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Ling-Cang Xu,1,2 Fang-Fang Zhou,1,2 Meng Li,1,2 Zhi-Wei Dai,1,2 Ke-Dan Cai,1,2 Bei-Xia Zhu,1,2 Qun Luo1,2 1Department of Nephrology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang Province, 315010, People’s Republic of China; 2Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang Province, 315010, People’s Republic of ChinaCorrespondence: Qun LuoDepartment of Nephrology, Hwa Mei Hospital, University of Chinese Academy of Sciences, No. 41, Northwest Street, Ningbo, Zhejiang Province, 315010, People’s Republic of ChinaTel/Fax +86-574-83870217Email nbeyluoqun@126.com; luoqun@ucas.ac.cnObjective: This study is to investigate the correlation between serum triiodothyronine (T3) levels and all-cause and cardiovascular mortality in PD patients.Methods: A total of 376 end-stage renal disease (ESRD) patients who started maintenance PD treatment in the Department of Nephrology in our hospital and stable treatment for ≥ 3 months were selected, and the total T3 (TT3) and free T3 (FT3) levels were determined. Among them, 168 cases with FT3 < 3.5 pmol/L and/or TT3 < 0.92 nmol/L were divided into the low serum T3 level group, and the remaining 208 cases were divided into normal serum T3 level group. The Cox survival analysis method was used to analyze the correlation between low serum T3 levels and all-cause and cardiovascular mortality in PD patient.Results: Compared with the normal serum T3 level group, patients with low serum T3 levels had higher systolic blood pressure and a higher proportion of heart disease, and lower levels of total T4, free T4, hemoglobin, serum albumin, blood calcium, serum total bilirubin, alanine aminotransferase, and 24-h urine volume (all P < 0.05). Binary Logistic regression analysis showed that heart disease (P = 0.003, OR: 2.628, 95% CI: 1.382– 4.997) and high TT4 level (P < 0.001, OR: 0.968, 95% CI: 0.956– 0.979) were related to low serum T3 levels in PD patients. Multivariate Cox regression analysis showed that low serum FT3 level was an independent risk factor for all-cause death in PD patients (HR = 0.633, 95% CI = 0.431– 0.930; P < 0.020).Conclusion: Low serum T3 levels in PD patients were associated with heart disease and TT4 levels. Low serum FT3 levels were associated with the risk of all-cause death in PD patients.Keywords: serum T3 level, peritoneal dialysis, all-cause death, cardiovascular death, correlation

Ying Wang,1,2,* Xin-Hong He,1,2,* Li-Chao Xu,1,2 Hao-Zhe Huang,1,2 Guo-Dong Li,1,2 Yao-Hui Wang,1,2 Wen-Tao Li,1,2 Guang-Zhi Wang3 1Department of Interventional Radiology, Fudan University Shanghai Cancer Center, Xuhui, Shanghai 200032, People’s Republic of China; 2Department of Medical Oncology, Fudan University Shanghai Cancer Center, Xuhui, Shanghai 200032, People’s Republic of China; 3Department of Medical Imaging Center, Affiliated Hospital, Weifang Medical University, Weifang 261053, People’s Republic of China *These authors contributed equally to this work Objective: The study aimed to investigate the efficacy of computed tomography (CT)-guided cryoablation debulking of unresectable pelvic recurrent colorectal cancer (CRC). Patients and methods: From January 2013 to April 2016, 30 patients (18 males and 12 females; aged 57.8±10.5 years) with unresectable pelvic recurrent CRC who had previously received radiotherapy or chemotherapy were included. A total of 35 tumors ranging from 1.2 to 6.3 cm underwent cryoablation. Tumor response was evaluated 1 month after cryoablation according to the Modified Response Evaluation Criteria in Solid Tumors. Logistic regression was used to analyze the risk factors for tumor response. Degree of pain palliation was also determined using the Numerical Rating Scale. Cox proportional hazard models were used to identify predictors of outcomes. Results: Cryoablation was successfully performed in all patients. Complete response (CR) was achieved for 27 tumors in 23 patients and partial response was achieved for eight tumors in seven patients 1 month after cryoablation. The rate of CR was 77.14%, and tumor size was an independent risk factor for CR. Pain relief was satisfactory in 21 symptomatic patients (P

Ling-Ling Zhu,1 Ling-Cheng Xu,2 Hui-Qin Wang,3 Jing-Fen Jin,3 Hua-Fen Wang,3 Quan Zhou21Cadre Department, 2Department of Pharmacy, 3Division of Nursing, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, ChinaAbstract: A utilization study was performed in a 2200-bed tertiary care teaching hospital. Data mining was performed on all nasogastric medication prescriptions for patients hospitalized in 2011. Nurses were interviewed by questionnaire. A PDCA (Plan-Do-Check-Act) cycle was used for continuous quality improvement. The proportion of patients with nasogastric tubes (NGT) was 3.2%. A large number of medical orders (n  6261) involved nasogastric medications with a package insert particularly noting that they should not be crushed or opened (group 1) or medications without a specific formulation recommendation in the package insert but having evidence discouraging NGT dosing (group 2). Of the nasogastrically administered sustained-release or controlled-release formulations, a sustained-release sodium valproate tablet formulation was the most prescribed drug and a sustained-release 2.5 mg felodipine tablet was prescribed with the highest proportion of NGT dosing [NGT/(NGT  oral)  12.3%]. Among the nasogastrically administered enteric-coated formulations, a myrtol-standardized enteric-coated capsule formulation was the most prescribed drug and a pantoprazole tablet formulation was prescribed with the highest proportion of NGT dosing [NGT/(NGT  oral)  19.3%]. Proportions of NGT dosing for amiodarone and carbamazepine (group 2) were 4.8% and 6.3%, respectively. The percentage of nurses with adequate knowledge about pharmaceutical dosage formulations was 60%. The rate of answering correctly as to whether medications in group 1 could be crushed or opened was only 30%. Awareness of evidence discouraging NGT dosing of medications in group 2 was zero. Most nurses (90%) left physicians and pharmacists with the entire responsibility for knowledge and decision-making concerning route of drug administration. After a 3-month preliminary intervention, irrational medical orders involving nasogastric administration of medications in group 1 were successfully abolished. The rate of answering correctly as to whether medications in group 1 could be crushed or opened increased to 100%. This utilization study indicates poor awareness concerning nasogastric administration of medication on the part of physicians and nurses, and preliminary intervention measures were efficient in improving knowledge through team cooperation and effort.Keywords: nasogastric tube, rational drug use, drug administration routes, drug absorption, pharmaceutical preparations, nursing

Background: Partial splenic artery embolization is an effective treatment for hypersplenism but often lacks long-term benefits. Purpose: To evaluate the long-term effects of coil embolization of the splenic artery in patients with liver cirrhosis and hypersplenism. Material and Methods: Forty-nine patients with liver cirrhosis and hypersplenism underwent coil embolization of the main splenic artery. The coils were deployed in the mid- or distal segment of the splenic artery to allow collateral blood flow to the spleen. The following data were collected from 2 weeks to 4 years after the embolization: technical success, length of hospital stay, white blood cell count, platelet count, splenic volume, and complication. Results: The technical success rate of splenic artery coil embolization was 100%. The post embolization syndrome rate was 75% (36/49) with no incidence of major complications. The mean length of hospital stay was 9 days. After embolization, the patient's white blood and platelet counts increased significantly, peaked at 2 weeks, and gradually decreased during the 4-year follow-up period, but remained at significantly higher levels than pre-embolization levels. Follow-up CT scans demonstrated a gradual increase in the volume of the enhanced portions of the spleens with a decrease in the volume of unenhanced portion. No significant changes occurred in the red blood cell count and liver function after the embolization. Conclusion: Embolization of the mid-and distal main splenic artery with coils is a safe and effective treatment of hypersplenism in cirrhosis with long-term hematologic benefits. [ABSTRACT FROM AUTHOR]

This article analyzes the experience with performance contracts between developing country governments and the managers of their state owned enterprises. It identifies how problems of information asymmetry, incentives, and commitment can lead to shirking. It applies this conceptual framework to a sample of 12 contracts with monopoly state enterprises in six developing countries and finds that all suffer from serious contracting problems and there is no pattern of improved performance that can be attributed to the contracts. [ABSTRACT FROM AUTHOR]

It is accepted that the contact activation complex of the intrinsic pathway of blood coagulation cascade produces active enzymes that lead to plasma coagulation following biomaterial contact. In this study, FXII was activated through contact with hydrophilic glass beads and hydrophobic octadecyltrichlorosilane-modified glass beads from neat buffer solutions. These FXII contact activation products generated from material interaction were found to suppress the procoagulant activity of exogenous αFXIIa, and this inhibition was dependent on surface wettability and the concentration of exogenous αFXIIa. Higher relative inhibition rates were generally observed at low concentrations of αFXIIa (1-2 μg/mL) while both hydrophobic and hydrophilic materials showed similar inhibition levels (~39%) at high concentrations of αFXIIa (20 μg/mL). The presence of prekallikrein in the activation system increased the amount of FXIIa produced during FXII contact activation, and also suppressed the apparent levels of inhibitors on hydrophilic surfaces, while having no effect on apparent levels of inhibitors on hydrophobic surface. The combination of FXII contact activation products and activator surfaces was found to dramatically increase inhibition of αFXIIa activity compared to the activation products alone, regardless of activator surface wettability and the presence of prekallikrein. This finding of inhibitors in the suite of proteins generated by contact activation provides additional knowledge into the complex series of interactions that occur when plasma comes into contact with material surfaces., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Submicron-textured surfaces have been a promising approach to mitigate biofilm development and control microbial infection. However, the use of the single surface texturing approach is still far from ideal for achieving complete control of microbial infections on implanted biomedical devices. The use of a surface topographic modification that might improve the utility of standard antibiotic therapy could alleviate the complications of biofilms on devices. In this study, we characterized the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa on smooth and submicron-textured polyurethane surfaces after 1, 2, 3, and 7 days, and measured the efficacy of common antibiotics against these biofilms. Results show that the submicron-textured surfaces significantly reduced biofilm formation and growth, and that the efficacy of antibiotics against biofilms grown on textured surfaces was improved compared with smooth surfaces. The antibiotic efficacy appears to be related to the degree of biofilm development. At early time points in biofilm formation, antibiotic treatment reveals reasonably good antibiotic efficacy against biofilms on both smooth and textured surfaces, but as biofilms mature, the efficacy of antibiotics drops dramatically on smooth surfaces, with lesser decreases seen for the textured surfaces. The results demonstrate that surface texturing with submicron patterns is able to improve the use of standard antibiotic therapy to treat device-centered biofilms by slowing the development of the biofilm, thereby offering less resistance to antibiotic delivery to the bacteria within the biofilm community., (© 2024 The Author(s). Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

Rechargeable lithium-ion batteries are integral to contemporary energy storage, yet current anode material systems struggle to meet the increasing demand for extended range capabilities. This work introduces a novel composite anode material composed of one-dimensional 2H-phase tin disulfide (SnS 2 ) nanoribbons enclosed within cavities of single-walled carbon nanotubes (SnS 2 @SWCNTs), achieved through precise atomic engineering. Employing aberration-corrected transmission electron microscopy, we precisely elucidated the crystal structure of SnS 2 within the confines of the SWCNTs. This deliberate design effectively addresses the inherent limitations of SnS 2 as a lithium-ion anode material, including its low electrical conductivity, considerable volume expansion effects, and unstable solid electrolyte interface membrane. Testing confirmed that SnS 2 transforms into the Li 5 Sn 2 alloy phase after full lithiation and back to SnS 2 after delithiation, showing excellent reversibility. The composite also benefits from edge effects, improving lithium storage through stronger binding and lower migration barriers, which were supported by calculations. This pioneering work advances high-performance anode materials for applications.

Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. Herein, a dualfunction submicron textured nitric oxide (NO)-releasing catheter was developed. The hemocompatibility and antithrombotic activity of vascular catheters were evaluated in both 20 h in vitro blood loop and 7 d in vivo rabbit model. Surface characterization assessments via atomic force microscopy show the durability of the submicron pattern after incorporation of NO donor S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-doped catheters exhibited prolonged and controlled NO release mimicking the levels released by endothelium. Fabricated catheters showed cytocompatibility when evaluated against BJ human fibroblast cell lines. After 20h in vitro evaluation of catheters in a blood loop, textured-NO catheters exhibited a 13-times reduction in surface thrombus formation compared to the control catheters, which had 83% of the total area covered by clots. After the 7 d in vivo rabbit model, analysis on the catheter surface was examined via scanning electron microscopy, where significant reduction of platelet adhesion, fibrin mesh, and thrombi can be observed on the NO-releasing textured surfaces. Moreover, compared to relative controls, a 63% reduction in the degree of thrombus formation within the jugular vein was observed. Decreased levels of fibrotic tissue decomposition on the jugular vein and reduced platelet adhesion and thrombus formation on the texture of the NO-releasing catheter surface are indications of mitigated foreign body response. This study demonstrated a biocompatible and robust dual-functioning textured NO PU catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. STATEMENT OF SIGNIFICANCE: Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. This study demonstrated a robust, biocompatible, dual-functioning textured nitric oxide (NO) polyurethane catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. The fabricated catheters exhibited prolonged and controlled NO release that mimics endothelium levels. After the 7 d in vivo model, a significant reduction in platelet adhesion, fibrin mesh, and thrombi was observed on the NO-releasing textured catheters, along with decreased levels of fibrotic tissue decomposition on the jugular vein. Results illustrate that NO-textured catheter surface mitigates foreign body response., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Hitesh Handa is a founder of Nytricx INC, which is involved in exploring possibilities of using nitric oxide-releasing materials for medical applications., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

A widely used type II pyrethroid pesticide cypermethrin (CYP) is one of endocrine disrupting chemicals (EDCs) with anti-androgenic activity to induce male reproductive toxicology. However, the mechanisms have not been fully elucidated. This study was to explore the effects of CYP on apoptosis of mouse Sertoli cells (TM4) and the roles of endoplasmic reticulum (ER)-mitochondria coupling involving 1,4,5-trisphosphate receptor type1-glucose-regulated protein 75-voltage-dependent anion channel 1 (IP3R1-GRP75-VDAC1). TM4 were cultured with different concentrations of CYP. Flow cytometry, calcium (Ca 2+ ) fluorescent probe, transmission electron microscopy and confocal microscopy, and western blot were to examine apoptosis of TM4, mitochondrial Ca 2+ , ER-mitochondria coupling, and expressions of related proteins. CYP was found to increase apoptotic rates of TM4 significantly. CYP was shown to significantly increase expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP). Concentration of mitochondrial Ca 2+ was increased by CYP treatment significantly. CYP significantly enhanced ER-mitochondria coupling. CYP was shown to increase expressions of IP3R, Grp75 and VDAC1 significantly. We suggest that CYP induces apoptosis in TM4 cells by facilitating mitochondrial Ca 2+ overload regulated by ER-mitochondria coupling involving IP3R1-GRP75-VDAC1. This study identifies a novel mechanism of CYP-induced apoptosis in Sertoli cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study is to inquire about the potential association between radiomics features and the pathological nature of thyroid nodules (TNs), and to propose an interpretable radiomics-based model for predicting the risk of malignant TN., Methods: In this retrospective study, computed tomography (CT) imaging and pathological data from 141 patients with TN were collected. The data were randomly stratified into a training group (n = 112) and a validation group (n = 29) at a ratio of 4:1. A total of 1316 radiomics features were extracted by using the pyradiomics tool. The redundant features were removed through correlation testing, and the least absolute shrinkage and selection operator (LASSO) or the minimum redundancy maximum relevance standard was used to select features. Finally, 4 different machine learning models (RF Hybrid Feature, SVM Hybrid Feature, RF, and LASSO) were constructed. The performance of the 4 models was evaluated using the receiver operating characteristic curve. The calibration curve, decision curve analysis, and SHapley Additive exPlanations method were used to evaluate or explain the best radiomics machine learning model., Results: The optimal radiomics model (RF Hybrid Feature model) demonstrated a relatively high degree of discrimination with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI, 0.70-0.97; P < 0.001) for the validation cohort. Compared with the commonly used LASSO model (AUC, 0.78; 95% CI, 0.60-0.91; P < 0.01), there is a significant improvement in AUC in the validation set, net reclassification improvement, 0.79 (95% CI, 0.13-1.46; P < 0.05), and integrated discrimination improvement, 0. 20 (95% CI, 0.10-0.30; P < 0.001)., Conclusion: The interpretable radiomics model based on CT performs well in predicting benign and malignant TNs by using quantitative radiomics features of the unilateral total thyroid. In addition, the data preprocessing method incorporating different layers of features has achieved excellent experimental results., Clinical Relevance Statement: As the detection rate of TNs continues to increase, so does the diagnostic burden on radiologists. This study establishes a noninvasive, interpretable and accurate machine learning model to rapidly identify the nature of TN found in CT., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Bacterial intracellular nucleotide second messenger signaling is involved in biofilm formation and regulates biofilm development. Interference with the bacterial nucleotide second messenger signaling provides a novel approach to control biofilm formation and limit microbial infection in medical devices. In this study, we tethered small-molecule derivatives of 4-arylazo-3,5-diamino-1 H -pyrazole on polyurethane biomaterial surfaces and measured the biofilm resistance and initial biocompatibility of modified biomaterials in in vitro and in vivo settings. Results showed that small-molecule-modified surfaces significantly reduced the Staphylococcal epidermidis biofilm formation compared to unmodified surfaces and decreased the nucleotide levels of c-di-AMP in biofilm cells, suggesting that the tethered small molecules interfere with intracellular nucleotide signaling and inhibit biofilm formation. The hemocompatibility assay showed that the modified polyurethane films did not induce platelet activation or red blood cell hemolysis but significantly reduced plasma coagulation and platelet adhesion. The cytocompatibility assay with fibroblast cells showed that small-molecule-modified surfaces were noncytotoxic and cells appeared to be proliferating and growing on modified surfaces. In a 7-day subcutaneous infection rat model, the polymer samples were implanted in Wistar rats and inoculated with bacteria or PBS. Results show that modified polyurethane significantly reduced bacteria by ∼2.5 log units over unmodified films, and the modified polymers did not lead to additional irritation/toxicity to the animal tissues. Taken together, the results demonstrated that small molecules tethered on polymer surfaces remain active, and the modified polymers are biocompatible and resistant to microbial infection in vitro and in vivo.

Bismuth oxyselenide (Bi 2 O 2 Se), an emerging 2D semiconductor material, has garnered substantial attention owing to its remarkable properties, including air stability, elevated carrier mobility, and ultrafast optical response. In this study, we conduct a comparative analysis of electron excitation and relaxation processes in monolayer and bilayer Bi 2 O 2 Se. Our findings reveal that monolayer Bi 2 O 2 Se exhibits parity-forbidden transitions between the band edges at the Γ point, whereas bilayer Bi 2 O 2 Se demonstrates parity activity, providing the bilayer with an advantage in light absorption. Employing nonadiabatic molecular dynamics simulations, we uncover a two-stage hot-electron relaxation process-initially fast followed by slow-in both monolayer and bilayer Bi 2 O 2 Se within the conduction band. Despite the presence of weak nonadiabatic coupling between the CBM + 1 and CBM, limiting hot electron relaxation, the monolayer displays a shorter relaxation time due to its higher phonon-coupled frequency and smaller energy difference. Our investigation sheds light on the layer-specific excitation properties of 2D Bi 2 O 2 Se layered materials, providing crucial insights for the strategic design of photonic devices utilizing 2D materials.

Filamentous fungi belonging to the genus Aspergillus are prodigious producers of alkaloids, particularly prenylated indole alkaloids, that often exhibit structurally diversified skeletons and potent biological activities. In this study, five prenylated indole alkaloids possessing a bicyclo[2.2.2]diazaoctane core ring system, including a novel derivative, namely aspertaichamide A (1), as well as four known compounds, (+)-stephacidin A (2), sclerotiamide (3), (-)-versicolamide B (4), and (+)-versicolamide B (5), were isolated and identified from A. taichungensis 299, an endophytic fungus obtained from the marine red alga Gelidium amansii. The chemical structures of the compounds were elucidated by comprehensive NMR and HRESIMS spectroscopic analyses. In addition to the previously reported prenylated indole alkaloids, aspertaichamide A (1) was characterized as having an unusual ring structure with the fusion of a 3-pyrrolidone dimethylbenzopyran to the bicyclo[2.2.2]diazaoctane moiety, which was rare in these kinds of compounds. The absolute configuration of 1 was determined by TDDFT-ECD calculations. In vitro cytotoxic assays revealed that the novel compound 1 possessed selective cytotoxic activity against five human tumor cell lines (A549, HeLa, HepG2, HCT-116, and AGS), with IC 50 values of 1.7-48.5 μM. Most importantly, compound 1 decreased the viability of AGS cells in a concentration-dependent manner with an IC 50 value of 1.7 μM. Further studies indicated that 1 may induce AGS cells programmed cell death via the apoptotic pathway., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

While titanacyclopropanes are used to react mainly with ester, amide, and cyano to undergo cyclopropanation, herein they react preferentially with pyridine N -oxide to accomplish C2-H alkylation beyond these functionalities with double regioselectivity. After being pyridylated at the less hindered C-Ti bond, the remaining C-Ti bond of titanacyclopropanes can be further functionalized by various electrophiles, allowing facile introduction of complex alkyls onto the C2 of pyridines. Its synthetic potential has been demonstrated by late-stage diversification of drugs.

Carbon capture, utilization, and storage (CCUS) technology is widely recognized as a key solution for mitigating global climate change. Consequently, it has received significant attention from countries worldwide. However, carbon dioxide corrosion poses a significant challenge to CCUS and represents a bottleneck to the large-scale development and application of this technology. To mitigate this issue, this review starts with a discussion of corrosion problems in CCUS. Later, the fundamentals of the carbon dioxide corrosion mechanism are introduced. Then, the influences of various factors that affect the corrosion are highlighted, such as water content, pH, flow rate, etc. Afterward, we summarize the commonly used methods for corrosion protection, with a particular focus on inhibitor, given their eco-friendly and effective nature. Lastly, challenges and prospects are discussed to motivate future studies on developing novel, high-performance green inhibitor and studying the corresponding protection mechanisms, hoping to make some contributions to carbon emission reduction., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Objective: In the previous study, we identified bone morphogenetic protein 4 (BMP4) responsible for non-syndromic cleft lip with or without cleft palate (NSCL/P). We aimed to elucidate the effects and mechanisms of BMP4 on epithelial-mesenchymal transition (EMT) through Smad1 signaling pathway to be involved in NSCL/P., Methods: The human oral epidermoid carcinoma cells (KBs) were transfected with plasmids or small interfering RNA (siRNA) to build the models. The migration of the cells was evaluated by transwell assay. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expressions of BMP4, E-cadherin, N-cadherin, EMT-related transcription factors snal1 and snal2, matrix metalloproteinase 2 (MMP2), MMP9, Smad1, and phosphorylated Smad1., Results: In the overexpression group, the migration number of cells was increased significantly. The protein expression of E-cadherin was decreased significantly, while the protein expression level of the N-cadherin was increased significantly. The protein and mRNA expressions of MMP2, MMP9, snal1, and snal2 were significantly higher. The expression level of Smad1 was not significantly changed, while the phosphorylation of Smad1 was significantly increased. In the BMP4-siRNA group, the migrating number cells was significantly decreased. The protein expression of E-cadherin was increased significantly, while the expression of N-cadherin was significantly decreased. The protein and mRNA expressions of MMP2, MMP9, snal1, and snal2 were significantly lower than that of the control group. The expressions of Smad1 and phosphorylation of Smad1 were not significantly changed., Conclusions: BMP4 enhances cell migration and promotes cell EMT through Smad1 signaling pathway. Abnormal BMP4 mediates migration and EMT through other relevant signaling pathways resulting in NSCL/P. The study provides new insight into the mechanisms of NSCL/P associated with BMP4.n., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study developed a machine learning-based force field for simulating the bcc-hcp phase transitions of iron. By employing traditional molecular dynamics sampling methods and stochastic surface walking sampling methods, combined with Bayesian inference, we construct an efficient machine learning potential for iron. By using SOAP descriptors to map structural data, we find that the machine learning force field exhibits good coverage in the phase transition space. Accuracy evaluation shows that the machine learning force field has small errors compared to DFT calculations in terms of energy, force, and stress evaluations, indicating excellent reproducibility. Additionally, the machine learning force field accurately predicts the stable crystal structure parameters, elastic constants, and bulk modulus of bcc and hcp phases of iron, and demonstrates good performance in predicting higher-order derivatives and phase transition processes, as evidenced by comparisons with DFT calculations and existing experimental data. Therefore, our study provides an effective tool for investigating the phase transitions of iron using machine learning methods, offering new insights and approaches for materials science and solid-state physics research., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Segmented polyurethane (PU) block copolymers are widely used in implantable cardiovascular medical devices due to their good biocompatibility and excellent mechanical properties. More specifically, PU Biospan MS/0.4 was used in ventricular assist devices over the past decades. However, this product is being discontinued and it has become necessary to find an alternative PU biomaterial for application in cardiovascular devices. One important criterion for assessing cardiac biomaterials is blood compatibility. In this study, we characterized the surface properties of four medical-grade PU biomaterials: Biospan MS/0.4, BioSpan S, BioSpan 2F, and CarboSil 20 80A, including surface chemistry, topography, microphase separation structure and wettability, and then measured the blood plasma coagulation responses using bovine and human blood plasma. Results showed that BioSpan 2F contains high amounts of fluorine and has the lowest surface free energy while the other materials have surfaces with silicone present. An in vitro coagulation assay shows that these materials demonstrated improved blood coagulation responses compared to the polystyrene control and there were no significant differences in coagulation time among all PU biomaterials. The chromogenic assay showed all PU materials led to low FXII contact activation, and there were no significant differences in FXII contact activation, consistent with plasma coagulation responses.

Biomaterial-associated microbial infection is one of the most frequent and severe complications associated with the use of biomaterials in medical devices. In previous studies, we developed new fluorinated polyphosphazenes, poly[bis(octafluoropentoxy) phosphazene] (OFP) and crosslinkable OFP (X-OFP), and demonstrated the inhibition of bacterial adhesion and biofilm formation, thereby controlling microbial infection. In this study, two additional fluorinated polyphosphazenes (PPs, defined as LS02 and LS03) with fluorophenoxy-substituted side groups, 4-fluorophenoxy and 4-(trifluoromethyl)phenoxy, respectively, based on X-OFP general structure, were synthesized and applied as coatings on stainless steel. The linkage of fluorophenoxy groups to the P-N backbone of PPs was found to increase the surface stiffness and significantly reduced Staphylococcus bacterial adhesion and inhibited biofilm formation. It also significantly reduced microbial infection compared to OFP, our prior X-OFPs or poly[bis(trifluoroethoxy) phosphazene] (TFE). The biofilm experiments show that the newly synthesized PPs LS02 and LS03 are biofilm free up to 28 days. Plasma coagulation and platelet adhesion/activation experiments also demonstrated that new PPs containing fluorophenoxy side groups are hemocompatible. The development of new crosslinkable fluorinated PPs containing fluorophenoxy-substituted side groups provides a new generation of polyphosphazene materials for medical devices with improved resistance to microbial infections and thrombosis formation., (© 2023 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

Cypermethrin (CYP) has been identified as one kind of endocrine-disrupting chemicals (EDCs) to induce male reproduction damage. This study aimed to investigate the effects and mechanisms of miR-30a-5p on CYP induced apoptosis of TM4 mouse Sertoli cells in vitro. In the present study, 0 μM, 10 μM, 20 μM, 40 μM and 80 μM CYP were used to treat TM4 cells for 24 h. The apoptosis of TM4 cells, the expression level of miR-30a-5p, the protein expressions and the interaction between miR-30a-5p and KLF9 were detected by flow cytometry, quantitative Real-Time PCR, Western blot and luciferase reporter assays. CYP induced apoptosis of TM4 cells, inhibited expression of miR-30a-5p in TM4 cells, and overexpression of miR-30a-5p partially recovered CYP induced cells apoptosis. Furthermore, KLF9 was a potential downstream target of miR-30a-5p predicted by publicly available databases. KLF9 expression level in TM4 cells was significantly elevated after treatment with CYP, and the induction was inhibited by miR-30a-5p mimics transfection. Meanwhile, dual-luciferase reporter assay demonstrated that miR-30a-5p directly targeted KLF9-3'UTR. Moreover, in the presence of CYP, the apoptosis regulator p53 expression was also increased in TM4 cells. Overexpression miR-30a-5p or down-regulation of KLF9 both attenuated the induction of CYP on p53 expression. Overall, the present study demonstrated that miR-30a-5p regulated CYP induced TM4 cells apoptosis by targeting KLF9/p53 axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Electrooxidation has emerged as an increasingly viable platform in molecular syntheses that can avoid stoichiometric chemical redox agents. Despite major progress in electrochemical C-H activations, these arene functionalizations generally require directing groups to enable the C-H activation. The installation and removal of these directing groups call for additional synthesis steps, which jeopardizes the inherent efficacy of the electrochemical C-H activation approach, leading to undesired waste with reduced step and atom economy. In sharp contrast, herein we present palladium-electrochemical C-H olefinations of simple arenes devoid of exogenous directing groups. The robust electrocatalysis protocol proved amenable to a wide range of both electron-rich and electron-deficient arenes under exceedingly mild reaction conditions, avoiding chemical oxidants. This study points to an interesting approach of two electrochemical transformations for the success of outstanding levels of position-selectivities in direct olefinations of electron-rich anisoles. A physical organic parameter-based machine learning model was developed to predict position-selectivity in electrochemical C-H olefinations. Furthermore, late-stage functionalizations set the stage for the direct C-H olefinations of structurally complex pharmaceutically relevant compounds, thereby avoiding protection and directing group manipulations., (© 2023. The Author(s).)

Staphylococcus epidermidis are common bacteria associated with biofilm related infections on implanted medical devices. Antibiotics are often used in combating such infections, but they may lose their efficacy in the presence of biofilms. Bacterial intracellular nucleotide second messenger signaling plays an important role in biofilm formation, and interference with the nucleotide signaling pathways provides a possible way to control biofilm formation and to increase biofilm susceptibility to antibiotic therapy. This study synthesized small molecule derivates of 4-arylazo-3,5-diamino-1 H-pyrazole (named as SP02 and SP03) and found these molecules inhibited S. epidermidis biofilm formation and induced biofilm dispersal. Analysis of bacterial nucleotide signaling molecules showed that both SP02 and SP03 significantly reduced cyclic dimeric adenosine monophosphate (c-di-AMP) levels in S. epidermidis at doses as low as 25 µM while having significant effects on multiple nucleotides signaling including cyclic dimeric guanosine monophosphate (c-di-GMP), c-di-AMP, and cyclic adenosine monophosphate (cAMP) at high doses (100 µM or greater). We then tethered these small molecules to polyurethane (PU) biomaterial surfaces and investigated biofilm formation on the modified surfaces. Results showed that the modified surfaces significantly inhibited biofilm formation during 24 h and 7-day incubations. The antibiotic ciprofloxacin was used to treat these biofilms and the efficacy of the antibiotic (2 µg/mL) was found to increase from 94.8% on unmodified PU surfaces to > 99.9% on both SP02 and SP03 modified surfaces (>3 log units). Results demonstrated the feasibility of tethering small molecules that interfere with nucleotide signaling onto polymeric biomaterial surfaces and in a way that interrupts biofilm formation and increases antibiotic efficacy for S. epidermidis infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Accurate prediction of reactivity and selectivity provides the desired guideline for synthetic development. Due to the high-dimensional relationship between molecular structure and synthetic function, it is challenging to achieve the predictive modelling of synthetic transformation with the required extrapolative ability and chemical interpretability. To meet the gap between the rich domain knowledge of chemistry and the advanced molecular graph model, herein we report a knowledge-based graph model that embeds the digitalized steric and electronic information. In addition, a molecular interaction module is developed to enable the learning of the synergistic influence of reaction components. In this study, we demonstrate that this knowledge-based graph model achieves excellent predictions of reaction yield and stereoselectivity, whose extrapolative ability is corroborated by additional scaffold-based data splittings and experimental verifications with new catalysts. Because of the embedding of local environment, the model allows the atomic level of interpretation of the steric and electronic influence on the overall synthetic performance, which serves as a useful guide for the molecular engineering towards the target synthetic function. This model offers an extrapolative and interpretable approach for reaction performance prediction, pointing out the importance of chemical knowledge-constrained reaction modelling for synthetic purpose., (© 2023. The Author(s).)

Nitric oxide (NO) releasing biomaterials are a promising approach against medical device associated microbial infection. In contrast to the bacteria-killing effects of NO at high concentrations, NO at low concentrations serves as an important signaling molecule to inhibit biofilm formation or disperse mature biofilms by regulating the intracellular nucleotide second messenger signaling network such as cyclic dimeric guanosine monophosphate (c-di-GMP) for many Gram-negative bacterial strains. However, Gram-positive staphylococcal bacteria are the most commonly diagnosed microbial infections on indwelling devices, but much less is known about the nucleotide messengers and their response to NO as well as the mechanism by which NO inhibits biofilm formation. This study investigated the cyclic nucleotide second messengers c-di-GMP, cyclic dimeric adenosine monophosphate (c-di-AMP), and cyclic adenosine monophosphate (cAMP) in both Staphylococcus aureus ( S. aureus ) Newman D2C and Staphylococcus epidermidis ( S. epidermidis ) RP62A after incubating with S -nitroso- N -acetylpenicillamine (SNAP, NO donor) impregnated polyurethane (PU) films. Results demonstrated that NO release from the polymer films significantly reduced the c-di-GMP levels in S. aureus planktonic and sessile cells, and these bacteria showed inhibited biofilm formation. However, the effect of NO release on c-di-GMP in S. epidermidis was weak, but rather, S. epidermidis showed significant reduction in c-di-AMP levels in response to NO release and also showed reduced biofilm formation. Results strongly suggest that NO regulates the nucleotide second messenger signaling network in different ways for these two bacteria, but for both bacteria, these changes in signaling affect the formations of biofilms. These findings provide cues to understand the mechanism of Staphylococcus biofilm inhibition by NO and suggest novel targets for antibiofilm interventions.

Introduction: Multimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies., Methods: In this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment., Results: There was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8 + effector T (CD8 + Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway., Conclusion: This study confirmed that MTT could more effectively activate peripheral CD8 + Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wang, Chen, Huang, Wang, He, Xu, Xu and Li.)

Challenging enantio- and diastereoselective cobalt-catalyzed C-H alkylation has been realized by an innovative data-driven knowledge transfer strategy. Harnessing the statistics of a related transformation as the knowledge source, the designed machine learning (ML) model took advantage of delta learning and enabled accurate and extrapolative enantioselectivity predictions. Powered by the knowledge transfer model, the virtual screening of a broad scope of 360 chiral carboxylic acids led to the discovery of a new catalyst featuring an intriguing furyl moiety. Further experiments verified that the predicted chiral carboxylic acid can achieve excellent stereochemical control for the target C-H alkylation, which supported the expedient synthesis for a large library of substituted indoles with C-central and C-N axial chirality. The reported machine learning approach provides a powerful data engine to accelerate the discovery of molecular catalysis by harnessing the hidden value of the available structure-performance statistics., (© 2023. The Author(s).)

Despite the availability and accuracy of modern spectroscopic characterization, the utilization of spectral information in chemical machine learning is still primitive. Here, we report an optical character recognition-based automatic process to utilize spectral information as molecular descriptors, which directly transforms experimental spectrum images to readable vectors. We demonstrate its machine learning application in the reaction yield dataset of Pd-catalyzed Buchwald-Hartwig cross-coupling with aryl halides. In addition, we also show that the predicted spectrum can serve as an alternative encoding source to support the model training., (© 2023 Wiley-VCH GmbH.)

Objective: The role E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8) has not been studied in pancreatic cancer., Method: Pancreatic cancer cell lines and the normal pancreatic cells were tested in vitro studies and male athymic nude mice were tested in vivo studies. Measuring cell viability by Cell Counting Kit-8 assay (CCK8), 5-ethynyl-2'- deoxyuridine (Edu) staining, and colony formation assay. Wound healing assay was implemented for cell migration and Transwell assay was performed for cell invasion to evaluate the histological status by hematoxylin and eosin staining and to detect the protein ubiquitination by ubiquitination assay. The protein expression was determined by immunohistochemistry staining and western blotting, and mRNA expression was measured by quantitative reverse transcription polymerase chain reaction., Result: The expression of MARCH8 was increased whereas PTPN4 was decreased in pancreatic cancer cells. Overexpression of MARCH8 promoted the growth, migration, and invasion of cells, and knockdown of PTPN4 had the similar effects both in vitro and in vivo. MARCH8 promoted PTPN4 protein degradation through ubiquitination. Moreover, PTPN4 suppressed the transcription activities of STAT3 by impairing the level of pSTAT3 (705), while inhibition of PTPN4 activated phosphorylation of STAT3., Conclusions: MARCH8 promoted pancreatic cancer growth and invasion through mediating the degradation of PTPN4 and activated the phosphorylation of STAT3., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated., Materials and Methods: The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients., Results: In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33-27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33-9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%)., Conclusion: The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiao, Qin, Wang, Liu, Wu, Ling, Qin, Wang, Yuan, Barreto, Kim, Mak, Li, Xu, Qiu, Wu, Jin, Xu, Zhong, Yang, Chen, Zeng, Shi, Zhu, Ding, Jia, Liu, Zhou, Shen, Yao, Guo, Li, Zhou, Dong, Lu, Coleman, Akce, Akladios, Puccetti and Zang.)

Using density functional theory and the non-equilibrium Green's function method, we theoretically investigated the structures, stabilities, electronic properties, and the direct-current (DC) and alternating-current (AC) transport properties of the line defects in two-dimensional material β 12 -borophene. Our results suggest that there exist six line defects that can enhance the stability of β 12 -borophene and the line defects have profound influences on the electronic structure of β 12 -borophene. Along the zigzag direction, the line defects can change the atomic orbital components of the Dirac cones in perfect β 12 -borophene, but the line defects along the armchair direction have complicated influences on the Dirac cones. In the case of DC transport, some of the line defects lead to the constant DC phenomenon and the negative differential resistance effect, and enhance the DC conductances since the line defects exhibit typical one-dimensional characteristics. In the case of AC transport, some of the line defects enhance the AC conductances in the medium-frequency and high-frequency ranges through the photon-assisted tunneling effect. The microscopic mechanisms of the enhanced DC and AC conductances are different. In addition, for a low-frequency range, the equivalent circuits of β 12 -borophene and the line defects were also suggested, which will be beneficial for designing borophene-based functional nanodevices.

Recent years have witnessed a boom of machine learning (ML) applications in chemistry, which reveals the potential of data-driven prediction of synthesis performance. Digitalization and ML modelling are the key strategies to fully exploit the unique potential within the synergistic interplay between experimental data and the robust prediction of performance and selectivity. A series of exciting studies have demonstrated the importance of chemical knowledge implementation in ML, which improves the model's capability for making predictions that are challenging and often go beyond the abilities of human beings. This Minireview summarizes the cutting-edge embedding techniques and model designs in synthetic performance prediction, elaborating how chemical knowledge can be incorporated into machine learning until June 2022. By merging organic synthesis tactics and chemical informatics, we hope this Review can provide a guide map and intrigue chemists to revisit the digitalization and computerization of organic chemistry principles., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Introduction: This study aimed to understand the transcriptome characteristics of the skeletal muscle of elderly (EL) men with metabolic syndrome (MS) and to find the hub genes and insight into the molecular mechanisms of skeletal muscle in the occurrence and development of MS., Methods: In this study, the limma package of R software was used to analyze the differentially expressed genes in the skeletal muscle of healthy young (YO) adult men, healthy EL men, and EL men diagnosed with MS (SX) for at least 10 years. Bioinformatics methods, such as GO enrichment analysis, KEGG enrichment analysis, and gene interaction network analysis, were used to explore the biological functions of differentially expressed genes, and weighted gene coexpression network analysis (WGCNA) was used to cluster differentially expressed genes into modules., Results: Among the YO group, EL group, and SX group, 65 co-differentially expressed genes were found maybe regulated by age factor and MS factor. Those co-differentially expressed genes were enriched into 25 biological process terms and 3 KEGG pathways. Based on the WGCNA results, a total of five modules were identified. Fifteen hub genes may play an essential role in regulating the function of skeletal muscle of EL men with MS., Conclusions: 65 differentially expressed genes and 5 modules may regulate the function of skeletal muscle of EL men with MS, among which fifteen hub genes may play an essential role in the occurrence and development of MS., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. &quot;Simotang Oral Liquid&quot; &quot;Simotang&quot; &quot;Si Mo Tang&quot; &quot;Si Mo Tang Oral Liquid&quot; were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.

Background: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease in clinical practice. It is mainly due to cardiovascular hypoplasia during embryonic development. The study aimed to find the etiology of TOF., Methods: Through the mRNA expression profile analysis of the GSE35776 dataset, differentially expressed genes (DEGs) were found, and the functional analysis and protein-protein interaction (PPI) network analysis were then performed on DEGs. Likewise, the hub genes and functional clusters of DEGs were analyzed using the PPI network. Differentially expressed miRNAs were analyzed from the GSE35490 dataset, followed by miRNet predicted transcription factors (TFs) and target genes. The key TF-miRNA-gene interaction mechanism was explored through the found significant difference between genes and target genes., Results: A total of 191 differentially expressed genes and 57 differentially expressed miRNAs were identified. The main mechanisms involved in TOF were mitochondria-related and energy metabolism- related molecules and pathways in GO and KEGG analysis. This discovery was identical in TFs and target genes. The key miRNAs, hsa-mir-16 and hsa-mir-124, were discovered by the Venn diagram. A co-expression network with the mechanism of action centered on two miRNAs was made., Conclusion: Hsa-mir-16 and hsa-mir-124 are the key miRNAs of TOF, which mainly regulate the expression of NT5DC1, ECHDC1, HSDL2, FCHO2, and ACAA2 involved in the conversion of ATP in the mitochondria and the metabolic rate of fatty acids (FA). Our research provides key molecules and pathways into the etiology of TOF, which can be used as therapeutic targets., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In central nervous system, axons fail to regenerate after injury while in peripheral nervous system, axons retain certain regenerative ability. Dorsal root ganglion (DRG) neuron has an ascending central axon branch and a descending peripheral axon branch stemming from one single axon and serves as a suitable model for the comparison of growth competence following central and peripheral axon injuries. Molecular alterations underpin different injury responses of DRG branches have been investigated from many aspects, such as coding gene expression, chromatin accessibility, and histone acetylation. However, changes of circular RNAs are poorly characterized. In the present study, we comprehensively investigate circular RNA expressions in DRGs after rat central and peripheral axon injuries using sequencing analysis and identify a total of 33 differentially expressed circular RNAs after central branch injury as well as 55 differentially expressed circular RNAs after peripheral branch injury. Functional enrichment of host genes of differentially expressed circular RNAs demonstrate the participation of Hippo signaling pathway and Notch signaling pathway after both central and peripheral axon injuries. Circular RNA changes after central axon injury are also linked with apoptosis and cellular junction while changes after peripheral axon injury are associated with metabolism and PTEN-related pathways. Altogether, the present study offers a systematic evaluation of alterations of circular RNAs in rat DRGs following injuries to the central and peripheral axon branches and contributes to the deciphering of essential biological activities and mechanisms behind successful nerve regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cao, Huang, Zheng, Zhang and Xu.)

Objectives: Crataegus pinnatifida (C. pinnatifida), including C. pinnatifida Bge. and its variant C. pinnatifida Bge. var. major N, E. Br., has traditionally been used as a homologous plant for traditional medicine and food in ethnic medical systems in China. Crataegus pinnatifida, especially its fruit, has been used for more than 2000 years to treat indigestion, stagnation of meat, hyperlipidemia, blood stasis, heart tingling, sores, etc. This review aimed to provide a systematic summary on the botany, traditional uses, phytochemistry, pharmacology and clinical applications of C. pinnatifida., Key Findings: This plant contains flavonoids, phenylpropanoids, terpenoids, organic acids, saccharides and essential oils. Experimental studies showed that it has hypolipidemic, antimyocardial, anti-ischemia, antithrombotic, anti-atherosclerotic, anti-inflammatory, antineoplastic neuroprotective activity, etc. Importantly, it has good effects in treating diseases of the digestive system and cardiovascular and cerebrovascular systems., Summary: There is convincing evidence from both in vitro and in vivo studies supporting the traditional uses of C. pinnatifida. However, multitarget network pharmacology and molecular docking technology should be used to study the interaction between the active ingredients and targets of C. pinnatifida. Furthermore, exploring the synergy of C. pinnatifida with other Chinese medicines to provide new understanding of complex diseases may be a promising strategy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Halometabolites, usually produced in marine environment, are an important group of natural halogenated compounds with rich biological functionality and drugability and thus play a crucial role in pharmaceutical and/or agricultural applications. In the exploration of novel halometabolites from marine microorganisms, the growing number of halogenated compounds makes it necessary to fully present these metabolites with diverse structures and considerable bioactivities. This review particularly focuses on the chemodiversity and bioactivities of halometabolites from marine-derived fungi. As a result, a total of 145 naturally halogenated compounds, including 118 chlorinated, 23 brominated, and four iodinated compounds, were isolated from 17 genera of marine-derived fungi. Interestingly, many of halometabolites, especially for the brominated and iodinated compounds, are generated by the substitution of bromide and iodide ions for the chloride ion in cultivation process. In addition, these compounds possess diverse structural types, which are classified into polyketides (62.7%), phenols (16.6%), alkaloids (14.5%), and terpenoids (6.2%). Their cytotoxic, antibacterial, and anti-inflammatory activities indicate the high potential of these halogenated compounds as lead compounds for drug discovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Xu, Liu, Zhang and Cao.)

The mitochondrial protein sirtuin 3 (SIRT3) can counteract cell damage caused by oxidative stress and inflammation, and contribute to cell survival primarily by improving mitochondrial function. However, the effects of SIRT3 in dopaminergic neuronal cells (DACs) remain unclear. In our previous studies, microglia activation-associated cytotoxicity was observed to promote the apoptosis of DACs, along with the decrease of SIRT3 expression. The aim of the present study was to explore the potential neuroprotective effect of SIRT3 expression against dopaminergic neuron injury caused by microglia activation, and clarify its possible mechanisms. SIRT3 overexpression in DACs reduced the production of intracellular reactive oxygen species (ROS), cell apoptosis rate, mitochondrial membrane potential (ΔΨm) depolarization, opening of mitochondrial permeability transition pore (mPTP) and cyclophilin D (CypD) protein level, and promoted cell cycle progression. However, SIRT3 siRNA-mediated knockdown further aggravated microglia activation-mediated cytotoxicity, including ROS accumulation, increased cell apoptosis and mPTP opening, elevated the CypD level, enhanced mitochondrial ΔΨm depolarization, concomitant to cell cycle arrest at G 0 /G 1 phase. The mechanisms of SIRT3 mitigated microglia activation-induced DAC dysfunction, which included decreased mPTP opening and Bax/Bcl-2 ratio, inhibition of mitochondrial cytochrome c release to the cytoplasm, reduced caspase-3/9 activity, increased LC3II/LC3I and beclin-1 protein expression levels, and decreased nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1β and IL-18 protein expression. In conclusion, these results indicated that SIRT3 expression attenuated cell damage caused by microglia activation through the mitochondrial apoptosis pathway in DACs. The mitophagy-NLRP3 inflammasome pathway may also be associated with this neuroprotection. These findings may provide new intervention targets for the survival of dopaminergic neurons and the prevention and treatment of Parkinson's disease., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Jiang et al.)

Sodium ion technology is increasingly investigated as a low-cost solution for grid storage applications. Among the reported cathode materials for sodium-ion batteries, Na 3 V 2 (PO 4 ) 2 FO 2 is considered as one of the most promising materials due to its high operation voltage and good cyclability. Here, the de-sodiumization process of Na 3 V 2 (PO 4 ) 2 FO 2 has been systematically examined using first-principles calculations to uncover the fundamental questions at the atomic level. Four stable intermediate products during the de-sodiumization process are firstly determined based on the convex hull, and three voltage platforms are then predicted. Except for two voltage platforms (3.37 V and 3.75 V) close to the experimental values, the platform up to 5.28 V exceeds the stability window (4.8 V) of a typical electrolyte, which was not observed experimentally. Excitingly, the change of volume is only 2% during the sodiumization process, which should be the reason for the good cycling stability of this material. Electronic structure analysis also reveals that the valence states of V ions will be changed from V 5+ to V 4+ during the sodiumization process, resulting in a weak Jahn-Teller distortion in VO 5 F octahedra, and then making the lattice-constants asymmetrically change. More seriously, combined with a bandgap of 2.0 eV, the conduction band minimum mainly composed of V-t 2g non-bonding orbitals has strong localized characteristics, which should be the intrinsic origin of poor electron transport properties for Na x V 2 (PO 4 ) 2 FO 2 . Nonetheless, benefiting from the layer-like structure features with F-segmentation, this material has an ultrafast sodium ionic conductivity comparable to that of NASICON, with an activation energy of only 82 meV. Therefore, our results indicate that maintaining layer-like features and regulating V atoms will be important directions to improve the performance of Na x V 2 (PO 4 ) 2 FO 2 .

Background: Patients with peritoneal dialysis commonly have severe disorders of lipid metabolism, with particularly severe changes in serum lipoprotein(α) [Lp(α)]. Serum Lp(α) may play a role in the risk of mortality in peritoneal dialysis patients. The aim was to investigate the correlation between high serum Lp(α) levels and all-cause mortality and death from cardiovascular events and infection in peritoneal dialysis patients., Methods: Three hundred and ninety-two patients with end-stage kidney disease who started peritoneal dialysis treatment between March 1, 2007 and May 31, 2020, were selected. Clinical data of all enrolled patients after 3 months of peritoneal dialysis were collected. Based on the median value of serum Lp(α) level, all enrolled patients were divided equally into a high serum Lp(α) level group (> 275.95 mg/L, n = 196) and a low serum Lp(α) level group (< 275.95 mg/L, n = 196). SPSS25.0 statistical software was used to analyze the factors affecting serum Lp(α) levels and the correlation between high serum Lp(α) levels and all-cause mortality and death from cardiovascular events and infection in peritoneal dialysis patients., Results: Binary multivariate logistic regression analysis showed that higher low-density lipoprotein (LDL) levels (OR = 1.614, 95% CI: 1.261 - 2.068, p = 0.000) and high Body Mass Index (BMI) levels (OR = 1.063, 95% CI: 1.004 - 1.126, p = 0.036) were the risk factors for the high serum Lp(α) levels. High serum albumin levels (OR = 0.959, 95% CI: 0.927 - 0.991, p = 0.014) and high parathyroid hormone levels (OR = 0.999, 95% CI: 0.997 - 1.000, p = 0.010) were protective factors for the high serum Lp(α) levels. The cumulative survival of patients in the high serum Lp(α) level group was lower in death from cardiovascular events as shown by Kaplan-Meier survival analysis (Log-rank test χ2 = 4.348, p = 0.037). Multivariate Cox regression analysis showed that high serum Lp(α) levels were an independent risk factor for death from cardiovascular events in peritoneal dialysis patients (HR = 1.002, 95% CI: 1.001 - 1.003, p = 0.001)., Conclusions: The occurrence of high serum Lp(α) levels in peritoneal dialysis patients was positively associated with LDL and BMI, and negatively associated with serum albumin and parathyroid hormone levels. High serum Lp(α) levels were related to the risk of death from cardiovascular events in peritoneal dialysis patients.

Cypermethrin (CP) exhibits anti-androgenic effects through antagonism on androgen receptor (AR) activation. This study was to identify whether AR-mediated disabled 2 interacting protein (DAB2IP)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway was involved in CP-induced mouse Sertoli cells (TM4) proliferation disorder. Real-Time Cell Analysis-iCELLigence system was to measure cell proliferation. Bioinformatic analyses were performed to identify AR-regulated genes. Quantitative Real-Time PCR and western blot were to detect the genes and proteins levels in AR-mediated DAB2IP/PI3K/AKT pathway. Results showed CP suppressed TM4 proliferation and the expression of AR. Activation of AR restored the inhibition efficacy of CP on TM4 proliferation. AR regulated DAB2IP expression and phosphorylation levels of PI3K and AKT in CP-exposed TM4 cells. In addition, knockdown of DAB2IP alleviated the inhibition efficacy of CP on cell proliferation and phosphorylation of PI3K and AKT. Taken together, AR was a modulator in CP-induced inhibition of Sertoli cells proliferation by negatively regulating DAB2IP/PI3K/AKT signaling pathway. The study may provide a new insight for the mechanisms of male reproductive toxicity induced by CP., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Surface topography modification with nano- or micro-textured structures has been an efficient approach to inhibit microbial adhesion and biofilm formation and thereby to prevent biomaterial-associated infection without modification of surface chemistry/bulk properties of materials and without causing antibiotic resistance. This manuscript focuses on submicron-textured patterns with ordered arrays of pillars on polyurethane (PU) biomaterial surfaces in an effort to understand the effects of surface pillar features and surface properties on adhesion and colonization responses of two staphylococcal strains. Five submicron patterns with a variety of pillar dimensions were designed and fabricated on PU film surfaces and bacterial adhesion and biofilm formation of Staphylococcal strains (Staphylococcus epidermidis RP62A and Staphylococcus aureus Newman D2C) were characterized. Results show that all submicron textured surface significantly reduced bacterial adhesion and inhibited biofilm formation, and bacterial adhesion linearly decreased with the reduction in top surface area fraction. Surface wettability did not show a linear correlation with bacterial adhesion, suggesting that surface contact area dominates bacterial adhesion. From this, it appears that the design of textured patterns should minimize surface area fraction to reduce the bacterial interaction with surfaces but in a way that ensures the mechanical strength of pillars in order to avoid collapse. These findings may provide a rationale for design of polymer surfaces for antifouling medical devices., (© 2022 Wiley Periodicals LLC.)

Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04±0.65 vs. 0.99±0.09 , F =30.36, P <0.001), and was closely related to T stage and clinical stage (Ⅰ-Ⅱ vs. Ⅲ-Ⅳ: 1.75±0.39 vs. 2.18±0.71, F =2.25 , P <0.05; T1-2 vs. T3-4: 1.71±0.42 vs. 2.20±0.69, F =2.06, P <0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P <0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells.