A positive prognosis of triple-negative breast cancer can be considered as one of the major challenges in clinical studies; accordingly, scientific research has the mission to find out novel chemotherapeutics to make it curable. In recent times, a good potential of dietary bioactive natural substances, called nutraceuticals, in suppressing cancer cell proliferation via gene expression regulation has been discovered: this effect and the lack of toxicity make nutraceuticals potentially effective agents against cancers. Monacolin K from red rice, a FDA-approved and well-tolerated compound generally employed to treat hypercholesterolemia, has been proved to have anti-proliferative and apoptotic effects in a wide panel of triple-negative breast cancers. Thus, an unbiased analysis of monacolin K-induced MDA-MB-231 cellular pathway alterations has been carried out by quantitative proteomics exploiting isobaric tags. Despite the positive modulation of some proteins already reported in the literature, an increased concentration of the tissue-type plasminogen activator PLAT has interestingly been found. This is a marker of good prognosis in mammary cancer, suggesting the anti-metastatic properties of this molecule as strongly associated with the alterations in the cytoskeleton organization and the consequent modulation of adhesion, motility and proteolysis. In accordance, some of the found monacolin K-induced phosphoproteome alterations have a tight connection to cell migration mechanisms. In this setting, the over-phosphorylation of Lamin A and of melanophilin induced by monacolin K has been very attractive. Moreover, monacolin K exerts its effect on the over-expression of the tissue inhibitor metalloproteinase-2 (TIMP-2), an endogenous metalloproteinase inhibitor. This protein modulates growth, migration and invasion of tumor cells and inhibits tumor angiogenesis.

Background: Right ventricular (RV) failure is a common complication in moderate-to-severe acute respiratory distress syndrome (ARDS). RV failure is exacerbated by hypercapnic acidosis and overdistension induced by mechanical ventilation. Veno-venous extracorporeal CO₂ removal (ECCO₂R) might allow ultraprotective ventilation with lower tidal volume (V_T) and plateau pressure (P_plat). This study investigated whether ECCO₂R therapy could affect RV function.

Methods: This was a quasi-experimental prospective observational pilot study performed in a French medical ICU. Patients with moderate-to-severe ARDS with PaO₂/FiO₂ ratio between 80 and 150 mmHg were enrolled. An ultraprotective ventilation strategy was used with V_T at 4 mL/kg of predicted body weight during the 24 h following the start of a low-flow ECCO₂R device. RV function was assessed by transthoracic echocardiography (TTE) during the study protocol.

Results: The efficacy of ECCO₂R facilitated an ultraprotective strategy in all 18 patients included. We observed a significant improvement in RV systolic function parameters. Tricuspid annular plane systolic excursion (TAPSE) increased significantly under ultraprotective ventilation compared to baseline (from 22.8 to 25.4 mm; p < 0.05). Systolic excursion velocity (S' wave) also increased after the 1-day protocol (from 13.8 m/s to 15.1 m/s; p < 0.05). A significant improvement in the aortic velocity time integral (VTIAo) under ultraprotective ventilation settings was observed (p = 0.05). There were no significant differences in the values of systolic pulmonary arterial pressure (sPAP) and RV preload.

Conclusion: Low-flow ECCO₂R facilitates an ultraprotective ventilation strategy thatwould improve RV function in moderate-to-severe ARDS patients. Improvement in RV contractility appears to be mainly due to a decrease in intrathoracic pressure allowed by ultraprotective ventilation, rather than a reduction of PaCO₂.

Keywords: Acute respiratory distress syndrome; Critical care echocardiography; Extracorporeal CO2 removal; Protective mechanical ventilation; Right ventricular dysfunction.

OBJECTIVE

To explore the influence of different positive end-expiratory pressure (PEEP) levels on cerebral blood flow (CBF) and cerebrovascular autoregulation in patients with acute respiratory distress syndrome(ARDS).

METHODS

A prospective study was conducted. Moderate or severe ARDS patients admitted to Department of Critical Care Medicine of Jiangxi Provincial People's Hospital from January 1st, 2013 to October 1st, 2013 were enrolled. The changes in hemodynamics, respiratory mechanics and gas exchange under different levels of PEEP were observed. CBF velocity of middle cerebral artery (MCA) was measured using transcranial Doppler (TCD), and breath-holding index (BHI) was also calculated.

RESULTS

35 patients with ARDS were included. The oxygenation index (OI), peak inspiratory pressure (PIP), plat pressure (Pplat) and central venous pressure (CVP) were markedly elevated (OI: 324.7±117.2 mmHg vs. 173.4±95.8 mmHg, t=5.913, P=0.000; PIP: 34.7±9.1 cmH2O vs. 26.1±7.9 cmH2O,t=4.222, P=0.000; Pplat: 30.5±8.4 cmH2O vs. 22.2±7.1 cmH2O, t=4.465, P=0.000; CVP: 12.1±3.5 mmHg vs. 8.8±2.2 mmHg, t=4.723, P=0.000) when PEEP was increased from (6.4±1.0) cmH2O to (14.5±2.0) cmH2O (1 cmH2O=0.098 kPa). But no significant difference in the heart rate (85.5±19.1 beats/min vs. 82.7±17.3 beats/min, t=0.643, P=0.523), mean arterial pressure (73.5±12.4 mmHg vs. 76.4±15.1 mmHg, t=0.878, P=0.383) and CBF velocity of MCA [peak systolic flow velocity (Vmax): 91.26±17.57 cm/s vs. 96.64±18.71 cm/s, t=1.240, P=0.219; diastolic flow velocity (Vmin): 31.54±7.71 cm/s vs. 33.87±8.53 cm/s, t=1.199, P=0.235; mean velocity (Vmean): 51.19±12.05 cm/s vs. 54.27±13.36 cm/s, t=1.013, P=0.315] was found. 18 patients with BHI<0.1 at baseline demonstrated that cerebral vasomotor reactivity was poor. BHI was slightly decreased with increase in PEEP (0.78±0.16 vs. 0.86±0.19, t=1.905, P=0.061).

CONCLUSIONS

Some of moderate or severe ARDS patients without central nervous system disease have independent of preexisting cerebral autoregulation impairment. However, independent of preexisting cerebral autoregulation may not further be impaired when a high PEEP was chosen.

By taking advantage of unique mechanism of aggregation-induced emission (AIE) phenomena, AIE Luminogen (AIEgen) have been provided a solution to overcome the limitations of conventional fluorophores bearing the feature of aggregation-caused quenching (ACQ) phenomena. Especially, AIEgens paved the way to develop fluorogenic probes ideal for fluores-cent imaging in live cell condition. Despite high demand for discovery of new AIEgens, it is still challenging to find a versatile molecular platform to generate diverse AIEgens. Herein, we report a new colorful molecular framework Kaleidolizine (KIz) as a molecular platform for AIEgen generation. The KIz system allows systematic tuning of emission wavelength from 455 nm to 564 nm via perturbation of the electron density of substituents on the indolizine core. Increase the water fraction of KIz solution in THF/water mixture induces fluorescence intensity increase up to a 120-fold. Crystal structure analysis, com-putational calculations, and solvatochromism studies suggest that a synergistic effect between the intramolecular charge transfer and restriction of intramolecular rotation acts as the AIE mechanism in the KIz system. Conjugation of the tri-phenylphosphonium moiety to KIz allows successful development of TPP-KIz for real-time bioimaging of innate mito-chondria in live cells, thereby revealing the potential of KIz as a versatile molecular platform to generate fluorogenic probes based on AIE phenomena. We do believe KIz system could serve as new reliable and generally applicable molecular plat-form to develop various AIEgens having desired photophysical properties along with excellent signal to noise ratio and with experimental convenience especially for fluorogenic live cell imaging.

Despite considerable efforts in prevention and therapy, breast cancer remains a major public health concern worldwide. Numerous studies using breast cancer cell lines have shown the antiproliferative and pro-apoptotic effects of docosahexaenoic acid (DHA). Some studies have also demonstrated the inhibitory effect of DHA on the migration and invasion of breast cancer cells, making DHA a potential anti-metastatic agent. Thus, DHA has shown its potential as a chemotherapeutic adjuvant. However, the molecular mechanisms triggering DHA effects remain unclear, and the aim of this study was to provide a transcriptomic basis for further cellular and molecular investigations. Therefore, MDA-MB-231 cells were treated with 100 µM DHA for 1`2 h or 24 h before RNA-seq analysis. The results show the great impact of DHA-treatment on the transcriptome, especially after 24 h of treatment. The impact of DHA is particularly visible in genes involved in the cholesterol biosynthesis pathway that is strongly downregulated, and the endoplasmic reticulum (ER)-stress response that is, conversely, upregulated. This ER-stress and unfolded protein response could explain the pro-apoptotic effect of DHA. The expression of genes related to migration and invasion (especially SERPINE1, PLAT, and MMP11) is also impacted by DHA. In conclusion, this transcriptomic analysis supports the antiproliferative, pro-apoptotic and anti-invasive effects of DHA, and provides new avenues for understanding its molecular mechanisms.

Keywords: ER-stress; apoptosis; breast cancer; cholesterol metabolism; docosahexaenoic acid; invasion; lipid metabolism; migration; unfolded protein response.

Though important for a variety of medical procedures, general anesthesia is not a problem free. Some anesthetics have been suggested to affect a number of signals, which are associated with memory consolidation and cognition. In the present study, we attempted to investigate the molecular mechanism of anesthesia-regulated processes. We found that under hypothermic condition, anesthetic of isoflurane enhances various signals expression in hippocampus, including Hspd1, Actb, Mgst1, THBS4, Syp, C1QC, Serpine, Plat, and Ngf, which were related to cellular stress, neural plasticity responses, and hippocampal injury. Importantly, isoflurane and propofol anesthesia reduced fibroblast growth factor (FGF2) and activity-regulated cytoskeleton-associated protein (Arc) expressions, enhanced glial fibrillary acidic protein (GFAP), Iba1 and phosphorylated-Eukaryotic elongation factor 2 (eEF2) levels as well as down-regulated mitogen-activated protein kinases (MAPKs) family members, including p38, ERK1/2 and JNK, in the hippocampus of animals. Moreover, the in vivo cold water swimming (CWS) experiment and in vitro hypothermic incubation of cells further confirmed our hypothesis that hypothermia is tightly linked to the reduction of FGF2 and Arc, augment of GFAP, Iba1 and p-eEF2, and the decreasing of MAPKs. Generally, our study provided new insights into the modulation of various signals by anesthesia-triggered hypothermia.

Sound detection happens in the inner ear via the mechanical deflection of the hair bundle of cochlear hair cells. The hair bundle is an apical specialization consisting of actin-filled membrane protrusions (called stereocilia) connected by tip links (TLs) that transfer the deflection force to gate the mechanotransduction channels. Here, we identified the hearing loss-associated Loxhd1/DFNB77 gene as being required for the mechanotransduction process. LOXHD1 consists of 15 polycystin lipoxygenase alpha-toxin (PLAT) repeats, which in other proteins can bind lipids and proteins. LOXHD1 was distributed along the length of the stereocilia. Two LOXHD1 mouse models with mutations in the 10^th PLAT repeat exhibited mechanotransduction defects (in both sexes). While mechanotransduction currents in mutant inner hair cells (IHCs) were similar to wild-type (WT) levels in the first postnatal week, they were severely affected by postnatal day 11. The onset of the MET phenotype was consistent with the temporal progression of postnatal LOXHD1 expression/localization in the hair bundle. The mechanotransduction defect observed in Loxhd1-mutant IHCs was not accompanied by a morphological defect of the hair bundle or a reduction in TL number. Using immunolocalization, we found that two proteins of the upper and lower TL protein complexes (Harmonin and LHFPL5) were maintained in the mutants, suggesting that the mechanotransduction machinery was present but not activatable. This work identified a novel LOXHD1-dependent step in hair bundle development that is critical for mechanotransduction in mature hair cells as well as for normal hearing function in mice and humans.SIGNIFICANCE STATEMENT:Hair cells detect sound-induced forces via the hair bundle, which consists of membrane protrusions connected by tip links. The mechanotransduction machinery forms protein complexes at the tip-link ends. The current study showed that LOXHD1, a multi-repeat protein responsible for hearing loss in humans and mice when mutated, was required for hair-cell mechanotransduction, but only after the first postnatal week. Using immunochemistry, we demonstrated that this defect was not caused by the mislocalization of the tip-link complex proteins Harmonin or LHFPL5, suggesting that the mechanotransduction protein complexes were maintained. This work identified a new step in hair bundle development, which is critical for both hair-cell mechanotransduction and hearing.

Nanometric chiral objects such as twisted or helical nanoribbons represent a new class of objects having important potential in a large panel of applications, taking advantage for example of electromechanical or optical chirality, local chiral environment for catalysis, and chiral recognition. Supramolecular chemistry has played a central role in the production of such structures either through chiral macromole-cules/foldamers, or the self-assembly of chiral molecules, the latter can also be used as templates for the sol-gel transcription to silica materials, offering them polymorphisms with further structural stability. Here, we report a totally different and dynamic approach to produce helical mesostructures. This study focuses on helical nanopores that are spontaneously formed in the platinum-assisted chemical etching of silicon by dynamic self-organization under a non-equilibrium state. The symmetry breaking of a helical nanopore formation is achieved by the spatial symmetry breaking of a spatiotemporal pattern at the nanoscale and without incorporation of chiral molecules. Rotational motion of the plat-inum nanocatalyst which is regarded as a spatiotemporal pattern at the etching frontier (the platinum/silicon interface) induces precession movement of the nanocatalyst, and the movement of the catalyst during the etching forms helical nanopores in the silicon. We consider that this study is an important milestone to understand the close relation between spatiotemporal pattern formation and the dynamic emergence of symmetry breaking in chemical reactions.

Breeding bulls infected with Besnoitia besnoiti may develop sterility during either acute or chronic infection. The aim of this study was to investigate the molecular pathogenesis of B. besnoiti infection with prognosis value in bull sterility. Accordingly, five well-characterized groups of naturally and experimentally infected males were selected for the study based on clinical signs and lesions compatible with B. besnoiti infection, serological results and parasite detection. A broad panel of molecular markers representative of endothelial activation and fibrosis was investigated and complemented with a histopathological approach that included conventional histology and immunohistochemistry. The results indicated the predominance of an intense inflammatory infiltrate composed mainly of resident and recruited circulating macrophages and to a lesser extent of CD3+ cells in infected bulls. In addition, a few biomarkers were associated with acute, chronic or subclinical bovine besnoitiosis. The testicular parenchyma showed a higher number of differentially expressed genes in natural infections (acute and chronic infections) versus scrotal skin in experimental infections (subclinical infection). In subclinical infections, most genes were downregulated except for the CCL24 and CXCL2 genes, which were upregulated. In contrast, the acute phase was mainly characterized by the upregulation of IL-1α, IL-6 and TIMP1, whereas in the chronic phase, the upregulation of ICAM and the downregulation of MMP13, PLAT and IL-1α were the most relevant findings. Macrophages could be responsible for the highest level of gene regulation in the testicular parenchyma of severely affected and sterile bulls, and all these genes could be prognostic markers of sterility.

Keywords: Besnoitia besnoiti; Bovine besnoitiosis; Breeding bull; Molecular markers; Testis.

Using technology to track endemic areas of communicable diseases is possible nowadays. Effectual use of such facilities, especially in developing countries, will increase earlier detection of cases as well as aid in the formulation of effective prevention strategies.

A retrospective data analysis was carried out by collecting the details of patients presented with positive dengue serology, during the outbreak season in the second half of 2012, at Kovai Medical Center and Hospital, Coimbatore, India. Clinical variables were analysed statistically using SPSS 20 and geographical mapping of the cases was carried out using EPI INFO 7 software.

1004 dengue positive cases were identified during the study period. Geographical mapping of the case clusters showed specific areas in the city as well as neighbouring districts, which were an indirect evidence of the causative mosquito's endemic breeding places. Overall mortality noted in this group was 1.3% and mortality in cases with severe thrombocytopenia was 4 in 1000 cases. Severe thrombocytopenia (Plat≤ 10,000) on admission increased odds ratio for mortality i.e. around 10 times higher than the rest of the cohorts.

Identification of endemic mosquito breeding places and implementation of proper preventive measures is always a crucial step in the prevention of further outbreaks. Effective registry using softwares by tertiary care hospitals will be obligatory to track the location of the cases as these hospitals are the nodal point of care for most of the cases in developing countries.

The cause of Sertoli cell-only syndrome (SCOS), a condition in which only Sertoli cells line the seminiferous tubules in the testis, is unknown. Three microarray data sets were downloaded from public databases and were used to compare SCOS and control group. A total of 291 genes differentially expressed (Log₂ |FC| ≥ 1 and adjusted p value < 0.05) in SCOS patients. Further 238 genes were significantly downregulated, and 53 genes were significantly upregulated. To identify the hub genes in the differentially expressed genes, we constructed a protein-protein interaction network, and CCNB1, CCNA2, AURKA, KIF11, CCNB2, CDC6, PRC1, NCAPG, KIF2C and PLK4 were screened from the network for the downregulated genes. Since the upregulated genes could not form a network, we concentrated on the genes with a higher fold change, and CPA3, NFIB, LONRF2, LYVE1, ATP8B4, IGF1, ITPR1 and PLAT were identified as the top 50% fold change genes in any of the three microarray data sets. Among downregulated hub genes, CDC6, CCNA2, CCNB1 and CCNB2 were involved in APC/C-mediated cell cycle progression. Among key upregulated genes, IGF1 was involved in the PI3K/AKT pathway, while the other genes have not been reported in Sertoli or Leydig cells. In conclusion, SCOS appears to be caused by disordered APC/C-mediated cell cycle progression and PI3K/AKT signalling.

Eicosanoids are inflammatory signaling lipids that are biosynthesized in response to cellular injury or threat. They were originally thought to be pro-inflammatory molecules, but members of at least one subclass, the lipoxins, are able to resolve inflammation. One step in lipoxin synthesis is the oxygenation of arachidonic acid by 15-lipoxygenase (15-LOX). 15-LOX contains two domains: a Ca2+ binding PLAT domain and a catalytic domain. 15-LOX is a soluble cytosolic protein until binding of Ca2+ to the PLAT domain promotes translocation to the membrane surface. The role of 15-LOX structural dynamics in this translocation has remained unclear. We investigated the dynamics of 15-LOX isoform B (15-LOX-2) upon binding of Ca2+ and ligands, as well as upon membrane association using hydrogen-deuterium exchange mass spectrometry (HDX-MS). We used HDX-MS to probe the solvent accessibility and backbone flexibility of 15-LOX-2, revealing significant differences in deuterium incorporation between the PLAT and catalytic domains, with the PLAT domain demonstrating higher flexibility. Comparison of HDX for 15-LOX-2 in the presence and absence of Ca2+ indicates there are few differences in structural dynamics. Furthermore, our HDX results involving nanodisc-associated 15-LOX-2 suggest that significant structural and dynamic changes in 15-LOX-2 are not required for membrane association. Our results also show that a substrate lipid binding to the active site in the catalytic domain does induce changes in incorporation of deuterium into the PLAT domain. Overall, our results challenge the previous hypothesis that Ca2+ binding induces major structural changes in the PLAT domain and support the hypothesis that is interdomain communication in 15-LOX-2.

Background: Though a large number of pregnant females have been affected by COVID-19, there is a dearth of information on the effects of SARS-CoV-2 infection on trophoblast function. We explored in silico, the potential interactions between SARS-CoV-2 proteins and proteins involved in the key functions of placenta.

Methods: Human proteins interacting with SARS-CoV-2 proteins were identified by Gordon et al. (2020). Genes that are upregulated in trophoblast sub-types and stages were obtained by gene-expression data from NCBI-GEO and by text-mining. Genes altered in pathological states like pre-eclampsia and gestational diabetes mellitus were also identified. Genes crucial in placental functions thus identified were compared to the SARS-CoV-2 interactome for overlaps. Proteins recurring across multiple study scenarios were analyzed using text mining and network analysis for their biological functions.

Results: The entry receptors for SARS-CoV-2 - ACE2 and TMPRSS2 are expressed in placenta. Other proteins that interact with SARS-CoV-2 like LOX, Fibulins-2 and 5, NUP98, GDF15, RBX1, CUL3, HMOX1, PLAT, MFGE8, and MRPs are vital in placental functions like trophoblast invasion and migration, syncytium formation, differentiation, and implantation. TLE3, expressed across first trimester placental tissues and cell lines, is involved in formation of placental vasculature, and is important in SARS-CoV (2003) budding and exit from the cells by COPI vesicles.

Conclusion: SARS-CoV-2 can potentially interact with proteins having crucial roles in the placental function. Whether these potential interactions identified in silico have effects on trophoblast functions in biological settings needs to be addressed by further in vitro and clinical studies.

Keywords: COVID-19; Placenta; Pregnancy; Protein-protein interaction; SARS-CoV-2; Trophoblast.

In this dataset we integrated figures comparing leaf number and rosette diameter in three Arabidopsis FT overexpressor lines (AtFTOE) driven by KNAT1 promoter, "A member of the KNOTTED class of homeodomain proteins encoded by the STM gene of Arabidopsis" [5], vs Wild Type (WT) Arabidopsis plats. Also, presented in the tables are some transcriptomic data obtained by RNA-seq Illumina HiSeq from rosette leaves of Arabidopsis plants of AtFTOE 2.1 line vs WT with accession numbers SRR2094583 and SRR2094587 for AtFTOE replicates 1-3 and AtWT for control replicates 1-2 respectively. Raw data of paired-end sequences are located in the public repository of the National Center for Biotechnology Information of the National Library of Medicine, National Institutes of Health, United States of America, Bethesda, MD, USA as Sequence Read Archive (SRA). Performed analyses of differential expression genes are visualized by Mapman and presented in figures. "Transcriptomic analysis of Arabidopsis overexpressing flowering locus T driven by a meristem-specific promoter that induces early flowering" [2], described the interpretation and discussion of the obtained data.

Objective: The objective of this study is to describe the algorithm and technical implementation of a mobile app that uses adaptive testing to assess an efficient mobile app for the diagnosis of delirium.

Materials and methods: The app was used as part of a NIH-funded project to assess the feasibility, effectiveness, administration time, and costs of the 2-step delirium identification protocol when performed by physicians and nurses, and certified nursing assistants (CNA). The cohort included 535 hospitalized patients aged 79.7 (SD = 6.6) years enrolled at 2 different sites. Each patient was assessed on 2 consecutive days by the research associate who performed the reference delirium assessment. Thereafter, physicians, nurses, and CNAs performed adaptive delirium assessments using the app. Qualitative data to assess the experience of administering the 2-step protocol, and the app usability were also collected and analyzed from 50 physicians, 189 nurses, and 83 CNAs. We used extensible hypertext markup language (XHTML) and JavaScript to develop the app for the iOS-based iPad. The App was linked to Research Electronic Data Capture (REDCap), a relational database system, via a REDCap application programming interface (API) that sent and received data from/to the app. The data from REDCap were sent to the Statistical Analysis System for statistical analysis.

Results: The app graphical interface was successfully implemented by XHTML and JavaScript. The API facilitated the instant updating and retrieval of delirium status data between REDCap and the app. Clinicians performed 881 delirium assessments using the app for 535 patients. The transmission of data between the app and the REDCap system showed no errors. Qualitative data indicated that the users were enthusiastic about using the app with no negative comments, 82% positive comments, and 18% suggestions of improvement. Delirium administration time for the 2-step protocol showed similar total time between nurses and physicians (103.9 vs 106.5 seconds). Weekly enrollment reports of the app data were generated for study tracking purposes, and the data are being used for statistical analyses for publications.

Discussion: The app developed using iOS could be easily converted to other operating systems such as Android and could be linked to other relational databases beside REDCap, such as electronic health records to facilitate better data retrieval and updating of patient's delirium status.

Conclusion: Our app operationalizes an adaptive 2-step delirium screening protocol. Its algorithm and cross-plat formed code of XHTML and JavaScript can be easily exported to other operating systems and hardware platforms, thus enabling wider use of the efficient delirium screening protocol that we have developed. The app is currently implemented as a research tool, but with adaptation could be implemented in the clinical setting to facilitate widespread delirium screening in hospitalized older adults.

Keywords: 2-step delirium protocol; API; JavaScript; REDCap; XHTML; app; delirium diagnosis.

Background: Consolidative hematopoietic cell transplantation (HCT) after CD19 chimeric antigen receptor (CAR) T cell therapy is frequently performed for patients with refractory/relapsed B cell acute lymphoblastic leukemia (B-ALL). However, there is controversy regarding the role of HCT following remission attainment.

Objectives: We evaluated the effect of consolidative HCT on leukemia-free survival (LFS) in pediatric and young adult subjects following CD19 CAR T cell induced remission.

Study design: We evaluated the effect of consolidative HCT on leukemia-free survival (LFS) in pediatric and young adult subjects treated with a 41BB-CD19 CAR T cell product on a Phase 1/2 trial, Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-02 (NCT02028455), using a time-dependent Cox proportional hazards statistical model. Fifty of 64 subjects enrolled onto PLAT-02 Phase 1 and early Phase 2 were evaluated, excluding 14 subjects who did not achieve remission, relapsed or died prior to day 63 post-CAR T cell therapy.

Results: An improved LFS (P=0.01) was observed in subjects who underwent consolidative HCT after CAR T cell therapy versus watchful waiting. Consolidative HCT improved LFS specifically in subjects who had no prior history of HCT, with a trend towards significance (P=0.09). This benefit was not evident when restricted to the cohort of 34 subjects with a history of a prior HCT (P=0.45). However, for subjects who had CAR T cell functional persistence of 63 days or less, inclusive of those with a history of prior HCT, HCT significantly improved LFS outcomes (P=0.01).

Conclusions: These data support consolidative HCT following CD19 CAR T cell-induced remission for patients with no prior history of HCT or for those with short functional CAR T cell persistence.

Keywords: CD19; Chimeric antigen receptor T cell; Hematopoietic cell transplantation; Leukemia.

Epidermal fragments enriched in guard cells (GCs) were isolated from the halophyte quinoa (Chenopodium quinoa Wild.) species, and the response at the proteome level was studied after salinity treatment of 300 mM NaCl for 3 weeks. In total, 2147 proteins were identified, of which 36% were differentially expressed in response to salinity stress in GCs. Up and downregulated proteins included signaling molecules, enzyme modulators, transcription factors and oxidoreductases. The most abundant proteins induced by salt treatment were desiccation-responsive protein 29B (50-fold), osmotin-like protein OSML13 (13-fold), polycystin-1, lipoxygenase, alpha-toxin, and triacylglycerol lipase (PLAT) domain-containing protein 3-like (eight-fold), and dehydrin early responsive to dehydration (ERD14) (eight-fold). Ten proteins related to the gene ontology term "response to ABA" were upregulated in quinoa GC; this included aspartic protease, phospholipase D and plastid-lipid-associated protein. Additionally, seven proteins in the sucrose-starch pathway were upregulated in the GC in response to salinity stress, and accumulation of tryptophan synthase and L-methionine synthase (enzymes involved in the amino acid biosynthesis) was observed. Exogenous application of sucrose and tryptophan, L-methionine resulted in reduction in stomatal aperture and conductance, which could be advantageous for plants under salt stress. Eight aspartic proteinase proteins were highly upregulated in GCs of quinoa, and exogenous application of pepstatin A (an inhibitor of aspartic proteinase) was accompanied by higher oxidative stress and extremely low stomatal aperture and conductance, suggesting a possible role of aspartic proteinase in mitigating oxidative stress induced by saline conditions.

Keywords: guard cell; proteomics analysis; quinoa; salt stress; stomata.

OBJECTIVE

To explore the value of HLA-DRB1 gene in predicting the outcome of unexplained recurrent spontaneous abortion (URSA) treated with paternal lymphocyte alloimmunization therapy (PLAT) in Henan Hans.

METHODS

Three hundred URSA patients were recruited. Following PLAT treatment, they were divided into two groups according to the outcome of pregnancy. Polymerase chain reaction sequence specific primer (PCR-SSP) were conducted to analyze the HLA-DRB1 gene.

RESULTS

For those who have received PLAT treatment, the frequency of HLA-DRB1*11 was significantly lower in successfully treated cases than those with abortion (0.052 vs. 0.110, P < 0.05, OR=0448), whilst the frequency of HLA-DRB1*15 was significantly greater in the former (0.207 vs. 0.100, P < 0.05, OR=2.352).

CONCLUSIONS

For patients who have received PLAT treatment, those with HLA-DRB1*15 are more likely to conceive that those with HLA-DRB1*11.

The design and laboratory evaluation of a new two-stage aerosol sampler is described. The first stage of the sampler employs an integral flat plat impactor to remove particles greater than 10 micrometers; particles that penetrate the impactor are collected on a 37 mm membrane filter with 5-micrometer pore size. The theoretical design parameters and experimental calibration data developed for the impactor sampling heads at flowrates of 2.0 and 3.0 liter per minute are presented, and their collection characteristics compared to those of present two-stage respirable dust samplers. The advantages and disadvantages of the two-stage impactor sampler are discussed.

The water logging has become the environmental problem of major cities with the sharp increase of impermeable urban pavement as the contributing cause. Abroad, the green roof has been widely used as a practical measure to intercept rainwater, yet the capacity of green roof to retain rainwater varies with climate conditions. As the hot and humid climate zone features high temperature, humidity and precipitation, it is meaningful to study the capacity of green roof to retain rainwater under such climatic condition. In this research, 3 plat forms were set up in Guangzhou in rainy and hot summer to test the capability of simple green roof to retain rainwater runoff, and the efficiency of green roof to retain rainwater under local climate conditions was worked out based on the meteorological observation and data measurement during the 13-month test period. The results showed that the simple green roof with a substrate thickness of 30, 50 and 70 mm could retain 27.2%, 30.9% and 32.1% of precipitation and reduce the average peak value by 18.9%, 26.2% and 27.7%, respectively. Given an urban built-up area of 1035.01 km2 in Guangzhou and a roof area percentage of approximately 37.3% and assuming the green roofs with 30 mm-thick substrate were applied within the area, the light, medium and heavy rain could be delayed at 72.8%, 22.6% and 17.4%, respectively. Accordingly, the rainwater retained could reach up to 14317×104 m3. It suggested the great potential of the simple green roof in retaining rainwater. The research could serve as reference for the hot and humid climate zone to alleviate water logging and visualize sponge city construction.