Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through ß-catenin/CREB interruption.

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments. In this work, a transferrin receptor (TfR) targeted immunostimulant (PTI) is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting ß-catenin signal pathway. To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001. On the one hand, the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumor-associated antigens. On the other hand, PTI will interrupt the binding between ß-catenin and cAMP response element-binding protein (CREB), regulating the gene transcription to downregulate programmed death ligand 1 (PD-L1) while upregulating C-C motif chemokine ligand 4 (CCL4). Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

Identification of age-related genes in rotator cuff tendon.

Aims: Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration. Methods: Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs. Results: We identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)). Conclusion: This study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT.

Alternating current electroluminescence devices: recent advances and functional applications.

Wearable smart devices and visualisation sensors based on alternating current electroluminescence (ACEL) have received considerable attention in recent years. Due to the unique properties of ACEL devices, such as high mechanical strength, adaptability to complex environments, and no need for energy level matching, ACEL is suitable for multifunctional applications and visualisation sensing platforms. This review comprehensively outlines the latest developments in ACEL devices, starting with an analysis of the mechanism, classification, and optimisation strategies of ACEL. It introduces the functional applications of ACEL in multicolour displays, high-durability displays, stretchable and wearable displays, and autonomous function displays. Particularly, it emphasises the research progress of ACEL in sensory displays under interactive conditions such as liquid sensing, environmental factor sensing, kinetic energy sensing, and biosensing. Finally, it forecasts the challenges and new opportunities faced by future functional and interactive ACEL devices in fields such as artificial intelligence, smart robotics, and human-computer interaction.

Community-based intervention for obstructive sleep apnea in the general population: a randomized controlled trial.

STUDY OBJECTIVES: To investigate the engagement and health outcomes of community-based intervention for obstructive sleep apnea (OSA) in the general population. METHODS: We conducted a 3-month randomized controlled trial in two communities in southern China. We initially screened the general population for high-risk OSA and further diagnosis using home sleep testing. Eligible participants were randomly (1:1) assigned to either a control or continuous positive airway pressure-based integrated intervention group. The primary outcomes were multimodal indicators reflecting health outcomes, including health-related quality of life (Short Form-36 [SF-36]), sleep-related symptoms, and cardiometabolic risk. RESULTS: Of the 2484 participants screened, 1423 identified as having high-risk OSA were considered for telephone invitations to participate in the trial. Of these, 401 participants responded positively (28.2%), 279 were diagnosed with OSA, and 212 were randomized. The intervention significantly improved several domains of SF-36, including physical functioning (intergroup difference, 2.8; p = .003), vitality (2.3; p = .031), and reported health transition (6.8; p = .005). Sleep-related symptoms, including Epworth Sleepiness Scale (-0.7; p = .017), Fatigue Severity Scale (-3.0; p = .022), Insomnia Severity Index (-1.8; p < .001), and Pittsburgh Sleep Quality Index (-0.7; p = .032), also showed significant improvements. Although the intervention did not significantly alter glycolipid metabolism, ventricular function, or cardiac structural remodeling, it achieved a significant reduction in systolic (-4.5 mmHg; p = .004) and diastolic blood pressure (BP; -3.7 mmHg; p < .001). CONCLUSIONS: Community-based intervention for previously undiagnosed OSA in the general population yielded improvements in health-related quality of life, sleep-related symptoms, and BP. However, engagement in the intervention program was low. CLINICAL TRIAL REGISTRATION: "Community Intervention Trial for OSA";URL: https://www.chictr.org.cn/showprojEN.html?proj=144927;Trial identification number: ChiCTR2100054800.

Self-Assembled PD-L1 Downregulator to Boost Photodynamic Activated Tumor Immunotherapy Through CDK5 Inhibition.

The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.

Efficient photocatalytic nitrogen fixation via oxygen vacancies in Zr-MOFs at ambient conditions.

Photocatalytic nitrogen fixation is seen to be a potential technology for nitrogen reduction due to its eco-friendliness, low energy consumption, and environmental protection. In this study, photocatalysts with abundant oxygen vacancies (Zr-naphthalene dicarboxylic acid (Zr-NDC) and Zr-phthalic acid (Zr-BDC)) were designed using 1,4-naphthalene dicarboxylic acid (H2NDC) and 1,4-phthalic acid (H2BDC) as ligands. Since the structure of H2NDC includes one extra benzene ring than H2BDC, the charge density differential of the organic ligand is probably altered. The hypothesis is proved by density function theory (DFT) calculation. The abundant oxygen vacancies of the catalyst offer numerous active sites for nitrogen fixation. Concurrently, the process of ligand-metal charge transfer facilitates photo-electron transfer, creating an active center for nitrogen reduction. Additionally, the functionalization of ligand amplifies another pathway for charge transfer, broadening the light absorption range of Metal-organic framework (MOF) and increasing its capacity for nitrogen reduction. In contrast to H2BDC, the benzene ring added in H2NDC structure acts as an electron energy storage tank with a stronger electron density difference favorable for photogenerated electron-hole separation resulting in higher photocatalytic activity in Zr-NDC. The experimental results show that the nitrogen fixation efficiency of Zr-NDC is 163.7 µmol g-1h-1, which is significantly better than that of Zr-BDC (29.3 µmol g-1h-1). This work utilizes cost-effective and non-toxic ingredients to design highly efficient photocatalysts, thereby significantly contributing to the practical implementation of green chemistry principles.

High-Throughput Multitarget Molecular Detection in an Automatic Light-Addressable Photoelectrochemical Sensing Platform.

Successively emerged high-throughput multitarget molecular detection methods bring significant development tides in chemical, biological, and environmental fields. However, several persistent challenges of intricate sample preparation, expensive instruments, and tedious and skilled operations still need to be further addressed. Here, we propose an automatic light-addressable photoelectrochemical (ALA-PEC) sensing platform for sensitive and selective detection of multitarget molecules. With Au nanoparticle-decorated TiO2 nanotube photonic crystals (Au-TiO2 NTPCs) as a photoelectrode and 8 kinds of antibiotics as target molecules, the ALA-PEC sensing system implements automatic detection of multimolecules in a short time with high sensitivity and good selectivity. Random samples with different amounts of antibiotics have been well-distinguished in the ALA-PEC system, and both the chemical components and concentrations have been well-illustrated in a pattern recognition model. It is worth noting that 8 samples are not the limit of the ALA-PEC sensing platform, which can be easily expanded to more complex detection arrays based on practical needs. The emerging ALA-PEC sensing platform provides a new solution for rapid screening and detection of multitarget and high-throughput substances and potentially brings the automatic, portable, sensitive, high-throughput, and cost-effective detection technique to an entire new realm.

Facile Synthesis of PtP2 Nanocrystals as Highly Active Electrocatalysts for Methanol Oxidation.

Although significant efforts have been made in the past few decades, the development of affordable, durable, and effective electrocatalysts for direct methanol fuel cells (DMFCs) remains a formidable challenge. Herein, we present a facile and efficient phosphorization approach for synthesizing PtP2 intermetallic nanocrystals and utilize them as electrocatalysts in the methanol oxidation reaction (MOR). Impressively, the synthesized PtP2 nanocatalysts exhibit a mass activity of 2.14 mA µg-1 and a specific activity of 6.28 mA cm-2, which are 5.1 and 9.5 times higher than those achieved by the current state-of-the-art commercial Pt/C catalyst, respectively. Moreover, the PtP2 nanocatalysts demonstrate improved stability toward acidic MOR by retaining 92.1% of its initial mass activity after undergoing 5000 potential cycles, far surpassing that of the commercial Pt/C (38%). Further DMFC tests present a 2.7 times higher power density than that of the commercial Pt/C, underscoring their potential for application in methanol fuel cells. Density functional theory calculations suggest that the accelerated MOR kinetics and improved CO tolerance on PtP2 can be attributed to the attenuated binding strength of CO intermediates and the enhanced stability due to strong Pt-P interaction. To our knowledge, this is the first report identifying the MOR performance on PtP2 intermetallic nanocrystals, highlighting their potential as highly active and stable nanocatalysts for DMFCs.

The effect of negative pressure wound therapy on the outcome of diabetic foot ulcers: A meta-analysis.

Negative pressure injury is one of the auxiliary methods of treating diabetes foot ulcers. It has been shown to be superior to conventional techniques in randomized controlled trials (RCTs). Nevertheless, the results of observational research are still scarce. A systematic review of RCTs and observations was carried out to evaluate the effectiveness and security of negative pressure wound therapy (NPWT) treatment for diabetes foot ulcers. Three English e-databases have been found for NPWT research. The meta-analyses of the comparative studies provided point estimates of results. Intermediate results were given as median and binary values were given in the form of odds ratios (OR). Seventeen trials, 13 RCTs and four randomized, controlled trials were found in the survey. Of these, 831 were treated with NPWT, 834 were treated with standard therapy. A total of 14 studies have been conducted to investigate the influence of NPWT on the healing of diabetic foot ulcers(DFU). In the study, NPWT was shown to speed up the healing of the wound in DFU patients(OR, 2.57; 95% CI, 1.72, 3.85 p < 0.0001). A subgroup analysis showed that NPWT was associated with an acceleration of the wound healing rate in 10 RCT trials (OR, 2.48; 95% CI, 1.58, 3.89 p < 0.001). In the four nRCT trials, NPWT was also shown to speed up the healing of the wound(OR, 2.95; 95% CI, 1.03, 8.42 p = 0.04). In 11 studies, the influence of NPWT on amputations of diabetes mellitus (DM) foot ulcers was investigated. The results showed that NPWT was associated with a reduction in amputations (OR, 0.53; 95% CI, 0.37, 0.74 p = 0.0002).In a subgroup of RCT trials, nine RCT trials showed a reduction in amputations(OR, 0.61; 95% CI, 0.43, 0.87 p = 0.007). In both nRCT trials, NPWT also showed a reduction in amputations (OR, 0.03; 95% CI, 0.00, 0.24 p = 0.001). Generally speaking, NPWT can help to heal the wound and lower the risk of amputations in people with diabetes. The subgroup analysis showed similar results for the RCT and non-RCT trials. NPWT can be used to treat diabetes foot ulcers caused by diabetes.

Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy-Upregulated Cyclooxygenase-2.

Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.

A Multimode Microfiber Specklegram Biosensor for Measurement of CEACAM5 through AI Diagnosis.

Carcinoembryonic antigen (CEACAM5), as a broad-spectrum tumor biomarker, plays a crucial role in analyzing the therapeutic efficacy and progression of cancer. Herein, we propose a novel biosensor based on specklegrams of tapered multimode fiber (MMF) and two-dimensional convolutional neural networks (2D-CNNs) for the detection of CEACAM5. The microfiber is modified with CEA antibodies to specifically recognize antigens. The biosensor utilizes the interference effect of tapered MMF to generate highly sensitive specklegrams in response to different CEACAM5 concentrations. A zero mean normalized cross-correlation (ZNCC) function is explored to calculate the image matching degree of the specklegrams. Profiting from the extremely high detection limit of the speckle sensor, variations in the specklegrams of antibody concentrations from 1 to 1000 ng/mL are measured in the experiment. The surface sensitivity of the biosensor is 0.0012 (ng/mL)-1 within a range of 1 to 50 ng/mL. Moreover, a 2D-CNN was introduced to solve the problem of nonlinear detection surface sensitivity variation in a large dynamic range, and in the search for image features to improve evaluation accuracy, achieving more accurate CEACAM5 monitoring, with a maximum detection error of 0.358%. The proposed fiber specklegram biosensing scheme is easy to implement and has great potential in analyzing the postoperative condition of patients.

Spinal cord injury: Olfactory ensheathing cell-based therapeutic strategies.

Spinal cord injury (SCI) is a highly disabling neurological disorder that is difficult to treat due to its complex pathophysiology and nerve regeneration difficulties. Hence, effective SCI treatments are necessary. Olfactory ensheathing cells (OECs), glial cells derived from the olfactory bulb or mucosa, are ideal candidates for SCI treatment because of their neuroprotective and regenerative properties, ample supply, and convenience. In vitro, animal model, and human trial studies have reported discoveries on OEC transplantation; however, shortcomings have also been demonstrated. Recent studies have optimized various OEC transplantation strategies, including drug integration, biomaterials, and gene editing. This review aims to introduce OECs mechanisms in repairing SCI, summarize the research progress of OEC transplantation-optimized strategies, and provide novel research ideas for SCI treatment.

Alternative Biological Material for Tissue Engineering of the Vagina: Porcine-Derived Acellular Vaginal Matrix.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and α-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of ß-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the ß-catenin/c-Myc/cyclin D1 pathway. CONCLUSION: This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

Chimeric Peptide-Engineered Self-Delivery Nanomedicine for Photodynamic-Triggered Breast Cancer Immunotherapy by Macrophage Polarization.

A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG8 -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.

Nasal Endoscopic Incision and Drainage Transnasal Retropterygoid Approach to Upper Parapharyngeal Abscess: A Novel Technique.

Parapharyngeal infection is a well-known disease of otorhinolaryngologists. Rapid onset, short duration, severe symptoms, and manifestations such as sore throat and dysphagia are common characteristics treated primarily by surgical incision and drainage. Traditional surgical approaches encompass endoscopic transoral/nasal, transparotid, transcervical, or a combination thereof. We report a novel technique of nasal endoscopic incision and drainage transnasal retropterygoid approach to an upper parapharyngeal abscess. This report presents a case of a 14-year-old man presented with severe right neck and head pain, who was found to have an upper parapharyngeal abscess during a nasal endoscopic parapharyngeal exploration via a retropterygoid approach. The intraoperative frozen section revealed chronic mucosal inflammation and mild to moderate dysplasia of the squamous epithelium, but no carcinoma.

Endoscopic surgery versus intensity-modulated radiotherapy in locally advanced recurrent nasopharyngeal carcinoma: a multicenter, case-matched comparison.

BACKGROUND: The management of locally advanced recurrent nasopharyngeal carcinoma (rNPC) is challenging. The objective of our study was to compare salvage endoscopic nasopharyngectomy (ENPG) with intensity-modulated radiotherapy (IMRT) in clinical outcomes and complications of locally advanced rNPC. METHODS: Patients with histologically confirmed rNPC in rT3-4N0-3M0 stages were retrospectively enrolled between January 2013 and December 2019 in this multicenter, case-matched study. The baseline clinicopathological characteristics of patients were balanced by propensity score matching between the ENPG and IMRT groups. ENPG was performed in patients with easily or potentially resectable tumors. The oncological outcomes as well as treatment-related complications were compared between two groups. RESULTS: A total of 176 patients were enrolled and 106 patients were matched. The ENPG group (n = 53) and the IMRT group (n = 53) showed comparable outcomes in the 3-year overall survival rate (68.4% vs. 65.4%, P = 0.401), cancer-specific survival rate (80.9% vs. 74.4%, P = 0.076), locoregional failure-free survival rate (36.6% vs. 45.3%, P = 0.076), and progression-free survival rate (27.5% vs. 32.3%, P = 0.216). The incidence of severe treatment-related complications of patients in the ENPG group was lower than that in the IMRT group (37.7% vs. 67.9%, P = 0.002). The most common complications were post perioperative hemorrhage (13.2%) in ENPG group and temporal lobe necrosis (47.2%) in IMRT group, respectively. CONCLUSION: Salvage ENPG exhibits comparable efficacy but less toxicities than IMRT in carefully screened patients with locally advanced rNPC, which may be a new choice of local treatment.

Research Advances in Clinical Applications, Anticancer Mechanism, Total Chemical Synthesis, Semi-Synthesis and Biosynthesis of Paclitaxel.

Paclitaxel, a natural secondary metabolite isolated and purified from the bark of the Taxus tree, is considered one of the most successful natural anticancer drugs due to its low toxicity, high potency and broad-spectrum anticancer activity. Taxus trees are scarce and slow-growing, and with extremely low paclitaxel content, the contradiction between supply and demand in the market is becoming more and more intense. Therefore, researchers have tried to obtain paclitaxel by various methods such as chemical synthesis, artificial culture, microbial fermentation and tissue cell culture to meet the clinical demand for this drug. This paper provides a comprehensive overview of paclitaxel extraction, combination therapy, total synthesis, semi-synthesis and biosynthesis in recent years and provides an outlook, aiming to provide a theoretical basis and reference for further research on the production and application of paclitaxel in the future.

Effects of xenon anesthesia on postoperative neurocognitive disorders: a systematic review and meta-analysis.

The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P < 0.001), time to extubation (P < 0.001), time to react on demand (P = 0.01), and time to time and spatial orientation (P = 0.04). However, the Aldrete score significantly increased with xenon anesthesia (P = 0.005). Postoperative complications did not differ between the anesthesia groups. Egger's test for bias showed no small-study effect, and a trim-and-fill analysis showed no apparent publication bias. In conclusion, xenon anesthesia probably did not affect the occurrence of postoperative neurocognitive dysfunction. However, xenon anesthesia may effectively shorten the emergence time of certain parameters without adverse effects.

Contribution of m5C RNA Modification-Related Genes to Prognosis and Immunotherapy Prediction in Patients with Ovarian Cancer.

Background: 5-Methylcytosine (m5C) RNA modification is closely implicated in the occurrence of a variety of cancers. Here, we established a novel prognostic signature for ovarian cancer (OC) patients based on m5C RNA modification-related genes and explored the correlation between these genes with the tumor immune microenvironment. Methods: Methylated-RNA immunoprecipitation sequencing helped us to identify candidate genes related to m5C RNA modification at first. Based on TCGA database, we screened the differentially expressed candidate genes related to the prognosis and constructed a prognostic model using LASSO Cox regression analyses. Notably, the accuracy of the model was evaluated by Kaplan-Meier analysis and receiver operator characteristic curves. Independent prognostic risk factors were investigated by Cox proportional hazard model. Furthermore, we also analyzed the biological functions and pathways involved in the signature. Finally, the immune response of the model was visualized in great detail. Results: Totally, 2,493 candidate genes proved to be involved in m5C modification of RNA for OC. We developed a signature with prognostic value consisting of six m5C RNA modification-related genes. Specially, samples have been split into two cohorts with low- and high-risk scores according to the model, in which the low-risk OC patients exhibited dramatically better overall survival time than those with high-risk scores. Besides, not only was this model a prognostic factor independent of other clinical characteristics but it predicted the intensity of the immune response in OC. Significantly, the accuracy and availability of the signature were verified by ICGC database. Conclusions: Our study bridged the gap between m5C RNA modification and the prognosis of OC and was expected to provide an effective breakthrough for immunotherapy in OC patients.

Vaginal reconstruction with a double-sided biomembrane-a preclinical experimental study on large animals.

Tissue engineering techniques bring the promise of vaginal reconstruction with low invasiveness and fewer complications. However, existing biomaterial scaffolds remain limited in efficient vaginal recovery, focusing only on regenerating an epithelial layer, but muscle layers are missing or abnormal. The lack of a multi-tissue hierarchical structure in the reconstructed vagina leads to shrinking, stenosis, and fibrosis. Here, an acellular matrix named a double-sided biomembrane (DBM) is demonstrated for vaginal recovery. The regeneration of epithelial and muscle layers is achieved simultaneously since the smooth side of the DBM is helpful for guiding epithelial cell growth, while its loose and porous side guides muscle cell growth. In addition, the DBM demonstrates excellent mechanical properties similar to vaginal tissue, and hydrophilicity. Therefore, neovaginas were observed in the fourth and twelfth weeks after DBMs were transplanted to repair full-thickness vaginal defects (4 cm) that we established in large animals. The DBMs can effectively promote rapid epithelialization, the formation of large muscle bundles, higher rates of angiogenesis, and the restoration of physiological function in a neovagina. That is, the injured vagina achieves nearly complete recovery in anatomy and function, similar to a normal vagina. These preclinical results indicate that the DBM has prospects for vaginal injury repair.