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A recent breakthrough in agricultural biotechnology is the introduction of RNAi-mediated strategies in pest control. However, the off-target effects of RNAi pest control are still not fully understood. Here, we studied the off-target effects of two insecticidal siRNAs in both target and non-target insects. The results revealed that off-target effects of insecticidal siRNAs occur widely in both target and non-target insects. We classified the expression-changed genes according to their homology to the siRNA-targeted gene, related KEGG pathways with the siRNA-targeted gene and continuous matches with siRNAs. Surprisingly, the unintended significant changes in gene expression levels did not strictly match with the number of contiguous nucleotides in the siRNAs. As expected, the expression of small portions of the homologous and KEGG-related genes were significantly changed. We calculated the Shannon entropy of the transcriptome profile of the insects after injecting them with insecticidal siRNAs. Though hundreds of genes were affected in their expression levels post siRNA-treatment, the Shannon entropy of the transcriptome remained unchanged, suggesting that the transcriptome expression was balanced. Our results provide evidence that siRNAs cross-reacted with individual genes in non-target species, but did not have significant effects on the integrity of the transcriptome profiles in either target or non-target species on a genomic scale. The metric we proposed can be used to estimate the off-target effects of insecticidal siRNAs, which might be useful for evaluating the safety of RNAi in pest control.

Geotechnical survey is an important prerequisite to the construction of offshore wind farms. However, the impact of underwater survey noises has not yet been studied in details. In this paper, we studied transmission of underwater noises from offshore exploratory drilling (OED) at the Xiamen port. The noises were categorized into three types: hammering noises (hammering down of casings, which were 180-mm diameter steel pipes), vibrating noises (vibration of casings that had been hammered down), and drilling noises (generated during the borehole drilling process). We considered the variation in intensity of these three noise types, and set up two fixed and one movable stations to measure and analyze the source and propagation characteristics of these noises. The results indicate that hammering noise is an impulsive sound with a dominant frequency below 10 kHz, and source levels (SLs) of 197.1 dB re 1μPa @ 1 m (rms over 95% energy duration. 1–64,000 Hz) and 212.9 dB re 1μPa @ 1 m (peak). Vibrating and drilling noises are non-impulsive sounds with the fundamental frequencies of 41 Hz and 45 Hz, and SLs of 158.9 dB re 1μPa rms @ 1 m and 155.9 dB re 1μPa rms @ 1 m, respectively. The impact assessment of OED noises on five groups of marine mammals with different audible frequency ranges (Low (LF), High (HF), and Very High (VHF) frequency cetaceans, sirenians (SI), and phocid pinnipeds (PW)) demonstrates that hammering noise can induce a high risk of hearing damage to their hearing, at as far as 300 meters for VHF group, while drilling noise can only induce hearing damage at about 40 meters. Marine mammals are susceptible to behavior alteration, with a detectable distance of 1.9 km from the source, and it is recommended to set a warning zone with a radius of 1.9 km during OED construction.

Purpose: To investigate the clinical features and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia (MP) with secondary MRSA bloodstream infections (MRSA-BSI) (termed MP-BSI) compared with MP alone and to study the incidence of MP-BSI among patients with MP. Methods: This was a retrospective, single-center study with clinical data derived from previous medical records. The cases were divided into groups: MP alone and MP-BSI. The determination of independent risk factors for MP-BSI relied on logistic regression analysis. Additionally, the crude outcomes were compared. Results: A total of 435 patients with MP were recruited, with 18.9% (82/435) having MP-BSI. The median age was 62 (interquartile range, 51,72) years, and 74.5% of the patients were male. Multivariate analysis revealed that immunosuppression, community-acquired MP (CA-MP), time from initial to targeted antibiotic use, high Sequential Organ Failure Assessment (SOFA) score, increased respiratory rate, and elevated γ-GT level (all p < 0.05) were independent risk factors for MP-BSI, while targeted treatment with linezolid was a protective factor. Patients with MP-BSI had a longer duration of hospitalization (median days, 27.5 vs. 19, p = 0.001), a higher 28-day mortality rate (24.4% vs. 11.0%, p = 0.001), and a higher in-hospital mortality rate (26.8% vs. 14.7%, p = 0.009) than those with MP alone. Conclusion: Secondary MRSA-BSI among patients with MP is not rare. Immunosuppression, CA-MP, time from initial to targeted antibiotic use, high SOFA score, increased respiratory rate and elevated γ-GT level are all independent risk factors for MP-BSI; however, linezolid, as a targeted antibiotic, is a protective factor. Moreover, patients with MP may have worse clinical outcomes when they develop MRSA-BSI.

In this work, we investigate the multimode Brownian oscillators in nonequilibrium scenarios with multiple reservoirs at different temperatures. For this purpose, an algebraic method is proposed. This approach gives the exact time-local equation of motion for the reduced density operator, from which we can easily extract not only the reduced system but also hybrid bath dynamical information. The resulting steady-state heat current is found to be numerically consistent with another discrete imaginary-frequency method followed by Meir–Wingreen's formula. It is anticipated that the development in this work would constitute an indispensable component of nonequilibrium statistical mechanics for open quantum systems. [ABSTRACT FROM AUTHOR]

Introduction: Ischemic stroke (IS) is a common and severe neurological disorder and is associated with high rates of mortality and morbidity. Inflammatory reaction in astrocytes is one of the important pathological factors of stroke. Improved understanding of the underlying molecular mechanisms should aid better treatment of the disease. This study aimed to test our hypothesis that a miR-499a played an important role in the inflammatory response in astrocytes induced by IS targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Methods: This study was comprised of two models: oxygen-glucose deprivation (OGD) and reoxygenation model. Quantitative real-time PCR (qRT-PCR) and Western blot were used to examine gene expression levels, and MTT assay analysis were used to examine cell states. The relationships between miR-499a and PTEN were confirmed by luciferase reporter assay. Results: MiR-499a was robustly downregulated with OGD induced injury in astrocytes. Forced transient expression of miR-499a in OGD astrocytes nearly completely reversed the inflammatory response. Knockdown of miR-499a by its specific inhibitor in healthy astrocytes induced the inflammatory response resembling those produced by OGD. On the other hand, PTEN was markedly upregulated in OGD astrocytes, which was reciprocal to the expression of miR-499a. PTEN was experimentally validated as a direct target gene for miR-499a. Overexpression of PTEN was able to induce an inflammatory response of astrocytes. Moreover, PTEN siRNA counteracted the inflammatory response induced by OGD. Conclusions: Taken together, our findings indicate miR-499a as an important factor to prevent inflammatory response and suggest miR-499a as a new molecule for the treatment of IS. The present study also demonstrated the relationship between miR-499a and PTEN, with PTEN as a downstream signaling mediator of miR-499a in the inflammatory response of astrocytes induced by IS.

Unethical pro-family behavior (UPFB) is prevalent in organizations and has adverse effects on organizations, but very few studies have examined the factors that lead to UPFB. We use a cognitive appraisal theoretical framework to argue that employees’ unethical pro-family (UPFB) behavior results from work and family conflicts (WFC/FWC) are mediated by threat appraisal and moderated family collectivism orientation. Based on the questionnaire data of 496 full-time employees from two-time points, we found that WFC/FWC was positively correlated with UPFB where threat appraisal played a mediating role in this relationship; Family collectivism orientation strengthens the threat appraisal-UPFB relationship and the mediation relationship between WFC/FWC and UPFB via threat appraisal. These findings offer an understanding of the theoretical and practical implications which could help organizations reduce UPFB. Finally, we discuss possible directions for future research.

Breast Cancer Type 1 Susceptibility Protein (BRCA1) is a tumor-suppressor protein that regulates various cellular pathways, including those that are essential for preserving genome stability. One essential mechanism involves a BRCA1-A complex that is recruited to double-strand breaks (DSBs) by RAP80 before initiating DNA damage repair (DDR). How RAP80 itself is recruited to DNA damage sites, however, is unclear. Here, we demonstrate an intrinsic correlation between a methyltransferase DOT1L-mediated RAP80 methylation and BRCA1-A complex chromatin recruitment that occurs during cancer cell radiotherapy resistance. Mechanistically, DOT1L is quickly recruited onto chromatin and methylates RAP80 at multiple lysines in response to DNA damage. Methylated RAP80 is then indispensable for binding to ubiquitinated H2A and subsequently triggering BRCA1-A complex recruitment onto DSBs. Importantly, DOT1L-catalyzed RAP80 methylation and recruitment of BRCA1 have clinical relevance, as inhibition of DOT1L or RAP80 methylation seems to enhance the radiosensitivity of cancer cells both in vivo and in vitro. These data reveal a crucial role for DOT1L in DDR through initiating recruitment of RAP80 and BRCA1 onto chromatin and underscore a therapeutic strategy based on targeting DOT1L to overcome tumor radiotherapy resistance. [ABSTRACT FROM AUTHOR]

Reconstructing critical-sized craniofacial bone defects is a global healthcare challenge. Current methods, like autologous bone transplantation, face limitations. Bone tissue engineering offers an alternative to autologous bone, with traditional approaches focusing on stimulating osteogenesis via the intramembranous ossification (IMO) pathway. However, IMO falls short in addressing larger defects, particularly in clinical scenarios where there is insufficient vascularisation. This review explores redirecting bone regeneration through endochondral ossification (ECO), a process observed in long bone healing stimulated by hypoxic conditions. Despite its promise, gaps exist in applying ECO to bone tissue engineering experiments, requiring the elucidation of key aspects such as cell sources, biomaterials and priming protocols. This review discusses various scaffold biomaterials and cellular sources for chondrogenesis and hypertrophic chondrocyte priming, mirroring the ECO pathway. The review highlights challenges in current endochondral priming and proposes alternative approaches. Emphasis is on segmental mandibular defect repair, offering insights for future research and clinical application. This concise review aims to advance bone tissue engineering by addressing critical gaps in ECO strategies. [ABSTRACT FROM AUTHOR]

Abstract Background Basal-like breast cancers (BLBCs) are a leading cause of cancer death due to their capacity to metastasize and lack of effective therapies. More than half of BLBCs have a dysfunctional BRCA1. Although most BRCA1-deficient cancers respond to DNA-damaging agents, resistance and tumor recurrence remain a challenge to survival outcomes for BLBC patients. Additional therapies targeting the pathways aberrantly activated by BRCA1 deficiency are urgently needed. Methods Most BRCA1-deficient BLBCs carry a dysfunctional INK4-RB pathway. Thus, we created genetically engineered mice with Brca1 loss and deletion of p16 INK4A , or separately p18INK4C , to model the deficient INK4-RB signaling in human BLBC. By using these mutant mice and human BRCA1-deficient and proficient breast cancer tissues and cells, we tested if there exists a druggable target in BRCA1-deficient breast cancers. Results Heterozygous germline or epithelium-specific deletion of Brca1 in p18INK4C - or p16 INK4A -deficient mice activated Pdgfrβ signaling, induced epithelial-to-mesenchymal transition, and led to BLBCs. Confirming this role, targeted deletion of Pdgfrβ in Brca1-deficient tumor cells promoted cell death, induced mesenchymal-to-epithelial transition, and suppressed tumorigenesis. Importantly, we also found that pharmaceutical inhibition of Pdgfrβ and its downstream target Pkcα suppressed Brca1-deficient tumor initiation and progression and effectively killed BRCA1-deficient cancer cells. Conclusions Our work offers the first genetic and biochemical evidence that PDGFRβ-PKCα signaling is repressed by BRCA1, which establishes PDGFRβ-PKCα signaling as a therapeutic target for BRCA1-deficient breast cancers.

Objective To analyze the conventional segmental positioning error of lung cancer with Halcyon and the outspread boundary of the target area, so as to improve the precision and efficacy of radiotherapy in patients with lung cancer with Halcyon. Methods Totally 142 patients from May 2019 to August 2020 in the radiotherapy department of Peking Union Medical College Hospital were selected in this study and 3 192 registration images were collected for data analysis of the whole course of treatment, and the errors of elevation direction (VRT), inlet and outlet direction (LNG) and left-right direction (LAT) were calculated. The outer boundary formula of target area=2.5∑+0.7 and combined with the ICRU50 and ICRU62 report analysis results. Results By SPSS 21.0 statistical analysis, the positioning errors of the three directions were as follows: VRT(0.07±1.59)mm, LNG(-0.15±4.40)mm, and LAT (0.08±3.50)mm. According to the analysis of ICRU50 and ICRU62 reports, the target margin is VRT=3.69 mm,LNG=6.60 mm and LAT=5.04 mm. Conclusions With conventional segmental treatment model, the boundary of the exotherm of the lung cancer patients in the target area of the Halcyon medical electron linac was VRT=3.69 mm, LNG=6.60 mm and LAT=5.04 mm, which provided the basis for the exotherm of the clinical target margin.

Acute promyelocytic leukemia (APL) is extremely fatal if treatment is delayed. Management of APL in pregnancy is a challenging situation. Arsenic trioxide (ATO) is successfully applied to treat APL. ATO can be transformed into different arsenic species [arsenite (AsIII), monomethylated arsenic (MMA, consists of MMAIII and MMAV), dimethylated arsenic (DMA, consists of DMAIII and DMAV), and arsenate (AsV)], which produce different toxic effects. Investigating the maternal and fetal exposure to arsenic species is critical in terms of assessing maternal and fetal outcomes, choice of optimal treatment, and making decisions for attempting to preserve the obstetrical and fetal wellbeing. In this study, maternal blood and amniotic fluid (AF) from APL patients treated with ATO in pregnancy and blood samples of non-pregnant patients were collected. Concentrations of inorganic arsenic (iAs, iAs = AsIII+AsV), MMA, and DMA were analyzed by high-performance liquid chromatography–hydride generation–atomic fluorescence spectrometry (HPLC–HG–AFS). The difference in arsenic species of plasma between pregnant patients and non-pregnant patients, distribution of arsenic compounds in AF and maternal plasma, and arsenic penetration into AF were explored. The outcomes of pregnant women treated with ATO and their fetus were analyzed. No significant differences in arsenic concentration, percentage, and methylation index [PMI: primary methylation index (MMA/iAs); SMI: secondary methylation index (DMA/MMA)] between pregnant women and non-pregnant women (p > 0.05) were observed. The mean ratios of AF to maternal plasma were as follows: iAs, 2.09; DMA, 1.04; MMA, 0.49; and tAs, 0.98. Abortion rate is higher with the diagnosis at an earlier gestational age, with 0%, 67%, and 100% of pregnancies ending in abortion during the third, second, and first trimester, respectively. The age of the pregnant women, the dose of ATO, and the duration of fetal exposure in utero had no influence on fetal outcomes. All APL women achieved complete remission (CR). Collectively, ATO and its metabolites can easily cross the placenta. Levels and distribution of arsenic species in maternal plasma and AF gave evidence that arsenic species had a different ability to penetrate the placenta into AF (iAs > DMA > MMA) and indicated a relatively high fetal exposure to ATO and its metabolites in utero. Gestational age at diagnosis was more likely to be closely related to fetal outcomes, but had no effects on mother outcomes.

BackgroundDelirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose dexmedetomidine, a highly selective α2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery.MethodsWe did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR-TRC-10000802.FindingsBetween Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 [9%] of 350 patients) than in the placebo group (79 [23%] of 350 patients; odds ratio [OR] 0·35, 95% CI 0·22-0·54; p

Objective Analysis of the pendulum error of pancreatic cancer patients by spiral tomography technique under the guidance of megavolt CT (megavoltage computed tomography, MVCT) image, and calculation of planned target volume, PTV) of the margin. Methods The MVCT image scan matched with the planned CT image, the error values of the left and right (X), head and feet (Y), abdominal back (Z) axis direction and cross-section rotation (roll) direction were recorded, and the error values were analyzed and calculated. Results A total of 592 MVCT scans were conducted. The X, Y, Z and roll direction swing error values were (-0.5±2.8)mm, (-1.1±6.4)mm, (6.0±4.4)mm, and (-0.2±0.7) respectively. The average error in the three directions of X, Y and Z was less than 5 mm, with 97.13% (575/592), 88.01% (521/592) and 37.84% (224/592), and roll direction rotation error of less than 1 degree, with 93.92% (556/592). According to the formula, the extra-boundary spacing values of The PTV in X, Y and Z 3 directions were 5.16, 9.9 and 7.53 mm respectively. Conclusions In order to improve the accuracy and efficacy of tomotherapy, The margin emission values of CTV to PTV in X, Y and Z three-dimensional directions are recommended as 5, 10 and 8 mm, respectively.

Small brown planthopper (SBPH, Laodelphax striatellus Fallén) is an important vector of major crop pathogen rice stripe virus (RSV). Controlling SBPH population is an efficient approach to control RSV. Long non-coding RNAs (lncRNA) have been reported to block virus replication in hosts. However, the function of lncRNAs in RSV infection and replication is still unknown. Here, we aimed to study regulatory mechanisms of lncRNA in an immune system during RSV infection. First, lncRNA genes were predicted from SBPH transcriptomes using a bioinformatics pipeline based on characteristics of lncRNA. We identified 4 786 lncRNA genes corresponding to 5 790 transcripts in SBPH from an RNA-Seq dataset of 15 transcriptomes. Differential expression analysis indicated that 3, 11, and 25 lncRNA genes were highly expressed in gut, salivary gland, and ovary, respectively, of viruliferous SBPH (Student's t-test, P

Understanding the traits related to species colonization and invasion, is a key question for both pest management and evolution. One of the key components is flight, which has been measured for a number of insect species through radar and tethered flight mill systems, but a general understanding of insect flight at a community level is lacking. In this study, we used flight mill experiments to quantify flight abilities of moth species, and simulation experiments to study which moths in mainland China have the potential for cross-island dispersal. We found that moths from superfamily Geometroidea (family Geometridae) have the weakest flight ability among the seven Lepidoptera superfamilies, which is characterized by the shortest longest single flight (LSF), the shortest time corresponding to the longest single flight (TLSF) (timecorrespondingtothelongestsingleflight), the lowest total distance flown (TDF), and the lowest average speed during the flight (VTDF). Surprisingly, the family Pyralidae (superfamily Pyraloidea) has the highest flight endurance of all 186 species of 12 families in this study, which is unexpected, given its small size and morphological traits yet it shows the longest LSF and TLSF. The comparison between species common to mainland and islands shows that flight distance (LSF) may be more important for species spread than flight speed. The results of mainland-island simulations show that when P(LSF>CD) (the proportion of individuals whose LSF is greater than the closest distance (CD) between mainland and island to the total number of individuals in the population) is less than 0.004, it is difficult for moth species to disperse to across islands without relying on external factors such as airflow. Over extended periods, with the immigration of species with strong flight abilities, islands are more likely to recruit species with stronger flight abilities.

As a rapid and simple method for the detection of multiple targets, immunoassay has attracted extensive attention due to the merits of high specificity and sensitivity. Notably, enzyme-linked immunosorbent assay (ELISA) is a widely used immunoassay, which can provide high detection sensitivity since the enzyme labels can promote the generation of catalytically amplified readouts. However, the natural enzyme labels usually suffer from low stability, high cost, and difficult storage. Inspired by the advantages of superior and tunable catalytic activities, easy preparation, low cost, and high stability, nanozymes have arisen to replace the natural enzymes in immunoassay; they also possess equivalent sensitivity and selectivity, as well as robustness. Up to now, various kinds of nanozymes, including mimic peroxidase, oxidase, and phosphatase, have been incorporated to construct immunosensors. Herein, the development of immunoassays based on nanozymes with various types of detection signals are highlighted and discussed in detail. Furthermore, the challenges and perspectives of the design of novel nanozymes for widespread applications are discussed.