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Background and Aims: Previous studies have demonstrated that peptidylarginine deiminase 4 (PAD4) functions as a suppressor, promoter, or both in cancer pathogenesis and therapeutic outcomes. Although PAD4 expression has been proposed to be one of the molecular features of gastric cancer (GC), the biological basis of PAD4 in GC progression and chemotherapy has not been formally established. Methods: Cell type-preferential expression of PAD4 was analyzed in both preclinical and clinical models. The colocalization of PAD4 expression and tumor-infiltrating neutrophils in GC patients was evaluated by immunofluorescence assay. The effects of forced expression of PAD4 on GC cell proliferation were evaluated both in vitro and in vivo. The effects of forced expression of PAD4 on the cytotoxicity of 5-fluorouracil and oxaliplatin were performed by EdU, Annexin V/PI, and comet assays. Co-immunoprecipitation assay was used to investigate the endogenous and exogenous interaction between PAD4 and p53. To investigate whether p53 participated in the chemopotentiating effects of PAD4, small interfering RNA (siRNA)-mediated knockdown of p53 was conducted in PAD4-overexpressing GC cells. Results: Contrary to the previous report, we initially observed that PAD4 was underexpressed in GC patients and presented as a favorable prognostic factor across the TCGA cohort. Interestingly, the normal gastric epithelial cell line GES-1 exhibited low-level expression of PAD4. In comparison, PAD4 was not detected in GC cell lines, including AGS, HGC-27, and MKN-45. Using an orthotopic mouse model of GC, we found that PAD4 was surprisingly abundant in HGC-27 cell line-derived xenografts. Immunofluorescence staining for PAD4 and neutrophil elastase indicated that PAD4 was mainly expressed in neutrophils but not in GC cells. PAD4 expression was upregulated in all-trans retinoic acid-induced neutrophil-like dHL-60 cells, which were used as a positive control for PAD4 expression. Surprisingly, the enforced expression of PAD4 suppressed the proliferation of GC cells in vitro and in vivo. In addition, cells harboring high PAD4 expression were more susceptible to G1/S boundary arrest, apoptotic death, and DNA damage by regulating p53 target proteins. Mechanistically, PAD4 might affect p53 function through physical interaction with p53, and the chemopotentiating effects of PAD4 could be compromised by p53 knockdown. Conclusions: PAD4 appeared to be constitutively expressed in tumor-infiltrating neutrophils but not in GC cells. Our findings highlight unique roles of PAD4, in which origin-dependent PAD4 might work complementarily on the progression and treatment vulnerability of GC. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. This study aimed to identify novel methylation-regulated biomarkers in NEC intestinal tissue through multiomics analysis. We analyzed DNA methylation and transcriptome datasets from ileum and colon tissues of patients with NEC. We identify methylation-related differential genes (MrDEGs) based on the rule that the degree of methylation in the promoter region is inversely proportional to RNA transcription. These MrDEGs included ADAP1, GUCA2A, BCL2L14, FUT3, MISP, USH1C, ITGA3, UNC93A and IL22RA1. Single-cell data revealed that MrDEGs were mainly located in the intestinal epithelial part of intestinal tissue. These MrDEGs were verified through Target gene bisulfite sequencing and RT-qPCR. We successfully identified and verified the ADAP1, GUCA2A, IL22RA1 and MISP, primarily expressed in intestinal epithelial villus cells through single-cell data. Through single-gene gene set enrichment analysis, we found that these genes participate mainly in the pathological process of T-cell differentiation and the suppression of intestinal inflammation in NEC. This study enhances our understanding of the pathogenesis of NEC and may promote the development of new precision medicine methods for NEC prediction and diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The mortality rate for liver cancer is extremely high but clinical treatments have not made much progress, so it is necessary to develop anticancer agents with lower toxicities and more effective liver-targeting drug delivery systems (LTDDSs). At present, LTDDSs mediated by the asialoglycoprotein receptor (ASGPR) show excellent effects at improving the liver-targeting and antitumor effects of drugs. However, the galactosyl ligands are typically prepared by chemical synthesis and have some shortcomings. The present work endeavors to explore the influences of plant galactolipids as natural galactosyl ligands for LTDDSs. Methods: Plant galactolipids were extracted from oat bran, and their characteristics were tested. Then, oat-galactolipid-modified curcumin-loaded liver-targeting vesicles (GCLTVs) and curcumin-loaded vesicles were prepared, which were used in a comparative study of the liver-targeting and liver anticancer effects in vitro and in vivo. Result: The experimental results show that the oat galactolipids and GCLTVs were prepared successfully. The hydrophilic–lipophilic balance, acid, ester, and saponification values of the oat galactolipids were 14.89, 47.22, 237.09, and 284.30, respectively. The morphology of the GCLTV was spherical, with an average particle size of 64.47 nm and average potential of −19.73 mV. The optimal proportion of galactolipids in the GCLTVs was selected as 30%. Compared with the curcumin-loaded vesicles, GCLTV uptakes were significantly higher at 1, 2, and 4 h; further, the galactolipid modification significantly improved the liver-targeting capability of the GCLTVs in vivo. The inhibitory effects of the GCLTVs on the proliferation of HepG2 cells were significantly higher than those of the curcumin-loaded vesicles after 24 and 48 h. The antitumor effects of GCLTVs in vivo based on H&E staining results on liver tissues were stronger than those of the curcumin-loaded vesicles, and the expressions of P53, Bcl-2, and Bax were correspondingly more significant. Conclusion: The GCLTVs show excellent liver-targeting capabilities in vitro and in vivo. Compared to the curcumin-loaded vesicles, the cytotoxicity and anticancer effects of the GCLTVs were significantly higher in vitro and in vivo. Thus, oat galactolipids could be used as a type of natural ligand of the ASGPR and a membrane material that would be beneficial for liver-targeting nanopreparations. [ABSTRACT FROM AUTHOR]

Here, we first study how the structure–activity connection of rhombohedral phase BHxFO (x = 0, 0.01, 0.03, and 0.05) nanoparticles is affected by low concentration Ho ion doping. To help to promote magnetic release in BHxFO, the results show that adding Ho causes internal structural distortion in a way that changes the length and angle of the Fe–O links and also makes the particles smaller. Adding magnetically active Ho3+ ions instead of Bi ions also improves the ferromagnetic coupling between Ho3+ and Fe3+ ions. This changes the behavior from antiferromagnetic to ferromagnetic. Furthermore, timely Ho doping is found to improve the photoelectric performance of BHxFO and efficiently lower its band gap. A broad plan for the doping modification and application promotion of BFO is presented in this paper. [ABSTRACT FROM AUTHOR]

Global concern about Alzheimer's disease (AD) is justified by its increasingly younger onset and significant economic burden. AD leads to neurodegeneration and cognitive decline, ultimately resulting in loss of autonomy. Against this background, the field of biomedical research has seen a surge of interest in the potential of carbon-based nanomaterials, mainly due to their ease of degradation and high biocompatibility. Carbon nanotubes (CNTs) have been extensively studied in AD, including developing biosensors, drug delivery systems, and molecular imaging. Here, we introduced the biosafety and biodegradability of CNTs, with a particular focus on their uptake and degradation in brain tissue. The utilization of CNT in the context of AD therapy can facilitate the advancement of control approaches regimens and ensure the clinical safety of patients. This is achieved through the employment of these nanotubes as carriers for the delivery of drugs to the central nervous system (CNS), the detection of neurotransmitters such as acetylcholine (Ach) and monoamines, the development of biosensors and molecular imaging materials, the inhibition of Aβ formation and the detection of phosphorylated tau proteins, the promotion of CNS regeneration, and the modulation of ion-associated AD. [ABSTRACT FROM AUTHOR]

Conductive filter membranes have shown great potential in alleviating membrane fouling. In this study, polypyrrole (PPy) was used as the conductive material and sodium anthraquinone-2-sulfonate (AQS) was used as the dopant to perform surface modification on the PVDF membrane. After modification, the contact angle of the membrane decreased from 79.40° to 48.57°, and the electrical conductivity of membrane increased from zero to 1.60 S/cm. The good hydrophilicity and electrical conductivity of PPy-AQS/PVDF endowed it with superior antifouling capabilities, reducing the static protein (BSA) adsorption from 0.147 mg/cm2 to 0.097 mg/cm2. Under the action of an electric field of −0.1 V, the flux decay rate of PPy-AQS/PVDF decreased, and the flux recovery rate improved. [ABSTRACT FROM AUTHOR]

Bidirectional energy storage inverters serve as crucial devices connecting distributed energy resources within microgrids to external large-scale power grids. Due to the disruptive impacts arising during the transition between grid-connected and islanded modes in bidirectional energy storage inverters, this paper proposes a smooth switching strategy based on droop control to mitigate such impacts. Firstly, this paper introduces the principle of droop control under inductive line impedance conditions, elaborating on the relevant components and the design rationale and parameter selection for the control components adopted in this study. During the transition from grid-connected to islanded mode, an improved Active Frequency Drift with Positive Feedback (AFDPF) method is introduced. Building upon the traditional AFDPF, this method optimizes the chopping coefficient by incorporating a positive feedback coefficient and a piecewise function, and proposes a tracking step size with the cube root of the frequency difference, thereby enhancing the efficiency of islanding detection while ensuring harmonic quality in the system. Conversely, during the transition from islanded to grid-connected mode, this paper proposes a composite pre-synchronization control strategy based on droop control, which enables precise tracking of the phase, amplitude, and frequency of the output voltage of the bidirectional energy storage inverter relative to the grid voltage. Finally, simulation models are established using MATLAB/Simulink(MathWorks, R2022b, U.S.), and an experimental platform with the TMS320F28378DPTPS controller built for verification. The results demonstrate that the proposed switching strategy exhibits excellent stability and achieves smooth transitions between grid-connected and islanded modes, outperforming traditional control strategies. [ABSTRACT FROM AUTHOR]

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Schizophrenia is a disastrous mental disorder. Identification of diagnostic biomarkers and therapeutic targets is of significant importance. In this study, five datasets of schizophrenia post-mortem prefrontal cortex samples were downloaded from the GEO database and then merged and de-batched for the analyses of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA). The WGCNA analysis showed the six schizophrenia-related modules containing 12,888 genes. The functional enrichment analyses indicated that the DEGs were highly involved in immune-related processes and functions. The immune cell infiltration analysis with the CIBERSORT algorithm revealed 12 types of immune cells that were significantly different between schizophrenia subjects and controls. Additionally, by intersecting DEGs, WGCNA module genes, and an immune gene set obtained from online databases, 151 schizophrenia-associated immune-related genes were obtained. Moreover, machine learning algorithms including LASSO and Random Forest were employed to further screen out 17 signature genes, including GRIN1, P2RX7, CYBB, PTPN4, UBR4, LTF, THBS1, PLXNB3, PLXNB1, PI15, RNF213, CXCL11, IL7, ARHGAP10, TTR, TYROBP, and EIF4A2. Then, SVM-RFE was added, and together with LASSO and Random Forest, a hub gene (EIF4A2) out of the 17 signature genes was revealed. Lastly, in a schizophrenia rat model, the EIF4A2 expression levels were reduced in the model rat brains in a brain-regional dependent manner, but can be reversed by risperidone. In conclusion, by using various bioinformatic and biological methods, this study found 17 immune-related signature genes and a hub gene of schizophrenia that might be potential diagnostic biomarkers and therapeutic targets of schizophrenia. [ABSTRACT FROM AUTHOR]

As a newly defined type of programmed cell death, ferroptosis is considered a potent weapon against tumors due to its distinct mechanism from other types of programmed cell death. Ferroptosis is triggered by the uncontrolled accumulation of hydroperoxyl polyunsaturated fatty acid-containing phospholipids, also called lipid peroxidation. The lipid peroxidation, generated through enzymatic and non-enzymatic mechanisms, drives changes in cell morphology and the destruction of membrane integrity. Here, we dissect the mechanisms of ferroptosis induced enzymatically or non-enzymatically, summarize the major metabolism pathways in modulating lipid peroxidation, and provide insights into the relationship between ferroptosis and tumor suppression. In this review, we discuss the recent advances of ferroptosis in tumor microenvironments and the prospect of potential therapeutic application. A review summarizes the recent advances in ferroptosis and tumor suppression, including the metabolic regulation of lipid peroxidation, the role of ferroptosis in tumor immunity response, and ferroptosis-based tumor therapeutics and clinical trials. [ABSTRACT FROM AUTHOR]

Objective: A robotic system was recently introduced to improve prosthetic alignment during total knee arthroplasty (TKA). The purpose of this multicenter, prospective, randomized controlled trial (RCT) was to determine whether robotic‐arm‐assisted TKA improves clinical and radiological outcomes when compared to conventional TKA. Methods: One hundred and thirty patients who underwent primary TKA were enrolled in this prospective, randomized controlled trial, which was conducted at three hospitals. Five patients were lost to follow‐up 6 weeks after surgery. Therefore, 125 participants (63 in the intervention group and 62 in the control group) remained in the final analysis. The primary outcome was the rate at which the mechanical axis of the femur deviated by less than 3° from the mechanical axis of the tibia. This was evaluated by full‐length weight‐bearing X‐rays of the lower limb 6 weeks postoperatively. Secondary outcomes included operation times, 6‐week postoperative functional outcomes evaluated by the American Knee Society score (KSS) and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), short form‐36 (SF‐36) health survey results, and the occurrence of adverse events (AEs) and serious adverse events (SAEs). Results: At 6 weeks postoperatively, we found that the rate of radiographic inliers was significantly higher in the intervention group (78.7% vs 51.6%; p = 0.00; 95% confidence interval, 10.9% to 43.2%). The operation was significantly longer in the intervention group than in the control group (119.5 vs 85.0 min; p = 0.00). There were no significant differences in the 6‐week postoperative functional outcomes, SF‐36, AEs, and SAEs between the two groups. There were no AEs or SAEs that were determined to be "positively related" to the robotic system. Conclusion: Robotic‐arm‐assisted TKA is safe and effective, as demonstrated in this trial. [ABSTRACT FROM AUTHOR]

Celastrus orbiculatus Thunb. is a vine used as a traditional Chinese medicinal herb. In this study, we focused on the anticancer cytotoxicity and underlying mechanism of previously unreported 3‐oxygen–substituted isoflavone analogue (3‐benzyloxychromone, 3‐Boc) from the herb. Initially, we established cell line–derived xenograft mouse model using H1299 non–small cell lung cancer (NSCLC) cells and found that the ethanol crude extracts of the stem part of C. orbiculatus (200 mg/kg) could substantially suppress the growth of xenograft tumors in athymic nu/nu mice. We compared 3‐Boc with three other flavonoid analogues isolated from the stem part of C. orbiculatus. Among these, 3‐Boc showed the most potent cytotoxicity against H1299 and H1975 NSCLC cells. Colony formation, EdU incorporation and Annexin V‐FITC/PI apoptosis assays demonstrated that 3‐Boc induced growth inhibition primarily by inhibiting DNA replication and inducing apoptotic death of NSCLC cells. Structure‐based target prediction and MD simulation suggested that 3‐Boc potentially suppressed the activity of glycogen synthase kinase‐3β (GSK‐3β) by interacting with the ATP–binding site. Western blot analysis indicated that 3‐Boc triggered the phosphorylation of Serine 21 of GSK‐3α or Serine 9 of GSK‐3β in a time‐ and dose‐dependent manner. To investigate the dependency of GSK‐3β, we established GSK‐3β knockout in H1299 cells. Depletion of GSK‐3β enhanced 3‐Boc–induced cytotoxicity compared with wild‐type counterparts through activated c‐Jun/ATF2 signaling pathway. Altogether, our study highlights the anticancer potential of C. orbiculatus and the discovery of novel 3‐oxygen–substituted chromone from the herb, which may have important implications for screening promising modulators of GSK‐3β and related signaling pathways in the treatment of cancer. Summary: A novel compound featured by 3‐Benzyloxychromone (3‐Boc), which was isolated from the stem of Celastrus orbiculatus Thunb, exhibited significant anticancer activity in NSCLC cells.3‐Boc was more likely to act as a potential ATP‐competitive inhibitor rather than an allosteric inhibitor of GSK‐3β.Depletion of GSK‐3β enhanced the sensitivity of NSCLC cells to 3‐Boc by activating the c‐Jun/ATF2 pathway. Significance Statement Natural products serve as good sources of lead molecules for anticancer drugs. We here characterized the anticancer effect of Celastrus orbiculatus Thunb. and reported a novel class of natural product featured by 3‐benzyloxychromone (3‐Boc). By targeting prediction and validation, we found that GSK‐3β was a potential target of 3‐Boc. Moreover, GSK‐3β ablation enhanced the sensitivity of NSCLC to 3‐Boc, which was dependent on the activation of the c‐Jun/ATF2 pathway. Our data further provided an experimental basis for the utilization and development of anticancer precursor from 3‐Boc found in the Celastrus species. [ABSTRACT FROM AUTHOR]

Liquid metal, as a novel material, has become ideal for the fabrication of flexible conductive fibers and has shown great potential in the field of biomedical sensing. This paper presents a comprehensive review of the unique properties of liquid metals such as gallium-based alloys, including their excellent electrical conductivity, mobility, and biocompatibility. These properties make liquid metals ideal for the fabrication of flexible and malleable biosensors. The article explores common preparation methods for liquid metal conductive fibers, such as internal liquid metal filling, surface printing with liquid metal, and liquid metal coating techniques, and their applications in health monitoring, neural interfaces, and wearable devices. By summarizing and analyzing the current research, this paper aims to reveal the current status and challenges of liquid metal conductive fibers in the field of biosensors and to look forward to their development in the future, which will provide valuable references and insights for researchers in the field of biomedical engineering. [ABSTRACT FROM AUTHOR]

Lactobacillus rhamnosus AFY02 (LR‐AFY02) is a newly discovered strain isolated and identified from naturally fermented yogurt in Xinjiang, China. This research aims to investigate the mechanism of action of LR‐AFY02 in mice with acute gouty arthritis. We examined the degree of foot swelling, pain threshold, blood biochemical indicators, histopathological changes, and mRNA expression. LR‐AFY02 can decrease the severity of mouse foot edema and raise the pain threshold. LR‐AFY02 can increase the enzyme activity of superoxide dismutase (SOD) and the level of glutathione (GSH) while lowering the enzyme activity of myeloperoxidase (MPO) and the level of malondialdehyde (MDA) in mice with acute arthritis. Interleukin‐6 (IL‐6), IL‐10, interleukin‐1 beta (IL‐1β), and tumor necrosis factor‐alpha (TNF‐α) levels in the blood of mice with acute arthritis are also decreased by LR‐AFY02. Histopathological findings demonstrated that LR‐AFY02 reduced tissue damage in the mouse foot and ankle joints. LR‐AFY02 may suppress the mRNA expression of extracellular signal‐regulated kinase 1/2 (ERK1/2), cyclooxygenase‐2 (COX‐2), prostaglandin E2 (PGE2), IL‐6, interferon gamma (IFN‐γ), and TNF‐α in the tissues of the ankle joints of mice with acute arthritis. Additionally, LR‐AFY02 has the ability to increase the expression of catalase (CAT), manganese superoxide dismutase (Mn‐SOD), and copper/zinc superoxide dismutase (Cu/Zn‐SOD). As a result, it is clear that L. rhamnosus AFY02 is more effective than glucosamine sulfate at preventing acute gouty arthritis. [ABSTRACT FROM AUTHOR]

Background. Gastric cancer (GC) is the most common malignant tumor and ranks third in the world. LncRNA H19 (H19), one of the members of lncRNA, is overexpressed in various tumors. However, many undetermined molecular mechanisms by which H19 promotes GC progression still need to be further investigated. Methodology. A series of experiments was used to confirm the undetermined molecular mechanism including wound healing and transwell assays. Key Results. In this study, a significant upregulation of H19 expression was detected in GC cells and tissues. The poor overall survival was observed in GC patient with high H19 expression. Overexpression of H19 promoted the migration of GC cells, while knockdown of H19 significantly inhibited cell migration. Moreover, miR‐148a‐3p had a certain negative correlation with H19. Luciferase reporter assay confirmed that H19 could directly bind to miR‐148a‐3p. As expected, miR‐148a mimics inhibited cell migration and invasion induced by H19 overexpression. The above findings proved that H19 functions as a miRNA sponge and verified that miR‐148a‐3p is the H19‐associated miRNA in GC. We also confirmed that SOX‐12 expression was upregulated in GC patient's samples. SOX‐12 expression was positively correlated with expression of H19 and was able to directly bind to miR‐148a‐3p. Importantly, in vitro wound healing assay showed that knockout of SOX‐12 could reverse the promoting effect of H19 overexpression on cell migration. Conclusion. In conclusion, H19 has certain application value in the diagnosis and prognosis of GC. Specifically, H19 accelerates GCs to migration and metastasis by miR‐138a‐3p/SOX‐12 axis. [ABSTRACT FROM AUTHOR]

Aqueous zinc‐ion batteries are anticipated to be the next generation of important energy storage devices to replace lithium‐ion batteries due to the ongoing use of lithium resources and the safety hazards associated with organic electrolytes in lithium‐ion batteries. Manganese‐based compounds, including MnOx materials, have prominent places among the many zinc‐ion battery cathode materials. Additionally, Cu doping can cause the creation of an oxygen vacancy, which increases the material's internal electric field and enhances cycle stability. MnOx also has great cyclic stability and promotes ion transport. At a current density of 0.2 A g−1, the Cu/MnOx nanocomposite obtained a high specific capacitance of 304.4 mAh g−1. In addition, Cu/MnOx nanocomposites showed A high specific capacity of 198.9 mAh g−1 after 1000 cycles at a current density of 0.5 A g−1. Therefore, Cu/MnOx nanocomposites are expected to be a strong contender for the next generation of zinc‐ion battery cathode materials in high energy density storage systems. [ABSTRACT FROM AUTHOR]

In different areas of the heart, action potential waveforms differ due to differences in the expressions of sodium, calcium, and potassium channels. One of the characteristics of myocardial infarction (MI) is an imbalance in oxygen supply and demand, leading to ion imbalance. After MI, the regulation and expression levels of K+, Ca2+, and Na+ ion channels in cardiomyocytes are altered, which affects the regularity of cardiac rhythm and leads to myocardial injury. Myocardial fibroblasts are the main effector cells in the process of MI repair. The ion channels of myocardial fibroblasts play an important role in the process of MI. At the same time, a large number of ion channels are expressed in immune cells, which play an important role by regulating the in- and outflow of ions to complete intracellular signal transduction. Ion channels are widely distributed in a variety of cells and are attractive targets for drug development. This article reviews the changes in different ion channels after MI and the therapeutic drugs for these channels. We analyze the complex molecular mechanisms behind myocardial ion channel regulation and the challenges in ion channel drug therapy. [ABSTRACT FROM AUTHOR]

Integrin β6 (ITGB6), a member of the integrin family of proteins, is only present in epithelial tissues and frequently associates with integrin subunit αv to form transmembrane heterodimers named integrin αvβ6. Importantly, ITGB6 determines αvβ6 expression and availability. In addition to being engaged in organ fibrosis, ITGB6 is also directly linked to the emergence of cancer, periodontitis, and several potential genetic diseases. Therefore, it is of great significance to study the molecular-biological mechanism of ITGB6, which could provide novel insights for future clinical diagnosis and therapy. This review introduces the structure, distribution, and biological function of ITGB6. This review also expounds on ITGB6-related diseases, detailing the known biological effects of ITGB6. [ABSTRACT FROM AUTHOR]

Type A acute aortic dissection (TA-AAD) patients are prone to life-threatening complications and death. This study aimed to analyze the association between eosinophil (EOS) recovery and clinical outcomes in TA-AAD. A total of 274 patients with TA-AAD were eligible for inclusion, and 54 patients died within 1 month. The patients with poor clinical outcomes showed significantly lower EOS count within 8 days after surgery. The time-dependent ROC analysis showed that EOS recovery days predicted 1-month death with an AUC of 0.886 and a cutoff of 6 days. EOS recovery within 6 days was associated with a lower incidence of postoperative infection, a poorer prognosis, and a lower risk of 1-month and 6-month mortality than those requiring more recovery days. Collectively, postoperative early recovery of EOS predicted lower mortality and better prognosis and may be applied as an effective, rapid, and simple tool for the risk stratification and prognostic prediction of patients with TA-AAD. Clinical trial registration number: NCT05409677. [ABSTRACT FROM AUTHOR]

Nano-engineering crystalline materials can be used to tailor their thermal properties. By adding new nanoscale phonon scattering centers and controlling their size, one can effectively decrease the phonon mean free path, hence the thermal conductivity of a fully crystalline material. In this Letter, we use the 3ω method in the temperature range of 100–300 K to experimentally report on the more than threefold reduction of the thermal conductivity of an epitaxially grown crystalline germanium thin film with embedded polydispersed crystalline Ge3Mn5 nano-inclusions with diameters ranging from 5 to 25 nm. A detailed analysis of the structure of the thin film coupled with Monte Carlo simulations of phonon transport highlights the role of the nano-inclusions volume fraction in the reduction of the phononic contribution to the thermal conductivity, in particular its temperature dependence, leading to a phonon mean free path that is set by geometrical constraints. [ABSTRACT FROM AUTHOR]

Objectives: Celastrus orbiculatus ethyl acetate extract (COE) is the main extract of the stem of the Chinese herbal C. orbiculatus, which has anti-tumor and anti-inflammatory biological effects. Our previous study showed that COE had a certain reversal effect on the precancerous lesions of gastric cancer (PLGC) in rats, but the exact mechanism of action remains elusive. We aimed to explore the therapeutic effects of COE on PLGC and the potential mechanisms. Methods: The PLGC rat model was successfully constructed by N-methyl-N´-nitro-N-nitrosoguanidine (MNNG) multifactorial induction method. Then, COE was prepared to treat the PLGC rat model. Hematoxylin & eosin staining was used to observe gastric mucosal lesions in rats, AB-PAS and HID-AB staining were used to observe intestinal metaplasia. PDCD4-ATG5 signaling pathway was detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR) in vivo, and autophagy level was detected by IHC, transmission electron microscopy, and RT-PCR in vivo. Besides, the PLGC (MC) cell model was successfully constructed by treating GES-1 cells with MNNG. Then, the morphology, proliferation, and apoptosis of MC cells, and the role of the PDCD4-ATG5 signaling pathway and autophagy in MC cells were evaluated by COE and after the overexpression of PDCD4 treatment. Key findings: COE significantly improved gastric mucosal injury and cellular heteromorphism and retarded the progression of PLGC in rats. Further studies indicated COE not only inhibited the level of autophagy but also interfered with the PDCD4-ATG5 signaling pathway in vivo. On the other hand, COE treatment could effectively reverse MC cell damage, inhibit MC cell proliferation, and promote MC cell apoptosis. Furthermore, COE also promoted PDCD4 and inhibited ATG5 expression in vitro, and the inhibitory effect of COE on ATG5-mediated autophagy was further enhanced after the overexpression of PDCD4. Conclusions: The study revealed that COE could regulate the PDCD4-ATG5 signaling pathway to inhibit autophagy in gastric epithelial cells, which contributes to reversing the progression of PLGC. [ABSTRACT FROM AUTHOR]

Ion channel drugs have been increasing used for chronic pain management with progress in the development of selective calcium channel modulators. Although ion channel drugs have been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat chronic pain. To standardize the clinical practice of ion channel drug for the treatment of chronic pain, the National Health Commission Capacity Building and Continuing Education Center for Pain Diagnosis and Treatment Special Ability Training Project established an expert group to form an expert consensus on the use of ion channel drugs for the treatment of chronic pain after repeated discussions on existing medical evidence combined with the well clinical experience of experts. The consensus provided information on the mechanism of action of ion channel drugs and their recommendations, caution use, contraindications, and precautions for their use in special populations to support doctors in their clinical decision-making. [ABSTRACT FROM AUTHOR]

The celebrated Blahut–Arimoto algorithm computes the capacity of a discrete memoryless point-to-point channel by alternately maximizing the objective function of a maximization problem. This algorithm has been applied to degraded broadcast channels, in which the supporting hyperplanes of the capacity region are again cast as maximization problems. In this work, we consider general broadcast channels and extend this algorithm to compute inner and outer bounds on the capacity regions. Our main contributions are as follows: first, we show that the optimization problems are max–min problems and that the exchange of minimum and maximum holds; second, we design Blahut–Arimoto algorithms for the maximization part and gradient descent algorithms for the minimization part; third, we provide convergence analysis for both parts. Numerical experiments validate the effectiveness of our algorithms. [ABSTRACT FROM AUTHOR]

In recent years, a number of initially approved magnetic iron oxide nanoparticle (IONP)-based nano-medicines have been withdrawn due to the obscure nano-bio effects. Therefore, there is an urgent need to study the cellular effects triggered by IONPs on cells. In this study, we investigate the time-course cellular effects on the response of RAW 264.7 cells caused by Si-IONPs via pharmacological and mass spectrometry-based proteomics techniques. Our results revealed that Si-IONPs were internalized by clathrin-mediated endocytosis within 1 hour, and gradually degraded in endolysosomes over time, which might influence autophagy, oxidative stress, innate immune response, and inflammatory response after 12 hours. Our research provides a necessary assessment of Si-IONPs for further clinical treatment. [ABSTRACT FROM AUTHOR]

Information about throughfall, stemflow, and canopy interception loss is essential for the water use efficiency of crops and the dynamic processes of water erosion. A two-year field experiment was conducted under natural rainfall conditions to observe the characteristics and factors that affect throughfall, stemflow, and canopy interception loss in corn (Zea mays L.) and soybean (Glycine max L.) fields in northeast China from 2019 to 2020. Nine measurement sites (A, B, C, D, E, F, G, H, and I) were distributed horizontally between two planting rows under the crop canopy. The mean value of the throughfall volume (TF) in measurement locations B, C, and G under the corn canopy and measurement locations B and C could represent the mean level of TF of corn and soybean fields, respectively. The volume of TF, stemflow (SF), and canopy interception loss (CI) of two growing seasons from 2019 to 2020 accounted for approximately 58.5%, 30.1%, and 11.4% of the gross rainfall (GR) of two growing seasons in corn fields, and 78.0%, 7.5%, and 14.5% of the GR in the soybean field, respectively. The TF and TFR of each rainfall event in the corn and soybean fields could be predicted by linear regression models with a normalized root mean square error (NRMSE) lower than 25.0%. These results and prediction models will be used in water management and soil erosion control in northeast China. [ABSTRACT FROM AUTHOR]

YEATS domain-containing protein GAS41 is a histone reader and oncogene. Here, through genome-wide CRISPR-Cas9 screenings, we identify GAS41 as a repressor of ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recognizing the H3K27-acetylation (H3K27-ac) marker, GAS41 is recruited to the SLC7A11 promoter, independent of NRF2 binding. By bridging the interaction between NRF2 and the H3K27-ac marker, GAS41 acts as an anchor for NRF2 on chromatin in a promoter-specific manner for transcriptional activation. Moreover, the GAS41-mediated effect on ferroptosis contributes to its oncogenic role in vivo. These data demonstrate that GAS41 is a target for modulating tumor growth through ferroptosis. Our study reveals a mechanism for GAS41-mediated regulation in transcription by anchoring NRF2 on chromatin, and provides a model in which the DNA binding activity on chromatin by transcriptional factors (NRF2) can be directly regulated by histone markers (H3K27-ac).GAS41 is recognized as a histone reader and oncogene, but the mechanism by which GAS41 contributes to tumorigenesis is not well understood. Here, the authors discover that GAS41 is a ferroptosis repressor that anchors NRF2 to chromatin, promoting tumor growth. [ABSTRACT FROM AUTHOR]

Background: Venovenous extracorporeal membrane oxygenation (VV ECMO) has been widely used for severe acute respiratory distress syndrome (ARDS) in recent years. However, the role of hemoadsorption in ARDS patients requiring VV ECMO is unclear. Methods: Therefore, we conducted a systematic review to describe the effect of hemoadsorption on outcomes of ARDS patients requiring VV ECMO and elucidate the risk factors for adverse outcomes. We conducted and reported a systematic literature review based on the principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The systematic review searched Embase, CINHAL, and Pubmed databases for studies on ARDS patients receiving hemoadsorption and VV ECMO. The demographic data, clinical data and biological data of the patients were collected. Results: We ultimately included a total of 8 articles including 189 patients. We characterized the population both clinically and biologically. Our review showed most studies described reductions in inflammatory markers and fluid resuscitation drug dosage in ARDS patients with Coronavirus disease 2019 (COVID-19) or sepsis after hemoadsorption. Conclusion: Because most of the studies have the characteristics of high heterogeneity, we could only draw very cautious conclusions that hemoadsorption therapy may enhance hemodynamic stability in ARDS patients with COVID-19 or sepsis receiving VV ECMO support. However, our results do not allow us to draw conclusions that hemoadsorption could reduce inflammation and mortality. Prospective randomized controlled studies with a larger sample size are needed in the future to verify the role of hemoadsorption in ARDS patients requiring VV ECMO. [ABSTRACT FROM AUTHOR]

Excellent morphology and low harmful defect states of the absorber layer are essential to fabricate the high‐performance Cu2ZnSn(S, Se)4 (CZTSSe) devices. Herein, the annealing time of precursor films in air is proved to have much impact on the quality of absorber layer and the performance of devices. Appropriately extending the air‐annealing time can promote the diffusion of Na into films and O absorption on the surface of precursor films, boost the growth of crystal grain, and lessen the harmful defect density and band‐tailing states of absorber. The appropriate extension of air‐annealing time also regulates the electrical properties of the absorber. The efficiency of CZTSSe devices is enhanced from 6.92% (1 min) to 10.1% (7 min), with the decreased VOC, Def. These enhanced properties demonstrate that regulating the air‐annealing time of precursor films can be a simple and direct way for improving the performance of CZTSSe devices. [ABSTRACT FROM AUTHOR]

Cancer is one of the most challenging diseases in the world. Recently, iron oxide nanoparticles (IONPs) are emerging materials with rapid development and high application value, and have shown great potential on tumor therapy due to their unique magnetic and biocompatible properties. However, some data hint us that IONPs were toxic to normal cells and vital organs. Thus, more data on biosafety evaluation is urgently needed. In this study, we compared the effects of silicon-coated IONPs (Si-IONPs) on two cell types: the tumor cells (Hela) and the normal cells (HEK293T, as 293 T for short), compared differences of protein composition, allocation and physical characteristics between these two cells. The major findings of our study pointed out that 293 T cells death occurred more significant than that of Hela cells after Si-IONPs treatment, and the rate and content of endocytosis of Si-IONPs in 293 T cells was more prominent than in Hela cells. Our results also showed Si-IONPs significant promoted the production of reactive oxygen species and disturbed pathways related to oxidative stress, iron homeostasis, apoptosis and ferroptosis in both two types of cells, however, Hela cells recovered from these disturbances more easily than 293 T. In conclusion, compared with Hela cells, IONPs are more likely to induce 293 T cells death and Hela cells have their own unique mechanisms to defense invaders, reminding scientists that future in vivo and in vitro studies of nanoparticles need to be cautious, and more safety data are needed for further clinical treatment. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are the primary source of tumor recurrence and chemoresistance, which complicates tumor treatment and has a significant impact on poor patient prognosis. Therefore, the discovery of inhibitors that specifically target CSCs is warranted. Previous research has established that the TGF-β/Smad signaling pathway is critical for the maintenance of CSCs phenotype, thus facilitating CSCs transformation. In this regard, Celastrus orbiculatus ethyl acetate extract (COE) was shown to exert anticancer properties; however, its therapeutic impact on gastric cancer stem cells (GCSCs) remains unknown. We here demonstrate that COE displayed a strong inhibitory effect on GCSCs growth and CSCs markers. Moreover, COE was shown to efficiently inhibit the development of tumor spheres and accelerate GCSCs apoptosis. Mechanistically, we established that COE could suppress the stemness phenotype of GCSCs by inhibiting the activity of the TGF-β/Smad signaling pathway. To summarize, our data indicate that COE suppresses the malignant biological phenotype of GCSCs via the TGF-β/Smad signaling pathway. These findings shed new light on the anticancer properties of COE and suggest new strategies for the development of efficient GCSCs therapeutics. [ABSTRACT FROM AUTHOR]

To establish and verify a model for labour dystocia occurring in the active phase, this study retrospectively analysed the clinical data of primiparas with singleton cephalic full-term foetuses, who had delivered after a trial of labour. The Chi-square test, t-test, Mann–Whitney U test and multivariate logistic regression analysis were used for statistical analysis. Based on the model a nomogram was established using the R programming language. Multivariate logistic regression analysis showed that the foetal abdominal circumference, premature rupture of membranes (PROM), prolonged latent phase, foetal station and foetal position at the early stage of the active phase were independent factors influencing labour dystocia occurring in the active phase. The established model could effectively and accurately support clinicians in the early identification of labour dystocia to improve maternal and infant outcomes. What is already known on this subject? Labour dystocia occurring during the active phase of the first stage, is the most commonly diagnosed as labour aberration. Previous studies have suggested that maternal age, body mass index, macrosomia and abnormal foetal position are the independent risk factors for labour dystocia. However, only the risk factors were reported, and few prediction models were established. What do the results of this study add? This study uses data in the real world to establish a prediction model of full-term singleton primipara with labour dystocia occurring in the active phase by logistic regression analysis. Foetal abdomen circumference, PROM, prolonged latent phase, the foetal station and foetal position at the early stage of the active phase are independent factors influencing labour dystocia that occurs in the active phase. In addition, a nomogram is established as a visual graph to predict the probability of it. What are the implications of these findings for clinical practice and/or further research? The nomogram based on the predictive model discarded complicated calculations and presented an easy visual graph-based method to predict the probability of labour dystocia occurring in the active phase. It helps to introduce interventions that could reduce the CS rate and occurrence of adverse maternal and foetal outcomes to ensure the safety of mothers and infants. [ABSTRACT FROM AUTHOR]

Background: Triptonodiol is a very promising antitumor drug candidate extracted from the Chinese herbal remedy Tripterygium wilfordii Hook. F., and related studies are underway. Methods: To explore the mechanism of triptonodiol for lung cancer treatment, we used network pharmacology, molecular docking, and ultimately protein validation. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through the David database. Molecular docking was performed using PyMoL2.3.0 and AutoDock Vina software. After screening, the major targets of triptonodiol were identified for the treatment of lung cancer. Target networks were established, Protein–protein interaction (PPI) network topology was analyzed, then KEGG pathway enrichment analysis was performed. Useful proteins were screened by survival analysis, and Western blot analysis was performed. Results: Triptonodiol may regulate cell proliferation, drug resistance, metastasis, anti-apoptosis, etc., by acting on glycogen synthase kinase 3 beta (GSK3B), protein kinase C (PKC), p21-activated kinase (PAK), and other processes. KEGG pathway enrichment analysis showed that these targets were associated with tumor, erythroblastic oncogene B (ErbB) signaling, protein phosphorylation, kinase activity, etc. Molecular docking showed that the target protein GSK has good binding activity to the main active component of triptonodiol. The protein abundance of GSK3B was significantly downregulated in non-small-cell lung cancer cells H1299 and A549 treated with triptonodiol for 24 h. Conclusion: The cellular-level studies combined with network pharmacology and molecular docking approaches provide new ideas for the development and therapeutic application of triptonodiol, and identify it as a potential GSK inhibitor. [ABSTRACT FROM AUTHOR]

Background: Polypyrimidine tract binding protein 1 (PTBP1) has been found to play an important role in the occurrence and development of various tumors. At present, the role of PTBP1 in gastric cancer (GC) is still unknown and worthy of further investigation. Methods: We used bioinformatics to analyze the expression of PTBP1 in patients with GC. Cell proliferation related experiments were used to detect cell proliferation after PTBP1 knockdown. Skeleton staining, scanning electron microscopy and transmission electron microscopy were used to observe the changes of actin skeleton. Proliferation and actin skeleton remodeling signaling pathways were detected by Western Blots. The relationship between PTBP1 and proliferation of gastric cancer cells was further detected by subcutaneous tumor transplantation. Finally, tissue microarray data from clinical samples were used to further explore the expression of PTBP1 in patients with gastric cancer and its correlation with prognosis. Results: Through bioinformatics studies, we found that PTBP1 was highly expressed in GC patients and correlated with poor prognosis. Cell proliferation and cycle analysis showed that PTBP1 down-regulation could significantly inhibit cell proliferation. The results of cell proliferation detection related experiments showed that PTBP1 down-regulation could inhibit the division and proliferation of GC cells. Furthermore, changes in the morphology of the actin skeleton of cells showed that PTBP1 down-regulation inhibited actin skeletal remodeling in GC cells. Western Blots showed that PTBP1 could regulate proliferation and actin skeleton remodeling signaling pathways. In addition, we constructed PTBP1 Cas9-KO mouse model and performed xenograft assays to further confirm that down-regulation of PTBP1 could inhibit the proliferation of GC cells. Finally, tissue microarray was used to further verify the close correlation between PTBP1 and poor prognosis in patients with GC. Conclusions: Our study demonstrates for the first time that PTBP1 may affect the proliferation of GC cells by regulating actin skeleton remodeling. In addition, PTBP1 is closely related to actin skeleton remodeling and proliferation signaling pathways. We suppose that PTBP1 might be a potential target for the treatment of GC. [ABSTRACT FROM AUTHOR]

Given rapid global urban development, increases to impervious surfaces, urban population growth, building construction, and energy consumption result in the urban heat island (UHI) phenomenon. However, the spatial extent of UHIs is not clearly mapped in many UHI studies based on a remote sensing approach. Therefore, we developed a method to extract the spatial extent of the UHI during the period from 2000 to 2021 in Nanjing, China, and explored the impact of urban two- and three-dimensional expansion on UHI spatial extent and UHI intensity. After cropland effects (i.e., bare soil) were eliminated, our proposed method combines the Getis-Ord-Gi* and the standard deviation of the normalized difference vegetation index (NDVI STD) to extract the UHI area from Landsat 5 and Landsat 8 images using land surface temperature (LST) spatial autocorrelation characteristics and the seasonal variation of vegetation. Our results show the following: (1) Bare farmland has a large influence on the extraction results of UHI—combined with the seasonal variation characteristics of NDVI STD, the impact of bare soil on UHI extraction was highly reduced, strongly improving the accuracy of UHI extraction. (2) The dynamics of the UHI area are consistent with the changes in the built-up area in Nanjing at both spatial and temporal scales, but with the increase of the urban green ratio, the UHI area of mature urban areas trends to decrease due to the cooling effect of green space. (3) The accumulation of population and GDP promote the vertical expansion of urban buildings. When the two-dimensional expansion of the city reaches saturation, the UHI intensity is primarily affected by three-dimensional urban expansion. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a multisystemic angiitis, and its most disastrous complication is coronary artery lesions (CALs). Recently, the role of long non‐coding RNAs (lncRNAs) in KD has been reported. rs1814343 is a lncRNA, but the relationship between the lncRNA rs1814343 polymorphism and KD risk remains elusive. Methods: We enrolled 1625 Kawasaki disease patients (583 patients with CAL and 1042 without CAL) and 1000 healthy controls from a southern Chinese population. We genotyped the rs1814343 C > T polymorphism in KD and control patients using the TaqMan method. The odds ratio (OR) and 95% confidence interval (CI) were used to estimate the strength of the association. Results: There was no significant association between the lncRNA rs1814343 C > T polymorphism and KD susceptibility. However, we stratified patients in this study by CAL and sex. First, compared with the control groups, we found that the rs1814343 genotype increased risk for KD patients with CAL (TT vs. CC + CT: OR = 1.36, 95% CI = 1.08–1.71, p = 0.009). Moreover, when KD patients were stratified by CAL, the TT genotypes of this lncRNA polymorphism contributed to a relatively higher occurrence of KD with CAL than that was found in the CC/CT genotype patients (TT vs. CC + CT: OR = 1.35, 95% CI = 1.07–1.69, p = 0.011). In addition, our research suggested that the TT variant genotype in the lncRNA rs1814343 had an obvious risk of KD with CAL susceptibility in male children. Conclusion: The lncRNA rs1814343 C > T polymorphism was related to higher susceptibility of KD with CAL. [ABSTRACT FROM AUTHOR]

Lung cancer is the most prevalent oncological disease worldwide, with non-small-cell lung cancer accounting for approximately 85% of lung cancer cases. Tripterygium wilfordii is a traditional Chinese herb that is widely used to treat rheumatism, pain, inflammation, tumors, and other diseases. In this study, we found that Triptonodiol extracted from Tripterygium wilfordii inhibited the migration and invasion of non-small-cell lung cancer and inhibited cytoskeletal remodeling, which has not been previously reported. Triptonodiol significantly inhibited the motility activity of NSCLC at low toxic concentrations and suppressed the migration and invasion of NSCLC. These results can be confirmed by wound healing, cell trajectory tracking, and Transwell assays. We found that cytoskeletal remodeling was inhibited in Triptonodiol-treated NSCLC, as evidenced by the reduced aggregation of actin and altered pseudopod morphology. Additionally, this study found that Triptonodiol induced an increase in complete autophagic flux in NSCLC. This study suggests that Triptonodiol reduces the aggressive phenotype of NSCLC by inhibiting cytoskeletal remodeling and is a promising anti-tumor compound. [ABSTRACT FROM AUTHOR]

Purpose: The location of the sciatic nerve deep within the thigh tissue makes it challenging to locate while the patient is in a supine position. The posterior intermuscular septum of the thigh, which encircles the posterior surface of the adductor magnus muscle (AMM), is where the sciatic nerve is located. Our hypothesis was that administering local anesthetic injections into this area could block the sciatic nerve. Therefore, our aim was to evaluate the effectiveness of sciatic nerve block achieved by injecting local anesthetic into the posterior intermuscular septum of the thigh, named the AMM approach. Methods: Twenty-six patients undergoing total knee arthroplasty were included in the study. We performed an ultrasound-guided sciatic nerve block by injecting 20 mL of 0.25% ropivacaine into the posterior surface of the adductor magnus muscle, using the AMM approach. Additionally, we administered a femoral nerve block with 20 mL of 0.4% ropivacaine. We assessed the sensory and motor effects of the blockade in the operated lower limb and recorded postoperative pain scores at 0, 4, 8, 12, 24, and 48 hours after the operation. Results: The AMM approach successfully block the sciatic nerve in all 26 patients. The onset of the sensory and motor blockades was achieved within 5.4 ± 1.9 min and 8.7 ± 3.5 min, respectively. We achieved a satisfactory position with the first puncture in 19 of 26 patients (73.1%). The muscle strength of the tibialis anterior immediately after surgery was 4 (ranging from 2 to 5). Additional rescue analgesics were required in 5 of the 26 patients (19.2%) during the first 24 hours postoperatively. Conclusion: The AMM approach is an innovative and effective method for sciatic nerve block. When combined with simultaneous femoral nerve block in patients undergoing total knee arthroplasty, it provides a useful analgesic treatment option. [ABSTRACT FROM AUTHOR]

We report on the fabrication and characterization of an organic distributed feedback laser excited from a semiconducting polymer gain layer, poly(2-methoxy-5-(2′-ethyl-hexyloxy)-p-phenyl-envinylene) (MEH-PPV). A holographic polymer dispersed liquid crystal grating is fabricated on top of the homogeneous MEH-PPV layer as an external cavity. We established a model to calculate the confinement factor Γ. With the change of laser structural parameters (the refractive index of the grating layer, the film thickness of the MEH-PPV layer, etc.), the confinement factor Γ changes accordingly. It was found that a single longitudinal lasing mode could be observed only when the confinement factor Γ was in a specific range. Choosing a reasonable thickness of gain film and prepolymer with higher refractive index can obtain a lower threshold emission laser. [ABSTRACT FROM AUTHOR]