Unraveling the Fundamentals of Axial Coordination FeN4+1 Sites Regulating the Peroxymonosulfate Activation for Fenton-Like Activity.

Precise modulation of the axial coordination microenvironment in single-atom catalysts (SACs) to enhance peroxymonosulfate (PMS) activation represents a promising yet underexplored approach. This study introduces a pyrolysis-free strategy to fabricate SACs with well-defined axial-FeN4+1 coordination structures. By incorporating additional out-of-plane axial nitrogen into well-defined FeN4 active sites within a planar, fully conjugated polyphthalocyanine framework, FeN4+1 configurations are developed that significantly enhance PMS activation. The axial-FeN4+1 catalyst excelled in activating PMS, with a high bisphenol A (BPA) degradation rate of 2.256 min-1, surpassing planar-FeN4/PMS systems by 6.8 times. Theoretical calculations revealed that the axial coordination between N and the Fe sites forms an optimized axial FeN4+1 structure, disrupting the electron distribution symmetry of Fe and optimizing the electron distribution of the Fe 3d orbital (increasing the d-band center from -1.231 to -0.432 eV). Consequently, this led to an enhanced perpendicular adsorption energy of PMS from -1.79 to -1.82 eV and reduced energy barriers for the formation of the key reaction intermediate (O*) that generates 1O2. This study provides new insights into PMS activation through the axial coordinated engineering of well-defined SACs in water purification processes.

Scoulerine: A natural isoquinoline alkaloid targeting SLC6A3 to treat RCC.

Scoulerine, an isoquinoline alkaloid derived from the corydalis plant, exhibits diverse therapeutic properties against tumors, Alzheimer's disease, and inflammation. This research delves into the pharmacological impact and underlying mechanism of scoulerine on renal cell carcinoma (RCC). Our findings suggest that Scoulerine displays promise as a potential therapeutic agent for RCC, demonstrating notable inhibitory effects in both in vivo and in vitro models. In addition, scoulerine inhibited the viability of 769-P and 786-O cell lines in a time-dependent and dose-dependent manner, and promoted the level of apoptosis associated with B-cell lymphoma-2 associated X protein (Bax). Moreover, the administration of scoulerine resulted in a significant suppression of the mitogen activated protein kinase (MAPK) signaling pathway. Subsequently, utilizing bioinformatics and spatial transcriptomic databases, we identified solute carrier family 6 Member 3 (SLC6A3) as the most promising target of scoulerine. Through experimental validation, we confirmed the functional and therapeutic relevance of SLC6A3 in scoulerine-mediated treatment of RCC. The results of our study indicate a significant affinity between scoulerine and SLC6A3, with competitive inhibition of this interaction leading to a reduction in the inhibitory impact of scoulerine on RCC cell viability. In conclusion, our findings suggest that scoulerine may induce apoptosis in RCC by targeting SLC6A3 and inhibiting the activation of the MAPK signaling pathway, thereby positioning it as a promising natural compound for potential future RCC treatment.

Prognostic impact of IL7R mutations on acute myeloid leukemia.

Background: Interleukin-7 receptor (IL7R) mutation has been demonstrated to be an adverse prognostic factor in acute lymphoblastic leukemia (ALL) patients. However, the effects of the IL7R mutation on acute myeloid leukemia (AML) have rarely been reported. Here, we investigated IL7R mutations and their effects on AML patients. Methods: A total of 346 newly diagnosed AML patients from January 2017 to July 2020 at Nanfang Hospital were analyzed in this study. A genomic panel of 167 gene targets was detected by next-generation sequencing. Results: Among 346 patients, 33 (9.5%) AML patients carried IL7R mutations. With a median follow-up of 50.7 months (95% confidence interval (CI) 17.3-62.2), the 5-year overall survival (OS) rates were 51.5% (95% CI 37.0%-71.0%) and 72.2% (95% CI 67.4%-77.3%; p = 0.008), the 5-year event-free survival (EFS) rates were 36.1% (95% CI 23.2%-57.1%) and 58.1% (95% CI 52.9%-63.8%; p = 0.005), the 5-year non-relapse mortality (NRM) were 21.4% (95% CI 8.5%-38.2%) and 6.2% (95% CI 3.7%-9.5%; p = 0.004) in the IL7R mutant (IL7R MUT ) group and non-IL7R mutant (IL7R WT ) group, respectively. There is no significant difference in the disease-free survival (75.1% vs 73.5%, p = 0.885) and cumulative incidence of relapse (25.7% vs 25.2%, p = 0.933) between IL7R MUT and IL7R WT group. Furthermore, patients who underwent hematopoietic stem cell transplantation (HSCT) still had more adverse outcomes in the IL7R MUT group than in the IL7R WT group (5-year OS: 61.9% vs 85.3%, p = 0.003). In the TET2 (p = 0.013) and DNA methyltransferase 3A (DNMT3A; p = 0.046) mutation subgroups, the presence of IL7R mutations was associated with worse OS than in AML patients without IL7R mutations. Conclusion: Our study demonstrated that the IL7R mutation is associated with an inferior prognosis for AML patients. Patients with IL7R mutations have higher NRM, shorter OS, and EFS than patients without IL7R mutations, even patients who have undergone HSCT. Future larger and multicentric prospective studies will be explored.

The effects of IL7R mutation on AML patients With the development of NGS, more and more cytogenetic and molecular markers have been found to be associated with prognosis of ALL. IL7R mutation is associated with an inferior prognosis for AML patients. Patients with IL7R mutation have higher NRM, shorter OS and EFS than patients without IL7R mutation, even patients who have undergone HSCT.

Single-cell profiling of intrahepatic immune cells reveals an expansion of tissue-resident cytotoxic CD4+ T lymphocyte subset associated with pathogenesis of alcoholic-associated liver diseases.

BACKGROUND & AIMS: The immunological mechanisms underpinning the pathogenesis of alcoholic-associated liver disease (ALD) remain incompletely elucidated. This study aims to explore the transcriptomic profiles of hepatic immune cells in ALD compared to healthy individuals and those with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We utilized single-cell RNA sequencing to analyze liver samples from healthy subjects, MASLD, and ALD patients, focusing on the immune cell landscapes within the liver. Key alterations in immune cell subsets were further validated using liver biopsy samples from additional patient cohorts. RESULTS: We observed a significant accumulation of CD4+ T cells in ALD patients' livers, surpassing the prevalence of CD8+ T cells, in contrast to MASLD and healthy counterparts, while natural killer (NK) cells and γδT cells exhibited reduced intrahepatic infiltration. In-depth transcriptional and developmental trajectory analyses unveiled that a distinct CD4+ subset characterized by granzyme K (GZMK) expression, displaying a tissue-resident signature and terminal effector state, prominently enriched among CD4+ T cells infiltrating the livers of ALD patient. Subsequent examination of an independent ALD patient cohort corroborated the substantial enrichment of GZMK+CD4+ T lymphocytes, primarily within liver fibrotic zones, suggesting their potential involvement in disease progression. Additionally, we noted shifts in myeloid populations, with expanded APOE+ macrophage and FCGR3B+ monocyte subsets in ALD samples relative to MASLD and healthy tissues. CONCLUSIONS: In summary, this study unravels the intricate cellular diversity within hepatic immune cell populations, highlighting the pivotal immune pathogenic role of the GZMK+CD4+ T lymphocyte subset in ALD pathogenesis.

Unveiling the role of RARs in stomach adenocarcinoma: clinical implications and prognostic biomarkers.

Background: Retinoic acid receptors (RARs) family are known to play a significant role in the occurrence and development of tumors. However, the relationship between RARs and stomach adenocarcinoma (STAD) has not yet been clearly identified. The aim of this study is to evaluate the expression profile and clinical value of the RARs family in STAD. Methods: The expression level, clinical characteristics, prognostic value, immunity-related evaluations, genetic alteration and methylation site of RARs in STAD were explored using a series of online databases including gene expression profiling interactive analysis (GEPIA), tumor immune estimation resource (TIMER), University of Alabama at Birmingham cancer data (UALCAN), Human Protein Atlas (HPA), Kaplan-Meier plotter, gene set cancer analysis (GSCA), cBioPortal, MethSurv, GeneMANIA, LinkedOmics, Metascape, Search tool for the retrieval of interacting genes (STRING), tumor immune single-cell hub (TISCH) and cancer cell line encyclopedia (CCLE). Results: We discovered dramatically increased expression of RARA and decreased expression of RARB in STAD tissues, and many clinical variables were closely related to RARs. Notably, higher expressions of RARA and RARB as well as lower expression of RARG correlated with worse overall survival (OS) for STAD patients. The clinical value of prognostic model indicated that RARs were identified to be potential prognostic biomarkers for STAD patients. Moreover, RARB was closely related to immune cell infiltration, which had effect on the role of RARB in STAD prognosis. And the genetic alteration of RARB was significantly associated with the longer disease-free survival (DFS) of STAD patients. Additionally, some CpG sites of the RARs family were related with the prognosis of STAD patients. Functional enrichment analyses indicated that several pathways in STAD might be pivotal pathways regulated by RARs. At the single-cell level, there was some extent of infiltration of tumor microenvironment-related cells in the RARs expression in STAD. Conclusions: Our results evaluated the expression profile and clinical values of RARs in patients with STAD, which provided a basis for future in-depth exploration of the specific mechanisms of each member of RARs in STAD.

Dipeptidyl peptidase-4 marks distinct subtypes of human adipose stromal/stem cells with different hepatocyte differentiation and immunoregulatory properties.

BACKGROUND: Human adipose-derived stromal/stem cells (hASCs) play important roles in regenerative medicine and numerous inflammatory diseases. However, their cellular heterogeneity limits the effectiveness of treatment. Understanding the distinct subtypes of hASCs and their phenotypic implications will enable the selection of appropriate subpopulations for targeted approaches in regenerative medicine or inflammatory diseases. METHODS: hASC subtypes expressing dipeptidyl peptidase-4 (DPP4) were identified via fluorescence-activated cell sorting (FACS) analysis. DPP4 expression was knocked down in DPP4+ hASCs via DPP4 siRNA. The capacity for proliferation, hepatocyte differentiation, inflammatory factor secretion and T-cell functionality regulation of hASCs from DPP4-, DPP4+, and control siRNA-treated DPP4+ hASCs and DPP4 siRNA-treated DPP4+ hASCs were assessed. RESULTS: DPP4+ hASCs and control siRNA-treated DPP4+ hASCs presented a lower proliferative capacity but greater hepatocyte differentiation capacity than DPP4- hASCs and DPP4 siRNA-treated DPP4+ hASCs. Both DPP4+ hASCs and DPP4- hASCs secreted high levels of vascular endothelial growth factor-A (VEGF-A), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6 (IL-6), whereas the levels of other factors, including matrix metalloproteinase (MMP)-1, eotaxin-3, fractalkine (FKN, CX3CL1), growth-related oncogene-alpha (GRO-alpha, CXCL1), monokine induced by interferon-gamma (MIG), macrophage inflammatory protein (MIP)-1beta, and macrophage colony-stimulating factor (M-CSF), were significantly greater in the supernatants of DPP4+ hASCs than in those of DPP4- hASCs. Exposure to hASC subtypes and their conditioned media triggered changes in the secreted cytokine profiles of T cells from healthy donors. The percentage of functional T cells that secreted factors such as MIP-1beta and IL-8 increased when these cells were cocultured with DPP4+ hASCs. The percentage of polyfunctional CD8+ T cells that secreted multiple factors, such as IL-17A, tumour necrosis factor alpha (TNF-α) and TNF-ß, decreased when these cells were cocultured with supernatants derived from DPP4+ hASCs. CONCLUSIONS: DPP4 may regulate proliferation, hepatocyte differentiation, inflammatory cytokine secretion and T-cell functionality of hASCs. These data provide a key foundation for understanding the important role of hASC subpopulations in the regulation of T cells, which may be helpful for future immune activation studies and allow them to be customized for clinical application.

Rapid Fabrication of Antilunar Dust Aluminum Surface by Nanosecond Laser Etching.

Although a dust-repellent surface is desirable for lunar exploration missions, its fabrication process is complicated and time-consuming. Herein, we report a simple and fast method to fabricate a lunar dust-repellent surface by texturing on an Al substrate via nanosecond laser etching. The laser-induced photothermal effect can rapidly create hierarchical papillary structures on 25 × 25 mm Al substrates (within 30 s). Both atomic force microscopy (AFM) and in situ scanning electron microscopy (SEM) reveal that such structures enable a reduced contact area between the Al substrate and lunar dust and thus reduced adhesion. The reduced dust adhesion force of Al substrates facilitates improving their antidust performance. By optimizing processing parameters, the Al substrate etched with a laser scanning spacing of 80 µm exhibits a lower dust adhesion force (9.58 nN) due to the smallest contact area with dust. Accordingly, its static antilunar dust performance (dust coverage of 1.95%) is significantly improved compared to the pristine Al substrate (dust coverage of 12.98%). Besides, the accumulated dust on the laser-etched Al substrates with low surface adhesion force is easily cleaned up by flipping and gravity (the dust residual rates are less than 17%). The Al substrate with excellent antidust ability presents good potential for lunar exploration missions.

HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study.

BACKGROUND: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region. METHODS: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results. RESULTS: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes. CONCLUSION: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.

Exploring the relationship between anal fistula and colorectal cancer based on Mendelian randomization and bioinformatics.

The association between anal fistula patients and colorectal cancer, as well as the potential pathophysiological mechanisms, remains unclear. To explore the relationship between anal fistula and colorectal cancer and its potential mechanisms. Analysis of GEO and TCGA databases. Disease-related genes were also referenced from Coremine Medical, GeneCard and OMIM. Core hub genes were identified through protein-protein interaction analysis by intersecting differentially expressed genes from the datasets with disease data. On one hand, a prognostic model was developed using genes and its prognostic role was validated. On the other hand, the optimal diagnostic genes were selected through machine learning. Mendelian randomization (MR) analysis was conducted to explore the potential causal link between anal fistula and colorectal cancer. Thirteen core genes were identified (TMEM121B, PDGFRA, MID2, WNT10B, HOXD13, BARX1, SIX2, MMP1, SNAL1, CDKN2A, ITGB3, TIMP1, CALB2). Functional enrichment analysis revealed that the intersecting genes between anal fistula and colorectal cancer were associated with extracellular matrix components, signalling pathways, cell growth, protein modification, as well as important roles in cellular activities, tissue and organ development, and biological function maintenance. These genes were also involved in pathways related to Wnt signalling and colorectal cancer development. Prognostic analysis and immune infiltration analysis indicated a close relationship between core hub genes and the prognosis and immune infiltration in colorectal cancer. Machine learning showed that core genes played an essential role in the diagnostic differentiation of colorectal cancer. MR results suggested no causal relationship between anal fistula and colorectal cancer. This study identified shared core genes between anal fistula and colorectal cancer, involved in various pathways related to tumour development. These genes play crucial roles in prognosis and diagnosis.

A comprehensive analysis of TRP-related gene signature, and immune infiltration in patients with colorectal cancer.

BACKGROUND: Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. METHODS: Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs' gene and protein expression was conducted using human colon cancer cells. RESULTS: Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. CONCLUSION: This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

Role of AMPK-regulated autophagy in retinal pigment epithelial cell homeostasis: A review.

The retinal pigment epithelium (RPE) is a regularly arranged monolayer of cells in the outermost layer of the retina. It is crucial for transporting nutrients and metabolic substances in the retina and maintaining the retinal barrier. RPE dysfunction causes diseases related to vision loss. Thus, understanding the mechanisms involved in normal RPE function is vital. Adenosine monophosphate-activated protein kinase (AMPK) is an RPE energy sensor regulating various signaling and metabolic pathways to maintain cellular energetic homeostasis. AMPK activation is involved in multiple signaling pathways regulated by autophagy in the RPE, thereby protecting the cells from oxidative stress and slowing RPE degeneration. In this review, we attempt to broaden the understanding of the pathogenesis of RPE dysfunction by focusing on the role and mechanism of AMPK regulation of autophagy in the RPE. The correlation between RPE cellular homeostasis and role of AMPK was determined by analyzing the structure and mechanism of AMPK and its signaling pathway in autophagy. The protective effect of AMPK-regulated autophagy on the RPE for gaining insights into the regulatory pathways of RPE dysfunction has been discussed.

PBMC-mediated modulation of macrophage polarization in RAW264.7 cells through STAT1/STAT6 signaling cascades.

Peripheral blood mononuclear cells (PBMC), sourced autologously, offer numerous advantages when procured: easier acquisition process, no in vitro amplification needed, decreased intervention and overall increased acceptability make PBMC an attractive candidate for cell therapy treatment. However, the exact mechanism by which PBMC treat diseases remains poorly understood. Immune imbalance is the pathological basis of many diseases, with macrophages playing a crucial role in this process. However, research on the role and mechanisms of PBMC in regulating macrophages remains scarce. This study employed an in vitro co-culture model of PBMC and RAW264.7 macrophages to explore the role and mechanisms of PBMC in regulating macrophages. The results showed that the co-culturing led to decreased expression of inflammatory cytokines and increased expression of anti-inflammatory cytokines in RAW264.7 or in the culture supernatant. Additionally, the pro-inflammatory, tissue matrix-degrading M1 macrophages decreased, while the anti-inflammatory, matrix-synthesizing, regenerative M2 macrophages increased in both RAW264.7 and monocytes within PBMC. Moreover, co-cultured macrophages exhibited a significantly decreased p-STAT1/STAT1 ratio, while the p-STAT6/STAT6 ratio significantly increased. This suggests that PBMC may inhibit M1 macrophage polarization by blocking STAT1 signaling cascades and may promote M2 macrophage polarization through the activation of STAT6 signaling cascades. Overall, this study sheds light on the role and mechanism of PBMC in regulating macrophages. Moreover, it was found that monocytes within co-cultured PBMC differentiated into M2 macrophages in the presence of macrophages. This finding provides experimental evidence for the use of PBMC in treating inflammatory diseases, especially macrophage-depleting inflammatory diseases such as osteoarthritis.

PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function.

Mechanical overloading and aging are two essential factors for osteoarthritis (OA) development. Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology, but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated. Herein, we found that PDZ domain containing 1 (PDZK1), one of the PDZ proteins, which belongs to the Na+/H+ Exchanger (NHE) regulatory factor family, is a key factor in biomechanically induced mitochondrial dysfunction and chondrocyte senescence during OA progression. PDZK1 is reduced by mechanical overload, and is diminished in the articular cartilage of OA patients, aged mice and OA mice. Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, whereas intraarticular injection of adeno-associated virus-expressing PDZK1 had a therapeutic effect. Moreover, PDZK1 loss impaired chondrocyte mitochondrial function with accumulated damaged mitochondria, decreased mitochondrion DNA (mtDNA) content and increased reactive oxygen species (ROS) production. PDZK1 supplementation or mitoubiquinone (MitoQ) application alleviated chondrocyte senescence and cartilage degeneration and significantly protected chondrocyte mitochondrial functions. MRNA sequencing in articular cartilage from Pdzk1 knockout mice and controls showed that PDZK1 deficiency in chondrocytes interfered with mitochondrial function through inhibiting Hmgcs2 by increasing its ubiquitination. Our results suggested that PDZK1 deficiency plays a crucial role in mediating excessive mechanical load-induced chondrocyte senescence and is associated with mitochondrial dysfunction. PDZK1 overexpression or preservation of mitochondrial functions by MitoQ might present a new therapeutic approach for mechanical overload-induced OA.

Establishment of a human induced pluripotent stem cell line (SDQLCHi079-A) from a patient with Johanson-Blizzard syndrome carrying heterozygous mutation in UBR1 gene.

Johanson-Blizzard syndrome (JBS) is an autosomal recessive disorder. We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a 2-year-old boy with Johanson-Blizzard syndrome carrying a compound heterozygous mutation of c.3167C>G (p.S1056X) and c.1911 + 14C>G(splicing) in the UBR1 gene. This iPSC line was free of exogenous gene, expressed stemness markers, exhibited differentiation potential, had normal karyotype and harbored the same mutations found in the patient. The iPSC cellline can serve as a disease model in drug development and novel personalized therapies.

Identification and functional analysis of a deduced geraniol synthase from Camphora officinarum.

The market demand for essential oil containing citral is increasing. Our research group identified a rare chemotype of Camphora officinarum whose leaves are high in citral content by examining over 1000 wild trees across the entire native distribution area of C. officinarum in China. Because C. officinarum is suitable for large-scale cultivation, it is therefore seen as a promising source of natural citral. However, the molecular mechanism of citral biosynthesis in C. officinarum is poorly understood. In this study, transcriptomic analyses of C. officinarum with different citral contents revealed a strong positive correlation between the expression of a putative geraniol synthase gene (CoGES) and citral content. The CoGES cDNA was cloned, and the CoGES protein shared high similarity with other monoterpene synthases. Enzymatic assays of CoGES with geranyl diphosphate (GPP) as substrate yielded geraniol as the single product, which is the precursor of citral. Further transient expression of CoGES in Nicotiana benthamiana resulted in a higher relative content of geranial and the appearance of a new substance, neral. These findings indicate that CoGES is a geraniol synthase-encoding gene, and the encoded protein can catalyze the transformation of GPP into geraniol, which is further converted into geranial and neral through an unknown mechanism in vivo. These findings expand our understanding of citral biosynthesis in Lauraceae plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01463-4.

Split intein converting peptide protein interaction into electrochemically assisted metal ion catalytic signal in the prenatal screening of pediatric epilepsy.

Dravet syndrome is a rare form of epilepsy starting from infancy that can plaque the affected individuals all though his/her life with repeated seizures, and this condition is currently without a complete cure. So prenatal screening of molecular markers of this condition is urgently needed to help couples conceiving new lives to steer clear of this potential danger. And such an assay should ideally be of low cost and could be completed in a point-of-care fashion. This work reports an attempt to construct such an assay using simple peptides in the place of conventional biosensing macro-molecules such as antibodies and enzymes. Specifically, a marker protein of this syndrome can bring the two pieces of a self-splitting peptide "intein" together, which in turn facilitate the formation of metal ion coordination site, recruiting cupric ion to generate catalytically amplified signal readout. Using this method, disease marker protein Nav of this syndrome can be quantitatively detected directly in amniotic fluid samples, and samples associated with potential risk factors such as family history of this syndrome shows statistically evident decrease of this marker protein. These results may promise future application of the proposed method in clinical practice to reduce the social burden of Dravet syndrome by reducing its actual incident rate.

Feasibility and Acceptability Evaluation of a Digital Therapeutic Program for Improving Cancer Prevention: A Quasi-experimental Pre-post Interventional Pilot Study.

Previous studies have proved that healthy behaviors hinder the onset and progression of tumors. Digital therapeutics (DTx), playing a pivotal role in facilitating behavioral adjustments through educational interventions, lifestyle support, and symptom monitoring, contribute to the goal of tumor prevention. We aim to optimize the evaluation of the feasibility and acceptability of DTx for cancer prevention. This involves assessing AITI's daily activity rates and user feedback, and comparing changes in behavioral habits and differences in SF-36 before and after the intervention. In a 4-week trial with 57 participants engaging actively, we found both the average daily activity rate and 4-week retention rate at 35 (61.4%). The USE Questionnaire scores (validity, ease of use, acquisition, and satisfaction) ranged from 68.06 to 83.10, indicating AITI's user-friendliness and acceptability. Furthermore, positive habit changes were noted among participants in exercise and diet (p < 0.0001), suggesting the effectiveness of the DTx approach in modifying behavioral habits related to physical activity and nutrition. This pilot study underscores the potential of DTx in advancing cancer prevention. However, larger and longer studies are needed to comprehensively assess its impact.

Double loading of nickel phosphide surface for efficient hydrogen evolution reaction.

Metal phosphide, as a highly conductive, chemically stable catalyst material, modulating its hydrogen adsorption is crucial to enhance hydrogen evolution reaction (HER) activity. In this study, we propose a double loading strategy to build Ag and AgP2 heterogeneous structures on Ni2P nanosheets (Ag-AgP2/Ni2P). This is the first application of AgP2 materials in HER. This innovative synthesis was achieved by liquid-phase adsorption of precursors and heat-treatment phosphorization, surface adsorbed AgNO3 is converted to Ag-AgP2 double loading at the same time as Ni2P formation. Density functional theory (DFT) calculations reveal that the double loading structure optimizes charge distribution and d-band center. Its hydrogen adsorption free energy is closer to electroneutrality than that of single loading and simple heterostructures. Benefiting from the special structure, Ag-AgP2/Ni2P exhibits excellent HER performance in alkaline media, requiring only 78 mV overpotential to reach 10 mA cm-2 and stability up to 200 h. This dual loading strategy broadens the perspective of heterogeneous electrocatalyst development.

Idiopathic multicentric Castleman disease and connective tissue disorder successfully treated by siltuximab: a pediatric case report.

Background: Castleman disease (CD) is a rare lymphoproliferative disease. Idiopathic multicentric CD (iMCD), representing a distinct entity in CD, is partly attributed to autoimmune abnormalities and the hyperplastic process in iMCD involving the immune system. Consequently, iMCD presents a range of overlapping manifestations with connective tissue disorder (CTD), resulting in an inability to tell whether they coexist or imitate each other. Reports of CD combined with CTD are rare, more cases are needed to be summarized and analyzed to improve the efficiency of diagnosis and accelerate the development of novel treatments. Case Description: A male pediatric patient was diagnosed with CTD in October 2019 and had been receiving regular treatment with tocilizumab and glucocorticoid or methotrexate since April 2020. He was further diagnosed with iMCD of the hyaline vascular subtype according to biopsy-proven histopathological features and imaging-proven multiple involvement in August 2021. He received 4 doses of rituximab and then a combination of thalidomide and dexamethasone for about 1 year. His clinical symptoms were well controlled throughout the disease for a long period, but inflammatory markers were repeatedly elevated, which eventually turned normal after switching to siltuximab from July 2023, although a significant elevation of interleukin-6 occurred. Conclusions: We reported a pediatric case diagnosed as CTD and iMCD, whose inflammation finally be well controlled by siltuximab. Hopefully, our work will add insight into such rare situations and it is undoubtedly that the pathophysiological mechanism of CD and CTD coexistence and prediction models of treatment response remains to be explored to facilitate the clinical management and optimal treatment.

Structural and biochemical characterization of a nucleotide hydrolase from Streptococcus pneumonia.

In this report, we structurally and biochemically characterized the unknown gene product SP1746 from Streptococcus pneumoniae serotype 4. Various crystal structures of SP1746 in the apo form and in complex with different nucleotides were determined. SP1746 is a globular protein, which belongs to the histidine-aspartate (HD) domain superfamily with two Fe3+ ions in the active site that are coordinated by key active site residues and water molecules. All nucleotides bind in a similar orientation in the active site with their phosphate groups anchored to the diiron cluster. Biochemically, SP1746 hydrolyzes different nucleotide substrates. SP1746 most effectively hydrolyzes diadenosine tetraphosphate (Ap4A) to two ADPs. Based on the aforementioned data, we annotated SP1746 as an Ap4A hydrolase, belonging to the YqeK family. Our in vitro data indicate a potential role for SP1746 in regulating Ap4A homeostasis, which requires validation with in vivo experiments in bacteria in the future.