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[Display omitted] • Rh 1 /BN is explored as a high-performance catalyst for NO 2 − electroreduction to NH 3 (NO 2 RR). • Rh 1 /BN in a flow cell exhibits an NH 3 yield rate of 2165.4 μmol h−1 cm−2 and FE NH3 of 97.83 % at −355.7 mA cm−2. • Combined MD/DFT simulations elucidate that single-atom Rh sites promote the hydrogenation of NO 2 −-to-NH 3 process. • This work highlights the potential of Rh single atom catalyst for practical ammonia electrosynthesis. Electrocatalytic NO 2 − reduction to NH 3 (NO 2 RR) holds great promise as a green method for high-efficiency NH 3 production. Herein, an Rh single-atom catalyst where isolated Rh supported on defective BN nanosheets (Rh 1 /BN) is reported to exhibit the exceptional NO 2 RR activity and selectivity. Extensive experimental and theoretical studies unveil that the high NO 2 RR performance of Rh 1 /BN arises from the single-atom Rh sites, which not only promote the activation and hydrogenation of NO 2 −-to-NH 3 process, but also hamper the undesired hydrogen evolution. Consequently, Rh 1 /BN assembled in a flow cell exhibits the highest NH 3 yield rate of 2165.4 μmol h−1 cm−2 and FE NH3 of 97.83 % at a high current density of 355.7 mA cm−2, ranking it the most efficient catalysts for NO 2 −-to-NH 3 conversion. [ABSTRACT FROM AUTHOR]

[Display omitted] • Atomically dispersed Pd on defective BN (Pd 1 /BN) is explored for NO 2 − electroreduction to NH 3 (NO 2 RR). • Pd 1 /BN exhibits a high NH 3 yield of 347.06 μmol h−1 cm−2 with an NH 3 -Faradaic efficiency of 91.7% at −0.6 V vs. RHE. • Mechanistic investigations reveal that Pd 1 /BN selectively adsorbs NO 2 − while boosting the hydrogenation process. • This work opens a new window for exploring high-performance SACs for ammonia electrosynthesis via NO 2 RR. Electrocatalytic NO 2 − reduction to NH 3 (NO 2 RR) offers a prospective strategy to concurrently achieve polluted NO 2 − removal and effective NH 3 electrosynthesis. In this work, we report atomically dispersed Pd on defective BN nanosheets (Pd 1 /BN) as an efficient catalyst for the NO 2 RR, achieving the highest NH 3 -Faradaic efficiency of 91.7% with an NH 3 yield rate of 347.1 μmol h−1 cm−2 at −0.6 V vs. RHE, superior to those of most previously reported electrocatalysts. Theoretical computations reveal the isolated Pd sites as catalytic centers to selectively adsorb NO 2 − and accelerate NO 2 −-to-NH 3 hydrogenation process with a minimized reaction barrier, eventually contributing to the considerably enhanced NO 2 RR selectivity and activity of Pd 1 /BN. [ABSTRACT FROM AUTHOR]

The rational design of electrocatalysis has emerged as one of the most thriving means for mitigating energy and environmental crises. The key to this effort is the understanding of the complex electrochemical interface, wherein the electrode potential as well as various internal factors such as H‐bond network, adsorbate coverage, and dynamic behavior of the interface collectively contribute to the electrocatalytic activity and selectivity. In this context, the authors have reviewed recent theoretical advances, and especially, the contributions to modeling the realistic electrocatalytic processes at complex electrochemical interfaces, and illustrated the challenges and fundamental problems in this field. Specifically, the significance of the inclusion of explicit solvation and electrode potential as well as the strategies toward the design of highly efficient electrocatalysts are discussed. The structure‐activity relationships and their dynamic responses to the environment and catalytic functionality under working conditions are illustrated to be crucial factors for understanding the complexed interface and the electrocatalytic activities. It is hoped that this review can help spark new research passion and ultimately bring a step closer to a realistic and systematic modeling method for electrocatalysis. [ABSTRACT FROM AUTHOR]

Aims Systemic inflammation occurs commonly during many human disease settings and increases vascular permeability, leading to organ failure, and lethal outcomes. Lipocalin 10 (Lcn10), a poorly characterized member of the lipocalin family, is remarkably altered in the cardiovascular system of human patients with inflammatory conditions. Nonetheless, whether Lcn10 regulates inflammation-induced endothelial permeability remains unknown. Methods and results Systemic inflammation models were induced using mice by injection of endotoxin lipopolysaccharide (LPS) or caecal ligation and puncture (CLP) surgery. We observed that the expression of Lcn10 was dynamically altered only in endothelial cells (ECs), but not in either fibroblasts or cardiomyocytes isolated from mouse hearts following the LPS challenge or CLP surgery. Using in vitro gain- and loss-of-function approaches and an in vivo global knockout mouse model, we discovered that Lcn10 negatively regulated endothelial permeability upon inflammatory stimuli. Loss of Lcn10 augmented vascular leakage, leading to severe organ damage and higher mortality following LPS challenge, compared to wild-type controls. By contrast, overexpression of Lcn10 in ECs displayed opposite effects. A mechanistic analysis revealed that both endogenous and exogenous elevation of Lcn10 in ECs could activate slingshot homologue 1 (Ssh1)-Cofilin signalling cascade, a key axis known to control actin filament dynamics. Accordingly, a reduced formation of stress fibre and increased generation of cortical actin band were exhibited in Lcn10-ECs, when compared to controls upon endotoxin insults. Furthermore, we identified that Lcn10 interacted with LDL receptor-related protein 2 (LRP2) in ECs, which acted as an upstream factor of the Ssh1-Confilin signalling. Finally, injection of recombinant Lcn10 protein into endotoxic mice showed therapeutic effects against inflammation-induced vascular leakage. Conclusion This study identifies Lcn10 as a novel regulator of EC function and illustrates a new link in the Lcn10-LRP2-Ssh1 axis to controlling endothelial barrier integrity. Our findings may provide novel strategies for the treatment of inflammation-related diseases. [ABSTRACT FROM AUTHOR]

Calmodulin-like proteins (CML) are important calcium signal transduction proteins in plants. CML genes have been analyzed in several plants. However, little information on CML in Phaseolus vulgare is available. In this study, we identified 111 PvCMLs distributed on eleven chromosomes. Phylogenetic analysis classified them into seven subfamilies. Cis-acting element prediction showed that PvCML contained elements related to growth and development, response to abiotic stress and hormones. Moreover, the majority of PvCMLs showed different expression patterns in most of the nine tissues and developmental stages which indicated the role of PvCML in the growth and development of common bean. Additionally, the common bean was treated with melatonin by seed soaking, and root transcriptome at the 5th day and qRT-PCR of different tissue at several stages were performed to reveal the response of PvCML to the hormone. Interestingly, 9 PvCML genes of subfamily VI were detected responsive to exogenous melatonin, and the expression dynamics of nine melatonin response PvCML genes after seed soaking with melatonin were revealed. Finally, the protein interaction network analysis of nine melatonin responsive PvCMLs was constructed. The systematic analysis of the PvCML gene family provides theoretical support for the further elucidation of their functions, and melatonin response molecular mechanism of the CML family in P. vulgaris. [ABSTRACT FROM AUTHOR]

Thermal recovery is one of the most effective techniques for viscous oil production, which has been widely used in the heavy oilfield development. The mechanisms and percolation characteristics of thermal recovery have attracted a lot of attention. However, the displacement characteristics and produced oil properties in the steam flood heavy oil process are rarely addressed. In this paper, steam flooding experiments with two heavy oil viscosities under the temperatures from 120 to 200 °C and velocities from 1 to 3 mL/min were carried out to examine the oil displacement efficiency and the produced oil properties. The results show that the majority of the oil is produced in the low water cut stage. Temperature increment is helpful for prolonging the water breakthrough time. The high injection velocity of steam contributes to a high recovery factor, even if it enters into the high water cut stage. The rheology of the produced oils severely changes because the SARA composition changes, and emulsification occurs during the steam flooding heavy oil process. With the increasing steam temperature, the relative content of resins in the produced oils decreases, and asphaltenes increase. With the increase in the injection volume and the injection velocity of steam, the content of resins and asphaltenes increases. This leads to an increment in the produced oil viscosities. The effect of injection velocity on the rheology properties of the produced oils increases with temperature increment. The finding of this work will provide the technical support for heavy oilfields development. [ABSTRACT FROM AUTHOR]

Background: Considering older adults are getting closer to the end-of-life and face death more directly. Attitudes to death not only affect the physical and mental health of older adults, but also affect their acceptance of hospice care, even the quality of death. This study aims to explore the status, influencing factors of attitudes toward death and demands of death education among the community-dwelling older adults in southwestern China.Methods: A cross-sectional survey was adopted to investigate 683 community-dwelling older adults in Chongqing, China. Non-parametric test and multiple linear regression analysis was used to explore the influencing factors of different attitudes toward death of older adults in community.Results: The multiple linear regression models showed that different dimensions of death attitudes were affected by one or more factors including number of diseases, discussion about life and death, marital status, and average income per month. And community-dwelling older adults have high level demand for death education.Conclusions: Under the taboo culture of death in China, this study is one of the few studies on the attitudes toward death and the demands for death education of the community-dwelling older adults. This study contributes to enrich the global death studies and provide reference for the death education for older adults. [ABSTRACT FROM AUTHOR]

Background: The rapid development of digital health has reduced the time and cost of medical treatment, bringing efficient and economical benefits. However, older adults all over the world are deficient in digital health knowledge and skills to varying degrees. This study intends to investigate the current status and influencing factors of digital health literacy among community-dwelling older adults in Southwest China, so as to provide theoretical reference for global digital health researches and the construction of gerontological digital health service models.Methods: A cross-sectional survey was conducted from September 2020 to April 2021 in Chongqing, China. 572 community-dwelling older adults (≥ 65 years) were surveyed by stratified sampling. Data on sociodemographic characteristics, Internet usage, attitude towards Internet health information and digital health literacy were collected. Wherein, the digital health literacy assessment adopted the Digital Health Literacy Assessment Scale for community-dwelling older adults, which was developed by the research group, proven to be with good internal consistency (0.941), split-half reliability (0.889), test-retest reliability (0.941), content validity (0.967), criterion validity (0.938) and construct validity. The influencing factors were explored by univariate analysis and multiple linear regression analysis.Results: The average score of digital health literacy was 37.10 (SD 18.65). Univariate analysis showed that there were statistically significant differences in the comparison of digital health literacy according to 16 variables, such as different age and education levels. Multiple linear regression analysis showed that education level, marital status, self-rated health status, degree of health concerns, duration of Internet usage, time spent using the Internet per day, frequency of Internet usage, frequency of receiving guidance passively from family members, perceived usefulness, perceived ease of use and perceived reliability were positively correlated with digital health literacy, while age and perceived risk were negatively correlated with digital health literacy.Conclusion: The overall digital health literacy of community-dwelling older adults in Southwest China is relatively low. In the future, health professionals should fully consider the diverse influencing factors of digital health literacy, assess individual differences and provide targeted intervention programs. Meanwhile, global public health authorities should integrate health resources effectively, and seek health service models for older adults in line with the development of the digital age to narrow the digital divide. [ABSTRACT FROM AUTHOR]

[Display omitted] • There is a strong synergism between Camellia Oleifera shell extract (COSE) and KI on steel in H 2 SO 4 solution. • COSE/KI can further retard both cathodic and anodic reactions comparing with either COSE or KI. • COSE/KI shows larger charge transfer resistance and smaller double-layer capacitance than COSE or KI. • The synergistic inhibited surface by COSE/KI appears almost no corrosion with the lowest surface roughness. • Rutin, quercetin and tea polyphenols are the effective components in COSE. To address the severe corrosion problems faced by steel, a natural corrosion inhibitor derived from Camellia Oleifera shell extract (COSE) was developed. The effectiveness of COSE as well as its synergistic mixture of COSE/KI in inhibiting the corrosion of steel in H 2 SO 4 was investigated using weightlessness and electrochemical techniques. The results show that the maximum inhibition efficiency of individual COSE is 77.28 % at 20 °C, and is increased to 93.08 % for the mixture of COSE/KI. The adsorption of COSE, KI and COSE/KI on steel surface conform to Langmuir adsorption isotherm. COSE/KI has a stronger adsorption than either COSE or KI. Electrochemical analysis indicates that COSE/KI is a hybrid inhibitor primarily focusing on the cathodic inhibition. Mixing COSE with KI shows considerably larger charge transfer resistance and smaller double-layer capacitance than individual COSE and KI. Characterization tests such as metallurgical microscopy, SEM, AFM and contact angle confirm that the addition of COSE/KI could reduce the roughness of steel surface, while increase the hydrophobicity, then effectively alleviate the corrosion on the steel surface. XPS analyses demonstrated that the corrosion inhibition layer on the steel surface was induced by the adsorption of the polar groups in COSE. The components responsible for COSE's effectiveness were thoroughly examined using FTIR and liquid chromatography-mass spectrometry (LC-MS), which identified the presence of compounds such as flavonoids and phenylpropanoids. The synergistic effect of the active ingredients (rutin, quercetin, tea saponin, tea polyphenols, et al.) with KI was also confirmed. Finally, theoretical calculations were conducted to analyze properties of rutin, quercetin and tea polyphenols on the iron layer. The results show all these molecules exhibit efficient inhibition, with quercetin showing better inhibitive ability by parallel adsorption. [ABSTRACT FROM AUTHOR]

Objective. We applied computed tomography (CT) to explore the imaging manifestations of rare parts of osteochondroma. Based on the medical images, deblurring using a convolutional neural network (CNN), and three-dimensional (3D) reconstruction of the images is performed in order to improve the image diagnosis. Methods. Twelve cases of osteochondroma in rare locations confirmed by surgical pathology or clinical long-term dynamic observation were retrospectively analyzed using medical imaging and image reconstruction. There are 7 males and 5 females, with an average age of 43 years. CT examinations were performed in all cases. Image deblurring via the GAN model is performed followed by the 3D reconstruction of the higher quality images is implemented. A retrospective study was performed on the imaging manifestations of the above cases; the imaging characteristics were summarized. Results. The imaging features are the following lesions, including 4 cases of the proximal radius, 4 cases of the scapula, 2 cases of the pelvis, and 2 cases of the proximal ribs. The cartilage caps, cortex, and sternum were typical structures of the bone surface of the studied cases. In the continuous imaging features, calcification was visible in some cases, and no significant enhancement was seen in enhanced scans; there was no obvious direction of lesion growth. The image processing techniques that we performed are useful in enhancing the quality of the medical diagnosis. Conclusions. Rare site osteochondroma has certain imaging features. In most cases, we can accurately diagnose rare site osteochondroma through these features via the image processing methods that are proposed in this paper. [ABSTRACT FROM AUTHOR]

Recently, diterpenoids have been shown to exhibit several health benefits including cancer prevention. In the present study, we examined the anticancer effects of sugiol diterpene against the endometrial carcinoma and attempted to explore the underlying mechanisms. The results showed that sugiol significantly (P < 0.05) inhibited the proliferation of the endometrial carcinoma cell lines (HEC-1-A, HEC-1-B, and KLE) as compared to the normal THESCs cells. The IC50 of sugiol against all the three endometrial carcinoma cell lines ranged between 14 and 18 µM as against an IC50 of 110 μM against the normal THESCs cells. Sugiol caused several changes in the morphology of the HEC-1-B cells characteristic of apoptosis. The DAPI and annexin PI assays confirmed the induction of apoptosis in HEC-1-B cells. Sugiol also triggered increase in Bax and decrease in Bcl-2 expression. The acridine orange staining revealed that the formation of autolysosomes in HEC-1-B cells upon treatment with sugiol suggestive of autophagy. The autophagy was further confirmed by increase in the expression of LC3B-II, Beclin-1, Atg5, and Atg12 and decrease in the expression of P62. The transwell assay showed that relative to the untreated HEC-1-B cells, the migration and invasion of the sugiol-treated HEC-1-B cells was significantly (P < 0.05) inhibited. Collectively, the finding of the present study revealed that sugiol suppresses the growth of human endometrial cells via induction of apoptosis and autophagy. Consistently, sugiol may prove to be an important lead molecule in the development of chemotherapy for endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases caused by abnormal immune activation and immune tolerance. Immunomodulatory cells (ICs) play a critical role in the maintenance and homeostasis of normal immune function and in the pathogenesis of RA. The human gastrointestinal tract is inhabited by trillions of commensal microbiota on the mucosal surface that play a fundamental role in the induction, maintenance, and function of the host immune system. Gut microbiota dysbiosis can impact both the local and systemic immune systems and further contribute to various diseases, such as RA. The neighbouring intestinal ICs located in distinct intestinal mucosa may be the most likely intermediary by which the gut microbiota can affect the occurrence and development of RA. However, the reciprocal interaction between the components of the gut microbiota and their microbial metabolites with distinct ICs and how this interaction may impact the development of RA are not well studied. Therefore, a better understanding of the gut microbiota, ICs, and their interactions might improve our knowledge of the mechanisms by which the gut microbiota contribute to RA and facilitate the further development of novel therapeutic approaches. In this review, we have summarized the roles of the gut microbiota in the immunopathogenesis of RA, especially the interactions between the gut microbiota and ICs, and further discussed the strategies for treating RA by targeting/regulating the gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OS) is a malignancy of the bone that has no clearly identified prognostic factors for diagnosis. In this study, we evaluated the regulatory role of long non-coding RNA (lncRNA) ANCR on the migration and invasion of OS cells as well as the possible mechanism involving the p38MAPK signalling pathway.Methods: ANCR expression was determined in OS tissues and OS cell lines (MG-63, S1353, U2OS, and UMR-106) by qRT-PCR. It was observed that ANCR was down-regulated in MG-63 and U2OS cells by 48 h of siRNA-ANCR (si-ANCR) transfection. The proliferation of transfected cells was determined using the CCK-8 and the EdU assays. The migration and invasion of transfected cells were determined by the Transwell assay. The expression of E-cadherin, N-cadherin, and phosphorylated p38MAPK (p-p38MAPK) proteins was determined by Western blot. In addition, combinatorial treatment of cells with si-ANCR + SB203580 (p38MAPK inhibitor) was performed to investigate the association between ANCR and MAPK signalling in OS cells.Results: ANCR was up-regulated in OS cells and tissues. ANCR silencing significantly inhibited the proliferation rate, decreased the percentage of migration and invasion cells, down-regulated N-cadherin, and up-regulated E-cadherin and p-p38MAPK in MG-63 and U2OS cells. Inhibition of the p38MAPK signalling pathway (SB203580) in MG-63 and U2OS cells rescued si-ANCR-induced inhibition of cell migration and invasion.Conclusions: Silencing of ANCR inhibited the migration and invasion of OS cells through activation of the p38MAPK signalling pathway. [ABSTRACT FROM AUTHOR]

• Continued SDSL shrinkage was exhibited in northern China from 2010 to 2020. • The western and eastern changed SDSL areas showed an opposite changing trend. • Western SDSL areas with aeolian activity intensified in 2015–2020 deserve attention. • Multiple factors' co-driving dominated the aeolian activity change in SDSL areas. • MAAI was superior to MFVCT in aeolian activity intensified SDSL areas. Timely monitoring of the sandy desert and sandy land (SDSL) dynamics and their driving factors is vital for ecological restoration policy-making to combat the expansion of the SDSL. Northern China, being the principal implementation area of ecological restoration projects, is ecologically fragile and encompasses almost all of the SDSL regions in China. To explore and compare the dominant driving factors for SDSL changes by extracting both aeolian activity information and vegetation indices, the SDSL datasets in northern China from 2010 to 2020 were first constructed in this study by the human–computer interactive interpretation method based on the series Landsat image data. The spatiotemporal dynamic characteristics of SDSL were subsequently analyzed, and the dominant driving factors of SDSL changes were further explored via the geodetector model by the fractional vegetation cover trend and the difference of aeolian activity index. The results showed a net decrease of 3,780.25 km2 in the total SDSL area between 2010 and 2020, and the decrease rate was 2.44 times higher in the shorter period of 2015–2020 compared to 2010–2015. The spatial differentiation between the western and eastern parts of the Helan Mountains was prominently exhibited by the relatively higher changed SDSL area in the eastern part (62.74% for aeolian activity weakened and 83.32% for aeolian activity intensified) and the increasingly changed SDSL area in the western part (from 33.09% to 39.60% in aeolian activity weakened and from 13.02% to 19.60% in aeolian activity intensified). Especially, the increased aeolian activity intensified SDSL area has happened on the southern edge of the Gurbantunggut Desert and along both sides of the Tarim River from 2015 to 2020 deserve attention. The co-driving of the multiple driving factors dominated the change of SDSL from 2010 to 2020, with the county mean value of the difference in aeolian activity index (MDAAI) and the county mean value of the trend in fractional vegetation cover (MFVCT) as dependent variables, respectively. Climatic factors of the mean annual average temperature, the mean annual cumulative precipitation, and the mean annual aridity index have a relatively larger explanatory power for the change of SDSL in both MDAAI and MFVCT. Anthropogenic factors of the mean annual afforestation area and the mean annual number of large livestock and sheep and goats (year-end) have a greater explanatory power in MDAAI, while the mean annual number of large livestock and sheep and goats (year-end) and the mean annual population density in MFVCT. In particular, the dependent variable MDAAI is better at identifing the dominant drivers of aeolian activity intensified SDSL area compared to MFVCT, with anthropogenic factors playing a stronger dominant role. [ABSTRACT FROM AUTHOR]

We screened bacteria that use E2 as its sole source of carbon and energy for growth and identified them as Rhodococcus, and we named them DSSKP-R-001. For a better understanding of the metabolic potential of the strain, whole genome sequencing of Rhodococcus DSSKP-R-001 and annotation of the functional genes were performed. The genomic sketches included a predicted protein-coding gene of approximately 5.4 Mbp with G + C content of 68.72% and 5180. The genome of Rhodococcus strain DSSKP-R-001 consists of three replicons: one chromosome and two plasmids of 5.2, 0.09, and 0.09, respectively. The results showed that there were ten steroid-degrading enzymes distributed in the whole genome of the strain. The existence and expression of estradiol-degrading enzymes were verified by PCR and RTPCR. Finally, comparative genomics was used to compare multiple strains of Rhodococcus. It was found that Rhodococcus DSSKP-R-001 had the highest similarity to Rhodococcus sp. P14 and there were 2070 core genes shared with Rhodococcus sp. P14, Rhodococcus jostii RHA1, Rhodococcus opacus B4, and Rhodococcus equi 103S, showing evolutionary homology. In summary, this study provides a comprehensive understanding of the role of Rhodococcus DSSKP-R-001 in estradiol-efficient degradation of these assays for Rhodococcus. DSSKP-R-001 in bioremediation and evolution within Rhodococcus has important meaning. [ABSTRACT FROM AUTHOR]

Sepsis is a systemic inflammatory response syndrome caused by infection of bacteria, fungi and/or viruses in clinical patients. It is known that inflammatory cytokine levels have an essential role in the progression of sepsis. The present study investigated the role of inflammatory markers in human peripheral blood mononuclear cells (hPBMCs) of patients with sepsis at an intensive care unit. In addition, the plasma levels of inflammatory cytokines were compared between sepsis patients and healthy individuals. The results demonstrated that the serum levels of interleukin-1, -17 and -6, as well as tumor necrosis factor-a, were upregulated in sepsis patients. The serum levels of high mobility group box 1 and C-reactive protein were increased in sepsis patients compared with those in healthy individuals. The expression levels of nuclear factor-κB-p65 and its inhibitor IκBα, as well as the ratio of CD25+ cells, and the levels of neutrophil gelatinase-associated lipocalin and peptidoglycan recognition protein were higher in hPBMCs in sepsis patients compared with those in healthy individuals. It was also indicated that balance of T helper type 1/2 cytokines was also disturbed in patients with sepsis compared with that in healthy individuals. In conclusion, these results indicated that inflammation is involved in the progression of sepsis by interfering with the expression of various molecules, suggesting a potential therapeutic strategy for the treatment of sepsis patients. [ABSTRACT FROM AUTHOR]

Direct-acting antiviral agents (DAAs) have shown higher cure rates for treating hepatitis C virus (HCV) by directly interfering with different steps of the HCV life cycle. To optimize drug combinations and accurately quantify the antiviral effect of DAAs treatments, mathematical models should include the intracellular virus replication processes. In this study, we develop a two-strain multiscale age-structured model that includes intracellular viral RNA replication and extracellular viral infection. We prove the existence, positivity, and boundedness of the solution, and derive the conditions for the existence and stability of the three steady states (non-infection steady state, boundary steady state, and coexistence steady state). Under certain biologically reasonable assumptions, we obtain the approximate solutions of the viral load decline of the two virus strains (sensitive and drug-resistant virus strains) during treatment, and the long-term approximation is shown to be in good agreement with the solution of the original model. We also carry out numerical simulations using the long-term approximate solution, providing insights into the influence of antiviral effects on the viral load change of the two virus strains during treatment with DAAs. • A multiscale mixed-ODE-PDE model is developed to study HCV infection. • The model includes intracellular RNA replication and extracellular viral infection. • We studied the existence and stability of the three steady states. • The approximate analytical solution is convenient for data comparison. [ABSTRACT FROM AUTHOR]

Numerous studies have examined the pathogenesis of osteoporosis. The causes of osteoporosis include endocrine factors, nutritional status, genetic factors, physical factors, and immune factors. Recent osteoimmunology studies demonstrated that the immune system and immune factors play important regulatory roles in the occurrence of osteoporosis, and people should pay more attention to the relationship between immunity and osteoporosis. Immune and bone cells are located in the bone marrow and share numerous regulatory molecules, signaling molecules, and transcription factors. Abnormal activation of the immune system alters the balance between osteoblasts and osteoclasts, which results in an imbalance of bone remodeling and osteoporosis. The incidence of osteoporosis is also increasing with the aging of China's population, and traditional Chinese medicine has played a vital role in the prevention and treatment of osteoporosis for centuries. Chinese medicinal plants possess unique advantages in the regulation of the immune system and the relationships between osteoporosis and the immune system. In this review, we provide a general overview of Chinese medicinal plants in the prevention and treatment of osteoporosis, focusing on immunological aspects. [ABSTRACT FROM AUTHOR]

The trade of goods among regions or nations associated with large environmental consequences. Yet balancing economic gains and environmental consequences induced by trade is still hindered by a lack of quantification of these two factors, especially for the environmental problems those are more locally oriented, such as the atmospheric pollution. Based on an environmental input–output analysis for 2010, we contrast economic gains (value added) against atmospheric pollutant emissions (sulfur dioxide (SO 2 ), nitric oxide (NO x ), primary fine particulate matter (PM 2.5 ) and non-methane volatile organic compounds (NMVOC)) and the widely concerned CO 2 emissions associated with international and interprovincial exports from Beijing–Tianjin–Hebei (BTH), the most polluted area in China. Our results show that exports contributed 55–62% of BTH’s production emissions and 54% of its total value added. BTH’s large exports of metals and metal products, nonmetal mineral products, chemical and transportation and warehousing, generated a larger share of pollutant emissions (36–46% of BTH’s total) than that of value added (17%) along the supply chain. Most of BTH’s embodied emissions in exports go to neighboring provinces and the developed east coastal regions in China, although the economic returns are comparatively low. Among BTH, industrial production in Beijing and Tianjin lead to more pollutant emission than value added in Hebei, due to reliance on pollution-intensive product imports from Hebei. Our results call for refocusing and restructuring of BTH’s industry and trade structures to balance the economic gains and environmental losses for each region. [ABSTRACT FROM AUTHOR]

This paper documents the history of vegetation assemblage in Honghe Wetland (NE China) during the last 6200 years. Vegetation changes were reconstructed based on high-resolution plant macrofossil analysis of sedimentary sequence obtained from Honghe National Nature Reserve located in Sanjiang Plain, in conjunction with Accelerator Mass Spectrometry (AMS) 14 C radiocarbon data. Results indicate that plant macrofossil composition of Honghe wetland ecosystem are dynamic and have undergone several significant changes. Around 2500 cal yr BP, plant composition transited from Equisetum fluviatile community to Carex lasiocarpa - Drepanocladus aduncus community, and then following by Drepanocladus aduncus community at 460 cal yr BP. Another major vegetation changes occurred at 220 cal yr BP, transitioning to Carex sp. community. By comparison between the plant macrofossil assemblages and the climate changes during the last 6200 cal yr BP, we suggest that ASM (Asian summer monsoon) is the main driving force for the vegetation succession before the impacts of human activities. Since some restoration programs have been undertaken at Honghe wetland, thus our results can provide valuable baseline data for assessment of the practicability and suitability of the former restoration plan and the further designing of conservation management and restoration targets. Since the vegetation composition of Honghe wetland is pronouncedly sensitive to water level, it can be inferred that wetland ecosystem can be restored to near-natural condition through the effective management and restoration by controlling the water source of the wetland. [ABSTRACT FROM AUTHOR]

Triptolide, a purified component of Tripterygiumwilfordii Hook F, has been shown to have immunosuppressive and anti-inflammatory properties in rheumatoid arthritis (RA). Although triptolide has demonstrated that it could suppress bone destruction in collagen-induced mice, its therapeutic mechanism remains unclear. Many studies have investigated the effect of triptolide on Tregs and Tregs-related cytokine involved in RA. Additionally, previous studies have implied that Tregs inhibit osteoclast differentiation and bone resorption. Thus, in this study we aimed to explore the regulatory mechanism by which triptolide influences the Treg-mediated production of IL-10 and TGF- β1 to affect osteoclast differentiation and bone resorption. In cocultures system of Tregs and mouse bone marrow macrophages (BMMs), Tregs inhibited the differentiation of osteoclasts and reduced the resorbed areas significantly and the production of both IL-10 and TGF- β1 was upregulated. When the coculture systems were pretreated with triptolide, they produced higher levels of IL-10 and TGF- β1. Our data indicate that triptolide enhances the suppressive effects of Tregs on osteoclast differentiation and bone resorption by enhancing the secretion of IL-10 and TGF- β1. Tregs are most likely involved in the triptolide-mediated regulation of bone metabolism and may provide a potential therapeutic target for the treatment of inflammatory bone destruction. [ABSTRACT FROM AUTHOR]

Abnormal DNA methylation is known as playing an important role in the tumorgenesis. It is helpful for distinguishing the specificity of diagnosis and therapeutic targets for cancers based on characteristics of DNA methylation patterns across cancers. High throughput DNA methylation analysis provides the possibility to comprehensively filter the epigenetics diversity across various cancers. We integrated whole-genome methylation data detected in 798 samples from seven cancers. The hierarchical clustering revealed the existence of cancer-specific methylation pattern. Then we identified 331 differentially methylated genes across these cancers, most of which (266) were specifically differential methylation in unique cancer. A DNA methylation correlation network (DMCN) was built based on the methylation correlation between these genes. It was shown the hubs in the DMCN were inclined to cancer-specific genes in seven cancers. Further survival analysis using the part of genes in the DMCN revealed high-risk group and low-risk group were distinguished by seven biomarkers (PCDHB15, WBSCR17, IGF1, GYPC, CYGB, ACTG2, and PRRT1) in breast cancer and eight biomarkers (ZBTB32, OR51B4, CCL8, TMEFF2, SALL3, GPSM1, MAGEA8, and SALL1) in colon cancer, respectively. At last, a protein-protein interaction network was introduced to verify the biological function of differentially methylated genes. It was shown that MAP3K14, PTN, ACVR1 and HCK sharing different DNA methylation and gene expression across cancers were relatively high degree distribution in PPI network. The study suggested that not only the identified cancer-specific genes provided reference for individual treatment but also the relationship across cancers could be explained by differential DNA methylation. [ABSTRACT FROM AUTHOR]

Osteoclasts are critical for bone resorption and use podosomes to attach to bone matrix. Osteoprotegerin (OPG) is a negative regulator of osteoclast function that can affect the formation and function of podosomes. However, the signaling pathways that link OPG to podosome function have not been well characterized. Therefore, this study examined the roles of intracellular calcium and MAPKs in OPG-induced podosome disassembly in osteoclasts. We assessed the effects of the intracellular calcium chelator Bapta-AM, ERK inhibitor U0126, and p38 inhibitor SB202190 on OPG-treated osteoclast differentiation, adhesion structures, intracellular free Ca 2+ concentration and the phosphorylation state of podosome associated proteins (Pyk2 and Src). Mouse monocytic RAW 264.7 cells were differentiated to osteoclasts using RANKL (30 ng/mL) and M-CSF (25 ng/mL). The cells were pretreated with Bapta-AM (5 μM), U0126 (5 μM), or SB202190 (10 μM) for 30 min, followed by 40 ng/mL OPG for 3 h. Osteoclastogenesis, adhesion structure, viability and morphology, intracellular free Ca 2+ concentration and the phosphorylation state of Pyk2 and Src were measured by TRAP staining, scanning electron microscopy, real-time cell analyzer, flow cytometry and western blotting, respectively. OPG significantly inhibited osteoclastogenesis, the formation of adhesion structures, and reduced the amount of phosphorylated Pyk2 and Src-pY527, but increased phosphorylation of Src-pY416. Bapta-AM, U0126, and SB202190 partially restored osteoclast differentiation and adhesion structures. Both Bapta-AM and U0126, but not SB202190, restored the levels of intracellular free Ca 2+ concentration, phosphorylated Pyk2 and Src-pY527. All three inhibitors blocked OPG-induced phosphorylation at Src-pY416. These results suggest OPG disrupts the attachment structures of osteoclasts and activates Src as an adaptor protein that competes for the reduced amount of phosphorylated Pyk2 through calcium- and ERK-dependent signaling pathways. p38 MAPK signaling may have a different role in OPG-induced osteoclast retraction. Our findings potentially offer novel insights into the signaling mechanisms downstream of OPG that affect osteoclast attachment to the extracellular matrix. [ABSTRACT FROM AUTHOR]

Dendrobium is an endangered genus in the orchid family with medicinal and horticultural value. Two preliminary genetic linkage maps were constructed using 90 F progeny individuals derived from an interspecific cross between D. nobile and D. moniliforme (both, 2 n = 38), using random amplified polymorphic DNA (RAPD) and intersimple sequence repeat (ISSR). A total of 286 RAPD loci and 68 ISSR loci were identified and used for genetic linkage analysis. Maps were constructed by double pseudo-testcross mapping strategy using the software Mapmaker/EXP ver. 3.0, and Kosambi map distances were constructed using a LOD score ≥ 4 and a recombination threshold of 0.4. The resulting frame map of D. nobile was 1474 cM in total length with 116 loci distributed in 15 linkage groups; and the D. moniliforme linkage map had 117 loci placed in 16 linkage groups spanning 1326.5 cM. Both maps showed 76.91% and 73.59% genome coverage for D. nobile and D. moniliforme, respectively. These primary maps provide an important basis for genetic studies and further medicinal and horticultural traits mapping and marker-assisted selection in Dendrobium breeding programmes. [ABSTRACT FROM AUTHOR]

It is becoming increasingly clear that China experienced significant hydrological changes during the mid‐to‐late Holocene transition—a period characterized by societal changes. However, the nature of the hydroclimate anomaly as well as the direct consequences on societies in Southeast China remains unclear. Here, we present a leaf wax record from the Shuizhuyang peat deposit in Southeast China spanning the Holocene. The δD values of C29n‐alkane (δDC29) showed a large positive shift up to 24‰ from 4.7 to 3.8 ka, which changed independent of vegetation proxies and could not be solely explained by precipitation δD variations. It is thus most likely to reflect abrupt drying, which is probably shaped by a more El Niño‐like mean state in the tropical Pacific Ocean. We hypothesize that such a significant change in hydroclimate might have promoted the development of mixed rice and millet farming on the southeast coast of China. Plain Language Summary: The mid‐to‐late Holocene transition with significant changes in climate and agriculture‐based civilization affords a valuable insight into abrupt climate changes and human adaption. Increasing studies have shown large shifts in hydrological regime in China during this critical transition. However, the hydrological expression and its potential impact on the agriculture practice in Southeast China remains unclear. In this study, we utilize the hydrogen isotope compositions (δD) of leaf waxes from the Shuizhuyang peat deposit on the southeast coast of China to reconstruct hydrological changes during the mid‐to‐late Holocene transition. We find that the mid‐to‐late Holocene transition on the southeast coast of China is characterized by an abrupt drying, which is primarily modulated by a more El Niño‐like mean state over the tropical Pacific Ocean. Such a significant change in hydroclimate might have promoted the development of mixed rice and millet farming on the southeast coast of China coeval to the mid‐to‐late Holocene hydrological shift. Key Points: Increasing aridity on the southeast coast of China from 4.7 to 3.8 ka captured by the hydrogen isotope compositions (δD) of leaf waxesThe abrupt drying is mainly shaped by a more El Niño‐like state over the tropical Pacific Ocean during the mid‐to‐late Holocene transitionSuch a shift in hydroclimate might have promoted the development of mixed rice and millet farming on the southeast coast of China [ABSTRACT FROM AUTHOR]

Compared with a silicon MOSFET device, the SiC MOSFET has many benefits, such as higher breakdown voltage, faster action speed and better thermal conductivity. These advantages enable the SiC MOSFET to operate at higher switching frequencies, while, as the switching frequency increases, the turn-on loss accounts for most of the loss. This characteristic severely limits the applications of the SiC MOSFET at higher switching frequencies. Accordingly, an SRD-type drive circuit for a SiC MOSFET is proposed in this paper. The proposed SRD-type drive circuit can suppress the turn-on oscillation of a non-Kelvin packaged SiC MOSFET to ensure that the SiC MOSFET can work at a faster turn-on speed with a lower turn-on loss. In this paper, the basic principle of the proposed SRD-type drive circuit is analyzed, and a double pulse platform is established. For the purpose of proof-testing the performance of the presented SRD-type drive circuit, comparisons and experimental verifications between the traditional gate driver and the proposed SRD-type drive circuit were conducted. Our experimental results finally demonstrate the feasibility and effectiveness of the proposed SRD-type drive circuit. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Zr modified Pt/TiO 2 catalysts exhibit excellent H 2 -SCR performances. • The weakened interaction between Pt and TiO 2 by Zr induces more Pt0 species. • More oxygen vacancies caused by the Zr-O v -Ti3+ bands facilitate the formation of adsorbed nitrates species. The development of Hydrogen Internal Combustion Engine (H 2 -ICEs) to replace conventional fuel engines is expected to be an effective way to reduce CO 2 emissions, but some NO x emitted from the H 2 -ICEs still should be eliminated by the selective catalytic reduction of NO x with H 2 (H 2 -SCR). Large amount of platinum oxide existed on Pt/TiO 2 leads to its low H 2 -SCR activity. In contrast, the Zr-modified Pt/TiO 2 catalysts exhibit a higher NO x conversion and N 2 selectivity in a wider temperature window (100–180 °C) than those of Pt/TiO 2. The appropriately weakened strong interaction between Pt and TiO 2 by Zr induces more Pt0 species, which are active sites for the activation of NO x and H 2 in H 2 -SCR reaction. More oxygen vacancies caused by the formation of Zr-O v -Ti3+ bands involve in the activation of NO x and the adsorption of nitrates (NO x −) species. Furthermore, in situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTs) demonstrates that Pt/Zr x Ti 1-x catalysts possess more adsorbed NO x − species and a faster reduction rate for them. Monodentate and bridged nitrates are considered to be more reactive with H 2 than bidentate nitrates at relatively low temperatures. This work provides directions for the development of high-performance H 2 -SCR catalysts and the modulation of the conversion temperature. [ABSTRACT FROM AUTHOR]

Background: Life-and-death education is intimately related to palliative-and-hospice care. It should be implemented among groups of all ages, especially for the elderly. This study aims to establish expert consensus on a set of scientific and systematic life-and-death education contents for the elderly and provide reference for the practice on the elderly.Methods: This study designed three rounds of expert consultation by using a Delphi method. A panel of 22 experts from the fields of palliative-and-hospice care, life-and-death education, geriatric nursing, humanities and ethics, and geriatric psychology participated in the study.Results: This study finally reached expert consensus on the contents of life-and-death education for the elderly, containing 4 first-level items, Life-and-death literacy promotion in the elderly; Life-and-death concept establishment of the elderly; Life-and-death planning of the elderly; Life-and-death thoughts of the elderly with affiliated 9 second-level items, and corresponding 23 detailed third-level items.Conclusions: The life-and-death education contents for the elderly offer a basis for publicity for health professionals, promote dialogues on death, preparation, and planning for death and dying. The life-and-death education contents system was clear in coherence containing definite and comprehensive contents, which enriched life-and-death education resources globally. The results could assist in the planning of palliative-and-hospice care services to improve quality of death of the elderly. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a prevalent global health concern associated with the loss of articular cartilage and subchondral bone. The lack of disease-modifying drugs for OA necessitates the exploration of novel therapeutic options. Our previous study has demonstrated that traditional Chinese medical herb Trachelospermum jasminoides (Lindl.) Lem. extract suppressed osteoclastogenesis and identified trachelogenin (TCG) as a representative compound. Here, we delved into TCG's potential to alleviate OA. Methods: We initially validated the in vivo efficacy of TCG in alleviating OA using a rat OA model. Subsequently, we isolated primary bone marrow-derived macrophages in vitro to investigate TCG's impact on osteoclastogenesis. We further employed a small molecule pull-down assay to verify TCG's binding target within osteoclasts. Finally, we isolated primary mouse chondrocytes in vitro to study TCG's regulatory effects and mechanisms on chondrocyte survival. Results: TCG preserved subchondral bone integrity and protected articular cartilage in a rat OA model. Subsequently, in vitro experiments unveiled TCG's capability to inhibit osteoclastogenesis and function through binding to Ras association proximate 1 (Rap1) and inhibiting its activation. Further study demonstrated that TCG inhibited Rap1/integrin αvβ3/c-Src/Pyk2 signaling cascade, and consequently led to failed F-actin ring formation. Besides, TCG promoted the proliferation of mouse primary chondrocytes while suppressing apoptosis in vitro. This is attributed to TCG's ability to upregulate HIF1α, thereby promoting glycolysis. Conclusion: TCG exerted inhibitory effects on osteoclastogenesis through binding to Rap1 and inhibiting Rap1 activation, consequently preventing subchondral bone loss. Moreover, TCG enhanced chondrocyte survival by upregulating HIF1α and promoting glycolysis. These dual mechanisms collectively provide a novel approach to prevented against cartilage degradation. [ABSTRACT FROM AUTHOR]

Background: In the global trend of actively promoting the participation of older adults in the digital age, the relevant negative issues featuring potential Internet Addiction (IA) among them has risen to be a new challenge facing the global public health. However, there is a severe lack of related research. This study aimed to gain a comprehensive understanding of the phenomenon and process of IA among the elderly. The purpose of this paper is to introduce factors that may influence IA in the demographic. Methods: This study employed qualitative descriptive research methods to investigate older adults' perceptions and experiences of IA. Semi-structured in-depth personal interviews were conducted between March and June 2023 with 36 senior citizens from urban communities in Chongqing, Southwest China. Data were analyzed via inductive content analysis methods. Results: Through data analysis, 2 main categories concerning IA in older adults were identified: risk factors and protective factors. The risk factor categories include 5 individual factors (e.g., Internet as the major avenue for pursuing personal hobbies and interests, etc.), 3 family factors (e.g., household WIFI increasing the risk of prolonged Internet use indoors, etc.), 2 peer factors (e.g., peer recommendation and guidance as catalysts for intensified Internet engagement, etc.), 2 socio-environmental factors (e.g., the widespread daily Internet use spurs offline intolerance, etc.), and 3 Internet platform factors (e.g., the plenitude of online content triggers endless viewing/browsing behaviors, etc.). The category of protective factors encompasses 2 individual factors (e.g., a higher level of perceived risk regarding internet health hazards, etc.) and 2 family factors (e.g., more family commitment, etc.). Conclusions: Older adults' Internet addictive behaviors are shaped by multiple and complex internal and external factors. A higher level of online health risk perception is a key protective factor to effectively avoid the occurrence and deterioration of IA among the aged, a distinct finding from this study. It is believed that the "individual-family-peer-community" synergy strategy is expected to become an essential direction for IA intervention for older adults, in order to promote healthy Internet use among older adults. [ABSTRACT FROM AUTHOR]

The increased cross section of overhead conductors can obviously improve the power transmission capacity. Whereas its large creep elongation may make the design works be more difficult. In this paper, time hardening model was proposed to analyze the creep properties of the large cross section conductor. To perform such analysis, the creep tests of the typical large cross section conductor JL1/G2A-1250/100-84/19 under different temperature conditions were carried out. Then the time hardening models excluding and including temperature coefficient were deduced respectively. The results showed that the calculation based on the time hardening model were well agreed with the results of laboratory tests and field observation. What is more, the accuracy of the time hardening model in this paper is higher than the fitting model. Finally, the section integration model was discussed based on the nonsynchronous stringing process so as to provide a new method for calculating the creep value of large cross section conductors. [ABSTRACT FROM AUTHOR]

Roundabout guidance receptor 2 (Robo2) is closely related to malignant tumors such as pancreatic cancer and liver fibrosis, but there is no relevant research on the role of Robo2 in HCC. The study will further explore the function and mechanism of Robo2 and its downstream target genes in HCC. Firstly, Robo2 protein levels in human HCC tissues and paired adjacent normal liver tissues were detected. Then we established HepG2 and Huh7 hepatoma cell lines with knock-down Robo2 by transfection with lentiviral vectors, and examined the occurrence of EMT, proliferation and apoptosis abilities in HCC cells by western blot, flow cytometry, wound healing assay and TUNEL staining. Then we verified the interaction between Robo2 and its target gene by Co-IP and immunofluorescence co-staining, and further explored the mechanism of Robo2 and YB-1 by rescue study. The protein expression level of Robo2 in HCC was considerably higher than that in the normal liver tissues. After successfully constructing hepatoma cells with knock-down Robo2, it was confirmed that down-regulated Robo2 suppressed EMT and proliferation of hepatoma cells, and accelerated the cell apoptosis. High-throughput sequencing and validation experiments verified that YB-1 was the downstream target gene of Robo2, and over-expression of YB-1 could reverse the apoptosis induced by Robo2 down-regulation and its inhibitory effect on EMT and proliferation. Robo2 deficiency inhibits EMT and proliferation of hepatoma cells and augments the cell apoptosis by regulating YB-1, thus inhibits the occurrence of HCC and provides a new strategy for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Background: Phosphoglycerate kinase 1 (PGK1) is a metabolic enzyme that participates in various biological and pathological processes. Dysregulated PGK1 has been observed in numerous malignancies. However, whether and how PGK1 affects non-small cell lung cancer (NSCLC) is not yet fully elucidated. Methods: Herein, the non-metabolic function of PGK1 in NSCLC was explored by integrating bioinformatics analyses, cellular experiments, and nude mouse xenograft models. The upstream regulators and downstream targets of PGK1 were examined using multiple techniques such as RNA sequencing, a dual-luciferase reporter assay, Co-immunoprecipitation, and Western blotting. Results: We confirmed that PGK1 was upregulated in NSCLC and this upregulation was associated with poor prognosis. Further in vitro and in vivo experiments demonstrated the promoting effects of PGK1 on NSCLC cell growth and metastasis. Additionally, we discovered that PGK1 interacted with and could be O-GlcNAcylated by OGT. The inhibition of PGK1 O-GlcNAcylation through OGT silencing or mutation at the T255 O-GlcNAcylation site could weaken PGK1-mediated NSCLC cell proliferation, colony formation, migration, and invasion. We also found that a low miR-24-3p level led to an increase in OGT expression. Additionally, PGK1 exerted its oncogenic properties by augmenting ERK phosphorylation and MCM4 expression. Conclusions: PGK1 acted as a crucial mediator in controlling NSCLC progression. The miR-24-3p/OGT axis was responsible for PGK1 O-GlcNAcylation, and ERK/MCM4 were the downstream effectors of PGK1. It appears that PGK1 might be an attractive therapeutic target for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that sleep deprivation (S-Dep) is a critical risk factor for depression. Electroacupuncture (EA) treatment has been reported to ameliorate posttraumatic stress disorder- (PSTD-) like behavior and enhance hippocampal neurogenesis. However, whether EA treatment has any beneficial effect on S-Dep-induced depression-like behavior is still unknown. In the present study, we focused on whether EA at Baihui (GV20) can ameliorate the deterioration effect of S-Dep in mice. Mice were randomly divided into normal, S-Dep, S-Dep + EA, and S-Dep + sham EA groups. Cognitive behavior test and in vitro assay were performed separately to avoid the influence of behavior test on synaptic transmission and protein expression. Depression-like behaviors were determined by forced swimming test (FST), tail suspension test (TST), and Morris water maze (MWM). Neurogenesis was identified by BrdU, DCX, and NeuN immunofluorescence staining. In vitro long-term potentiation was detected by high frequency stimulation (HFS) at Schaffer collateral-CA1 synapses in hippocampal slices. Brain-derived neurotropic factor (BDNF) and tropomyosin receptor kinase B (TrkB) protein expression level were assayed by western blot. Our results indicated that D-Sep mice demonstrated depression-like behaviors determined by prolonged immobility duration in FST and TST; D-Sep mice also manifested spatial memory retention deficit in MWM. Furthermore, EA treatment ameliorated D-Sep-induced depression-like behaviors and spatial memory retention deficit. Mechanically, EA treatment alleviated neuron progenitor cell proliferation and differentiation, ameliorated the field excitatory postsynaptic potentials (fEPSPs) slope impaired by S-Dep, and elevated BDNF/TrkB protein expression. Taken together, our data suggested that EA treatment has a protective effect on S-Dep-induced depression-like behavior and cognitive impairment, which may be through regulating BDNF/TrkB protein expression. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease, but its pathogenesis is still unclear. Bioinformatics methods were used to explore the differentially expressed genes (DEGs) and to elucidate the pathogenesis of IPF at the genetic level. The microarray datasets GSE110147 and GSE53845 were downloaded from the Gene Expression Omnibus (GEO) database and analyzed using GEO2R to obtain the DEGs. The DEGs were further analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment using the DAVID database. Then, using the STRING database and Cytoscape, a protein–protein interaction (PPI) network was created and the hub genes were selected. In addition, lung tissue from a mouse model was validated. Lastly, the network between the target microRNAs (miRNAs) and the hub genes was constructed with NetworkAnalyst. A summary of 240 genes were identified as DEGs, and functional analysis highlighted their role in cell adhesion molecules and ECM–receptor interactions in IPF. In addition, eight hub genes were selected. Four of these hub genes (VCAM1, CDH2, SPP1, and POSTN) were screened for animal validation. The IHC and RT-qPCR of lung tissue from a mouse model confirmed the results above. Then, miR-181b-5p, miR-4262, and miR-155-5p were predicted as possible key miRNAs. Eight hub genes may play a key role in the development of IPF. Four of the hub genes were validated in animal experiments. MiR-181b-5p, miR-4262, and miR-155-5p may be involved in the pathophysiological processes of IPF by interacting with hub genes. [ABSTRACT FROM AUTHOR]

Background: With the development of domestic animal husbandry, the spread of brucellosis has accelerated, and the scope of the epidemic has expanded. The timely and accurate diagnosis of human brucellosis continues to challenge clinicians in endemic areas. Droplet digital PCR (ddPCR) technology can quickly and accurately determine DNA load in samples, providing laboratory evidence for diagnosis, prognosis and management of brucellosis patients. In this study, a ddPCR method was established to accurately quantify Brucella DNA load in whole blood samples, and its diagnostic, prognostic, and therapeutic value for human brucellosis was evaluated. Methods: Annealing temperature, primers, and probe targeting the Brucella bcsp31 gene were optimised, and the sensitivity, specificity and repeatability of the ddPCR assay were assessed using 94 whole blood samples from 61 confirmed and 33 suspected cases. Results were compared with those of quantitative PCR (qPCR). Nine follow-up brucellosis patients were also analysed by the two methods after 2 and 6 months of treatment. Results: Optimal primer and probe concentrations were 800 nmol/L and 400 nmol/L, respectively, and the optimal annealing temperature was 55.3 °C. The ddPCR results showed that the limit of detection was 1.87 copies per reaction, with high repeatability. The positive rates for ddPCR and qPCR were 88.5% and 75.4% among 61 serum agglutination test (SAT) positive patients. In addition, 57.6% (19/33) of suspected sero-negative samples were positive by ddPCR, but only 36.3% (12/33) were positive by qPCR. Analysis of nine post-therapy follow-up brucellosis patients revealed that the Brucella DNA load in the whole blood samples decreased after 2 and 6 months of treatment, and was slightly increased following relapse and continuous exposure. Conclusion: The ddPCR assay showed good accuracy for whole blood samples, and could be a potential diagnostic and prognostic tool for detecting Brucella. Author summary: Brucellosis is an important zoonosis, it is still a global public health issue. Based on an evaluation from the World Health Organization (WHO), brucellosis cases have been reported in more than 170 countries, with ~500,000 new cases reported each year. During the past decade, outbreaks of human brucellosis have been reported in increasing numbers, and with an apparent geographic expansion from the historically affected north of China to southern provinces, due to increased movement of humans, animals, and animal food products from brucellosis-endemic regions. In recent years, advanced molecular detection methods have improved laboratory diagnosis, and could serve as important alternatives to culture and serological methods. In this study, a ddPCR method was established to accurately quantify Brucella DNA load in whole blood samples, and its diagnostic, prognostic, and therapeutic value for human brucellosis was evaluated. The ddPCR results showed that the limit of detection was 1.87 copies per reaction, with high repeatability. The positive rates for ddPCR was 88.5% among 61 SAT positive patients. In addition, 57.6% (19/33) of suspected sero-negative samples were positive by ddPCR. The ddPCR assay showed good accuracy for whole blood samples, and could be a potential diagnostic and prognostic tool for detecting Brucella. [ABSTRACT FROM AUTHOR]

Rotation and fertilization are important methods used to improve crop yield. In particular, crop rotation is an effective means of enhancing ecosystem diversity; however, there exist relatively few studies regarding the effects of long-term maize–soybean rotation and fertilization on soil microbial communities. To further understand the changes in soil microbial community structure under long-term maize–soybean rotation and fertilization, we used a 9-year-old experimental site with maize–soybean rotation as the research object and soybean continuous cropping as a control. We explored the growth effects of soybean and the changes in soil microbial communities under the soybean–maize rotation system and fertilization treatments by analyzing the physicochemical properties of the soil, crop agronomic traits, yield, and changes in soil microbial community structure. The results show that, in comparison with soybean continuous cropping, the yield of soybeans was increased by 12.11% and 21.42% under maize–soybean rotation with different fertilization treatments, respectively. Additionally, there was a significant increase in the agronomic effects of nitrogen following rotation combined with fertilization. Moreover, the soil pH, SOM, and nutrient status were also improved. Bryobacter, Gemmatimonas, and Rhodanobacter were the dominant bacteria. Rotation treatment increased the relative abundance of Bryobacter and Rhodanobacter, and fertilization treatment increased the relative abundance of Gemmatimonas. Rotation also increased the stability of the bacterial community structure and strengthened the symbiotic relationship between species. The prediction of nitrogen-related functional genes indicates that rotation increased soil ammonification and nitrification. Heterocephalacria and Mrakia were the dominant fungal genera under crop rotation. The abundance of Saccharomyces Mrakia was significantly positively correlated with ammonium nitrogen levels and crop yield. Crop rotation increased the abundance of Saccharomyces Mrakia and reduced the abundance of Fusarium, but fertilization increased the abundance of Fusarium. Functional gene prediction also indicates that the relative abundance of plant pathogens was significantly reduced. This study provides a theoretical basis for soil microbial diversity and ecosystem service function in long-term soybean–maize rotation. [ABSTRACT FROM AUTHOR]

Sleep disorder is a state of sleep loss caused by various reasons, which leads to a series of changes, such as emotion, learning and memory, and immune function. “Tranquilizing and allaying excitement” was widely used in clinical treatment of insomnia; however, the mechanism was still not very clear. We randomly divided rats into three groups: control group, sleep deprivation group, and acupuncture treatment group. We observed BDNF and SYP expression in hippocampus in these three groups. Both protein contents and mRNA contents of BDNF and SYP were measured by western blot, immunohistochemistry, and RT-PCR analysis. The sleep deprivation model was established using modified multiple platform sleep deprivation method (MMPM). Our study explored the BDNF and SYP abnormality in hippocampus caused by sleep deprivation and “tranquilizing and allaying excitement” intervention regulated the abnormal expression of BDNF and SYP caused by sleep deprivation on the short run and the long run. Our study provided a molecular evidence that “tranquilizing and allaying excitement” treatment in rats with sleep disorder affects learning and memory ability. [ABSTRACT FROM AUTHOR]

A colloidal gold (ICS) test was developed for rapid detection of zearalenone (ZEN) in wheat samples. The mAb against ZEN was prepared in our laboratory and labelled with colloidal gold as a probe for the ICS test. The conditions were optimized and 30 nm colloidal gold nanoparticles were chosen for optimal performance. Millipore 135 was chosen as the NC membrane for its level of sensitivity. The optimum amount of coated antigen ZEN-OVA and anti-ZEN mAb was 0.5 mg/mL and 8 μg/mL, respectively. The ICS test, which has a detection limit of 15 ng/mL for ZEN, could be completed in 5 min. Analysis of ZEN in 202 wheat samples over three consecutive years revealed that data obtained from the ICS test were in a good agreement with LC-MS/MS data. This result demonstrated that the ICS test could be used as a qualitative tool to screen on-site for ZEN. [ABSTRACT FROM AUTHOR]

Osteoprotegerin (OPG) is a new member of the tumor necrosis factor (TNF) receptor superfamily, which can inhibit the differentiation and activity of osteoclasts by binding to nuclear factor kappa B receptor activator (RANK) competitively with nuclear factor kappa B receptor activator ligand (RANKL). The previous experiments found that OPG can induce apoptosis of mature osteoclasts in vitro, which can inhibit the activity of mature osteoclasts, thereby exerting its role in protecting bone tissue. In addition, pyroptosis is a new type of cell death that is different from apoptosis. It is unclear whether OPG can induce mature osteoclast pyroptosis and thereby play its role in protecting bone tissue. In this study, the results showed that compared with the control group, the survival rate of osteoclasts in the OPG group was significantly reduced, and the contents of IL-1β, IL-18, and LDH in the supernatant both increased. Many osteoclast plasma membranes were observed to rupture in bright fields, and OPG induced loss of their morphology. Flow cytometry was used to analyze the pyroptosis rate; OPG significantly increased the osteoclast pyroptosis rate. To further reveal the mechanism of OPG-induced osteoclast pyroptosis, we examined the expression level of pyroptosis-related genes and proteins, and the results found that OPG increased the expression of NLRP3, ASC, caspase-1, and GSDMD-N compared with the control group. In summary, OPG can induce osteoclast pyroptosis, and its mechanism is related to the expression levels of ASC, NLRP3, caspase 1 and GSDMD, which were included in the classical pathway of pyroptosis. [ABSTRACT FROM AUTHOR]

Avian influenza A virus H5N1 is a highly pathogenic and persistently a major threat to global health. Vaccines and antibodies targeting hemagglutinin (HA) protein are the primary management strategies for the epidemic virus. Although camelids possess unique immunological features, the immune response induced by specific antigens has not yet been thoroughly investigated. Herein, we immunized an alpaca with the HA antigen of the H5N1 virus and performed single-cell transcriptome profiling for analysis of longitudinal peripheral blood mononuclear cell (PBMCs) behavior using single-cell sequencing technology (scRNA-seq). We revealed multiple cellular immunities during the immunization. The monocytes continued to expand after immunization, while the plasma cells reached their peak three days after the second antigen stimulation. Both monocytes and B cells were stimulated by the HA antigen and produced cell-type-specific cytokines to participated in the immune response. To our knowledge, this is the first study to examine the HA-specific immunological dynamics of alpaca PBMCs at the single-cell level, which is beneficial for understanding the anti-viral immune system and facilitating the development of more potent vaccines and antibodies in camelid animals. [ABSTRACT FROM AUTHOR]

The effective use of nutrient-rich crop straw is an important way to use resources efficiently and to sustain agricultural development. This meta-analysis study collected and analyzed the data of 6788 observations published in 238 peer-reviewed papers to investigate differences in soil C-N fractions and yields of paddy soils under different straw-return amounts. This large dataset was also used to quantify the degree of influence of factors such as climate characteristics, soil properties, N fertilizer application rates, straw-rotting agent addition, rice varieties, and straw return methods. The results showed that straw return amounts improved soil alkaline-hydrolysable N (7%), total N (10%), organic C (11%), the C:N ratio (8%), rice N accumulation (12%), and overall yield (18%). The most significant effect was in northeast China fields for total soil nitrogen (TN) content and yield with increases of 13% and 22%, respectively. We also found more effective N utilization and a greater rice yield when 220–260 kg ha−1 N fertilizer was applied with 20–30 kg ha−1 straw-rotting agent with the total amount of straw return. These findings have important implications for choosing appropriate conditions and field management practices and to improve rice yield in China. [ABSTRACT FROM AUTHOR]

Environmental and occupational exposure to cadmium has been shown to induce kidney damage, liver injury, neurodegenerative disease, and osteoporosis. However, the mechanism by which cadmium induces autophagy in these diseases remains unclear. Studies have shown that cadmium is an effective inducer of oxidative stress, DNA damage, ER stress, and autophagy, which are thought to be adaptive stress responses that allow cells exposed to cadmium to survive in an adverse environment. However, excessive stress will cause tissue damage by inducing apoptosis, pyroptosis, and ferroptosis. Evidently, oxidative stress-induced autophagy plays different roles in low- or high-dose cadmium exposure-induced cell damage, either causing apoptosis, pyroptosis, and ferroptosis or inducing cell survival. Meanwhile, different cell types have different sensitivities to cadmium, which ultimately determines the fate of the cell. In this review, we provided a detailed survey of the current literature on autophagy in cadmium-induced tissue damage. A better understanding of the complex regulation of cell death by autophagy might contribute to the development of novel preventive and therapeutic strategies to treat acute and chronic cadmium toxicity. [ABSTRACT FROM AUTHOR]

Osteoprotegerin (OPG) is known to inhibit differentiation and activation of osteoclasts (OCs) by functioning as a decoy receptor blocking interactions between RANK and RANKL. However, the exact role of OPG in the survival/apoptosis of OCs remains unclear. OPG caused increased rates of apoptosis of both OCs and osteoclast precursor cells (OPCs). The expression of Fas and activated caspase-8 was increased by both 20 ng/mL and 40 ng/mL of OPG, but was markedly decreased at 80 ng/mL. Interestingly, we noted that while levels of Fas ligand (FasL) increased with increasing doses of OPG, the soluble form of FasL in the supernatant decreased. The results of a co-immunoprecipitation assay suggested that the decrease of sFasL might be caused by the binding of OPG. This would block the inhibition of the apoptosis of OCs and OPCs. Furthermore, changes in expression levels of Bax/Bcl-2, cleaved-caspase-9, cleaved-caspased-3 and the translocation of cytochrome c, illustrated that OPG induced apoptosis of OCs and OPCs via the classic Fas/FasL apoptosis pathway, and was mediated by mitochondria. Altogether, our results demonstrate that OPG induces OCs and OPCs apoptosis partly by the Fas/FasL signaling pathway. [ABSTRACT FROM AUTHOR]

• Increased PD-1 expression in CD4 and Th2 cells in Allergen-specific immunotherapy. • Allergen exposure increases PD-1 expression on CD4+T cells. • Allergen exposure did not affect CTLA-4 in CD4+ T and Th2+T cells. • T cell exhaustion plays an important role in Allergen-specific immunotherapy. Recent evidence has shown that T cell exhaustion is implicated in Allergen-specific Immunotherapy (AIT). However, how T cell exhaustion plays a role in AIT is far from clear. Our study aimed to investigate T cell exhaustion associated with allergen exposure during AIT in mice. Ovalbumin (OVA) − sensitized C57BL/6J asthma mouse and AIT mouse models were constructed. Quantitative real-time PCR (qRTPCR) and flow cytometry were used to monitor the occurrence of local and systemic CD4+ T cells and Th2+T cells exhaustion in OVA-sensitized mice. The inhibitory surface marker programmed cell death protein 1 (PD-1) on CD4+ T cells and Th2+T cells was significantly upregulated in AIT mice compared with asthmatic and control mice. The level of PD-1 on the surface of CD4+T cells of asthma mice was significantly higher than that of control mice. The inhibitory surface marker cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on CD4+ T cells and Th2+T cells showed no significant difference between the AIT, asthma and control mice. Collectively, our study indicated that the expression of PD-1 on CD4+ T cells and Th2+T cells was increased in AIT. Allergen exposure promotes the expression of PD-1 on the surface of CD4+ T cells. T cell exhaustion plays an important role in AIT. [ABSTRACT FROM AUTHOR]

Pressure injuries, also known as pressure ulcers, are regions of localized damage to the skin and/or underlying tissue. Repeated rounds of ischemia–reperfusion (I/R) have a major causative role for tissue damage in pressure injury. Ischemia prevents oxygen/nutrient supply, and restoration of blood flow induces a burst of reactive oxygen species that damages blood vessels, surrounding tissues and can halt blood flow return. Minimizing the consequences of repeated I/R is expected to provide a protective effect against pressure injury. Sulfaphenazole (SP), an off patent sulfonamide antibiotic, is a potent CYP 2C6 and CYP 2C9 inhibitor, functioning to decrease post-ischemic vascular dysfunction and increase blood flow. The therapeutic effect of SP on pressure injury was therefore investigated in apolipoprotein E knockout mice, a model of aging susceptible to ischemic injury, which were subjected to repeated rounds of I/R-induced skin injury. SP reduced overall severity, improved wound closure and increased wound tensile strength compared to vehicle-treated controls. Saliently, SP restored tissue perfusion in and around the wound rapidly to pre-injury levels, decreased tissue hypoxia, and reduced both inflammation and fibrosis. SP also demonstrated bactericidal activity through enhanced M1 macrophage activity. The efficacy of SP in reducing thermal injury severity was also demonstrated. SP is therefore a potential therapeutic option for pressure injury and other ischemic skin injuries. [ABSTRACT FROM AUTHOR]

Previous studies have revealed that miRNAs participate in the pathogenesis of ovarian cancer; however, whether miR-600 is also involved remains unclear. In this study, we aimed to investigated the role of miR-600 in ovarian cancer progression. Here, miR-600 expression was significantly upregulated in ovarian cancer tissues and stem cells. Functional studies showed that miR-600 promoted ovarian cancer cell stemness, proliferation and metastasis. Mechanistic studies revealed that Kruppel like factor 9 (KLF9) was indicated as the target of miR-600. The luciferase reporter assay suggested that miR-600 directly bound to the 3′-untranslated region of KLF9. Additionally, miR-600 expression was negatively associated with KLF9 expression in human ovarian cancer tissues. Si-KLF9 partially abolished the discrepancy of self-renewal, growth and metastasis capacity between miR-600 knockdown ovarian cancer cells and control cells. In conclusion, our results suggest that miR-600 promotes ovarian cancer cell stemness, proliferation and metastasis via directly downregulating KLF9, and impairing miR-600 levels may be a new treatment strategy for ovarian cancer in the future. [ABSTRACT FROM AUTHOR]