MELATONIN ATTENUATES RENAL ISCHEMIA-REPERFUSION INJURY BY REGULATING MITOCHONDRIAL DYNAMICS AND AUTOPHAGY THROUGH AMPK/DRP1.

ABSTRACT: Ischemia-reperfusion injury (IRI) often stems from an imbalance between mitochondrial dynamics and autophagy. Melatonin mitigates IRI by regulating mitochondrial dynamics. However, the precise molecular mechanism underlying the role of melatonin in reducing IRI through modulating mitochondrial dynamics remains elusive. The objective of this study was to investigate whether pretreatment with melatonin before IRI confers protective effects by modulating mitochondrial dynamics and mitophagy. Melatonin pretreatment was administered to HK-2 cells and live rats before subjecting them to hypoxia-reoxygenation or IRI, respectively. Cells and rat kidney models were evaluated for markers of oxidative stress, autophagy, mitochondrial dynamics, and the expression of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and phospho-AMPKα (P-AMPK). After renal IRI, increased mitochondrial fission and autophagy were observed, accompanied by exacerbated cellular oxidative stress injury and aggravated mitochondrial dysfunction. Nevertheless, melatonin pretreatment inhibited mitochondrial fission, promoted mitochondrial fusion, and attenuated autophagy levels. This intervention was correlated with a notable reduction in oxidative stress injury and remarkable restoration of mitochondrial functionality. Ischemia-reperfusion injury led to a decline in P-AMPK levels, whereas melatonin pretreatment increased the level of P-AMPK levels. Silencing AMPK with small interfering RNA exacerbated mitochondrial damage, and in this context, melatonin pretreatment did not alleviate mitochondrial fission or autophagy levels but resulted in sustained oxidative stress damage. Collectively, these findings indicate that melatonin pretreatment shields the kidneys from IRI by mitigating excessive mitochondrial fission, moderating autophagy levels, and preserving appropriate mitochondrial fission, all in an AMPK-dependent manner.

Nanoscale detection of carbon dots-induced changes in actin skeleton of neural cells.

Understanding the cytotoxicity of fluorescent carbon dots (CDs) is crucial for their applications, and various biochemical assays have been used to study the effects of CDs on cells. Knowledge on the effects of CDs from a biophysical perspective is integral to the recognition of their cytotoxicity, however the related information is very limited. Here, we report that atomic force microscopy (AFM) can be used as an effective tool for studying the effects of CDs on cells from the biophysical perspective. We achieve this by integrating AFM-based nanomechanics with AFM-based imaging. We demonstrate the performance of this method by measuring the influence of CDs on living human neuroblastoma (SH-SY5Y) cells at the single-cell level. We find that high-dose CDs can mechanically induce elevated normalized hysteresis (energy dissipation during the cell deformation) and structurally impair actin skeleton. The nanomechanical change highly correlates with the alteration of actin filaments, indicating that CDs-induced changes in SH-SY5Y cells are revealed in-depth from the AFM-based biophysical aspect. We validate the reliability of the biophysical observations using conventional biological methods including cell viability test, fluorescent microscopy, and western blot assay. Our work contributes new and significant information on the cytotoxicity of CDs from the biophysical perspective.

Recent Advances of Aminopeptidases-Responsive Small-Molecular Probes for Bioimaging.

Aminopeptidases, enzymes with critical roles in human body, are emerging as vital biomarkers for metabolic processes and diseases. Aberrant aminopeptidase levels are often associated with diseases, particularly cancer. Small-molecule probes, such as fluorescent, fluorescent/photoacoustics, bioluminescent, and chemiluminescent probes, are essential tools in the study of aminopeptidases-related diseases. The fluorescent probes provide real-time insights into protein activities, offering high sensitivity in specific locations, and precise spatiotemporal results. Additionally, photoacoustic probes offer signals that are able to penetrate deeper tissues. Bioluminescent and chemiluminescent probes can enhance in vivo imaging abilities by reducing the background. This comprehensive review is focused on small-molecule probes that respond to four key aminopeptidases: aminopeptidase N, leucine aminopeptidase, Pyroglutamate aminopeptidase 1, and Prolyl Aminopeptidase, and their utilization in imaging tumors and afflicted regions. In this review, the design strategy of small-molecule probes, the variety of designs from previous studies, and the opportunities of future bioimaging applications are discussed, serving as a roadmap for future research, sparking innovations in aminopeptidase-responsive probe development, and enhancing our understanding of these enzymes in disease diagnostics and treatment.

Chromium immobilization from wastewater via iron-modified hydrochar: Different iron fabricants and practicality assessment.

The recycling of industrial solid by-products such as red mud (RM) has become an urgent priority, due to their large quantities and lack of reutilization methods can lead to resource wastage. In this work, RM was employed to fabricate green hydrochar (HC) to prepare zero-valent iron (ZVI) modified carbonous materials, and conventional iron salts (IS, FeCl3) was applied as comparison, fabricated HC labeled as RM/HC and IS/HC, respectively. The physicochemical properties of these HC were comprehensively characterized. Further, hexavalent chromium (Cr(VI)) removal performance was assessed (375.66 and 337.19 mg/g for RM/HC and IS/HC, respectively). The influence of dosage and initial pH were evaluated, while isotherms, kinetics, and thermodynamics analysis were also conducted, to mimic the surface interactions. The stability and recyclability of adsorbents also verified, while the practical feasibility was assessed by bok choy-planting experiment. This work revealed that RM can be used as a high value and green fabricant for HC the effective removal of chromium contaminants from the wastewater.

Proteomic analysis of mitochondria associated membranes in renal ischemic reperfusion injury.

BACKGROUND: The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. METHODS: A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein-Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. RESULTS: A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value < 0.05 and HR/N > 1.5 or HR/N < 0.66 set as the threshold criteria. Enrichment analysis of differentially expressed proteins unveiled biological processes such as mRNA splicing, apoptosis regulation, and cell division, while molecular functions were predominantly associated with energy metabolic activity. These proteins play key roles in the cellular responses during HR, offering insights into the IRI mechanisms and potential therapeutic targets. The validation of hub genes MFN2 and BNIP3 both in vitro and vivo was consistent with the proteomic findings. MFN2 demonstrated a protective role in maintaining the integrity of mitochondria associated membranes (MAMs) and mitigating mitochondrial damage following hypoxia/reoxygenation injury, this protective effect may be associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: The proteins located in mitochondria associated membranes (MAMs) are implicated in crucial roles during renal ischemic reperfusion injury (IRI), with MFN2 playing a pivotal regulatory role in this context.

Immunologic Crosstalk of Endoplasmic Reticulum Stress Signaling in Bladder Cancer.

Bladder cancer (BC) is a common malignant tumor of the urinary system. While current approaches involving adjuvant chemotherapy, radiotherapy, and immunotherapy have shown significant progress in BC treatment, challenges, such as recurrence and drug resistance, persist, especially in the case of muscle-invasive bladder cancer (MIBC). It is mainly due to the lack of pre-existing immune response cells in the tumor immune microenvironment. Micro-environmental changes (such as hypoxia and under-nutrition) can cause the aggregation of unfolded and misfolded proteins in the lumen, which induces endoplasmic reticulum (ER) stress. ER stress and its downstream signaling pathways are closely related to immunogenicity and tumor drug resistance. ER stress plays a pivotal role in a spectrum of processes within immune cells and the progression of BC cells, encompassing cell proliferation, autophagy, apoptosis, and resistance to therapies. Recent studies have increasingly recognized the potential of natural compounds to exhibit anti-BC properties through ER stress induction. Still, the efficacy of these natural compounds remains less than that of immune checkpoint inhibitors (ICIs). Currently, the ER stress-mediated immunogenic cell death (ICD) pathway is more encouraging, which can enhance ICI responses by mediating immune stemness. This article provides an overview of the recent developments in understanding how ER stress influences tumor immunity and its implications for BC. Targeting this pathway may soon emerge as a compelling therapeutic strategy for BC.

Identification of the role of MCM6 in bladder cancer prognosis, immunotherapy response, and in vitro experimental investigation using multi-omics analysis.

BACKGROUND: The tumor-promoting effects of MCM6 in numerous tumors have been widely revealed, yet its specific role in bladder cancer (BLCA) is still elusive. The objective of this research was to explore the underlying impact of MCM6 on BLCA. METHODS: Integrating transcriptomic and proteomic data, MCM6 was identified to be strongly correlated with BLCA through weighted gene co-expression network analysis(WGCNA) and venn analyses. Then, the clinical value of MCM6 was validated with public database data. The different molecular/immune characteristics and the benefit of immunotherapy were also found in MCM6-defined subgroups. Additionally, single-cell RNA sequencing (scRNA-seq) data was choose for quantify MCM6 expression in the distinct BLCA cell types. The biological role of MCM6 were evaluated via in vitro functional experiments. RESULTS: It was testified that the MCM6 could distinguish patients outcome in TCGA and GEO cohorts. Moreover, compared with the MCM6 low-expression group, the MCM6 high-expression group was related to more tumor-promoting related pathways, aggressive phenotypes, and benefit from immunotherapy. Analysis of scRNA-seq data resulted in MCM6 was mainly expressed in BLCA epithelial cells and the proportion of MCM6-expressing tumor epithelial cells is higher than the normal epithelial cells. Moreover, vitro experiments demonstrated that MCM6 knockdown repressed proliferation, cell cycle, migration, and invasion of BLCA cells. CONCLUSION: This research indicated MCM6 is a promising marker for both prognosis and immunotherapy benefit and could promote the cells proliferation, invasion and migration in BLCA.

Exploring potential targets of HPV&BC based on network pharmacology and urine proteomics.

BACKGROUND: Bladder cancer (BC) caused by Human papillomavirus (HPV) infection remains a complex public health problem in developing countries. Although the HPV vaccine effectively prevents HPV infection, it does not benefit patients with BC who already have HPV. METHODS: Firstly, the differential genes of HPV-related BC patients were screened by transcriptomics, and then the prognostic and clinical characteristics of the differential genes were analyzed to screen out the valuable protein signatures. Furthermore, the compound components and targets of Astragali Radix (AR) were analyzed by network pharmacology, and the intersection targets of drug components and HPV_BC were screened out for pathway analysis. In addition, the binding ability of the compound to the Astragali-HPV_BC target was verified by molecular docking and virtual simulation. Finally, to identify potential targets in BC patients through urine proteomics and in vitro experiments. RESULTS: Eleven HPV_BC-related protein signatures were screened out, among which high expression of EGFR, CTNNB1, MYC, GSTM1, MMP9, CXCR4, NOTCH1, JUN, CXCL12, and KRT14 had a poor prognosis, while low expression of CASP3 had a poor prognosis. In the analysis of clinical characteristics, it was found that high-risk scores, EGFR, MMP9, CXCR4, JUN, and CXCL12 tended to have higher T stage, pathological stage, and grade. Pharmacological and molecular docking analysis identified a natural component of AR (Quercetin) and it corresponding core targets (EGFR). The OB of the natural component was 46.43, and the DL was 0.28, respectively. In addition, EGFR-Quercetin has high affinity. Urine proteomics and RT-PCR showed that EGFR was expressed explicitly in BC patients. Mechanism analysis revealed that AR component targets might affect HPV_BC patients through Proteoglycans in the cancer pathway. CONCLUSION: AR can target EGFR through its active component (Quercetin), and has a therapeutic effect on HPV_BC patients.

Which surgical approach is more favorable for pheochromocytoma of different sizes (< 6 cm vs. ≥ 6 cm)? A single retrospective center experience.

BACKGROUND: To compare the surgical effects of lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) for pheochromocytoma of different sizes. METHODS: Data on patients with pheochromocytoma from 2014 to 2023 were collected from our hospital. According to different surgical approaches and tumor size, all patients were divided into four groups: tumor size < 6 cm for LTA and PRA and tumor size ≥ 6 cm for LTA and PRA. We compared these two surgical methods for pheochromocytoma of different sizes. RESULTS: A total of 118 patients with pheochromocytoma underwent successful laparoscopic surgery, including PRA group (n = 80) and LTA group (n = 38). In tumor size < 6 cm, the outcomes were no significant difference in LTA and PRA. In tumor size ≥ 6 cm, there was a significant difference in operation time (214.7 ± 18.9 vs. 154.3 ± 8.2, P = 0.007) and intraoperative blood loss (616.4 ± 181.3 vs. 201.4 ± 45.8, P = 0.037) between LTA and PRA. CONCLUSION: LTA and PRA were performed safely with similar operative outcomes in patients with pheochromocytoma size < 6 cm. While both LTA and PRA were executed with a commendable safety profile and comparable operative results in patients afflicted by pheochromocytomas < 6 cm, the PRA technique distinctly showcased advantages when addressing large-scale pheochromocytomas (≥ 6 cm). Notably, this manifested in reduced operative time, diminished intraoperative blood loss, decreased hospitalization expenses, and a paucity of procedural complications.

Terahertz label-free detection of nicotine-induced neural cell changes and the underlying mechanisms.

Nicotine exposure can lead to neurological impairments and brain tumors, and a label-free and nondestructive detection technique is urgently required by the scientific community to assess the effects of nicotine on neural cells. Herein, a terahertz (THz) time-domain attenuated total reflection (TD-ATR) spectroscopy approach is reported, by which the effects of nicotine on normal and cancerous neural cells, i.e., HEB and U87 cells, are successfully investigated in a label/stain-free and nondestructive manner. The obtained THz absorption coefficients of HEB cells exposed to low-dose nicotine and high-dose nicotine are smaller and larger, respectively, than the untreated cells. In contrast, the THz absorption coefficients of U87 cells treated by nicotine are always smaller than the untreated cells. The THz absorption coefficients can be well related to the proliferation properties (cell number and compositional changes) and morphological changes of neural cells, by which different types of neural cells are differentiated and the viabilities of neural cells treated by nicotine are reliably assessed. Collectively, this work sheds new insights on the effects of nicotine on neural cells, and provides a useful tool (THz TD-ATR spectroscopy) for the study of chemical-cell interactions.

Efficient and effective immobilization of tetracycline and copper from wastewater by zero-valent iron fabricated hydrochar derived from walnut peel.

Antibiotics and heavy metals often coexist as non-point-source contaminants in wastewater and their quite contrary physiochemical properties make their co-removal processes challenging. In this work, a bifunctional zero-valent iron-modified hydrochar derived from walnut peel (MWPHC) was synthesized, which was then applied for the simultaneous removal of tetracycline (TC) and Cu(II) from wastewater. Based on the characterizations, Fe0 species were successfully distributed on the surface of the walnut peel substrates. The TC and Cu(II) could be synergistically immobilized, and bridging effects were observed between them, and MWPHC exhibited excellent ability on the simultaneous removal of TC (qmax = 433.59 mg/g) and Cu(II) (qmax = 586.25 mg/g). Furthermore, the engineering feasibility of the MWPHC was evaluated using column and regeneration experiments. These results shed light on the tailored MWPHC as an environmental functional material for pollution control of co-existing antibiotic and heavy metal contaminants in agro-industrial wastewater.

Iron-rich red mud and iron oxide-modified biochars: A comparative study on the removal of Cd(II) and influence of natural aging processes.

Red mud (RM) is a byproduct of various processes in the aluminum industry and has recently been utilized for synthesizing RM-modified biochar (RM/BC), which has attracted significant attention in terms of waste reutilization and cleaner production. However, there is a lack of comprehensive and comparative studies on RM/BC and the conventional iron-salt-modified biochar (Fe/BC). In this study, RM/BC and Fe/BC were synthesized and characterized, and the influence on environmental behaviors of these functional materials with natural soil aging treatment was analyzed. After aging, the adsorption capacity of Fe/BC and RM/BC for Cd(II) decreased by 20.76% and 18.03%, respectively. The batch adsorption experiments revealed that the main removal mechanisms of Fe/BC and RM/BC are co-precipitation, chemical reduction, surface complexation, ion exchange, and electrostatic attraction, etc. Furthermore, practical viability of RM/BC and Fe/BC was evaluated through leaching and regenerative experiments. These results can not only be used to evaluate the practicality of the BC fabricated from industrial byproducts but can also reveal the environmental behavior of these functional materials in practical applications.

An ultrasensitive split-type electrochemical immunosensor based on controlled-release strategy for detection of CA19-9.

In this study, a novel split-type electrochemical immunosensor based on controlled release strategy was proposed for sensitive analysis and detection of tumor marker carbohydrate antigen 199 (CA19-9). Specifically, glucose (Glu) was encapsulated in carrier mesoporous silica (MSN) with encapsulation technology, and surface functionalized Zinc sulfide (ZnS) caps were used as "gatekeepers". The complex is formed by encapsulating Glu within MSN with ZnS (ZnS@MSN-Glu) as a signal amplifier labeled on the signal antibody (Ab2). And the Ab2 can detect the presence of antibodies. To reduce the interference of biological analysis, the immune recognition process of ZnS@MSN-Glu-Ab2 bioconjugate and antigen was carried out in 96-well microplate, which did not interfere with the electrochemical analysis process. Therefore, the low sensitivity detection caused by biofouling of nanomaterials and immunoreaction on the testing platform is eliminated. Subsequently, the opening and timed release of mesopores were controlled by external stimuli, the disulfide bond cleavage by dithiothreitol (DTT), and glucose was effectively released. Then nickel cobalt layered double hydroxide (NiCo-LDH) were directly hydrothermally grown on carbon cloth (CC) electrodeposited with copper selenide (CuSe) nanosheets to construct three-dimensional (3D) cactus-like NiCo-LDH/CuSe/CC sensing platform. It can realize the catalytic oxidation of released glucose, triggering glucose-mediated signal amplification. The synergistic effect of the 3D cactus structure and active nanomaterials promotes electron conduction. Taking the detection of carbohydrate antigen CA19-9 as an example, the immunosensor shows a wide linear concentration range (0.001-100 U/mL) with the limit of detection of 0.0005 U/mL, realizing highly sensitive detection of CA19-9. This biosensing technique has considerable advantages and provides an innovative approach for trace detection of other biomarkers.

Candy-like heterojunction nanocomposite of WO3/Fe2O3-based semiconductor gas sensor for the detection of triethylamine.

A highly efficient gas sensor for the detection of triethylamine based on candy-like WO3/Fe2O3 nanocomposite was prepared. The control of morphology and sensing performance of n-n heterojunction WO3/Fe2O3 nanocomposites were successfully achieved by the modulation of Fe element content. When the ratio of Fe to W is 0.4, the candy-like nanocomposite of WO3/Fe2O3 with great performance is obtained. It is interesting that the candy-like nanocomposite of WO3/Fe2O3 with a large specific surface area exhibits better selectivity and sensitivity for sensing TEA gases at a lower operating temperature (260 °C) compared with the gas sensor prepared by using WO3 alone. To verify the feasibility, the sensing mechanism was investigated and real sample tests were conducted and discussed. Finally, a TEA gas sensor with low limit of detection, short response/recovery time (15/162 s), and high sensitivity was developed. In addition, the prepared gas sensor has satisfactory stability and selectivity and has practical application value.

Construction of noninvasive prognostic model of bladder cancer patients based on urine proteomics and screening of natural compounds.

BACKGROUND: Bladder cancer (BCa) has a high incidence and recurrence rate worldwide. So far, there is no noninvasive detection of BCa therapy and prognosis based on urine multi-omics. Therefore, it is necessary to explore noninvasive predictive models and novel treatment modalities for BCa. METHODS: First, we performed protein analysis of urine from five BCa patients and five healthy individuals using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Combining multi-omics data to mine particular and sensitive molecules to predict BCa prognosis. Second, urine proteomics data were combined with TCGA transcriptome data to select differential genes that were specifically highly expressed in urine and tissues. Further, the Lasso equation was used to screen specific molecules to construct a noninvasive prediction model of BCa. Finally, natural compounds of specific molecules were selected by combined network pharmacology and molecular docking to complete molecular structure docking. RESULTS: A noninvasive predictive model was constructed using PSMB5, P4HB, S100A16, GET3, CNP, TFRC, DCXR, and MPZL1, specific molecules screened by multi-omics, and clinical features, which had good predictive value at 1, 3, and 5 years of prediction. High expression of these target genes suggests a poor prognosis in patients with BCa, and they were mainly involved in cell adhesion molecules and the IGF pathway. In addition, the corresponding drugs and natural compounds were selected by network pharmacology, and the molecular structure 7NHT of PSMB5 was found to be well docked to Ellagic acid, a natural compound in Hetaoren that we found. The 3D structure 6I7S of P4HB was able to bind to Stigmasterol in Shanzha stably, and the structure 6WRV of TFRC as an iron transport carrier was also able to bind to Stigmasterol in Shanzha stably. The structures 1WOJ, 3D3W, and 6IGW of CNP, DCXR, and MPZL1 can also play an important role in combination with the natural compounds (S)-Stylopine, Kryptoxanthin, and Sitosterol in Maqianzi, Yumixu, and Laoguancao. CONCLUSION: The noninvasive prediction model based on urinomics had excellent potential in predicting the prognosis of patients with BCa. The multi-omics screening of specific molecules combined with pharmacology and compound molecular docking can promote the research and development of novel drugs.

Selenite elimination via zero-valent iron modified biochar synthesized from tobacco straw and copper slag: Mechanisms and agro-industrial practicality.

Cost-effectively improving the performance of biochar is essential for its large-scale practical application. In this work, the agro-industrial by-products copper slag and tobacco straw were employed for the preparation of modified biochar (CSBC). The obtained CSBC exhibited satisfactory capacity on Se(IV) immobilization of 190.53 mg/g, with surface interactions determined by the monolayer and mainly chemisorption. The removal mechanisms included chemical reduction, electrostatic attraction, co-precipitation, and formation of complexations. Interestingly, the existence of Cu2Se structure after adsorption indicated the involvement of Cu species within Se(IV) elimination. Moreover, the industrial agricultural practicality of CSBC was evaluated by regeneration tests, economic assessment, and pot experiments. The results demonstrate that iron species-modified biochar prepared from two agro-industrial by-products is a promising and feasible candidate for selenite removal from wastewater.

Integrated molecular analyses of an interferon-γ based subtype with regard to outcome, immune characteristics, and immunotherapy in bladder cancer and experimental verification.

This study attempted to explore the role of interferon-γ related genes (IRGs) in the prognosis and immunotherapy of bladder cancer (BC). Based on data downloaded from public databases, molecular subtypes with different IRG expression patterns were determined via nonnegative matrix factorization clustering. On the basis of IRGs, interferon-γ related gene signature (IRGS) was developed through Cox regression analyses. We identified that two molecular subgroups with different outcome and immune profiles. It was proved that IRGS possessed prediction efficiency for BC prognosis. Compared with low IRGS group, high IRGS group was related to less anti-cancer immune cells infiltration, less tumor mutation burden score, more cancer stem cell index, and less benefit from immunotherapy. Differential expression of six model genes (IRF5, LATS2, MTHFD2, VAMP8, HLA-G and PTPN6) was validated between paired tissues by RT-qPCR. This study presents a prognostic model, which could serve as an indicator for the benefit of BC immunotherapy.

Evaluating the prognostic value of CD56 in pediatric acute myeloid leukemia.

BACKGROUND: Many cytogenetic changes and gene mutations are associated with acute myeloid leukemia (AML) survival outcomes. CD56 is related to poor prognosis when expressed in adult AML patients. However, the prognostic value of CD56 in children with AML has rarely been reported. In this research, we aimed to evaluate the prognostic value of CD56 in childhood AML. METHODS: The present retrospective study included 145 newly diagnosed pediatric patients with de novo AML (excluding AML-M3) in two hospitals between January 2015 and April 2021. RESULTS: The total median (range) age was 75 (8-176) months, and the median follow-up time was 35 months. No significant difference in the 3-year overall survival rate was noted between the CD56-positive and CD56-negative groups (67.0% vs. 79.3%, P = 0.157) who received chemotherapy. However, among high-risk patients, the CD56-positive group had a worse overall survival rate and event-free survival rate (P < 0.05). Furthermore, among high-risk patients, the CD56-positive group had higher relapse and mortality rates than the CD56-negative group (P < 0.05). CONCLUSIONS: CD56 represents a potential factor of poor prognosis in specific groups of children with AML and should be considered in the risk stratification of the disease. Given the independent prognostic value of CD56 expression, we should consider integrating this marker with some immunophenotypic or cytogenetic abnormalities for comprehensive analysis.

Schlafen family is a prognostic biomarker and corresponds with immune infiltration in gastric cancer.

The Schlafen (SLFN) gene family plays an important role in immune cell differentiation and immune regulation. Previous studies have found that the increased SLFN5 expression in patients with intestinal metaplasia correlates with gastric cancer (GC) progression. However, no investigation has been conducted on the SLFN family in GC. Therefore, we systematically explore the expression and prognostic value of SLFN family members in patients with GC, elucidating their possible biological function and its correlation with tumor immune cells infiltration. TCGA database results indicated that the SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN13 expression was significantly higher in GC. The UALCAN and KM plotter databases indicated that enhanced the SLFN family expression was associated with lymph node metastasis, tumor stage, and tumor grade and predicted an adverse prognosis. cBioportal database revealed that the SLFN family had a high frequency of genetic alterations in GC (about 12%), including mutations and amplification. The GeneMANIA and STRING databases identified 20 interacting genes and 16 interacting proteins that act as potential targets of the SLFN family. SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 may be implicated in the immunological response, according to Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, Timer and TISIDB databases indicate that SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 are involved in the immune response. Furthermore, Timer, TCGA, and TISIDB databases suggested that the SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 expression in GC is highly linked with immune cell infiltration levels, immune checkpoint, and the many immune cell marker sets expression. We isolated three samples of peripheral blood mononuclear cell (PBMC) and activated T cells; the results showed the expression of SLFN family members decreased significantly when T cell active. In conclusion, the SLFN family of proteins may act as a prognostic indicator of GC and is associated with immune cell infiltration and immune checkpoint expression in GC. Additionally, it may be involved in tumor immune evasion by regulating T cell activation.

Efficient removal of mercury and chromium from wastewater via biochar fabricated with steel slag: Performance and mechanisms.

Biochar derived from biomass is regarded as a promising adsorbent for wastewater treatment, but the high cost of modification is still a challenge for its large-scale practical applications. In this study, we employed steel slag as a low-cost fabricant and synthesized hydrothermally carbonized steel slag (HCSS), as a stable environmentally functional material for heavy metal removal. Typically, positively and negatively charged heavy metal contaminants of Hg2+ and Cr2O7 2- were employed to testify the performance of HCSS as an adsorbent, and good capacities [(283.24 mg/g for Hg (II) and 323.16 mg/g for Cr (VI)] were found. The feasibility of HCSS on real wastewater purification was also evaluated, as the removal efficiency was 94.11% and 88.65% for Hg (II) and Cr (VI), respectively. Mechanism studies revealed that the modification of steel slag on bio-adsorbents offered copious active sites for pollutants. As expected, oxygen-containing functional groups in HCSS acted as the main contributor to adsorption capacity. Moreover, some reactive iron species (i.e., Fe2+) played an essential role in chemical reduction of Cr (VI). The adsorptive reactions were pH-dependent, owing to other more mechanisms, such as coprecipitation, ion-exchange, and electrostatic attraction. This promising recycling approach of biomass waste and the design of agro-industrial byproducts can be highly suggestive of the issues of resource recovery in the application of solid waste-derived environmentally functional materials for heavy metal remediation.