Peptide-Based Electrical Array Sensor for Discriminating Heavy Metal Ions.

Charge transport in molecular junctions provides an excellent way to investigate the response of molecules to intrinsic changes and external stimuli, exhibiting powerful potential for developing sensors. However, achieving multianalyte recognition remains a challenge. Herein, we innovatively developed an electrical array sensor based on peptide self-assembled layers for discriminating various heavy metal ions. Three peptide sequences were designed as sensing units with varying binding affinities for different metal ions. Electrical measurements demonstrated that different metal ions diversely affect the charge transport of peptide junctions. By using principal component analysis, a clear discrimination between the five kinds of heavy metal ions can be achieved. In the analysis of real samples, the array sensor showed a reliable anti-interference capability. The array sensor offers possibilities for large-area molecular junctions to construct functional molecular sensing devices.

Deciphering the Roles of Interfacial Amino Acids in Inter-Protein Charge Transport.

Elucidating charge transport (CT) through proteins is critical for gaining insights into ubiquitous CT chain reactions in biological systems and developing high-performance bioelectronic devices. While intra-protein CT has been extensively studied, crucial knowledge about inter-protein CT via interfacial amino acids is still absent due to the structural complexity. Herein, by loading cytochrome c (Cyt c) on well-defined peptide self-assembled monolayers to mimic the protein-protein interface, we provide a precisely controlled platform for identifying the roles of interfacial amino acids in solid-state CT via peptide-Cyt c junctions. The terminal amino acid of peptides serves as a fine-tuning factor for both the interfacial interaction between peptides and Cyt c and the immobilized Cyt c orientation, resulting in a nearly 10-fold difference in current through peptide-Cyt c junctions with varied asymmetry. This work provides a valuable platform for studying CT across proteins and contributes to the understanding of fundamental principles governing inter-protein CT.

Brush-like Co/CoSe nanoheterostructures embedded in N-doped carbon for rechargeable Zn-air batteries.

Rational design and preparation of high-performance bifunctional oxygen electrocatalysts with effective sites and excellent mass/electron transfer structures are in demand for Zn-air batteries to overcome the sluggish oxygen reduction/evolution kinetics. Herein, a scalable and facile strategy is proposed to obtain brush-like Co/CoSe nanoheterostructures embedded in N-doped carbon catalysts with optimized active sites and hierarchical nanostructures. Systematic investigation indicates that nanoheterogeneous interfaces with appropriate composition deliver significantly improved electrochemical activity. As a result, a zinc-air battery assembled with the obtained Co/CoSe nanoheterostructures embedded in the N-doped carbon (CoSe/Co@NC-1) catalyst exhibits outstanding electrochemical performance with a peak power density of 215 mW cm-2 and excellent stability for 475 hours (2850 cycles). These results indicate that this strategy is an effective method for fabricating multicomponent and hierarchically nanostructured materials with enhanced catalytic efficiency for advanced energy devices.

Virtual screening of novel mTOR inhibitors for the potential treatment of human colorectal cancer.

The abnormal activation of the mTOR pathway is closely related to the occurrence and progression of cancer, especially colorectal cancer. In this study, a rational virtual screening strategy has been established and MT-5, a novel mTOR inhibitor with a quinoline scaffold, was obtained from the ChemDiv database. MT-5 showed potent kinase inhibitory activity (IC50: 8.90 µM) and antiproliferative effects against various cancer cell lines, especially HCT-116 cells (IC50: 4.61 µM), and this was 2.2-fold more potent than that of the cisplatin control (IC50: 9.99 µM). Western blot, cell migration, cycle arrest, and apoptosis assays were performed with HCT-116 cells to investigate the potential anticancer mechanism of MT-5. Metabolic stability results in vitro indicated that MT-5 exhibited good stability profiles in artificial gastrointestinal fluids, rat plasma, and liver microsomes. In addition, the key contribution of the residues around the binding pocket of MT-5 in binding to the mTOR protein was also investigated from a computational perspective.

Secondary Structure-Dependent Charge Transport in iLOV Protein Junctions.

The composition and structure of proteins are crucial for charge migration in the solid-state charge transport (CTp). Despite much progress, it is still challenging to explore the relationship between conformational change and CTp in the complex protein system. Herein, we design three improved light-oxygen-voltage (iLOV) domains, and efficiently regulate the CTp of the iLOV self-assembled monolayers (SAMs) by pH induced conformation variation. The current density can be controlled in the range of one order of magnitude. Interestingly, the CTp of iLOV displays negative linear relations with the ß-sheet contents. Single-level Landauer fitting and transition voltage spectroscopy analysis suggest that ß-sheet-dependent CTp would be related to the coupling between iLOV and electrodes. This work proposes a new strategy to explore the CTp in complex molecular system. Our findings deepen the understanding on protein structure-CTp relationship, and provide predictive mode of protein CTp responses for the design of functional bioelectronics.

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer.

The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MicroRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, this study aimed to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, and human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that inhibiting miR-122-5p expression led to the activation of p53. This inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration, and promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than the corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for developing targeted drugs.

Solid-state self-catalyzed growth of N-doped carbon tentacles on an M(Fe, Co)Se surface for rechargeable Zn-air batteries.

A scalable and facile solid-catalyzed growth approach is reported to integrate N-doped carbon tentacles with metal selenide nanoparticles, showing great potential for mass production of non-precious metal catalysts for rechargeable Zn-air batteries.

Image-free active autofocusing with dual modulation and its application to Fourier single-pixel imaging.

Autofocusing is widely used in applications where sharp image acquisition or projection is needed. Here we report an active autofocusing method for sharp image projection. The method works with wide-field structured illumination and single-pixel detection. To find the focus position, the method illuminates the target object with a set of 3-step phase-shifting Fourier basis patterns repeatedly and collects the backscattered light by using a single-pixel detector through a grating. Dual modulation-dynamic modulation by the time-varying structured illumination and static modulation by the grating-embeds the depth information for the target object in the resulting single-pixel measurements. As such, the focus position can be determined by recovering the Fourier coefficients from the single-pixel measurements and searching for the coefficient with the maximum magnitude. High-speed spatial light modulation not only enables rapid autofocusing but also makes the method work even when the lens system is in continuous motion or the focal length of the lens is continuously adjusted. We experimentally validate the reported method in a self-built digital projector and demonstrate the application of the method in Fourier single-pixel imaging.

Supramolecular Enhancement of Charge Transport through Pillar[5]arene-Based Self-Assembled Monolayers.

Intermolecular charge transport is one of the essential modes for modulating charge transport in molecular electronic devices. Supermolecules are highly promising candidates for molecular devices because of their abundant structures and easy functionalization. Herein, we report an efficient strategy to enhance charge transport through pillar[5]arene self-assembled monolayers (SAMs) by introducing cationic guests. The current density of pillar[5]arene SAMs can be raised up to about 2.1 orders of magnitude by inserting cationic molecules into the cavity of pillar[5]arenes in SAMs. Importantly, we have also observed a positive correlation between the charge transport of pillar[5]arene-based complex SAMs and the binding affinities of the pillar[5]arene-based complexation. Such an enhancement of charge transport is attributed to the efficient host-guest interactions that stabilize the supramolecular complexes and lower the energy gaps for charge transport. This work provides a predictive pattern for the regulation of intermolecular charge transport in guiding the design of next generation switches and functional sensors in supramolecular electronics.

Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family.

The high mortality rate of patients with diabetic foot ulcers is urging the appearance of an effective biomedical drug. Senescence is one of the major reasons of aging-induced decline in the diabetic wound. Our previous studies have demonstrated the anti-senescence effect of secretomes derived from human fetal mesenchymal stem cells (hfMSC). The present study tends to explore the potential role of hfMSC secretome (HFS) in wound healing through anti-aging. Meanwhile, we try to overcome several obstacles in the clinical application of stem cell secretome. A verticle bioreactor and microcarriers are employed to expand hfMSC and produce the HFS on a large scale. The HFS was then subjected to lyophilization (L-HFS). The PLGA (poly lactic-co-glycolic acid) particles were used to encapsulate and protect L-HFS from degradation in the streptozotocin (STZ)-induced diabetic rat model. Results showed that HFS-PLGA significantly enhanced wound healing by promoting vascularization and inhibiting inflammation in the skin wound bed. We further analyzed the contents of HFS. Isobaric tag for relative and absolute quantitation (ITRAQ) and label-free methods were used to identify peptides in the secretome. Bioinformatics analysis indicated that exosome production-related singling pathways and heat-shock protein family could be used as bio-functional markers and quality control for stem cell secretome production.

Effect of COVID-19 epidemic on management of diabetic patients / 中华全科医师杂志

The outbreak of COVID-19 as an acute communicable disease has also changed the epidemiological status of diabetes mellitus and other noncommunicable chronic diseases. During the COVID-19 epidemic period, it was observed that there were increased morbidity of diabetes, difficulties in blood sugar control and increased acute complications for diabetic patients. This may be attributed to lifestyle changes during the epidemics, such as the reduced exercise time and increased sedentary time, more snacks and sugary food intake, as well as anxiety and depression. However, it is not known the long-term impact of COVID-19 epidemic on the management of diabetic patients, so it is necessary to closely monitor the exposed diabetic patients in the future.

Coagulation Factors for Diagnosis of Periprosthetic Joint Infection / 中山大学学报(医学科学版)

ObjectivePeriprosthetic joint infections （PJI） are currently the most calamitous complication after arthroplasty. Although achievements have been made in many markers for the diagnosis of PJI， the lack of a gold standard remains a great obstacle for early diagnosis. This study aimed to investigate the association between coagulation markers and the development of PJI in patients undergoing revision total joint arthroplasty （TJA）. MethodsWe conducted a retrospective cohort study with a total of 2 517 patients who underwent hip or knee arthroplasties from January 2011 to January 2022 （2 394 with primary TJA， 87 with aseptic revision and 36 with PJI）. We applied univariate analysis and multivariate logistic regression to analyze differences of coagulation factors between primary TJA and aseptic revision or PJI group. Receiver operating characteristic （ROC） curve and area under the curve （AUC） were used to measure the diagnostic value of coagulation factors in predicting PJI. ResultsCoagulation factors and their ratios including plasma fibrinogen （FBG）， prothrombin time （PT）， thrombin time （TT）， activated partial thromboplastin time （APTT）， platelet （PLT）， mean platelet volume （MPV）， platelet distribution width （PDW）， plateletcrit （PCT）， PLT / MPV， PLT / PDW and PLT / PCT were included in this study. High FGB level was strongly correlated with the risk of PJI compared to other coagulation factors. The optimal threshold value of FBG was 4.53 g/L with a sensitivity of 47.22%， a specificity of 93.07% （Primary TJA group vs. PJI group）. Similarly， the optimal threshold value of FBG was 4.44 g/L with a sensitivity of 47.22%， a specificity of 95.40% between the other two groups （Aseptic revision group vs. PJI group）. ROC curve analysis demonstrated moderate diagnostic performance of FBG （AUC value）， indicating a potential to be a diagnostic marker for PJI. ConclusionsFBG is significantly correlated with PJI and it can be used as a potential non-invasive marker for early detection. It may serve as a safe and cost-effective tool for assessing PJI in clinical work.

Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2 / 医学前沿

Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.

Clearance pathways of near-infrared-II contrast agents.

Near-infrared-II (NIR-II) bioimaging gradually becomes a vital visualization modality in the real-time investigation for fundamental biological research and clinical applications. The favorable NIR-II contrast agents are vital in NIR-II imaging technology for clinical translation, which demands good optical properties and biocompatibility. Nevertheless, most NIR-II contrast agents cannot be applied to clinical translation due to the acute or chronic toxicity caused by organ retention in vivo imaging. Therefore, it is critical to understand the pharmacokinetic properties and optimize the clearance pathways of NIR-II contrast agents in vivo to minimize toxicity by decreasing organ retention. In this review, the clearance mechanisms of biomaterials, including renal clearance, hepatobiliary clearance, and mononuclear phagocytic system (MPS) clearance, are synthetically discussed. The clearance pathways of NIR-II contrast agents (classified as inorganic, organic, and other complex materials) are highlighted. Successively analyzing each contrast agent barrier, this review guides further development of the clearable and biocompatible NIR-II contrast agents.

Targeting the Retinoblastoma/E2F repressive complex by CDK4/6 inhibitors amplifies oncolytic potency of an oncolytic adenovirus.

CDK4/6 inhibitors (CDK4/6i) and oncolytic viruses are promising therapeutic agents for the treatment of various cancers. As single agents, CDK4/6 inhibitors that are approved for the treatment of breast cancer in combination with endocrine therapy cause G1 cell cycle arrest, whereas adenoviruses induce progression into S-phase in infected cells as an integral part of the their life cycle. Both CDK4/6 inhibitors and adenovirus replication target the Retinoblastoma protein albeit for different purposes. Here we show that in combination CDK4/6 inhibitors potentiate the anti-tumor effect of the oncolytic adenovirus XVir-N-31 in bladder cancer and murine Ewing sarcoma xenograft models. This increase in oncolytic potency correlates with an increase in virus-producing cancer cells, enhanced viral genome replication, particle formation and consequently cancer cell killing. The molecular mechanism that regulates this response is fundamentally based on the reduction of Retinoblastoma protein expression levels by CDK4/6 inhibitors.

Upregulation of N-Type Voltage-Gated Calcium Channels Induces Neuropathic Pain in Experimental Autoimmune Neuritis.

Objective: Guillain-Barré syndrome (GBS) is a common autoimmune disease of the peripheral nervous system, and there is still no effective treatment for GBS. This investigation intends to figure out the effect and mechanism of N-type voltage-gated calcium (Cav2.2) channels on neuropathic pain in GBS. Methods: An experimental autoimmune neuritis (EAN) model was established in Lewis rats induced by myelin P253-78 peptide and complete Freund's adjuvant. Luxol fast blue (LFB) staining was used for observing the degree of cell infiltration and demyelination in the sciatic nerve of rats, ELISA for detecting IL-6 and TNF-α expression in the serum, qRT-PCR, and Western blot for measuring the expression of iNOS, MCP-1, and Cav2.2 in the sciatic nerve, respectively. Results: EAN led to significant decreases in the mechanical withdrawal threshold, thermal withdrawal threshold, and mechanical hyperalgesia threshold and an increase in the withdrawal threshold to cold stimulation. The serum IL-6 and TNF-α expression was significantly increased, and the mRNA and protein expression of iNOS, MCP-1, and Cav2.2 in the sciatic nerve were significantly increased in the EAN rats. However, silencing Cav2.2 expression could significantly reverse the above EAN-caused results. Conclusion: Silencing Cav2.2 expression can significantly reduce the clinical score, pathological injury, and mechanical allodynia, reducing the release of inflammatory factors, thus improving neuropathic pain in EAN rats.

A rapid and high sensitivity RNA detection based on NASBA and G4-ThT fluorescent biosensor.

In recent years, various newly emerged and re-emerged RNA viruses have seriously threatened the global public health. There is a pressing need for rapid and reliable nucleic acid-based assays for detecting viral RNA. Here, we successfully developed a highly sensitive, easy-to-operate G4-ThT-NASBA system to detect viral RNA that no need for labeled primers and probes. Next, we tested the system for detecting the Classical Swine Fever Virus (CSFV), an RNA virus that causes a highly contagious disease in domestic pigs and wild boar and easily causes huge economic losses. Results showed that the system, integrated the G4-ThT fluorescent biosensor and NASBA (Nuclear acid sequence-based amplification),is capable to detect as little as 2 copies/µL of viral RNA without interfering by other swine viral RNA. Moreover, we were able to detect CSFV RNA within 2 h in serum samples taken from the field in a real-time mode. These findings indicate that the G4-ThT-NASBA system is a rapid, high sensitivity and easy-to-operate technique for RNA detection. The method also has the real-time detection capability which may be easily integrated in a highly automated system such as microfluidic chips.

Hard-soft chemistry guides the adaptable charge transport in lysine-doped heptapeptide junctions.

Counterions always coexist with charged peptides in charge transport processes, which are excellent candidate components for tunable molecular electronic devices. Here, we introduced hard-soft acid base theory to analyze the counterion-modulated peptide charge transport. We demonstrate that the peptide charge transport is improved by enhanced peptide-counterion interactions.

Robust multi-angle structured illumination lensless microscopy via illumination angle calibration.

Multi-angle structured illumination lensless (MASIL) microscopy enables high-resolution image recovery over a large field of view. Successful image recovery of MASIL microscopy, however, relies on an accurate knowledge of the multi-angle illumination. System misalignments and slight deviations from the true illumination angle may result in image artifacts in reconstruction. Here we report a MASIL microscopy system that is robust against illumination misalignment. To calibrate the illumination angles, we design and use a double-sided mask, which is a glass wafer fabricated with a ring-array pattern on the upper surface and a disk-array pattern on the lower surface. As such, the illumination angles can be decoded from the captured images by estimating the relative displacement of the two patterns. We experimentally demonstrate that this system can achieve successful image recovery without any prior knowledge of the illumination angles. The reported approach provides a simple yet robust resolution for wide-field lensless microscopy. It can solve the LED array misalignment problem and calibrate angle-varied illumination for a variety of applications.

Ringing-free fast Fourier single-pixel imaging.

Fourier single-pixel imaging (FSI) allows an image to be reconstructed by acquiring the Fourier spectrum of the image using a single-pixel detector. Fast FSI is typically achieved by acquiring a truncated Fourier spectrum, that is, only low-frequency Fourier coefficients are acquired, with the high-frequency coefficients discarded. However, the truncation of the Fourier spectrum leads to undesirable ringing artifacts in the resulting image. Ringing artifacts produce false edges in the image and reduce the image contrast, resulting in image quality degeneration. The artifact is particularly severe in dynamic FSI, where the sampling ratio is generally ultra-low. We propose an effective and fast deringing algorithm to achieve ringing-free fast FSI. The algorithm eliminates ringing artifacts through 2D sub-pixel shifting and preserves image details through image fusion. Both static and dynamic imaging results demonstrate that the proposed method can reconstruct ringing-free images from under-sampled data in FSI. The deringing algorithm not only provides FSI with the capability of fast high-quality single-pixel imaging but also might prove its applicability in other areas, such as Fourier-based data compression algorithms.