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We analyze more than 15 yr of γ -ray data obtained with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) for the region of the young supernova remnant (SNR) RCW 103, since the nearby source 4FGL J1616.2−5054e, counterpart to HESS J1616−518 and ≃13′ away from the SNR, is determined to be extended in the more recent Fermi-LAT source catalog. Different templates for 4FGL J1616.2−5054e and RCW 103 are tested, and we find that a point source (PS) with a power-law (PL) spectrum at the southern limb of the SNR best describes the detected γ -ray emission. The photon index of the PL emission is Γ ≃ 2.31 (or α ≃ 2.4 in a log-parabola model), softer than the previously reported Γ ≃ 2.0 when the counterpart to HESS J1616−518 was considered to be a PS (which likely caused misidentification of extended emission at RCW 103). In order to produce the γ -ray emission in a hadronic scenario, we estimate that protons with an index ∼2.4 PL energy distribution are needed. These results fit with those from multiwavelength observations that have indicated the remnant at the southern limb is interacting with a molecular cloud.

We search for possible pulsar TeV halos among the very-high-energy (VHE) sources reported in different VHE surveys, among which in particular we use the results from the first Large High Altitude Air Shower Observatory catalog of γ -ray sources. Six candidates are found. They share similar properties of containing a middle-aged, γ -ray–bright pulsar in their positional error circles (the respective pulsars are J0248+6021, J0359+5414, J0622+3749, J0633+0632, J2006+3102, and J2238+5903), being in a rather clean field without any common Galactic VHE-emitting supernova remnants or (bright) pulsar wind nebulae (PWNe), and showing an absence of any γ -ray emissions in 0.1–500 GeV after removing the pulsars’ emissions. Combining these candidates with several reported (candidate) TeV halos, we obtain relationships between their luminosity at 50 TeV ( L _50TeV ) and the corresponding pulsars’ spin-down energy ( $\dot{E}$ ), which are ${L}_{50\mathrm{TeV}}\sim {\dot{E}}^{0.9}$ and ${L}_{50\mathrm{TeV}}/\dot{E}\sim 6.4\times {10}^{-4}$ , respectively. The relationships are nearly identical to previously reported ones. We probe possible connections between the extent/sizes of the VHE sources and the pulsars’ ages, and find a weak older-and-smaller trend. By comparing to the VHE detection results for PWNe, it is clear that the (candidate) TeV halos have hard emissions by either having power-law indices smaller than 2 in 1–25 TeV or by only being detected in 25–100 TeV. In addition, we also consider seven other VHE sources as possible TeV halos based on the results from different studies of them, but they do not fit cleanly with the properties listed above, indicating their potentially complex nature.

In recent years, the level of digitalization and intelligence in the energy sector has profoundly changed the management mode of the energy sector. However, in the process of promoting the digital transformation of the energy sector, we also face some difficulties. One of the main manifestations is the lack of energy data sharing, and the difficulty of realizing the convergence and integration of various types of energy data. In addition, there is insufficient mastery of customer-side energy use data and a lag in the perception of customer demand, which requires the improvement and enhancement of energy efficiency diagnosis and energy saving services. At the same time, we have not yet established advanced digital technology monitoring means to grasp the user’s energy use and carbon emissions in real time. Therefore, this paper proposes the study of high-precision accounting methods for regional carbon emissions under the carbon peak goal. Based on the energy consumption and production activities of each region, a greenhouse gas emission inventory is compiled, so that carbon emissions can be accurately calculated. The high-precision accounting method of carbon emissions is analyzed, and by establishing a more complete database and model, and constructing a regional online monitoring system under the peak carbon target, we aim to improve the efficiency of data acquisition and processing, as well as how to combine carbon emission accounting with the peak carbon target, in order to provide support for the formulation of a more effective emission reduction policy. The testing experiments after flow and CO2 concentration measurements show that the accuracy of the experiments on regional carbon emissions is as high as 97.5%.

Due to the anisotropy properties of graphite flakes (G _f ), the control of their orientation inside copper (Cu) matrice is strictly correlated with the final properties of such metal matrix composite (MMC). In this study, MMCs are fabricated by powder metallurgy process using three types of Cu powder particles (flake, dendritic, and spherical) as well as different powder filling methods. By using Cu flake powder with a relatively lower apparent density as compared to the two other Cu powder types (dendritic and spherical), high aligned G _f could be easily obtained, after uniaxial hot pressing, in a one-step powder filling approach. For the other two types of powders, a comparable orientation degree of G _f could be achieved only via several steps of delicate powder pressing. In-plane thermal conductivities of Cu/G _f composites were enhanced by improving the orientation degree of G _f , agreeing with effective medium approximation predictions (Maximum TC up to 540 W mK ^−1 ). A modeling, based on the apparent density of Cu powders, was discussed to show the effect of the alignment process on the final thermal property of such MMCs. This model supplies a basic guideline to obtain highly orientated G _f .

The Pacific oyster Crassostrea gigas is one of the most important cultured marine species around the world. Production of Pacific oysters in China has depended primarily on hatchery produced seeds since 2016, with the successful introduction and development of triploid oysters. However, the seed supply of Pacific oysters is threatened by recurring mass mortality events in recent years. Vibriosis is the most commonly encountered disease associated with intensive oyster culture in hatcheries and nurseries. Vibrio alginolyticus and Bacillus hwajinpoensis were the two strains with pathogenic and probiotic effects, respectively, identified during the Pacific oyster larvae production. To monitor their colonization process in Pacific oyster larvae, green fluorescent protein (GFP) and red fluorescent protein (RFP) were labeled to the pathogenic V. alginolyticus and the probiotic B. hwajinpoensis stain, respectively. The pathogenic and probiotic effects of the two strains during the colonization process were then assessed. Stabile expression of GFP and RFP were observed in corresponding stains, and the capabilities of growth, biofilm formation and in vitro adhesion of GFP- and RFP- tagged stains were not significantly different from those of the wild-type strains. Usage of probiotics of 105 CFU/mL significantly inhibited the growth of pathogenic V. alginolyticus and reduced the mortality of D-sharped larvae. Both the pathogenic and probiotic strains employed a similar route to enter and colonize the oyster larvae, which indicates that competing with pathogens for binding and spreading sites were one of the mechanisms of B. hwajinpoensis to provide the probiotic effects to oyster larvae. In summary, employment of fluorescence-tagged pathogenic and probiotic strains simultaneously provides us with an excellent bioassay model to investigate the potential mechanisms of probiotics.

This study investigates the location accuracy distribution of the lightning detection networks (LDNs) deployed on inclined terrains, an aspect frequently encountered in complex terrains but hitherto disregarded in previous studies. By designing eight substation LDNs deployed on slope-type (ST), mountain-type (MT) and basin-type (BT) terrains, respectively, we employed Monte Carlo simulations to analyze their spatial location accuracy distribution based on time-of-arrival technology. Significant differences among the LDNs on inclined terrains and between them and the LDN on plain-type (PT) terrain were revealed. Compared to the PT LDN, LDNs on inclined terrains exhibited a reduction in high-precision location regions and a shift in the distribution pattern of location accuracy. The ST LDN showed marked deviations in the high-precision vertical location toward the lower slope side with increases in the elevation angle and consistently smaller high-precision vertical location areas compared to MT and BT LDNs. The variations in elevation angles of MT and BT LDNs had a substantial impact on the spatial distribution patterns of both horizontal and vertical location accuracy, with BT LDNs featuring larger vertical high-precision areas than MT LDNs. Our conclusions were further corroborated through an analysis of an actual LDN, which combined characteristics from both ST and MT terrain patterns.

Osmanthus fragrans ‘Yinbi Shuanghui’ is a colored leaf variety of O. fragrans. To study the mechanism of leaf color formation in O. fragrans ‘Yinbi Shuanghui’, we selected green and colored leaves with two different parts, namely yellow and green, as our research materials. We analyzed the expression changes related to leaf color in genes by performing qRT-PCR in the different leaf parts, finding that OfPAO was significantly up-regulated in the yellow part of colored leaves, and we initially determined that OfPAO was the key gene involved in the formation of colored leaves. Then, we constructed an OfPAO overexpression vector, before transforming it into tobacco through an Agrobacterium-mediated transformation to obtain transgenic plants. We found that the transgenic tobacco leaf color of OfPAO was lighter than that of the null carrier, the chlorophyll content in leaves decreased, and the expression of genes involved in the chlorophyll degradation pathway in OfPAO transgenic tobacco was up-regulated, suggesting that OfPAO regulates chlorophyll degradation, leading to changes in leaf color. According to the results of transcriptome sequencing and the genome data of O. fragrans ‘Rixianggui’, we cloned CDS and the promoter sequence of OfPAO, and the promoter regions 901-1307 of the OfPAO were sequenced through bisulfite genomic sequencing PCR (BSP), finding that the methylation level of CHH in the yellow part of colored leaves was lowest in colored and green leaves at 145 bp. The methylation of CHH in the promoter of OfPAO in O. fragrans ‘Yinbi Shuanghui’ was negatively correlated with the gene expression level, suggesting that the methylation of the promoter of OfPAO may regulate the expression of OfPAO, affecting chlorophyll degradation in the leaves.

MYCN amplification drives the development of neuronal cancers in children and adults. Given the challenge in therapeutically targeting MYCN directly, we searched for MYCN-activated metabolic pathways as potential drug targets. Here we report that neuroblastoma cells with MYCN amplification show increased transcriptional activation of the serine-glycine-one-carbon (SGOC) biosynthetic pathway and an increased dependence on this pathway for supplying glucose-derived carbon for serine and glycine synthesis. Small molecule inhibitors that block this metabolic pathway exhibit selective cytotoxicity to MYCN-amplified cell lines and xenografts by inducing metabolic stress and autophagy. Transcriptional activation of the SGOC pathway in MYCN-amplified cells requires both MYCN and ATF4, which form a positive feedback loop, with MYCN activation of ATF4 mRNA expression and ATF4 stabilization of MYCN protein by antagonizing FBXW7-mediated MYCN ubiquitination. Collectively, these findings suggest a coupled relationship between metabolic reprogramming and increased sensitivity to metabolic stress, which could be exploited as a strategy for selective cancer therapy. SIGNIFICANCE: This study identifies a MYCN-dependent metabolic vulnerability and suggests a coupled relationship between metabolic reprogramming and increased sensitivity to metabolic stress, which could be exploited for cancer therapy.See related commentary by Rodriguez Garcia and Arsenian-Henriksson, p. 3818.

OBJECTIVES: Chronic hepatitis B (CHB) can progress into liver fibrosis and cirrhosis with poor outcomes. Early and accurate diagnosis of liver fibrosis/cirrhosis is important to guide the preventive strategy of their related complications. METHODS: A Chinese multicenter cross-sectional study was conducted to develop and validate a novel noninvasive program for staging liver fibrosis in untreated patients with CHB. Liver histology was evaluated independently by 2 pathologists. The alanine aminotransferase ratio, Hepascore, and aspartate aminotransferase to platelet index values were calculated. Liver stiffness measurement (LSM) and diameter of the spleen were measured. Logistic regression with ℓ1 penalty of regression coefficients was used to select the optimal predictors. The diagnostic accuracy for the stage of liver fibrosis was assessed by the area under the receiver operator characteristic curve with 95% confidence interval (CI). RESULTS: A total of 1,200 patients with CHB were included, of whom 800 and 400 were in training and validation sets, respectively. LSM, platelets, age, hyaluronic acid, and diameter of the spleen were the top 5 predictors associated with any stage of liver fibrosis and integrated into a novel noninvasive program, named as the Chin-CHB score. The area under the receiver operator characteristic curve of the Chin-CHB score was 0.893 (95% CI: 0.77-0.92) for diagnosing significant fibrosis, 0.897 (95% CI: 0.85-0.95) for advanced fibrosis, and 0.909 (95% CI: 0.87-0.95) for cirrhosis. The diagnostic performance of the Chin-CHB score was similar between training and validation sets. The Chin-CHB score had better diagnostic performance than aspartate aminotransferase to platelet index, alanine aminotransferase ratio, LSM alone, and Hepascore for diagnosing any stage of liver fibrosis. CONCLUSIONS: The Chin-CHB score had good diagnostic performance for any stage of liver fibrosis.

Autophagy is important for hepatic homeostasis, nutrient regeneration, and organelle quality control. We investigated the mechanisms by which liver injury occurred in the absence of autophagy function. We found that mice deficient in autophagy because of the lack of autophagy-related gene 7 or autophagy-related gene 5, key autophagy-related genes, manifested intracellular cholestasis with increased levels of serum bile acids, a higher ratio of tauromuricholic acid/taurocholic acid in the bile, increased hepatic bile acid load, abnormal bile canaliculi, and altered expression of hepatic transporters. In determining the underlying mechanism, we found that autophagy sustained and promoted the basal and up-regulated expression of farnesoid X receptor (Fxr) in the fed and starved conditions, respectively. Consequently, expression of Fxr and its downstream genes, particularly bile salt export pump, and the binding of FXR to the promoter regions of these genes, were suppressed in autophagy-deficient livers. In addition, codeletion of nuclear factor erythroid 2-related factor 2 (Nrf2) in autophagy deficiency status reversed the FXR suppression. Furthermore, the cholestatic injury of autophagy-deficient livers was reversed by enhancement of FXR activity or expression, or by Nrf2 deletion. Conclusion: Together with earlier reports that FXR can suppress autophagy, our findings indicate that autophagy and FXR form a regulatory loop and deficiency of autophagy causes abnormal FXR functionality, leading to the development of intracellular cholestasis and liver injury.

Abstract Background Calpains are a family of calcium-dependent thiol proteases that participate in a wide variety of biological activities. In our recent study, calpain is increased in the sera of scleroderma or systemic sclerosis (SSc). However, the role of calpain in interstitial lung disease (ILD) has not been reported. ILD is a severe complication of SSc, which is the leading cause of death in SSc. The pathogenesis of SSc-related ILD remains incompletely understood. This study investigated the role of myeloid cell calpain in SSc-related ILD. Methods A novel line of mice with myeloid cell-specific deletion of Capns1 (Capns1-ko) was created. SSc-related ILD was induced in Capns1-ko mice and their wild-type littermates by injection 0.l mL of bleomycin (0.4 mg/mL) for 4 weeks. In a separate experiment, a pharmacological inhibitor of calpain PD150606 (Biomol, USA, 3 mg/kg/day, i.p.) daily for 30 days was given to mice after bleomycin injection on daily basis. At the end of the experiment, the animals were killed, skin and lung tissues were collected for the following analysis. Inflammation, fibrosis and calpain activity and cytokines were assessed by histological examinations and ELISA, and immunohistochemical analyses, western blot analysis and Flow cytometry analysis. Results Calpain activities increased in SSc-mouse lungs. Both deletion of Capns1 and administration of PD150606 attenuated dermal sclerosis as evidenced by a reduction of skin thickness and reduced interstitial fibrosis and inflammation in bleomycin model of SSc mice. These effects of reduced calpain expression or activity were associated with prevention of macrophage polarization toward M1 phenotype and consequent reduced production of pro-inflammatory cytokines including TNF-α, IL-12 and IL-23 in lung tissues of Capns1-ko mice with bleomycin model of SSc. Furthermore, inhibition of calpain correlated with an increase in the protein levels of PI3K and phosphorylated AKT1 in lung tissues of the bleomycin model of SSc mice. Conclusions This study for the first time demonstrates that the role of myeloid cell calpain may be promotion of macrophage M1 polarization and pro-inflammatory responses related PI3K/AKT1 signaling. Thus, myeloid cell calpain may be a potential therapeutic target for bleomycin model of SSc-related ILD.

Multichannel metasurfaces become one of the most significant development trends, as they exhibit versatile manipulation abilities on electromagnetic fields and provide a promising approach to constitute compact devices with various complex functions, especially in optical encryption due to its capabilities of multichannel, high complexity, and high concealment. However, the existent multichannel metasurfaces based optical encryption technology can only realize two channels in the near-field, or perform three channels in near- and far-field. In this paper, a four-channel display metasurface used to encrypt information by three optical parameters as security keys is firstly proposed and experimentally demonstrated, which is different from the previous three-channel metasurface combined nanoprinting and hologram in near- and far-field. The novel design strategy of the four-channel metasurface can effectively enhance the information capacity and increase the difficulty of leaks without causing manufacturing challenges and additional costs. In addition, the simulation and experimental results demonstrate that the designed metasurface with four independent channels can separately display distinguishable nanoprinting images under decoding keys of special optical parameters. The proposed four-channel display metasurface with advantages of high capacity and ultracompactness will pave a way for multichannel applications in nano display, information storage, optical anticounterfeiting, and other relevant fields.

Abstract Background The use of beneficial microorganisms as an alternative for pest control has gained increasing attention. The objective of this study was to screen beneficial rhizosphere bacteria with the ability to enhance tomato anti-herbivore resistance. Results Rhizosphere bacteria in tomato field from Fuqing, one of the four locations where rhizosphere bacteria were collected in Fujian, China, enhanced tomato resistance against the tobacco cutworm Spodoptera litura, an important polyphagous pest. Inoculation with the isolate T6–4 obtained from the rhizosphere of tomato field in Fuqing reduced leaf damage and weight gain of S. litura larvae fed on the leaves of inoculated tomato plants by 27% in relative to control. Analysis of 16S rRNA gene sequence identities indicated that the isolate T6–4 was closely related to Stenotrophomonas rhizophila supported with 99.37% sequence similarity. In the presence of S. litura infestation, inoculation with the bacterium led to increases by a 66.9% increase in protease inhibitor activity, 53% in peroxidase activity and 80% in polyphenol oxidase activity in the leaves of inoculated plants as compared to the un-inoculated control. Moreover, the expression levels of defense-related genes encoding allene oxide cyclase (AOC), allene oxide synthase (AOS), lipoxygenase D (LOXD) and proteinase inhibitor (PI-II) in tomato leaves were induced 2.2-, 1.7-, 1.4- and 2.7-fold, respectively by T6–4 inoculation. Conclusion These results showed that the tomato rhizosphere soils harbor beneficial bacteria that can systemically induce jasmonate-dependent anti-herbivore resistance in tomato plants.

Background: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma cells. In the development of MM, almost all patients undergo a relatively benign course from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM), which further progresses to active myeloma. However, the prognostic value of cuproptosis in MM remains unknown.Method: In this study, we systematically investigated the genetic variants, expression patterns, and prognostic value of cuproptosis-related genes (CRGs) in MM. CRG scores derived from the prognostic model were used to perform the risk stratification of MM patients. We then explored their differences in clinical characteristics and immune patterns and assessed their value in prognosis prediction and treatment response. Nomograms were also developed to improve predictive accuracy and clinical applicability. Finally, we collected MM cell lines and patient samples to validate marker gene expression by quantitative real-time PCR (qRT-PCR).Results: The evolution from MGUS and SMM to MM was also accompanied by differences in the CRG expression profile. Then, a well-performing cuproptosis-related risk model was developed to predict prognosis in MM and was validated in two external cohorts. The high-risk group exhibited higher clinical risk indicators. Cox regression analyses showed that the model was an independent prognostic predictor in MM. Patients in the high-risk group had significantly lower survival rates than those in the low-risk group (p < 0.001). Meanwhile, CRG scores were significantly correlated with immune infiltration, stemness index and immunotherapy sensitivity. We further revealed the close association between CRG scores and mitochondrial metabolism. Subsequently, the prediction nomogram showed good predictive power and calibration. Finally, the prognostic CRGs were further validated by qRT-PCR in vitro.Conclusion: CRGs were closely related to the immune pattern and self-renewal biology of cancer cells in MM. This prognostic model provided a new perspective for the risk stratification and treatment response prediction of MM patients.

Abstract Background The grass carp has great economic value and occupies an important evolutionary position. Genomic information regarding this species could help better understand its rapid growth rate as well as its unique body plan and environmental adaptation. Results We assembled the chromosome-level grass carp genome using the PacBio sequencing and chromosome structure capture technique. The final genome assembly has a total length of 893.2 Mb with a contig N50 of 19.3 Mb and a scaffold N50 of 35.7 Mb. About 99.85% of the assembled contigs were anchored into 24 chromosomes. Based on the prediction, this genome contained 30,342 protein-coding genes and 43.26% repetitive sequences. Furthermore, we determined that the large genome size can be attributed to the DNA-mediated transposable elements which accounted for 58.9% of the repetitive sequences in grass carp. We identified that the grass carp has only 24 pairs of chromosomes due to the fusion of two ancestral chromosomes. Enrichment analyses of significantly expanded and positively selected genes reflected evolutionary adaptation of grass carp to the feeding habits. We also detected the loss of conserved non-coding regulatory elements associated with the development of the immune system, nervous system, and digestive system, which may be critical for grass carp herbivorous traits. Conclusions The high-quality reference genome reported here provides a valuable resource for the genetic improvement and molecular-guided breeding of the grass carp.

While SlPti5 has been shown to play a crucial role in the regulation of antagonistic genes in Solanum lycopersicum and Arabidopsis against pathogen infection, there have been no comprehensive studies on the effects of SlPti5 on the regulatory response mechanism of reactive oxygen species (ROS) system and hormone pathways during growth and disease resistance of tomato plants. Here, we investigated the function of SlPti5 in the defense response of tomato against Botrytis cinerea utilizing a virus-induced gene silencing (VIGS)-based system. Expression profile analysis showed that SlPti5 was significantly induced upon B. cinerea infection, with high expression levels in the leaves and fruit of tomato. VIGS-based silencing of SlPti5 inhibited early vegetative growth, increased the plant's susceptibility to infection, promoted the development of ROS, affected the expression of genes involved in the ROS scavenging system, and attenuated the expression of genes associated with pathogenesis and the ethylene/jasmonic acid signaling pathways. In sum, our data demonstrated that SlPti5 stimulates the immune response of tomato plant to Botrytis cinerea infection by involving the ethylene (ET)- and jasmonic acid (JA)-mediated pathways and modulating the expression of some key pathogenesis-related (PR) genes.

Abstract Objective By analyzing the perioperative, postoperative complications and long-term overall survival time, we summarized the 8-year experience of minimally invasive McKeown esophagectomy for esophageal cancer in a single medical center. Methods This retrospective follow-up study included 1023 consecutive patients with esophageal cancer who underwent MIE-McKeown between Mar 2013 and Oct 2020. Relevant variables were collected and evaluated. Overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan–Meier method. Results For 1023 esophageal cancer undergoing MIE-McKeown, the main intraoperative complications were bleeding (3.0%, 31/1023) and tracheal injury (1.7%, 17/1023). There was no death occurred during operation. The conversion rate of thoracoscopy to thoracotomy was 2.2% (22/1023), and laparoscopy to laparotomy was 0.3% (3/1023). The postoperative morbidity of complications was 36.2% (370/1023), of which anastomotic leakage 7.7% (79/1023), pulmonary complication 13.4% (137/1023), chylothorax 2.3% (24/1023), and recurrent laryngeal nerve injury 8.8% (90/1023). The radical resection rate (R0) was 96.0% (982/1023), 30-day mortality was 0.3% (3/1023). For 1000 cases with squamous cell carcinoma, the estimated 3-year and 5-year overall survival was 37.2% and 17.8% respectively. In addition, neoadjuvant chemotherapy offered 3-year disease-free survival rate advantage in advanced stage patients (for stage IV: 7.2% vs. 1.8%). Conclusions This retrospective single center study demonstrates that MIE-McKeown procedure is feasible and safe with low perioperative and postoperative complications’ morbidity, and acceptable long-term oncologic results.