A Gradient Composite Structure Enables a Stable Microsized Silicon Suboxide-Based Anode for a High-Performance Lithium-Ion Battery.

The practical application of microsized anodes is hindered by severe volume changes and fast capacity fading. Herein, we propose a gradient composite strategy and fabricate a silicon suboxide-based composite anode (d-SiO@SiOx/C@C) consisting of a disproportionated microsized SiO inner core, a homogeneous composite SiOx/C interlayer (x ≈ 1.5), and a highly graphitized carbon outer layer. The robust SiOx/C interlayer can realize a gradient abatement of stress and simultaneously connect the inner SiO core and carbon outer layer through covalent bonds. As a result, d-SiO@SiOx/C@C delivers a specific capacity of 1023 mAh/g after 300 cycles at 1 A/g with a retention of >90% and an average Coulombic efficiency of >99.7%. A full cell assembled with a LiNi0.8Co0.15Al0.05O2 cathode displays a remarkable specific energy density of 569 Wh/kg based on total active materials as well as excellent cycling stability. Our strategy provides a promising alternative for designing structurally and electrochemically stable microsized anodes with high capacity.

Ace Deficiency Induces Intestinal Inflammation in Zebrafish.

Inflammatory bowel disease (IBD) is a nonspecific chronic inflammatory disease resulting from an immune disorder in the intestine that is prone to relapse and incurable. The understanding of the pathogenesis of IBD remains unclear. In this study, we found that ace (angiotensin-converting enzyme), expressed abundantly in the intestine, plays an important role in IBD. The deletion of ace in zebrafish caused intestinal inflammation with increased expression of the inflammatory marker genes interleukin 1 beta (il1b), matrix metallopeptidase 9 (mmp9), myeloid-specific peroxidase (mpx), leukocyte cell-derived chemotaxin-2-like (lect2l), and chemokine (C-X-C motif) ligand 8b (cxcl8b). Moreover, the secretion of mucus in the ace-/- mutants was significantly higher than that in the wild-type zebrafish, validating the phenotype of intestinal inflammation. This was further confirmed by the IBD model constructed using dextran sodium sulfate (DSS), in which the mutant zebrafish had a higher susceptibility to enteritis. Our study reveals the role of ace in intestinal homeostasis, providing a new target for potential therapeutic interventions.

Vibrational spectroscopy for decoding cancer microbiota interactions: Current evidence and future perspective.

The role of human microbiota in cancer initiation and progression is recognized in recent years. In order to investigate the interactions between cancer cells and microbes, a systematic analysis using various emerging techniques is required. Owing to the label-free, non-invasive and molecular fingerprinting characteristics, vibrational spectroscopy is uniquely suited to decode and understand the relationship and interactions between cancer and the microbiota at the molecular level. In this review, we first provide a quick overview of the fundamentals of vibrational spectroscopic techniques, namely Raman and infrared spectroscopy. Next, we discuss the emerging evidence underscoring utilities of these spectroscopic techniques to study cancer or microbes separately, and share our perspective on how vibrational spectroscopy can be employed at the intersection of the two fields. Finally, we envision the potential opportunities in exploiting vibrational spectroscopy not only in basic cancer-microbiome research but also in its clinical translation, and discuss the challenges in the bench to bedside translation.

Bmp4 in Zebrafish Enhances Antiviral Innate Immunity through p38 MAPK (Mitogen-Activated Protein Kinases) Pathway.

Bone morphogenetic proteins (BMPs) are a group of structurally and functionally related signaling molecules that comprise a subfamily, belonging to the TGF-ß superfamily. Most BMPs play roles in the regulation of embryonic development, stem cell differentiation, tumor growth and some cardiovascular and cerebrovascular diseases. Although evidence is emerging for the antiviral immunity of a few BMPs, more BMPs are needed to determine whether this function is universal. Here, we identified the zebrafish bmp4 ortholog, whose expression is up-regulated through challenge with grass carp reovirus (GCRV) or its mimic poly(I:C). The overexpression of bmp4 in epithelioma papulosum cyprini (EPC) cells significantly decreased the viral titer of GCRV-infected cells. Moreover, compared to wild-type zebrafish, viral load and mortality were significantly increased in both larvae and adults of bmp4-/- mutant zebrafish infected with GCRV virus. We further demonstrated that Bmp4 promotes the phosphorylation of Tbk1 and Irf3 through the p38 MAPK pathway, thereby inducing the production of type I IFNs in response to virus infection. These data suggest that Bmp4 plays an important role in the host defense against virus infection. Our study expands the understanding of BMP protein functions and opens up new targets for the control of viral infection.

Tuning Mass Transport in Electrocatalysis Down to Sub-5†nm through Nanoscale Grade Separation.

Nano and single-atom catalysis open new possibilities of producing green hydrogen (H2 ) by water electrolysis. However, for the hydrogen evolution reaction (HER) which occurs at a characteristic reaction rate proportional to the potential, the fast generation of H2 nanobubbles at atomic-scale interfaces often leads to the blockage of active sites. Herein, a nanoscale grade-separation strategy is proposed to tackle mass-transport problem by utilizing ordered three-dimensional (3d) interconnected sub-5 nm pores. The results reveal that 3d criss-crossing mesopores with grade separation allow efficient diffusion of H2 bubbles along the interconnected channels. After the support of ultrafine ruthenium (Ru), the 3d mesopores are on a superior level to two-dimensional system at maximizing the catalyst performance and the obtained Ru catalyst outperforms most of the other HER catalysts. This work provides a potential route to fine-tuning few-nanometer mass transport during water electrolysis.

Elevated neutrophil counts, triglycerides, monocyte/high-density lipoprotein (HDL) ratios, and lower HDL in patients with retinal vein occlusion.

Introduction Aim to evaluate associations of peripheral blood immune cells and blood lipid profile levels with retinal vein occlusion (RVO). Methods This retrospective study included 127 patients with RVO and 108 controls. Patients with RVO were divided into branch RVO (BRVO), central RVO (CRVO), ischemic RVO, or non-ischemic RVO groups. Medical records were collected and analyzed. Results The RVO group had higher mean neutrophil, triglyceride (TG), and monocyte/high-density lipoprotein (HDL) ratio (MHR) levels and lower HDL levels (P=0.037, P<0.001, P=0.004, and P=0.002, respectively). TG and MHR levels were significantly higher in the BRVO and CRVO groups compared with the control group (P<0.001, P=0.016, respectively), but there was no difference in BRVO and CRVO group (P=0.972, P=0.916, respectively). Mean HDL levels were significantly lower in the BRVO and CRVO groups than in the control group (P=0.005), but the difference between the BRVO group and CRVO group was not significant (P=0.290). Neutrophils, TG, and MHR were independent risk factors for RVO. HDL was an independent protective factor for RVO. Age was an independent risk factor for ischemic RVO. Conclusions Lower HDL, and higher neutrophil, TG and MHR levels are associated with RVO. Age is an independent risk factor for ischemic RVO.

Cancer cells display increased migration and deformability in pace with metastatic progression.

In this study, we explored the relation between metastatic states vs the capacity of confined migration, amoeboid transition, and cellular stiffness. We compared across an isogenic panel of human breast cancer cells derived from MDA-MB-231 cells. It was observed that cells after lung metastasis have the fastest migration and lowest stiffness, with a significantly higher capacity to transition into an amoeboid mode. Our findings illustrate that metastasis is a selective process favoring motile and softer cells. Moreover, the observation that circulating tumor cells resemble the parental cell line, but not lung-metastatic cells, suggests that cells with higher deformability and motility are likely selected during extravasation and colonization.

Lithium from breast-milk inhibits thyroid iodine uptake and hormone production, which are remedied by maternal iodine supplementation.

BACKGROUND: Lithium is especially taken as a maintenance medication for Bipolar Disorder. In women with bipolar disorder, lithium is often effective during postpartum period, but breast-feeding for medicated mothers is controversial because of harmful effects for her child. At present, the biological mechanisms of lithium are not well-understood, affecting its usage and overall health implications. PROCEDURE: We developed a rat lithium and breast-feeding model at human therapeutic levels to study the effects of lithium exposure through breast-milk on pups' thyroid function. Novel laser analytical spectroscopy, along with traditional blood and immunohistochemical tests, were applied to further investigate the mechanisms behind the thyroid dysfunction. Maternal iodine supplementation was evaluated as a therapeutic method to address the pups' thyroid dysfunction. RESULTS: Pups exposed to lithium via breastmilk, even with the dam on a sub-therapeutic level, experienced weight gain, reduced blood thyroxine (T4 ), and elevated blood urea nitrogen, indicating effects on thyroid and kidney function. We show that lithium inhibited iodine uptake by thyroid follicles, initiating a mechanism that reduced iodination of tyrosine, thyroglobulin cleavage, and thyroid hormone production. Importantly, infant thyroid function can be significantly improved by administering supplementary iodine to the medicated dam's diet during breast-feeding. CONCLUSION: These results elucidate the mechanisms of lithium in thyroid function, provide valuable information on use postpartum, and suggest a clinically applicable remedy to side-effects. The results are particularly important for patients (and their infants) who respond well to lithium and need, or choose, to breast-feed.

Treatment of diaphyseal forearm defects caused by infection using Ilizarov segmental bone transport technique.

BACKGROUND: The Ilizarov segmental bone transport technique can be applied in the reconstruction of the bone defects with less invasive fashion and more versatility compared to other methods, while most studies were focused on the lower extremity. The purpose of this study was to evaluate the effectiveness of the Ilizarov segmental bone transport technique in the treatment of diaphyseal forearm bone defects caused by infection. METHODS: This study included 12 patients with diaphyseal forearm bone defects caused by infection, who underwent bone transport procedures using the monolateral external fixator at our institution from January 2010 to January 2018, including 10 males and 2 females with a mean age of 39 years (range 23-57 years). Patient's demographic data and clinical outcomes at least two years follow-up after removing the external fixator were collected and retrospectively analyzed. The functional results were evaluated by the questionnaire of Disability of Arm, Shoulder and Hand (DASH) and the modified Mayo wrist score (MWS) at the final follow-up. RESULTS: There were 10 radii and 2 ulnae bone transport procedures collected. The average defect size was 5.1 cm (4-6.5 cm). All patients were successfully followed up with a mean period of 28.2 months (24 to 36 months) and achieved infection-free union. There was no recurrence of infection observed. The mean external fixation time was 232.6 days (182 to 276 days), and the mean external fixation index was 46.3 days/cm (40.9 to 61.8 days/cm). The mean DASH score was 30.6(18 to 49) preoperative, while 13.8 (5 to 26) at the final follow-up. The average modified MWS improved from 68.8 (55 to 80) pre-operatively to 83.8 (65 to 90) at the final follow-up. All the differences between the preoperative and final scores were statistically significant (p < 0.05). Almost all the patients achieved satisfactory clinical outcomes and were able to perform activities of daily living. CONCLUSIONS: Ilizarov segmental bone transport technique is an alternative and effective method for the treatment of diaphyseal forearm bone defects caused by infection, and this method acquired satisfactory clinical outcomes.

Long bone fracture reduction and deformity correction using the hexapod external fixator with a new method: a feasible study and preliminary results.

BACKGROUND: The hexapod external fixator (HEF), such as the Taylor spatial frame (TSF), offering the ability of multidirectional deformities correction without changing the structure, whereas there are so many parameters for surgeons to measure and subjective errors will occur inevitably. The purpose of this study was to evaluate the effectiveness of a new method based on computer-assisted three-dimensional (3D) reconstruction and hexapod external fixator for long bone fracture reduction and deformity correction without calculating the parameters needed by the traditional usage. METHODS: This retrospective study consists of 25 patients with high-energy tibial diaphyseal fractures treated by the HEF at our institution from January 2016 to June 2018, including 22 males and 3 females with a mean age of 42 years (range 14-63 years). Hexapod external fixator treatments were conducted to manage the multiplanar posttraumatic deformities with/without poor soft-tissue that were not suitable for internal fixation. Computer-assisted 3D reconstruction and trajectory planning of the reduction by Mimics were applied to perform virtual fracture reduction and deformity correction. The electronic prescription derived from the length changes of the six struts were calculated by SolidWorks. Fracture reduction was conducted by adjusting the lengths of the six struts according to the electronic prescription. Effectiveness was evaluated by the standard anteroposterior (AP) and lateral X-rays after reduction. RESULTS: All patients acquired excellent functional reduction and achieved bone union in our study. After correction, the mean translation (1.0 ± 1.1 mm) and angulation (0.8 ± 1.2°) on the coronal plane, mean translation (0.8 ± 1.0 mm) and angulation (0.3 ± 0.8°) on the sagittal plane were all less than those (6.1 ± 4.9 mm, 5.2 ± 3.2°, 4.2 ± 3.5 mm, 4.0 ± 2.5°) before correction (P < 0.05). CONCLUSIONS: The computer-assisted three-dimensional reconstruction and hexapod external fixator-based method allows surgeons to conduct long bone fracture reduction and deformity correction without calculating the parameters needed by the traditional usage. This method is suggested to apply in those unusually complex cases with extensive soft tissue damage and where internal fixation is impossible or inadvisable.

Prognostic factors in patients who underwent surgery for common peroneal nerve injury: a nest case-control study.

BACKGROUND: Common peroneal nerve (CPN) injury is one of the most common nerve injuries in the lower extremities and the motor functional recovery of injured common peroneal nerve (CPN) was often unsatisfactory, the mechanism of which is still controversial. The purpose of this retrospective study was to determine the prognostic factors in patients who underwent surgery for CPN injury and provide a tool for clinicians to assess the patients' prognosis. METHODS: This is a retrospective cohort study of all patients who underwent neural exploration for injured CPN from 2009 to 2019. A total of 387 patients with postoperative follow-up more than 12 months were included in the final analysis. We used univariate logistics regression analyses to explore explanatory variables which were associated with recovery of neurological function. By applying multivariable logistic regression analysis, we determined variables incorporated into clinical prediction model, developed a nomogram by the selected variables, and then assessed discrimination of the model by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: The case group included 67 patients and the control group 320 patients. Multivariate logistic regression analysis showed that area (urban vs rural, OR = 3.35), occupation("blue trouser" worker vs "white-trouser" worker, OR = 4.39), diabetes (OR = 11.68), cardiovascular disease (OR = 51.35), knee joint dislocation (OR = 14.91), proximal fibula fracture (OR = 3.32), tibial plateau fracture (OR = 9.21), vascular injury (OR = 5.37) and hip arthroplasty (OR = 75.96) injury increased the risk of poor motor functional recovery of injured CPN, while high preoperative muscle strength (OR = 0.18) and postoperative knee joint immobilization (OR = 0.11) decreased this risk of injured CPN. AUC of the nomogram was 0.904 and 95% CI was 0.863-0.946. CONCLUSIONS: Area, occupation, diabetes, cardiovascular disease, knee joint dislocation, proximal fibula fracture, tibial plateau fracture, vascular injury and hip arthroplasty injury are independent risk factors of motor functional recovery of injured CPN, while high preoperative muscle strength and postoperative knee joint immobilization are protective factors of motor functional recovery of injured CPN. The prediction nomogram can provide a tool for clinicians to assess the prognosis of injured CPN.

Management of high-energy tibial shaft fractures using the hexapod circular external fixator.

BACKGROUND: The hexapod external fixator (HEF) is increasingly used for high-energy tibial shaft fracture care as more general orthopedic surgeons are gaining expertise of this versatile device. The purpose of this study was to evaluate the clinical effectiveness of the HEF for definitive management in patients with high-energy tibial shaft fractures. METHODS: The study was conducted on 34 patients with tibial shaft fractures who were admitted or referred to our institution and consented to HEF treatment from Jan 2016 to June 2019, including 27 males and 7 females with a mean age of 39 years (range 18 to 65 years). Patients' clinical and radiological data, and the final clinical outcomes at a minimum of 12 months follow-up were collected and retrospectively analyzed. All complications were documented according to Paley's classification. The clinical outcomes were evaluated using the Association for the Study and Application of the Method of Ilizarov criteria (ASAMI) at the last clinical visit. RESULTS: All patients remained in the HEF for a mean of 26 weeks (range 15 to 52 weeks) and acquired complete bone union. The satisfactory alignment was achieved in all patients, and all the patients were able to perform daily activities with no difficulty at the last clinical visit. Complications included pin tract infection (44%), delayed union (6%), nonunion (3%), and joint stiffness (3%). The ASAMI bony result was excellent in 31 patients and good in 3. The ASAMI functional result was excellent in 27 patients, good in 6, and fair in 1. CONCLUSIONS: Definitive management using the hexapod external fixator is an alternative and effective method for high-energy tibial shaft fractures, including technical advantages of early trauma-control, the versatility of achieving excellent alignment, and the continuity of device until bone union.

Acetylcholinesterase-catalyzed silver deposition for ultrasensitive electrochemical biosensing of organophosphorus pesticides.

Herein, an electrochemical biosensing platform with acetylcholinesterase (AChE)-catalyzed silver deposition was developed for the ultrasensitive detection of organophosphorus pesticides (OPs). The biosensing mechanism is based on the fact that AChE can catalyze the rapid hydrolysis of indoxyl acetate to form hydroxyindole, which in turn reduces silver ions to metallic silver, resulting in the deposition of silver on the gold electrode. Upon sweeping positive voltages on the gold electrode using linear sweep voltammetry (LSV), the deposited silver on the gold electrode surface undergoes a rapid electrochemical oxidation reaction. Due to its lower oxidation potential under facile conditions with a relatively sharp peak, a small amount of deposited silver generated from AChE-catalysis could result in a significant change in the LSV response. In the presence of OPs, the AChE-catalyzed hydrolysis of indoxyl acetate is blocked, and then the silver deposition on the gold electrode declines, leading to a remarkable decrease in the LSV response and, thus producing a large signal output for the ultrasensitive detection of chlorpyrifos, a proof-of-concept OP in this work. The change in the LSV peak current intensity is linearly correlated with the logarithmic value of the chlorpyrifos concentration ranging from 10 pM to 10 nM with a low detection limit of 4.0 pM. To the best of our knowledge, this is the first example of a biosensing platform for ultrasensitive OP assay using AChE-controlled silver deposition to enhance the output of electronic signals.

Complications of bone transport technique using the Ilizarov method in the lower extremity: a retrospective analysis of 282 consecutive cases over 10 years.

BACKGROUND: The treatment of large bone defects in lower limbs is a serious challenge for orthopedic surgeons and patients. The bone transport technique using the Ilizarov method has become the main treatment option for the reconstruction of bone defect. However, inevitable difficulties and complications related to bone transport technique have been reported by many studies. The purpose of this study was to evaluate the effectiveness and complications of bone transport technique using Ilizarov method in the treatment of bone defect of lower extremity. METHODS: The study was conducted on 282 patients who underwent bone transport procedures using Ilizarov method at our institution from January 2007 to June 2017. Patient's demographic data, complications and clinical outcomes at minimum of 2 years follow-up were collected and retrospectively analyzed. All difficulties that related to bone transport were documented according to Paley's classification. The clinical outcomes were evaluated using Association for the Study and Application of the Method of Ilizarov criteria (ASAMI) at last clinical visit. RESULTS: There were 243 male and 39 females with a mean age of 40 years (range 18-65 years). The mean defect was 6.56 ± 2.15 cm, whereas single level transport in 221 cases and double level transport in 61 cases. There were 189 problems, 166 obstacles and 406 complications (257 minor and 149 major complications), and the average complication rate per patients consists of 0.91 minor and 0.53 major complications. The top five complications were pin-site infection (65.96%), axial deviation (40.78%), joint stiffness (23.76%), soft tissue incarceration (22.34%) and delayed union of the docking site (13.48%).The ASAMI bony result was excellent in 233 patients, good in 32, fair in 5 and poor in 12. The ASAMI functional result was excellent in 136 patients, good in 88, fair in 47, poor in 11. CONCLUSION: Bone transport is a reliable method for reconstruction of bone defects in the femur and tibia. Awareness of predictable complications is beneficial to prevent or early detection of the expected complication which can improve the risk-benefit balance.

Silicon oxides: a promising family of anode materials for lithium-ion batteries.

Silicon oxides have been recognized as a promising family of anode materials for high-energy lithium-ion batteries (LIBs) owing to their abundant reserve, low cost, environmental friendliness, easy synthesis, and high theoretical capacity. However, the extended application of silicon oxides is severely hampered by the intrinsically low conductivity, large volume change, and low initial coulombic efficiency. Significant efforts have been dedicated to tackling these challenges towards practical applications. This Review focuses on the recent advances in the synthesis and lithium storage properties of silicon oxide-based anode materials. To present the progress in a systematic manner, this review is categorized as follows: (i) SiO-based anode materials, (ii) SiO2-based anode materials, (iii) non-stoichiometric SiOx-based anode materials, and (iv) Si-O-C-based anode materials. Finally, future outlook and our personal perspectives on silicon oxide-based anode materials are presented.

Zebrafish fatty acids receptor Gpr84 enhances macrophage phagocytosis.

GPR84 was identified as a receptor for medium-chain fatty acids with carbon chain lengths of 9-14. It has previously been reported that lipopolysaccharide (LPS) induces significantly up-regulation of zebrafish gpr84, and zebrafish gpr84 overexpression markedly increased the LPS-stimulated production of the cytokine IL-12. Here we expanded on these studies to further investigate the roles of zebrafish Gpr84 in immune reaction. Flow cytometric assay was used to assess the effects of zebrafish Gpr84 on the phagocytosis of bacteria by macrophages. It was found that overexpression of zebrafish gpr84 significantly increased both the phagocytic ability (PA) and phagocytic index (PI) values of the macrophages engulfing the bacteria, suggesting that zebrafish Gpr84 was able to promote the phagocytosis of bacteria by the macrophages. The data proves the direct effect of Gpr84 in immune reaction.

Direct-laser-writing of three-dimensional porous graphene frameworks on indium-tin oxide for sensitive electrochemical biosensing.

The fabrication of graphene electrode with three-dimensional (3D) porous architecture would be highly desirable for electrochemical (bio-)sensing. Direct-laser-writing (DLW) on polyimide sheet has been recognized as an advance approach to pattern 3D porous graphene frameworks (3DPGFs)-based electrode. Herein, taking advantages of this straightforward and cost-effective DLW technique, we demonstrated the scalable and robust fabrication of a new type of 3DPGFs-based electrode patterned on the surface of indium-tin oxide (ITO) glass, denoted as 3DPGF@ITO. In this study, polyimide layer was synthesized on ITO glass surface not only to act as a sacrificial precursor for the in situ growth of 3DPGFs, but also to serve as a passivation layer for the effective separation of 3DPGFs working area and ITO contact pad. Importantly, the laser-induced 3DPGFs on ITO surface exhibit a 3D hierarchical and macroporous architecture consisting of interconnected multi-layered graphene sheets with large surface area and abundant edge-plane-like defective sites. These appealing features render the proposed 3DPGF@ITO electrode with marked improvement in electrochemical performance over traditional commercial electrodes. Finally, the developed 3DPGF@ITO electrode was successfully applied as a working electrode to selectively detect three important biospecies, namely, ascorbic acid, dopamine, and uric acid, in their ternary mixture with a high resolution of oxidation potentials. Thus, we envision that the 3DPGF@ITO electrode will open highly promising perspectives for the development of sensitive electrode-based (bio-)sensors.

Vinyl Functionalized Porous Silica Nanospheres Prepared by Poly(1-vinyl-2-pyrrolidone) Grafted Surface-Protected Selective Etching Strategy.

A new effective surface poly(1-vinyl-2-pyrrolidone) (PVP) grafted layer protected selective etching strategy has been used for preparing vinyl functionalized porous silica nanospheres (V-PSNSs). The main reaction mechanism was relied on the vinyl groups distributed on the surface of outer vinyl silica nanospheres (V-SiO2) which can be polymerized with another vinyl monomer, such as 1-vinyl-2-pyrrolidone (VP), in the presence of initiator. It was observed from the research results that only grafting PVP on the surface of outer vinyl silica nanospheres (V-SiO2) can V-PSNSs be obtained, because grafting PVP was able to protect outer V-SiO2 from being etched prior to inner pure silica (sSiO2). In addition, effect of the amounts of sSiO2@V-SiO2 as another monomer substrate on the formation of PVP grafted sSiO2@V-SiO2 (sSiO2@V-SiO2/PVP) was discussed. The results showed that the less of the sSiO2@V-SiO2 amounts, the thinner of the PVP grafted layer on the surface of sSiO2@V-SiO2, the poorer protection ability of the surface. In the present study, V-PSNSs with 29 m2g-1 of BET surface areas and 0.1 cm3g-1 pore volumes were successfully synthesized by grafting 0.3 g of VP on the surface of 0.3 g of sSiO2@V-SiO2 and subsequent etching.

AC Electroosmosis-Enhanced Nanoplasmofluidic Detection of Ultralow-Concentration Cytokine.

Label-free, nanoparticle-based plasmonic optical biosensing, combined with device miniaturization and microarray integration, has emerged as a promising approach for rapid, multiplexed biomolecular analysis. However, limited sensitivity prevents the wide use of such integrated label-free nanoplasmonic biosensors in clinical and life science applications where low-abundance biomolecule detection is needed. Here, we present a nanoplasmofluidic device integrated with microelectrodes for rapid, label-free analysis of a low-abundance cell signaling protein, detected by AC electroosmosis-enhanced localized surface plasmon resonance (ACE-LSPR) biofunctional nanoparticle imaging. The ACE-LSPR device is constructed using both bottom-up and top-down sensor fabrication methods, allowing the seamless integration of antibody-conjugated gold nanorod (AuNR) biosensor arrays with microelectrodes on the same microfluidic platform. Applying an AC voltage to microelectrodes while scanning the scattering light intensity variation of the AuNR biosensors results in significantly enhanced biosensing performance. The AC electroosmosis (ACEO) based enhancement of the biosensor performance enables rapid (5-15 min) quantification of IL-1ß, a pro-inflammatory cytokine biomarker, with a sensitivity down to 158.5 fg/mL (9.1 fM) for spiked samples in PBS and 1 pg/mL (58 fM) for diluted human serum. Together with the optimized detection sensitivity and speed, our study presents the first critical step toward the application of nanoplasmonic biosensing technology to immune status monitoring guided by low-abundance cytokine measurement.

The role of E2F2 in cancer progression and its value as a therapeutic target.

The E2F family of transcription factors plays a crucial role in the regulation of cell cycle progression and cell proliferation. Accumulative evidence indicates that aberrant expression or activation of E2F2 is a common phenomenon in malignances. E2F2 has emerged as a key player in the development and progression of various types of tumors. A wealth of research has substantiated that E2F2 could contribute to the enhancement of tumor cell proliferation, angiogenesis, and invasiveness. Moreover, E2F2 exerts its influence on a myriad of cellular processes by engaging with a spectrum of auxiliary factors and downstream targets, including apoptosis and DNA repair. The dysregulation of E2F2 in the context of carcinogenesis may be attributable to a multitude of mechanisms, which encompass modifications in upstream regulatory elements or epigenetic alterations. This review explores the function of E2F2 in cancer progression and both established and emerging therapeutic strategies aiming at targeting this oncogenic pathway, while also providing a strong basis for further research on the biological function and clinical applications of E2F2.