Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids.

Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.

Mimicked Spinal Cord Fibers Trigger Axonal Regeneration and Remyelination after Injury.

Spinal cord injury (SCI) causes tissue structure damage and composition changes of the neural parenchyma, resulting in severe consequences for spinal cord function. Mimicking the components and microstructure of spinal cord tissues holds promise for restoring the regenerative microenvironment after SCI. Here, we have utilized electrospinning technology to develop aligned decellularized spinal cord fibers (A-DSCF) without requiring synthetic polymers or organic solvents. A-DSCF preserves multiple types of spinal cord extracellular matrix proteins and forms a parallel-oriented structure. Compared to aligned collagen fibers (A-CF), A-DSCF exhibits stronger mechanical properties, improved enzymatic stability, and superior functionality in the adhesion, proliferation, axonal extension, and myelination of differentiated neural progenitor cells (NPCs). Notably, axon extension or myelination has been primarily linked to Agrin (AGRN), Laminin (LN), or Collagen type IV (COL IV) proteins in A-DSCF. When transplanted into rats with complete SCI, A-DSCF loaded with NPCs improves the survival, maturation, axon regeneration, and motor function of the SCI rats. These findings highlight the potential of structurally and compositionally biomimetic scaffolds to promote axonal extension and remyelination after SCI.

Spleen stiffness determined by spleen-dedicated device accurately predicted esophageal varices in cirrhosis patients.

Background: The advantages of spleen stiffness in prediction of high-risk varices (HRV) in cirrhosis patients have been confirmed. Recently, a new device utilizing a 100 Hz probe dedicated to spleen stiffness measurement (SSM) was developed. Objectives: To validate the clinical applicability of SSM@100 Hz in predicting HRV by comparing it with other non-invasive tests (NITs). Design: A prospective cohort study. Methods: A total of 171 cirrhosis patients who underwent esophagogastroduodenoscopy (EGD) examination were included in this study. SSM using a 100 Hz probe and liver stiffness measurement using a 50 Hz probe were performed. Additionally, 22 healthy controls underwent spleen stiffness evaluation using the 100 Hz probe. Results: The failure rates of spleen stiffness examination in patients with cirrhosis and in healthy controls were 2.9% and 4.5%, respectively. The means of SSM values were 56.4 ± 21.6 and 13.8 ± 6.7 kPa in cirrhosis and controls. SSM increased proportionally with the severity of esophageal varices. The area under receiver operating characteristic (ROC) for spleen stiffness in predicting HRV was 0.881 (95% confidence interval 0.829-0.934), with a cutoff value of 43.4 kPa. The accuracy, false negative rate and EGD spare rate were 86.5%, 2.5% and 24.3%, respectively. For HRV prediction, SSM was comparable to expanded Baveno VI and VII and superior to other NITs. As to viral versus non-viral cirrhosis and compensated versus decompensated cirrhosis, the cut-off and performance of SSM were different. Conclusion: SSM@100 Hz demonstrates high accuracy in predicting HRV with a low missed HRV rate. Our findings suggest that SSM@100 Hz can be used independently due to its simplicity and effectiveness. However, further studies are needed to determine appropriate cutoff values based on the cause of cirrhosis and liver function. Trail Registration: ChiCTR2300070270.

Comparison of Ultrasound and CT Imaging for the Diagnosis of Coronavirus Disease and Influenza A Pneumonia.

OBJECTIVE: The outbreak of coronavirus disease (COVID-19) coincided with the season of influenza A pneumonia, a common respiratory infectious disease. Therefore, this study compared ultrasonography and computed tomography (CT) for the diagnosis of the two diseases. METHODS: Patients with COVID-19 or influenza A infection hospitalized at our hospital were included. The patients were examined by ultrasonography every day. The CT examination results within 1 day before and after the day of the highest ultrasonography score were selected as the controls. The similarities and differences between the ultrasonography and CT results in the two groups were compared. RESULTS: There was no difference between the ultrasonography and CT scores (P = .307) for COVID-19, while there was a difference between ultrasonography and CT scores for influenza A pneumonia (P = .024). The ultrasonography score for COVID-19 was higher than that for influenza A pneumonia (P = .000), but there was no difference between the CT scores (P = .830). For both diseases, there was no difference in ultrasonography and CT scores between the left and right lungs; there were differences between the CT scores of the upper and middle lobes, as well as between the upper and lower lobes of the lungs; however, there was no difference between the lower and middle lobes of the lungs. CONCLUSION: Ultrasonography is equivalent to the gold standard CT for diagnosing and monitoring the progression of COVID-19. Because of its convenience, ultrasonography has important application value. Furthermore, the diagnostic value of ultrasonography for COVID-19 is higher than that for influenza A pneumonia.

Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys.

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.

Advances in Microgravity Directed Tissue Engineering.

Tissue engineering aims to generate functional biological substitutes to repair, sustain, improve, or replace tissue function affected by disease. With the rapid development of space science, the application of simulated microgravity has become an active topic in the field of tissue engineering. There is a growing body of evidence demonstrating that microgravity offers excellent advantages for tissue engineering by modulating cellular morphology, metabolism, secretion, proliferation, and stem cell differentiation. To date, there have been many achievements in constructing bioartificial spheroids, organoids, or tissue analogs with or without scaffolds in vitro under simulated microgravity conditions. Herein, the current status, recent advances, challenges, and prospects of microgravity related to tissue engineering are reviewed. Current simulated-microgravity devices and cutting-edge advances of microgravity for biomaterials-dependent or biomaterials-independent tissue engineering to offer a reference for guiding further exploration of simulated microgravity strategies to produce engineered tissues are summarized and discussed.

Spinal cord tissue engineering via covalent interaction between biomaterials and cells.

Noncovalent interactions between cells and environmental cues have been recognized as fundamental physiological interactions that regulate cell behavior. However, the effects of the covalent interactions between cells and biomaterials on cell behavior have not been examined. Here, we demonstrate a combined strategy based on covalent conjugation between biomaterials (collagen fibers/lipid nanoparticles) and various cells (exogenous neural progenitor cells/astrocytes/endogenous tissue-resident cells) to promote neural regeneration after spinal cord injury (SCI). We found that metabolic azido-labeled human neural progenitor cells conjugated on dibenzocyclooctyne-modified collagen fibers significantly promoted cell adhesion, spreading, and differentiation compared with noncovalent adhesion. In addition, dibenzocyclooctyne-modified lipid nanoparticles containing edaravone, a well-known ROS scavenger, could target azide-labeled spinal cord tissues or transplanted azide-modified astrocytes to improve the SCI microenvironment. The combined application of these covalent conjugation strategies in a rat SCI model boosted neural regeneration, suggesting that the covalent interactions between cells and biomaterials have great potential for tissue regeneration.

Transplantation of neural stem progenitor cells from different sources for severe spinal cord injury repair in rat.

Neural stem progenitor cell (NSPC) transplantation has been regarded as a promising therapeutic method for spinal cord injury (SCI) repair. However, different NSPCs may have different therapeutic effects, and it is therefore important to identify the optimal NSPC type. In our study, we compared the transcriptomes of human fetal brain-derived NSPCs (BNSPCs), spinal cord-derived NSPCs (SCNSPCs) and H9 embryonic stem-cell derived NSPCs (H9-NSPCs) in vitro and subsequently we transplanted each NSPC type on a collagen scaffold into a T8-9 complete SCI rat model in vivo. In vitro data showed that SCNSPCs had more highly expressed genes involved in nerve-related functions than the other two cell types. In vivo, compared with BNSPCs and H9-NSPCs, SCNSPCs exhibited the best therapeutic effects; in fact, SCNSPCs facilitated electrophysiological and hindlimb functional recovery. This study demonstrates that SCNSPCs may be an appropriate candidate cell type for SCI repair, which is of great clinical significance.

Lung ultrasonography findings of coronavirus disease 2019 patients: Comparison between primary and secondary regions of China.

BACKGROUND: An unexplained pneumonia occurred in Wuhan, China in December 2019, later identified and named coronavirus disease 2019 (COVID-19). This study aimed to compare the ultrasonographic features of the lung between patients with COVID-19 in Wuhan (the primary region) and those in Beijing (the secondary region) and to find the value of applying ultrasound in COVID-19. METHODS: A total of 248 COVID-19 cases were collected, including long-term residents in Wuhan (138), those who had a short-term stay in Wuhan (72), and those who had never visited Wuhan (38). Ultrasound examination was performed daily; the highest lung ultrasound score (LUS) was the first comparison point, while the LUS of the fifth day thereafter was the second comparison point. The differences between overall treatment and ultrasonography of left and right lungs among groups were compared. RESULTS: The severity decreased significantly after treatment. The scores of the groups with long-term residence and short-term stay in Wuhan were higher than those of the group that had never been to Wuhan. CONCLUSION: Ultrasonography is effective for dynamic monitoring of COVID-19. The ultrasonographic features of patients in the Wuhan area indicated relatively severe disease. Thus, Wuhan was the main affected area of china.

Inflammatory Microenvironment-Responsive Nanomaterials Promote Spinal Cord Injury Repair by Targeting IRF5.

Spinal cord injury (SCI) involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages rather than prohealing M2 macrophages, and oxidative stress. Interferon regulatory factor 5 (IRF5) is a promising therapeutic target in regulation of macrophage reprogramming from the M1 to M2 phenotype. However, knockdown of IRF5 expression mediated by small interfering RNA (siRNA) is limited by instability and poor cellular uptake. In the present study, polyethylenimine-conjugated, diselenide-bridged mesoporous silica nanoparticles are tailored to regulate macrophage polarization by controllably delivering siRNA to silence IRF5. The MSN provides reactive oxygen species (ROS)-responsive degradation and release, while polyethylenimine-function offers efficient loading of siRNA-IRF5 and enhanced endosome escape. As a consequence, the intelligent nanomaterial effectively transfects the siRNA-IRF5 with its remaining high stability and bioactivity, thereby effectively regulating the M1-to-M2 macrophage conversion in vitro and in vivo. Importantly, administration of the functional nanomaterial in crush SCI mice suppresses excessive inflammation, enhances neuroprotection, and promotes locomotor restoration. Collectively, the ROS-responsive nanomedicine provides a gene silencing strategy for regulating macrophage polarization and oxidative balance in SCI repair.

Clinical study of injectable collagen scaffold with autologous fat cells for repair of severe vocal fold injury.

Cell retention and survival after transplantation remains a major problem for long-term efficiency in therapy of severe vocal fold injury with autologous cells. In this study, injectable collagen scaffold was used to deliver autologous fat cells (AFCs) for repairing of severe vocal fold injury. We found injectable collagen scaffold could enhance the retention and survival of green fluorescent protein (GFP) labeled fat cells in the transplantation sites in rats. Based on these data, a randomized controlled clinical trial was conducted to evaluate the safety and efficiency of transplantation of collagen scaffold with AFCs for severe vocal fold injury. Ten patients with vocal fold paralysis were randomly assigned to control (AFCs only) and intervention (AFCs + collagen) groups. AFCs with or without collagen scaffold were injected into vocal folds of patients under general anesthesia, respectively. The safety and efficacy were regularly assessed during 24 months post-surgery. No obvious complications occurred in all patients during the follow-up. The collagen scaffold maintained the stability of implants after injection and reconstructed the vocal fold structure. The improvement of voice quality of patients was observed through voice quality evaluation with the voice handicap index (VHI) questionnaire, as well as acoustic analysis of maximum phonation time, jitter, and shimmer. The VHI score of patients in AFCs + collagen group improved significantly than those in AFCs group at 6, 12 and 24 months post-surgery. It demonstrates the injectable collagen scaffold is safe and efficient for delivering AFCs for vocal fold injury.

Pilot study on the value of echocardiography combined with lung ultrasound to evaluate COVID-19 pneumonia.

BACKGROUND: This study aimed to investigate the relationship between echocardiography results and lung ultrasound score (LUS) in coronavirus disease 2019 (COVID-19) pneumonia patients and evaluate the impact of the combined application of these techniques in the evaluation of COVID-19 pneumonia. METHODS: Hospitalized COVID-19 pneumonia patients who underwent daily lung ultrasound and echocardiography were included in this study. Patients with tricuspid regurgitation within three days of admission were enrolled. Moreover, the correlation and differences between their pulmonary artery pressure (PAP) and LUS on days 3, 8, and 13 were analyzed. The inner diameter of the pulmonary artery root as well as the size of the atria and ventricles were also considered. RESULTS: The PAP on days 3, 8, and 13 of hospitalization was positively correlated with the LUS (r = 0.448, p = 0.003; r = 0.738, p < 0.001; r = 0.325, p = 0.036, respectively). On day 8, the values of both PAP and LUS were higher than on days 3 and 13 (p < 0.01). Similarly, PAP and LUS were significantly increased in 92.9% (39/42) and 90.5% (38/42) of patients, respectively, and at least one of these two values was positive in 97.6% (41/42) of cases. The inner diameters of the right atrium, right ventricle, and pulmonary artery also differed significantly from their corresponding values on days 3 and 13 (p < 0.05). CONCLUSIONS: PAP is positively correlated with LUS in COVID-19 pneumonia. The two values could be combined for a more precise assessment of disease progression and recovery status.

Lineage tracing reveals the origin of Nestin-positive cells are heterogeneous and rarely from ependymal cells after spinal cord injury.

Nestin is expressed extensively in neural stem/progenitor cells during neural development, but its expression is mainly restricted to the ependymal cells in the adult spinal cord. After spinal cord injury (SCI), Nestin expression is reactivated and Nestin-positive (Nestin+) cells aggregate at the injury site. However, the derivation of Nestin+ cells is not clearly defined. Here, we found that Nestin expression was substantially increased in the lesion edge and lesion core after SCI. Using a tamoxifen inducible CreER(T2)-loxP system, we verified that ependymal cells contribute few Nestin+ cells either to the lesion core or the lesion edge after SCI. In the lesion edge, GFAP+ astrocytes were the main cell type that expressed Nestin; they then formed an astrocyte scar. In the lesion core, Nestin+ cells expressed αSMA or Desmin, indicating that they might be derived from pericytes. Our results reveal that Nestin+ cells in the lesion core and edge came from various cell types and rarely from ependymal cells after complete transected SCI, which may provide new insights into SCI repair.

Efficient preparation of (R)-2-(2,5-difluorophenyl)pyrrolidine via a recycle process of resolution.

An efficient preparation of (R)-2-(2,5-difluorophenyl)pyrrolidine ((R)-1) from the racemate based on a recycle process of resolution/racemization was described. In the process, the desired (R)-1 was obtained by resolution with D-malic acid in 95% EtOH. Meanwhile, the undesired (S)-1 could be racemized in the presence of potassium hydroxide in DMSO. After three times of recycle process, the desired freebase (R)-1 was obtained in a yield of 61.7% with excellent ee (98.4%).

Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury.

BACKGROUND: Microtubule-stabilizing agents have been demonstrated to modulate axonal sprouting during neuronal disease. One such agent, Epothilone D, has been used to treat spinal cord injury (SCI) by promoting axonal sprouting at the lesion site after SCI. However, the role of Epothilone D in the differentiation of neural stem cells (NSCs) in SCI repair is unknown. In the present study, we mainly explored the effects and mechanisms of Epothilone D on the neuronal differentiation of NSCs and revealed a potential new SCI treatment. METHODS: In vitro differentiation assays, western blotting, and quantitative real-time polymerase chain reaction were used to detect the effects of Epothilone D on NSC differentiation. Retrograde tracing using a pseudotyped rabies virus was then used to detect neuronal circuit construction. RNA sequencing (RNA-Seq) was valuable for exploring the target gene involved in the neuronal differentiation stimulated by Epothilone D. In addition, lentivirus-induced overexpression and RNA interference technology were applied to demonstrate the function of the target gene. Last, an Apol8-NSC-linear ordered collagen scaffold (LOCS) graft was prepared to treat a mouse model of SCI, and functional and electrophysiological evaluations were performed. RESULTS: We first revealed that Epothilone D promoted the neuronal differentiation of cultured NSCs and facilitated neuronal relay formation in the injured site after SCI. Furthermore, the RNA-Seq results demonstrated that Apol8 was upregulated during Epothilone D-induced neuronal relay formation. Lentivirus-mediated Apol8 overexpression in NSCs (Apol8-NSCs) promoted NSC differentiation toward neurons, and an Apol8 interference assay showed that Apol8 had a role in promoting neuronal differentiation under the induction of Epothilone D. Last, Apol8-NSC transplantation with LOCS promoted the neuronal differentiation of transplanted NSCs in the lesion site as well as synapse formation, thus improving the motor function of mice with complete spinal cord transection. CONCLUSIONS: Epothilone D can promote the neuronal differentiation of NSCs by upregulating Apol8, which may provide a promising therapeutic target for SCI repair.

Binary scaffold facilitates in situ regeneration of axons and neurons for complete spinal cord injury repair.

The limited regrowth of transected axons and insufficient regeneration of lost neurons in adult mammals collectively hinder complete spinal cord injury (SCI) repair. Hence, designing an ideal bio-scaffold which could coordinate the regeneration of axons and neurons in situ might be able to effectively facilitate the reconstruction of neural circuits and the recovery of nerve function after complete SCI. In this study, a sponge-like collagen scaffold with good drug release characteristics and good nerve cell compatibility was prepared and used as a drug delivery platform. When doubly modified with Taxol liposomes and collagen-binding neurotrophic factor 3, the scaffold dually alleviated myelin-derived inhibition on neurite outgrowth of neurons and neuronal differentiation of neural stem cells in vitro. Meanwhile, the binary-drug modified scaffold was also able to simultaneously promote both axonal and neuronal regeneration when implanted into a complete transected SCI model. Additionally, the regenerated axons and neurons throughout the lesion site formed extensive synaptic connections. Finally, complete SCI rats that received binary scaffold implantation exhibited optimal neuroelectrophysiological recovery and hindlimb locomotor improvement. Taken together, implantation of the binary scaffold can establish neural bridging networks for functional recovery, representing a clinically promising strategy for complete SCI repair.

A functional scaffold to promote the migration and neuronal differentiation of neural stem/progenitor cells for spinal cord injury repair.

After spinal cord injury (SCI), endogenous neural/progenitor stem cells (NSPCs) were activated in neural tissue adjacent to the injured segment, but few cells migrated to the injury epicenter and differentiated into neurons. N-cadherin regulates mechanical adhesion between NSPCs, and also drives NSPCs migration and promotes NSPCs differentiation. In this study, linearly ordered collagen scaffold (LOCS) was modified with N-cadherin through a two-step cross-linking between thiol and amino group. The results indicated that N-cadherin modification improved the adhesion of NSPCs on collagen scaffold and increased the differentiation into neurons. When LOCS-Ncad was transplanted into complete transected rat spinal cords, more NSPCs migrated to the lesion center and more newborn neurons appeared within the injury site. Furthermore, rats transplanted with LOCS-Ncad showed significantly improved locomotor recovery compared with the rats without implants. Collectively, our results suggest that LOCS-Ncad may be a promising treatment option to facilitate SCI repair by recruiting endogenous NSPCs to the lesion center and promoting neuronal differentiation.

Epidermal growth factor receptor-extracellular-regulated kinase blockade upregulates TRIM32 signaling cascade and promotes neurogenesis after spinal cord injury.

Nerve regeneration is blocked after spinal cord injury (SCI) by a complex myelin-associated inhibitory (MAI) microenvironment in the lesion site; however, the underlying mechanisms are not fully understood. During the process of neural stem cell (NSC) differentiation, pathway inhibitors were added to quantitatively assess the effects on neuronal differentiation. Immunoprecipitation and lentivirus-induced overexpression were used to examine effects in vitro. In vivo, animal experiments and lineage tracing methods were used to identify nascent neurogenesis after SCI. In vitro results indicated that myelin inhibited neuronal differentiation by activating the epidermal growth factor receptor (EGFR)-extracellular-regulated kinase (ERK) signaling cascade. Subsequently, we found that tripartite motif (TRIM) 32, a neuronal fate-determining factor, was inhibited. Moreover, inhibition of EGFR-ERK promoted TRIM32 expression and enhanced neuronal differentiation in the presence of myelin. We further demonstrated that ERK interacts with TRIM32 to regulate neuronal differentiation. In vivo results indicated that EGFR-ERK blockade increased TRIM32 expression and promoted neurogenesis in the injured area, thus enhancing functional recovery after SCI. Our results showed that EGFR-ERK blockade antagonized MAI of neuronal differentiation of NSCs through regulation of TRIM32 by ERK. Collectively, these findings may provide potential new targets for SCI repair.

Diagnostic effect of shear wave elastography imaging for differentiation of malignant liver lesions: a meta-analysis.

BACKGROUND: Shear wave elastography (SWE) imaging have been proposed for characterization of focal liver lesions. We conducted a meta-analysis to evaluate the accuracy and clinical utility of SWE imaging for differentiation of malignant and benign hepatic lesions. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically reviewed to search for studies published between January 1, 1990, and November 30, 2018. The studies published in English relating to the evaluation the diagnostic accuracy of SWE imaging for distinguishing malignant and benign liver lesions were retrieved and examined for pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios, using bivariate random-effects models. The hierarchical summary receiver operating characteristic (HSROC) curve was estimated to assess the SWE imaging accuracy. The clinical utility of SWE imaging for differentiation of malignant liver lesions was evaluated by Fagan plot. RESULTS: A total of 15 studies, involving 1894 liver lesions in 1728 patients, were eligible for the meta-analysis. The pooled sensitivity and specificity for identification of malignant liver lesions were 0.82 (95% CI: 0.77-0.86) and 0.82 (95% CI: 0.76-0.87), respectively. The AUC was 0.89 (95% CI: 0.86-0.91). When the pre-test probability was 50%, after SWE imaging measurement over the cut-off value (positive result), the corresponding post-test probability for the presence of malignant liver lesions was 82%; the post-test probability was 18% after negative measurement. CONCLUSIONS: SWE imaging showed high sensitivity and specificity in differentiating malignant and benign liver lesions and may be promising for noninvasive evaluation of liver lesions. TRIAL REGISTRATION: The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42018104510 .

QED cascade saturation in extreme high fields.

Upcoming ultrahigh power lasers at 10 PW level will make it possible to experimentally explore electron-positron (e-e+) pair cascades and subsequent relativistic e-e+ jets formation, which are supposed to occur in extreme astrophysical environments, such as black holes, pulsars, quasars and gamma-ray bursts. In the latter case it is a long-standing question as to how the relativistic jets are formed and what their temperatures and compositions are. Here we report simulation results of pair cascades in two counter-propagating QED-strong laser fields. A scaling of QED cascade growth with laser intensity is found, showing clear cascade saturation above threshold intensity of ~1024 W/cm2. QED cascade saturation leads to pair plasma cooling and longitudinal compression along the laser axis, resulting in the subsequent formation of relativistic dense e-e+ jets along transverse directions. Such laser-driven QED cascade saturation may open up the opportunity to study energetic astrophysical phenomena in laboratory.