Pediatric WNT medulloblastoma predisposition in intraoperative blood loss: a retrospective observational cohort study.

Introduction: Molecular subgroups influence the vascular architecture within medulloblastomas, particularly the wingless (WNT) subgroup, which contributes to its propensity for primary tumor hemorrhage. Whether this mechanism affects intraoperative blood loss remains unknown. This study aimed to assess the association between WNT medulloblastoma and the predisposition for blood loss. Methods: This was a retrospective observational study using data from a neuro-oncology center comprising molecular data on patients treated between December 31, 2014, and April 30, 2023. Differences between WNT and other subgroups in the risk of primary outcome-intraoperative blood loss were assessed using multivariable-adjusted linear regression. Results: Of the 148 patients included in the analysis, 18 patients (12.2%) had WNT, 42 (28.4%) had sonic hedgehog (SHH) TP53-wildtype, 7 (4.7%) had SHH TP53-mutant, and 81 (54.7%) were non-WNT/ non-SHH. The WNT subgroup more frequently underwent primary intratumoral hemorrhage (22% vs. 3.8%; p = 0.011). The median intraoperative blood loss was 400.00 (interquartile range [IQR] 250, 500) mL for WNT and 300.00 [200, 400] mL for the other subgroups (p = 0.136), with an adjusted ß of 135.264 (95% confidence intervals [CI], 11.701-258.827; p = 0.032). Similar results were observed in both midline and noninfiltrative margin medulloblastoma. Discussion: WNT medulloblastoma is typically associated with primary intratumoral hemorrhage and intraoperative blood loss. The validity of determining the surgical approach based on predicted molecular subtypes from imaging data is questionable. However, attempting to engage in risk communication with patients in a molecular-specific way is worthwhile to validate.

Neurosurgical short-term outcomes for pediatric medulloblastoma patients and molecular correlations: a 10-year single-center observation cohort study.

This study examined the risk factors for short-term outcomes, focusing particularly on the associations among molecular subgroups. The analysis focused on the data of pediatric patients with medulloblastoma between 2013 and 2023, as well as operative complications, length of stay from surgery to adjuvant treatment, 30-day unplanned reoperation, unplanned readmission, and mortality. 148 patients were included. Patients with the SHH TP53-wildtype exhibited a lower incidence of complications (45.2% vs. 66.0%, odds ratio [OR] 0.358, 95% confidence interval [CI] 0.160 - 0.802). Female sex (0.437, 0.207 - 0.919) was identified as an independent protective factor for complications, and brainstem involvement (1.900, 1.297 - 2.784) was identified as a risk factor. Surgical time was associated with an increased risk of complications (1.004, 1.001 - 1.008), duration of hospitalization (1.006, 1.003 - 1.010), and reoperation (1.003, 1.001 - 1.006). Age was found to be a predictor of improved outcomes, as each additional year was associated with a 14.1% decrease in the likelihood of experiencing a prolonged length of stay (0.859, 0.772 - 0.956). Patients without metastasis exhibited a reduced risk of reoperation (0.322, 0.133 - 0.784) and readmission (0.208, 0.074 - 0.581). There is a significant degree of variability in the occurrence of operative complications in pediatric patients with medulloblastoma. SHH TP53-wildtype medulloblastoma is commonly correlated with a decreased incidence of complications. The short-term outcomes of patients are influenced by various unmodifiable endogenous factors. These findings could enhance the knowledge of onconeurosurgeons and alleviate the challenges associated with patient/parent education through personalized risk communication. However, the importance of a dedicated center with expertise surgical team and experienced neurosurgeon in improving neurosurgical outcomes appears self-evident.

Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn.

OBJECTIVE: Matrix metalloproteinase 13 (MMP13) is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens, modifying protein structures and regulating inflammatory responses, but its role in deep vein thrombosis (DVT) has not been determined. The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT. METHODS: We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT. After screening genes possibly related to MMP13 in DVT mice, the expression levels of candidate genes in human umbilical vein endothelial cells (HUVECs) and the venous wall were evaluated. The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro. RESULTS: Among the differentially expressed genes, interleukin 1 beta, podoplanin (Pdpn), and factor VIII von Willebrand factor (F8VWF) were selected for analysis in mice. When MMP13 was inhibited, the expression level of PDPN decreased significantly in vitro. In HUVECs, overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation, while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation. CONCLUSIONS: Inhibiting the expression of MMP13 could reduce the burden of DVT in mice. The mechanism involves downregulating the expression of Pdpn through MMP13, which could provide a novel gene target for DVT diagnosis and treatment.

Room-temperature highly sensitive triethylamine detection by few-layer Nb2CTxMXene nanosheets.

MXene, a class of two-dimensional materials that are emerging as rising stars in the field of materials, are receiving much attention in sensing. Ti3C2TxMXene, the most maturely researched MXene, is widely used in energy, biomedical, laser, and microwave shielding applications and has also been expanded to gas sensing and wearable electronics applications. Compared with Ti3C2Tx, Nb2CTxMXene is more difficult to etch and has higher resistances at room temperature; so, few studies have been reported on their use in the sensing field. Based on the preparation of few-layer Nb2CTxMXene by intercalation, this study thoroughly examined their gas-sensing properties. The successfully prepared few-layer Nb2CTxshowed good selectivity and high sensitivity to triethylamine at room temperature, with response values up to 47.2% for 50 ppm triethylamine and short response/recovery time (22/20 s). This study opens an important path for the design of novel Nb-based MXene sensors for triethylamine gas detection.

The detection efficacy of noninvasive prenatal genetic testing (NIPT) for sex chromosome abnormalities and copy number variation and its differentiation in pregnant women of different ages.

Objective: To analyze the efficacy of noninvasive prenatal genetic testing (NIPT) in detecting fetal sex chromosome abnormalities and copy number variation (CNV), compare the efficacy between NIPT and serological screening alone, and further analyze the fetal sex chromosome abnormalities and CNV differentiation in pregnant women of different ages, so as to provide a reference for the prevention and control of fetal birth defects. Methods: Clinical data from 22,692 pregnant women admitted to our hospital from January 2013 to December 2022 were retrospectively analyzed. All participants underwent serological screening and NIPT screening to compare fetal chromosomal abnormalities between the two screening modalities. 145 women whose fetus were diagnosed as sex chromosome abnormalities and 36 women whose fetus were diagnosed as CNV abnormalities based on NIPT screening were selected for prenatal diagnosis by amniocentesis or karyotyping. Taking prenatal diagnosis as the standard, the four-grid table method was used to detect the positive predictive value of NIPT screening for fetal sex chromosomal abnormalities and CNV. According to the age, pregnant women were divided into 18-30 years old (n = 9844), 31-35 years old (n = 7612), >35 years old (n = 5236), and then the detection rates of sexual fetal chromosomal abnormalities, CNV and total chromosomal abnormalities were compared in pregnant women. Results: Among the 22,692 pregnant women in this study, the high-risk proportion of serologic screening with 4.38% was higher than that of NIPT screening with 1.93% (P < 0.05). Among the 145 women with fetal sex chromosome abnormalities screened by NIPT, 122 cases of fetal sex chromosome abnormalities were diagnosed prenatally, including 45, X/47, XXX/47, XYY/47, XXY. The positive predictive values of NIPT screening were 25.00%, 58.82%, 85.71%, and 85.71%, respectively, with an overall predictive value of 44.26%. The positive predictive value of fetal sex chromosome abnormalities in NIPT screening was higher than that of serological screening (P < 0.05). Among the 36 pregnant women with fetal CNV, NIPT screening showed that CNVs≤10 Mb and CNVs>10 Mb were 33.33% and 66.67%, respectively. There were 12 cases of prenatal diagnosis of fetal CNV, among which the NIPT-screened positive predictive values of fetal copy number deletion, duplicate, deletion and duplicate were 50.00%, 57.14% and 100.00%, respectively, with an overall predictive value of 58.33%. The positive predictive value of CNV in NIPT screening was higher than that of serological screening without statistically significant difference (P > 0.05). The results of NIPT screening showed that the detection rate of fetal sex chromosome abnormalities and total abnormalities of pregnant women over 35 years of age was significantly higher than that of pregnant women aged 18-30 and 31-35 years (P < 0.05). Conclusion: NIPT screening could greatly improve the detection efficacy of fetal sex chromosome abnormalities, CNV and other chromosome abnormalities, and decline the false positive rate. However, the positive predictive value of NIPT screening was relatively low, and further prenatal testing and genetic counseling are still required. In addition, NIPT screening for fetal sex chromosome abnormalities, and the detection rate of total abnormalities in pregnant women older than 35 years old were increased significantly, and pregnancy at an advanced age may be one of the risk factors for fetal chromosomal abnormalities.

The insertion and management of an external ventricular drain in pediatric patients with hydrocephalus associated with medulloblastoma.

An external ventricular drain (EVD) is used to facilitate cerebrospinal fluid (CSF) removal in medulloblastoma patients suffering from hydrocephalus. It is essential to recognize that EVD management plays a crucial role in influencing the incidence of drain-related complications. However, the ideal method for EVD management remains undetermined. Our research sought to examine the safety of EVD placement and the impact of EVD on the incidences of intracranial infections, postresection hydrocephalus, and posterior fossa syndrome (PFS). We conducted a single-center observational study involving a cohort of 120 pediatric medulloblastoma patients who were treated from 2017 to 2020. The rates of intracranial infection, postresection hydrocephalus, and PFS were 9.2%, 18.3%, and 16.7%, respectively. EVD did not influence the occurrence of intracranial infection (p = 0.466), postresection hydrocephalus (p = 0.298), or PFS (p = 0.212). A gradual EVD weaning protocol correlated with an elevated incidence of postresection hydrocephalus (p = 0.033), whereas a rapid weaning approach resulted in 4.09 ± 0.44 fewer drainage days (p < 0.001) than the gradual weaning strategy. EVD placement (p = 0.010) and intracranial infection (p = 0.002) were linked to delayed speech return, whereas a longer duration of drainage was conducive to the recovery of language function (p = 0.010). EVD insertion was not correlated with the incidence of intracranial infection, postoperative hydrocephalus, or PFS. The optimal EVD management method should encompass a rapid EVD weaning strategy, followed by prompt drain closure. We have presented additional evidence to improve the safety of EVD insertion and management in neurosurgical patients to ultimately facilitate the establishment of standardized institutional/national implementation and management protocols.

Nickel nanoparticle decorated silicon carbide as a thermal filler in thermal conductive aramid nanofiber-based composite films for heat dissipation applications.

Aramid nanofibers (ANFs) have shown potential applications in the fields of nanocomposite reinforcement, battery separators, thermal insulation and flexible electronics. However, the inherent low thermal conductivity limits the application of ANFs, currently, to ensure long lifetime in electronics. In this work, new nickel (Ni) nanoparticles were employed to decorate the silicon carbide (SiC) filler by a rapid and non-polluting method, in which nickel acetate tetrahydrate (Ni(CH3COO)2·4H2O) and SiC were mixed and heated under an inert atmosphere. The composites as thermal fillers were applied to prepare an aramid nanofiber (ANF)-based composite film. Our results showed that the decoration of SiC by an appropriate amount of Ni nanoparticles played an important role in improving the thermal conductivity, hydrophobicity, thermal stability, and puncture resistance of the ANF composite film. After adjusting the balling time at 10 h, the optimized content of 10 mol% Ni nanoparticles improved the thermal conductivity to 0.502 W m-1 K-1, 298.4% higher than that of the original ANF film. Moreover, increasing the content of thermal fillers to 30 wt% realized a high thermal conductivity of 0.937 W m-1 K-1, which is 643.7% higher than that of the pristine ANF film. Moreover, the compatibility between thermal fillers and ANFs and thermal stability were improved for the ANF-composite films. The effective heat transfer function of our composite films was further confirmed using a LED lamp and thermoelectric device. In addition, the obtained composite films show certain mechanical properties and better hydrophobicity; these results exhibit their great potential applications in electronic devices.

Research progress in intelligent control of intrapartum oxytocin (unrevised version).

With the development of precision medicine and artificial intelligence, the infusion of many drugs has been intelligently controlled according to patients' conditions. However, the infusion of oxytocin (OT) still relies on medical staff responsible for implementing artificial regulation based on observation of fetal electronic monitoring and other maternal and fetal conditions. In this review, we discussed recent trends in intelligent infusion systems, the development status and dilemma of intelligent control of OT infusion, the drug intelligent feedback control system principle, and current risks and challenges to further promote obstetric informatization.

Incidence and Risk Factors for Necessitating Cerebrospinal Fluid Diversion Following Medulloblastoma Surgery in Children.

BACKGROUND: There are insufficient data on pediatric patients with medulloblastoma who require cerebrospinal fluid (CSF) diversion following resection. Therefore, this study aimed to determine the incidence and the characteristics associated with it in this subset of patients. METHODS: We conducted a single-center, retrospective, observational cohort study of patients aged 18 years or less who underwent medulloblastoma resection at our department between 2010 and 2021. The primary outcome was the incidence of CSF diversion surgery required after resection. Participant demographics, tumor biology, and interventions were analyzed using univariate- and multivariate-adjusted models. RESULTS: Of the 183 patients admitted to our department, 131 (71.6%) participated in this study. The incidence of permanent CSF diversion was 26.0% (95% confidence interval [CI]: 18.7 to 34.3). Factors independently associated with requirement of permanent CSF diversion were medulloblastoma volume >46.4 cm3 (odds ratio [OR]: 2.919, 95% CI: 1.191 to 7.156) and CSF channel invasion (OR: 2.849, 95% CI: 1.142 to 7.102). The duration of manifestation may be a covariate of tumor volume with increased risk of requirement for permanent CSF diversion (OR: 1.006, 95% CI: 1.000 to 1.013), and tumor volume may be a predictor in patients who underwent subtotal resection (OR: 4.900, 95% CI: 0.992 to 24.208, P = 0.05). Finally, patients who required permanent CSF diversion were divided according to medulloblastoma molecular subgroups, and no significant differences were found. CONCLUSION: We report major predictive factors for permanent CSF diversion surgery in patients with medulloblastoma. Our study suggests that the presence of postresection hydrocephalus is not high enough to warrant permanent, prophylactic CSF diversion in all patients.

Impact of de-branched starch molecules and fatty acid complexes on the attenuation of ageing-induced cognitive impairment.

BACKGROUND: Ageing and associated cognitive impairments are becoming serious issues around the world. In this study, the physiological properties of three kinds of complexes of fatty acid (capric, stearic and oleic acid, respectively) and de-branched starch molecules were investigated via a d-galactose-induced ageing model. This study revealed differences in the regulation of cognitive impairment and brain damage following intervention of different complexes, which might highlight a potent approach for the prevention of this chronic disease. RESULTS: Data indicated that three complexes improved response time and cognitive function and the bio-parameter markers associated with oxidative stress in ageing rats. Among them, the complexes prepared from de-branched starch-oleic acid showed a greater improvement compared to others. In addition, de-branched starch-capric acid complex showed a higher improvement in the morphology of colon cells and hippocampal neuronal cells. The consumption of de-branched starch-capric acid and -oleic acid complexes generated more short-chain fatty acids in the gut. More importantly, the complexation of de-branched starch with either caprate or stearate enhanced gut Akkermansia. Therefore, it was proposed that the richness in Akkermansia and gut metabolites might be associated with reduced damage of the hippocampal neuronal cells induced by the ageing progress. Moreover, the AMPK (AMP-activated protein kinase) pathway was activated in liver in de-branched starch-capric acid complex diet. In summary, de-branched starch-capric acid complex exhibited a greater effect on the attenuation of ageing-induced cognitive impairment. CONCLUSION: This study might highlight a new approach for intervening in the cognitive impairment during the ageing progress via a food supply. © 2023 Society of Chemical Industry.

A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Advances of Drugs Electroanalysis Based on Direct Electrochemical Redox on Electrodes: A Review.

The strong development of mankind is inseparable from the proper use of drugs, and the electroanalytical research of drugs occupies an important position in the field of analytical chemistry. This review mainly elaborates the research progress of drugs electroanalysis based on direct electrochemical redox on various electrodes for the recent decade from 2011 to 2021. At first, we summarize some frequently used electrochemical data processing and electrochemical mechanism research derivation methods in the literature. Then, according to the drug therapeutic and application/usage purposes, the research progress of drugs electrochemical analysis is classified and discussed, where we focus on drugs electrochemical reaction mechanism. At the same time, the comparisons of electrochemical sensing performance of the drugs on various electrodes from recent studies are listed, so that readers can more intuitively compare and understand the electroanalytical sensing performance of each modified electrode for each of the drug. Finally, this review discusses the shortcomings and prospects of the drugs electroanalysis based on direct electrochemical redox research.

Photonic Crystal-Embedded Molecularly Imprinted Contact Lenses for Controlled Drug Release.

As a noninvasive eye disease detection and drug delivery device, contact lenses can improve eye bioavailability and enable continuous drug delivery. In order to monitor the release of drugs in real time, molecularly imprinted contact lenses (MICLs) based on photonic crystals (PCs) were prepared for the treatment of diabetes-related diseases. The specific adsorption of molecularly imprinted polymers on dexamethasone sodium phosphate (DSP) increased the drug loading and optimized the drug release behavior. At the same time, the drug release ensures the rapid color report during the loading and releasing of drugs due to the volume and refractive index change of the hydrogel matrix. The continuous and slow release of DSP by MICLs in artificial tears was successfully monitored through structural color changes, and the cytotoxicity test results showed that the MICL had good biocompatibility. Therefore, MICLs with a PC structure color have great biomedical potentiality in the future.

Prognostic Value of miR-137 in Children with Medulloblastoma and its Regulatory Effect on Tumor Progression.

Medulloblastoma is a malignant tumor with high incidence and poor prognosis in adolescents and children. MicroRNA-137 (miR-137) has been found to be abnormally expressed in cancers such as pancreatic cancer. The purpose of this study is to explore the expression of miR-137 in MB and its role in cell physiological activities to determine the significance of miR-137 in the prognosis of MB. First, the expression of miR-137 in MB tissues and cell lines was analyzed by qRT-PCR. Then the Kaplan-Meier survival curve was used to analyze the significance of miR-137 expression in the prognosis, and the Cox regression model was used to explore the correlation between miR-137 expression and clinical characteristics. The effects of miR-137 on MB cell activities were analyzed by MTT assay, Transwell assays, and flow cytometry. It can be concluded from the results that the expression of miR-137 is down-regulated in MB tissues and cells. The down-regulation of miR-137 was significantly related to the poor prognosis of MB, and significantly related to clinical indicators. Up-regulated miR-137 inhibited cell proliferation, migration, invasion, and cell cycle progression, as well as induced cell apoptosis by targeting KDM1A. This study can conclude that miR-137 may be used as a prognostic biomarker of MB.

mRNA Profiling for miR-124-mediated Repair in Spinal Cord Injury.

The miRNA miR-124 has been reported to be a promising target for the repair of spinal cord injury (SCI), which is a devastating neurological condition. This study aimed to investigate the underlying molecular mechanisms of miR-124-mediated SCI repair. We established miR-124 SCI model rats and further treated them with agomiR-124 for 14 days. After that, their spinal cords were sectioned, and levels of NeuN, GFAP, and NF-200 were measured via immunofluorescence or via immunohistochemistry. In addition, the spinal dorsal horns were collected for sequencing of total RNA. Differentially expressed (DE) mRNAs were then profiled and a number of these were further verified with qPCR. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to predict the potential functions of the DE mRNAs. AgomiR-124 was found to significantly inhibit the decrease of neurons and the activation of astrocytes, while promoting NF-200 expression in the dorsal horn. At fourteen days after agomiR-124 treatment, a total of 85 mRNAs were upregulated and 80 mRNAs were downregulated. We focused our analysis of the DE mRNAs on the top 20 most DE mRNAs, and found four upregulated genes (Nploc4, Yme1l1, LOC103693564, and Aspa) and four downregulated genes (Epb41l2, LOC100911685, LOC100910833, and Smarcc1), which are likely to be of interest to SCI researchers. In addition, we noted that Tal1 is a potential target gene of miR-124, and that a low level of this gene promoted the proliferation of neuronal precursor cells and inhibited their differentiation. In conclusion, miR-124 was able to mediate SCI repair by altering the expression of various mRNAs in rats. The miR-124/Tal1 axis may participate in the treatment of SCI by agomiR-124 by repopulating neural stem cells.

Transcriptome analysis of Klf15­mediated inhibitory functions in a mouse deep venous thrombosis model.

Krüppel­like family (KLF) members are important regulators of proinflammatory activation in the vasculature. A transcriptome study involving RNA sequencing (RNA­seq) and quantitative PCR (qPCR) was performed to investigate Klf15 and Klf15­regulated gene levels in C57BL/6 mice with inferior vena cava thrombi and in control (Blank) mice. A total of 2,206 differentially expressed genes (DEGs), including 1,330 upregulated and 876 downregulated genes, were identified between the deep venous thrombosis (DVT) group and the Blank group. Additionally, 1,041 DEGs (235 upregulated and 806 downregulated) were identified between the Klf15­small interfering RNA (siRNA) and Klf15­negative control (NC) groups. The DEGs were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and qPCR was conducted to validate the results. A total of seven significant DEGs were selected from the RNA­seq results. Matrix metalloproteinases (Mmp)12, Mmp13, Mmp19, Arg1, Ccl2, heme oxygenase­1 and Fmo3 levels were significantly higher, while Klf15 levels were lower, in the DVT group than in the Blank group. Fmo3 and Mmp19 have not been previously identified as DVT­associated DEGs. Klf15, Mmp12 and Mmp13 levels were compared between the Klf15­siRNA and Klf15­NC groups. Mmp12 and Mmp13 expression was significantly higher, while that of Klf15 was lower, in the Klf15­siRNA group than in the Klf15­NC group. Critical roles of Klf15, Mmp12 and Mmp13 have been identified, which have not previously been shown to help regulate DVT initiation and progression. Moreover, Klf15­mediated regulation of DVT may be modulated by downregulation of various genes, such as Mmp12 and Mmp13, potentially providing a theoretical foundation and diagnostic criteria for DVT treatment.

Applications of Hydrogels with Special Physical Properties in Biomedicine.

As a polymer matrix containing a large amount of water, hydrogels have been widely used in many fields such as biology and medicine due to its similarity to extracellular matrix components, and its contact with blood, body fluids, and human tissue does not affect the metabolic processes of living organisms. However, due to the lack of unique physical properties of traditional polymer hydrogels, its further application in the high-end field is limited. With the progress of study, a series of hydrogels with special structures, such as double network hydrogel, composite hydrogel, Tetra-PEG gel, and topological gel, have improved the situation to a large extent. At the same time, the progress of research on the biocompatibility and biodegradability of hydrogels, which are expected to be used in biomedical fields, is also worthy of attention. This review introduces four such types of high-strength polymeric hydrogels and the mechanisms for improving their mechanical strength. Moreover, a discussion will be made around specific methods for imparting special physical properties to hydrogels and applications in the field of biomedicine such as cell culture, medical surgery, tissue engineering, and biosensing. At the end of the review, the main reasons and contradictions for the limits of the current applications are explained. An outlook on the future research in related fields and the importance of carrying out research in this area to promote medical progress are emphasized.

Upregulation of the long noncoding RNA lncPolE contributes to intervertebral disc degeneration by negatively regulating DNA polymerase epsilon.

Long noncoding RNAs (lncRNAs) are critical regulators of gene transcription. Our previous results have demonstrated that iron deficiency accelerates intervertebral disc degeneration (IDD) by affecting the stability of the DNA polymerase epsilon (Polε) complex. Here, we discovered that the novel lncRNA lncPolE functions as a negative regulator of Polε. The expression of lncPolE in IDD tissues was upregulated compared to its expression in healthy control tissues, and this was in contrast to the PolE1 expression levels. The increased lncPolE level was significantly correlated with the severity of IDD. Ectopic expression of lncPolE in human nucleus pulposus cells (hNPCs) was able to decrease PolE1 levels and cause apoptosis, while the specific knockdown of lncPolE in primary NP cells (pNPCs) from IDD patients can restore PolE1 levels. Interestingly, iron depletion or supplementation can affect the expression of lncPolE. Further analyses indicated that the downregulation of DNA methylation in the promoter region of lncPolE caused its overexpression. Collectively, our results suggest that the aberrant expression of lncPolE contributes to the pathogenesis of IDD by negatively regulating PolE1 in iron deficient conditions, and this may provide a new avenue to alleviate IDD progression in clinical treatment.

Synthesis, characterization, and cytotoxicity assessment of N-acetyl-l-cysteine capped ZnO nanoparticles as camptothecin delivery system.

The chemical stability, good biocompatibility and high drug loading capacity of zinc oxide nanoparticles (ZnO NPs) and their biomedical potentials make them a promising candidate for drug delivery. The aim of this study was to develop and assess a simple procedure for surface functionalization of ZnO NPs by N-acetyl-l-cysteine (NAC) for anticancer camptothecin (CPT) delivery. NAC capped ZnO NPs were successfully made using ZnCl2 and NaOH in the presence of NAC. CPT was covalently conjugated to the surface of as-synthesized ZnO-NAC NPs. To characterize the synthesized conjugate product (ZnO-NAC-CPT NPs), X-ray diffraction, Fourier Transform Infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, and dynamic light scattering method were used. Our results indicated that the ZnO-NAC-CPT NPs exhibit near-spherical morphology and uniform dispersion with an average diameter of ∼70 nm. The hemolysis assay showed that ZnO-NAC-CPT NPs has almost no hemolytic activity. In addition, MTT cytotoxicity assessment on A549 lung cancer cells revealed a drop of IC50 values from 1.17 µg/mL (free CPT) to 0.66 µg/mL (ZnO-NAC-CPT NPs). This result showed an augmented cancer-inhibitory effect of nanoconjugate complex. In conclusion, the novel ZnO-NAC-CPT NPs could be considered for new therapeutic endeavors.