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Understanding the temporal and spatial variation of hydrochemical components in large freshwater lakes is crucial for effective management and conversation. In this study, we identify the temporal-spatial characteristics and driving factors of the hydrochemical components in Baiyangdian Lake using geochemical methods (Gibbs diagram, Piper diagram and End-element diagram of ion ratio) and multivariate statistical techniques (Principal component analysis and Correlation analysis). 16 sets of samples were collected from Baiyangdian Lake in May (normal season), July (flood season), and December (dry season) of 2022. Results indicate significant spatial variation in Na+, Cl−, SO42− and NO3− , suggesting a strong influence of human activities. Cation concentrations exhibit greater seasonal variation in the dry season compared to the flood season, while the concentrations of the four anions show inconsistent seasonal changes due to the combined effects of river water chemical composition and human activities. The hydrochemical type of Baiyangdian Lake is primarily HCO3·Cl-Na·Ca2+, Mg2+ and HCO3− originate mainly from silicate and carbonate rock dissolution, while K+, Na+ and Cl− originate mainly from sewage and salt dissolution in sediments. SO42− may mainly stem from industrial wastewater, while NO3− primarily originates from animal feces and domestic sewage. Through the use of Principal Component Analysis, it is identified that water-rock interaction (silicate and carbonate rocks dissolution, and dissolution of salt in sediments), carbonate sedimentation, sewage, agricultural fertilizer and manure, and nitrification are the main driving factors of the variation of hydrochemical components of Baiyangdian Lake across three hydrological seasons. These findings suggest the need for effective control of substandard domestic sewage discharge, optimization of agricultural fertilization strategies, and proper management of animal manure to comprehensively improve the water environment in Baiyangdian Lake.

In this manuscript, utilizing interpolative contractions with fractional forms, some unique fixed-point results were studied in the context of extended $ b $-metric spaces. For the validity of the presented results some examples are given. In the last section an existence theorem is provided to study the existence of a solution for the Fredholm integral equation.

Abstract Background The surgically facilitated orthodontic strategy has been a promising strategy for orthodontic treatment recently. Therefore, the present meta-analysis was conducted to assess the available scientific evidence regarding the clinical outcomes, including the potential detrimental effects associated with these surgical procedures, with the aim of providing much more evidence-based information for clinical practice. Methods An electronic search of three databases (PubMed, Cochrane, and Embase) and a manual search of relevant articles published up to May 2023 were carried out. Clinical trials (≥ 10 subjects) that utilized surgically facilitated orthodontic strategies with clinical and/or radiographic outcomes were included. Meta-analyses and sub-group analyses were performed to analyze the standardized mean difference (SMD) or weighted mean difference (WMD), and confidence interval (CI) for the recorded variables. Results Nineteen studies published from Oct 2012 to May 2023 met the inclusion criteria. Based on the analysis outcomes, corticotomy treatment significantly decreased the alignment duration (WMD: -1.08 months; 95% CI = -1.65, -0.51 months, P = 0.0002), and accelerated the canine movement (WMD: 0.72 mm; 95% CI = 0.63, 0.81 mm, P

ABSTRACTObjectives The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients.Methods On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology.Results On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS.Conclusions In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

Hydrological runoff prediction is vital for water resource management. The non-linear and non-stationary runoff series and the complex hydrological features for large-scale basins make it difficult to predict. Long short-term memory (LSTM) is effective for runoff prediction but unstable for large-scale basins. This study develops three hybrid models combined with two-stage decomposition and LSTM, including wavelet transformation (WT) combined with complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), variational mode decomposition (VMD), and local mean decomposition (LMD), to predict the daily runoff of the Pearl River in China. The results indicate CEEMDAN's broader signal decomposition applicability for runoff series preprocessing, while VMD is simpler to extract high-runoff characteristics. VMD–WT–LSTM is appropriate for predicting high and median runoff, whereas CEEMDAN–WT–LSTM is better for low-runoff and high and median runoffs with low-violent fluctuations. These hybrid models provide satisfactory predictions for NSE and R2 indicators, and 97.2% of indicators fall within the acceptable range for high-runoff predictions. The hybrid models outperform traditional and standalone models in high-runoff but none of the decomposition methods in this research can identify low-runoff sub-sequence. This study provided runoff prediction methods requiring fewer data and processing time, and these methods are promising alternatives for daily runoff prediction in large-scale basins. HIGHLIGHTS Data-driven model is the trend of runoff prediction model.; Signal decomposition technology can decompose the runoff features.; Wavelet transformation can decompose highly fluctuating runoffs.; The LSTM-based hybrid model is suitable for river runoff prediction.; Signal decomposition-LSTM model outperforms the standalone model.;

Abstract Biomarker detection is key to identifying health risks. However, designing sensitive and single-use biosensors for early diagnosis remains a major challenge. Here, we report submonolayer lasers on optical fibers as ultrasensitive and disposable biosensors. Telecom optical fibers serve as distributed optical microcavities with high Q-factor, great repeatability, and ultralow cost, which enables whispering-gallery laser emission to detect biomarkers. It is found that the sensing performance strongly depends on the number of gain molecules. The submonolayer lasers obtained a six-order-of-magnitude improvement in the lower limit of detection (LOD) when compared to saturated monolayer lasers. We further achieve an ultrasensitive immunoassay for a Parkinson’s disease biomarker, alpha-synuclein (α-syn), with a lower LOD of 0.32 pM in serum, which is three orders of magnitude lower than the α-syn concentration in the serum of Parkinson’s disease patients. Our demonstration of submonolayer biolaser offers great potentials in high-throughput clinical diagnosis with ultimate sensitivity.

In this paper, we will introduce the idea of grand variable weighted Herz spaces $ {{\dot{K} ^{\alpha(\cdot), \epsilon), \theta}_{ q(\cdot)}(\tau)}} $ in which $ \alpha $ is also a variable. Our main purpose in this paper is to prove the boundedness of Hardy operators on grand variable weighted Herz spaces.

Abstract Background B-cell lymphoma 2 (Bcl-2) family proteins are key regulators of apoptosis, which possess four conserved Bcl-2 homologies (BH) domains. Among the BH domains, the BH3 domain is considered as a potent ‘death domain’ while the BH4 domain is required for anti-apoptotic activity. Bcl-2 can be converted to a pro-apoptotic molecule through the removal or mutation of the BH4 domain. Bcl-2 is considered as an inducer of angiogenesis, which can promote tumor vascular network formation and further afford nutrients and oxygen to promote tumor progression. However, whether disrupting the function of the BH4 domain to convert Bcl-2 into a pro-apoptotic molecule could make Bcl-2 possess the potential for anti-angiogenic therapy remains to be defined. Methods CYD0281 was designed and synthesized according to the lead structure of BDA-366, and its function on inducing a conformational change of Bcl-2 was further evaluated via immunoprecipitation (IP) and immunofluorescence (IF) assays. Moreover, the function of CYD0281 on apoptosis of endothelial cells was analyzed via cell viability, flow cytometry, and western blotting assays. Additionally, the role of CYD0281 on angiogenesis in vitro was determined via endothelial cell migration and tube formation assays and rat aortic ring assay. Chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models, breast cancer cell xenograft tumor on CAM and in mouse models as well as the Matrigel plug angiogenesis assay were used to explore the effects of CYD0281 on angiogenesis in vivo. Results We identified a novel potent small-molecule Bcl-2-BH4 domain antagonist, CYD0281, which exhibited significant anti-angiogenic effects both in vitro and in vivo, and further inhibited breast cancer tumor growth. CYD0281 was found to induce conformational changes in Bcl-2 through the exposure of the BH3 domain and convert Bcl-2 from an anti-apoptotic molecule into a cell death inducer, thereby resulting in the apoptosis of vascular endothelial cells. Conclusions This study has revealed CYD0281 as a novel Bcl-2-BH4 antagonist that induces conformational changes of Bcl-2 to convert to a pro-apoptotic molecule. Our findings indicate that CYD0281 plays a crucial role in anti-angiogenesis and may be further developed as a potential anti-tumor drug candidate for breast cancer. This work also provides a potential anti-angiogenic strategy for breast cancer treatment.

Abstract Hepatocellular carcinoma (HCC) is an aggressive and fatal disease caused by a subset of cancer stem cells (CSCs). It is estimated that there are approximately 100 000 long noncoding RNAs (lncRNAs) in humans. However, the mechanisms by which lncRNAs affect tumor stemness remain poorly understood. In the present study, it is found that DIO3OS is a conserved lncRNA that is generally downregulated in multiple cancers, including HCC, and its low expression correlates with poor clinical outcomes in HCC. In in vitro cancer cell lines and an in vivo spontaneous HCC mouse model, DIO3OS markedly represses tumor development via its suppressive role in CSCs through downregulation of zinc finger E‐box binding homeobox 1 (ZEB1). Interestingly, DIO3OS represses ZEB1 post‐transcriptionally without affecting its mRNA levels. Subsequent experiments show that DIO3OS interacts with the NONO protein and restricts NONO‐mediated nuclear export of ZEB1 mRNA. Overall, these findings demonstrate that the DIO3OS‐NONO‐ZEB1 axis restricts HCC development and offers a valuable candidate for CSC‐targeted therapeutics for HCC.

Histone deacetylase 6 (HDAC6), an almost exclusively cytoplasmic enzyme, plays an essential role in many biological processes and exerts its deacetylation-dependent/independent effects on a variety of target molecules, which has contributed to the flourishing growth of relatively isoform-specific enzyme inhibitors. Renal transplantation (RT) is one of the alternatively preferred treatments and the most cost-effective treatment approaches for the great majority of patients with end-stage renal disease (ESRD). HDAC6 expression and activity have recently been shown to be increased in kidney disease in a number of studies. To date, a substantial amount of validated studies has identified HDAC6 as a pivotal modulator of innate and adaptive immunity, and HDAC6 inhibitors (HDAC6i) are being developed and investigated for use in arrays of immune-related diseases, making HDAC6i a promising therapeutic candidate for the management of a variety of renal diseases. Based on accumulating evidence, HDAC6i markedly open up new avenues for therapeutic intervention to protect against oxidative stress–induced damage, tip the balance in favor of the generation of tolerance-related immune cells, and attenuate fibrosis by inhibiting multiple activations of cell profibrotic signaling pathways. Taken together, we have a point of view that targeting HDAC6 may be a novel approach for the therapeutic strategy of RT-related complications, including consequences of ischemia-reperfusion injury, induction of immune tolerance in transplantation, equilibrium of rejection, and improvement of chronic renal graft interstitial fibrosis after transplantation in patients. Herein, we will elaborate on the unique function of HDAC6, which focuses on therapeutical mechanism of action related to immunological events with a general account of the tantalizing potential to the clinic.

Abstract Previous palaeoenvironmental reconstructions have implied that East Asia was dominated by a zonal climate pattern during the Eocene, with an almost latitudinal arid/semiarid band at ~ 30° N. However, this long-standing model has recently been challenged by growing body of multidisciplinary evidence. Some studies indicated that central China was characterized by climatic fluctuations between humid and drier conditions during the Early Eocene, akin to the present East Asian monsoon (EAM) regime. Using palynological assemblages in the Tantou Basin, central China, we quantitatively reconstructed climate changes from the Late Palaeocene to Early Eocene to better understand climate change in central China. Palynological assemblages revealed that the coniferous and broad-leaved mixed forest in this area received no less than 800 mm of annual precipitation and experienced a climate change from warm and wet to relatively cool and dry. According to palaeoclimate curves, a sudden climate change occurred in the Early Eocene, with the mean annual temperature and precipitation decreasing by 5.1 °C and 214.8 mm, respectively, and the climate became very similar to the present climate, which is controlled by the monsoon. Therefore, this significant climate change during the Early Eocene may signal the emergence of the EAM in East Asia.

Objective: The present study was aimed to identify hub genes associated with recurrent spontaneous abortion (RSA) via both bioinformatics analysis and clinical verification, also to evaluate the related pathways and immune infiltration situation of RSA, for exploring its underlying mechanism. Materials and methods: We screened candidate hub genes associated with RSA via bioinformatic analysis in the microarray datasets GSE22490 downloaded from the Gene Expression Omnibus (GEO) database. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to validate these hub genes. Several kinds of enrichment analysis were carried out to find out the pathways related to RSA. Additionally, CIBERSORT was used for evaluation of local immune Infiltration status of RSA. Results: There were 536 differentially expressed genes (DEGs) including 301 upregulated and 235 downregulated genes in RSA group compared with healthy control group. Four hub genes (STAT3, TLR2, TLR4 and CD86) were finally screened out according to the protein–protein interaction (PPI) network analysis, RT-qPCR and Western blotting. Enrichment analysis showed that Toll-like receptor signaling pathway, neutrophil chemotaxis, chemokine signaling pathway and Fc gamma receptor-mediated phagocytosis were strongly associated with RSA. And in immune infiltration analysis, RSA tissue was found containing a higher proportion of monocytes and eosinophils. Conclusion: This study screened out four hub genes and several important pathways changed in the trophoblastic tissue of RSA patients. We also found that monocytes and eosinophils may be involved in RSA. These findings provide theoretical basis for further studies on the mechanisms of RSA.

Laccases, as a kind of multicopper oxidase, play an important role in pigment synthesis and growth in fungi and are involved in their interactions with host plants. In Setosphaeria turcica, 9 laccase-like multicopper oxidases have been identified, and StLAC2 is involved in the synthesis of the melanin that accumulates in the cell wall. The function of another major laccase gene, StLAC6, was studied here. The knockout of StLAC6 had no effect on the growth, morphology or invasion ability of S. turcica, but the morphology and function of peroxisomes of knockout mutants were abnormal. The knockout of the StLAC6 gene resulted in increased contents of phenolic compounds and melanin and the sensitivity to fungicides increased compared with wild type strains. In the mutants of StLAC6, there is a significant change of the expression levels of other laccase genes. This study provides a new insight into laccase functions and the relationship of the laccase gene family in plant pathogenic fungi.

A two-way parabolic equation (2W-PE) method based on complex-valued neural networks (CVNNs) and a physics-informed neural network (PINN) is proposed to predict the spatial field in the environment of dielectric obstacles with high efficiency and accuracy. In the framework of the 2W-PE method, CVNNs are used to calculate the lumped transmission field and the lumped reflection field considering the influence of the obstacle, thus avoiding the long calculation time caused by the internal multilayered reflection processes. The incident directions and field strength of the waves on the regional boundaries vary greatly with the propagation environment, so coefficients of the boundary conditions are obtained by using the PINN. Next, the training results are applied to the examples using the continuation method and compared with the numerical results of the method of moments (MoM). The proposed 2W-PE method has high computational accuracy and efficiency, which reflects the applicability of machine learning in solving the computational efficiency problem of radio wave propagation. Therefore, this study provides a very effective and reliable method for solving the spatial field in the obstacle environment.

Background Tacrolimus is a new type immunosuppressant. The aim of this study was to evaluate the effectiveness of topical tacrolimus 0.1% ointment at 2 different frequencies in treating patients with exfoliative cheilitis. Methods A total of 40 patients with exfoliative cheilitis were randomly divided into the QD group receiving topical tacrolimus 0.1% ointment once a day or the QOD group receiving topical tacrolimus 0.1% ointment once-two-day. Patients were also applied wet dressing of saline twice a day. The effectiveness of treatment was defined as the percentage of improvement in signs or symptoms. Results 37 patients completed the 2-week treatment. And, a full set was analyzed. The effectiveness of topical tacrolimus 0.1% ointment for relief in objective sign and subjective symptom was 50% and 67.5%% in the QD group, respectively. For the QOD group, the effectiveness of sign and symptom relief was 50% and 73.5%. There was no significant difference of effectiveness between application topical tacrolimus once a day and once 2 days. Conclusion Our data suggested that application of topical tacrolimus 0.1% ointment once a day and once 2 days had similar clinical effectiveness for sign and symptom relief in patients with exfoliative cheilitis.

Abstract Transforming acidic coiled-coil containing protein1 (TACC1) is closely related to transcription, translation and centrosome dynamics. Dysregulation of TACC1 is associated with multiple malignancies. Alternative splicing (AS) of TACC1 produces multiple variants, which are of great significance in cancer biology. However, the expression and biological functions of TACC1 variants in head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we found for the first time that TACC1 variants exhibited a characteristic expression pattern and that TACC1 variant25 (TACC1v25) was downregulated in HNSCC tissues and cell lines. Overexpression of TACC1v25 in Cal27 and Fadu cells significantly inhibited proliferation and promoted autophagy. Moreover, expression levels of nuclear pERK and p-mTOR were significantly decreased, while the expression of Beclin-1 and the LC3II/LC3I ratio were increased in TACC1v25-overexpressed Cal27 and Fadu cells. After the addition of AKT activator SC79 to TACC1v25-overexpressed Cal27 and Fadu cells, the autophagy levels were remarkably rescued. In conclusion, TACC1v25 inhibits HNSCC progression through the ERK and AKT/mTOR pathways by inhibiting proliferation and increasing autophagy. TACC1v25 might have potential use as a tumour suppressor in HNSCC.

The 7 + 3 regimen is the front-line induction chemotherapy in patients with newly diagnosed acute myeloid leukemia, with a response rate of 60-80%. But it’s not suitable for all patients especially old/unfit patients because of a higher treatment related toxicity. Therefore, safer and more effective induction therapies are required. In this retrospective study, 50 patients with newly diagnosed acute myeloid leukemia received decitabine combined with HAAG (homoharringtonine, aclarubicin, low-dose cytarabine and G-CSF) as induction chemotherapy. Complete remission (CR) rate was 96% (48/50) and overall response rate was 100%. Of note, All 7 patients harboring FLT3-ITD mutation achieved CR. The median overall survival (OS) was 40.0 months (range 2.0, 58.0). The OS at 1, 3, and 5 years were 75.3%, 54.2%, and 49.3%. The median relapse free survival (RFS) was 38.0 months (range 2.0, 58.0). The RFS at 1, 3, and 5 years were 67.3%, 48.9%, and 45.1%. The OS and RFS of patients who received hematopoietic stem cell transplantation (HSCT) were significantly higher than those who did not undergo HSCT (p=0.017; 0.016). The incidence of grade 3-4 neutropenia and thrombocytopenia was 84% and 88%. Meanwhile, the incidence of grade 3-4 infection and bleeding was only 16% and 6%. There was no early death. In conclusion, DAC+HAAG regimen is effective and well-tolerated as induction therapy in patients with newly diagnosed AML.

ObjectiveThis study aimed to explore transcranial electrical stimulation (tES) to relieve peripartum anxiety and depressive symptoms in women undergoing cesarean section with combined spinal–epidural anesthesia.MethodsThis double-blind, randomized, sham-controlled trial was conducted in the Affiliated Hospital of Xuzhou Medical University from March 2021 and May 2021. One hundred and forty-eight full-term parturients giving birth by elective cesarean section were selected, and 126 were included in the intent-to-treat analysis. Parturients were provided standardized anesthesia and randomized to the active-tES (a-tES) group and sham-tES group. Parturients and outcome assessors were blinded to treatment allocation. The primary outcome was the changes in peripartum mental health disorders, including anxiety, assessed by the Pregnancy-Related Anxiety Questionnaire-Revised 2 (PRAQ-R2). Secondary outcomes included peripartum depressive symptoms, assessed by the Edinburgh Postnatal Depression Scale (EPDS), maternal satisfaction, fatigue level, sleep quality index, and pain score during and after operation. Data were collected before entering the operating room (T0), between post-anesthesia and pre-surgery (T1), before leaving the operating room (T2), and at 24 h post-surgery (T3).ResultsOne hundred and twenty-six eligible parturients were enrolled in the two groups: a-tES group (N = 62) and sham-tES group (N = 64). Treatment with tES resulted in significantly lower scores of anxiety compared with sham-tES (T2: P < 0.001; T3: P = 0.001). Moreover, the a-tES groups showed a significant reduction in depression scores (T2: P = 0.003; T3: P = 0.032).ConclusionIn this randomized pilot study, tES treatment is efficacious in alleviating peripartum anxiety and depressive symptoms in women undergoing cesarean section and has been demonstrated to be a novel strategy for improving peripartum mental health disorders.Clinical Trial Registration[www.chictr.org.cn], identifier [ChiCTR2000040963].

Galactic supernova remnants (SNRs) play an important role in our understanding of supernovae and their feedback on the interstellar environment. SNR G352.7-0.1 is special for its thermal composite morphology and double-ring structure. We have performed spectroscopic mapping of the ^12 CO and ^13 CO J = 2–1 lines toward G352.7-0.1 with the Atacama Pathfinder Experiment telescope. Broad ^12 CO lines are found in the northeastern ring at a local-standard-of-rest velocity range of ∼−50 to −30 km s ^−1 , suggesting that the remnant is interacting with molecular clouds at ∼−51 km s ^−1 . Thus, we adopt a distance of ∼10.5 kpc for this SNR. The momentum and kinetic energy of the shocked gas along the line of sight are estimated to be ∼10 ^2 M _☉ km s ^−1 and ∼10 ^46 erg, respectively. We also find an expanding structure around the remnant, which is possibly related to the wind-blown bubble of the progenitor star. From Fermi-LAT data in the energy range 0.1–500 GeV, we find no gamma-ray counterparts to G352.7-0.1.

Background: The ongoing COVID-19 pandemic has disproportionately affected the sleep health of older adults, but the limited number of studies on insomnia symptoms of older Chinese adults differed in terms of screener of insomnia, sample size, and prevalence, making mental health planning for this population difficult. This meta-analysis estimated the prevalence of insomnia symptoms in older Chinese adults during the COVID-19 pandemic.Methods: Both Chinese (CNKI, Wanfang, VIP) and English (PubMed, EmBase, PsycInfo) databases were systematically searched to identify cross-sectional studies containing data on the prevalence of insomnia symptoms in older Chinese adults during the pandemic. Risk of bias (RoB) of included studies was assessed with the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data.Results: Nine studies with a total of 27,207 older Chinese adults were included. RoB scores of these studies ranged between zero and six. The pooled prevalence rates of insomnia symptoms and moderate and severe insomnia symptoms were 24.6% [95% confidence interval (CI): 19.5–30.5%] and 11.1% (95% CI: 7.2–16.9%), respectively. In subgroup analysis, significantly higher prevalence rates were observed in studies defining insomnia symptoms as “Insomnia Severity Index (ISI) ≥ 8” than in those defining them as “ISI ≥ 15” (32.6 vs. 15.6%, P < 0.001) and in older adults living in the COVID-19 epicenter than in those living in other places (35.2 vs. 23.3%, P = 0.006).Conclusion: Nearly one out of every four older Chinese adults suffered from insomnia symptoms during the pandemic. Mental health services for this population during the pandemic should include supportive activities aimed at improving mental well-being, periodic assessment of insomnia symptoms, and psychiatric assessment and treatment when necessary.

Anaerobic digesters have been widely used to treat wastewaters in livestock farms. With the increasing risk of antibiotic resistance originated from livestock husbandry, removal of antibiotics and antibiotic resistance genes (ARGs) via anaerobic digesters deserved more attention. Here we investigated the removal of antibiotics and ARGs in swine wastewater by three on-farm full-scale anaerobic digesters, including buried biogas digester (BBD), up-flow anaerobic sludge blanket (UASB) and high density polyethylene covered biogas digester (HDPE-BD). Variations of antibiotic resistome in swine wastewater were further revealed by metagenomic sequencing. Results showed the removal efficiencies for antibiotics, ARGs and mobile genetic elements (MGEs) varied in the three digesters, ranging from 65.1% to 98.1%, 3.5%-71.0% and 26.9%-77.2%, respectively. In general, UASB and HDPE-BD showed better removal efficiencies than BBD. However, enrichment of metal resistance genes (MRGs) was noted in UASB. Pathogens could not be effectively removed by all of the three digesters. What’s more, accumulation of pathogens was found in UASB (removal efficiencies: −8.5%-13.6%). Bacterial community succession, horizontal genetic transfer and biocide and metal resistance genes (BMRGs) profiles jointly structured the variation of antibiotic resistome during anaerobic digestion. A total of 334 high-quality bins were identified from swine wastewater, 96 of which belonged to phylum of Firmicutes, Bacteroidetes and Proteobacteria carried ARGs. Proteobacteria was the dominant multi-drug resistant flora. Meanwhile, ARG-carrying pathogens (Bacteroides and Mycolicibacter) were found in the swine wastewater, suggesting a potential threat to human and animal health. The findings from this study showed that HDPE-BD is the most eco-friendly and effective anaerobic digester in controlling risks from antibiotic resistance determinants in swine wastewater.

Summary: Mitochondrial biogenesis is a cell response to external stimuli which is generally believed to suppress apoptosis. However, during the process of apoptosis, whether mitochondrial biogenesis occurs in the early stage of the apoptotic cells remains unclear. To address this question, we constructed the COX8-EGFP-ACTIN-mCherry HeLa cells with recombinant fluorescent proteins respectively tagged on the nucleus and mitochondria and monitored the mitochondrial changes in the living cells exposed to gamma-ray radiation. Besides in situ detection of mitochondrial fluorescence changes, we also examined the cell viability, nuclear DNA damage, reactive oxygen species (ROS), mitochondrial superoxide, citrate synthase activity, ATP, cytoplasmic and mitochondrial calcium, mitochondrial mass, mitochondrial morphology, and protein expression related to mitochondrial biogenesis, as well as the apoptosis biomarkers. As a result, we confirmed that significant mitochondrial biogenesis took place preceding the radiation-induced apoptosis, and it was closely correlated with the apoptotic cells at late stage. The involved mechanism was also discussed.

Tumor growth and metastasis are responsible for breast cancer-related mortality. Andrographolide (Andro) is a traditional anti-inflammatory drug used in the clinic that inhibits NF-κB activation. Recently, Andro has been found in the treatment of various cancers. Andro inhibits breast cell proliferation and invasion and induces apoptosis via activating various signaling pathways. Therefore, the underlying mechanisms with regard to the antitumor effects of Andro still need to be further confirmed. Herein, a MMTV-PyMT spontaneous luminal-like breast cancer lung metastatic transgenic tumor model was employed to estimate the antitumor effects of Andro on breast cancer in vivo. Andro significantly inhibited tumor growth and metastasis in MMTV-PyMT mice and suppressed the cell proliferation, migration, and invasion of MCF-7 breast cancer cells in vitro. Meanwhile, Andro significantly inhibited the expression of NF-κB, and the downregulated NF-κB reduced miR-21-5p expression. In addition, miR-21-5p dramatically inhibited the target gene expression of programmed cell death protein 4 (PDCD4). In the current study, we demonstrated the potential anticancer effects of Andro on luminal-like breast cancer and indicated that Andro inhibits the expression of miR-21-5p and further promotes PDCD4 via NF-κB suppression. Therefore, Andro could be an antitumor agent for the treatment of luminal-like breast cancer in the clinic.

Land space underpins an ecological civilization. A thorough grasp of regional natural resources and subsequent optimization of the ecological security pattern are both essential for the comprehensive development and overall planning of the management of natural resources. In this study, we established and optimized the ecological security pattern in Shaanxi Province, China. Landscape patches distinguished by high importance of ecosystem services (carbon fixation and oxygen release, water conservation, habitat maintenance, and soil conservation) and high sensitivity of ecological environment to human interference (ecological sensitivity index) were extracted as ecological sources. An ecological resistance surface was built based on the following resistance factors: land-use type, topographic position index, and soil erosion intensity. A minimum cumulative resistance model was used to identify ecological corridors. Our results showed that those ecological sources with high to extreme ecological importance and sensitivity together covered an area of 67,457 km2 (32.8% of the total land area of Shaanxi Province). A total of 32 ecological nodes were identified at the center of important ecological sources to serve as main areas for implementing ecological protection projects. In addition, 72 ecological corridors were identified, towards which efforts should be targeted to maintain their functions for the inter-connection and serial connection of ecological nodes and source patches. The ecological corridors create favorable habitats for wildlife and superior spaces for ecological migration based on the blue and green linear corridor system. According to these findings, we propose establishing an ecological security pattern featuring “two barriers, three belts, and multiple corridors” in Shaanxi Province and that the green ecological security barriers should be strengthened based on their natural background and resource endowments.

Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.

To predict the propagation of radio waves in the environment of dielectric ground and dielectric obstacles, a new two-way parabolic equation (2W-PE) method based on the domain decomposition principle and surface impedance boundary conditions (SIBC) is proposed. First, we decompose the obstacle area into different subdomains and derive the SIBC in each subdomain in detail; then, the discrete hybrid Fourier transform (DMFT) in the upper subdomain and finite difference (FD) algorithm in the lower subdomain is used to solve 2W-PE combined with SIBC, respectively. After that, we explain the algorithm steps in the process of calculating the total field, compared with the traditional 2W-PE, and then finally introduce the method of moments (MoM) combined with the enhanced discrete complex image (E-DCIM) method for accuracy verification of the new 2W-PE algorithm. The simulation results show that no matter how the obstacle medium parameters change, the results of 2W-PE method proposed in this paper and MoM are always in good agreement, which proves the accuracy of 2W-PE and its superiority in speed. Therefore, this paper provides a reliable and efficient method for solving the problem of radio wave propagation in the presence of obstacles, especially in the case of low-lossy obstacles.

Angiogenesis dysregulation contributes to inflammation, infections, immune disorders, and carcinogenesis. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader that recognizes histone proteins and acts as a transcriptional regulator to trigger tumor growth and the inflammatory response. The pan-bromodomain and extra-terminal domain (BET) inhibitor, (+)-JQ1 (1), was reported to inhibit angiogenesis. However, owing to the non-selectivity action of (+)-JQ1 towards all BET family members, the role of BRD4 and that of its bromodomains (BD1 and BD2) in angiogenesis remains elusive. Herein, we identified a potent BRD4 inhibitor, ZL0513 (7), which exhibited significant anti-angiogenic effects in chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. This inhibitor also directly suppressed the viability and tube formation of human umbilical vascular endothelial cells (HUVECs). Moreover, ZL0513 (7) was found to inhibit the phosphorylation of c-jun and c-fos, important members of activating protein-1 (AP-1) transcription factor complexes that enhance angiogenesis. The findings on this novel BRD4 inhibitor indicate that, in addition to being a powerful pharmacological tool for further elucidating the roles and functions of BRD4 and its BD domains in angiogenesis, it may serve as a potential therapeutic strategy for targeting the vasculature in various angiogenesis-dysregulated human diseases.

Composting has been widely used to turn livestock manure into organic fertilizer. However, livestock manure contains various contaminants including antibiotics and antibiotic resistance genes (ARGs). Here we investigated the variation of antibiotic resistome and its influencing factors during a commercial livestock manure composting. The results showed that composting could effectively reduce the relative abundance of ARGs and mobile genic elements (MGEs). As the dominant phylum in the composting samples, the key potential bacterial host of ARGs were Actinobacteria such as Leucobacter, Mycobacterium and Thermomonosporaceae unclassified. Meanwhile, Legionella pneumophila, Staphylococcus saprophyticus, Haemophilus ducreyi and Siccibacter turicensis may be the key potential pathogenic host of ARGs because of their co-occurrence with ARG subtypes. Redundancy analysis showed that the dissipation of ARGs during composting was linked to various environmental factors such as moisture. Bacterial succession as well as profile of biocide and metal resistance genes (BMRGs) were the determinants which constructed the antibiotic resistome during manure composting. However, the residues of ARGs and pathogens in compost products may still pose risks to human and crops after fertilization. Keywords: Antibiotic resistance genes, Livestock manure, Composting, Microbial community, Pathogens, Antibiotic resistome

Respiratory diseases are leading causes of death and disability around the globe, with a diverse range of health problems. Treatment of respiratory diseases and infections has been verified to be thought-provoking because of the increasing incidence and mortality rate. Hydrogen sulfide (H2S) is one of the recognized gaseous transmitters involved in an extensive range of cellular functions, and physiological and pathological processes in a variety of diseases, including respiratory diseases. Recently, the therapeutic potential of H2S for respiratory diseases has been widely investigated. H2S plays a vital therapeutic role in obstructive respiratory disease, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung injury, pulmonary inflammation, bronchial asthma and bronchiectasis. Although the therapeutic role of H2S has been extensively studied in various respiratory diseases, a concrete literature review will have an extraordinary impact on future therapeutics. This review provides a comprehensive overview of the effective role of H2S in respiratory diseases. Besides, we also summarized H2S production in the lung and its metabolism processes in respiratory diseases.

Abstract Background Myxozoa is a well-known economically and ecologically important group of metazoan parasites, phylogenetically related to Cnidaria. High diversity of myxosporeans has been recorded in Russia and China; however, most of the species were solely morphologically characterised. Here, we identified a new gibel carp-infecting Myxobolus species and morphologically and molecularly compared the Russian and Chinese isolates of this new myxosporean. Results Myxobolus pronini n. sp. was found free in the abdominal cavity of Carassius auratus gibelio (Bloch, 1782) in Lake Baikal watershed, Russia, and embedded in the visceral serous membranes of the same fish species in Lake Taibai, Hubei province, China. The morphometric data of the plasmodia and mature spores exhibited some differences between the Russian and Chinese isolates, but SSU rDNA sequences indicated that these two geographical isolates are conspecific. The mature spores from the two locations are obovate in frontal view, with wider anterior than posterior end and lemon-shaped in sutural view. Spores of the Russian isolate were 14.3–16.2 (mean 15.1 ± 0.2) μm long, 9.6–10.8 (10.1 ± 0.1) μm wide and 6.4–7.4 (6.7 ± 0.15) μm thick; those of the Chinese isolate were 13.8–15.6 (14.7 ± 0.24) μm long, 9.6–13.3 (9.6 ± 0.65) μm wide and 6.2–7.2 (6.6 ± 0.16) μm thick. The newly-generated rDNA sequences (including SSU rDNA, ITS and LSU rDNA) from the two isolates represented some variations within the intraspecific range. Homology search by BLAST showed that the newly obtained rDNA sequences do not match any sequences available on GenBank. Phylogenetic analysis based on the aligned partial SSU rDNA sequences indicated that this novel species clustered with several gibel carp-infecting Myxobolus spp. with round anterior end of spores. Additionally, phylogenetic analysis based on all obtained ITS sequences showed that distinct genetic geographical differentiation occurred for this new parasite. Conclusions Myxobolus pronini n. sp. is described by integrating morphological, ecological and molecular evidence. Two geographical isolates of this species showed some morphological and genetic differences but within the intraspecific range of variation.

Background: Our previous study found that insulin-like growth factor binding protein-associated protein (IGFBPrP1) drives hepatic stellate cells (HSCs) activation, and IGFBPrP1 and transforming growth factor β1 (TGFβ1) likely interact with each other to promote HSCs activation. TGFβ1 reportedly promotes autophagy and contributes to HSCs activation; however, the mechanism between IGFBPrP1 and autophagy in liver fibrogenesis is yet unknown. Moreover, long noncoding RNA (lncRNA) H19 participates in autophagy regulation and plays a crucial function in liver fibrosis. Aims: To define the relationship between IGFBPrP1 and autophagy and the role of H19 in IGFBPrP1-induced hepatic fibrosis. Methods: IGFBPrP1 and autophagy were detected in bile duct ligation (BDL)-induced hepatic fibrosis. Adenovirus-mediated IGFBPrP1 was transfected into mouse liver and JS-1 cells with or without LY294002 or rapamycin to examine the effects of IGFBPrP1 on HSCs activation and autophagy as well as the PI3K/AKT/mTOR pathway. lncRNA H19 in liver fibrosis tissues and JS-1 cells induced by IGFBPrP1 were detected, then autophagy and HSCs activation level were detected in JS-1 cells by IGFBPrP1 with H19 overexpression or knowdown. Results: IGFBPrP1 expression and autophagy level were concomitantly increased in liver tissue with BDL-induced hepatic fibrosis. Furthermore, we found that IGFBPrP1 stimulated autophagy and HSCs activation in vivo and in vitro, and PI3K/AKT/mTOR signaling pathway was involved in the regulation of autophagy by IGFBPrP1. In addition, H19 promoted autophagy by interacting with the PI3K/AKT/mTOR pathway in IGFBPrP1-induced HSCs activation. Conclusions: IGFBPrP1 promoted autophagy and contributed to HSCs activation via mutual regulation between H19 and the PI3K/AKT/mTOR pathway.

Shift work and jet lag, characterized by circadian misalignment, can disrupt several physiological activities, but whether they affect the rhythm of glucose uptake and insulin sensitivity remain unclear. In the present study, female C57BL/6J mice were maintained for four weeks under the condition of 8-hour phase advance and delay every 3-4 days to mimic shift work. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were performed repeatedly at Zeitgeber time (ZT) 0, ZT6, ZT12, and ZT18. Glucose-stimulated insulin secretion (GSIS) test was performed at ZT6. We found that the average level of daily glucose tolerance did not decrease but the phase of glucose tolerance advanced by 2.27 hours and the amplitude attenuated by 20.4% in shift work mice. At ZT6, IPITT showed blood glucose at 30 min after insulin injection decreased faster in shift work mice (-3.50±0.74mmol/L, -61.58±7.89%) than that in control mice (-2.11±1.10mmol/L, -33.72±17.24%), but IPGTT and GSIS test showed no significant difference between the two groups. Food intake monitor showed that the feeding time of shift work mice continued to advance. Restricting feed to a fixed 12-hour period alleviated the increase of insulin sensitivity induced by shift-work. We also observed that an increase of blood glucose and liver glycogen at ZT0, as well as a phase advance of liver clock genes and some glucose metabolism-related genes such as forkhead box O1 (Foxo1) and peroxisome proliferator activated receptor alpha (Pparα) in shift work mice. Our results showed that light change-simulated shift work altered insulin sensitivity during the light phase and shifted glucose tolerance rhythms in female mice, suggesting a causal association between long-term shift work and type 2 diabetes.

The author wishes to make the following correction to this paper [...]

Saikosaponin d (SSd) is a major hepatoprotective component of saikosaponins derived from Radix Bupleuri, which was also linked to hepatotoxicity. Previous studies have demonstrated that caspases play a key role in SSd-induced liver cell death. Our in vitro and in vivo studies also showed that treatment with caspase inhibitor z-VAD-fmk could significantly reduce the L02 hepatocyte cells death and lessen the degree of liver damage in mice caused by SSd. In order to further reveal the underlying mechanisms of caspase inhibition in SSd-induced hepatotoxicity, mass spectrometry based untargeted metabolomics was conducted. Significant alterations in metabolic profiling were observed in SSd-treated group, which could be restored by caspase inhibition. Bile acids and phospholipids were screened out to be most significant by spearman correlation analysis, heatmap analysis and S-Plot analysis. These findings were further confirmed by absolute quantitation of bile acids via targeted metabolomics approach. Furthermore, cytokine profiles were analyzed to identify potential associations between inflammation and metabolites. The study could provide deeper insight into the hepatotoxicity of SSd and the efficacy of caspase inhibition.

Self-powered nanogenerators composed of poly(vinylidene fluoride) (PVDF) have received much attention. Solution blow spinning (SBS) is a neoteric process for preparing nanofiber mats with high efficiency and safely, and SBS is a mature fiber-forming technology that offers many advantages over conventional electrospinning methods. Herein, we adopted the SBS method to prepare independent PVDF nanofiber membranes (NFMs), and successfully employed them as nanogenerators. Finally, we tested the change in the output current caused by mechanical compression and stretching, and studied its durability and robustness by charging the capacitor, which can drive tiny electronic devices. The results show that the PVDF nanogenerators by using this SBS equipment can not only be used in wearable electronic textiles, but are also suitable for potential applications in micro-energy harvesting equipment.

Slit2 (slit guidance ligand 2), a ligand of the Roundabout1 (Robo1) transmembrane receptor, is often overexpressed in colorectal carcinomas (CRCs). In this study, we performed data mining in the Metabolic gEne RApid Visualizer (MERAV) database and found that Slit2 and TGF-β1 (Transforming growth factor-β1) are highly expressed in carcinomas relative to those in tumor-free tissues from healthy volunteers or wild type mice. Furthermore, expression of Slit2 and TGF-β1 in CRCs increases with pathological stages. Serum levels of Slit2 in patients with CRC and in ApcMin/+ mice with spontaneous intestinal adenoma were significantly increased compared with those in healthy controls. Specific blockage of Slit2 binding to Robo1 inactivated TGF-β/Smads signaling and inhibited tumor cell migration and metastasis, which can be partially restored by treatment with TGF-β1. However, specific inhibition of TGF-β1/Smads signaling reduced CRC tumor cell migration and invasion without affecting cell proliferation. This study suggests that activation of Slit2/Robo1 signaling in CRC induces tumor metastasis partially through activation of the TGF-β/Smads pathway.

To meet the urgent need of society for advanced photocatalytic materials, novel visible light driven heterostructured composite was constructed based on graphitic carbon nitride (g-C3N4) and fibrous TiO2. The g-C3N4/TiO2 (CNT) composite was prepared through electrospinning technology and followed calcination process. The state of the g-C3N4 and fibrous TiO2 was tightly coupled. The photocatalytic performance was measured by degrading the Rhodamine B. Compared to commercial TiO2 (P25®) and electrospun TiO2 nanofibers, the photocatalytic performance of CNT composite was higher than them. The formation of CNT heterostructures and the enlarged specific surface area enhanced the photocatalytic performance, suppressing the recombination rate of photogenerated carriers while broadening the absorption range of light spectrum. Our studies have demonstrated that heterostructured CNT composite with an appropriate proportion can rational use of visible light and can significantly promote the photogenerated charges transferred at the contact interface between g-C3N4 and TiO2.

[This corrects the article DOI: 10.1371/journal.pone.0155507.].

The early Cenozoic was characterized by a very warm climate especially during the Early Eocene. To understand climatic changes in eastern Asia, we reconstructed the Early Eocene vegetation and climate based on palynological data of a borehole from Wutu coal mine, East China and evaluated the climatic differences between eastern Asia and Central Europe. The Wutu palynological assemblages indicated a warm temperate vegetation succession comprising mixed needle- and broad-leaved forests. Three periods of vegetation succession over time were recognized. The changes of palynomorph relative abundance indicated that period 1 was warm and humid, period 2 was relatively warmer and wetter, and period 3 was cooler and drier again. The climatic parameters estimated by the coexistence approach (CA) suggested that the Early Eocene climate in Wutu was warmer and wetter. Mean annual temperature (MAT) was approximately 16°C and mean annual precipitation (MAP) was 800-1400 mm. Comparison of the Early Eocene climatic parameters of Wutu with those of 39 other fossil floras of different age in East China, reveals that 1) the climate became gradually cooler during the last 65 million years, with MAT dropping by 9.3°C. This cooling trend coincided with the ocean temperature changes but with weaker amplitude; 2) the Early Eocene climate was cooler in East China than in Central Europe; 3) the cooling trend in East China (MAT dropped by 6.9°C) was gentler than in Central Europe (MAT dropped by 13°C) during the last 45 million years.

A series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly, 5q showed the most potent activity towards MG63 cells with an IC50 value of 5.06 ± 0.25 μM. Morphological observation and 4,6-diamidino-2-phenylindole (DAPI) staining assay showed that 5q-treated MG63 cells displayed significant apoptosis characteristics. Moreover, flow cytometric detection of phosphatidylserine externalization revealed that 5q induced MG63 apoptosis in a dose-dependent manner. Real-time PCR and western blot assay further confirmed that 5q had strong effects to induce MG63 cell apoptosis, suggesting that the action was associated with down-regulation of the anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, and induced activation of caspase-3, 8, and 9. The present results provide a new chemotype for anticancer drug development and continuing investigation into candidates with coumarin/2-cyanoacryloyl scaffold is warranted.

Simultaneous identification of donkey-hide gelatin and bovine-hide gelatin in deer-horn glue was established by rapid-resolution liquid chromatography-triple quadrupole mass spectrometry. Water containing 1% NH4HCO3 was used for sample dissolution and trypsin was used for hydrolysis of the gelatins. After separation by a SB-C18 reversed-phase analytical column, collagen marker peptides were detected by mass spectrometry in positive electrospray ionization mode with multiple reaction monitoring. The method was specific, precise and reliable, and suitable for detection of adulterants derived from donkey-hide gelatin and bovine-hide gelatin in deer-horn glue.

Studies have indicated that the aggregation of activated platelets with cancer cells facilitates tumor metastasis; the adhesion molecule P-selectin may be an important mediator of this process, but the detailed mechanism is unclear. In the current study, we established a B16F10 (B16) cell metastatic model in P-selectin knockout (P-sel-/-) mice to determine the effect of P-selectin-mediated platelet adhesion on metastasis. Compared with C57 mice, P-sel-/- mice developed fewer metastatic foci, and cell proliferation within the metastatic tumors was inhibited by P-selectin deficiency. The platelet refusion assay demonstrated that mice with P-sel-/- platelets developed fewer lung metastatic foci (P

In this manuscript, utilizing interpolative contractions with fractional forms, some unique fixed-point results were studied in the context of extended b-metric spaces. For the validity of the presented results some examples are given. In the last section an existence theorem is provided to study the existence of a solution for the Fredholm integral equation. [ABSTRACT FROM AUTHOR]