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Microglia, as immune cells in the central nervous system, possess the ability to adapt morphologically and functionally to their environment. Glymphatic system, the principal waste clearance system in the brain, exhibits circadian rhythms. However, the impact of microglia on the glymphatic system function remains unknown. In this study, we explored the intricate relationship between microglia and the glymphatic system. Examining diurnal patterns, we identified synchronized behaviors in glymphatic activity and microglial morphology, peaking during sleep and exhibiting distinct changes in branching complexity. Depleting microglia using PLX5622 or in P2Y12 knockout mice enhanced glymphatic function. Chemogenetic manipulation of microglia demonstrated that activating HM3D improved glymphatic function, while inhibiting HM4D unexpectedly increased microglial complexity. These findings highlight the dynamic influence of microglia on the glymphatic system. [ABSTRACT FROM AUTHOR]

Donor‐specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first‐line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre‐TPE serum correlated well with DSA value in post‐TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non‐responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non‐responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre‐TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT. [ABSTRACT FROM AUTHOR]

Background: Diabetic lower extremity ulcer, including diabetic foot ulcer (DFU) and leg ulcer, is one of the refractory complications of diabetes, the treatment of which is challenging, expensive, and lengthy. Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor (rhGM-CSF) is an immunomodulatory cytokine that has been mainly applied in the treatment of hematological diseases. Clinical evidence regarding GM-CSF in the treatment of diabetic lower extremity ulcers is limited. This study is the first case series that investigates the repurpose effects of rhGM-CSF on diabetic ulcer healing in real clinical practice. Methods: Nine patients diagnosed with diabetes and refractory lower extremity ulcer (ulcer duration ≥ 2 weeks) were included from September 2021 to February 2023 in the Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Patients with Wagner grade ≥ 4 and SINDAD ≥ 5 were excluded. The included subjects were treated with rhGM-CSF plus standard of care (SOC) including glycemic control, foot care education, debridement of necrotic tissues, topical wound dressings, offloading, and infection control when necessary. The observation endpoint was complete epithelialization. Their clinical manifestations, laboratory tests, and therapeutic effects were extracted and analyzed. Results: The case series included 9 cases aged from 29 to 80 years and all the patients were male. Seven of 9 patients presented neuropathic ulcer. Only one case showed non-infected ulcer from tissue samples and one case presented ankle brachial index (ABI) < 0.9. It was observed that the ulcer areas among these 9 patients gradually declined throughout the whole treatment period with the average healing velocity 0.32 ± 013 cm2/day and the mean time to complete healing 16.0 ± 3.7 days. The relative area (percentage of initial ulcer area) decreased to 66.7 ± 13.0% on average after the first treatment. Ulcers in all the 9 patients achieved complete epithelialization after 4– 8 times treatments. Conclusion: The case series suggests rhGM-CSF as a promising therapeutic strategy for the treatment of diabetic ulceration. More robust data from randomized controlled trials are required to further evaluate its clinical efficacy. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis. [ABSTRACT FROM AUTHOR]

Endothelial impairment and dysfunction are closely related to the pathogenesis of steroid-associated osteonecrosis of the femoral head (SONFH). Recent studies have showed that hypoxia inducible factor-1α (HIF-1α) plays a crucial role in endothelial homeostasis maintenance. Dimethyloxalylglycine (DMOG) could suppress HIF-1 degradation and result in nucleus stabilization by repressing prolyl hydroxylase domain (PHD) enzymatic activity. Our results showed that methylprednisolone (MPS) remarkably undermined biological function of endothelial progenitor cells (EPC) by inhibiting colony formation, migration, angiogenesis, and stimulating senescence of EPCs, while DMOG treatment alleviated these effects by promoting HIF-1α signaling pathway, as evidenced by senescence-associated β-galactosidase (SA-β-Gal) staining, colony-forming unit, matrigel tube formation, and transwell assays. The levels of proteins related to angiogenesis were determined by ELISA and Western blotting. In addition, active HIF-1α bolstered the targeting and homing of endogenous EPCs to the injured endothelium in the femoral head. Histopathologically, our in vivo study showed that DMOG not only alleviated glucocorticoid-induced osteonecrosis but also promoted angiogenesis and osteogenesis in the femoral head as detected by microcomputed tomography (Micro-CT) analysis and histological staining of OCN, TRAP, and Factor Ⅷ. However, all of these effects were impaired by an HIF-1α inhibitor. These findings demonstrate that targeting HIF-1α in EPCs may constitute a novel therapeutic approach for the treatment of SONFH. [ABSTRACT FROM AUTHOR]

LiMnxFe1−xPO4-C cathode materials for lithium ion batteries were synthesized via solid-state method using Li2CO3, MnCO3, NH4H2PO4, FePO4 and sucrose as starting raw materials, followed by high-temperature reduction-annealing. A series of calcination experiments at different temperatures reveal that Mn2+-containing materials exhibit a lower temperature for olivine phase formation, for example LiMn0.5Fe0.5PO4 olivine phase forms at 275 °C, while manganese-free crystalline LiFePO4 generally forms at the required temperature of 350 °C. Increasing Mn2+ content is found to enhance crystallization degree of LiMnxFe1−xPO4 material prepared at lower calcination temperatures. X-ray photoelectron spectroscopy (XPS) results confirm that Mn valence state (+2) remains unchanged up to ~250 °C when calcined in ambient atmosphere. The above-mentioned beneficial effect of manganese on phase formation and crystallization of olivine can be well attributed to the stable nature of Mn2+ and its strong propensity to form olivine phases. [ABSTRACT FROM AUTHOR]

This article, titled "[Retracted] Effect of metformin on cell proliferation, apoptosis, migration and invasion in A172 glioma cells and its mechanisms," was published in Molecular Medicine Reports in 2019. However, it has since been retracted by the journal due to concerns about the authenticity of the data presented. A concerned reader pointed out that the data in Figures 2 and 6 were similar to data from other articles by different authors. The authors were asked for an explanation but did not respond. The journal apologizes for any inconvenience caused. [Extracted from the article]

Background: Histone deacetylase 9 (HDAC9) is a member of the HDAC gene family that plays essential roles in the organization of transcriptional regulation by catalyzing deacetylation of histone proteins. However, the effects of HDAC9 on osteonecrosis of femoral head (ONFH) have not been investigated. The present study aimed to reveal whether histone deacetylase 9 (HDAC9) regulated osteogenic differentiation. Methods: A lentiviral knockdown HDAC9 model was established in hBMSCs. Osteoblast-specific gene expression, such as Runx2, OCN was examined by qRT-PCR and Western blot, respectively. Though transcriptome sequencing and enrichment analysis, related signal pathways caused by down-regulation of HDAC9 were screened. The effect of HDAC9 on MAPK signaling pathway was determined by Western blot. Eventually, tert-Butylhydroquinone (tBHQ) was used to examine the effect of MAPK activation on osteogenesis in HDAC9 knockdown hBMSCs. Results: A lentiviral knockdown HDAC9 model was successfully established in hBMSCs. HDAC9 knockdown significantly inhibited osteoblast-specific gene expression, such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and mineral deposition in vitro. Moreover, a total of 950 DEGs were identified in HDAC9-knockdown hBMSCs. We discovered that the MAPK signaling pathway might be related to this process by pathway enrichment analysis. HDAC9 knockdown significantly reduced the expression level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). Finally, the decreased osteogenesis due to HDAC9 knockdown was partly rescued by a MAPK signaling pathway activator. Conclusion: Taken together, these results suggest that HDAC9 knockdown inhibits osteogenic differentiation of hBMSCs, partially through the MAPK signaling pathway. HDAC9 may serve as a potential target for the treatment of ONFH. [ABSTRACT FROM AUTHOR]

Background: There is controversy over whether use of new oral anticoagulants (NOACs) associates with increased hemorrhage risk compared with non-NOAC. Meanwhile, determining which NOAC to use remains unclear. We aimed to summarize the evidence about NOACs in venous thromboembolism (VTE) prevention for patients with total hip and knee arthroplasty (THA and TKA). Methods: We searched RCTs assessing NOACs for VTE prophylaxis in adults undergoing THA and TKA in Medline, Embase, and Cochrane up to May 2021. Primary outcomes were VTE [included deep vein thrombosis (DVT) and pulmonary embolism (PE)], major VTE, and major bleeding. The rank probabilities of each treatment were summarized by the surface under the cumulative ranking curve area (SUCRA). Results: 25 RCTs with 42,994 patients were included. Compared with non-NOAC, NOACs were associated with a decreased risk of VTE (RR 0.68; 95% CI 0.55–0.84) and major VTE (RR = 0.52; 95% CI 0.35–0.76). Additionally, rivaroxaban, apixaban, and edoxaban but not dabigatran and betrixaban, did confer a higher efficacy compared with non-NOAC. None of the individual NOACs increased the risk of bleeding, while apixaban and betrixaban were even associated with a decreased risk of bleeding. In the comparison of different NOACs, rivaroxaban was associated with the greatest benefits in VTE (SUCRA = 79.6), DVT (SUCRA = 88.8), and major VTE (SUCRA = 89.9) prevention. Furthermore, subgroup analysis confirmed that NOACs associated with a higher efficacy tendency in patients with follow-up duration <60 days than follow-up duration ≥60 days. Conclusion: Evidence suggests that NOACs exert more benefits on VTE prophylaxis, and none of the individual NOACs increased hemorrhage compared with non-NOAC. Among various NOACs, rivaroxaban is recommended in patients with lower bleeding risk, and apixaban is recommended in patients with higher bleeding risk. Systematic Review Registration : [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021266890]. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNA PANDAR is an emerging non-coding RNA mapping to 6p21.2. It underlies metastatic progression and chromosomal instability in a variety of cancers. Despite the fact that recent studies have revealed that lncRNA PANDAR may be a potential prognostic biomarker for patients with cancer, there has still been controversy on the prognostic value of PANDAR. Methods: Databases of PubMed, Embase, SinoMed, and Web of Science were carefully searched and the literature which investigated the prognostic value of PANDAR expression among human cancers was collected for further analysis. Odds ratios (ORs) or hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled to estimate the relation between PANDAR expression and survival or clinicopathological characteristics of cancer patients. Results: There were 13 eligible studies in total, with 1,465 patients enlisted in this meta-analysis. All the eligible studies complied with the case-control study. The outcome showed that the elevated expression level of PANDAR was significantly related to poor overall survival (OS) (pooled HR 1.72, 95%CI 1.14–2.60). However, high or low expression of PANDAR did not differ in the prediction of event-free survival (EFS). Moreover, we discovered that high PANDAR expression was closely related to decreased OS in colorectal cancer (pooled HR 3.43, 95%CI 2.06–5.72) and reduced expression level of PANDAR was markedly related to poor OS (pooled HR 0.65, 95%CI 0.45–0.88) in non-small cell lung cancer. However, the expression level of PANDAR had no significant association with OS in renal cell carcinoma (pooled HR 1.19, 95%CI 0.56–2.50). Moreover, after analysis, we discovered that the high expression level of PANDAR was associated closely with the depth of invasion (pooled OR 3.95, 95%CI 2.36–6.63), lymph node metastasis (pooled OR 1.92, 95%CI 0.93–3.98), tumor stage (pooled OR 2.05, 95%CI 0.99–4.27), and distant metastasis (pooled OR 2.87, 95%CI 1.60–5.16). Conclusions: Our study revealed that increased PANDAR expression may serve as an adverse prognostic biomarker for cancer patients, thus helping the clinical decision-making process. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to determine the effects of metformin on the inhibition of proliferation, apoptosis, invasion and migration of A172 human glioma cells in vitro and determine the underlying mechanism. The effects of metformin at different concentrations (0, 0.1, 1 and 10 mmol/l) on the inhibition of A172 cell proliferation were detected using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was detected by flow cytometry. Caspase-3 activity was analyzed by spectrophotometry. The invasion and migration of cells were detected by Transwell assays. The levels of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), AMP-activated protein kinase (AMPK), phosphorylated-(p)AMPK and mechanistic target of rapamycin (mTOR) protein expression were detected by western blot analysis, and changes in the malondialdehyde (MDA) content and activity of superoxide dismutase (SOD) were determined. Compared with the control group, metformin significantly increased the inhibition of proliferation and apoptosis, and significantly reduced the invasion and migration of A172 cells in dose- and time-dependent manners (P<0.05). In addition, compared with the control group, metformin significantly enhanced the activity of caspase-3, increased the expression of AMPK/pAMPK/Bax proteins and reduced the expression of mTOR/Bcl-2 proteins (P<0.05). Metformin increased the MDA content and reduced the activity of SOD in a dose-dependent manner (P<0.05). Metformin may inhibit glioma cell proliferation, migration and invasion, and promote its apoptosis; the effects may be associated with the AMPK/mTOR signaling pathway and oxidative stress. [ABSTRACT FROM AUTHOR]

Abstract: Dissolved organic matters (DOM) are critical in the formation of the mutagenic disinfection byproducts (DBPs). In this study, five DOM fractions were isolated and investigated from a contaminated river and a clean reservoir source waters using resin adsorption. The DOM fractions were characterized with excitation–emission matrix, and several typical DBPs formation potentials and the mutagenicity of each DOM fraction were measured. Among these fractions, hydrophobic neutrals (HON), hydrophilic acids (HIA) and hydrophilic bases (HIB) generated the highest carbon-containing DBPs in the river source water, as did HIB and hydrophobic bases (HOB) in reservoir water. Hydrophobic acids (HOA), HON, and HIA were the three most important fractions forming nitrogen-containing DBPs. Following chlorination, the mutagenicity of HON, HIA, HOA and HIB was 1503, 626, 422 and 116ng 4-NQO/mg DOC in river water, respectively. Only HIA and HOA were mutagenic with 85 and 10ng 4-NQO/mg DOC in reservoir water, respectively. The soluble microbial products like substances and aromatic proteins contributed significantly to the mutagenicity of river water; whereas the humic acid-like and fulvic acid-like substances were the primary contributors to the mutagenicity of reservoir water. [Copyright &y& Elsevier]

A lobule-mimetic cell-patterning technique for on-chip reconstruction of centimetre-scale liver tissue of heterogeneous hepatic and endothelial cells via an enhanced field-induced dielectrophoresis (DEP) trap is demonstrated and reported. By mimicking the basic morphology of liver tissue, the classic hepatic lobule, the lobule-mimetic-stellate-electrodes array was designed for cell patterning. Through DEP manipulation, well-defined and enhanced spatial electric field gradients were created for in-parallel manipulation of massive individual cells. With this liver-cell patterning labchip design, the original randomly distributed hepatic and endothelial cells inside the microfluidic chamber can be manipulated separately and aligned into the desired pattern that mimicks the morphology of liver lobule tissue. Experimental results showed that both hepatic and endothelial cells were orderly guided, snared, and aligned along the field-induced orientation to form the lobule-mimetic pattern. About 95% cell viability of hepatic and endothelial cells was also observed after cell-patterning demonstration via a fluorescent assay technique. The liver function of CYP450-1A1 enzyme activity showed an 80% enhancement for our engineered liver tissue (HepG2+HUVECs) compared to the non-patterned pure HepG2 for two-day culturing. [ABSTRACT FROM AUTHOR]

In this paper, we employ the first-principle total energy method to investigate the effect of P impurity on mechanical properties of NiAl grain boundary (GB). According to “energy”, the segregation of P atom in NiAlΣ5 GB reduces the cleavage energy and embrittlement potential, demonstrating that P impurity embrittles NiAlΣ5 GB. The first-principle computational tensile test is conducted to determine the theoretical tensile strength of NiAlΣ5 GB. It is demonstrated that the maximum ideal tensile strength of NiAlΣ5 GB with P atom segregation is 144.5 GPa, which is lower than that of the pure NiAlΣ5 GB (164.7 GPa). It is indicated that the segregation of P weakens the theoretical strength of NiAlΣ5 GB. The analysis of atomic configuration shows that the GB fracture is caused by the interfacial bond breaking. Moreover, P is identified to weaken the interactions between Al–Al bonds and enhance Ni–Ni bonds. [ABSTRACT FROM AUTHOR]

First-principles calculations based on the density functional theory (DFT) and ultra-soft pseudopotential are employed to study the atomic configuration and charge density of impurity P in NiAl Σ5 grain boundary (GB). The negative segregation energy of a P atom proves that a P atom can easily segregate in the NiAl GB. The atomic configuration and formation energy of the P atom in the NiAl GB demonstrate that the P atom tends to occupy an interstitial site or substitute a Al atom depending on the Ni/Al atoms ratio. The P atom is preferable to staying in the Ni-rich environment in the NiAl GB forming P–Ni bonds. Both of the charge density and the deformation charge imply that a P atom is more likely to bond with Ni atoms rather than with Al atoms. The density of states further exhibits the interactions between P atom and Ni atom, and the orbital electrons of P, Ni and Al atoms all contribute to P–Ni bonds in the NiAl GB. It is worth noting that the P–Ni covalent bonds might embrittle the NiAl GB and weakens the plasticity of the NiAl intermetallics. [ABSTRACT FROM AUTHOR]

The composition and microbial community structure of the drinking water system biofilms were investigated using microstructure analysis and 454 pyrosequencing technique in Xiamen city, southeast of China. SEM (scanning electron microscope) results showed different features of biofilm morphology in different fields of PVC pipe. Extracellular matrix material and sparse populations of bacteria (mainly rod-shaped and coccoid) were observed. CLSM (confocal laser scanning microscope) revealed different distributions of attached cells, extracellular proteins, α-polysaccharides, and β-polysaccharides. The biofilms had complex bacterial compositions. Differences in bacteria diversity and composition from different tap materials and ages were observed. Proteobacteria was the common and predominant group in all biofilms samples. Some potential pathogens (Legionellales, Enterobacteriales, Chromatiales, and Pseudomonadales) and corrosive microorganisms were also found in the biofilms. This study provides the information of characterization and visualization of the drinking water biofilms matrix, as well as the microbial community structure and opportunistic pathogens occurrence. [ABSTRACT FROM AUTHOR]

Presents a study which examined factors affecting work and welfare program participation among poor single mothers. Features of the Personal Responsibility and Work Opportunity Reconciliation Act; Description of data collected from the 1992-1994 National Survey of Families and Households; Bivariate probit analysis; Results.

Dissolved organic nitrogen (DON) can act as precursor of nitrogenous disinfection by-products formed during chlorination disinfection. The performances of biological fluidized bed (continuous stirred tank reactor, CSTR) and bio-ceramic filters (plug flow reactor, PFR) were compared in this study to investigate the influence of mixing regime on DON formation in drinking water treatment. In the shared influent, DON ranged from 0.71 mg L −1 to 1.20 mg L −1 . The two biological fluidized bed reactors, named BFB1 (mechanical stirring) and BFB2 (air agitation), contained 0.12 and 0.19 mg L −1 DON in their effluents, respectively. Meanwhile, the bio-ceramic reactors, labeled as BCF1 (no aeration) and BCF2 (with aeration), had 1.02 and 0.81 mg L −1 DON in their effluents, respectively. Comparative results showed that the CSTR mixing regime significantly reduced DON formation. This particular reduction was further investigated in this study. The viable/total microbial biomass was determined with propidium monoazide quantitative polymerase chain reaction (PMA-qPCR) and qPCR, respectively. The results of the investigation demonstrated that the microbes in BFB2 had higher viability than those in BCF2. The viable bacteria decreased more sharply than the total bacteria along the media depth in BCF2, and DON in BCF2 accumulated in the deeper media. These phenomena suggested that mixing regime determined DON formation by influencing the distribution of viable, total biomass, and ratio of viable biomass to total biomass. [ABSTRACT FROM AUTHOR]

We have studied the phase behaviors of sphere-forming triblock copolymers in confined spaces using the mean-field dynamic density functional theory. The focus is on the morphologies induced by cylindrical nanopores. The effects of the pore diameter and the surface field strength on the phase behaviors are investigated systematically. Typical structures different from the bulk morphologies are observed, which are consistent with available experiments. A series of novel morphologies are predicted in our simulation. Furthermore, the shape effect of the pore cross section on the helical structures is studied. The results of our simulation should provide a guide for designing polymeric nanomaterials confined in cylindrical nanochannels. [ABSTRACT FROM AUTHOR]

• Morin exerts anti-inflammation in septic mice. • Morin downregulates tau hyperphosphorylation and Aβ deposition in septic mice. • Morin protects synapse integrity in CLP septic mice. Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments in the rest life of septic survivors. The potential pathological changes of SAE are complicated and have not been fully understood. Morin, a flavone compound exhibiting neuroprotective activity and anti-inflammation effect, was employed to treat with CLP-induced septic mice in our study. The data from a novel object recognition test and tail suspension test indicated that morin treatment reversed cognitive dysfunction and relieved depressive-like behaviors in septic mice. Morin down-regulated the expressions of IL-6, MCP-1, TNF-α and IL-10 in serum and diminished microglia activation in septic mice. Additionally, Western blot results showed that morin reduced the phosphokinase GSK3β activity and elevated the phosphatase PP2A activity, which led to lower tau phosphorylation. Morin reduced Aβ deposition and protected the synapse integrity, which might be the possible mechanism of protecting cognitive functions in septic mice. In conclusion, we identified that morin exerted anti-inflammation and anti-neurodegeneration effects in septic mice, and prevented further cognitive impairments. [ABSTRACT FROM AUTHOR]

Cytochrome c-1 (CYC1) is an important subunit of mitochondrial complex III. However, its role in tumor progression is unclear. We found that CYC1 was upregulated in breast tumor tissues, especially in tissues with lymph node metastasis. And higher expression of CYC1 correlates with poor prognosis in breast cancer patients using online databases and tools. Then we confirmed that CYC1 contributed to metastasis and proliferation in two highly metastatic human breast cancer cell lines. Digging into the biological function of CYC1, we found the activity of mitochondrial complex III decreased due to silencing CYC1. Then the ratio of AMP to ATP increased and AMPK was activated. Analyzing units of other mitochondrial complexes, we did not find knockdown of CYC1 expression reduced expression of any other unit of OXPHOS. We concluded that CYC1 promoted tumor metastasis via suppressing activation of AMPK and contributed to tumor growth via facilitating production of ATP. Our results indicated that CYC1 plays crucial roles in breast cancer progression and might be a predictive factor assisting future patient diagnosis. [ABSTRACT FROM AUTHOR]

In the weak segregation limit, the structure evolution of the hexagonal cylindrical phase of diblock copolymers in films was investigated. Employing the Landau-Brazovskii mean field theory, we obtained three amplitude parameters as functions of temperature, surface field strength and film thickness. By controlling confinement size and surface field strength, lamellae and undulated lamellae appear in the cylindrical bulk phase of diblock copolymers. "Phase diagrams" of confinement-induced structures are constructed at different surface field strengths. The obtained theoretical results are in agreement with relevant theoretical and experimental results. [ABSTRACT FROM AUTHOR]

Objective To study the expression and switching of Th1/Th2 cytokines gene in human gliomas and its effects on occurring and developing of human gliomas. Methods Interleukin(IL)-2 and interferon-γ represent Th1 type cytokines. IL-4, IL-6, IL-10, and IL-13 represent Th2 type cytokines. The gene expressions of Th1/Th2 cytokines in human glioma cells, glioma infiltrating lymphocytes, and glioma cell lines were detected by reverse transcription p01ymerase chain reaction (RT-PCR). The biological activity of cytokines in the supernatant of glioma cell lines was assayed by enzyme-linked immunosorbent assay (ELISA) method. Results The total positive rates of Th1 and Th2 type cytokines gene in human glioma cells were 14.77% and. 75%. The total positive rates of Th1 and Th2 type eytokines gene in glioma infiltrating lymphocytes were 22.73% and 68.17%. There was obviously predominant expression of Th2 type cytokines in human glioma tissues, glioma infiltrating lymphocytes, and glioma cell lines. There was no unbalanced expression of Th1/Th2 cytokines in normal brain tissues. Conclusion There is a predominant expression of Th2 type cytokines in human glioma cells. The switching of Th1/Th2 cytokines gene may play an important role in the occurring and developing of human gliomas. [ABSTRACT FROM AUTHOR]

Melanoma is a highly invasive malignant tumor originating from melanocytes, with increasing incidence in recent years. Ferroptosis is an iron-dependent and non-apoptotic form of programmed cell death characterized by the accumulation of lipid peroxides and reactive oxygen species. Morphologically, ferroptosis exhibits the alteration in cells, such as reduced mitochondrial volume, increased density of bilayer membrane, and a decrease or disappearance of mitochondrial cristae. Ferroptosis has shown tremendous potential and applicability in regulating the development of melanoma. As melanoma progresses, certain biomarkers associated with ferroptosis display characteristic patterns of expression. These changes not only reveal the sensitivity of tumor cells to ferroptosis but also provide potential targets for diagnosis and treatment. Besides, inducing ferroptosis has been well-documented to inhibit the growth of melanoma and enhance the efficacy of tumor immunotherapy. Hence, this review emphasizes the roles and regulatory mechanisms of ferroptosis in melanoma development, the involved immune regulation, as well as the potential for diagnosis and treatment of melanoma. The continuous explorations will endow novel strategies for developing ferroptosis-based therapies for melanoma., Competing Interests: Declaration of competing interest All the authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Traditional Chinese medicine (TCM) offers the advantage of effectively relieving rheumatoid arthritis (RA) with minimal side effects. The Juanbi recipe is a commonly utilized TCM treatment for RA, yet its pharmacological mechanism remains unclear. Network pharmacology serves as an effective tool for identifying pharmaceutical ingredients and potential therapeutic targets of TCM, thereby uncovering its mechanisms. This study aimed to identify the core target genes and explore the mechanisms underlying the treatment of RA with the Juanbi recipe., Methods: This study adopted the method of network pharmacology to filter key gene targets of Juanbi recipe in RA treatment. Single-cell ribonucleic acid (RNA) sequencing data was used to screen the key genes to form the core genes of Juanbi recipe in RA treatment. The molecular docking technique was used to verify the core target genes and explore the mechanisms of Juanbi recipe in RA treatment. The RA model of mice was induced by the collagen-induced arthritis and the effect of Juanbi recipe was evaluated by intragastric administrating of extraction of Juanbi recipe. Enzyme linked immunosorbent assay was used to analysis serum inflammatory factors. Hematoxylin and eosin staining was used to evaluate inflammation and immunohistochemical (IHC) staining was used to evaluate core target genes and pathways in synovium of ankle., Results: This study screened out 281 active molecules in Juanbi recipe, found 105 key target genes of Juanbi recipe in RA treatment, and drew an "ingredient - molecule - gene" diagram. Juanbi recipe reduced the levels of serum interleukin (IL)-1 and IL-6, the inflammatory infiltration in synovium, demonstration that Juanbi recipe reduced both systemic and synovial inflammatory response. Single cell RNA sequencing data were used to select six core target genes and six core active molecules of Juanbi recipe in RA treatment. The pathways of Juanbi recipe in RA treatment involved in activator protein-1 ( AP-1 ) and nuclear factor kappa B ( NF-κB ) pathway. Results of western blot and IHC staining showed that Juanbi recipe decreased the expressions of c-jun and p65 , which demonstrated that Juanbi recipe inhibited the expression of AP-1 and NF-κB pathway in RA., Conclusions: The core active molecules of Juanbi recipe could inhibit key factors of AP-1 and NF-κB pathway to inhibit the inflammation, which played a protective role in RA., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoj.amegroups.com/article/view/10.21037/aoj-23-72/coif). The authors have no conflicts of interest to declare., (2024 Annals of Joint. All rights reserved.)