Characterization and commissioning of a new collaborative multi-modality radiotherapy platform.

TaiChi, a new multi-modality radiotherapy platform that integrates a linear accelerator, a focusing gamma system, and a kV imaging system within an enclosed O-ring gantry, was introduced into clinical application. This work aims to assess the technological characteristics and commissioning results of the TaiChi platform. The acceptance testing and commissioning were performed following the manufacturer's customer acceptance tests (CAT) and several AAPM Task Group (TG) reports/guidelines. Regarding the linear accelerator (linac), all applicable validation measurements recommended by the MPPG 5.a (basic photon beam model validation, intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT) validation, end-to-end(E2E) tests, and patient-specific quality assurance (QA)) were performed. For the focusing gamma system, the absorbed doses were measured using a PTW31014 ion chamber (IC) and PTW60016 diode detector. EBT3 films and a PTW60016 diode detector were employed to measure the relative output factors (ROFs). The E2E tests were performed using PTW31014 IC and EBT3 films. The coincidences between the imaging isocenter and the linac/gamma mechanical isocenter were investigated using EBT3 films. The image quality was evaluated regarding the contrast-to-noise ratio (CNR), spatial resolution, and uniformity. All tests included in the CAT met the manufacturer's specifications. All MPPG 5.a measurements complied with the tolerances. The confidence limits for IMRT/VMAT point dose and dose distribution measurements were achieved according to TG-119. The point dose differences were below 1.68% and gamma passing rates (3%/2 mm) were above 95.1% for the linac E2E tests. All plans of patient-specific QA had point dose differences below 1.79% and gamma passing rates above 96.1% using the 3%/2 mm criterion suggested by TG-218. For the focusing gamma system, the differences between the calculated and measured absorbed doses were below 1.86%. The ROFs calculated by the TPS were independently confirmed within 2% using EBT3 films and a PTW60016 detector. The point dose differences were below 2.57% and gamma passing rates were above 95.3% using the 2%/1 mm criterion for the E2E tests. The coincidences between the imaging isocenter and the linac/gamma mechanical isocenter were within 0.5 mm. The image quality parameters fully complied with the manufacturer's specifications regarding the CNR, spatial resolution, and uniformity. The multi-modality radiotherapy platform complies with the CAT and AAPM commissioning criteria. The commissioning results demonstrate that this platform performs well in mechanical and dosimetry accuracy.

Polyphenol-assisted albumin-based biomineralization nanocarriers with NIR-II-targeted photothermal performance towards broad-spectrum radical scavenging.

The oxidative stress is a state of imbalance in the body's oxidative balance, which can cause or worsen many diseases. Several studies have focused on the direct scavenging of free radicals, however, the strategy of precisely controlling antioxidant activities remotely and spatiotemporally has rarely been reported. Herein, we report a method inspired by the albumin-triggered biomineralization process with polyphenol-assisted strategy to prepare nanoparticles (TA-BSA@CuS) with NIR-II-targeted photo-enhanced antioxidant capacity. Systematic characterization demonstrated that the introduction of polyphenol (tannic acid (TA)) induced the formation of a CuO-doped heterogeneous structure and CuS nanoparticles. Compared with the TA-free CuS nanoparticles, TA-BSA@CuS exhibited excellent photothermal property in the NIR-II region, which is ascribed to the TA-induced Cu defects and doped CuO. Moreover, the photothermal property of CuS improved the broad-spectrum free radical scavenging efficiency of TA-BSA@CuS, and its H2O2 clearance rate increased by 47.3% under NIR-II irradiation. Meanwhile, TA-BSA@CuS exhibited low biological toxicity and intracellular free radical scavenging ability. Moreover, the excellent photothermal property of TA-BSA@CuS endowed it with good antibacterial ability. Therefore, we expect that this work will pave the way for the synthesis of polyphenolic compounds and the improvement in their antioxidant capacity.

Ectopic expression of HIOMT improves tolerance and nitrogen utilization efficiency in transgenic apple under drought stress.

Melatonin enhances plant tolerance to various environmental stressors. Although exogenous application of melatonin has been investigated, the role of endogenous melatonin metabolism in the response of apples to drought stress and nutrient utilization remains unclear. Here, we investigated the effects of ectopically expressing the human melatonin synthase gene HIOMT on transgenic apple plants under drought stress conditions. The tolerance of transgenic apple lines that ectopically expressed HIOMT improved significantly under drought conditions. After 10 days of natural drought stress treatment, the transgenic apple plants showed higher relative water content, chlorophyll levels and Fv/Fm, and lower relative electrolyte leakage and hydrogen peroxide accumulation, than wild-type plants. The activities of peroxidase, superoxide dismutase and catalase, as well as genes in the ascorbate-glutathione cycle, increased more in transgenic apple plants than in the wild-type. The ectopic expression of HIOMT also markedly alleviated the inhibitory effects of long-term drought stress on plant growth, photosynthetic rate and chlorophyll concentrations in apple plants. The uptake and utilization of 15N increased markedly in the transgenic lines under long-term moderate drought stress. Drought stress sharply reduced the activity of enzymes involved in nitrogen metabolism, but ectopic expression of HIOMT largely reversed that response. The expression levels of genes of nitrogen metabolism and uptake were more upregulated in transgenic apple plants than the wild-type. Overall, our study demonstrates that ectopic expression of HIOMT enhanced the tolerance of apple plants to drought stress, and transgenic apple plants showed improved growth due to higher nutrient utilization efficiency under drought conditions.

[The current applicating state of neural network-based electroencephalogram diagnosis of Alzheimer's disease].

The electroencephalogram (EEG) signal is a general reflection of the neurophysiological activity of the brain, which has the advantages of being safe, efficient, real-time and dynamic. With the development and advancement of machine learning research, automatic diagnosis of Alzheimer's diseases based on deep learning is becoming a research hotspot. Started from feedforward neural networks, this paper compared and analysed the structural properties of neural network models such as recurrent neural networks, convolutional neural networks and deep belief networks and their performance in the diagnosis of Alzheimer's disease. It also discussed the possible challenges and research trends of this research in the future, expecting to provide a valuable reference for the clinical application of neural networks in the EEG diagnosis of Alzheimer's disease.

Engineering Antioxidative Cascade Metal-Phenolic Nanozymes for Alleviating Oxidative Stress during Extracorporeal Blood Purification.

Oxidative stress is a compelling risk factor in chronic kidney diseases and is further aggravated for individuals during extracorporeal blood purification, ultimately leading to multiple complications. Herein, antioxidative cascade metal-phenolic nanozymes (metal-tannic acid nanozymes, M-TA NMs) are synthesized via metal ions-mediated oxidative coupling of polyphenols; then M-TA NMs engineered hemoperfusion microspheres (Cu-TAn@PMS) are constructed for alleviating oxidative stress. M-TA NMs show adjustable broad-spectrum antioxidative activities toward multiple reactive nitrogen and oxygen species (RNOS) due to the adjustable catalytic active centers. Importantly, M-TA NMs could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. Detailed structural and spectral analyses reveal that the existence of a transition metal could decrease the electronic energy band gaps of M-TA NMs to offer better electron transfers for RNOS scavenging. Notably, dynamic blood experiments demonstrate that Cu-TAn@PMS could serve as an antioxidant defense system for blood in hemoperfusion to scavenge intracellular reactive oxygen species (ROS) effectively even in the complex blood environment and further protect endogenous antioxidative enzymes and molecules. In general, this work developed antioxidative cascade nanozymes engineered microspheres with excellent therapeutic efficacy for the treatment of oxidative stress-related diseases, which exhibited potential for clinical blood purification and extended the biomedical applications of nanozymes.

Estimates of PM2.5 concentrations spatiotemporal evolution across China considering aerosol components in the context of the Reform and Opening-up.

With astonishing and rapid development in China since the Reform and Opening-up in 1978, serious air pollution has become a great challenge. A better understanding of the response of PM2.5 pollution to socioeconomic development after the Reform and Opening-up policy is benefit for pollution control. However, heterogeneous influences of biophysical and socioeconomic activities on PM2.5 pollution pose great challenges in statistical simulation of PM2.5. Few statistical model regards aerosol species as the explanatory variables for heterogeneous formation mechanism to retrieve PM2.5 concentration. In this research, monthly PM2.5 concentration in China during 1980-2020 was reconstructed by a novel statistical strategy considering aerosol components (AC-RF). Three cross-validation (CV) methods, sample-based CV, spatial-based CV and temporal-based CV results indicated satisfactory performance of AC-RF model with correlation coefficient (R) of 0.92, 0.90, 0.86, respectively. A three-stage concluded on PM2.5 concentration annual variation in China was drawn as followed: Before 2000, PM2.5 level in China represented smooth evolution and mainly influenced by natural events with polluted region locating in Xinjiang province, North China and Central China. Since 2000, PM2.5 concentration increased to high level in the context of rapid socioeconomic development. Severe air pollution covered Jing-Jin-Ji agglomeration, Central China and Sichuan Basin. During 2012-2020, PM2.5 declined and polluted region shrank, which was benefited by the strictest-ever air pollution control measures. Based on aerosol components analysis, sulfate aerosol exhibited the most significant increase trend in recent 40 years and black aerosol variation is the most closely related to PM2.5 pollution. In conclusion, unsustainable development is the culprit for air quality deterioration. Strict and continuous air pollution control strategies are effective for air quality improvement.

Alloyed nanostructures integrated metal-phenolic nanoplatform for synergistic wound disinfection and revascularization.

New materials for combating bacteria-caused infection and promoting the formation of microvascular networks during wound healing are of vital importance. Although antibiotics can be used to prevent infection, treatments that can disinfect and accelerate wound healing are scarce. Herein, we engineer a coating that is both highly compatible with current wound dressing substrates and capable of simultaneously disinfecting and revascularizing wounds using a metal-phenolic nanoplatform containing an alloyed nanostructured architecture (Ag@Cu-MPNNC). The alloyed nanostructure is formed by the spontaneous co-reduction and catalytic disproportionation reaction of multiple metal ions on a foundation metal-phenolic supramolecular layer. This synergistic presence of metals greatly improves the antibacterial activity against both Gram-negative and Gram-positive pathogenic bacteria, while demonstrating negligible cytotoxicity to normal tissue. In infected rat models, the Ag@Cu-MPNNC could kill bacteria efficiently, promoting revascularization and accelerate wound closure with no adverse side effects in infected in vivo models. In other words, this material acts as a combination therapy by inhibiting bacterial invasion and modulating bio-nano interactions in the wound.

Molecularly-imprinted hydrogel beads via self-sacrificing micro-reactors as safe and selective bilirubin adsorbents.

For patients who are suffering from liver dysfunction or metabolic obstruction, excessive bilirubin (BIL) in their bodies may cause jaundice with irreversible cerebral injury. Traditional exchange transfusion and photodynamic therapy pose a risk of serious adverse reactions or limited curative effects. Therefore, as a generally used treatment, hemoperfusion (HP) purifies patients' blood with solid adsorbents. However, the development of clinical BIL absorbents is greatly impeded by low selectivity and unsatisfactory blood compatibility. Herein, inspired by oviparity, we propose BIL-imprinted poly(acrylic acid-co-sodium p-styrenesulfonate)-reduced graphene oxide (PAA-SS-rGO@BIL) hydrogel beads as BIL adsorbents via self-sacrificing micro-reactors. In the micro-reactors, cross-linked polymerization is achieved and a solidified gel is formed. The received hydrogel beads show outstanding selective adsorption capabilities toward BIL due to the recognition sites, and π-π and hydrophobic interactions. Such hydrogel beads possess superior blood compatibility owing to their bioinspired heparin-mimicking gel structure. Simulated BIL selective adsorption experiments in vitro demonstrate that the BIL concentrations in the plasma of a patient with severe jaundice can be restored to a moderate level within 3 hours. Therefore, hydrogel beads offer new options for clinical BIL adsorption.

Heterologous Expression of the Melatonin-Related Gene HIOMT Improves Salt Tolerance in Malus domestica.

Melatonin, a widely known indoleamine molecule that mediates various animal and plant physiological processes, is formed from N-acetyl serotonin via N-acetylserotonin methyltransferase (ASMT). ASMT is an enzyme that catalyzes melatonin synthesis in plants in the rate-determining step and is homologous to hydroxyindole-O-methyltransferase (HIOMT) melatonin synthase in animals. To date, little is known about the effect of HIOMT on salinity in apple plants. Here, we explored the melatonin physiological function in the salinity condition response by heterologous expressing the homologous human HIOMT gene in apple plants. We discovered that the expression of melatonin-related gene (MdASMT) in apple plants was induced by salinity. Most notably, compared with the wild type, three transgenic lines indicated higher melatonin levels, and the heterologous expression of HIOMT enhanced the expression of melatonin synthesis genes. The transgenic lines showed reduced salt damage symptoms, lower relative electrolyte leakage, and less total chlorophyll loss from leaves under salt stress. Meanwhile, through enhanced activity of antioxidant enzymes, transgenic lines decreased the reactive oxygen species accumulation, downregulated the expression of the abscisic acid synthesis gene (MdNCED3), accordingly reducing the accumulation of abscisic acid under salt stress. Both mechanisms regulated morphological changes in the stomata synergistically, thereby mitigating damage to the plants' photosynthetic ability. In addition, transgenic plants also effectively stabilized their ion balance, raised the expression of salt stress-related genes, as well as alleviated osmotic stress through changes in amino acid metabolism. In summary, heterologous expression of HIOMT improved the adaptation of apple leaves to salt stress, primarily by increasing melatonin concentration, maintaining a high photosynthetic capacity, reducing reactive oxygen species accumulation, and maintaining normal ion homeostasis.

Photoenhanced Dual-Functional Nanomedicine for Promoting Wound Healing: Shifting Focus from Bacteria Eradication to Host Microenvironment Modulation.

Pathogenic bacterial infection has become a serious medical threat to global public health. Once the skin has serious defects, bacterial invasion and the following chain reactions will be a thorny clinical conundrum, which takes a long time to heal. Although various strategies have been used to eradicate bacteria, the treatment which can simultaneously disinfect and regulate the infection-related host responses is rarely reported. Herein, inspired by the host microenvironment, a photoenhanced dual-functional nanomedicine is constructed (Hemin@Phmg-TA-MSN) for localized bacterial ablation and host microenvironment modulation. The "NIR-triggered local microthermal therapy" and positively charged surface endow the nanomedicine with excellent bacterial capture and killing activities. Meanwhile, the nanomedicine exhibits broad-spectrum reactive oxygen species (ROS) scavenging activity via the synergistic effect of hemin and tannic acid with photoenhanced electron and hydrogen transfers. Furthermore, the in vivo experiments demonstrate that the dual-functional nanomedicine not only presents robust bacterial eradication capability, but also triggers the oxidative stress and inflammatory microenvironment regulation. The work not only shows a facile and effective way for infected wound management but also provides a new horizon for designing novel and efficient anti-infection therapy shifting focus from bacteria treatment to host microenvironment modulation.

Selective potassium uptake via biocompatible zeolite-polymer hybrid microbeads as promising binders for hyperkalemia.

Patients with chronic kidney disease are at high risk of hyperkalemia that is associated with various life-threatening complications. Treatments primarily rely on orally administered potassium binding agents, along with low curative effects and various side effects. Herein, direct serum potassium uptake was realized via zeolite-heparin-mimicking-polymer hybrid microbeads. The preparation process involved the synthesis of the heparin-mimicking polymer via the in situ cross-linking polymerization of acrylic acid and N-vinylpyrrolidone in polyethersulfone solution, the fabrication of microbeads via zeolite-mixing, electro-spraying and phase-inversion, and the subsequent aqueous-phase modifications based on ion-exchange and metal-leaching. An ultra-high (about 88%) amount of zeolite could be incorporated and well locked inside the polymer matrix. Potassium uptake capability was verified in water, normal saline and human serum, showing high selectivity and fast adsorption. The microbeads exhibited satisfying blood compatibility, negligible hemolysis ratio, prolonged clotting time, inhibited contact activation, and enhanced antifouling property toward serum proteins and cells. The proposed approach toward zeolite-heparin-mimicking-polymer hybrid microbeads provided a cheap, efficient and safe treatment protocol of hyperkalemia for the high-risk patients.

A self-cleaning zwitterionic nanofibrous membrane for highly efficient oil-in-water separation.

The oil and bacteria adhesion during membrane separation process brings great challenges to the operation costs and membrane service life. Meantime, the strong chemical corrosion in sewage seriously limits the durability of membrane as well. Herein, a facile strategy is developed for fabricating highly stable and efficient zwitterionic nanofibrous membrane (NFM) with self-cleaning feature via the combination of in-situ cross-linking of poly (sulfobetaine methacrylate) (PSBMA) and electrospun poly (ether sulfone) (PES) nanofibers. Owing to the introduction of zwitterionic functional groups, the PSBMA/PES NFM exhibits superior antifouling ability (over 3 cycles of crude oil fouling/self-cleaning and up to 7 days of bacteria adhesion/repelling tests). Moreover, the membrane also presents remarkable chemical stability in acidic, alkaline and salty environments; and exhibits excellent separation performance for both layered oil/water mixture and oil-in-water emulsion as well. Furthermore, the membrane is capable to remove bacteria during the continuous oil/water mixture separation. Overall, the proposed strategy provides a new perspective into developing long-term antifouling membrane materials for complicated oily wastewater remediation in various corrosive environments.

Multipulse dynamics in a Mamyshev oscillator.

We report on the multipulse dynamics in an erbium-doped fiber Mamyshev oscillator. It was demonstrated that, in addition to the single pulse, the multipulse patterns could be observed by adjusting the pump power, where the multiple pulses operated in random distributed state or bound state. Particularly, the multiple pulses could exhibit apparent difference in intensity, which was attributed to the unique step-like saturable absorption property of the Mamyshev oscillator. The individual pulse spectrum could be assessed by utilizing dispersive Fourier transform technique. It was found that the multiple pulses with different intensities correspond to different spectral profiles. These findings give some new insights into the pulse dynamics in Mamyshev oscillators.

A chitosan modified asymmetric small-diameter vascular graft with anti-thrombotic and anti-bacterial functions for vascular tissue engineering.

Rapid endothelialization and prevention of restenosis are two vital challenges for the preparation of a small-diameter vascular graft (SDVG), while postoperative infection after implantation is often neglected. In the present study, carboxymethyl chitosan (CMC) and chitosan (CS) were chosen as the anti-thrombotic and anti-bacterial components, respectively; and then an asymmetric vascular graft was fabricated by co-electrospinning of poly(ε-caprolactone) (PCL)/CMC and PCL/CS. The mechanical properties of the asymmetric vascular graft were much better than those of the native vessels. In vitro blood compatibility tests indicated that the inner layer of the graft could inhibit thrombosis effectively. The outer layer of the graft had a certain anti-bacterial effect owing to the addition of chitosan. Besides, the inner layer of the graft could greatly promote the growth of endothelial cells. It is believed that the asymmetric SDVG with anti-thrombotic and anti-bacterial functions could contribute to the future clinical implantation of tissue engineered vascular grafts.

Positively-charged polyethersulfone nanofibrous membranes for bacteria and anionic dyes removal.

Given the complexity of pollutants in wastewater, development of facile and effective multifunctional materials, which can not only kill bacteria but also remove dyes from wastewater, is in high demand. Herein, a facile strategy for the preparation of positively-charged nanofibrous membranes (NFMs) is reported via the combination of electrospinning and in-situ cross-linked polymerization of poly ([2-(methacryloyloxy)-ethyl] trimethyl ammonium chloride) (PMETAC) in poly (ether sulfone) (PES) solution. The quaternary ammonium salt polymer of PMETAC enabled the NFMs with positive charge to kill bacteria and remove anionic dyes. The antibacterial tests including agar plate counting and live/dead staining indicate that the NFMs show strong antibacterial ability with bacterial killing ratios of nearly 99% for both Escherichia coli and Staphylococcus aureus, as well as remarkable recyclability towards killing bacteria. The dyes adsorption experiments show that the NFMs exhibit high adsorption capacity for anionic dyes up to 208 mg g-1 for Congo Red (CR) and good reusability toward CR. Impressively, the membrane adsorption column test indicates that the CR dye removal ratio is up to 100% for the first time, and that is still as high as 96.5% for the third time with a fresh dye solution. Given the above advantages, such fascinating NFMs may provide new perspectives in the exploitation of multifunctional membrane materials for complex water remediation.

Melatonin increases the performance of Malus hupehensis after UV-B exposure.

Melatonin, an evolutionarily conserved molecule, is implicated in numerous physiological processes in plants. To explore the potential roles of melatonin in response to UV-B radiation, we examined the influence of exogenous melatonin on Malus hupehensis Rehd. seedlings under two levels of UV-B radiation. Under UV-B stress, seedlings showed significant reduction in plant growth, biomass production, and root system development. However, 1 µM melatonin solution markedly alleviated these effects, especially at the higher dosage of UV-B radiation. The inhibitory effects of UV-B radiation on photosynthetic parameters, chlorophyll fluorescence parameters, stomatal apertures, chlorophyll levels and leaf membrane damages were also markedly alleviated with melatonin application. Melatonin treatment was also associated with higher activity and expression of genes encoding antioxidant enzymes (ascorbate peroxidase, catalase and peroxidase) and greater decline of H2O2 content in leaves exposed to UV-B. Moreover, exogenous melatonin treatment and UV-B stress increased the concentration of endogenous melatonin. The content of several phenolic compounds, including chlorogenic acid, phloridzin and quercetin-3-galactoside, also increased under UV-B stress, and these were further elevated significantly with melatonin addition. This study provides insight into the role(s) of endogenous melatonin in response to UV-B stress, and will facilitate application of exogenous melatonin in agriculture.

Pulsating soliton with chaotic behavior in a fiber laser.

We reported, to the best of our knowledge, the first experimental evidence of the pulsating soliton with chaotic behavior in an ultrafast fiber laser. By virtue of a dispersive Fourier transformation method, the chaotic behavior of soliton pulsation is visualized by the fact that the mode-locked spectrum collapses abruptly in an unpredictable way during the pulsating process. The obtained results provide the experimental demonstration of the chaotic behavior in the pulsating soliton, which would also give some new insights into the soliton pulsation dynamics in dissipative systems.

The mitigation effects of exogenous melatonin on replant disease in apple.

Melatonin mediates many physiological processes in plants. The problem of apple replant disease is unsolved. Our study objectives were to evaluate the regulatory effect of melatonin on plant resistance to this challenge and investigate the preliminary mechanism by which melatonin helps alleviate the effects of this disease. Two-year-old trees of "Fuji" apple (Malus domestica), grafted onto rootstock M.26, were grown in "replant" soil for 6 months in the absence or presence of a 200 µmol/L melatonin supplement. The addition of melatonin to the soil significantly increased the rates of plant growth and net photosynthesis and chlorophyll concentrations under replant conditions. This molecule elevated the levels of K in leaves and roots and enhanced the activity of soil enzymes. Such supplementation also changed the composition of the bacterial and fungal communities in the soil. We concluded that the application of melatonin to a replant soil can protect their chloroplasts from oxidative damage and release the apple root from membrane damage, and also lead to increased soil enzyme activity and soil quality while altering the composition of bacterial and fungal communities. These changes can then promote seedling growth, stimulate photosynthesis, and elevate K levels, thereby alleviating the effects of apple replant disease.

Effects of Exogenous Dopamine on the Uptake, Transport, and Resorption of Apple Ionome Under Moderate Drought.

The frequency and intensity of water deficits is expected to increase because of global warming. Drought stress is often one of the most limiting factors for plant growth. We conducted greenhouse pot experiments to address how dopamine affects the drought-resistance traits of apple trees at the physiological and molecular levels. Our factorial design consisted of dopamine and no-dopamine applications combined with well-watered and moderate-drought conditions. Seedling biomass, photosynthesis rates, chlorophyll concentrations, and stomatal apertures were markedly reduced under stress but dopamine treatment mitigated the inhibiting effects of drought on plant growth and helped maintain strong photosynthesis, chlorophyll levels, and stomatal functioning. Concentrations of most macro-, micro-, and trace elements decreased in response to drought. This stress also diminished the uptake and transport of elements in the leaves and stems, but increased the partitioning of elements in the roots. Nutrient resorption proficiency decreased while nutrient resorption efficiency increased for most analyzed elements. Exogenous dopamine significantly increased the concentrations, uptake, and transport of nutrients under drought stress, and also altered their distribution within the whole plant. However, this molecule had a negative effect on nutrient resorption. Although transcript levels of a key chlorophyll degradation gene, pheide a oxygenase, and senescence-associate gene 12 were elevated upon drought treatment, dopamine significantly suppressed the upregulation of those genes under such stress conditions. These observations indicate that dopamine has an important anti-senescence effect that might be helpful for regulating nutrient uptake, transport, and resorption, and ultimately influencing overall plant growth. Thus, understanding the role of dopamine in drought tolerance introduces new possibilities to use this compound for agricultural purposes.

Mapping QTLs for water-use efficiency reveals the potential candidate genes involved in regulating the trait in apple under drought stress.

BACKGROUND: Improvement of water-use efficiency (WUE) can effectively reduce production losses caused by drought stress. A better understanding of the genetic determination of WUE in crops under drought stress has great potential value for developing cultivars adapted to arid regions. To identify the genetic loci associated with WUE and reveal genes responsible for the trait in apple, we aim to map the quantitative trait loci (QTLs) for carbon isotope composition, the proxy for WUE, applying two contrasting irrigating regimes over the two-year experiment and search for the candidate genes encompassed in the mapped QTLs. RESULTS: We constructed a high-density genetic linkage map with 10,172 markers of apple, using single nucleotide polymorphism (SNP) markers obtained through restriction site-associated DNA sequencing (RADseq) and a final segregating population of 350 seedlings from the cross of Honeycrisp and Qinguan. In total, 33 QTLs were identified for carbon isotope composition in apple under both well-watered and drought-stressed conditions. Three QTLs were stable over 2 years under drought stress on linkage groups LG8, LG15 and LG16, as validated by Kompetitive Allele-Specific PCR (KASP) assays. In those validated QTLs, 258 genes were screened according to their Gene Ontology functional annotations. Among them, 28 genes were identified, which exhibited significant responses to drought stress in 'Honeycrisp' and/or 'Qinguan'. These genes are involved in signaling, photosynthesis, response to stresses, carbohydrate metabolism, protein metabolism and modification, hormone metabolism and transport, transport, respiration, transcriptional regulation, and development regulation. They, especially those for photoprotection and relevant signal transduction, are potential candidate genes connected with WUE regulation in drought-stressed apple. CONCLUSIONS: We detected three stable QTLs for carbon isotope composition in apple under drought stress over 2 years, and validated them by KASP assay. Twenty-eight candidate genes encompassed in these QTLs were identified. These stable genetic loci and series of genes provided here serve as a foundation for further studies on marker-assisted selection of high WUE and regulatory mechanism of WUE in apple exposed to drought conditions, respectively.