Unveiling the shield: Troglitazone's impact on epilepsy-induced nerve injury through ferroptosis inhibition.

BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.

Past and present: a bibliometric study on the treatment of recurrent ovarian cancer.

Background: Ovarian cancer (OC) is a gynecological malignancy with a high mortality rate worldwide. The unfavorable prognosis of OC is mainly attributed to the recurrent propensity. Recently, mortality from OC has exhibited a downward trend. These favorable patterns are likely to be driven by advancements in novel therapeutic regimens. However, there is a lack of visualize analysis of the application of these new drugs on women with recurrent OC (ROC). Therefore, we aimed to provide a bibliometric analysis of the evolving paradigms in the ROC treatment. Methods: Documents on ROC treatment were systematically collected from the MEDLINE database and Web of Science Core Collection (WOSCC). The retrieved documents were exported in the plain text file format, and files were named and saved to the paths specified by the Java application. Microsoft Excel (version 2010), Citespace (6.2.R4) and VOSviewer (1.6.19) were used for data analysis, and included the following: 1) annual publication trend; 2) contributions of countries, institutions and authors; 3) co-citation of journals and references; and 4) co-occurrence of keywords. Results: A total of 914 documents published in the MEDLINE and 9,980 ones in WOSCC were retrieved. There has been an upward trend in the productivity of publications on ROC treatment on by years. The United States was the leading contributor in this field, and the University of Texas System stood out as the most productive institution. Giovanni Scambia and Maurie Markman were the research leaders in the field of ROC treatment. The journal Gynecologic Oncology had the highest citation frequency. The reference entitled with "Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer" got highest centrality of 0.14 in the co-citation network. Keyword analysis revealed that the focus of current ROC treatment was on platinum-based anticancer drugs, paclitaxel, angiogenesis inhibitors (AIs), immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase inhibitors (PARPis). Conclusion: Scholars from a multitude of countries have been instrumental in the advancement of ROC treatment. The research hotspots and trend in the field of predominantly originated from leading international journals and specialized periodicals focused on gynecologic oncology. Maintenance therapy using AIs or (and) PARPis has emerged as a significant complement to platinum-based chemotherapy for patients with ROC.

Case Report: Scalp pityriasis versicolor may be a neglected problem.

Pityriasis versicolor, a common skin fungal infection, is typically observed on trunk and limb skin. Here, we highlight an unusual presentation: scalp involvement, often overlooked due to its asymptomatic, mildly scaly patches. We report four pediatric cases, emphasizing the potential underestimation of this scalp variant. This case series underscores the importance of considering this diagnosis in patients with unexplained scalp hypopigmentation, especially in males with short hair who may readily notice these subtle changes. The report contributes to the understanding of this variant's clinical presentation and emphasizes the need for awareness among clinicians to ensure accurate diagnosis and appropriate management.

Early colorectal cancer screening-no time to lose.

In this editorial, we comment on the article entitled "Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?" by Agatsuma et al. Colorectal cancer (CRC) is emerging as an important health issue as its incidence continues to rise globally, adversely affecting the quality of life. Although the public has become more aware of CRC prevention, most patients lack screening awareness. Some poor lifestyle practices can lead to CRC and symptoms can appear in the early stages of CRC. However, due to the lack of awareness of the disease, most of the CRC patients are diagnosed already at an advanced stage and have a poor prognosis.

Sm-like 5 knockdown inhibits proliferation and promotes apoptosis of colon cancer cells by upregulating p53, CDKN1A and TNFRSF10B.

BACKGROUND: The role of Sm-like 5 (LSM5) in colon cancer has not been determined. In this study, we investigated the role of LSM5 in progression of colon cancer and the potential underlying mechanism involved. AIM: To determine the role of LSM5 in the progression of colon cancer and the potential underlying mechanism involved. METHODS: The Gene Expression Profiling Interactive Analysis database and the Human Protein Atlas website were used for LSM5 expression analysis and prognosis analysis. Real-time quantitative polymerase chain reaction and Western blotting were utilized to detect the expression of mRNAs and proteins. A lentivirus targeting LSM5 was constructed and transfected into colon cancer cells to silence LSM5 expression. Proliferation and apoptosis assays were also conducted to evaluate the growth of the colon cancer cells. Human GeneChip assay and bioinformatics analysis were performed to identify the potential underlying mechanism of LSM5 in colon cancer. RESULTS: LSM5 was highly expressed in tumor tissue and colon cancer cells. A high expression level of LSM5 was related to poor prognosis in patients with colon cancer. Knockdown of LSM5 suppressed proliferation and promoted apoptosis in colon cancer cells. Silencing of LSM5 also facilitates the expression of p53, cyclin-dependent kinase inhibitor 1A (CDKN1A) and tumor necrosis factor receptor superfamily 10B (TNFRSF10B). The inhibitory effect of LSM5 knockdown on the growth of colon cancer cells was associated with the upregulation of p53, CDKN1A and TNFRSF10B. CONCLUSION: LSM5 knockdown inhibited the proliferation and facilitated the apoptosis of colon cancer cells by upregulating p53, CDKN1A and TNFRSF10B.

Ultralow-Frequency Tip-Enhanced Raman Scattering Discovers Nanoscale Radial Breathing Mode on Strained 2D Semiconductors.

Collective excitations including plasmons, magnons, and layer-breathing vibration modes emerge at an ultralow frequency (<1 THz) and are crucial for understanding van der Waals materials. Strain at the nanoscale can drastically change the property of van der Waals materials and create localized states like quantum emitters. However, it remains unclear how nanoscale strain changes collective excitations. Herein, ultralow-frequency tip-enhanced Raman spectroscopy (TERS) with sub-10 nm resolution under ambient conditions is developed to explore the localized collective excitation on monolayer semiconductors with nanoscale strains. A new vibrational mode is discovered at around 12 cm-1 (0.36 THz) on monolayer MoSe2 nanobubbles and it is identified as the radial breathing mode (RBM) of the curved monolayer. The correlation is determined between the RBM frequency and the strain by simultaneously performing deterministic nanoindentation and TERS measurement on monolayer MoSe2. The generality of the RBM in nanoscale curved monolayer WSe2 and bilayer MoSe2 is demonstrated. Using the RBM frequency, the strain of the monolayer MoSe2 on the nanoscale can be mapped. Such an ultralow-frequency vibration from curved van der Waals materials provides a new approach to study nanoscale strains and points to more localized collective excitations to be discovered at the nanoscale.

Multivariate associations between neuroanatomy and cognition in unmedicated and medicated individuals with schizophrenia.

Previous studies that focused on univariate correlations between neuroanatomy and cognition in schizophrenia identified some inconsistent findings. Moreover, antipsychotic medication may impact the brain-behavior profiles in affected individuals. It remains unclear whether unmedicated and medicated individuals with schizophrenia would share common neuroanatomy-cognition associations. Therefore, we aimed to investigate multivariate neuroanatomy-cognition relationships in both groups. A sample of 59 drug-naïve individuals with first-episode schizophrenia (FES) and a sample of 115 antipsychotic-treated individuals with schizophrenia were finally included. Multivariate modeling was conducted in the two patient samples between multiple cognitive domains and neuroanatomic features, such as cortical thickness (CT), cortical surface area (CSA), and subcortical volume (SV). We observed distinct multivariate correlational patterns between the two samples of individuals with schizophrenia. In the FES sample, better performance in token motor, symbol coding, and verbal fluency tests was associated with greater thalamic volumes but lower CT in the prefrontal and anterior cingulate cortices. Two significant multivariate correlations were identified in antipsychotic-treated individuals: 1) worse verbal memory performance was related to smaller volumes for the most subcortical structures and smaller CSA mainly in the temporal regions and inferior parietal lobule; 2) a lower symbol coding test score was correlated with smaller CSA in the right parahippocampal gyrus but greater volume in the right caudate. These multivariate patterns were sample-specific and not confounded by imaging quality, illness duration, antipsychotic dose, or psychopathological symptoms. Our findings may help to understand the neurobiological basis of cognitive impairments and the development of cognition-targeted interventions.

The cytochrome P4501A1 (CYP1A1) inhibitor bergamottin enhances host tolerance to multidrug-resistant Vibrio vulnificus infection.

PURPOSE: Vibrio vulnificus (V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. METHODS: An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. RESULTS: In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival (p = 0.014), reduced the serum creatinine (p = 0.002), urea nitrogen (p = 0.030), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1ß: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1ß, IL-6, TNF-α in liver (IL-1ß: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1ß: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid (p = 0.225), liver (p = 0.186), or kidney (p = 0.637). CONCLUSION: Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Transdermal delivery of elastin peptide assisted by betaine-based deep eutectic solvent to ameliorate skin photoaging.

The unique amino acid composition of elastin peptide (EP) makes it an excellent resource to obtain antioxidant peptides. It exhibits high elastase inhibitory activity with the potential to resist skin aging and is currently used in a many cosmetic products. However, the inherent low permeability of the skin limits its ability to penetrate the skin. To address this issue, a deep eutectic solvent (SAB) with excellent bioactivity was synthesized from betaine and succinic acid and used as a permeation enhancer to improve the absorption and utilization of EP in this paper. The results showed that low SAB concentrations significantly increased the transdermal delivery of EP. The 3D epidermal skin model (EpiKutis®) demonstrated that SAB/EP induced the synthesis of hyaluronic acid (HA) and filaggrin (FLG), accelerated skin barrier repair, and reduced water loss. Additionally, the zebrafish embryonic model showed that SAB/EP could reduce melanin secretion, decrease melanin deposition, and have an ameliorative effect on skin photoaging. Cellular experiments proved that SAB/EP can stimulate human skin fibroblasts to secrete procollagen I and elastin, improving skin elasticity and anti-wrinkle. The combination of EP and DES is a new attempt that is expected to be used as a safe and effective anti-wrinkle cosmetic material.

How the secrets behind photocurrents are revealed in Ag-TiO2 heterostructures-based plasmonic photoelectrochemical systems: A collaborative approach of EC-SERS and photoelectrochemical methods.

Plasmon-mediated chemical reactions (PMCR) have garnered growing interest as a promising concept for photocatalysis. However, in electrochemical systems at solid-liquid interfaces, the photo-induced charge transfer on the surface of metal-semiconductor heterostructures involves complex processes and mechanisms, which are still poorly understood. We explore the plasmon-mediated carrier transfer mechanism and the synergistic effect of light and electric fields on Ag-TiO2 heterostructures, through a combination of electrochemical surface-enhanced Raman spectroscopy and photoelectrochemical methods, with para-aminothiophenol (PATP) serving as a probe molecule. The results show that photocurrent responses are dependent on not only excitation wavelengths and applied potentials, but also the irreversibility of redox. The relationship between photocurrent responses and the chemical transformation between PATP and 4,4'-dimercaptoazobenzene is established, reflecting the photo-induced charge transfer of the heterostructures. The collaboration of spectroscopic and photoelectrochemical methods provide valuable insights into the chemical transformation and kinetic information of adsorbed molecules on the heterostructure during PMCR, offering opportunities for modulating of photocatalytic activities of hot carriers.

Reticular chemistry guided single-linker constructed pillar-layered metal-organic frameworks via an in situ "one-pot" strategy.

In the present work, we report a "two-in-one" strategy to construct single-linker-based pillar-layered metal-organic frameworks (PL-MOFs) guided by reticular chemistry via an in situ "one-pot" approach. Two carboxyl groups and one pyridine group are integrated into one molecular skeleton to form bifunctional organic linkers via the reaction of pyridine-containing aldehyde and bicarboxylate-containing o-phenylenediamine. During the synthesis of organic linkers, two zinc-based PL-MOFs, non-interpenetrated HIAM-3016-op and two-fold interpenetrated HIAM-3017-op, can be simultaneously constructed. The different interpenetrations for these two PL-MOFs can be attributed to the increased length of the pyridine-containing moiety. HIAM-3017-op can be utilized for Cr2O72- detection with excellent sensitivity and selectivity. The present work not only provides a novel insight to design and prepare PL-MOFs with specific structures guided by reticular chemistry, but also indicates the universality of the in situ "one-pot" strategy to construct porous materials.

Surface modification prepared porous copper oxide/(Cu-S)n metal-organic framework/reduced graphene oxide hierarchical structure for highly selective electrochemical quercetin detection.

Electrochemical alkalization of (Cu-S)n metal-organic framework (MOF) and graphene oxide ((Cu-S)n MOF/GO) composite yields a new CuO/(Cu-S)n MOF/RGO (reduced GO) composite with porous morphology on screen printed carbon electrode (SPCE) which facilitated the electron transfer properties in electrochemical quercetin (QUE) detection. A selective QUE detection ability has been demonstrated by the constructed electrochemical sensor (CuO/(Cu-S)n MOF/RGO/SPCE), which also has a broad dynamic range of 0.5 to 115 µM in pH 3 by differential pulse voltammetry. The detection limit is 0.083 µM (S/N = 3). In this study, it was  observed that the real samples contained 0.34 mg mL-1 and 27.7 µg g-1 QUE in wine and onion, respectively.

Molecular basis of human noradrenaline transporter reuptake and inhibition.

Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types1. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter (NET) located in the presynaptic membrane2. Here we report the cryo-electron microscopy (cryo-EM) structures of the human NET in both its apo state and when bound to substrates or antidepressant drugs, with resolutions ranging from 2.5 Å to 3.5 Å. The two substrates, noradrenaline and dopamine, display a similar binding mode within the central substrate binding site (S1) and within a newly identified extracellular allosteric site (S2). Four distinct antidepressants, namely, atomoxetine, desipramine, bupropion and escitalopram, occupy the S1 site to obstruct substrate transport in distinct conformations. Moreover, a potassium ion was observed within sodium-binding site 1 in the structure of the NET bound to desipramine under the KCl condition. Complemented by structural-guided biochemical analyses, our studies reveal the mechanism of substrate recognition, the alternating access of NET, and elucidate the mode of action of the four antidepressants.

Lung ultrasound score evaluation of the effect of pressure-controlled ventilation volume-guaranteed on patients undergoing laparoscopic-assisted radical gastrectomy.

BACKGROUND: Laparoscopic-assisted radical gastrectomy (LARG) is the standard treatment for early-stage gastric carcinoma (GC). However, the negative impact of this procedure on respiratory function requires the optimized intraoperative management of patients in terms of ventilation. AIM: To investigate the influence of pressure-controlled ventilation volume-guaranteed (PCV-VG) and volume-controlled ventilation (VCV) on blood gas analysis and pulmonary ventilation in patients undergoing LARG for GC based on the lung ultrasound score (LUS). METHODS: The study included 103 patients with GC undergoing LARG from May 2020 to May 2023, with 52 cases undergoing PCV-VG (research group) and 51 cases undergoing VCV (control group). LUS were recorded at the time of entering the operating room (T0), 20 minutes after anesthesia with endotracheal intubation (T1), 30 minutes after artificial pneumoperitoneum (PP) establishment (T2), and 15 minutes after endotracheal tube removal (T5). For blood gas analysis, arterial partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) were observed. Peak airway pressure (Ppeak), plateau pressure (Pplat), mean airway pressure (Pmean), and dynamic pulmonary compliance (Cdyn) were recorded at T1 and T2, 1 hour after PP establishment (T3), and at the end of the operation (T4). Postoperative pulmonary complications (PPCs) were recorded. Pre- and postoperative serum interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with those at T0, the whole, anterior, lateral, posterior, upper, lower, left, and right lung LUS of the research group were significantly reduced at T1, T2, and T5; in the control group, the LUS of the whole and partial lung regions (posterior, lower, and right lung) decreased significantly at T2, while at T5, the LUS of the whole and some regions (lateral, lower, and left lung) increased significantly. In comparison with the control group, the whole and regional LUS of the research group were reduced at T1, T2, and T5, with an increase in PaO2, decrease in PaCO2, reduction in Ppeak at T1 to T4, increase in Pmean and Cdyn, and decrease in Pplat at T4, all significant. The research group showed a significantly lower incidence of PPCs than the control group within 3 days postoperatively. Postoperative IL-1ß, IL-6, and TNF-α significantly increased in both groups, with even higher levels in the control group. CONCLUSION: LUS can indicate intraoperative non-uniformity and postural changes in pulmonary ventilation under PCV-VG and VCV. Under the lung protective ventilation strategy, the PCV-VG mode more significantly improved intraoperative lung ventilation in patients undergoing LARG for GC and reduced lung injury-related cytokine production, thereby alleviating lung injury.

DdmDE eliminates plasmid invasion by DNA-guided DNA targeting.

Horizontal gene transfer is a key driver of bacterial evolution, but it also presents severe risks to bacteria by introducing invasive mobile genetic elements. To counter these threats, bacteria have developed various defense systems, including prokaryotic Argonautes (pAgo) and the D NA D efense M odule DdmDE system. Through biochemical analysis, structural determination, and in vivo plasmid clearance assays, we elucidate the assembly and activation mechanisms of DdmDE, which eliminates small, multicopy plasmids. We demonstrate that DdmE, a pAgo-like protein, acts as a catalytically inactive, DNA-guided, DNA-targeting defense module. In the presence of guide DNA, DdmE targets plasmids and recruits a dimeric DdmD, which contains nuclease and helicase domains. Upon binding to DNA substrates, DdmD transitions from an autoinhibited dimer to an active monomer, which then translocates along and cleaves the plasmids. Together, our findings reveal the intricate mechanisms underlying DdmDE-mediated plasmid clearance, offering fundamental insights into bacterial defense systems against plasmid invasions.

Durability analysis of metakaolin recycled concrete under sulphate dry and wet cycle.

This study aims to enhance the durability, cost-effectiveness, and sustainability of recycled fine aggregate concrete (RFAC) subjected to the combined effects of wet-dry cycles and sulfate erosion. Dry-wet cycle tests were conducted in RFAC with different admixtures of biotite metakaolin (MK) and 15% fly ash (FA) mix (M) under 5% sulfate erosion environment. The effect of 0%, 30%, 60% and 90% recycled fine aggregate (RFA) replacement of natural fine aggregate on mass loss, cubic compressive strength, relative dynamic modulus test of RFAC, damage modeling and prediction of damage life of concrete were investigated. The results showed that the concrete cubic compressive strength and relative dynamic modulus were optimal for recycled concrete at 15% MK biotite dosing and 60% RFA substitution, and its maximum service life was accurately predicted to be about 578 cycles under 5% sulfate dry-wet cycling using Weibull function model. This study is pioneering in addressing the durability of RFAC under sulfate attack combined with wet-dry cycling, employing a novel approach of incorporating MK and FA into RFAC. The findings highlight the practical application potential for using MK and FA in RFAC to produce durable and sustainable construction materials, particularly in sulfate-exposed environments. This research addresses a critical challenge in the construction industry, providing valuable insights for developing more durable and eco-friendly construction materials and contributing to long-term sustainability goals.

[Numerical study of the effect of geometrical parameters of straight impellers on the flow and hemolysis performance of centrifugal blood pumps].

Red blood cells are destroyed when the shear stress in the blood pump exceeds a threshold, which in turn triggers hemolysis in the patient. The impeller design of centrifugal blood pumps significantly influences the hydraulic characteristics and hemolytic properties of these devices. Based on this premise, the present study employs a multiphase flow approach to numerically simulate centrifugal blood pumps, investigating the performance of pumps with varying numbers of blades and blade deflection angles. This analysis encompassed the examination of flow field characteristics, hydraulic performance, and hemolytic potential. Numerical results indicated that the concentration of red blood cells and elevated shear stresses primarily occurred at the impeller and volute tongue, which drastically increased the risk of hemolysis in these areas. It was found that increasing the number of blades within a certain range enhanced the hydraulic performance of the pump but also raised the potential for hemolysis. Moreover, augmenting the blade deflection angle could improve the hemolytic performance, particularly in pumps with a higher number of blades. The findings from this study can provide valuable insights for the structural improvement and performance enhancement of centrifugal blood pumps.

Receptor tyrosine kinase-like orphan receptor 1: A novel antitumor target in gastrointestinal cancers.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the type I receptor tyrosine kinase family. ROR1 is pivotal in embryonic development and cancer, and serves as a biomarker and therapeutic target. It has soluble and membrane-bound subtypes, with the latter highly expressed in tumors. ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms. Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis. Additionally, ROR1 may regulate the cell cycle, stem cell characteristics, and interact with other signaling pathways to affect cancer progression. This review explores the structure, expression and role of ROR1 in the development of gastrointestinal cancers. It discusses current antitumor strategies, outlining challenges and prospects for treatment.

Short stature with brachydactyly caused by a novel mutation in the IHH gene and response to 4-year growth hormone therapy: a case report.

Background: The etiology of short stature is heterogeneous. The disturbance of endochondral ossification and cartilage matrix synthesis caused by genetic mutations often causes short height combined with skeletal deformities in children. Some patients with minor skeletal abnormalities, such as short fingers and mild limb shortening, may be overlooked by clinicians and misdiagnosed as idiopathic short stature (ISS) or growth hormone deficiency (GHD). Case Description: We conducted a detailed investigation of laboratory and imaging examinations on a family with short stature and non-classical brachydactyly type A1 (BDA1) and summarized the clinical features. They received whole exome sequencing (WES) to reveal the possible genetic variation. A heterozygous mutation in the Indian hedgehog gene (IHH) (c.387_388insC, p.Thr130Hisfs*18) was found in the two siblings and their mother. The siblings both started recombinant human growth hormone (rhGH) therapy (rhGH: 33 µg/kg/day) and followed up for 4 years. After treatment, the siblings' height improved significantly, and they acquired a significant increase in the height standard deviation score (SDS) (the boy: +2.54, the girl: +1.86) during the 4-year therapy. No noticeable adverse effect was observed during rhGH treatment. Conclusions: We found a novel heterozygous pathogenic mutation in the IHH gene in a family and detailed the phenotype with short stature and non-classical BDA1. The therapy of rhGH showed promising effects. To avoid misdiagnosis, clinicians should not overlook minor skeletal anomalies in patients with short stature, especially those with a family history.