White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: A randomized placebo-controlled diffusion tensor imaging study.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored. METHODS: Diffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton. RESULTS: Voxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD than the placebo group in several tracts. CONCLUSION: The main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism. CLINICAL TRIAL REGISTRATION: EUDRA-CT 2016-001719-19; "Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study."; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE.

Optimizing mangrove afforestation: Mollusc biodiversity comparisons reveal optimal mudflat-mangrove area ratio.

In recent decades, mangrove wetlands globally have suffered from human activities and climate change, leading to issues like area reduction, degraded ecological functions and declining biodiversity. Restoration efforts, primarily through mangrove afforestation (i.e. mangrove plantation in mudflats), have been widespread, yet they often overlook the significance of unvegetated mudflats. In addition, under the condition that the total area of suitable mudflats is limited, the problem of what is the threshold of mangrove forests and unvegetated mudflats to better protect mangrove biodiversity has not been solved. Therefore, this study conducted a field survey of molluscs in mangrove wetlands in Hainan Island in China and explored the relative importance of mangroves and unvegetated mudflats through taxonomic alpha diversity and functional diversity. The results showed that (1) mollusc abundance of unvegetated mudflats was notably higher than this of mangrove forests, and the species richness, functional richness and functional vulnerability were significantly lower than those of mangrove forests; (2) the abundance and functional vulnerability of molluscs were mainly affected by sediment properties (pH, interstitial water salinity, median diameter, total nitrogen, C/N ratio), while the species richness and functional richness of molluscs were primarily influenced by vegetation structure (plant density); and (3) retaining at least 20% of the unvegetated mudflat area could well protect the biodiversity of mangrove wetlands. To our knowledge, our study is the first to propose the proportion of mangrove forests and unvegetated mudflats on the basis of benthic biodiversity, providing theoretical support and decision-making reference for mangrove protection and restoration.

High-Entropy Materials for Application: Electricity, Magnetism, and Optics.

High-entropy materials (HEMs) have recently emerged as a prominent research focus in materials science, gaining considerable attention because of their complex composition and exceptional properties. These materials typically comprise five or more elements mixed approximately in equal atomic ratios. The resultant high-entropy effects, lattice distortions, slow diffusion, and cocktail effects contribute to their unique physical, chemical, and optical properties. This study reviews the electrical, magnetic, and optical properties of HEMs and explores their potential applications. Additionally, it discusses the theoretical calculation methods and preparation techniques for HEMs, thereby offering insights and prospects for their future development.

Comparison of the coexistence pattern of mangrove macrobenthos between natural and artificial reforestation.

The abandoned pond-to-mangrove restoration project provides greater advantages than tidal flats afforestation in restoring mangrove ecosystem services and will be the primary method for mangrove restoration in the future. The existing methods for abandoned pond-to-mangrove restoration include artificial restoration through 'dike-breaking, filling with imported soil and tree planting' and natural restoration through 'dike-breaking and natural succession'. However, little is known about which restoration strategy (natural or artificial restoration) provides more benefits to the biodiversity of mangrove macrobethos. Given a prevailing view suggested that artificial restoration should be the preferred approach for accelerating recovery of biodiversity and vegetation structure in tropical regions, we hypothesised higher macrobenthic biodiversity and more complex community structure in artificial restoration than in natural restoration. To test this hypothesis, macrobenthic biodiversity and ecological processes were monitored in a typical abandoned pond-to-mangrove area of Dongzhaigang Bay, China, where artificial and natural restoration methods were used concurrently. Differences in macrobenthic biodiversity, community structure and ecological processes were compared using diversity indices, complex network analysis and null models. Similar species composition and ecological niche overlap and width among macrobenthos were observed at artificial and natural restoration sites. The biotic heterogeneity and interaction among macrobenthos were higher at the natural restoration sites than at the artificial restoration sites. Macrobenthos community assembly at natural and artificial restoration sites was both determined by deterministic processes, with environmental filtering dominating, which explained 52% and 54% of the variations in macrobenthic community structures respectively. Although our findings did not validate the research hypothesis, higher biotic heterogeneity and species interaction among macrobenthos could support natural restoration as the primary method for abandoned pond-to-mangrove projects, because it is a nature-based solution for mangrove restoration.

Public Attitudes towards and Management Strategies for Community Cats in Urban China.

Managing community cats in urban China is a contentious and emerging issue, with debates centering on the most effective and humane approaches. This study aimed to investigate public attitudes towards community cats and various management strategies. A survey was conducted involving 5382 urban residents in China. Their attitudes towards the positive and negative roles of community cats in urban areas and their support for different management methods were examined, including trap-and-kill, taking no action, centralized management, and trap-neuter-return (TNR) and its variations. Results indicated that 63% of participants were willing to coexist with community cats, 71% opposed trap-and-kill, and 61% agreed or strongly agreed with the TNR method and its variations. Older residents or those with higher incomes were more likely to support coexistence with community cats. In contrast, younger or lower-income residents were more likely to support non-coexistence. Residents in first- or second-tier cities (e.g., Beijing, Hangzhou, and Jinan Cities in China) were more inclined to support trap-and-kill and less likely to support coexistence than their counterparts in fourth-tier cities (e.g., county-level cities in China). Moreover, those with lower education or incomes were more supportive of trap-and-kill and taking no action as the methods to manage community cats than those with relatively higher education or incomes. Those with higher incomes held more positive attitudes towards community cats and were more supportive of TNR and its variations than their counterparts with lower incomes. Males were more inclined to support trap-and-kill and taking no action and less inclined to support centralized management and TNR than females. The implications of the findings on TNR with adoption programs in urban China are discussed. These novel findings underscore the need for targeted educational campaigns to promote humane and effective management strategies, addressing public concerns and community cats' welfare. The study's insights are critical for informing policy and improving community cat management in urban China.

Emerging perspectives on precision therapy for Parkinson's disease: multidimensional evidence leading to a new breakthrough in personalized medicine.

PD is a prevalent and progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Genes play a significant role in the onset and progression of the disease. While the complexity and pleiotropy of gene expression networks have posed challenges for gene-targeted therapies, numerous pathways of gene variant expression show promise as therapeutic targets in preclinical studies, with some already in clinical trials. With the recognition of the numerous genes and complex pathways that can influence PD, it may be possible to take a novel approach to choose a treatment for the condition. This approach would be based on the symptoms, genomics, and underlying mechanisms of the disease. We discuss the utilization of emerging genetic and pathological knowledge of PD patients to categorize the disease into subgroups. Our long-term objective is to generate new insights for the therapeutic approach to the disease, aiming to delay and treat it more effectively, and ultimately reduce the burden on individuals and society.

The Experience of Cervical Cancer Patients Undergoing Hysterectomy: A Qualitative Study.

INTRODUCTION: Due to different social and cultural backgrounds, cervical cancer patients' experience of the treatment process and quality of life after treatment will be different. This study sought to gain in-depth understanding of the experiences of Chinese cervical cancer patients as regards their quality of life and physical symptoms. METHODOLOGY: Semi-structured interviews were used to collect data. We recruited 15 women with cervical cancer in eastern China for in-depth interviews. All data were entered into the NVivo 12 software program for analysis. RESULTS: Four themes emerged from the data: (a) uncertainty; (b) physical suffering; (c) psychological pressure; and (d) challenges of marriage and family. DISCUSSION: Cervical cancer patients showed concerns about the disease itself and the physical discomfort it causes, as well as changes in social relations. Health professionals need to talk about these issues and develop strategies to address them accordingly.

A Survey of Public Opinion on Community Cats' General Health and Relationship Quality with Residents in Urban China.

The management and coexistence of community cats in urban areas is a growing concern amid global urbanization. Through a survey-based investigation, we examine the residents' perceptions of the general health of community cats and human-cat relationships in urban China. The data from 5382 participants revealed that approximately 70% of participants perceived community cats as being in good health, and 60% reported harmonious or non-conflict coexistence between residents and these cats. Around 45% of the participants rescued or helped community cats, 38% expressed their intention to adopt, and 18% complained about the issues of community cats to management staff. Linear, logistic, and multilevel-logistic regressions were employed to examine the associations between the types of cities and communities or the participants' socio-demographics and the perceived well-being of community cats or human-cat relationships. The results show that the cats in fourth-tier cities (e.g., county-level cities) had poorer living conditions than in first-tier cities (e.g., Beijing), while the cats in urban village communities (e.g., villages in the city) were less likely to exhibit good health than in ordinary commercial housing communities. The results also show that socio-demographic variables, such as educational attainment, marital status, and income level, predicted participants' relationships with community cats. This study is the first of its kind. It provides valuable insights for stakeholders to develop effective policies and interventions on cat management, emphasizing the need for tailored strategies in diverse urban settings and populations.

Monospecific mangrove reforestation changes relationship between benthic mollusc diversity and biomass: Implication for coastal wetland management.

Anthropogenic causes are overtaking natural factors to reshape patterns of biodiversity and ecosystem functioning. Mangrove reforestation aimed at reversing losses of mangroves has been conducted worldwide for several decades. However, how reforestation influences the link between ecological processes that shape community diversity and the consequent effects on ecosystem functions such as biomass production is less well known. Here we used data collected before and after mangrove planting to examine the effects of reforestation on molluscan species richness and biomass production by testing the changes in species richness, compositional similarities, distance-decay effects (community similarity decreases with increasing geographical distance) in metacommunity across a regional scale of 480 km (23-27 °N) in southeast Chinese coasts. Additionally, we further detected the impact of landscape configuration caused by different intensities of reforestation on the mollusc community. After the mangrove reforestation, mollusc species richness and biomass increased significantly. The increases in species richness and biomass of mollusc community were mediated by reducing distance-decay effect, indicating an increase in relationship strength between species richness and biomass might be associated with a decrease in distance-decay effect with rising mangrove habitat. We highlight the importance of considering the effects of anthropogenic changes on the relationship between biodiversity and ecosystem functioning. Quantifying the distance-decay effect of these influences enables management decisions about coastal restoration to be based upon ecological mechanisms rather than wishful thinking or superficial appearance.

Contact with nature for emotion regulation: the roles of nature connectedness and beauty engagement in urban young adults.

Contact with nature has emotional benefits, but the psychological mechanism and potential moderator underlying the association between nature contact and emotion regulation remain unclear. The present study investigated how self-reported frequency of nature contact is associated with the use of emotion regulation strategies and explored the mediating role of nature connectedness (i.e., psychological connection to nature) and the moderating role of engagement with natural beauty. Employing mediation and moderated mediation analyses, in a cross-sectional sample of 2097 young adults aged 18-35 years old (M = 24.01, SD = 4.80) residing in urban China, we obtained three major findings. First, nature connectedness mediated the associations between direct/indirect nature contact and cognitive reappraisal as well as expressive suppression. Second, engagement with natural beauty moderated the path from direct/indirect nature contact to cognitive reappraisal in the mediation models. Third, engagement with natural beauty moderated the path from indirect nature contact to nature connectedness in the mediation models. Our study is the first to reveal mediating and moderating factors in the relationships among direct/indirect contact with nature, nature connectedness, engagement with natural beauty, and emotion regulation strategies. These findings provide support for the emotional health of nature contact and have implications for nature-based education and urban planning.

Prevalence of psychological problems among caregivers of children and adolescents with neurodevelopmental disorders during the COVID-19 pandemic: A meta-analysis and systematic review.

BACKGROUND: The COVID-19 pandemic impacted children and adolescents with neurodevelopmental disorders, which caused difficulties and increased caregivers' burden. AIM: The objective of this study was to assess the prevalence of psychological problems among caregivers of children and adolescents with neurodevelopmental disorders. Methods and procedures We searched the PubMed, Embase and Web of Science databases for relevant studies published from December 2019 to March 2023. Random effects models were used to calculate the pooled prevalence of psychological problems among caregivers. Subgroup analyses were used to detect potential heterogeneity and sensitivity analyses were performed to evaluate the robustness of the included studies. Egger's and Begg's tests were used to examine publication bias. Outcomes and results Twenty studies involving 14,743 participants were included in this systematic review and meta-analysis. The main psychological problems among caregivers were anxiety (36.6%, 95% confidence interval [CI] 19.6-53.7%), depression (41.1%, 95%CI 35.4-46.8%), and stress (58.9%, 95%CI 45.1-72.7%). There were differences in prevalence by study year, national economic level, continent, and sample size. Conclusions and implications Our study showed that caregivers of children and adolescents with neurodevelopmental disorders had a high prevalence of anxiety, depression, and stress during the COVID-19 pandemic. Therefore, the psychological problems of these caregivers should not be overlooked. We recommend that the government should provide caregivers with more medical and financial assistance. What this paper adds? The current study is the first systematic review and meta-analysis focusing on parents whose children have neurodevelopmental disorders during the COVID-19 pandemic. The results show that the prevalence of psychological problems among caregivers of children with neurodevelopmental disorders is particularly prevalent, which suggests that we should attach importance to the parenting pressure and mental health of this special group.

Aspartyl-tRNA synthetase 2 orchestrates iron-sulfur metabolism in hematopoietic stem cells via fine-tuning alternative RNA splicing.

Aspartyl-tRNA synthetase 2 (Dars2) is involved in the regulation of mitochondrial protein synthesis and tissue-specific mitochondrial unfolded protein response (UPRmt). The role of Dars2 in the self-renewal and differentiation of hematopoietic stem cells (HSCs) is unknown. Here, we show that knockout (KO) of Dars2 significantly impairs the maintenance of hematopoietic stem and progenitor cells (HSPCs) without involving its tRNA synthetase activity. Dars2 KO results in significantly reduced expression of Srsf2/3/6 and impairs multiple events of mRNA alternative splicing (AS). Dars2 directly localizes to Srsf3-labeled spliceosomes in HSPCs and regulates the stability of Srsf3. Dars2-deficient HSPCs exhibit aberrant AS of mTOR and Slc22a17. Dars2 KO greatly suppresses the levels of labile ferrous iron and iron-sulfur cluster-containing proteins, which dampens mitochondrial metabolic activity and DNA damage repair pathways in HSPCs. Our study reveals that Dars2 plays a crucial role in the iron-sulfur metabolism and maintenance of HSPCs by modulating RNA splicing.

Differences in the evolution of urban and rural surface thermal environment and their responses to urban renewal in Shanghai, China.

The rapid and extensive urbanization has profound impacts on urban thermal environment. It is of great significance to comprehensively understand how urbanization affects the evolution of urban thermal environment for urban ecological safety, environmental quality, and residents' health. Based on daily land surface temperature (LST) products of MODIS Aqua satellite in the summer of 2002-2020, we investigated the evolution of urban-rural differences in surface summer thermal environment in Shanghai during 2002-2020 and its response to urban spatial renewal. We used normalized land surface temperature (NLST) and urban heat island ratio index (URI) as the surface thermal environment measurement indicators, by combining vegetation index and impervious surface cove-rage, and used M-K trend analysis and interpretation analysis. The results showed that the linear growth rate of LST in Shanghai was 0.09 ℃·a-1 (2002-2020), and that URI showed a trend of first increasing (2002-2010) and then decreasing (2010-2020). The mean summer LST was generally in the order of urban core>suburban>rural. 1.6% of the areas showed a significant cooling trend, of which 54.0% were distributed in the urban core. 39.5% of the regions showed a significant warming trend, of which 77.6% were distributed in the suburban. In general, there were concentrated significant cooling areas in the highly urbanized urban areas, while there was a significant warming trend in the suburban. The transformation from urban expansion to urban renewal was the main reason for the emergence of concentrated and significant cooling areas in the urban. Nearly 20% of the urban area showed a signi-ficant increase of vegetation coverage. Urban renewal projects such as gathering vegetation or dispersing impervious surfaces in highly urbanized areas are important ways to effectively improve the urban residential thermal environment.

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer: Extraction of active ingredients as an example.

The automation of traditional Chinese medicine (TCM) pharmaceuticals has driven the development of process analysis from offline to online. Most of common online process analytical technologies are based on spectroscopy, making the identification and quantification of specific ingredients still a challenge. Herein, we developed a quality control (QC) system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry (mini-MS). It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time. Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata (Fuzi) during decoction were used as examples, and the scientific principle of Fuzi compatibility was also investigated. Finally, the system was verified to work stably at the hourly level for pilot-scale extraction. This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.

Drivers of the spatiotemporal patterns of the mangrove crab metacommunity in a tropical bay.

Revealing community patterns and driving forces is essential in community ecology and a prerequisite for effective management and conservation efforts. However, the mangrove ecosystem and its important fauna group such as the crabs, still lack multi-processes research under metacommunity framework, resulting in evidence and theorical application gaps. To fill these gaps, we selected China's most representative mangrove bay reserve in tropical zone as a stable experimental system and conducted a seasonal investigation (July 2020, October 2020, January 2021, and April 2021) of mangrove crabs. We performed a multi-approach analysis using both pattern-based and mechanistic method to distinguish the processes driving the mangrove crab metacommunity. Our results showed that the crab metacommunity exhibits a Clementsian pattern in the bay-wide mangrove ecosystem but is influenced by both local environmental heterogeneity and spatial processes, thus representing a combined paradigm of species sorting and mass effect. Moreover, the long-distance spatial constraints are more pronounced compared to the local environmental factors. This is reflected in the greater importance of the broad-scale Moran's Eigenvector Maps, the distance-decay pattern of similarity, and the difference in beta diversity dominated by the turnover component. This pattern changes throughout the year, mainly due to changes in dominant functional groups caused by the stress of changes in water salinity and temperature induced by air temperature and precipitation. This research provides multi-dimension research data and relevant analysis, offering clear evidence for understanding the patterns and related driving forces of crab metacommunity in tropical bay mangroves, and verifies the applicability of some general laws in the system. Future studies can address more diverse spatiotemporal scales, gaining a clearer understanding to serve the conservation of mangrove ecosystems and economically important fishery species.

Vegetation growth enhancement modulated by urban development status.

Cities are natural laboratories for studying the vegetation response to global change due to their own climatic, atmospheric, and biological conditions. However, whether the urban environment promoted vegetation growth is still uncertain. Using the Yangtze River Delta (YRD), an economic powerhouse of modern China, as a case study, this paper investigated the impact of urban environment on vegetation growth at three scales: cities, sub-cities (rural-urban gradient) -pixels. Based on the satellite observations of vegetation growth indicated during 2000-2020, we explored the direct (replacement of original land by impervious surfaces) and indirect impact (e.g., climatic environment) of urbanization on vegetation growth and their trends with urbanization level. We found that significant greening accounted for 43.18 %, and significant browning accounted for 3.60 % of the pixels in the YRD. Urban area was turning green faster than suburban area. Moreover, land use change intensity (D) was a representation of the direct impact ωd of urbanization. The direct impact of urbanization on vegetation growth was positively correlated with the intensity of land use change. Furthermore, vegetation growth enhancement due to indirect impact ωi occurred in 31.71 %, 43.90 % and 41.46 % of the YRD cities in 2000, 2010 and 2020. And vegetation enhancement occurred in 94.12 % of highly urbanized cities in 2020, while in medium and low urbanization cities, the averaged indirect impact was near zero or even negative, proving that vegetation growth enhancement was modulated by urban development status. Also, the growth offset (τ) was most pronounced in high urbanization cities (4.92 %), but there was no growth compensation in medium urbanization cities (-4.48 %) and low urbanization cities (-57.47 %). When urbanization intensity reached a threshold value of 50 % in highly urbanized cities, the growth offset (τ) tended to saturate and remained unchanged. Our findings have important implications for understanding the vegetation response to continuing urbanization process and future climate change.

A mechanism study of DUSP1 in inhibiting malignant progression of endometrial carcinoma by regulating ERK/AP-1 axis and dephosphorylation of EPHA2.

Background: Endometrial carcinoma is one of the most common female malignancies worldwide. Based on our preliminary investigation, DUSP1 was identified as a potential biomarker for endometrial carcinoma prognosis, but its function and mechanism remained unclear. Methods: In this study, genes highly correlated with DUSP1 in endometrial cancer were found through correlation analysis, and the promoter sequence of DUSP1 was analyzed by PROMO program. Next-generation phosphorylation mass spectrometry was used to explore new downstream target proteins and pathways of DUSP1 in endometrial carcinoma. The mRNA and protein expression levels were detected by real-time quantitative PCR, immunohistochemistry and Western blotting. The cell survival and proliferation were analyzed by CCK8 assay, cell apoptosis was analyzed by Annexin-V-APC and PI dual staining assay, and the cell invasion was analyzed by Transwell method. Results: (1) There was a high correlation between the expression of DUSP1 and the genes involved in AP-1 complex and its co-expression network. (2) Promoter sequence analysis predicted that the members of AP-1 complex might be the upstream transcriptional regulators of DUSP1. (3) Transfection experiments proved DUSP1 can inhibit tumor growth and invasion, and promote apoptosis by regulating ERK pathway. (4) The results of phosphorylation mass spectrometry showed that overexpression of DUSP1 mainly dephosphorylated EPHA2 in endometrial carcinoma, and co-immunoprecipitation verified the protein interaction between DUSP1 and EPHA2. (5) Overexpression or knockdown of EPHA2 significantly changed the phosphorylation level of EPHA2. (6) The expression of EPHA2 protein was high in patients with more aggressive endometrial cancer. (7) Using EPHA2 inhibitor could significantly slow down the growth rate of tumor cells. Conclusion: (1) There exists a mutual regulation relationship between DUSP1 and AP-1 co-expression network in endometrial carcinoma. (2) It is reported for the first time that DUSP1 phosphatase acts on the ser899 site of EphA2 in endometrial carcinoma. (3) DUSP1 can inhibit tumor growth and invasion, and promote apoptosis by regulating MAPK pathway through directly dephosphorylating ERK, or by dephosphorylating EPHA2.

Metformin attenuates fibroblast activation during pulmonary fibrosis by targeting S100A4 via AMPK-STAT3 axis.

Fibroblasts activation is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis pathogenesis, and transforming growth factor (TGF)-ß1 plays a key regulatory role in fibroblast activation. It has been reported that metformin (MET) alleviated bleomycin (BLM)-induced pulmonary fibrosis (PF) by regulating TGF-ß1-induced fibroblasts activation, but the underlying mechanisms still deserve further investigations. In this study, MET blocked α-smooth muscle actin (α-SMA) accumulation in vivo accompanied with S100A4 expression and STAT3 phosphorylation inhibition, resulting in attenuating the progression of lung fibrosis after BLM administration. We determined that S100A4 plays critical roles in fibroblasts activation in vitro, evidenced by siRNA knockdown of S100A4 expression downregulated TGF-ß1 induced α-SMA production in Human fetal lung fibroblast (HFL1) cells. Importantly, we found for the first time that the expression of S100A4 in fibroblasts was regulated by STAT3. Stattic, an effective small molecule inhibitor of STAT3 phosphorylation, reduced S100A4 level in TGF-ß1- treated HFL1 cells accompanied with less α-SMA production. We further found that MET, which inhibits STAT3 phosphorylation by AMPK activation, also inhibits fibroblasts activation by targeting S100A4 in vitro. Together all these results, we conclude that S100A4 contributes to TGF-ß1- induced pro-fibrogenic function in fibroblasts activation, and MET was able to protect against TGF-ß1-induced fibroblasts activation and BLM-induced PF by down-regulating S100A4 expression through AMPK-STAT3 axis. These results provide a useful clue for a clinical strategy to prevent PF.

Rapid quality evaluation of Chinese herbal medicines using a miniature mass spectrometer: Lygodium japonicum (Thunb.) Sw. as an example.

The quality of Chinese herbal medicine (CHM) raw materials is essential, and mass spectrometry (MS)-based technologies have been playing key roles in the quality control of CHMs. However, the use of miniature mass spectrometry (mini-MS) for quality control of CHMs has rarely been reported. In this work, we developed a rapid analytical method for the quality evaluation of CHMs based on paper spray ionization (PSI)-mini-MS/MS. The quality evaluation of Lygodium japonicum (Thunb.) Sw. was used as an example. Following a "multi-component" quality evaluation strategy, nine active constituents of L. japonicum were selected to be used as analytes for quality control. We confirmed that the precursor-product ion information in the MS/MS spectra of each analyte in the herbal extracts was consistent with the standards. Also, we developed a mini-MS-based quantitative method for each analyte using its quantification ion. The quantitative methodology was rigorously validated using quality control samples. Finally, the quality evaluation of L. japonicum was carried out using the established MS/MS method combined with statistical analysis. A wide range of common quality issues with L. japonicum can be effectively determined, including whether it is adulterated with sand and distinguishing among different parts and species. This study demonstrates that mini-MS for quality evaluation of CHMs is feasible. Mini-MS for quality evaluation of herbal medicines will potentially have a good prospect due to its many advantages such as low cost, low power consumption, and portability in the future.

Melatonin ameliorates bleomycin-induced pulmonary fibrosis via activating NRF2 and inhibiting galectin-3 expression.

Pulmonary fibrosis (PF) is a chronic interstitial lung disease with no effective therapies. Galectin-3 (Gal-3), a marker of oxidative stress, plays a key role in the pathogenesis of PF. Fibroblast-myofibroblast differentiation (FMD) is an important source of fibrotic cells in PF. Previous studies showed that melatonin (MT) exerted anti-fibrotic effect in many diseases including PF through its antioxidant activity. In the present study we investigated the relationships among Gal-3, NRF2, ROS in FMD and their regulation by MT. We established an in vitro model of FMD in TGF-ß1-treated human fetal lung fibroblast1 (HFL1) cells and a PF mouse model via bleomycin (BLM) intratracheal instillation. We found that Gal-3 expression was significantly increased both in vitro and in vivo. Knockdown of Gal-3 in HFL1 cells markedly attenuated TGF-ß1-induced FMD process and ROS accumulation. In TGF-ß1-treated HFL1 cells, pretreatment with NRF2-specific inhibitor ML385 (5 µM) significantly increased the levels of Gal-3, α-SMA and ROS, suggesting that the expression of Gal-3 was regulated by NRF2. Treatment with NRF2-activator MT (250 µM) blocked α-SMA and ROS accumulation accompanied by reduced Gal-3 expression. In BLM-induced PF model, administration of MT (5 mg·kg-1·d-1, ip for 14 or 28 days) significantly attenuated the progression of lung fibrosis through up-regulating NRF2 and down-regulating Gal-3 expression in lung tissues. These results suggest that Gal-3 regulates TGF-ß1-induced pro-fibrogenic responses and ROS production in FMD, and MT activates NRF2 to block FMD process by down-regulating Gal-3 expression. This study provides a useful clue for a clinical strategy to prevent PF. Graphic abstract of the mechanisms. MT attenuated BLM-induced PF via activating NRF2 and inhibiting Gal-3 expression.