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The increasingly severe antibiotic pollution has become one of the most critical issues. In this study, a zinc peroxide/peroxymonosulfate (ZnO 2 /PMS) double-oxidation system was developed for tetracycline (TC) degradation. A small amount of ZnO 2 (10 mg) and PMS (30 mg) could effectively degrade 82.8% of TC (100 mL, 50 mg/L), and the degradation process could be well described by the pseudo-second-order kinetic model. Meanwhile, the ZnO 2 /PMS double-oxidation system showed high adaptability in terms of reaction temperature (2-40 °C), initial pH value (4-12), common inorganic anions (Cl - , NO 3 - , SO 4 2- and HCO 3 - ), natural water source and organic pollutant type. The quenching experiment and electron paramagnetic resonance (EPR) characterization results confirmed that the main reactive oxygen species (ROS) was singlet oxygen ( 1 O 2 ). Moreover, three possible pathways of TC degradation were deduced according to the analyses of intermediates. On the basis of comparative characterization and experiment results, a synergistic activation mechanism was further proposed for the ZnO 2 /PMS double-oxidation system, accounting for the superior degradation performance. The released OH - and H 2 O 2 from ZnO 2 could activate PMS to produce major 1 O 2 and minor superoxide radicals (•O 2 - ), respectively.

The delay in wound healing caused by chronic wounds or pathological scars is a pressing issue in clinical practice, imposing significant economic and psychological burdens on patients. In particular, with the aging of the population and the increasing incidence of diseases such as diabetes, impaired wound healing is one of the growing health problems. MicroRNA (miRNA) plays a crucial role in wound healing and regulates various biological processes. Our results show that miR-618 was significantly upregulated during the inflammatory phase of wound healing.Subsequently, miR-618 promotes the secretion of pro-inflammatory cytokines and regulates the proliferation and migration of keratinocytes. Mechanistically, miR-618 binds to the target gene- Atp11b and inhibits the PI3K-Akt signaling pathway, inhibiting the epithelial-mesenchymal transition (EMT) of keratinocytes. In addition, the PI3K-Akt signaling pathway induces the enrichment of nuclear miR-618, and miR-618 binds to the promoter of Lin7a to regulate gene transcription. Intradermal injection of miR-618 antagomir around full-thickness wounds in peridermal mice effectively accelerates wound closure compared to control. In conclusion, miR-618 antagomir can be a potential therapeutic agent for wound healing.

Grain boundary (GB) precipitation-induced cracking is a significant issue for S31254 super austenitic stainless steel during hot working. Investigating the deformation behavior based on precipitate morphology and distribution is essential. In this study, continuous smaller and intermittent larger precipitates were obtained through heat treatments at 950 °C and 1050 °C. The microstructure evolution and mechanical properties influenced by precipitates were experimentally investigated using an in situ tensile stage inside a scanning electron microscope (SEM) combined with electron backscatter diffraction (EBSD). The results showed that continuous precipitates at 950 °C had a stronger pinning effect on the GB, making grain rotation difficult and promoting slip deformation in the plastic interval. Continuous precipitates caused severe stress concentration near GB and reduced coordinated deformation ability. Additionally, the crack propagation path changed from transcrystalline to intercrystalline. Furthermore, internal precipitates were a crucial factor affecting the initial crack nucleation position. Interconnected precipitates led to an intergranular fracture tendency and severe deterioration of the material's plasticity, as observed in fracture morphology.

Ding'an (DA) pig, a prominent local breed in Hainan Province, exhibits notable advantages in coarse feeding tolerance and high-quality meat. To explore the potential genetic mechanism of coarse feeding tolerance in DA pigs, 60-day-old full sibling pairs of DA and DLY (Duroc-Landrace-Yorkshire) pigs were subjected to fed normal (5%) and high (10%) crude fiber diets for 56 days, respectively. The findings showed that increasing the crude fiber level had no impact on the apparent digestibility of crude fiber, intramuscular fat, and marbling scores in DA pigs, whereas these factors were significantly reduced in DLY pigs ( p < 0.05). Through differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) of the colonic mucosal transcriptome data, 65 and 482 candidate genes with coarse feeding tolerance in DA pigs were identified, respectively. Joint analysis screened four key candidate genes, including LDHB , MLC1 , LSG1 , and ESM1 , potentially serving as key regulated genes for coarse feeding tolerance. Functional analysis revealed that the most significant pathway enriched in differential genes associated with coarse feeding tolerance in Ding'an pigs was the signaling receptor binding. The results hold substantial significance for advancing our understanding of the genetic mechanisms governing coarse feeding tolerance in Ding'an pigs.

We utilized a first-principle density functional theory for a comprehensive analysis of CsPbX 3 (X = F, Cl, Br, I) to explore its physical and chemical properties, including its mechanical behavior, electronic structure and optical properties. Calculations show that all four materials have good stability, modulus of elasticity, hardness and wear resistance. Additionally, CsPbX 3 demonstrates a vertical electron leap and serves as a semiconductor material with direct band gaps of 3.600 eV, 3.111 eV, 2.538 eV and 2.085 eV. In examining its optical properties, we observed that the real and imaginary components of the dielectric function exhibit peaks within the low-energy range. Furthermore, the dielectric function gradually decreases as the photon energy increases. The absorption spectrum reveals that the CsPbX 3 material exhibits the highest UV light absorption, and as X changes (with the increase in atomic radius within the halogen group of elements), the light absorption undergoes a red shift, becoming stronger and enhancing light utilization. These properties underscore the material's potential for application in microelectronic and optoelectronic device production. Moreover, they provide a theoretical reference for future investigations into CsPbX 3 materials.

Temperature-sensitive carboxylated cellulose nanocrystals/N-isopropyl acrylamide aerogels (CCNC-NIPAMs) were developed as novel pesticide-controlled release formulas. Ammonium persulfate (APS) one-step oxidation was used to prepare bagasse-based CCNCs, and then the monomer N-isopropyl acrylamide (NIPAM) was successfully introduced and constructed into the temperature-sensitive CCNC-NIPAMs through polymerization. The results of the zeta potential measurement and Fourier infrared transform spectrum (FTIR) show that the average particle size of the CCNCs was 120.9 nm, the average surface potential of the CCNCs was -34.8 mV, and the crystallinity was 62.8%. The primary hydroxyl group on the surface of the CCNCs was replaced by the carboxyl group during oxidation. The morphology and structure of CCNC-NIPAMs were characterized via electron microscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), compression performance, porosity analysis, and thermogravimetric (TG) analysis. The results demonstrate that CCNC-NIPAM has a high porosity and low density, as well as good thermal stability, which is conducive to loading and releasing pesticides. In the swelling, drug loading, and controlled release process, the CCNC-NIPAM exhibited significant temperature sensitivity. Under the same NIPAM reaction amount, the equilibrium swelling rate of the CCNC-NIPAM first increased and then decreased with increasing temperature, and the cumulative drug release ratio of the CCNC-NIPAM at 39 °C was significantly higher than that at 25 °C. The loading efficiency of the CCNC-NIPAM on the model drug thiamethoxam (TXM) was up to 23 wt%, and the first-order model and Korsmyer-Peppas model could be well-fitted in the drug release curves. The study provides a new method for the effective utilization of biomass and pesticides.

Silicon nitride ceramics are regarded as a promising material for high-temperature structural applications due to their remarkable characteristics, including high strength, hardness, thermal conductivity, low dielectric properties, and resistance to creep at elevated temperatures. However, their susceptibility to catastrophic fracture at high temperatures remains a concern. Herein, Si 3 N 4 /BN fibrous monolithic ceramics have been successfully prepared by employing wet-spinning and hot-pressing techniques. We delved into the design and optimization of the spinning slurry and examined how the Si 3 N 4 /BN fiber diameter affects the ceramics' microstructure and mechanical properties. The spinning slurry exhibited exceptional stability and spinnability. Decreasing the fiber diameter contributed to material densification and improved mechanical properties. Notably, when the fiber diameter is 0.9 mm, the fabricated Si 3 N 4 /BN fibrous monolithic ceramics demonstrate a carbon content of 0.82%, a three-point bending strength of 357 ± 24 MPa, and a fracture toughness of 8.8 ± 0.36 MPa·m 1/2 . This investigation offers valuable insights into producing high-performance Si 3 N 4 /BN composite ceramics utilizing hot-pressing technology.

Japanese encephalitis (JE), found in pigs, is a serious mosquito-borne zoonotic infectious disease caused by the Japanese encephalitis virus (JEV). JEV is maintained in an enzootic cycle between mosquitoes and amplifying vertebrate hosts, mainly pigs and wading birds. It is transmitted to humans through the bite of an infected mosquito, allowing the pathogen to spread and cause disease epidemics. However, there is little research on JEV genotype variation in mosquitoes and pigs in Fujian province. Previous studies have shown that the main epidemic strain of JEV in Fujian Province is genotype III. In this study, a survey of mosquito species diversity in pig farms and molecular evolutionary analyses of JEV were conducted in Fujian, China, in the summer of 2019. A total of 19,177 mosquitoes were collected at four sites by UV trap. Four genera were identified, of which the Culex tritaeniorhynchus was the most common mosquito species, accounting for 76.4% of the total (14,651/19,177). Anopheles sinensi (19.25%, 3691/19,177) was the second largest species. High mosquito infection rateswere an important factor in the outbreak. The captured mosquito samples were milled and screened with JEV-specific primers. Five viruses were isolated, FJ1901, FJ1902, FJ1903, FJ1904, and FJ1905. Genetic affinity was determined by analyzing the envelope (E) gene variants. The results showed that they are JEV gene type I and most closely related to the strains SH-53 and SD0810. In this study, it was found through genetic evolution analysis that the main epidemic strain of JE in pig farms changed from gene type III to gene type I. Compared with the SH-53 and SD0810 strains, we found no change in key sites related to antigenic activity and neurovirulence of JEV in Fujian JEV and pig mosquito strains, respectively. The results of the study provide basic data for analyzing the genotypic shift of JEV in Fujian Province and support the prevention and control of JEV.

Sodium excretion, a critical process in sodium homeostasis, occurs in many tissues, including the kidney and intestine. Unlike in the kidney, the hormonal regulation of intestinal sodium excretion remains unclear. Atrial natriuretic peptide (ANP) is a crucial hormone in renal natriuresis. Corin is a protease critical for ANP activation. Corin and ANP are expressed mainly in the heart. In this study, we investigated corin, ANP, and natriuretic peptide receptor A (Npra) expression in mouse intestines. Corin and ANP expression was co-localized in enteroendocrine cells, whereas Npra expression was on the luminal epithelial cells. In Corin knockout (KO) mice, fecal Na + and Cl - excretion decreased compared with that in wild-type (WT) mice. Such a decrease was not found in conditional Corin KO mice lacking cardiac corin selectively. In kidney conditional Corin KO mice lacking renal corin, fecal Na + and Cl - excretion increased, compared to that in WT mice. When WT, Corin KO, and the kidney conditional KO mice were treated with aldosterone, the differences in fecal Na + and Cl - levels disappeared. These results suggest that intestinal corin may promote fecal sodium excretion in a paracrine mechanism independent of the cardiac corin function. The increased fecal sodium excretion in the kidney conditional Corin KO mice likely reflected an intestinal compensatory response to renal corin deficiency. Our results also suggest that intestinal corin activity may antagonize aldosterone action in the promotion of fecal sodium excretion. These findings help us understand the hormonal mechanism controlling sodium excretion the intestinal tract.

Hawthorn ( Crataegus pinnatifida var. major ), a cultivated fruit tree, is native and unique to China. Its fruits have high nutritional, health, and medicinal values. However, the development and ripening process of hawthorns is accompanied by dramatic changes in flavor, aroma, and bioactive phytochemicals, which are the fundamental factors that contribute to the potential health benefits and establishment of fruit quality. Therefore, an exploration of the dynamic changes in metabolites and their regulatory networks during the development of hawthorn fruits can elucidate the formation mechanisms of active substances in hawthorn fruits. In this study, we used a broad targeted metabolomics approach to identify and analyze the dynamics of metabolites in hawthorn fruits at five developmental stages. The results revealed 998 primary and secondary metabolites that were classified into 15 categories. The accumulation levels of most sugars increased during fruit development and then accelerated at the fruit ripening stage. The accumulation levels of a few organic acids (e.g., citric acid, isocitric acid, and quinic acid) continuously increased. Many organic acids exhibited significant decreasing trends. Among the 561 secondary metabolites detected, 189 were phenolic acids and 199 were flavonoids. The levels of many flavonoids were significantly reduced at later stages of fruit development; in contrast, the levels of two anthocyanins significantly increased during fruit ripening. Correlation analysis revealed that there is a certain correlation within and between primary as well as secondary metabolites during fruit development. Furthermore, the integration of metabolomic and transcriptomic data in this study revealed that changes in the expression of some differentially expressed genes (DEGs) were associated with the accumulation of metabolites such as sugars, organic acids, and flavonoids, e.g., the upregulated expression levels of CS (citrate synthase) genes were consistent with the continued accumulation of citric acid. Overall, this study demonstrates the metabolic changes that occur during the development of hawthorn fruit, explores the molecular mechanisms that underlie metabolite changes during fruit development, and lays a strong theoretical foundation for the improvement of hawthorn fruit quality and the development of functional components.

Escherichia coli ( E. coli ) bloodstream infections (BSIs) are among the most predominant causes of death in infants and children worldwide. NDM-5 (New Delhi Metallo-lactamase-5) is responsible for one of the main mechanisms of carbapenem resistance in E. coli . To analyze the phenotypic and genomic characteristics of NDM-5-producing E. coli from bloodstream infections (BSIs), a total of 114 E. coli strains was collected from a children's hospital in Jiangsu province, China. Eight bla NDM-5 -carrying E. coli strains were identified which were all carbapenem-resistant and carried diverse antimicrobial resistance genes apart from bla NDM-5 . They belonged to six distinct sequence types (STs) and serotypes including one each for ST38/O7:H8, ST58/O?:H37, ST131/O25:H4, ST156/O11:H25 and ST361/O9:H30 and three strains are originating from a single clone belonging to ST410/O?:H9. Apart from bla NDM-5 , the E. coli strains isolated from BSIs also carried other β-lactamase genes, including bla CMY-2 ( n = 4), bla CTX-M-14 ( n = 2), bla CTX-M-15 ( n = 3), bla CTX-M-65 ( n = 1), bla OXA-1 ( n = 4) and bla TEM-1B ( n = 5). The bla NDM-5 genes were located on three different types of plasmids, which were IncFII/I1 ( n = 1), IncX3 ( n = 4) and IncFIA/FIB/FII/Q1 ( n = 3). The former two types were conjugatively transferable at frequencies of 10 -3 and 10 -6 , respectively. The dissemination of NDM-producing strains, which exhibit resistance to the last-line antibiotics, carbapenems, may increase the muti-antimicrobial resistance burden among E. coli BSIs and further threaten public health.

Streptococcus suis is a significant pathogen in pigs and a newly emerging zoonotic agent in humans. The presence of multiple serotypes and strains with diversified sequence types in pig herds highlights the need for the identification of broadly cross-reactive universal vaccine antigen targets, capable of providing cross-protection against S. suis infection. Subunit vaccines based on the conserved proteins shared between different S. suis serotypes are potential candidates for such a universally protective vaccine. In the present study, phosphate ABC transporter ATP-binding protein PstB (PstB), an immunogenic protein of the S. suis bacterium, was expressed and purified, and then subjected to cross-protection evaluation in mice. The PstB protein showed nearly 100% amino acid similarity across a panel of 31 S. suis isolates representing different serotypes, which were collected from different countries. A recombinant PstB (rPstB) protein ( S. suis serotype 2) was recognized by rabbit sera specific to this serotype, and induced high levels of IFN-γ and IL-4 in mice immunized with the recombinant protein. These cytokines are considered important for protection against S. suis infection. Immunization of mice with rPstB resulted in an 87.5% protection against challenge with S. suis serotype 2 and 9 strains, suggesting a high level of cross-protection for S. suis serotypes 2 and 9. A lower protection rate (62.5%) was observed in mice challenged with the S. suis serotype 7 strain. These data demonstrate that PstB is a promising target antigen for development as a component of a universal subunit vaccine against multiple S. suis serotypes.

Stone matrix asphalt (SMA) mixture has been widely used in pavement engineering for its preferable in-service performance. However, deterioration of SMA pavement in skid resistance is apparent under traffic loading. There remains lacking attention on skid resistance attenuation of SMA pavement, which in turn is important for skid durability design in practice. Hence, this study aims to perform a thorough investigation to reveal the skid resistance attenuation law of SMA pavement. Multiple types of SMA-13 mixtures prepared by different material designs were selected to conduct a kneading test that simulates real surface states of in-service SMA pavement. Pressure-sensitive film and a 3D laser scanner were utilized for evaluating anti-skid performance and skid durability. The finite element (FE) method is introduced to simulate vehicle braking distance for skid-resistance evaluation. The results show that skid resistance attenuation of SMA pavement consists of two stages: In the first stage, the skid resistance of SMA pavement experiences a short enhancement, followed by a long-term weakening stage. Abundant surface texture of SMA helps to mitigate the impact of traffic load on skid resistance. The FE analysis and pressure-sensitive film results demonstrate the potential of skid durability design of SMA pavement based on the skid resistance attenuation law.

Pyruvate kinase (PK) is one of the three rate-limiting enzymes of glycolysis, and it plays a pivotal role in energy metabolism. In this study, we have identified 10 PK genes from the rice genome. Initially, these genes were divided into two categories: cytoplasmic pyruvate kinase (PKc) and plastid pyruvate kinase (PKp). Then, an expression analysis revealed that OsPK1 , OsPK3 , OsPK4 , OsPK6 , and OsPK9 were highly expressed in grains. Moreover, PKs can form heteropolymers. In addition, it was found that ABA significantly regulates the expression of PK genes ( OsPK1 , OsPK4 , OsPK9 , and OsPK10 ) in rice. Intriguingly, all the genes were found to be substantially involved in the regulation of rice grain quality and yield. For example, the disruption of OsPK3 , OsPK5 , OsPK7 , OsPK8 , and OsPK10 and OsPK4 , OsPK5 , OsPK6 , and OsPK10 decreased the 1000-grain weight and the seed setting rate, respectively. Further, the disruption of OsPK4 , OsPK6 , OsPK8 , and OsPK10 through the CRISPR/Cas9 system showed an increase in the content of total starch and a decrease in protein content compared to the WT. Similarly, manipulations of the OsPK4 , OsPK8 , and OsPK10 genes increased the amylose content. Meanwhile, the grains of all CRISPR mutants and RNAi lines, except ospk6 , showed a significant increase in the chalkiness rate compared to the wild type. Overall, this study characterizes the functions of all the genes of the PK gene family and shows their untapped potential to improve rice yield and quality traits.

Obtaining accurate angle parameters using direction-of-arrival (DOA) estimation algorithms is crucial for acquiring channel state information (CSI) in massive multiple-input multiple-output (MIMO) systems. However, the performance of the existing algorithms deteriorates severely due to mutual coupling between antenna elements in practical engineering. Therefore, for solving the array mutual coupling, the array output signal vector is modeled by mutual coupling coefficients and the DOA estimation problem is transformed into block sparse signal reconstruction and parameter optimization in this paper. Then, a novel sparse Bayesian learning (SBL)-based algorithm is proposed, in which the expectation-maximum (EM) algorithm is used to estimate the unknown parameters iteratively, and the convergence speed of the algorithm is enhanced by utilizing the approximate approximation. Moreover, considering the off-grid error caused by discretization processes, the grid refinement is carried out using the polynomial roots to realize the dynamic update of the grid points, so as to improve the DOA estimation accuracy. Simulation results show that compared with the existing algorithms, the proposed algorithm is more robust to mutual coupling and off-grid error and can obtain better estimation performance.

High levels of ammonium (NH 4 + ) in soils inhibit plant growth and nitrogen utilization efficiency. Elucidating the underlying mechanisms of NH 4 + toxicity is essential for alleviating the growth inhibition caused by high NH 4 + . Our previous work showed that [Ca 2+ ] cyt -associated protein kinase 1 (CAP1) regulates root hair growth in response to NH 4 + in Arabidopsis thaliana , and the cap1-1 mutant produces short root hairs under NH 4 + stress conditions. However, it is unclear whether CAP1 functions in other physiological processes in response to NH 4 + . In the present study, we found that CAP1 also plays a role in attenuating NH 4 + toxicity to promote shoot growth. The cap1-1 mutant produced smaller shoots with smaller epidermal cells compared with the wild type in response to NH 4 + stress. Disruption of CAP1 enhanced the NH 4 + -mediated inhibition of the expression of cell enlargement-related genes. The cap1-1 mutant showed elevated reactive oxygen species (ROS) levels under NH 4 + stress, as well as increased expression of respiratory burst oxidase homologue genes and decreased expression of catalase genes compared with the wild type. Our data reveal that CAP1 attenuates NH 4 + -induced shoot growth inhibition by promoting cell wall extensibility and ROS homeostasis, thereby highlighting the role of CAP1 in the NH 4 + signal transduction pathway.

Atrial natriuretic peptide (ANP)-mediated natriuresis is known as a cardiac endocrine function in sodium and body fluid homeostasis. Corin is a protease essential for ANP activation. Here, we studied the role of renal corin in regulating salt excretion and blood pressure. We created corin conditional knockout (cKO), in which the Corin gene was selectively disrupted in the kidney (kcKO) or heart (hcKO). We examined the blood pressure, urinary Na + and Cl - excretion, and cardiac hypertrophy in wild-type, corin global KO, kcKO, and hcKO mice fed normal- and high-salt diets. We found that on a normal-salt diet (0.3% NaCl), corin kcKO and hcKO mice had increased blood pressure, indicating that both renal and cardiac corin is necessary for normal blood pressure in mice. On a high-salt diet (4% NaCl), reduced urinary Na + and Cl - excretion, increased body weight, salt-exacerbated hypertension, and cardiac hypertrophy were observed in corin kcKO mice. In contrast, impaired urinary Na + and Cl - excretion and salt-exacerbated hypertension were not observed in corin hcKO mice. These results indicated that renal corin function is important in enhancing natriuresis upon high salt intakes and that this function cannot be compensated by the cardiac corin function in mice.

The microstructural evolution of the rail steels manufactured by Hanyang Iron Works was investigated through optical microscopy (OM), scanning electron microscopy (SEM) and electron backscattered diffraction (EBSD). The OM and SEM images reveal that the microstructures are ferrite with a small amount of pearlite in the rail steel 1904, reticular ferrite and pearlite in the rail steels 1911 and 1921, and full pearlite in the rail steels 1917 and 1919, respectively. The EBSD results show that the rail steel 1904 holds the smallest average grain diameter owing to the pearlite with small size. Moreover, the average grain diameter of the pearlite cluster decreases in the rail steels manufactured after 1908, except for 1921, when it was on the verge of bankruptcy. The rail steels 1917 and 1919 exhibit a higher proportion of low angle grain boundaries and local misorientation with angles lower than 1°. Besides, the grain boundary misorientation holds a lower proportion in the range of 40~50° in the rail steels 1917 and 1919.

Ultra-thin wearing course (UTWC) as an asphalt overlay is widely used in pavement maintenance for extending pavement service life. Researchers focused on improving and evaluating its performance, yet few researchers compare the performance of typical UTWCs. Moreover, some traditional asphalt mixture tests are improper for UTWC due to the thicknesses of UTWC, which is thinner than the traditional asphalt overlay. This study further evaluated the advantages and disadvantages of typical UTWCs. A series of tests were conducted to compare the comprehensive performance of three typical UWTC products, including SMA-10, Novachip-B, and GT-10. Moreover, this study improved the rutting test to evaluate its rutting performance more accurately. Rutting specimens of 20 mm thick and 50 mm thick composite specimens (20 mm UTWC + 30 mm Portland cement concrete slabs) were prepared. Two types of PCC slabs were used, including unprocessed PCC slabs and PCC slabs with preset cracks. The test results showed that Novachip-B showed the best water stability and weakest raveling resistance, while GT-10 showed the best fatigue and anti-skid performance. The rutting performance of UTWCs was reduced because of the influence of preset cracks. The rutting depth of GT-10 was only 60-90% of that of others, showing the comprehensive performance of GT-10 was better than that of others. These results provide a significant reference for the research and application of UTWC.

Atrial natriuretic peptide (ANP) is a key regulator in body fluid balance and cardiovascular biology. In addition to its role in enhancing natriuresis and vasodilation, ANP increases lipolysis and thermogenesis in adipose tissue. Corin is a protease responsible for ANP activation. It remains unknown if corin has a role in regulating adipose tissue function. Here, we examined adipose tissue morphology and function in corin knockout (KO) mice. We observed increased weights and cell sizes in white adipose tissue (WAT), decreased levels of uncoupling protein 1 (Ucp1), a brown adipocyte marker in WAT and brown adipose tissue (BAT), and suppressed thermogenic gene expression in BAT from corin KO mice. At regular room temperature, corin KO and wild-type mice had similar metabolic rates. Upon cold exposure at 4 °C, corin KO mice exhibited impaired thermogenic responses and developed hypothermia. In BAT from corin KO mice, the signaling pathway of p38 mitogen-activated protein kinase, peroxisome proliferator-activated receptor c coactivator 1a, and Ucp1 was impaired. In cell culture, ANP treatment increased Ucp1 expression in BAT-derived adipocytes from corin KO mice. These data indicate that corin mediated-ANP activation is an important hormonal mechanism in regulating adipose tissue function and body temperature upon cold exposure in mice., Competing Interests: The authors declare that they have no conflicts of interest related to this study.

Atrial natriuretic peptide (ANP) is a crucial element of the cardiac endocrine function that promotes natriuresis, diuresis, and vasodilation, thereby protecting normal blood pressure and cardiac function. Corin is a type II transmembrane serine protease that is highly expressed in the heart, where it converts the ANP precursor to mature ANP. Corin deficiency prevents ANP activation and causes hypertension and heart disease. In addition to the heart, corin is expressed in other tissues, including those of the kidney, skin, and uterus, where corin-mediated ANP production and signaling act locally to promote sodium excretion and vascular remodeling. These results indicate that corin and ANP function in many tissues via endocrine and autocrine mechanisms. In heart failure patients, impaired natriuretic peptide processing is a common pathological mechanism that contributes to sodium and body fluid retention. In this review, we discuss most recent findings regarding the role of corin in non-cardiac tissues, including the kidney and skin, in regulating sodium homeostasis and body fluid excretion. Moreover, we describe the molecular mechanisms underlying corin and ANP function in supporting orderly cellular events in uterine spiral artery remodeling. Finally, we assess the potential of corin-based approaches to enhance natriuretic peptide production and activity as a treatment of heart failure.

The transmission of a large amount of video and picture content brings more challenges to wireless communication networks. Unmanned aerial vehicle (UAV)-aided small cells with active content caching deployed on cellular networks are recognized as a promising way to alleviate wireless backhaul and support flexible coverage. However, a UAV cannot operate for a long time due to limited battery life, and its caching capacity is also limited. For this, a multi-UAV content-caching strategy and cooperative, complementary content transmission among UAVs are jointly studied in this paper. Firstly, a user-clustering-based caching strategy is designed, where user clustering is based on user similarity, concurrently taking into consideration similarities in content preference and location. Then, cooperative, complementary content transmission between multiple UAVs is modeled as a coalition formation game (CFG) to maximize the utility of the whole network. Finally, the effectiveness of the proposed algorithms is demonstrated through numerical simulations.

Production of natural rubber by Parthenium argentaum (guayule) requires increased yield for economic sustainability. An RNAi gene silencing strategy was used to engineer isoprenoid biosynthesis by downregulation of squalene synthase (SQS), such that the pool of farnesyl diphosphate (FPP) substrate might instead be available to initiate natural rubber synthesis. Downregulation of SQS resulted in significantly reduced squalene and slightly increased rubber, but not in the same tissues nor to the same extent, partially due to an apparent negative feedback regulatory mechanism that downregulated mevalonate pathway isoprenoid production, presumably associated with excess geranyl pyrophosphate levels. A detailed metabolomics analysis of isoprenoid production in guayule revealed significant differences in metabolism in different tissues, including in active mevalonate and methylerythritol phosphate pathways in stem tissue, where rubber and squalene accumulate. New insights and strategies for engineering isoprenoid production in guayule were identified.

Due to aging of the world's population, stroke has become increasingly prevalent, leading to a rise in socioeconomic burden. In the recent past, stroke research and treatment have become key scientific issues that need urgent solutions, with a sharp focus on stem cell transplantation, which is known to treat neurodegenerative diseases related to traumatic brain injuries, such as stroke. Indeed, stem cell therapy has brought hope to many stroke patients, both in animal and clinical trials. Mesenchymal stem cells (MSCs) are most commonly utilized in biological medical research, due to their pluripotency and universality. MSCs are often obtained from adipose tissue and bone marrow, and transplanted via intravenous injection. Therefore, this review will discuss the therapeutic mechanisms of MSCs and extracellular vehicles (EVs) secreted by MSCs for stroke, such as in attenuating inflammation through immunomodulation, releasing trophic factors to promote therapeutic effects, inducing angiogenesis, promoting neurogenesis, reducing the infarct volume, and replacing damaged cells.

Despite the success of immunotherapies in lung cancer, development of new biomarkers for patient selection is urgently needed. This study aims to explore minimally invasive approaches to characterize circulating T cell receptor beta chain (TCR-β) repertoire in a cohort of advanced non-small cell lung cancer (NSCLC) patients treated with first-line pembrolizumab. Peripheral blood samples were obtained at two time points: i) pretreatment (PRE) and ii) first response assessment (FR). Next-generation sequencing (NGS) was used to analyze the hypervariable complementary determining region 3 (CDR3) of TCR-β chain. Richness, evenness, convergence, and Jaccard similarity indexes plus variable (V) and joining (J)-gene usage were studied. Our results revealed that increased richness during treatment was associated with durable clinical benefit (DCB; p = 0.046), longer progression-free survival (PFS; p = 0.007) and overall survival (OS; p = 0.05). Patients with Jaccard similarity index ≥0.0605 between PRE and FR samples showed improved PFS ( p = 0.021). Higher TRBV20-1 PRE usage was associated with DCB ( p = 0.027). TRBV20-1 levels ≥9.14% in PRE and ≥9.02% in FR significantly increased PFS ( p = 0.025 and p = 0.016) and OS ( p = 0.035 and p = 0.018). Overall, analysis of circulating TCR-β repertoire may provide information about the immune response in anti-PD-1 treated NSCLC patients; in this scenario, it can also offer important information about the clinical outcome.

Background: The human gut harbors around 10 13 -10 14 microorganisms, collectively referred to as gut microbiota. Recent studies have found that the gut microbiota may have an impact on the interaction between immune regulation and anti-cancer immunotherapies., Methods: In order to characterize the diversity and composition of commensal microbiota and its relationship with response to immune checkpoint blockade (ICB), 16S ribosomal DNA (rDNA) sequencing was performed on 69 stool samples from advanced non-small cell lung cancer (NSCLC) patients prior to treatment with ICB., Results: The use of antibiotics and ICB-related skin toxicity were significantly associated with reduced gut microbiota diversity. However, antibiotics (ATB) usage was not related to low ICB efficacy. Phascolarctobacterium was enriched in patients with clinical benefit and correlated with prolonged progression-free survival, whereas Dialister was more represented in patients with progressive disease, and its higher relative abundance was associated with reduced progression-free survival and overall survival, with independent prognostic value in multivariate analysis., Conclusions: Our results corroborate the relation between the baseline gut microbiota composition and ICB clinical outcomes in advanced NSCLC patients, and provide novel potential predictive and prognostic biomarkers for immunotherapy in NSCLC.

The recent coronavirus outbreak has captured worldwide attention. This study investigated the anxiety of the Chinese public and its relationship with social support during the early stage of the COVID-19 pandemic, thereby providing empirical support for interventions on improving the public's mental health. On the basis of an online questionnaire survey conducted on 10-18 February 2020, this study shows that 19.8%, 68.5%, and 11.1% of the respondents suffered mild anxiety, moderate anxiety, and severe anxiety, respectively. Significant differences are reported in state anxiety between people with different household incomes. There are significant differences in trait anxiety and state anxiety between different social support groups. Social support and trait anxiety are negatively correlated. Social support and state anxiety are negatively correlated. Social support affects state anxiety both directly and indirectly (through the mediation of trait anxiety). Therefore, during the COVID-19 pandemic, increasing public support for society can effectively reduce public anxiety.

Verticillium dahliae ( V. dahliae ) infects roots and colonizes the vascular vessels of host plants, significantly reducing the economic yield of cotton and other crops. In this study, the protein VdTHI20, which is involved in the thiamine biosynthesis pathway, was characterized by knocking out the corresponding VdTHI20 gene in V. dahliae via Agrobacterium tumefaciens -mediated transformation (ATMT). The deletion of VdTHI20 resulted in several phenotypic defects in vegetative growth and conidiation and in impaired virulence in tobacco seedlings. We show that VdTHI20 increases the tolerance of V. dahliae to UV damage. The impaired vegetative growth of ΔVdTHI20 mutant strains was restored by complementation with a functional copy of the VdTHI20 gene or by supplementation with additional thiamine. Furthermore, the root infection and colonization of the ΔVdTHI20 mutant strains were suppressed, as indicated by green fluorescent protein (GFP)-labelling under microscope observation. When the RNAi constructs of VdTHI20 were used to transform Nicotiana benthamiana, the transgenic lines expressing dsVdTHI20 showed elevated resistance to V. dahliae. Together, these results suggest that VdTHI20 plays a significant role in the pathogenicity of V. dahliae. In addition, the pathogenesis-related gene VdTHI20 exhibits potential for controlling V. dahliae in important crops., Competing Interests: The authors declare no conflict of interest.

The therapeutic application of antimicrobial peptides (AMPs), a potential type of peptide-based biomaterial, is impeded by their poor antimicrobial activity and potential cytotoxicity as a lack of understanding of their structure-activity relationships. In order to comprehensively enhance the antibacterial and clinical application potency of AMPs, a rational approach was applied to design amphiphilic peptides, including head-to-tail cyclic, linear and D-proline antimicrobial peptides using the template (IR) n P(IR) n P ( n = 1, 2 and 3). Results showed that these amphiphilic peptides demonstrated antimicrobial activity in a size-dependent manner and that cyclic peptide OIR3, which contained three repeating units (IR)3, had greater antimicrobial potency and cell selectivity than liner peptide IR3, DIR3 with D-Pro and gramicidin S (GS). Surface plasmon resonance and endotoxin neutralization assays indicated that OIR3 had significant endotoxin neutralization capabilities, which suggested that the effects of OIR3 were mediated by binding to lipopolysaccharides (LPS). Using fluorescence spectrometry and electron microscopy, we found that OIR3 strongly promoted membrane disruption and thereby induced cell lysis. In addition, an LPS-induced inflammation assay showed that OIR3 inhibited the pro-inflammatory factor TNF-α in RAW264.7 cells. OIR3 was able to reduce oxazolone-induced skin inflammation in allergic dermatitis mouse model via the inhibition of TNF-α, IL-1β and IL-6 mRNA expression. Collectively, the engineered head-to-tail cyclic peptide OIR3 was considerable potential candidate for use as a clinical therapeutic for the treatment of bacterial infections and skin inflammation.

Cotton plays an important role in the economy of many countries. Many studies have revealed that numerous genes and various metabolic pathways are involved in anther development. In this research, we studied the differently expressed mRNA and lncRNA during the anther development of cotton between the cytoplasmic male sterility (CMS) line, C2P5A, and the maintainer line, C2P5B, using RNA-seq analysis. We identified 17,897 known differentially expressed (DE) mRNAs, and 865 DE long noncoding RNAs (lncRNAs) that corresponded to 1172 cis -target genes at three stages of anther development using gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of DE mRNAs; and cis -target genes of DE lncRNAs probably involved in the degradation of tapetum cells, microspore development, pollen development, and in the differentiation, proliferation, and apoptosis of the anther cell wall in cotton. Of these DE genes, LTCONS&#95;00105434, LTCONS&#95;00004262, LTCONS&#95;00126105, LTCONS&#95;00085561, and LTCONS&#95;00085561, correspond to cis -target genes Ghir&#95;A09G011050.1, Ghir&#95;A01G005150.1, Ghir&#95;D05G003710.2, Ghir&#95;A03G016640.1, and Ghir&#95;A12G005100.1, respectively. They participate in oxidative phosphorylation, flavonoid biosynthesis, pentose and glucuronate interconversions, fatty acid biosynthesis, and MAPK signaling pathway in plants, respectively. In summary, the transcriptomic data indicated that DE lncRNAs and DE mRNAs were related to the anther development of cotton at the pollen mother cell stage, tetrad stage, and microspore stage, and abnormal expression could lead to anther abortion, resulting in male sterility of cotton., Competing Interests: The authors declare no conflict of interest.

Antibacterial peptides (APMs) are a new type of antibacterial substance. The relationship between their structure and function remains indistinct; in particular, there is a lack of a definitive and fixed template for designing new antimicrobial peptides. Previous studies have shown that porcine Protegrin-1 (PG-1) exhibits considerable antimicrobial activity and cytotoxicity. In this study, to reduce cytotoxicity and increase cell selectivity, we designed histidine-rich peptides based on the sequence template RR(XY) 2 X D PGX(YX) 2 RR-NH 2 , where X represents I, W, V, and F. The results showed that the peptides form more β-hairpin structures in a lipid-rich environment that mimics cell membranes. Among them, the antimicrobial peptide HV2 showed strong antibacterial activity against Gram-negative strains and almost no toxicity to normal cells. The results of our analysis of its antibacterial mechanism showed that peptide HV2 acts on the bacterial cell membrane to increase its permeability, resulting in cell membrane disruption and death. Furthermore, peptide HV2 inhibited bacterial movement in a concentration-dependent manner and had a more robust anti-inflammatory effect by inhibiting the production of TNF-α. In summary, peptide HV2 exhibits high bactericidal activity and cell selectivity, making it a promising candidate for future use as an antibiotic.

Tire⁻pavement interactions, like friction and rolling resistance, are significantly influenced by pavement macro-texture and micro-texture. Accurate texture measurement at the micro-texture level is vital to achieve the desired level of safety, comfort, and sustainability of the pavement. However, the existence of dropouts and spikes in the collected data is still inevitable based on current laser devices, which leads to erroneous texture characterization. This study utilized an advanced laser sensor to measure three-dimensional (3D) pavement texture at the micro-level at a given speed. Using a proposed interpolation method, the dropout areas in the raw measurements were filled up. Butterworth's high-pass and low-pass filters were applied to separate two texture components from the profile. Based on a statistical analysis for the micro-texture amplitude, an appropriate threshold was determined in order to identify the spikes. A three-step-spike-removal method was proposed and found to be effective in clearing the spikes. The 3D pavement profiles were finally reconstructed without dropouts and spikes. Mean profile depth (MPD) was calculated with different baselines. It was found that the presence of spikes leads to a greater MPD value and the MPD is sensitive to the baseline length. A shorter baseline is recommended to mitigate the impact of spikes on the accuracy of the MPD.

In order to study the structure-activity relationships of xanthene derivatives, four series of N -substituted 14-aryl-14 H -dibenzo[ a , j ]xanthene-3,11-dicarboxamide derivatives were synthesized. The structures of all compounds were identified by ¹H-NMR, HR-MS and IR spectra, in which compounds 6a-h were further identified by 13 C-NMR spectra. The in vitro antitumor activity of the synthesized compounds was tested by MTT assay. Most of them displayed strong inhibitory activity on human hepatocellular carcinoma cell lines (SK-HEP-1, HepG2 and SMMC-7721 cells) and acute promyelocytic leukemia NB4 cells. Compounds 6c - 6e exhibited significant inhibitory activity against NB4 cells with IC 50 values of 0.52 μM and 0.76 μM, respectively, much lower than 5.31 μM of the positive control As₂O₃.

Artocarpus heterophyllus, a popular tropical fruit commonly known as the jackfruit tree, is normally planted in subtropical or tropical areas. Since a variety of phytochemicals isolated from A. heterophyllus have been found to possess potently anti-inflammatory, antiviral and antimalarial activities, researchers have devoted much interest to its potential pharmaceutical value. However, the exact mechanism underlying its anti-inflammatory activity is not well characterized. In this study, seven natural products isolated from A. heterophyllus, including 25-Hydroxycycloart-23-en-3-one (HY), Artocarpin (AR), Dadahol A (DA), Morachalcone A (MA), Artoheterophyllin B (AB), Cycloheterophyllin (CY) and Moracin C (MC) were collected. Lipopolysaccharide (LPS)-stimulated inflammatory response in RAW264.7 macrophages were used in this study. Among these compounds, MC significantly inhibited LPS-activated reactive oxygen species (ROS) and nitric oxide (NO) release without marked cytotoxicity. Furthermore, MC effectively reduced LPS stimulated up-regulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and serval pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α)). Mechanistic studies revealed that the anti-inflammatory effect of MC was associated with the activation of the mitogen activated protein kinases (MAPKs) (including p38, ERK and JNK) and nuclear factor-κB (NF-κB) pathways, especially reducing the nuclear translocation of NF-κB p65 subunit as revealed by nuclear separation experiment and confocal microscopy.

Marine environments are a rich source of Actinobacteria and have the potential to produce a wide variety of biologically active secondary metabolites. In this study, we used four selective isolation media to culture Actinobacteria from the sediments collected from the Chukchi Shelf in the Arctic Ocean. A total of 73 actinobacterial strains were isolated. Based on repetitive DNA fingerprinting analysis, we selected 30 representatives for partial characterization according to their phylogenetic diversity, antimicrobial activities and secondary-metabolite biosynthesis genes. Results from the 16S rRNA gene sequence analysis indicated that the 30 strains could be sorted into 18 phylotypes belonging to 14 different genera: Agrococcus, Arsenicicoccus, Arthrobacter, Brevibacterium, Citricoccus, Janibacter, Kocuria, Microbacterium, Microlunatus, Nocardioides, Nocardiopsis, Saccharopolyspora, Salinibacterium and Streptomyces. To our knowledge, this paper is the first report on the isolation of Microlunatus genus members from marine habitats. Of the 30 isolates, 11 strains exhibited antibacterial and/or antifungal activity, seven of which have activities against Bacillus subtilis and Candida albicans. All 30 strains have at least two biosynthetic genes, one-third of which possess more than four biosynthetic genes. This study demonstrates the significant diversity of Actinobacteria in the Chukchi Shelf sediment and their potential for producing biologically active compounds and novel material for genetic manipulation or combinatorial biosynthesis.