Systematic Analysis of Zinc Finger-Homeodomain Transcription Factors (ZF-HDs) in Barley (Hordeum vulgare L.).

Zinc finger-homeodomain transcription factors (ZF-HDs) are pivotal in regulating plant growth, development, and diverse stress responses. In this study, we found 8 ZF-HD genes in barley genome. Theses eight HvZF-HD genes were located on five chromosomes, and classified into ZHD and MIF subfamily. The collinearity, gene structure, conserved motif, and cis-elements of HvZF-HD genes were also analyzed. Real-time PCR results suggested that the expression of HvZF-HD4, HvZF-HD6, HvZF-HD7 and HvZF-HD8 were up-regulated after hormones (ABA, GA3 and MeJA) or PEG treatments, especially HvZF-HD6 was significantly induced. These results provide useful information of ZF-HD genes to future study aimed at barley breeding.

Effectiveness of a Teach-Back Education Program on Perioperative Pain in Patients With Lung Cancer: An Intervention Study Using Behavior Change Wheel.

OBJECTIVE: To assess the effect of a teach-back educational intervention using Behavior Change Wheel (BCW) framework on perioperative pain among patients with lung cancer. METHODS: A prospective quasi-experimental study was conducted in 88 patients with lung cancer from a tertiary hospital in China. According to the order of admission, they were allocated to either control group or intervention group, with 44 patients in each group. Patients in the control group received routine nursing care, while patients in the intervention group were given a teach-back education program based on BCW framework. The visual analog scale (VAS) was adopted to evaluate patients' pain on the day of surgery (T0), 1 (T1), 2 (T2), and 3 (T3) days after surgery. We also recorded the use of patient-controlled analgesia (PCA), the length of hospital stay, and the degree of patients' satisfaction. RESULTS: Rest pain, pain when coughing, and pain during activity that patients in the intervention group experienced were significantly less severe than those in the control group on T0 and T1. The pain when coughing in the intervention group was also significantly milder on T2 and T3. In addition, the number of self-control time, use duration, and total dose of PCA were significantly lower in the intervention group. Moreover, patients' satisfaction of nursing service was significantly higher in the intervention group. CONCLUSION: A teach-back education program based on BCW framework was effective in pain management among the perioperative patients with lung cancer. This study demonstrates the application of teach-back method and the BCW in the development of patient education intervention to mitigate perioperative pain.

Cerebral Protection of Intraoperative Infusion of Dexmedetomidine in Patients with Chronic Cerebrovascular Stenosis Undergoing Endovascular Interventional Therapies: A Prospective Randomized Controlled Trial.

BACKGROUND: To investigate the cerebral protective effect of intraoperative dexmedetomidine infusion on patients with chronic cerebral vascular stenosis receiving endovascular interventional therapy. METHODS: Sixty patients with carotid artery or cerebral artery stenosis or occlusion stenting under elective general anesthesia were divided into dexmedetomidine group (group D) and normal saline group (group N). Group D was given dexmedetomidine loading dose 1.0 µg/kg after peripheral vein opening for 10 min, and then adjusted infusion rate to 0.5 µg/kg/h until stopped 30 min before end. RESULTS: At 7 days after operation, the contents of S100ß, neuron-specific enolase (NSE) and interleukin-6 (IL-6) in group D were apparently lower than those in group N (P < 0.05), while the contents of IL-1ß and tumor necrosis factor-α in 2 groups showed no statistical significance (P > 0.05). Additionally, at 4 days and 7 days after operation, the scores of Mini-Mental State Scale (MMSE) and Wechsler Memory Scale (WMS) in group D were significantly higher than those in group N (P < 0.05). Thirty days after surgery, the cerebral hemodynamic indexes (relative mean transit time, relative time to peak) in group D were significantly improved, and obviously better than those in group N (P < 0.05). CONCLUSIONS: The S-100ß, NSE, and inflammatory mediator IL-6 in group D were significantly decreased compared with group N, the MMSE and WMS cognitive function scores, and the cerebral blood perfusion were apparently improved in group D, clarifying dexmedetomidine has protective effect on nerve tissue injury by inhibiting inflammation.

[Current Status and New Drugs Progress in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia--Review].

The overall therapeutic outcome of acute myeloid leukemia (AML) is poor, and relapse and refractory are the main reasons for treatment failure. Leukemia cells of relapsed and refractory AML (R/R-AML) patients are usually resistant to conventional chemotherapy, and new treatment regimens are urgently needed to further improve the survival rate and prolong the survival time of these patients.There are no recommended unified treatment regimens other than entering clinical trials.At present,the main options are salvage chemotherapy and hematopoietic stem cell transplantation (HSCT), and HSCT is the only possible cure for R/R-AML, but the prognosis of most of these patients is still poor.In recent years,the treatment status of AML has progressed rapidly, and the new therapies are emerging, many new drugs have become the research focus. Some progress has been made in improving chemosensitivity and overcoming chemoresistance by combining the new drugs with the original chemotherapeutic drugs, which provide a new treatment option and improve the overall prognosis for R/R-AML patients. This article will review the current treatment status and the latest progress in new drug research of R/R-AML.

Vacuum Foam Drying Method Improved the Thermal Stability and Long-Term Shelf Life of a Live Attenuated Newcastle Disease Virus Vaccine.

Vaccines used for managing Newcastle disease virus (NDV) rely heavily on cold chain, and this results in major constraints in their successful application, shipping, and storage. This study was undertaken to improve the thermotolerance properties of live attenuated NDV vaccines using vacuum foam drying (VFD) technology. The live attenuated NDV vaccine formulated in 15% trehalose, 2.5% gelatin, 0.05% pluronic, and 25 mmol/L potassium phosphate buffer (T5) and dried using VFD showed improved heat tolerance in comparison to the vaccine formulated in T5 as well, but dried using freeze-drying (FD) method. The T5-formulated VFD vaccine was stored at 37°C for 120 days, 45°C for 7 days, and 60°C for 3 days; the virus titer loss decreased by no more than 1.0 Log10. In contrast, the FD vaccine prepared in T5 could only be stored at 37°C for 7-10 days. Furthermore, the T5-formulated NDV-VFD vaccine remained infectious when heated at 100°C for 30 min. Shelf-life studies confirmed the improved thermal tolerance of the T5-formulated NDV-VFD vaccine since it could be stably stored at 2-8°C for 42 months and 25°C for 15 months. Moreover, immunization of 1-month-old specific pathogen-free (SPF) chickens with the T5-formulated NDV-VFD vaccine stored at 25 and 37°C could produce hemagglutination inhibition (HI) antibody levels comparable to those of commercial NDV-FD vaccines, which require strict adherence to the cold chain. In conclusion, not only did the VFD technology improve the thermostability and long-term shelf life of the vaccine, it also maintained its immunogenicity.

[Application of two noninvasive scores in predicting the risk of respiratory failure in full-term neonates: a comparative analysis]. / ä¸¤ç§æ— åˆ›è¯„åˆ†æ³•åœ¨è¶³æœˆæ–°ç”Ÿå„¿å‘¼å¸è¡°ç«­é£Žé™©é¢„æµ‹ä¸­çš„åº”ç”¨æ¯”è¾ƒ.

OBJECTIVES: To study the value of Silverman-Anderson score versus Downes score in predicting respiratory failure in full-term neonates. METHODS: The convenience sampling method was used to select the full-term neonates with lung diseases who were hospitalized in the neonatal intensive care unit from July 2020 to July 2021. According to the diagnostic criteria for neonatal respiratory failure, they were divided into a respiratory failure group (65 neonates) and a non-respiratory failure group (363 neonates). Silverman-Anderson score and Downes score were used for evaluation. The receiver operating characteristic analysis was used to compare the value of the two noninvasive scores in predicting respiratory failure in full-term neonates. RESULTS: Among the 428 full-term neonates, 65 (15.2%) had respiratory failure. The Silverman-Anderson score had a significantly shorter average time spent on evaluation than the Downes score [(90±8) seconds vs (150±13) seconds; P<0.001]. The respiratory failure group had significantly higher points in both the Silverman-Anderson and Downes scores than the non-respiratory failure group (P<0.001). The Silverman-Anderson score had an AUC of 0.876 for predicting respiratory failure, with a sensitivity of 0.908, a specificity of 0.694, and a Youden index of 0.602 at the optimal cut-off value of 4.50 points. The Downes score had an AUC of 0.918 for predicting respiratory failure, with a sensitivity of 0.723, a specificity of 0.953, and a Youden index of 0.676 at the optimal cut-off value of 6.00 points. The Downes score had significantly higher AUC for predicting respiratory failure than the Silverman-Anderson score (P=0.026). CONCLUSIONS: Both Silverman-Anderson and Downes scores can predict the risk of respiratory failure in full-term neonates. The Silverman-Anderson score requires a shorter time for evaluation, while the Downes score has higher prediction efficiency. It is recommended to use Downes score with higher prediction efficiency in general evaluation, and the Silverman-Anderson score requiring a shorter time for evaluation can be used in emergency.

Dexmedetomidine inhibits inflammatory response and oxidative stress through regulating miR-205-5p by targeting HMGB1 in cerebral ischemic/reperfusion.

OBJECTIVE: To investigate effects of dexmedetomidine (DEX) on miR-205-5p/HMGB1 axis in cerebral ischemic/reperfusion (I/R) injury. METHODS: Both in vivo I/R rat model and in vitro hypoxia/reoxygenation (H/R) cell model using rat hippocampal neurons cells were established. miR-205-5p was overexpressed or inhibited by transfection of miR-205-5p mimics or inhibitor. HMGB1 was overexpressed by transfection overexpression plasmids (OE-HMGB1). TTC staining was used for measurement of infraction volume. Oxidative stress was evaluated by measurement of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) and inflammation was evaluated by measurement of IL-1ß, IL-6 and TNF-α. Dual luciferase reporter assay was performed to confirm binding between miR-205-5p and HMGB1. The expression levels of miR-205-5p, and HMGB1 were measured using RT-qPCR. Western blotting was used to test the protein expression levels of HMGB1, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase (GPx), glutathione reductase (GR), heme oxygenase 1 (HO-1) and catalase (CAT). RESULTS: Treatment of DEX significantly reduced brain infraction volume, decreased Longa's neurological function score and inhibited oxidative stress and inflammation in brain tissues of I/R rats, which were all reversed by inhibition of miR-205-5p. Both treatment of DEX or overexpression of miR-205-5p restricted oxidative stress and inflammation in H/R rat hippocampal neurons cells. The inhibition of miR-205-5p reversed the effects of DEX, while the overexpression of HMGB1 reversed the effects of miR-205-5p overexpression in H/R rat hippocampal neurons cells. Dual luciferase reporter assay showed miR-205-5p directly targeted HMGB1. CONCLUSION: DEX improved I/R injury by suppressing brain oxidative stress and inflammation DEX improved I/R injury by suppressing brain oxidative stress and inflammation through activating miR-205-5p/HMGB1 axis through activating miR-205-5p/HMGB1 axis.

The Spatiotemporal Evolution Analysis of Ecosystem Pattern in Wenchuan (Magnitude 8.0) Earthquake Disaster Area, China.

The ecological system is the basis of human survival and global environmental protection. In the process of development, countries will pay close attention to the changing state of the ecosystem. Taking the ecosystem pattern as the research object, a three-layer analysis method was proposed. The transfer matrix and landscape index were used as the first layer to analyze the basic changes. Grey correlation, range-coupling coordination and relative priority were used as the second layer to analyze the reasons of the change. The interval-entropy weight, TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution), was used as the third layer to evaluate the quality of the change. The ten counties in the worst-hit areas of the Wenchuan earthquake were analyzed from different angles, with county region, intensity zone and ecosystem as the objects, and the following results were obtained: (1) Taking Mianzhu City as an example, from 2000 to 2010 and 2018, the conversion ratio of forest, grassland and farmland is 54.24, 59.19, 17.21, 20.06, 37.39 and 52.86%, which were distributed in the north, central and southern parts, respectively. (2) Taking the ninth intensity zone as an example, the forest landscape fragmentation increased, disturbance decreased, and species diversity increased. There is a high influence and restriction relationship between ecosystem and landscape pattern in the total landscape area change. Additionally, the relationship between them tends to develop in a benign way. As of 2018, it is in the change state of moderate imbalance-ecosystem lag. (3) Taking the county ecosystem change as an example, urban type is the best in the counties of ecosystem change, of which Shifang is the best and Pingwu is the worst. The results show that this method can effectively compare and analyze the changes in the multi-regional ecosystem pattern, which has the characteristics of universality and can also be applied to the research of ecosystem pattern change in special regions.

The transverse diameter of right common femoral vein by ultrasound in the supine position for predicting post-spinal hypotension during cesarean delivery.

BACKGROUND: Post-spinal anesthesia hypotension during cesarean delivery is caused by decreased systemic vascular resistance due to the blockage of the autonomic nerves, which is further worsened by inferior vena cava (IVC) compression by the gravid uterus. This study aimed to assess whether peak velocity and diameter of the IVC below the xiphoid or right common femoral vein (RCFV) in the inguinal region, as measured on ultrasound, could reflect the degree of IVC compression and further identify parturients at risk of post-spinal hypotension. METHODS: Fifty-six parturients who underwent elective cesarean section with spinal anesthesia were included in this study; peak velocities and anteroposterior diameters of the IVC and peak velocities and transverse diameters of the RCFV were measured using ultrasound before anesthesia. The primary outcome was the ultrasound measurements of IVC and RCFV acquired before spinal anesthesia and their association with post-spinal hypotension. Hypotension was defined as a drop in systolic arterial pressure by > 20% from the baseline. Multinomial logistic regression analysis was used to identify the association between the measurements of IVC, RCFV, and post-spinal hypotension during cesarean delivery. Receiver operating characteristic curves were used to test the abilities of the identified parameters to predict post-spinal hypotension; the areas under the curve and optimum cut-off values for the predictive parameters were calculated. RESULTS: A longer transverse diameter of the RCFV was associated with the occurrence of post-spinal hypotension (odds ratio = 2.022, 95% confidence interval [CI] 1.261-3.243). The area under the receiver operating characteristics curve for the prediction of post-spinal hypotension was 0.759 (95% CI 0.628-0.890, P = 0.001). A transverse diameter of > 12.2 mm of the RCFV could predict post-spinal hypotension during cesarean delivery. CONCLUSIONS: A longer transverse diameter of RCFV was associated with hypotension and could predict parturients at a major risk of hypotension before anesthesia. TRIAL REGISTRATION: This study was registered at http://www.chictr.org.cn on 16, May, 2018. No. ChiCTR1800016163 .

Live vaccine preserved at room temperature: Preparation and characterization of a freeze-dried classical swine fever virus vaccine.

The heat-stable live-attenuated classical swine fever virus (CSFV) vaccine is an urgent need in many countries of Asia, Europe and Latin America. In this study, the thermostability of lyophilized live-attenuated CSFV vaccine formulations were investigated using accelerated stability at 37 °C for 10 days. The freeze-dried heat-stable formulation ST16, containing excipient combinations of trehalose, glycine, thiourea and phosphate buffer shows the superior thermostability. Moreover, the lyophilized vaccine with formula ST16 kept loss of viral activity less than 0.5 log10 during 24 months at storage temperatures of 2-8 °C. In thermal study, ST16 stabilized the vaccine within 1.0 log10 loss after storage at up to 25 °C for 6 months and room temperature for 7 months. Even under the harshest storage conditions of 37 °C for 25 days and 45 °C for 2 weeks, the virus titer dropped less than 1.0 log10 using ST16. Besides, it is notable that ST16 excluded gelatin and exogenous proteins, which might cause allergic reactions, thus avoiding immune side effects. The vaccine formulated ST16 proved to be safe and effective when immunized to piglets in vivo. The characteristics of dried vaccines were analyzed by X-ray powder diffraction, residual water measurements, differential scanning calorimetry and it was found that vaccine antigen were preserved in an amorphous matrix with high glass transition temperature above 60 °C and low residual water content below 2%, which made the vaccine more stable during storage.

[Progress in goat genome studies].

The goat genome is the research basis for the protection and utilization of goat resources, which is important for breeding and improving goat breeds. At present, with the continuous improvement of goat reference genome, various important research progress in goat origin, evolution and adaptability has been achieved. In this review, we summarize the research progress in the goat genome in detail, encompassing goat genome structure, genome map (genetic, physical and comparative maps), goat high throughput sequencing and SNP chip development. We aim to provide a theoretical foundation for the development of goat genome selection.

[Preparation and evaluation of carboxymethyl chitosan/sodium alginate hydrogel for cartilage tissue engineering].

OBJECTIVE: This study aimed to optimize the preparation of carboxymethyl chitosan/sodium alginate (CMCS/OSA) compound hydrogels. This study also aimed to investigate the applicability of the hydrogels in cartilage tissue engi-neering. METHODS: Three groups of CMCS/OSA composite hydrogels with amino-to-aldehyde ratios of 2∶1, 1∶1 and 1∶2 were prepared. The microstructure, physical properties, and cell biocompatibility of the three groups of CMCS/OSA com-posite hydrogels were evaluated. Samples were subjected to scanning electron microscopy, rheological test, adhesion tension test, swelling rate test, and cell experiments to identify the CMCS/OSA composite hydrogel with the cross-linking degree that can meet the requirements for scaffolds in cartilage tissue engineering. RESULTS: The experimental results showed that the CMCS/OSA hydrogel with a amine-to-aldhyde ratio of 1∶1 had good porosity, suitable gelling time, strong adhesive force, stable swelling rate, and good cellular biocompatibility. CONCLUSIONS: The CMCS/OSA compound hydrogel prepared with a 1∶1 ratio of amino and aldehyde groups has potential applications in cartilage tissue engineering.

[Development of cartilage extracellular matrix in cartilage tissue engineering].

Cartilage tissue engineering, an effective way to repair cartilage defects, requires an ideal scaffold to promote the regeneration performance of stem cells. Cartilage extracellular matrix (CECM) can imitate the living environment of cartilage cells to the greatest extent. CECM not only exhibits good biocompatibility with chondrocytes and stem cells, which can meet the basic requirements of scaffolds, but also promotes chondrocytes to secrete matrix and induce stem cells to differentiate into chondrocytes; as such, this matrix is a better scaffold and has more advantages than existing ones. The promotion and induction effects could be related to various cartilage-related proteins inside. However, the practical application of this technique is hindered by problems, such as poor mechanical properties and insufficient cell penetration of CECM. Association with other materials can compensate for these inadequacies to a certain degree, and finding a combination mode with optimized performance is the application trend of CECM. This review focuses on research of CECM materials in cartilage tissue engineering.

Silk fibroin/cartilage extracellular matrix scaffolds with sequential delivery of TGF-ß3 for chondrogenic differentiation of adipose-derived stem cells.

A 3-D scaffold that simulates the microenvironment in vivo for regenerating cartilage is ideal. In this study, we combined silk fibroin and decellularized cartilage extracellular matrix by temperature gradient-guided thermal-induced phase separation to produce composite scaffolds (S/D). Resulting scaffolds had remarkable mechanical properties and biomimeticstructure, for a suitable substrate for attachment and proliferation of adipose-derived stem cells (ADSCs). Moreover, transforming growth factor ß3 (TGF-ß3) loaded on scaffolds showed a controlled release profile and enhanced the chondrogenic differentiation of ADSCs during the 28-day culture. The S/D scaffold itself can provide a sustained release system without the introduction of other controlled release media, which has potential for commercial and clinical applications. The results of toluidine blue, Safranin O, and immunohistochemical staining and analysis of collagen II expression showed maintenance of a chondrogenic phenotype in all scaffolds after 28-day culture. The most obvious phenomenon was with the addition of TGF-ß3. S/D composite scaffolds with sequential delivery of TGF-ß3 may mimic the regenerative microenvironment to enhance the chondrogenic differentiation of ADSCs in vitro.

Time-series analysis in imatinib-resistant chronic myeloid leukemia K562-cells under different drug treatments.

Chronic myeloid leukemia (CML) is characterized by the accumulation of active BCR-ABL protein. Imatinib is the first-line treatment of CML; however, many patients are resistant to this drug. In this study, we aimed to compare the differences in expression patterns and functions of time-series genes in imatinib-resistant CML cells under different drug treatments. GSE24946 was downloaded from the GEO database, which included 17 samples of K562-r cells with (n=12) or without drug administration (n=5). Three drug treatment groups were considered for this study: arsenic trioxide (ATO), AMN107, and ATO+AMN107. Each group had one sample at each time point (3, 12, 24, and 48 h). Time-series genes with a ratio of standard deviation/average (coefficient of variation) >0.15 were screened, and their expression patterns were revealed based on Short Time-series Expression Miner (STEM). Then, the functional enrichment analysis of time-series genes in each group was performed using DAVID, and the genes enriched in the top ten functional categories were extracted to detect their expression patterns. Different time-series genes were identified in the three groups, and most of them were enriched in the ribosome and oxidative phosphorylation pathways. Time-series genes in the three treatment groups had different expression patterns and functions. Time-series genes in the ATO group (e.g. CCNA2 and DAB2) were significantly associated with cell adhesion, those in the AMN107 group were related to cellular carbohydrate metabolic process, while those in the ATO+AMN107 group (e.g. AP2M1) were significantly related to cell proliferation and antigen processing. In imatinib-resistant CML cells, ATO could influence genes related to cell adhesion, AMN107 might affect genes involved in cellular carbohydrate metabolism, and the combination therapy might regulate genes involved in cell proliferation.

Time-series Analysis in Imatinib-resistant Chronic Myeloid Leukemia K562-cells under Different Drug Treatments / 华中科技大学学报（医学）（英德文版）

Chronic myeloid leukemia (CML) is characterized by the accumulation of active BCR-ABL protein.Imatinib is the first-line treatment of CML;however,many patients are resistant to this drug.In this study,we aimed to compare the differences in expression patterns and functions of time-series genes in imatinib-resistant CML cells under different drug treatments.GSE24946 was downloaded from the GEO database,which included 17 samples of K562-r cells with (n=12) or without drug administration (n=5).Three drug treatment groups were considered for this study:arsenic trioxide (ATO),AMN107,and ATO+AMN107.Each group had one sample at each time point (3,12,24,and 48 h).Time-series genes with a ratio of standard deviation/average (coefficient of variation) ＞0.15 were screened,and their expression patterns were revealed based on Short Time-series Expression Miner (STEM).Then,the functional enrichment analysis of time-series genes in each group was performed using DAVID,and the genes enriched in the top ten functional categories were extracted to detect their expression patterns.Different time-series genes were identified in the three groups,and most of them were enriched in the ribosome and oxidative phosphorylation pathways.Time-series genes in the three treatment groups had different expression patterns and functions.Time-series genes in the ATO group (e.g.CCNA2 and DAB2)were significantly associated with cell adhesion,those in the AMN107 group were related to cellular carbohydrate metabolic process,while those in the ATO+AMN107 group (e.g.AP2M1) were significantly related to cell proliferation and antigen processing.In imatinib-resistant CML cells,ATO could influence genes related to cell adhesion,AMN107 might affect genes involved in cellular carbohydrate metabolism,and the combination therapy might regulate genes involved in cell proliferation.

Preparation and heat resistance study of porcine reproductive and respiratory syndrome virus sugar glass vaccine.

To improve the preservation period without cold-chain of the live attenuated vaccine of porcine reproductive and respiratory syndrome (PRRS), a set of thermostable formulations composed of trehalose, tryptone and other protectants were dried by vacuum foam drying (VFD) along with PRRSV solutions. In the 37°C and 45°C resistance ageing test, the dried foam vaccine showed significant thermostability, and the virus titer lost 0.8 Log10 at 37°C for 4months, 1.0 Log10 at 45°C for 25days. Furthermore, the foam vaccine could be stored at 25°C for at least one year. Besides, the vaccine preserved in 37°C, 25°C and 4°C for 3months were inoculated on 20-days old piglet, and the serum titer was monitoring by ELISA kit. Inoculated two weeks later, the ELISA titer were all qualified and had the similar level compared to the commercial vaccines of the lyophilization dosage.

[The transcriptome research progresses of skin hair follicle development].

Recently, transcriptome sequencing technology has achieved significant progresses in gene network regulation of important economic traits in animals. As the derivative of mammalian skin, hair follicle is capable of self-renew. Its proliferation and differentiation result in hair formation. Researches have revealed that many growth factors and receptors coordinate genes and environment, as well as play an extremely important role during hair growth. In this review, we summarize the progresses that transcriptome sequencing technologies have achieved in researches of hair follicle development and renegeration in a variety of species, such as humans, mice, goats. We aim to provide theoretical mechanisms for the artificial interference of villus growth cycle, and new ideas for therapeutic treatment of skin hair follicle- related diseases.