad incorporation into conjugated polymers for practical applications. Herein, we describe the synthesis of the electron-rich, fused pentacyclic pyrazino[2,3-b:5,6-b']diindolizine (PDIz) motif and detail its optical and redox behavior. The PDIz ring system exhibits a lower oxidation potential and a reduced optical band gap than the isoelectronic pentacene while retaining greater air stability in both solution and the solid state. The enhanced stability and electron density, together with readily installed solubilizing groups and polymerization handles, allow for the use of the PDIz motif in the synthesis of a series of conjugated polymers with band gaps as small as 0.71 eV. The tunable absorbance throughout the biologically relevant near-infrared I and II regions enables the use of these PDIz-based polymers as efficient photothermal therapeutic reagents for laser ablation of cancer cells.

Characteristics, likelihood and challenges of road traffic injuries in China before COVID-19 and in the postpandemic era.

Through a review of previous studies, this paper analysed the epidemiological characteristics and attempts to determine the various trends of road traffic injuries (RTIs) in China before and after the coronavirus disease 2019 (COVID-19). This paper proposed effective measures and suggestions for responding to RTIs in China. Moreover, this paper aimed to provide some references for studies on RTIs in the future. According to a reference review, 50 articles related to RTIs were published and viewed in the China National Knowledge Infrastructure (CNKI), Wanfang database, Weipu (VIP) database and PubMed/MEDLINE database. Articles were selected according to the exclusion and inclusion criteria and then classified and summarized. Regarding cases, RTIs in China were highest in summer, autumn, and in rural areas and lowest in February. Men, elderly individuals and people living in rural areas were more susceptible to RTIs. In addition, thanks to effective and proactive policies and measures, the number of RTIs and casualties in China has substantially decreased, while there has been a growing number of traffic accidents along with the increase in nonmotor vehicles. However, it is worth noting that the number of RTIs obviously fell during the COVID-19 pandemic due to traffic lockdown orders and home quarantine policies. Nevertheless, accidents related to electric bicycles increased unsteadily because of the reduction in public transportation use at the same time. The factors that cause RTIs in China can be divided into four aspects: human behaviours, road conditions, vehicles and the environment. As a result, measures responding to RTIs should be accordingly proposed. Moreover, the road traffic safety situation in developing countries was more severe than that in developed countries. RTIs in China showed a downward trend attributed to road safety laws and various policies, and the downward trend was more significant during the COVID-19 pandemic owing to traffic lockdowns and home quarantine measures. It is urgent and necessary to promote road traffic safety, reduce injuries, and minimize the burden of injuries in developing countries.

Danggui Buxue Decoction: Comparative pharmacokinetic research on six bio-active components in different states by ultra-performance liquid chromatography-tandem mass spectrometry after oral administration.

Danggui Buxue Decoction is a classic formula containing Astragali Radix and Angelicae Sinensis Radix in a 5:1 ratio and has been extensively used to treat blood deficiency for thousands of years. The aim of the study was to investigate the differences in plasma protein binding, pharmacokinetics, and tissue distribution of Danggui Buxue Decoction in normal and blood-deficient rats by ultra-performance liquid chromatography-tandem mass spectrometry. The effects on peripheral blood routine were verified. The compounds exhibited higher plasma protein binding and absorption in the model group compared to the control group, except formononetin. The six ingredients were distributed widely, and the highest concentrations were detected in the heart and uterus. As has been demonstrated in the previous study of the effect of Danggui Buxue Decoction, its potential is to serve as an effective traditional Chinese medicine formula for treating cardiovascular diseases and impacting estrogenic properties, which reveals the potential target organs of Danggui Buxue Decoction the heart and uterus. Our findings suggested that the absorption and distribution of different components in Danggui Buxue Decoction varies depending on the pathological state, molecular weight, lipid solubility, transporter-mediated efflux, and other factors.

Neurobiochemical biomarkers and other risk factors for post-traumatic acute stress disorder.

Trauma is a leading cause of mortality and morbidity around the world and many trauma patients could suffer from a series of cognitive and mental disorders including acute stress disorder (ASD). Yet, little research has been done to investigate the influencing factors and pathogenesis of post-traumatic ASD. Therefore, this study investigated main influencing factors and neurobiochemical biomarkers of ASD in trauma patients with a purpose of early clinical identification and intervention. The patients were followed up by general questionnaire and Acute Stress Disorder scale (ASDS). Using the diagnostic criteria of ASD, the study participants were divided into ASD group and non-ASD group. The generalized estimating equation (GEE) multivariate analysis suggested that life stress, sleep less than 8 h, trauma from road traffic crash, overall pain intensity, injury severity, overall fear after trauma were risk factors for ASD. Neutrophil to lymphocyte ratio (NLR) showed a downward trend in both groups (P < 0.05), and the ASD group was higher than the non-ASD group (P = 0.015). Glu to GABA ratio (GGR) in the ASD group were higher than the non-ASD group (P < 0.001). Both patient demographics and patient's condition could impact the risk of developing ASD after a major injury.

Interventional effect of processing temperature on anti-angiogenesis of Coptis chinensis and screening of active components by UPLC-MS/MS on quail chick chorioallantoic membrane model.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch. (CC), as a commonly used heat-clearing and toxin-resolving traditional Chinese herbal medicine, has gained increased attention for its anti-tumor activity. However, little is known about the anti-tumor angiogenesis effect of CC and its possible bioactive components. Also, it has been shown that temperature affects the quality of CC, albeit whether and how it affects the anti-angiogenic activity of CC is currently unknown. AIM OF THE STUDY: To determine the processing temperatures (40, 60, 80, 120, 140, 150, 160 and 200 °C) at which CC has the strongest anti-angiogenic effect and speculate the possible bioactive components. MATERIALS AND METHODS: The q-CAM model was constructed to explore the anti-angiogenesis agents of CC. The angiogenesis inhibition effects of CC samples at different processing temperatures and its seven alkaloids were determined based on morphological observation and vascular area proportion analysis. UPLC-MS/MS was employed to screen the potent active components of CC on anti-angiogenesis. RESULTS: All the intervention by CC at different processing temperatures and its seven alkaloids could inhibit angiogenesis on q-CAM vessels, as evidenced by a poor vasular development in morphological observation and a low vascular area proportion in vascular quantitative analysis, most evident in CC processed at 40 °C and palmatine. LC-MS revealed that palmatine displayed strongest inhibitory effect on q-CAM vessels with a high absorption due to its stable structure. And the maternal nucleus transformation phenomenon of CC alkaloids was found in the quail embryo metabolism. CONCLUSIONS: The q-CAM models in conjunction with the UPLC-MS/MS technique could be a useful tool for assessing tumor angiogenesis and screening tumor-targeted medicines. Processing temperature can affect the anti-angiogenesis effect of CC because of its function on the content of alkaloids, and palmatine can be considered as a prospective anti-angiogenic drug.

Planning and Monitoring Equitable Clinical Trial Enrollment Using Goal Programming.

Randomized clinical trial (RCT) studies are the gold standard for scientific evidence on treatment benefits to patients. RCT outcomes may not be generalizable to clinical practice if the trial population is not representative of the patients for which the treatment is intended. Specifically, enrollment plans may not adequately include groups of patients with protected attributes, such as gender, race, or ethnicity. Inequities in RCTs are a major concern for funding agencies such as the National Institutes of Health (NIH) and for policy makers. We address this challenge by proposing a goal-programming approach, explicitly integrating measurable enrollment goals, to design equitable enrollment plans for RCTs. We evaluate our model in both single and multisite settings using the enrollment criteria and study population from the Systolic Blood Pressure Intervention Trial (SPRINT) study. Our model can successfully generate equitable enrollment plans that satisfy multiple goals such as sample representativeness and minimum total financial cost. Our model can detect deviations from a target plan during the enrollment process and update the plan to reduce deviations in the remaining process. Finally, through appropriate site selection in the planning stage, the model can demonstrate the possibility of enrolling a nationally representative study population if geographic constraints exist in multisite recruitment (e.g., clinical centers in a particular region). Our model can be used to prospectively produce and retrospectively evaluate how equitable enrollment plans are based on subjects' protected attributes, and it allows researchers to provide justifications on validity of scientific analysis and evaluation of subgroup disparities.

ESTIMATION OF FETAL AND PEDIATRIC DOSES FROM CHEST CT EXAMINATIONS USING VIRTUALDOSE SOFTWARE.

Pregnant women and children sometimes had to undergo chest computed tomography (CT) scans during the Corona Virus Disease 2019 (COVID-19) pandemic. This study estimated the fetal and pediatric doses from chest CT scans. Organ doses and effective doses were calculated using the VirtualDose-CT software. Two groups of computational human phantoms, pregnant females and pediatric patients were used in this study. The results of doses normalized to volumetric CT Dose Index (CTDIvol) can be used universally for other dosimetry studies. Based on our calculations and international survey data of CTDIvol, fetal absorbed doses from COVID-19-related chest CT were found to be 0.04-0.36, 0.05-0.44 and 0.07-0.61 mGy for 3, 6 and 9 months of pregnancy, respectively. When the scan range is extended to the abdominal region, fetal doses increase by almost 4-fold. Effective doses for COVID-19-related chest CT were 1.62-13.77, 1.58-13.46, 1.57-13.33 and 1.29-10.98 mSv for the newborn, 1-, 5- and 10-y-old children, respectively. In addition, the effects of specific axial scan ranges exceeding the thorax region were evaluated. Although doses from chest CT scans are small, such data allow radiologists and patients to be informed of the dose levels and ways to avoid unnecessary radiation.

Charge Transfer in Spatially Defined Organic Radical Polymers.

Charge transfer in nonconjugated redox-active polymers is influenced by redox site proximity and polymer flexibility, but it is challenging to observe these effects independently. In this work, spatially defined radical-containing polymers are synthesized by using acyclic diene metathesis (ADMET) polymerization of α,ω-dienes bearing a central activated ester. Postpolymerization functionalization with 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO) introduces TEMPO radical groups onto the polymer backbone through amide linkages to yield spatially defined polymers with radical units every 9, 11, 15, and 21 carbons. Increased radical spacing leads to reduced spin-spin coupling and increased chain flexibility. The glass transition temperatures (Tg) range from 47.6 to -13.8 °C, depending on the radical spacing. The spatially defined TEMPO-substituted polymer with a spacing length of 15 carbons displays the lowest Tg and the shortest hopping distance, as shown through molecular dynamics simulations. Also, this polymer displays kinetics 1000 times faster than the commonly studied TEMPO-containing polymer poly(2,2,6,6-tetramethylpiperidinyloxy-4-ylacrylamide) (PTAm). Remarkably, comparison of the diffusion and kinetics attributed to the redox reaction reveals that both the apparent diffusion coefficient and the self-exchange reaction rate constant are correlated to the polymer's Tg as log[Dapp] and log[kex,app] ∼ Tg, respectively. Critically, these data demonstrate that controlling the spacing of redox-active groups along a polymer backbone strongly influences backbone flexibility and radical packing, which leads to synergetic improvements in the charge transfer kinetics of nonconjugated redox-active polymers.

Real-world study of antiresorptive-related osteonecrosis of jaw based on the US food and drug administration adverse event reporting system database.

Objective: This study aims to explore the risk signals of osteonecrosis of the jaw induced by antiresorptive drugs and provide references for the clinical safety application. Method: According to the FDA's Adverse Event Reporting System (FAERS), from January 2004 to September 2021, we chose "Osteonecrosis of the jaw (10064658)" and "Exposed bone in jaw (10071014)" as preferred terms, "antiresorptive drugs" as the target drugs, and primary suspect drug as the drug role code in the dataset. We evaluated the association between drugs and adverse events by using reporting odds ratio (ROR) based on disproportionality analysis. We took the High-Level Terms (HLT) of MedDRA® as the classification level of indications to calculate ROR to compare the signal difference of ONJ in different indications. In addition, patients with antiresorptive-induced osteonecrosis of the jaw and the time of onset of the condition following different antiresorptive medications were collected for the study. Results: The FAERS contained 18,421 reports relating to jaw osteonecrosis from January 2004 to September 2021. A total of eight antiresorptive agents were included in the analysis. From high to low, the ROR of ONJ induced by antiresorptive agents (regardless of indication) is pamidronate (ROR = 494.8), zoledronic acid (ROR = 431.9), denosumab (ROR = 194.8), alendronate (ROR = 151.2), risedronate (ROR = 140.2), etidronic acid (ROR = 64.5), ibandronate (ROR = 40.8), and romosozumab (ROR = 6.4). HLT ROR values for "metabolic bone disorders" were the lowest for each drug, while HLT ROR values were high for "tumor-related indications," including breast and nipple neoplasms malignant, plasma cell myelomas, and prostatic neoplasms malignant. The onset time for osteonecrosis of the jaw as median (Q1, Q3), osteoporosis-related indications, and the onset time for ONJ were 730 (368, 1268), 489.5 (236.3, 909.8), 722.5 (314, 1055), 761 (368, 1720), and 153 (50, 346) for zoledronic acid, denosumab, ibandronate, risedronate, and romosozumab, respectively. Cancer-related indications: the onset time for ONJ were 680.5 (255.3, 1283), 488 (245, 851), and 696.5 (347, 1087) for zoledronic acid, denosumab, and pamidronate, respectively. Conclusion: When antiresorptive drugs are used for metastasis, they have the largest risk signal, followed by malignancy, and the smallest is osteoporosis. The onset time of ONJ may not be related to the indications. The onset time of ONJ for BPs was about 2 years, denosumab about 1.3 years, and romosozumab less than 1 year, which may be related to sequential treatment. When used according to the instructions, the risk of ONJ caused by denosumab was higher than that of zoledronic acid, regardless of the indication. Based on these findings, researchers will continue to monitor and identify risk factors.

Cold Atmospheric Plasma Suppressed MM In Vivo Engraftment by Increasing ROS and Inhibiting the Notch Signaling Pathway.

Multiple myeloma (MM) is the second most common hematologic malignancy. MM stem cells (MMSCs) are thought to be the main causes of in vivo engraftment and eventual recurrence. As a notable new technology, cold atmospheric plasmas (CAPs) show a promising anti-tumor effect, due to their production of various ROS. In this study, we found that different types of plasma could inhibit MM's ability to form cell colonies, suppress MM in vivo engraftment, and extend survival times. We demonstrated that NAC (a ROS scavenger) could block ROS increases and reverse the inhibition of MM's cell-colony-formation ability, which was induced by the plasma treatment. By using a stem cell signaling array, we found that the Notch pathway was inhibited by the plasma treatment; this was further confirmed by conducting real-time PCRs of three MM cell lines. Together, these results constitute the first report of plasma treatment inhibiting MM in vivo engraftment and prolonging survival time by suppressing the Notch pathway via ROS regulation.