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Background: Treating postherpetic neuralgia (PHN), which is characterized with a long‐lasting lancinating mechanical allodynia or hyperalgesia, is a big challenge as it is hard to achieve complete resolution. A synthetic triterpenoid, CDDO (2‐cyano‐3,12‐dioxoolean‐1,9‐dien‐28‐oic acid) can exert pleiotropic effects including anti‐inflammation and neuroprotective activities. Nevertheless, the antinociceptive effect of CDDO and its derivatives remains unknown. Resiniferatoxin (RTX) is easily feasible, and an RTX‐treated rodent model can mimic the PHN‐like symptoms. Therefore, RTX‐treated rats were used to serve as a PHN rats' model in the study to elucidate whether a synthetic triterpenoid, CDDO, can improve mechanical allodynia in RTX‐treated rats. Methods: The antinociceptive effects of CDDO were assessed by behavioral tests, western blotting, and immunohistochemistry. Paw withdrawal mechanical threshold was determined using calibrated forceps. Results: Administration of RTX led to mechanical allodynia, neuronal cell death, and glial cell activation in the spinal cord of RTX‐treated rats. A synthetic triterpenoid, CDDO, blocked RTX‐induced mechanical allodynia, rescued neuronal cell death, and inhibited glial cell activation in the spinal cord of RTX‐treated rats. Conclusions: Our study provides a novel result that a synthetic triterpenoid, CDDO, can interfere neuronal cell death and glial cell activation in the spinal cord of RTX‐treated rats. Hence, CDDO is an alternative therapeutic choice for PHN. [ABSTRACT FROM AUTHOR]

Green finance and investment in renewable energy (RE) sources are two of the most important climate change strategies that might have a long-term impact. Micro- and macro-level data from 2010 to 2021 in China used to gain a new analysis of the impact of green finance, inflationary pressures, and geopolitical risk in improving sustainability. Regression estimation methods were used to tackle this while considering direct and indirect associations between the parameter estimates. According to recent research, environmental taxes, such as those on carbon emissions, have been shown to have a large and favorable effect on profitability in RES. The volatility of oil prices and geopolitical risk, on the other hand, has a negative influence on the investment pattern for sustainable energy sources in China. The research also shows that green rules have a significant role in reducing the impact of green finance on RE production. Green companies in China should be pushed so that RE investments are regarded as a long-term strategy, according to the conclusions of the research. The study's theoretically, and empirically conclusions have supplied policymakers and environmentalists with useful information for developing and implementing environmental initiatives with long-term financial benefits. • This study focused solely on the economic and environmental consequences of renewable energy sector in China. • Green rules have a tempering effect while enhancing the association between green finance and renewable energy expenditure. • Renewable energy greatly benefits from green funding. [ABSTRACT FROM AUTHOR]

Chronic pain is a universal public health problem with nearly one third of global human involved, which causes significant distressing personal burden. After painful stimulus, neurobiological changes occur not only in peripheral nervous system but also in central nervous system where somatosensory cortex is important for nociception. Being an ion channel, transient receptor potential vanilloid 1 (TRPV1) act as an inflammatory detector in the brain. Thymic stromal lymphopoietin (TSLP) is a potent neuroinflammation mediator after nerve injury. Bleomycin is applied to treat dermatologic diseases, and its administration elicits local painful sensation. However, whether bleomycin administration can cause chronic pain remains unknown. In the present study, we aimed to investigate how mice develop chronic pain after receiving repeated bleomycin administration. In addition, the relevant neurobiological brain changes after noxious stimuli were clarified. C57BL/6 mice aged five- to six-weeks were randomly classified into two group, PBS (normal) group and bleomycin group which bleomycin was intradermally administered to back five times a week over a three-week period. Calibrated forceps testing was used to measure mouse pain threshold. Western blots were used to assess neuroinflammatory response; immunofluorescence assay was used to measure the status of neuron apoptosis, glial reaction, and neuro-glial communication. Bleomycin administration induced mechanical nociception and activated both TRPV1 and TSLP/TSLPR/pSTAT5 signals in mouse somatosensory cortex. Through these pathways, bleomycin not only activates glial reaction but also causes neuronal apoptosis. TRPV1 and TSLP/TSLPR/pSTAT5 signaling had co-labeled each other by immunofluorescence assay. Taken together, our study provides a new chronic pain model by repeated intradermal bleomycin injection by activating TRPV1 and glial reaction-mediated neuroinflammation via TSLP/TSLPR/pSTAT5 signals. • Bleomycin triggers chronic mechanical nociception by enhancing TRPV1 channels in somatosensory cortex. • Bleomycin triggers chronic mechanical nociception by regulating TSLP/TSLPR/pSTAT5 signals. • TRPV1 interacts with TSLP/TSLPR/pSTAT5 signals to activate glial reaction-mediated neuroinflammation. [ABSTRACT FROM AUTHOR]

Background: Patients who have Parkinson's disease (PD) comorbid with dementia is common. With the prolonged life expectancy, dementia is gradually becoming prevalent and affects most patients' life qualities. However, the efficacy of current treatments in dementia of PD is limited. Previous studies indicated the potential roles of Chinese herbal medicine (CHM) in treating dementia, yet the correlation between CHM usage and risk of dementia in PD patients is unclear. Methods: This case–control study was nested within a National Health Insurance database of patients over 50 years with newly diagnosed PD from year 2000 to 2010. Among these PD patients, dementia and nondementia groups were discussed, respectively, in terms of the duration of taking CHM (≥90 vs. <90 days), age (50–64 vs. ≥65 years) and gender. Results: The risk of dementia in patients with PD is lower in CHM users compared with non-CHM users, especially in those taking CHM for more than 90 days (adjusted odds ratio [aOR] 0.58; 95% confidence interval [95% CI] 0.39–0.87). The use of CHM was significantly related to the lower risk of dementia in the subgroups of patients with age ≥65 years for CHM usage <90 days (aOR 0.68; 95% CI 0.53–0.88), patients with age ≥65 years for CHM usage ≥90 days (aOR 0.63; 95% CI 0.42–0.94), female patients using CHM for ≥90 days (aOR 0.43; 95% CI 0.22–0.84), and male patients using CHM for <90 days (aOR 0.62; 95% CI 0.43–0.88). Conclusions: The authors demonstrated the association of CHM usage with lower risk of dementia in patients with PD, especially in women with the usage of CHM for more than 90 days. Since no arbitrary causal conclusions could be drawn from retrospective cohort studies, the finding in this study could be used to generate a hypothesis for a subsequent design of prospective longitudinal study. [ABSTRACT FROM AUTHOR]

With great interest, we read a retrospective cohort study from Zhu I et al i .[1] investigating the relationship between bone mineral density (BMD) level and stroke risk. Since all causes of stroke were combined into one outcome variable of interest in this study, the relationship between BMD values and stroke types is unclear. [Extracted from the article]

Abstract: Embedded-type surface electrodes with silver nanowire (AgNW) and carbon nanotube (CNT) as conductive fillers and organosoluble polyimide (PI) as a matrix were investigated for their electrical conductivity and electrical durability under cyclic bending. The chosen polyimide was constituted with 4,4′-oxydiphthalic dianhydride and 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane through a one-step process. Two types of surface electrodes of CNT/PI and AgNW/PI were prepared at 90°C. The flexible CNT/PI and AgNW/PI surface electrodes not only had high electrical conductivities of 6.3 and 100S/cm, respectively, after 30 spraying cycles but also kept electrical durability after 1200-time bending tests. The ITO-coated ITO/PI and ITO/AgNW/PI electrodes, for a comparative purpose, had severe electrical failure under cyclic bending. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver and is among the top three causes of cancer-associated death worldwide. However, the clinical use of chemotherapy for HCC has been limited by various challenges, emphasizing the urgent need for novel agents with improved anticancer properties. We recently synthesized and characterized a series of 4,11-diaminoanthra[2,3-b]furan-5,10-dione derivatives that exhibit potent apoptotic activity against an array of cancer cell lines, including variants with multidrug resistance. Their effect on liver cancer cells, however, was unknown. Here, we investigated three selected 4,11-diaminoanthra[2,3-b]furan-5,10-dione derivatives (compounds 1–3) for their cytotoxicity and the underlying molecular mechanisms in wild-type or p53-deficient HCC cells. Cytotoxicity was determined by WST-1 assays and cell impedance measurements and apoptosis was analyzed by flow cytometry. The interaction between compounds and tumor-associated NADH oxidase (tNOX, ENOX2) was studied by cellular thermal shift assay (CETSA). We found that compound 1 and 2 induced significant cytotoxicity in both HepG2 and Hep3B lines. CETSA revealed that compounds 1 and 2 directly engaged with tNOX, leading to a decrease in the cellular NAD+/NADH ratio. This decreased the NAD+-dependent activity of Sirtuin 1 (SIRT1) deacetylase. In p53-wild-type HepG2 cells, p53 acetylation/activation was enhanced, possibly due to the reduction in SIRT1 activity, and apoptosis was observed. In p53-deficient Hep3B cells, the reduction in SIRT1 activity increased the acetylation of c-Myc, thereby reactivating the TRAIL pathway and, ultimately leading to apoptosis. These compounds thus trigger apoptosis in both cell types, but via different pathways. Taken together, our data show that derivatives 1 and 2 of 4,11-diaminoanthra[2,3-b]furan-5,10-diones engage with tNOX and inhibit its oxidase activity. This results in cytotoxicity via apoptosis through tNOX-SIRT1 axis to enhance the acetylation of p53 or c-Myc in HCC cells, depending on their p53 status. [ABSTRACT FROM AUTHOR]

Chemical modifications of the anthraquinone scaffold are aimed at optimization of this exceptionally productive class of antitumor drugs. In particular, our previously reported anthra[2,3- b ]furan-3-carboxamides demonstrated a high cytotoxic potency in cell culture and in vivo. In this study, we expanded our series of anthra[2,3- b ]furan-3-carboxamides by modifying the key functional groups and dissected the structure-activity relationship within this chemotype. The majority of new compounds inhibited the growth of mammalian tumor cell lines at submicromolar to low micromolar concentrations. We found that 4,11-hydroxy groups as well as the carbonyl moiety in the carboxamide fragment were critical for cytotoxicity whereas the substituent at the 2-position of anthra[2,3- b ]furan was not. Importantly, the new derivatives were similarly potent against wild type cells and their variants resistant to doxorubicin due to P-glycoprotein (Pgp) expression or p53 inactivation. The most cytotoxic derivatives 6 and 9 attenuated plasmid DNA relaxation by topoisomerase 1. Finally, we demonstrated that 6 and 9  at 1 μM induced intracellular oxidative stress, accumulation in G2/M phase of the cell cycle, and apoptosis in gastric carcinoma cell lines regardless of their p53 status. These results further substantiate the potential of anthra[2,3- b ]furan-3-carboxamides as antitumor drug candidates. [ABSTRACT FROM AUTHOR]

Background: Platinum resistance enhances DNA damage repair through nucleotide excision repair mechanisms involving the excision repair cross-complementing group 1 ( ERCC1), X-ray cross-complementing group 1 ( XRCC1), and excision repair cross-complementing group 2 ( ERCC2). We evaluated the correlation between the expression of these three DNA repair genes and clinical outcomes in patients with rectal cancer receiving FOLFOX-based preoperative chemoradiotherapy (CRT). Methods: Using immunohistochemistry, we examined the expression of ERCC1, ERCC2, and XRCC1 in pre-CRT cancer tissues from 86 patients with rectal cancer who had undergone curative resection and preoperative CRT with FOLFOX-4 to identify potential predictors of clinical outcomes. Results: Following CRT, 57 and 29 patients were classified as responders (pathological tumor regression grade TRG 0 and TRG 1) and poor responders (TRG 2 and TRG 3), respectively. The multivariate analysis revealed that ERCC1 overexpression was correlated with a poor CRT response [ p < 0.0001; odds ratio (OR), 9.397; 95% confidence interval (CI) 2.721-32.457]. Furthermore, a poor response to CRT (pathological TRG of 2-3) ( p = 0.18; OR 5.685; 95% CI 1.349-23.954) and abnormal pre-CRT serum carcinoembryonic antigen levels (>5 ng/mL) ( p = 0.03; OR 6.288; 95% CI 1.198-33.006) were independent predictors of postoperative relapse. By contrast, ERCC2 and XRCC1 expression did not play predictive roles in the analyzed patients. Conclusions: ERCC1 overexpression is associated with a poor preoperative CRT response in patients with rectal cancer receiving FOLFOX-based preoperative CRT. ERCC1 is a potential biomarker for identifying patients who can benefit from customized treatment programs. [ABSTRACT FROM AUTHOR]

This case is described of an eleven-month-old infant with lower limbs swelling and the left elbow skeletal malformation following a fall. The radionuclide bone scan was performed to exclude bone infection or congenital skeletal anomaly. The images unexpectedly showed multiple increased radioactive foci throughout the whole body. It was a strong probability of child abuse. All lesions are readily apparent on the following plain film radiographs and MRI. [ABSTRACT FROM AUTHOR]

The microenvironment of neuron cells plays a crucial role in regulating neural development and regeneration. Hyaluronic acid (HA) biomaterial has been applied in a wide range of medical and biological fields and plays important roles in neural regeneration. PC12 cells have been reported to be capable of endogenous NGF synthesis and secretion. The purpose of this research was to assess the effect of HA biomaterial combining with PC12 cells conditioned media (PC12 CM) in neural regeneration. Using SH-SY5Y cells as an experimental model, we found that supporting with PC12 CM enhanced HA function in SH-SY5Y cell proliferation and adhesion. Through RP-nano-UPLC-ESI-MS/MS analyses, we identified increased expression of HSP60 and RanBP2 in SH-SY5Y cells grown on HA-modified surface with cotreatment of PC12 CM. Moreover, we also identified factors that were secreted from PC12 cells and may promote SH-SY5Y cell proliferation and adhesion. Here, we proposed a biomaterial surface enriched with neurotrophic factors for nerve regeneration application. [ABSTRACT FROM AUTHOR]

Abstract: Background: The thyroid hormone, thyroxine (T4), is a tyrosine-based hormone produced by the thyroid gland, which is essential in regulating a number of biological processes, including growth, neurodevelopment, carbohydrate metabolism, oxygen consumption and protein synthesis. Data on human thyroid hormone metabolism were gathered since the middle of the 1970s mainly by the use of radioactive iodinated (125I or 131I) hormones. Methods: We describe an isotope dilution-matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) method for the simultaneous determination of endogenous thyroid hormone and its 13C6-labeled analogue in serum. The 13C6-thyroxine (13C6-T4) was used as an internal standard; T4 and its isotopically labeled analogue were measured in the selected reaction monitoring mode for the transitions from m/z 777.8 to 732.1 and from m/z 784.2 to 738.1, respectively. Results: Serum samples were prepared and concentrated by a solid-phase extraction chromatography method. The recovery rate was measured by 125I-T4 and can be up to 82.8±2.8%. The detection limit and linear range for T4 were 5ng/ml and 5–400ng/ml, respectively. The correlation coefficient (R2) between radioimmunoassay (RIA) and isotope dilution-MALDI-TOF MS for detection of serum T4 was 0.982. Conclusion: This assay has a good relationship against a commercial RIA and the isotope dilution-mass spectrometry method and may serve as a reference method for quantitative analysis of T4. [Copyright &y& Elsevier]

This study aimed to investigate the diagnostic performance of semi-quantitative parameters of thallium-201 myocardial perfusion imaging (MPI) for coronary artery disease (CAD). From January to December 2017, patients were enrolled who had undergone Tl-201 MPI and received cardiac catheterization for coronary artery disease within three months of MPI. Receiver operating characteristics (ROC) analysis was used to determine the optimal cutoff values of semi-quantitative parameters. A comparison of the sensitivity and specificity of these parameters based on different subgroupings was further performed. A total of 130 patients were enrolled for further analysis. Among the collected parameters, the stress total perfusion deficit (sTPD) had the highest value of the area under curve (0.813) under the optimal cutoff value of 3.5%, with a sensitivity and specificity of 73.5% and 74.5%, respectively (p = 0.0000), for the diagnosis of CAD. With further subgrouping analysis based on history of diabetes or dyslipidemia, the sensitivity and specificity showed similar results. Based on the currently collected data and image acquisition conditions, the sTPD parameter has a clinical role for the diagnosis of CAD with a cutoff value of 3.5%. [ABSTRACT FROM AUTHOR]