Background Hesperidin is a citrus flavonoid with anti-inflammatory and antioxidant potential. However, its protective effects on bovine mammary epithelial cells(b MECs) exposed to oxidative stress have not been elucid...Background Hesperidin is a citrus flavonoid with anti-inflammatory and antioxidant potential. However, its protective effects on bovine mammary epithelial cells(b MECs) exposed to oxidative stress have not been elucidated.Results In this study, we investigated the effects of hesperidin on H_(2)O_(2)-induced oxidative stress in b MECs and the underlying molecular mechanism. We found that hesperidin attenuated H_(2)O_(2)-induced cell damage by reducing reactive oxygen species(ROS) and malondialdehyde(MDA) levels, increasing catalase(CAT) activity, and improving cell proliferation and mitochondrial membrane potential. Moreover, hesperidin activated the Keap1/Nrf2/ARE signaling pathway by inducing the nuclear translocation of Nrf2 and the expression of its downstream genes NQO1 and HO-1, which are antioxidant enzymes involved in ROS scavenging and cellular redox balance. The protective effects of hesperidin were blocked by the Nrf2 inhibitor ML385, indicating that they were Nrf2 dependent.Conclusions Our results suggest that hesperidin could protect b MECs from oxidative stress injury by activating the Nrf2 signaling pathway, suggesting that hesperidin as a natural antioxidant has positive potential as a feed additive or plant drug to promote the health benefits of bovine mammary.展开更多
Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.Th...Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.展开更多
The corrosion and pitting behavior of pure aluminum 1060 exposed to Nansha Islands marine atmosphere for 34 months was investigated based on mass loss measurement,scanning electron microscopy(SEM),energy dispersive sp...The corrosion and pitting behavior of pure aluminum 1060 exposed to Nansha Islands marine atmosphere for 34 months was investigated based on mass loss measurement,scanning electron microscopy(SEM),energy dispersive spectroscopy(EDS),X-ray photoelectron spectroscopy(XPS),and electrochemical impedance spectroscopy(EIS).The results indicated that serious pitting corrosion occurred on the surfaces of pure aluminum.The corrosion rate after exposure for 13 months was approximately 1.28 g/(m^(2)·a).The XPS results showed that the corrosion products were Al_(2)O_(3),Al(OH)_(3),and AlCl_(3).Moreover,the corrosion product layer was more protective than the native oxide film,and the protectiveness first increased and then decreased.Finally,the shape of the pits was evaluated using statistical analysis.展开更多
Partial coalescence is a complicated flow phenomenon.In the present study,the coalescence process is simulated with the volume of fluid(VOF)method.The numerical results reveal that a downward high-velocity region play...Partial coalescence is a complicated flow phenomenon.In the present study,the coalescence process is simulated with the volume of fluid(VOF)method.The numerical results reveal that a downward high-velocity region plays a significant role in partial coalescence.The high-velocity region pulls the droplet downward continuously which is an important factor for the droplet turning into a prolate shape and the final pinch-off.The shift from partial coalescence to full coalescence is explained based on the droplet shape before the pinch-off.With the droplet impact velocity increasing,the droplet shape will get close to a sphere before the pinch-off.When the shape gets close enough to a sphere,the partial coalescence shifts to full coalescence.The effect of film thickness on the coalescence process is also investigated.With large film thickness,partial coalescence happens,while with small film thickness,full coalescence happens.In addition,the results indicate that the critical droplet impact velocity increases with the increase of surface tension coefficient but decreases with the increase of viscosity and initial droplet diameter.And there is a maximum critical Weber number with the increase of surface tension coefficient and initial droplet diameter.展开更多
Background As one of the most common musculoskeletal ailments,chronic nonspecific low-back pain(CNLBP)causes persistent disability and substantial medical expenses.Epidemiological evidence shows that the incidence rat...Background As one of the most common musculoskeletal ailments,chronic nonspecific low-back pain(CNLBP)causes persistent disability and substantial medical expenses.Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising.Recent guidelines indicate a reduced role for medicines in the management of CNLBP.Objective The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm,compared to nonsteroidal anti-inflammatory drug(NSAID)with a capsaicin plaster,in the treatment of CNLBP.Design,setting,participants and interventions We designed a prospective multicenter randomized clinical trial enrolling patients from January 1,2022 to December 31,2022.A total of 156 patients with CNLBP were randomized into two parallel groups.Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally.Patients in the test group were treated with cupping and scraping using a medical device and medicated balm.Main outcome measures Primary outcome was pain recorded using the visual analogue scale(VAS).Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale(JOA)and the traditional Chinese medicine(TCM)syndrome integral scale(TCMS)as assessment tools.Results Between baseline and postintervention,all changes in outcome metric scales were statistically significant(P<0.001).Compared to the control group,patients in the test group had a significantly greater treatment effect in all outcome variables,as indicated by lower VAS and TCMS scores and higher JOA scores,after the one-week intervention period(P<0.001).Further,according to the findings of multivariate linear regression analysis,the participants’pain(VAS score)was related to their marital status,age,smoking habits and body mass index.No adverse reactions were reported for any participants in this trial.Conclusion The effectiveness of TCM combined with the new physiotherapy tool is superior to that of NSAID combined with topical plasters,regarding to pain intensity,TCM symptoms and quality of life.The TCM plus physiotherapy also showed more stable and long-lasting therapeutic effects.展开更多
The evolution of corrosion behavior of 316 L stainless steels exposed to salt lake atmosphere for 8 years was investigated.The results showed that the stainless steel in salt lake atmosphere had a greater corrosion ra...The evolution of corrosion behavior of 316 L stainless steels exposed to salt lake atmosphere for 8 years was investigated.The results showed that the stainless steel in salt lake atmosphere had a greater corrosion rate during the initial exposure time and relatively lower corrosion rate during the subsequent exposure time.Dust depositions accumulated on the downward surface caused severe local corrosion of stainless steel.As exposure time prolonged,the relative amount of Croxide and Feoxidein the corrosion products gradually increased,which may directly affect the corrosion rate of stainless steels.Moreover,the maximum pit depth followed a power function with respect to exposure time.展开更多
Copper (Cu) is an essential trace mineral element for all forms of life, and is an important structural component and co-factor for a variety of metalloenzymes (Pefia et al., 1999; Bertinato and L'Abbe, 2004). In...Copper (Cu) is an essential trace mineral element for all forms of life, and is an important structural component and co-factor for a variety of metalloenzymes (Pefia et al., 1999; Bertinato and L'Abbe, 2004). In humans, Cu deficiency is not common because of the ubiquitous occurrence of Cu and ease of gastrointestinal absorption (Zidar et al., 1977; Uauy et al., 1998).展开更多
Berberine hydrochloride is commonly used to treat bacterial dysentery,gastroenteritis and other diseases.Many manufacturers are available on the market today,while the production process and formulation are quite diff...Berberine hydrochloride is commonly used to treat bacterial dysentery,gastroenteritis and other diseases.Many manufacturers are available on the market today,while the production process and formulation are quite different,which may directly affect the therapeutic effect of the drug.To this end,11 different production producers of berberine hydrochloride tablets were collected according to the pharmacopeia berberine hydrochloride dissolution method(basket method).In addition the dissolution process was carried out in four elution media with different pH,and the difference was similar(f2).Factors were calculated to evaluate in vitro dissolution requirements,and in vitro dissolution of different manufacturers of berberine hydrochloride tablets was determined by high performance liquid chromatography(HPLC).The method was verified by linearity,precision,stability and robustness.Based on the f2 value,there was a significant difference in the dissolution behavior of the formulations of most berberine hydrochloride tablet brands.This research provided the basis for further in-depth research in the later period.Although the drug specifications(0.1 g)were the same,the dissolution curve was different.This phenomenon may be attributed to the fact that the excipients and crystal form of the tablets affected the release and dissolution of the tablets in vitro.展开更多
The corrosion behavior of pure aluminum 1060 subjected to a wet-dry cyclic accelerated test in simulated Nansha marine atmosphere in the dark and under UV illumination has been investigated by means of scanning electr...The corrosion behavior of pure aluminum 1060 subjected to a wet-dry cyclic accelerated test in simulated Nansha marine atmosphere in the dark and under UV illumination has been investigated by means of scanning electron microscopy(SEM),electrochemical impedance spectroscopy(EIS),and Mott–Schottky measurements in this work.The results show that under the two conditions,the native oxide films are constantly destroyed and the thicknesses of the oxide films continuously decrease in the first 24 days of the corrosion test.In particular,UV illumination can diminish the pitting corrosion susceptibility of the native oxide films to an extent in terms of a photo-induced modifi cation of the native oxide film on the pure aluminum surfaces.Besides,UV illumination can also reduce the carrier concentration in the oxide films,thus reducing the conductivity and the corrosion rate.展开更多
Rice(Oryza sativa)provides>20%of the consumed calories in the human diet.However,rice is also a leading source of dietary cadmium(Cd)that seriously threatens human health.Deciphering the genetic network that underl...Rice(Oryza sativa)provides>20%of the consumed calories in the human diet.However,rice is also a leading source of dietary cadmium(Cd)that seriously threatens human health.Deciphering the genetic network that underlies the grain-Cd accumulation will benefit the development of low-Cd rice and mitigate the effects of Cd accumulation in the rice grain.In this study,we identified a QTL gene,OsCS1,which is allelic to OsMTP11 and encodes a protein sequestering Cd in the leaf during vegetative growth and preventing Cd from being translocated to the grain after heading in rice.OsCS1 is predominantly expressed in leaf vascular parenchyma cells,where it binds to a vacuole-sorting receptor protein OsVSR2 and is translocated intracellularly from the trans-Golgi network to pre-vacuolar compartments and then to the vacuole.In this trafficking process,OsCS1 actively transports Cd into the endomembrane system and sequesters it in the vacuoles.There are natural variations in the promoter of OsCS1 between the indica and japonica rice subspecies.Duplication of a G-box-like motif in the promoter region of the superior allele of OsCS1 from indica rice enhances the binding of the transcription factor OsIRO2 to the OsCS1 promoter,thereby promoting OsCS1 expression.Introgression of this allele into commercial rice varieties could significantly lower grain-Cd levels compared to the inferior allele present in japonica rice.Collectively,our findings offer new insights into the genetic control of leaf-to-grain Cd translocation and provide a novel gene and its superior allele for the genetic improvement of low-Cd variety in rice.展开更多
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDA26040304)。
文摘Background Hesperidin is a citrus flavonoid with anti-inflammatory and antioxidant potential. However, its protective effects on bovine mammary epithelial cells(b MECs) exposed to oxidative stress have not been elucidated.Results In this study, we investigated the effects of hesperidin on H_(2)O_(2)-induced oxidative stress in b MECs and the underlying molecular mechanism. We found that hesperidin attenuated H_(2)O_(2)-induced cell damage by reducing reactive oxygen species(ROS) and malondialdehyde(MDA) levels, increasing catalase(CAT) activity, and improving cell proliferation and mitochondrial membrane potential. Moreover, hesperidin activated the Keap1/Nrf2/ARE signaling pathway by inducing the nuclear translocation of Nrf2 and the expression of its downstream genes NQO1 and HO-1, which are antioxidant enzymes involved in ROS scavenging and cellular redox balance. The protective effects of hesperidin were blocked by the Nrf2 inhibitor ML385, indicating that they were Nrf2 dependent.Conclusions Our results suggest that hesperidin could protect b MECs from oxidative stress injury by activating the Nrf2 signaling pathway, suggesting that hesperidin as a natural antioxidant has positive potential as a feed additive or plant drug to promote the health benefits of bovine mammary.
基金supported by the National Natural Science Foundation of China(Grant No.82104701)Science Fund Program for Outstanding Young Scholars in Universities of Anhui Province(Grant No.2022AH030064)+3 种基金Key Project at Central Government Level:the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(Grant No.2060302)Foundation of Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application(Grant No.2021KFKT10)China Agriculture Research System of MOF and MARA(Grant No.CARS-21)Talent Support Program of Anhui University of Chinese Medicine(Grant No.2020rcyb007).
文摘Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.
基金the National Natural Science Foundation of China(No.51671197)Special Project of Chinese Academy of Sciences(No.XDA130040502).
文摘The corrosion and pitting behavior of pure aluminum 1060 exposed to Nansha Islands marine atmosphere for 34 months was investigated based on mass loss measurement,scanning electron microscopy(SEM),energy dispersive spectroscopy(EDS),X-ray photoelectron spectroscopy(XPS),and electrochemical impedance spectroscopy(EIS).The results indicated that serious pitting corrosion occurred on the surfaces of pure aluminum.The corrosion rate after exposure for 13 months was approximately 1.28 g/(m^(2)·a).The XPS results showed that the corrosion products were Al_(2)O_(3),Al(OH)_(3),and AlCl_(3).Moreover,the corrosion product layer was more protective than the native oxide film,and the protectiveness first increased and then decreased.Finally,the shape of the pits was evaluated using statistical analysis.
基金the National Natural Science Foundation of China(Grant No.51876102)the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(Grant No.51621062).
文摘Partial coalescence is a complicated flow phenomenon.In the present study,the coalescence process is simulated with the volume of fluid(VOF)method.The numerical results reveal that a downward high-velocity region plays a significant role in partial coalescence.The high-velocity region pulls the droplet downward continuously which is an important factor for the droplet turning into a prolate shape and the final pinch-off.The shift from partial coalescence to full coalescence is explained based on the droplet shape before the pinch-off.With the droplet impact velocity increasing,the droplet shape will get close to a sphere before the pinch-off.When the shape gets close enough to a sphere,the partial coalescence shifts to full coalescence.The effect of film thickness on the coalescence process is also investigated.With large film thickness,partial coalescence happens,while with small film thickness,full coalescence happens.In addition,the results indicate that the critical droplet impact velocity increases with the increase of surface tension coefficient but decreases with the increase of viscosity and initial droplet diameter.And there is a maximum critical Weber number with the increase of surface tension coefficient and initial droplet diameter.
基金supported by the 13th Five-Year Army Key Discipline Construction Project(No.2020SZ06-17).
文摘Background As one of the most common musculoskeletal ailments,chronic nonspecific low-back pain(CNLBP)causes persistent disability and substantial medical expenses.Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising.Recent guidelines indicate a reduced role for medicines in the management of CNLBP.Objective The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm,compared to nonsteroidal anti-inflammatory drug(NSAID)with a capsaicin plaster,in the treatment of CNLBP.Design,setting,participants and interventions We designed a prospective multicenter randomized clinical trial enrolling patients from January 1,2022 to December 31,2022.A total of 156 patients with CNLBP were randomized into two parallel groups.Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally.Patients in the test group were treated with cupping and scraping using a medical device and medicated balm.Main outcome measures Primary outcome was pain recorded using the visual analogue scale(VAS).Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale(JOA)and the traditional Chinese medicine(TCM)syndrome integral scale(TCMS)as assessment tools.Results Between baseline and postintervention,all changes in outcome metric scales were statistically significant(P<0.001).Compared to the control group,patients in the test group had a significantly greater treatment effect in all outcome variables,as indicated by lower VAS and TCMS scores and higher JOA scores,after the one-week intervention period(P<0.001).Further,according to the findings of multivariate linear regression analysis,the participants’pain(VAS score)was related to their marital status,age,smoking habits and body mass index.No adverse reactions were reported for any participants in this trial.Conclusion The effectiveness of TCM combined with the new physiotherapy tool is superior to that of NSAID combined with topical plasters,regarding to pain intensity,TCM symptoms and quality of life.The TCM plus physiotherapy also showed more stable and long-lasting therapeutic effects.
基金supported by the National Natural Science Foundation of China(Nos.51601199 and 51671197)。
文摘The evolution of corrosion behavior of 316 L stainless steels exposed to salt lake atmosphere for 8 years was investigated.The results showed that the stainless steel in salt lake atmosphere had a greater corrosion rate during the initial exposure time and relatively lower corrosion rate during the subsequent exposure time.Dust depositions accumulated on the downward surface caused severe local corrosion of stainless steel.As exposure time prolonged,the relative amount of Croxide and Feoxidein the corrosion products gradually increased,which may directly affect the corrosion rate of stainless steels.Moreover,the maximum pit depth followed a power function with respect to exposure time.
基金jointly supported by the National Key Technology Support Program(No.2015BAD05B02)the National Natural Science Foundation of China(Nos.31270426,31470443 and 31371596)
文摘Copper (Cu) is an essential trace mineral element for all forms of life, and is an important structural component and co-factor for a variety of metalloenzymes (Pefia et al., 1999; Bertinato and L'Abbe, 2004). In humans, Cu deficiency is not common because of the ubiquitous occurrence of Cu and ease of gastrointestinal absorption (Zidar et al., 1977; Uauy et al., 1998).
基金National Institutes for Food and Drug Control(Grant No.017ZX09101001).
文摘Berberine hydrochloride is commonly used to treat bacterial dysentery,gastroenteritis and other diseases.Many manufacturers are available on the market today,while the production process and formulation are quite different,which may directly affect the therapeutic effect of the drug.To this end,11 different production producers of berberine hydrochloride tablets were collected according to the pharmacopeia berberine hydrochloride dissolution method(basket method).In addition the dissolution process was carried out in four elution media with different pH,and the difference was similar(f2).Factors were calculated to evaluate in vitro dissolution requirements,and in vitro dissolution of different manufacturers of berberine hydrochloride tablets was determined by high performance liquid chromatography(HPLC).The method was verified by linearity,precision,stability and robustness.Based on the f2 value,there was a significant difference in the dissolution behavior of the formulations of most berberine hydrochloride tablet brands.This research provided the basis for further in-depth research in the later period.Although the drug specifications(0.1 g)were the same,the dissolution curve was different.This phenomenon may be attributed to the fact that the excipients and crystal form of the tablets affected the release and dissolution of the tablets in vitro.
基金supported by the National Natural Science Foundation of China(No.51671197)the Special Project of the Chinese Academy of Sciences(No.XDA130040502)。
文摘The corrosion behavior of pure aluminum 1060 subjected to a wet-dry cyclic accelerated test in simulated Nansha marine atmosphere in the dark and under UV illumination has been investigated by means of scanning electron microscopy(SEM),electrochemical impedance spectroscopy(EIS),and Mott–Schottky measurements in this work.The results show that under the two conditions,the native oxide films are constantly destroyed and the thicknesses of the oxide films continuously decrease in the first 24 days of the corrosion test.In particular,UV illumination can diminish the pitting corrosion susceptibility of the native oxide films to an extent in terms of a photo-induced modifi cation of the native oxide film on the pure aluminum surfaces.Besides,UV illumination can also reduce the carrier concentration in the oxide films,thus reducing the conductivity and the corrosion rate.
基金jointly supported by the Strategic Priority Research Program of the CAS(XDA24010404)the National Natural Science Foundation of ChinaNational Natural Science Foundation of China(U19A2026 and 31972490)+1 种基金the Major Program of Natural Science Foundation of Hunan Province(2021JC0007)the Hunan Key Technologies R&D Program Hunan Key Technologies R&D Program(2023NK1010).
文摘Rice(Oryza sativa)provides>20%of the consumed calories in the human diet.However,rice is also a leading source of dietary cadmium(Cd)that seriously threatens human health.Deciphering the genetic network that underlies the grain-Cd accumulation will benefit the development of low-Cd rice and mitigate the effects of Cd accumulation in the rice grain.In this study,we identified a QTL gene,OsCS1,which is allelic to OsMTP11 and encodes a protein sequestering Cd in the leaf during vegetative growth and preventing Cd from being translocated to the grain after heading in rice.OsCS1 is predominantly expressed in leaf vascular parenchyma cells,where it binds to a vacuole-sorting receptor protein OsVSR2 and is translocated intracellularly from the trans-Golgi network to pre-vacuolar compartments and then to the vacuole.In this trafficking process,OsCS1 actively transports Cd into the endomembrane system and sequesters it in the vacuoles.There are natural variations in the promoter of OsCS1 between the indica and japonica rice subspecies.Duplication of a G-box-like motif in the promoter region of the superior allele of OsCS1 from indica rice enhances the binding of the transcription factor OsIRO2 to the OsCS1 promoter,thereby promoting OsCS1 expression.Introgression of this allele into commercial rice varieties could significantly lower grain-Cd levels compared to the inferior allele present in japonica rice.Collectively,our findings offer new insights into the genetic control of leaf-to-grain Cd translocation and provide a novel gene and its superior allele for the genetic improvement of low-Cd variety in rice.