Cell-free fat extract promotes axon regeneration and retinal ganglion cells survival in traumatic optic neuropathy.

Injuries to axons within the central nervous system (CNS) pose a substantial clinical challenge due to their limited regenerative capacity. This study investigates the therapeutic potential of Cell-free fat extract (CEFFE) in CNS injury. CEFFE was injected intravitreally after the optic nerve was crushed. Two weeks post-injury, quantification of regenerated axons and survival rates of retinal ganglion cells (RGCs) were performed. Subsequently, comprehensive gene ontology (GO) an-notation elucidated the cellular origins and functional attributes of CEFFE components. Molecular mechanisms underlying CEFFE's therapeutic effects were explored through Western blotting (WB). Additionally, levels of inflammatory factors within CEFFE were determined using enzyme-linked immunosorbent assay (ELISA), and histological staining of microglia was conducted to assess its impact on neuroinflammation. CEFFE demonstrated a significant capacity to promote axon re-generation and enhance RGCs survival. GO annotation revealed the involvement of 146 proteins within CEFFE in axonogenesis and neurogenesis. WB analysis unveiled the multifaceted pathways through which CEFFE exerts its therapeutic effects. Elevated levels of inflammatory factors were detected through ELISA, and CEFFE exhibited a modulatory effect on microglial activation in the retinal tissue following optic nerve crush (ONC). The present study highlights the therapeutic promise of CEFFE in the management of CNS injuries, exemplified by its ability to foster axon regeneration and improve RGCs survival.

Stromal Vascular Fraction Gel (SVF-Gel) Combined with Nanofat for Tear Trough Deformity.

BACKGROUND: Tear trough deformity makes patients appear tired. Patients with less severe tear trough deformity prefer a less invasive method to correct the deformity. The infraorbital area is a multilayered tissue, and the aging of various components leads to tear trough deformity. To this end, we utilized the different characteristics of different fat derivatives to correct tear trough deformity. METHODS: Thirty-two patients with Barton Grade I/II tear trough deformity were enrolled in this study between September 2020 and March 2021. We injected Stromal Vascular Fraction Gel (SVF-Gel) into the suborbicularis oculi fat layer and Nanofat into the subcutaneous. After 12 months of follow-up, we evaluated the changes using standardized clinical photogrammetric techniques, volume, global aesthetic improvement scale, and patient self-evaluation. RESULTS: There were no major complications in any of the 32 patients. The measured data points demonstrated improvements in all aesthetic parameters. The width of the tear trough and the distance from the pupil to the tear trough improved. The Global Aesthetic Improvement Scale (GAIS) showed a high score (2.45±0.64 points), with patient self-assessment showing satisfactory results. CONCLUSION: SVF-Gel combined with Nanofat injection can effectively correct tear trough deformities. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Knockdown of Porf-2 restores visual function after optic nerve crush injury.

Retinal ganglion cells (RGCs), the sole output neurons in the eyes, are vulnerable to diverse insults in many pathological conditions, which can lead to permanent vision dysfunction. However, the molecular and cellular mechanisms that contribute to protecting RGCs and their axons from injuries are not completely known. Here, we identify that Porf-2, a member of the Rho GTPase activating protein gene group, is upregulated in RGCs after optic nerve crush. Knockdown of Porf-2 protects RGCs from apoptosis and promotes long-distance optic nerve regeneration after crush injury in both young and aged mice in vivo. In vitro, we find that inhibition of Porf-2 induces axon growth and growth cone formation in retinal explants. Inhibition of Porf-2 provides long-term and post-injury protection to RGCs and eventually promotes the recovery of visual function after crush injury in mice. These findings reveal a neuroprotective impact of the inhibition of Porf-2 on RGC survival and axon regeneration after optic nerve injury, providing a potential therapeutic strategy for vision restoration in patients with traumatic optic neuropathy.

LncRNA WEE2-AS1 is a diagnostic biomarker that predicts poor prognoses in patients with glioma.

BACKGROUND: Glioma is characterized by high morbidity, high mortality, and poor prognosis. Despite tremendous advances in the treatment of glioma, the prognosis of patients with glioma is still unsatisfactory. There is an urgent need to discover novel molecular markers that effectively predict prognosis in patients with glioma. The investigation of the role of WEE2-AS1 in various tumors is an emerging research field, but the biological function and prognostic value of WEE2-AS1 in glioma have rarely been reported. This study aimed to assess the value of WEE2-AS1 as a potential prognostic marker of glioma. METHODS: Gene expression (RNA-Seq) data of patients with glioma were extracted from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The Wilcoxon rank sum test was used to analyze the expression of WEE2-AS1 in the cells and tissues of glioma. The Kruskal-Wallis rank sum test, Wilcoxon rank sum test, and logistic regression were used to evaluate the relationship between clinical variables and expression of WEE2-AS1. Cox regression analysis and the Kaplan-Meier method were used to evaluate the prognostic factors in glioma. A nomogram based on Cox multivariate analysis was used to predict the impact of WEE2-AS1 on glioma prognosis. Gene Set Enrichment Analysis (GSEA) was used to identify key WEE2-AS1-associated signaling pathways. Spearman's rank correlation was used to elucidate the association between WEE2-AS1 expression and immune cell infiltration levels. RESULTS: We found that WEE2-AS1 was overexpressed in a variety of cancers, including glioma. High expression of WEE2-AS1 was associated with glioma progression. We determined that the expression of WEE2-AS1 might be an independent risk factor for the survival and prognosis of patients with glioma. We further observed that the mechanism of WEE2-AS1-mediated tumorigenesis involved neuroactive ligand-receptor interaction, cell cycle, and the infiltration of immune cells into the glioma microenvironment. CONCLUSION: These findings demonstrate that WEE2-AS1 is a promising biomarker for the diagnosis and prognosis of patients with glioma. An increased understanding of its effects on the regulation of cell growth may lead to the development of clinical applications that improve the prognostic status of patients with glioma.

Novel method for correcting cephalic rotation in Asian nasal tip plasty.

BACKGROUND: To correct nasal tip cephalic rotation, SEG made of cartilage or Medpor are often used in rhinoplasty. These techniques require extensive experience for the surgeon, and not all patients can accept this procedure. In this research, we introduce a new method to correct nasal tip cephalic rotation that is relatively simple and rapid. METHODS: Fifty-nine patients who had rhinoplasty using our scaffold were enrolled in the study between January 2020 and January 2021. The authors evaluated the change of nasolabial angel by photogrammetry using standardized clinical photogrammetric techniques. Patients' satisfaction regarding postoperative results was also surveyed. RESULTS: The mean postoperative follow-up duration was 12 months. No complication (infection, extrusion, and displacement) was happened in all patients. Analysis showed our scaffold can correct nasal tip cephalic rotation effectively (98.61±1.21 preoperatively and 89.68±0.99 postoperatively, P<0.0001). And the patient satisfaction rate is 98%. CONCLUSION: We constructed an integrated scaffold by simply folding and suturing a high-density polyethylene sheet (Su-Por) sheet to correct nasal tip cephalic rotation. Using the scaffold we designed, we did not need to alter the structure of the nasal septum, which reduced the operative duration and simplified the surgical procedure.

Experimental Study on the Biological Outcome of Auricular Cartilage and Costal Cartilage at Different Time Periods After Autologous Cartilage Rhinoplasty.

Since autologous cartilage is a good transplant material, it is widely used in various fields of clinical medicine. In this study, we collected clinical specimens obtained at different numbers of years after transplantation and used histologic staining to explore the post-transplantation changes in auricular cartilage and costal cartilage. A retrospective analysis was performed on patients who underwent primary autologous cartilage rhinoplasty and secondary rhinoplasty from 2017 to 2021, and the remaining autologous cartilage tissue after surgery was used for histologic testing. As time progressed after transplantation, the density of costal chondrocytes decreased first and then increased, while the secretion of type II collagen and extracellular matrix both decreased slightly. There was a clear boundary between the cartilage tissue and the surrounding connective tissue, and there was no ingrowth of blood vessels in the cartilage. Auricular cartilage showed a decrease in the integrity of the matrix edge. Moreover, local fibrosis was visible, and vascular ingrowth was observed at the edge of the cartilage. The content of type II collagen first increased and then decreased, and the cell secretion function was lower than that of normal chondrocytes. The results of the study suggest that the histologic outcome of elastic cartilage after transplantation is significantly different from that of hyaline cartilage. Moreover, costal cartilage was more stable than auricular cartilage after transplantation.

Biological Changes of Autologous Auricular Cartilage in Rhinoplasty.

Autologous auricular cartilage is used extensively as a good graft material in rhinoplasty. In this study, clinical specimens from patients who underwent revision rhinoplasty with auricular cartilage grafts were collected to compare the changes before and after auricular cartilage transplantation with the use of histologic, immunohistochemical, and quantitative assays. Patients who underwent revision rhinoplasty from 2018 to 2022 were analyzed. Fresh auricular cartilage left after surgery and auricular cartilage graft tissue were examined and compared. Compared with fresh auricular cartilage, local fibrosis was seen in the transplanted auricular cartilage with a slight decrease in elastic fibers, type II collagen, and extracellular matrix secretion. Quantitative assays showed a decrease in glycosaminoglycan, DNA, and total collagen content in the transplanted auricular cartilage tissue. The results of the study suggest that the histologic characteristics, cell functionality, and biochemical composition of the grafted cartilage changed to a certain extent after autologous auricular cartilage graft rhinoplasty. These results provide insights into the selection of graft/filler materials for rhinoplasty and what changes to expect.

Inverse lithography source and mask optimization via Bayesian compressive sensing.

Source and mask optimization (SMO) is a key technique to guarantee the lithographic fidelity for 14-5 nm technology nodes. The balance between lithography fidelity and computational efficiency is a big issue for SMO. Our earlier works of compressive sensing SMO (CS-SMO) effectively accelerated the SMO procedure by sampling monitoring pixels. However, the imaging fidelity of the results of these methods can be further improved. This paper proposes a novel Bayesian compressive sensing source and mask optimization (BCS-SMO) method, to the best of our knowledge, to achieve the goals of fast SMO and high fidelity patterns simultaneously. The SMO procedure can be achieved by solving as a series of re-weighted l1-norm reconstruction problems, and the weights can be updated in every iteration. The results demonstrate that, with similar computational efficiency, the BCS-SMO method can significantly improve lithographic fidelity over the current CS-SMO method.

Analysis of Factors Affecting Postoperative Drainage After Comprehensive Rhinoplasty.

This study aimed to explore and analyze the factors influencing the drainage volume after comprehensive rhinoplasty. The clinical data of 102 patients who underwent comprehensive rhinoplasty at Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine from August 2019 to August 2021 were retrospectively analyzed. The effects of age, sex, body mass index, whether an osteotomy was performed, and whether a nasal septum flap was obtained on the indwelling time of the drainage tube after the operation were analyzed by single factor analysis and multiple logistic regression analysis. Age, body mass index, whether it was a primary rhinoplasty, whether an osteotomy was performed, and whether a nasal septum flap was obtained were the influencing factors for drainage time after augmentation rhinoplasty ( P <0.05). Sex had little effect on the drainage time after comprehensive rhinoplasty ( P >0.05). Body mass index, whether an osteotomy was performed and whether a nasal septum flap was obtained were the independent influencing factors for the postoperative drainage time ( P <0.05). For patients with multiple independent influencing factors, individualized management during the perioperative period should be promoted, and reasonable treatment strategies should be formulated, so as to reduce the indwelling time of the drainage tube after the operation.

Construction of a lncRNA-associated competing endogenous RNA regulatory network after traumatic brain injury in mouse.

Traumatic brain injury (TBI) is a major public health problem worldwide which causes high mortality and disability. Functioning as microRNA (miRNA) sponges, long non-coding RNA (lncRNA) regulates the expression of protein-coding genes in a competing endogenous RNA (ceRNA) network. However, the lncRNA-associated ceRNA in TBI remains unclear. In this study, we processed the raw SRR files of mice cortex samples of sham injury (n = 3) and TBI groups (n = 3) to count files. Then, the expression profiles of lncRNAs and mRNAs were identified, and 86 differentially expressed (DE) lncRNAs and 1201 DEmRNAs between sham and TBI groups were identified. The DEmRNAs were used to perform enrichment analyses. Next, a lncRNA-miRNA-mRNA regulatory ceRNA network was constructed. The network consisted of 23 mRNAs, 5 miRNAs and 2 lncRNAs. The expression alternations of the 5 miRNAs were validated via qRT-PCR. The subnetwork of hub lncRNA Neat1 was extracted. We identified a potential inflammatory associated regulatory axis: Neat1/miR-31-5p/Myd88 axis. The PPI network based on DEmRNA involved in ceRNA network was constructed PPI networks to identify the hub genes. Finally, DElncRNAs and DEmRNAs were selected randomly and validated by qRT-PCR. In conclusion, with the lncRNA-miRNA-mRNA ceRNA network provided above, we can improve our understanding of the regulatory mechanisms and interaction among lncRNAs, miRNAs and mRNAs in TBI process.

Optimized spatially modulated polarimetry with an efficient calibration method and hybrid gradient descent reconstruction.

High accuracy and fast polarization measurements at a low light field are significant in various applications, spanning from quantum optics to diagnosis of living biological tissue. In this paper, we developed an optimized spatially modulated polarimetry (OSMP) with an efficient calibration method that establishes a quantitative link between the intensity distribution of an arbitrary incident polarization state and four intensity distributions of specific input polarization states. Such a calibration method not only considers the total polarimetric errors induced by polarization elements and the focusing lens but also simplifies the procedure of calibration. A hybrid gradient descent (HGD) algorithm, combining the rapidity of optimization of gradient descent (GD) algorithm and the accuracy of optimization of direct enumeration (DE) algorithm, was proposed to restructure the Stokes parameters. Experiment results illustrate that the proposed method can significantly improve the speed and accuracy of polarization measurements over existing spatially modulated polarimeters based on the vortex wave retarder, whether in strong or low light fields.

Sampling-based imaging model for fast source and mask optimization in immersion lithography.

Current source and mask optimization (SMO) research tends to focus on advanced inverse optimization algorithms to accelerate SMO procedures. However, innovations of forward imaging models currently attract little attention, which impacts computational efficiency more significantly. A sampling-based imaging model is established with the innovation of an inverse point spread function to reduce computational dimensions, which can provide an advanced framework for fast inverse lithography. Simulations show that the proposed SMO method with the help of the proposed model can further speed up the algorithm-accelerated SMO procedure by a factor of 3.

Maf1 regulates axonal regeneration of retinal ganglion cells after injury.

Retinal ganglion cells (RGCs) are the sole output neurons that carry visual information from the eye to the brain. Due to various retinal and optic nerve diseases, RGC somas and axons are vulnerable to damage and lose their regenerative capacity. A basic question is whether the manipulation of a key regulator of RGC survival can protect RGCs from retinal and optic nerve diseases. Here, we found that Maf1, a general transcriptional regulator, was upregulated in RGCs from embryonic stage to adulthood. We determined that the knockdown of Maf1 promoted the survival of RGCs and their axon regeneration through altering the activity of the PTEN/mTOR pathway, which could be blocked by rapamycin. We further observed that the inhibition of Maf1 prevented the retinal ganglion cell complex from thinning after optic nerve crush. These findings reveal a neuroprotective effect of knocking down Maf1 on RGC survival after injury and provide a potential therapeutic strategy for traumatic optic neuropathy.

Exposure latitude aware source and mask optimization for extreme ultraviolet lithography.

Extreme ultraviolet (EUV) lithography is a new generation of integrated circuit manufacturing technology with great development prospects. EUV lithography has more significant demand for high exposure latitude (EL) due to greater requirements for the stability of the light source. Source and mask optimization (SMO) technology is widely used to compensate for imaging distortion. In this paper, we propose an EL-aware SMO (ELASMO) method that uses a low-resist threshold sensitivity (LRS) penalty function to improve the EL in EUV lithography. Compared to conventional SMO, the proposed ELASMO method can significantly enhance the aerial image contrast, improve the EL, and enlarge the process window while ensuring high imaging fidelity.

Vectorial pupil optimization to compensate for a polarization effect at full exposure field in lithography.

Recently, a single vectorial pupil optimization (VPO) was proposed to compensate for the polarization effect induced by thick mask and image optics at one field point in a lithography system, which does not work at full field points. In this paper, we propose a multi-objective VPO (MOVPO) method to obtain a universal vectorial pupil that can compensate for the polarization aberration at full field points. A novel multi-objective cost function, to the best of our knowledge, is built and includes uneven image pattern errors causing by polarization aberration (PA) at full field points in the MOVPO method. Comprehensive simulations demonstrate that the proposed MOVPO method can effectively improve the consistency of imaging and enlarge the overlapped process window at full field points.

Rigorous imaging-based measurement method of polarization aberration in hyper-numerical aperture projection optics.

Imaging-based measurement methods of polarization aberration (PA) are indispensable in hyper-numerical aperture projection optics for advanced lithography. However, the current methods are derived from the Kirchhoff model and ignore the 3D mask effect of the test mask, which will impact the measurement accuracy. In this paper, a novel imaging-based measurement method of PA is proposed based on a rigorous imaging model to improve the measurement accuracy. Through the quantitative description of the 3D mask effect, a rigorous imaging-based measurement model of PA is established. A synchronous orientation measurement method is designed to effectively reduce the cost of establishing the overdetermined equations. A deep neural network is used to retrieve the PA accurately. Simulations show that the proposed method effectively eliminates the impact of the 3D mask effect of test mask on PA measurement, and the measurement error is reduced by 72% compared with the measurement method based on the Kirchhoff model.

Transcriptome Analyses Reveal Systematic Molecular Pathology After Optic Nerve Crush.

The function of glial cells in axonal regeneration after injury has been the subject of controversy in recent years. Thus, deeper insight into glial cells is urgently needed. Many studies on glial cells have elucidated the mechanisms of a certain gene or cell type in axon regeneration. However, studies that manipulate a single variable may overlook other changes. Here, we performed a series of comprehensive transcriptome analyses of the optic nerve head over a period of 90 days after optic nerve crush (ONC), showing systematic molecular changes in the optic nerve head (ONH). Furthermore, using weighted gene coexpression network analysis (WGCNA), we established gene module programs corresponding to various pathological events at different times post-ONC and found hub genes that may be potential therapeutic targets. In addition, we analyzed the changes in different glial cells based on their subtype markers. We revealed that the transition trend of different glial cells depended on the time course, which provides clues for modulating glial function in further research.

Vectorial pupil optimization to compensate polarization distortion in immersion lithography system.

Polarization distortion innately exists in hyper numerical aperture immersion lithography system. Polarization distortion, mainly including polarization aberration (PA) of lithography projection optics and thick mask induced polarization distortion, would seriously impact on lithography imaging quality. Some computational lithography technologies, such as robust optical proximity correction and robust source and mask optimization, have been introduced and developed to reduce the impact of polarization distortion on lithography imaging. In this paper, we innovate a vectorial pupil optimization (VPO) method to further extend degrees of freedom for pupil optimization and compensate polarization distortion for immersion lithography system. An analytical relationship between lithography imaging and active vectorial pupil, and the gradient-based algorithm is adopted to effectively solve VPO. Extensive simulations demonstrate the VPO method simultaneously compensate the PA of projection optics and the thick mask induced polarization distortion sufficiently. Based on PA-aware source mask optimization, the VPO method can further reduce the impact of polarization distortion on lithography imaging. Compared to current pupil wavefront optimization, the proposed VPO effectively reduces the pattern error by 37.2%, which demonstrates the VPO method can improve lithography pattern fidelity.

Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response.

Understanding the mechanisms of activity-dependent gene transcription underlying adaptive behaviors is challenging at neuronal-subtype resolution. Using cell-type specific molecular analysis in agouti-related peptide (AgRP) neurons, we reveal that the profound hunger-induced transcriptional changes greatly depend on plant homeodomain finger protein 6 (PHF6), a transcriptional repressor enriched in AgRP neurons. Loss of PHF6 in the satiated mice results in a hunger-state-shifting transcriptional profile, while hunger fails to further induce a rapid and robust activity-dependent gene transcription in PHF6-deficient AgRP neurons. We reveal that PHF6 binds to the promoters of a subset of immediate-early genes (IEGs) and that this chromatin binding is dynamically regulated by hunger state. Depletion of PHF6 decreases hunger-driven feeding motivation and makes the mice resistant to body weight gain under repetitive fasting-refeeding conditions. Our work identifies a neuronal subtype-specific transcriptional repressor that modulates transcriptional profiles in different nutritional states and enables adaptive eating behavior.