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Abstract Anti‐cancer peptides (ACPs) represent a promising potential for cancer treatment, although their mechanisms need to be further elucidated to improve their application in cancer therapy. Lycosin‐I, a linear amphipathic peptide isolated from the venom of Lycosa singorensis, shows significant anticancer potential. Herein, it is found that Lycosin‐I, which can self‐assemble into a nanosphere structure, has a multimodal mechanism of action involving lipid binding for the selective and effective treatment of leukemia. Mechanistically, Lycosin‐I selectively binds to the K562 cell membrane, likely due to its preferential interaction with negatively charged phosphatidylserine, and rapidly triggers membrane lysis, particularly at high concentrations. In addition, Lycosin‐I induces apoptosis, cell cycle arrest in the G1 phase and ferroptosis in K562 cells by suppressing the PI3K‐AKT‐mTOR signaling pathway and activating cell autophagy at low concentrations. Furthermore, intraperitoneal injection of Lycosin‐I inhibits tumor growth of K562 cells in a nude mouse xenograft model without causing side effects. Collectively, the multimodal effect of Lycosin‐I can provide new insights into the mechanism of ACPs, and Lycosin‐I, which is characterized by high potency and specificity, can be a promising lead for the development of anti‐leukemia drugs.

Pancreatic adenocarcinoma (PAAD) is an aggressive, heterogeneous malignancy. We studied the potential of ferroptosis-related tumor vaccines for PAAD treatment. Ferroptosis-related genes, gene expression profiles, and clinical information were extracted from the FerrDB, UCSC Xena, and International Cancer Genome Consortium databases. Differential expression levels and prognostic indices were calculated, genetic alterations and correlations with immune-infiltrating cells were explored, and consensus clustering analysis was performed to identify ferroptosis subtypes and gene modules. Immune enrichment scores were calculated using gene set enrichment analysis, and gene modules were screened using weighted gene co-expression network analysis. The ferroptosis subtype distribution was visualized using graph learning-based dimensionality reduction analysis of the Monocle package with a Gaussian distribution. We identified four ferroptosis-related tumor antigens, AGPS, KDM5A, NRAS, and OSBPL9, which were associated with pancreatic cancer prognosis and antigen-presenting cell infiltration. We determined three minor ferroptosis subtypes, with different clinical prognosis and tumor immune status. Of the subtypes, FS3 may be more suitable for mRNA therapy. We constructed a PAAD ferroptosis landscape to identify the ferroptosis status of patients and predict their prognosis. Finally, we found that the eigengene of the green module was an independent prognostic factor, with a significantly better prognosis in the high-score group than in the low-score group. In conclusion, we identified four ferroptosis-related genes as targets for mRNA vaccines and three ferroptosis subtypes, providing a theoretical basis for the anti-PAAD mRNA vaccine and defining suitable patients for vaccination.

Abstract Background Accumulating studies have reported indispensable functions of circular RNAs (circRNA) in tumor progression through regulation of gene expression. However, circRNA expression profiles and functions in human ovarian carcinoma (OC) are yet to be fully established. Methods In this research, deep sequencing of circRNAs from OC samples and paired adjacent normal tissues was performed to establish expression profiles and circ-PHC3 levels between the groups further compared using RT-qPCR. The effects of ectopic overexpression of miR-497-5p and SOX9 and siRNA-mediated knockdown of circ-PHC3 and an miR-497-5p inhibitor were explored to clarify the regulatory mechanisms underlying circ-PHC3 activity in OC proliferation and metastasis. Information from public databases and the luciferase reporter assay were further utilized to examine the potential correlations among circ-PHC3, miR-497-5p and SOX9. Results Our results showed significant upregulation of circ-PHC3 in both OC cell lines and tissues. In the luciferase reporter assay, downregulation of circ-PHC3 led to suppression of metastasis and proliferation, potentially through targeted effects on the miR-497-5p/SOX9 axis in OC. SOX9 overexpression or miR-497-5p suppression rescued OC cell proliferation and invasion following silencing of circ-PHC3. Moreover, SOX9 inhibition induced restoration of OC cell invasion and proliferation under conditions of overexpression of miR-497-5p. Thus, circ-PHC3 appears to exert effects on cancer stem cell differentiation through regulation of the miR-497-5p/SOX9 axis. Conclusion Taken together, our findings suggest that circ-PHC3 enhances OC progression through functioning as an miR-497-5p sponge to promote SOX9 expression, supporting its potential as a promising candidate target for OC therapy.

Microbially induced calcite precipitation (MICP) is a promising, more eco-friendly alternative method for landslide prevention and foundation reinforcement. In this study, we investigated the optimization of injection methods within the MICP process in porous media to enhance calcite mass and consolidation effect. The results demonstrated that staged injections with considerable advantages significantly improved precipitated calcite mass by 23.55% compared with continuous injection methods. However, extended retention times in staged injections reduced reinforcement effects. Moreover, setting the additional time in all injection methods can improve the consolidation area and effect without added injections. Apart from the injection methods, the changes in porosity and substance concentration also directly affected calcite masses and the reinforcement effect. Both the total calcite mass and the reinforcement effect should be taken into account when selecting appropriate injection methods. In terms of influencing factors on the total calcite mass, substance concentration ≫ average porosity ≫ additional time > retention time in staged injection. For the consolidation effect, substance concentration ≫ retention time in staged injection > average porosity ≫ additional time. The 5 h retention time in staged injections was recommended as the optimum injection method in the geotechnical conditions for average porosity from 0.25 to 0.45, with the changes in different reactant concentrations.

The self-assembly of molecular knots in water is challenging. Here, authors report the self-assembly of a trefoil knot in water via imine condensation, without relying on external templates; the handedness of the trefoil knot is determined by the chirality of the bisamino precursor.

The fixed service charge pricing model adopted by traditional electric vehicle aggregators (EVAs) is difficult to effectively guide the demand side resources to respond to the power market price signal. At the same time, real-time pricing strategy can flexibly reflect the situation of market supply and demand, shift the charging load of electric vehicles (EVs), reduce the negative impact of disorderly charging on the stable operation of power systems, and fully tap the economic potential of EVA participating in the power market. Based on the historical behavior data of EVs, this paper considers various market factors such as peak-valley time-of-use tariff, demand-side response mode and deviation balance of spot market to formulate the objective function of EVA comprehensive revenue maximization and establishes a quarter-hourly vehicle-to-grid (V2G) dynamic time-sharing pricing model based on deep deterministic policy gradient (DDPG) reinforcement learning algorithm. The EVA yield difference between peak-valley time-of-use tariff and hourly pricing strategy under the same algorithm is compared through the case studies. The results show that the scheme with higher pricing frequency can guide the charging behavior of users more effectively, tap the economic potential of power market to a greater extent, and calm the load fluctuation of power grid.

The rapid development of renewable energy power has improved global energy and environmental problems. However, with the high volatility of renewable energy, it is an important challenge to guarantee the consumption of renewable energy and the reliable operation of high percentage renewable energy power systems. To solve this problem, this paper proposes a tracking absorption strategy for renewable energy based on the interaction between the supply side and the demand side, which adjusts the charging process of electric vehicles (EVs) through electric vehicle aggregator (EVA) to realize the tracking absorption of renewable energy abandoned electricity. In view of this process, we analyze the interaction among power grid, EVA and renewable energy generation (REG) as well as their market characteristics. The master-slave game model of EVA and REG was constructed considering the charging behavior characteristics of EVs and the output characteristics of REGs. Then the model solving strategy based on soft actor-critic (SAC) algorithm is proposed, and the REG pricing strategy and EVA scheduling strategy are calculated to optimize the mutual benefits. The case analysis shows that, under the same scale of electric vehicles, the proposed method can promote about 93.89% of the power abandonment consumption of wind power system, 96.00% of the photovoltaic system, and 97.41% of the wind-solar system. This strategy reduces the electricity purchase cost of EVA, promotes the interaction among renewable energy, vehicles and power grid, and improves the utilization efficiency of renewable energy.

The further liberalization of China’s electricity market encourages demand-side entities to participate in electricity market transactions. Electric vehicles (EVs) are developing rapidly and have high regulating potential, and are the main force for demand-side participation in the auxiliary service market. Aiming at the problems of dispatching accuracy and economy in EV participation in auxiliary service market, this paper analyzes the bidding strategy and dispatching scheme of EV-storage participation in auxiliary service market, and proposes EV-storage optimal allocation strategy with the goal of economic optimum. In the process of optimal allocation, based on the market rules of third-party subject participation in auxiliary services, the bidding strategy of EV-storage coordinated EV participation in auxiliary services market considering daily load scale changes is designed, while the conditional value at risk (CVaR) method is used to determine the short-term coordinated energy storage capacity and efficiency storage capacity considering the uncertainty of EV response situation; then, based on the annual EV load scale change, the benefit calculation function is constructed by considering various factors such as auxiliary service market revenue, spread revenue, investment cost and market opportunity cost of EV-storage participation in the auxiliary market. Finally, taking EV aggregation participation in the valley-filling ancillary service market as an example, it is verified that the strategy proposed in this paper can effectively improve the responsiveness of EV participation in the ancillary service market and increase the revenue of electric vehicle aggregator (EVA).

When grid impedance cannot be ignored, high-frequency harmonic amplification often occurs when Doubly-Fed Induction Generator (DFIG) generation system is connected to a non-ideal grid with background noise. This paper analyzes the mechanism of high-frequency harmonic amplification of DFIG wind power generation system under non-ideal grid, and quantifies the damping through the equivalent RLC one-port impedance model. The concept of voltage amplification factor is proposed to guide the design of virtual resistor for harmonic suppression. Based on the design results, the virtual resistor is realized by an active damper connected in parallel with the DFIG system at the point of common coupling (PCC). Considering the limit of this device, this paper designs the lower limit of the virtual resistor in case of over-modulation problem. Finally, a controller hardware-in-the-loop experiment is carried out based on the RT-LAB platform, and the experimental results verified the correctness of the analysis and the effectiveness of the device.

The hydrogenation of CO2 into valuable chemicals is greatly demanded, but suffers from complex product distribution. Here, the authors reported that, as a support and ligand, silica boosts cobalt catalysts to selectively hydrogenate CO2 into the desired methanol product.

As we continually reflect on the wars of the 20th century, identification of the remains of victims takes an increasingly prominent position in ongoing research. Existing work on the identification of human remains from 20th century wars primarily covers the determination of phenotypic characteristics, kinship and geographic origins, supporting the establishment of genetic information databases. Compared with standard forensic methods, DNA analyses have revealed greater effectiveness. The process of DNA analysis includes DNA extraction, genetic marker testing and data analysis. Protocols from ancient DNA research can be applied to degraded remains, and next-generation sequencing (NGS) techniques can compensate for shortcomings in the most commonly-used PCR-capillary electrophoresis typing. As it stands, wide-ranging inter-governmental and inter-institutional collaboration is necessary in order to set up NGS-based public databases, and thereby promote the identification of human remains and archaeological forensics.

Maoming is located in the southwest region of Guangdong Province and is the cradle of Gaoliang culture, which is the representative branch of Lingnan cultures. Historical records showed that the amalgamations between Gaoliang aborigines and distinct ethnic minorities had some influences on the shaping of Gaoliang culture, especially for the local Tai-kadai language-speaking Baiyue and Han Chinese from Central China. However, there is still no exact genetic evidence for the influences on the genetic pool of Maoming Han, and the genetic relationships between Maoming Han and other Chinese populations are still unclear. Hence, in order to get a better understanding of the paternal genetic structures and characterize the forensic features of 27 Y-chromosomal short tandem repeats (Y-STRs) in Han Chinese from Guangdong Maoming, we firstly applied the AmpFLSTR® Yfiler® Plus PCR Amplification Kit (Thermo Fisher Scientific, Waltham, MA, United States) to genotype the haplotypes in 431 Han males residing in Maoming. A total of 263 different alleles were determined across all 27 Y-STRs with the corresponding allelic frequencies from 0.0004 to 0.7401, and the range of genetic diversity (GD) was 0.4027 (DYS391) to 0.9596 (DYS385a/b). In the first batch of 27 Yfiler data in Maoming Han, 417 distinct haplotypes were discovered, and nine off-ladder alleles were identified at six Y-STRs; in addition, no copy number variant or null allele was detected. The overall haplotype diversity (HD) and discrimination capacity (DC) of 27 Yfiler were 0.9997 and 0.9675, respectively, which demonstrated that the 6-dye and 27-plex system has sufficient system effectiveness for forensic applications in Maoming Han. What is more, the phylogenetic analyses indicated that Maoming Han, which is a Southern Han Chinese population, has a close relationship with Meizhou Kejia, which uncovered that the role of the gene flows from surrounding Han populations in shaping the genetic pool of Maoming Han cannot be ignored. From the perspectives of genetics, linguistics, and geographies, the genetic structures of Han populations correspond to the patterns of the geographical-scale spatial distributions and the relationships of language families. Nevertheless, no exact genetic evidence supports the intimate relationships between Maoming Han and Tai-Kadai language-speaking populations and Han populations of Central Plains in the present study.

Guangdong province is situated in the south of China with a population size of 113.46 million. Hakka is officially recognized as a branch of Han Chinese, and She is the official minority group in mainland China. There are approximately 25 million Hakka people who mainly live in the East and North regions of China, while there are only 0.7 million She people. The genetic characterization and forensic parameters of these two groups are poorly defined (She) or still need to be explored (Hakka). In this study, we have genotyped 475 unrelated Guangdong males (260 Hakka and 215 She) with Promega PowerPlex® Y23 System. A total of 176 and 155 different alleles were observed across all 23 Y-STRs for Guangdong Hakka (with a range of allele frequencies from 0.0038 to 0.7423) and Guangdong She (0.0047–0.8605), respectively. The gene diversity ranged from 0.4877 to 0.9671 (Guangdong Hakka) and 0.3277–0.9526 (Guangdong She), while the haplotype diversities were 0.9994 and 0.9939 for Guangdong Hakka and Guangdong She, with discrimination capacity values of 0.8885 and 0.5674, respectively. With reference to geographical and linguistic scales, the phylogenetic analyses showed us that Guangdong Hakka has a close relationship with Southern Han, and the genetic pool of Guangdong Hakka was influenced by surrounding Han populations. The predominant haplogroups of the Guangdong She group were O2-M122 and O2a2a1a2-M7, while Guangdong She clustered with other Tibeto-Burman language-speaking populations (Guizhou Tujia and Hunan Tujia), which shows us that the Guangdong She group is one of the branches of Tibeto-Burman populations and the Huonie dialect of She languages may be a branch of Tibeto-Burman language families.

This study aimed to identify the biological processes associated with long-term survival in high-grade serous ovarian cancer (HGSOC). HGSOC cases obtained from The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) database were divided into long-term survivors (LTS) and normal-term survivors (NTS) based on survival cutoffs defined by the HGSOC cohort in the SEER database. Differentially expressed genes (DEGs) were screened using the generalized linear modeling (GLM) method. Gene Ontology (GO) functional and KEGG pathway enrichment analyses were performed using DAVID Bioinformatics Resources. DEG-related protein-protein interactions (PPI) were extracted from the STRING database and hub genes were identified using CytoHubba in the Cytoscape program. In total, 157 DEGs, including 155 upregulated and 2 downregulated genes, were identified. Upregulated genes were statistically enriched in 80 GO terms and 11 KEGG pathways related to energy and substrate metabolism, such as protein absorption, digestion, and metabolism as well as signaling pathways, including chromatin silencing, regulation of ERK1 and ERK2 cascade, and regulation of MAPKKK. ALB and POMC were the common hub genes. These findings reveal that protein anabolism is crucial to long-term survival, regulated by activation of the MAPK/ERK signaling pathway and chromatin silencing. Comprehensive understanding of the molecular mechanisms via further exploration may contribute toward an effective treatment for ovarian cancer.

Abstract Background This study investigated UGP2 (uridine diphosphate-glucose pyrophosphorylase-2) and CFL1 (cofilin-1) expression in pancreatic ductal carcinoma (PDC), paracancerous tissue (PT), benign lesions (BL), and normal tissue (NT) and their clinicopathological significance. Methods Surgical specimens, which were collected from 106 cases of pancreatic ductal carcinoma, 35 cases of paracancerous tissues, 55 cases of benign lesions and 13 cases of normal pancreatic tissues, were fixed with 4% formaldehyde to prepare conventional paraffin-embedded sections. EnVision immunohistochemical was used to stain for UGP2 and CFL1. Kaplan-Meier survival analysis was performed to assess the correlation of expression pattern with survival. Results We found that positive UGP2 and CFL1 expression in PDC were significantly higher than those in PT, BL, and NT. In PT and BL with positive UGP2 and CFL1 expression, mild to severe atypical hyperplasia or intraepithelial neoplasia of grades II–III was observed in ductal epithelium. Positive UGP2 and CFL1 expression in cases with high differentiation, no lymph node metastasis, no surrounding invasion, and TNM (tumor-node-metastasis) staging I or/and II were significantly lower than those in cases with poor differentiation, lymph node metastasis, surrounding invasion, and TNM stage III and/or IV. Positive UGP2 expression in male patients was significantly lower than that in female patients. UGP2 and CFL1 expression in PDC were positively correlated. Kaplan-Meier survival analysis showed the degree of differentiation, tumor maximal diameter, TNM stage, lymph node metastasis, and surrounding invasion, and UGP2 and CFL1 expression were closely related to the average survival time of patients with PDC. The survival time of patients with positive UGP2 and CFL1 expression was significantly shorter than that of patients with negative expression. Cox multivariate analysis showed that poor differentiation, tumor maximal diameter ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, and positive UGP2 and CFL1 expression was negatively correlated with the postoperative survival rate and positively correlated with the mortality of patients with PDC. Conclusion Positive expression of UGP2 and CFL1 can serve a valuable prognostic factor in pancreatic cancer.

Abstract Background Malignant tumors in the proximal fibula are rare but life-threatening; however, biopsy is not routine due to the high risk of peroneal nerve injury. Our aim was to determine preoperative clinical indicators of malignancy. Methods Between 2004 and 2016, 52 consecutive patients with proximal fibular tumors were retrospectively reviewed. Details of the clinicopathological characteristics including age, gender, location of tumors, the presenting symptoms, the duration of symptoms, and pathological diagnosis were collected. Descriptive statistics were calculated, and univariate and multivariate regression were performed. Results Of these 52 patients, 84.6% had benign tumors and 15.4% malignant tumors. The most common benign tumors were osteochondromas (46.2%), followed by enchondromas (13.5%) and giant cell tumors (13.5%). The most common malignancy was osteosarcomas (11.5%). The most common presenting symptoms were a palpable mass (52.0%) and pain (46.2%). Pain was the most sensitive (100%) and fourth specific (64%); both high skin temperature and peroneal nerve compression had the highest specificity (98%) and third sensitivity (64%); change in symptoms had the second highest specificity (89%) while 50% sensitivity. Using multivariate regression, palpable pain, high skin temperature, and peroneal nerve compression symptoms were predictors of malignancy. Conclusions Most tumors in the proximal fibula are benign, and the malignancy is rare. Palpable pain, peroneal nerve compression symptoms, and high skin temperature were specific in predicting malignancy.

Considering the inherent characteristics of the park heating load, such as transmission delay, fuzzy heating comfort, etc., it can be used as a flexible load to participate in the optimal scheduling. Aiming at the minimum operation cost of the integrated energy system in the park, a collaborative optimal scheduling model of the park's integrated energy system with the participation of comprehensive demand response of electric heating load is constructed. The simulation results show that, compared with the optimization results of traditional power demand response, the application of integrated demand response of electric heating load improves the flexibility of production of cogeneration units in the park, reduces the total energy consumption cost of demand side users and the operation cost of the system on the premise of ensuring the balance of supply and demand of the system, improves the energy utilization efficiency, and realizes the environmental protection and economy of the system function.

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At the present stage, China’s energy development has the following characteristics: continuous development of new energy technology, continuous expansion of comprehensive energy system scale, and wide application of multi-energy coupling technology. Under the new situation, the accurate prediction of power load is the key to alleviate the problem that the planning and dispatching of the current power system is more complex and more demanding than the traditional power system. Therefore, firstly, this paper designs the calculation method of the power load demand of the grid under the multi-energy coupling mode, aiming at the important role of the grid in the power dispatching in the comprehensive energy system. This load calculation method for regional power grid operating load forecasting is proposed for the first time, which takes the total regional load demand and multi-energy coupling into consideration. Then, according to the participants and typical models in the multi-energy coupling mode, the key factors affecting the load in the multi-energy coupling mode are analyzed. At this stage, we fully consider the supply side resources and the demand side resources, innovatively extract the energy system structure characteristics under the condition of multi-energy coupling technology, and design a key factor index system for this mode. Finally, a least squares support vector machine optimized by the minimal redundancy maximal relevance model and the adaptive fireworks algorithm (mRMR-AFWA-LSSVM) is proposed, to carry out load forecasting for multi-energy coupling scenarios. Aiming at the complexity energy system analysis and prediction accuracy improvement of multi-energy coupling scenarios, this method applies minimal redundancy maximal relevance model to the selection of key factors in scenario analysis. It is also the first time that adaptive fireworks algorithm is applied to the optimization of adaptive fireworks algorithm, and the results show that the model optimization effect is good. In the case of A region quarterly load forecasting in southwest China, the average absolute percentage error of a least squares support vector machine optimized by the minimal redundancy maximal relevance model and the adaptive fireworks algorithm (mRMR-AFWA-LSSVM) is 2.08%, which means that this model has a high forecasting accuracy.

Objectives The aim of this study was to identify patient- and treatment-specific independent risk factors for the recurrence of proximal fibular tumors and complications of their surgical management. Methods Patients who underwent surgical treatment of proximal fibular tumors at our institution from 2004 to 2015 were retrospectively reviewed. All patients had a pathologically confirmed diagnosis and were followed up for at least 12 months for recurrence and complications. All patients were evaluated with respect to seven patient-, disease-, and treatment-specific variables. Results In the univariate analysis, peroneal nerve palsy at presentation and malignancy were associated with an increased risk of recurrence, iatrogenic peroneal nerve injury, and wound healing problems. The multivariate analysis showed that peroneal nerve palsy at presentation was an independent risk factor for recurrence and iatrogenic peroneal nerve injury and that malignancy was an independent risk factor for wound healing problems. Conclusions Peroneal nerve palsy and malignant potential are independent risk factors for complications of surgical treatment of proximal fibular tumors. The recognition of these factors may contribute to proper management and help to prevent recurrence and postoperative complications.

Genetically engineered mouse models play a pivotal role in the modeling of diseases, exploration of gene functions, and the development of novel therapies. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated genome editing technology has revolutionized the process of developing such models by enabling precise genome modifications of the multiple interested genes simultaneously. Following genome editing, an efficient genotyping methodology is crucial for subsequent characterization. However, current genotyping methods are laborious, timeconsuming, and costly. Here, using targeting the mouse trypsinogen genes as an example, we introduced common applications of CRISPR-Cas9 editing and a streamlined cost-effective genotyping workflow for CRISPR-edited mouse models, in which Sanger sequencing is required only at the initial steps. In the F0 mice, we focused on identifying the presence of positive editing by PCR followed by Sanger sequencing without the need to know the exact sequences, simplifying the initial screening. In the F1 mice, Sanger sequencing and algorithms decoding were used to identify the precise editing. Once the edited sequence was established, a simple and effective genotyping strategy was established to distinguish homozygous and heterozygous status by PCR from tail DNA. The genotyping workflow applies to deletions as small as one nucleotide, multiple-gene knockout, and knockin studies. This simplified, efficient, and cost-effective genotyping shall be instructive to new investigators who are unfamiliar with characterizing CRISPR-Cas9-edited mouse strains. [ABSTRACT FROM AUTHOR]