Isolation, characterization and therapeutic evaluation of a new Acinetobacter virus Abgy202141 lysing Acinetobacter baumannii.

Acinetobacter baumannii is an opportunistic pathogen that easily resists currently available antibiotics. Phages are considered alternative therapeutic agents to conventional antibiotics for the treatment of multidrug-resistant bacteria. We isolated an Acinetobacter virus Abgy202141 from underground sewage in a residential area of Guiyang City in China. Transmission electron microscopy (TEM) analysis showed that Acinetobacter virus Abgy202141 has an icosahedral head attached to a tail. This phage infects A. baumannii strain GY-4, and was found to have a short latent period of 5 min and with a burst size of 189 particles per infected host cell. Additionally, Acinetobacter virus Abgy202141 remained stable at different concentrations of chloroform and varying pH levels and temperatures. Based on SDS-PAGE analysis, it contained 14 proteins with molecular weights ranging from 12 to 125 kDa. The double-strand (ds) DNA genome of Acinetobacter virus Abgy202141 consisted of 41,242 bp with a GC content of 39.4%. It contained 50 open reading frames (ORFs), of which 29 ORFs had identified functions, but no virulence-related genes, antibiotic-resistance genes, or tRNAs were found. Phylogenetic analysis indicated that Acinetobacter virus Abgy202141 was a new phage in the Friunavirus genus. Acinetobacter virus Abgy202141 also showed the ability to prevent A. baumannii infections in the Galleria mellonella in vivo model.

Resource utilization of MSWI fly ash supporting TiO2/BiOCl nanocomposite for enhanced photocatalytic degradation of sodium isopropyl xanthate: Mechanism and performance evaluation.

The removal of organic pollutants in water environments and the resource utilization of solid waste are two pressing issues around the world. Facing the increasing pollution induced by discharge of mining effluents containing sodium isopropyl xanthate (SIPX), in this work, municipal solid waste incineration fly ash (MSWI FA) was pretreated by hydrothermal method to produce stabilized FA, which was then innovatively used as support for the construction of FA/TiO2/BiOCl nanocomposite (FTB) with promoted photocatalytic activity under visible light and natural sunlight. When the content of FA was 20 wt% and the mass ratio of TiO2 to BiOCl was 4:6, a remarkable performance for the optimal FTB (20-FTB-2) was achieved. Characterizations demonstrated that TiO2 and BiOCl uniformly dispersed on FA contributing to high surface area and broad light adsorption of FTB, which exhibits excellent adsorption capacity and light response ability. Build in electric field formed in the interface of TiO2/BiOCl heterojunction revealed by density functional theory calculations accelerated the separation of photoinduced e- and h+, leading to high efficiency for SIPX degradation. The synergetic effect combined with adsorption and photocatalytic degradation endowed 20-FTB-2 superior SIPX removal efficiency over 99% within 30 min under visible light and natural sunlight irradiation. The photocatalytic degradation pathways of SIPX were determined through theoretical calculations and characterizations, and the toxic byproduct CS2 was effectively eliminated through oxidation of •O2-. For 20-FTB-2, reusability of photocatalyst was showed by cycle tests, also the concentrations of main heavy metals (Pb, Zn, Cu, Cr, and Cd) in the liquid phases released during photocatalyst preparation process (< 1 mg/L) and photodegradation process (< 8.5 µg/L) proved the satisfactory stability with low toxicity. This work proposed a novel strategy to develop efficient and stable support-based photocatalysts by utilizing MSWI FA and realize its resource utilization.

Understanding suicidal ideation disparity between sexual minority and heterosexual Chinese young men: a multiple mediation model of social support sources, self-esteem, and depressive symptoms.

Objectives: Although sexual minorities have reported higher levels of suicidal ideation than heterosexuals across cultures, the role of various psychosocial factors underlying this disparity among young men has been understudied, particularly in China. This study examined the multiple mediating effects of psychosocial factors between sexual orientation and suicidal ideation in Chinese sexual minority and heterosexual young men. Methods: 302 Chinese cisgender men who identified as gay or bisexual, and 250 cisgender heterosexual men (n=552, aged 18-39 years) completed an online questionnaire measuring perceived social support, self-esteem, depressive symptoms, and suicidal ideation. Results: Young sexual minority men reported significantly higher suicidal ideation and lower social support than their heterosexual peers. Structural equation modelling revealed two multiple indirect pathways. One pathway indicated that sexual orientation was indirectly related to suicidal ideation via family support and depressive symptoms. Another pathway indicated that sexual orientation was indirectly related to suicidal ideation via support from friends, self-esteem, and depressive symptoms. Conclusions: This study is among the first to examine the potentially cascading relationships between sexual orientation and psychosocial factors with suicidal ideation in a Chinese sample of young men. The findings highlight several promising psychosocial targets (i.e., improving family/friend support and increasing self-esteem) for suicide interventions among sexual minority males in China.

Exploring the antioxidant potential of nekemias species extracts on edible oils: In vitro assessment and lipid oxidation inhibition.

Synthetic antioxidants have long been used to protect edible oils from oxidation. However, concerns about their potential health risks and environmental impact have led to a growing interest in natural antioxidants. In this study, we explore the antioxidant properties of extracts from four Nekemias plant species: Nekemias grossedentata (AGR), Nekemias megalophylla (AME), Nekemias chaffanjonii (ACH), and Nekemias cantoniensis (ACA) by obtaining the values for different tests. We investigate their bioactive compound content and evaluate their antioxidant capabilities on six edible oils categorized into three lipid systems based on their fatty acid compositions: oleic acid, linoleic acid, and linolenic acid. Our findings demonstrate that AGR and AME extracts, rich in bioactive compounds, exhibit strong antioxidant activities in vitro, effectively inhibiting lipid oxidation, especially in oleic acid-rich oils like camellia oil. The antioxidant effects of these extracts are comparable to synthetic antioxidants such as TBHQ and superior to natural antioxidant Tea Polyphenols (TP). While the extracts also show antioxidant potential in linoleic and linolenic acid systems, the stability of their effects in these oils is lower than in oleic acid system. These results suggest that Nekemias species extracts have the potential to serve as natural additives for extending the shelf life of edible oils, contributing to the exploration of natural antioxidants.

Lycium barbarum glycopeptide (wolfberry extract) slows N-methyl-N-nitrosourea-induced degradation of photoreceptors.

JOURNAL/nrgr/04.03/01300535-202410000-00030/figure1/v/2024-02-06T055622Z/r/image-tiff Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum (L. barbarum) polysaccharide (LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide (LbGP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of LbGP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of LbGP as a protective pre-treatment on days 1-7; intraperitoneal administration of 40 mg/kg N-methyl-N-nitrosourea to induce photoreceptor injury on day 7; and continuation of orally administered LbGP on days 8-14. Treatment with LbGP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. LbGP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, LbGP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.

Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade.

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy. METHODS: We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno-collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in-house samples. Additionally, novel therapeutic targets were identified based on these established immuno-collagenic subtypes. RESULTS: Our categorization divided tumors into three subtypes: "soft & hot" (low collagen activity and high immune infiltration), "armored & cold" (high collagen activity and low immune infiltration), and "quiescent" (low collagen activity and immune infiltration). Notably, "soft & hot" tumors exhibited the most robust response to ICB therapy across various cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7-H3), an available drug target, as strongly expressed in "armored & cold" tumors, relating with poor prognosis. CONCLUSION: This study introduces histopathology-based universal immuno-collagenic subtypes capable of predicting ICB responses across diverse cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

Chemerin promotes invasion of oral squamous cell carcinoma by stimulating IL-6 and TNF-α production via STAT3 activation.

AIMS: Elevated levels of adipokine chemerin have been identified in oral squamous cell carcinoma (OSCC) and found to be associated with metastasis to the cervical lymph nodes. The underlying mechanism through which chemerin affects OSCC progression is unclear. The aims of this study were firstly to determine chemerin levels and cytokine concentrations in serum from patients with OSCC and in OSCC cell cultures, and secondly to observe chemerin effects on OSCC cell cytokine secretion, migration, and invasion in vitro. METHODS: Serum samples were collected from 20 patients diagnosed with OSCC, including groups with (LN+) and without (LN-) cervical lymph node metastasis. A Luminex liquid suspension assay was used to quantify serum concentrations of 27 types of cytokines. Correlations between chemerin and cytokines (i.e., IL-6, IL-15, GM-CSF, RANTES, TNF-α, and VEGF) were analyzed. ELISAs (enzyme-linked immunosorbent assays) were used to determine concentrations of chemerin and selected cytokines in serum and in supernatants of OSCC cell cultures (SCC9 and SCC25 cell lines). OSCC cells were stimulated with human recombinant chemerin, STAT3 inhibitor, or IL-6 together with TNF-α neutralizing antibodies. Phosphorylated STAT3 protein levels were measured with western blot analysis. OSCC cell migration and invasion were investigated with Transwell assays. RESULTS: Compared to the LN- group, OSCC patients with cervical lymph node metastasis had higher levels of IL-6 (P = 0.006), IL-15 (P = 0.020), GM-CSF (P = 0.036), RANTES (P = 0.032), TNF-α (P = 0.005), VEGF (P = 0.006), and chemerin (P = 0.001). Patients' serum chemerin levels correlated directly with IL-6, GM-CSF, TNF-α, and VEGF levels in OSCC patients. Exogenous recombinant chemerin treatment promoted secretion of IL-6 and TNF-α via activation of STAT3 in OSCC cells. Chemerin induced OSCC-cell migration and invasion, and these effects were reduced by IL-6 and TNF-α neutralizing antibodies. CONCLUSION: Our findings indicate that chemerin may play a role in advancing OSCC progression by increasing production of IL-6 and TNF-α, perhaps via a mechanism involving STAT3 signaling.

Direct Access to Thio- and Seleno-acetamides Bearing (Benzo)thiazoles by a Base-Promoted One-Pot Two-Step Three-Component Reaction of 2-Amino(benzo)thiazoles with Aryl Acetyl Chlorides and Dichalcogenides.

Highly efficient and practical carbon-chalcogen (S, Se) and amide bonds formation methodologies for the synthesis of thio- and seleno-acetamides were developed, via the base-promoted one-pot two-step reactions of 2-amino(benzo)thiazoles and aryl acetyl chlorides with dichalcogenides. This cross-coupling reaction afforded the goal products that had been chalcogenated regioselectively in moderate to good yields. Further transformations of the new synthesized compounds, DFT calculations and preliminary mechanism studies are discussed as well.

Pubertal exposure to Microcystin-LR arrests spermatogonia proliferation by inducing DSB and inhibiting SIRT6 dependent DNA repair in vivo and in vitro.

The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2 µg/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.

A promising target for breast cancer: B7-H3.

Breast cancer (BC) is the second-leading factor of mortality for women globally and is brought on by a variety of genetic and environmental causes. The conventional treatments for this disease have limitations, making it difficult to improve the lifespan of breast cancer patients. As a result, extensive research has been conducted over the past decade to find innovative solutions to these challenges. Targeting of the antitumor immune response through the immunomodulatory checkpoint protein B7 family has revolutionized cancer treatment and led to intermittent patient responses. B7-H3 has recently received attention because of its significant demodulation and its immunomodulatory effects in many cancers. Uncontrolled B7-H3 expression and a bad outlook are strongly associated, according to a substantial body of cancer research. Numerous studies have shown that BC has significant B7-H3 expression, and B7-H3 induces an immune evasion phenotype, consequently enhancing the survival, proliferation, metastasis, and drug resistance of BC cells. Thus, an innovative target for immunotherapy against BC may be the B7-H3 checkpoint.In this review, we discuss the structure and regulation of B7-H3 and its double costimulatory/coinhibitory function within the framework of cancer and normal physiology. Then we expound the malignant behavior of B7-H3 in BC and its role in the tumor microenvironment (TME) and finally focus on targeted drugs against B7-H3 that have opened new therapeutic opportunities in BC.

Tumor-associated macrophages in non-small-cell lung cancer: From treatment resistance mechanisms to therapeutic targets.

Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related deaths worldwide. Different treatment approaches are typically employed based on the stage of NSCLC. Common clinical treatment methods include surgical resection, drug therapy, and radiation therapy. However, with the introduction and utilization of immune checkpoint inhibitors, cancer treatment has entered a new era, completely revolutionizing the treatment landscape for various cancers and significantly improving overall patient survival. Concurrently, treatment resistance often poses a critical challenge, with many patients experiencing disease progression following an initial response due to treatment resistance. Increasing evidence suggests that the tumor microenvironment (TME) plays a pivotal role in treatment resistance. Tumor-associated macrophages (TAMs) within the TME can promote treatment resistance in NSCLC by secreting various cytokines activating signaling pathways, and interacting with other immune cells. Therefore, this article will focus on elucidating the key mechanisms of TAMs in treatment resistance and analyze how targeting TAMs can reduce the levels of treatment resistance in NSCLC, providing a comprehensive understanding of the principles and approaches to overcome treatment resistance in NSCLC.

Chemical Micromotors Move Faster at Oil-Water Interfaces.

Many real-world scenarios involve interfaces, particularly liquid-liquid interfaces, that can fundamentally alter the dynamics of colloids. This is poorly understood for chemically active colloids that release chemicals into their environment. We report here the surprising discovery that chemical micromotors─colloids that convert chemical fuels into self-propulsion─move significantly faster at an oil-water interface than on a glass substrate. Typical speed increases ranged from 3 to 6 times up to an order of magnitude and were observed for different types of chemical motors and interfaces made with different oils. Such speed increases are likely caused by faster chemical reactions at an oil-water interface than at a glass-water interface, but the exact mechanism remains unknown. Our results provide valuable insights into the complex interactions between chemical micromotors and their environments, which are important for applications in the human body or in the removal of organic pollutants from water. In addition, this study also suggests that chemical reactions occur faster at an oil-water interface and that micromotors can serve as a probe for such an effect.

Bone morphogenetic protein 9 is a candidate prognostic biomarker and host-directed therapy target for sepsis.

Defining next-generation immune therapeutics for the treatment of sepsis will involve biomarker-based therapeutic decision-making. Bone morphogenetic protein 9 (BMP9) is a cytokine in the transforming growth factor-ß superfamily. Here, circulating BMP9 concentrations were quantified in two independent cohorts of patients with sepsis. Decreased concentrations of serum BMP9 were observed in the patients with sepsis at the time of admission as compared with healthy controls. Concentrations of BMP9 at the time of admission were also associated with 28-day mortality, because patients with sepsis at a higher risk of death had lower BMP9 concentrations. The mechanism driving the contribution of BMP9 to host immunity was further investigated using in vivo murine sepsis models and in vitro cell models. We found that BMP9 treatment improved outcome in mice with experimental sepsis. BMP9-treated mice exhibited increased macrophage influx into the peritoneal cavity and more efficient bacterial clearance than untreated mice. In vitro, BMP9 promoted macrophage recruitment, phagocytosis, and subsequent bacterial killing. We further found that deletion of the type 1 BMP receptor ALK1 in macrophages abolished BMP9-mediated protection against polymicrobial sepsis in vivo. Further experiments indicated that the regulation of macrophage activation by the BMP9-ALK1 axis was mainly mediated through the suppressor of mother against decapentaplegic 1/5 signaling pathway. Together, these results suggest that BMP9 can both serve as a biomarker for patient stratification with an independent prognostic value and be developed as a host-directed therapy for sepsis.

Construction of novel Ag/AgI/Bi4Ti3O12 plasmonic heterojunction: A study focusing on the performance and mechanism of photocatalytic removal of tetracycline.

As a result of the insufficient absorption of visible light, the application of Bi4Ti3O12 in the field of photocatalysis is limited. Ag/AgI was uniformly modified on the surface of the nanoflower bulb of Bi4Ti3O12 by simple precipitation method and photodeposition. The fabricated Ag/AgI/Bi4Ti3O12 obtained an ultra-high tetracycline (TC) removal rate under visible light irradiation. And the synergetic effects caused by the surface plasmon resonance (SPR) effect of Ag, the photosensitivity of AgI and the p-n heterojunction are the key to improving the photocatalytic performance of materials. Besides, four plausible photodegradation pathways of TC were proposed and its intermediates were evaluated for toxicity, showing a significant decrease in toxicity after photoreaction.

Associations between HIFs and tumor immune checkpoints: mechanism and therapy.

Hypoxia, which activates a variety of signaling pathways to enhance tumor cell growth and metabolism, is among the primary features of tumor cells. Hypoxia-inducible factors (HIFs) have a substantial impact on a variety of facets of tumor biology, such as epithelial-mesenchymal transition, metabolic reprogramming, angiogenesis, and improved radiation resistance. HIFs induce hypoxia-adaptive responses in tumor cells. Many academics have presented preclinical and clinical research targeting HIFs in tumor therapy, highlighting the potential applicability of targeted HIFs. In recent years, the discovery of numerous pharmacological drugs targeting the regulatory mechanisms of HIFs has garnered substantial attention. Additionally, HIF inhibitors have attained positive results when used in conjunction with traditional oncology radiation and/or chemotherapy, as well as with the very promising addition of tumor immunotherapy. Immune checkpoint inhibitors (CPIs), which are employed in a range of cancer treatments over the past decades, are essential in tumor immunotherapy. Nevertheless, the use of immunotherapy has been severely hampered by tumor resistance and treatment-related toxicity. According to research, HIF inhibitors paired with CPIs may be game changers for multiple malignancies, decreasing malignant cell plasticity and cancer therapy resistance, among other things, and opening up substantial new pathways for immunotherapy drug development. The structure, activation mechanisms, and pharmacological sites of action of the HIF family are briefly reviewed in this work. This review further explores the interactions between HIF inhibitors and other tumor immunotherapy components and covers the potential clinical use of HIF inhibitors in combination with CPIs.

Enhancement of catalytic detoxification of polycyclic aromatic hydrocarbons in fly ash from municipal solid waste incineration via magnetic hydroxyapatite-assisted hydrothermal treatment.

The emission of carcinogenic, teratogenic, and mutagenic polycyclic aromatic hydrocarbons (PAHs) during municipal solid waste incineration (MSWI) of fly ash (FA) has attracted significant attention. Hydrothermal treatment (HT) has emerged as a practical approach for degrading PAHs during MSWI of FA by utilizing magnetite (Fe3O4) as a catalyst and hydrogen peroxide (H2O2) as an oxidizing agent. In this study, as an alternative to traditional hydroxyapatite (HAP), eggshell-derived magnetic hydroxyapatite (MHAP) was synthesized and applied in the hydrothermal catalytic degradation of PAHs in MSWI FA in an H2O2 system for the first time. The degradation efficiency of the PAHs is influenced not only by H2O2 but also by the choice of hydroxyapatite. Adding HAP or MHAP during hydrothermal treatment with H2O2 substantially reduced the overall PAH concentration and toxicity equivalent quantity (TEQ), superior to that without H2O2. MHAP demonstrated superior catalytic activity compared to HAP in the presence of H2O2 in the hydrothermal system. The hydrothermal detoxification of the PAHs increased with increasing MHAP dosage. By employing 0.5 mol/L H2O2 as the oxidant and 15 wt% MHAP as the catalyst, a total PAH degradation rate of 88.9 % was achieved, with a remarkable TEQ degradation rate of 98.3 %. Notably, the level of 4-6-ring PAHs, particularly benzo(a) pyrene (BaP) and dibenz(a,h)anthracene (DahA), with a TEQ of 1.0, was significantly reduced (by 69.4 % and 46.0 %, respectively). MHAP remained stable during the hydrothermal catalytic process, whereas H2O2 was effectively activated by MHAP and decomposed to produce strongly oxidizing hydroxyl (•OH) under hydrothermal conditions. •OH produced from the decomposition of H2O2 and metals on the surface of MHAP act as catalytically active centers, efficiently converting high-ring PAHs to low-ring PAHs. These findings provide valuable insights and a technological foundation for PAH detoxification in MSWI FA via hydrothermal catalytic oxidation.

Clinical characteristics and associated factors of posttraumatic epilepsy after traumatic brain injury in children: A retrospective case-control study.

BACKGROUND: Traumatic brain injury (TBI) affects approximately 69 million individuals annually, often resulting in well-documented complications such as epilepsy. Although numerous studies have been performed on posttraumatic epilepsy (PTE) in adults over the past decade, research on chronic consequences of TBI in children remains limited. Herein, we retrospectively assessed children who had experienced moderate to severe TBI to determine their clinical characteristics and identify associated factors associated with the development of PTE in the pediatric population. METHODS: The study population comprised children aged 0-18 years who had experienced moderate to severe TBI and underwent treatment at the Children's Hospital of Chongqing Medical University between 2011 and 2021. They were categorized into two groups: the PTE group, comprising individuals diagnosed with PTE within a one-year follow-up period, and the nPTE group, consisting of those who did not develop PTE during the same timeframe. The primary objective was to investigate the clinical characteristics and identify related associated factors. The relationship between various clinical factors and the incidence of PTE was assessed through univariate and multivariate logistic regression. RESULTS: A total of 132 patients were assessed. Most participants were male (65%) and the age distribution skewed towards younger children, with a median age of 41.0 months (interquartile range: 45.3). Upon their last clinical visit, 64 children (49%) were diagnosed with PTE. Notably, the first posttraumatic seizure predominantly occurred within the first week following the traumatic event. Further analyses revealed that increasing injury severity, as indicated by a lower Glasgow Coma Scale (GCS) score (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.54-1.12, p= 0.018), a contusion load ≥3 (OR: 8.1, 95% CI: 2.3-28.9, p= 0.001), immediate posttraumatic seizures (IPTS) (OR: 8.9, 95% CI: 2.5-31.2, p < 0.001), and early posttraumatic seizures (EPTS) (OR: 54, 95% CI: 11-276, p < 0.001), were all significantly associated with a higher risk of developing PTE. CONCLUSION: This study highlights that the onset of PTE was associated with the markers of injury severity or PTS and identified GCS scores, contusion loads of ≥3, IPTS, and EPTS as independent associated factors significantly associated with the development of PTE.

Elevated serum level of progranulin is associated with increased mortality in critically ill patients with candidemia.

Candidemia is a severe disease with high mortality in both intensive care unit (ICU) and non-ICU settings. Considering that progranulin (PGRN) is a potential therapeutic target for the candidemia caused by Candida albicans, we determined the serum level of PGRN after candidemia and evaluated its association with mortality. A retrospective discovery cohort (62 patients) and a validation cohort (70 patients) were enrolled. Blood was collected on day of first blood culture positivity for C. albicans, and serum PGRN levels were then measured. In the discovery cohort, all serum PGRN studied were expressed at higher levels in candidemia patients than in bacteremia patients and healthy volunteers, non-survivors presented with significantly higher serum PGRN concentrations when compared with survivors. Serum PGRN concentration was associated with 30-day mortality and patients at a higher risk of death showed higher serum PGRN levels. These results were confirmed in the independent validation cohort. Interestingly, in vitro study demonstrated that macrophages, neutrophils and lymphocytes may be the major source of PGRN production after C. albicans infection instead of epithelial cells. Our findings highlight that serum PGRN appears as a biomarker in candidemia patients and as a promising tool for mortality risk stratification in managing candidemia.

Electroosmotic flow spin tracers near chemical nano/micromotors.

We report the first experimental observation of tracer spinning in place alongside chemically powered individual nano/micromotors. The torques are primarily generated by the electroosmotic flow on the motor surface. Such spinning is observed in various combinations of nano/micromotors and tracers of different shapes, sizes and chemical compositions.

Remodeling of Mitochondrial Metabolism by a Mitochondria-Targeted RNAi Nanoplatform for Effective Cancer Therapy.

Emerging evidence has demonstrated the significant contribution of mitochondrial metabolism dysfunction to promote cancer development and progression. Aberrant expression of mitochondrial genome (mtDNA)-encoded proteins widely involves mitochondrial metabolism dysfunction, and targeted regulation of their expression can be an effective strategy for cancer therapy, which however is challenged due to the protection by the mitochondrial double membrane. Herein, a mitochondria-targeted RNAi nanoparticle (NP) platform for effective regulation of mitochondrial metabolism and breast cancer (BCa) therapy is developed. This nanoplatform is composed of a hydrophilic polyethylene glycol (PEG) shell, a hydrophobic poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) core, and charged-mediated complexes of mitochondria-targeting and membrane-penetrating peptide amphiphile (MMPA) and small interfering RNA (siRNA) embedded in the core. After tumor accumulation and internalization by tumor cells, these NPs can respond to the endosomal pH to expose the MMPA/siRNA complexes, which can specifically transport siRNA into the mitochondria to down-regulate mtDNA-encoded protein expression (e.g., ATP6 and CYB). More importantly, because ATP6 down-regulation can suppress ATP production and enhance reactive oxygen species (ROS) generation to induce mitochondrial damage and mtDNA leakage into tumor tissues, the NPs can combinatorially inhibit tumor growth via suppressing ATP production and repolarizing tumor-associated macrophages (TAMs) into tumor-inhibiting M1-like macrophages by mtDNA.