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International audience; To guarantee the blue skies for the 2022 Winter Olympics held in Beijing and Zhangjiakou from February 4 to 20, Beijing and its surrounding areas adopted a series of emission control measures. This provides an opportunity to determine the impacts of large-scale temporary control measures on the air quality in Beijing during this special period. Here, we applied the WRF-CMAQ model to quantify the contributions of emission reduction measures and meteorological conditions. Results show that meteorological conditions in 2022 decreased PM2.5 in Beijing by 6.9 and 11.8 μg/m3 relative to 2021 under the scenarios with and without emission reductions, respectively. Strict emission reduction measures implemented in Beijing and seven neighboring provinces resulted in an average decrease of 13.0 μg/m3 (-41.2%) in PM2.5 in Beijing. Over the entire period, local emission reductions contributed more to good air quality in Beijing than nonlocal emission reductions. Under the emission reduction scenario, local, controlled regions, other regions, and boundary conditions contributed 47.7%, 42.0%, 5.3%, and 5.0% to the PM2.5 concentrations in Beijing, respectively. The results indicate that during the cleaning period with the air masses from the northwest, the abatements of PM2.5 were mainly caused by local emission reductions. However, during the potential pollution period with the air masses from the east-northeast and west-southwest, the abatements of PM2.5 were caused by both local and nonlocal emission reductions almost equally. This implies that regional coordinated prevention and control strategies need to be arranged scientifically and rationally when heavy pollution events are forecasted.

We study the classical expander codes, introduced by Sipser and Spielman [M. Sipser and D. A. Spielman, 1996]. Given any constants 0 < ��, �� < 1/2, and an arbitrary bipartite graph with N vertices on the left, M < N vertices on the right, and left degree D such that any left subset S of size at most �� N has at least (1-��)|S|D neighbors, we show that the corresponding linear code given by parity checks on the right has distance at least roughly {�� N}/{2 ��}. This is strictly better than the best known previous result of 2(1-��) �� N [Madhu Sudan, 2000; Viderman, 2013] whenever �� < 1/2, and improves the previous result significantly when �� is small. Furthermore, we show that this distance is tight in general, thus providing a complete characterization of the distance of general expander codes. Next, we provide several efficient decoding algorithms, which vastly improve previous results in terms of the fraction of errors corrected, whenever �� < 1/4. Finally, we also give a bound on the list-decoding radius of general expander codes, which beats the classical Johnson bound in certain situations (e.g., when the graph is almost regular and the code has a high rate). Our techniques exploit novel combinatorial properties of bipartite expander graphs. In particular, we establish a new size-expansion tradeoff, which may be of independent interests., LIPIcs, Vol. 215, 13th Innovations in Theoretical Computer Science Conference (ITCS 2022), pages 43:1-43:3

Fish are often faced with selection pressure from human activities (e.g., fish angling). Therefore, morphological, physiological, personality, and life history characteristics have evolved directly in fish populations under this human-made selection. Here, we investigate the phenotypic basis of vulnerability to angling in juvenile Qingbo (Spinibarbus sinensis). The standard metabolic rate (SMR), maximum metabolic rate (MMR), and personality (i.e., exploration, activity and boldness) of juvenile S. sinensis were determined. An angling experiment was then conducted and the hormones (i.e., ghrelin) of the individuals were examined in a laboratory at 24.9 ± 0.1 °C. Our results showed that only frequency with which the fish touched the novel object in exploration was higher in the LVA (low vulnerability to angling) phenotype than the HVA (high vulnerability to angling) phenotype, but energy metabolism (SMR; MMR; AS, aerobic scope; FAS, factorial aerobic scope), hormone (ghrelin levels) and personality (exploration, activity and boldness) did not differ between the HVA and the LVA phenotype. Principal components analysis showed that exploration was associated with boldness while activity was not associated with boldness. The AS, exploration and boldness score were inhibitory factors for the HVA outcomes, but ghrelin, activity score and exploration score did not contribute to outcomes of the HVA. These results suggest that energy metabolism, hormone levels and personality are not predictors of vulnerability to angling in Qingbo under the laboratory condition, but individuals with higher tendency to explore the novel environment are more likely to be bolder.

As a robust antagonist of myostatin (MSTN), follistatin (FST) is an important regulator of skeletal muscle development, and the delivery of FST to muscle tissue represents a potential therapeutic strategy for muscular dystrophies. The N terminus and FSI domain of FST are the functional domains for MSTN binding. Here, we aimed to achieve site-specific integration of FSI-I-I, including the signal peptide, N terminus, and three FSI domains, into the last codon of the porcine MSTN gene using a homology-mediated end joining (HMEJ)-based strategy mediated by CRISPR-Cas9. Based on somatic cell nuclear transfer (SCNT) technology, we successfully obtained FSI-I-I knockin pigs. H&E staining of longissimus dorsi and gastrocnemius cross-sections showed larger myofiber sizes in FSI-I-I knockin pigs than in controls. Moreover, the Smad and Erk pathways were inhibited, whereas the PI3k/Akt pathway was activated in FSI-I-I knockin pigs. In addition, the levels of MyoD, Myf5, and MyoG transcription were upregulated while that of MRF4 was downregulated in FSI-I-I knockin pigs. These results indicate that the FSI-I-I gene mediates skeletal muscle hypertrophy through an MSTN-related signaling pathway and the expression of myogenic regulatory factors. Overall, FSI-I-I knockin pigs with hypertrophic muscle tissue hold great promise as a therapeutic model for human muscular dystrophies., Graphical abstract, The FSI-I-I, including the signal peptide, N terminus, and three FSI domains of FST, were site-specifically integrated into the last codon of the MSTN gene in porcine using a HMEJ-based strategy mediated by CRISPR-Cas9. The FSI-I-I knockin pigs obtained based on somatic cell nuclear transfer exhibited increased skeletal muscle mass.

Increasing evidences showed that ovulatory dysfunction, possibly caused by luteinized unruptured follicular follicle syndrome (LUFS), is one of the reasons for endometriosis-related infertility. The present study was conducted to explore the potential effect of elevated progesterone in follicular fluid (FF) on ovulation in endometriosis. A prospective study including 50 ovarian endometriosis patients and 50 control patients with matched pairs design was conducted with alterations in FF and peritoneal fluid (PF) components identified by metabolomics analyses and differentially expressed genes in granulosa cells (GCs) identified by transcriptome analysis. Patients with endometriosis exhibited a significantly higher progesterone level in serum, FF, and PF. Granulosa cells from endometriosis patients revealed decreased expression of HPGD, COX-2, and suppressed NF-ĸB signaling. Similarly, progesterone treatment in vitro downregulated HPGD and COX2 expression and suppressed NF-ĸB signaling in granulosa tumor-like cell line KGN (Bena Culture Collection, China) and primarily cultured GCs, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIĸBα/IĸBα ratio, and nucleus translocation of p65. On the contrary, TNF-α treatment increased expression of IL1R1, IRAK3, pIĸBα, p65, and HPGD in GCs. One potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation. In conclusion, we found that intrafollicular progesterone might downregulate HPGD and COX-2 in GCs via suppressing the NF-ĸB signaling pathway, shedding light on the mechanism underlying the endometriosis-related ovulatory dysfunction.

Major depressive disorder (MDD) refers to a widespread psychiatric disorder. Astrocytes play a pivotal role in regulating inflammation which is a well-acknowledged key component in depression pathogenesis. However, the effects of the neuroinflammation-inducing A1-like astrocytes on MDD are still unknown. TWIK-related K+ channel 1 (TREK-1) has been demonstrated to regulate the action of antidepressants. Nevertheless, its mechanisms and effects on A1-like astrocyte stimulation in MDD are not clear. Therefore, we conducted in vivo and in vitro experiments using TREK-1 specific inhibitor spadin. In vivo, rats were subjected to a 6-week chronic unpredictable mild stress (CUMS) followed by spadin treatment. Behavioral tests were employed to surveil depressive-like behaviors. Hippocampal proteomic analysis was carried out with the purpose of identifying differentially expressed proteins after CUMS and spadin treatments. In vitro, astrocyte-conditioned medium and spadin were used to treat rat astrocyte cell line. The activated microglia, inflammatory factors, A1 astrocyte markers, and activated nuclear factor kappa B (NF-κB) pathway were later analyzed using immunofluorescence, western blot, and RT-qPCR. Our findings indicated that blockage of TREK-1 reduced CUMS-induced depressive-like behavior in rats, inhibited the microglial stimulation, reduced inflammatory factor levels, and suppressed the activation of A1-like reactive astrocytes in the hippocampus. We also verified that the suppression of A1-like astrocytes by spadin necessitated the NF-κB pathway. According to the findings, blocking TREK-1 inhibited the activation of A1-like reactive astrocytes via the NF-κB signaling pathway in MDD. Our study preliminarily identifies a novel antidepressant mechanism of TREK-1 action and provides a therapeutic path for MDD.

Data collection underlocal differential privacy (LDP)has been gradually on the stage. Compared with the implementation of LDP on the single attribute data collection, that on multi-dimensional data faces great challenges as follows: (1)Communication cost. Multivariate data collection needs to retain the correlations between attributes, which means that more complex privatization mechanisms will result in more communication costs. (2)Noise scale. More attributes have to share the privacy budget limited by data utility and privacy-preserving level, which means that less privacy budget can be allocated to each of them, resulting in more noise added to the data. In this work, we innovatively reverse the complex multi-dimensional attributes, i.e., the majornegativefactor that leads to the above difficulties, to act as abeneficialfactor to improve the efficiency of privacy budget allocation, so as to realize a multi-dimensional data collection under LDP with high comprehensive performance. Specifically, we first present aMultivariatek-ary Randomized Response (kRR)mechanism, calledMulti-kRR. It applies the RR directly to each attribute to reduce the communication cost. To deal with the impact of a large amount of noise, we propose a Markov-based dynamic privacy budget allocation mechanism Markov-kRR, which determines the present privacy budget (flipping probability) of an attribute related to the state of the previous attributes. Then, we fix the threshold of flipping times in Markov-kRR and propose an improved mechanism called MarkFixed-kRR, which can obtain more optimized utility by choosing the suitable threshold. Finally, extensive experiments demonstrate the efficiency and effectiveness of our proposed methods.

A visible-light-induced decarboxylative radical selenocyanation reaction of aliphatic carboxylic acids with the electrophilic N-selenocyanatophthalimide has been developed.

A tandem electrophilic thiocyanation/carbocyclization of alkynes has been developed, affording thiocyanato-substituted phenanthrenes, dihydronaphthalenes, 2H-chromenes and dihydroquinolines in moderate to excellent yields.

A DNA polymerase-powered self-propelled DNA walking strategy is proposed for dual-signal, amplified electrochemical detection of nucleic acids.

Neural systems are shaped by multiple constraints, balancing region communication with the cost of establishing and maintaining physical connections. It has been suggested that the lengths of neural projections be minimized, reducing their spatial and metabolic impact on the organism. However, long-range connections are prevalent in the connectomes across various species, and thus, rather than rewiring connections to reduce length, an alternative theory proposes that the brain minimizes total wiring length through a suitable positioning of regions, termed component placement optimization. Previous studies in nonhuman primates have refuted this idea by identifying a nonoptimal component placement, where a spatial rearrangement of brain regions in silico leads to a reduced total wiring length. Here, for the first time in humans, we test for component placement optimization. We show a nonoptimal component placement for all subjects in our sample from the Human Connectome Project (N = 280; aged 22–30 years; 138 females), suggesting the presence of constraints—such as the reduction of processing steps between regions—that compete with the elevated spatial and metabolic costs. Additionally, by simulating communication between brain regions, we argue that this suboptimal component placement supports dynamics that benefit cognition.

An electrophilic dearomatizative thiocyanation/spirocyclization of benzofurans with N-thiocyanatosuccinimide has been accomplished by Lewis acid catalysis with CuOTf under mild conditions.

On account of the enormous role of various government policies, it is very important and valuable to find remarkable independent variables from many practical factors of influencing American economy via choosing suitable methods and effective "optimal" models or equations. Based on the American economic data in practice, in order to creatively analyze and predict American economy under two different government policies, we analyze the relationship between each factor and the economy and obtain some greater impact factors to American gross domestic product (in short, GDP) by using a class of stepwise regression, and then we give optimal analysis and predict the influence to American GDP via employing support vector machine models. Further, we establish data comparison to provide beneficial reference for choosing from two different government policies. Finally, we propose some work for future research.

Although flexible humidity sensors are essential for human health monitoring, it is still challenging to achieve high sensitivity and easy disposal with simple, low-cost fabrication processes. This study presents the design and fabrication of highly reliable hand-drawn interdigital electrodes from pencil-on-paper treated with NaCl solution for highly sensitive hydration sensors working over a wide range of relative humidity (RH) levels from 5.6% to 90%. The applications of the resulting flexible humidity sensor go beyond the monitoring of respiratory rate and proximity to characterizations of human skin types and evaluations of skin barrier functions through insensible sweat measurements. The sensor array can also be integrated with a diaper to result in smart diapers to alert for an early diaper change. The design and fabrication strategies presented in this work could also be leveraged for the development of wearable, self-powered, and recyclable sensors and actuators in the future.

The association between obstructive sleep apnea (OSA) and cancer risks gaining more and more attention. Data on the association between OSA and lung cancer risk are limited. This study is to investigate whether a link exists between low-dose computed tomography (LDCT) scanning of the chest findings, carcinoembryonic antigen (CEA) and OSA in patients suspected of OSA.The cross-sectional study included patients aged 18 years or older who underwent continuous nocturnal polysomnography at our sleep center between February 2019 and November 2020. All subjects underwent chest LDCT and CEA. Patients with an apnea-hypopnea index (AHI) of ≥ 15/h were classified as clinically significant OSA group, whereas patients with an AHI 15/h were classified as control group.A total of 277 patients were enrolled in the study. 176 patients were categorized into the OSA group, while 101 patients were categorized into the control group. There is no relationship between any OSA-related parameter and presence of lung nodule or presence of ≥ 6 mm lung nodule in the binary logistic regression analysis. OSA group demonstrated a significant higher value of CEA than control group. Stepwise multiple linear regression analysis showed that lowest OOSA was independently related to the elevated of serum CEA level, but not with presence of pulmonary nodule or ≥ 6 mm pulmonary nodule in LDCT. Further well-designed longitudinal studies with pathology available are needed to identify the association between OSA and risk of lung cancer.

In the current paper, we considered the Fisher information matrix from the generalized Rayleigh distribution (GR) distribution in ranked set sampling (RSS). The numerical results show that the ranked set sample carries more information about λ and α than a simple random sample of equivalent size. In order to give more insight into the performance of RSS with respect to (w.r.t.) simple random sampling (SRS), a modified unbiased estimator and a modified best linear unbiased estimator (BLUE) of scale and shape λ and α from GR distribution in SRS and RSS are studied. The numerical results show that the modified unbiased estimator and the modified BLUE of λ and α in RSS are significantly more efficient than the ones in SRS.

Thyroid hormones (THs) regulate multiple physiological activities in the liver, including cellular metabolism, differentiation, and cell growth, and play important roles in the pathogenesis of hepatocellular carcinoma (HCC). Thyroid peroxidase (TPO) is a key molecule involved in the THs synthesis and signaling pathway. As an epigenetic modification, DNA methylation has a critical role in tumorigenesis with diagnostic potential. However, the connection between THs and DNA methylation has been rarely investigated.The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning, and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays, and evaluated their clinical implications.We identified that the methylation of the TPO promoter was downregulated in the HCC tissues (P0.0001) with a mean difference ranging from 18.5% to 22.3%. This methylation pattern correlated with several clinical factors, including a multi-satellite tumor, fibrous capsule, and the presence of tumor thrombus. The receiver operator characteristic (ROC) curve analysis further confirmed that the percent methylated reference (PMR) values for TPO were predictive of the tumor [the area under the curve (AUC) ranged from 0.755 to 0.818] and the thrombosis in the HCC patients (the AUC ranged from 0.706 to 0.777).These findings demonstrated that epigenetic alterations of TPO, as indicated by the PMR values, were a potential biomarker for HCC patients with tumor thrombosis.

Nanocrystals with high drug loading have become a viable strategy for solubilizing drugs with poor aqueous solubility. It remains challenging, however, to synthesize nanocrystals with sufficient stability and targeting potential. Here, we report a novel nanocrystal platform synthesized using paclitaxel (PTX) and Fmoc-8-amino-3,6-dioxaoctanoic acid (Fmoc-AEEA)-conjugated chondroitin sulfate (CS) (CS-Fmoc) via π-π stacking to afford a stable formulation with CD44 targetability (PTX NC@CS-Fmoc). The PTX NC@CS-Fmoc exhibited rodlike shapes with an average hydrodynamic size of 173.6 ± 0.7 nm (PDI = 0.11 ± 0.04) and a drug loading of up to 31.3 ± 0.6%. Next, PTX NC@CS-Fmoc was subjected to lyophilization in the absence of cryoprotectants for long-term storage, and after redispersion, PTX NC@CS-Fmoc displayed an average hydrodynamic size of 205.3 ± 2.9 nm (PDI = 0.15 ± 0.01). In murine Panc02 cells, PTX NC@CS-Fmoc showed higher internalization efficiency than that of PTX nanocrystals without CS modification (PTX NC@F127) (