Virtual Growing Child (VGC): A general normative comparative system via quantitative dynamic MRI for quantifying pediatric regional respiratory anomalies with application in thoracic insufficiency syndrome (TIS).

Background: A normative database of regional respiratory structure and function in healthy children does not exist. Methods: VGC provides a database with four categories of regional respiratory measurement parameters including morphological, architectural, dynamic, and developmental. The database has 3,820 3D segmentations (around 100,000 2D slices with segmentations). Age and gender group analysis and comparisons for healthy children were performed using those parameters via two-sided t-testing to compare mean measurements, for left and right sides at end-inspiration (EI) and end-expiration (EE), for different age and gender specific groups. We also apply VGC measurements for comparison with TIS patients via an extrapolation approach to estimate the association between measurement and age via a linear model and to predict measurements for TIS patients. Furthermore, we check the Mahalanobis distance between TIS patients and healthy children of corresponding age. Findings: The difference between male and female groups (10-12 years) behave differently from that in other age groups which is consistent with physiology/natural growth behavior related to adolescence with higher right lung and right diaphragm tidal volumes for females(p<0.05). The comparison of TIS patients before and after surgery show that the right and left components are not symmetrical, and the left side diaphragm height and tidal volume has been significantly improved after surgery (p <0.05). The left lung volume at EE, and left diaphragm height at EI of TIS patients after surgery are closer to the normal children with a significant smaller Mahalanobis distance (MD) after surgery (p<0.05). Interpretation: The VGC system can serve as a reference standard to quantify regional respiratory abnormalities on dMRI in young patients with various respiratory conditions and facilitate treatment planning and response assessment. Funding: The grant R01HL150147 from the National Institutes of Health (PI Udupa).

Assessment of 3D hemi-diaphragmatic motion via free-breathing dynamic MRI in pediatric thoracic insufficiency syndrome.

Purpose: Thoracic insufficiency syndrome (TIS) affects ventilatory function due to spinal and thoracic deformities limiting lung space and diaphragmatic motion. Corrective orthopedic surgery can be used to help normalize skeletal anatomy, restoring lung space and diaphragmatic motion. This study employs free-breathing dynamic MRI (dMRI) and quantifies the 3D motion of each hemi-diaphragm surface in normal and TIS patients, and evaluates effects of surgical intervention. Materials and Methods: In a retrospective study of 149 pediatric patients with TIS and 190 healthy children, we constructed 4D images from free-breathing dMRI and manually delineated the diaphragm at end-expiration (EE) and end-inspiration (EI) time points. We automatically selected 25 points uniformly on each hemi-diaphragm surface, calculated their relative velocities between EE and EI, and derived mean velocities in 13 homologous regions for each hemi-diaphragm to provide measures of regional 3D hemi-diaphragm motion. T-testing was used to compare velocity changes before and after surgery, and to velocities in healthy controls. Results: The posterior-central region of the right hemi-diaphragm exhibited the highest average velocity post-operatively. Posterior regions showed greater velocity changes after surgery in both right and left hemi-diaphragms. Surgical reduction of thoracic Cobb angle displayed a stronger correlation with changes in diaphragm velocity than reduction in lumbar Cobb angle. Following surgery, the anterior regions of the left hemi-diaphragm tended to approach a more normal state. Conclusion: Quantification of regional motion of the 3D diaphragm surface in normal subjects and TIS patients via free-breathing dMRI is feasible. Derived measurements can be assessed in comparison to normal subjects to study TIS and the effects of surgery.

Narrow linewidth laser based on a sidewall grating active distributed Bragg reflector.

We demonstrated a narrow linewidth semiconductor laser based on a deep-etched sidewall grating active distributed Bragg reflector (SG-ADBR). The coupling coefficients and reflectance were numerically simulated for deep-etched fifth-order SG-ADBR, and a reflectance of 0.86 with a bandwidth of 1.04 nm was obtained by the finite element method for a 500-period SG-ADBR. Then the fifth-order SG-ADBR lasers were fabricated using projection i-line lithography processes. Single-mode lasing at 1537.9 nm was obtained with a high side-mode suppression ratio (SMSR) of 65 dB, and a continuous tuning range of 10.3 nm was verified with SMSRs greater than 53 dB. Furthermore, the frequency noise power spectral density was characterized, from which a Lorentzian linewidth of 288 kHz was obtained.

Regulation of interstitial fluid flow in adventitia along vasculature by heartbeat and respiration.

Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT, and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.

A DNA barcode library for woody plants in tropical and subtropical China.

The application of DNA barcoding has been significantly limited by the scarcity of reliable specimens and inadequate coverage and replication across all species. The deficiency of DNA barcode reference coverage is particularly striking for highly biodiverse subtropical and tropical regions. In this study, we present a comprehensive barcode library for woody plants in tropical and subtropical China. Our dataset includes a standard barcode library comprising the four most widely used barcodes (rbcL, matK, ITS, and ITS2) for 2,520 species from 4,654 samples across 49 orders, 144 families, and 693 genera, along with 79 samples identified at the genus level. This dataset also provides a super-barcode library consisting of 1,239 samples from 1,139 species, 411 genera, 113 families, and 40 orders. This newly developed library will serve as a valuable resource for DNA barcoding research in tropical and subtropical China and bordering countries, enable more accurate species identification, and contribute to the conservation and management of tropical and subtropical forests.

Timing umbilical therapy in treatment of neurogenic bladder after spinal cord injury based on midnight-noon and ebb-flow doctrine: a randomized controlled trial. / åŸºäºŽå­åˆæµæ³¨ç†è®ºæ‹©æ—¶è„ç–—æ²»ç–—è„Šé«“æŸä¼¤åŽç¥žç»æºæ€§è†€èƒ±ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical efficacy of timing umbilical therapy for neurogenic bladder after spinal cord injury based on the midnight-noon and ebb-flow doctrine. METHODS: Sixty patients with neurogenic bladder after spinal cord injury were randomly divided into a trial group and a control group, with 30 patients in each group. In the trial group, based on the midnight-noon and ebb-flow doctrine, umbilical therapy was given at the time zone, 15:00 to 17:00. In the control group, umbilical therapy was delivered at any time zones except the period 15:00 to 17:00. The herbal plaster was remained on the umbilicus for 4 h each time, once daily. One course of treatment was composed of 2 weeks and the treatment lasted 4 weeks. Before and after treatment, the urodynamic indexes (maximum urinary flow rate [Qmax], maximum detrusor pressure [Pdet-max], residual urine volume [RUV]), voiding diary (average daily number of voiding, average daily number of leakage, average daily voided volume), neurogenic bladder symptom score (NBSS), the score of urinary symptom distress scale (USDS) and the score of World Health Organization quality of life assessment-BREF (WHOQOL-BREF) were compared between the two groups; and the clinical efficacy of the two groups was assessed. RESULTS: After treatment, Qmax, Pdet-max, the average daily voided volume and the scores of WHOQOL-BREF were increased (P<0.05); and RUV, the average daily number of voiding, the average daily number of leakage, NBSS and the scores of USDS were all reduced (P<0.05) in comparison with those before treatment in the two groups. When compared with those in the control group, Qmax, Pdet-max, the average daily voided volume and the score of WHOQOL-BREF were all higher (P<0.05); and RUV, the average daily number of voiding, the average daily number of leakage, NBSS and the score of USDS were lower (P<0.05) in the trial group. The total effective rate was 96.7% (29/30) in the trial group, higher than that (76.7%, 23/30) in the control group (P<0.05). CONCLUSIONS: Timing umbilical therapy, based on the midnight-noon and ebb-flow doctrine, effectively relieves the symptoms of dysuria and improves the quality of life in patients with neurogenic bladder after spinal cord injury.

Chemical Constituents of the Deep-sea Gammarid Shrimp-Derived Fungus Penicillium citrinum XIA-16.

One new alkaloid, (S)-2-acetamido-4-(2-(methylamino)phenyl)-4-oxobutanoic acid (1), was isolated from the deep-sea-derived Penicillium citrinum XIA-16, together with 25 known compounds including ten polyketones (2-11), eight alkaloids (12-19), six steroids (20-25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3-induced ferroptosis (EC50 =2.0 µM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10 µM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %.

Citriquinolinones A and B: Rare Isoquinolinone-Embedded Citrinin Analogues and Related Metabolites from the Deep-Sea-Derived Aspergillus versicolor 170217.

A systematic chemical investigation of the deep-sea-derived fungus Aspergillus versicolor 170217 resulted in the isolation of six new (1-6) and 45 known (7-51) compounds. The structures of the new compounds were established on the basis of exhaustive analysis of their spectroscopic data and theoretical-statistical approaches including GIAO-NMR, TDDFT-ECD/ORD calculations, DP4+ probability analysis, and biogenetic consideration. Citriquinolinones A (1) and B (2) feature a unique isoquinolinone-embedded citrinin scaffold, representing the first exemplars of a citrinin-isoquinolinone hybrid. Dicitrinones K-L (3-4) are two new dimeric citrinin analogues with a rare CH-CH3 bridge. Biologically, frangula-emodin (32) and diorcinol (17) displayed remarkable anti-food allergic activity with IC50 values of 7.9 ± 3.0 µM and 13.4 ± 1.2 µM, respectively, while diorcinol (17) and penicitrinol A (20) exhibited weak inhibitory activity against Vibrio parahemolyticus, with MIC values ranging from 128 to 256 µM.

Green synthesis of metal-organic framework loaded dexamethasone on wood aerogels for enhanced cranial bone regeneration.

Bone defects have attracted increasing attention in clinical settings. To date, there have been no effective methods to repair defective bones. Balsa wood aerogels are considered as an excellent source of chemicals for chemical modification to facilitate the in situ immobilization of zeolitic imidazolate framework-8. Furthermore, dexamethasone has received considerable attention for bone tissue engineering. In this study, for the first time, a simple but effective one-pot method for developing a novel zeolitic imidazolate framework-8 with different concentrations of dexamethasone was developed. These findings illustrate that the novel scaffold has a significant positive impact on osteogenic differentiation in vitro and repairs defects in vivo, suggesting that it can be used in bone tissue engineering.

[Analysis of Carbon Storage Potential of CO2 Foamed Concrete].

The technology of carbon capture, utilization, and storage (CCUS) is an important component of carbon neutral technology systems. To confirm the carbon storage potential of CO2 foamed concrete (CFC), this study addressed the principle of carbon storage in CFC materials. It is apparent that carbon storage of CFC materials includes carbon fixation in concrete skeletons and carbon storage in CFC bubbles. The carbon fixation of CFC skeletons is realized by CO2 mineralization. As the concrete skeleton in CFC is in the CO2 atmosphere, the carbonation of CFC materials or CO2 mineralization is more complete. Research shows that the carbonation rate of CFC materials can reach almost 30% after acidification, foaming with high CO2 pressure and curing in the atmosphere. The carbonation rate is higher than the rate in concrete curing with CO2. A mathematical model was established to calculate carbon fixation capacity in CFC materials, and the carbon fixation and storage capacity in CFC material were estimated. The results showed that more than 99% carbon storage of CFC was realized by the chemical carbonization of the concrete skeleton. Comparatively, the potential of carbon storage in the bubble of CFC was small. In this study, carbon storage capacity was divided into three categories, i.e., theoretical maximum capacity, relative reliable capacity, and expected capacity or potential. The carbonation rate for theoretical maximum capacity was 100%, when all the concrete was considered to be carbonated. As the carbonation rate of concrete during the whole life cycle is approximately 55% all over the world, 50% was set as the carbonation rate for relative reliable capacity calculation. If at high temperatures, CO2 curing with high pressure or accessory ingredients applied to silicate concrete can improve carbonation rate to be over 80%, when the carbon storage capacity is considered to be expected capacity or potential. In 2017-2021, the theoretical maximum capacity of carbon storage was 3.623×109 t CO2 in China, with 7.25×108 t·a-1. The relative reliable capacity was 3.75×108 t·a-1, and the expected capacity was 5.80×108 t·a-1. If the carbonation rate was 30%, the carbon storage of concrete produced annually in China during the whole life cycle reached 2.18×108 t, which was more than the carbon sink of Daxing'anling forest for one year. In coal electricity integrated mining areas and large thermal, metallurgical, cement chemical, and other high-energy consuming enterprises, CFC has a good prospect of development to promote the recycling of solid waste and waste gas. Meanwhile, it is pointed out that the stability of CFC before solidification is a technical problem to be solved in the next step.

Unidirectional light emission in a deformed circular-side triangular microresonator.

A waveguide-connected deformed circular-side triangular microresonator is proposed and fabricated. Room temperature unidirectional light emission is experimentally demonstrated in the far-field pattern with a divergence angle of 38°. Single mode lasing at 1545.4 nm is realized at an injection current of 12 mA. The emission pattern changes drastically upon the binding of a nanoparticle with radius down to several nanometers, predicting applications in electrically pumped, cost-effective, portable and highly sensitive far-field detection of nanoparticles.

Narrow linewidth optical frequency comb based on a directly modulated microcavity laser with optical feedback.

A narrow linewidth optical frequency comb (OFC) based on a directly modulated microcavity laser with external optical feedback is investigated numerically and demonstrated experimentally. Based on the numerical simulations with rate equations, the evolution of the optical and electrical spectra is presented for the direct-modulated microcavity laser with increased feedback strength, and the linewidth property is improved at suitable feedback conditions. The simulation results also show good robustness for the generated OFC in terms of feedback strength and phase. Moreover, the OFC generation experiment is performed by combining with the dual-loop feedback structure to suppress the side mode, and an OFC with a side-mode suppression ratio of 31 dB is realized. Thanks to the high electro-optical response of the microcavity laser, a 15-tone OFC with a frequency interval of 10 GHz is obtained. Finally, the linewidth of each comb tooth is measured to be around 7 kHz under the feedback power of 47 µW, which indicates an enormous compression of approximately 2000 times compared with the free-running continuous-wave microcavity laser.

Wideband multiwavelength Brillouin fiber laser with switchable channel spacing.

A multiwavelength Brillouin fiber laser (MBFL) with a switchable channel spacing is demonstrated using a 1.55-µm single-mode AlGaInAs/InP hybrid square-rectangular laser as a seeding source. The scheme employs a highly nonlinear fiber loop with a feedback path to generate a 10-GHz-spacing MBFL. Then, assisted by a tunable optical bandpass filter, MBFLs with spacing from 20 GHz to 100 GHz at a step of 10 GHz are generated in another highly nonlinear fiber loop based on the cavity-enhanced four-wave mixing. More than 60 lasing lines with an optical signal-to-noise ratio over 10 dB are obtained successfully in all the switchable spacings. The total output power and the channel spacing of the MBFLs are proved to be stable.

Highly efficient waveguide-coupled output in asymmetrically deformed square cavity microlasers.

We propose and demonstrate deformed square cavity microlasers for realizing highly efficient output from a connected waveguide. The square cavities are deformed asymmetrically by replacing two adjacent flat sides with circular arcs to manipulate the ray dynamics and couple the light to the connected waveguide. The numerical simulations show that the resonant light can efficiently couple to the fundamental mode of the multi-mode waveguide by carefully designing the deformation parameter utilizing global chaos ray dynamics and internal mode coupling. An enhancement of approximately six times in the output power is realized in the experiment compared to the non-deformed square cavity microlasers, while the lasing thresholds are reduced by about 20%. The measured far-field pattern shows highly unidirectional emission agreeing well with the simulation, which confirms the feasibility of the deformed square cavity microlasers for practical applications.

Polarized Object Surface Reconstruction Algorithm Based on RU-GAN Network.

There are six possible solutions for the surface normal vectors obtained from polarization information during 3D reconstruction. To resolve the ambiguity of surface normal vectors, scholars have introduced additional information, such as shading information. However, this makes the 3D reconstruction task too burdensome. Therefore, in order to make the 3D reconstruction more generally applicable, this paper proposes a complete framework to reconstruct the surface of an object using only polarized images. To solve the ambiguity problem of surface normal vectors, a jump-compensated U-shaped generative adversarial network (RU-Gan) based on jump compensation is designed for fusing six surface normal vectors. Among them, jump compensation is proposed in the encoder and decoder parts, and the content loss function is reconstructed, among other approaches. For the problem that the reflective region of the original image will cause the estimated normal vector to deviate from the true normal vector, a specular reflection model is proposed to optimize the dataset, thus reducing the reflective region. Experiments show that the estimated normal vector obtained in this paper improves the accuracy by about 20° compared with the previous conventional work, and improves the accuracy by about 1.5° compared with the recent neural network model, which means the neural network model proposed in this paper is more suitable for the normal vector estimation task. Furthermore, the object surface reconstruction framework proposed in this paper has the characteristics of simple implementation conditions and high accuracy of reconstructed texture.

Ferroptosis Inhibitory Compounds from the Deep-Sea-Derived Fungus Penicillium sp. MCCC 3A00126.

Two new xanthones (1 and 2) were isolated from the deep-sea-derived fungus Penicillium sp. MCCC 3A00126 along with 34 known compounds (3-36). The structures of the new compounds were established by spectroscopic data. The absolute configuration of 1 was validated by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated for cytotoxicity and ferroptosis inhibitory activities. Compounds 14 and 15 exerted potent cytotoxicity against CCRF-CEM cells, with IC50 values of 5.5 and 3.5 µM, respectively, whereas 26, 28, 33, and 34 significantly inhibited RSL3-induced ferroptosis, with EC50 values of 11.6, 7.2, 11.8, and 2.2 µM, respectively.

Ovatodiolide inhibits SARS-CoV-2 replication and ameliorates pulmonary fibrosis through suppression of the TGF-ß/TßRs signaling pathway.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to pose threats to public health. The clinical manifestations of lung pathology in COVID-19 patients include sustained inflammation and pulmonary fibrosis. The macrocyclic diterpenoid ovatodiolide (OVA) has been reported to have anti-inflammatory, anti-cancer, anti-allergic, and analgesic activities. Here, we investigated the pharmacological mechanism of OVA in suppressing SARS-CoV-2 infection and pulmonary fibrosis in vitro and in vivo. Our results revealed that OVA was an effective SARS-CoV-2 3CLpro inhibitor and showed remarkable inhibitory activity against SARS-CoV-2 infection. On the other hand, OVA ameliorated pulmonary fibrosis in bleomycin (BLM)-induced mice, reducing inflammatory cell infiltration and collagen deposition in the lung. OVA decreased the levels of pulmonary hydroxyproline and myeloperoxidase, as well as lung and serum TNF-ɑ, IL-1ß, IL-6, and TGF-ß in BLM-induced pulmonary fibrotic mice. Meanwhile, OVA reduced the migration and fibroblast-to-myofibroblast conversion of TGF-ß1-induced fibrotic human lung fibroblasts. Consistently, OVA downregulated TGF-ß/TßRs signaling. In computational analysis, OVA resembles the chemical structures of the kinase inhibitors TßRI and TßRII and was shown to interact with the key pharmacophores and putative ATP-binding domains of TßRI and TßRII, showing the potential of OVA as an inhibitor of TßRI and TßRII kinase. In conclusion, the dual function of OVA highlights its potential for not only fighting SARS-CoV-2 infection but also managing injury-induced pulmonary fibrosis.

Tetracyclic Steroids Bearing a Bicyclo[4.4.1] Ring System as Potent Antiosteoporosis Agents from the Deep-Sea-Derived Fungus Rhizopus sp. W23.

Chemical investigation of the deep-sea-derived fungus Rhizopus sp. W23 resulted in the identification of six new (1-3, 6, 8, 9) and 12 known (4, 5, 10-19) cyclocitrinol analogues, together with one handling artifact (7), all featuring an unusual 7/7/6/5-tetracyclic scaffold and bicyclo[4.4.1] A/B rings. Norcyclocitrinoic acids A and B (1, 2) represent the second occurrence of 24,25-bisnor cyclocitrinols. Structures were assigned to new steroids on the basis of extensive spectroscopic analysis and X-ray crystallography. Compound 13 significantly enhances osteoblastogenesis and inhibits adipogenesis in mature bone marrow stromal cells at 5 µM, indicating a potential to be an antiosteoporosis lead.

Electroacupuncture improves motor function of rats with osteoarthritis by alleviating joint inflammation through the Wnt-7B/β-catenin signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of electroacupuncture on osteoarthritis in rats and explore the possible mechanism.@*METHODS@#Thirty SD rats were randomly divided into osteoarthritis model group, electro-acupuncture group and control group (n=10), and in the former two groups, early osteoarthritis was induced using a modified DMM surgical modeling method. After successful modeling, the rats in the electro-acupuncture group were treated with electro-acupuncture at bilateral "Housanli" and "Anterior knee point". Behavioral tests of the rats were performed and scored using the LequesneMG scale. Subchondral bone degeneration was observed in each group, and serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP were measured using ELISA. The mRNA and protein expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7, and MMP-3 in the cartilage tissue of the knee joints were detected using RT-PCR and Western blotting.@*RESULTS@#In behavioral tests, the rats in the model and electroacupuncture groups had significantly higher LequesneMG scores after modeling than those in the control group (P < 0.05). After 20 days of treatment, LequesneMG scores were significantly lowered in rats in the electroacupuncture as compared with the model rats (P < 0.05). Imaging examination revealed obvious subchondral bone damage in both the electroacupuncture group and the model group, but the damages were significantly milder with former group. Compared with the model rats, the rats receiving electroacupuncture had significantly lower serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP (P < 0.05) with also lower expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7 and MMP-3 in the cartilage tissues at both the mRNA and protein levels (P < 0.05).@*CONCLUSION@#Electroacupuncture can alleviate joint pain and improve subchondral bone damage in rats with osteoarthritis by reducing IL-1β levels in the joint cartilage tissue and serum to alleviate joint inflammation and by reducing such cytokines as ADAMTS-7 and MMP-3 via regulating the Wnt-7B/β-catenin signaling pathway.

Chemical Constituents of the Deep-Sea-Derived Penicillium citreonigrum MCCC 3A00169 and Their Antiproliferative Effects.

Six new citreoviridins (citreoviridins J-O, 1-6) and twenty-two known compounds (7-28) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J-O (1-6) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2-C-7. Pyrenocine A (7), terrein (14), and citreoviridin (20) significantly induced apoptosis for HeLa cells with IC50 values of 5.4 µM, 11.3 µM, and 0.7 µM, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells.