Impaired cell fate through gain-of-function mutations in a chromatin reader.

Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by 'reader' proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatin-reader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.

A UTX-MLL4-p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription.

Enhancer activation is a critical step for gene activation. Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1+/H3K27ac+) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription. The UTX-MLL4 complex enhances p300-dependent H3K27 acetylation through UTX-dependent stimulation of p300 recruitment, while MLL4-mediated H3K4 monomethylation, reciprocally, requires p300 function. Importantly, MLL4-generated H3K4me1 further enhances p300-dependent transcription. This work reveals a previously unrecognized cooperativity among enhancer-associated chromatin modulators, including a unique function for UTX, in establishing an "active enhancer landscape" and defines a detailed mechanism for the joint deposition of H3K4me1 and H3K27ac.

Transcriptomic analysis reveals the regulatory mechanisms of messenger RNA (mRNA) and long non-coding RNA (lncRNA) in response to waterlogging stress in rye (Secale cereale L.).

BACKGROUND: Waterlogging stress (WS) negatively impacts crop growth and productivity, making it important to understand crop resistance processes and discover useful WS resistance genes. In this study, rye cultivars and wild rye species were subjected to 12-day WS treatment, and the cultivar Secale cereale L. Imperil showed higher tolerance. Whole transcriptome sequencing was performed on this cultivar to identify differentially expressed (DE) messenger RNAs (DE-mRNAs) and long non-coding RNAs (DE-lncRNAs) involved in WS response. RESULTS: Among the 6 species, Secale cereale L. Imperil showed higher tolerance than wild rye species against WS. The cultivar effectively mitigated oxidative stress, and regulated hydrogen peroxide and superoxide anion. A total of 728 DE-mRNAs and 60 DE-lncRNAs were discovered. Among these, 318 DE-mRNAs and 32 DE-lncRNAs were upregulated, and 410 DE-mRNAs and 28 DE-lncRNAs were downregulated. GO enrichment analysis discovered metabolic processes, cellular processes, and single-organism processes as enriched biological processes (BP). For cellular components (CC), the enriched terms were membrane, membrane part, cell, and cell part. Enriched molecular functions (MF) terms were catalytic activity, binding, and transporter activity. LncRNA and mRNA regulatory processes were mainly related to MAPK signaling pathway-plant, plant hormone signal transduction, phenylpropanoid biosynthesis, anthocyanin biosynthesis, glutathione metabolism, ubiquitin-mediated proteolysis, ABC transporter, Cytochrome b6/f complex, secondary metabolite biosynthesis, and carotenoid biosynthesis pathways. The signalling of ethylene-related pathways was not mainly dependent on AP2/ERF and WRKY transcription factors (TF), but on other factors. Photosynthetic activity was active, and carotenoid levels increased in rye under WS. Sphingolipids, the cytochrome b6/f complex, and glutamate are involved in rye WS response. Sucrose transportation was not significantly inhibited, and sucrose breakdown occurs in rye under WS. CONCLUSIONS: This study investigated the expression levels and regulatory functions of mRNAs and lncRNAs in 12-day waterlogged rye seedlings. The findings shed light on the genes that play a significant role in rye ability to withstand WS. The findings from this study will serve as a foundation for further investigations into the mRNA and lncRNA WS responses in rye.

Photoinduced Transition-MetalExternal Photosensitizer Free Benzylic Fluorination of Unactivated Alkylarenes.

A green and efficient protocol for the direct monofluorination of unactivated alkylarenes under visible-light irradiation has been developed, without any extraneous transition-metal catalysts or photosensitizers. This method is compatible with a broad spectrum of functional groups, including carboxylic and alcoholic scaffolds, under mild reaction conditions. Gram-scale synthesis of a fluorine-containing pharmaceutical analogue was successfully executed, underscoring the strategy's reliability and practicality. Furthermore, mechanistic studies suggest that a single-electron transfer mechanism might be responsible for the generation of the benzylic radicals in initiation step.

Serum long non-coding Ribonucleic Acid H19 serves as a biomarker for systemic lupus erythematosus and participates in the disease progression.

AIM: This study aimed to investigate the expression of H19 and its possible molecular mechanism in systemic lupus erythematosus (SLE). METHODS: The expression of H19 and miR-19b in serum and peripheral blood mononuclear cells (PBMCs) were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Receiver operator characteristic (ROC) curve was constructed to evaluate the diagnostic value of serum H19 in SLE. Pearson correlation coefficient was used to analyze the correlation between serum levels of H19 and miR-19b. Flow cytometry and Cell counting kit-8 (CCK-8) assay were performed to detect cell apoptosis and viability. The levels of pro-inflammatory and anti-inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter gene assay was conducted to verify the interaction between H19 and miR-19b. RESULTS: The expression of H19 and miR-19b in SLE group were up-regulated and down-regulated, respectively. Serum H19 has certain clinical diagnostic value in SLE. In in vitro studies, overexpression of H19 can significantly inhibit the viability of PBMCs and promote apoptosis and inflammatory response of PBMCs by interacting with miR-19b. CONCLUSIONS: The expression of H19 is upregulated in patients with SLE and plays a role in cell function and inflammation by targeting miR-19b in PBMCs, which may be one of the pathological mechanisms of SLE.

Uneven primary healthcare supply of rural doctors and medical equipment in remote China: community impact and the moderating effect of policy intervention.

BACKGROUND: Unequal access to primary healthcare (PHC) has become a critical issue in global health inequalities, requiring governments to implement policies tailored to communities' needs and abilities. However, the place-based facility dimension of PHCs is oversimplified in current healthcare literature, and formulating the equity-oriented PHC spatial planning remains challenging without understanding the multiple impacts of community socio-spatial dynamics, particularly in remote areas. This study aims to push the boundary of PHC studies one step further by presenting a nuanced and dynamic understanding of the impact of community environments on the uneven primary healthcare supply. METHODS: Focusing on Shuicheng, a remote rural area in southwestern China, multiple data are included in this village-based study, i.e., the facility-level healthcare statistics data (2016-2019), the statistical yearbooks, WorldPop, and Chinese GDP's spatial distribution data. We evaluate villages' PHC service capacity using the number of doctors and essential equipment per capita, which are the major components of China's PHC delivery. The indicators describing community environments are selected based on extant literature and China's planning paradigms, including town- and village-level factors. Gini coefficients and local spatial autocorrelation analysis are used to present the divergences of PHC capacity, and multilevel regression model and (heterogeneous) difference in difference model are used to examine the driving role of community environments and the dynamics under the policy intervention. RESULTS: Despite the general improvement, PHC inequalities remain significant in remote rural areas. The village's location, aging, topography, ethnic autonomy, and economic conditions significantly influence village-level PHC capacity, while demographic characteristics and healthcare delivery at the town level are also important. Although it may improve the hardware setting in village clinics (coef. = 0.350), the recent equity-oriented policy attempts may accelerate the loss of rural doctors (coef. = - 0.517). Notably, the associations between PHC and community environments are affected inconsistently by this round of policy intervention. The town healthcare centers with higher inpatient service capacity (coef. = - 0.514) and more licensed doctors (coef. = - 0.587) and nurses (coef. = - 0.344) may indicate more detrimental policy effects that reduced the number of rural doctors, while the centers with more professional equipment (coef. = 0.504) and nurses (coef. = 0.184) are beneficial for the improvement of hardware setting in clinics. CONCLUSIONS: The findings suggest that the PHC inequalities are increasingly a result of joint social, economic, and institutional forces in recent years, underlining the increased complexity of the PHC resource allocation mechanism. Therefore, we claim the necessity to incorporate a broader understanding of community orientation in PHC delivery, particularly the interdisciplinary knowledge of the spatial lens of community, to support its sustainable development. Our findings also provide timely policy insights for ongoing primary healthcare reform in China.

Stochastic process is main factor to affect plateau river fish community assembly.

Plateau river ecosystems are often highly vulnerable and responsive to environmental change. The driving mechanism of fish diversity and community assembly in plateau rivers under changing environments presents a significant complexity to the interdisciplinary study of ecology and environment. This study integrated molecular biological techniques and mathematical models to identify the mechanisms influencing spatial heterogeneity of freshwater fish diversity and driving fish community assembly in plateau rivers. By utilizing environmental-DNA metabarcoding and the null model, this study revealed the impact of the stochastic process on fish diversity variations and community assembly in the Huangshui Plateau River of the Yellow River Basin (YRB) in China. This research identified 30 operational taxonomic units (OTUs), which correspond to 20 different fish species. The findings of this study revealed that the fish α-diversity in the upstream region of Xining is significantly higher than in the middle-lower reach (Shannon index: P = 0.017 and Simpson: P = 0.035). This pattern was not found to be related to any other environmental factors besides altitude (P = 0.023) that we measured. Further, the study indicated that the assembly of fish communities in the Huangshui River primarily depends on stochastic ecological processes. These findings suggested that elevation was not the primary factor impacting the biodiversity patterns of fish in plateau rivers. In plateau rivers, spatial heterogeneity of fish community on elevation is mainly determined by stochastic processes under habitat fragmentation, rather than any other physicochemical environmental factors. The limitations of connectivity in the downstream channel of the river could be taken the mainly responsibility for stochastic processes of fish community in Huangshui River. Incorporating ecological processes in the eDNA approach holds great potential for future monitoring and evaluation of fish biodiversity and community assembly in plateau rivers.

Nurses' mental workload and public health emergency response capacity in COVID-19 pandemic: A cross-sectional study.

AIMS: The aim of this study was to assess the level of mental workload of Chinese nurses through a latent profile analysis and to explore its relationship with public health emergency response capacity. DESIGN: A cross-sectional design with a convenience sample. METHODS: A convenience sample of nurses from five tertiary hospitals in Chengdu between May and December 2022. Demographic, work-related information, Nurse's version of NASA's Task Load Index Scale and Nurse's Public Health Emergency Response Capacity Scale were used in this study. RESULTS: The mean scores for mental workload and emergency response capacity for nurses were (57.19 ± 15.67) and (3.58 ± 0.77) respectively. We found that the mental workload of nurses fell into three potential categories. In addition, there were differences in psychological training and supply of epidemic prevention materials in the department among nurses with different mental workload subtypes. There was a moderate negative correlation between nurses' mental workload and public health emergency response capacity. CONCLUSION: Our results show that there is still a strong mental workload on a proportion of nurses, and enhanced psychological training and material supply support are beneficial in relieving nurses' mental workload. The better the nurses' capacity to cope with public health emergencies, the lower their mental workload. IMPACT: Nursing managers should pay ongoing attention to the mental workload status of nurses in the latter stages of a pandemic and individual differences in nurses' mental workload. In addition, nursing managers should be aware of the impact of public health emergency response capacity on nurses' mental workload. They can intervene in nurses mental workload from a new perspective. PATIENT OR PUBLIC CONTRIBUTION: 560 registered nurses participated in this study.

Floristic changes and environmental drivers of soil fungi and archaea in different salt-tolerant plant communities in the intertidal habitat of coastal wetlands.

Microorganisms are crucial elements of terrestrial ecosystems, which play significant roles in improving soil physicochemical properties, providing plant growth nutrients, degrading toxic and harmful chemicals, and biogeochemical cycling. Variations in the types and quantities of root exudates among different plants greatly alter soil physicochemical properties and result in variations in the diversity, structure, and function of soil microorganisms. Not much is understood about the differences of soil fungi and archaea communities for different plant communities in coastal wetlands, and their response mechanisms to environmental changes. In this study, fungal and archaea communities in soils of Suaeda salsa, Phragmites australis, and Spartina alterniflora in the intertidal habitat of coastal wetlands were selected for research. Soil fungi and archaea were analyzed for diversity, community structure, and function using high throughput ITS and 16S rRNA gene sequencing. The study revealed significant differences in fungi and archaea's diversity and community structure in the rhizosphere soil of three plant communities. At the same time, there is no significant difference in the functional groups. SOM, TP, AP, MC, EC and SOM, TN, TP, AP, MC, EC are the primary environmental determinants affecting changes in soil fungal and archaeal communities, respectively. Variations in the diversity, community structure, and ecological functions of fungi and archaea can be used as indicators characterizing the impact of external disturbances on the soil environment, providing a theoretical foundation for the effective utilization of soil microbial resources, thereby achieving the goal of environmental protection and health promotion.

Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.

Signal peptide-CUB-EGF-like repeat-containing protein 1-promoted FLT3 signaling is critical for the initiation and maintenance of MLL-rearranged acute leukemia.

A hallmark of mixed lineage leukemia gene-rearranged (MLL-r) acute myeloid leukemia that offers an opportunity for targeted therapy is addiction to protein tyrosine kinase signaling. One such signal is the receptor tyrosine kinase Fms-like receptor tyrosine kinase 3 (FLT3) upregulated by cooperation of the transcription factors homeobox A9 (HOXA9) and Meis homeobox 1 (MEIS1). Signal peptide-CUB-EGF-like repeat-containing protein (SCUBE) family proteins have previously been shown to act as a co-receptor for augmenting signaling activity of a receptor tyrosine kinase (e.g., vascular endothelial growth factor receptor). However, whether SCUBE1 is involved in the pathological activation of FLT3 during MLL-r leukemogenesis remains unknown. Here we first show that SCUBE1 is a direct target of HOXA9/MEIS1 that is highly expressed on the MLL-r cell surface and predicts poor prognosis in de novo acute myeloid leukemia. We further demonstrate, by using a conditional knockout mouse model, that Scube1 is required for both the initiation and maintenance of MLL-AF9-induced leukemogenesis in vivo. Further proteomic, molecular and biochemical analyses revealed that the membrane-tethered SCUBE1 binds to the FLT3 ligand and the extracellular ligand-binding domains of FLT3, thus facilitating activation of the signal axis FLT3-LYN (a non-receptor tyrosine kinase) to initiate leukemic growth and survival signals. Importantly, targeting surface SCUBE1 by an anti-SCUBE1 monomethyl auristatin E antibody-drug conjugate led to significantly decreased cell viability specifically in MLL-r leukemia. Our study indicates a novel function of SCUBE1 in leukemia and unravels the molecular mechanism of SCUBE1 in MLL-r acute myeloid leukemia. Thus, SCUBE1 is a potential therapeutic target for treating leukemia caused by MLL rearrangements.

A study on the antibacterial activity and antimicrobial resistance of pyridinium cationic pillar[5]arene against Staphylococcus aureus and Escherichia coli.

An increasing number of infections caused by multidrug-resistant (MDR) Staphylococcus aureus （S. aureus） and Escherichia coli （E. coli） have severely affected human society. Thus, it is essential to develop an alternative type of antibacterial agents that has a different bacterial resistance mechanism from that of traditional antibiotics. After the synthesis and structural characterization of a cationic pillar[5]arene with pyridinium groups (PP5), the antibacterial and antibiofilm activities as well as its microbial resistance were systematically investigated. In-depth evaluation of biological studies revealed that PP5 was an active antibacterial agent, with surprising antibiofilm formation ability against E. coli and S. aureus. From the results of differential scanning calorimetry and transmission electron microscopy, it was concluded that the microbicidal activity of PP5 was due to the physical disruption of the pathogen's membrane and the subsequent leakage of cytoplasmic components, which could greatly reduce the rapid generation of resistance. It was presented that the easily available PP5 has high activity to inhibit Gram-positive and Gram-negative bacteria and/or their biofilms with low cytotoxicity. This pillar[5]arene derivative can be used as a good candidate for controlling drug-resistant pathogenic bacterial infections and treating MDR bacteria.

Causal inference of sex hormone-binding globulin on venous thromboembolism: evidence from Mendelian randomisation.

BACKGROUND: Previous cohort studies have shown that exogenous sex hormone use, such as testosterone replacement therapy and oestrogen-containing contraceptives, can increase the risk of venous thromboembolism (VTE). However, the relationship between endogenous sex hormone levels and VTE remains unclear. The goal of the present study was to explore the causal roles of endogenous sex hormones, including hormone-binding globulin (SHBG), bioactive testosterone (BT), and total testosterone (TT), in VTE and its two subgroups, deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: We used a genome-wide association study of sex hormones as exposure data and Finnish VTE data as the outcome. Inverse variance weighting, MR-Egger, and weighted median were used for two-sample Mendelian randomisation (MR). Sensitivity analyses included MR-Egger, MR-PRESSO, Cochrane Q test, MR Steiger, leave-one-out analysis, and funnel plot, combined with multivariate MR and replicated MR analyses using larger VTE data from the global biobank meta-analysis initiative. Linkage disequilibrium score regression (LDSC) was used to determine genetic associations and estimate sample overlap. RESULTS: Our findings genetically predicted that an increase in serum SHBG levels by one standard deviation (SD) caused 25% higher odds for VTE (OR: 1.25, 95% CI: 1.01-1.55) and 58% higher odds for PE (OR: 1.58, 95% CI: 1.20-2.08). LDSC supported the genetic correlation between these two traits and replicated analyses confirm SHBG's genetic effect on VTE in both sexes (OR: 1.46, 95% CI: 1.20-1.78) and in females (OR: 1.49, 95% CI: 1.17-1.91). In addition, an increase in serum TT levels by one SD caused 32% higher odds for VTE (OR: 1.32, 95% CI: 1.08-1.62) and 31% higher odds for DVT (OR: 1.31, 95% CI: 1.01-1.69); however, LDSC and replicated analyses did not find a genetic correlation between TT and VTE or its subtypes. No significant correlation was observed between BT and all three outcome traits. CONCLUSION: Our study provides evidence that elevated serum SHBG levels, as predicted by genetics, increase VTE risk. However, the causal effect of testosterone levels on VTE requires further investigation.

LC-MS-Guided Isolation of Cyanogripeptides A-C, Cyclolipopeptides with ß-Methyl-Leucine Residues, from an Actinoalloteichus cyanogriseus LHW52806.

Cyanogripeptides A-C (1-3), three new cyclolipopeptides with unusual ß-methyl-leucine residues, were identified from an Actinoalloteichus cyanogriseus LHW52806 using an LC-MS-guided strategy. The structures of compounds 1-3 were elucidated by 1D/2D NMR, HR-MS/MS, and the advanced Marfey's method. The absolute configuration of the ß-methyl-leucine residue was determined by a combination of stereoselective biosynthesis of (2S,3R)-ß-methyl-leucine, racemization to its epimer (2R,3R)-ß-methyl-leucine, and the advanced Marfey's method. The biosynthetic pathway of cyanogripeptides was deduced by analyzing the genome of A. cyanogriseus LHW52806. Compound 3 exhibited antibacterial activity against Helicobacter pylori G27, Helicobacter pylori 26695, and Mycolicibacterium smegmatis ATCC607 with MIC values of 32 µg/mL.

Phakellisins A-E, cyclopeptides from a marine sponge Phakellia sp. guided by LC-MS.

A chemical investigation of the marine sponge Phakellia sp. from the South China Sea yielded five new cyclopeptides, phakellisins A-E (1-5). Structures of these compounds were determined by comprehensive analysis of 1D/2D NMR, HRESIMS/MS spectroscopic data and the advanced Marfey's method. All compounds were evaluated for their cytotoxic activity. Compound 1 showed a strong inhibitory activity against WSU-DLCL-2 cells with an IC50 value of 5.25 ± 0.2 µM by induction of G0/G1 cell cycle arrest and apoptosis.

Identification and characterization of Prx5 and Prx6 in Chilo suppressalis in response to environmental stress.

The antioxidant proteins, peroxiredoxins (Prxs), function to protect insects from reactive oxygen species-induced toxicity. In this study, two Prx genes, CsPrx5, and CsPrx6, were cloned and characterized from the paddy field pest, Chilo suppressalis, containing open reading frames of 570 and 672 bp encoding 189 and 223 amino acid polypeptides, respectively. Then, we investigated the influence of various stresses on their expression levels using quantitative real-time PCR (qRT-PCR). The results showed expression of CsPrx5 and CsPrx6 in all developmental stages, with eggs having the highest level. CsPrx5 and CsPrx6 showed higher expression in the epidermis and fat body, and CsPrx6 also showed higher expression in midgut, fat body, and epidermis. Increasing concentrations of insecticides (chlorantraniliprole and spinetoram) and hydrogen peroxide (H2 O2 ) increased the expression levels of CsPrx5 and CsPrx6. In addition, the expression levels of CsPrx5 and CsPrx6 were almost markedly upregulated in larvae under temperature stress or fed by vetiver. Thus, CsPrx5 and CsPrx6 upregulation might increase the C. suppressalis defense response by reducing the impact of environmental stress, providing a better understanding of the relationship between environmental stresses and insect defense systems.

New insights into the mechanism of ammonia toxicity: Focus on Cactus.

The NF-κB signaling pathway is the most critical pathway in innate immunity. IκB (Cactus) is the primary cytoplasmic inhibitor of NF-κB (Dorsal). In this study, we found that ammonia exposure could significantly induce the expression of Cactus, in a dose-dependent manner in different tissues, with the highest expression in the gill of Corbicula fluminea. The expression pattern-related elements (Tube and Dorsal) in the NF-κB signaling pathway were also analyzed, showing significant up-regulation in 48 h. There was an inhibitory effect between up-regulated Cactus and Dorsal in 72 h, which may regulate Dorsal as a negative feedback pathway function to control the expression of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Besides, through molecular docking simulation, we found that the Cactus could be directly activated by NH3, complementing the regulatory mechanism of the Cactus. To further test our hypothesis, the levels of pro-inflammatory cytokines decreased after adding PDTC (the antioxidant of Cactus/IκB), suggesting that PDTC can prevent the degradation of Cactus, inhibit Dorsal translocating into the nucleus, and activate the pro-inflammatory cytokines. This revealed the inhibitory effect of Cactus on activating Dorsal/NF-κB factors in the NF-κB signaling pathway. Thus, we suggested that the Cactus is an essential regulator of ammonia-activated inflammation in C. fluminea, which was reported to be activated only by bacteria and immune stimulators. Our study provides a new perspective on the mechanism of ammonia toxicity in invertebrates.

Unique and generic crossed metabolism in response to four sub-lethal environmental stresses in the oriental fruit fly, Bactrocera dorsalis Hendel.

Bactrocera dorsalis is a well-known invasive pest that causes considerable ecological and economic losses worldwild. Although it has a wide environmental tolerance, few studies have reported its mechanism of adaptation to multiple sub-lethal environmental stresses. In this study, 38, 41, 39 and 34 metabolites changed significantly in B. dorsalis under four sub-lethal stresses (heat, cold, desiccation and hypoxia), as found by the metabolomic method. Therein, lactic acid and pyruvic acid were induced, whereas metabolites in the tricarboxylic acid (TCA) cycle such as citric acid, α-ketoglutarate acid, malic acid and fumaric acid were reduced under at least one of the stresses. Enzyme activity and quantitative polymerase chain reaction (qPCR) analyses verified the repression of pyruvic acid proceeding into the TCA cycle. In addition, the levels of several cryoprotectants and membrane fatty acids in B. dorsalis were altered. The findings indicated that B. dorsalis has evolved shared metabolic pathways to adapt to heat, hypoxia and desiccation stresses, such as reducing energy consumption by activating the anaerobic glycolytic metabolism. Cryoprotectants and membrane fatty acids were produced to improve the efficiency of stress resistance. This study revealed the unique and generic crossed physiological mechanism of insects to adapt to various environmental stresses.

Active control of sound transmission through a floor-level slit.

The floor-level slit between the door and the floor is one weak point in building noise insulation. In this paper, an active noise control system is proposed to reduce the sound transmission through a floor-level slit with evenly distributed secondary sources on its top boundary. The system performance is first investigated based on the analytical and numerical models, and simulation results indicate a decrease in active control performance with increasing frequency. The upper limit frequency of 10 dB effective control increases with a higher number of secondary sources, and the corresponding wavelength of the upper limit frequency is approximately the interval between the secondary sources when a plane wave is incident normally. Although the upper limit frequency decreases with the slit height, it approaches a constant when the slit height becomes significantly smaller than the wavelength in the incident sound. The experimental results based on a typical floor-level door slit support the findings in the numerical simulations. For a slit with a width of 0.9 m and a height of 0.005 m, the upper limit frequency of 10 dB noise reduction can reach up to 2830 Hz when ten secondary sources are employed in the experiments.

Transmission loss and directivity of sound transmitted through a slit on ground.

An analytical model is proposed for sound transmission through a slit on a rigid ground based on the modal superposition method to investigate the transmission loss (TL). A simple formula is derived for estimation of the TL for plane waves with and without the ground, which gives a more precise prediction than existing approaches. It is found that a larger slit height generally decreases the TL, except at the resonant frequencies of the slit. The slit width has little effect on the TL at high frequencies, and the slit depth affects the resonant frequencies significantly even though it has little effect on the overall TL. Compared with the same size slit in the free field, the rigid ground reduces the TL at most frequencies, and that reduction is a constant between 3 and 9 dB in the low frequency range. It is also found that the sound transmitted through the slit is almost omnidirectional at low frequencies, while most of the sound energy at high frequencies falls within the range where the long side of the slit is located. The experimental results demonstrate the validity of the analytical model and the findings in numerical simulations.