Characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for immune checkpoint inhibitor-related pneumonitis.

As immune checkpoint inhibitors (ICIs) are widely used, a series of immune-related adverse events (irAEs) have been reported, including immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis). The incidence of ICI-pneumonitis is higher in reality than in clinical trials. The diagnosis is challenging, mainly based on clinical and imaging features, and requires the exclusion of other causes. The data on the biological mechanisms of ICI-pneumonitis are scarce, resulting in little knowledge of the best treatment for ICI-pneumonitis. Bronchoalveolar lavage (BAL) may be helpful to identify the biological differences or find predictive biomarkers, and may in turn help to develop phenotype-specific targeted drugs to treat ICI-pneumonitis. Herein, we outline the characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for ICI-pneumonitis. Through careful sorting and literature review, we find crosstalk between pathogenic Th17/Th1 cells (i.e., Th17.1) and pro-inflammatory monocytes, and activation of Th17(/Th1)/IL-17A (/IFN-γ) pathways may play a key role in the pathogenesis of ICI-pneumonitis. Disruption of the interaction between pathogenic Th17/Th1 cells and pro-inflammatory monocytes (such as, anti-IL-23) may be a potential treatment for ICI-pneumonitis. We first describe the possible pathophysiological mechanisms of ICI-pneumonitis, hoping to contribute to the optimization of diagnosis and treatment, as well as provide readers with research inspiration.

[Responses of intraspecific and interspecific variations of plant functional traits to grazing in degraded grassland]. / é€€åŒ–è‰åœ°ç‰©ç§ç§å† å’Œç§é—´åŠŸèƒ½æ€§çŠ¶å˜å¼‚å¯¹æ”¾ç‰§çš„å“åº”.

Understanding the responses of functional trait variation for grassland plants to grazing disturbance is highly helpful to clarify the community assembly mechanism, functional diversity maintenance, plant adaptation and their strategies. We investigated plant functional traits (plant height, root length, leaf area, root area, leaf dry matter content, shoot dry matter content, root dry matter content, specific leaf area, specific root length and root/ shoot ratio) and the responses of their variation characteristics to grazing disturbance in enclosure and grazing grasslands in Horqin Sandy Land. The results showed that the interspecific variation of functional trait was obviously higher than the intraspecific variation in degraded grassland. The relative contribution of interspecific variation to the overall trait variation ranged from 70.2% to 95.1%, while that of intraspecific variation only contributed 4.9% to 29.8%. However, that did not imply the intraspecific variation could be ignored in the community assembly. The interspecific variation in grazing grassland was lower than that in enclosed grassland, while the intraspecific variation increased but the interspecific variation decreased in grazing grassland. Grazing resulted in the decrease of leaf area and leaf dry matter content but the increase of specific root length for pastoral-resistant grasses. However, pastoral-tolerant forbs would improve their dominance in the community by decreasing specific root length and increa-sing leaf area and leaf dry matter content. The traits sensitive to grazing were leaf area, leaf dry matter content, specific root length, and specific leaf area. Leaf traits and root traits were significantly positively correlated within and with each other. Grazing would enhance the synergy of root traits while reduce the synergy of leaf traits. That meant grazing could change the trade-off strategy of functional traits in individual and population levels, and thus affect vegetation structure and function in community level.

STAT3-mediated upregulation of LINC00520 contributed to temozolomide chemoresistance in glioblastoma by interacting with RNA-binding protein LIN28B.

A considerable number of glioblastoma (GBM) patients developed drug resistance to Temozolomide (TMZ) during chemotherapy, resulting in therapeutic failure and tumor recurrence. However, the exact mechanism of TMZ chemoresistance in GBM is still poorly clarified. As a novel identified lncRNA, LINC00520 was located on chromosome 14 and overexpressed in multiple human cancers. This study was designed and conducted to investigate the role and underlying mechanism of LINC00520 in GBM chemoresistance to TMZ. The qRT-PCR assay demonstrated that LINC00520 was significantly overexpressed in TMZ-sensitive and/or TMZ-resistant GBM cells (P < 0.001). The silencing of LINC00520 markedly reduced the cell viability, suppressed colony formation, induced cell apoptosis and G1/S phase arrest in TMZ-resistant cells (P < 0.001). In contrast, overexpression of LINC00520 conferred TMZ-resistant phenotype of GBM cells in vitro (P < 0.001). The orthotopic xenograft model was established and the results indicated that the volume of tumor xenografts in vivo was markedly inhibited by TMZ treatment after the silencing of LINC00520 (P < 0.001). Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay revealed a strong affinity of transcription factor STAT3 to the promoter regions of LINC00520, suggesting that STAT3 mediated the aberrant expression of LINC00520 in GBM. Further experiments demonstrated that LINC00520 could interact with RNA-binding protein LIN28B to inhibit autophagy and reduce DNA damage, thereby contributing to TMZ chemoresistance in GBM. These findings suggested that STAT3/LINC00520/LIN28B axis might be a promising target to improve TMZ chemoresistance of GBM.

Radical Tandem Bicyclization Triggered by the α-Position of α,ß-Unsaturated Ketones Bearing Nonterminal 1,6-Enynes: Synthesis of the 5H-Benzo[a]fluoren-5-one Skeleton.

A novel method for the synthesis of 5H-benzo[a]fluoren-5-one from inactive nonterminal 1,6-alkynes through a free radical tandem bicyclization process has been established. This process achieved a continuous cyclization triggered rarely by the α-position of α,ß-unsaturated ketones. The reaction constructed three C-C bonds in one step with the readily accessible substrates and excellent substrate compatibility.

Endothelial cells in colorectal cancer.

The dependence of tumor growth on neovascularization has become an important aspect of cancer biology. Tumor angiogenesis is one of the key mechanisms of tumorigenesis, growth and metastasis. The key events involved in this process are endothelial cell proliferation, migration, and vascular formation. Recent studies have revealed the importance of tumor-associated endothelial cells (TECs) in the development and progression of colorectal cancer (CRC), including epithelial proliferation, stem cell maintenance, angiogenesis, and immune remodeling. Decades of research have identified that the molecular basis of tumor angiogenesis includes vascular endothelial growth factors (VEGFs) and their receptor family, which are the main targets of antiangiogenesis therapy. VEGFs and their receptors play key roles in the pathology of angiogenesis, and their overexpression indicates poor prognosis in CRC. This article reviews the characteristics of the tumor vasculature and the role of TECs in different stages of CRC and immune remodeling. We also discuss the biological effects of VEGFs and their receptor family as angiogenesis regulators and emphasize the clinical implications of TECs in clinical treatment.

Inhibitory Effect of Volatiles Emitted From Alcaligenes faecalis N1-4 on Aspergillus flavus and Aflatoxins in Storage.

Controlling aflatoxigenic Aspergillus flavus and aflatoxins (AFs) in grains and food during storage is a great challenge to humans worldwide. Alcaligenes faecalis N1-4 isolated from tea rhizosphere soil can produce abundant antifungal volatiles, and greatly inhibited the growth of A. flavus in un-contacted face-to-face dual culture testing. Gas chromatography tandem mass spectrometry revealed that dimethyl disulfide (DMDS) and methyl isovalerate (MI) were two abundant compounds in the volatile profiles of N1-4. DMDS was found to have the highest relative abundance (69.90%, to the total peak area) in N1-4, which prevented the conidia germination and mycelial growth of A. flavus at 50 and 100 µL/L, respectively. The effective concentration for MI against A. flavus is 200 µL/L. Additionally, Real-time quantitative PCR analysis proved that the expression of 12 important genes in aflatoxin biosynthesis pathway was reduced by these volatiles, and eight genes were down regulated by 4.39 to 32.25-folds compared to control treatment with significant differences. And the A. flavus infection and AFs contamination in groundnut, maize, rice and soybean of high water activity were completely inhibited by volatiles from N1-4 in storage. Scanning electron microscope further proved that A. flavus conidia inoculated on peanuts surface were severely damaged by volatiles from N1-4. Furthermore, strain N1-4 showed broad and antifungal activity to other six important plant pathogens including Fusarium graminearum, F. equiseti, Alternaria alternata, Botrytis cinerea, Aspergillus niger, and Colletotrichum graminicola. Thus, A. faecalis N1-4 and volatile DMDS and MI may have potential to be used as biocontrol agents to control A. flavus and AFs during storage.

Effect of Knockout Serum Replacement During Postwarming Recovery Culture on the Development and Quality of Vitrified Parthenogenetic Porcine Blastocysts.

The postwarming recovery culture, as one of the steps in cryopreservation process, is directly correlated with the survival and quality of embryos. Generally, recovery medium includes undefined serum or serum components that may cause the instability of results and other problems. The objective of this study was to evaluate the effect of knockout serum replacement (KSR) as a substitute for serum during recovery culture on the development and quality of vitrified parthenogenetic porcine blastocysts. Fetal bovine serum (FBS) was used as a positive control. The expanded blastocysts on day 5 were vitrified by the Cryotop method, and recovered with 10% (v/v) KSR or 10% (v/v) FBS for 48 hours after warming. Survival and hatching rates of vitrified blastocysts were significantly increased by KSR or FBS supplementation. The vitrified blastocysts recovered in KSR or FBS exhibited significantly decreased percentages of membrane damage and apoptosis, and increased total cells. Addition of KSR or FBS during recovery culture significantly reduced reactive oxygen species levels, and improved mitochondrial activity and adenosine triphosphates content in the vitrified blastocysts. Vitrification did not affect the gene expression of PCNA, CDX2, and CPT1, but significantly increased mRNA levels of POU5F1 and uPA. KSR added to the recovery medium significantly upregulated mRNA levels of PCNA and CPT1, and downregulated POU5F1 mRNA levels. The expression levels of PCNA, CDX2, CPT1, and uPA in vitrified blastocysts were significantly upregulated by addition of FBS to recovery medium. Moreover, the BAX: BCL2L1 ratio was similar between fresh and vitrified blastocysts, and KSR or FBS supplementation had no effect on the value. In conclusion, our data showed that KSR supplementation during recovery culture can improve the development and quality of vitrified parthenogenetic porcine blastocysts. These findings provide a useful reference that KSR could be used to replace FBS as a defined serum supplement for recovery culture of vitrified blastocysts.

Detection of goat meat adulteration by real-time PCR based on a reference primer.

Economically motivated adulteration (EMA) has become one of the most concerned food safety issues. However, existing mainstream PCR methods could neither achieve qualitative detection purposes, nor detect all possible meat species involved in adulteration. When meat has been adulterated with unidentified species but the result indicates no adulteration, it is a false negative; when meat has not been adulterated deliberately but has somehow been polluted during its processing or packaging, a false positive emerges. A novel reference primer based real-time PCR approach was developed in this study for quantitative determination of goat meat adulterated with pork. By calculating the ratio of Ct (specificity/reference), a good linear correlation (R2 = 0.9929) could be deduced for the goat meat content. We also successfully amplified simulated samples and the results showed high accuracy with an average recovery of 108.74% for the samples.

Altered microstructure of brain white matter in females with anorexia nervosa: a diffusion tensor imaging study.

OBJECTIVE: Structural studies have reported anorexia nervosa (AN) patients with abnormal gray matter in several brain regions and dysfunction in some connected neural circuits. However, the role of white matter (WM) in AN patients has rarely been investigated. The present study aimed to assess alterations in WM microstructure of the entire brain in females with AN using a voxel-based method on diffusion tensor imaging (DTI) data. MATERIALS AND METHODS: The study enrolled 8 female patients with AN and 14 age-matched females as controls (CW). The DTI data was collected from each subject to calculate the fractional anisotropy (FA) maps of the whole brain by the DTI-Studio software. Subsequently, a 2-sample t-test (P<0.05, corrected) was performed to detect the difference in FA maps of AN and CW group, and a Pearson's correlation analyzed the relationship between mean FA value of brain regions and body mass index (BMI). RESULTS: Compared with CW, AN patients revealed a significant decrease in FA maps in the left superior frontal gyrus, medial frontal gyrus, anterior cingulate cortex, middle frontal gyrus, inferior frontal gyrus, thalamus, and bilateral insula. Moreover, significantly positive correlations were established between the mean FA value of the left inferior frontal gyrus, insula as well as thalamus and BMI in AN patients. CONCLUSIONS: Our findings supported the presence of WM abnormality in patients with AN. The significant differences of FA maps, in patients with AN, were associated with their aberrant BMI. The results further improved our understanding of the pathophysiological mechanisms underlying AN.

Cryotop vitrification of porcine parthenogenetic embryos at the early developmental stages.

The objective of this study was to evaluate the effects of early developmental stages at which Cryotop vitrification is performed on subsequent survival and in vitro development of porcine parthenogenetic activation embryos. The zygotes that were cultured for 4, 8, and 18 hours post electric activation (h.p.a.) and two- and four-cell embryos were vitrified, warmed, and continuously cultured for the remaining period. The zygotes vitrified at 4, 8, and 18 h.p.a. showed similar percentages of survival, cleavage, and blastocyst formation. No difference in viability was observed after vitrification of two- and four-cell embryos, but the embryos vitrified at the two-cell stage exhibited significantly higher blastocyst formation rate than those vitrified at the four-cell stage. However, vitrifying embryos resulted in significantly decreased survival and development rates, regardless of the developmental stage of the embryos. In addition, the final developmental stage, diameter, apoptotic index, and the number of inner cell mass, trophectoderm, and total cells of blastocysts derived from embryos vitrified at any stage of the early culture were similar to those of fresh blastocysts. In conclusion, our data indicate that the early-stage porcine parthenogenetically activated embryos including the zygote, two cells, and four cells have a high ability to survive cryopreservation; these viable embryos after vitrification can produce respectable development rates and good-quality blastocysts.

A new class of dendritic metallogels with multiple stimuli-responsiveness and as templates for the in situ synthesis of silver nanoparticles.

A new class of poly(aryl ether) dendritic ligands containing a pyridine functionality at the focal point and the corresponding Ag(I) complexes through metal-ligand coordination were designed, synthesized, and fully characterized. Compared with the dendritic ligands, the corresponding dendritic complexes exhibited much better gelation ability for various organic solvents at very low critical gelation concentrations. The gel-sol phase transition temperatures and morphologies could be finely tuned by binding silver ion to the ligand. A preliminary study revealed that multiple noncovalent interactions, such as Ag(I) -pyridine coordination, solvophobic interaction, and π-π stacking, synergistically enable the formation of stable metallogels. Interestingly, these metallogels could intelligently respond to multiple external stimuli including temperature, chemicals, and shear stress, leading to gel-sol phase transitions. In addition, these dendritic metallogels were successfully applied as templates for the in situ formation and stabilization of silver nanoparticles without the use of any chemical reducing/stabilizing agents.

[Algae removal of high algae raw water by coagulation enhanced by ozonation].

Apparent molecular weight distribution (AMWD) and resin fractionation were used to characterize organic matters of the raw water. Removal of algae, change and removal of dissolved organic carbon (DOC), disinfection by products (DBPs) control during the preozonation enhanced coagulation treatments in the jar-scale and pilot-scale experiment were studied. Algae activity (AA) was measured and used to elucidate the mechanisms of algae removal by above treatments. Results show that algae removal can be improved distinctively by proper preozonation, as the ozone dose 1.0 mg x L(-1), for instance. Algae removal could be increased from 55%-85% by traditional coagulation to 95% by enhanced coagulation after preozonation; and the best removal achieved 99.3% with ozone 1.0 mg x L(-1) and PACl 3.0 mg x L(-1); the residual THMFP (Trihalomethanes formation potential) was lowered from 117 microg x L(-1) by traditional coagulation to 46 microg x L(-1). But higher dose of ozone (as > or = 2.0 mg x L(-1)) impairs organic matter removal, although it decreases algae activity further. Significant differences were found in algae removal by AA detection between ozonation and traditional coagulation. Traditional coagulation had little effect on AA no matter the different PAC1 doses; while AA decreased clearly after ozonation. AA was lowered below 12 under 0.5-2.0 mg x L(-1) ozonation; and it kept decreasing with increase of ozone dosage. During the following coagulation, coagulant or some of its hydrolysised components enhanced the AA decrease by ozonation. Compared to the method of normal microscopy counting, AA test expresses the influence of algae living state by water treatment processes more clearly; which would provide treatment process designer with more distinct information about algae removal mechanisms and how to arrange the treatment processes to improve algae removal.

[Analysis of relation between the usage of corticosteroid in treatment and arthralgia as a sequela of SARS patients].

OBJECTIVE: To analyze relation between the use of corticosteroids in the treatment for severe acute respiratory syndrome (SARS) patients and arthralgia as a sequela. METHODS: Clinical date of 30 SARS patients without other diseases in whom corticosteroid was used were reviewed including total dosage, duration of use, the highest dosage and its duration, and speed of reduction in dosage. The information about arthralgia was investigated one month after discharge of SARS patients from the hospital. RESULTS: The average total dosage of methylprednisolone was (4 244.16+/-2 292.30) mg, and the duration of use of the treatment was (25.36+/-5.88) days (ranging from 12 to 35 days). The maximum dosage was (321.33+/-174.03) mg/d, and the duration of its use was (7.73+/-4.08) days. The speed of reduction of dosage of corticosteroids was (21.33+/-10.18) mg/d. There were 26 of 30 patients (86.67 percent) experienced arthralgia symptom during convalescence. In 3.6 percent of patients arthralgia occurred within one month after SARS, 53.85 percent of the patients experienced low-grade arthralgia. By unifactor analysis, the total dosage and its duration of use, the highest dosage and its duration, speed of reduction of dosage of corticosteroids were correlated with the degree of arthralgia, respectively. The duration of arthralgia was correlated with the total dosage, the duration of high dosage, and high dosage. Age was not correlated with either the degree or the persisting time of arthralgia. The degree of arthralgia was only correlated with the total dosage, and the duration of arthralgia was correlated with administration time of glucocorticosteroids by multifactor analysis. CONCLUSION: There is a dosage- effect relation between the degree of arthralgia and the total dosage of corticosteroid, and a time-effect relation between the duration of arthralgia and length of the use of corticosteroids.