A CYP78As-small grain4-coat protein complex â ¡ pathway promotes grain size in rice.

CYP78A, a cytochrome P450 subfamily that includes rice (Oryza sativa L.) BIG GRAIN2 (BG2, CYP78A13) and Arabidopsis thaliana KLUH (KLU, CYP78A5), generate an unknown mobile growth signal (referred to as a CYP78A-derived signal) that increases grain (seed) size. However, the mechanism by which the CYP78A pathway increases grain size remains elusive. Here, we characterized a rice small grain mutant, small grain4 (smg4), with smaller grains than its wild type due to restricted cell expansion and cell proliferation in spikelet hulls. SMG4 encodes a multidrug and toxic compound extrusion (MATE) transporter. Loss of function of SMG4 causes smaller grains while overexpressing SMG4 results in larger grains. SMG4 is mainly localized to endoplasmic reticulum (ER) exit sites (ERESs) and partially localized to the ER and Golgi. Biochemically, SMG4 interacts with coat protein complex Ⅱ (COPⅡ) components (Sar1, Sec23, and Sec24) and CYP78As (BG2, GRAIN LENGTH 3.2 [GL3.2], and BG2-LIKE 1 [BG2L1]). Genetically, SMG4 acts, at least in part, in a common pathway with Sar1 and CYP78As to regulate grain size. In summary, our findings reveal a CYP78As-SMG4-COPⅡ regulatory pathway for grain size in rice, thus providing new insights into the molecular and genetic regulatory mechanism of grain size.

TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer.

BACKGROUND: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. METHODS: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). RESULTS: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. CONCLUSIONS: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.

Atmospheric Oxidation Capacity Elevated during 2020 Spring Lockdown in Chengdu, China: Lessons for Future Secondary Pollution Control.

This study presents the measurement of photochemical precursors during the lockdown period from January 23, 2020, to March 14, 2020, in Chengdu in response to the coronavirus (COVID-19) pandemic. To derive the lockdown impact on air quality, the observations are compared to the equivalent periods in the last 2 years. An observation-based model is used to investigate the atmospheric oxidation capacity change during lockdown. OH, HO2, and RO2 concentrations are simulated, which are elevated by 42, 220, and 277%, respectively, during the lockdown period, mainly due to the reduction in nitrogen oxides (NOx). However, the radical turnover rates, i.e., OH oxidation rate L(OH) and local ozone production rate P(O3), which determine the secondary intermediates formation and O3 formation, only increase by 24 and 48%, respectively. Therefore, the oxidation capacity increases slightly during lockdown, which is partly attributed to unchanged alkene concentrations. During the lockdown, alkene ozonolysis seems to be a significant radical primary source due to the elevated O3 concentrations. This unique data set during the lockdown period highlights the importance of controlling alkene emission to mitigate secondary pollution formation in Chengdu and may also be applicable in other regions of China given an expected NOx reduction due to the rapid transformation to electrified fleets in the future.

Exploring #MentholBan on TikTok: a Thematic and Semantic Network Analysis.

INTRODUCTION: In April 2021, the U.S. Food and Drug Administration (FDA) announced its intention to ban the sale of menthol cigarettes and cigars. Decades of research support the premise a menthol ban will reduce initiation and disparities in tobacco-related disease among menthol smokers. The tobacco industry opposed such a policy and worked for decades to shape public opposition. Social media discourse can inform our understanding of public opinion about the proposed ban and guide communication strategies and policy implementation. METHODS: This research employed a mixed-methods design to explore TikTok posts discussing the announced menthol ban. Using a TikTok web scraper to extract all content in the #mentholban hashtag (n=171), we coded for 11 themes, characterized content with descriptive statistics, and created a semantic network of co-occurring hashtags. RESULTS: We found primarily negative attitudes towards the US ban announcement and a large volume of menthol "hacks" to circumvent the bans. Our semantic network analysis revealed strong co-occurrences between #mentholban and popularity-seeking hashtags. The metadata associated with each TikTok demonstrated that most posters in #mentholban are not "influencers" in the sense of having many followers, aside from a few niche organizations with multiple posts. We found that perceived political and racial motivations shaped posters' assessments of the menthol ban. Furthermore, we uncovered how individuals and organizational actors shaped menthol ban content on TikTok. CONCLUSION: Our study indicates targeted marketing from alternative menthol product companies and advocacy organizations. The latter of these organizations is more likely to saturate the TikTok landscape with multiple posts and strategic hashtags. IMPLICATIONS: This study pursued an exploration of tobacco policy discussion on TikTok, specifically related to the FDA proposed menthol ban. TikTok is newer platform and our study provides early evidence of policy discussion emerging there, including the types of accounts creating the content and their valence toward the policy.

The APC/CTE E3 Ubiquitin Ligase Complex Mediates the Antagonistic Regulation of Root Growth and Tillering by ABA and GA.

The antagonistic regulation of seed germination by the phytohormones abscisic acid (ABA) and gibberellic acid (GA) has been well-established. However, how these phytohormones antagonistically regulate root growth and branching (tillering in rice, Oryza sativa) remains obscure. Rice TILLER ENHANCER (TE) encodes an activator of the APC/CTE E3 ubiquitin ligase complex that represses tillering but promotes seed germination. In this study, we identified a dual role of GA and APC/CTE in regulating root growth. High GA levels can activate APC/CTE to promote the degradation of rice SHORT-ROOT1 (OsSHR1, a key factor promoting root growth) in the root meristem (RM) or MONOCULM1 (MOC1, a key factor promoting tillering) in the axillary meristem (AM), leading to restricted root growth and tillering, while low GA levels can activate the role of APC/CTE in stimulating RM cell division to promote root growth. In addition, moderate enhancement of ABA signaling helps maintain the RM and AM size, sustaining root growth and tillering by antagonizing the GA-promoted degradation of OsSHR1 and MOC1 through the SnRK2-APC/CTE regulatory module. We conclude that APC/CTE plays a key role in regulating plant architecture by mediating the crosstalk between ABA and GA signaling pathways.

Short- and long-term impacts of the COVID-19 epidemic on urban PM2.5 variations: Evidence from a megacity, Chengdu.

As the new coronavirus pandemic enters its third year, its long-term impact on the urban environment cannot be ignored, especially in megacities with more than millions of people. Here, we analyzed the changes in the concentration levels, emission sources, temporal variations and holiday effects of ambient fine particulate matter (PM2.5) and its chemical components in the pre- and post-epidemic eras based on high-resolution, long time-series datasets of PM2.5 and its chemical components in Chengdu. In the post-epidemic era, the PM2.5 concentration in Chengdu decreased by 7.4%, with the components of PM2.5 decreasing to varying degrees. The positive matrix factorization (PMF) results indicated that the emissions from soil dust and industrial production were significantly lower during the COVID-19 lockdown period and post-epidemic era than those in the pre-epidemic era. In contrast, the contribution of secondary aerosols to PM2.5 during these two periods increased by 2.7% and 6.6%, respectively. Notably, we found that PM2.5 and its components substantially decreased on workdays and holidays in the post-epidemic era due to the reduced traffic volume and outdoor activities. This provides direct evidence that changes in the habitual behavior patterns of urban residents in the post-epidemic era could exert an evident positive impact on the urban environment. However, the higher PM2.5 concentration was observed due to the increased consumption of regular (As4S4, Xionghuang in Chinese) and "sulfur incense" during the Dragon Boat Festival holiday in the post-epidemic era. Finally, we examined the potential effects of sporadic COVID-19 outbreaks on the PM2.5 concentration in Chengdu, and there was no decrease in PM2.5 during two local COVID-19 outbreak events due to the strong influence of secondary pollution processes.

Young Leaf White Stripe encodes a P-type PPR protein required for chloroplast development.

Pentatricopeptide repeat (PPR) proteins function in post-transcriptional regulation of organellar gene expression. Although several PPR proteins are known to function in chloroplast development in rice (Oryza sativa), the detailed molecular functions of many PPR proteins remain unclear. Here, we characterized a rice young leaf white stripe (ylws) mutant, which has defective chloroplast development during early seedling growth. Map-based cloning revealed that YLWS encodes a novel P-type chloroplast-targeted PPR protein with 11 PPR motifs. Further expression analyses showed that many nuclear- and plastid-encoded genes in the ylws mutant were significantly changed at the RNA and protein levels. The ylws mutant was impaired in chloroplast ribosome biogenesis and chloroplast development under low-temperature conditions. The ylws mutation causes defects in the splicing of atpF, ndhA, rpl2, and rps12, and editing of ndhA, ndhB, and rps14 transcripts. YLWS directly binds to specific sites in the atpF, ndhA, and rpl2 pre-mRNAs. Our results suggest that YLWS participates in chloroplast RNA group II intron splicing and plays an important role in chloroplast development during early leaf development.

Progressively narrow the gap of PM2.5 pollution characteristics at urban and suburban sites in a megacity of Sichuan Basin, China.

Nowadays, the fine particle pollution is still severe in some megacities of China, especially in the Sichuan Basin, southwestern China. In order to understand the causes, sources, and impacts of fine particles, we collected PM2.5 samples and analyzed their chemical composition in typical months from July 2018 to May 2019 at an urban and a suburban (background) site of Chengdu, a megacity in this region. The daily average concentrations of PM2.5 ranged from 5.6-102.3 µg/m3 and 4.3-110.4 µg/m3 at each site. Secondary inorganics and organic matters were the major components in PM2.5 at both sites. The proportion of nitrate in PM2.5 has exceeded sulfate and become the primary inorganic component. SO2 was easier to transform into sulfate in urban areas because of Mn-catalytic heterogeneous reactions. In contrast, NO2 was easily converted in suburbs with high aerosol water content. Furthermore, organic carbon in urban was much greater than that in rural, other than elemental carbon. Element Cr and As were the key cancer risk drivers. The main sources of PM2.5 in urban and suburban areas were all secondary aerosols (42.9%, 32.1%), combustion (16.0%, 25.2%) and vehicle emission (15.2%, 19.2%). From clean period to pollution period, the contributions from combustion and secondary aerosols increased markedly. In addition to tightening vehicle controls, urban areas need to restrict emissions from steel smelters, and suburbs need to minimize coal and biomass combustion in autumn and winter.

NAADP/SERCA3-Dependent Ca2+ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation.

RATIONALE: Ca2+ signaling is a key and ubiquitous actor of cell organization and its modulation controls many cellular responses. SERCAs (sarco-endoplasmic reticulum Ca2+-ATPases) pump Ca2+ into internal stores that play a major role in the cytosolic Ca2+ concentration rise upon cell activation. Platelets exhibit 2 types of SERCAs, SERCA2b and SERCA3 (SERCA3 deficient mice), which may exert specific roles, yet ill-defined. We have recently shown that Ca2+ mobilization from SERCA3-dependent stores was required for full platelet activation in weak stimulation conditions. OBJECTIVE: To uncover the signaling mechanisms associated with Ca2+ mobilization from SERCA3-dependent stores leading to ADP secretion. METHODS AND RESULTS: Using platelets from wild-type or Serca3-deficient mice, we demonstrated that an early (within 5-10 s following stimulation) secretion of ADP specifically dependent on SERCA3 stored Ca2+ is exclusively mobilized by nicotinic acid adenosine dinucleotide-phosphate (NAADP): both Ca2+ mobilization from SERCA3-dependent stores and primary ADP secretion are blocked by the NAADP receptor antagonist Ned-19, and reciprocally both are stimulated by permeant NAADP. In contrast, Ca2+ mobilization from SERCA3-dependent stores and primary ADP secretion were unaffected by inhibition of the production of IP3 (inositol-1,4,5-trisphosphate) by phospholipase-C and accordingly were not stimulated by permeant IP3. CONCLUSIONS: Upon activation, an NAADP/SERCA3 Ca2+ mobilization pathway initiates an early ADP secretion, potentiating platelet activation, and a secondary wave of ADP secretion driven by both an IP3/SERCA2b-dependent Ca2+ stores pathway and the NAADP/SERCA3 pathway. This does not exclude that Ca2+ mobilized from SERCA3 stores may also enhance platelet global reactivity to agonists. Because of its modulating effect on platelet activation, this NAADP-SERCA3 pathway may be a relevant target for anti-thrombotic therapy. Graphic Abstract: A graphic abstract is available for this article.

Skeleton Graph-Neural-Network-Based Human Action Recognition: A Survey.

Human action recognition has been applied in many fields, such as video surveillance and human computer interaction, where it helps to improve performance. Numerous reviews of the literature have been done, but rarely have these reviews concentrated on skeleton-graph-based approaches. Connecting the skeleton joints as in the physical appearance can naturally generate a graph. This paper provides an up-to-date review for readers on skeleton graph-neural-network-based human action recognition. After analyzing previous related studies, a new taxonomy for skeleton-GNN-based methods is proposed according to their designs, and their merits and demerits are analyzed. In addition, the datasets and codes are discussed. Finally, future research directions are suggested.

The Viral Load of Human Cytomegalovirus Infection in Children following Hematopoietic Stem Cell Transplant by Chip Digital PCR.

Objective: To detect viral load in human cytomegalovirus (HCMV) infection children after hematopoietic stem cell transplant (HSCT) by chip digital PCR (cdPCR). Methods: The plasmid pUC57-UL83 containing the HCMV-UL83 gene and HCMV AD169 strain were used to evaluate the sensitivity of cdPCR. Either HSV-1, HSV-2, VZV, EBV, HHV-6, or HHV-7 was used to evaluate the specificity of HCMV cdPCR. The cdPCR was compared with quantitative PCR (qPCR) by detecting HCMV infection in 125 children's whole blood samples following HSCT. Results: The limit of detection (LOD) of HCMV cdPCR was 103 copies/ml and the qPCR LOD was 297 copies/ml for plasmid pUC57-UL83. The result of HCMV cdPCR was 146 copies/ml for the HCMV AD169 strain, indicating that the sensitivity of cdPCR was higher than that of qPCR. There is no cross-reaction between HCMV cdPCR and other herpes viruses. The incidence of HCMV infection was 30.40% in 125 children following HSCT by cdPCR. The range of the HCMV viral load was from 107 copies/ml to 6600 copies/ml by cdPCR. Conclusions: cdPCR is more sensitive than qPCR for detecting HCMV viral load. Furthermore, the cdPCR could be used to detect the viral load of HCMV infection before or after HSCT in children.

A mutation of the human EPHB2 gene leads to a major platelet functional defect.

The ephrin transmembrane receptor family of tyrosine kinases is involved in platelet function. We report the first EPHB2 variant affecting platelets in 2 siblings (P1 and P2) from a consanguineous family with recurrent bleeding and normal platelet counts. Whole-exome sequencing identified a c.2233C>T variant (missense p.R745C) of the EPHB2 gene. P1 and P2 were homozygous for this variant, while their asymptomatic parents were heterozygous. The p.R745C variant within the tyrosine kinase domain was associated with defects in platelet aggregation, αIIbß3 activation, and granule secretion induced by G-protein-coupled receptor (GPCR) agonists and convulxin, as well as in thrombus formation on collagen under flow. In contrast, clot retraction, flow-dependent platelet adhesion, and spreading on fibrinogen were only mildly affected, indicating limited effects on αIIbß3 outside-in signaling. Most importantly, Lyn, Syk, and FcRγ phosphorylation, the initial steps in glycoprotein VI (GPVI) platelet signaling were drastically impaired in the absence of platelet-platelet contact, indicating a positive role for EPHB2 in GPVI activation. Likewise platelet activation by PAR4-AP showed defective Src activation, as opposed to normal protein kinase C activity and Ca2+ mobilization. Overexpression of wild-type and R745C EPHB2 variant in RBL-2H3 (rat basophilic leukemia) cells stably expressing human GPVI confirmed that EPHB2 R745C mutation impaired EPHB2 autophosphorylation but had no effect on ephrin ligand-induced EPHB2 clustering, suggesting it did not interfere with EPHB2-ephrin-mediated cell-to-cell contact. In conclusion, this novel inherited platelet disorder affecting EPHB2 demonstrates this tyrosine kinase receptor plays an important role in platelet function through crosstalk with GPVI and GPCR signaling.

Immune checkpoint inhibitors for the management of advanced non-small-cell lung carcinoma: a meta-analysis.

This study is a meta-analysis assessing the safety and efficacy of programmed cell death-1/cell death-ligand 1 (PD-1/PD-L1) inhibitors in order to improve their efficacy in advanced non-small-cell lung cancer. We retrieved studies of anti-PD-1/PD-L1 therapies for non-small-cell lung cancer from electronic databases; 17 clinical trials were analyzed. The pooled hazard ratios for overall and progression-free survival (PFS), and the odds ratios (ORs) for the objective response rate (ORR) and adverse effects were calculated using Review Manager 5.3. The pooled hazard ratios for overall and PFS were 0.69 and 0.74, respectively, and the pooled OR for the ORR was 1.78, implying a significant improvement in overall survival (OS), PFS, and ORR with administration of PD-1/PD-L1 inhibitors. In subgroup analysis, the ORs of the ORR were 2.48 in PD-L1 positive versus negative tumors, and 0.99 for a high dose of PD-1/PD-L1 inhibitors versus a low dose. The ORs for the occurrence of any treatment-related adverse effects and grades 3-5 treatment-related adverse effects were 0.33 and 0.30, respectively, suggesting a good safety profile. PD-1/PD-L1 immunotherapy has superior outcomes in terms of the ORR, OS, and PFS with tolerable adverse effects when compared with chemotherapy.

Aerosol optical properties under different pollution levels in the Pearl River Delta (PRD) region of China.

To clarify the aerosol hygroscopic growth and optical properties of the Pearl River Delta (PRD) region, integrated observations were conducted in Heshan City of Guangdong Province from October 19 to November 17, 2014. The concentrations and chemical compositions of PM2.5, aerosol optical properties and meteorological parameters were measured. The mean value of PM2.5 increased from less than 35 (excellent) to 35-75 µg/m3 (good) and then to greater than 75 µg/m3 (pollution), corresponding to mean PM2.5 values of 24.9, 51.2, and 93.3 µg/m3, respectively. The aerosol scattering hygroscopic growth factor (f(RH = 80%)) values were 2.0, 2.12, and 2.18 for the excellent, good, and pollution levels, respectively. The atmospheric extinction coefficient (σext) and the absorption coefficient of aerosols (σap) increased, and the single scattering albedo (SSA) decreased from the excellent to the pollution levels. For different air mass sources, under excellent and good levels, the land air mass from northern Heshan had lower f(RH) and σsp values. In addition, the mixed aerosol from the sea and coastal cities had lower f(RH) and showed that the local sources of coastal cities have higher scattering characteristics in pollution periods.

The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3/P38 MAPK signaling pathway.

BACKGROUND: The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear. METHODS: We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus. RESULTS: We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time. CONCLUSIONS: miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.

Bioactive glass functionalized chondroitin sulfate hydrogel with proangiogenic properties.

Blood vessels play an important role in bone defect repair and growth, and a critical challenge of bone defect repair is the promotion of blood vessel formation. Most of the current methods promote vascularization by adding specific growth factors, which are costly and easy to inactivate. In this study, we developed a covalently cross-linked aminated bioactive glass nanoparticle-chondroitin sulfate methacrylate (ABGN-CSMA) organic-inorganic composite hydrogel with angiogenic properties. The amino groups of the ABGNs form covalent bonds with the carboxyl groups on CSMA. Surface amination modification of BGNs not only improved the dispersion of BGNs in CSMA but also significantly improved the mechanical properties of the composite hydrogel. The largest storage modulus (1200 Pa), the largest loss modulus (560 Pa) and the strongest resistance to deformation of the hydrogel are seen at 10% concentration of ABGNs. Simultaneously, the local pH stability and sustained ion release of the composite hydrogel are conducive to cell adhesion, proliferation, and angiogenesis. This work provides evidence for the development of covalently cross-linked organic-inorganic composite hydrogels with angiogenic properties.

A Positive Tetraspanin 8 (TSPAN8)/ß-Catenin Regulatory Loop Enhances the Stemness of Colorectal Cancer Cells.

BACKGROUND The expression of TSPAN8 (tetraspanin 8) is upregulated in colorectal cancer; however, its roles in colorectal cancer progression are never been revealed. This work aimed to investigate TSPAN8 effects and the molecular basis in regulating colorectal cancer stemness. MATERIAL AND METHODS Real-time quantitative polymerase chain reaction and western blot analysis were used to detect the expression of TSPAN8 expression in clinical samples and the expression of stemness genes in colorectal cancer cells. Sphere forming analysis was performed to detect TSPAN8 effects on sphere forming ability of colorectal cancer cells. Co-IP and ChIP analysis were performed to confirm the molecular basis contributing to TSPAN8-mediated effects on colorectal cancer stemness. RESULTS TSPAN8 expression is increased in colorectal cancer tissues. Knockdown of TSPAN8 reduced the expression of stemness genes and sphere forming capacity in colorectal cancer cells. Mechanistically, TSPAN8 directly interacted ß-catenin and enhanced its protein expression, which is necessary for TSPAN8-mediated effects on colorectal cancer stemness. Conversely, ß-catenin directly bound to TSPAN8 promoter and enhanced TSPAN8 transcription. CONCLUSIONS TSPAN8 promotes colorectal cancer stemness through a positive TSPAN8/ß-catenin regulatory loop.

An ent-Kaurane Diterpenoid Isolated from Rabdosia excisa Suppresses Bcr-Abl Protein Expression in Vitro and in Vivo and Induces Apoptosis of CML Cells.

Chronic myelogenous leukemia (CML) is a disease of the blood stem cells that features the oncoprotein Bcr-Abl. Tyrosine kinase inhibitors (TKIs) are used to treat CML patients, but these have limited efficacy due to the emergence of resistance via genetic mutation. Kamebakaurin is an ent-kaurane diterpenoid that has been isolated from Rabdosia excisa (Maxim.) H.Hara. Herein, we investigate the potential of kamebakaurin as a chemotherapy reagent for the treatment of CML. We conducted in vitro and in vivo biological experiments and found that kamebakaurin potently inhibits cell proliferation, mainly by enhancing cell apoptosis and down-regulating Bcr-Abl protein levels. In addition, kamebakaurin was found to inhibit tumor growth and has no side effects on five internal organs for in vivo experiment. These results suggest that kamebakaurin is a potential anticancer agent and is a key compound for further investigations.

Insights into the phenomenon of an explosive growth and sharp decline in haze: A case study in Beijing.

A severe haze episode occurred in winter in the North China Plain (NCP), and the phenomenon of an explosive growth and sharp decline in PM2.5 (particulate matter with an aerodynamic diameter equal to or less than 2.5 µm) concentration was observed. To study the systematic causes for this phenomenon, comprehensive observations were conducted in Beijing from November 26 to December 2, 2015; during this period, meteorological parameters, LIDAR data, and the chemical compositions of aerosols were determined. The haze episode was characterized by rapidly varying PM2.5 concentration, and the highest PM2.5 concentration reached 667 µg/m3. During the haze episode, the NCP was dominated by a weak high-pressure system and continuously low PBL (planetary boundary layer) heights, which are unfavorable conditions for the diffusion of pollutants. The large increases in the concentrations of SNA (SO42-, NO3- and NH4+) during the haze implied that the formation of SNA was the largest contribution. Water vapor also played a vital role in the formation of haze by promoting the chemical transformation of secondary pollutants, which led to higher PM2.5 concentrations. The spatial distributions of PM2.5 in Beijing at different times and the backward trajectories of the air masses also indicated that pollutants from surrounding provinces in particular, contributed to the higher PM2.5 concentration.

Characteristics of one-year observation of VOCs, NOx, and O3 at an urban site in Wuhan, China.

A continuous online observation of ozone and its precursors (NOx, VOCs) was carried out in central urban Wuhan from September 2016 to August 2017. The concentration levels of ozone, NOx, VOCs and their variations in urban Wuhan were analyzed, as well as effects of VOCs on ozone photochemical generation and the main controlling factors for ozone production. During the observation period, the average concentrations of ozone and NOx in Wuhan was 22.63 and 30.14 ppbv, respectively, and the average concentration of VOCs was 32.61 ppbv (42.3% alkanes, 13.0% alkenes, 10.0% aromatics, 7.3% acetylene, 9.9% OVOCs, and 10.5% halohydrocarbons). Ozone concentration was higher in spring and summer as compared with autumn and winter, wheras VOCs and NOx concentratios were lower in spring and summer but higher in autumn and winter. Aromatics and alkenes, two of VOCs species, showed the highest contributions to ozone formation potential in Wuhan (35.7% alkenes, 35.4 aromatics, 17.5% alkanes, 8.6% OVOCs, 1.6% halogenated hydrocarbons, and 1.4% acetylene). Among all VOCs species, those with the highest contribution were ethylene, m-xylene, toluene, propylene and o-xylene. The contribution of these five compounds to the total ozone formation potential concentration was 43.90%. Ozone-controlling factors in Wuhan changed within one day; during the early morning hours (6:00-9:00), VOCs/NOx was low, and ozone generation followed a VOCs-limited regime. However, during the peak time of ozone concentration (12:00-16:00), the ratio of VOCs/NOx was relatively high, suggesting that ozone generation followed a NOx-limited regime.