METTL3 promotes the osteogenic differentiation of human periodontal ligament cells by increasing YAP activity via IGF2BP1 and YTHDF1-mediated m6A modification.

AIMS: N6-Methyladenosine (m6A) has been confirmed to play a dynamic role in osteoporosis and bone metabolism. However, whether m6A is involved in the osteogenic differentiation of human periodontal ligament cells (hPDLCs) remains unclear. The present study aimed to verify the role of methyltransferase-like 3 (METTL3)-mediated m6A modification in the osteogenic differentiation of hPDLCs. METHODS: The METTL3, Runx2, Osx, and YAP mRNA expression was determined by qPCR. METTL3, RUNX2, OSX, YTHDF1, YAP, IGF2BP1, and eIF3a protein expression was measured by Western blotting and immunofluorescence assays. The levels of m6A modification were evaluated by methylated RNA immunoprecipitation (MeRIP) and dot blot analyses. MeRIP-seq and RNA-seq were used to screen potential candidate genes. Nucleic acid and protein interactions were detected by immunoprecipitation. Alizarin red staining was used to evaluate the osteogenic differentiation of hPDLCs. Gene transcription and promoter activities were assessed by luciferase reporter assays (n ≥ 3). RESULTS: The expression of METTL3 and m6A modifications increased synchronously with the osteogenic differentiation of hPDLCs (p = .0016). YAP was a candidate gene identified by MeRIP-seq and RNA-seq, and its mRNA and protein expression levels were simultaneously increased. METTL3 increased the m6A methylated IGF2BP1-mediated stability of YAP mRNA (p = .0037), which in turn promoted osteogenic differentiation (p = .0147). Furthermore, METTL3 increased the translation efficiency of YAP by recruiting YTHDF1 and eIF3a to the translation initiation complex (p = .0154), thereby promoting the osteogenic differentiation of hPDLCs (p = .0012). CONCLUSION: Our study revealed that METTL3-initiated m6A mRNA methylation promotes osteogenic differentiation of hPDLCs by increasing IGF2BP1-mediated YAP mRNA stability and recruiting YTHDF1 and eIF3a to the translation initiation complex to increase YAP mRNA translation. Our findings reveal the mechanism of METTL3-mediated m6A modification during hPDLC osteogenesis, providing a potential therapeutic target for periodontitis and alveolar bone defects.

Targeting the tumor microenvironment in primary central nervous system lymphoma: Implications for prognosis.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma, and there is limited research on its tumor microenvironment (TME). Nevertheless, more and more studies have evidence that TME has essential effects on tumor cell proliferation, immune escape, and drug resistance. Thus, it is critical to elucidate the role of TME in PCNSL. The understanding of the PCNSL TME is gradually unfolding, including factors that distinguish it from systemic diffuse large B-cell lymphoma (DLBCL). The TME in PCNSL exhibits both transcriptional and spatial intratumor heterogeneity. Cellular interactions between tumor cells and stroma cells reveal immune evasion signaling. The comparative analysis between PCNSL and DLBCL suggests that PCNSL is more likely to be an immunologically deficient tumor. In PCNSL, T cell exhaustion and downregulation of macrophage immune function are accompanied by suppressive microenvironmental factors such as M2 polarized macrophages, endothelin B receptor, HLA depletion, PD-L1, and TIM-3. MMP-9, Integrin-ß1, and ICAM-1/LFA-1 play crucial roles in transendothelial migration towards the CNS, while CXCL13/CXCR5, CD44, MAG, and IL-8 are essential for brain parenchymal invasion. Further, macrophages, YKL-40, CD31, CD105, PD-1/PD-L1 axis, osteopontin, galectin-3, aggregative perivascular tumor cells, and HLA deletion may contribute to poor outcomes in patients with PCNSL. This article reviews the effect of various components of TME on the progression and prognosis of PCNSL patients to identify novel therapeutic targets.

Polyethylene glycol-polyvinylidene fluoride/TiO2 nanocomposite polymer coatings with efficient antifouling strategies: Hydrophilized defensive surface and stable capacitive deionization.

Capacitive deionization (CDI) is flourishing as an energy-efficient and cost-effective water desalination method. However, challenges such as electrode degradation and fouling have hindered the practical deployment of CDI technology. To address these challenges, the key point of our strategy is applying a hydrophilic coating composed of polyethylene glycol (PEG)-functionalized nano-TiO2/polyvinylidene fluoride (PVDF) to the electrode interface (labeled as APPT electrode). The PEG/PVDF/TiO2 layer not only mitigates the co-ion depletion, but also imparts the activated carbon (AC) electrode hydrophilicity. As anticipated, the APPT electrode possessed an enhanced desalination capacity of 83.54 µmol g-1 and a low energy consumption of 17.99 Wh m-3 in 10 mM sodium chloride solution compared with the bare AC electrode. Notably, the APPT maintained about 93.19 % of its desalination capacity after 50 consecutive adsorption-desorption cycles in the presence of bovine serum albumin (BSA). During the trial, moreover, no obvious overall performance decline was noted in concentration reduction (Δc), water recovery (WR) and productivity (P) over 50 cycles. This strategy realizes energy-efficient, antifouling and stable brackish water desalination and has great promise for practical applications.

METTL3 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells through IGF2BP1-Mediated Regulation of Runx2 Stability.

N6-Methyladenosine (m6A) has been reported to play a dynamic role in osteoporosis and bone metabolism. However, whether m6A is involved in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) remains unclear. Here, we found that methyltransferase-like 3 (METTL3) was up-regulated synchronously with m6A during the osteogenic differentiation of hPDLSCs. Functionally, lentivirus-mediated knockdown of METTL3 in hPDLSCs impaired osteogenic potential. Mechanistic analysis further showed that METTL3 knockdown decreased m6A methylation and reduced IGF2BP1-mediated stability of runt-related transcription factor 2 (Runx2) mRNA, which in turn inhibited osteogenic differentiation. Therefore, METTL3-based m6A modification favored osteogenic differentiation of hPDLSCs through IGF2BP1-mediated Runx2 mRNA stability. Our study shed light on the critical roles of m6A on regulation of osteogenic differentiation in hPDLSCs and served novel therapeutic approaches in vital periodontitis therapy.

Identification of endocrine-disrupting chemicals targeting key DCM-associated genes via bioinformatics and machine learning.

Dilated cardiomyopathy (DCM) is a primary cause of heart failure (HF), with the incidence of HF increasing consistently in recent years. DCM pathogenesis involves a combination of inherited predisposition and environmental factors. Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with endogenous hormone action and are capable of targeting various organs, including the heart. However, the impact of these disruptors on heart disease through their effects on genes remains underexplored. In this study, we aimed to explore key DCM-related genes using machine learning (ML) and the construction of a predictive model. Using the Gene Expression Omnibus (GEO) database, we screened differentially expressed genes (DEGs) and performed enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to DCM. Through ML techniques combining maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) logistic regression, we identified key genes for predicting DCM (IL1RL1, SEZ6L, SFRP4, COL22A1, RNASE2, HB). Based on these key genes, 79 EDCs with the potential to affect DCM were identified, among which 4 (3,4-dichloroaniline, fenitrothion, pyrene, and isoproturon) have not been previously associated with DCM. These findings establish a novel relationship between the EDCs mediated by key genes and the development of DCM.

Easily scale 3D conductive gradient fiber membrane for contaminants removal and fouling mitigation under electrochemical assistance.

An electrochemical membrane filtration system provides an innovative approach to enhance contaminant removal and mitigate membrane fouling. There is an urgent need to develop portable, versatile, and efficient electrochemical membranes for affordable wastewater treatment. Here, a 3D conductive gradient fiber membrane (CC/PVDF) with a gradient porous structure was prepared using a two-step phase inversion method. Methyl orange (MO) was utilized as model organic substance to investigate the electrochemical performance of the CC/PVDF membrane. At applied potentials of +2 V, +3 V, -2 V and -3 V, the removal efficiency of MO was 5.1, 5.3, 4.8, and 5.1 times higher than at 0 V. A dramatic flux loss of 35.02% occurred on the membrane without electrochemistry, interestingly, whereas the flux losses were only 23.59%-10.24% in the applied potential after 30 min of filtration, which were approximately 1.18, 1.28, 1.29 and 1.38 times as high as that without electrochemistry, respectively. The enhanced removal and anti-fouling performances of the membranes were attributed to the functions of electrochemical degradation, electrostatic repulsion, and electrically enhanced wettability. Electrochemical generation of Hydrogen peroxide, along with HO• radicals, was detected and direct electron transfer and HO• were proved to be the dominant oxidants responsible for MO degradation. The intermediate oxidation products were identified by mass spectrometry, and an electrochemical degradation pathway of MO was proposed based on bond-breaking oxidation, ring-opening reactions, and complete oxidation. All the findings emphasize that the ECMF system possesses superior efficiency and creative potential for water purification applications.

Utility of contrast-enhanced MRI radiomics features combined with clinical indicators for predicting induction chemotherapy response in primary central nervous system lymphoma.

PURPOSE: To assess the utility of combining contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics features with clinical variables in predicting the response to induction chemotherapy (IC) for primary central nervous system lymphoma (PCNSL). METHODS: A total of 131 patients with PCNSL (101 in the training set and 30 in the testing set) who had undergone contrast-enhanced MRI scans were retrospectively analyzed. Pyradiomics was utilized to extract radiomics features, and the clinical variables of the patients were gathered. Radiomics prediction models were developed using different combinations of feature selection methods and machine learning models, and the best combination was ultimately chosen. We screened clinical variables associated with treatment outcomes and developed clinical prediction models. The predictive performance of radiomics model, clinical model, and combined model, which integrates the best radiomics model and clinical characteristics, was independently assessed and compared using Receiver Operating Characteristic (ROC) curves. RESULTS: In total, we extracted 1598 features. The best radiomics model we selected as the best utilized T-test and Recursive Feature Elimination (RFE) for feature selection and logistic regression for model building. Serum Interleukin 2 Receptor (IL-2R) and Eastern Cooperative Oncology Group (ECOG) Score were utilized to develop a clinical predictive model for assessing the response to induction chemotherapy. The results of the testing set revealed that the combined prediction model (radiomics and IL-2R) achieved the highest area under the ROC curve at 0.868 (0.683, 0.967), followed by the radiomics model at 0.857 (0.681, 0.957), and the clinical prediction model (IL-2R and ECOG) at 0.618 (0.413, 0.797). The combined model was significantly more accurate than the clinical model, with an AUC of 0.868 compared to 0.618 (P < 0.05). While the radiomics model had slightly better predictive power than the clinical model, this difference was not statistically significant (AUC, 0.857 vs. 0.618, P > 0.05). CONCLUSIONS: Our prediction model, which combines radiomics signatures from CE-MRI with serum IL-2R, can effectively stratify patients with PCNSL before high-dose methotrexate (HD-MTX) -based chemotherapy.

LncRNA urothelial cancer associated 1 promotes the osteogenic differentiation of human periodontal ligament stem cells by regulating the miR-96-5p/Osx axis.

OBJECTIVES: To investigate the expression of long non-coding RNA (lncRNA) urothelial cancer associated 1 (UCA1) in human periodontal ligament stem cells (hPDLSCs), its effect on osteogenic differentiation of hPDLSCs and its mechanism. DESIGN: The expression of osteogenic genes Osx, Runx2, Ocn and Opn was explored by qPCR. Protein expression in hPDLSCs was estimated by Western blot. The osteogenic differentiation of hPDLSCs was detected by Alizarin red staining assays. The interaction between UCA1 and miR-96-5p was explored by RNA pulldown assay and dual luciferase assay. The interaction between miR-96-5p and Osx 3'-UTR was measured by dual luciferase assay. RESULTS: The expression of UCA1 and miR-96-5p was negatively correlated in hPDLSCs. During the osteogenic differentiation of hPDLSCs, the expression of UCA1 was increased, while the expression of miR-96-5p was decreased. Knockdown of UCA1 in hPDLSCs inhibited osteogenic differentiation but induced upregulation of miR-96-5p expression, and vice versa. In addition, miR-96-5p partially reversed the positive effect of UCA1 on osteogenic differentiation of hPDLSCs. Notably, UCA1 was identified as a miR-96-5p sponge, and miR-96-5p targeted Osx. CONCLUSIONS: Our results demonstrated that the novel UCA1/miR-96-5p/Osx pathway regulates osteogenic differentiation of hPDLSCs and sheds new insights and targets for periodontitis therapeutics.

A High-Sensitivity Low-Nanoflow LC-MS Configuration for High-Throughput Sample-Limited Proteomics.

This work demonstrates the utility of high-throughput nanoLC-MS and label-free quantification (LFQ) for sample-limited bottom-up proteomics analysis, including single-cell proteomics (SCP). Conditions were optimized on a 50 µm internal diameter (I.D.) column operated at 100 nL/min in the direct injection workflow to balance method sensitivity and sample throughput from 24 to 72 samples/day. Multiple data acquisition strategies were also evaluated for proteome coverage, including data-dependent acquisition (DDA), wide-window acquisition (WWA), and wide-window data-independent acquisition (WW-DIA). Analyzing 250 pg HeLa digest with a 10-min LC gradient (72 samples/day) provided >900, >1,800, and >3,000 protein group identifications for DDA, WWA, and WW-DIA, respectively. Total method cycle time was further reduced from 20 to 14.4 min (100 samples/day) by employing a trap-and-elute workflow, enabling 70% mass spectrometer utilization. The method was applied to library-free DIA analysis of single-cell samples, yielding >1,700 protein groups identified. In conclusion, this study provides a high-sensitivity, high-throughput nanoLC-MS configuration for sample-limited proteomics.

Relationship between driver gene mutations and clinical pathological characteristics in older lung adenocarcinoma.

Objectives: Lung adenocarcinoma (LUAD) is the most common newly diagnosed malignant tumor in older people. As older patients age, organ function decreases, leading to increased adverse reactions to treatment. The epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase tyrosine (ALK) tyrosine kinase inhibitors (TKIs) therapy are more effective and well-tolerated than chemotherapy, while the rate of genetic testing and subsequent targeted treatment among older patients remains relatively low, the clinical benefit limitation for those patients. This study aims to investigate the mutation characteristics of LUAD diver gene and its relationship with clinicopathological features in older LUAD. Materials and methods: A total of 275 patients were diagnosed as LUAD and were over sixty years old. We utilized next-generation sequencing technology to detect and analyze gene mutations in postoperative tissue specimens, including EGFR, KRAS, ALK, ROS1, RET, MET, BRAF, HER2, PIK3CA and NRAS. Results: A total of 90.18% (248/275) of older LUAD patients experienced genetic mutations. The EGFR (192, 69.82%) had the highest mutation rate among ten genes, followed by KRAS (21, 7.64%), MET (21, 7.64%), ERBB2 (15, 5.45%), RET (9, 3.27%), ALK (8, 2.91%), ROS1 (8, 2.91%), PIK3CA (6, 2.18%), BRAF (5, 1.82%) and NRAS (1, 0.36%). We also found thirty patients (15.63%) with EGFR mutations also having other gene mutations. The L858R mutation and exon19 deletion were the predominant EGFR mutations, accounting for 84.90% of EGFR-mutated patients. In addition, fifty-one kinds of EGFR mutations were detected, distributed in the protein tyrosine kinase catalytic domain (43, 84.31%), cysteine enriched domain (4, 7.84%), receptor binding domain (3, 5.88%), and EGFR transmembrane domain (1,1.96%). Ten cases of gene fusion mutation were detected. Two rare partner genes, PKHD1 (P60:R34) and STK39 (R33:S11), were detected by ROS1 gene fusion. RET gene fusion revealed a rare companion gene KCND2 (R11:K2). The EGFR mutations were more prevalent in female, non-smoking patients (p < 0.05), and the KRAS mutations were more common in male and smoking patients (p < 0.01). In addition, the BRAF mutations were more likely to occur in the right lung (p < 0.05). Conclusion: Older LUAD populations exhibit diverse genetic mutations, which may also exist simultaneously. Simultaneous detection of multiple genes by NGS can accelerate and enhance targeted treatment benefits for older LUAD patients, ultimately improving their quality of life.

Effect of non-surgical periodontal treatment on cytokines/adipocytokines levels among periodontitis patients with or without obesity: a systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review and meta-analysis was to evaluate the effects of non-surgical periodontal therapy (NSPT) on inflammatory-related cytokines/adipocytokines in periodontitis patients with or without obesity. METHODS: We followed the preferred reporting items for systematic reviews and meta-analyses statement and registered the study (CRD42022375331) in the Prospective International Register of Systematic Reviews. We screened randomized-controlled trials and controlled clinical trials from six databases up to December 2022. Quality assessment was performed with RoB-2 and ROBINS-I tools for randomized trials and non-randomized trials, respectively. Meta-analysis was carried out using a random-effect model. RESULTS: We included seventeen references in the systematic analysis, and sixteen in the meta-analysis. Baseline results of pro-inflammatory biomarkers, including serum interleukin (IL)-6, serum and gingival crevicular fluid (GCF), tumor necrosis factor (TNF)-a, serum C-reactive protein (CRP)/hs-CRP, and serum and GCF resistin, were higher in obesity subjects than in normal weight subjects. The effect of NSPT with respect to levels of cytokines/adipocytokines, including IL-6, TNF-a, CRP/hs-CRP, resistin, adiponectin, leptin and retinol binding protein 4 (RBP4), were then analyzed in the systematic and meta-analysis. After three months of NSPT, serum (MD = -0.54, CI = -0.62 - -0.46), and GCF (MD = -2.70, CI = -4.77 - -0.63) levels of IL-6, along with the serum RBP4 (MD = -0.39, CI = -0.68-0.10) decreased in periodontitis individuals with obesity. NSPT also improved GCF adiponectin levels after three months (MD = 2.37, CI = 0.29 - 4.45) in periodontitis individuals without obesity. CONCLUSIONS: Obese status altered the baseline levels of cytokines/adipocytokines (serum IL-6, serum and GCF TNF-a, serum CRP/hs-CRP, and serum and GCF resistin). Then NSPT can shift the levels of specific pro-inflammatory mediators and anti-inflammatory mediators in biological fluids, both in obesity and non-obesity individuals. NSPT can reduce serum and GCF IL-6 levels together with serum RBP4 level in individuals with obesity after 3 months, besides, there is no sufficient evidence to prove that obese patients have a statistically significant decrease in the levels of other cytokines compared to patients with normal weight. NSPT can also increase GCF adiponectin level in normal weight individuals after 3 months. Our findings imply the potential ideal follow-up intervals and sensitive biomarkers for clinical bioanalysis in personalized decision-making of effect of NSPT due to patients' BMI value.

Long non­coding RNA SNHG5 promotes osteogenic differentiation of human periodontal ligament stem cells via mediating miR­23b­3p/Runx2 axis.

The treatment of bone loss due to periodontitis has posed a great challenge for physicians for decades. Therefore, it is of extraordinary significance to identify an effective regeneration scheme for alveolar bone. This study aimed to investigate long non-coding RNA (lncRNA) small nucleolar RNA host gene 5 (SNHG5) whether sponges microRNA-23b-3p (miR-23b-3p) to achieve the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Results revealed that the expression of SNHG5 was upregulated whereas that of miR-23b-3p was downregulated in osteogenic hPDLSCs. Alizarin red staining assays and qRT-PCR demonstrated that SNHG5 silencing or miR-23b-3p overexpression inhibits hPDLSCs osteogenic differentiation and vice versa. In addition, miR-23b-3p partially abolished the promotive effect of SNHG5 on osteogenic differentiation of hPDLSCs. Dual luciferase report and RNA pulldown assay verified that miR-23b-3p is a regulatory target of SNHG5 and that Runx2 is a gene target of miR-23b-3p. In brief, the results demonstrate that SNHG5 promotes the osteogenic differentiation of hPDLSCs by regulating the miR-23b-3p/Runx2 axis. Our study provides novel mechanistic insights into the critical role of lncRNA SNHG5 as a miR-23b-3p sponge to regulate Runx2 expression in hPDLSCs and may serve as a potential therapeutics target for periodontitis.

Challenges in the management of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma. Stereotactic biopsy remains the gold standard for the pathological diagnosis of PCNSL. However, certain new auxiliary diagnostic methods are considered to have good application prospects; these include cytokine and tumor circulating DNA, among others. Although new drugs such as immunomodulators, immune checkpoint inhibitors, chimeric antigen receptor T-cells, and Bruton tyrosine kinase inhibitors have brought hope owing to their improved efficacy, the high recurrence rate and subsequent high mortality remain barriers to long-term survival. Increasing emphasis is therefore being placed on consolidation treatments. Consolidation treatment strategies include whole brain radiotherapy, autologous hematopoietic stem cell transplantation, and non-myeloablative chemotherapy. As studies directly comparing the effectiveness and safety of different consolidation treatment schemes are lacking, the optimal consolidation strategy remains uncertain. This article will review the diagnosis and treatment of PCNSL, focusing on the progress in research pertaining to consolidation therapy.

Robust self-cleaning membrane with superhydrophilicity and underwater superoleophobicity for oil-in-water separation.

The discharge of oily wastewater has increased dramatically and will bring serious environmental problems. In this work, a self-cleaning and anti-fouling g-C3N4/TiO2/PVDF composite membrane was fabricated via the layer-by-layer approach. The surface of as-prepared composite membrane displayed a superhydrophilic and underwater superoleophobic behavior under irradiation with visible light. Also, upon irradiation with visible light, the fabricated g-C3N4/TiO2/PVDF composite membrane displayed enhanced permeation flux and improved oil removal efficiency as a result of the generation of hydroxyl free radicals during the photocatalytic filtration process. Significantly, irradiation with visible light remarkably improved reusability of the composite membrane by initiating photocatalytic decomposition of deposited oil foulants, which enabled removal of over 99.75% of oils, thus reaching a nearly 100% flux recovery ratio. Furthermore, the g-C3N4/TiO2/PVDF composite membrane exhibited great anti-fouling behavior in photocatalysis-assisted filtration. The mechanistic study revealed that underwater superhydrophobicity and the generation of free hydroxyl radicals jointly contributed to membrane anti-fouling. The greatest advantages of this g-C3N4/TiO2/PVDF composite membrane are that not only does it degrades the oil pollutants, but it also makes the membrane less vulnerable to fouling.

Establishing a high-performance anti-fouling PEI-ZIF-PAA membrane with improved Lewis acid-base interactions and hydrophilicity.

Membrane fouling and the trade-off between membrane permeability and selectivity restrict the potential applications of membrane filtration for water treatment. ZIF-8 was found having great permeability and antibiofouling performance, but with issue on particle aggregation makes it difficult to achieve high ZIFs loading and fabricate a defect-free molecular sieving membrane in previous research. In this study, we formed a scalable antibiofouling surface with improved permeability and fouling resistance on a PEI-ZIF-PAA membrane using a layer-by-layer assembly technique. The synergistic effects of being sandwiched between two different polyelectrolyte layers with opposite charges endowed the ZIF nanoparticles with improved stability and scalability for membrane modification. The PEI-ZIF-PAA membrane exhibited a satisfactory water flux of 120.78 LMH, which was 46.97% higher than that of the pristine PES membrane. The normalized water flux loss was serious in the absence of ZIF-8, and the flux increased with the ZIF-8 concentration. Antifouling tests suggested that the PEI-ZIF-PAA membrane possessed good antifouling performance due to the much higher surface hydrophilicity and positive Lewis acid-base interactions with foulants. The HA rejection increased with the ZIF-8 concentration and reached a maximum of 92.1% in the presence of 1.00% (w/v) ZIF-8. The membrane regeneration was tested under physical and chemical cleaning with flux recovery rates of about 85% and 95%. XDLVO analysis showed that the total interaction energy between HA and the PEI-ZIF-8-PAA membrane was 26.45 mJ/m2, and the superior antifouling performance was mainly attributed to Lewis acid-base interactions. This study indicates that ZIF-8 nanocrystals are promising materials for fabricating novel membranes for sewage treatment.

Efficacy and safety of chimeric antigen receptor T-cells treatment in central nervous system lymphoma: a PRISMA-compliant single-arm meta-analysis.

BACKGROUND: Chimeric antigen receptor (CAR) T cells are used to treat refractory and recurrent B-cell lymphoma. When administered intravenously, CAR T cells can be detected in cerebrospinal fluid, and thus represent a promising method for the treatment of central nervous system lymphoma (CNSL). This meta-analysis aimed to clarify the effectiveness and safety of CAR T-cell therapy in the treatment of CNSL. METHODS: Studies involving patients with CNSL who received CAR T-cell therapy that reported overall response (OR), complete response (CR), and partial response (PR) were included. A random-effects or fixed-effects model with double arcsine transformation was used for the pooled analysis and 95% confidence intervals (CI) were determined for all outcomes. RESULTS: Eight studies, comprising 63 patients, were identified and were included in the meta-analysis. The pooled OR and CR rates after treatment with CAR T cells were 69% (95% CI, 56-81%) and 51% (95% CI, 37-64%), respectively. The pooled rate of progressive disease after remission was 38% (95% CI, 21-55%). The pooled rate for neurotoxicity grade 3 or above was 12% (95% CI, 3-24%, I2 = 0.00%, p = 0.53). No treatment-related deaths were reported. CONCLUSIONS: CAR T-cell therapy is a promising option for the treatment of CNSL owing to a high short-term remission rate and controllable side effects. However, the high recurrence rate after remission must be addressed. Long-term follow-up data with large sample sizes are also needed to better assess the effectiveness and safety of CAR T-cell therapy. REGISTRATION: This meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) (CRD42022301332).

[Safety and efficacy of different doses of tranexamic acid in posterior cervical laminectomy with lateral mass screw fixation and bone graft fusion].

Objective: To investigate the safety and efficacy of different doses of tranexamic acid (TXA) in posterior cervical laminectomy with lateral mass screw fixation and bone graft fusion by a prospective clinical study. Methods: The middle-aged and elderly patients with cervical spondylotic myelopathy, who were admitted between January 2020 and January 2022 and scheduled to undergo posterior cervical laminectomy with lateral mass screw fixation and bone graft fusion, were studied as the research subjects. Among them, 165 patients met the selection criteria and were included in the study. The patients were allocated into 3 groups ( n=55) by random double-blind lottery. Groups A and B were given intravenous infusion of TXA at 30 minutes before operation according to the standards of 15 and 30 mg/kg, respectively; and group C was given normal saline in the same way. There was no significant difference in gender, age, body mass index, and preoperative D-dimer, hemoglobin (Hb), and hematocrit (HCT) between groups ( P>0.05). The intraoperative bleeding, intraoperative blood transfusion, postoperative drainage volume, drainage days, and postoperative hospital stay were recorded. The Hb, HCT, and D-dimer were compared before operation and at 3 days after operation. Venous ultrasonography of the lower extremities was taken after operation to assess thrombosis; and the postoperative hematoma and epilepsy were also observed. Results: All operations were successfully completed, and the incisions healed by first intention. The differences in intraoperative bleeding volume, postoperative drainage volume, drainage days, and postoperative hospital stay between groups were significant ( P<0.05). The above indexes were significantly less in group B than in groups A and C. During operation, 14 patients in group A and 23 patients in group C were transfused, and no patient in group B had blood transfusions. Compared with groups A and C, the blood transfusion volume in group B significantly decreased ( P<0.05), and the difference between groups A and C was not significant ( P>0.05). There was no significant difference in the differences of D-dimer, Hb, and HCT before and after operation between groups ( P>0.05). At 5 days after operation, the venous ultrasonography of the lower extremities showed that the 2 cases of intermuscular venous thrombosis occurred in groups A, B, and C, respectively. No hematoma or epilepsy occurred after operation. Conclusion: The application of 15 and 30 mg/kg TXA in posterior cervical laminectomy with lateral mass screw fixation and bone graft fusion can reduce intraoperative bleeding and postoperative drainage volume, postoperative drainage days, and postoperative hospital stay. And application of 30 mg/kg TXA can reduce intraoperative blood transfusion, without increasing the risk of lower extremity venous thrombosis, hematoma, and epilepsy.

Exploration of interaction property between nonylphenol and G protein-coupled receptor 30 based on molecular simulation and biological experiments.

Nonylphenol (NP), a representative of environmental hormones, can cause extensive biological effects in the human body. In this study, we first analyzed the mutual binding modes of NP and G protein coupled estrogen receptor 30 (GPR30) by molecular simulation. The 3D structure of GPR30 was successfully constructed. We found that the binding sites of NP on GPR30 are similar to that of 17ß-Estradiol (E2) on GPR30. The GPR30-E2 bond complex is more stable than GPR30-NP bond complex. Next CCK-8 assay was used to detect the regulatory effect of NP on SKBR-3 cell proliferation. When NP and E2 were used alone, low concentration could promote cell proliferation, while high concentration was the opposite. The presence of E2 can promote the cell proliferation effect of NP, and inhibit the inhibitory intensity. NP could promote both the cell proliferation effect and inhibition intensity of E2. Based on our results, we conclude that the binding modes of NP and GPR30 is similar to that of E2 and GPR30. In biology, NP can play estrogen role by activating GPR30 receptor, but it can also produce cytotoxicity at higher concentration.

Genetic characterization of hepatitis E virus from wild boar in China.

Hepatitis E virus (HEV), the causative agent of hepatitis E (HE), is classified into four major genotypes (1-4), with wild boar being the main natural reservoir for genotypes 3 and 4. However, little is known about the prevalence of HEV infection in wild boars in China. In this study, RT-nested PCR and RT-quantitative PCR were used to detect the HEV RNA in tissue samples taken from 331 free-ranging wild boars collected between 2018 and 2020 from 24 regions across China, and the partial ORF2 genes or complete genomes of the positive samples were sequenced. Furthermore, antibodies against HEV in 216 serum samples from wild boars were tested by ELISA. As a result, HEV RNA was detected in nine out of 331 liver samples of wild boars (2.72%), which were distributed in eight regions. Genetic and evolutionary analysis of partial ORF2 sequences indicated that the HEV strains identified in this study share 83.9%-100% nucleotide sequence identity and belong to subtypes 4d (n = 6), 4g (n = 2), and 4h (n = 1), and similar phylogeny was obtained using the complete genome sequences of seven wild boar HEV strains. Additionally, the HEV viral loads were higher in the liver than in other tissues and blood. Moreover, 61 out of 216 sera (28.2%) from wild boars tested positive for anti-HEV antibodies. To our knowledge, this is the first study to report the epidemiological situations of HEV infections in free-ranging wild boars in China, and the obtained data are valuable for prevention and control of HE.

Pollution and Cleaning of PDMS Pervaporation Membranes after Recovering Ethyl Acetate from Aqueous Saline Solutions.

The removal of volatile organic compounds (VOCs) from wastewater containing nonvolatile salts has become an important and interesting case of the application of the pervaporation (PV) process. The aim of this study was to evaluate the influence of salts on the PV removal of ethyl acetate from wastewater using a polydimethylsiloxane (PDMS) membrane. The fouled membrane was then characterized via scanning electron microscopy-energy-dispersive X-ray analysis (SEM-EDX) to investigate salt permeation. The membrane backflushing process was carried out by periodically flushing the permeate side of the tubular membrane. The results demonstrated that salts (NaCl and CaCl2) could permeate through the PDMS membrane and were deposited on the permeate side. The presence of salts in the feed solution caused a slight increase in the membrane selectivity and a decrease in the permeate flux. The flux decreased with increasing salt concentration, and a notable effect occurred at higher feed-salt concentrations. A permeate flux of up to 98.3% of the original flux was recovered when the permeation time and backflushing duration were 30 and 5 min, respectively, indicating that the effect of salt deposition on flux reduction could be mitigated. Real, organic, saline wastewater was treated in a pilot plant, which further verified the feasibility of wastewater PV treatment.