Design and activity evaluation of new EGFR tyrosine kinase inhibitors containing cyclic polyamines.

The EGFR-TK pathway is pivotal in non-small-cell lung cancer (NSCLC) treatment, drugs targeting both EGFR wild-type and mutant tumor cells are still urgently needed. The focus of our study is on ATP-competitive inhibitors crucial for NSCLC therapy, specifically targeting the epidermal growth factor receptor (EGFR). A series of derivatives of Erlotinib and Icotinib were developed by incorporating a macrocyclic polyamine into a quinazoline scaffold to enhance their inhibitory activity against drug-resistant cells. The compounds exhibit modest activity against EGFR triple mutants (EGFRdel19/T790M/C797S). Compound b demonstrated slightly improved inhibition activity against PC-9del19/T790M/C797S (IC50 = 496.3 nM). This could provide some insights for optimizing EGFR inhibitors, particularly in the context of EGFR triple mutants.

Environmental factors associated with the filamentous green algae Cladophora blooms: A mesocosm experiment in a shallow eutrophic lake.

The process of ecological restoration in eutrophic lakes, often results in the blooming of the filamentous green algae Cladophora. This consequently affects the growth of submerged plants and the restoration of vegetation. However, the blooming process of Cladophora and the environmental factors affecting their growth are poorly understood. This has become a difficult problem in the management of lakes. The study therefore focused on succession process of Cladophora blooms and their driving factors through mesocosm experiments in Caohai Lake. The results of our experiment indicated that Cladophora growth was mainly affected by water temperature, turbidity and soluble reactive phosphorus concentration of the habitat where Elodea nuttallii and Cladophora coexist. Nuisance Cladophora was mainly affected by turbidity (>19.24 NTU) when the water temperature was above 15.7 °C. With increasing Cladophora biomass and decreasing turbidity (<4.88 NTU), Cladophora biomass accumulation was mainly limited by the soluble reactive phosphorus concentration (<3.2 µg/L). Recorded turbidity range of 9.54-13.19 NTU was found to cause dramatic changes in the biomass of Cladophora. The results also showed that the outbreak of Cladophora blooms was mainly attributed to turbidity when the water temperature was appropriate in eutrophic lakes. These findings suggest that successful management efforts should strengthen the monitoring of transparency change in addition to controlling the phosphorus concentration to limit the Cladophora overgrowth on lake ecological restoration.

Aryl Diazonium Salts: Powerful Arylating Agents for Catellani-Type ortho-Arylation.

The Catellani reaction provides an efficient synthetic approach to polyfunctionalized arenes. However, the selective ortho-arylating reagents employed in these reactions have been strictly limited to activated bromoarenes. As demonstrated in this work, aryl diazonium salts bearing both electron-donating and electron-withdrawing substituents, after in situ transformations with KI into the corresponding iodoarenes, were efficient arylating reagents for Catellani type ortho-arylation approaches.

Soil bacterial microbiota predetermines rice yield in reclaiming saline-sodic soils leached with brackish ice.

BACKGROUND: Saline-sodic lands threaten the food supply and ecological security in the western Songnen Plain of northeast China, and the gypsum is commonly adopted for restoration. However, the dynamics of soil bacterial community and the correlation with crop yield during restoring processes remain poorly understood. Here, we elucidated the soil chemical properties and bacterial communities and their associations with rice yield under different flue gas desulphurization gypsum (FGDG) application rates combined with brackish ice leaching. RESULTS: The increased application rate of FGDG generally improved soil reclamation effects, as indicated by soil chemical properties, bacterial diversity, and rice yield. Compared with fresh ice irrigation, the rice yield in brackish ice treatment increased by 15.84%, and the soil alkalinity and sodium adsorption ratio (SAR) decreased by 35.19% and 10.30%, respectively. The bacterial alpha diversity significantly correlated and predicted rice yield as early as brackish ice melt, suggesting the bacterial diversity was a sensitive indicator in predicting rice yield. Meanwhile, the bacterial communities in the control possessed a high abundance of oligotrophic Firmicutes, while eutrophic bacterial taxa (e.g. Proteobacteria) were enriched after brackish water irrigation and FGDG application. Moreover, we also established a Random Forest model and identified a bacterial consortium that explained an 80.0% variance of rice yield. CONCLUSION: Together, our results highlight the reclaiming effect of brackish ice in the saline-sodic field and demonstrate the sensitivity and importance of the soil bacterial community in predicting crop yield, which would provide essential knowledge on the soil quality indication and bio-fertilizer development for soil reclamation. © 2021 Society of Chemical Industry.

Nitrogen-cycling microbial community functional potential and enzyme activities in cultured biofilms with response to inorganic nitrogen availability.

Biofilms mediate crucial biochemical processes in aquatic ecosystems. It was hypothesized that eutrophication may promote the growth of biofilms, resulting in larger numbers of functional genes. However, the metabolic activity and the roles of biofilms in N cycling will be affected by ambient inorganic nitrogen availability, not by the abundance of functional genes. Biofilms were cultured either with replete inorganic nitrogen (N-rep) or without exogenous inorganic nitrogen supply (N-def) in a flow incubator, and the N-cycling gene abundances (nifH, N2 fixation; amoA, ammonia oxidation, archaea and bacteria; nirS and nirK, denitrification) and enzyme activities (nitrogenase and nitrate reductase) were analyzed. The results showed that, comparing the N-def and N-rep biofilms, the former contained lower nifH gene abundance, but higher nitrogenase activity (NA), while the latter contained higher nifH gene abundance, but lower NA. Different patterns of NA diel variations corresponded to the dynamic microbial community composition and different stages of biofilm colonization. Ammonia oxidizing bacteria (AOB), detected only in N-def biofilms, were responsible for nitrification in biofilms. N-rep biofilms contained high nirS and nirK gene abundance and high denitrification enzyme activity, but N-def biofilms contained significantly lower denitrification gene abundance and activity. In general, the strong N2 fixation in N-def biofilms and strong denitrification in N-rep biofilms assured the balance of aquatic ecosystems. The results suggested that evaluation of the functional processes of N cycling should not only focus on genetic potential, but also on the physiological activity of biofilms.

One Pot Synthesize α-Fe2O3/Graphene Composites and Their Photocatalytic Properties.

α-Fe2O3 and graphene composite (α-Fe2O3/G) was prepared by a facile one-step hydrothermal method with an aim of improving photocatalytic efficiency of the α-Fe2O3. Composition of reduced graphene oxide and α-Fe2O3 were simultaneously achieved during the hydrothermal reaction. The structures and morphologies of the composites were characterized by X-ray diffraction and transmission electron microscopy. The photoelectrochemical properties were investigated by the Mott-Schottky, electrochemical impedance spectra and UV-vis diffusion spectra measurements. The photodegradation results showed that α-Fe2O3/G composites had a much better photocatalytic performance than pure α-Fe2O3 due to extended light absorption range and lower electron­hole recombination rate. It provided a new insight into the effect of graphene on photocatalytic activity for high efficient catalysts.

Fish consumption and lung cancer risk: systematic review and meta-analysis.

There is evidence pointing to a possible role of diet on cancer etiology. Prior studies evaluating the relationship between fish consumption and lung cancer risk reported inconclusive results. The aim of this study was to achieve a comprehensive assessment of the relationship between fish consumption and lung cancer risk through systematic review and meta-analysis. Case control and cohort studies up to September 1, 2012 about fish consumption and lung cancer risk were confirmed by an online search. Separate relative risk (RR) or odds ratio (OR) estimates with 95% confidence interval (CI) of the relationship between lung cancer risk and fish consumption level from the included articles were combined by Stata11.0 software. Publication bias was evaluated by Egger's linear regression test and funnel plot. Twenty articles (17 case-control and 3 cohort studies) comprising 8799 cases of lung cancer and 17,072 noncases were included in the final analysis. The pooled results from all studies indicated that high fish consumption was significantly associated with a decreased risk of lung cancer (pooled RR: 0.79; 95% CI: 0.69-0.92). There was heterogeneity among the studies (I(2) = 73%, P < 0.05). Pooled RR in case control and cohort studies were 0.76 (95% CI: 0.63-0.91) and 0.95 (95% CI: 0.73-1.24), respectively. Omission of any single study had little effect on the combined risk estimates. This article had no publication bias. This study identifies a significant association between fish consumption and lung cancer, confirming a protective role of fish in lung cancer. More well-designed prospective studies are required to further verify the effect of fish consumption on lung cancer.

Cyclooxygenase-2 expression is associated with poor overall survival of patients with gastric cancer: a meta-analysis.

BACKGROUND: Cyclooxygenase-2 (COX-2) is believed to be involved in gastric carcinogenesis. However, it is still controversial whether COX-2 expression can be regarded as a prognostic factor for gastric cancer patients. AIM: To obtain a more accurate relationship between COX-2 overexpression and prognosis in gastric cancer by meta-analysis. METHOD: Relevant articles published up to May 2013 were searched by use of several keywords in electronic databases. Separate hazard ratio (HR) estimates and 95 % confidence intervals (95 % CI) for COX-2 overexpression and overall survival (OS) and disease-free survival (DFS) with gastric cancer were extracted. Combined HR with 95 % CI was calculated by use of Stata11.0 software to estimate the size of the effect. Publication bias testing and sensitivity analysis were also performed. RESULTS: A total of 27 studies which included 3,891 gastric cancer patients were combined in the final analysis. Combined results suggested that COX-2 overexpression was associated with an unfavorable OS (HR 1.58, 95 % CI 1.36-1.84) but not DFS (HR 1.15, 95 % CI 0.93-1.43) among patients with gastric cancer. Publication bias was absent. Sensitivity analysis suggested that the results of this meta-analysis were robust. CONCLUSIONS: The results of this meta-analysis suggest that high COX-2 expression may be an independent risk factor for poor OS of patients with gastric cancer. More large prospective studies are now needed to further clarify the prognostic value of COX-2 expression for DFS in gastric cancer.

No evidence of genetic causation between iron and infertility: a Mendelian randomization study.

Background: Observational studies have explored the impact of iron homeostasis on infertility; however, establishing definitive causal relationships remains challenging. This study utilized a two-sample Mendelian randomization approach to investigate the potential causal relationship between iron status and infertility. Materials and methods: Four indicators of iron status-serum iron, ferritin, transferrin saturation, and total iron binding capacity, were considered as exposure factors. Infertility was the outcome variable for both men and women. Robust causality was assessed using the primary inverse-variance-weighted method, complemented by three supplementary Mendelian randomization approaches. Sensitivity analyses were performed to enhance the precision and reliability of the results. Results: No statistically significant associations were identified between the four indicators of iron status and infertility. These results remained consistent across multiple Mendelian randomization methodologies. Conclusion: In conclusion, there is no evidence of a genetic causal relationship between iron status and infertility. Nevertheless, this does not preclude the possibility of a connection between iron status and infertility at different mechanistic levels.

Prognostic value of survivin expression in breast cancer patients: a meta-analysis.

The prognostic role of survivin expression in breast cancer patients has been widely reported. However, controversy still remains. Thus, a meta-analysis was conducted to obtain a more precise estimation of the relationship between survivin expression and overall survival (OS) in breast cancer patients. Relevant articles were selected for further assessment by online search in PubMed, EMBASE, and China National Knowledge Infrastructure. Pooled hazard ratios (HR) with 95 % confidence interval (95 % CI) were used to estimate the strength of the association between survivin expression and OS in breast cancer patients. Funnel plots of Begger's and Egger's linear regression test were used to evaluate the publication bias. Heterogeneity and sensitivity analysis were also assessed. Fifteen studies were included in the final analysis with the total number of 2,202 patients. There was a significant association between positive survivin expression and a poor OS consequence in patients with breast cancer (pooled HR 1.80, 95 % CI 1.55-2.09). No significant heterogeneity was observed among all the eligible studies (x (2) = 21.87, p = 0.081, I (2) = 36.0 %). Publication bias was absent. Sensitivity analysis revealed that the results of this meta-analysis were robust. Our results suggested that high survivin expression had an unfavorable prognostic role for patients with breast cancer.

Effects of different types of vegetation cover on soil microorganisms and humus characteristics of soda-saline land in the Songnen Plain.

Introduction: In the soda-saline grasslands of the Songnen Plain, Jilin Province, China, the prohibition of grazing has led to significant changes in plant communities and soil properties. However, the intricate interplay between soil physical and chemical attributes, the soil microbial community, and their combined influence on soil humus composition remains poorly understood. Methods: Our study aimed to evaluate the impact of natural vegetation restoration on soil properties, microbial community diversity, and composition in the soda-saline soil region of the Songnen Plain. We conducted assessments of soil physical and chemical properties, analyzed community diversity, and composition at a soil depth range of 0-20 cm. The study covered soils with dominant soda-saline vegetation species, including Suaeda glauca Bunge, Puccinellia chinampoensis Ohwi, Chloris virgata Swarta, Phragmites australis (Clay.), Leymus chinensis (Trin.), and Tzvelev. We compared these vegetated soils to bare land devoid of any plants. Results: We found that soil organic content (SOC) in vegetation restoration areas was higher than in bare land, with SOC content varying between 3.64 and 11.15 g/kg in different vegetated areas. Notably, soil pH emerged as a pivotal factor, explaining 11.4% and 12.2% of the variance in soil bacteria and fungi, respectively. There were correlations between SOC content and the relative abundance of specific microbial groups, with Acidobacteria and Mortierella showing a positive correlation, while Actinobacteria, Gemmatimonadetes, and Ascomycota exhibited significant negative correlations with SOC. Discussion: The disparities in SOC composition and content among the soda-saline vegetation types were primarily attributed to variations in pH. Consequently, reducing soil pH is identified as a critical step in the process of vegetation restoration in soda-saline land. Prohibiting grazing has the potential to increase soda-saline SOC content and enhance microbial diversity, with Leymus chinensis and Phragmites australis showing particularly promising results in terms of higher SOC carbon content and microbial diversity.

Ignition control and waste heat assessment of spontaneous combustion gangue hill by gravity heat pipe group: a case study in Shanxi Province, China.

Spontaneous combustion gangue hill has attracted great attention due to serious environmental pollution and terrible geological disasters. However, the rich thermal resources inside are often ignored. In order to control the spontaneous combustion of gangue hill and utilize the internal waste heat resources, this project studied the combined treatment effect of 821 gravity heat pipes, laid 47 sets of temperature monitoring devices, evaluated the storage of waste heat resources, and proposed different waste heat utilization methods. The results show that (1) the positions of spontaneous combustion are all located on the windward slope. The highest temperature is in the range of 6 ~ 12 m underground, exceeding 700 ℃. (2) The single-tube experiment of gravity heat pipe shows that the effective temperature control radius is 2 m. The cooling effect is obvious in the range of 3 ~ 5 m underground. However, the temperature rises at the depth of 1 m underground. (3) After 90 days of treatment of the gravity heat pipe group, the temperature at the depths of 3 m, 4 m, 5 m, and 6 m in the high-temperature zone dropped by 56 ℃, 66 ℃, 63 ℃, and 42 ℃, respectively. The maximum temperature drop exceeds 160 ℃. The average temperature drop in the middle- and low-temperature areas is between 9 and 21 °C. (4) The concentration of harmful gases (CO, SO2, and H2S) decreases by more than 90%. The hazard level is greatly reduced. (5) The amount of waste heat resources contained within 10 m of the spontaneous combustion gangue hill is 7.83E13J. Waste heat resources can be used for indoor heating and greenhouse cultivation. And, under the temperature difference of 50 °C, 100 °C, and 150 °C, the electric energy generated by the heat through the thermoelectric conversion device in the high-temperature zone of the gangue hill is 4056.8 kWh, 7468.2 kWh, and 10,603 kWh, respectively.

Morphological Features of Fractures Developed by Direct Shearing of Intact Granites after Water Cooling Cycles.

Rock fractures are considered as favorable objects for enhanced geothermal development. The fracture morphologies play an important role in enhanced geothermal development. Therefore, the study of fracture morphologies has a certain guiding significance for the geothermal reservoir. Water cooling and water cooling cycles can change the morphology of fracture surfaces formed by the shear failure of intact granites. To date, however, there is little work on the effect of water cooling and water cooling cycles on the morphology of fracture surfaces formed by direct shearing of intact granites. In this study, the direct shear tests of intact granites treated by water cooling cycles at different temperatures were conducted, and the variations in the laws of shear strength of intact granites and morphologies of fracture surfaces with temperature or cycle times were analyzed. Test results showed that the shear strength and shear stiffness of intact granites decreased nonlinearly with the increase of temperature or cycle times, but the height and apparent dip angle of asperities on the fracture surface increased with the increase of temperature or cycle times, and the overall uniformity of the fracture surface was improved. The height distribution frequency of asperities on fracture surfaces can be divided into four types: right-biased peak type, left-biased peak type, left-biased middle peak, and left-biased flat peak. The asperities on the fracture surface formed by the shearing of intact granites have asymmetric characteristics. The maximum apparent dip angle and average apparent dip angle in the reverse shear direction are larger than those in the shear direction, and the initial contact area ratio between the shear direction and reverse shear direction is in the range of fluctuation between 1.4 and 2.

The Effects of Claw Health and Bone Mineral Density on Lameness in Duroc Boars.

To investigate the effects of claw lesion types and bone mineral density on lameness in boars, the data of claw lesion score, gait score, and bone mineral density, measured by a Miniomin ultrasound bone densitometer, were collected from a total of 739 Duroc boars. Firstly, we discovered that the prevalence of claw lesions was as high as 95.26% in boars. The percentage of lameness of boars with SWE was higher than those with other claw lesions. Meanwhile, the results showed that the probability of lameness was higher in boars with lower bone mineral density (p < 0.05). Logistic regression models, including variables of boar age, body weight, serum mineral level, and housing type, were used to identify the influencing factors of bone mineral density in this study. The results found that bone mineral density increases with age before reaching a maximum value at 43 months of age, and begins to decrease after 43 months of age. Elevated serum Ca levels were significantly associated with an increase in bone mineral density (p < 0.05). Aside from the above findings, we also made an interesting discovery that boars in the individual pen model significantly increased bone mineral density compared to those in the individual stall model. In conclusion, claw lesions and bone mineral density were significantly associated with lameness. Age, serum Ca, and housing type are the potential influencing factors for bone mineral density in boars.

Association study between C10orf90 gene polymorphisms and colorectal cancer.

Background: Colorectal cancer (CRC) is the third most common malignant tumor in the world. The morbidity and mortality rates in Western countries have decreased, but they are still on the rise in China. C10orf90 is associated with a variety of cancers, but the correlation between C10orf90 and CRC is not yet known. Methods: A total of 1,339 subjects were randomly enrolled in our study. After extracting their DNA, three single-nucleotide polymorphisms (SNPs) of C10orf90 were genotyped to analyze the potential relationship between these variants and CRC risk. PLINK software packages (version 1.07) were used to evaluate multiple genetic models by calculating the odds ratio (OR) and 95% confidence interval (95% CI). The best SNP-SNP interaction model was defined by the multifactor dimensionality reduction (MDR) analysis. Results: C10orf90 rs12412320 was significantly associated with CRC risk (p = 0.006) and might be associated with the lower CRC risk (OR: 0.78; 95% CI: 0.65-0.93). The relationship of rs12412320 with lower CRC risk was found in people aged >60 years and ≤60 years, women, non-smokers, or non-drinkers. Rs11245008 in people aged ≤60 years and rs11245007 among men had a higher CRC susceptibility. Rs12412320 was related to the lower risk of advanced stages (III/IV stage), while rs11245007 might be associated with the higher risk of advanced stages (III/IV stage). Moreover, rs12412320 had the most significant relationship with the susceptibility to rectal cancer. Conclusion: This study is the first to report between C10orf90 gene polymorphisms and CRC risk in Chinese people, which suggests that C10orf90 rs12412320 might play a crucial role in preventing CRC occurrence.

Factors influencing the bone mineral density in Duroc boars.

BACKGROUND: Leg weakness affects animal welfare and is one of the primary reasons for culling of boars. Low bone mineral density (BMD) is one of the primary factors contributing to leg weakness. Low BMD also appeared to be associated with severe bone pain and has the highest risk of skeletal fragility. Surprisingly, few studies have been performed on the factors influencing BMD in pigs. Therefore, the primary aim of this study was to identify the influencing factors on boar BMD. Herein, the BMD data were determined through the use of ultrasonography from 893 Duroc boars. Logistic regression model was utilized in the analysis of BMD, in which the explanatory variables in the model were lines, ages, body weights, backfat thicknesses and serum mineral element concentrations (Ca, P, Mg, Cu, Fe, Zn, Mn, Se, Pb and Cd). RESULTS: Results showed that factors significantly influencing BMD included serum Ca, P concentrations, ages and backfat thicknesses (P < 0.05), in which serum Ca concentrations were positively correlated with BMD (P < 0.01), whereas increasing concentrations of serum P decreased BMD (P < 0.01). The serum Ca/P ratio showed significant quadratic effects on BMD (r = 0.28, P < 0.01), and the Ca/P ratio to achieve the best BMD was determined to be 3.7. Furthermore, BMD also changed with age quadratically (r = 0.40, P < 0.01), and reached a peak value around 47 months. Interestingly, a quadratic (r = 0.26, P < 0.01) increase in the BMD was observed as backfat thickness increased, and the inflection point was calculated at around 17 mm. CONCLUSION: In conclusion, BMD characteristics of boars could be detected by ultrasonic method, and serum Ca, serum P, age, and backfat thickness contributed to the greatest effect on BMD.

In Situ Observation and Phase-Field Simulation Framework of Duplex Stainless-Steel Slab during Solidification.

The melting and solidification process of S32101 duplex stainless steel (DSS) was investigated using high-temperature confocal microscopy (HTCM). The method of concentric HTCM was employed to study microstructure evolution during the solidification process of S32101 DSS. This method could artificially create a meniscus-shaped solid-liquid interface, which dramatically improved the quality of in situ observations. During the heating stage, γ-austenite transformed to δ-ferrite, and this transformation manifested itself in the form of grain boundaries (GBs) moving. The effects of cooling rate on the solidification pattern and microstructure were revealed in the present research. An enhanced cooling rate led to a finer microstructure, and the solidification pattern changed from cellular to dendritic growth. As the temperature decreased, the commencement and growth of precipitates were observed. In this paper, the experimental data, including parameters such as temperature, cooling rate, and growth mode, were used as the benchmark for the simulation. A simulation framework using Micress linked to a 1D heat transfer model enabling consistent analysis of solidification dynamics in DSS across the whole cast slab was established. Simulating the dendrite growth and elemental segregation of DSS at specific cooling rates shows that this framework can be a powerful tool for solving practical production problems.

Effect of Wu Qin Xi exercises on pain and function in people with knee osteoarthritis: A systematic review and meta-analysis.

Background: As a chronic disease that affects the whole world, there is no definite treatment for knee osteoarthritis (KOA). Wu Qin Xi (WQX) is still in preliminary exploration as a traditional Chinese exercise in the treatment of osteoarthritis of the knee. The purpose of this study was to conduct a meta-analysis of previous studies and to investigate the efficacy of the WQX exercises on pain and function in patients with KOA. Methods: We searched six databases (Pubmed, Embase, Cochrane Library, Wanfang, CQVIP, and CNKI) for articles on WQX for KOA up to May 10, 2022. Literature search, study selection, data extraction, and quality evaluation were performed by two independent authors. In terms of statistical results, we presented mean differences (MD), 95% CI, and I 2 to show heterogeneity, and, based on that, we chose either a random effects model or a fixed effects model. Results: Seven studies were selected for inclusion in this meta-analysis. The WQX intervention group showed statistical differences for both the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and its various bylaws, the Visual Analogue Score (VAS), and the presence of general functional exercise in the control group. We also demonstrated the clinically meaningful efficacy of WQX treatment by calculating minimum clinical importance difference (MCID) values that met the MCID values on the WOMAC score. A sensitivity analysis was also performed in this study by subgroup analysis for greater heterogeneity, and it was inferred that the difference in follow-up time was a likely source of heterogeneity. Conclusion: Despite some limitations, the current study showed a definite effect of WQX in improving pain symptoms and joint function in patients with KOA. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022332209.

DNA Methylation Changes and Its Associated Genes in Mulberry (Morus alba L.) Yu-711 Response to Drought Stress Using MethylRAD Sequencing.

Drought stress remains one of the most detrimental environmental cues affecting plant growth and survival. In this work, the DNA methylome changes in mulberry leaves under drought stress (EG) and control (CK) and their impact on gene regulation were investigated by MethylRAD sequencing. The results show 138,464 (37.37%) and 56,241 (28.81%) methylation at the CG and CWG sites (W = A or T), respectively, in the mulberry genome between drought stress and control. The distribution of the methylome was prevalent in the intergenic, exonic, intronic and downstream regions of the mulberry plant genome. In addition, we discovered 170 DMGs (129 in CG sites and 41 in CWG sites) and 581 DMS (413 in CG sites and 168 in CWG sites). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicates that phenylpropanoid biosynthesis, spliceosome, amino acid biosynthesis, carbon metabolism, RNA transport, plant hormone, signal transduction pathways, and quorum sensing play a crucial role in mulberry response to drought stress. Furthermore, the qRT-PCR analysis indicates that the selected 23 genes enriched in the KEGG pathways are differentially expressed, and 86.96% of the genes share downregulated methylation and 13.04% share upregulation methylation status, indicating the complex link between DNA methylation and gene regulation. This study serves as fundamentals in discovering the epigenomic status and the pathways that will significantly enhance mulberry breeding for adaptation to a wide range of environments.

Metabolomics Response to Drought Stress in Morus alba L. Variety Yu-711.

Mulberry is an economically significant crop for the sericulture industry worldwide. Stresses such as drought exposure have a significant influence on plant survival. Because metabolome directly reflects plant physiological condition, performing a global metabolomic analysis is one technique to examine this influence. Using a liquid chromatography-mass spectrometry (LC-MS) technique based on an untargeted metabolomic approach, the effect of drought stress on mulberry Yu-711 metabolic balance was examined. For this objective, Yu-711 leaves were subjected to two weeks of drought stress treatment and control without drought stress. Numerous differentially accumulated metabolic components in response to drought stress treatment were revealed by multivariate and univariate statistical analysis. Drought stress treatment (EG) revealed a more differentiated metabolite response than the control (CK). We found that the levels of total lipids, galactolipids, and phospholipids (PC, PA, PE) were significantly altered, producing 48% of the total differentially expressed metabolites. Fatty acyls components were the most abundant lipids expressed and decreased considerably by 73.6%. On the other hand, the prenol lipids class of lipids increased in drought leaves. Other classes of metabolites, including polyphenols (flavonoids and cinnamic acid), organic acid (amino acids), carbohydrates, benzenoids, and organoheterocyclic, had a dynamic trend in response to the drought stress. However, their levels under drought stress decreased significantly compared to the control. These findings give an overview for the understanding of global plant metabolic changes in defense mechanisms by revealing the mulberry plant metabolic profile through differentially accumulated compounds.