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Understanding the spatial associations of ecosystem services (ESs) driven by socio-ecological factors is essential for regional ecosystem management and effective resource allocation. Yet previous studies of mechanisms driving ESs have focused mainly on the supply or demand for ESs, rarely consider their threshold effects and supply–demand ratios. Taking the upper reach of Ganjiang watershed (URGW) in southern China as an example, the supply, demand, and supply–demand ratio of ESs (ESDRs) were quantified for grain production (GP), water yield (WY), soil retention (SR), carbon sequestration (CS), and green space recreation (GR). Correlation analysis and random forest models were used to investigate the spatial associations of five ESDRs and the relative importance and marginal effects of 9 socio-ecological factors upon them. At the watershed scale, only SR incurred a supply–demand deficit (ESDR 0). When considered across 188 sub-watersheds, all ESs had different supply–demand deficits. The trade-offs in ESDRs mainly derived from two ESs (GP, SR) and the other three ESs (WY, CS, GR). The supply–demand ratio of SR was mainly determined by topography (i.e., slope gradient), while land use (i.e., proportions of cropland and forest land areas) played a decisive role in the supply–demand ratios of GP and WY. The supply–demand ratios of GR and CS showed similar spatial distribution, driven mainly by the normalized difference vegetation index and human population density. Specific socio-ecological factors (e.g., slope gradient and proportion of forest land area) had significant threshold effects on the ESDRs. Accordingly, research on the mechanisms driving ESs should consider ESs’ supply and demand in tandem, and pay particular attention to the potential threshold effects of socio-ecological factors.

Background and aim: Takayasu's arteritis (TA) is a chronic inflammation that frequently involves the aorta and its major branches. It has been known that atherosclerosis can occur in some TA patients. Objectives: This study aimed to identify the risk factors associated with the development of atherosclerosis in TA. Methods: This retrospective study enrolled a total of 101 TA patients. All patients were divided into two groups according to the absence or presence of atherosclerosis. Baseline demographic features and clinical characteristics were compared between two groups. A logistic model was applied to determine the risk factors associated with the development of atherosclerosis. Results: Our data suggested that the disease duration of patients in the atherosclerosis group was significantly longer than that of patients in the non-atherosclerosis group [96(18.00, 180.00) versus 48.00(12.00, 111.00) months] ( P = .015). In addition, the average age of patients with atherosclerosis was significantly older compared to patients without atherosclerosis [44.00(38.00, 48.00)versus 28.50(24.00，37.00)years] ( P < .001). Logistic regression analysis showed that the risk of developing atherosclerosis increased by 9.2% per 1 year increase in the disease duration ( P = .005, OR 1.092, 95%CI: 1.027-1.162). Patients with TG/HDL-C ratio more than 0.8875 were associated with a 5.861fold increase of risk developing atherosclerosis ( P < .001, OR 5.861, 95%CI: 2.299-14.939). Conclusion: Our study indicated that prolonged disease duration and elevated TG/HDL-C ratio are associated with the development of atherosclerosis in TA patients.

Lung cancer is a type of cancer with higher morbidity and mortality. In spite of the impressive response rates of nab-paclitaxel (nab-PTX) or programmed cell death-1 (PD-1) and its ligand inhibitors, the effective treatment remains limited. Currently, alternative strategies aim at drug combination of nab-PTX and PD-1/PD-L1 inhibitors. Even as the clinical impact of the combined agents continues to increase, basic research studies are still limited and the mechanisms underlying this synergy are not well studied. In this study, we evaluated the antitumor efficacy and the molecular mechanisms of action of nab-PTX in combination with anti-PD-1 antibody, using Lewis lung carcinoma (LLC) cell and subcutaneously transplanted tumor models. The combination of nab-PTX and anti-PD-1 antibody displayed stronger antitumor effects, manifested at tumor volume, proliferation and apoptosis through Ki67 and TUNEL staining. In-vivo experiments showed significant increases in CD4+ T cells, CD8+ T cells, IFN-γ, TNF-α, IL-2, PF, and Gzms-B, exerting antitumor effects with reductions in MDSCs and IL-10 after the treatments. Furthermore, transcriptomic analysis indicated 20 overlapped differentially expressed genes, and Serpin peptidase inhibitor clade C Member 1 (Serpinc1) was downregulated during treatment in vivo, whose expression level was markedly related to metastasis and overall survival of lung cancer patients. Functional enrichment analysis of the target gene revealed primary GO terms related to tumor, which warrants further investigation. We also found that Serpinc1 overexpression promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of LLC cells in vitro, possibly regulating the associated factors via the Pi3K/AKT pathway. In summary, our results reveal the synergistic antitumor responses of nab-PTX combined with anti-PD-1 antibody, in which Serpinc1 may play an important role, providing a target gene for combination treatment strategy.

PurposeCurrently, the underlying neurophysiological mechanism of acute tinnitus is still poorly understood. This study aimed to explore differences in brain functional connectivity (FC) within and between resting-state networks (RSNs) in acute tinnitus patients with hearing loss (ATHL). Furthermore, it also evaluated the correlations between FC alterations and clinical characteristics.MethodsTwo matched groups of 40 patients and 40 healthy controls (HCs) were included. Independent component analysis (ICA) was employed to obtain RSNs and FC differences were calculated within RSNs. In addition, the relationships between networks were conducted using functional network connectivity (FNC) analysis. Finally, an analysis of correlation was used to evaluate the relationship between FNC abnormalities and clinical data.ResultsResults of this study found that seven major RSNs including the auditory network (AN), cerebellum network (CN), default mode network (DMN), executive control network (ECN), sensorimotor network (SMN), ventral attention network (VAN), and visual network (VN) were extracted using the group ICA in both groups. Furthermore, it was noted that the ATHL group showed aberrant FC within the CN, ECN, and VN as compared with HCs. Moreover, different patterns of network interactions were observed between groups, including the SMN-ECN, SMN-CN, ECN-AN, DMN-VAN, and DMN-CN connections. The correlations between functional disconnection and clinical characteristics in ATHL were also found in this study.ConclusionIn conclusion, this study indicated widespread alterations of intra- and inter-network connectivity in ATHL, suggesting that multiple large-scale network dysfunctions and interactions are involved in the early stage. Furthermore, our findings may provide new perspectives to understand the neuropathophysiological mechanism of acute tinnitus.

Critical ecological land is indispensable for ecosystem stability, ecosystem service provision, and ecosystem function. Assessing and monitoring the stability of critical ecological land is an effective strategy of ensuring regional ecological security. The present study focused on Xinfeng County, China, a southern hilly region, as the study area, and evaluated water conservation, soil and water conservation, biodiversity conservation, leisure and sightseeing functions, in addition to land use status, in 2000, 2010, and 2020. Afterward, ecological ecosystem service function was evaluated to identify critical ecological land. A complex network method was used to analyze ecological network stability to more comprehensively analyze characteristics of critical ecological land in time and space. According to the results, the landscape types of critical ecological land in 2000, 2010, and 2020 were primarily forest land and grassland, with the majority being forest land with high vegetation density and cover, validating the accuracy and feasibility of our method. Under the “random attack” scenario, the robustness of network connectivity in 2000, 2010, and 2020 had a consistent decreasing trend. However, under the “intentional attack” scenario, connectivity robustness changes more intense in 2010 and 2020, and the ecological network in 2020 shows instability and fragility. Additionally, according to the spatial distribution characteristics of critical ecological land, a network protection strategy is put forward to guide and support subsequent ecological protection work.

Under the influence of global climate change and urbanization processes, the number of available water resources (AWRs) in basins has become significantly more uncertain, which has restricted the sustainable development of basins. Therefore, it is important for us to understand the relationship between land use (LU) patterns and climate change on AWRs in a basin for sustainable development. To this end, the vector autoregressive (VAR) method was adopted to construct a quantitative model for AWRs in the basin in this study. Taking the Yiluo River Basin (YRB) as an example, the dynamic relationship between the five elements of agricultural land (AD), woodland (WD), grassland (GD), construction land (CD), and annual precipitation (PREP) and AWRs in the basin was studied. The results show the following: (1) The constructed VAR model was stable, indicating that the use of the proposed VAR model to characterize the degree of the effect of LU pattern and PREP on AWRs in the YRB was reasonable and effective. (2) AWRs in the YRB showed a downward trend, and their responses to the change in LU and PREP were delayed. The changes in the AWRs in the YRB tended to occur the year after changes to the LU pattern and PREP occurred. (3) In the long run, the degree of the contribution of each influencing factor to changes to AWRs was 23.76% (AD), 6.09% (PREP), 4.56% (CD), 4.40% (WD), and 4.34% (GD), which meant that the impact of the LU pattern was more than 90%. This study provides new ideas for similar research, water resource allocation, and LU planning in other river basins from a macroscopic perspective.

The bacterium Vibrio cholerae can colonize the human intestine and cause cholera, but spends much of its life cycle in seawater. Here, Liu et al. identify a fructose uptake system that is important for the growth of the bacteria in seawater, where fructose concentrations are low.

Abstract Background Migraine is a common neurological disease that is often accompanied by psychiatric comorbidities. However, the relationship between abnormal brain function and psychiatric comorbidities in migraine patients remains largely unclear. Therefore, the present study sought to explore the correlations between the resting-state functional deficits and psychiatric comorbidities in migraine without aura (MwoA) patients. Methods Resting-state functional magnetic resonance images were obtained. In addition, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were obtained. Thereafter regional abnormalities in MwoA patients with and without anxiety (MwoA-A and MwoA-OA) were chosen as seeds to conduct functional connectivity (FC) analysis. Results Compared to the healthy controls (HCs), the MwoA-A and MwoA-OA patients had abnormal ALFF and ReHo values in the right lingual gyrus (LG). They also had abnormal FC of the right LG with the ipsilateral superior frontal gyrus (SFG) and middle cingulate cortex (MCC). Additionally, the MwoA-A patients showed higher ReHo values in the left posterior intraparietal sulcus (pIPS) and abnormal FC of the right LG with ipsilateral pIPS and primary visual cortex, compared to the MwoA-OA patients. Moreover, the MwoA-OA patients showed an increase in the FC with the right posterior cingulate cortex/precuneus (PCC/PCUN), left middle frontal gyrus (MFG) and left inferior temporal gyrus (ITG) relative to the HCs. Furthermore, the ALFF values of the right LG positively were correlated with anxiety scores in MwoA-A patients. The abnormal LG-related FCs with the PCC/PCUN, MFG and ITG were negatively associated with the frequency of headaches in MwoA-OA patients. Conclusions This study identified abnormal visual FC along with other core networks differentiating anxiety comorbidity from MwoA. This may therefore enhance the understanding of the neuropsychological basis of psychiatric comorbidities and provide novel insights that may help in the discovery of new marks or even treatment targets.

With a rich abundance of natural polyphenols, green tea has become one of the most popular and healthiest nonalcoholic beverages being consumed worldwide. Epigallocatechin-3-gallate (EGCG) is the predominant catechin found in green tea, which has been shown to promote numerous health benefits, including metabolic regulation, antioxidant, anti-inflammatory, and anticancer. Clinical studies have also shown the inhibitory effects of EGCG on cancers of the male and female reproductive system, including ovarian, cervical, endometrial, breast, testicular, and prostate cancers. Autophagy is a natural, self-degradation process that serves important functions in both tumor suppression and tumor cell survival. Naturally derived products have the potential to be an effective and safe alternative in balancing autophagy and maintaining homeostasis during tumor development. Although EGCG has been shown to play a critical role in the suppression of multiple cancers, its role as autophagy modulator in cancers of the male and female reproductive system remains to be fully discussed. Herein, we aim to provide an overview of the current knowledge of EGCG in targeting autophagy and its related signaling mechanism in reproductive cancers. Effects of EGCG on regulating autophagy toward reproductive cancers as a single therapy or cotreatment with other chemotherapies will be reviewed and compared. Additionally, the underlying mechanisms and crosstalk of EGCG between autophagy and other cellular processes, such as reactive oxidative stress, ER stress, angiogenesis, and apoptosis, will be summarized. The present review will help to shed light on the significance of green tea as a potential therapeutic treatment for reproductive cancers through regulating autophagy.

Introduction: Distal tears are an important issue after thoracic endovascular aortic repair as they directly affect thrombosis in the false lumen. However, it is difficult to treat distal tears in clinical practice due to the potential complications that may occur.Case report: We report the case of a 58-year-old male patient who received a GORE C-TAG stent placement by means of a “triple periscope technique” (a stent graph was placed in the superior mesenteric artery (SMA) and the bilateral renal artery). Post-CTA imaging three months later indicated that the distal dissecting aortic aneurysm was successfully isolated, and the three abdominal branches were well-perfused, interestingly the celiac branch with well–perfusion via collateral circulation pathway between the celiac trunk and the superior mesenteric artery.Conclusions: The periscope technique used in this report for reconstructing the branch vessel involved in the dissecting aneurysm was easy to learn and operate. Combined with another skill that initial deployment in the distal segment of stent-graft, distal entry tear of aortic dissecting aneurysm could be ensured with accurate coverage, as well as well-perfusion in the abdominal branches.

Cardiotonic steroids (CTS) are a group of compounds existing in animals and plants. CTS are commonly referred to cardiac glycosides (CGs) which are composed of sugar residues, unsaturated lactone rings and steroid cores. Their traditional mechanism of action is to inhibit sodium-potassium ATPase to strengthen the heart and regulate heart rate, so it is currently widely used in the treatment of cardiovascular diseases such as heart failure and tachyarrhythmia. It is worth noticing that recent studies have found an avalanche of inestimable values of CTS applications in many fields such as anti-tumor, anti-virus, neuroprotection, and immune regulation through multi-molecular mechanisms. Thus, the pharmacological activities and applications of CTS have extensive prospects, which would provide a direction for new drug research and development. Here, we review the potential applications of CTS in cardiovascular system and other systems. We also provide suggestions for new clinical practical strategies of CTS, for many diseases. Four main themes will be discussed, in relation to the impact of CTS, on 1) tumors, 2) viral infections, 3) nervous system diseases and 4) immune-inflammation-related diseases.

The genus Cronobacter includes seven species; however, the strains of Cronobacter sakazakii, Cronobacter malonaticus, and Cronobacter turicensis were highly correlated with clinical infections. Rapid and reliable identification of these three species of Cronobacter is important in monitoring and controlling diseases caused by these bacteria. Here, we identified four pairs of novel marker genes for the Cronobacter genus, C. sakazakii, C. malonaticus, and C. turicensis based on large-scale comparative genomic analysis from 799 Cronobacter and 136,146 non-Cronobacter genomes, including 10 Franconibacter and eight Siccibacter, which are close relatives of Cronobacter. Duplex and multiplex PCR methods were established based on these newly identified marker genes. The reliability of duplex and multiplex PCR methods was validated with 74 Cronobacter and 90 non-Cronobacter strains. Strains of C. sakazakii, C. malonaticus, and C. turicensis could be detected accurately at both the genus and species level. Moreover, the newly developed methods enable us to detect 2.5 × 103 CFU/ml in pure culture. These data indicate that the accurate and sensitive established methods for Cronobacter can serve as valuable tools for the identification of these strains recovered from food, environmental, and clinical samples.

The current assessment of the positive and negative benefits of agricultural water use lacks a depiction of the overall internal energy flow, which lead to the identification and analysis of agricultural water use benefits are not comprehensive enough. Based on the “water supply - water use and consumption - drainage - pollutant carrying” link in the ecological economic system of agricultural water resources, the energy conversion relationship of each link were analyzed, and the main connotation and composition of the positive and negative benefits of agricultural water use were raised, then a set of emergy quantitative method system of the positive and negative benefits of agricultural water use was built. Taking Zhengzhou city as an example, the positive and negative benefits of agricultural water use in 2017 were calculated. The research results show that the negative benefits of agricultural water resources eco-economic system production account for 37.93% of the positive benefits. The main reason for the negative benefits is non-point source pollution caused by TN, TP and COD.Consequently, developing production and social policies to limit the amount of non-point source pollution caused by pollutants in agricultural production is an effective way to increase the efficiency of agricultural water production while reducing the negative benefits generated.

In the past decade, the incidence of recurrent pregnancy loss (RPL) has increased significantly, and immunological disorders have been considered as one of the possible causes contributing to RPL. The presence of antinuclear antibodies (ANAs) is regarded as a typical antibody of autoimmunity. However, the relationship between the presence of ANAs and RPL, the underlying mechanism, and the possible role of immunotherapy is still controversial. The aim of this mini review is to assess the association between ANAs and RPL and the effects of immunotherapy on pregnancy outcomes in women with positive ANAs and a history of RPL from the available data and to provide a relevant reference basis for clinical application in this group of women.

The trade-offs and synergies reveal the profit and loss relationship between ecosystem services, which is of great significance to the sustainable development of natural resources. The ecosystem services in Jiangxi Province, such as net primary productivity (NPP), soil conservation (SC) and water yield (WY) during 2000–2020, were estimated in this study. The correlation coefficient was adopted to analyze the trade-offs and synergies between the three ecosystem services by static space correlation and dynamic space correlation from such perspectives as Watershed, county and grid. Moreover, the influence of the three ecosystem services and the relations between them were explored from four aspects: landform, NDVI, accumulated temperature and precipitation. The results showed that the ecological environment quality in Jiangxi Province was improved and that the distribution of ecosystem services had significant regional characteristics. In the static analysis, ecosystem services at all scales were remarkably synergistic, and synergies weakened rapidly and even turned into trade-offs as the scale decreased. In the dynamic analysis, ecosystem services at all scales were mainly synergistic; the proportion of significant samples was much lower than that in the static analysis, the degree of trade-offs/synergies decreased with the decrease in scale, and the decrease was smaller than that in the static analysis. The major constraints for SC were landform and NDVI. The main constraint for WY was precipitation, and that for NPP was NDVI. Affected by various factors, NPP and SC were stably synergistic, NPP and WY were in a stable trade-off relationship, and the relationship between SC and WY was unstable. The trade-offs and synergies changed with factors and zoning.

As natural selenium (Se)-rich soil in China is generally characterized by a high geological background of cadmium (Cd), the safe utilization of such seleniferous soil remains a challenge. The accumulating evidence shows that the threshold value of the Se:Cd ratio is a determinant of regulating Cd accumulation in plants. However, the factors modulating the soil’s Se:Cd ratio in selenium-enriched regions are not well understood. Here, a comprehensive study aimed at quantitatively analyzing the effects of land-use types, parent-material types, and soil properties on the distribution and influencing factors of Se, Cd, and the Se:Cd ratios. According to land use and parent-material types, 77 soil samples were collected in Yuanzhou District, a typical naturally seleniferous area in the subtropical hilly area. The results suggested that, compared with quaternary red clays (qrc), the Se content of soils derived from river and lake sediments (rls) and weathered acidic crystalline rocks (wacr) decreased by 5.81%–19.75%, while the weathered quartzite (wq)-derived soils was increased significantly. The soil Cd content in an orchard was significantly reduced compared with that in a paddy field. A redundancy analysis (RDA) revealed that SOM, Total K, and Total P significantly affected the changes in Se and Cd contents. In addition, the land-use type had the most significant effect on the Se:Cd ratio, with a regression coefficient of −0.6999 analyzed by the binary logistic regression model (p < 0.05). Furthermore, pH and Total K were the critical soil properties in controlling the Se:Cd ratio. The study indicated that the Se:Cd ratio in natural selenium-rich soil was mainly regulated by land-use types. Therefore, it is a feasible measure to regulate the Se:Cd ratio by using agronomic practices, mainly regulating soil pH, for the safe utilization of selenium-rich soil with a high Cd background.

Robust soil organic matter (SOM) mapping is required by farms, but their generation requires a large number of samples to be chemically analyzed, which is cost prohibitive. Recently, research has shown that visible and near-infrared (vis-NIR) reflectance spectroscopy is a fast and accurate technique for estimating SOM in a cost-effective manner. However, few studies have focused on using vis-NIR spectroscopy as a covariate to improve the accuracy of spatial modeling. In this study, our objective was to compare the mapping accuracy from a spatial model using kriging methods with and without the covariate of vis-NIR spectroscopy. We split the 261 samples into a calibration set (104) for building the spectral predictive model, a test set for generating the vis-NIR augmented set from the prediction of the fitted spectral predictive model (131), and a validation set (26) for evaluating map accuracy. We used two datasets (235 samples) for Kriging: a laboratory-based dataset (Ld, observations from calibration and test datasets) and a laboratory-based dataset with vis-NIR augmented predictions (Au.p, observations from calibration and predictions from test dataset), a laboratory-based dataset with vis-NIR spectra as the covariance (Ld.co) and augmented dataset with predictions using vis-NIR with vis-NIR spectra for the covariance (Au.p.co). The first one to seven accumulated principal components of vis-NIR spectra were used as the covariates when we used the measurement of Ld.co and Au.p.co. The map accuracy was evaluated by the validation set for the four datasets using Kriging. The results indicated that adding vis-NIR spectra as covariates had great potential in improving the map accuracy using kriging, and much higher accuracies were observed for Ld.p.co (RMSE of 5.51 g kg−1) and Au.p.co (RMSE of 5.66 g kg−1) than without using vis-NIR spectra as covariates for Ld (RMSE of 7.12 g kg−1) and Au.p (RMSE of 7.69 g kg−1). With a similar model performance to Ld.p.co, Au.p.co can reduce the cost of laboratory analysis for 60% of soil samples, demonstrating its advantage in cost-efficiency for spatial modeling of soil information. Therefore, we conclude that vis-NIR spectra can be used as a cost-effective technique to obtain augmented data to improve fine-resolution spatial mapping of soil information.

Background Acute kidney injury (AKI) is one of the most common and serious complications in patients with type B aortic dissection (TBAD). This study aimed at investigating the incidence and risk factors of in-hospital AKI in TBAD patients involving the renal artery who underwent thoracic endovascular aortic repair (TEVAR) only. Methods A total of 256 patients who were diagnosed as TBAD combined with renal artery involvement were included in this retrospective study. All patients were divided into the AKI group and the non-AKI group according to the KDIGO criteria. The risk factors for AKI were identified using a multivariate logistic regression model. Results A total of 256 patients were included in this study, and the incidence of AKI was 18% (46/256). Patients in the AKI group were more likely to have a higher proportion of the youth, a higher level of body mass index, and a shorter time from onset to admission. Multivariate logistic regression analysis revealed that the youth (age ≤40 years) (OR: 2.853, 95%CI: 1.061–7.668, p = .038) were prone to AKI, and lower estimated glomerular filtration rate (eGFR) (OR: 1.526, per 15-ml/min/1.73 m2 decrease, 95%CI: 1.114–2.092; p = .009), higher diastolic blood pressure (DBP) (OR: 1.418, per 10-mmHg increase; 95%CI: 1.070–1.879; p = .015), and fasting blood glucose (FBG) ≥7 mmol/L on admission (OR: 2.592; 95%CI: 1.299–5.174; p = .007) were independent risk factors for AKI. Conclusions Higher incidence of AKI had been perceived in this study, most of them were young and middle-aged patients. Renopreventive measures should be considered in those high-risk patients with younger age, lower eGFR, higher DBP, and higher FBG on admission.

BackgroundLeiomyosarcoma (LMS) is a malignant smooth muscle neoplasm, in which the efficacy of immune checkpoint blockade (ICB) is very limited. What is worse, loss of PTEN, known as a negative factor for ICB, frequently occurred in LMS. Seeking new strategies for LMS patients harboring loss of PTEN is important and challenging.Case PresentationA 42-year-old Chinese male was diagnosed as having unresectable LMS of the iliopsoas. After the failure of two prior chemotherapy regimens, whole-exome sequencing revealed that tumor tissue had high tumor mutation burden (689 Muts), high microsatellite instability, and some somatic mutations, including PTEN (copy number loss and p.N323fs), MSH6 (p.F1088fs), TP53 p.R273C, ASXL1 p.G645fs, ATR p.S1843P, and CDKN2A p.A118P. Then, antiangiogenic agent (pazopanib or anlotinib) plus pembrolizumab was administered from January 2 to August 6, 2018. However, pazopanib was stopped on June 18 due to the grade 2/3 adverse effect of hand–foot skin reaction, and anlotinib was administered. Considering that the tumor shrunk after immunotherapy, he underwent radical resection on September 6, 2018. The final pathological diagnosis confirmed pathologic complete response (CR). Until the latest follow-up (September 15, 2021), no progressive disease was observed and total disease-free survival has exceeded 36 months.ConclusionWe presented a patient with an unresectable mismatch repair (MMR)-deficient LMS harboring biallelic loss of PTEN who achieved CR from a combination strategy of antiangiogenesis plus pembrolizumab. Such a strategy might be a promising strategy to overcome the ICB resistance caused by the loss of PTEN. Such conclusions need to be further confirmed in further investigations.

Machine learning (ML) has been largely applied for predicting migraine classification. However, the prediction of efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in migraine is still in the early stages. This study aims to evaluate whether the combination of machine learning and amygdala-related functional features could help predict the efficacy of NSAIDs in patients with migraine without aura (MwoA). A total of 70 MwoA patients were enrolled for the study, including patients with an effective response to NSAIDs (M-eNSAIDs, n = 35) and MwoA patients with ineffective response to NSAIDs (M-ieNSAIDs, n = 35). Furthermore, 33 healthy controls (HCs) were matched for age, sex, and education level. The study participants were subjected to resting-state functional magnetic resonance imaging (fMRI) scanning. Disrupted functional connectivity (FC) patterns from amygdala-based FC analysis and clinical characteristics were considered features that could promote classification through multivariable logistic regression (MLR) and support vector machine (SVM) for predicting the efficacy of NSAIDs. Further, receiver operating characteristic (ROC) curves were drawn to evaluate the predictive ability of the models. The M-eNSAIDs group exhibited enhanced FC with ipsilateral calcarine sulcus (CAL), superior parietal gyrus (SPG), paracentral lobule (PCL), and contralateral superior frontal gyrus (SFG) in the left amygdala. However, the M-eNSAIDs group showed decreased FC with ipsilateral caudate nucleus (CAU), compared to the M-ieNSAIDs group. Moreover, the M-eNSAIDs group showed higher FC with left pre-central gyrus (PreCG) and post-central gyrus (PoCG) compared to HCs. In contrast, the M-ieNSAIDs group showed lower FC with the left anterior cingulate cortex (ACC) and right SFG. Furthermore, the MwoA patients showed increased FC with the left middle frontal gyrus (MFG) in the right amygdala compared to HCs. The disrupted left amygdala-related FC patterns exhibited significant correlations with migraine characteristics in the M-ieNSAIDs group. The MLR and SVM models discriminated clinical efficacy of NSAIDs with an area under the curve (AUC) of 0.891 and 0.896, sensitivity of 0.971 and 0.833, and specificity of 0.629 and 0.875, respectively. These findings suggest that the efficacy of NSAIDs in migraine could be predicted using ML algorithm. Furthermore, this study highlights the role of amygdala-related neural function in revealing underlying migraine-related neuroimaging mechanisms.

Abstract Background Treating patients with advanced sarcomas is challenging due to great histologic diversity among its subtypes. Leiomyosarcoma (LMS) and de-differentiated liposarcoma (DDLPS) are two common and aggressive subtypes of soft tissue sarcoma (STS). They differ significantly in histology and clinical behaviors. However, the molecular driving force behind the difference is unclear. Methods We collected 20 LMS and 12 DDLPS samples and performed whole exome sequencing (WES) to obtain their somatic mutation profiles. We also performed RNA-Seq to analyze the transcriptomes of 8 each of the LMS and DDLPS samples and obtained information about differential gene expression, pathway enrichment, immune cell infiltration in tumor microenvironment, and chromosomal rearrangement including gene fusions. Selected gene fusion events from the RNA-seq prediction were checked by RT-PCR in tandem with Sanger sequencing. Results We detected loss of function mutation and deletion of tumor suppressors mostly in LMS, and oncogene amplification mostly in DDLPS. A focal amplification affecting chromosome 12q13–15 region which encodes MDM2, CDK4 and HMGA2 is notable in DDLPS. Mutations in TP53, ATRX, PTEN, and RB1 are identified in LMS but not DDLPS, while mutation of HERC2 is only identified in DDLPS but not LMS. RNA-seq revealed overexpression of MDM2, CDK4 and HMGA2 in DDLPS and down-regulation of TP53 and RB1 in LMS. It also detected more fusion events in DDLPS than LMS (4.5 vs. 1, p = 0.0195), and the ones involving chromosome 12 in DDLPS stand out. RT-PCR and Sanger sequencing verified the majority of the fusion events in DDLPS but only one event in LMS selected to be tested. The tumor microenvironmental signatures are highly correlated with histologic types. DDLPS has more endothelial cells and fibroblasts content than LMS. Conclusions Our analysis revealed different recurrent genetic variations in LMS and DDLPS including simultaneous upregulation of gene expression and gene copy number amplification of MDM2 and CDK4. Up-regulation of tumor related genes is favored in DDLPS, while loss of suppressor function is favored in LMS. DDLPS harbors more frequent fusion events which can generate neoepitopes and potentially targeted by personalized immune treatment.

Abstract Background Resting-state functional magnetic resonance imaging (Rs-fMRI) has confirmed sensorimotor network (SMN) dysfunction in migraine without aura (MwoA). However, the underlying mechanisms of SMN effective functional connectivity in MwoA remain unclear. We aimed to explore the association between clinical characteristics and effective functional connectivity in SMN, in interictal patients who have MwoA. Methods We used Rs-fMRI to acquire imaging data in 40 episodic patients with MwoA in the interictal phase and 34 healthy controls (HCs). Independent component analysis was used to profile the distribution of SMN and calculate the different SMN activity between the two groups. Subsequently, Granger causality analysis was used to analyze the effective functional connectivity between the SMN and other brain regions. Results Compared to the HCs, MwoA patients showed higher activity in the bilateral postcentral gyri (PoCG), but lower activity in the left midcingulate cortex (MCC). Moreover, MwoA patients showed decreased effective functional connectivity from the SMN to left middle temporal gyrus, right putamen, left insula and bilateral precuneus, but increased effective functional connectivity to the right paracentral lobule. There was also significant effective functional connectivity from the primary visual cortex, right cuneus and right putamen to the SMN. In the interictal period, there was positive correlation between the activity of the right PoCG and the frequency of headache. The disease duration was positively correlated with abnormal effective functional connectivity from the left PoCG to right precuneus. In addition, the headache impact scores were negatively correlated with abnormal effective functional connectivity from the left MCC to right paracentral lobule, as well as from the right precuneus to left PoCG. Conclusions These differential, resting-state functional activities of the SMN in episodic MwoA may contribute to the understanding of migraine-related intra- and internetwork imbalances associated with nociceptive regulation and chronification.

Abstract Background Anlotinib is a novel, orally administered, multitarget receptor tyrosine kinase inhibitor. It functions by inhibiting tumor angiogenesis and proliferative signaling pathways. In this study, we aimed to investigate the efficacy and safety of anlotinib plus epirubicin in a sarcoma patient‐derived xenografts (PDX) model. Methods We firstly established a PDX model using fresh tumor tissues that were surgically removed from a patient diagnosed with malignant fibrous histiocytoma. Thirty‐six PDX models were divided into six groups and treated with anlotinib alone (low‐dose, 1.5 or high‐dose, 3.0 mg/kg/day, oral gavage), or with anlotinib plus epirubicin (3.0 mg/kg/once weekly, i.p.) when the tumors grew to 150‐200 mm3. After 5 weeks of treatment, the mice were sacrificed, and the tumors were measured by weight and processed for IHC and H&E staining. IHC staining was performed to detect CD31, EGFR, MVD, and Ki‐67 on paraffin sections. H&E stainings were performed to examine the microcosmic changes that occurred in the tumor tissues and myocardium, respectively. Results After 5 weeks, treatment with anlotinib or epirubicin alone significantly inhibited tumor growth in the sarcoma PDX model compared with the vehicle control. Tumor volume in the high‐dose anlotinib group was significantly smaller than the low‐dose anlotinib group (P

Abstract. To compare efficacy and safety of nab-paclitaxel plus gemcitabine (AG) with nab-paclitaxel plus S-1 (AS) as first-line treatment for metastatic pancreatic cancer, we conducted a retrospective analysis by reviewing medical records of 53 metastatic pancreatic cancer patients in our institution. They received either AG (nab-paclitaxel 125 mg/m2 on days 1, 8 and gemcitabine 1000 mg/m2 on days 1, 8) or AS (nab-paclitaxel 125 mg/m2 on days 1, 8 and S-1 80–120 mg on days 1–14) chemotherapy. We found that AS had higher objective response rate (36% vs 21.4%), better disease control rate (84% vs 75%), prolonged time to progression (TTP, 7.1 vs 5 months), and improved overall survival (OS, 15.3 vs 12 months) when compared with AG. In Cox proportional hazards model, sex was significantly associated with TTP (P value = .031) and metastatic sites plus treatment after progression were significantly associated with OS (P value = .028 and .01, respectively). The incidence rate of chemotherapy-related adverse events was similar in both groups. Neutropenia (50% and 60%, all grade; 21.4% and 36%, grade 3 or 4, in AG and AS group) and sensory neuropathy (21.4% and 24%, all grade; 3.6% and 4%, grade 3 or 4, in AG and AS group) were the most common hematologic and non-hematologic toxicity. Thus, we believed that AS is a reasonable and convenient alternative for patients treated with AG as first-line chemotherapy for metastatic pancreatic cancer.

Background. Visual symptoms are common in patients with migraine, even in interictal periods. The purpose was to assess the association between dynamic functional connectivity (dFC) of the visual cortex and clinical characteristics in migraine without aura (MwoA) patients. Methods. We enrolled fifty-five MwoA patients as well as fifty gender- and age-matched healthy controls. Regional visual cortex alterations were investigated using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF). Then, significant regions were selected as seeds for conducting dFC between the visual cortex and the whole brain. Results. Relative to healthy controls, MwoA patients exhibited decreased ReHo and ALFF values in the right lingual gyrus (LG) and increased ALFF values in the prefrontal cortex. The right LG showed abnormal dFC within the visual cortex and with other core brain networks. Additionally, ReHo values for the right LG were correlated with duration of disease and ALFF values of the right inferior frontal gyrus and middle frontal gyrus were correlated with headache frequency and anxiety scores, respectively. Moreover, the abnormal dFC of the right LG with bilateral cuneus was positively correlated with anxiety scores. Conclusions. The dFC abnormalities of the visual cortex may be involved in pain integration with multinetworks and associated with anxiety disorder in episodic MwoA patients.

The COVID-19 pandemic has drastically shifted the way people work. While many businesses can operate remotely, a large number of jobs can only be performed on-site. Moreover as businesses create plans for bringing workers back on-site, they are in need of tools to assess the risk of COVID-19 for their employees in the workplaces. This study aims to fill the gap in risk modeling of COVID-19 outbreaks in facilities like offices and warehouses. We propose a simulation-based stochastic contact network model to assess the cumulative incidence in workplaces. First-generation cases are introduced as a Bernoulli random variable using the local daily new case rate as the success rate. Contact networks are established through randomly sampled daily contacts for each of the first-generation cases and successful transmissions are established based on a randomized secondary attack rate (SAR). Modification factors are provided for SAR based on changes in airflow, speaking volume, and speaking activity within a facility. Control measures such as mask wearing are incorporated through modifications in SAR. We validated the model by comparing the distribution of cumulative incidence in model simulations against real-world outbreaks in workplaces and nursing homes. The comparisons support the model’s validity for estimating cumulative incidences for short forecasting periods of up to 15 days. We believe that the current study presents an effective tool for providing short-term forecasts of COVID-19 cases for workplaces and for quantifying the effectiveness of various control measures. The open source model code is made available at github.com/abhineetgupta/covid-workplace-risk.

Phase change materials attract tremendous interest for building energy conservation due to their auto-temperature regulation and thermal energy storage capacity. However, its practical application is hindered due to the leakage problem and poor photothermal conversion efficiency. To address these issues, a scalable wood-based phase change material was prepared by impregnating polyethylene glycol (PEG) into wood particles doped with Fe _3 O _4 and subsequent a hot press in this study. PEG was encapsulated by wood particles through its abundant pore structure and leakage rate of prepared wood-based phase change material (FWPCM) was only 2.9%, which solved the leakage problem effectively. FWPCM presented high latent heat of 73 J g ^−1 and slowed down the temperature change obviously. Addition of Fe _3 O _4 powder endowed FWPCM a high photothermal conversion efficiency and thermal conductivity (0.3545 W/(m*K) was increased by 125% compared to PW. So FWPCM had potential to be used as building engineering material for energy collecting, storage and conversion benefited by its great thermal performance, superior durability, simple preparing process and acceptable mechanical property.

The rapid quantitative assessment of soil organic carbon (SOC) is essential for understanding SOC dynamics and developing management strategies in forest ecosystems. Compared with traditional laboratory methods, visible and near-infrared spectroscopy is an efficient and inexpensive technique widely used to predict SOC content. Herein, we compared three different spiking strategies. That is, a large-scale global soil spectral library (global-SSL; 3122 samples) was used as the basis for predicting SOC content in a small-scale local soil spectral library (local-SSL; 89 samples) in Wugong Mountain, Jiangxi Province, China. Partial least squares regression models using global-SSL ‘spiking’ with local samples did not necessarily achieve more accurate predictions than models using local-SSL. Using the developed strategy, a calibration set can be established by selecting the top N spectral samples from global-SSL with high similarity to each local sample, together with the ‘spiking’ set from local-SSL. It is possible to individually improve the prediction results based on local samples (R2 = 0.90, RMSE = 7.19, RPD = 3.38) and still allow for quantitative prediction from fewer local calibration samples (R2 = 0.83, RMSE = 8.71, RPD = 2.68). The developed method is cost-effective and accurate for local-scale SOC assessment in target forest areas using a large soil spectral library.

In order to improve the mechanical properties, nutritional value and fresh-keeping ability of conventional sodium alginate edible composite membranes, a new type of edible composite film was prepared by adding water-blocking agent carnauba wax, plasticizer glycerin, antioxidant and nutritional enhancer sodium ascorbate on a basis of traditional sodium alginate composite film. In this study, the physical, mechanical and structural properties of different film components were investigated. The results showed the components did not simply combine, but produced interaction forces which improved the stability and mechanical properties of composite film. When the amount of calcium ascorbate was 0.4%, the water vapor transmittance of the composite film reached a minimum of 0.65 g·mm/(cm2·d·kPa), and the tensile strength and elongation at break reached the maximum, which were 398.64 MPa and 17.93%, respectively. Additionally, the sodium alginate-carnauba wax film exhibited better performance on the preservation of fresh-cut apples. Compared with other composite films, the color and hardness of fresh-cut apples coated with this composite film were better maintained, and the losses of titration acid content and soluble solid content were reduced. Moreover, the weight loss rate, increase in polyphenol oxidase activity and total colony count were inhibited. All results determined that the edible film has good application value in the field of fresh-cut fruit preservation, which provides a theoretical basis for further research on edible film.

Abstract Background Resting-state functional magnetic resonance imaging (fMRI) has confirmed disrupted visual network connectivity in migraine without aura (MwoA). The thalamus plays a pivotal role in a number of pain conditions, including migraine. However, the significance of altered thalamo-visual functional connectivity (FC) in migraine remains unknown. The goal of this study was to explore thalamo-visual FC integrity in patients with MwoA and investigate its clinical significance. Methods Resting-state fMRI data were acquired from 33 patients with MwoA and 22 well-matched healthy controls. After identifying the visual network by independent component analysis, we compared neural activation in the visual network and thalamo-visual FC and assessed whether these changes were linked to clinical characteristics. We used voxel-based morphometry to determine whether functional differences were dependent on structural differences. Results The visual network exhibited significant differences in regions (bilateral cunei, right lingual gyrus and left calcarine sulcus) by inter-group comparison. The patients with MwoA showed significantly increased FC between the left thalami and bilateral cunei and between the right thalamus and the contralateral calcarine sulcus and right cuneus. Furthermore, the neural activation of the left calcarine sulcus was positively correlated with visual analogue scale scores (r = 0.319, p = 0.043), and enhanced FC between the left thalamus and right cuneus in migraine patients was negatively correlated with Generalized Anxiety Disorder scores (r = − 0.617, p = 0.005). Conclusion Our data suggest that migraine distress is exacerbated by aberrant feedback projections to the visual network, playing a crucial role in migraine physiological mechanisms. The current study provides further insights into the complex scenario of migraine mechanisms.

Introduction Long non-coding RNAs (lncRNAs) have been implicated in the initiation and progression of malignant tumor. The aim of the present study was to investigate whether LINC00336 contributes to the tumorigenesis of bladder cancer (BCa). Material and methods LncRNA expression profiling in BCa tissues was analyzed using lncRNA microarray. Cell viability, invasion and apoptosis were detected using CCK8, Transwell and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC) double staining, respectively. Results LncRNA microarray and RT-qPCR revealed that LINC00336 was significantly up-regulated in BCa tissues and cell lines compared with the corresponding control group. Kaplan-Meier and multivariate regression analysis demonstrated that LINC00336 could serve as an independent risk factor for predicting the prognosis of BCa patients. In vitro experimental measurements showed that knockdown of LINC00336 had the ability to block cell proliferation and invasion, as well as to induce cell cycle arrest and apoptosis. Conclusions These findings indicated that LINC00336 might serve as an oncogene in the initiation and progression of BCa, and LINC00336 may be a valuable and promising therapeutic target for the treatment of BCa.

Background: Immune checkpoint inhibitors (ICIs) are employed to treat various cancers, including soft tissue sarcomas (STSs), and less than 20% of patients benefit from this treatment. Vascular endothelial growth factor (VEGF) promotes the immunosuppressive tumor microenvironment and contributes to ICI-resistant therapy. Anti-VEGF receptor tyrosine-kinase inhibitors (TKIs) combined with ICIs have shown antitumor activity in patients with alveolar soft-part sarcoma (ASPS). However, they have not been extensively studied to treat other STS subtypes, such as leiomyosarcoma (LMS), dedifferentiated liposarcoma (DDLPS), undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), and angiosarcoma (AS).Methods: In this retrospective study, we collected data from 61 patients who were diagnosed with advanced STS based on imaging and histology, including LMS, DDLPS, and UPS. Among them, 41 patients were treated with ICIs combined with TKIs and 20 patients received ICI therapy. The endpoints of progression-free survival (PFS) and overall response rate (ORR) were analyzed in the two groups, and the overall response [partial response (PR), stable disease (SD), and progressive disease (PD)] of each patient was determined using RECIST 1.1 evaluation criteria.Results: In total, 61 STS patients had the following subtypes: LMS (n = 20), DDLPS (n = 17), UPS (n = 8), ASPS (n = 7), MFS (n = 7), and AS (n = 2). The median PFS (mPFS) was significantly prolonged after ICI treatment in combination with TKIs (11.74 months, 95% CI 4.41–14.00) compared to ICI treatment alone (6.81 months, 95% CI 5.43–NA) (HR 0.5464, p = 0.043). The 12-month PFS rates of patients who received ICI–TKI treatment were increased from 20.26% (95% CI 0.08–0.53) to 42.90% (95% CI 0.27–0.68). In the combination therapy group, 12 patients (30%) achieved PR, 25 patients (62.5%) achieved SD, and 3 patients (7.5%) achieved PD for 3 months or longer. In the non-TKI-combination group, 2 patients (9.5%) achieved PR, 14 patients (66.7%) achieved SD, and 5 patients (23.8%) achieved PD within 3 months. The ORRs in the two groups were 30.0% (ICI–TKI combination) and 9.5% (ICI only), respectively. A notable ORR was observed in the ICI–TKI combination group, especially for subtypes ASPS (66.7%), MFS (42.9%), and UPS (33.3%). The PD-L1 expression (n = 33) and tumor mutation burden (TMB, n = 27) were determined for each patient. However, our results showed no significant difference in PFS or response rates between the two groups.Conclusion: This study suggests that ICI–TKI treatment has antitumor activity in patients with STS, particularly the ASPS and MFS subtypes. Moreover, effective biomarkers to predict clinical outcomes are urgently needed after combination therapy in the STS subtypes.

Morganella morganii, which is often regarded as a human commensal organism, can be an opportunistic pathogen, causing a variety of clinical infections with serious morbidity and mortality. An efficient and convenient method for subtyping and identifying M. morganii strains in epidemiological surveillance and control is urgently needed. Serotyping based on bacterial surface polysaccharide antigens (O-antigen or K-antigens) is a standard subtyping method for many gram-negative bacteria. Here, through whole genome sequencing and comparative genomics analysis of 27 strains, we developed a molecular serotyping scheme based on the genetic variation of O-antigen gene clusters (O-AGC) in M. morganii, and 11 distinct O-AGC types were identified. A conventional serotyping scheme was also developed by the production of antisera and agglutination experiments, which was shown to be perfectly consistent with the molecular serotyping scheme, confirming that the variation in M. morganii O-AGC correlated with phenotypic O-antigen diversification. Furthermore, a microsphere-based suspension array (MSA) with high specificity was developed based on the specific genes within each O-AGC type. The sensitivity of MSA was determined to be 0.1 ng of genomic DNA and 103 CFU of pure culture. We further analyzed 104 M. morganii genomes available in GenBank, and an additional six novel O-AGC types were identified, indicating that the extension of this molecular serotyping scheme is convenient. Our work provides an important tool for the detection and epidemiological surveillance of M. morganii, and this method has the potential to be widely utilized, especially for bacterial genera/species without an efficient typing approach.

Liposarcoma (LPS) is a rare and heterogeneous malignancy of adipocytic origin. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes, showing similar genetic characterizations but distinct biological behaviors and clinical prognosis. Compared to WDLPS, DDLPS is more aggressive and has the potential of metastasis, as the malignant adipocytic tumor’s metabolic changes may have taken place during the tumorigenesis of LPSs. Therefore, to investigate the lipid alterations between the two subtypes, high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) based untargeted lipidomic analysis was performed onto LPS tissues from 6 WDLPS and 7 DDLPS patients. The lipidomic analysis showed the upregulated phosphatidylcholines and phosphoethanolamines in DDLPS, and the upregulated triglycerides and diglycerides in WDLPS, which might be due to the uncompleted adipocytic dedifferentiation leading to such tumorigenesis. Such a finding was also confirmed by the similarity comparison of two LPS subtypes to the transcriptome of stromal vascular fraction at different differentiation stages. Transcriptomic analysis also demonstrated that metabolic pathways including the pentose phosphate pathway (PPP) were upregulated in WDLPS compared to DDLPS. Therefore, the cell line LPS853 was treated with the PPP inhibitor 6-aminonicotinamide ex vivo and the proliferation and invasion of LPS853 was significantly promoted by PPP inhibition, suggesting the potential role of PPP in the development and differentiation of LPS. In conclusion, this study described the altered lipid profiles of WDLPS and DDLPS for the first time, revealing the different differentiation stages of the two subtypes and providing a potential metabolic target for LPS treatment.

Objective: To evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) and quantitative parameters in early prediction of tumor response to chemoradiotherapy (CRT) in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). Patients and Methods: In this prospective study, patients with biopsy-proved and histopathologically proved LAPC who underwent regular CRT were recruited. DCE-US evaluations were performed before and four months after CRT. SonoVue-enhanced contrast-enhanced ultrasound (CEUS) was performed by an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, USA) equipped with a 5C1 MHz convex array transducer. Time–intensity curves were created by VueBox software (Bracco, Italy), and various DCE-US quantitative parameters were obtained. Taking Response Evaluation Criteria in Solid Tumors (RECIST) based on computed tomography (CT) or magnetic resonance imaging (MRI) as the gold standard, DCE-US parameters were compared between the treatment responder group (RG) and non-responder group (NRG). The correlation between the DCE-US parameters and the serum carbohydrate antigen 19-9 (CA 19-9) level was also analyzed. Results: Finally, 21 LAPC patients (mean age 59.3 ± 7.2 years) were included. In comparing the RG (n = 18) and NRG (n = 3), no significant change could be found among the mean size of the lesions (31.2 ± 8.1 mm vs. 27.2 ± 8.3 mm, p = 0.135). In comparing the TICs between the two groups, the LAPC lesions in the RG took a longer time to reach peak enhancement and to wash out. Among all the DCE-US parameters, RT (rise time), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiWoAUC (wash-in and wash-out area under the curve) decreased significantly after CRT in the RG (p < 0.05). The RT ratio, WiAUC ratio, WoAUC ratio and WiWoAUC ratio were closely correlated with the change in serum CA 19-9 level in the RG (p < 0.05). Conclusion: DCE-US might be a potential imaging method for non-invasive follow-up for early response in LAPC patients treated by CRT.

Previous studies have demonstrated that the effects of monensin on methanogenesis and ruminal fermentation in ruminants were time-dependent. To elucidate the underlying mechanism, we investigated the ruminal bacterial community successions during the adaptation to monensin supplementation and subsequent withdrawal in goats. The experiment included a baseline period of 20 days followed by a treatment period of 55 days with 32 mg monensin/d and a washout period of 15 days. Monensin supplementation reduced the α diversity and changed the structure of ruminal microflora. The α diversity was gradually restored during adaption, but the structure was still reshaped. The temporal dynamics of 261 treatment- and/or time-associated ruminal bacteria displayed six patterns, with two as monensin-sensitive and four as monensin-resistant. The monensin sensitivity and resistance of microbes do not follow a clear dichotomy between Gram-positive and Gram-negative cell types. Moreover, the temporal dynamic patterns of different bacterial species within the same genus or family also displayed variation. Of note, the relative abundance of the total ruminal cellulolytic bacteria gradually increased following monensin treatment, and that of the total amylolytic bacteria were increased by monensin, independent of the duration. In conclusion, under the pressure of monensin, the ruminal ecosystem was reshaped through a series of succession processes, and the carbohydrate-degrading bacteria presented a higher level of adaptability.

Rumen microorganisms can be used in in vitro anaerobic fermentation to encourage the sustainable exploitation of agricultural wastes. However, the understanding of active microbiota under in vitro ruminal fermentation conditions is still insufficient. To investigate how rumen microbes actively participate in the fermentation process in vitro, we resolved the metaproteome generated from ruminal fermentation broth after seven days of in vitro incubation. Herein, the sample-specific database for metaproteomic analysis was constructed according to the metagenomic data of in vitro ruminal fermentation. Based on the sample-specific database, we found in the metaproteome that Bacteroidetes and Firmicutes_A were the most active in protein expression, and over 50% of these proteins were assigned to gene categories involved in energy conversion and basic structures. On the other hand, a variety of bacteria-derived extracellular proteins, which contained carbohydrate-active enzyme domains, were found in the extracellular proteome of fermentation broth. Additionally, the bacterial intracellular/surface moonlighting proteins (ISMPs) and proteins of outer membrane vesicles were detected in the extracellular proteome, and these ISMPs were involved in maintaining microbial population size through potential adherence to substrates. The metaproteomic characterizations of microbial intracellular/extracellular proteins provide new insights into the ability of the rumen microbiome to maintain in vitro ruminal fermentation.

The retina is composed of 11 types of cells, including neurons, glial cells and vascular bed cells. It contains five types of neurons, each with specific physiological, morphological, and molecular definitions. Currently, single-cell RNA sequencing (sRNA-seq) is emerging as one of the most powerful tools to reveal the complexity of the retina. The continuous discovery of retina-related gene targets plays an important role in helping us understand the nature of diseases. The revelation of new cell subpopulations can focus the occurrence and development of diseases on specific biological activities of specific cells. In addition, sRNA-seq performs high-throughput sequencing analysis of epigenetics, transcriptome and genome at the single-cell level, with the advantages of high-throughput and high-resolution. In this paper, we systematically review the development history of sRNA-seq technology, and summarize the new subtypes of retinal cells and some specific gene markers discovered by this technology. The progress in the diagnosis of retinal related diseases is also discussed.

Although the direction aspect is as important as the distance aspect when retrieving spatial objects, the studies of direction-aware queries are limited. The direction-based surrounder query cannot guarantee good directional diversity. In this paper, we propose the direction-aware nearest neighbor query (DNN query), which can recommend the nearest objects and ensure that the results have good directional diversity. Given a query point q and an angular threshold θ, the DNN query searches for the nearest neighbors on various directions around q. The DNN query can apply to the scenario where the user searches for the nearest objects around him. It can also apply to the scenario where the user searches for the photos of a geographic object according to the locations where the photos are taken. It can find photos that capture different views of the query object. In this paper, we propose the point-DNN query, where the query object is a point, and extend it to the range-DNN query, where the query object is a rectangle. We design algorithms to answer the DNN queries and also conduct comprehensive experiments to evaluate the performances of the algorithms.

Escherichia coli K1 is the most popular neonatal meningitis-causing Gram-negative bacterium. As a key virulence determinant, the K1 capsule enhances the survival of E. coli K1 in human brain microvascular endothelial cells (HBMECs) upon crossing the blood–brain barrier; however, the regulatory mechanisms of capsule synthesis during E. coli K1 invasion of HBMECs remain unclear. Here, we identified YbdO as a transcriptional regulator that promotes E. coli K1 invasion of HBMECs by directly activating K1 capsule gene expression to increase K1 capsule synthesis. We found that ybdO deletion significantly reduced HBMEC invasion by E. coli K1 and meningitis occurrence in mice. Additionally, electrophoretic mobility shift assay and chromatin immunoprecipitation–quantitative polymerase chain reaction analysis indicated that YbdO directly activates kpsMT and neuDBACES expression, which encode products involved in K1 capsule transport and synthesis by directly binding to the kpsM promoter. Furthermore, ybdO transcription was directly repressed by histone-like nucleoid structuring protein (H-NS), and we observed that acidic pH similar to that of early and late endosomes relieves this transcriptional repression. These findings demonstrated the regulatory mechanism of YbdO on K1 capsule synthesis, providing further insights into the evolution of E. coli K1 pathogenesis and host–pathogen interaction.

The process by which bacteria sense environmental cues to regulate their virulence is complex. Several studies have focused on regulating the expression of the locus of enterocyte effacement pathogenicity island in the typical gut pathogenic bacterium, O157.

Due to the irreversibility of heavy metal pollution, the presence of heavy metals in farmland soil is associated with severe ecological risks that endanger both the environment and human health. Cadmium (Cd) and mercury (Hg) are two toxic heavy metals found widely in polluted soil. Cd is not readily fixed in the soil and is therefore easily accumulated by plants, while Hg has a wide range of pollution sources. The aims of this study were to explore the spatial variation in Cd and Hg concentrations in farmland soil in Poyang Lake Plain, China, and to assess their potential ecological risks as influenced by natural and human factors. A total of 283 soil samples were obtained from Fengcheng city, central Jiangxi Province. Data were then analyzed using geostatistics, the potential ecological risk index, Pearson’s correlation analysis, and Geodetector. The results showed moderate variation in soil Cd and Hg concentrations, with a remarkable difference in their spatial distribution. Cd concentrations in the northwest and northeast of Fengcheng were below the regional background level in Jiangxi; in most remaining areas, Cd concentrations were between the regional background level and national risk screening value. Areas with Hg concentrations lower than the regional background level were largely concentrated in the south, east and north of Fengcheng, and gradually increased towards the central, where they exceeded the regional background level but were below the national risk screening value. Overall, the potential ecological risk level of Cd was predominantly low, while that of Hg was moderate. The comprehensive potential ecological risk was low in most areas for both Cd and Hg, with some scattered areas of moderate risk. Moreover, the comprehensive potential ecological risk index of both Cd and Hg was significantly correlated with soil pH, total phosphorous, elevation, distance from a river (p < 0.01), and distance from a road (p < 0.05). The most significant factor influencing the comprehensive potential ecological risk index of these two heavy metals was soil pH of 5.2–5.6, followed by total p ≤ 0.52 mg kg−1. In conclusion, moderate pollution of Cd and Hg occurred in farmland soil in Poyang Lake Plain where their comprehensive potential ecological risk level was generally low and mainly influenced by soil pH and total phosphorous.

Ecological quality (EQ) is the foundation of all ecosystem services (ESs) and is critical for the improvement of human welfare. To clarify the link between ecosystems and human well-being, the present study investigated the relationship between EQ and ESs in the Pingjiang watershed in a red soil hilly region (southern China) in 2016. The remote sensing ecological index (RSEI) and the ecosystem service index (ESI), respectively, were used to characterize EQ and four major ESs, i.e., water yield (WY), soil conservation (SC), carbon storage (CS), and food supply (FS). The relationship between EQ and ESs was explored at the sub-watershed scale. Results showed that the EQ of the Pingjiang watershed decreased from the surroundings to the central south. The spatial distributions of SC, CS, and ESI were similar to the EQ distribution, while FS exhibited an opposite trend. The spatial aggregation patterns of RSEI and ESI were somewhat similar, with a Spearman’s correlation coefficient (r) of 0.690 (P

Alterations of brain functional connectivity in patients with type 2 diabetes mellitus (T2DM) have been reported by resting-state functional magnetic resonance imaging studies, but the underlying precise neuropathological mechanism remains unclear. This study is aimed at investigating the implicit alterations of functional connections in T2DM by integrating functional connectivity strength (FCS) and Granger causality analysis (GCA) and further exploring their associations with clinical characteristics. Sixty T2DM patients and thirty-three sex-, age-, and education-matched healthy controls (HC) were recruited. Global FCS analysis of resting-state functional magnetic resonance imaging was performed to explore seed regions with significant differences between the two groups; then, GCA was applied to detect directional effective connectivity (EC) between the seeds and other brain regions. Correlations of EC with clinical variables were further explored in T2DM patients. Compared with HC, T2DM patients showed lower FCS in the bilateral fusiform gyrus, right superior frontal gyrus (SFG), and right postcentral gyrus, but higher FCS in the right supplementary motor area (SMA). Moreover, altered directional EC was found between the left fusiform gyrus and bilateral lingual gyrus and right medial frontal gyrus (MFG), as well as between the right SFG and bilateral frontal regions. In addition, triglyceride, insulin, and plasma glucose levels were correlated with the abnormal EC of the left fusiform, while disease duration and cognitive function were associated with the abnormal EC of the right SFG in T2DM patients. These results suggest that T2DM patients show aberrant brain function connectivity strength and effective connectivity which is associated with the diabetes-related metabolic characteristics, disease duration, and cognitive function, providing further insights into the complex neural basis of diabetes.

Previous studies on the space of flows have mainly focused on a single flow element and have given less consideration to the joint effect of complex correlations among multiple flows. To fill this gap, in the context of the coordinated development of the urban agglomeration of the Yellow River Ji-shaped bend (UAYB), in this study, three flows, namely population flow, logistics flow, and information flow, are selected to research the spatial patterns of the UAYB. The results show the following: (1) The information flow among cities in the UAYB is the strongest, followed by logistics flow and population flow. (2) Hohhot, Ordos, Yinchuan, and Taiyuan are the core cities and have attracted more flows to converge there; different flows have formed different central features. (3) Regarding the correlation of the three flows, information flow has a strong correlation with the other two flows. (4) From the perspective of the joint effects of the three flows considered, the hierarchy of UAYB is dominated by Hohhot and Taiyuan and sub-dominated by Yinchuan and Ordos; four prominent city groups have been formed with these four cities as the center. On the basis of our results, we put forward some recommendations on the integrated development of cities at various levels within the UAYB to provide a reference for its spatial optimization strategy.

Despite the rising interest in understanding the various uses of space of flows, few studies have combined the traditional static urban development level with dynamic space of flows concepts. In the context of the coordinated development of the urban agglomeration of the Yellow River Ji-shaped bend (UAYB), this study identifies the hierarchical spatial structure of the UAYB through a combination of Baidu migration big data and traditional data. The following conclusions can be drawn. (1) The cities with the strongest regional comprehensive power are Ordos, Taiyuan, Hohhot, Yinchuan, and Yulin, which cause the UAYB to present a significant “center-periphery” spatial pattern. (2) The biggest population flows mostly occur between cities in the same province, while interprovincial population flows mainly exist between cities with the strongest comprehensive power. (3) The hierarchical spatial structure of the UAYB forms a multitree structure, with Ordos as the core. (4) The attractiveness of the UAYB is very weak, being only slightly attractive to individual surrounding provinces, while the population outflow index to economically developed areas is high. Several policy implications are proposed, which can provide important insights for planning intercity connections among the UAYB, in order to achieve more coordinated regional development.

Reasonable delineation of the urban growth boundary (UGB) plays a vital role in guiding orderly urban space growth and ensuring urban environmental health. Existing methodologies for UGB delineation have failed to address the significance of ecological security. Therefore, this study presents a framework that couples ecological security pattern (ESP) establishment and construction land expansion (CLE) simulation to delineate the UGB. The proposed framework is applied to the Nanchang Metropolitan Area (NCMA) in southeastern China. First, we established the regional ESP of the NCMA in 2018 based on an improved minimum cumulative resistance model. The areas of low-, medium-, and high-level ESP were 1050.75, 736.42, and 720.59 km2, respectively. Second, we implemented a multi-scenario simulation of CLE in the NCMA in 2025 based on a cellular automata–Markov model. A natural development scenario was superior to urban growth and ecological protection scenarios for social, economic, and ecological development at the regional scale. Accordingly, we delineated the UGB of the NCMA in 2025 with a scale of 687.87 km2, based on dynamic adjustment using the results of ESP establishment and CLE simulation in the natural development scenario. The rationality and scientificity of the proposed framework were verified by comparing the scale and layout of the delineated UGB with the regional planning of Nanchang City. The framework incorporating dynamic adjustment with ESP establishment and multi-scenario CLE simulation provides a useful tool for the delineation of the UGB in similar urbanized cities. Its application is conducive to achieving a win–win outcome of regional ecological security and urban development.

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high morbidity and mortality. However, there is no effective therapy method to improve its clinical outcomes to date. Here we report an injectable gelatin hydrogel that is capable of suppressing inflammation and enhancing functional recovery in a mouse model of ICH. Thiolated gelatin was synthesized by EDC chemistry and then the hydrogel was formed through Michael addition reaction between the thiolated gelatin and polyethylene glycol diacrylate. The hydrogel was characterized by scanning electron microscopy, porosity, rheology, and cytotoxicity before evaluating in a mouse model of ICH. The in vivo study showed that the hydrogel injection into the ICH lesion reduced the neuron loss, attenuated the neurological deficit post-operation, and decreased the activation of the microglia/macrophages and astrocytes. More importantly, the pro-inflammatory M1 microglia/macrophages polarization was suppressed while the anti-inflammatory M2 phenotype was promoted after the hydrogel injection. Besides, the hydrogel injection reduced the release of inflammatory cytokines (IL-1β and TNF-α). Moreover, integrin β1 was confirmed up-regulated around the lesion that is positively correlated with the M2 microglia/macrophages. The related mechanism was proposed and discussed. Taken together, the injectable gelatin hydrogel suppressed the inflammation which might contribute to enhance the functional recovery of the ICH mouse, making it a promising application in the clinic.

Enterobacter cloacae is a well-characterized opportunistic pathogen that is closely associated with various nosocomial infections. The O-antigen, which is one of the most variable constituents on the cell surface, has been used widely and traditionally for serological classification of many gram-negative bacteria. E. cloacae is divided into 30 serotypes, based on its O-antigen diversity. In this study, by using genomic and comparative-genomic approaches, we analyzed the O-antigen gene clusters of 26 E. cloacae serotypes in depth. We also identified the sero-specific gene for each serotype and developed a multiplex polymerase chain reaction (PCR) method. The sensitivity of the assay was 0.1 ng for genomic DNA and 103 colony forming units for pure cultures. The assay reliability was evaluated by double-blinded testing with 81 clinical strains. Furthermore, we established a valid, genome-based tool for in silico serotyping of E. cloacae. By screening 431 E. cloacae genomes deposited in GenBank, 304 were classified into current antigenic scheme, and 112 were allocated into 55 putative novel serotypes. Our results represent the first genetic basis of the O-antigen diversity and variation of E. cloacae, providing a rationale for studying the O-antigen associated evolution and pathogenesis of this bacterium. In addition, we extended the current serotyping system for E. cloacae, which is important for detection and epidemiological surveillance purposes for this important pathogen.