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Mesenchymal stem cells (MSCs) have demonstrated promising advantages in the therapies of many diseases, while its multi-directional differentiation potential and immunotoxicity are the major concerns hindered their clinical translation. In this study, human umbilical Mesenchymal stem cell (hUC-MSCs) were labeled with a near-infrared fluorescent dye DiR before infused into cynomolgus monkeys, and the amount of hUC-MSCs in the peripheral blood were dynamically estimated from 5 min to 28 days post a single administration at 3 × 106 cells/kg and 2 × 107 cells/kg intravenously. As results, some hUC-MSCs distributed to the whole body within 5 min, while most of the cells accumulate in the lungs along with the systemic blood circulation, and subsequently released into the blood. The toxicity potentials of hUC-MSCs were investigated in another 30 cynomolgus monkeys, and the cells were repeatedly administrated at doses of 3 × 106 cells/kg and 2 × 107 cells/kg for 5 times on a weekly basis, with a recovery period of 1 months. hUC-MSCs showed no obvious toxic effects in cynomolgus monkeys, except xenogeneic immune rejection to human stem cells. Low levels of the hUC-MSC gene were detected in the peripheral blood of a few animals administered 2 × 107 cells/kg at 30 min subsequent to the first and last administration, and there was no significant difference in the copy number of the hUC-MSC gene in the blood samples compared with the first and last administration, indicating that the hUC-MSC was not significantly amplified in vivo, and it its safe in non-human primates. Our study for the first time verified the safety of long-term use of hUC-MSCs in primates. We have pioneered a technology for the real-time detection of hUC-MSCs in peripheral blood and provide dynamicand rapid monitoring of the distribution characteristics of hUC-MSCs in vivo. Here, we provide data supporting the application of such products for clinical treatment and the application of stem cells in major refractory diseases and regenerative medicine. [ABSTRACT FROM AUTHOR]

The development of urbanization and the protection of the ecological environment are important aspects of sustainable development in urban agglomerations; thus, their coordination and synergy are crucial. Scholars in both China and other countries have conducted extensive research on the relationship between urbanization and the ecological environment from the perspective of coordinated development. However, there is a lack of research on the synergistic effects of urbanization and the ecological environment. Taking the Chengdu–Chongqing urban agglomeration as an example, this study uses the Haken model to analyze the synergistic evolution mechanism, development patterns, and future trends of urbanization and the ecological environment. This study draws the following conclusions: (1) while a synergistic development mechanism has been established between urbanization and the ecological environment, the current system is still in a stage of low-level synergy, and the control system's parameter for the direction and path of evolution is urbanization. (2) From 2001 to 2020, the level of synergistic development between urbanization and the ecological environment was relatively low, mainly moving from low-level synergy to medium–low-level synergy to medium-level synergy. (3) There is a significant spatial disparity in the levels of synergistic development, for which the leading region centers on Chengdu and Chongqing in the northwest and southeast, respectively, and the lagging region comprises the eastern part of the urban agglomeration, mainly represented by Dazhou, Kaizhou, and Yunyang. (4) The future trend of synergistic development between urbanization and the ecological environment in the Chengdu–Chongqing urban agglomeration is promising but requires increased infrastructure construction in mountainous urban areas, enhanced cooperation and circulation in transportation, logistics, information and other aspects, and balanced improvements in the level of synergistic development between urbanization and the ecological environment. The study of the synergistic development effect of urbanization and the ecological environment in urban agglomerations is of great significance for reducing the negative impact of urbanization on the ecological environment, increasing the positive interaction between the two, and promoting sustainable development in urban agglomerations. [ABSTRACT FROM AUTHOR]

Human activities have notably affected the Earth's climate through greenhouse gases (GHG), aerosol, and land use/land cover change (LULCC). To investigate the impact of forest changes on regional climate under different shared socioeconomic pathways (SSPs), changes in surface air temperature and precipitation over China under low and medium/high radiative forcing scenarios from 2021 to 2099 are analyzed using multimodel climate simulations from the Coupled Model Intercomparison Project Phase 6 (CMIP6). Results show that the climate responses to forest changes are more significant under the low radiative forcing scenario. Deforestation would increase the mean, interannual variability, and the trend of surface air temperature under the low radiative forcing scenario, but it would decrease those indices under the medium/high radiative forcing scenario. The changes in temperature show significant spatial heterogeneity. For precipitation, under the low radiative forcing scenario, deforestation would lead to a significant increase in northern China and a significant decrease in southern China, and the effects are persistent in the near term (2021–40), middle term (2041–70), and long term (2071–99). In contrast, under the medium/high radiative forcing scenario, precipitation increases in the near term and long term over most parts of China, but it decreases in the middle term, especially in southern, northern, and northeast China. The magnitude of precipitation response to deforestation remains comparatively small. [ABSTRACT FROM AUTHOR]

Human multidrug resistance protein 4 (hMRP4, also known as ABCC4), with a representative topology of the MRP subfamily, translocates various substrates across the membrane and contributes to the development of multidrug resistance. However, the underlying transport mechanism of hMRP4 remains unclear due to a lack of high-resolution structures. Here, we use cryogenic electron microscopy (cryo-EM) to resolve its near-atomic structures in the apo inward-open and the ATP-bound outward-open states. We also capture the PGE1 substrate-bound structure and, importantly, the inhibitor-bound structure of hMRP4 in complex with sulindac, revealing that substrate and inhibitor compete for the same hydrophobic binding pocket although with different binding modes. Moreover, our cryo-EM structures, together with molecular dynamics simulations and biochemical assay, shed light on the structural basis of the substrate transport and inhibition mechanism, with implications for the development of hMRP4-targeted drugs. Cryo-EM structures, MD simulations, and biochemical assays of human multidrug resistance-associated protein 4 in apo inward-open, ATP-bound outward-open, PGE1 substrate-bound, and sulindac inhibitor-bound states provide insights into substrate transport and inhibition mechanism. [ABSTRACT FROM AUTHOR]

3-nitro-1,2,4-triazol-5-one (NTO)–based polymer-bonded explosives (PBXs) have been widely used in insensitive munitions, but the main properties of NTO-based PBXs such as compatibility, safety performance, and mechanical properties are rarely reported. In this work, molecular dynamics simulation was carried out to study interface interactions of NTO-based PBXs, in which hydroxy-terminated polybutadiene (HTPB), ethylene–vinyl acetate copolymer (EVA), glycidyl azide polymer (GAP), poly-3-nitratomethyl-3-methyl oxetane (Poly-NIMMO), and ester urethane (Estane5703) are selected as binders. The binding energy analysis indicates that the order of compatibility is NTO/GAP > NTO/Estane5703 > NTO/HTPB > NTO/Poly-NIMMO > NTO/EVA. Radial distribution function analysis results show that the interface interaction is mainly the hydrogen bond between H atoms of NTO and O atoms of Estane5703, HTPB, EVA, and Poly-NIMMO or N atoms of GAP. The values of cohesive energy density verify that the safety is NTO/GAP > NTO/Poly-NIMMO > NTO/HTPB > NTO/EVA > NTO/Estane5703. Mechanical properties results show that GAP and EVA would improve the plasticity of the systems effectively. Furthermore, it can be found that the most favorable interactions occur between the NTO (1 0 0) crystal face and binders. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus that produces severe fever with thrombocytopenia syndrome (SFTS). It is widespread in Japan, South Korea, and Central and Eastern China. The epidemic has developed rapidly through China in recent years. SFTS cases have been reported in 25 provinces in China, mainly distributed in rural areas in mountainous and hilly areas. The infection has a high case fatality rate and no specific treatments or vaccinations. Therefore, early diagnosis and treatment of SFTS infection is important to survival and disease control. In this article, we provide an overview on different aspects of SFTS with an emphasis on management, to explore the current treatment and prophylactic measures further. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is implicated in the aberrant proliferation and malignant transformation of gastric mucosal cells, heightening the risk of gastric cancer (GC). HN1 is involved in the development of various tumors. However, precise mechanistic underpinnings of HN1 promoting GC progression in H. pylori remain elusive. The study collected 79 tissue samples of GC patients, including 47 with H. pylori-positive GC and 32 H. pylori-negative controls. Using human gastric epithelial cells (GES-1) and human gastric adenocarcinoma cells (HGC-27), the effect of overexpression / knocking down of HN1 and H. pylori infection was evaluated on cell function (proliferation, migration, apoptosis), cytoskeleton, and expression of cell malignant phenotype factors that promote the malignant biological behavior of cancer cells. The expression of HN1 in GC tissues is higher than that in paracancerous tissue and is closely related to infiltration, lymphatic metastasis, distant metastasis, survival, and H. pylori infection. Downregulation of HN1 effectively hinders the ability of H. pylori strains 26695 and SS1 to promote migration of GES-1 and HGC-27 cells, while lowering the expression of key indicators associated with malignant phenotype. Downregulated GSK3B, β-catenin, and Vimentin after knockdown Integrinβ1, but HN1 expression remained largely unchanged, when HN1 and Integrinβ1 were knocked down, GSK3B, β-catenin, and Vimentin expression were considerably reduced. Our research demonstrated the crucial role of HN1 in H. pylori-induced acquisition of a malignant phenotype in GES-1 cells. Knockdown of HN1 blocked the pathogenic mechanism of H. pylori-induced GC and downregulated the expression of GSK3Β, β-catenin and Vimentin via Integrin β1. [ABSTRACT FROM AUTHOR]

Infantile hemangioma is a common and challenging benign vascular tumor. Although involution is spontaneous, approximately 10% of infantile hemangioma of large size or in specific locations may cause ulceration, severe cosmetic and functional problems that may require intervention. Treatment options include oral propranolol, topical timolol, and oral corticosteroids. However, the clinical response is not always satisfactory. We report the case of a 4-month-old boy who presented with an irregular erythematous plaque on his left shoulder 3 days after birth. Infantile hemangioma was diagnosed. Topical application of 0.5 ml of 0.5% timolol maleate eye drops for half an hour each time three times a day was initiated. After nearly 3 months of follow-up, the size of the lesion gradually increased. Finally, after 115 days of treatment with itraconazole oral solution (the total dose was about 4025 mg), the refractory infantile hemangioma was successfully treated. Hepatic and renal function remained normal with only mild diarrhea during the course of oral medication. Treatment compliance of oral itraconazole in infants has been reported to be good. Dermoscopy and magnetic resonance imaging (MRI) played a crucial role in in vivo observation of the hemangioma changes with vascular regression during the treatment process. [ABSTRACT FROM AUTHOR]

Vindoline is a plant derived monoterpene indole alkaloid (MIA) with potential therapeutic applications and more importantly serves as the precursor to vinblastine and vincristine. To obtain a yeast strain for high yield production of vindoline from tabersonine, multiple metabolic engineering strategies were employed via the CRISPR/Cas9 mediated multiplex genome integration technology in the present study. Through increasing and tuning the copy numbers of the pathway genes, pairing cytochrome P450 enzymes (CYPs) with appropriate cytochrome P450 reductases (CPRs), engineering the microenvironment for functional expression of CYPs, enhancing cofactor supply, and optimizing fermentation conditions, the production of vindoline was increased to a final titer as high as ∼16.5 mg/L, which is more than 3,800,000-fold higher than the parent strain and the highest tabersonine to vindoline conversion yield ever reported. This work represents a key step of the engineering efforts to establish de novo biosynthetic pathways for vindoline, vinblastine, and vincristine. Liu et al. optimize vindoline biosynthesis in yeast from tabersonine by altering the copy numbers of pathway genes, pairing CYPs with CPRs, engineering the microenvironment for functional expression of CYPs, enhancing cofactor supplies, and optimizing fermentation conditions. By doing so, the authors increased the production of vindoline to a final titer as high as ∼16.5 mg/L. [ABSTRACT FROM AUTHOR]

In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extracted from angelica dahuricae and notopterygium Notopterygii, which has anti-inflammatory, vasodilator, anticoagulant, block calcium channel, anticonvulsant, and anti oxygen free radical injury properties. Therefore,the present study examined its effects on VD rats and the underlying molecular mechanisms, in order to provide promising therapeutic methods. VD was established by modified ligation of perpetual two-vessel occlusion (2VO). After 2VO surgery, IMP (2.5, 5, and 10 mg/kg) was administered by intraperitoneal injection for 12 consecutive weeks to evaluate therapeutic effects. Cognitive function was verified by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin–Eosin staining. Real-Time PCR and Western blot were used for detecting pro- and antiapoptotic biomarkers, and the hippocampus synaptic damage was examined by Transmission electron microscope. We revealed that 2VO-induced cognitive impairment, hippocampus CA1 neuron damage, apoptosis and synaptic damage. IMP-treatment significantly improved 2VO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that IMP inhibited apoptosis through the down regulation of Bax, Caspase-3 and upregulation of Bcl-2. Meanwhile, IMP-treatment markedly improved synaptic ultrastructure morphology, increased the SAZ length, PSD thickness and up-regulated PSD-95 expression. Collectively, our findings demonstrated that IMP was effective in the treatment of 2VO-induced VD via inhibiting apoptosis of hippocampus neurons and reducing the synaptic plasticity destroy. [ABSTRACT FROM AUTHOR]

Toxic solvents and chemicals are usually used to prepare carbon nitride. Therefore, a low-toxic template-free method was proposed to prepare gauze-like porous graphitic carbon nitride (CCM18) with high specific surface area. The morphology, crystal and surface structure, specific surface area and optical properties of CCM18 were characterized, and the removal efficiency for tetracycline hydrochloride (TC) degradation under simulated sunlight was evaluated. The results showed that CCM18 has a specific surface area of 107.4 m2 g-1, stronger light absorption capacity and a band gap energy of 2.92 eV. The degradation rate of TC by CCM18 was more than twice that of BCN. The experiment of radical scavengers confirmed that superoxide radicals (O2-) and hydroxyl radical (OH) were the major active species. The enhanced performance of CCM18 for TC degradation (82%) and the stability of CCM18 that can be reused multiple times indicated the prospect of industrial application. [ABSTRACT FROM AUTHOR]

Highlights: A facile one‐step hydrothermal method for producing gram‐scale 1T@2H-MoS2 by imbedding the guest molecules and ions was developed. The influence of different MoS2 phase for electromagnetic absorbing properties was explored by analyzing electromagnetic parameters of 1T/2H MoS2 and 2H MoS2 with 50%, 40%, 30%, 20%, 15%, and 10% filler loading. Taking the advantage of 1T/2H MoS2, the flexible CF@1T/2H MoS2 was also synthesized to mind the request of flexible portable microwave absorption electronic devices.Phase engineering is an important strategy to modulate the electronic structure of molybdenum disulfide (MoS2). MoS2-based composites are usually used for the electromagnetic wave (EMW) absorber, but the effect of different phases on the EMW absorbing performance, such as 1T and 2H phase, is still not studied. In this work, micro-1T/2H MoS2 is achieved via a facile one-step hydrothermal route, in which the 1T phase is induced by the intercalation of guest molecules and ions. The EMW absorption mechanism of single MoS2 is revealed by presenting a comparative study between 1T/2H MoS2 and 2H MoS2. As a result, 1T/2H MoS2 with the matrix loading of 15% exhibits excellent microwave absorption property than 2H MoS2. Furthermore, taking the advantage of 1T/2H MoS2, a flexible EMW absorbers that ultrathin 1T/2H MoS2 grown on the carbon fiber also performs outstanding performance only with the matrix loading of 5%. This work offers necessary reference to improve microwave absorption performance by phase engineering and design a new type of flexible electromagnetic wave absorption material to apply for the portable microwave absorption electronic devices. [ABSTRACT FROM AUTHOR]

Whether copyrights should exist in content generated by an artificial intelligence is a frequently discussed issue in the legal literature. Most of the discussion focuses on economic rights, whereas the relationship of artificial intelligence and moral rights remains relatively obscure. However, as moral rights traditionally aim at protecting the author's "personal sphere", the question whether the law should recognize such protection in the content produced by machines is pressing; this is especially true considering that artificial intelligence is continuously further developed and increasingly hard to comprehend for human beings. This paper first provides the background on the protection of moral rights under existing international, U.S. and European copyright laws. On this basis, the paper then proceeds to highlight special issues in connection with moral rights and content produced by artificial intelligence, in particular whether an artificial intelligence itself, the creator or users of an artificial intelligence should be considered as owners of moral rights. Finally, the present research discusses possible future solutions, in particular alternative forms of attribution rights or the introduction of related rights. [ABSTRACT FROM AUTHOR]

As a major carbon emitter, the power sector plays a crucial role in realizing the goal of carbon peaking and carbon neutrality. This study constructed a low-carbon power system based on the LEAP model (LEAP-GBA) with 2020 as a statistic base aiming of exploring the low-carbon transformation pathway of the power sector in the Guangdong–Hong Kong, and Macao Greater Bay Area (GBA). Five scenarios are set up to simulate the demand, power generation structure, carbon emissions, and power generation costs in the power sector under different scenarios. The results indicate that total electricity demand will peak after 2050, with 80% of it coming from industry, buildings and residential use. To achieve net-zero emissions from the power sector in the GBA, a future power generation mix dominated by nuclear and renewable energy generation and supplemented by fossil energy generation equipped with CCUS technologies. BECCS technology and nuclear power are the key to realize zero carbon emissions from the power sector in the GBA, so it should be the first to promote BECCS technology testing and commercial application, improve the deployment of nuclear power sites, and push forward the construction of nuclear power and technology improvement in the next 40 years. [ABSTRACT FROM AUTHOR]

Varicella-zoster virus (VZV) leads to chicken pox on primary infection and herpes zoster on reactivation. Recent studies suggest that microRNA2911 (MIR2911), honeysuckle (HS)-encoded atypical microRNA, has potential as a therapeutic agent against influenza and EV71 virus infections. Here, we report that MIR2911 directly inhibits VZV replication by targeting the IE62 gene. The luciferase reporter assay and bioinformatics prediction revealed that MIR2911 could target the IE62 gene of VZV. The VZV-encoded IE62 protein expression was inhibited significantly by synthetic MIR2911, while the expression of the mutants, whose MIR2911-binding sites were modified, was not inhibited. The RNA extracted from HS decoction and synthetic MIR2911 considerably suppressed VZV infection. However, it did not influence viral replication of a mutant virus with alterations in the nucleotide sequences of IE62. At the same time, the RNA extracted from HS decoction treated with the anti-MIR2911 antagomir could not inhibit the VZV replication, demonstrating that VZV replication was specifically and sufficiently inhibited by MIR2911. These results indicated that, by targeting the IE62 gene, MIR2911 may effectively inhibit VZV replication. Our results also suggest a potential novel strategy for the treatment and prevention of diseases caused by VZV infection. [ABSTRACT FROM AUTHOR]

Before vaccines were introduced, mobility restriction was one of the primary control measures in the early stage of the coronavirus disease 2019 (COVID-19) pandemic. Because different age groups face disproportionate health risks, differences in their mobility changes affect the effectiveness of pandemic control measures. This study aimed to investigate the relationship between multiscale mobility patterns in different age groups and COVID-19 transmission before and after control measures implementation. Data on daily confirmed case numbers, anonymized mobile phone data, and 38 socioeconomic factors were used to construct negative binomial regression models of these relationships in the Taipei metropolitan area in May 2021. To avoid overfitting, the socioeconomic factor dimensions were reduced by principal component analysis. The results showed that inter-district mobility was a greater promoter of COVID-19 transmission than was intra-district mobility (coefficients: pre-alert, 0.52 and 0.43; post-alert, 0.41 and 0.36, respectively). Moreover, both the inter-district mobility of people aged 15–59 and ≥ 60 years were significantly related to the number of confirmed cases (coefficients: pre-alert, 0.82 and 1.05; post-alert, 0.48 and 0.66, respectively). The results can help agencies worldwide formulate public health responses to emerging infectious diseases. [ABSTRACT FROM AUTHOR]

Hierarchical CoFeO/NiFeO nanocomposites are prepared via a facile hydrothermal method, in which CoFeO nanoparticles are coated by NiFeO nanoparticles to form a novel nanostructure. Comparing with the single component of either CoFeO electrodes or NiFeO electrodes, the as-prepared hierarchical CoFeO/NiFeO nanocomposites electrodes deliver a higher specific capacitance of 269 F g at a current density of 1 A g and exhibit capacity retention of 81% after 10000 charge-discharge cycles. The improved electrochemical performance demonstrates that hierarchical CoFeO/NiFeO nanocomposites are promising materials and provide a new idea for future generation supercapacitors. [ABSTRACT FROM AUTHOR]

Before vaccines were introduced, mobility restriction was one of the primary control measures in the early stage of the coronavirus disease 2019 (COVID-19) pandemic. Because different age groups face disproportionate health risks, differences in their mobility changes affect the effectiveness of pandemic control measures. This study aimed to investigate the relationship between multiscale mobility patterns in different age groups and COVID-19 transmission before and after control measures implementation. Data on daily confirmed case numbers, anonymized mobile phone data, and 38 socioeconomic factors were used to construct negative binomial regression models of these relationships in the Taipei metropolitan area in May 2021. To avoid overfitting, the socioeconomic factor dimensions were reduced by principal component analysis. The results showed that inter-district mobility was a greater promoter of COVID-19 transmission than was intra-district mobility (coefficients: pre-alert, 0.52 and 0.43; post-alert, 0.41 and 0.36, respectively). Moreover, both the inter-district mobility of people aged 15–59 and ≥ 60 years were significantly related to the number of confirmed cases (coefficients: pre-alert, 0.82 and 1.05; post-alert, 0.48 and 0.66, respectively). The results can help agencies worldwide formulate public health responses to emerging infectious diseases. [ABSTRACT FROM AUTHOR]

In this paper, an integrated dynamic acceleration/deceleration (IDAD) interpolation algorithm which combines the acceleration/deceleration before interpolation (ADBI) and acceleration/deceleration after interpolation (ADAI) is proposed. The IDAD scheme could confine the maximum contour error at the junction of a linear line (G01) block under consideration of the command and servo dynamic errors. The contour error formulation for the IDAD is derived analytically and then utilized for interpolation design. Because the error formulation could predict the command and dynamic errors analytically, the IDAD could adjust the connecting velocity of two blocks such that the overall contour errors are bounded within the given tolerance. The simulation results validate the proposed algorithm that can reduce the contour errors by 50 % but only an increase of 10 % machining time as compared to the integrated acceleration/deceleration (IAD) interpolation technique. [ABSTRACT FROM AUTHOR]

Graphene sheets (GNs) have high conductivity, but they exhibit weak electromagnetic (EM) wave absorption performance. Here, poly (3,4-ethylenedioxythiophene) (PEDOT) nanofibers were decorated on the surface of GNs in which the residual defects and groups act as the active sites and therefore are beneficial for the deposition of PEDOT nanofibers. The SEM images display that PEDOT nanofibers are successfully decorated on the surface of GNs through in situ polymerization. The diameter of the PEDOT nanofibers were ranged from 15 to 50 nm with hundreds of nanometers in length. The EM wave absorption properties of graphene, PEDOT, and GNs-PEDOT were also investigated. Compared to pure graphene and PEDOT, the EM wave absorption properties of GNs-PEDOT improved significantly. The maximum value of R was up to −48.1 dB at 10.5 GHz with a thickness of only 2 mm. Meanwhile, the absorption bandwidth of R values below −10 dB was 9.4 GHz (5.8-12.3, 12.9-15.8 GHz) in the thickness of 1.5-3 mm. The enhancement is attributed to the modification of PEDOT and the unique structure of nanofibers. On one hand, the deposition of PEDOT nanofibers on the surface of GNs decreases the conductivity of graphene, and makes impedance match better. On the other hand, the unique structure of PEDOT nanofibers results in relatively large specific surfaces areas, providing more active sites for reflection and scattering of EM waves. Therefore, our findings demonstrate that the deposition of conducting polymers on GNs by non-covalent bond is an efficient way to fabricate strong EM wave absorbers. [ABSTRACT FROM AUTHOR]

In this paper, we consider the generic stability of the weakly efficient solution mapping for set-valued optimization problems. Firstly, we obtain the upper semicontinuity of the weakly efficient solution mapping for set-valued optimization problems. Secondly, we show that, in the sense of Baire category, most set-valued optimization problems are stable. Finally, we give sufficient conditions ensuring the existence of essential. Our results extend and improve the corresponding results of Song et al. (J. Optim. Theory Appl. 156:591-599, 2013). [ABSTRACT FROM AUTHOR]

To preliminarily explore a nondrug intervention method and evaluate its effects (sleep quality, physical examination indicators, and general physical symptoms) on people with sleep disorders. The intervention was based on regular balneotherapy, coupled with targeted health education, appropriate exercise, diet management, and other sleep-promoting measures. It was the combined effects that we evaluated. We recruited 31 volunteers with sleep disorders to receive a 7-day sleep-promoting experience in Tianxing International Hot Spring City, Nanchuan District, Chongqing. The intervention adopted a plan that combined balneotherapy with various sleep-promoting measures. Persisting baths in hot springs 1–2 times per day targeted health lectures about 1 h every morning, appropriate exercise every day (sleep-aid yoga, forest hiking, morning exercises, etc.), and diet management (the principle is to control oil, salt, and sugar, diversify food, keep meat and vegetable balanced, and control total calories. The dinner is light and easy to digest). During the intervention period, all participants followed the above intervention plan, and they lived in the spa resort to accept unified arrangement. This study adopted a self-contrast method by comparing the changes in sleep quality, physical examination indicators, and general physical symptoms before and after the intervention through physical examinations and questionnaire surveys. After the intervention, the subjects' total score of Insomnia Severity Index (ISI) decreased significantly (P = 0.006), and all seven dimensions showed a decrease, four of which included early morning awakening, sleep dissatisfaction, noticeability of sleep problems by others, and distress caused by sleep problems decreased significantly (all P < 0.05). The subjects' body mass index, waist circumference, fasting blood glucose, and triglycerides decreased significantly (all P < 0.05), and systolic blood pressure increased significantly (P = 0.006). Total cholesterol, high-density lipoprotein, low-density lipoprotein, and diastolic blood pressure did not change significantly (all P > 0.05). To some extent, all general health problems were improved than before the intervention (the improvement rate was up to 70% or more). The non-pharmacological intervention of balneotherapy combined with various sleep-promoting measures showed positive effects on sleep quality, general physical symptoms, and some physical examination indicators of sleep disorders. This comprehensive intervention may be an effective way to improve people's health with sleep disorders. [ABSTRACT FROM AUTHOR]

Based on the output data of Beijing Climate Center Atmospheric General Circulation Model version 2.0.1 (BCC_AGCM2.0.1), this study evaluates the simulated precipitation and associated circulation during the Meiyu period over the Yangtze-Huaihe River Basin (YHRB). The results show that BCC_AGCM2.0.1 can reasonably reproduce the spatial pattern of Meiyu over the YHRB. However, compared to the observation, the model underestimated (overestimated) the torrential and heavy (moderate and light) rainy days, indicating that the more (less) simulated light (torrential) rainy days result in more (less) modeled total rainy days (Meiyu precipitation amount). The simulated Meiyu onset begins in early June, earlier about 20 days than the climatological observation. For duration, Meiyu persists for 15 days, about 5 days shorter than the observation, which may be due to the simulated land-sea thermal contrast is earlier in early June. During the Meiyu period, the distribution patterns of the upper troposphere atmospheric circulation can be well simulated by BCC_AGCM2.0.1, but the obvious deficiency lies in the lower-troposphere air temperature and wind field, especially over Tibetan Plateau area. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl− system. An oxindolyl alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated inhibition of the ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation but accounts for 20% of the apoA1 in atherosclerosis-laden arteries. OxTrp72-apoA1 recovered from human atheroma or plasma is lipid poor, virtually devoid of cholesterol acceptor activity and demonstrated both a potent proinflammatory activity on endothelial cells and an impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n = 627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a proatherogenic process in the artery wall. [ABSTRACT FROM AUTHOR]

Bamboo charcoal/LiSnO composites for lithium-ion batteries were synthesized by a sol-gel route. The structure, morphology, and electrochemical properties of the composites were detected by means of X-ray diffraction, scanning electron microscope, Raman spectroscopy, thermal gravimetric analysis, and electrochemical measurements. The results showed that LiSnO particles were loaded on the surface of bamboo charcoal and some of them entered into the hole. The bamboo charcoal/LiSnO composites exhibited good electrochemical performance with high capacity and good cycling stability (616.5 mAh g after 50 cycles). The composites showed a better electrochemical property than LiSnO and bamboo charcoal. [ABSTRACT FROM AUTHOR]

The major limitation preventing the expansion of Satsuma mandarin ( Citrus unshiu) production in the Gulf Coast regions of the US is the risk of freeze damage. Poncirus trifoliata (L.) Raf has been widely used as a cold hardy rootstock for citrus production in freeze-prone environments. In this study, relative quantitative real-time RT-PCR was used to study cold responsive genes in Satsuma mandarin ( C. unshiu), C. unshiu grafted on P. trifoliata rootstock and P. trifoliata following exposure to cold shock or cold acclimation treatments. Major changes in gene expression occurred in the different species during cold stress especially with respect to nitrate transporter, auxin responsive GH3, UDP-glycosyltransferase (UGT) and chalcone-flavanone isomerase. Very high levels of nitrate transporter were reached early in Poncirus following 60 h of cold shock treatment at 4°C, and in C. unshiu after 3 weeks of gradual cold acclimation. Also, high levels of auxin responsive GH3 were reached in Poncirus following both cold shock and cold acclimation, while levels in C. unshiu were low or reduced. Poncirus rootstock significantly affected gene expression in C. unshiu scion, resulting in a reduction of nitrate transporter, UGT and trehalose 6-phosphate synthase expression levels, and an increase in auxin responsive GH3 gene during cold acclimation. The impact of rootstock on citrus scion during cold stress might be associated with partitioning of nutrients and hormones. [ABSTRACT FROM AUTHOR]

Apo2L/TRAIL (tumor necrosis factor-related apoptosis inducing ligand (TRAIL), also known as Apo2L) is a potentially important anticancer agent awaiting clinical trials. Unfortunately, however, some cancer cells exhibit resistance to Apo2L/TRAIL, which could limit the use of this potentially promising anticancer agent. Although the molecular basis of the inherent or acquired resistance to Apo2L/TRAIL remains unclear, previous studies indicate that Bax deficiency can confer resistance to Apo2L/TRAIL. Proteasome inhibition is also emerging as a promising therapeutic strategy to manage human malignancies. Here, we report that proteasome inhibitor MG132 upregulates Apo2L/TRAIL death receptor 5 expression in both Bax-proficient and -deficient HCT116 cells. MG132 effectively cooperated with Apo2L/TRAIL to induce apoptosis in both Bax-proficient and -deficient cells that was coupled with caspases-8 and -3 activation and Bid cleavage. Although both agents in combination also induced cytochrome c and Smac release from mitochondria into cytosol and activated caspase-9 in Bax-proficient cells, their effects on these events were significantly diminished in Bax-deficient cells. These results suggest that Bax is not absolutely required for death receptor 5-dependent apoptotic signals and MG132 by upregulating DR5 effectively cooperates with Apo2L/TRAIL to overcome Bax deficiency-induced resistance to Apo2L/TRAIL. Our results have important clinical implications in that the use of Apo2L/TRAIL and proteasome inhibitors in combination could prove to be a novel therapeutic strategy to manage the Apo2L/TRAIL-resistant tumors.Oncogene (2004) 23, 2554-2558. doi:10.1038/sj.onc.1207351 Published online 22 December 2003 [ABSTRACT FROM AUTHOR]

We report the cloning and characterization of a novel p53 and DNA damage-regulated gene (PDRG). The human and mouse PDRG sequences are highly homologous and contain open reading frames of 133 amino acids each with molecular masses of 15.5 and 15.3?kDa, respectively. PDRG codes for a novel protein that does not show similarity to any known protein in the databases. Human PDRG is predominantly expressed in normal testis and exhibits reduced but detectable expression in other organs. GFP-tagged PDRG was predominantly detected as aggregates that appeared to reside in a distinct subcellular compartment. PDRG mRNA was upregulated by ultraviolet radiation (UV) but downregulated by tumor suppressor p53. UV is known to transcriptionally upregulate the expression of certain genes by activating the transcription factor Oct-1, while p53 has been reported to suppress transcription of certain genes by directly binding to a novel head-to-tail response element. Cloning and sequence analysis of PDRG promoter revealed the presence of Oct-1-binding element and a putative head-to-tail-type p53-binding site. Indeed, UV as well as exogenous Oct-1 independently increased PDRG promoter activity, suggesting that UV could mediate PDRG upregulation via Oct-1. Exogenous wild-type p53 was found to downregulate the PDRG promoter activity indicating that wild-type p53 transcriptionally suppresses the expression of PDRG and may mediate its effect via the putative head-to-tail response element. Furthermore, stable expression of exogenous PDRG was found to decrease the clonogenic survival after UV irradiation, which highlights the significance of PDRG in facilitating UV-induced killing.Oncogene (2003) 22, 7247-7257. doi:10.1038/sj.onc.1207010 [ABSTRACT FROM AUTHOR]

Pharmacological inhibition of type 4 cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE4) produces antidepressant-like effects in animals; however, it is not known which of the four PDE4 subtypes mediates these actions. In the present study, immunoblot analysis showed loss of phosphodiesterase 4D (PDE4D) expression in the cerebral cortex and hippocampus of PDE4D knockout (PDE4D−/−) mice, but unchanged PDE4A and PDE4B expression, relative to the wild type (PDE4D+/+) and heterozygous knockout (PDE4D+/−) mice. This reduced expression was accompanied by a reduction in PDE4 activity, while non-PDE4 activity was unchanged. PDE4D−/− mice exhibited decreased immobility in tail-suspension and forced-swim tests, which is indicative of an antidepressant-like effect on behavior. Desipramine and fluoxetine produced similar antidepressant-like effects in all three genotypes, even though their behavioral baselines differed markedly. By contrast, the PDE4 inhibitor rolipram only produced antidepressant-like effects in PDE4D+/+ mice. Consistent with this, rolipram potentiated isoproterenol-induced cyclic AMP formation only in the PDE4D+/+ mice. These results suggest that PDE4D is an essential mediator of the antidepressant-like effects of rolipram, and that PDE4D-regulated cyclic adenosine monophosphate signaling may play a role in the pathophysiology and pharmacotherapy of depression. [Copyright &y& Elsevier]

Both DR4 and DR5 have recently been identified as membrane death receptors that are activated by their ligand TRAIL to engage the intracellular apoptotic machinery. TRID (also named as TRAIL-R3) is an antagonist decoy receptor and lacks the cytoplasmic death domain. TRID protects from TRAIL-induced apoptosis by competing with DR4 and DR5 for binding to TRAIL. TRID has been shown to be overexpressed in normal human tissues but not in malignantly transformed cell lines. DR5 is a p53-regulated gene and we have recently reported that DR5 expression is induced in response to genotoxic stress in both a p53-dependent and independent manner (Sheikh et al., 1998). In the current study, we demonstrate that TRID gene expression is also induced by the genotoxic agents ionizing radiation and methyl methanesulfonate (MMS) in predominantly p53 wild-type cells, whereas UV-irradiation does not induce TRID gene expression. Consistent with these results, exogenous wild-type p53 also upregulates the expression of endogenous TRID in p53-null cells. Thus, TRID appears to be a p53 target gene that is regulated by genotoxic stress in a p53-dependent manner. Using primary gastrointestinal tract (GIT) tumors and their matching normal tissue, we also demonstrate for the first time that TRID expression is enhanced in primary tumors of the GIT. It is, therefore, possible that TRID overexpressing GIT tumors may gain a selective growth advantage by escaping from TRAIL-induced apoptosis. [ABSTRACT FROM AUTHOR]

The mechanism of Taxol-induced apoptosis was investigated in MCF-7 human breast carcinoma cells. Taxol-induced apoptosis was associated with phosphorylation of both c-Raf-1 and Bcl-2 and activation of ERK and JNK MAP kinases. The serine protease inhibitor N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) effectively blocked apoptosis, but N-p-tosyl-L-lysine chloromethyl ketone (TLCK), another serine protease inhibitor, was without effect. TPCK treatment also prevented phosphorylation of c-Raf-1 and Bcl-2 in response to Taxol treatment. The serine protease inhibitor did not alter JNK activity, but it enhanced Taxol-induced activation of ERK1/2. Treatment of cells with the inhibitor of MEK activation, PD98059, prevented Taxol-induced ERK activation both in the presence and absence of TPCK, but did not influence survival of either Taxol- or Taxol plus TPCK-treated cells. In addition, PD98059 had no effect on c-Raf-1 or Bcl-2 phosphorylation. Thus, while the Taxol-induced phosphorylations of c-Raf-1 and Bcl-2 proteins appear to be coupled, these events can be disassociated from ERK1/2 activation. In summary, these findings suggest that phosphorylation of c-Raf-1 and Bcl-2, but not ERK1/2, are important signaling events in Taxol-induced apoptosis of MCF-7 breast cancer cells and that a TPCK inhibitable protease(s) is required for these processes. [ABSTRACT FROM AUTHOR]

Introduction: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug–drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. Methods: HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12 weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24 weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. Results: No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17–6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF. Conclusion: E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article. Trial registration: ClinicalTrials.gov; identifier, NCT06019273. [ABSTRACT FROM AUTHOR]

Individuals living in rural areas have a higher incidence rate of stroke than their urban counterparts in China. However, few studies have investigated the association between blood malondialdehyde (MDA), an end product of lipid oxidation caused by reactive oxygen species (ROS), and stroke risk in rural populations. We aimed to investigate whether blood MDA levels contribute to a higher stroke risk in a Chinese elderly population from rural areas. Data from 2011 to 2012 from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national cohort of older adults in China, were analyzed. Smooth curve and multivariable correction analyses were used to evaluate the association between blood MDA levels and stroke risk in elderly populations from rural and urban areas, respectively. The median age of all included participants (N = 1598) was 84.04 years. The results of the smooth curve model revealed a gradual upward trend in the association of blood MDA levels with stroke risk in rural participants but not in urban participants. Similarly, the conditional logistic regression analysis suggested a significant association between MDA levels and stroke risk in rural participants but not in urban participants after adjustments for related confounding factors (age, sex, current smoker, current drinker, regular exercise, BMI and cardiovascular diseases (hypertension, heart disease, atrial fibrillation and diabetes)) were made. In brief, among the elderly population in China, elevated blood MDA levels were associated with increased stroke risk in rural participants but not in urban participants. [ABSTRACT FROM AUTHOR]

Electromagnetically induced transparency (EIT) analogs in classical oscillator systems have been investigated due to their potential in optical applications such as nonlinear devices and the slow-light field. Metamaterials are good candidates that utilize EIT-like effects to regulate optical light. Here, an actively reconfigurable EIT metamaterial for controlling THz waves, which consists of a movable bar and a fixed wire pair, is numerically and experimentally proposed. By changing the distance between the bar and wire pair through microelectromechanical system (MEMS) technology, the metamaterial can controllably regulate the EIT behavior to manipulate the waves around 1.832 THz, serving as a dynamic filter. A high transmittance modulation rate of 38.8% is obtained by applying a drive voltage to the MEMS actuator. The dispersion properties and polarization of the metamaterial are also investigated. Since this filter is readily miniaturized and integrated by taking advantage of MEMS, it is expected to significantly promote the development of THz-related practical applications such as THz biological detection and THz communications. [ABSTRACT FROM AUTHOR]

In this paper, we consider a predator–prey model with Allee effect, fear effect and prey refuge. By considering the prey refuge as a parameter, we give the threshold condition for the stability of the system, and prove that the system undergoes a supercritical Hopf bifurcation. We show that increasing the prey refuge or Allee effect can make the dynamical behavior of the system more complicated; the fear effect or Allee effect has no influence on the prey density, but can lead to a decrease of the predator population at positive equilibrium. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

We study the effects of centralized health management based on hot spring resorts on the physical examination index and sleep quality of people at high risk of chronic diseases. We recruited 114 volunteers at high risk of chronic diseases. We then divided them into 57 in the intervention group and 57 in the control group. The intervention group collectively received 4 weeks (28 days) of comprehensive health management interventions at Tongjing Hotspring Resort, including regular schedules, balanced diet, appropriate exercise, targeted health education, etc. The main outcomes are physical examination indicators (height, weight, waist circumference, blood pressure, lipids, and glucose) and sleep quality. Both groups underwent a questionnaire and physical examination at baseline, 2 weeks and 4 weeks. Intragroup comparisons grouped by exposure criteria showed decreases in BMI, waist circumference, triglycerides, total cholesterol, and blood glucose in the intervention group at both 2 and 4 weeks (all P < 0.05); however, in the control group, only triglycerides decreased at 4 weeks (P < 0.05). Intergroup comparisons showed BMI and waist circumference were significantly lower in the intervention group than in the control group at 4 weeks (all P < 0.05). Intragroup comparisons of insomnia severity index (ISI) scores showed a significant decrease in the intervention group at both 2 and 4 weeks (all P < 0.001) with no significant change in the control group (P > 0.05). Intergroup comparisons showed that the insomnia severity index (ISI) scores were significantly higher in the intervention group than in the control group at baseline (P = 0.006) but became significantly lower than the control group at 2 and 4 weeks (all P < 0.001). Thus, this pattern significantly improved BMI, waist circumference, triglycerides, and sleep in the intervention group. Trial registration number: Chinese Clinical Trials Registry: ChiCTR2100053201, registered 14 Nov 2021. (Retroactive Registration) [ABSTRACT FROM AUTHOR]

Very recently [J. Phys. Chem. A 2018, 122 (11), 3087-3095], we proposed to employ the Pauli energy to identify and determine strong covalent interactions (SCI), whose bond order are equal to or larger than two. This is done through the signature isosurface shape between the two bonding atoms. We discovered that the signature shape for a double, triple, and quadruple covalent bond is like a dumbbell, donut (torus), and four-beats, respectively. Systems with even higher bond orders were examined and confirmed. This work is a follow-up study of our previous work. The dependence of the signature isosurface shape on the choice of methodologies and basis sets is systematically investigated. Its effectiveness and robustness in determining bond orders are highlighted again with more examples. In addition, using the molybdenum dimer in different environments, e.g., in vacuum, sandwiched between molecules, and encapsulated in the C80 cage, as illustrative examples, we show that, generally speaking, bond strength and bond order are two different chemical concepts. For systems containing transition metals, it is not always true that a short metal-metal bond length corresponds to a larger bond order. Put together, these results should provide additional pieces of convincing evidence showing that the SCI index is a robust and reliable density-based descriptor to accurately determine multiple covalent bond orders. [ABSTRACT FROM AUTHOR]

Asian cultivated rice is believed to have been domesticated from a wild progenitor, Oryza rufipogon, offering promising sources of alleles for world rice improvement. Here we first present a high-quality chromosome-scale genome of the typical O. rufipogon. Comparative genomic analyses of O. sativa and its two wild progenitors, O. nivara and O. rufipogon, identified many dispensable genes functionally enriched in the reproductive process. We detected millions of genomic variants, of which large-effect mutations could affect agronomically relevant traits. We demonstrate how lineage-specific expansion of gene families may have contributed to the formation of reproduction isolation. We document thousands of genes with signatures of positive selection that are mainly involved in the reproduction and response to biotic- and abiotic stresses. We show that selection pressures may serve as forces to govern substantial genomic alterations that form the genetic basis of rapid evolution of mating and reproductive systems under diverse habitats. Li et al. provide a chromosome-based genome of the ancestral rice relative Oryza rufipogon using SMRT, 10x and Hi-C. Using comparative genomics analysis, they identify genes important for agronomical traits and provide insights for the evolution of reproductive systems which can facilitate rice breeding programs. [ABSTRACT FROM AUTHOR]

Chronic and systematic inflammation have been related to increased risks of osteopenia and related fracture. However, studies concerning the association between low-grade inflammation and the bone mineral density (BMD) and strength of the femoral neck are still few and inconsistent. This study aimed to examine the relationships between blood inflammatory biomarkers and BMD and femoral neck strength in an adult-based cohort. We retrospectively analyzed a total of 767 participants included in the Midlife in the United States (MIDUS) study. The blood levels of inflammatory markers, including interleukin-6 (IL6), soluble IL-6 receptor, IL-8, IL-10, TNF-α and C-reactive protein (CRP), in these participants were measured, and their associations with the BMD and strength of the femoral neck were determined. We analyzed these 767 subjects with data concerning the BMD, bending strength index (BSI), compressive strength index (CSI), and impact strength index (ISI) in the femoral neck and inflammatory biomarkers. Importantly, our results suggest that strongly negative associations exist between the blood soluble IL6 receptor levels and the BMD (per SD change, Sβ = −0.15; P < 0.001), CSI (per SD change, Sβ = −0.07; P = 0.039), BSI (per SD change, Sβ = −0.07; P = 0.026), and ISI (per SD change, Sβ = −0.12; P < 0.001) in the femoral neck after adjusting for age, gender, smoked cigarettes regularly, number of years drinking, BMI and regular exercise. However, the inflammatory biomarkers, including blood IL-6 (per SD change, Sβ = 0.00; P = 0.893), IL-8 (per SD change, Sβ = −0.00; P = 0.950), IL-10 (per SD change, Sβ = −0.01; P = 0.854), TNF-α (per SD change, Sβ = 0.04; P = 0.260) and CRP (per SD change, Sβ = 0.05; P = 0.137), were not strongly associated with the BMD in the femoral neck under the same conditions. Similarly, there was no significant difference in the relationships between the inflammatory biomarkers (IL-6, IL-8, IL-10, TNF-α and CRP) and the CSI, BSI, and ISI in the femoral neck. Interestingly, in concomitant inflammation-related chronic diseases, only arthritis affected the soluble IL-6 receptor and the CIS (interaction P = 0.030) and SIS (interaction P = 0.050) in the femoral neck. In this cross-sectional analysis, we only observed that high blood levels of soluble IL-6 receptor were strongly associated with reduced BMD and bone strength in the femoral neck. The independent associations between the other inflammatory indicators, including IL-6, IL-8, IL-10, TNF-α and CRP, and the BMD and femoral neck strength in an adult-based cohort were not significant. [ABSTRACT FROM AUTHOR]

Aim: We have previously reported that polyfunctional T cell responses can be induced to the cancer testis antigen NY-ESO-1 in melanoma patients injected with mature autologous monocyte-derived dendritic cells (DCs) loaded with long NY-ESO-1-derived peptides together with α-galactosylceramide (α-GalCer), an agonist for type 1 Natural Killer T (NKT) cells. Objective: To assess whether inclusion of α-GalCer in autologous NY-ESO-1 long peptide-pulsed DC vaccines (DCV + α-GalCer) improves T cell responses when compared to peptide-pulsed DC vaccines without α-GalCer (DCV). Design, setting and participants: Single-centre blinded randomised controlled trial in patients ≥ 18 years old with histologically confirmed, fully resected stage II–IV malignant cutaneous melanoma, conducted between July 2015 and June 2018 at the Wellington Blood and Cancer Centre of the Capital and Coast District Health Board. Interventions: Stage I. Patients were randomised to two cycles of DCV or DCV + α-GalCer (intravenous dose of 10 × 106 cells, interval of 28 days). Stage II. Patients assigned to DCV + α-GalCer were randomised to two further cycles of DCV + α-GalCer or observation, while patients initially assigned to DCV crossed over to two cycles of DCV + α-GalCer. Outcome measures: Primary: Area under the curve (AUC) of mean NY-ESO-1-specific T cell count detected by ex vivo IFN-γ ELISpot in pre- and post-treatment blood samples, compared between treatment arms at Stage I. Secondary: Proportion of responders in each arm at Stage I; NKT cell count in each arm at Stage I; serum cytokine levels at Stage I; adverse events Stage I; T cell count for DCV + α-GalCer versus observation at Stage II, T cell count before versus after cross-over. Results: Thirty-eight patients gave written informed consent; 5 were excluded before randomisation due to progressive disease or incomplete leukapheresis, 17 were assigned to DCV, and 16 to DCV + α-GalCer. The vaccines were well tolerated and associated with increases in mean total T cell count, predominantly CD4+ T cells, but the difference between the treatment arms was not statistically significant (difference − 6.85, 95% confidence interval, − 21.65 to 7.92; P = 0.36). No significant improvements in T cell response were associated with DCV + α-GalCer with increased dosing, or in the cross-over. However, the NKT cell response to α-GalCer-loaded vaccines was limited compared to previous studies, with mean circulating NKT cell levels not significantly increased in the DCV + α-GalCer arm and no significant differences in cytokine response between the treatment arms. Conclusions: A high population coverage of NY-ESO-1-specific T cell responses was achieved with a good safety profile, but we failed to demonstrate that loading with α-GalCer provided an additional advantage to the T cell response with this cellular vaccine design. Clinical trial registration: ACTRN12612001101875. Funded by the Health Research Council of New Zealand. [ABSTRACT FROM AUTHOR]

The sterilisation of surgical instruments is a major factor in infection control in the operating room (OR). All items used in the OR must be sterile for patient safety. Therefore, the present study evaluated the effect of far-infrared radiation (FIR) on the inhibition of colonies on packaging surface during the long-term storage of sterilised surgical instruments. From September 2021 to July 2022, 68.2% of 85 packages without FIR treatment showed microbial growth after incubation at 35 °C for 30 days and at room temperature for 5 days. A total of 34 bacterial species were identified, with the number of colonies increasing over time. In total, 130 colony-forming units were observed. The main microorganisms detected were Staphylococcus spp. (35%) and Bacillus spp. (21%) , Kocuria marina and Lactobacillus spp. (14%), and mould (5%). No colonies were found in 72 packages treated with FIR in the OR. Even after sterilisation, microbial growth can occur due to movement of the packages by staff, sweeping of floors, lack of high-efficiency particulate air filtration, high humidity, and inadequate hand hygiene. Thus, safe and simple far-infrared devices that allow continuous disinfection for storage spaces, as well as temperature and humidity control, help to reduce microorganisms in the OR. [ABSTRACT FROM AUTHOR]

The design of materials that can simulate the magical and complex phenomena in nature through simple theoretical and process design are essential and challenging. Here we describe a tough polyhexahydrotriazine film actuator bent in response to dichloromethane through simple theory and technological design, and its curving behavior is consistent with the snapping of a Venus flytrap. Theoretical calculation demonstrates that the driving force of the actuator derives from the C–H/π interaction and halogen bond interaction between dichloromethane and polymer chains. Driven by two supramolecular interactions, the actuator bends and accumulates elastic potential energy, releasing elastic potential energy through snapping deformation, which can lift objects 20 times heavier than itself. Over time, the actuator remains bent, and the degree of bending increases, allowing it to wrap tightly around the object, with potential applications in protective materials and intelligent crawling systems. In addition, the actuator possesses good mechanical properties, solvent resistance, and thermal properties, with the ability to resist extreme conditions. [ABSTRACT FROM AUTHOR]

Imperatorin, an active ingredient extracted from Angelica and Qianghuo, has anti-inflammatory, anti-oxidative stress damage, blocking calcium channels, and other properties. Our preliminary findings revealed the protective role of imperatorin in the treatment of vascular dementia, we further explored the underlying mechanisms concerning the neuroprotection function of imperatorin in vascular dementia. The cobalt chloride (COCl2)-induced chemical hypoxia and hypoglycemia of hippocampal neuronal cells was applied as in vitro vascular dementia model. Primary neuronal cells was isolated from the hippocampal tissue of SD suckling rats within 24 h of birth. Hippocampal neurons were identified by immunofluorescence staining of microtubule-associated protein 2. Silencing or overexpression of Nrf2 was conducted by transfection of corresponding plasmids in hippocampal neuronal cells. Cell viability was detected by MTT assay to determine the optimal modeling concentration of CoCl2. Mitochondrial membrane potential, intracellular reactive oxygen species and apoptosis rate was measured by flow cytometry. The expression of anti-oxidative proteins was detected by quantitative real-time PCR and western blot, including Nrf2, NQO-1 and HO-1. Nrf2 nuclear translocation was detected using laser confocal microscopy. The modeling concentration of CoCl2 was 150umol/l, and the best interventional concentration of imperatorin was 7.5umol/l. Significantly, imperatorin facilitated the nuclear localization of Nrf2, promoted the expressions of Nrf2, NQO-1, and HO-1 relative to the model-control group. Moreover, imperatorin reduced the mitochondrial membrane potential and ameliorated CoCl2-induced hypoxic apoptosis in hippocampal neurons. On the contrary, silencing Nrf2 completely abrogated the protective effects of imperatorin. Imperatorin might be an effective drug for preventing and treating vascular dementia. [ABSTRACT FROM AUTHOR]

To accurately identify atoms on noisy transmission electron microscope images, a deep learning (DL) approach is employed to estimate the map of probabilities at each pixel for being an atom with element discernment. Thanks to a delicately-designed loss function and the ability to extract features, the proposed DL networks can be trained by a small dataset created from approximately 30 experimental images, each with a size of 256 × 256 pixels2. The accuracy and robustness of the network were verified by resolving the structural defects of graphene and polar structures in PbTiO3/SrTiO3 multilayers from both the general TEM images and their imitated images on which intensities of some pixels lost randomly. Such a network has the potential to identify atoms from very few images of beam-sensitive material and explosive images recorded in a dynamical atomic process. The idea of using a small-dataset-trained DL framework to resolve a specific problem may prove instructive for practical DL applications in various fields. [ABSTRACT FROM AUTHOR]