Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7). Apart from four well-known low-risk subgroups including PML::RARA (G1), CBFB::MYH11 (G2), RUNX1::RUNX1T1 (G3), biallelic CEBPA mutations or -like (G4), four meta-subgroups with poor outcomes were recognized. The G5 (myelodysplasia-related/-like) subgroup enriched clinical, cytogenetic and genetic features mimicking secondary AML, and hotspot mutations of IKZF1 (p.N159S) (n = 7). In contrast, most NPM1 mutations and KMT2A and NUP98 fusions clustered into G6-G8, showing high expression of HOXA/B genes and diverse differentiation stages, from hematopoietic stem/progenitor cell down to monocyte, namely HOX-primitive (G7), HOX-mixed (G8), and HOX-committed (G6). Through constructing prediction models, the eight gene expression subgroups could be reproduced in the Cancer Genome Atlas (TCGA) and Beat AML cohorts. Each subgroup was associated with distinct prognosis and drug sensitivities, supporting the clinical applicability of this transcriptome-based classification of AML. These molecular subgroups illuminate the complex molecular network of AML, which may promote systematic studies of disease pathogenesis and foster the screening of targeted agents based on omics.

Ultra-Large Scale Stitchless AFM: Advancing Nanoscale Characterization and Manipulation with Zero Stitching Error and High Throughput.

The atomic force microscopy (AFM) is an important tool capable of characterization, measurement, and manipulation at the nanoscale with a vertical resolution of less than 0.1 nm. However, the conventional AFMs' scanning range is around 100 µm, which limits their capability for processing cross-scale samples. In this study, it proposes a novel approach to overcome this limitation with an ultra-large scale stitchless AFM (ULSS-AFM) that allows for the high-throughput characterization of an area of up to 1 × 1 mm2 through a synergistic integration with a compliant nano-manipulator (CNM). Specifically, the compact CNM provides planar motion with nanoscale precision and millimeter range for the sample, while the probe of the ULSS-AFM interacts with the sample. Experimental results show that the proposed ULSS-AFM performs effectively in different scanning ranges under various scanning modes, resolutions, and frequencies. Compared with the conventional AFMs, the approach enables high-throughput characterization of ultra-large scale samples without stitching or bow errors, expanding the scanning area of conventional AFMs by two orders of magnitude. This advancement opens up important avenues for cross-scale scientific research and industrial applications in nano- and microscale.

A sonographic endometrial thickness <7 mm in women undergoing in vitro fertilization increases the risk of placenta accreta spectrum.

BACKGROUND: The prevalence of placenta accreta spectrum, a potentially life-threatening condition, has exhibited a significant global rise in recent decades. Effective screening methods and early identification strategies for placenta accreta spectrum could enable early treatment and improved outcomes. Endometrial thickness plays a crucial role in successful embryo implantation and favorable pregnancy outcomes. Extensive research has been conducted on the impact of endometrial thickness on assisted reproductive technology cycles, specifically in terms of pregnancy rates, live birth rates, and pregnancy loss rates. However, limited knowledge exists regarding the influence of endometrial thickness on placenta accreta spectrum. OBJECTIVE: This study aimed to evaluate the association between preimplantation endometrial thickness and the occurrence of placenta accreta spectrum in women undergoing assisted reproductive technology cycles. STUDY DESIGN: A total of 4637 women who had not undergone previous cesarean delivery and who conceived by in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment and subsequently delivered at the Third Affiliated Hospital of Guangzhou Medical University between January 2008 and December 2020 were included in this study. To explore the relationship between endometrial thickness and placenta accreta spectrum, we used smooth curve fitting, threshold effect, and saturation effect analysis. Multivariate logistic regression analysis was performed to evaluate the independent association between endometrial thickness and placenta accreta spectrum while adjusting for potential confounding factors. Propensity score matching was performed to reduce the influence of bias and unmeasured confounders. Furthermore, we used causal mediation effect analysis to investigate the mediating role of endometrial thickness in the relationship between gravidity and ovarian stimulation protocol and the occurrence of placenta accreta spectrum. RESULTS: Among the 4637 women included in this study, pregnancies with placenta accreta spectrum (159; 3.4%) had significantly thinner endometrial thickness (non-placenta accreta spectrum, 10.08±2.04 mm vs placenta accreta spectrum, 8.88±2.21 mm; P<.001) during the last ultrasound before embryo transfer. By using smooth curve fitting, it was found that changes in endometrial thickness had a significant effect on the incidence of placenta accreta spectrum up to a thickness of 10.9 mm, beyond which the effect plateaued. Then, the endometrial thickness was divided into the following 4 groups: ≤7, >7 to ≤10.9, >10.9 to ≤13, and >13 mm. The absolute rates of placenta accreta spectrum in each group were 11.91%, 3.73%, 1.35%, and 2.54%, respectively. Compared with women with an endometrial thickness from 10.9 to 13 mm, the odds of placenta accreta spectrum increased from an adjusted odds ratio of 2.27 (95% confidence interval, 1.33-3.86) for endometrial thickness from 7 to 10.9 mm to an adjusted odds ratio of 7.15 (95% confidence interval, 3.73-13.71) for endometrial thickness <7 mm after adjusting for potential confounding factors. Placenta previa remained as an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 11.80; 95% confidence interval, 7.65-18.19). Moreover, endometrial thickness <7 mm was still an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 3.91; 95% confidence interval, 1.57-9.73) in the matched cohort after PSM. Causal mediation analysis revealed that approximately 63.9% of the total effect of gravidity and 18.6% of the total effect of ovarian stimulation protocol on placenta accreta spectrum were mediated by endometrial thickness. CONCLUSION: The findings of our study indicate that thin endometrial thickness is an independent risk factor for placenta accreta spectrum in women without previous cesarean delivery undergoing assisted reproductive technology treatment. The clinical significance of this risk factor is slightly lower than that of placenta previa. Furthermore, our results demonstrate that endometrial thickness plays a significant mediating role in the relationship between gravidity or ovarian stimulation protocol and placenta accreta spectrum.

Far-UVC Photolysis of Peroxydisulfate for Micropollutant Degradation in Water.

Increasing radical yields to reduce UV fluence requirement for achieving targeted removal of micropollutants in water would make UV-based advanced oxidation processes (AOPs) less energy demanding in the context of United Nations' Sustainable Development Goals and carbon neutrality. We herein demonstrate that, by switching the UV radiation source from conventional low-pressure UV at 254 nm (UV254) to emerging Far-UVC at 222 nm (UV222), the fluence-based concentration of HO• in the UV/peroxydisulfate (UV/PDS) AOP increases by 6.40, 2.89, and 6.00 times in deionized water, tap water, and surface water, respectively, with increases in the fluence-based concentration of SO4•- also by 5.06, 5.81, and 55.47 times, respectively. The enhancement to radical generation is confirmed using a kinetic model. The pseudo-first-order degradation rate constants of 16 micropollutants by the UV222/PDS AOP in surface water are predicted to be 1.94-13.71 times higher than those by the UV254/PDS AOP. Among the tested water matrix components, chloride and nitrate decrease SO4•- but increase HO• concentration in the UV222/PDS AOP. Compared to the UV254/PDS AOP, the UV222/PDS AOP decreases the formation potentials of carbonaceous disinfection byproducts (DBPs) but increases the formation potentials of nitrogenous DBPs.

Membrane fusion and drug delivery with carbon nanotube porins.

Drug delivery mitigates toxic side effects and poor pharmacokinetics of life-saving therapeutics and enhances treatment efficacy. However, direct cytoplasmic delivery of drugs and vaccines into cells has remained out of reach. We find that liposomes studded with 0.8-nm-wide carbon nanotube porins (CNTPs) function as efficient vehicles for direct cytoplasmic drug delivery by facilitating fusion of lipid membranes and complete mixing of the membrane material and vesicle interior content. Fusion kinetics data and coarse-grained molecular dynamics simulations reveal an unusual mechanism where CNTP dimers tether the vesicles, pull the membranes into proximity, and then fuse their outer and inner leaflets. Liposomes containing CNTPs in their membranes and loaded with an anticancer drug, doxorubicin, were effective in delivering the drug to cancer cells, killing up to 90% of them. Our results open an avenue for designing efficient drug delivery carriers compatible with a wide range of therapeutics.

Study on the spatiotemporal distribution of algal blooms and its influencing factors in young reservoirs based on remote sensing interpretation.

Algal blooms caused by excessive proliferation of phytoplankton in young reservoirs have been frequently reported, seriously threatening the unstable aquatic ecosystem, water quality safety and public health. Thus, there is an urgent need to investigate the dynamics of phytoplankton in these young reservoirs, and many current studies on phytoplankton in young reservoirs are based on point monitoring information. This study used remote sensing interpretation to invert the chlorophyll-a concentration in 131 images of Zipingpu Reservoir from 2013 to 2021, and analyzed the spatiotemporal characteristics of algal blooms. Partial least squares-structural equation modeling was used to identify the environmental influencing factors of algal blooms. The results showed that the average chlorophyll-a concentration in the reservoir was 4.49 mg/m3, and the frequency of algal blooms was 28%. The maximum area of algal blooms shows a significant increase trend in the interannual (increase by 0.05%/yr in the proportion of water surface area), and the average blooms area shows a weaker increase trend (0.01%/yr). The prone period of algal bloom is from April to August every year. The solar duration and wind speed had significant direct positive effects on the maximum and average algal bloom area, which was the similar effects in different years and months (path coefficient exceeds 0.44). TP also has a significant direct positive effect on the average algal bloom area between different years (path coefficient of 0.30). The suitable meteorological factors level making the bloom-prone period from April to August, the prevailing westerly and southerly winds provide transport for the aggregation of phytoplankton and algal blooms outbreak in the northeastern waters. This study expand the monitoring frequency and spatial information of algal blooms, which provided a reference for young reservoir management and prevention of blooms.

Intra-Beam Interference Mitigation for the Downlink Transmission of the RIS-Assisted Hybrid Millimeter Wave System.

Millimeter-wave (mmWave) communication systems leverage the directional beamforming capabilities of antenna arrays equipped at the base stations (BS) to counteract the inherent high propagation path loss characteristic of mmWave channels. In downlink mmWave transmissions, i.e., from the BS to users, distinguishing users within the same beam direction poses a significant challenge. Additionally, digital baseband precoding techniques are limited in their ability to mitigate inter-user interference within identical beam directions, representing a fundamental constraint in mmWave downlink transmissions. This study introduces an innovative analog beamforming-based interference mitigation strategy for downlink transmissions in reconfigurable intelligent surface (RIS)-assisted hybrid analog-digital (HAD) mmWave systems. This is achieved through the joint design of analog beamformers and the corresponding coefficients at both the RIS and the BS. We first present derived closed-form approximation expressions for the achievable rate performance in the proposed scenario and establish a stringent upper bound on this performance in a large number of RIS elements regimes. The exclusive use of analog beamforming in the downlink phase allows our proposed transmission algorithm to function efficiently when equipped with low-resolution analog-to-digital/digital-to-analog converters (A/Ds) at the BS. The energy efficiency of the downlink transmission is evaluated through the deployment of six-bit A/Ds and six-bit pulse-amplitude modulation (PAM) signals across varying numbers of activated RIS elements. Numerical simulation results validate the effectiveness of our proposed algorithms in comparison to various benchmark schemes.

Advances in Adjoint Functions of Connection Number in Water Resources Complex Systems: A Systematic Review.

The adjoint function of connection number has unique advantages in solving uncertainty problems of water resource complex systems, and has become an important frontier and research hotspot in the uncertainty research of water resource complex problems. However, in the rapid evolution of the adjoint function, some problems greatly limit the application of the adjoint function in the research of water resources. Therefore, based on bibliometric analysis, development, practical application issues, and prospects of the hot directions are analyzed. It is found that the development of the connection number of water resource set pair analysis can be divided into three stages: (1) relatively sluggish development before 2005, (2) a period of rapid advancement in adjoint function research spanning from 2005 to 2017, and (3) a subsequent surge post-2018. The introduction of the adjoint function of connection number promotes the continuous development of set pair analysis of water resources. Set pair potential and partial connection number are the crucial research directions of the adjoint function. Subtractive set pair potential has rapidly developed into a relatively independent and important trajectory. The research on connection entropy is comparatively less, which needs to be further strengthened, while that on adjacent connection number is even less. The adjoint function of set pair potential can be divided into three major categories: division set pair potential, exponential set pair potential, and subtraction set pair potential. The subtraction set pair potential, which retains the original dimension and quantity variation range of the connection number, is widely used in water resources and other fields. Coupled with the partial connection number, a series of new connection number adjoint functions have been developed. The partial connection number can be mainly divided into two categories: total partial connection number, and semi-partial connection number. Among these, the calculation expression and connotation of total partial connection numbers have not yet reached a consensus, accompanied by the slow development of high-order partial connection numbers. Semi-partial connection number can describe the mutual migration movement between different components of the connection number, which develops rapidly. With the limitations and current situation described above, promoting the exploration and application of the adjoint function of connection number in the field of water resources and other fields of complex systems has become the focus of future research.

Connection number based model for coordination development evaluation of regional water resources, social economy and ecological environment complex system.

The development of social economy often requires a large consumption of water resources, and will also discharge a large amount of pollutants to the environment. Currently, the rapid development of regional water resources, social economy and ecological environment (WSE) complex system encounters significant challenges, and the coordination development of WSE complex system becomes important and necessary condition of regional sustainable development. Therefore, to scientifically evaluate the coordination development state of WSE system, based on the establishment of evaluation index system, the connection number and distance coordination model coupling approach for the coordination development evaluation of WSE complex system was proposed in this manuscript. The application results of the proposed method in Anhui Province, China indicate that, during 2011-2020, the coordination level of Anhui province is relatively high, and the coordination grade of most cities are in grade I or II. The coordination development degree of Anhui province presented a distinct improving trend with time, from most cities in grade IV or V in 2011 to most cities in grade II in 2020, from the worst 0.0580 in 2011 to the best 0.9200 in 2020. In terms of space, the coordinated development level of southern Anhui is higher than that of northern Anhui. Meanwhile, the coordination development status of the 16 cities in Anhui province can be divided into three patterns according to its historical variation characteristics, i.e., coordination development mode, ecological environment backward mode, and social and economic backward mode. Compared with the commonly used coordination evaluation method, the method of this paper can solve the problem of homogenization, and its calculation results are more reasonable and practical.

NDVI-based spatial and temporal vegetation trends and their response to precipitation and temperature changes in the Mu Us Desert from 2000 to 2019.

This paper explores the relationship between normalized vegetation index (NDVI) response to precipitation and temperature conditions by analyzing the spatial and temporal variation of vegetation cover (NDVI) in Mu Us Desert during 2000-2019. MODIS vegetation indices are designed to provide consistent spatial and temporal comparisons of vegetation conditions. Maximum Value Composites (MVC) is an internationally used statistical method for NDVI data. Based on MODIS remote sensing data, the NDVI of Mu Us Desert sandy land from 2000 to 2019 was analyzed by using the linear regression slope method. In 2000-2010 and 2010-2019, there was a difference in the change rate of vegetation index in Mu Us Desert, with the average slope of 0.0650/10a for the former and 0.0782/10a for the latter. The trends of NDVI values in the study area during 2000-2019 were roughly the same as those of precipitation, and slightly different from those of temperature, but the overall correlation between NDVI values and both was good. There is a significant positive correlation between NDVI and annual precipitation (0.687), and a weak correlation with temperature (0.264). The vegetation growth in Mu Us Desert is affected by both precipitation and temperature.

Phospholipase D- and phosphatidic acid-mediated phospholipid metabolism and signaling modulate symbiotic interaction and nodulation in soybean (Glycine max).

Symbiotic rhizobium-legume interactions, such as root hair curling, rhizobial invasion, infection thread expansion, cell division and proliferation of nitrogen-fixing bacteroids, and nodule formation, involve extensive membrane synthesis, lipid remodeling and cytoskeleton dynamics. However, little is known about these membrane-cytoskeleton interfaces and related genes. Here, we report the roles of a major root phospholipase D (PLD), PLDα1, and its enzymatic product, phosphatidic acid (PA), in rhizobium-root interaction and nodulation. PLDα1 was activated and the PA content transiently increased in roots after rhizobial infection. Levels of PLDα1 transcript and PA, as well as actin and tubulin cytoskeleton-related gene expression, changed markedly during root-rhizobium interactions and nodule development. Pre-treatment of the roots of soybean seedlings with n-butanol suppressed the generation of PLD-derived PA, the expression of early nodulation genes and nodule numbers. Overexpression or knockdown of GmPLDα1 resulted in changes in PA levels, glycerolipid profiles, nodule numbers, actin cytoskeleton dynamics, early nodulation gene expression and hormone levels upon rhizobial infection compared with GUS roots. The transcript levels of cytoskeleton-related genes, such as GmACTIN, GmTUBULIN, actin capping protein 1 (GmCP1) and microtubule-associating protein (GmMAP1), were modified in GmPLDα1-altered hairy roots compared with those of GUS roots. Phosphatidic acid physically bound to GmCP1 and GmMAP1, which could be related to cytoskeletal changes in rhizobium-infected GmPLDα1 mutant roots. These data suggest that PLDα1 and PA play important roles in soybean-rhizobium interaction and nodulation. The possible underlying mechanisms, including PLDα1- and PA-mediated lipid signaling, membrane remodeling, cytoskeleton dynamics and related hormone signaling, are discussed herein.

Drought identification based on Palmer drought severity index and return period analysis of drought characteristics in Huaibei Plain China.

The threshold level method for drought identification is challenging due to the problems of selection of drought index reflecting the drought process associated with water supply and demand as well as the underlying physical meaning of drought thresholds. The frequently used hydrological drought indices (e.g., runoff) are susceptible to being affected by human activities, and drought characteristics are incapable of revealing spatial and temporal comparability. Furthermore, the drought process with the same severity but a longer duration is more likely to be evaluated as a more severe event, which contradicts the actual drought situation. In this study, the Palmer drought severity index (PDSI) method, in which the meteorological factors less influenced by human activities were taken as the input, was adopted to determine the dry/wet states and the PDSI value at each period firstly. The dry/wet states were defined with dry period, wet period, transition period, transition period in dry spell, and transition period in a wet spell. Following that, drought identification criteria were established through the dry/wet states and PDSI value according to the consistency of the identified results and the actual drought situations. Particularly, drought severity and peak intensity were taken as drought characteristics in this paper, and the joint return periods of the characteristics were estimated based on the Gumbel-Hougaard copula function. And eventually, a case study was conducted in Huaibei Plain, China. The results showed that the most severe droughts identified by PDSI had a good consistency with the actual drought situations, drought severity and peak intensity were applicable to reflect the drought impacts. It is worth noting that the implications of the joint return period and the relationships among different types of them. The occurrence probability of a multi-characteristic drought event should be calculated by the integration of joint probability density function over the region corresponding to the event of interest, and the joint frequency of drought characteristics should not be used as the occurrence probability of the drought disaster losses greater (or less) than that caused by the drought with the same characteristics. In addition, drought processes identified by PDSI and standardized precipitation indices (SPI) from monthly and seasonal scales were compared, indicating the drought identified results through PDSI are almost consistent with the actual situations.

Quantitative Evaluation and Obstacle Factor Diagnosis of Agricultural Drought Disaster Risk Using Connection Number and Information Entropy.

To promote the application of entropy concepts in uncertainty analysis of water resources complex system, a quantitative evaluation and obstacle factor diagnosis model of agricultural drought disaster risk was proposed using connection number and information entropy. The results applied to Suzhou City showed that the agricultural drought disaster risks in Suzhou during 2007-2017 were all in middle-risk status, while it presented a decreasing trend from 2010. The information entropy values of the difference degree item bI were markedly lower than those of the difference degree b, indicating that bI provided more information in the evaluation process. Furthermore, the status of drought damage sensitivity and drought hazard were improved significantly. Nevertheless, high exposure to drought and weak drought resistance capacity seriously impeded the reduction of risk. Thus, the key to decreasing risk was to maintain the level of damage sensitivity, while the difficulties were to reduce exposure and enhance resistance. In addition, the percentage of the agricultural population, population density, and percentage of effective irrigation area were the main obstacle factors of risk and also the key points of risk control in Suzhou. In short, the results suggest that the evaluation and diagnosis method is effective and conducive to regional drought disaster risk management.

Lipidomic and transcriptomic profiling of developing nodules reveals the essential roles of active glycolysis and fatty acid and membrane lipid biosynthesis in soybean nodulation.

Symbiotic rhizobia-legume interactions are energy-demanding processes, and the carbon supply from host cells that is critically required for nodulation and nitrogen fixation is not fully understood. Investigation of the lipidomic and carbohydrate profiles with the transcriptome of developing nodules revealed highly activated glycolysis, fatty acid (FA), 2-monoacylglycerol (2-MAG), and membrane lipid biosynthesis and transport during nodule development. RNA-sequence profiling of metabolic genes in roots and developing nodules highlighted the enhanced expression of genes involved in the biosynthesis and transport of FAs, membrane lipids, and 2-MAG in rhizobia-soybean symbioses via the RAML-WRI-FatM-GPAT-STRL pathway, which is similar to that in legume-arbuscular mycorrhizal fungi symbiosis. The essential roles of the metabolic pathway during soybean nodulation were further supported by analysis of transgenic hairy roots overexpressing soybean GmWRI1b-OE and GmLEC2a-OE. GmLEC2a-OE hairy roots produced fewer nodules, in contrast to GmWRI1b-OE hairy roots. GmLEC2a-OE hairy roots displayed different or even opposite expression patterns of the genes involved in glycolysis and the synthesis of FAs, 2-MAG, TAG, and membrane lipids compared to GmWRI1b-OE hairy roots. Glycolysis, FA and membrane lipid biosynthesis were repressed in GmLEC2a-OE but increased in GmWRI1b-OE hairy roots, which may account for the reduced nodulation in GmLEC2a-OE hairy roots but increased nodulation in GmWRI1b-OE hairy roots. These data show that active FA, 2-MAG and membrane lipid biosynthesis are essential for nodulation and rhizobia-soybean symbioses. These data shed light on essential and complex lipid metabolism for soybean nodulation and nodule development, laying the foundation for the future detailed investigation of soybean nodulation.

PtBRI1.2 promotes shoot growth and wood formation through a brassinosteroid-mediated PtBZR1-PtWNDs module in poplar.

Brassinosteroid-insensitive-1 (BRI1) plays important roles in various signalling pathways controlling plant growth and development. However, the regulatory mechanism of BRI1 in brassinosteroid (BR)-mediated signalling for shoot growth and wood formation in woody plants is largely unknown. In this study, PtBRI1.2, a brassinosteroid-insensitive-1 gene, was overexpressed in poplar. Shoot growth and wood formation of transgenic plants were examined and the regulatory genes involved were verified. PtBRI1.2 was localized to the plasma membrane, with a predominant expression in leaves. Ectopic expression of PtBRI1.2 in Arabidopsis bri1-201 and bri1-5 mutants rescued their retarded-growth phenotype. Overexpression of PtBRI1.2 in poplar promoted shoot growth and wood formation in transgenic plants. Further studies revealed that overexpression of PtBRI1.2 promoted the accumulation of PtBZR1 (BRASSINAZOLE RESISTANT1) in the nucleus, which subsequently activated PtWNDs (WOOD-ASSOCIATED NAC DOMAIN transcription factors) to up-regulate expression of secondary cell wall biosynthesis genes involved in wood formation. Our results suggest that PtBRI1.2 plays a crucial role in regulating shoot growth and wood formation by activating BR signalling.

Petroleum extract of Farfarae Flos alleviates nasal symptoms by regulating the Th1-Th2 cytokine balance in a mouse model of Allergic Rhinitis.

Farfarae Flos is a traditional Chinese medicine that has long been used to treat allergies. In this study, we aimed to investigate the effect of a petroleum extract of Farfarae Flos (PEFF) in a mouse model of allergic rhinitis (AR) and to explore the underlying molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with ovalbumin (OVA). PEFF was administered intranasally and AR nasal symptoms were assessed on a semi-quantitative scale according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The mechanism of action of PEFF was evaluated by histological analysis of nasal mucosa architecture and inflammatory status; ELISA-based quantification of serum OVA-specific IgE, interferon-γ (IFN-γ), and interleukin-4 (IL-4) concentrations; and immunohistochemical and western blot analysis of T-bet and GATA3 protein expression in nasal mucosa and spleen tissues. The results showed intranasal administration of PEFF alleviated AR symptom scores and reduced both the infiltration of inflammatory cells and tissue damage in the nasal mucosa. PEFF significantly decreased serum concentrations of OVA-specific IgE (P<0.01) and IL-4 (P<0.05) and significantly increased IFN-γ (P<0.01). PEFF also upregulated the expression of T-bet protein (P<0.05) but downregulated GATA3 protein (P<0.05) in nasal mucosa and spleen tissues. In conclusion, PEFF effectively reduces AR nasal symptoms and serum IgE levels in a mouse model and may act by correcting the imbalance between Th1 and Th2 responses.

Comparison of Combined Hemodialysis and Hemoperfusion with Hemoperfusion Alone in 106 Patients with Diabetic Ketoacidosis and Acute Renal Failure: A Retrospective Study from a Single Center in China.

BACKGROUND Acute kidney injury with acute renal failure is associated with severe diabetic ketoacidosis. This retrospective study was conducted at a single center in China and aimed to compare combined hemodialysis and hemoperfusion (hemodialysis+hemoperfusion) with hemoperfusion alone in 106 patients with diabetic ketoacidosis and acute renal failure. MATERIAL AND METHODS The 106 patients were divided into 2 groups according to different dialysis programs, with 53 cases in each group. Hemodialysis was performed using a single-pass 4008S FX8 HeLix-One hollow fiber hemodialyzer (Fresenius Medical Care, St. Wendel, Germany). Hemoperfusion was performed using HA130 resin adsorbents. RESULTS There were no significant differences in terms of sex, age, duration of diabetes, A1c, pH, and admission blood glucose between the 2 groups (P=0.54, 0.564, 0.53, 0.78, 0.82, 0.51). There were no significant differences in fasting blood glucose, blood urea nitrogen, osmotic pressure, and creatinine between the 2 groups before treatment (P=0.146, 0.978, 0.786, 0.983). After treatment, blood urea nitrogen and creatinine in the dual-treatment group were lower than in the control group, and the osmotic pressure was higher than that in the control group (P=0.000, 0.000, 0.000). The dual-treatment group experienced a lower prevalence of dizziness (5.7%), anemia (7.5%), bone pain (7.5%), hypertension (3.8%), and pruritus (5.7%) than the control group (P<0.05). CONCLUSIONS Compared with hemoperfusion alone, hemodialysis+hemoperfusion significantly reduced pruritus and anemia, improved renal function, and was associated with significantly fewer adverse events in patients with diabetic ketoacidosis and acute renal failure.

circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in head and neck. Autophagy and circular RNAs (circRNAs) play critical roles in cancer progression and chemoresistance. However, the function and mechanism of circRNA in autophagy regulation of LSCC remain unclear. METHODS: The autophagy-suppressive circRNA circPARD3 was identified via RNA sequencing of 107 LSCC tissues and paired adjacent normal mucosal (ANM) tissues and high-content screening. RT-PCR, Sanger sequencing, qPCR and fluorescence in situ hybridization were performed to detect circPARD3 expression and subcellular localization. Biological functions of circPARD3 were assessed by proliferation, migration, invasion, autophagic flux, and chemoresistance assays using in vitro and in vivo models. The mechanism of circPARD3 was investigated by RNA immunoprecipitation, RNA pulldown, luciferase reporter assays, western blotting and immunohistochemical staining. RESULTS: Autophagy was inhibited in LSCC, and circPARD3 was upregulated in the LSCC tissues (n = 100, p < 0.001). High circPARD3 level was associated with advanced T stages (p < 0.05), N stages (p = 0.001), clinical stages (p < 0.001), poor differentiation degree (p = 0.025), and poor prognosis (p = 0.002) of LSCC patients (n = 100). Functionally, circPARD3 inhibited autophagy and promoted LSCC cell proliferation, migration, invasion and chemoresistance. We further revealed that activation of the PRKCI-Akt-mTOR pathway through sponging miR-145-5p was the main mechanism of circPARD3 inhibited autophagy, promoting LSCC progression and chemoresistance. CONCLUSION: Our study reveals that the novel autophagy-suppressive circPARD3 promotes LSCC progression and chemoresistance through the PRKCI-Akt-mTOR pathway, providing new insights into circRNA-mediated autophagy regulation and potential biomarker and target for LSCC treatment.

Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown. METHODS: RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C, let-7c-5p, and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry. RESULTS: circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3, which promoted the epithelial-mesenchymal transition and finally facilitated the malignant progression of LSCC. CONCLUSIONS: circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.