ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

ObjectiveBased on the traditional quality evaluation methods summarized in previous dynasties， this paper systematically contrasted the quality differences between wild Polygalae Radix（WPR） and cultivated Polygalae Radix（CPR） from the aspects of character， microscope and chemical composition by modern scientific and technological means， providing a basis for high-quality production and quality control. MethodsCPR and local WPR in Yulin city， Shaanxi province from 1 to 6 years were collected， and a systematic comparative analysis was conducted using traditional pharmacognosy research methods combined with modern multi-omics analysis techniques， including character traits（length， weight， diameter）， cross-sectional microscopic features（proportions of cork， phloem， xylem， etc）， cell wall component content（hemicellulose， cellulose， lignin）， extracts content（water-soluble extract and alcohol-soluble extract）， carbohydrate content（starch， water-soluble polysaccharides）， contents of total flavonoids， total saponins and specific marker compounds（3，6′-disinapoyl sucrose， polygalaxanthone Ⅲ， tenuifoliside A， tenuifoliside C， sibiricose A₅ and A₆） and other indexes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to conduct comparative analysis of secondary metabolites in WPR and CPR， and multivariate statistical analysis such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to screen the key differential components of them. ResultsIn terms of appearance， there were significant differences between WPR and CPR. The characteristics of WPR conformed to the "thick wrinkles on the epidermis" recorded in ancient books， featuring a wrinkled surface and grayish-brown appearance. However， CPR had a finer texture and a yellowish white appearance， with weight， length， and diameter increasing with longer cultivation periods. In terms of microscopy， WPR exhibited a thick cork layer with fissures in the phloem， whereas CPR had a thinner cork layer with uniformly arranged cork cells. Younger PR specimens showed numerous phloem fissures in cross-sections， while older specimens display progressively denser arrangements of phloem parenchyma cells. In terms of the contents of various major components， the contents of water-soluble extract， starch and total saponins in WPR were inversely proportional to the root diameter， while the contents of water-soluble extract， water-soluble polysaccharides and total saponins in CPR decreased with the increase of planting years. The content of xanthones in WPR was significantly higher than that of CPR， while the contents of other major components showed no significant change pattern. Among the six indicator components， the average content of sibiricose A₅ in WPR was significantly higher than that of CPR， followed by slightly higher content of tenuifoliside A. In CPR， the relative content of 3，6′-disinapoyl sucrose and tenuifoliside A was the highest. The former showed an increase in volatility with increasing cultivation years， while the latter showed a decrease in volatility. The results of differential compound analysis based on UPLC-Q-TOF-MS showed that there were significant differences in metabolites between WPR and CPR samples. Among them， the seven compounds with the largest differences among WPR samples of different thicknesses were polygalasaponins， and for CPR with different planting years， the main differential compounds were oligosaccharide esters. ConclusionThere are differences between WPR and CPR in character， microscopic structure and chemical composition， and some components are inversely proportional with the increase of diameter and cultivation duration due to the distribution characteristics. However， the longer the cultivation years of PR， the closer it is to the "thick wrinkles on the epidermis" of WPR， which has been respected by generations. It is suggested that this traditional character combined with modern component contents should be used as the index of artificial cultivation and quality control of PR.

This article systematically analyzed the historical evolution of the name， origin， harvesting and others of Longan Arillus by referring to the ancient and modern literature， in order to provide a foundation for developing famous classical formulas containing this herb. After textual research， it indicated that Longan Arillus was first recorded under the name of longan in Shennong Bencaojing of the Han dynasty. During the Ming and Qing dynasties， Longan Arillus gradually replaced longan as the standard name recorded in the materia medica， with additional aliases including Yizhi， Lizhinu and Yuanyan. The source of Longan Arillus used in the past dynasties was the arillus of the Sapindaceae plant Dimocarpus longan. The production regions recorded in the past dynasties were mainly Fujian， Guangdong， Guangxi， Hainan， Sichuan and others. Since the Qing dynasty， Longan Arillus produced in Fujian， Guangdong and Guangxi have been regarded as the finest and authentic varieties， with Fujian， Guangxi， and Guangdong remaining the primary authentic production areas today. In ancient times， the fruits were primarily harvested in August of the lunar calendar. However， modern longan cultivation typically involves harvesting ripe fruits during summer and autumn. Post-harvest processing involves removing moisture through sun-drying or baking before drying for medicinal use. Throughout history， processing methods have primarily focused on raw product， though techniques such as wine soaking and powdering have also been employed. Since modern times， it has been concluded that its quality is the best one with thick flesh， sweet taste， brownish-yellow color and tender texture. Longan Arillus possesses a sweet and warm nature， entering the heart and spleen meridians. Its primary functions are tonifying the heart and spleen， nourishing the blood and calming the spirit， which is consistent in ancient and modern times. Based on the textual research， it is suggested to use the arillus of D. longan when developing the famous classical formulas containing Longan Arillus. Processing methods should be selected according to the formula requirements， where no specific processing is indicated， the raw products is recommended for medicinal use.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， harvesting and processing， and other aspects of Manjiao and Zanthoxyli Radix by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， in order to provide a basis for the development of famous classical formulas containing the two medicinal materials. According to the herbal textual research， Manjiao was first recorded in Shennong Bencaojing of the Han dynasty with aliases such as Zhujiao， Goujiao and Zhijiao. Throughout history， Manjiao was sourced from the stems and roots of Zanthoxylum armatum in the Rutaceae family， and its leaves and fruits can also be used in medicine. The traditional recorded production area was mainly in Yunzhong（now Tuoketuo region in Inner Mongolia）， with mentions in Zhejiang， Hunan， Fujian， Guangdong， Guangxi， Yunnan， Taiwan， and other provinces. Presently， this species is distributed from the south of Shandong， to Hainan， Taiwan， Tibet and other regions. The roots can be harvested year-round， while the fruits are harvested in autumn after maturity. In ancient times， the roots and stems were mostly used for brewing or soaking in wine， whereas nowadays， the roots are often sliced and then used as a raw material in traditional Chinese medicine， and the fruits should be stir-fried before use. Manjiao has a bitter taste and warm property， and was historically used to treat wind-cold dampness， joint pain， limb numbness， and knee pain. Modern researches have summarized its effects as dispelling wind， dispersing cold， promoting circulation， and relieving pain， and it is used for treating rheumatoid arthritis， toothache， bruises， as well as an anthelmintic. Zanthoxyli Radix initially known as Rudi Jinniugen， recorded in Bencao Qiuyuan of the Qing dynasty， with the alternate name of Liangbianzhen. In recent times， it is more commonly referred to as Liangmianzhen， sourced from the dried roots of Z. nitidum of the Rutaceae family， mainly produced in Guangxi and Guangdong. It can be harvested throughout the year， cleaned， sliced， and dried after harvesting. Zanthoxyli Radix is pungent， bitter， warm and slightly toxic， with the functions of promoting blood circulation， removing stasis， relieving pain， dispelling wind， and resolving swelling. Based on the results of herbal textual research， it is clarified that the ancient Manjiao and the modern Zanthoxyli Radix are not the same species. This article corrects the mistaken belief of by previous scholars that Zanthoxyli Radix is the same as ancient Manjiao， and suggests that formulas described as Manjiao should use Z. armatum as the medicinal herb， while those described as Liangmianzhen or Rudi Jinniu should use Z. nitidum. The processing was performed according to the processing requirements prescribed in the formulas， otherwise， the raw products are recommended for use.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， harvesting and processing， and other aspects of Manjiao and Zanthoxyli Radix by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， in order to provide a basis for the development of famous classical formulas containing the two medicinal materials. According to the herbal textual research， Manjiao was first recorded in Shennong Bencaojing of the Han dynasty with aliases such as Zhujiao， Goujiao and Zhijiao. Throughout history， Manjiao was sourced from the stems and roots of Zanthoxylum armatum in the Rutaceae family， and its leaves and fruits can also be used in medicine. The traditional recorded production area was mainly in Yunzhong（now Tuoketuo region in Inner Mongolia）， with mentions in Zhejiang， Hunan， Fujian， Guangdong， Guangxi， Yunnan， Taiwan， and other provinces. Presently， this species is distributed from the south of Shandong， to Hainan， Taiwan， Tibet and other regions. The roots can be harvested year-round， while the fruits are harvested in autumn after maturity. In ancient times， the roots and stems were mostly used for brewing or soaking in wine， whereas nowadays， the roots are often sliced and then used as a raw material in traditional Chinese medicine， and the fruits should be stir-fried before use. Manjiao has a bitter taste and warm property， and was historically used to treat wind-cold dampness， joint pain， limb numbness， and knee pain. Modern researches have summarized its effects as dispelling wind， dispersing cold， promoting circulation， and relieving pain， and it is used for treating rheumatoid arthritis， toothache， bruises， as well as an anthelmintic. Zanthoxyli Radix initially known as Rudi Jinniugen， recorded in Bencao Qiuyuan of the Qing dynasty， with the alternate name of Liangbianzhen. In recent times， it is more commonly referred to as Liangmianzhen， sourced from the dried roots of Z. nitidum of the Rutaceae family， mainly produced in Guangxi and Guangdong. It can be harvested throughout the year， cleaned， sliced， and dried after harvesting. Zanthoxyli Radix is pungent， bitter， warm and slightly toxic， with the functions of promoting blood circulation， removing stasis， relieving pain， dispelling wind， and resolving swelling. Based on the results of herbal textual research， it is clarified that the ancient Manjiao and the modern Zanthoxyli Radix are not the same species. This article corrects the mistaken belief of by previous scholars that Zanthoxyli Radix is the same as ancient Manjiao， and suggests that formulas described as Manjiao should use Z. armatum as the medicinal herb， while those described as Liangmianzhen or Rudi Jinniu should use Z. nitidum. The processing was performed according to the processing requirements prescribed in the formulas， otherwise， the raw products are recommended for use.

This article systematically analyzes the historical evolution of the name， origin， quality evaluation， harvesting， processing and other aspects of Picrorhizae Rhizoma by referring to the medical books， prescription books， and other documents of the past dynasties， combined with relevant modern research materials， in order to provide a basis for the development and utilization of famous classical formulas containing this medicinal herb. The research results indicate that Picrorhizae Rhizoma was first recorded in New Revised Materia Medica from the Tang dynasty. Throughout history， Huhuanglian has been used as its official name， and there are also aliases such as Gehu Luze， Jiahuanglian and Hulian. The main source of past dynasties is the the rhizomes of Picrorhiza kurrooa and P. scrophulariiflora. In ancient times， Picrorhizae Rhizoma was mainly imported by foreign traders via Guangzhou and other regions， and also produced in China， mainly in Xizang. In ancient times， it was harvested and dried in early August of the lunar calendar， while in modern times， it is mostly harvested from July to September， with the best quality being those with thick and crispy rhizomes without impurities， and bitter taste. Throughout history， Picrorhizae Rhizoma was collected， washed， sliced， and dried before being used as a raw material for medicine， it has a bitter and cold taste， mainly used to treat bone steaming， hot flashes， infantile chancre fever， and dysentery. There is no significant difference in taste and efficacy between ancient and modern times. Based on the research results， it is recommended that the rhizomes of P. scrophulariiflora in the 2020 edition of Chinese Pharmacopoeia， or the rhizomes of P. kurrooa， can be used in famous classical formulas containing this medicinal herb， which can be processed according to the processing requirements marked by the original formula. For those without clear processing requirements， the dried raw products are used as medicine.

This article systematically analyzes the historical evolution of the name， origin， academic name， medicinal parts， origin， harvesting， processing and other aspects of Abri Herba and Abri Mollis Herba by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the modern literature， so as to provide a basis for the development of famous classical formulas containing this type of medicinal materials. According to the herbal textual research， Abri Herba was first recorded in Lingnan Caiyaolu， with other aliases such as Huangtoucao and Xiye Longlincao. It originates from the dried whole plant of Abrus cantoniensis， a Fabaceae plant， which can be used medicinally except for its fruits. Currently， this species is mainly distributed in Guangdong and Guangxi， and also found in Hunan and Thailand， it can be harvested throughout the year， mainly in spring and autumn. The roots， stems， and leaves can be used for medicinal purposes， but the pods are toxic and need to be removed. After harvesting， impurities and pods are removed， and it is dried and processed for medicinal use. Abri Herba has a sweet and slightly bitter taste， is cool in nature， and is associated with the liver and stomach meridians， it is used for clearing heat and relieving dampness， dispersing blood stasis and relieving pain， and is mainly used to treat jaundice-type hepatitis， stomach pain， rheumatic bone pain， contusion and ecchymosis pain， and mastitis. Abri Mollis Herba was first recorded in the 1982 edition of Zhongyaozhi as another origin for Abri Herba， and was singled out in some monographs such as Xinhua Bencao Gangyao in 1988 for use， while some other monographs use it as a local habitual products or confused products of Abri Herba with aliases such as Daye Jigucao， Qingtingteng， and Maoxiangsi. It comes from the dried whole herb of A. mollis without pods， and is mainly produced in Guangxi and Guangdong， and occasionally found in Hong Kong， Hainan and Fujian. The collection and processing are similar to Abri Herba， after harvesting， impurities and pods are removed， and it is dried and cut for medicinal use. Abri Mollis Herba has a sweet and light taste， is cool in nature， and is associated with the liver and stomach meridians， with the efficacy of clearing heat and detoxifying， and promoting dampness， it is mainly used to treat infectious hepatitis， mastitis， furuncles， burns and scalds， and pediatric malnutrition. Based on the research， A. mollis was first recorded to be used as a medicine in the same origin as A. cantoniensis， and as plants of the same genus， have similar morphological characteristics， and their medicinal parts， collection and processing， properties and flavors， and meridian affiliations are consistent. And in the folk， Abri Mollis Herba is often used as Abri Herba， which has been used for a long time and is now dominated by the cultivation of A. mollis. So it is recommended that the subsequent version of Chinese Pharmacopoeia should include A. mollis in the origin of Abri Herba， and it is also recommended that in famous classical formulas refered to Jiguccao can use A. cantoniensis and A. mollis as the sources of the herb， refered to Mao Jiguccao can use A. mollis as the sources of the herb. Processing is carried out according to the requirements specified in the original formulas， and raw products are recommended to be included in the medicine if there are no requirements.

This article systematically analyzes the historical evolution of the name， origin， academic name， medicinal parts， origin， harvesting， processing and other aspects of Abri Herba and Abri Mollis Herba by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the modern literature， so as to provide a basis for the development of famous classical formulas containing this type of medicinal materials. According to the herbal textual research， Abri Herba was first recorded in Lingnan Caiyaolu， with other aliases such as Huangtoucao and Xiye Longlincao. It originates from the dried whole plant of Abrus cantoniensis， a Fabaceae plant， which can be used medicinally except for its fruits. Currently， this species is mainly distributed in Guangdong and Guangxi， and also found in Hunan and Thailand， it can be harvested throughout the year， mainly in spring and autumn. The roots， stems， and leaves can be used for medicinal purposes， but the pods are toxic and need to be removed. After harvesting， impurities and pods are removed， and it is dried and processed for medicinal use. Abri Herba has a sweet and slightly bitter taste， is cool in nature， and is associated with the liver and stomach meridians， it is used for clearing heat and relieving dampness， dispersing blood stasis and relieving pain， and is mainly used to treat jaundice-type hepatitis， stomach pain， rheumatic bone pain， contusion and ecchymosis pain， and mastitis. Abri Mollis Herba was first recorded in the 1982 edition of Zhongyaozhi as another origin for Abri Herba， and was singled out in some monographs such as Xinhua Bencao Gangyao in 1988 for use， while some other monographs use it as a local habitual products or confused products of Abri Herba with aliases such as Daye Jigucao， Qingtingteng， and Maoxiangsi. It comes from the dried whole herb of A. mollis without pods， and is mainly produced in Guangxi and Guangdong， and occasionally found in Hong Kong， Hainan and Fujian. The collection and processing are similar to Abri Herba， after harvesting， impurities and pods are removed， and it is dried and cut for medicinal use. Abri Mollis Herba has a sweet and light taste， is cool in nature， and is associated with the liver and stomach meridians， with the efficacy of clearing heat and detoxifying， and promoting dampness， it is mainly used to treat infectious hepatitis， mastitis， furuncles， burns and scalds， and pediatric malnutrition. Based on the research， A. mollis was first recorded to be used as a medicine in the same origin as A. cantoniensis， and as plants of the same genus， have similar morphological characteristics， and their medicinal parts， collection and processing， properties and flavors， and meridian affiliations are consistent. And in the folk， Abri Mollis Herba is often used as Abri Herba， which has been used for a long time and is now dominated by the cultivation of A. mollis. So it is recommended that the subsequent version of Chinese Pharmacopoeia should include A. mollis in the origin of Abri Herba， and it is also recommended that in famous classical formulas refered to Jiguccao can use A. cantoniensis and A. mollis as the sources of the herb， refered to Mao Jiguccao can use A. mollis as the sources of the herb. Processing is carried out according to the requirements specified in the original formulas， and raw products are recommended to be included in the medicine if there are no requirements.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， harvesting， processing and others of Chrysanthemi Indici by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， in order to provide a basis for the development of famous classical formulas containing this medicinal herb. According to the research， Chrysanthemi Indici was first recorded under the name Kuyi in Bencao Jingjizhu， with aliases such as Yeshanju， Huangjuzai and Lubianju. The botanical source of Chrysanthemi Indici throughout history was Chrysanthemum indicum of the Asteraceae family. It is now distributed in most areas of China， and since the Qing dynasty， the product from Suichang， Zhejiang has been highly regarded. The whole plant can be used as medicine. According to the natural growth laws， the roots were collected in the first lunar month， leaves in the third， stems in the fifth， flowers in the ninth， and fruits in the eleventh， all of which were dried in the shade. In modern times， Chrysanthemi Indici is harvested during their initial blooming in autumn and winter. Since Bencao Gangmu listed Chrysanthemi Indici as a single medicinal material and clarified that all parts have medicinal value， ancient herbal texts began to record the independent medicinal use of Chrysanthemi Indici Flos， and the use of flowers as medicine has become mainstream. In modern times， the quality of Chrysanthemi Indici Flos is summarized to be best when they are dry， yellow， complete， and fragrant. Because Chrysanthemi Indici has a bitter and pungent taste， and is warm， it can eliminate and disperse， often using the power of alcohol to reach and ascend， and is commonly used to treat carbuncles， boils， and scrofula， with consistent properties and effects throughout ancient and modern times. Based on the research results， it is suggested that Chrysanthemi Indici involved in the formulas can be used as C. indicum， which can be used according to the medicinal parts labeled in the original formulas and the requirements of processing， while those without clear medicinal parts and requirements of processing should be used as the whole plant of the dried raw products.

Objective:To investigate the effect of DExH-box helicase 9(DHX9)O-linked N-acetylglucosamine(O-GlcNAc)modifi-cation(O-GlcNAcylation)on the proliferation of hepatitis B virus(HBV)-associated hepatoma cells.Methods:The pAdTrack-TO4-DHX9-3Flag recombinant adenovirus plasmid was constructed by molecular cloning and transfected into HEK293 cells for packaging and amplification of the recombinant adenovirus AdDHX9.The interaction between DHX9 and O-GlcNAc transferase(OGT)was con-firmed using co-immunoprecipitation.The co-localization between DHX9 and OGT was measured by immunofluorescence.The level of DHX9 O-GlcNAcylation was determined using succinylated wheat germ agglutinin(sWGA)and glycosylated immunoprecipitation(IP).The effect of DHX9 O-GlcNAcylation on the proliferation of HBV-associated hepatoma cells was assessed using the colony-forming assay and cell growth curves.Results:The recombinant adenovirus AdDHX9 was successfully obtained,and DHX9 expression was confirmed by Western blot.DHX9 interacted with OGT,and the two proteins were co-localized on the nucleus.The sWGA and gly-cosylated IP experiments showed that DHX9 underwent O-GlcNAcylation,which was further enhanced by HBV infection.The colony-forming assay demonstrated that the number of cell clones was increased in the AdDHX9 group(386.667±15.630)compared with the AdGFP control group(142.667±7.572,P<0.001).Moreover,cell growth curves demonstrated that the overall cell growth rate was en-hanced in the AdDHX9 group(22.860±0.770)compared with the AdGFP control group(13.670±0.517,P<0.001).Conclusion:HBV infection promotes DHX9 O-GlcNAcylation,which enhances the proliferation of HBV-associated hepatoma cells.