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Abstract Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a soluble form of TREM-1 released during inflammation. Elevated sTREM-1 levels have been found in neuropsychiatric systemic lupus erythematosus (NPSLE) patients; yet, the exact mechanisms remain unclear. This study investigated the role of sTREM-1 in brain damage and its underlying mechanism. The sTREM-1 recombinant protein (2.5 μg/3 μL) was injected into the lateral ventricle of C57BL/6 female mice. After intracerebroventricular (ICV) injection, the damage in hippocampal neurons increased, and the loss of neuronal synapses and activation of microglia increased compared to the control mice (treated with saline). In vitro. after sTREM-1 stimulation, the apoptosis of BV2 cells decreased, the polarization of BV2 cells shifted to the M1 phenotype, the phagocytic function of BV2 cells significantly improved, while the PI3K–AKT signal pathway was activated in vivo and in vitro. PI3K–AKT pathway inhibitor LY294002 reversed the excessive activation and phagocytosis of microglia caused by sTREM-1 in vivo and in vitro, which in turn improved the hippocampus damage. These results indicated that sTREM-1 activated the microglial by the PI3K–AKT signal pathway, and promoted its excessive phagocytosis of the neuronal synapse, thus inducing hippocampal damage. sTREM-1 might be a potential target for inducing brain lesions.

In this paper, a process of corrugated wide limit alignment (CWLA) was used to improve the stretch formability of large-dimension AZ31 Mg alloy sheets by inducing tensile twins. The effects of {10 1¯ 2} tensile twins on microstructure evolution, mechanical properties and stretch formability of AZ31 Mg alloy sheet was studied. The results indicated that the CWLA samples exhibited a weakened basal texture and a high fraction of twin boundaries due to the twinning and recrystallization behavior. After CWLA and annealing for 30min at 300 °C, the strain-hardening exponent value increased from 0.2 to 9.4, the Lankford value decreased from 2.85 to 0.37, and the Erishen value was increased by ∼95% compared to the as-received samples. The present study would provide a new insight into the development of Mg alloys having excellent stretch formability.

Tyrosinase is an important rate-limiting enzyme in melanin biosynthesis. To find potential tyrosinase inhibitors with anti-melanogenic activity, a series of indole-thiazolidine-2,4-dione derivatives 5a~5z were synthesized by incorporating indole with thiazolidine-2,4-dione into one compound and assayed for their biological activities. All compounds displayed tyrosinase inhibitory activities and 5w had the highest anti-tyrosinase inhibitory activity with an IC50 value of 11.2 μM. Inhibition kinetics revealed 5w as a mixed-type tyrosinase inhibitor. Fluorescence quenching results indicated that 5w quenched tyrosinase fluorescence in a static process. CD spectra and 3D fluorescence spectra results suggested that the binding of 5w with tyrosinase could change the conformation and microenvironment of tyrosinase. Molecular docking also represented the binding between 5w and tyrosinase. Moreover, 5w could inhibit tyrosinase activity and melanogenesis both in B16F10 cells and the zebrafish model. Therefore, compound 5w could serve as a tyrosinase inhibitor with anti-melanogenic activity.

In the coal-grain composite area (CGCA) of eastern China with a high groundwater table (HGT), underground coal mining subsidence has caused extensive submergence of farmland, posing a significant threat to regional food security. Currently, land reclamation techniques in mining subsidence areas primarily focus on post-mining reclamation (PMR) of stable subsidence land with a low reclamation rate. This study investigated the application of concurrent mining and reclamation (CMR) technology for unstable subsidence land in a representative HGT mining area, namely the Guqiao Coal Mine in the Huainan Coalfield. Firstly, mining subsidence prediction and geographic information technology were employed to simulate the spatio-temporal evolution of dynamic mining subsidence, taking into consideration the mining plan. Subsequently, phased reclamation parameters were quantitatively designed by integrating the dynamic mining subsidence and surface reclamation measures. Lastly, scenario simulations were conducted to discuss the effectiveness of CMR in comparison with non-reclamation (NR) and PMR. Additionally, reclamation and ecological restoration strategies for coal mining subsidence areas with comprehensive governance modes were proposed. The findings indicated that mining activities have led to a reduction in both the quantity and quality of original farmland, with 70% of the farmland submerged and rendered uncultivable. In contrast to PMR, which achieved a reclamation rate of 29%, CMR can significantly increase the farmland reclamation rate to 69% while also prolonging the service life of farmland. This study provides theoretical support and technical references for promoting sustainable mining practices, protecting farmland, and facilitating the high-quality development of coal resource-based cities.

Microsampling elemental analysis is widely used for gemstone and mineralogy traceability. Using laser ablation inductively coupled plasma mass spectrometry combined with chemometrics, the contents of 56 elements in turquoise samples from 5 distinct producing areas in 3 nations were measured. An origin identification model for turquoise samples from various producing areas was established through random forest importance analysis, principal component analysis, and linear discriminant analysis. When combined with random forest importance screening, the traceability efficiency of principal component analysis is significantly improved. Moreover, by taking 48 elements as characteristic variables and introducing them into the discriminant model, a Fisher discriminant model for identifying the origin of turquoise was successfully established. The effective element fingerprint information of turquoise species is closely related to the species origin, and the accuracy of cross-validation reaches 99.5%, demonstrating the feasibility of the proposed model for the identification of the origin of turquoise samples.

The immunity potency upon natural infection or vaccination is the main concern for the vaccine strategy of severe acute respiratory syndrome coronavirus 2（SARS COV-2 variant）, especially the recently reported Omicron variant (B.1.1.529). In this study, 200 recipients immunized with three doses of a COVID-19-inactivated vaccine were enrolled, whose serum samples were collected within 2 months after the third immunization. The neutralizing activity of sera against the pseudotyped Omicron variant, prototype, and Delta variant was determined. Our results demonstrated that the positive neutralization activity was 95.5% for the Omicron variant, 99.5% for the prototype, and 98.5% for the Delta variant. The geometric mean titers （GMT） for the Omicron variant was 49 and maintained sustained immune levels for 2 months, which decreased by 4.9-fold and 3.0-fold compared with the prototype (GMT, 239) and Delta variant (GMT, 148), respectively. In summary, our study demonstrated that three doses of a COVID-19-inactivated vaccine effectively yielded potent cross-neutralizing activity against the Omicron variant at 2 months after the third vaccination.

The cloud storage service provides the storage and access function for massive data, reducing the management cost for large amounts of data. The data integrity verification scheme in cloud storage can be employed to help users confirm the integrity of outsourced data. Although public data integrity verification schemes allow users to outsource data integrity verification to third-party auditor (TPA), there are still many problems with centralized TPA in terms of security and efficiency. In recent years, researchers have tried to apply blockchain technology to solve the centralization problem of traditional methods, but these schemes do not pay attention to the problem of efficiency degradation caused by the use of blockchain technology. This paper proposes an efficient data integrity verification scheme for multi-cloud storage services by using blockchain technology. The overall verification can verify the integrity of multiple CSPs, which solves the problems of low computational efficiency. Local verification can trace the source to the specific damaged CSP, which is more secure and reliable. In addition, this paper puts the data verification process directly in the blockchain for public execution and provides data integrity verification services without the assistance of any third-party audit platform, avoiding the security problems caused by untrusted TPA. Theoretical analysis and experiments verify the safety and effectiveness of the scheme.

Abstract Background Ankylosing spondylitis is a progressive, disabling joint disease that affects millions worldwide. Given its unclear etiology, studies of ankylosing spondylitis relied heavily on drug-induced or transgenic rodent models which retain only partial clinical features. There is obviously a lack of a useful disease model to conduct comprehensive mechanistic studies. Methods We followed a group of cynomolgus monkeys having joint lesions reported of spinal stiffness for 2 years by conducting hematological testing, radiographic examination, family aggregation analysis, pathological analysis, and genetic testing. Results The results confirmed that these diseased animals suffered from spontaneous ankylosing spondylitis with clinical features recapitulating human ankylosing spondylitis disease progression, manifested by pathological changes and biochemical indicators similar to that of ankylosing spondylitis patients. Conclusion The study offers a promising non-human primate model for spontaneous ankylosing spondylitis which may serve as an excellent substitute for its pre-clinical research.

Abstract Background Neonates possess an immature and plastic immune system, which is a major cause of some diseases in newborns. Necrotizing enterocolitis (NEC) is a severe and devastating intestinal disease that typically affects premature infants. However, the development of intestinal immune cells in neonates and their roles in the pathological process of NEC have not been elucidated. Results We examined the ontogeny of intestinal lamina propria lymphocytes in the early life of mice and found a high percentage of RORγt+ cells (containing inflammatory Th17 and ILC3 populations) during the first week of life. Importantly, the proportion of RORγt+ cells of intestinal lamina propria further increased in both NEC mice and patients tissue than the control. Furthermore, the application of GSK805, a specific antagonist of RORγt, inhibited IL-17A release and ameliorated NEC severity. Conclusions Our data reveal the high proportion of RORγt+ cells in newborn mice may directly contribute to the development of NEC.

This thesis starts with a worrisome observation tied to various phenomena across modern built environments: humans today are experiencing a weakened relatedness to and reduced intimacy with the world around them. In stark contrast to the general trend, however, most Chinese literati gardens maintain their traditional rich conditions, enabling their visitors to experience a unique, high-quality experience of relatedness to and intimacy with the world, which may serve as an antidote to the existing disruptive modern condition. What lessons can be learned from the Chinese literati gardens to address this weakened intimacy of relatedness in modern built environments? Motivated by this question, this thesis takes the Heideggerian notion of Nearness as its foundation. Through a contextually relevant interpretation of the meaning of Nearness in Heideggerian discourse, it first establishes a theoretical framework through which to assess how the experience of Nearness—the ontological relatedness to and intimacy with the world— generally occurs within built environments. Next, taking the Master of the Nets Garden as a case study, it reveals the various embedded spatial-experiential settings and complex mechanisms that continuously facilitate rich, strong, and multi-dimensional experiences of Nearness. Finally, it reflects on some of the key relevant issues, including what benefits and enlightenments the findings of this thesis could bring to current architectural practices. Overall, by exploring this essential aspect of the literati garden, the thesis equips contemporary spatial practitioners with the theoretical and practical tools necessary to recapture the high-quality experiences of Nearness within their works in the modern era.

Th17 cells are powerful inflammation promoters in the pathogenesis of abdominal aortic aneurysms (AAAs). Myeloid-derived suppressor cells (MDSCs) can promote the differentiation of Th17 cells in chronic inflammatory autoimmune injury. Here, we aim to examine whether MDSCs regulate the differentiation of Th17 cells to participate in the development of AAA. We demonstrated an abnormal accumulation of MDSCs in AAA patients, which was positively associated with Th17 cells. We established angiotensin II-induced apolipoprotein E knockout mice and found the impaired immunosuppressive function of M-MDSCs. After systemic injection of anti-Gr-1 antibody in AAA mice to deplete circulating MDSCs, AAA formation and the differentiation of Th17 cells were abolished, and the overexpression of inducible T-cell costimulator (ICOS) on Th17 cells was reversed accordingly. Regulating the expression of ICOS ligand (ICOSL) on MDSCs affects the differentiation of Th17 cells. The adoptive transfer of ICOSLlowMDSCs in AAA mice inhibited the differentiation of Th17 cells and the development of AAA. Meanwhile, rIL-3 promoted the survival and immunosuppressive dysfunction of MDSCs, upregulated ICOSL expression on MDSCs by inhibiting activation of the PI3K/AKT signaling pathway, and regulated MDSCs to promote the differentiation of Th17 cells via the ICOSL-ICOS axis. An increase in serum IL-3, ICOSL+MDSCs, and ICOS+Th17 cells was detected in AAA patients, and IL-3 levels were positively correlated with the proportion of ICOSL+MDSC cells. In conclusion, we uncovered a pivotal role of MDSCs in promoting the differentiation of Th17 cells through the IL-3-ICOSL-ICOS axis during AAA, providing an important theoretical basis for understanding the pathogenesis of AAA.

The increasingly aging society led to a rise in the prevalence of chronic wounds (CWs), posing a significant burden to public health on a global scale. One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive (hyper)inflammation. A variety of immunomodulatory therapies have been proposed to address this condition. Yet, to date, current delivery systems for immunomodulatory therapy remain inadequate and lack efficiency. This highlights the need for new therapeutic delivery systems, such as nanosystems, to manage the pathological inflammatory imbalance and, ultimately, improve the treatment outcomes of CWs. While a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects, the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively scarce. Therefore, this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs, discuss important advancements in our understanding of CW healing, and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of CWs. In addition, we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field.

ObjectiveTo determine the effectiveness of transcranial magnetic stimulation in improving cerebellar ataxia.Data sourcesPubMed, EMBASE, the Cochrane Library, Springer, Science Direct, the China National Knowledge Infrastructure (CNKI) and the China Science and Technology Journal Database (VIP) were searched until 2022.Review methodsTrials with transcranial magnetic stimulation on the effects on cerebellar ataxia were included, and the effect size was evaluated using the standardized mean difference (SMD) or mean difference (MD) and a 95% confidence interval (CI).ResultsEight studies comprising 272 participants, published between 2014 and 2022, were included. The results revealed that the effect of TMS on patients with cerebellar ataxia as assessed by the International Cooperative Ataxia Rating Scale (ICRAS), the Scale for the Assessment and Rating of Ataxia (SARA), the Berg Balance Scale (BBS), and the Timed Up and Go (TUG) test was statistically significant (P < 0.01) with low heterogeneity among the studies (I2 = 4, 27, 0, and 0% respectively).ConclusionThe effects of transcranial magnetic stimulation in improving cerebellar ataxia in the affected patients are significant. TMS targeting the cerebellar structures can induce changes in the excitability of the cerebellar-thalamus-cortical pathways; thus, it is necessary to carry out large-scale research with good design and high quality in the future.

IntroductionFor working parents with dependent children, parenthood is essential to their “life” component, which could profoundly influence their work experiences. Since depressive moods rise sharply in adolescence, this study aims to investigate the relationship between children's depressive moods and parental family-work interaction. Integrating the literature on emotions and family-work interaction, I propose that adolescents' depressive moods (over the past 2 weeks) decrease parents' work engagement via increased parents' family-work conflict. Further, I hypothesize that adolescent performance-avoidance, a key trait related to adolescents' long-term emotional experiences, moderates the indirect relationship.MethodsUsing a multiple-source, time-lagged design, I tested hypotheses using data collected from 468 adolescent-parent dyadic from China.ResultsI found that adolescents' depressive moods relate negatively to their parents' work engagement via increased parents' family-work conflict when adolescents have low levels of performance-avoidance. When an adolescent has a high level of performance-avoidance, parents show a relatively higher degree of family-work conflict and lower work engagement regardless of adolescents' depressive moods.DiscussionI discuss the theoretical and practical implications for employee family-work interaction and work engagement.

Abstract Chalcogenide phase change materials (PCMs) have been extensively applied in data storage, and they are now being proposed for high resolution displays, holographic displays, reprogrammable photonics, and all-optical neural networks. These wide-ranging applications all exploit the radical property contrast between the PCMs’ different structural phases, extremely fast switching speed, long-term stability, and low energy consumption. Designing PCM photonic devices requires an accurate model to predict the response of the device during phase transitions. Here, we describe an approach that accurately predicts the microstructure and optical response of phase change materials during laser induced heating. The framework couples the Gillespie Cellular Automata approach for modelling phase transitions with effective medium theory and Fresnel equations. The accuracy of the approach is verified by comparing the PCM’s optical response and microstructure evolution with the results of nanosecond laser switching experiments. We anticipate that this approach to simulating the switching response of PCMs will become an important component for designing and simulating programmable photonics devices. The method is particularly important for predicting the multi-level optical response of PCMs, which is important for all-optical neural networks and PCM-programmable perceptrons.

Abstract Background Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe complication, which involves pathological damage to the brain and cognitive function. However, its exact mechanism of action still remains unclear. In this study, we explored the role of microglia in the cognitive dysfunction of NPSLE mice. We also analyzed and compared the metabolites in the hippocampal tissues of the lupus model and control mice. Methods MRL/MpJ-Faslpr (MRL/lpr) female mice were used as the NPSLE mouse model. Metabolomics was used to assess hippocampal glycolysis levels. Glucose, lactic acid, IL-6, and IL-1β of the hippocampus were detected by ELISA. Based on the glycolysis pathway, we found that pyruvate kinase isoform M2 (PKM2) in the hippocampus was significantly increased. Thus, the expression of PKM2 was detected by qRT-PCR and Western blotting, and the localization of PKM2 in microglia (IBA-1+) or neurons (NeuN+) was assessed by immunofluorescence staining. Flow cytometry was used to detect the number and phenotype of microglia; the changes in microglial phagocytosis and the β-catenin signaling pathway were detected in BV2 cells overexpressing PKM2. For in vivo experiments, MRL/lpr mice were treated with AAV9-shPKM2. After 2 months, Morris water maze and conditional fear tests were applied to investigate the cognitive ability of mice; H&E and immunofluorescence staining were used to evaluate brain damage; flow cytometry was used to detect the phenotype and function of microglia; neuronal synapse damage was monitored by qRT-PCR, Western blotting, and immunofluorescence staining. Results Glycolysis was elevated in the hippocampus of MRL/lpr lupus mice, accompanied by increased glucose consumption and lactate production. Furthermore, the activation of PKM2 in hippocampal microglia was observed in lupus mice. Cell experiments showed that PKM2 facilitated microglial activation and over-activated microglial phagocytosis via the β-catenin signaling pathway. In vivo, AAV9-shPKM2-treated mice showed decreased microglial activation and reduced neuronal synapses loss by blocking the β-catenin signaling pathway. Furthermore, the cognitive impairment and brain damage of MRL/lpr mice were significantly relieved after microglial PKM2 inhibition. Conclusion These data indicate that microglial PKM2 have potential to become a novel therapeutic target for treating lupus encephalopathy.

Lu et al. develop a deep-learning based detection system for identifying pathological myopia and myopic macular legions in retinal fundus images. The system performance is comparable to human experts, but much faster, easing the burden of human time on screening for myopia.

Gas diffusion in nano-scale porous media of deeply burried shale includes bulk diffusion (Fick and Knudsen diffusions) and surface diffusion. To reveal the migration mechanism of this process, the influence of temperature and pressure on diffusion coefficient needs to be quantitatively evaluated. A case study was made with the Cambrian Niutitang Formation in the Maoping area, Zigui, western Hubei, South China. Gas diffusion was simulated by isobaric diffusion experiments under different temperature and pressure conditions. The results indicated that: (1) The diffusion coefficient DF decreases with increasing of pressure (when the pressure is higher than 30 MPa, DF tends to be constant), and increases with increasing of temperature; (2) In the high temperature-pressure setting, DF is affected significantly by pressure and generally tends to decrease. Moreover, the impacts of temperature, pressure, porosity and lithology were quantitatively calculated, and a mathematical model of gas diffusion was established, which had comparable results with simulation experiment. The following conclusions were thus drawn: (1)Higher temperature will cause stronger molecular kinetic energy, resulting in increasing bulk and surface diffusion coefficients, while higher pressure will slightly strengthen the Fick and surface diffusions, but significantly limit the Knudsen diffusion, and cause lower total diffusion coefficient; (2) Larger pore size leads to stronger bulk diffusion, but weaker surface diffusion. Finally, according to the studies of a specific research block, high pressure setting is conducive to the preservation of nano-scale porous gas reservoir in shale, while the uplift accompanied by pressure release is the main stage of shale gas loss.

Abstract Recent studies indicate that Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) can function as the signal of pattern recognition receptors, which play a pivotal role in the pathogenesis of the autoimmune disease. Systemic lupus erythematosus (SLE) is a classic autoimmune disease. Previous reports mainly focused on the potential role of TLRs in regulating the development of SLE, but little is known about the role of CLRs in the progression of SLE. Our previous studies showed that the inflammation-mediated accumulation of myeloid-derived suppressor cells (MDSCs) including granulocytic (G-MDSCs) and monocytic (M-MDSCs) participated in the pathogenesis of lupus. Mice deficient in Card9 (the downstream molecule of CLRs) were more susceptible to colitis-associated cancer via promoting the expansion of MDSCs. Whether the abnormal activation of CLRs regulates the expansion of MDSCs to participate in the pathogenesis of lupus remains unknown. In the present study, the expressions of CLRs were examined in both SLE patients and mouse models, revealing the expression of Dectin3 was positively correlated with SLEDAI. Dectin3 deficiency retarded the lupus-like disease by regulating the expansion and function of MDSCs. The mechanistic analysis revealed that Dectin3 deficiency promoted FoxO1-mediated apoptosis of MDSCs. Syk-Akt1-mediated nuclear transfer of FoxO1 increased in Dectin3-deficient MDSCs. Notedly, the accumulation of M-MDSCs mainly decreased in Dectin3−/− lupus mice, and the nuclear transfer of FoxO1 negatively correlated with the expression of LOX-1 on M-MDSCs. The silencing of FoxO1 expression in Dectin3−/− mice promoted the expansion of LOX-1+ M-MDSCs in vivo, and LOX-1+ M-MDSCs increased the differentiation of Th17 cells. Both LOX-1 expression on M-MDSCs and Dectin3 expression on MDSCs increased in patients with SLE. These data indicated that increased LOX-1+ M-MDSCs were related to the exacerbation of SLE development and might be potential target cells for the treatment of SLE.

Abstract Background Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal malignancy, which produces osteoid, bone, or chondroid material and is located in the soft tissue without attachment to skeletal bones and periosteum. One of the things that ESOS originated from mesentery is much rarer. Case presentation A 75-year female had a history of pain in the left lower abdomen for more than 4 months. Abdominal computerized tomography (CT) and magnetic resonance imaging revealed a large, irregular, and solid-cystic mass (largest diameter was 11.5 cm). The tumor was radically removed during an open operation. It was composed of abundant osteoid and polyhedral-shaped tumor cells with high atypia and high mitotic activity microscopically. The final pathological diagnosis was osteoblastic osteosarcoma, arising from the sigmoid mesocolon with negative margins. A 9-month follow-up by CT exhibited signs of peritoneal metastasis. Conclusions Given the rarity of cases of mesenteric ESOS, diagnosis mainly depended on pathology findings or should be taken into consideration when the mesenteric mass was found. Its most effective treatment had not been determined, with surgical excision being generally accepted. Ensuring negative surgical margins may be an important factor affecting prognosis.

Abstract Background Restenosis after angioplasty is a major challenge for the treatment of coronary artery diseases. Facilitation of vascular smooth muscle cell (VSMC) apoptosis may be an attractive approach to decrease the incidence of restenosis. We synthesized a 16-amino acid mitofusin-2 (Mfn-2) gene related peptide (MRSP) based on the sequence of the p21ras signature motif, the smallest functional sequence of the Mfn-2 gene with proapoptotic properties in VSMC. We investigated whether MRSP enhanced apoptotic activities to inhibit VSMC accumulation and neointimal hyperplasia in rats with carotid balloon injury. Methods VSMCs were treated with different concentrations of MRSP, the PI3K agonist 740 Y-P and the inhibitor LY294002. Cell apoptosis and related pathway molecules were assessed. MRSP was also given to rats with carotid artery balloon injury. Neointimal hyperplasia and cell apoptotic pathways were detected. Results In vitro experiments revealed that MRSP treatment significantly increased VSMC apoptosis and induced increases in procaspase-9 cleavage, caspase-3 activation, cytochrome c release from mitochondria to the cytoplasm and the Bax/Bcl-2 ratio but not caspase-8 expression, indicating that the mitochondrial apoptotic cascade was activated by MRSP, which might be attributed to suppression of the PI3K/Akt signaling pathway. We further found that the PI3K agonist 740 Y-P prevented and that the inhibitor LY294002 strengthened the proapoptotic effects of MRSP. MRSP strongly inhibited neointimal hyperplasia and VSMC accumulation, but increased VSMC apoptosis in the vascular wall after balloon injury. Moreover, MRSP substantially enhanced Bax and cleaved caspase-3 expression and decreased Bcl-2 levels in intima, accompanied by decreased levels of phosphorylated Akt and PI3K in vivo. Conclusions Taken together, the present study showed that MRSP treatment results in a strong proapoptotic effect by activating the mitochondrial apoptotic cascade through suppression of the PI3K/Akt pathway.

Since the moon’s revolution cycle is exactly the same as its rotation cycle, we can only see the moon always facing Earth in the same direction. Based on the clean particle radiation environment of the moon, a neutral atomic telemetry base station could be established on the lunar surface facing Earth to realize long-term continuous geomagnetic activity monitoring. Using the 20°×20° field of view, the 0.5°×0.5° angle resolution, and the ~0.17 cm²sr geometric factor, a two-dimensional ENA imager is being designed. The magnetospheric ring current simulation at a 4–20 keV energy channel for a medium geomagnetic storm (Kp=5) shows the following: 1) at ~60 Rᴇ (Rᴇ is the Earth radius), the imager can collect 10⁴ ENA events for 3 min to meet the statistical requirements for 2D coded imaging data inversion, so as to meet requirements for the analysis of the substorm ring current evolution process of magnetic storms above medium; 2) the ENA radiation loss puzzles in the magnetopause and magnetotail plasma sheet regions have been deduced and revealed using the 2-D ENA emission model. High spatial-temporal resolution ENA imaging monitoring of these two important regions will provide the measurement basis for the solar wind energy input process and generation mechanism; 3) the average sampling interval of ENA particle events is about 16 ms at the moon’s orbit; the spectral time difference for the set energy range is on the order of minutes, which can provide location information to track the trigger of geomagnetic storm particle events.

ObjectivesWith the deepening of non-drug intervention research on human mental health, more and more attention has been paid to the benefits of horticultural activities and green exercise on physical and psychological health. This study compared the affect improvement between horticultural activities with the same intensity and green exercise and that with or without green plants to verify the value of horticultural activities and green exercise in improving human affect and the importance of green plants.MethodsA total of 160 subjects aged 18–26 years (average age 22.5 years) were recruited and randomly divided into a control group, a horticultural activity group with green plants, a horticultural activity group without green plants, and a green exercise group. Demographics, sociological variables, and daily physical activity levels were investigated. Green space at Zhejiang Normal University was selected as the test site. After finishing the preparation work, the subjects sat quietly for 8 min before the pre-test. The horticultural group completed 20 min of horticultural activities {8 min of digging [40%*HRR(heart rate reserve) + RHR(resting heart rate)] + 8 min of transplantation [(50%*HRR + RHR) + 4 min of watering (30%*HRR + RHR)]}. The group returned to a calm state (no less than 20 min) for the post-test. The green exercise group completed a 20-min power bike ride. The activity intensity and activity time of the green exercise group were determined according to the activity intensity and time of the horticultural group. Dependent variables were collected, including blood pressure, positive/negative affects, heart rate variability (RMSSD, SDNN, and LF/HF), and controlled covariate environmental parameters (field temperature, humidity, and noise).Results(1) A significant difference was observed in the improvement effect except for negative affect between the green horticultural activity group and the green exercise group (F = 3.310; ɳp2 = 0.046; p = 0.037). No significant difference was observed in other affect indicators. (2) In the same pattern of with and without green plant horticultural activity group, the green plant horticultural activity group had a better effect on the improvement of affect, and the two groups had a better negative affect (F = 3.310; ɳp2 = 0.046; p = 0.037), SDNN index of heart rate variability(F = 1.035; ɳp2 = 0.015; p = 0.039), and RMSSD index (F = 2.225; ɳp2 = 0.032; p = 0.014), and no significant difference was observed in the improvement effect of other affect indicators between the two groups.ConclusionsHaving green horticulture can give the same intensity as green exercise and affect improvement. Findings suggest that people can choose green exercise or horticultural activities according to their preferences and physical characteristics in the two physical activities. Under the same pattern of horticultural activities, green plants are the key factor in improving the affect of horticultural activities. Choosing suitable plant types in horticultural activities is positively significant in enhancing affect.

PurposeUniversity freshmen are particularly vulnerable as they are undergoing the transition from high school to university with a range of changes. Sleep problems among this group in the Qinghai–Tibet Plateau of China were barely studied. This study aimed to explore sleep disturbance, and its association with quality of life (QoL) and demographic and clinical characteristics among university freshmen in Qinghai–Tibet Plateau, China.MethodsA multistage stratified cluster random sampling method was performed to recruit student participants with a structured questionnaire to collect sociodemographic and clinical characteristics, and lifestyle behaviors. Sleep disturbance including three aspects of sleep disturbance (i.e., difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA)) was assessed using standardized measurement. Multiple logistic regression models were applied to analyze the data.ResultsAmong included 2,769 freshmen, the prevalence of sleep disturbance was 14.8% (95% CI: 14.2–15.5%), and corresponding prevalence of DIS, DMS, and EMA was 8.2% (95% CI: 7.7–8.7%), 8.3% (95% CI: 7.8–8.8%), and 4.2% (95% CI: 3.8–4.6%), respectively. Freshmen with sleeping disturbance had significantly lower QoL in physical [F(1, 2769) = 60.23, p < 0.001], psychological [F(1, 2769) = 46.18, p < 0.001], social [F(1, 2769) = 23.04, p < 0.001], and environment [F(1, 2769) = 6.07, p = 0.01] domains. Multiple logistic regression analyses revealed that having breakfast five times a week or less (less than three times, OR = 1.79, 95% CI: 1.34–2.40; 3–5 times, OR = 1.40, 95% CI: 1.09–1.79), self-perceived severe Internet dependence (OR = 1.71, 95% CI: 1.11–2.65), self-perceived poor health status (OR = 3.44, 95% CI: 2.06–5.74), high academic stress (OR = 1.42, 95% CI: 1.13–1.78), poor relationship with classmates (OR = 3.44, 95% CI: 1.53–7.71), and severe ADHD symptoms (OR = 1.08, 95% CI: 1.05–1.12) were positively associated with sleeping disturbance.ConclusionSleep disturbance was common among freshmen and is associated with poorer QoL. Prevention and intervention strategies should be developed and implemented, especially among the vulnerable university freshman groups.

Extensive research has implicated inflammation and oxidative stress in the development of multiple diseases, such as diabetes, hepatitis, and arthritis. Kinsenoside (KD), a bioactive glycoside component extracted from the medicinal plant Anoectochilus roxburghii, has been shown to exhibit potent anti-inflammatory and anti-oxidative abilities. In this review, we summarize multiple effects of KD, including hepatoprotection, pro-osteogenesis, anti-hyperglycemia, vascular protection, immune regulation, vision protection, and infection inhibition, which are partly responsible for suppressing inflammation signaling and oxidative stress. The protective action of KD against dysfunctional lipid metabolism is also associated with limiting inflammatory signals, due to the crosstalk between inflammation and lipid metabolism. Ferroptosis, a process involved in both inflammation and oxidative damage, is potentially regulated by KD. In addition, we discuss the physicochemical properties and pharmacokinetic profiles of KD. Advances in cultivation and artificial synthesis techniques are promising evidence that the shortage in raw materials required for KD production can be overcome. In addition, novel drug delivery systems can improve the in vivo rapid clearance and poor bioavailability of KD. In this integrated review, we aim to offer novel insights into the molecular mechanisms underlying the therapeutic role of KD and lay solid foundations for the utilization of KD in clinical practice.

PurposeTo apply deep learning (DL) techniques to develop an automatic intelligent classification system identifying the specific types of myopic maculopathy (MM) based on macular optical coherence tomography (OCT) images using transfer learning (TL).MethodIn this retrospective study, a total of 3,945 macular OCT images from 2,866 myopic patients were recruited from the ophthalmic outpatients of three hospitals. After culling out 545 images with poor quality, a dataset containing 3,400 macular OCT images was manually classified according to the ATN system, containing four types of MM with high OCT diagnostic values. Two DL classification algorithms were trained to identify the targeted lesion categories: Algorithm A was trained from scratch, and algorithm B using the TL approach initiated from the classification algorithm developed in our previous study. After comparing the training process, the algorithm with better performance was tested and validated. The performance of the classification algorithm in the test and validation sets was evaluated using metrics including sensitivity, specificity, accuracy, quadratic-weighted kappa score, and the area under the receiver operating characteristic curve (AUC). Moreover, the human-machine comparison was conducted. To better evaluate the algorithm and clarify the optimization direction, the dimensionality reduction analysis and heat map analysis were also used to visually analyze the algorithm.ResultsAlgorithm B showed better performance in the training process. In the test set, the algorithm B achieved relatively robust performance with macro AUC, accuracy, and quadratic-weighted kappa of 0.986, 96.04% (95% CI: 0.951, 0.969), and 0.940 (95% CI: 0.909–0.971), respectively. In the external validation set, the performance of algorithm B was slightly inferior to that in the test set. In human-machine comparison test, the algorithm indicators were inferior to the retinal specialists but were the same as the ordinary ophthalmologists. In addition, dimensionality reduction visualization and heatmap visualization analysis showed excellent performance of the algorithm.ConclusionOur macular OCT image classification algorithm developed using the TL approach exhibited excellent performance. The automatic diagnosis system for macular OCT images of MM based on DL showed potential application prospects.

As the sixth leading cause of cancer death, esophageal cancer is threatening the life of people worldwide. Traditional treatments, such as surgery, chemotherapy, radiotherapy, are facing always augmented challenges including invasion, multidrug resistance (MDR), off-target toxicity. Chemo & Photodynamic synergistic therapy represents one promising strategy for improved treatment efficiency. But it is still hindered by the lack of tumor targeting, deleterious side effects, and unfavorable microenvironment for photodynamic therapy (PDT). To overcome those obstacles, one theranostic nano-assambly drug, GCDs-Ce6/Pt-EGF, was designed and fabricated. Green fluorescence carbon dots (GCDs) with the excellent optical properties, modifiability and low toxicity were prepared as drug carrier. Epidermal growth factor (EGF) was conjugated to the nano-assembly to realize tumor specific targeting. Chlorin e6 (Ce6) in the presence of laser irradiation achieved PDT by generating proapoptosis reactive oxygen species (ROS). Moreover, Ce6 incorporated into GCDs endowed the nano-assambly imaging ability and facilitate image-guided therapy. Pt(IV), cisplatin prodrug, in the nano-assambly depleted the glutathione (GSH) of tumor microenvironment when it was reduced to cytotoxicity Pt(II). Compared with single treatment, GCDs-Ce6/Pt-EGF exhibited enhanced tumor cell killing capacity and better biosafety in vitro and in vivo, especially for EGFR bearing tumor. It paved ways for developing novel theranostic agent to be potentially applied in clinic.

Rapid urban development and increase in construction have significantly altered the surface coverage of cities, resulting in a rise in impervious surfaces such as roofs, streets, and pavements. These changes act as barriers against rainwater infiltration into the soil, leading to a substantial increase in surface runoff. Managing surface runoff has become a critical task in civil engineering and urban planning, as it can mitigate damage and provide opportunities for utilizing excess water. However, traditional flood control and guidance systems tend to be extensive and expensive, prompting researchers to explore cost-effective alternatives that consider all design parameters and variables. In this research, we propose an innovative approach that combines the NSDE (non-dominated sorting differential evolution) metaheuristic algorithm as an optimizer with the SWMM (storm water management model) as a simulator. The objective is to design efficient surface runoff collection networks by thoroughly investigating their hydraulic behaviors. This study focuses on the Chitgar watershed in Tehran, Iran, utilizing the SWMM model and NSDE multi-objective metaheuristic algorithm to determine the optimal dimensions of the channel and its intersecting structures. The aim is to minimize costs and reduce water leakage from the network. A comparison is made between the optimized design results and the existing network plan (without any design modifications). The analysis reveals substantial reductions in water leakage for all three design scenarios: a 7.66% reduction when considering only bridges, a 7.35% reduction with only the canal, and an impressive 95.26% reduction when both the canal and bridges are incorporated. These findings demonstrate the superiority of the optimized designs in terms of cost-effectiveness and the efficient management of surface runoff.

Twisted graphene multilayers are highly tunable flatband systems for developing new phases of matter. Thus far, while orbital ferromagnetism has been observed in valley-polarized phases, the long-range orders of other correlated phases as well as the quantum phase transitions between different orders mostly remain unknown. Here, we report an observation of Coulomb-interaction-driven first-order quantum phase transitions and ferromagnetism in twisted double bilayer graphene (TDBG). At zero magnetic field, the transitions are revealed in a series of steplike abrupt resistance jumps with a prominent hysteresis loop when either the displacement field (D) or the carrier density (n) is tuned across a symmetry-breaking boundary near half filling, indicating a formation of ordered domains. It is worth noting that the good tunability and switching of these states give rise to a memory performance with a large on/off ratio. Moreover, when both spin and valley play the roles at finite magnetic field, we observe abundant first-order quantum phase transitions among normal metallic states from the charge-neutral point, orbital ferromagnetic states from quarter filling, and spin-polarized states from half filling. We interpret these first-order phase transitions in the picture of phase separations and spin-domain percolations driven by multifield tunable Coulomb interactions, in agreement with the Lifshitz transition and the Hartree-Fock calculations. The observed multifield tunable domain structure and its hysteresis resembles the characteristics of multiferroics, revealing intriguing magnetoelectric properties. Our result enriches the correlated phase diagram in TDBG for discovering novel exotic phases and quantum phase transitions, and it will benefit other twisted moiré systems as well.

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases (NDDs) threatening the lives of millions of people worldwide, including especially elderly people. Currently, due to the lack of a timely diagnosis and proper intervention strategy, AD and PD largely remain incurable. Innovative diagnosis and therapy are highly desired. Exosomes are small vesicles that are present in various bodily fluids, which contain proteins, nucleic acids, and active biomolecules, and which play a crucial role especially in intercellular communication. In recent years, the role of exosomes in the pathogenesis, early diagnosis, and treatment of diseases has attracted ascending attention. However, the exact role of exosomes in the pathogenesis and theragnostic of AD and PD has not been fully illustrated. In the present review, we first introduce the biogenesis, components, uptake, and function of exosomes. Then we elaborate on the involvement of exosomes in the pathogenesis of AD and PD. Moreover, the application of exosomes in the diagnosis and therapeutics of AD and PD is also summarized and discussed. Additionally, exosomes serving as drug carriers to deliver medications to the central nervous system are specifically addressed. The potential role of exosomes in AD and PD is explored, discussing their applications in diagnosis and treatment, as well as their current limitations. Given the limitation in the application of exosomes, we also propose future perspectives for better utilizing exosomes in NDDs. Hopefully, it would pave ways for expanding the biological applications of exosomes in fundamental research as well as theranostics of NDDs.

To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (1–20) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC50 values of 3.44 ± 0.36~41.24 ± 0.26 μM compared to the positive control acarbose (IC50 value: 640.57 ± 5.13 μM). In particular, compound 11 displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds 9, 11, 13, 18, and 19 were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds 9, 11, 13, 18, and 19 and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound 11 were also investigated.

Endophytic microbes are a ubiquitous group of plant-associated communities that colonize the intercellular or intracellular host tissues while providing numerous beneficial effects to the plants. All the plant species are thought to be associated with endophytes, majorly constituted with bacteria and fungi. During the last two decades, there has been a considerable movement toward the study of endophytes associated with coffee plants. In this review, the main consideration is given to address the coffee-associated endophytic bacteria and fungi, particularly their action on plant growth promotion and the biocontrol of pests. In addition, we sought to identify and analyze the gaps in the available research. Additionally, the potential of endophytes to improve the quality of coffee seeds is briefly discussed. Even though there are limited studies on the subject, the potentiality of coffee endophytes in plant growth promotion through enhancing nitrogen fixation, availability of minerals, nutrient absorption, secretion of phytohormones, and other bioactive metabolites has been well recognized. Further, the antagonistic effect against various coffee pathogenic bacteria, fungi, nematodes, and also insect pests leads to the protection of the crop. Furthermore, it is recognized that endophytes enhance the sensory characteristics of coffee as a new field of study.

Abstract In this research, the authors concentrated on a rarely studied part in the power transformer's insulation structure: the connection part of radial and axial spacers. An experimental model was constructed to simulate this part. It was experimentally observed that the partial discharge starting in the oil gap created by the axial and radial spacers. Characteristics of the abovementioned partial discharge under repeated lightning impulses were also investigated. A longer interval time seemed to accelerate the insulation property deterioration of the constructed model, which is contrary to those reported in other studies. It was because that the partial discharge occurrence was prevented by the residual space charge at the surface of oil/insulation if the time interval of the repeated impulses was not long enough. Therefore, it is proposed that a long enough interval time or a polarity test is expected in the factory test to exclude the influence of the residual space charge and understand the real insulation property of power transformers.

A three-dimensional numerical model of heading face was established based on Guoerzhuang Coal Mine in Handan, Hebei Province. The effects of different coal seam depths, driving speed and coal mechanical strength on the coal wall sudden extrusion are analyzed by using 3DEC discrete element simulation software, and the orthogonal experiment method is used to rank the influencing factors according to the degree of importance. The results show that there is a positive linear correlation between the maximum horizontal displacement of the fixed point on the heading face and the change of the buried depth, and the direction of the coal wall extrusion displacement is close to the central axis of the roadway, and the horizontal displacement is obviously larger than the vertical displacement. Under the condition of the buried depth of 600 to 1 000 meters, the width of stress concentration area of working face is about 10 meters, and the position of the stress peak is about 5 meters from the working face. The factors affecting the coal wall sudden extrusion in heading face are in the following order: buried depth of coal seam > driving speed > mechanical strength of coal body. The research results provide a reference for further understanding of the coal wall sudden extrusion and preventive measures.

Abstract Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Myeloid-derived suppressor cells (MDSCs) have been found to be involved in the regulation of SLE development. However, little is known about the association between MDSC subsets and the factors that draw MDSCs into abnormal expansion. This study found that the percentage of M-MDSCs increased in mice with pristane-induced lupus. Toll-like receptor (TLR)7 signal activation and high interferon-α (IFN-α) level promoted M-MDSC differentiation in vitro. Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-α-induced bone marrow (BM) differentiation into MDSCs in vitro. In terms of mechanism, whole-genome transcriptome profiling was performed by RNA sequencing, revealing that the expression of the transcription factor IRF-8 was higher in M-MDSCs isolated from pristane-induced lupus mice, compared with control mice. IRF-8 was identified to be crucial for TLR7- and IFN-α-induced BM differentiation into MDSCs in vitro. Furthermore, interferon (IFN) regulatory factor8 (IRF-8) was targeted by miR-451a in M-MDSC differentiation. Of note, metformin-modified M-MDSCs could relieve lupus symptoms in pristane-induced lupus mice. The findings revealed a novel mechanism linking IRF-8/miR-451a to M-MDSC differentiation via the AMPK/mTOR signal pathway during lupus development. This study might provide an important reference for SLE therapy by targeting M-MDSCs.

Abstract Background The objectives of this review were to evaluate the vaccine effectiveness (VE) of the two-dose varicella vaccine for healthy children in China and explore the application of the approach of Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) in observational studies on VE. Methods We searched for observational studies on two-dose varicella VE for children in China aged 1–12 years that were published from 1997 to 2019, and assessed the quality of each study using the Newcastle Ottawa Scale (NOS). We used meta-analysis models to obtain the pooled two-dose VE, and the studies were divided into subgroups and analysed according to whether or not it was an outbreak investigation and its NOS score. The quality of evidence of VEs were rated by approach of the GRADE system. Results A total of 12 studies and 87,196 individuals were included. The pooled two-dose VE was 90% (95% confidence interval [CI]: 69–97%). The VE of outbreak studies (87% [95% CI: 76–93%]) was lower than non-outbreak studies (99% [95% CI: 98–99%]). There was no significant difference in VEs by different NOS quality. The quality of the evidence assessment of pooled two-dose VE was “low”, which was rated down by one category in limitations and publication bias respectively and rated up by two category in large effect. The quality of evidence assessment in subgroup of NOS score ≥ 7 was “moderate”. Conclusions The VE of two-dose varicella vaccine is relatively high in preventing varicella, and is recommended for countries which need further control for varicella. However, higher quality evidence is needed as a supplement for stronger recommendations. The approach of GRADE could be applied for rating the quality of evidence in observational study.

Abstract Background Neuropsychiatric manifestations occur in up to 75% of adult systemic lupus erythematosus (SLE) patients and are one of the major causes of death in SLE patients. Cognitive dysfunction is a typical clinical feature of neuropsychiatric SLE (NPSLE), which seriously affects the quality of life of patients. Dyslipidaemia and thyroid symptoms, which are prevalent in SLE patients, have both been related to neuropsychiatric disturbances, including significant psychiatric and cognitive disturbances. This study aimed to investigate whether cognitive dysfunction in patients with SLE was related to the expression of serum thyroid hormone and lipoprotein levels. Methods A total of 121 patients with SLE and 65 healthy controls (HCs) at Nanjing Drum Tower Hospital completed a cognitive function test, and 81 SLE patients were divided into a high-cognition (n = 33) group and a low-cognition group (n = 48). The clinical and laboratory characteristics of the patients were compared; moreover, correlations between serum HDL-C, LDL-C, F-T3 and F-T4 levels and cognitive function were analysed. Serum levels of APOE, APOA1, IGF-1, and IGFBP7 in 81 patients were detected by ELISA, and the correlation between these four proteins and cognition was analysed separately. Results The patients with SLE with abnormal cognitive function were less educated than the HCs. For low-cognition patients, the levels of albumin, F-T3 (P

C24H18CuN12S2, monoclinic, P21/c (no. 4), a = 11.038(2) Å, b = 8.9312(18) Å, c = 16.083(5) Å, β = 125.66(2)°, V = 1288.2(6) Å3, Z = 2, R gt(F) = 0.0265, wR ref(F 2) = 0.0974, T = 293 K.

Background: Although unplanned hospital readmission is an important indicator for monitoring the perioperative quality of hospital care, few published studies of hospital readmission have focused on surgical patient populations, especially in the elderly. We aimed to investigate if machine learning approaches can be used to predict postoperative unplanned 30-day hospital readmission in old surgical patients.Methods: We extracted demographic, comorbidity, laboratory, surgical, and medication data of elderly patients older than 65 who underwent surgeries under general anesthesia in West China Hospital, Sichuan University from July 2019 to February 2021. Different machine learning approaches were performed to evaluate whether unplanned 30-day hospital readmission can be predicted. Model performance was assessed using the following metrics: AUC, accuracy, precision, recall, and F1 score. Calibration of predictions was performed using Brier Score. A feature ablation analysis was performed, and the change in AUC with the removal of each feature was then assessed to determine feature importance.Results: A total of 10,535 unique surgeries and 10,358 unique surgical elderly patients were included. The overall 30-day unplanned readmission rate was 3.36%. The AUCs of the six machine learning algorithms predicting postoperative 30-day unplanned readmission ranged from 0.6865 to 0.8654. The RF + XGBoost algorithm overall performed the best with an AUC of 0.8654 (95% CI, 0.8484–0.8824), accuracy of 0.9868 (95% CI, 0.9834–0.9902), precision of 0.3960 (95% CI, 0.3854–0.4066), recall of 0.3184 (95% CI, 0.259–0.3778), and F1 score of 0.4909 (95% CI, 0.3907–0.5911). The Brier scores of the six machine learning algorithms predicting postoperative 30-day unplanned readmission ranged from 0.3721 to 0.0464, with RF + XGBoost showing the best calibration capability. The most five important features of RF + XGBoost were operation duration, white blood cell count, BMI, total bilirubin concentration, and blood glucose concentration.Conclusion: Machine learning algorithms can accurately predict postoperative unplanned 30-day readmission in elderly surgical patients.