WTAP dysregulation-mediated HMGN3-m6A modification inhibited trophoblast invasion in early-onset preeclampsia.

Early-onset preeclampsia (ePE) originates from abnormal implantation and placentation that involves trophoblast invasion, but its pathophysiology is not entirely understood. N6-methyladenosine (m6A) regulators mediate the progression of various cancers. The invasiveness of trophoblast cells is similar to that of tumor cells. However, little is known regarding the potential role of m6A modification in ePE and the underlying mechanism. This study aimed to explore the m6A level in placental tissue samples collected from ePE patients and to investigate whether m6A modification was an essential part of PE pathogenesis. The m6A level in placental tissue samples of 80 PE participants was examined. MeRIP-microarray, RNA-Seq, luciferase reporter assay, and RNA immunoprecipitation chip (RIP) assay were performed. The m6A level in the ePE group was significantly reduced compared with the control group. Wilms' tumor 1-associating protein (WTAP) regulated trophoblast cell migration and invasion. Mechanistically, the high mobility group nucleosomal binding domain 3 (HMGN3) gene was a target gene of WTAP in trophoblast (p < .05). WTAP enhanced the stability of HMGN3 mRNA through binding with its 3'-UTR m6A site(+485A, +522A). HMGN3 was recognized by m6A recognition protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which was inhibited when knocking down WTAP. Both m6A and WTAP levels were downregulated in ePE. The m6A modification mediated by WTAP/IGF2BP1/HMGN3 axis might contribute to abnormal trophoblast invasion. Our work provided a foundation for further exploration of RNA epigenetic regulatory patterns in ePE, and indicated a new treatment strategy for ePE.

Farming on the Ocean via Desalination (FOOD).

Today, agricultural irrigation consumes the largest amount of freshwater globally, while humans are threatened by water scarcity. To eliminate the trade-off between hunger and thirst, here, we show off-grid maritime agriculture based on a floating solar-driven agro-desalination wooden dome. In this dome, part of the visible light is transmitted for photosynthesis, and the remaining solar energy drives solar desalination, providing enough water (>4 mm day-1) for irrigation. Based on this water-food synergy, the stages of germination and growth are demonstrated. This technology can, to a large extent, support food security and sustainable agriculture and, in principle, be used to create self-circulation systems at sea to help humans survive weather extremes such as floods and droughts.

Transcriptome and Metabolite Conjoint Analysis Reveals the Seed Dormancy Release Process in Callery Pear.

Seed dormancy transition is a vital developmental process for seedling propagation and agricultural production. The process is precisely regulated by diverse endogenous genetic factors and environmental cues. Callery pear (Pyrus calleryana Decne) is an important rootstock species that requires cold stratification to break seed dormancy, but the mechanisms underlying pear seed dormancy release are not yet fully understood. Here, we analyzed the transcriptome profiles at three different stages of cold stratification in callery pear seeds using RNA sequencing combined with phytohormone and sugar content measurements. Significant alterations in hormone contents and carbohydrate metabolism were observed and reflected the dormancy status of the seeds. The expressions of genes related to plant hormone metabolism and signaling transduction, including indole-3-acetic acid (IAA) biosynthesis (ASAs, TSA, NITs, YUC, and AAO) genes as well as several abscisic acid (ABA) and gibberellic acid (GA) catabolism and signaling transduction genes (CYP707As, GA2ox, and DELLAs), were consistent with endogenous hormone changes. We further found that several genes involved in cytokinin (CTK), ethylene (ETH), brassionolide (BR), and jasmonic acid (JA) metabolism and signaling transduction were differentially expressed and integrated in pear seed dormancy release. In accordance with changes in starch and soluble sugar contents, the genes associated with starch and sucrose metabolism were significantly up-regulated during seed dormancy release progression. Furthermore, the expression levels of genes involved in lipid metabolism pathways were also up-regulated. Finally, 447 transcription factor (TF) genes (including ERF, bHLH, bZIP, NAC, WRKY, and MYB genes) were observed to be differentially expressed during seed cold stratification and might relate to pear seed dormancy release. Our results suggest that the mechanism underlying pear seed dormancy release is a complex, transcriptionally regulated process involving hormones, sugars, lipids, and TFs.

GDF15 knockdown promotes erastin-induced ferroptosis by decreasing SLC7A11 expression.

Ferroptosis is an iron-dependent form of regulated cell death. GDF15 affects various properties of cancer cells, but the role of GDF15 in ferroptosis has not been reported. In the present study, we found that GDF15 knockdown led to decreased expression of SLC7A11, which is a key component of system Xc- and a regulator of ferroptosis, indicating that GDF15 might play important roles in ferroptosis. CCK8 assay showed that GDF15 knockdown promoted erastin-induced ferroptosis in MGC803 cells. qRT-PCR and western blotting results demonstrated that GDF15 inhibition attenuated the increased SLC7A11 expression induced by erastin. Further study revealed that GDF15 knockdown promoted the decreased level of extracellular glutamate and intracellular GSH as well as the increased level of lipid ROS in the presence of erastin in MGC803 cells. Overall, the study shows that GDF15 knockdown promotes erastin-induced ferroptosis in MGC803 cells by attenuating the expression of SLC7A11 and the function of system Xc-.

ALG3-CDG: lethal phenotype and novel variants in Chinese siblings.

Congenital disorders of glycosylation (CDG) are a group of genetic, mostly multisystem disorders, which often involve the central nervous system. ALG3-CDG is one the some 130 known CDG. Here we report two siblings with a severe phenotype and intrauterine death. Whole-exome sequencing revealed two novel variants in ALG3: NM_005787.6:c.512G>T (p.Arg171Leu) inherited from the mother and NM_005787.6:c.511C>T (p.Arg171Trp) inherited from the father.

Computational systems pharmacology analysis of cannabidiol: a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation.

With treatment benefits in both the central nervous system and the peripheral system, the medical use of cannabidiol (CBD) has gained increasing popularity. Given that the therapeutic mechanisms of CBD are still vague, the systematic identification of its potential targets, signaling pathways, and their associations with corresponding diseases is of great interest for researchers. In the present work, chemogenomics-knowledgebase systems pharmacology analysis was applied for systematic network studies to generate CBD-target, target-pathway, and target-disease networks by combining both the results from the in silico analysis and the reported experimental validations. Based on the network analysis, three human neuro-related rhodopsin-like GPCRs, i.e., 5-hydroxytryptamine receptor 1 A (5HT1A), delta-type opioid receptor (OPRD) and G protein-coupled receptor 55 (GPR55), were selected for close evaluation. Integrated computational methodologies, including homology modeling, molecular docking, and molecular dynamics simulation, were used to evaluate the protein-CBD binding modes. A CBD-preferred pocket consisting of a hydrophobic cavity and backbone hinges was proposed and tested for CBD-class A GPCR binding. Finally, the neurophysiological effects of CBD were illustrated at the molecular level, and dopamine receptor 3 (DRD3) was further predicted to be an active target for CBD.

IL-1ß promotes the nuclear translocaiton of S100A4 protein in gastric cancer cells MGC803 and the cell's stem-like properties through PI3K pathway.

It has been shown that nuclear expression of S100A4 is significantly correlated with increased metastasis and reduced survival in patients with gastric cancer and many other cancers. However, the factors which could influence the nuclear contents of S100A4 in cancer cells are not clear. It has also been reported that Interleukin-1ß (IL-1ß) promotes the nuclear translocation of S100A4 in chondrocytes. Previous studies have shown that IL-1ß promotes the stemness of colon cancer cells, and S100A4 is also involved in maintaining cancer-initiating cells in head and neck cancers. We speculate that IL-1ß might promote the nuclear translocation of S100A4 protein in MGC803 gastric cancer cells and therefore enhance their stem-like properties. The results from Western-blot and qRT-PCR analysis showed that IL-1ß increased the nuclear and total cellular content of S100A4 protein and S100A4 mRNA level in MGC803 cells. LY294002, a pharmacological inhibitor of Phosphoinositide 3-kinase (PI3K) reversed the above effects. Functional studies indicated that IL-1ß promoted the colony-forming and spheroid-forming capabilities of the cells and the expression of SOX2 and NANOG gene. PI3K or S100A4 inhibition reversed the IL-1ß-mediated increase in colony and spheroid-forming capabilities of the cells. LY294002 also reversed the elevated SOX2 and NANOG expression induced by IL-1ß. Our study demonstrated that IL-1ß promote the nuclear translocation of S100A4 protein in gastric cancer cells MGC803, which are PI3K dependent, suggesting the existence of IL-1ß-PI3K-S100A4 pathway for the first time. The study also showed that IL-1ß promoted stem-like properties of the cells through the new pathway.

miR-3189-3p Mimics Enhance the Effects of S100A4 siRNA on the Inhibition of Proliferation and Migration of Gastric Cancer Cells by Targeting CFL2.

GDF15 is a downstream gene of S100A4. miR-3189 is embedded in the intron of GDF15-and coexpressed with it. miR-3189-3p functions to inhibit the proliferation and migration of glioblastoma cells. We speculated that S100A4 might regulate miR-3189-3p to affect its function in gastric cancer cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that miR-3189-3p expression was significantly downregulated in MGC803 cells after S100A4 knockdown. Overexpression of miR-3189-3p significantly inhibited the proliferation and migration of the cells. Moreover, miR-3189-3p mimics enhanced the effects of an S100A4 siRNA on the inhibition of cell proliferation and migration. Dual luciferase reporter assays, qRT-PCR, and Western blotting verified that CFL2 is a direct target of miR-3189-3p. CFL2 mediates the regulation of miR-3189-3p on the proliferation and migration of MGC803 cells. Data mining based on Kaplan-Meier plots showed that high CFL2 expression is associated with poor overall survival and first progression in gastric cancer. These data suggested that miR-3189-3p mimics enhanced the effects of the S100A4 siRNA on the inhibition of gastric cancer cell proliferation and migration by targeting CFL2. The findings suggested that when targeting S100A4 to treat gastric cancer, consideration and correction for counteracting factors should obtain a satisfactory effect.

Effect of inorganic salt ions on the adsorption of quinoline using coal powder.

In this study, coal powder was used as the adsorbent for quinoline. The effect of inorganic salt ions on the adsorption was explored, and the results suggest that the addition of inorganic salt ions can enhance both the removal rate and the amount of quinoline adsorbed. The removal rate and adsorbed amount of quinoline were 83.87% and 1.26 mg/g without inorganic salt ions. Under the same adsorption conditions, the removal rate and adsorbed amount of quinoline could reach 90.21% and 1.35 mg/g when Na+ was present in the solution, and 94.47% and 1.42 mg/g with the presence of Ca2+. In addition, the adsorption of quinoline using coal fitted the Freundlich isothermal adsorption model. Changes in the Gibbs free energy, entropy and heat of adsorption were all negative, indicating that the adsorption was spontaneous and exothermic. The changes in the absolute value of Gibbs free energy under both Na+ and Ca2+ were higher than that in the blank(without inorganic salt ions). The pseudo-second-order kinetic model was found to fit the adsorption kinetic data well, and the activation energy of adsorption under Na+ and Ca2+ were lower than that in the blank. These indicate that the addition of inorganic salt ions was beneficial to the adsorption process.

FAM107B is regulated by S100A4 and mediates the effect of S100A4 on the proliferation and migration of MGC803 gastric cancer cells.

FAM107B expression was decreased in stomach cancer and many other kinds of cancer. The forced expression of FAM107B in HeLa cells diminished proliferation in response to growth factors, suggesting that FAM107B might play important roles in many types of cancers. But the mechanisms underlying the decreased expression of FAM107B in cancers are not clear, the functional significance needs to be further clarified. Our previous findings from cDNA microarray showed that there are 179 differentially expressed genes after S100A4 inhibition in gastric cancer cells MGC803. FAM107B was an upregulated one among them. In the present study, we confirmed that FAM107B expression was upregulated in MGC803 cells after S100A4 inhibition by qRT-PCR. We demonstrated for the first time that FAM107B was downregulated by S100A4. The results from CCK-8 and transwell assay showed that FAM107B inhibition by siRNA led to significantly increased proliferation and migrating abilities of MGC803 cells, respectively, indicating that FAM107B plays important roles in inhibiting the proliferation and migration of MGC803 cells. The rescue experiment showed that FAM107B-siRNA transfection reversed the reduced proliferation and migration abilities induced by S100A4 inhibition in the cells. These findings suggest that, as a downstream effector, FAM107B at least partly mediates the effect of S100A4 on the proliferation and migration of MGC803 cells. In conclusion, we first provide experimental evidence suggesting that FAM107B was downregulated by S100A4 in gastric cancer MGC803 cells. And FAM107B at least partially mediates the biological effect of S100A4 in the cells.

Scalable Bright and Pure Single Photon Sources by Droplet Epitaxy on InP Nanowire Arrays.

High-quality quantum light sources are crucial components for the implementation of practical and reliable quantum technologies. The persistent challenge, however, is the lack of scalable and deterministic single photon sources that can be synthesized reproducibly. Here, we present a combination of droplet epitaxy with selective area epitaxy to realize the deterministic growth of single quantum dots in nanowire arrays. By optimization of the single quantum dot growth and the nanowire cavity design, single emissions are effectively coupled with the dominant mode of the nanowires to realize Purcell enhancement. The resonance-enhanced quantum emitter system boasts a brightness of millions of counts per second with nanowatt excitation power, a short radiation lifetime of 350 ± 5 ps, and a high single-photon purity with g(2)(0) value of 0.05 with continuous wave above-band excitation. Finite-difference time-domain (FDTD) simulation results show that the emissions of single quantum dots are coupled into the TM01 mode of the nanowires, giving a Purcell factor ≈ 3. Our technology can be used for creating on-chip scalable single photon sources for future quantum technology applications including quantum networks, quantum computation, and quantum imaging.

Optically Tunable Electrical Oscillations in Oxide-Based Memristors for Neuromorphic Computing.

The application of hardware-based neural networks can be enhanced by integrating sensory neurons and synapses that enable direct input from external stimuli. This work reports direct optical control of an oscillatory neuron based on volatile threshold switching in V3O5. The devices exhibit electroforming-free operation with switching parameters that can be tuned by optical illumination. Using temperature-dependent electrical measurements, conductive atomic force microscopy (C-AFM), in situ thermal imaging, and lumped element modelling, it is shown that the changes in switching parameters, including threshold and hold voltages, arise from overall conductivity increase of the oxide film due to the contribution of both photoconductive and bolometric characteristics of V3O5, which eventually affects the oscillation dynamics. Furthermore, V3O5 is identified as a new bolometric material with a temperature coefficient of resistance (TCR) as high as -4.6% K-1 at 423 K. The utility of these devices is illustrated by demonstrating in-sensor reservoir computing with reduced computational effort and an optical encoding layer for spiking neural network (SNN), respectively, using a simulated array of devices.

Effectiveness of modified inferior oblique muscle belly transposition for V-pattern exotropia combined with mild to moderate inferior oblique muscle overaction.

AIM: To investigate the effectiveness of a modified inferior oblique muscle belly transposition for treatment of V-pattern exotropia combined with mild to moderate inferior oblique muscle overaction. METHODS: Thirteen cases (23 affected eyes) of V-pattern exotropia with inferior oblique muscle overaction (+ or ++) who underwent the modified inferior oblique muscle belly transposition procedure were retrospectively reviewed. The amount of V-pattern, grade of inferior oblique overaction, degree of vertical strabismus, abnormal head posture, and the fovea-disc angle were evaluated before and after surgery. RESULTS: The V-pattern was corrected in all cases, and the amount of V-pattern reduced by 17.85±5.13 prism diopter (PD) on average (t=16.07, P<0.001). The surgical cure rate for mild to moderate inferior oblique muscle overaction was 87.0% (20/23). The degree of the fovea-disc angle has a mean reduction of 5.45°±2.87° (t=3.95, P=0.003) after surgery. The mean vertical deviation in 5 cases with a small-angle hypertropia (5.23±3.06 PD) in the primary position reduced by 3.15±1.86 PD (t=6.10, P<0.001). No serious complications were observed. CONCLUSION: The modified inferior oblique muscle belly transposition procedure can effectively treat mild to moderate inferior oblique overaction and relieve the V-pattern, which is safe and easy to perform.

EID1 plays a protective role in early-onset pre-eclampsia via promoting proliferation and invasion in trophoblast cells.

INTRODUCTION: Pre-eclampsia is a pregnancy-specific syndrome, which is partly due to abnormal proliferation and invasion of trophoblast cells. EP300 interacting inhibitor of differentiation 1 (EID1) participates in cell proliferation and invasion. This study aims to investigate the roles of EID1 in trophoblast cells and pre-eclampsia. MATERIAL AND METHODS: The expression of EID1 in placental tissues from 60 women with pre-eclampsia and 60 health pregnancies was detected by real-time PCR and immunohistochemical staining. EID1 was overexpressed or silenced by transfection of plasmid or siRNA in HTR-8/SVneo trophoblast cells, and then cell proliferation, cell cycle transition, migration, and invasion were determined by CCK-8 assay, flow cytometry, immunofluorescent staining, immunoblotting, and transwell assays. In addition, the activity of Akt/b-catenin signaling was measured by immunofluorescent staining and Western blot. RESULTS: EID1 mRNA level was decreased in placental tissues of pre-eclampsia patients, especially early-onset pre-eclampsia, accompanied by more severe clinical manifestation and a higher rate of fetal growth restriction (FGR). Gain- and loss-of-function experiments demonstrated that EID1 promoted proliferation and cell cycle transition, migration, and invasion in HTR-8/SVneo cells and its knockdown played opposite roles, suggesting that EID1 may be required for normal gestation. Akt/b-catenin signaling was activated after EID1 forced expression and deactivated after its silencing. CONCLUSIONS: EID1 promoted proliferation and invasion of cultured trophoblast cells with possible involvement of Akt/b-catenin signaling. These findings may provide novel insights for the diagnosis and treatment of early-onset pre-eclampsia in a clinic.

Association of Serum Interleukin-8 and Serum Amyloid A With Anxiety Symptoms in Patients With Cerebral Small Vessel Disease.

Objective: Cerebral small vessel disease (CSVD) is a clinical syndrome caused by pathological changes in small vessels. Anxiety is a common symptom of CSVD. Previous studies have reported the association between inflammatory factors and anxiety in other diseases, but this association in patients with CSVD remains uncovered. Our study aimed to investigate whether serum inflammatory factors correlated with anxiety in patients with CSVD. Methods: A total of 245 CSVD patients confirmed using brain magnetic resonance imaging (MRI) were recruited from December 2019 to December 2021. Hamilton Anxiety Rating Scale (HAMA) was used to assess the anxiety symptoms of CSVD patients. Patients with HAMA scores ≥7 were considered to have anxiety symptoms. The serum levels of interleukin-1ß (IL-1ß), IL-2R, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were detected. We compared levels of inflammatory factors between the anxiety and non-anxiety groups. Logistic regression analyses examined the correlation between inflammatory factors and anxiety symptoms. We further performed a gender subgroup analysis to investigate whether this association differed by gender. Results: In the fully adjusted multivariate logistic regression analysis model, we found that lower levels of IL-8 were linked to a higher risk of anxiety symptoms. Moreover, higher levels of SAA were linked to a lower risk of anxiety symptoms. Our study identified sex-specific effects, and the correlation between IL-8 and anxiety symptoms remained significant among males, while the correlation between SAA and anxiety symptoms remained significant among females. Conclusions: In this study, we found a suggestive association between IL-8, SAA, and anxiety symptoms in CSVD participants. Furthermore, IL-8 and SAA may have a sex-specific relationship with anxiety symptoms.

Enhanced Contactless Salt-Collecting Solar Desalination.

Solar desalination is expected to solve the problem of global water shortage. Yet its stability is plagued by salt accumulation. Here, a paper-based thermal radiation-enabled evaporation system (TREES) is demonstrated to achieve sustainable and highly efficient salt-collecting desalination, featuring a dynamic evaporation front based on the accumulated salt layer where water serves as its own absorber via energy down-conversion. When processing 7 wt % brine, it continuously evaporates water at a high rate─2.25 L m-2 h-1 under 1 sun illumination─which is well beyond the input solar energy limit for over 366 h. It is revealed that such enhanced evaporation arises from the unique vertical evaporation wall of the paper-TREES, which captures the thermal energy from the heated bottom efficiently and gains extra energy from the warmer environment. These findings provide novel insights into the design of next-generation salt-harvesting solar evaporators and take a step further to advance their applications in green desalination.

Development of a transgenic zebrafish model expressing GFP in the notochord, somite and liver directed by the hfe2 gene promoter.

Hemojuvelin, also known as RGMc, is encoded by hfe2 gene that plays an important role in iron homeostasis. hfe2 is specifically expressed in the notochord, developing somite and skeletal muscles during development. The molecular regulation of hfe2 expression is, however, not clear. We reported here the characterization of hfe2 gene expression and the regulation of its tissue-specific expression in zebrafish embryos. We demonstrated that the 6 kb 5'-flanking sequence upstream of the ATG start codon in the zebrafish hfe2 gene could direct GFP specific expression in the notochord, somites, and skeletal muscle of zebrafish embryos, recapitulating the expression pattern of the endogenous gene. However, the Tg(hfe2:gfp) transgene is also expressed in the liver of fish embryos, which did not mimic the expression of the endogenous hfe2 at the early stage. Nevertheless, the Tg(hfe2:gfp) transgenic zebrafish provides a useful model to study liver development. Treating Tg(hfe2:gfp) transgenic zebrafish embryos with valproic acid, a liver development inhibitor, significantly inhibited GFP expression in zebrafish. Together, these data indicate that the tissue specific expression of hfe2 in the notochord, somites and muscles is regulated by regulatory elements within the 6 kb 5'-flanking sequence of the hfe2 gene. Moreover, the Tg(hfe2:gfp) transgenic zebrafish line provides a useful model system for analyzing liver development in zebrafish.

Corrigendum: Long Non-Coding RNA Gas5 is Associated with Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21.

[This corrects the article DOI: 10.3389/fgene.2020.00188.].

Sustainable Solar Evaporation from Solute Surface via Energy Downconversion.

Solar-powered interfacial evaporation, a cost-effective and ecofriendly way to obtain freshwater from contaminated water, provides a promising path to ease the global water crisis. However, solute accumulation has severely impacted efficient light-to-heat-to-vapor generation in conventional solar evaporators. Here, it is demonstrated that an interfacial solar thermal photo-vapor generator is an efficient light-to-heat photo-vapor generator that can evaporate water stably in the presence of solute accumulation. An energy downconversion strategy which shifts sunlight energy from visible-near infrared to mid infrared-far infrared bands turns water from transparent to its own absorber, thus changing the fixed evaporation surface (black absorber) in a traditional solar evaporator to a dynamic front (solute surface). Light reflected from the solute can be recycled to drive evaporation. The prototype evaporator can evaporate at a high speed of 1.94 kg m-2 h-1 during a persistent solute accumulation process for 32 h. Such an ability to produce purified water while recycle valuable heavy metals from waste water containing heavy metal ions can inspire more advanced solar-driven water treatment devices.

An integrated metabolic and transcriptomic analysis reveals the mechanism through which fruit bagging alleviates exocarp semi-russeting in pear fruit.

Fruit semi-russeting is an undesirable quality trait that occurs in fruit production. It is reported that preharvest fruit bagging could effectively alleviate fruit exocarp semi-russeting, but the physiological and molecular mechanisms remain unclear. In the present study, we performed an in-depth investigation into pear fruit semi-russeting from morphologic, metabolic and transcriptomic perspectives by comparing control (semi-russeted) and bagged (non-russeted) 'Cuiguan' pear fruits. The results showed that significant changes in cutin and suberin resulted in pear fruit semi-russeting. Compared with the skin of bagged fruits, the skin of the control fruits presented reduced cutin contents accompanied by an accumulation of suberin, which resulted in fruit semi-russeting; α, ω-dicarboxylic acids accounted for the largest proportion of typical suberin monomers. Moreover, combined transcriptomic and metabolic analysis revealed a series of genes involved in cutin and suberin biosynthesis, transport and polymerization differentially expressed between the two groups. Furthermore, the expression levels of genes involved in the stress response and in hormone biosynthesis and signaling were significantly altered in fruits with contrasting phenotypes. Finally, a number of transcription factors, including those of the MYB, NAC, bHLH and bZIP families, were differentially expressed. Taken together, the results suggest that the multilayered mechanism through which bagging alleviates pear fruit semi-russeting is complex, and the large number of candidate genes identified provides a good foundation for future functional studies.