Molecular insight on the binding of halogenated organic phosphate esters to human serum albumin and its effect on cytotoxicity of halogenated organic phosphate esters.

Halogenated Organic Phosphate Esters (OPEs) are commonly found in plasticizers and flame retardants. However, they are one kind of persistent contaminants that can pose a significant threat to human health and ecosystem as new environmental estrogen. In this study, two representative halogenated OPEs, tris(1,3-dichloro-2-propyl) phosphate (TDCP) and tris(2,3-dibromopropyl) phosphate (TDBP), were selected as experimental subjects to investigate their interaction with human serum albumin (HSA). Despite having similar structures, the two ligands exhibited contrasting effects on enzyme activity of HSA, TDCP inhibiting enzyme activity and TDBP activating it. Furthermore, both TDCP and TDBP could bind to HSA at site I, interacted with Arg222 and other residues, and made the conformation of HSA unfolded. Thermodynamic parameters indicated the main driving forces between TDBP and HSA were hydrogen bonding and van der Waals forces, while TDCP was mainly hydrophobic force. Molecular simulations found that more hydrogen bonds of HSA-TDBP formed during the binding process, and the larger charge area of TDBP than TDCP could partially account for the differences observed in their binding abilities to HSA. Notably, the cytotoxicity of TDBP/TDCP was inversely proportional to their binding ability to HSA, implying a new method for determining the cytotoxicity of halogenated OPEs in vitro.

Biology of Euwallacea interjectus, an emerging poplar pest, reared on an ambrosia beetle artificial diet and medium of fungal symbiont.

Euwallacea interjectus, a recently discovered pest in poplar plantations, poses a significant economic threat due to its role in causing widespread tree mortality. This pest's cryptic behaviour has hindered research and control efforts, making laboratory rearing a valuable tool for studying its development and biology. We investigated the development period and biological characteristics of E. interjectus using artificial diets and fungal medium. Our findings revealed that the development time for eggs, larvae, and pupae averages approximately 6, 18, and 6 days, respectively. Notably, first and second instar larvae displayed peak moulting periods at 3.45 ± 0.64 SD and 7.92 ± 1.77 SD days, respectively. Furthermore, we measured head capsule widths of postmolt larvae, yielding values of 318.02 ± 7.38 SD µm for first-instar larvae, 403.01 ± 11.08 SD µm for second-instar larvae, and 549.54 ± 20.74 SD µm for third-instar larvae. Our research also uncovered a positive correlation between the number of progeny (eggs, larvae, pupae, and adults) and the mean length of the gallery system. Interestingly, the haplodiploid reproductive strategy did not significantly affect the number of offspring produced by the foundress. Additionally, we observed that foundresses displayed higher fecundity when subjected to nutrient-rich diets as compared to nutrient-poor diets. Our results will deepen our understanding of the biology of E. interjectus and provide criteria for larval instar classification. Additionally, managing nutrient availability within the colony could be considered a viable approach to regulating population size.

Alteration of Thyroid Hormones in Mouse Models of Alzheimer's Disease and Aging.

INTRODUCTION: Aging is characterized by the deterioration of a wide range of functions in tissues and organs, and Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Hypothyroidism occurs when there is insufficient production of thyroid hormones (THs) by the thyroid. The relationship between hypothyroidism and aging as well as AD is controversial at present. METHODS: We established an animal model of AD (FAD4T) with mutations in the APP and PSEN1 genes, and we performed a thyroid function test and RNA sequencing (RNA-Seq) of the thyroid from FAD4T and naturally aging mice. We also studied gene perturbation correlation in the FAD4T mouse thyroid, bone marrow, and brain by further single-cell RNA sequencing (scRNA-seq) data of the bone marrow and brain. RESULTS: In this study, we found alterations in THs in both AD and aging mice. RNA-seq data showed significant upregulation of T-cell infiltration- and cell proliferation-related genes in FAD4T mouse thyroid. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that upregulated genes were enriched in the functional gene modules of activation of immune cells. Downregulated energy metabolism-related genes were prominent in aging thyroids, which reflected the reduction in THs. GSEA showed a similar enrichment tendency in both mouse thyroids, suggesting their analogous inflammation state. In addition, the regulation of leukocyte activation and migration was a common signature between the thyroid, brain, and bone marrow of FAD4T mice. CONCLUSIONS: Our findings identified immune cell infiltration of the thyroid as the potential underlying mechanism of the alteration of THs in AD and aging.

Predicting Long-Term Stability of an Oral Delivered Antibody Drug Product with Accelerated Stability Assessment Program Modeling.

The oral delivery of protein therapeutics offers numerous advantages for patients but also presents significant challenges in terms of development. Currently, there is limited knowledge available regarding the stability and shelf life of orally delivered protein therapeutics. In this study, a comprehensive assessment of the stability of an orally delivered solid dosage variable domain of heavy-chain antibody (VHH antibody) drug product was conducted. Four stability related quality attributes that undergo change as a result of thermal and humidity stress were identified. Subsequently, these attributes were modeled using an accelerated stability approach facilitated by ASAPprime software. To the best of our knowledge, this is the first time that this approach has been reported for an antibody drug product. We observed overall good model quality and accurate predictions regarding the protein stability during storage. Notably, we discovered that protein aggregation, formed through a degradation pathway, requires additional adjustments to the modeling method. In summary, the ASAP approach demonstrated promising results in predicting the stability of this complex solid-state protein formulation. This study sheds light on the stability and shelf life of orally delivered protein therapeutics, addressing an important knowledge gap in the field.

Association of urinary polycyclic aromatic hydrocarbon metabolites with gestational diabetes mellitus and gestational hypertension among pregnant women in Southwest China: A cross-sectional study.

The association of polycyclic aromatic hydrocarbons (PAHs) with gestational diabetes mellitus (GDM) and gestational hypertension during pregnancy has not yet been established. To investigate the association between PAH exposure and GDM and gestational hypertension, we conducted a cross-sectional study of 4206 pregnant women from the Zunyi birth cohort in southwestern China. Gas chromatography/mass spectrometry was used to detect the urinary levels of 10 monohydroxylated PAHs (OH-PAHs). GDM and gestational hypertension were diagnosed and the relevant information was documented by specialist obstetricians and gynecologists. Logistic regression and restricted cubic spline regression were employed to investigate their single and nonlinear associations. Stratified analyses of pregnancy and body mass index data were conducted to determine their moderating effects on the abovementioned associations. Compared with the first quartile of urinary ∑OH-PAHs, the third or fourth quartile in all study participants was associated with an increased risk of GDM (quartile 3: odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.03-1.77) and gestational hypertension (quartile 3: OR = 1.88, 95% CI: 1.26-2.81; quartile 4: OR = 1.58, 95% CI: 1.04-2.39), respectively. Nonlinear associations of 1-OH-PYR with GDM (cutoff level: 0.02 µg/g creatinine [Cr]) and 1-OH-PHE with gestational hypertension (cutoff level: 0.06 µg/g Cr) were also observed. In pregnant women with overweight or obesity, 1-OH-PHE and 3-OH-PHE were more strongly associated with gestational hypertension. Our results indicate that exposure to PAH during pregnancy may significantly increase the maternal risks of GDM and gestational hypertension; however, this finding still needs to be confirmed through larger-scale prospective studies and biological evidence.

Probing the Protein-Excipient Interaction in the Orally Delivered Protein by Solid-State Hydrogen-Deuterium Exchange Mass Spectrometry and Molecular Dynamics.

The oral administration of protein therapeutics in solid dosage form is gaining popularity due to its benefits, such as improved medication adherence, convenience, and ease of use for patients compared to traditional parental delivery. However, formulating oral biologics presents challenges related to pH barriers, enzymatic breakdown, and poor bioavailability. Therefore, understanding the interaction between excipients and protein therapeutics in the solid state is crucial for formulation development. In this Letter, we present a case study focused on investigating the role of excipients in protein aggregation during the production of a solid dosage form of a single variable domain on a heavy chain (VHH) protein. We employed solid-state hydrogen-deuterium exchange coupled with mass spectrometry (ssHDX-MS) at both intact protein and peptide levels to assess differences in protein-excipient interactions between two formulations. ssHDX-MS analysis revealed that one formulation effectively prevents protein aggregation during compaction by blocking ß-sheets across the VHH protein, thereby preventing ß-sheet-ß-sheet interactions. Spatial aggregation propensity (SAP) mapping and cosolvent simulation from molecular dynamics (MD) simulation further validated the protein-excipient interaction sites identified through ssHDX-MS. Additionally, the MD simulation demonstrated that the interaction between the VHH protein and excipients involves hydrophilic interactions and/or hydrogen bonding. This novel approach holds significant potential for understanding protein-excipient interactions in the solid state and can guide the formulation and process development of orally delivered protein dosage forms, ultimately enhancing their efficacy and stability.

Characterization of synthetic guide ribonucleic acids through hydrophilic interaction chromatography coupled with mass spectrometry.

In this study, we aimed to develop a hydrophilic interaction liquid chromatography (HILIC) method for the analysis of single guide ribonucleic acid (sgRNA), a critical reagent used in CRISPR genome editing. Our results showed that effective profiling of sgRNA can be achieved by suppressing the surface charge of the stationary phase in HILIC. We identified hydrogen bonding as the primary retention mechanism with potential weak partitioning in HILIC separation of large oligonucleotides like 100-mer sgRNA. Moreover, we demonstrated that direct coupling of HILIC with mass spectrometry (MS) allows the intact mass analysis of sgRNA and its impurities with minimal adduct present. Finally, we characterized the post peak shown in the low temperature HILIC and identified it as sgRNA aggregates. Our findings provide valuable insight into the characterization of sgRNA and highlight the potential of HILIC-MS as a powerful analytical tool for relatively large oligonucleotide analysis.

Impacts of Halogen Substitutions on Bisphenol A Compounds Interaction with Human Serum Albumin: Exploring from Spectroscopic Techniques and Computer Simulations.

Bisphenol A (BPA) is an endocrine-disrupting compound, and the binding mechanism of BPA with carrier proteins has drawn widespread attention. Halogen substitutions can significantly impact the properties of BPA, resulting in various effects for human health. Here, we selected tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) to investigate the interaction between different halogen-substituted BPAs and human serum albumin (HSA). TBBPA/TCBPA spontaneously occupied site I and formed stable binary complexes with HSA. Compared to TCBPA, TBBPA has higher binding affinity to HSA. The effect of different halogen substituents on the negatively charged surface area of BPA was an important reason for the higher binding affinity of TBBPA to HSA compared to TCBPA. Hydrogen bonds and van der Waals forces were crucial in the TCBPA-HSA complex, while the main driving factor for the formation of the TBBPA-HSA complex was hydrophobic interactions. Moreover, the presence of TBBPA/TCBPA changed the secondary structure of HSA. Amino acid residues such as Lys199, Lys195, Phe211, Arg218, His242, Leu481, and Trp214 were found to play crucial roles in the binding process between BPA compounds and HSA. Furthermore, the presence of halogen substituents facilitated the binding of BPA compounds with HSA.

Transcriptome analysis of Euwallacea interjectus reveals differentially expressed unigenes related to developmental stages and egg laying.

Euwallacea interjectus (Curculionidae: Scolytinae) is an ambrosia beetle species in its early stages of research. Therefore, studying the related molecular mechanism associated with the development and egg laid is essential. Transcriptome sequencing was used in this study to compare the gene expression of the beetles at different developmental stages and female adults before and after oviposition. A total of 40,047 annotated unigenes were obtained. There were 4225 differentially expressed unigenes (DEUs) from larva to prepupa stage, 3651 DEUs between prepupa and pupa, 1675 DEUs generated from pupa to adult, and 4762 DEUs between females before and after oviposition. The most significant pathway differences between different development stages and before and after oviposition were selected through functional annotation of DEUs between different stages. Among them, there were many pathways related to protein metabolism including: neuroactive ligand-receptor interaction, endoplasmic reticulum and RNA transport. This study provides valuable information on the molecular regulation mechanism of development and the egg laid of E. interjectus.

Prospective assessment of pancreatic ductal adenocarcinoma diagnosis from endoscopic ultrasonography images with the assistance of deep learning.

BACKGROUND: Endosonographers are highly dependent on the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to develop a deep-learning radiomics (DLR) model based on endoscopic ultrasonography (EUS) images for identifying PDAC and to explore its true clinical benefit. METHODS: A retrospective data set of EUS images that included PDAC and benign lesions was used as a training cohort (N = 368 patients) to develop the DLR model, and a prospective data set was used as a test cohort (N = 123 patients) to validate the effectiveness of the DLR model. In addition, seven endosonographers performed two rounds of reader studies on the test cohort with or without DLR assistance to further assess the clinical applicability and true benefits of the DLR model. RESULTS: In the prospective test cohort, DLR exhibited an area under the receiver operating characteristic curves of 0.936 (95% confidence interval [CI], 0.889-0.976) with a sensitivity of 0.831 (95% CI, 0.746-0.913) and 0.904 (95% CI, 0.820-0.980), respectively. With DLR assistance, the overall diagnostic performance of the seven endosonographers improved: one endosonographer achieved a significant expansion of specificity (p = .035,) and another achieved a significant increase in sensitivity (p = .038). In the junior endosonographer group, the diagnostic performance with the help of the DLR was higher than or comparable to that of the senior endosonographer group without DLR assistance. CONCLUSIONS: A prospective test cohort validated that the DLR model based on EUS images effectively identified PDAC. With the assistance of this model, the gap between endosonographers at different levels of experience narrowed, and the accuracy of endosonographers expanded.

Panax notoginseng preparation plus aspirin versus aspirin alone on platelet aggregation and coagulation in patients with coronary heart disease or ischemic stroke: A meta-analysis of randomized controlled trials.

Purpose: We aimed to evaluate the effects of Panax notoginseng preparations (PNP) containing Panax Notoginseng Saponins (PNS) or Panaxatriol Saponin (PTS) on platelet aggregation and coagulation in the adjuvant treatment of coronary heart disease (CHD) and ischemic stroke (IS). Methods: Randomized controlled trials (RCTs) comparing the combination of PNP and aspirin (ASA) versus ASA alone for CHD or IS were searched in eight databases. Subgroup analysis was performed according to saponin category. When statistical heterogeneity was significant, sensitivity analysis was performed using the leave-one-out approach. Funnel plot, Egger' test, and Begg' test was adopted to detect publication bias. Results: Twenty RCTs involving 2216 patients were analyzed. Compared with ASA alone, PNP plus ASA had a stronger inhibitory effect on in PAgR [PNS, WMD = -6.10 (-7.25, -4.95), p < 0.00001; PTS, WMD = -3.53 (-4.68, -2.38), p < 0.00001]; PNS plus ASA better reduced FIB [WMD = -0.43 (-0.49, -0.36)] and DD [WMD = -0.59 (-0.67, -0.51), p < 0.00001], while PLT (p = 0.07) and PT (p = 0.34) were not significantly different; PTS plus ASA better prolonged PT [WMD = 1.90 (1.47, 2.32), p < 0.00001] and PT-INR [WMD = 0.22 (0.11, 0.32), p < 0.0001], whereas no significant difference in DD (p = 0.1) and bleeding-related events (positive fecal occult blood, p = 0.96; upper gastrointestinal bleeding, p = 0.67; subcutaneous hemorrhage, p = 0.51; bulbar conjunctival hemorrhage, p = 0.51; hematuria, p = 0.58). There was no significant difference between PNP plus ASA and ASA alone in terms of gastrointestinal side effect (PNS, p = 0.65; PTS, p = 0.56) and urticaria (PNS, p = 0.57; PTS, p = 0.55). Conclusion: PNP combined with ASA might produce stronger antiplatelet aggregation and anticoagulation effects without increasing bleeding risk, gastrointestinal side effects, and urticaria compared with ASA alone. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022339234.

[Application of Immune Checkpoint Inhibitors in EGFR Mutant 
Advanced Non-small Cell Lung Cancer].

In recent years, immune checkpoint inhibitors (ICIs) have greatly improved the survival rate of non-small cell lung cancer (NSCLC) patients without driver mutation. Compared with wild-type tumors, tumors with epidermal growth factor receptor (EGFR) mutations have greater heterogeneity in immune microenvironment characteristics such as programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB). Whether ICIs is suitable for NSCLC patients with EGFR mutation has been controversial. Clinical studies have shown that immunomonotherapy has no significant effect on patients with EGFR mutant NSCLC. ICIs combined with chemotherapy and antiangiogenic drugs show good survival benefits. This paper overviews the clinical research and related mechanism of ICIs single drug or combination therapy inadvanced NSCLC patients with EGFR mutation.
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A heat shock 70kDa protein MaltHSP70-2 contributes to thermal resistance in Monochamus alternatus (Coleoptera: Cerambycidae): quantification, localization, and functional analysis.

BACKGROUND: Heat Shock Proteins 70 (HSP70s) in insects act on a diverse range of substrates to assist with overcoming extreme high temperatures. MaltHSP70-2, a member of HSP70s, has been characterized to involve in the thermotolerance of Monochamus alternatus in vitro, while quantification and localization of MaltHSP70-2 in various tissues and its functional analysis in vivo remain unclear. RESULTS: In this study, temporal expression of MaltHSP70-2 indicated a long-last inductive effect on MaltHSP70-2 expression maintained 48 hours after heat shock. MaltHSP70-2 showed a global response to heat exposure which occurring in various tissues of both males and females. Particularly in the reproductive tissues, we further performed the quantification and localization of MaltHSP70-2 protein using Western Blot and Immunohistochemistry, suggesting that enriched MaltHSP70-2 in the testis (specifically in the primary spermatocyte) must be indispensable to protect the reproductive activities (e.g., spermatogenesis) against high temperatures. Furthermore, silencing MaltHSP70-2 markedly influenced the expression of other HSP genes and thermotolerance of adults in bioassays, which implied a possible interaction of MaltHSP70-2 with other HSP genes and its role in thermal resistance of M. alternatus adults. CONCLUSIONS: These findings shed new insights into thermo-resistant mechanism of M. alternatus to cope with global warming from the perspective of HSP70s functions.

The predictive value of fibrinogen-to-albumin ratio in the active, severe active, and poor prognosis of systemic lupus erythematosus: A single-center retrospective study.

OBJECTIVE: To evaluate the prediction and effect of fibrinogen-to-albumin ratio (FAR) on active, severe active, and poor prognosis of systemic lupus erythematosus (SLE). METHODS: One hundred and sixty-eight patients with SLE who were treated in our hospital were enrolled, the clinical data, laboratory indexes, and disease prognosis of all patients were collected and analyzed. RESULTS: Triglyceride (TG), FAR, ESR, and anti-dsDNA (+) were the influencing factors, while complement 3 (C3) was the protective factor of active SLE, the odds ratio (OR) values were 2.968, 3.698, 2.114, 2.727, and 0.652, respectively (p < 0.05). FAR, ESR, and anti-dsDNA (+) were the influencing factors, while C3 was the protective factor of severe active SLE, the OR values were 3.791, 1.953, 2.187, and 0.742, respectively (p < 0.05). SLE disease activity index (SLEDAI), TG, FAR, and anti-dsDNA (+) were the influencing factors, while C3 was the protective factor of poor prognosis SLE, the OR values were 3.024, 2.293, 3.012, 2.323, and 0.801, respectively (p < 0.05). FAR and FIB were positively correlated with SLEDAI, while ALB was negatively correlated with SLEDAI, the related coefficient (r) were 0.398, 0.267, -0.270, respectively. The receiver operating curve (ROC) analysis showed that the predictive values of FAR for active, severe active and poor prognosis SLE were 0.769, 0.769, and 0.734, respectively, were significant higher than FIB and ALB (p < 0.05). CONCLUSION: Fibrinogen-to-albumin ratio was an influencing factor of active, severe active, and poor prognosis SLE had higher predictive value than FIB and ALB for the activity and prognosis of SLE.

The cytochrome P450s of Leptographium qinlingensis: Gene characteristics, phylogeny, and expression in response to terpenoids.

Leptographium qinlingensis is one of the major fungal associates of the Chinese white pine beetle (Dendroctonus armandi) and is an active participant in the large-scale death of Pinus armandi. Beetles and associated fungi have evolved efficient systems for overcoming the toxicity of host defense chemicals, which consist of a multitude of monoterpenes and diterpenes. As fungal cytochromes (CYPs) can detoxify and degrade various xenobiotic compounds, we identified 11 CYPs from L. qinlingensis to analyze their potential function in detoxifying or degrading host chemical defense. These 11 CYPs of L. qinlingensis belong to 6 clans and cluster into 3 clades, clade 2, clade 8 and clade 10, based on their phylogenetic relationships. Moreover, we also analyzed the transcript levels of CYPs following treatment with terpenes or expression in mycelia grown on terpenoids as a carbon source. The results in this paper showed that several CYPs were upregulated after treatment with terpenes or growth on terpenoids as the only carbon source. Our research provides some insight into the function of CYPs from bark beetle symbiotic fungi in the detoxification of pine defense compounds or their relationships with the utilization of terpenoids.

Impact of Prasugrel and Ticagrelor on Platelet Reactivity in Patients With Acute Coronary Syndrome: A Meta-Analysis.

Background: This meta-analysis mainly aimed to compare the impact of prasugrel and ticagrelor on platelet reactivity (PR) in patients with acute coronary syndrome (ACS). Methods: We searched four electronic databases to identify randomized controlled trials and cohort studies comparing the impact of prasugrel and ticagrelor on PR in patients with ACS. We performed group analyses according to three detection methods, drug dose [loading dose (LD) and maintenance dose (MTD)] and LD effect time, and assessed the robustness of the results through sensitivity analysis. Results: Twenty-five studies with 5,098 patients were eligible. After LD, the incidence of high on-treatment platelet reactivity (HTPR) of ticagrelor was significantly lower than that of prasugrel within 6-18 h based on vasodilator-stimulated phosphoprotein (VASP) test [RR = 0.25 (0.07, 0.85), P = 0.03], there was no significant difference between ticagrelor and prasugrel in the following results: platelets inhibitory effect within 24-48 h based on VerifyNow P2Y12 (VN) assay (P = 0.11) and VASP test (P = 0.20), and the incidence of HTPR within 2-6 h based on VN assay (P = 0.57) and within 24-48 h based on VN assay (P = 0.46) and VASP test (P = 0.72), the incidence of low on-treatment platelet reactivity (LTPR) within 6-18 h based on VASP test (P = 0.46) and 48 h based on VN assay (P = 0.97) and VASP test (P = 0.73). After MTD, the platelet inhibitory effect of ticagrelor was stronger than that of prasugrel based on VN assay [WMD = -41.64 (-47.16, -36.11), P < 0.00001]and VASP test [WMD = -9.10 (-13.88, -4.32), P = 0.0002], the incidence of HTPR of ticagrelor was significantly lower than that of prasugrel based on VN assay [RR = 0.05 (0.02, 0.16), P < 0.00001], the incidence of LTPR of ticagrelor was significantly higher than prasugrel based on VN assay [RR = 6.54 (4.21, 10.14), P < 0.00001] and VASP test [RR = 2.65 (1.78, 3.96), P < 0.00001], the results of Multiple Electrode Aggregometry (MEA) test was inconsistent with the other two detection methods in platelet inhibitory effect and the incidence of HTPR and LTPR. There was no significant difference between ticagrelor and prasugrel in the following clinical outcomes: all-cause death (P = 0.86), cardiovascular death (P = 0.49), myocardial infarction (P = 0.67), stroke (P = 0.51), target vessel revascularization (P = 0.51), stent thrombosis (P = 0.90), TIMI major bleeding (P = 0.86) and bleeding BARC type ≥ 2 (P = 0.77). The risk of bleeding BARC type 1 of ticagrelor was significantly higher than prasugrel [RR = 1.44 (1.03, 2.02), P = 0.03]. Conclusions: Compared with prasugrel, ticagrelor might have a stronger platelet inhibition effect, with a lower incidence of HTPR and a higher incidence of LTPR and bleeding BARC type 1, while there might be no significant difference in the risk of thrombosis/ischemic, bleeding BARC Type ≥ 2 and TIMI major bleeding. A higher incidence of LTPR might indicate a higher risk of bleeding BARC type 1. The results of VN assay were consistent with that of VASP test, and not with the MEA test. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304205, identifier: CRD42022304205.

Comparative Transcriptome Analysis Reveals Molecular Insights in Overwintering Monochamus alternatus (Coleoptera: Cerambycidae).

Monochamus alternatus, the dominant vector of Bursaphelenchus xylophilus (Aphelenchida: Aphelenchoididae), has caused immense damage to forest resources. In China, this vector was native to the southern regions but has spread northward recently. To adapt to more challenging environments in the northern winter, M. alternatus has evolved an intricate strategy for overwintering, which remains largely unknown. Herein, we compared the transcriptome data of the overwintering and non-overwintering larvae of M. alternatus larvae to investigate the molecular mechanisms in overwintering. A total of 53.10 GB clean bases and 28, 245 unigenes were obtained by RNA-seq. Analysis of 2597 upregulated and 2429 downregulated unigenes, as well as the enrichment of DEGs showed that many genes and pathways were jointly involved in the overwintering period. Besides, the accuracy of the RNA-seq data was tested by using qPCR experiment involving 13 selected genes. The results revealed that the overwintering process relied largely on the energy allocation trade-off. Specifically, overwintering M. alternatus inhibited energy-intensive activities, such as growth and molting, detoxification, and trehalose transport, and the reserved energy was skewed towards the synthesis of antifreeze compounds and immune response to cope with the deleterious effects of winter.

Ozone pollution threatens the production of major staple crops in East Asia.

East Asia is a hotspot of surface ozone (O3) pollution, which hinders crop growth and reduces yields. Here, we assess the relative yield loss in rice, wheat and maize due to O3 by combining O3 elevation experiments across Asia and air monitoring at about 3,000 locations in China, Japan and Korea. China shows the highest relative yield loss at 33%, 23% and 9% for wheat, rice and maize, respectively. The relative yield loss is much greater in hybrid than inbred rice, being close to that for wheat. Total O3-induced annual loss of crop production is estimated at US$63 billion. The large impact of O3 on crop production urges us to take mitigation action for O3 emission control and adaptive agronomic measures against the rising surface O3 levels across East Asia.

Ethylenediurea offers moderate protection against ozone-induced rice yield loss under high ozone pollution.

Tropospheric ozone (O3) is the main phytotoxic air pollutant threatening food security, while ethylenediurea (EDU) can effectively mitigate O3-induced crop yield loss. EDU's mode of action, however, remains unclear, and the underlying physiological mechanisms of mitigating O3-induced crop yield loss are poorly understood. We cultivated hybrid rice seedlings under two O3 treatments (NF, nonfiltered ambient air; and NF60, ambient air plus 60 ppb O3) and sprayed foliage with 0 or 450 ppm EDU every ten days and determine photosynthesis-related traits, biomass indicators, and yield components. We found that EDU significantly increased the leaf nitrogen (N) allocation to photosynthesis (NP) and the grain N accumulation, while the grain N accumulation was positively correlated with NP and root biomass. EDU significantly increased the rice yield mainly by increasing the individual grain weight rather than the number of panicles and grains. While EDU protected from yield loss, the degree of protection was only 31% under NF60 treatment, thus EDU was unable to offer complete protection under high O3 pollution. These results will be conducive to a better understanding of the EDU protection mechanism and better application of EDU under high O3 pollution in the future.

Phylogeny of Leptographium qinlingensis cytochrome P450 genes and transcription levels of six CYPs in response to different nutrition media or terpenoids.

The ascomycete Leptographium qinlingensis is one of the major externally living fungal associates of Dendroctonus armandi, which can kill host trees when it invades Chinese white pine (Pinus armandii). We identified and phylogenetically analysed the cytochrome P450 (CYP) genes in the transcriptome of L. qinlingensis. Furthermore, the expression profiles of six CYPs in the mycelium of L. qinlingensis grown on different media or treated with terpenoids were detected, as well as their growth rates on different nutritional media and inhibition by terpenoids. The CYP evolution predicted that most of the CYPs occurred in a putative common ancestor shared between L. qinlingensis and Grosmannia clavigera. The growth rates and inhibition test result shows that L. qinlingensis has more similarity with G. clavigera, which can retrieve nutrition from pine wood and utilize monoterpenes as the sole carbon source. CYP582C and CYP52Z4 of L. qinlingensis might be involved in the metabolism of fatty acids and detoxification of terpenes and phenolics after the analysis of their transcription levels with different treatments.