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OBJECTIVES: This study aims to develop and validate a radiomics nomogram based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to noninvasively predict axillary lymph node (ALN) metastasis in breast cancer. METHODS: This retrospective study included 263 patients with histologically proven invasive breast cancer and who underwent DCE-MRI examination before surgery in two hospitals. All patients had a defined ALN status based on pathological examination results. Regions of interest (ROIs) of the primary tumor and ipsilateral ALN were manually drawn. A total of 1,409 radiomics features were initially computed from each ROI. Next, the low variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) algorithms were used to extract the radiomics features. The selected radiomics features were used to establish the radiomics signature of the primary tumor and ALN. A radiomics nomogram model, including the radiomics signature and the independent clinical risk factors, was then constructed. The predictive performance was evaluated by the receiver operating characteristic (ROC) curves, calibration curve, and decision curve analysis (DCA) by using the training and testing sets. RESULTS: ALNM rates of the training, internal testing, and external testing sets were 43.6%, 44.3% and 32.3%, respectively. The nomogram, including clinical risk factors (tumor diameter) and radiomics signature of the primary tumor and ALN, showed good calibration and discrimination with areas under the ROC curves of 0.884, 0.822, and 0.813 in the training, internal and external testing sets, respectively. DCA also showed that radiomics nomogram displayed better clinical predictive usefulness than the clinical or radiomics signature alone. CONCLUSIONS: The radiomics nomogram combined with clinical risk factors and DCE-MRI-based radiomics signature may be used to predict ALN metastasis in a noninvasive manner.

The high wind pressure and velocity of the outdoor environment make super-high-rise tower crown space distinct from general tall through space. This segregation causes the crown space to be particularly prone to smoke short-circuiting influenced by the outside wind environment if a fire occurs indoors, and causes deficient smoke exhaust efficiency in a fire. The goal of this study was to investigate the general principle regarding the effect of the outdoor wind environment on smoke exhaust efficiency of such spaces under the crown space. We measured external wind direction and wind pressure in the smoke exhaust in the tower crown and developed setting plans for the exhaust outlets and make-up air inlet. Airpak was used to create the external wind environment and compare simulations to see if smoke short-circuiting occurred. We analyzed the causes, summarized solutions that did not result in short-circuiting of smoke flow, and made adjustments. We provide an ideal plan for the setting direction and vent velocity of the make-up air inlet and exhaust outlet in the crown spaces of super-tall towers to improve the design of smoke exhaust systems in such spaces.

Natural disasters, new urbanization and urban renewal activities generated a large amount of construction and demolition waste (C&DW), and managing C&DW has become an urgent problem to be solved in the construction of “Zero-waste cities”. Based on the calculation of C&DW generation in China from 2005 to 2019, this study analyzed the temporal and spatial characteristics of C&DW generation in China, and empirically explored the factors influencing factors C&DW of China using spatial autocorrelation and geographically weighted regression. The results showed that: (1) C&DW generation in China increased every year, and the overall distribution was characterized as “high in the east and low in the west”, with distinct regional differences. The provinces with the highest per capita C&DW generation were Zhejiang, Jiangsu, Beijing, Shanghai, and Fujian. The generation intensity of C&DW in China and all its provinces showed a decreasing trend every year. The regions with rapid growth of C&DW generation in China were concentrated in the eastern coastal areas, with distinct differences between the east and west, and there was significant spatial heterogeneity in the growth trend. (2) There is a significant spatial autocorrelation in C&DW generation in China. Overall, the hot spots for C&DW generation were distributed in Jiangsu, Zhejiang, and Shandong provinces, and the spatial agglomeration effect of C&DW generation in provinces was evident. (3) Factors such as population size, per capita Gross Domestic Product and the scale of the construction industry played a positive role in promoting C&DW generation in each province, whereas labor efficiency played a negative role inhibiting C&DW generation; there was significant temporal and spatial heterogeneity. Finally, differentiation and cross-regional joint treatment strategies according to regional conditions were proposed to achieve precise measures of C&DW reduction management.

In this paper, heat transfer characteristics of phase change material in rectangular containers are numerically analyzed. The inclination angles of the container refer to 0?, 90?, and 180?. Both theoretical and practical periodic temperature boundary conditions are taken into consideration, in which the periodic temperature boundary conditions include 50-80?C and 65-80?C. The comparison study is carried out through the liquid fraction and temperature histories during the heat transfer process under these different boundary conditions. It is indicated that there are large differences between the calculated results under the theoretical and the practical periodic temperature boundary conditions when the temperature boundary is 50-80?C, while the theoretical and the practical periodic temperature boundary conditions of 65-80?C have relatively little effect on the numerical results of the heat transfer process of the phase change material. Furthermore, compared with the temperature increasing stage, the numerical results calculated under the theoretical and the practical boundary conditions have more significant differences in the temperature decreasing stage. The research conclusion of this paper can provide a theoretical basis for the application of phase change material under periodic temperature boundary conditions.

Background Breast cancer (BRCA) is one of the most frequent malignant tumors in women worldwide. Lysosomes are known to regulate tumor cell proliferation by manipulating growth factor signaling and providing nutrition. However, the role of lysosomes and lysosome-related genes (LRGs) in BRCA is yet unclear. Therefore, this study aimed to identify the lysosomal-related biomarkers for predicting the prognosis and immunotherapeutic response of BRCA. Results Based on the expression of 15 prognostic LRGs, BRCA cases were divided into two subtypes with significantly different overall survival (OS). In all, 537 differentially expressed lysosome-related genes (DELRGs) were identified and they were significantly enriched in the PI3K-Akt signaling pathway, protein digestion and absorption, and regulation of actin cytoskeleton. Then, the risk model was constructed based on five biomarkers, namely, QPRT, EIF4EBP1, IGJ, UGDH, and IL1R1. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves revealed that the risk model could accurately predict the prognosis of BRCA cases, and age, stage, and risk score were regarded as independent prognostic indicators. According to Gene set enrichment analysis (GSEA), the risk model might be related to the cell cycle, cytokine receptor interaction, and ATP synthesis coupled electron transport pathways. Moreover, the risk score showed significant positive correlation with CTLA4, while negative correlation with PD1. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) indicated the expression levels of EIF4EBP1 and UGDH were significantly higher in BRCA tissue compared with normal samples. Conclusion We identified two BRCA subtypes based on LRGs and constructed a risk model using five biomarkers. These findings may provide a theoretical basis and reference value for research and treatment in the direction of lysosomes in BRCA.

We reported the metastatic chordoma in the right gluteus maximus of a 73-year-old man. The patient was initially diagnosed with sacrococcygeal chordoma and treated with surgical resection. Unfortunately, he had a gluteal metastasis and recurrence and suffered the third-operation therapy. Chordoma is a rare malignant tumor and may metastasize, but the metastasis and recurrence of chordoma at the right gluteus maximus following sacrococcygeal region are extraordinarily rare. This unusual case report may be helpful to clinical workers in diagnosing chordoma.

Biochar amendment is considered as an efficient practice for improving carbon storage in soils. However, to what extent that biochar application promotes organic carbon in saline-sodic soils remains poorly understood. By comparing soil organic carbon (SOC) contents change before and after biochar addition, we deciphered the driving factors or processes that control SOC change in response to biochar application. A limited increase in SOC was observed, about by 1.16%–12.80%, even when biochar was applied at the rate of 10% of bulk soil weight. Biochar application enhanced soil dissolved organic carbon (DOC) significantly by up to 67%. It was estimated that about 50% SOC was allocated to small macroaggregates (250–2000 µm, CPOC), and SOC in silt and clay-sized particles (< 53 µm) decreased obviously after biochar addition. Microbial biomass increased with biochar amendment, of which actinomycetes (ACT), fungus (FUN), protozoon (PRO), and bacteria with straight-chain saturated fatty acids (OB) increased remarkably. Multiple linear regression models implied that DOC was governed by ACT and soil N: P ratio, while SOC mostly depended on CPOC. The principal component analysis and the partial least square path model (PLS-PM) indicated that biochar addition aggravated nitrogen limitation in saline-sodic soils, and effects of microorganisms on regulating SOC greatly depended on nitrogen bioavailability. Biochar application had vastly changed interactions between environmental factors and SOC in saline-sodic soils. Effects of nutrients on SOC shifted to great inhibition from strong stimulation after biochar addition, meanwhile, aggregation was the only factor presenting positive effects on SOC. How to eliminate nutrient limitation and better soil aggregation process should be considered in priority when biochar was used to improve SOC in saline-sodic soils.

Purpose: The aim of this study was to examine the diagnostic efficacy of hippocampal subregions volume and texture in differentiating amnestic mild cognitive impairment (MCI) from normal aging changes. Materials and Methods: Ninety MCI subjects and eighty-eight well-matched healthy controls (HCs) were selected from the ADNI-1 or ADNI-2 Database.Twelve hippocampal subregions volume and texture features were extracted using Freesurfer and MaZda based on T1 weighted magnetic resonance images. Then, two-sample t-test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were developed to select a subset of the original features. Finally, a support vector machine (SVM) was used to perform the classification task and the area under the curve (AUC), sensitivity, specificity, and accuracy were calculated to evaluate the diagnostic efficacy of the model. Results: The volume features with high discriminative power were mainly located in the bilateral CA1 and bilateral CA4, while texture feature were gray-level non-uniformity, run length non-uniformity and fraction. Our model based on hippocampal subregions volume and texture features achieved better classification performance with an AUC of 0.90. Conclusions: Based on hippocampal subregions volume and texture can be used to diagnose MCI. Moreover, we found that the features that contributed most to the model were mainly textural features, followed by volume. These results may guide future studies using structural scans to classify patients with MCI.

Chronic coronary heart disease (CHD) is correlated with an increased risk of cognitive impairment (CI), but the mechanisms underlying these changes remain unclear. The aim of the present study was to explore the potential changes in regional spontaneous brain activities and their association with CI, to explore the pathophysiological mechanisms underlying CI in patients with CHD.A total of 71 CHD patients and 73 matched healthy controls (HCs) were included in this study. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess the participants' cognitive functions. Regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation(fALFF) values were calculated to determine regional spontaneous brain activity. Coronary artery calcium (CAC) score provides a measure of the total coronary plaque burden. Mediation analyses were performed to test whether CHD's effects on cognitive decline are mediated by decreased regional spontaneous brain activity.Patients with CHD had significantly lower MMSE and MoCA scores than the HCs. Compared with the HCs, the patients with CHD demonstrated significantly decreased ReHo and fALFF values in the bilateral medial superior frontal gyrus (SFGmed), left superior temporal gyrus (TPOsup) and left middle temporal gyrus (TPOmid). Impaired cognitive performance was positively correlated with decreased activities in the SFGmed. Mediation analyses revealed that the decreased regional spontaneous brain activity in the SFGmed played a critical role in the relationship between the increase in CAC score and the MoCA and MMSE scores.The abnormalities of spontaneous brain activity in SFGmed may provide insights into the neurological pathophysiology underlying CHD associated with cognitive dysfunction.

In this paper, the province construction and demolition waste (CDW) generation in China from 2005 to 2018 is calculated by using the area estimation method. Together with the use of the gravity model and the social network analysis method (SNA), the characteristics and effects of the spatial correlation structure network of China's province construction and demolition waste generation are studied. It has been found that from 2005 to 2018, the construction and demolition waste in China had seen a significant rise, and the spatial difference in province generation is significant. During that time, China's inter-provincial construction and demolition waste generation demonstrated significant characteristics of a spatial correlation network with a complex network hierarchy and showed a trend of year-by-year increase in its overall network density and number of correlation. In this spatial connection network, nine provinces, including Beijing, Tianjin, Shanghai, Jiangsu, Zhejiang, Fujian, Shandong, Hubei and Guangdong, played a core role as "bridges", Beijing, Shanghai, Jiangsu, Guangdong, Shandong, Fujian and Zhejiang provinces are "beneficiaries", Chongqing, Tianjin, Hubei, Anhui, Sichuan, Henan, Jiangxi, Hunan and Hebei are "brokers" while other provinces are "the damaged". Indexes such as network density, network hierarchy and network efficiency all have a significant impact on the national construction and demolition waste generation intensity. The reduction of network density, the improvement of network hierarchy and network efficiency can significantly reduce the difference in construction and demolition waste generation intensity. The structure of spatial correlation network has significant influence on the difference of construction and demolition waste generation intensity.

Up to now, few studies pay attention on the effects of crab burrowing on soil properties of newly formed mudflats. However, this information is important to protect and manage the new-formed area. Therefore, a field observation was carried out to investigate the effects of crab burrowing on soil properties of newly formed mudflats in the Yellow River Delta. Crab burrow parameters and soil properties were measured at three fixed locations. Results indicated that crab burrowing greatly affected soil texture, but not soil nutrient. Soil textural feature was changed from clay to silt by significantly increasing the proportion of sand (+3.82%) and decreasing the proportion of clay (–4.76%). Crab burrowing showed significantly negative effects on soil bulk density, pH, soil salinity, and proportion of clay (p 0.05). Overall, crab burrowing had distinct positive effects on surface soil properties, especially the soil texture. These results suggest that crab burrowing would improve surface soil conditions, which in turn would stimulate other life processes and promote the stability of newly formed wetlands.

This study compared soil organic carbon (SOC) in wetlands dominated by native and one invasive plant specie to better understand how short-term Spartina alterniflora colonization affected carbon circulation in the Yellow River Delta (YRD). Freshwater marsh dominated by Phragmites australis (FM) had the highest SOC, total nitrogen (TN), and water-extractable organic carbon (WEOC) contents, whereas SOC contents varied only slightly among salt marshes covered by Suaeda salsa (SM2), S. alterniflora (SM3) and bare flat (MD). Invasion by S. alterniflora substantially changed the molecular characteristics of SOC. The spectral characteristics of Fourier-transform infrared spectroscopy (FTIR) of humic acids (HAs) were similar from 4000 to 1800 cm−1 but differed greatly from 1800 to 1000 cm−1 among four wetlands. Pyrolysis-gas chromatography/mass spectrometry technology (Py-GC/MS) was used to characterize molecular fingerprints of HAs. Aliphatics (27.38%), lignin (16.64%), nitrogen-containing compounds (Nc) (16.16%), polysaccharides (16.93%), and phenol (13.42%) were dominant in FM, and aliphatics, alkyl, and Nc were primary in HAs from MD, SM2, and SM3. Lignin moieties were only found in HAs from FM and SM3, which accounted for about 16.64% and 1.6% of the total ion current, respectively. The absorption bands of the FTIR spectrum around 3340 and 1650 cm−1 in FM samples were much larger than those in the other three wetlands. However, the ratio of the peak areas at 1620 and 2930 cm−1 (R1620/2930) in SM3, was lower than that in MD and SM2, and it meant carbon in SM3 was less stable. Proportions of lignin and phenol moieties to total ion counts (TIC) in MD and SM2 were 3.3% and 3.4%, while these proportions in FM and SM were 30% and 7.5%, respectively. It showed S. alterniflora invasion into salt marsh would increase SOC contents and its stability, while it will inverse if freshwater marsh was supplanted by S. alterniflora in the YRD.

Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) are the most commonly reported sexually transmitted bacteria worldwide and usually present as co-infections. Increasing resistance of Ng to currently recommended dual therapy of azithromycin and ceftriaxone presents therapeutic challenges for syndromic management of Ng-Ct co-infections. Development of a safe, effective, and inexpensive dual therapy for Ng-Ct co-infections is an effective strategy for the global control and prevention of these two most prevalent bacterial sexually transmitted infections. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a validated drug target with two approved drugs for indications other than antibacterials. Nonetheless, any new drugs targeting GAPDH in Ng and Ct must be specific inhibitors of bacterial GAPDH that do not inhibit human GAPDH, and structural information of Ng and Ct GAPDH will aid in finding such selective inhibitors. Here, we report the X-ray crystal structures of Ng and Ct GAPDH. Analysis of the structures demonstrates significant differences in amino acid residues in the active sites of human GAPDH from those of the two bacterial enzymes suggesting design of compounds to selectively inhibit Ng and Ct is possible. We also describe an efficient in vitro assay of recombinant GAPDH enzyme activity amenable to high-throughput drug screening to aid in identifying inhibitory compounds and begin to address selectivity.

Background Postpartum depression (PPD) is a common mood disorder with increasing incidence year by year. However, the dynamic changes in local neural activity remain unclear. In this study, we utilized the dynamic amplitude of low-frequency (dALFF) to investigate the abnormal temporal variability of local neural activity. Methods Twenty-four patients with PPD and nineteen healthy postpartum women controls (HCs) matched for age, education level and body mass index were examined by resting-state functional magnetic resonance imaging (rs-fMRI). A sliding-window method was used to assess the dALFF, and a k-means clustering method was used to identify dALFF states. Two-sample t-test was used to compare the differences of dALFF variability and state metrics between PPD and HCs. Pearson correlation analysis was used to analyze the relationship between dALFF variability, states metrics and clinical severity. Results (1) Patients with PPD had lower variance of dALFF than HCs in the cognitive control network, cerebellar network, and sensorimotor network. (2) Four dALFF states were identified, and the number of transitions between the four dALFF states increased in the patients compared with that in HCs. (3) Multiple dALFF states were found to be correlated with the severity of depression. The variance of dALFF in the right middle frontal gyrus was negatively correlated with the Edinburgh postnatal depression scale score. Conclusion This study provides new insights into the brain dysfunction of PPD from the perspective of dynamic local brain activity, and highlights its important role in understanding the neurophysiological mechanisms of PPD.

The prefiltered image was imported into the local higher-order singular value decomposition (HOSVD) denoising algorithm (GL-HOSVD)-optimized diffusion-weighted imaging (DWI) image, which was compared with the deviation correction nonlocal mean (NL mean) and low-level edge algorithm (LR + edge). Regarding the peak signal-to-noise ratio (PSNR), root mean square error (RMSE), sensitivity, specificity, accuracy, and consistency, the application effect of the GL-HOSVD algorithm in DWI was investigated, and its adoption effect in the examination of ischemic penumbra (IP) of early acute cerebral infarction (ACI) patients was evaluated. A total of 210 patients with ACI were selected as the research subjects, who were randomly rolled into two groups. Those who were checked by conventional DWI were set as the control group, and those who used DWI based on the GL-HOSVD denoising algorithm were set as the observation group, with 105 people in each. Positron emission tomography (PET) test results were set as the gold standard to evaluate the application value of the two examination methods. It was found that under different noise levels, the peak signal-to-noise ratio (PSNR) of the GL-HOSVD algorithm and the root mean square error (RMSE) of the FA parameter were better than those of the nonlocal means (NL-means) of deviation correction and low-rank edge algorithm (LR + edge). The sensitivity, specificity, accuracy, and consistency (8.76%, 81.25%, 87.62%, and 0.52) of the observation group were higher than those of the control group (57.78%, 53.33%, 57.14%, and 0.35) ( P < 0.05 ). Moreover, the apparent diffusion coefficient (ADC) of the DWI images of the observation group was basically consistent with that of the PET images, while the control group had a poor display effect and low definition. In summary, under different noise levels, the GL-HOSVD algorithm had a good denoising effect and greatly reduced fringe artifacts. DWI after denoising had high sensitivity, specificity, accuracy, and consistency in the detection of IP, which was worthy of clinical application and promotion.

Dissolved organic matter (DOM) plays an important role in promoting or suppressing methylmercury (MeHg) production in wetlands. However, the effects of DOM spectral characteristics on MeHg levels remain poorly understood in boreal peatlands in Northeast China, where is undergoing remarkable climate warming. In the present work, soil samples were collected from 22 peatlands in the Greater Khingan Mountains (GKM) to test the hypothesis that DOM spectral properties control MeHg levels. DOM was characterized by UV-Vis absorption and fluorescence spectroscopy; the three-dimensional fluorescence excitation-emission matrix (EEM) was used to unveil the origin of DOM. The average total mercury (THg) and MeHg contents were 112.76 µg/kg and 12.43 µg/kg across all peatlands, respectively. There was a significantly positive correlation between MeHg and the longitude spanning the range from 120 to 123°E (p 0.05). Proportions of MeHg to THg (%MeHg), 12.3% on average, were positively correlated with DOM humification degree at p 0.05 level. Protein-like components of DOM (P-like) were negatively related to %MeHg. DOM had positive effects on THg, and P-like components, HIX and BIX can negatively affect THg as well as MeHg. Our findings demonstrate that the spectral characteristics of DOM in soil are crucial to the content of methyl mercury in the GKM soil.

Postpartum depression (PPD) is a common mood disorder with increasing incidence year by year. However, the dynamic changes in local neural activity of patients with PPD remain unclear. In this study, we utilized the dynamic amplitude of low-frequency fluctuation (dALFF) method to investigate the abnormal temporal variability of local neural activity and its potential correlation with clinical severity in PPD.Twenty-four patients with PPD and nineteen healthy primiparous mothers controls (HCs) matched for age, education level and body mass index were examined by resting-state functional magnetic resonance imaging (rs-fMRI). A sliding-window method was used to assess the dALFF, and a k-means clustering method was used to identify dALFF states. Two-sample t-test was used to compare the differences of dALFF variability and state metrics between PPD and HCs. Pearson correlation analysis was used to analyze the relationship between dALFF variability, states metrics and clinical severity.(1) Patients with PPD had lower variance of dALFF than HCs in the cognitive control network, cerebellar network and sensorimotor network. (2) Four dALFF states were identified, and patients with PPD spent more time on state 2 than the other three states. The number of transitions between the four dALFF states increased in the patients compared with that in HCs. (3) Multiple dALFF states were found to be correlated with the severity of depression. The variance of dALFF in the right middle frontal gyrus was negatively correlated with the Edinburgh postnatal depression scale score.This study provides new insights into the brain dysfunction of PPD from the perspective of dynamic local brain activity, highlighting the important role of dALFF variability in understanding the neurophysiological mechanisms of PPD.

Soil macroinvertebrates as ecosystem engineers play significant, but largely ignored, roles in affecting mercury (Hg) cycle by altering soil physical-chemical properties. Ant is likely expanded into boreal mires with climate warming, however, its impacts on Hg cycle remained poorly understood. We compared total Hg (THg) and methylmercury (MeHg) contents in soils from antmounds (Lasius flavus) and the nearby ambient in a boreal mire in Northeast China. The present work seeks to unravel factors that controlling MeHg levels in case of ant appearance or absence. The average THg was 179 µg/kg in the ant mound and was 106.1 µg/kg in nearby soils, respectively. The average MeHg was 10.9 µg/kg in the ant mound and was 12.9 µg/kg in nearby soils, respectively. The ratios of MeHg to THg (%MeHg) were 7.61% in ant mounds and 16.75% in nearby soils, respectively. Ant colonization caused THg enrichment and MeHg depletion, and this change was obvious in the 10-20 cm depth soil layer where ants mainly inhabited. Spectrometry characteristics of soil dissolved organic matter (DOM) exert a stronger control than microorganisms on MeHg variation in soils. A structural equation model revealed that the molecular weight of DOM inhibited MeHg irrespective of ant presence or absence, while humification conducive to MeHg significantly in ant mound soils. Microorganisms mainly affected Hg methylation by altering the molecular weight and humification of DOM. We propose that the effects of ant colonization on MeHg rested on DOM feature variations caused by microorganisms in boreal mires.

Purpose This study investigated whether thymosin (T) β4 protects against oxygen-glucose deprivation/reperfusion (OGD/R) injury in rat cortical neurons, as well as the underlying mechanisms. Methods Primary rat cortical neurons were transfected with Tβ4 overexpression plasmid; the transfection efficiency was confirmed by detecting Tβ4 expression by fluorescence quantitative PCR and Western blotting. The OGD/R model was established and apoptotic cells were quantified by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling. Structural changes in the endoplasmic reticulum were visualized by transmission electron microscopy. The expression levels of 78-kDa glucose-regulated protein (GRP) 78, C/EBP-homologous protein (CHOP), B-cell lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax) were determined by Western blotting. The effect of Tβ4 on OGD/R injury was evaluated by adding exogenous Tβ4 to neuronal cultures. Results Cortical neurons were identified by the expression of neuron-specific enolase. In OGD/R cells, the rate of apoptosis was increased and GRP78, CHOP, and Bax were upregulated whereas Bcl-2 was downregulated relative to the control group. These effects were reversed by Tβ4 overexpression. Endoplasmic reticulum (ER) stress was observed in the OGD/R group, but this was abolished in neurons overexpressing Tβ4. The protective effect of Tβ4 against OGD/R injury was also demonstrated in cells treated with exogenous Tβ4 (10 ng/mL), which blocked OGD/R-induced apoptosis by inhibiting ER stress-related and pro-apoptotic protein expression. Conclusion Tβ4 prevents OGD/R-induced ER stress-dependent apoptosis in cortical neurons, and is a potential treatment for cerebral ischemia-reperfusion injury.

Cryptosporidium is a leading cause of pediatric diarrhea worldwide. Currently there is neither a vaccine nor a consistently effective drug available for this disease. Selective 5-aminopyrazole-4-carboxamide-based bumped-kinase inhibitors (BKIs) are effective in both in vitro and in vivo models of Cryptosporidium parvum. Potential cardiotoxicity in some BKIs led to the continued exploration of the 5-aminopyrazole-4-carboxamide scaffold to find safe and effective drug candidates for Cryptosporidium. A series of newly designed BKIs were tested for efficacy against C. parvum using in vitro and in vivo (mouse infection model) assays, and safety issues. Compound 6 (BKI 1708) was found to be efficacious at 8 mg/kg dosed once daily (QD) for 5 days with no observable signs of toxicity up to 200 mg/kg dosed QD for 7 days. Compound 15 (BKI 1770) was found to be efficacious at 30 mg/kg dosed twice daily (BID) for 5 days with no observable signs of toxicity up to 300 mg/kg dosed QD for 7 days. Compounds 6 and 15 are promising pre-clinical leads for cryptosporidiosis therapy with acceptable safety parameters and efficacy in the mouse model of cryptosporidiosis.

World urbanization has been increasing at a rapid pace over the past few decades, particularly in developing countries. The urban heat island (UHI) effect, which occurs during rapid urbanization, profoundly affects human life and health. The cooling-effect (CE) of urban wetlands can effectively mitigate the impact of UHI. In this study, we estimated the intensity of UHI and quantitatively assessed the CE of urban wetlands in cities of northeast China by using split-window algorithm (SWA) to estimate land surface temperatures (LST) from Landsat-8 TIRS. We used correlation analysis to examine the relationships between characteristics of wetlands and surrounding buildings and two cooling-effect indices: normalized cooling capability index (NCCI) and normalized cooling efficiency index (NCEI). Our results have shown that the cooling-effect of rivers is much higher than that of other wetlands types and green spaces. The average NCCI of wetlands is 42.3 times higher than that of green spaces. A strong positive relationship exists between the cooling capability of urban wetlands and the area, shape and hydrologic connectivity of wetlands. Wetlands with more complex shape have better cooling-effect. The average NCCI of wetlands connected to other surface waters six times higher than that of isolated wetlands. There is a negative relationship between the cooling capability of urban wetlands and height and density of surrounding buildings. These findings are helpful for designing urban wetlands and for urban planning to minimize the potential environmental impacts of UHI.

Subgroup A of the avian leukosis virus (ALV-A) can cause severe pathological lesions and death in infected chickens, and its reported hosts have increased recently. To assess the susceptibility of adult chickens, quails, and pigeons to ALV-A, three sets of 250-day-old birds were intraperitoneally inoculated with ALV-A. Viremia and cloacal virus shedding were dynamically detected using an immunofluorescence assay (IFA), ALV-P27 antigen ELISA or RT-PCR; pathological lesions were assessed using tissue sections; ALV-A in tissues was detected by IFA; and ALV-A antibody responses were detected using antibody ELISA kits and an immune diffusion test. The results indicated that persistent viremia occurred in 80% (8/10) of infected chickens, and transient viremia occurred in 17% (2/12) of infected quails, but no viremia occurred in infected pigeons. Cloacal virus shedding occurred intermittently in 80% (8/10) of infected chickens and in 8% (1/12) of infected quails but did not occur in infected pigeons. Severe inflammatory pathological lesions occurred in the visceral tissues of most infected chickens, and mild lesions occurred in a few of the infected quails, but no pathological lesions occurred in the infected pigeons. The ALV-A virus was detected in the visceral tissues of most infected chickens but not in the infected quails and pigeons. Obviously different ALV-A antibody responses occurred in the infected chickens, quails and pigeons. It can be concluded that adult chickens, quails and pigeons have dramatically different susceptibilities to ALV-A. This is the first report on artificial infection by ALV-A in different birds.

The intestinal protozoan Cryptosporidium is a leading cause of diarrheal disease and mortality in young children. There is currently no fully effective treatment for cryptosporidiosis, which has stimulated interest in anticryptosporidial development over the last ∼10 years with numerous lead compounds identified including several tRNA synthetase inhibitors. In this study, we report the results of a dairy calf efficacy trial of the methionyl-tRNA (CpMetRS) synthetase inhibitor 2093 and the spontaneous emergence of drug resistance. Dairy calves experimentally infected with Cryptosporidium parvum initially improved with 2093 treatment, but parasite shedding resumed in two of three calves on treatment day five. Parasites shed by each recrudescent calf had different amino acid altering CpMetRS mutations, coding either an aspartate 243 to glutamate (D243E) or a threonine 246 to isoleucine (T246I) mutation. Transgenic parasites engineered to have either the D243E or T246I CpMetRS mutation using CRISPR/Cas9 grew normally but were highly 2093 resistant; the D243E and T246I mutant expressing parasites respectively had 2093 EC50S of 613- or 128-fold that of transgenic parasites with wild-type CpMetRS. In studies using recombinant enzymes, the D243E and T246I mutations shifted the 2093 IC50 by >170-fold. Structural modeling of CpMetRS based on an inhibitor-bound Trypanosoma brucei MetRS crystal structure suggested that the resistance mutations reposition nearby hydrophobic residues, interfering with compound binding while minimally impacting substrate binding. This is the first report of naturally emerging Cryptosporidium drug resistance, highlighting the need to address the potential for anticryptosporidial resistance and establish strategies to limit its occurrence.ImportanceCryptosporidium is a leading protozoan cause of diarrhea in young children with no reliable treatment. We report results of a dairy calf drug efficacy trial and the spontaneous emergence of drug resistance. Cryptosporidium parvum infected calves initially improved with drug treatment, but infection relapsed in two animals. Parasites shed by each recrudescent calf had mutations in the gene encoding the drug target that altered its amino acid sequence. Recapitulation of the drug target mutations by CRISPR/Cas9 genome editing resulted in highly drug-resistant parasites, and recombinant mutant enzymes were resistant to inhibition. This is the first report of naturally emerging Cryptosporidium drug resistance. There is a currently a great opportunity to impact public health with new drugs to treat cryptosporidiosis, and this report highlights the need to address the potential for anticryptosporidial resistance and establish strategies to limit its occurrence in order to realize their full potential.One-sentence summaryDrug-target point mutations mediating anticryptosporidial resistance spontaneously arose in the dairy calf C. parvum infection model.

Background: Early differential diagnosis of coronavirus disease 2019 (COVID-19) and Mycoplasma Pneumonia (MP) are hampered by non-specific symptoms, the lack of rapid responding laboratory measures and the presence of family aggregation. Chest computed tomography (CT) plays a significant role to detect the distribution, density and morphology of lesions caused by either COVID-19 or MP. Objectives: To compare the symptoms, laboratory parameters, and chest CT results of adults with COVID-19 and MP and to assess the use of these findings in the differential diagnosis of these diseases. Patients and Methods: The initial clinical manifestations, laboratory results, and chest CT findings of 45 adult patients with COVID-19 (COVID-19 group) and 55 adult patients with MP (MP group) were reviewed retrospectively. All of the patients were diagnosed in the public hospitals in the epidemic area from 20 January to 28 February 2020. Results: Muscle ache and fatigue were more frequently present in the COVID-19 group (P = 0.009 and 0.029, respectively). Increased procalcitonin levels were more common in the MP group (P = 0.001). The chest CT results indicated that bilateral lung involvement, ground glass opacities, “crazy-paving” patterns, and air bronchogram signs were more common in the COVID-19 group (P < 0.001 for all), respectively. However, single lobe involvement, pulmonary consolidations, lobular central nodules, generalized bronchial wall thickening with luminal stenosis, and bronchial mucus impaction were more common in the MP group (P < 0.001 for all). Receiver operating characteristic analysis of a model established using CT parameters indicated a good or excellent performance in distinguishing COVID-19 from MP. Conclusion: COVID-19 and MP have similar clinical manifestations and laboratory results in early stage. However, the chest CT findings are valuable in the differential diagnosis of these two diseases, particularly in patients from COVID-19 epidemic areas.

Increasing water discharge has resulted in rising dissolved organic matter (DOM) in draining peatlands. However, how contents and spectral characteristics of DOM changed by increasing terrestrial ants in peatland with water level decreasing, were not well revealed. In the present work, chemical and molecular composition of DOM in ant and nearby soils were characterized using UV–Visible absorption and fluorescence excitation-emission matrix (EEM) combined with parallel factor analysis (PARAFAC). Results indicated that four fluorescence components were identified, of which endogenetic fluorophores accounted for a higher proportion (79.21 ± 0.06%) of the total variability of all four. DOM from ant mound soils had lower aromaticity, humification degree, and smaller molecular size than those from control soil. The influence of microorganisms on the content and structure of DOM was crucial in the ant mound soil, whereas the effect from soil physicochemical properties was apparently more pronounced in the control soil. The study demonstrated that the endogenetic and microbial substances were closely related to the compositional variability of DOM in ant and control soils of peatlands.