Heavy-Atom Tunneling in Ring-Closure Reactions of Beryllium Ozonide Complexes.

Quantum mechanical tunneling (QMT) has long been recognized as crucial for understanding chemical reaction mechanisms, particularly in reactions involving light atoms like hydrogen. However, recent findings have expanded this understanding to include heavy-atom tunneling reactions. In this report, we present the observation of two heavy-atom tunneling reactions involving the spontaneous conversions from end-on bonded beryllium ozonide complexes, OBeOOO (A) and BeOBeOOO (C), to their corresponding side-on bonded ozonide isomers, OBe(η2-O3) (B) and BeOBe(η2-O3) (D), respectively, in a cryogenic neon matrix. This discovery is supported by the weak temperature dependence of the rate constants and unusually large 16O/18O kinetic isotope effects. Quantum chemistry calculations reveal extremely low barriers (<1 kcal/mol) for both ring-closure reactions. Additionally, instanton theory calculations on both reactions unveil that the tunneling processes involve the concerted motion of all four oxygen atoms.

Advances and mechanisms of fungal symbionts in improving the salt tolerance of crops.

Soil salinization leads to reduced crop yields and waste of land resources, thereby impacting global food security. To meet the increasing demand for food and simultaneously alleviate pressure on soil resources, the development of sustainable agriculture is imperative. In contrast to physical and chemical methods, bioremediation represents an efficient and environmentally friendly approach. Fungal symbionts have been found to be associated with most plants in natural ecosystems, colonizing and residing within the internal tissues of host plants. Moreover, the potential of fungal symbionts in improving saline-alkaline soil has been widely recognized and confirmed. Numerous reports have documented the effectiveness of arbuscular mycorrhizal fungi in alleviating salt stress in plants. Meanwhile, research on other endophytic fungi for mitigating plant salt stress has emerged in recent years, which contributes to refining mechanisms for enhancing plant salt tolerance. In this review, we summarized various mechanisms by which endophytic fungi enhance plant salt tolerance. We also provided an overview of the challenges and development directions in the field of fungal symbiosis, with the aim of offering a viable strategy for the bioremediation of saline-alkali soils.

WI-TMLEGA: Weight Initialization and Training Method Based on Entropy Gain and Learning Rate Adjustment.

Addressing the issues of prolonged training times and low recognition rates in large model applications, this paper proposes a weight training method based on entropy gain for weight initialization and dynamic adjustment of the learning rate using the multilayer perceptron (MLP) model as an example. Initially, entropy gain was used to replace random initial values for weight initialization. Subsequently, an incremental learning rate strategy was employed for weight updates. The model was trained and validated using the MNIST handwritten digit dataset. The experimental results showed that, compared to random initialization, the proposed initialization method improves training effectiveness by 39.8% and increases the maximum recognition accuracy by 8.9%, demonstrating the feasibility of this method in large model applications.

Prognostic impact of metformin in solid cancer patients receiving immune checkpoint inhibitors: novel evidences from a multicenter retrospective study.

Objective: Metformin as a common antidiabetic drug, has recently found to exert its anti-cancer and immunomodulatory effect in numerous preclinical studies. This study aims to clarify the prognostic impact of metformin use in solid cancer patients receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective cohort enrolling 516 solid cancer patients who received ICI-based therapy between 2018 and 2023 at three hospitals was analyzed. The primary endpoints included overall survival (OS) and progression-free survival (PFS). In addition, a bioinformatics analysis based on TCGA and GSE cohort was performed to investigate the prognostic significance of metformin target genes (MTGs) and their correlation with immune infiltration in non-small cell lung cancer (NSCLC) patients. Results: In the entire cohort, a total of 76 patients received metformin before and/or during ICI therapy. The global analysis demonstrated that metformin use was unrelated with the OS (p = 0.064) and PFS (p = 0.059) of ICI-treated cancer patients, which was confirmed in the subgroups of esophagus, hepatobiliary or pancreatic cancer (all p > 0.05). However, metformin use was significantly correlated with better OS (p = 0.012) and PFS (p = 0.005) in ICI-treated lung cancer patients. Metformin use was also identified as an independent favorable prognostic factor for these patients. The bioinformatics analysis identified five favorable prognostic MTGs (RPS6KA5, RORA, SH3BP5, NUPR1, and CD40LG) for NSCLC patients, all of which was downregulated in lung cancer tissues as compared with normal tissues. The expressions of five MTGs not only could effectively stratify the OS of NSCLC patients, but also was correlated with infiltration of immune cells such as CD4+ and CD8+ T cells. Conclusion: Metformin use was significantly correlated with better OS and PFS in ICI-treated lung cancer patients. MTGs has the potential to serve as novel clinical biomarkers or druggable targets for cancer immunotherapy. Considering study limitations, the actual impact of metformin use on ICI therapy needs to be clarified by more clinical trials.

Carbon Dot Nanozyme Ameliorating Ischemia-Reperfusion-Induced Muscle Injury by Antioxidation and Downregulating iNOS/COX-2 Pathway.

Skeletal muscle ischemia-reperfusion (IR) injury is a prevalent type of muscle injury caused by events, such as trauma, arterial embolism, and primary thrombosis. The development of an IR injury is associated with oxidative stress and an excessive inflammatory response. Nanozymes, which have exceptional free radical scavenging activities, have gained significant attention for treating oxidative stress. This study demonstrates that carbon dot (C-dot) nanozymes possess superoxide dismutase (SOD)-like activity and can act as free radical scavengers. The carbon dot nanozymes are presented to mitigate inflammation by downregulating the iNOS/COX-2 pathway and scavenging reactive oxygen-nitrogen species to reduce oxidative stress, thereby suppressing inflammation. In the IR injury of skeletal muscle mice, we demonstrate that C-dots can effectively reduce inflammatory cytokines and tissue edema in skeletal muscle following IR injury in the limb. These findings suggest that C-dots have potential as a therapeutic approach for IR injury of skeletal muscle with negligible systemic toxicity. This offers a promising strategy for clinical intervention.

Direct Observation of HOON Intermediate in the Photochemistry of HONO.

The photochemistry of nitrous acid (HONO), encompassing dissociation into OH and NO as well as the reverse association reaction, plays a pivotal role in atmospheric chemistry. Here, we report the direct observation of nitrosyl-O-hydroxide (HOON) in the photochemistry of HONO, employing matrix-isolation IR and UV-vis spectroscopy. Despite a barrier of approximately 30 kJ/mol, HOON undergoes spontaneous rearrangement to the more stable HONO isomer through quantum mechanical tunneling, with a half-life of 28 min at 4 K. Kinetic isotope effects and instanton theory calculations reveal that the tunneling process involves the concerted motion of the NO moiety (65.2%) and the hydrogen atom (32.3%). Our findings underscore the significance of HOON as a key intermediate in the photolytic dissociation-association cycle of HONO at low temperatures.

Overexpressed pigment epithelium-derived factor alleviates pulmonary hypertension in two rat models induced by monocrotaline and SU5416/hypoxia.

BACKGROUND: Pulmonary hypertension (PH) is a progressive and fatal cardiopulmonary disease characterized by vascular remodeling and is associated with endothelial-to-mesenchymal transition (EndoMT). The pigment epithelium-derived factor (PEDF), a secretory protein widely distributed in multiple organs, has been shown to demonstrate anti-EndoMT activity in cardiovascular diseases. In the present study, the role of PEDF in PH was investigated. METHODS: For PEDF overexpression, Sprague Dawley rats were infected with an adeno-associated virus through injection via the internal jugular vein. To establish PH models, the animals were subjected to monocrotaline or Sugen/hypoxia. Four weeks later, pulmonary artery angiography was performed, and hemodynamic parameters, right ventricular function, and vascular remodeling were evaluated. EndoMT and cell proliferation in the pulmonary arteries were assessed via immunofluorescence staining. Moreover, pulmonary artery endothelial cells (PAECs) isolated from experimental PH rats were cultured to investigate the underlying molecular mechanisms involved. RESULTS: PEDF expression was significantly downregulated in PAECs from PH patients and PH model rats. Overexpressed PEDF alleviated the development of PH by improving pulmonary artery morphology and perfusion, reducing pulmonary artery pressure, improving right ventricular function, and alleviating vascular remodeling. PEDF inhibits EndoMT and reduces excessive PAEC proliferation. Moreover, PEDF overexpression reduced EndoMT in cultured PAECs by competitively inhibiting the binding of wnt to LRP6 and downregulating phosphorylation at the 1490 site of LRP6. CONCLUSIONS: Our findings suggest that PEDF may be a potential therapeutic target for PH. We also found that PEDF can inhibit EndoMT in PAECs and may exert these effects by inhibiting the Wnt/LRP6/ß-catenin pathway.

Opportunities and challenges of computer aided diagnosis in new millennium: A bibliometric analysis from 2000 to 2023.

BACKGROUND: After entering the new millennium, computer-aided diagnosis (CAD) is rapidly developing as an emerging technology worldwide. Expanding the spectrum of CAD-related diseases is a possible future research trend. Nevertheless, bibliometric studies in this area have not yet been reported. This study aimed to explore the hotspots and frontiers of research on CAD from 2000 to 2023, which may provide a reference for researchers in this field. METHODS: In this paper, we use bibliometrics to analyze CAD-related literature in the Web of Science database between 2000 and 2023. The scientometric softwares VOSviewer and CiteSpace were used to visually analyze the countries, institutions, authors, journals, references and keywords involved in the literature. Keywords burst analysis were utilized to further explore the current state and development trends of research on CAD. RESULTS: A total of 13,970 publications were included in this study, with a noticeably rising annual publication trend. China and the United States are major contributors to the publication, with the United States being the dominant position in CAD research. The American research institutions, lead by the University of Chicago, are pioneers of CAD. Acharya UR, Zheng B and Chan HP are the most prolific authors. Institute of Electrical and Electronics Engineers Transactions on Medical Imaging focuses on CAD and publishes the most articles. New computer technologies related to CAD are in the forefront of attention. Currently, CAD is used extensively in breast diseases, pulmonary diseases and brain diseases. CONCLUSION: Expanding the spectrum of CAD-related diseases is a possible future research trend. How to overcome the lack of large sample datasets and establish a universally accepted standard for the evaluation of CAD system performance are urgent issues for CAD development and validation. In conclusion, this paper provides valuable information on the current state of CAD research and future developments.

Time to change? Present and prospects of hemorrhoidal classification.

As a common benign anal condition, the high incidence and recurrence of hemorrhoids pose challenges for both patients and doctors. The classification of hemorrhoids plays a crucial role in assessing, diagnosing, and treating the condition. By using appropriate classification and corresponding treatment strategies, we can achieve higher cure rates and lower recurrence rates of hemorrhoids. Since the introduction of the Miles classification in 1919, various classifications have been developed, which include objective classifications based on anatomical or instrumental assessment and subjective classifications based on symptoms and patient sensations. These classifications aim to accurately evaluate the condition. In this study, we discuss the evaluation values of each classification in terms of their advantages, disadvantages, treatment relevance, reproducibility, practicality, and assessment value. We also analyze the significant and essential factors, principles of use, and components of assessment indicators of hemorrhoidal classification. This study proposes several strategies to address the limitations of current hemorrhoidal assessment methods. All these will provide a reference for the development regarding the assessment and classification of hemorrhoids and clinical diagnosis and management of hemorrhoids.

Comparative cost analysis of implanting devices in different cardiac resynchronization therapeutic strategies.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment option for heart failure patients. However, the implementation of triple-chamber pacemakers can be cost-prohibitive. His-Purkinje system pacing (HPSP) can also enable cardiac resynchronization, and it can be achieved with relatively inexpensive conventional pacemakers. HYPOTHESIS: This article aims to comparatively evaluate the cost of implanting devices in different CRT strategies to provide meaningful guidance for clinical decision-making by electrophysiologists. METHODS: Data was collected on the prices, designed life, and price/designed life of multiple mainstream models of CRT-P, CRT-D, dual-chamber pacemakers, and single-chamber pacemakers that were sold in the Chinese market in 2022. The prices, designed lives, and price/designed life of different pacemaker models were then compared. RESULTS: The costs of CRT-P and CRT-D (13008.44 ± 2752.30 USD and 22043.36 ± 3676.25 USD) were significantly higher than those of conventional pacemakers (dual-chamber: 11142.39 ± 4273.85 USD and single-chamber: 5634.28 ± 2032.80 USD) (p < .05). Additionally, the price/designed life of conventional pacemakers (dual-chamber: 839.63 ± 258.62 US dollar/year and single-chamber: 435.86 ± 125.44 US dollar/year) was significantly better than that of CRT-P and CRT-D (1386.91 ± 266.73 and 2585.53 ± 520.27 US dollar/year, respectively) (p < .05). CONCLUSION: Conduction system pacing (CSP)-based CRT is more cost-effective than BVP-based CRT. Furthermore, CSP-based CRT can achieve cardiac resynchronization with conventional pacemakers and may be a good option for HF patients who do not need defibrillation.

New Stable and Fast Ring-Polymer Molecular Dynamics for Calculating Bimolecular Rate Coefficients with an Example of OH + CH4.

The accurate and efficient calculation of the rate coefficients of chemical reactions is a key issue in the research of chemical dynamics. In this work, by applying the dimension-free ultrastable Cayley propagator, the thermal rate coefficients of a prototypic high dimensional chemical reaction OH + CH4 → H2O + CH3 in the temperature range of 200 to 1500 K are investigated with ring polymer molecular dynamics (RPMD) on a highly accurate full-dimensional potential energy surface. Kinetic isotope effects (KIEs) for three isotopologues of the title reaction are also studied. The results demonstrate excellent agreement with experimental data, even in the deep tunneling region. Especially, the Cayley propagator shows a high calculation efficiency with little loss of accuracy. The present results confirmed the applicability of the RPMD method, particularly the speed-up using a Cayley propagator, in theoretical calculations of bimolecular reaction rates.

Indocyanine green fluorescence-navigated thoracoscopy versus traditional inflation-deflation approach in precise uniportal segmentectomy: a short-term outcome comparative study.

Background: Uniportal video-assisted thoracoscopic surgery (VATS) segmentectomy is widely used in the field of thoracic surgery. However, anatomical variations in the bronchi and lung vessels may be critical obstacles during precise pulmonary segmentectomy. Thus, it is necessary to optimize uniportal VATS segmentectomy and to accurately identify the plane between lung segments by precisely transecting the bronchi and blood vessels of the lung segments. The indocyanine green fluorescence (ICGF)-based method has the potential to be a feasible and effective technique to facilitate the uniportal VATS segmentectomy. The present study aims at comparing the short-term outcomes of ICGF versus the traditional inflation-deflation method for uniportal VATS segmentectomy. Methods: The perioperative clinical data in 200 consecutive patients undergoing uniportal VATS segmentectomy from December 2018 to August 2020 at Shanghai Chest Hospital were analyzed retrospectively. The targeted segment structures were identified and dissected precisely by using ICGF-based (N=100) or the traditional inflation-deflation (N=100) methods. The parameters of intraoperative blood loss and operation time, postoperative drainage volume, air leakage time, drainage tube retention time, length of hospital stay, and complications in the ICGF group were collected. Further, the operation time between the ICGF and the inflation-deflation groups was compared. The data summary and statistical analysis were performed by SPSS 19.0. P value <0.05 was considered statistically significant. Results: No massive hemorrhage, hypoxemia, allergy, conversion to lobectomy, or wedge resection was noted during the surgery. ICGF groups resulted in a shorter operative time (90±11.46 vs. 118±10.59 min, P<0.001). No postoperative complications were observed, e.g., bronchopleural fistula, hemoptysis, or atelectasis. All patients were discharged as routinely scheduled. No disease recurrence or metastasis was found during the follow-ups. Conclusions: Our study indicated that the ICGF-based navigation approach is a simple, effective, and reliable technique that can greatly facilitate the uniportal VATS segmentectomy.

[Comparison of locking plate and intramedullary nail in treatment of Neer two- and three-part fractures of the proximal humerus in the elderly].

Objective: To compare the effectiveness of locking plate and intramedullary nail in treatment of Neer two- and three-part fractures of the proximal humerus in the elderly. Methods: A retrospective analysis was conducted on 86 elderly patients with Neer two- and three-part fractures of the proximal humerus met the selection criteria between January 2015 and December 2018. Forty-six patients were treated with locking plate fixation (locking plate group), and 40 patients with intramedullary nail fixation (intramedullary nail group). There was no significant difference in gender, age, cause of injury, fracture side and type, time from injury to operation, and comorbidities between the two groups ( P>0.05). Visual analogue scale (VAS) score, American Shoulder and Elbow Surgery (ASES) score, Constant-Murley score, and shoulder range of motion (forward flexion, abduction, and external rotation) were compared between the two groups. X-ray films were taken to assess the fracture healing, and the neck-shaft angle was measured at 2 days after operation and at last follow-up, and the difference between the two time points was calculated. Results: Patients in both groups were followed up 18-40 months, with an average of 30.4 months. There was no significant difference in follow-up time between the two groups ( t=-0.986, P=0.327). X-ray films reexamination showed that the fractures of two groups healed, and the healing time was (11.3±2.1) weeks in locking plate group and (10.3±2.0) weeks in intramedullary nail group, which had significant difference between the two groups ( t=2.250, P=0.027). The difference of neck-shaft angle was (7.63±7.01)° in locking plate group and (2.85±2.82)° in intramedullary nail group, which had significant difference between the two groups ( t=4.032, P<0.001). There was no significant difference in Constant-Murley score, ASES score, VAS score, and shoulder range of motion between the two groups at last follow-up ( P>0.05). Complications occurred in 13 cases (28.3%) of locking plate group and in 4 cases (10.0%) of intramedullary nail group, and the difference between the two groups was significant ( χ 2=4.498, P=0.034). Conclusion: Both locking plates and intramedullary nails can be used for the treatment of Neer two- and three-part fractures of the proximal humerus in the elderly. The intramedullary nail fixation surgery is more minimally invasive, which has fewer postoperative complications and faster fracture healing.

Design, synthesis, and preclinical evaluation of a novel bifunctional macrocyclic chelator for theranostics of cancers.

PURPOSE: This study was to design and synthesize a novel bifunctional chelator, named Dar, primarily validated by conjugating to tumor targeting motifs, labeled with radiometals, and performed preclinical evaluation of tumor imaging and cancer therapy in murine tumor models. METHOD: The designed Dar was synthesized and characterized by X-ray crystallography, 1H/13C NMR, and mass spectrometry. Dar-PSMA-617 was conjugated and radiolabeled with 68Ga, 177Lu, and 89Zr. The in vivo behavior of 68 Ga/89Zr-labeled Dar-PSMA-617 were evaluated using micro-PET imaging and biodistribution from image quantitation and tissue radioactivity counting, with 68Ga/89Zr-labeled NOTA/DOTA/DFO-PSMA-617 analogs as controls, respectively. The [177Lu]-Dar-PSMA-617, with [177Lu]-DOTA-PSMA-617 as control, was evaluated in competitive cell uptake, tumor cell internalization, and efflux studies. The treatment efficacy of [177Lu]Lu-Dar-PSMA-617, with [177Lu]Lu-DOTA-PSMA-617 as control, was evaluated in PSMA-positive LNCaP tumor-bearing mice. In addition, the ability of Dar for radiolabeling nanobody was tested by conjugating Dar to KN035 nanobody. The resultant [89Zr]Zr-Dar-KN035 nanobody, with [89Zr]Zr-DFO-KN035 as control, was evaluated by micro-PET imaging and biodistribution in a mouse model bearing MC38&MC38-hPD-L1 colon cancer. RESULTS: 68Ga, 89Zr, and 177Lu-radiolabeled Dar-PSMA-617 complexes were able to be produced under mild condition with high radiochemical yield and purity successfully. [177Lu]Lu-Dar-PSMA-617 had higher cellular uptake yet similar internalization and efflux properties in LNCaP cells, as compared to [177Lu]Lu-DOTA-PSMA-617. Micro-PET images demonstrated significantly higher tumor uptake of [68Ga]Ga-Dar-PSMA-617, than that of the analog [68Ga]Ga-DOTA-PSMA-617. The tumor uptake values of [68Ga]Ga-Dar-PSMA-617 at multiple time points are comparable to that of [68Ga]Ga-NOTA-PSMA-617, although a higher and persistently prolonged kidney retention was resulted in during the study period. The Dar chelator can also successfully mediate the radiolabeling with 89Zr, while the resultant [89Zr]Zr-Dar-PSMA-617 demonstrated a similar biodistribution with [89Zr]Zr-DFO-PSMA-617 measured at 96 h p.i. The treatment with [177Lu]Lu-Dar-PSMA-617 significantly inhibited the tumor growth, showing much better efficacy than that of [177Lu]Lu-DOTA-PSMA-617 at the same injected radioactivity and mass dose. Dar was covalently linked to KN035 nanobody and enabled radiolabeling with 89Zr in high yield and radiochemical purity at room temperature. The resultant [89Zr]Zr-Dar-KN035, with [89Zr]Zr-DFO-KN035 as control, demonstrated superior tumor uptake and detection capability in PET imaging studies. CONCLUSION: The Dar, as a novel bifunctional chelator for medicating the labeling of radiometals onto tumor targeting carriers, was successfully synthesized and chemically characterized. Test radiolabeling, on PSMA-617 and a nanobody as tool targeting molecule carriers, demonstrated the Dar has potential as a universal bifunctional chelator for radiolabeling various radiometals (at least 68Ga, 177Lu, and 89Zr tested) commonly used for clinical imaging and therapy. Using a novel Dar chelator results in altered in vivo behavior of the carriers even though labeled with the same nuclide. This capability makes Dar an alternative to the existing choices for radiolabeling new carrier molecules with various radiometals, especially the radiometals with large radius.

Nucleophilic radiosynthesis of boron neutron capture therapy-oriented PET probe [18F]FBPA using aryldiboron precursors.

A reliable copper-mediated nucleophilic radiosynthesis of the PET imaging probe [18F]FBPA was developed using novel aryldiboron precursors. The carrier-free [18F]FBPA with radiochemical purity >99% was prepared routinely via the two-step synthesis with an automatic module and can be used for clinical PET imaging of tumours.

Fibular strut allograft influences reduction and outcomes after locking plate fixation of comminuted proximal humeral fractures in elderly patients: a retrospective study.

BACKGROUND: Proximal humeral fractures (PHFs) are the third most commonly occurring fractures in elderly patients. Most of these fractures can be treated with conservative methods, but the optimal surgical treatment strategy for unstable fractures in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes between locking compression plate (LCP) fixation and LCP fixation with fibular allograft implantation for the treatment of comminuted PHFs. METHODS: We retrospectively reviewed 60 patients (mean age, 72.75 years) with closed 3- or 4-part fractures, and a minimum of 2 years of follow-up. Fracture reduction was quantitatively determined by humeral head height (HHH) and neck-shaft angle (NSA). The clinical outcome was evaluated by Constant-Murley score (CMS) and American Shoulder and Elbow Surgeons (ASES) score. RESULT: The average radiological changes were higher in the LCP group than in the locking plate with fibular allograft group (HHH of 4.16 mm vs 1.18 mm [p < 0.001] and NSA of 9.94° versus 3.12° [p < 0.001]) . The final average outcome scores were lower in the LCP group than in the FA group (CMS of 73.00 vs 78.96 [p = 0.024] and ASES score of 72.80 vs 78.64 [p = 0.022]). The FA group showed better forward elevation (p = 0.010) and abduction (p = 0.002); however, no significant differences were observed for shoulder external rotation or internal rotation. The number of complications was higher in the LCP group (28.57%) than in the FA group (1.2%) (p < 0.001). CONCLUSION: For comminuted PHFs in elderly patients, LCP fixation combined with a fibular allograft is reasonable option to ensure satisfactory radiological and clinical outcomes. TRIAL REGISTRATION: ZDYJLY(2018)New-9 . Name of registry: IEC for clinical Research of Zhongda Hospital, Affiliated to Southeast University. Date of registration: 2018-05-17.

Site-dependent fluorescence enhanced polymers with a self-restricted GFP chromophore for living cell imaging.

The ß-barrel structure of green fluorescent protein (GFP) provides a confined environment to enhance its fluorescence efficiency. Inspired by the unique structure of GFP, we reported a self-restricted GFP chromophore analogue which was rationally grafted onto the middle or the terminal of poly(ethylene glycol)-block-poly(N-isopropyl acrylamide) (PEG-b-PNIPAM) via click chemistry to obtain PEG-GA-PNIPAM and PEG-PNIPAM-GA (GA: MeOBDPI). These structures were characterized through NMR, GPC, and FT-IR. By varying the length of PNIPAM and the location of the GFP chromophore, self-assembly behaviour and fluorescence intensity were correspondingly changed. PEG-GA-PNIPAM and PEG-PNIPAM-GA were assembled into nano-sized spherical micelles above the low critical solution temperature (LCST). The size of the micelles increased with the length of the PNIPAM block. These optical properties were carefully evaluated by UV-Vis and fluorescence spectroscopy. The results indicated that increasing the length of the PNIPAM block enhanced the fluorescence in water, and PEG-PNIPAM74-GA has more remarkable fluorescence intensity than PEG-GA-PNIPAM106 in living cells such as MCF-7 cells. Furthermore, the fluorescence behaviour of PEG-PNIPAM74-GA was studied in MCF-7 cells and L929 cells. The result showed that PEG-PNIPAM74-GA was mostly located in the cytoplasm. Compared with the CellTracker™ Red CMTPX dye, it could enter into MCF-7 cells and L929 cells more easily in DMEM with 10% FBS. Therefore, PEG-PNIPAM74-GA has potential application prospects for living cell imaging.

Association between connexin 40 and potassium voltage-gated channel subfamily A member 5 expression in the atrial myocytes of patients with atrial fibrillation.

Structural and electrical remodeling within the atrium mediate the pathogenesis of atrial fibrillation (AF). Two key genes that sever a role in this remodeling are connexin 40 (Cx40) and potassium voltage-gated channel subfamily A member 5 (KCNA5), respectively. Electrical remodeling is considered to induce structural remodeling during AF. In the present study, the left atrial appendage section and atrial myocytes of patients with AF were evaluated. It was observed that Cx40 and KCNA5 mRNA (P<0.05) and protein (P<0.01) expression was significantly downregulated in AF compared with rheumatic heart disease. In addition, a positive correlation between the mRNA expression Cx40 and KCNA5 was observed in the atrial myocytes of patients with AF (P<0.05; r=0.42). The association between Cx40 and KCNA5 expression was subsequently investigated in primary cultured atrial myocytes using siRNA transfection. In atrial myocytes, downregulation of Cx40 inhibited the expression of KCNA5. Similarly, silencing of KCNA5 suppressed the expression of Cx40. These results indicate that synergistic regulation may occur between Cx40 and KCNA5 expression. Furthermore, the combined effects of electrical and structural remodeling in the atrial myocytes of patients with AF may contribute to the pathogenesis of AF.

Linoleic acid induces red blood cells and hemoglobin damage via oxidative mechanism.

Hidden blood loss typically occurs following total hip arthroplasty (THA) and total knee arthroplasty (TKA) and is thought to be related to free fatty acid (FFA). To study the effect of linoleic acid on red blood cells and to examine the pathogenesis of hidden blood loss in vivo, we generated an animal model by injecting linoleic acid into the tail veins of rats. We collected blood samples and determined red blood cell count (RBC) and levels of hemoglobin (Hb), as well as the oxidation and reducing agents in the blood, including glutathione peroxidase (GSH-PX), total superoxide dismutase (T-SOD), hydrogen peroxide (H2O2), and ferryl hemoglobin (Fe4+=O2-), which is generated by the oxidation of Hb. Hidden blood loss occurred when linoleic acid was administered at a concentration of 60 mmol/L; RBC and Hb levels were significantly reduced by 24 h post-injection. This was followed by erythrocyte deformation, reduced activity of GSH-PX and T-SOD, and decreased levels of H2O2. This was accompanied by an increase in ferryl species, which likely contributes to oxidative stress in vivo. Our findings suggest that linoleic acid enhances acute red blood cell injury. Hb and RBC began to increase by 72 h, potentially resulting from linoleic acid metabolism. Thus, elevated levels of linoleic acid in the blood cause acute oxidative damage to red blood cells, eventually leading to partial acute anemia. These findings highlight the pathophysiology underlying hidden blood loss.

[Effects of bidirectional EphB4-EphrinB2 signaling on bone remodeling].

Bidirectional Eph-Ephrin signaling as a focal point of research in cell-cell communications is critical for generation of nerves and vesssels as well as invation and metastasis of tumor cells. The roles for Ephrin-Eph bidirectional signaling in bone remodeling were important. EphrinB2 is expressed on osteoblasts and EphB4 is expressed on osteoclasts. Forward signaling through the EphB4 receptor into mesenchymal precursors promotes osteoblast differentiation, while reverse signaling through the EphrinB2 ligand into osteoclast suppresses differentiation. Signaling between the ligand EphrinB2 and the receptors EphB4 explains bidirectional signaling between osteoblasts and osteoclasts,bone absorption and remodeling, which may lay a theoretical foundation for identifying drug targeting and preventing and treating bone loss.