Surface Ammonium Ions Assisted Decoration of Monodisperse Cobalt Nanoparticles on Molybdenum Oxide Films as Efficient Electrocatalysts for Hydrogen Evolution Reaction.

The high expense associated with electrocatalysts poses a challenge to the advancement of a hydrogen-based energy economy. The utilization of nonprecious metal-based electrocatalysts that are easily prepared and cost-effective is imperative for the future sustainability of a hydrogen society. The semiconductive MoO3-x has been identified as a promising nonprecious electrocatalyst for the hydrogen evolution reaction (HER). Nevertheless, enhancing its relatively low electrocatalytic activity toward HER remains a top priority. This study illustrates the manipulation of surface ammonium ions (NH4+) to produce uniform and distinct cobalt nanoparticles (Co NPs) on active MoO3-x supports, resulting in a more effective heterostructured composite electrocatalyst for HER. The presence of NH4+ ions in the MoO3-x film was extensively examined using infrared spectroscopy, X-ray photoelectron spectroscopy, and UV-visible colorimetric techniques. Additionally, the firmly attached NH4+ ions were employed as binding sites to precipitate Co-containing complex ions. Due to the monolayer-like adsorption of NH4+ ions, only a small quantity of Co precipitate was formed, which was subsequently electrochemically transformed into Co atoms that diffused and created well-separated uniform metallic Co nanoparticles (with an average size of less than 10 nm) on the MoO3-x film. The resulting heterostructure displays a 4.5-fold increase in current density for HER compared to the MoO3-x electrocatalyst through electrochemical assessments. The enhanced catalytic activity was ascribed to the optimized adsorption/desorption of the species involved in water reduction at the heterointerfaces and improved charge transfer rates. These nanoheterostructures hold great promise for a variety of applications in heterogeneous electrocatalysis, while the novel approach could potentially direct the creation of more heterostructures.

Metformin reduces basal subpopulation and attenuates mammary epithelial cell stemness in FVB/N mice.

Metformin shows promise in breast cancer prevention, but its underlying mechanisms remain unclear. This study investigated the impact of metformin on the repopulation dynamics of mammary epithelial cells (MECs) and the signaling pathways in non-tumorigenic FVB/N mice. This study aimed to enhance our understanding of the role of metformin in reducing the susceptibility of MECs in premalignant tissues to oncogenic factors. In this study, female mice were administered 200 mg/kg/day of metformin via intraperitoneal (i.p.) injection from 8 to 18 weeks of age. After this treatment period, morphogenesis, flow cytometry, analyses of MEC stemness, and RNA sequencing were performed. The study findings indicated that metformin treatment in adult mice reduced mammary gland proliferation, as demonstrated by decreased Ki67+ cells and lateral bud formation. Additionally, metformin significantly reduced both basal and mammary repopulating unit subpopulations, indicating an impact on mammary epithelial cell repopulation. Mammosphere, colony-forming cell, and 3D culture assays revealed that metformin adversely affected mammary epithelial cell stemness. Furthermore, metformin downregulated signaling in key pathways including AMPK/mTOR, MAPK/Erk, PI3K/Akt, and ER, which contribute to its inhibitory effects on mammary proliferation and stemness. Transcriptome analysis with RNA sequencing indicated that metformin induced significant downregulation of genes involved in multiple critical pathways. KEGG-based pathway analysis indicated that genes in PI3K/Akt, focal adhesion, ECM-receptor, small cell lung cancer and immune-modulation pathways were among the top groups of differentially regulated genes. In summary, our research demonstrates that metformin inhibits MEC proliferation and stemness, accompanied by the downregulation of intrinsic signaling. These insights suggest that the regulatory effects of metformin on premalignant mammary tissues could potentially delay or prevent the onset of breast cancer, offering a promising avenue for developing new preventive strategies.

Uridine phosphorylase-1 promotes cell viability and cell-cycle progression in human epidermal keratinocytes via the glycolytic pathway.

Glycolysis is vital for the excessive proliferation of keratinocytes in psoriasis, and uridine phosphorylase-1 (UPP1) functions as an enhancer of cancer cell proliferation. However, little is known about whether UPP1 promotes keratinocyte proliferation and accelerates psoriasis development. This study revealed that UPP1 facilitates cell viability and cell-cycle progression in human epidermal keratinocytes (HEKs) by modulating the glycolytic pathway. Bioinformatics analysis of UPP1 gene expression and its correlation with the Reactome revealed that UPP1 mRNA expression, cell-cycle progression, the interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway and glycolysis were positively associated with psoriasis. Cell proliferation, the cell cycle and glycolysis were evaluated after UPP1 was silenced or overexpressed. The results showed that UPP1 overexpression increased cell proliferation, cell-cycle progression and glycolysis, which was contrary to the effects of UPP1 silencing. However, the STAT3 inhibitor diminished UPP1 expression because STAT3 can bind to the UPP1 promoter. In conclusion, UPP1 was significantly activated by the IL-6/STAT3 pathway and could modulate glycolysis to regulate cell proliferation and cell-cycle progression in keratinocytes during the development of psoriasis.

Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation.

Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

Causal relationship between gut microbiota and diabetic nephropathy: A bidirectional mendelian randomization study.

In this study, we summarized the key findings and potential implications of association studies investigating the relationship between gut microbiota composition and risks for Diabetic nephropathy (DN). We used Mendelian randomization (MR) analysis to explore the relationship between gut microbiota and DN using two different publicly available DN databases. The results were also summarized using five mainstream MR analysis methods. We controlled for various possible biases in the results. The results showed that specific bacterial genera were associated with increased or decreased risk of DN. These associations can be attributed to a variety of factors, including metabolites produced by certain bacteria. Most of our findings are consistent with the existing research findings, but there are still some differences with the existing results. In addition, we also pointed out that some microbiota that may be associated with DN but remain unnoticed can bring new research directions. Our work made use of MR, a reliable technique for examining causal correlations using genetic data investigating potential processes, carrying out longitudinal studies, looking into intervention options, and using a multi-omics approach may be future research avenues. Further, our findings also point to a few unexplored possible study paths for DN in the future. These initiatives may improve our reconciliation of the internal relationships between the gut microbiota and DN and pave the way for more precise prevention and treatment methods. However, it is also critical to recognize any potential restrictions, such as those caused by sample size, population variety, and analytical techniques.

Application of thromboelastography to predict the severity of bleeding after chimeric antigen receptor (CAR)-T cell therapy in patients with hematological malignancy.

OBJECTIVES: We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)-T cell therapy. METHODS: A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non-severe bleeding group. The thromboelastography data was collected on the day of CAR-T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR-T cell infusion. RESULTS: The patients of the severe bleeding group had lower platelet (p < .007), maximum amplitude (p = .002), coagulation index (p = .005), and longer coagulation time (p = .019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0-10, opposite on Days 10-20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR-T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84-0.95; p < .001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35-5.32; p = .006) were significantly associated with high bleeding severity. CONCLUSIONS: Thromboelastography was considered to be a good predictor of bleeding severity.

Visible-Light-Enhanced Hydrogen Evolution through Anodic Furfural Electro-Oxidation Using Nickel Atomically Dispersed Copper Nanoparticles.

A novel copper nanoparticle variant, denoted as Cu98Ni2 NPs, which incorporate Ni atoms in an atomically dispersed manner, has been successfully synthesized via a straightforward one-pot electrochemical codeposition process. These nanoparticles were subsequently employed as an anode to facilitate the oxidation of furfural, leading to the production of hydrogen gas. Voltammetric measurements revealed that the inclusion of trace amounts of Ni atoms in the nanoparticles resulted in a pronounced synergistic electronic effect between Cu and Ni. Consequently, a 43% increase in current density at 0.1 V was observed in comparison to pure Cu NPs. Importantly, when the Cu98Ni2 NPs were irradiated with visible light, a remarkable current density enhancement factor of 505% at 0.1 V was achieved relative to that of pure Cu NPs in the absence of light. This enhancement can be attributed to localized surface plasmon resonance induced by visible light, which triggers photothermal and photoelectric effects. These effects collectively contribute to the significant overall improvement in the electrocatalytic oxidation of furfural, leading to enhanced hydrogen evolution.

Regulation of microglia polarization after cerebral ischemia.

Stroke ranks second as a leading cause of death and permanent disability globally. Microglia, innate immune cells in the brain, respond rapidly to ischemic injury, triggering a robust and persistent neuroinflammatory reaction throughout the disease's progression. Neuroinflammation plays a critical role in the mechanism of secondary injury in ischemic stroke and is a significant controllable factor. Microglia activation takes on two general phenotypes: the pro-inflammatory M1 type and the anti-inflammatory M2 type, although the reality is more complex. The regulation of microglia phenotype is crucial to controlling the neuroinflammatory response. This review summarized the key molecules and mechanisms of microglia polarization, function, and phenotypic transformation following cerebral ischemia, with a focus on the influence of autophagy on microglia polarization. The goal is to provide a reference for the development of new targets for the treatment for ischemic stroke treatment based on the regulation of microglia polarization.

The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.

INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.

Influence of lateral single jets for thermal protection of reentry nose cone with multi-row disk spike at hypersonic flow: computational study.

The main challenge for the advancement of current high-speed automotives is aerodynamic heating. In this study, the application of lateral jet for thermal protection of the high-speed automotives is extensively studied. The simulation of the lateral coolant jet is done via Computational fluid dynamic at high-velocity condition. Finding optimum jet configuration for reduction of the aerodynamic heating is the main goal of this research. Two different coolant jets (Helium and Carbon dioxide) are investigated as coolant jet and flow study and fuel penetration mechanism are fully presented. In addition, the thermal load on the main body of nose cone is compared for different configurations. Our results specify that the injection of lateral jet near the tip of spike is effective for thermal protection of main body via deflection of bow shock. Also, Carbon dioxide jet with lower diffusivity is more effective for the protection of forebody with multi-row disk from sever aerodynamic heating.

Role of hypoxia-inducible factor-1α and survivin in breast cancer recurrence and prognosis.

Objective: To analyze the expression of hypoxia-inducible factor-1α (HIF-1α) and survivin in breast cancer, and different molecular subtypes of breast cancer and to assess their relationship with recurrence and prognosis. Methods: The expression levels of HIF-1α and survivin genes in breast cancer were investigated using bioinformatics. Their protein expression levels were then verified through immunohistochemistry (IHC), and their relationship with recurrence and prognosis was assessed. Results: Expression levels of HIF-1α and survivin genes and proteins were increased in breast cancer tissues compared with normal tissues. Both were associated with clinical features of breast cancer and differentially expressed in different molecular subtypes of breast cancer, and both are related to the signal pathway of breast cancer growth and invasion. HIF-1α and survivin gene and protein expression levels were correlated, and both were associated with breast cancer recurrence (R = 0.380, P < 0.05; R = 0.673, P < 0.05, respectively). According to The Cancer Genome Atlas (TCGA) database, HIF1A and BIRC5 gene were not associated with breast cancer prognosis (P ≥ 0.05); however, HIF-1α and survivin protein were associated with recurrence patient's overall survival (OS) (P < 0.05). Conclusion: HIF-1α and survivin are highly expressed in breast cancer and can be used as potential biomarkers to predict recurrence and assess prognosis.

Optical coherence tomography for in vivo longitudinal monitoring of artificial dermal scaffold.

OBJECTIVES: Artificial dermal scaffold (ADS) has undergone rapid development and been increasingly used for treating skin wound in clinics due to its good biocompatibility, controllable degradation, and low risk of disease infection. To obtain good treatment efficacy, ADS needs to be monitored longitudinally during the treatment process. For example, scaffold-tissue fit, cell in-growth, vascular regeneration, and scaffold degradation are the key properties to be inspected. However, to date, there are no effective, real-time, and noninvasive techniques to meet the requirement of the scaffold monitoring above. MATERIALS AND METHODS: In this study, we propose to use optical coherence tomography (OCT) to monitor ADS in vivo through three-dimensional imaging. A swept source OCT system with a handheld probe was developed for in vivo skin imaging. Moreover, a cell in-growth, vascular regeneration, and scaffold degradation rate (IRDR) was defined with the volume reduction rate of the scaffold's collagen sponge layer. To measure the IRDR, a semiautomatic image segmentation algorithm was designed based on U-Net to segment the collagen sponge layer of the scaffold from OCT images. RESULTS: The results show that the scaffold-tissue fit can be clearly visualized under OCT imaging. The IRDR can be computed based on the volume of the segmented collagen sponge layer. It is observed that the IRDR appeared to a linear function of the time and in addition, the IRDR varied among different skin parts. CONCLUSION: Overall, it can be concluded that OCT has a good potential to monitor ADS in vivo. This can help guide the clinicians to control the treatment with ADS to improve the therapy.

Blocking of PI3-kinase beta protects against cerebral ischemia/reperfusion injury by reducing platelet activation and downstream microvascular thrombosis in rats.

Phosphoinositide 3-kinase beta (PI3Kß) plays an important role in platelet activation and thrombosis, but its role in stroke pathology remains unknown. In this study, we investigated whether inhibition of PI3Kß protects against cerebral ischemia/reperfusion (I/R) injury by preventing circulating platelet activation and downstream microvascular thrombosis. We used a rat intraluminal filament model of transient middle cerebral artery occlusion (tMCAO) because the rapid restoration of cerebral blood flow to the ischemic area in both tMCAO and endovascular thrombectomy provides clinical relevance for this model. The results showed that TGX221, a selective PI3Kß inhibitor, treatment immediately before the onset of reperfusion dose-dependently reduced infarct volume and improved neurological function. The protective effects were associated with blocking platelet activation and thrombotic response, thereby reducing downstream microvascular thrombosis, and maintaining reperfusion efficiency. These results suggest that PI3Kß might be a promising target for treating downstream microvascular thrombosis induced by cerebral I/R injury and offer a novel adjunctive treatment to improve reperfusion therapy for acute ischemic stroke.

Plasmon-enhanced photocatalysis using gold nanoparticles encapsulated in nanoscale molybdenum oxide shell.

Using solar energy to enhance the transformation rate of organic molecules is a promising strategy to advance chemical synthesis and environmental remediation. Plasmonic nanoparticles responsive to sunlight show great promise in the catalysis of chemical reactions. In this work, we used a straightforward wet-chemistry method to synthesize plasmonic octahedral gold nanoparticles (NPs) coated with thin molybdenum oxide (MoO3-x), Au@MoO3-xNPs, which exhibited strong surface plasmon resonance in a broad wavelength range. The synthesized Au@MoO3-xNPs were characterized by UV-vis, SEM, TEM, EDS, XPS, and the electrochemical technique of cyclic voltammetry (CV). The catalytic performance of Au@MoO3-xNPs under visible light irradiation was investigated using the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) as a model reaction. The presence of a thin capping layer of MoO3-xon our Au NPs contributed to the broadening of their range of absorption of visible light, resulting in a stronger intra-particle plasmonic resonance and the modulation of surface energy and electronic state. Accordingly, the kinetics of plasmon photocatalytic transformation of 4-NP to 4-AP was significantly accelerated (by a factor of 8.1) under visible light, compared to uncapped Au NPs in the dark. Our as-synthesized Au@MoO3-xNPs is an example that the range of plasmonic wavelengths of NPs can be effectively broadened by coating them with another plasmon-active (semiconducting) material, which substantially improves their plasmonic photocatalytic performance. Meanwhile, the synthesized Au@MoO3-xNPs can be used to accelerate the transformation of organic molecules under visible light irradiation.

Suppression of exosomal hsa_circ_0001005 eliminates the Vemurafenib resistance of melanoma.

OBJECTIVES: More and more evidences show that circular RNAs (circRNAs) can be used as miRNA sponge to regulate the drug resistance of malignancies, including melanoma. However, how exosomal circRNAs participate in the therapeutic resistance of melanoma remains ambiguous. METHODS: Vemurafenib-resistant A375 cells were cultured and then the circRNA profile of exosomes from the parental A375 and A375-resistant cells were sequenced. Transmission electron microscopy (TEM), exogenous nanoparticle tracking analysis (NTA) and Western Blot assays were leveraged to confirm the successful collection of exosomes from A375 and A375R cells. Another five published RNA-seq data and microRNA-seq data, and seven miRNA databases were collected to construct a competing endogenous RNA (ceRNA) network. Comprehensive bioinformatic analysis was adopted to identify key molecules related to the drug resistance, including multiscale embedded gene co-expression network analysis (MEGENA). Then, qRT-PCR, cell viability and colony formation were used to estimate the function of hub circRNAs. The role of has_circ_0001005 in vivo was verified via xenograft assay. The Tumor online Prognostic analyses Platform (ToPP) was leveraged to develop the has_circ_0001005-related prognostic models for melanoma patients based on TCGA data. RESULTS: Compared with parental cells, hsa_circ_0001005 expression was significantly increased in resistant cells and their exosomes. The elevated level of hsa_circ_0001005 was related to the poor clinical prognosis of melanoma patients. Hsa_circ_0001005 found in melanoma was mainly secreted by drug-resistant cells as exosomes. Exosomal hsa_circ_0001005 activated multiple canonical pathways related to drug resistance through sponging four miRNAs, thus suppressing the drug sensitivity of melanoma. Knocking down hsa_circ_0001005 in vitro, we found that the inhibition of hsa_circ_0001005 could hinder the clone formation of melanoma. Further in vivo animal experiments suggested that suppression of hsa_circ_0001005 can increase the sensitivity to Vemurafenib of melanoma cells. Finally, we also constructed the functional regulatory ceRNA network and prognostic risk models for hsa_circ_0001005, and further survival analysis reveals that the regulatory network and prognostic risk models obviously affected the prognosis of melanoma patients. CONCLUSIONS: This study confirmed that the level of hsa_circ_0001005 in exosomes is the key factor affecting drug resistance of melanoma, which provides a new potential therapeutic target for melanoma patients.

Remimazolam for the Prevention of Emergence Delirium in Children Following Tonsillectomy and Adenoidectomy Under Sevoflurane Anesthesia: A Randomized Controlled Study.

Purpose: To identify the effectiveness of remimazolam at the end of tonsillectomy and adenoidectomy for preventing emergence delirium in children under sevoflurane anesthesia. Patients and Methods: One hundred and four patients aged 3-7 years scheduled for tonsillectomy and adenoidectomy under sevoflurane anesthesia were recruited. Patients were randomly assigned to receive either remimazolam 0.2 mg kg-1 (intervention, n=52) or 0.9% normal saline (control, n=52) at the end of the procedure. The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) score ≥10. Secondary outcomes were peak PAED score, emergence time, postoperative pain intensity, length of postanesthesia care unit (PACU) stay, parental satisfaction, and postoperative behavior changes three days postoperatively. Results: Emergence delirium occurred in 6 of 51 (12%) patients receiving remimazolam versus 22 of 50 (44%) patients receiving saline (risk difference 32% [95% confidence interval, 16% to 49%], relative risk 0.27 [95% confidence interval, 0.12 to 0.60]; P<0.001). The peak PAED scores (median [interquartile range]) were lower in the remimazolam group than in the saline group (7 [6-8] versus 9 [8-11], P<0.001). Likewise, parental satisfaction was improved in the remimazolam group compared with the saline group (9 [8-10] versus 8 [7-8], P<0.001). There was no difference between groups concerning postoperative pain scores, length of PACU stay, or postoperative behavior changes. Conclusion: In children undergoing tonsillectomy and adenoidectomy, administration of remimazolam 0.2 mg kg-1 at the end of the surgery, compared with 0.9% saline, resulted in a significantly lower likelihood of emergence delirium after sevoflurane anesthesia.

Involvement of microRNAs and their potential diagnostic, therapeutic, and prognostic role in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 85%-90% of primary liver cancer. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'UTR of mRNA. Abnormal expression and regulation of miRNAs are involved in the occurrence and progression of HCC, and miRNAs can also play a role in the diagnosis and treatment of HCC as oncogenes or tumor suppressors. METHODS: In the past decades, a large number of studies have shown that miRNAs play an essential regulatory role in HCC and have potential as biomarkers for HCC. We reviewed the literature to summarize these studies. RESULTS: By reviewing the literature, we retrospected the roles of miRNAs in the development, diagnosis, treatment, and prognosis of HCC, and put forward prospects for the further research on miRNAs in the precision treatment of HCC. CONCLUSION: MicroRNAs are important regulators and biomarkers in the occurrence, progression, outcome, and treatment of HCC, and can provide new targets and strategies for improving the therapeutic effect of HCC.

Function of PHEX mutations p.Glu145* and p.Trp749Arg in families with X-linked hypophosphatemic rickets by the negative regulation mechanism on FGF23 promoter transcription.

X-linked hypophosphatemic rickets (XLH) is characterized by increased circulating fibroblast growth factor 23 (FGF23) concentration caused by PHEX (NM_000444.5) mutations. Renal tubular resorption of phosphate is impaired, resulting in rickets and impaired bone mineralization. By phenotypic-genetic linkage analysis, two PHEX pathogenic mutations were found in two XLH families: c.433 G > T, p.Glu145* in exon 4 and c.2245 T > C, p.Trp749Arg in exon 22. Immunofluorescence showed that the localization of p.Glu145* and p.Trp749Arg mutant and secretory PHEX (secPHEX) changed, with decreased expression. In a HEK293T cell model co-transfected with PHEX, secPHEX, and FGF23, wild-type PHEX, secPHEX, and FGF23 proteins were distributed in the cell membrane or endoplasmic reticulum, while the mutant was located in the nuclear membrane and cytoplasm. qPCR of p.Glu145* revealed decreased PHEX and secPHEX mRNA expression in cells, with no difference in mRNA expression of p.Trp749Arg. Both mutations decreased intracellular PHEX endopeptidase activity. Western blot analysis showed decrease in mutant and secPHEX protein expression and no FGF23 protein expression in single-transfected PHEX and secPHEX cells. In cells co-transfected with FGF23, PHEX and secPHEX mutation promoted FGF23 expression. Dual-luciferase reporter gene was used to detect the effect of PHEX on FGF23 promoter. The dual-luciferase reporter gene showed that after PHEX overexpression, the activity of mutant firefly luciferase was significantly higher than that of wild type. The regulatory mechanism between PHEX and FGF23 is still unclear, but we found that PHEX is a direct transcriptional inhibitor of FGF23 and affects the expression of FGF23. This study verified the pathogenicity of the two variants and revealed the possible regulatory mechanism between PHEX and FGF23.

Intrapleural Perfusion With Staphylococcal Enterotoxin C for Malignant Pleural Effusion: A Clustered Systematic Review and Meta-Analysis.

Introduction: The staphylococcal enterotoxin C (SEC), a commercially available bio-product from Staphylococcus aureus (S. aureus), has been widely used to control MPE. Objectives: We designed and performed a new systematic review (SR) and meta-analysis to clarify the perfusion protocols with SEC, determine their clinical effectiveness and safety, and reveal the indication and optimum usage for achieving the desired responses. Methodology: All randomized controlled trials (RCTs) about SEC for MPE were collected from electronic databases (from inception until July 2021), and clustered into multiple logical topics. After evaluating their methodological quality, we pooled the data from each topic using the meta-analysis or descriptive analysis, and summarized the evidence quality using the grading of recommendation assessment, development, and evaluation (GRADE) approach. Results: All 114 studies were clustered into SEC perfusion alone or plus chemical agents. The SEC alone showed a better complete response (CR), a lower pleurodesis failure, and adverse drug reactions (ADRs), and a higher fever than cisplatin (DDP) alone. The SEC and chemical agents developed 10 perfusion protocols. Among them, only SEC and DDP perfusion showed a better CR, a lower failure, disease progression and ADRs, and a higher fever than DDP alone. The SEC (100-200 ng per time, one time a week for one to four times) with DDP (30-40 mg, or 50-60 mg each time) significantly improved clinical responses for patients with moderate to large volume, Karnofsky performance status (KPS) scores ≥40, ≥50, or ≥60, and anticipated survival time (AST) ≥2 or 3 months. Most results were moderate to low quality. Conclusion: Current pieces of evidence indicate that super-antigen SEC is a pleurodesis agent, which provides an attractive alternative to existing palliative modalities for patients with MPE. Among 10 protocols, the SEC and DDP perfusion is a most commonly used, which shows a significant improvement in clinical responses with low ADRs. These findings also provide a possible indication and optimal usage for SEC and DDP perfusion.

Comparison of dobutamine and levosimendan for treatment of sepsis-induced cardiac dysfunction: A protocol for systematic review and meta-analysis.

BACKGROUND: Levosimendan and dobutamine are extensively used to treat sepsis-induced cardiomyopathy. Previous studies on whether levosimendan is superior to dobutamine are still controversial. We performed a protocol for systematic review and metaanalysis to compare the efficacy and safety of levosimendan versus dobutamine for the treatment of sepsis-induced cardiomyopathy. METHODS: This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol statement. We will search the following databases: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database. The search time will be set from database establishment to February 2022. After literature screening, 2 reviewers will extract data from the respects of general information, methodology, and results. Risk of bias is assessed using the Cochrane Risk of Bias Tool for randomized controlled trials. We will apply RevMan 5.4 software for statistical analysis. RESULTS: The results will be submitted to a peer-reviewed journal once completed. CONCLUSION: Septic patients with myocardial dysfunction may partly benefit from levosimendan than dobutamine, mainly embodied in cardiac function improvement.