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Benzophenone-4 (BP-4), a widely utilized organic ultraviolet (UV) filter, is recognized as a pseudo-persistent contaminant in aquatic environments. To elucidate the effects and mechanisms of BP-4 on marine diatoms, an investigation was conducted on the growth rate, photosynthetic pigment content, photosynthetic parameters, antioxidant enzyme activity, malondialdehyde (MDA) levels, cellular structure, and transcriptome profile of the model species, Phaeodactylum tricornutum. The results showed a pronounced inhibition of algal growth upon exposure to BP-4, with a 144 h-EC50 value of 201 mg·L−1. In addition, BP-4 exposure resulted in a significant reduction in biomass, disruption of cell membrane integrity, and increased MDA accumulation, with levels escalating 3.57-fold at 125 mg·L−1 of BP-4. In the BP-4-treated samples, 1556 differentially expressed genes (DEGs) were identified, of which 985 were upregulated and 571 were downregulated. Gene ontology and KEGG pathway enrichment analysis revealed that the carbon fixation and carbon metabolism processes in P. tricornatum were disrupted in response to BP-4 exposure, along with excessive reactive oxygen species (ROS) production. The upregulation of genes associated with photosynthetic pigment (chlorophyll and carotenoids) synthesis, phospholipid synthesis, ribosome biogenesis, and translation-related pathways may be regarded as a component of P. tricornatum's tolerance mechanism towards BP-4. These results provide preliminary insights into the toxicity and tolerance mechanisms of BP-4 on P. tricornatum. They will contribute to a better understanding of the ecotoxicological impacts of BP-4 on the marine ecosystem and provide valuable information for elimination of BP-4 in aquatic environment by bioremediation.

Oxybenzone (OBZ; benzophenone-3, CAS# 131–57–7), as a new pollutant and ultraviolet absorbent, shows a significant threat to the survival of phytoplankton. This study aims to explore the acute toxic effects of OBZ on the growth of the microalga Selenastrum capricornutum, as well as the mechanisms for its damage to the primary metabolic pathways of photosynthesis and respiration. The results demonstrated that the concentrations for 50 % of maximal effect (EC50) of OBZ for S. capricornutum were 9.07 mg L−1 and 8.54 mg L−1 at 72 h and 96 h, respectively. A dosage of 4.56 mg L−1 OBZ significantly lowered the photosynthetic oxygen evolution rate of S. capricornutum in both light and dark conditions for a duration of 2 h, while it had no effect on the respiratory oxygen consumption rate under darkness. OBZ caused a significant decline in the efficiency of photosynthetic electron transport due to its damage to photosystem II (PSII), thereby decreasing the photosynthetic oxygen evolution rate. Over-accumulated H2O2 was produced under light due to the damage caused by OBZ to the donor and acceptor sides of PSII, resulting in increased peroxidation of cytomembranes and inhibition of algal respiration. OBZ’s damage to photosynthesis and respiration will hinder the conversion and reuse of energy in algal cells, which is an important reason that OBZ has toxic effects on S. capricornutum. The present study indicated that OBZ has an acute toxic effect on the microalga S. capricornutum. In the two most important primary metabolic pathways in algae, photosynthesis is more sensitive to the toxicity of OBZ than respiration, especially in the dark.

Abstract Background In nature, green apple are associated with the accumulation of chlorophyll, while red apple varieties are associated with anthocyanins accumulation. Notably, in this study, the green skin color apple variety ‘white winter pearmain’ treated with ultraviolet-B (UV-B) exhibited red skins and marked anthocyanin accumulation, while visible light could not. But there are few reports on the biosynthesis difference of anthocyanins in green apple by visible light and UV-B-treatment. Here, we explored the difference of metabolites and genes expression level in green apple by transcriptomic and metabolic. Results The metabolic analysis revealed that there were 152 and 178 significantly changed metabolites in the visible light and UV-B-treated green apple, respectively, compared to the control, and flavone, flavonol, and anthocyanin were the most significantly increased; and transcriptomic analysis showed that 37,110 and 37,709 differentially expressed genes, including 382 and 475 transcription factors (TFs) were detected in light and UV-B-treatment fruit, respectively. Quantitative reverse transcription PCR (qRT-PCR) results confirmed changes in the expression levels of genes encoding metabolites involved in the flavonoid synthesis pathways. The flavonoid metabolic flux in the UV-B treatment increased the accumulation of cyanidin 3-glucoside and cyanidin 3, 5-diglucoside compared to under the light-treatment. Furthermore, we performed qRT-PCR analysis of anthocyanin biosynthesis genes and predicted the gene of MD00G1134400 (a UDP glucose-flavonoid 3–0-glucosyltransferase) may be a candidate gene for anthocyanins accumulation and highly expressed in UV-B-treatment fruit. Expression profiles of several transcription factors of the families MYB, bHLH, NAC were highly correlated with the content of the anthocyanin. Conclusions The composition and contents of anthocyanins in green apple in UV-B-treatment very greatly. A series of metabolites and candidate genes were revealed through combined analysis of metabolome and transcriptome. These results provide an important data for dissecting candidate genes and molecular basis governing green apple color formation in response to visible light and UV-B light.

To investigate the effects of forced-air pre-cooling at different postharvest intervals on the shelf quality of honey peaches under cold chain circulation conditions, a study was conducted using ‘Zaosheng’ honey peaches as the experimental material. The experiment comprised of two groups: One group of honey peaches underwent forced-air pre-cooling 3 hours after harvest, while the other group underwent pre-cooling 6 hours after harvest. Following pre-cooling, the honey peaches were transported at a low temperature 5 ℃ for 12 hours, followed by an additional 12 hours of low-temperature delivery. Subsequently, the honey peaches were stored on simulated shelves at 25 ℃ for 5 days. The quality changes of honey peaches during shelf life were observed and sensory evaluation was carried out. The weight loss rate, decay rate, color difference, hardness, brittleness, soluble solid, titratable acid, VC, total phenol content and aroma components of honey peaches were measured and analyzed. The results indicated that the effect of pre-cooling at 6 hours after harvest on the shelf quality of honey peaches was found to be insignificant. Conversely, pre-cooling at 3 hours after harvest demonstrated significant benefits in terms of maintaining higher appearance quality and sensory scores of honey peaches. It also notably reduced the decay rate, inhibited the decline in L* value and the increase in a* value (P

Introduction: Biapenem is a carbapenem antibiotic widely used in Asia, can be used for the treatment of adults and children with infections due to susceptible bacteria. Although biapenem is utilized in the treatment of a diverse range of bacterial infections, current pharmacokinetic data in the context of septic populations remain limited. Consequently, our research aims to evaluate the pharmacokinetics and efficacy of biapenem within a septic population to optimize biapenem therapy.Methods: In this study, we characterized the pharmacokinetics of biapenem in septic patients using a population pharmacokinetic (PPK) approach. The clinical PK data to develop the PPK model were obtained from 317 septic patients admitted to Nanjing Drum Tower Hospital between 2018 and 2022. All patients were randomized to the modeling and validation cohorts at a 3:1 ratio, with PPK modeling and validation performed utilizing the NONMEM software.Results: The model found to best describe the available data was a two-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V2), and intercompartmental clearance (Q). A covariate analysis identified that creatinine clearance (CLCR) was a significant covariate influencing biapenem CL, while blood urea nitrogen (BUN) was a significant covariate influencing biapenem Q. Accoding to the clinical outcome analyses, 70% of the time that the free antimicrobial drug concentration exceeds the MIC (fT>MIC) is associated with favourable clinical outcomes. The PPK model was then used to perform Monte Carlo simulations to evaluate the probability of attaining 70% fT>MIC.Conclusions: A final PPK model of biapenem was established for patients with sepsis. The current daily dosage regimen of 1.2 g may insufficient to achieve 70% fT>MIC in septic patients. The dosage regimen of 600 mg every 6 h appears to be the optimal choice.

This article focuses on zircon U-Pb isotope dating and a whole-rock elemental analysis of granodiorites, monzonitic granites, granodioritic porphyries, and alkali feldspar granites in the Yangmugang area of the Lesser Xing’an–Zhangguangcai Range. The zircon U-Pb isotope-dating results revealed that these granitic rocks formed during the late Early Jurassic period (182.9–177.2 Ma). Their geochemical characteristics and zircon saturation temperatures suggest that the granodiorites are moderately differentiated I-type granites and the monzonitic granite, granodioritic porphyries, and alkali feldspar granites are highly differentiated I-type granites. The degree of magma differentiation progressively increased from granodiorites to alkali feldspar granites. By combining the regional Nd and Hf isotope compositions, it was inferred that the magma source involved the melting of lower crustal material from the Mesoproterozoic to the Neoproterozoic eras. By integrating these findings with contemporaneous intrusive rock spatial variations, it was indicated that the late Early Jurassic granitoids in the Lesser Xing’an–Zhangguangcai Range formed within an extensional tectonic setting after the collision and closure of the Songnen–Zhangguangcai Range and Jiamusi blocks. Additionally, this study constrains the closure of the Mudanjiang Ocean to the late Early Jurassic period (177.2 Ma).

Abstract Introduction Pharmacist-driven (PD) dosing and monitoring services have been shown to improve the clinical and economic outcomes in patients treated with different antibiotics, other than teicoplanin. This study investigates the impact of PD dosing and monitoring services on the clinical and economic outcomes of non-critically ill patients receiving teicoplanin treatment. Methods A single-center retrospective study was conducted. Patients were divided into the PD group and the non-PD (NPD) group. Primary outcomes included the achievement of target serum concentration, and a composite endpoint of all-cause mortality, intensive care unit (ICU) admission, and sepsis or septic shock development during hospitalization or within 30 days of hospital admission. The cost of teicoplanin, overall medication cost, and total cost during hospital stay were also compared. Results A total of 163 patients from January to December 2019 were included and assessed. Seventy patients were assigned to the PD group and 93 to the NPD group. The PD group had a higher percentage of patients reaching the target trough concentration (54% versus 16%, p

SYP-14288 is a fungicide as an uncoupler of oxidative phosphorylation, which is effective in controlling fungal pathogens like Rhizoctonia solani. To determine whether R. solani can develop SYP-14288 resistance and possibly multi-drug resistance (MDR), an SYP-14288-resistant mutant of R. solani X19-7 was generated from wild-type strain X19, and the mechanism of resistance was studied through metabolic and genetic assays. From metabolites of R. solani treated with SYP-14288, three compounds including M1, M2, and M3 were identified according to UPLC-MS/MS analysis, and M1 accumulated faster than M2 and M3 in X19-7. When X19-7 was treated by glutathione-S-transferase (GST) inhibitor diethyl maleate (DEM) and SYP-14288 together, or by DEM plus one of tested fungicides that have different modes of action, a synergistic activity of resistance occurred, implying that GSTs promoted metabolic resistance against SYP-14288 and therefore led to MDR. By comparing RNA sequences between X19-7 and X19, six cytochrome P450s (P450s) and two GST genes were selected as a target, which showed a higher expression in X19-7 than X19 both before and after the exposure to SYP-14288. Furthermore, heterologous expression of P450 and GST genes in yeast was conducted to confirm genes involved in metabolic resistance. In results, the P450 gene AG1IA_05136 and GST gene AG1IA_07383 were related to fungal resistance to multiple fungicides including SYP-14288, fluazinam, chlorothalonil, and difenoconazole. It was the first report that metabolic resistance of R. solani to uncouplers was associated with P450 and GST genes.

Network function virtualization can significantly improve the flexibility and effectiveness of network appliances via a mapping process called service function chaining. However, the failure of any single virtualized network function causes the breakdown of the entire chain, which results in resource wastage, delays, and significant data loss. Redundancy can be used to protect network appliances; however, when failures occur, it may significantly degrade network efficiency. In addition, it is difficult to efficiently map the primary and backups to optimize the management cost and service reliability without violating the capacity, delay, and reliability constraints, which is referred to as the reliability‐aware service chaining mapping problem. In this paper, a mixed integer linear programming formulation is provided to address this problem along with a novel online algorithm that adopts the joint protection redundancy model and novel backup selection scheme. The results show that the proposed algorithm can significantly improve the request acceptance ratio and reduce the consumption of physical resources compared to existing backup algorithms.

The fungicide SYP-14288 has a high efficiency, low toxicity, and broad spectrum in inhibiting both fungi and oomycetes, but its mode of action (MoA) remains unclear on inhibiting fungi. In this study, the MoA was determined by analyzing the metabolism and respiratory activities of Rhizoctonia solani treated by SYP-14288. Wild-type strains and SYP-14288-resistant mutants of R. solani were incubated on potato dextrose agar amended with either SYP-14288 or one of select fungicides acting on fungal respiration, including complex I, II, and III inhibitors; uncouplers; and ATP synthase inhibitors. Mycelial growth was measured under fungicides treatments. ATP content was determined using an ATP assay kit, membrane potential of mitochondria was detected with the JC-1 kit, and respiratory rate was calculated based on the measurement of oxygen consumption of R. solani. A model of metabolic fingerprinting cluster was established to separate oxidation inhibitors and phosphorylation inhibitors. All the results together displayed a clear discrimination between oxidation inhibitors and phosphorylation inhibitors, and the latter inhibited ATP synthase production having or uncoupling activities. Based on the model, SYP-14288 was placed in phosphorylation inhibitor group, because it significantly reduced ATP content and membrane potential of mitochondria while increasing respiratory rate in R. solani. Therefore, the MoA of SYP-14288 on R. solani was confirmed to involve phosphorylation inhibition and possibly uncoupling activity.

With the large-scale commercial application of data center networks, the security problem of data center network is attracting more and more attention. However, security functions are usually placed on proprietary hardware, which makes the delivery of security service inflexible and of high cost. The emerging software-defined networking and network function virtualization in a joint manner are promising technology that can solve these outlined problems through a process named security service chaining (SSC) composition. Determining the composition of SSC that optimizes the resource allocation is a challenging problem, particularly without violating security and resource requirements. This problem is called the dynamic SSC composition problem, and an integer linear programming formulation with implementation in GLPK is provided. A novel heuristic solution is provided based on the breadth first search algorithm. The obtained experimental results show that the proposed algorithm can perform better than the compared ones, and the advantage of the proposed mechanism is also demonstrated via NetFPGA-10G prototype.

The probenazole fungicide is used for controlling rice blast (Magnaporthe grisea) primarily by inducing disease resistance of the plant. To investigate the mechanism of induced plant defense, rice seedlings were treated with probenazole at 15 days post emergence, and non-treated plants were used for the control. The plants were infected with M. grisea 5 days after chemical treatment and incubated in a greenhouse. After 7 days, rice seedlings were sampled. The metabolome of rice seedlings was chemically extracted and analyzed using gas chromatography and mass spectrum (GC-MS). The GC-MS data were processed using analysis of variance (ANOVA), principal component analysis (PCA) and metabolic pathway elucidation. Results showed that probenazole application significantly affected the metabolic profile of rice seedlings, and the effect was proportionally leveraged with the increase of probenazole concentration. Probenazole resulted in a change of 54 metabolites. Salicylic acid, γ-aminobutyrate, shikimate and several other primary metabolites related to plant resistance were significantly up-regulated and some metabolites such as phenylalanine, valine and proline were down-regulated in probenazole-treated seedlings. These results revealed a metabolic pathway of rice seedlings induced by probenazole treatment regarding the resistance to M. grisea infection.

Southern root-knot nematode (Meloidogyne incognita) is an obligate, sedentary endoparasite of more than 3000 plant species, that causes heavy economic losses and limit the development of protected agriculture of China. As a biological pesticide, emamectin benzoate has effectively prevented lepidopteran pests; however, its efficacy to control M. incognita remains unknown. The purpose of the present study was to test soil application of emamectin benzoate for management of M. incognita in laboratory, greenhouse and field trials. Laboratory results showed that emamectin benzoate exhibited high toxicity to M. incognita, with LC50 and LC90 values 3.59 and 18.20 mg L(-1), respectively. In greenhouse tests, emamectin benzoate soil application offered good efficacy against M. incognita while maintaining excellent plant growth. In field trials, emamectin benzoate provided control efficacy against M. incognita and resulted in increased tomato yields. Compared with the untreated control, there was a 36.5% to 81.3% yield increase obtained from all treatments and the highest yield was received from the highest rate of emamectin benzoate. The results confirmed that emamectin benzoate has enormous potential for the control of M. incognita in tomato production in China.