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Abstract Super-enhancers are a class of DNA cis-regulatory elements that can regulate cell identity, cell fate, stem cell pluripotency, and even tumorigenesis. Increasing evidence shows that epigenetic modifications play an important role in the pathogenesis of various types of cancer. However, the current research is far from enough to reveal the complex mechanism behind it. This study found a super-enhancer enriched with abnormally active histone modifications in pancreatic ductal adenocarcinoma (PDAC), called DKK1-super-enhancer (DKK1-SE). The major active component of DKK1-SE is component enhancer e1. Mechanistically, AP1 induces chromatin remodeling in component enhancer e1 and activates the transcriptional activity of DKK1. Moreover, DKK1 was closely related to the malignant clinical features of PDAC. Deletion or knockdown of DKK1-SE significantly inhibited the proliferation, colony formation, motility, migration, and invasion of PDAC cells in vitro, and these phenomena were partly mitigated upon rescuing DKK1 expression. In vivo, DKK1-SE deficiency not only inhibited tumor proliferation but also reduced the complexity of the tumor microenvironment. This study identifies that DKK1-SE drives DKK1 expression by recruiting AP1 transcription factors, exerting oncogenic effects in PDAC, and enhancing the complexity of the tumor microenvironment.

Abstract Esterases are crucial biocatalysts in chiral compound synthesis. Herein, a novel esterase EstSIT01 belonging to family V was identified from Microbacterium chocolatum SIT101 through genome mining and phylogenetic analysis. EstSIT01 demonstrated remarkable efficiency in asymmetrically hydrolyzing meso-dimethyl ester [Dimethyl cis-1,3-Dibenzyl-2-imidazolidine-4,5-dicarboxyate], producing over 99% yield and 99% enantiomeric excess (e.e.) for (4S, 5R)-monomethyl ester, a crucial chiral intermediate during the synthesis of d-biotin. Notably, the recombinant E. coli expressing EstSIT01 exhibited over 40-fold higher activity than that of the wild strain. EstSIT01 displays a preference for short-chain p-NP esters. The optimal temperature and pH were 45 °C and 10.0, with K m and k cat values of 0.147 mmol/L and 5.808 s− 1, respectively. Molecular docking and MD simulations suggest that the high stereoselectivity for meso-diester may attribute to the narrow entrance tunnel and unique binding pocket structure. Collectively, EstSIT01 holds great potential for preparing chiral carboxylic acids and esters.

Abstract Most fine ambient particulate matter (PM2.5)-based epidemiological models use globalized concentration-response (CR) functions assuming that the toxicity of PM2.5 is solely mass-dependent without considering its chemical composition. Although oxidative potential (OP) has emerged as an alternate metric of PM2.5 toxicity, the association between PM2.5 mass and OP on a large spatial extent has not been investigated. In this study, we evaluate this relationship using 385 PM2.5 samples collected from 14 different sites across 4 different continents and using 5 different OP (and cytotoxicity) endpoints. Our results show that the relationship between PM2.5 mass vs. OP (and cytotoxicity) is largely non-linear due to significant differences in the intrinsic toxicity, resulting from a spatially heterogeneous chemical composition of PM2.5. These results emphasize the need to develop localized CR functions incorporating other measures of PM2.5 properties (e.g., OP) to better predict the PM2.5-attributed health burdens.

Highlights Electrodeposited amorphous IrO x thin electrodes are first developed for proton exchange membrane electrolyzer cells. An ultralow loading of 0.075 mg cm−2 archives superior performance to catalyst-coated membrane (2 mg cm−2). > 96% of catalyst savings and > 42-fold higher catalyst utilization are demonstrated.

Abstract Background The purinergic P2X7 receptor (P2X7R) plays an important role in the crosstalk between pancreatic stellate cells (PSCs) and cancer cells, thus promoting progression of pancreatic ductal adenocarcinoma (PDAC). Single nucleotide polymorphisms (SNPs) in the P2X7R have been reported for several cancers, but have not been explored in PDAC. Materials and methods Blood samples from PDAC patients and controls were genotyped for 11 non-synonymous SNPs in P2X7R and a risk analysis was performed. Relevant P2X7R-SNP GFP variants were expressed in PSCs and cancer cells and their function was assayed in the following tests. Responses in Ca2+ were studied with Fura-2 and dye uptake with YO-PRO-1. Cell migration was monitored by fluorescence microscopy. Released cytokines were measured with MSD assay. Results Risk analysis showed that two SNPs 474G>A and 853G>A (rs28360447, rs7958316), that lead to the Gly150Arg and Arg276His variants, had a significant but opposite risk association with PDAC development, protecting against and predisposing to the disease, respectively. In vitro experiments performed on cancer cells and PSCs expressing the Gly150Arg variant showed reduced intracellular Ca2+ response, fluorescent dye uptake, and cell migration, while the Arg276His variant reduced dye uptake but displayed WT-like Ca2+ responses. As predicted, P2X7R was involved in cytokine release (IL-6, IL-1β, IL-8, TNF-α), but the P2X7R inhibitors displayed varied effects. Conclusion In conclusion, we provide evidence for the P2X7R SNPs association with PDAC and propose that they could be considered as potential biomarkers.

Abstract The placenta is a unique organ for ensuring normal embryonic growth in the uterine. Here, we found that maternal RNA transcription in Dlk1-Dio3 imprinted domain is essential for placentation. PolyA signals were inserted into Gtl2 to establish a mouse model to prevent the expression of maternal RNAs in the domain. The maternal allele knock-in (MKI) and homozygous (HOMO) placentas showed an expanded junctional zone, reduced labyrinth and poor vasculature impacting both fetal and maternal blood spaces. The MKI and HOMO models displayed dysregulated gene expression in the Dlk1-Dio3 domain. In situ hybridization detected Dlk1, Gtl2, Rtl1, miR-127 and Rian dysregulated in the labyrinth vasculature. MKI and HOMO induced Dlk1 to lose imprinting, and DNA methylation changes of IG-DMR and Gtl2-DMR, leading to abnormal gene expression, while the above changes didn’t occur in paternal allele knock-in placentas. These findings demonstrate that maternal RNAs in the Dlk1-Dio3 domain are involved in placental vasculature, regulating gene expression, imprinting status and DNA methylation.

Abstract The inland river basins of northwestern China are structured as mountain-basin systems. Water resources originate in the flow-producing area (FPA), are utilized and operated in the oasis area and are dissipated in the desert area. In this study, a Soil and Water Assessment Tool (SWAT) model was constructed in the Manas River Basin (MRB) FPA. Meanwhile, it simulated climate change and runoff evolution trends in the FPA of the MRB under different four climate change scenarios of Coupled Model Intercomparison Project Phase 5. The main findings showed that (1) the years 1979–1980 were chosen as the model warm-up period, 1979–2000 as the model calibration period and 2001–2015 as the model validation period to complete the construction of the SWAT model for MRBFPA. From 1981 to 2015, three performance parameters indicated that the model accuracy meets the requirements (NSE = 0.81, R 2 = 0.81 and PBIAS = 1.44) and can be used for further studies; (2) the hydrological elements (e.g. runoff, potential evapotranspiration, evapotranspiration, soil water content, snowmelt) in the MRBFPA were analysed by the constructed SWAT model; (3) the climate change in the MRBFPA is close to the RCP 8.5 scenario, and the future changes in water resources under this scenario will range from 659 to 2308 (million)m3. Compared to the multi-year historical mean value (12.95 × 108 m3), the future fluctuation in the amount of water resources available in this basin is increasing.

The Loess Plateau is marked by intense neotectonic activity and frequent earthquakes. Its unique physico-mechanical properties, combined with the granular overhead pore structure of loess, render it prone to seismic landslides triggered by strong earthquakes. Different types of loess seismic landslides have distinct formation mechanisms, disaster-causing characteristics, and risk assessment programs. In this study, the risk of seismic-collapsed loess landslides as one of the types of loess seismic landslides was evaluated on the Loess Plateau. A risk zoning map for seismic-collapsed loess landslides on the Loess Plateau, considering various exceedance probabilities, was compiled by assessing eight factors. These factors include peak ground acceleration, microstructure of loess, and were evaluated using both the minimum disaster-causing seismic peak ground acceleration zoning method and the analytic hierarchy process. The following conclusions were obtained: (1) Earthquakes are the primary inducing factor for seismic-collapsed loess landslides, with other factors serving as influencers, among which the microstructure of loess carries the highest weight; (2) Across various exceedance probabilities, the likelihood of seismic-collapsed loess landslides occurring at 63% of the 50-year exceedance probability is low. Moreover, as the minimum hazard-causing seismic peak ground acceleration increases, the risk of occurrence of seismic-collapsed loess landslides rises, leading to a gradual expansion of the area share in moderate and high-risk zones; (3) Hazard evaluation results align well with existing data on seismic-collapsed loess landslides and findings from field investigations. The case of seismic-collapsed loess landslides induced by the M6.2 magnitude earthquake in Jishishan County, China, is presented as an illustration. The combined use of the minimum hazard-causing seismic peak ground acceleration zoning method and the analytic hierarchy process method offers a reference for geohazard hazard assessment, with earthquakes as the primary inducing factor and other factors as influencers.

Abstract Aminoacyl-tRNA synthetase (aaRS) is a core component for genetic code expansion (GCE), a powerful technique that enables the incorporation of noncanonical amino acids (ncAAs) into a protein. The aaRS with polyspecificity can be exploited in incorporating additional ncAAs into a protein without the evolution of new, orthogonal aaRS/tRNA pair, which hence provides a useful tool for probing the enzyme mechanism or expanding protein function. A variant (N346A/C348A) of pyrrolysyl-tRNA synthetase from Methanosarcina mazei (MmPylRS) exhibited a wide substrate scope of accepting over 40 phenylalanine derivatives. However, for most of the substrates, the incorporation efficiency was low. Here, a MbPylRS (N311A/C313A) variant was constructed that showed higher ncAA incorporation efficiency than its homologous MmPylRS (N346A/C348A). Next, N-terminal of MbPylRS (N311A/C313A) was engineered by a greedy combination of single variants identified previously, resulting in an IPE (N311A/C313A/V31I/T56P/A100E) variant with significantly improved activity against various ncAAs. Activity of IPE was then tested toward 43 novel ncAAs, and 16 of them were identified to be accepted by the variant. The variant hence could incorporate nearly 60 ncAAs in total into proteins. With the utility of this variant, eight various ncAAs were then incorporated into a lanthanide-dependent alcohol dehydrogenase PedH. Incorporation of phenyllactic acid improved the catalytic efficiency of PedH toward methanol by 1.8-fold, indicating the role of modifying protein main chain in enzyme engineering. Incorporation of O-tert-Butyl-L-tyrosine modified the enantioselectivity of PedH by influencing the interactions between substrate and protein. Enzymatic characterization and molecular dynamics simulations revealed the mechanism of ncAAs affecting PedH catalysis. This study provides a PylRS variant with high activity and substrate promiscuity, which increases the utility of GCE in enzyme mechanism illustration and engineering. Graphical Abstract

The Karst region is a critical ecological barrier and functional zone in China. Understanding the spatiotemporal evolution of its ecosystem services and its relationship with human activities and climate change is of importance for achieving regional ecological protection and high-quality development. In this study, we used the InVEST model and CASA model to evaluate the spatiotemporal evolution pattern of ecosystem services in the study area from 2000 to 2020. The XGBoost–SHAP model was used to reveal the key indicators and thresholds of changes in major ecosystem services in the study area due to climate change and human activities. The results showed significant land use changes in the study area from 2000 to 2020, particularly the conversion of cropland to construction land, which was more intense in economically developed areas. The areas of forest and grassland increased initially but later decreased due to the impact of human activities and natural factors. Habitat quality (HQ) showed an overall declining trend, while soil retention (SR) and water yield (WY) services exhibited significant interannual variations due to climate change. The changes in rainfall had a particularly notable impact on these services; in years with excessive rainfall, soil erosion intensified, leading to a decline in SR services, whereas in years with moderate rainfall, SR and WY services improved. Carbon fixation (CF) services were enhanced with the expansion of forest areas. The XGBoost–SHAP model further revealed that the effects of rainfall and sunshine duration on ecosystem services were nonlinear, while population density and the proportion of construction land had a significant negative impact on habitat quality and soil retention. The expansion of construction land had the most significant negative impact on habitat quality, whereas the increase in forest land significantly improved carbon fixation and the soil retention capacity. By revealing the mechanisms of the impact of climate change and human activities on ecosystem services, we aimed to provide support for the promotion of ecological conservation and sustainable development strategies in the study area, as well as to provide an important reference for areas with geographic similarities to the study area.

The Dlk1-Dio3 domain is important for normal embryonic growth and development. The heart is the earliest developing and functioning organ of the embryo. In this study, we constructed a transcriptional termination model by inserting termination sequences and clarified that the lack of long non-coding RNA (lncRNA) expression in the Dlk1-Dio3 domain caused the death of maternal insertion mutant (MKI) and homozygous mutant (HOMO) mice starting from E13.5. Parental insertion mutants (PKI) can be born and grow normally. Macroscopically, dying MKI and HOMO embryos showed phenomena such as embryonic edema and reduced heart rate. Hematoxylin and eosin (H.E.) staining showed thinning of the myocardium in MKI and HOMO embryos. In situ hybridization (IHC) and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) showed downregulation of lncGtl2, Rian, and Mirg expression in MKI and HOMO hearts. The results of single-cell RNA sequencing (scRNA-Seq) analysis indicated that the lack of lncRNA expression in the Dlk1-Dio3 domain led to reduced proliferation of epicardial cells and may be an important cause of cardiac dysplasia. In conclusion, this study demonstrates that Dlk1-Dio3 domain lncRNAs play an integral role in ventricular development.

Opsins are a class of transmembrane proteins encoded by opsin genes, and they play a variety of functional roles. Short wavelength-sensitive opsin 2 (sws2), one of the five classes of visual opsin genes, mainly senses blue light. Previous research has indicated that sws2 is essential for melanocyte formation in fish; however, its specific role in skin color differentiation remains to be elucidated. Here, we identified the sws2 gene in a prized reef-dwelling fish, Plectropomus leopardus. The full-length P. leopardus sws2 gene encodes a protein consisting of 351 amino acids, and exhibits substantial homology with other fish species. The expression of the sws2 gene was widespread across P. leopardus tissues, with high expression in eye and skin tissues. Through immunohistochemistry and in situ hybridization analyses, we discovered that the sws2 gene was primarily localized in the rod and cone cells of the retina, and epidermal cells of the skin. Furthermore, dsRNA interference was used for sws2 gene knockdown in living P. leopardus to elucidate its function in skin color differentiation. Black-color-related genes, melanin contents, and tyrosinase activity in the skin significantly decreased after sws2 knockdown (p < 0.05), but red-color-related genes and carotenoid and lutein contents significantly increased (p < 0.05). Retinoic acid injection produced the opposite results. Our results suggested that the sws2 gene influences P. leopardus skin color regulation by affecting vitamin synthesis and melanin-related gene expression levels. This study establishes a foundation for elucidating the molecular mechanisms by which sws2 regulates melanocyte formation in fish skin.

The gas-phase metallicity of galaxies is regulated by multiple astrophysical processes, which makes it a crucial diagnostic of galaxy formation and evolution. Beyond the fundamental mass–metallicity relation, a debate about the secondary galaxy property to predict the metallicity of galaxies arises. Motivated by this, we systematically examine the relationship between gas-phase metallicity and other galaxy properties, i.e., the star formation rate (SFR) and galaxy size, in addition to stellar mass in both observation and simulation. We utilize the data from the Mapping Nearby Galaxies at Apache Point Observatory survey and the TNG50 simulations. We find that the combination of ${M}_{* }/{R}_{{\rm{e}}}^{\beta }$ with β ∼ 0.6–1 is in much stronger correlation to the metallicity than stellar mass alone, regardless of whether the SFR is included or not, in both observation and simulation. This indicates that galaxy size plays a more important role in determining gas-phase metallicity of galaxies than SFR. In addition, The Next Generation simulation predicts that the SFR, although being a subdominant role, becomes increasingly important in the high- z universe. Finally, we speculate that the SFR modulates metallicity on the temporal dimension, synchronized with time-varying gas inflows, and galaxy size regulates metallicity on the spatial dimension by affecting the gravitational potential and the mass-loading factor.

The progression of numerous malignancies has been linked to N6-methyladenosine (m6A) alteration. However, the opposite trend of m6A levels in the development and metastasis of cancer has not been reported. This study aimed to evaluate the biological function and mechanism of fat mass and obesity-associated protein (FTO) in regulating m6A modification in prostate cancer development and epithelial–mesenchymal transition (EMT). An EMT model of LNCaP and PC-3 cells was established with transforming growth factor-β treatment, and FTO knockout cell line was established in prostate cancer cells using the CRISPR/Cas9 gene editing technology. The level of m6A modification in tumor tissues was higher than that in normal prostate tissues; m6A levels were decreased after EMT. FTO deletion increased m6A expression and enhanced PC-3 cell motility, invasion, and EMT both in vitro and in vivo. RNA sequencing and functional investigations suggested that DDIT4, a novel EMT target gene, plays a role in m6A-regulated EMT, which was recognized and stabilized by the m6A effector IGF2BP2/3. Decreased FTO expression was an independent indicator of worse survival, and the level of DDIT4 was considerably elevated in patients with bone metastasis. Thus, this study revealed that the m6A demethylase FTO can play different roles in prostate cancer as a regulator of EMT and an inhibitor of m6A modification. Moreover, DDIT4 can be suggested as a possible biomarker for prostate cancer metastasis prediction.

Abstract Background Patients with remitted major depressive disorder (rMDD) show abnormal functional connectivity of the central executive network (CEN), salience networks (SN) and default mode network (DMN). It is unclear how these change during remission, or whether changes are related to function. Methods Three spatial networks in 17 patients with rMDD were compared between baseline and the six-month follow-up, and to 22 healthy controls. Correlations between these changes and psychosocial functioning were also assessed. Results In the CEN, patients at baseline had abnormal functional connectivity in the right anterior cingulate, right dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL) compare with HCs. There were functional connection differences in the right DLPFC and left IPL at baseline during follow-up. Abnormal connectivity in the right DLPFC and medial prefrontal cortex (mPFC) were found at follow-up. In the SN, patients at baseline had abnormal functional connectivity in the insula, left anterior cingulate, left IPL, and right precuneus; compared with baseline, patients had higher connectivity in the right DLPFC at follow-up. In the DMN, patients at baseline had abnormal functional connectivity in the right mPFC. Resting-state functional connectivity of the IPL and DLPFC in the CEN correlated with psychosocial functioning. Conclusions At six-month follow-up, the CEN still showed abnormal functional connectivity in those with rMDD, while anomalies in the SN and DMN has disappeared. Resting-state functional connectivity of the CEN during early rMDD is associated with psychosocial function. Clinical trials Registration Pharmacotherapy and Psychotherapy for MDD after Remission on Psychology and Neuroimaging. https://www.clinicaltrials.gov/ , registration number: NCT01831440 (15/4/2013).

Abstract Oxygen isotope anomaly of nitrate aerosol (∆17O-NO3 −) contributes to understanding the atmospheric nitrogen chemistry in the polar oceans. Here, ∆17O-NO3 − of the aerosol samples was analyzed based on a cruise from East Asia to the Arctic Ocean to explore the nitrate formation mechanisms. ∆17O-NO3 − decreased with the increase of latitude, especially when after entering the Arctic Circle. ∆17O-NO3 − (e.g., 11.5‰–21.2‰) was extremely low while crossing the sea ice-covered Arctic Ocean. This is most likely influenced by the combined enhancement of hydroxyl (OH) and peroxy (HO2 + RO2) radicals derived by sea ice under permanent sunlight period. In addition, the obvious increase in the ∆17O-NO3 − of return trip with shortened daytime indicated the advantage of nocturnal pathways (NO3 related) with the higher ∆17O endmembers. The mutation of ∆17O-NO3 − can reflect the change of NOx conversion pathways to nitrate, and it can be more sensitive to the change of radical chemistry related to atmospheric oxidation.

Abstract Traditional federated learning algorithms suffer from considerable performance reduction with non-identically and independently distributed datasets. This paper proposes a federated learning algorithm based on parallel-ensemble learning, which improves performance for image classification on these datasets. The training process of this algorithm includes basic federation learning and meta federation learning. First, several basic models are trained through cross-validation of federated learning, and then the meta-model is trained using the prediction results of the validation sets. In the training process, the training of different basic models is parallel. In prediction, meta-model is used to aggregate the output of the basic models to get the final prediction results. Our algorithm can achieve higher accuracy than traditional federated learning when using non-independent identically distributed datasets for image classification. Our algorithm aggregates different models through federated learning based on parallel-ensemble method, and improves the image classification performance of federated learning on non-independent identically distributed datasets.

In this paper, a recursive filtering problem is analyzed for nonlinear systems with sensor saturation under duty cycle scheduling (DCS). The sensor saturation is taken into account to describe practical engineering better. The DCS is introduced to conserve energy by alternating sensor nodes between active and dormant states. The considered problem aims to design a collaboration-prediction-based recursive filtering algorithm for nonlinear systems with sensor saturation such that, under the sparse measurements due to DCS, satisfactory filtering performance is guaranteed. By solving a set of matrix difference equations, the upper bound on the filtering error covariance is first obtained, and then the gain matrix of the filter that minimizes the upper limit is calculated. In addition, the boundedness of the upper bound of the filtering error covariance is analyzed. Finally, the effectiveness of the proposed collaboration-prediction-based recursive filtering algorithm is verified by the simulation example.

The rapid urbanization in the region has caused a shift in land-use structure and, as a result, the degrading of ecosystems. Elucidating the spatial–temporal evolution of ecosystem services (ESs) and ecological function zoning, it was beneficial to develop land use optimization strategy structures for different regions to support regional sustainable development. Taking the Nanjing Metropolitan Area (NMA), China, as a research area, we investigated the spatial–temporal evolution of land use and ESs in 2000, 2005, 2010, 2015, and 2020 by using biophysical models, quantified the trade-offs/ synergies and constraint effects among ESs using Spearman coefficients and constraint lines, and subsequently realized ecological function zoning through the Self-Organizing Feature Map (SOM) and Support Vector Machine (SVM) models on this basis. The results indicated that: (1) constructed land was the greatest area expansion type (an increase of 2,864.46 km2), while cropland was the primary source of its increase (89.69% of the total transfer of constructed land); (2) Habitat Quality (HQ), Landscape Aesthetics (LA), Net Primary Production (NPP), Soil Retention (SR), Nitrogen Retention (NR), and Water Yield (WY) showed a general spatial pattern of “high in the southern mountains and low in the northern plains”, whereas Crop Production (CP) was more susceptible to create trade-offs with other ESs and has four types of constraint effects; (3) to ensure the maximal spatial variation in geography condition, we combined the SOM-SVM to divide the NMA area into 6 ecosystem service zones and advised land development and utilization by zoning characteristics. In addition, we compared the outcomes of zoning before and after SVM optimization to demonstrate the suitability of combining the SOM-SVM approach in zoning. Our research can provide a reference for the sustainable management of regional land resources and landscape planning.

ObjectiveTo study the effect of physical exercise on non-suicidal self-injury in adolescents and to verify the chain mediating role of perceived social support and self-concept. Methods: A survey study was conducted on 1,426 adolescents in Chengdu, Sichuan Province. A chain mediation model was used to verify whether perceived social support and self-concept played a mediating role.ResultsPhysical exercise was significantly negatively associated with non-suicidal self-injury in adolescents (β = −0.53, p

Abstract Leveraging the interactions between ionomer and catalyst can increase the performance of proton exchange membrane fuel cells. The impacts of the equivalent weight (EW) of perfluorosulfonic acid–based ionomers on the platinum group metal‐free electrode structure and fuel cell performance have not been fully explored. Four membrane electrode assemblies (MEAs) were prepared by using a commercial Fe–N–C catalyst, two perfluorosulfonic acid ionomers with different EWs, that is, Aquivion 720 (A720) and Nafion 1100 (N1100), and two ionomer‐to‐catalyst (I/C) ratios. The four MEAs were characterized to understand the impact of the ionomer EW and content on the capacitance, proton conductivity, and mass transport on the cathode. The mass transport resistance was measured for the first time using a new oxygen reduction reaction limiting current method enabling to couple the effects of oxygen diffusion with liquid water generation. Low EW ionomer combined with a moderate I/C results in improved performance due to its enhanced proton conductivity. However, when used at high I/C, it can cause severe water flooding at high current density due to the enhanced liquid water uptake, especially at high relative humidity, resulting in lower catalyst utilization and higher mass transport resistance.

Forests serve as the largest carbon reservoir in terrestrial ecosystems, playing a crucial role in mitigating global warming and achieving the goal of “carbon neutrality”. Forest biomass is intrinsically related to carbon sinks and sources in forest ecosystems, and thus, the accurate monitoring of forest biomass is of great significance in ensuring ecological security and maintaining the global carbon balance. Significantly, remote sensing is not only able to estimate forest biomass at a large spatial scale but does so quickly, accurately, and without loss. Moreover, it can obtain forest biomass in areas inaccessible to human beings, which have become the main data source for forest biomass estimation at present. For this reason, this study analyzes the current research status, research hotspots, and future research trends in the field of remote sensing monitoring of forest biomass based on 1678 forest biomass remote sensing monitoring results from 1985 to 2023 obtained from the Web of Science Core Collection database. The results showed that the following: (1) The number of publications showed an exponential upward trend from 1985 to 2023, with an average annual growth rate of 2.64%. The top ten journals contributed to 53.76% of the total number of publications and 52.89% of the total number of citations in the field. (2) In particular, Remote Sensing of Environment has maintained a leading position in the field for an extended period, boasting the highest impact factor. Additionally, the author Saatchi S. stands out with the highest total number of citations for articles. (3) Keyword clustering analysis revealed that the main research topics in the remote sensing monitoring of forest biomass can be categorized into the following: optical remote sensing, LiDAR remote sensing, SAR remote sensing, and carbon stock. The explosion of keywords in the last six years indicates that an increasing number of researchers are focusing on carbon, airborne LiDAR data, biomass mapping, and constructing optimal biomass models.

Enzyme inactivation is crucial for enhancing the shelf life of lightly milled rice (LMR), yet the impact of diverse superheated steam (SS) treatment conditions on lipolytic enzyme efficiency, physicochemical properties, and volatile profiles of LMR remains unclear. This study investigated varying SS conditions, employing temperatures of 120 °C, 140 °C, and 160 °C and exposure times of 2, 4, 6, and 8 min. The research aimed to discern the influence of these conditions on enzyme activities, physicochemical characteristics, and quality attributes of LMR. Results indicated a significant rise in the inactivation rate with increased treatment temperature or duration, achieving a notable 70% reduction in enzyme activities at 120 °C for 6 min. Prolonged exposure to higher temperatures also induced pronounced fissures on LMR surfaces. Furthermore, intensive SS treatment led to a noteworthy 5.52% reduction in the relative crystallinity of LMR starch. GC/MS analysis revealed a consequential decrease, ranging from 44.7% to 65.7%, in undesirable odor ketones post-SS treatment. These findings underscore the potential of SS treatment in enhancing the commercial attributes of LMR.

Polystyrene foam is one of the most widely used plastic products because of its light weight,low apparent density,uneasy decomposition,low cost and so on.At the same time,the amount of waste is also increasing,and this kind of polymer is difficult to degrade in nature and its combustion will produce toxic substances.The different recovery of the waste brings a lot of problems to the environment.Recycling or resource utilization of WFPS can not only improve the environment,but also conform to the concept of "low carbon".The recovery methods of WFPS,including solvent recovery and pyrolysis recovery,were introduced in detail.The recycling and reuse of WFPS in the fields of energy,construction and environmental protection were summarized.It is pointed out that the WFPS recovery technology with high-efficiency,environmental protection and low-cost needs to be further developed.Combined with the recycling status of WFPS in China,the prospects of recycling and reuse technology of WFPS in the future are proposed as following: 1) Development of large-scale solvent recovery technology that takes into account both economy and environmental protection;2) Research and development of high-efficiency catalysts for catalytic cracking and recovery of monomers;3) Focusing on high value-added WFPS resource utilization technology research.

Abstract Coin selection method refers to the process undergone when selecting a set of unspent transaction outputs (UTXOs) from a cryptocurrency wallet or account to use as inputs in each transaction. The most applied coin selection method that UTXO-based cryptocurrencies currently employ is an algorithm that decides on a certain set of UTXOs that matches the target amount and limits the transaction fee. However this approach trades off favourable maintenance overhead of the entire network for low transaction fees, as many low-value UTXOs known as “dust” is produced. Over time, this will impact the scalability and management of the cryptocurrency network as the global set of UTXOs become larger. Therefore, there is an urgency to find a higher-performing coin selection method suitable for UTXO-based cryptocurrencies. This paper proposes a method based on the greedy and genetic algorithm for effectively choosing sets of UTXOs in Bitcoin. The main objective of this coin selection strategy is to get as close as possible to the target while also maintaining and possibly reducing the number of UTXO inputs.

Dry reforming of methane into syngas typically requires high temperatures, which can cause aggregation and deterioration of the catalyst. Here, the authors report a lanthanum nickel oxide catalyst prepared by in situ hydrogen reduction of LaNi0.05Co0.05Cr0.9O3 on a LaCrO3 perovskite support that remains stable for over 100 h at 750 °C.

Abstract Background p16, p53, and proliferating cell nuclear antigen (pcna) genes play significant roles in many chromatin modifications and have been found to be highly expressed in a variety of tumor tissues. Therefore, they have been used as target genes for some tumor therapies. However, the differential expressions of the p16, p53, and pcna genes in human sarcomas and their effects on prognosis have not been widely reported. Methods The Oncomine dataset was used to analyze the transcription levels of p16, p53, and pcna genes, and the gene expression profile interactive analysis (GEPIA) dataset was used to analyze the differential expressions of p16, p53, and pcna. The expression levels of p16, p53, and pcna were further analyzed by Western Blotting. GEPIA and Kaplan–Meier analyses were used to analyze the prognostic value of p16, p53, and pcna. Furthermore, p16, p53, and pcna gene mutations and their association with overall survival (OS) and disease-free survival (DFS) were analyzed using cBioPortal datasets. In addition, genes co-expressed with p16, p53, and pcna were analyzed using Oncomine. The DAVID dataset was used to analyze the functional enrichment of p16, p53, pcna, and their co-expressed genes by Gene Ontology (GO) and Metascape were used to construct a network map. Finally, the immune cell infiltration of p16, p53, and pcna in patients with sarcoma was reported by Tumor Immune Estimation Resource (TIMER). Results p16, p53, and pcna were up-regulated in human sarcoma tissues and almost all sarcoma cell lines. Western Blotting showed that the expression of p16, p53, and pcna was elevated in osteosarcoma cell lines. The expression of pcna was correlated with OS, the expression of p16, p53, and pcna was correlated with relapse-free survival, and the genetic mutation of p16 was negatively correlated with OS and DFS. We also found that p16, p53, and pcna genes were positively/negatively correlated with immune cell infiltration in sarcoma. Conclusions The results of this study showed that p16, p53, and pcna can significantly affect the survival and immune status of sarcoma patients. Therefore, p16, p53, and pcna could be used as potential biomarkers of prognosis and immune infiltration in human sarcoma and provide a possible therapeutic target for sarcoma.

Abstract Exploring the epigenetic regulation mechanism of colorectal cancer (CRC) from the perspective of N6-methyladenosine (m6A) modification may provide a new target for tumor therapy. Analysis using high-throughput RNA-seq profile from TCGA found that the gene expression of Methyltransferase-like 3 (METTL3) was significantly upregulated among 20 m6A binding proteins in CRC, which was also validated in CRC cancer tissues and cell lines. Moreover, transcriptome sequencing in METTL3 knockdown cells using CRISPR/Cas9 editing suggested that EphA2 and VEGFA were differential expression, which were enriched in the vasculature development, PI3K/AKT and ERK1/2 signal pathway through the functional enrichment analysis. The results in vitro revealed that METTL3 as the m6A “writers” participates the methylation of EphA2 and VEGFA, which were recognized by the m6A “readers”, insulin-like growth factor 2 mRNA binding protein 2/3 (IGF2BP2/3), to prevent their mRNA degradation. In addition, EphA2 and VEGFA targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC. The study suggests that intervention with m6A-binding proteins (METTL3 and IGF2BP2/3) may provide a potential diagnostic or prognostic target of VM-based anti-metastasis drugs for CRC.

Modulating the extracellular matrix microenvironment is critical for achieving the desired macrophage phenotype in immune investigations or tumor therapy. Combining de novo protein design and biosynthesis techniques, herein, we designed a biomimetic polypeptide self-assembled nano-immunomodulator to trigger the activation of a specific macrophage phenotype. It was intended to be made up of (​GGS​GGP​GGG​PAS​AAA​NSA​SRA​TSN​SP)n, the RGD motif from collagen, and the IKVAV motif from laminin. The combination of these domains allows the biomimetic polypeptide to assemble into extracellular matrix-like nanofibrils, creating an extracellular matrix-like milieu for macrophages. Furthermore, changing the concentration further provides a facile route to fine-tune macrophage polarization, which enhances antitumor immune responses by precisely resetting tumor-associated macrophage immune responses into an M1-like phenotype, which is generally considered to be tumor-killing macrophages, primarily antitumor, and immune-promoting. Unlike metal or synthetic polymer-based nanoparticles, this polypeptide-based nanomaterial exhibits excellent biocompatibility, high efficacy, and precise tunability in immunomodulatory effectiveness. These encouraging findings motivate us to continue our research into cancer immunotherapy applications in the future.

The strategy of rational design to engineer enzymes is to predict the potential mutants based on the understanding of the relationships between protein structure and function, and subsequently introduce the mutations using the site-directed mutagenesis. Rational design methods are universal, relatively fast and have the potential to be developed into algorithms that can quantitatively predict the performance of the designed sequences. Compared to the protein stability, it was more challenging to design an enzyme with improved activity or selectivity, due to the complexity of enzyme molecular structure and inadequate understanding of the relationships between enzyme structures and functions. However, with the development of computational force, advanced algorithm and a deeper understanding of enzyme catalytic mechanisms, rational design could significantly simplify the process of engineering enzyme functions and the number of studies applying rational design strategy has been increasing. Here, we reviewed the recent advances of applying the rational design strategy to engineer enzyme functions including activity and enantioselectivity. Five strategies including multiple sequence alignment, strategy based on steric hindrance, strategy based on remodeling interaction network, strategy based on dynamics modification and computational protein design are discussed and the successful cases using these strategies are introduced.

ObjectsThis study aimed to elucidate the effect of cognitive bias modification on depression.MethodsThis research included 10 randomized studies searching four major databases: PubMed, Embase, PsycINFO, and Cochrane Library, with a total sample size of 467. Moreover, they were examined for quality and possible publication bias.ResultsCognitive bias modification (CBM) had statistically significant results, g = −0.64, 95% CI = [−0.97–0.32]. The interpretation of cognitive bias modification shows the highest effect size, g = −1.45, 95% CI = [−2.05–0.88]. When the training place is located in the laboratory, the training effect is significant, g = −1.11, 95% CI = [−1.62–0.61]. The difference is statistically significant when the training environment was changed to home, g = −0.28, 95% CI = [−0.51–0.05]. CBM has a statistical effect on moderate-to-severe depression, g = −0.70, 95% CI = [−1.04–0.36].ConclusionWe found that CBM had a moderate therapeutic effect on depression, whether the setting was at home or in the lab. Especially when the interpretation of cognitive bias modification (CBM-I) was used, we got the highest effect value. Furthermore, CBM has a statistical effect on moderate-to-severe depression.

It is generally believed that higher dietary diversity is associated with better health status. The dietary diversity of individuals may change with age; however, evidence on the trajectory of change in the long-term and whether it is related to all-cause mortality is still scant. In this study, we used data from the China Health and Nutrition Survey (CHNS) collected in five follow-ups between 2004 and 2015 to explore the association between changes in dietary diversity scores (DDS) and all-cause mortality, as well as the dynamic change in DDS with age. In total, 6,737 subjects (aged between 30 and 60 at enrollment) were included in the analysis. Latent Class Trajectory Modeling (LCTM) was used to explore the different trajectories of DDS changes among participants. Four classes were identified: class 1 with the lowest average DDS (3.0) that showed a gradual decline during the follow-ups; class 2 with relatively low DDS (4.0) that experienced slight growth; class 3 with medium DDS (5.2) that also demonstrated similar growth rate to class 2; and class 4 with the highest DDS (6.7) maintained at a high level. Cox proportional hazards regression models were applied to investigate the association between the DDS trajectories and the risk of death. Only class 4, which was characterized by the highest and stable DDS, had significant reduced risk of all-cause mortality of 71.0% (hazard ratio [HR]: 0.29; 95% confidence interval [CI]: 0.10–0.83), 68% (HR: 0.32; 95% CI: 0.11–0.89), and 66.0% (HR: 0.34; 95% CI: 0.12–0.94), compared to classes 1, 2, and 3, respectively, while the first three classes showed no significant inter-class differences. When considering the average DDS during the study period, each point of increase in DDS corresponded to a 22% reduced risk of mortality (HR: 0.78; 95% CI: 0.69–0.89). In summary, reaching and maintaining a higher DDS was associated with a decreased risk of all-cause mortality. Therefore, promoting diversified eating and increasing the accessibility of varieties of foods should be paid more attention from policymakers and be more emphasized in dietary guidelines.

ObjectivesDiabetes and its complications are commonly associated with depressive symptoms, and few studies have investigated the diagnosis effect of depressive symptoms in patients with diabetes. The present study used a network-based approach to explore the association between depressive symptoms, which are annotated from electronic health record (EHR) notes by a deep learning model, and the diagnosis of type 2 diabetes mellitus (T2DM) and its complications.MethodsIn this study, we used anonymous admission notes of 52,139 inpatients diagnosed with T2DM at the first affiliated hospital of Nanjing Medical University from 2008 to 2016 as input for a symptom annotation model named T5-depression based on transformer architecture which helps to annotate depressive symptoms from present illness. We measured the performance of the model by using the F1 score and the area under the receiver operating characteristic curve (AUROC). We constructed networks of depressive symptoms to examine the connectivity of these networks in patients diagnosed with T2DM, including those with certain complications.ResultsThe T5-depression model achieved the best performance with an F1-score of 91.71 and an AUROC of 96.25 compared with the benchmark models. The connectivity of depressive symptoms in patients diagnosed with T2DM (p = 0.025) and hypertension (p = 0.013) showed a statistically significant increase 2 years after the diagnosis, which is consistent with the number of patients diagnosed with depression.ConclusionThe T5-depression model proposed in this study can effectively annotate depressive symptoms in EHR notes. The connectivity of annotated depressive symptoms is associated with the diagnosis of T2DM and hypertension. The changes in the network of depressive symptoms generated by the T5-depression model could be used as an indicator for screening depression.

In this study, we investigate the profitability of 10 well-known Japanese candlestick charting patterns using daily-based data on the component stocks of the Chinese SSE50 index, which involves a lengthy sample period from January 2000 to December 2018. The main contribution of this paper is that we conduct the first predictive power examination of Japanese candlestick patterns on the Chinese SSE50 stocks while taking into account trend and overbought/oversold conditions, and their profitability over different holding periods. Experimental results indicate that several bullish candlestick patterns such as Long White and Bullish Gap can produce a significant positive average return over certain holding periods. In addition, empirical results show that none of the bearish candlestick patterns we examined offers predictive power. However, without considering trend and overbought/oversold conditions, we find that the bearish pattern Gravestone Doji over a 10-day holding period has superior profitability if it is applied as a contrary trading signal. The robustness of our results is confirmed based upon a bootstrap analysis and an out-of-sample test. The findings of this study are beneficial for the market traders engaged in transaction of the SSE50 component stocks.

The ultimate goal of depression treatment is to achieve functional recovery. Psychosocial functioning is the main component of functional impairment in depressed patients. The concept of psychosocial functioning has an early origin; however, its concept and connotation are still ambiguous, which is the basic and key problem faced by the relevant research and clinical application. In this study, we start from the paradox of symptoms remission and functional recovery, describe the concept, connotation, and characteristics of psychosocial functioning impairment in depressed patients, and re-emphasize its importance in depression treatment to promote research and clinical applications related to psychosocial functioning impairment in depressed patients to achieve functional recovery.

Over the past 40 years of reform and opening up, human activities in the Yangtze River Delta region have caused major changes in land use patterns and ecosystem functions. Clarifying the spatiotemporal change characteristics and future development trends of ecosystem service functions is the basis for rational land development and utilization. In this study, the InVEST model and the CASA model were used to calculate habitat quality, water conservation, carbon sequestration and oxygen release, and soil conservation ecosystem services in the Yangtze River Delta urban agglomeration from 1980 to 2020. The spatial pattern, change law, and future trend of these services were analyzed using the Theil–Sen median trend analysis, Mann–Kendall test, and Hurst index analysis. The results show that the four types of ecosystems in the Yangtze River Delta urban agglomeration (habitat quality, water conservation, carbon sequestration and oxygen release, and soil conservation) exhibited an overall spatial pattern of being high in the southwest mountainous area and low in the northeast plain, and the conversion from constructed to agriculture was the most frequent type of land conversion over the past 40 years. From 1980 to 2020, the average level of habitat quality showed a downward trend and is expected to continue to deteriorate in the future. Water conservation, carbon sequestration and oxygen release, and soil conservation showed a fluctuating upward trend, with the latter two primarily predicted to have a future trend of improvement. The changes in ecosystem services exhibit gradient effects and horizontal spatial differentiation. The decline in ecosystem service functions is more pronounced in the vicinity of large cities. It is thus necessary to accelerate the transformation of the economic development model, and abandon the extensive urbanization development model, and promote high-quality urbanization development on the basis of improving resource and environmental carrying capacities.

Abstract Nicotinamide adenine dinucleotide phosphate (NADPH), as a well-known cofactor, is widely used in the most of enzymatic redox reactions, playing an important role in industrial catalysis. However, the absence of a comparable method for efficient NADP+ to NADPH cofactor regeneration radically impairs efficient green chemical synthesis. Alcohol dehydrogenase (ADH) enzymes, allowing the in situ regeneration of the redox cofactor NADPH with high specific activity and easy by-product separation process, are provided with great industrial application potential and research attention. Accordingly, herein a NADP+-specific ADH from Clostridium beijerinckii was selected to be engineered for cofactor recycle, using an automated algorithm named Protein Repair One-stop Shop (PROSS). The mutant CbADH-6M (S24P/G182A/G196A/H222D/S250E/S254R) exhibited a favorable soluble and highly active expression with an activity of 46.3 U/mL, which was 16 times higher than the wild type (2.9 U/mL), and a more stable protein conformation with an enhanced thermal stability: Δ $${T}_{1/2}^{60\mathrm{min}}$$ T 1 / 2 60 min = + 3.6 °C (temperature of 50% inactivation after incubation for 60 min). Furthermore, the activity of CbADH-6M was up-graded to 2401.8 U/mL by high cell density fermentation strategy using recombinant Escherichia coli, demonstrating its industrial potential. Finally, the superb efficiency for NADPH regeneration of the mutant enzyme was testified in the synthesis of some fine chiral aromatic alcohols coupling with another ADH from Lactobacillus kefir (LkADH).

Successful development of protein therapeutics depends critically on achieving stability under a range of conditions. A deeper understanding of the drivers of instability across different stress conditions, will enable the engineering of more robust protein scaffolds. We compared the impacts of low pH and high temperature stresses on the structure of a humanized antibody fragment (Fab) A33, using atomistic molecular dynamics simulations, using a recent 2.5 Å crystal structure. This revealed that low-pH induced the loss of native contacts in the domain CL. By contrast, thermal stress led to 5–7% loss of native contacts in all four domains, and simultaneous loss of >30% of native contacts in the VL-VH and CL-CH interfaces. This revealed divergent destabilising pathways under the two different stresses. The underlying cause of instability was probed using FoldX and Rosetta mutation analysis, and packing density calculations. These agreed that mutations in the CL domain, and CL-CH1 interface have the greatest potential for stabilisation of Fab A33. Several key salt bridge losses underpinned the conformational change in CL at low pH, whereas at high temperature, salt bridges became more dynamic, thus contributing to an overall destabilization. Lastly, the unfolding events at the two stress conditions exposed different predicted aggregation-prone regions (APR) to solvent, which would potentially lead to different aggregation mechanisms. Overall, our results identified the early stages of unfolding and stability-limiting regions of Fab A33, and the VH and CL domains as interesting future targets for engineering stability to both pH- and thermal-stresses simultaneously.

Bone integration on the surface of titanium prosthesis is critical to the success of implant surgery. Good Bone integration at the contact interface is the basis of long-term stability. TiO2 nanotubes have become one of the most commonly used modification techniques for artificial joint prostheses and bone defect implants due to their good biocompatibility, mechanical properties and chemical stability. TiO2 nanotubes can promote F-actin polymerization in bone mesenchymal stem cells (BMSCs) and osteogenic differentiation. The possibility of F-actin as an upstream part to regulate GCN5 initiation of osteogenesis was discussed. The results of gene loss and functional acquisition assay, immunoblotting assay and fluorescence staining assay showed that TiO2 nanotubes could promote the differentiation of BMSCs into osteoblasts. The intervention of TiO2 nanotubes can make BMSCs form stronger F-actin fibre bundles, which can drive the differentiation process of osteogenesis. Our results showed that F-actin mediated nanotube-induced cell differentiation through promoting the expression of GCN5 and enhancing the function of GCN5 and GCN5 was a key regulator of the osteogenic differentiation of BMSCs induced by TiO2 nanotubes as a downstream mediated osteogenesis of F-actin, providing a novel insight into the study of osteogenic differentiation on surface of TiO2 nanotubes.

Located in an important biodiversity conservation area in the Yangtze River Delta, the habitats of many species have been severely eroded because of human activities such as tourism development. There is no relevant species conservation plan in place in the region, and scientific guidance on ecosystem change and corridor construction is urgently needed. In this study, we first assess ecosystem service functions based on the InVEST model; then, we assess ecological sensitivity and identify landscape resistance surfaces by constructing ecosystem sensitivity indicators; finally, we construct ecological security patterns by combining landscape resistance surfaces and circuit theory identification. The main results are as follows: (1) The high value area of ecosystem services is located in the southwest, while the northeast part of the study area has lower ecosystem services, and there is a trade-off between the ecosystem services in the study area. (2) There are 38 ecological sources in southern Anhui, with a total area of more than 5742.79 km2, that are the basic guarantees of ecological security, mainly located in the northeast of the study area, and woodland and grassland are the most important components, accounting for 18.4% of the total study area. (3) The ecological security pattern in the study area consists of 63 ecological sources, 37 important corridors, and 26 potential corridors, of which there are 28 pinch point areas and 6 barrier point patches in the study area, mainly located within Huangshan City and Xuancheng City. We recommend that when implementing restoration and rehabilitation measures in the future, policy makers should give priority to pinch points and barrier areas.

Triboelectric nanogenerator (TENG) can convert tiny mechanical energy into precious electrical energy. Constant improvements to the output performance of TENG is not only the driving force for its sustainable development, but also the key to expand its practical applicability in modern smart devices. However, most previous studies were conducted at room temperature, ignoring the influence of temperature on the output performance of TENG. Additionally, due to thermionic emission effect, the electrons transferred to a dielectric surface can be released into a vacuum after contact electrification. Therefore, TENG cannot maintain an effective electrical output under high-temperature conditions. Here, a series of high-temperature operatable flexible TENGs (HO-TENGs) based on nanofiber/microsphere hybrid membranes (FSHMs) was fabricated by electrospinning and electrospraying. The Voc of HO-TENG is 212 V, which is 2.33 times higher than that of control TENG. After 10,000 cycle stability tests, the HO-TENG shows excellent durability. Especially, this HO-TENG can maintain 77% electrical output at 70 °C compared to room temperature, showing excellent high-temperature operability. This study can not only provide a reference for the construction of advanced high-performance TENG, but also provide a certain experimental basis for efficient collection of mechanical energy in high-temperature environment and promote the application of TENG devices in harsh environments.

The perovskite microlaser is a competitive candidate of light source for optical communication and integrated photonic circuits. Understanding the fundamental mechanism of lasing is crucial for the upcoming devices. The ultrafast establishment of lasing modes within a 2D perovskite microplate cavity at room temperature is investigated. The transient red shift of lasing modes can be found. Analysis based on electron–hole plasma (EHP) and a dynamic Drude‐like model are carried out with simulations on the transient dielectric response and the mode shift. In addition, the integrated lasing gain profile have a red shift at high excitation intensity, which is explained with EHP‐induced bandgap renormalization. The conflict between the experimental phenomena and the exciton–polariton theory confirms that under intense excitation, the exciton–polariton is ruled out for the origin of lasing. These results provide a direct understanding of the lasing evolving in a 2D perovskite microcavity. Suppressing the EHP‐related transient shift of cavity modes will advance the lasing applications.

AbstractThere are abundant limestone resources in Weibei area. However, under the influence of a complex geological environment and harsh external environment, they often suffer from various types of serious geological disasters, which seriously threaten the safety of the people in the mining area and the development of mining resources. Therefore, it is urgent to carry out relevant governance. Firstly, combined with the field engineering geological data of a typical limestone quarry slope in Weibei, this paper makes a detailed geological survey of the study area. Then, the geometric model of the limestone mine slope is established to analyze the stress relationship between each block and its failure mode. Finally, a deep Newtonian force monitoring and early-warning system is set up in the dangerous area of large deformation of the slope to carry out the early warning treatment of reinforcement. The results show that (1) limestone is the main component of the mine, followed by mudstone, with developed joints and fissures, broken rock mass, and high hidden danger of engineering geological disasters; (2) in addition to bending and toppling failure on the surface of the mine slope, there are three failure modes: toppling failure along the joint surface, combined failure along the joint and plane, and failure along the outward structural plane; and (3) the NPR anchor cable is used to strengthen the slope, and the real-time monitoring of the slope force changes is realized, which has a particular reference significance for the study of similar significant deformation failure mechanisms of the slope and imminent slide warning.

Designing reliable, scalable and high speed computing systems remains a challenge. Here, the authors identify noncentrosymmetric orthorhombic phase in HZO film and demonstrate a CMOS compatible 3D Vertical HZO-based ferroelectric diode array with self-selective property and 20 ns of speed operation.

Follicular thyroid carcinoma (FTC) is a common endocrine malignancy with highly aggressive features. In this study, next-generation sequencing technology was used to identify aberrant expression of sialyltransferase (ST) family members in FTC. Aberrant high expression of alpha-2,6-sialyltransferase 2 (ST6GAL2) was demonstrated to promote tumorigenesis of FTC in vitro and in vivo. Furthermore, ST6GAL2 promoted tumorigenesis by inactivating the Hippo signaling pathway. Resveratrol is a native compound extracted from Vitis species, and many studies have confirmed its protective cardiovascular and antineoplastic effects. Here we found that resveratrol can inhibit the tumorigenesis of FTC by suppressing the expression of ST6GAL2, further activating the Hippo pathway. In summary, this study revealed the role of the ST6GAL2-Hippo signaling pathway in FTC tumorigenesis and indicated that resveratrol, a commonly found antineoplastic compound, could inhibit tumorigenesis of FTC by regulating the abovementioned pathways. Keywords: follicular thyroid carcinoma, resveratrol, Hippo signaling pathway, sialyltransferase families

Perovskite oxides were widely used as precursors for developing metal-support type catalysts. It is attractive to explore the catalytic properties of the oxides themselves for dry reforming of methane (DRM). We synthesized LaNixCr1−xO3 (x = 0.05–0.5) samples in powder form using the sol-gel self-combustion method. Ni atoms are successfully doped into the LaCrO3 perovskite lattice. The perovskite grains are polycrystalline, and the crystallite size decreases with increasing Ni content. We demonstrated that the LaNixCr1−xO3 perovskites show intrinsically catalytic activity for DRM reactions. Reducing the Ni content is helpful to reduce carbon deposition resulting from the metal Ni nanoparticles that usually coexist with the highly active perovskite oxides. The CH4 conversion over the LaNi0.1Cr0.9O3 sample reaches approximately 84% at 750 °C, and the carbon deposition is negligible.

The Dlk1-Dio3 imprinted domain on mouse chromosome 12 contains three well-characterized paternally methylated differentially methylated regions (DMRs): IG-DMR, Gtl2-DMR, and Dlk1-DMR. These DMRs control the expression of many genes involved in embryonic development, inherited diseases, and human cancer in this domain. The first maternal methylation DMR discovered in this domain was the Meg8-DMR, the targets and biological function of which are still unknown. Here, using an enhancer-blocking assay, we first dissected the functional parts of the Meg8-DMR and showed that its insulator activity is dependent on the CCCTC-binding factor (CTCF) in MLTC-1. Results from RNA-seq showed that the deletion of the Meg8-DMR and its compartment CTCF binding sites, but not GGCG repeats, lead to the downregulation of numerous genes on chromosome 12, in particular the drastically reduced expression of Dlk1 and Rtl1 in the Dlk1-Dio3 domain, while differentially expressed genes are enriched in the MAPK pathway. In vitro assays revealed that the deletion of the Meg8-DMR and CTCF binding sites enhances cell migration and invasion by decreasing Dlk1 and activating the Notch1-Rhoc-MAPK/ERK pathway. These findings enhance research into gene regulation in the Dlk1-Dio3 domain by indicating that the Meg8-DMR functions as a long-range regulatory element which is dependent on CTCF binding sites and affects multiple genes in this domain.

Crude oil price direction forecasting presents an extremely challenging task that attracts considerable attention from academic scholars, individual investors and institutional investors. In this research, we proposed an integration method by adopting the Multi-Class Support Vector Machine (MCSVM) and the Non-Dominated Sorting Genetic Algorithm II (NSGA-II) for forecasting and trading simulation in two well-known crude oil markets. Firstly, the proposed approach applied the MCSVM to train a multi-class classification model, and it adopted the NSGA-II to optimize the threshold values of trading rules. Then, the trained MCSVM model was used to forecast the movement direction and magnitude levels. Next, the proposed method forecasted the direction of crude oil price movements one week later and executed trading simulation according to the direction and magnitude level predictions. Finally, after a testing period lasted for four years, the performances of the proposed approach were gauged in terms of direction prediction correctness and investment yields. Experimental results demonstrated that the proposed approach produced outstanding results not only on hit ratio and accumulated return but also return-risk ratio. It indicates that the proposed approach can provide beneficial suggestions for individual investors, institutional investors, as well as for government officers engaged in energy investment policies making.

Manganese oxides are often used as catalysts for oxygen reduction reactions due to their low price and high stability, and they have been extensively studied. However, the poor electrical conductivity and low intrinsic activity of manganese oxides restrict its application in oxygen reduction. In this paper, the manganese oxide octahedral molecular sieve is used as the research object, and the oxygen reduction performance of the material is adjusted by the surface reduction etching treatment of sodium borohydride. After being treated with 8 mmol/L sodium borohydride, the oxygen vacancy content of the manganese oxide octahedral molecular sieve was 26%. The manganese oxide octahedral molecular sieve showed the best performance, and its half-wave potential was 0.821 V. Tests show that the material has excellent electrical conductivity and high oxygen reduction kinetics. The generation of appropriate oxygen vacancies on the surface directly improves the chemical properties of the material surface, regulates the ratio of Mn3+/Mn4+ on the surface of the nanorod, and increases the oxygen reduction adsorption sites on the surface of the material. On the other hand, the electrical conductivity of the material is adjusted to increase the electron transfer rate during the oxygen reduction process, thereby enhancing the oxygen reduction activity.

Abstract Background High thermostability is required for trypsin to have wider industrial applications. Target mutagenesis at flexible regions has been proved to be an efficient protein engineering method to enhance the protein thermostability. Results The flexible regions in porcine trypsin were predicted using the methods including molecular dynamic simulation, FlexPred, and FoldUnfold. The amino acids 78–90 was predicted to be the highly flexible region simultaneously by the three methods and hence selected to be the mutation target. We constructed five variants (D3, D5, D7, D9, and D11) by truncating the region. And the variant D9 showed higher thermostability, with a 5 °C increase in T opt, 5.8 °C rise in $$T_{50}^{10}$$ T5010 , and a 4.5 °C rise in T m, compared to the wild-type. Moreover, the half-life value of the variant D9 was also found to be dramatically improved by 46 min. Circular dichroism and intrinsic fluorescence indicated that the structures had no significant change between the variant D9 and the wild-type. The surface hydrophobicity of D9 was measured to be lower than that of wild-type, indicating the increased hydrophobic interaction, which could have contributed to the improved thermostability of D9. Conclusions These results showed that the thermostability of variant D9 was increased. The variant D9 could be expected to be a promising tool enzyme for its wider industrial applications. The method of truncating the flexible region used in our study has the potential to be used for enhancing the thermostability of other proteins.