With the continuous development of network technology, complex network systems generate massive unbalanced attack traffic. Due to the severe imbalance in the quantities of normal samples and attack samples, as well as among different types of attack samples, intrusion detection systems suffer from low detection rates for rare class attack data. In this paper, we propose a geometric synthetic minority oversampling technique based on optimized kernel density estimation algorithm. This method can generate diverse rare class attack data by learning the distribution of rare class attack data while maintaining similarity with the original sample features. Meanwhile, the balanced data is input to a feature extraction module built upon multiple denoising autoencoders, reducing information redundancy in high-dimensional data and improving the detection performance for unknown attacks. Subsequently, a soft voting ensemble learning technique is utilized for multi-class anomaly detection on the balanced and dimensionally reduced data. Finally, an intrusion detection system is constructed based on data preprocessing, imbalance handling, feature extraction, and anomaly detection modules, and validated on the NSL-KDD and N-BaIoT datasets. Comparative experiments with baseline models and other state-of-the-art methods demonstrate that the proposed system improves the detection rate of rare class attack data. Furthermore, it achieves a good overall detection rate on the Internet of Things dataset (N-BaIoT), indicating its strong applicability.

Increasing numbers of researchers are interested in the importance of dietary fiber for the gut microbiota, microbiotal metabolite SCFA, energy metabolism and gut health of the host. However, studies have demonstrated that long-term and longitudinal observation may be needed to evaluate the effect of dietary fiber better, and few such works have been made in chickens. Therefore, we successively fed low-fiber, high--fiber and low-fiber diets to two breeds of chickens during different growth periods (1—8, 9—20 and 21—50 weeks), aiming to longitudinally observe the long-term effect of altered dietary fiber on the gut microbiota, SCFA and development of cecum of chickens with age. The results showed that the composition and function of the gut microbiota, SCFA and the development of the cecum were different during different periods, which was largly affected by dietary fiber. However, the causes of some effects were different during the different periods. For example, compared with that in low-fiber chickens at 8 weeks, dominant fiber-degradation bacteria such as Bacteroidetes, Alloprevotella and SCFA-producing bacteria such as Faecalibacterium increased due to a high-fiber diet at 20 weeks, while due to a high feed intake in 50 weeks. Moreover, the concentration of SCFA in 20 weeks was significantly higher than in 8 weeks and 50 weeks, but the causes of this difference were also distinct. It was proposed that a long-term observation was needed to evaluate the effect of dietary fiber better on chickens. The metabolite pathways of ATP-binding cassette (ABC) transporters encoded by Firmicutes were enriched in 8 weeks, while a two-component system and β–glucosidase encoded by Bacteroidetes were enriched in 20 and 50 weeks. The trend was the same in two breeds of chickens except for Alloprevotella. In addition, the total content of SCFA in the contents of cecum was also affected by the size of the cecum. Surprisingly, the length of the cecum shortened from 20—50 weeks, maybe due to reduced dietary fiber.

It is of merit to study the appropriate amount of fiber to add to free-range chickens feed to improve the microbial diversity and gut health in times of plant fiber deprivation. OptiCell is a useful source of fiber as a type of eubiotic lignocellulose, and its positive effects on the growth performance and laying performance of chickens has already been proven. However, few researchers have researched the effects of adding OptiCell on the gut microbiota of chickens. In this research we added three different levels of OptiCell (0%, 2% and 4%) to the feed of caged and free-range Bian chickens from September to November, aiming to observe the effects of adding OptiCell and different feeding modes on the gut microbial diversity and gut health of chickens, and aiming to determine an appropriate amount of OptiCell. The results showed that adding OptiCell could increase the thickness of the cecum mucus layer and the abundance of Akkermansia and Faecalibacterium in caged chickens, and 4% OptiCell was optimum. In addition, adding OptiCell increased the microbial diversity and the abundance of the butyrate-producing bacteria Faecalibacterium and Roseburia of fee-range chickens. The α-diversity and the length of the small intestine with 2% OptiCell in free-range chickens were better than with 2% OptiCell in caged chickens. In addition, compared with caged chickens, the free-range chickens had longer small intestine and lower GLP-1. Taken together, an appropriate amount of OptiCell benefitted the microbial diversity and health of chickens; it was necessary to add dietary fiber to the feed of free-range chickens when plant fibers was lacking, and 2% OptiCell was found to be optimum.

Cisplatin-based chemotherapy has long been viewed as the first-line chemotherapy for advanced and metastatic urothelial carcinoma (UC). However, many patients with UC have been classified as “cisplatin-ineligible patient”, which requires alternative chemotherapy due to their poor responses. In fact, vast majority of those who initially responded to cisplatin-based chemotherapy eventually progressed. Understanding of UC tumor immunology provided an immunopathogenic bases for immune checkpoint inhibitors, targeting PD-1 and CTLA-4, to treat cisplatin ineligible metastatic UC and patients with platinum-refractory metastatic UC. In 2020, data from the trail further showed that PD-L1 inhibitors benefit prolonged survival and progression-free survival as maintenance therapy. Besides immune-targeting therapies, manipulation of tumor microenvironment via metabolic pathways alternation, such as inhibiting tumor glycolysis, lactate accumulation and exogenous glutamine uptake, has been investigated in the past few years. In this comprehensive review, we started by introducing traditional chemotherapy of UC, and summarized current evidences supporting the use of immune checkpoint inhibitors and highlighted ongoing clinical trials. Lastly, we reviewed the tumor metabolic characteristic and the anti-tumor treatments targeting metabolic pathways.

Ultra-high temperature oxidation-resistant alloys (UTORAs) have received a lot of attention due to the increased research demand for deep space exploration around the world. But UTORAs have the disadvantages of easy oxidation and chalking. So, in this study, a UTORA was prepared by hot-press sintering on VZrHfNbTa (HEA) substrate coated with hafnium. The bonding mechanism, resistance to high-temperature oxidation, and hardness of the sample tests were carried out. The results show that zirconium in the matrix will diffuse into the hafnium coating during the high-temperature sintering process and form the HfZr alloy transition layer, the coating thickness of the composite is about 120 μm, and the diffusion distance of zirconium in the hafnium coating is about 60 μm, this transition layer chemically combines the hafnium coating and the HEA substrate into a monolithic alloy composite. The results of high-temperature oxidation experiments show that the oxidation degree of the hafnium-coated VZrHfNbTa composite material was significantly lower than that of the VZrHfNbTa HEA after oxidation in air at 1600 °C for 5 h. The weight gain of the coated sample after oxidation is 56.56 mg/cm2, which was only 57.7 % compared to the weight gain of the uncoated sample (98.09 mg/cm2 for uncoated), and the surface of the uncoated HEA showed obvious dents, oxidation, and pulverization occurred on the surface and interior of the sample. In contrast, the coated composite alloy sample mainly underwent surface oxidation sintering to form a dense HfO2 protective layer, and the internal oxidation of the hafnium-coated VZrHfNbTa composite alloy was significantly lower than that of the uncoated VZrHfNbTa HEA.

This study provides a novel method to prepare metal-ceramic composites from magnetically selected iron ore using microwave heating. By introducing three different microwave susceptors (Activated Carbon, SiC, and a mixture of Activated Carbon and SiC) during the microwave process, effective control of the ratio of metallic and ceramic phases has been achieved easily. The effects of the three susceptors on the microstructure of the metal-ceramics and the related reaction mechanisms were also investigated in detail. The results show that the metal phase (Fe) and ceramic phase (Fe2SiO4, FeAl2O4) can be maintained, but the metal phase to ceramic phase changed significantly. In particular, the microstructures appeared as well-distributed nanosheet structures with diameters of ~400 nm and thicknesses of ~20 nm when SiC was used as the microwave susceptor.

Sweet pepper is an important vegetable in the world. Bacterial leaf spot caused by the pathogen Xanthomonas perforans, is a limiting factor that significantly reduces the quality and yield of sweet pepper To control this disease, the use of chemical fungicides is currently the main disease control method. Thus, we want to develop an alternative method by using antagonistic microorganisms. Under this demand, Bacillus amyloliquefaciens PMB04 has strong antagonistic effects against pathogens and can inhibit the occurrence of diseases. B. amyloliquefaciens PMB04 has the potential for the development of a disease control product. Primarily, PMB04 revealed to contain a strong inhibitory effect against all isolated X. perforans strains. In the inoculation assay, the severity of bacterial spot disease on sweet peppers was reduced by PMB04 bacterial suspensions. To increase the convenience of field application for future prospects, the development of PMB04 fermentation liquid was carried out with different ratios of brown sugar and yeast extract in a 30-liter fermentation tank subsequently. Results exhibited that the fermentation liquid of 3-1 formula obtained the highest bacterial population in a 30-liter fermentation tank. The fermentation liquid of 0.5-0.5 formula was the most stable formula under two different conditions in terms of consistent bacterial population and sporulation. In addition, the 200-fold dilution of 3-1 and 0.5-0.5 fermentation liquids revealed best control efficacy on bacterial leaf spot of sweet pepper. Additionally, the results of the 0.5-0.5 fermentation liquid (PMB4FL) with different dilution concentrations also showed that the 200- and 500-fold dilutions had the best control efficacy. To understand the effect of commonly used copper-containing fungicides on sweet peppers on the application of microbial agent PMB4FL, the effects of copper hydroxide and tribasic copper sulfate on the growth of X. perforans strains and B. amyloliquefaciens PMB04 were assayed. The results exhibited that the above two fungicides did not have any inhibitory effect on the growth of PMB04, but had a strong inhibitory effect on the X. perforans strain. In the follow-up control experiment, the treatment of copper hydroxide had no synergistic effect with PMB4FL to control bacterial leaf spot. We concluded that the use of PMB4FL fermentation liquid alone on the leaves can effectively control the occurrence of bacterial leaf spot in sweet pepper crops.

Alternative splicing can produce transcripts that affect cancer development and shows potential for cancer diagnosis and treatment. However, intron retention (IR), a type of alternative splicing, has been less systematically studied in cancer biology research. Here, we generated a pan-cancer IR landscape for more than 10,000 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). We characterized differentially retained introns between tumor and normal samples and identified retained introns associated with survival. We discovered 988 differentially retained introns in 14 cancers, some of which demonstrated diagnostic potential in multiple cancer types. We also inferred a large number of prognosis-related introns in 33 cancer types, and the associated genes included well-known cancer hallmarks such as angiogenesis, metastasis, and DNA mutations. Notably, we discovered a novel intron retention event inside 5′UTR of STN1 that is associated with the survival of lung cancer patients. The retained intron reduces translation efficiency by producing upstream open reading frames (uORFs) and thereby inhibits colony formation and cell migration of lung cancer cells. Besides, the IR-based prognostic model achieved good stratification on certain cancers, as illustrated in acute myeloid leukemia. Taken together, we performed a comprehensive IR survey at a pan-cancer level, and the results implied that IR has the potential to be diagnostic and prognostic cancer biomarkers, as well as new drug targets.

Strigolactones (SLs) are a novel emerging plant hormones, which play important roles in regulating plant organ development and environmental stress tolerance. Even though the SL related genes have been identified and well characterized in some plants. The information of SL related genes in soybean is not fully established yet, especially in response to salt stress. In this study, we identified nine SL biosynthesis genes: two D27, two CCD7, two CCD8, and three MAX1, and seven SL signaling genes: two D14, two MAX2 and three D53 in soybean genome. We found that SL biosynthesis and signaling genes are conserved during evolution in different species. Syntenic analysis of these genes revealed their location on nine chromosomes as well as existence of ten pairs of duplication genes. Moreover, plant hormone and stress-responsive elements were identified in the promoter regions of SL biosynthesis and signaling genes. By using quantitative real-time PCR (qRT-PCR), we confirmed that SL genes have different tissue expression in roots, stems and leaves. Further, we also explored the expression profiles of SL biosynthesis and signaling genes under salt stress. These results suggested that SL signaling genes may play important regulatory roles in response to salt stress. In conclusion, we identified and provided valuable information on the soybean SL biosynthesis and signaling genes, and established a foundation for further functional analysis of soybean SL related genes in response to salt stress.

Space-based gravitational wave detection is extremely sensitive to disturbances. The Keplerian configuration cannot accurately reflect the variations in spacecraft configuration. Planetary gravitational disturbances are one of the main sources. Numerical simulation is an effective method to investigate the impact of perturbation on spacecraft orbits. This study shows that, in the context of the Taiji project, Earth’s gravity is an essential factor in the change in heliocentric formation configuration, contributing to the relative acceleration between spacecrafts in the order of O(10−6)m·s−2. Considering 00:00:00 on October 27, 2032 as the initial orbiting moment, under the influence of Earth’s gravitational perturbation, the maximum relative change in armlengths and variation rates of armlengths for Taiji is 1.6×105km, 32m·s−1 respectively, compared with the unperturbed Keplerian orbit. Additionally, by considering the gravitational perturbations of Venus and Jupiter, the armlength and relative velocity for Taiji are reduced by 16.01% and 17.45%, respectively, compared with when only considering that of Earth. The maximum amplitude of the formation motion indicator changes with the orbit entry time. Results show that the relative velocity increase between the spacecrafts is minimal when the initial orbital moment occurs in July. Moreover, the numerical simulation results are inconsistent when using different ephemerises. The differences between ephemeris DE440 and DE430 are smaller than those between DE440 and DE421.

The objective of this study was to synthesize 9-/13-position substituted berberine derivatives and evaluated their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e) and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in compare with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at 9-/13-position of berberine may have facilitated its penetration into test cell and hence enhanced its photocytotoxicity on human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e and 7e induced HepG2 cells to arrest at S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine (1) and its derivatives 5e, 6e and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e and 7e greatly enhanced photocytotoxicity. Taking together, the test data led us to conclude that berberine derivatives with a dodecyl group at 9-/13-position could be great candidates for the anti-liver cancer medicines developments.

While pioglitazone reduces insulin resistance and hepatic gluconeogenesis effectively in patients with T2DM, these benefits remained controversial in patients with ESRD. We compared MACCEs and mortality (overall, infection-related, and MACCE-related) of pioglitazone to that of DPP4-inhibitors in patients with T2DM and ESRD. From Taiwan’s national health insurance database, 647 pioglitazone users and 6080 DPP4-inhibitors users between April 1st, 2006 and December 31th, 2016 were followed from the 91th date after the ESRD certification till study outcomes, independently; withdraw from the NHI program, death, or Dec. 31th, 2017. After weighting, risks of MACCEs (10.48% vs 12.62% per person-years, [HR]: 0.85, 95% [CI]: 0.729–0.985) and all-cause mortality (12.86% vs 13.22% per person-years, [HR]: 0.88, 95% [CI]: 0.771–0.995) are significantly lower in pioglitazone group. Subgroup analysis found lower MACCEs risk in the pioglitazone users without insulin therapy (6.44% vs 10.04% [HR]: 0.59, 95% [CI]: 0.42–0.82) and lower MACCEs related death (2.76% vs 3.84% [HR]: 0.61, 95% [CI]: 0.40–0.95) in the pioglitazone group with dyslipidemia, when comparing with DPP4-inhibitors users. Pioglitazone is associated with lower all-cause mortality and MACCEs in diabetic patients with ESRD, compared to DPP4-inhibitors. These benefits were further significant in the non-insulin users and patients with dyslipidemia.