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Liang Shan,1– 4 Fengling Wang,1 Dandan Zhai,1 Xiangyun Meng,1 Jianjun Liu,1 Xiongwen Lv2– 4 1Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China; 3Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, 230032, China; 4The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, ChinaCorrespondence: Jianjun Liu, Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China, Tel/Fax +86 0551 62965335, Email Jianjun_liu2020@163.com Xiongwen Lv, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China, Tel/Fax +86 0551 65161000, Email Xiongwen_lv2019@163.comBackground: Biliary atresia (BA) is a severe neonatal progressive cholangiopathy of unknown etiology. A timely Kasai portoenterostomy (KPE) improves survival of the native liver in patients with BA, although liver transplantation remains the ultimate treatment for most (60%– 80%) patients. However, postoperative adverse effects of liver transplantation may be significant. In addition, patients require lifelong immunosuppressive therapy after liver transplantation.Case Summary: Here, we report a case of a newborn female baby (birthday: 10– 03-2018) with congenital BA (confirmed at 76 days of life) who survived KPE (first surgery at 85 days of life) and underwent successful living-related liver transplantation (LRLT) (second surgery at 194 days of life). Additionally, we reviewed the existing literature on BA. After KPE (at 85 days of life), the liver function of the baby did not improve, and the indicators of liver and kidney function showed a trend of aggravation, indicating that the liver function had been seriously damaged before KPE (at 85 days of life), demonstrating the urgent need for liver transplantation surgery. The female baby survived after part of her father’s liver was successfully transplanted into her body (at 194 days of life). The patient recovered successfully. No other diseases were found at the 4-year follow-up, and all indices of liver and kidney functions tended to be normal.Conclusion: This case highlights the following. Postoperative alkaline phosphatase was consistently above the normal range, although the reason for this was unclear; neither tacrolimus nor cyclosporine A has formulations designed specifically for infants, which does not meet the needs of clinical individualized medication, suggesting that these anti-rejection drugs are future development directions. Only one case of congenital BA has been found thus far in Hefei, and this case has extremely important reference significance for the prevention, treatment, and diagnosis of BA in Hefei, Anhui province. Keywords: biliary atresia, Kasai portoenterostomy, living-related liver transplantation, immunosuppressive drug, therapeutic drug monitoring

Diguo Zhai,1,2 Qingwei Chen,1,2 Ying Yao,3 Taotao Ru,1,2 Guofu Zhou1,2 1Guangdong Provincial Key Laboratory of Optical Information Materials and Technology, Institute of Electronic Paper Displays, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou, 510006, People’s Republic of China; 2National Center for International Research on Green Optoelectronics, South China Normal University, Guangzhou, 510006, People’s Republic of China; 3Anhui Provincial Library, Hefei, 230000, People’s Republic of ChinaCorrespondence: Taotao Ru; Qingwei Chen, Lab of Light and Physio-Psychological Health-National Center for International Research on Green Optoelectronics-South China Academy of Advanced Optoelectronics-South China Normal University, No. 55, West Zhongshan Road, Tianhe District, Guangzhou, 510631, People’s Republic of China, Tel +86 15603063417 ; +86 15521094813, Email taotao.ru@m.scnu.edu.cn; qingwei.chen@m.scnu.edu.cnPurpose: To explore whether sleep electroencephalogram (EEG) microarousals of different standard durations predict daytime mood and attention performance in healthy individuals after mild sleep restriction.Participants and Methods: Sixteen (nine female) healthy college students were recruited to examine the correlations between nocturnal EEG microarousals of different standard durations (≥ 3 s, ≥ 5 s, ≥ 7 s, ≥ 9 s) under mild sleep restriction (1.5 h) and the following morning’s subjective alertness, mood, sustained attention, and selective attention task performance.Results: Results revealed that mild sleep restriction significantly reduced subjective alertness and positive mood, while having no significant effect on negative mood, sustained attention and selective attention performance. The number of microarousals (≥ 5 s) was negatively associated with positive mood at 6:30. The number of microarousals was significantly and positively correlated with the response time difference value of disengagement component of the selective attention task at around 7:30 (≥ 5 s and ≥ 7 s) and 9:00 (≥ 5 s). The number of microarousals (≥ 7 s) was significantly and positively correlated with the inaccuracy difference value of orientation component of the selective attention task at around 9:00.Conclusion: The number of EEG microarousals during sleep in healthy adults with mild sleep restriction was significantly and negatively related to their daytime positive affect while positively associated with the deterioration of disengagement and orientation of selective attention performance, but this link is dependent on the standard duration of microarousals, test time and the type of task.Keywords: microarousal, alertness, sustained attention, selective attention, sleep restriction

Liang Shan,1– 4,* Ning Zhao,2– 4,* Fengling Wang,1 Dandan Zhai,1 Jianjun Liu,1 Xiongwen Lv2– 4 1Department of Pharmacy, the Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, 230032, People’s Republic of China; 3Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, 230032, People’s Republic of China; 4The Key Laboratory of Major Autoimmune Diseases, Hefei, Anhui Province, 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianjun Liu, Department of Pharmacy, the Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China, Tel +86 551 62965335, Fax +86 551 62965335, Email Jianjun_liu2020@163.com Xiongwen Lv, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, 230032, People’s Republic of China, Tel +86 55165161000, Fax +86 551 65161000, Email Xiongwen_lv2019@163.comAbstract: The use of caffeine in treating various liver diseases has made substantial progress in the past decade owing to advances in science, technology, and medicine. However, whether caffeine has a preventive effect on hepatocellular carcinoma (HCC) and its mechanism are still worth further investigation. In this review, we summarize and analyze the efficacy and safety of caffeine in the prevention of HCC. We conducted a review of articles published in PubMed and Web of Science in the past 2 decades until December 6, 2023, which were searched for using the terms “Caffeine” and “Hepatocellular Carcinoma.” Studies have found that coffee intake is negatively correlated with HCC risk, especially caffeinated coffee. Recent studies have found that caffeine has beneficial effects on liver health, decreasing levels of enzymes responsible for liver damaging and slowing the progression of hepatic fibrosis and cirrhosis. Caffeine also acts against liver fibrosis through adenosine receptors (ARs), which promote tissue remodeling by inducing fibrin and collagen production. Additionally, new studies have found that moderate consumption of caffeinated beverages can decrease various the levels of various collagens in patients with chronic hepatitis C. Furthermore, polyphenolic compounds in coffee can improve fat homeostasis, reduce oxidative stress, and prevent liver steatosis and fibrosis. Moreover, many in vitro studies have shown that caffeine can protect liver cells and inhibit the activation and proliferation of hepatic stellate cells. Taken together, we describe the benefits of caffeine for liver health and highlight its potential values as a drug to prevent various hepatic diseases. As a protective agent of liver inflammation, non-selective AR inhibitor caffeine can inhibit the growth of HCC cells by inhibiting adenosine and AR binding to initiate immune response, providing a basis for the future development of caffeine as an adjuvant drug against HCC.Keywords: coffee, caffeine, hepatocellular carcinoma, adenosine, adenosine receptor

Hao Deng,1,* Yumei Wang,1,* Yue Zhou,1,* Dongliang Zhai,1 Jie Chen,1 Shilei Hao,2 Xiaoliang Chen1 1Department of Nuclear Medicine, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 2Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoliang Chen, Department of Nuclear Medicine, Chongqing University Cancer Hospital, No. 181 HanYu St, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel/Fax +86 023-65079156, Email chenxiaoliang26@163.com Shilei Hao, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, 174 Shazhengjie, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel +86023-135 9463 5765, Email Shilei_hao@cqu.edu.cnBackground: Prostate cancer (PCa) ranks second in the incidence of all malignancies in male worldwide. The presence of multi-organ metastases and tumor heterogeneity often leads to unsatisfactory outcomes of conventional radiotherapy treatments. This study aimed to develop a novel folate-targeted nanohydroxyapatite (nHA) coupling to deliver adriamycin (Doxorubicin, DOX), 32P, and 99mTc simultaneously for the diagnosis and treatment of prostate-specific membrane antigen (PSMA) positive prostate cancer.Methods: The spherical nHA was prepared by the biomimetic method and characterized. Folic acid (FA) was coupled to nHA with polyethylene glycol (PEG), and the grafting ratio of PEG-nHA and FA-PEG-nHA was determined by the thermogravimetric analysis (TGA) method. In addition, 32P, 99mTc, and DOX were loaded on nHA by physisorption. And the labeling rate and stability of radionuclides were measured by a γ-counter. The loading and release of DOX at different pH were determined by the dialysis method. Targeting of FA-PEG-nHA loaded with 99mTc was verified by in vivo SPECT imaging. In vitro anti-tumor effect of 32P/DOX-FA-PEG-nHA was assessed with apoptosis assay. The safety of the nano-drugs was verified by histopathological analysis.Results: The SEM images showed that the synthesized nHA was spherical with uniform particle size (average diameter of about 100nm). The grafting ratio is about 10% for PEG and about 20% for FA. The drug loading and the delayed release of DOX at different pH confirmed its long-term therapeutic ability. The labeling of 32P and 99mTc was stable and the labeling rate was great. SPECT showed that FA-PEG-nHA showed well in vivo tumor targeting and less damage to normal tissues.Conclusion: FA-targeted nHA loaded with 32P, 99mTc, and DOX may be a new diagnostic and therapeutic strategy for targeting PSMA-positive prostate cancer tumors, which may achieve better therapeutic results while circumventing the severe toxic side effects of conventional chemotherapeutic agents.Keywords: prostate cancer, folic acid targeting, nanohydroxyapatite, 99mTc/ 32P, adriamycin

Kai-Michael Beeh,1 Eric Derom,2 José Echave-Sustaeta,3 Lars Grönke,4 Alan Hamilton,5 Dongmei Zhai,6 Leif Bjermer71Insaf GmbH Institut für Atemwegsforschung, Wiesbaden, Germany; 2Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium; 3Servicio de Neumología, Hospital Universitario Quirón, Madrid, Spain; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 5Boehringer Ingelheim, Burlington, ON, Canada; 6InVentiv Health Clinical, Wilmington, DE, USA; 7Department of Respiratory Medicine and Allergology, Lund University, Lund, SwedenBackground: Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.Objective: The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.Methods: This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks. The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0–12) relative to the baseline after 6 weeks.Results: Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0–12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively). Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0–24).Conclusion: Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate. Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD. Keywords: COPD, maintenance treatment, lung function, tiotropium, FEV1, inhaled corticosteroid

Osteosarcoma (OS) is a primary bone cancer mostly found in adolescents and elderly individuals. The treatment of OS is still largely dependent on traditional chemotherapy. However, the high incidence of drug resistance remains one of the greatest impediments to limiting improvements in OS treatment. Recent findings have indicated that the transcription factor FOXM1 plays an important role in various cancer-related events, especially drug resistance. However, the possible role of FOXM1 in the resistance of OS to methotrexate (MTX) remains to be explored. Here, we find that FOXM1, which confers resistance to MTX, is highly expressed in OS tissues and MTX-resistant cells. FOXM1 overexpression promotes MTX resistance by enhancing autophagy in an HMMR/ATG7-dependent manner. Importantly, silencing of FOXM1 or inhibiting autophagy reverses drug resistance. These findings demonstrate a new mechanism for FOXM1-induced MTX resistance and provide a promising target for improving OS chemotherapy outcomes.

The doped perovskite BaBiO3 exhibits a maximum superconducting transition temperature (Tc) of 34 K and was the first high-Tc oxide to be discovered, yet pivotal questions regarding the nature of both the metallic and superconducting states remain unresolved. Although it is generally thought that superconductivity in the bismuthates is of the conventional s-wave type, the pairing mechanism is still debated, with strong electron-phonon coupling and bismuth valence or bond disproportionation possibly playing a role. Here we use diffuse x-ray scattering and Monte Carlo modeling to study the local structure of Ba1-xKxBiO3 across its insulator-metal boundary. We find no evidence for either long- or short-range disproportionation, which resolves a major conundrum, as disproportionation and the related polaronic effects are likely not relevant for the metallic and superconducting states. Instead, we uncover nanoscale structural correlations that break inversion symmetry, with far-reaching implications for the electronic physics. This unexpected finding furthermore establishes that the bismuthates belong to the broader classes of materials with hidden spin-orbit coupling and a tendency towards inversion-breaking displacements. Superconductivity was discovered in the bismuthate (Ba,K)BiO3 soon after the discovery of the cuprate high-temperature superconductors. Here, the authors study (Ba,K)BiO3 using diffuse x-ray scattering and Monte Carlo modeling, finding that nanoscale structural correlations break inversion symmetry locally, while preserving inversion symmetry on average over large length scales. [ABSTRACT FROM AUTHOR]

This paper describes a method for analyzing the effect of load uncertainty on unit commitment risk, which is the probability of having insufficient committed capacity to compensate for unit failures and/or unanticipated load variation. This risk is evaluated using the usual Markov model for unit failures and a Gauss-Markov load model for load uncertainty. A rescheduling policy is essential for stochastic risk evaluation; thus one is described in this paper. The risk and the average operating reserve are evaluated using Monte Carlo simulation, and the Monte Carlo simulation is applied to the IEEE-RTS in order to demonstrate the effect of load uncertainty on the risk and on the average amount of required operating reserve. This paper is the first to combine a stochastic load model with the usual Markov unit failure model for unit commitment risk evaluation.

Load uncertainty contributes to system operational risk; thus the study of system operating reserve or unit commitment risk requires a load model that includes the uncertainty in load as well as the variation with time. This paper proposes a Gauss-Markov load model, and this random process model includes both the time variation and the uncertainty in load. This load model is used to predict, conditional on what is known at a previous hour, the mean and the variance of the system hourly load. This mean and variance are required for a system operating reserve study and a broad spectrum of production simulations. In this paper, the proposed load model is first described, then the model is justified, and finally the model is illustrated via an example.

CFRP composites are widely used in aerospace due to their excellent mechanical properties, however, due to the anisotropy of the individual plies, the electro magnetic interference(EMI) shielding efficiency(SE) for vertically polarized waves of the unidirectional fiber laminates is poor. In order to protect electronics within these equipments from increasingly severe electromagnetic interference, it is particularly important to enhance the electromagnetic shielding efficiency of the CFRP. In this paper, Al particles were introduced and a conductive network was constructed in the CFRP interlaminar region by condensing the Al particles on the prepreg surface. The effects of different Al particle contents on EMI SE and mechanical properties of composites were studied. With the increase of Al particle contents, the electrical conductivity and the EMI SE of CFRP composites increase. When the Al mass fraction in the resin is 33.3%, the in-plane conductivity of the composites increases by 3 orders of magnitude, the EMI SE of the Al particle sandwich CFRP composites is improved by more than 10 dB in the frequency range of 3-17 GHz. With the increase of Al particle contents, the interlaminar shear strength and bending strength of the composites increase first and then decrease. When the Al mass fraction in the resin is 33.3%, the interlaminar shear strength (ILSS) of the composites increases by 5.2% to 80.5 MPa, and when the Al mass fraction in the resin is 50%, the bending strength of the composites increases by 20% to 1441.0 MPa and the bending modulus increases by 10.2% to 101.83 GPa. It can be seen that the mechanical properties and electromagnetic shielding effectiveness of the Al particles sandwich CFRP composite can be improved simutaneously. It is a kind of structure electromagnetic shielding integrated composite with broad application prospects.

Meminductor has attracted more and more attention as the new memory element. In this paper, a new generic meminductor model is proposed and analyzed. Its emulator is designed and its pinched hysteresis loop is presented. Based on the established meminductor and using a traditional capacitor and resistor, a new simple chaotic circuit presenting double-scroll chaotic attractors is proposed and its dynamical behaviors including phase portrait, Lyapunov exponents, Poincare mapping, power spectrum, bifurcation and the sensibility of initial value are analyzed. Meanwhile, it has been found that hidden attractors and transient chaotic phenomena under different initial value. Finally, the hardware circuit for the proposed simple double-scroll chaotic system is constructed and some experimental results are presented for validating the correctness of the theoretical analysis. [ABSTRACT FROM AUTHOR]

Macrobrachium nipponense is a major farmed species freshwater shrimp in China and its genetic diversity is of high value in aquaculture. The construction of the Three Gorges Project has slowed down the water velocity in the Three Gorges Reservoir (TGR) and made the water more clear, which is more favourable for the survival and reproduction of M. nipponense. However, there are lack of studies on the genetic diversity of M. nipponense populations in the TGR. In this study, mitochondrial COI gene sequences were used as molecular marker to analyze the genetic diversity, genetic differentiation and historical demography of eight M. nipponense populations in the TGR. The results showed that the M. nipponense populations in TGR have high genetic diversity. There was some genetic differentiation between the four populations in lower reaches of the TGR and four populations in the upper reaches of the TGR. We also found that there was a significant correlation between genetic distance and geographical distance among the M. nipponense populations in the TGR. The M. nipponense population in the TGR has experienced population reduction in the recent year, which might be related to the ice age movement in the Little Ice Age and human activities. This study provides a theoretical basis for the rational development and protection of M. nipponense resources in the TGR.