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Abstract Background Pre-hospital delay in China is a serious issue with unclear relevant reasons, seriously impeding the adoption of appropriate measures. Herein, we analyzed the onset-to-door time (ODT) in Chinese patients with acute ischemic stroke (AIS) and its influencing factors. Methods We prospectively recruited 3,459 patients with AIS from nine representative tertiary general hospitals in China between January and June 2022. Patients were divided into ODT ≤ 3 h and ODT > 3 h groups. Following single-factor analysis, binary logistic regression analysis was performed to evaluate the risk factors leading to pre-hospital delay. Results In total, 763 (21.83%) patients arrived at the hospital within 3 h of onset. After adjusting for confounding factors, the risk factors for ODT were residence in rural areas (odds ratio [OR]: 1.478, 95% credibility interval [CI]: 1.024–2.146) and hospital transfer (OR: 7.479, 95% CI: 2.548–32.337). The protective factors for ODT were location of onset ≤ 20 km from the first-visit hospital (OR: 0.355, 95% CI: 0.236–0.530), transportation by emergency medical services (OR: 0.346, 95% CI: 0.216–0.555), history of atrial fibrillation (OR: 0.375, 95% CI: 0.207–0.679), moderate stroke (OR: 0.644, 95% CI: 0.462–0.901), and severe stroke (OR: 0.506, 95% CI: 0.285–0.908). Conclusions Most patients with AIS fail to reach a hospital within the critical 3-h window. The following measures are recommended to reduce pre-hospital delays: reasonable distribution of hospitals accessible to nearby residents, minimizing interhospital transfer, paying attention to patients with mild stroke, and encouraging patients to use ambulance services. Pre-hospital delays for patients can be reduced by implementing these measures, ultimately improving the timeliness of treatment and enhancing patient prognosis. This study was carried out amid the COVID-19 pandemic, which presented challenges and constraints.

Abstract: Climate change induced extreme weather events will increase in intensity and frequency, leading to longer and widespread electricity outages. As an example, Winter Storm Uri in Texas left over 4.5 million customers without power between 14 and 18 February 2021. The social justice consequences of these events remain an outstanding question, as outage data are, typically, only available at the county level, obscuring detailed experiences. We produce a first-of-its-kind unique spatially resolved dataset of interruptions using satellite data on nighttime lights to track blackouts at the census block group (CBG) level. Correlating this dataset with demographic data reveals that minority CBGs were 1.5–3 times more likely to suffer from interruptions compared to predominantly white CBGs, whereas income status was positively correlated with the likelihood of interruption. The presence of critical facilities—including police and fire stations, hospitals, and water treatment facilities—in a CBG reduced the chances of interruptions by around 16 % , a small difference that does not otherwise explain the disparity among communities. We suggest explanations, test a subset of them, and propose further work needed to explain what drives these disparities.

Abstract Fibroblast growth factors (FGFs) control various cellular functions through fibroblast growth factor receptor (FGFR) activation, including proliferation, differentiation, migration, and survival. FGFR amplification in ER + breast cancer patients correlate with poor prognosis, and FGFR inhibitors are currently being tested in clinical trials. By comparing three-dimensional spheroid growth of ER + breast cancer cells with and without FGFR1 amplification, our research discovered that FGF2 treatment can paradoxically decrease proliferation in cells with FGFR1 amplification or overexpression. In contrast, FGF2 treatment in cells without FGFR1 amplification promotes classical FGFR proliferative signaling through the MAPK cascade. The growth inhibitory effect of FGF2 in FGFR1 amplified cells aligned with an increase in p21, a cell cycle inhibitor that hinders the G1 to S phase transition in the cell cycle. Additionally, FGF2 addition in FGFR1 amplified cells activated JAK-STAT signaling and promoted a stem cell-like state. FGF2-induced paradoxical effects were reversed by inhibiting p21 or the JAK-STAT pathway and with pan-FGFR inhibitors. Analysis of patient ER + breast tumor transcriptomes from the TCGA and METABRIC datasets demonstrated a strong positive association between expression of FGF2 and stemness signatures, which was further enhanced in tumors with high FGFR1 expression. Overall, our findings reveal a divergence in FGFR signaling, transitioning from a proliferative to stemness state driven by activation of JAK-STAT signaling and modulation of p21 levels. Activation of these divergent signaling pathways in FGFR amplified cancer cells and paradoxical growth effects highlight a challenge in the use of FGFR inhibitors in cancer treatment.

Radiative cooling coatings are widely used owing to their excellent cooling performance and energy efficiency. However, there is a lack of comprehensive research on their weather resistance, long-term performance and effects on building load. To fill this research gap, seven coatings were selected for experimental observation and simulation research. The results revealed noticeable differences among different coatings regarding anti-aging properties, cooling performance and building load reduction. Some coatings exhibited yellowing, cracking and peeling after weathering tests, accompanied by a decline in their radiative properties. Long-term tests showed that the cooling performance of all coatings gradually decreased due to natural aging, and the rate of decline was proportional to the weathering of the coatings. Building load simulations revealed the potential effect of coating selection on cooling and heating loads, thereby suggesting that different coatings should be selected based on actual usage scenarios in different climatic zones.

ContextThe coexistence of hypertension and elevated homocysteine (Hcy) levels has a mutually reinforcing impact on the susceptibility to cardio-cerebrovascular disease.ObjectiveThe aim was to assess the prevalence, clinical correlation, and demographic characteristics of hyperhomocysteinemia (HHcy) within the Chinese urban population with hypertension.MethodsA cohort of 473 individuals with hypertension were selected from four communities in Shenzhen, China. Demographic attributes, clinical profiles, and lifestyle behaviors were gathered and compared between individuals with and without HHcy. A logistic regression model was employed to examine potential factors associated with the prevalence of HHcy. Correlation between Hcy levels and clinical characteristics was assessed through multiple linear regression analysis.ResultsThe prevalence of HHcy in the population with hypertension was 31.3%. In comparison to individuals without HHcy, those with HHcy exhibited a higher proportion of males, a higher prevalence of smoking and alcohol consumption, and a higher proportion of cases with the homozygous (TT) genotype at the MTHFR C677T polymorphism. Moreover, individuals with HHcy had lower levels of folic acid (FA), and lower fruit and vitamin B12 intake. Furthermore, the risk factors for HHcy were male (B = 1.430, OR = 4.179) and MTHFR (TT) (B = 1.086, OR = 2.961). In addition, the multiple linear regression analysis revealed a significant association between Hcy levels and gender (B = -2.784, P = 0.004), MTHFR genotypes (B = 1.410, P = 0.005), and FA levels (B = -0.136, P = 0.030).ConclusionThe high prevalence of HHcy among hypertensive patients in this Chinese urban population underscores the necessity for interventions targeting modifiable risk factors such as dietary choices and lifestyle practices.

The authors make the following additions and corrections to the paper, C. Baiz et al., Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction. Chem. Rev. 2020, 120, 7152?7218. 1. The below funding sources should be added to the Acknowledgments section on pages 7204 and 7205: NHG acknowledges support from the National Science Foundation (CHE-1905395). AT thanks the Advanced Materials for Energy-Water Systems (AMEWS) Center (DE-AC02-06CH11357) for support. Thus, the Acknowledgments should be as follows: This work was supported by IBS-R023-D1 (MC). BB wishes to thank the European Union’s Horizon 2020 under the Marie Sk?odowska-Curie Grant Agreement No. 665778, as well as the National Science Centre, Poland (grant no. 2016/23/P/ST4/01720). CRB acknowledges generous support from the National Science Foundation (CHE-847199, BIO-1815354 ) , the National Ins t i t u tes o f Hea l t h (R35GM133359), and the Welch Foundation (F-1891). NHG acknowledges support from the National Science Foundation (CHE-1905395). MWDH-H and JDH thank the University of Nottingham, Green Chemicals Beacon for funding toward this research. AT thanks the Advanced Materials for Energy-Water Systems (AMEWS) Center (DEAC02-06CH11357) for support. MCT acknowledges support from Department of Energy (DE-SC0018983), National Science Foundation (1552996), and National Institutes of Health (GM114500). AGD would like to thank Prof. Andrei Tokmakoff for discussing amide modes when he was a Ph.D. student. LW acknowledges the support from the National Institutes of Health through Award R01GM130697. SAC acknowledges support from National Science Foundation (CHE-1565471). 2. The affiliations of Minhaeng Cho and Kijeong Kwak on page 7201 should be corrected as follows: Minhaeng Cho ? Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science (IBS), Seoul 02841, Republic of Korea; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea Kijeong Kwac ? Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science (IBS), Seoul 02841, Republic of Korea 3. Reference 329 on page 7214 should be replaced with the following paper: (329) Sul, S; Karaiskaj, D.; Jiang Y.; Ge, N.-H. Conformations of N-Acetyl-L-Prolinamide by Two-Dimensional Infrared Spectroscopy. J. Phys. Chem. B 2006, 110, 19891?19905. 4. A correction in the biography of Magnus Hanson-Heine on page 7203 should be made. MH-H received his Ph.D. in 2014, not 2010.

Abstract Background Atypical teratoid rhabdoid tumor (AT/RT) occurs at a younger age and is associated with a worse prognosis than medulloblastoma; however, these two tumor entities are mostly indistinguishable on neuroimaging. The aim of our study was to differentiate AT/RT and medulloblastoma based on their clinical and MRI features to enhance treatment planning and outcome prediction. Methods From 2005–2021, we retrospectively enrolled 16 patients with histopathologically diagnosed AT/RT and 57 patients with medulloblastoma at our institute. We evaluated their clinical data and MRI findings, including lesion signals, intratumoral morphologies, and peritumoral/distal involvement. Results The age of children with AT/RT was younger than that of children with medulloblastoma (2.8 ± 4.9 [0–17] vs. 6.5 ± 4.0 [0–18], p

Histamine modulates immunity by binding to histamine receptor 2 (H2R). Cimetidine, an H2R antagonist that inhibits gastric acid secretion and treats gastrointestinal ulcers, interferes with histamine-mediated immunomodulation and may have anticancer activity. This study examined cimetidine’s effect on the anticancer effect of anti-PD-L1 in colon cancer. The MTT assay, colony formation assay, and DNA histograms assessed cell viability, clonogenicity, and cell cycle distribution, respectively. Flow cytometry measured H2R and PD-L1 expression and estimated specific immune cell lineages. For the in vivo study, tumor cells were subcutaneously implanted into the right flank of BALB/c mice. Cimetidine had no significant effect on CT26 cell viability, clonogenicity, or cell cycle distribution. It also did not affect H2R and PD-L1 expression levels in CT26 cells. In vivo, anti-PD-1 and anti-PD-L1 suppressed CT26 tumor growth, whereas cimetidine showed mild antitumor activity. In the combined experiment, cimetidine significantly attenuated anti-PD-1 and anti-PD-L1′ antitumor effects without major toxicity. In the tumor microenvironment, anti-PD-L1 increased CD3+ T, CD4+ T, and CD8+ T cells and M1 macrophages. Combined treatment with cimetidine reversed this. Cimetidine also reversed anti-PD-1 and anti-PD-L1′s decrease in circulating and tumor-associated neutrophils. Cimetidine attenuated anti-PD-L1′s antitumor effect and modulated the tumor microenvironment in colon cancer.

Scientific evidence attests that the epidermis receives excessive ultraviolet B (UVB) radiation, triggering the generation of substantial quantities of reactive oxygen species (ROS), which disrupted the delicate equilibrium of oxidation–reduction, leading to oxidative stress and inflammation. The historical use of honeysuckle polyphenols (HPs) has garnered our attention due to their efficacy in inhibiting oxidative damage. In this study, HPs were prepared from honeysuckle flowers employing an ultrasonic-assisted extraction method and quantitatively analyzed by a LC–MS/MS, and the mechanisms underlying HPs’ antioxidative and anti-inflammatory effects on a UVB-irradiated HaCaT cell model were systematically investigated. The results showed that HPs had a significant cellular repair effect on UVB-irradiated HaCaT cells (p < 0.001). The mechanism of action indicated that HPs could allow Nrf2 to enter the nucleus by regulating the dissociation of Nrf2 from Keap1, which further increases the activity of downstream proteases (SOD and CAT), increases ROS scavenging, and reduces the intracellular malondialdehyde (MDA) level. In addition, HPs could down-regulate Toll-like receptor 4 (TLR4) and inhibit NF-κB (P65) dissociating from IκBα, resulting in a decrease in NF-κB (P65) entry into the nucleus and a decrease in inflammatory factors (TNF-α, IL-6, and IL-1β). In addition, four key compounds in HPs, including chlorogenic acid, quercetin, isorhamnetin, and luteolin, were selected to verify the mechanism of HPs repairing UVB damage using molecular docking techniques. The experiment suggested that four key active compounds could effectively occupy the Kelch homologue (Kelch) structural domain of Keap1, competitively bind with Nrf2, and facilitate the promotion of Nrf2 binding, ultimately enhancing the translocation of Nrf2 into the nucleus. In addition, four key active compounds could effectively interact with NF-κB (P65) through hydrogen bonding, van der Waals forces, and electrostatic forces to inhibit its entry into the nucleus. In summary, HPs can effectively repair the damage of HaCaT cells by UVB radiation and can be used to develop health and cosmetic products for the treatment of UV radiation-induced diseases.