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The article is devoted to the analysis of real geographical loci in the poem cycle "Murmansk echoes", written by the poet-pre-symbolist K. K. Sluchevsky in 1888 under the impression of a trip to the Murmansk region. The conducted research using historical, functional and comparative methods allows us to comprehend the nature of Sluchevsky's literary work and the philosophical ideas embedded in his poetry. The author of the article pays special attention to the study of landscapes, which are an expression of emotions and personal feelings of K. K. Sluchevsky, reflecting the concept of the poet's life and his philosophy; consideration of such an aspect of the topic as Sluchevsky's use of real loci to expand time and space. The scientific novelty lies in the fact that the work for the first time studied the influence of real geographical loci on the poetry of K. K. Sluchevsky, the depiction of artistic images in northern Russia, the life and customs of local pomors, investigated the changes in perspective in the real locus and the expansion of time, revealed the general "mythologeme" of the space of the real locus. As a result of the research, the author comes to the conclusion that the geographical locus allows the poet not only to convey impressions about what he saw, but also to open his inner life, and most importantly, to recreate a holistic picture of the universe through concrete and small things.

Endovascular mechanical thrombectomy (EVMT) has shown significant efficacy in improving neurological functions in patients with intracranial internal carotid artery occlusion (IICAO), but its clinical outcomes are variable. We examined the relationship between favorable clinical outcomes after EVMT in IICAO and a set of predictors.In this retrospective study, 189 patients with IICAO treated by EVMT at 3 centers from November 2015 to December 2020 were included and analyzed. Non-contrast computed tomography and computed tomography angiography were evaluated on admission. The morphology of IICAO was categorized into Ia, Ib, L, or T types, depending on the involvement of the posterior communicating artery origin, proximal anterior cerebral artery, and middle cerebral artery. The Willis' circle was categorized as integrated or compromised Willis' circle. In combination with the involvement of the IICAO and the integrity of Willis' circle, we used the primary collateral grade (PCG) to describe the presence of functional Willisian collaterals. Baseline data including demographics, characteristics, vascular risk factors, and initial National Institutes of Health Stroke Scale scores were collected. Hemorrhagic transformation was evaluated using the 24-hour non-contrast computed tomography after EVMT. Favorable outcomes based on modified Rankin scale, were defined as 0-2 at 90 days.A total of 189 patients were included (median age, 69 years; 126 male [66.7%]). 104 patients [55.0%] showed reperfusion after EVMT, but 72 patients [38.1%] achieved favorable outcomes at 90 days. The mortality rate of type Ib was significantly higher than that with type Ia (χEvaluation of PCG by determining the type of IICAO and the integrity of Willis' circle may serve as a valuable indicator for the prognosis and as an essential reference for screening patients before EVMT.

Allergic rhinitis (AR) is considered to be 1 of the most difficult diseases to treat globally. It has a serious impact on the quality of life and social economy of patients and has become an important global health problem. Several drugs have been recommended to treat AR, but their effectiveness and mechanism of action in these patients remain unclear. The purpose of this study will be to compare the efficacy and mechanism of action of 2 drugs for the treatment of AR (moderate to severe): a Dermatophagoides Farinae Drops Sublingual Immunotherapy and a Momethasone Furoate nasal spray as an adjunct to the treatment of subjects with AR.A randomized, prospective, double-blind (patient and evaluator) clinical trial. The participants (n = 60) will be randomly distributed into 2 groups. The experimental group will receive a sublingual Immunotherapy for 3 months. The control group will receive the mometasone furoate nasal spray for 3 months. Before treatment, 1 month and 3 months after treatment, total nasal symptom score scale, Visual analogue Scale and Quality of Life questionnaire of rhinoconjunctivitis will be measured and Changes of the serums of IgE, interferon-γ, IL-4, IL-17, tumor necrosis factor-α, IL-5, IL-9, IL-13, IL-25, IL-33, vascular endothelial growth factor, TSLP and IL-22 in both groups. The measurements will be performed by the same researcher who was unaware of the participants' subgroup.We believe that the treatment of perennial AR with sublingual Immunotherapy and nasal hormones will be more effective in these patients. Furthermore, the sublingual Immunotherapy mainly acts mostly on the cellular immunity, while nasal hormones mainly act on local inflammatory responses. We expect to clarify which treatments are more effective and how they work in improving perennial AR.

Here, we describe a new photoelectrochemical imaging method termed light-addressable square wave voltammetry (LASWV). It measures local SWV currents at an unstructured electrolyte/insulator/semiconductor (EIS) field-effect substrate by illuminating and addressing the substrate with an intensity-constant laser. Due to the continuous generation of charge carriers in the light-irradiated semiconductor, the drift and diffusion of photoinjected carriers within the semiconductor bulk would slow down the equilibrium processes of charge and discharge in one potential pulse cycle. Therefore, even though SWV is sampled at the end of the direct and reverse pulses to reject capacitive currents, in our approach, photoinduced capacitive current can still be detected as an effective sensory signal. The obtained current-potential (I-V) curve shows a typical shape corresponding to the accumulation, depletion, and inversion regions of field-effect devices. We demonstrated that LASWV can be used as a field-effect chemical sensor to measure the solution pH and monitor enzymatic reactions. More importantly, since the charge carriers are only generated in the illuminated area, the laser spot in the device can be used as a virtual probe to record local electrochemical properties such as impedance with microresolution.

The light-addressable electrochemical sensor (LAES) is a recently emerged bioanalysis technique combining electrochemistry with the photoelectric effect in a semiconductor. In an LAES, a semiconductor substrate is illuminated locally to generate charge carriers in a well-defined area, thereby confining the electrochemical process to a target site. Benefiting from the unique light addressability, an LAES can not only detect multiple analytes in parallel within a single sensor plate but also act as a bio(chemical) imaging sensor to visualize the two-dimensional distribution of specific analytes. An LAES usually has three working modes: a potentiometric mode using light-addressable potentiometric sensors (LAPS) and an impedance mode using scanning photoinduced impedance microscopy (SPIM), while an amperometric mode refers to light-addressable electrochemistry (LAE) and photoelectrochemical (PEC) sensing. In this review, we describe the detection principles of each mode of LAESs and the concept of light addressability. In addition, we highlight the recent progress and advance of LAESs in spatial resolution, sensor system design, multiplexed detection, and bio(chemical) imaging applications. An outlook on current research challenges and future prospects is also presented.

Visualization of the electrochemical reaction is essential for comprehensively understanding the electrochemical reaction mechanism and precisely characterizing dynamic electrochemical processes. Herein, we propose a simple device that combines light-addressable potentiometric sensor (LAPS) imaging and microelectrodes to serve as a general electroanalysis platform for the label-free sensing and imaging of electrochemical reactions. In this device, two microelectrodes are assembled on the LAPS chip. Electrochemical reactions occurring on the microelectrodes can be qualitatively and quantitatively observed and visualized using a LAPS chip that is sensitive to the reaction products. Validations were performed to monitor the effect of water electrolysis and potassium ferrocyanide oxidation surrounding the microelectrodes, respectively. We believe that this study will provide an excellent platform for the visualization and monitoring of electrochemical reactions and broaden the application scope of LAPS imaging to a general electroanalysis tool that is widely applicable in several fields.

The application of silicon (Si) substrate as photoelectrode in light-addressable electrochemistry (LAE) is severely limited due to its ease of surface oxidation. The resulted silicon oxide (SiO

To establish and validate a model to predict acute kidney injury (AKI) following wasp stings.In this multicentre prospective study, 508 patients with wasp stings from July 2015 to December 2019 were randomly divided into a training set (n = 381) and a validation set (n = 127) for internal and external validation. Risk factors were identified, and a model was established to predict the probability of AKI following multiple wasp stings using an individual nomogram and a predictive formula. The performances of the model were assessed by using the area under the curve (AUC), accuracy (ACC) of the receiver operating characteristic curve and decision curve analysis.The number of stings, aspartate aminotransferase147 U/L, lactate dehydrogenase477 U/L, time from stings to admission12 h and activated partial thromboplastin time49 s were demonstrated to be independent risk factors for AKI following wasp stings (all P value 0.05) and were incorporated into the model. The performances of the model were validated (AUC = 0.950 [95% CI: 0.923 to 0.969], ACC = 0.916 and AUC = 0.953 [95% CI: 0.900 to 0.982], ACC = 0.906 in the training set and validation set, respectively). The predictive formula and the nomogram of the model could be utilized to predict AKI following wasp stings, which have sufficient accuracies, good predictive capabilities and good net benefits.The predictive formula and the individual nomogram of the model might serve as promising predictive tools to assess the probability of AKI following wasp stings.

Hepatocellular carcinoma (HCC) is a malignant tumor that seriously perils human health. Recent years have seen much effect in revealing the pathological association between lncRNA and HCC. Herein, we identified lncRNA DHRS4-AS1 as a potential tumor suppressor in HCC. Firstly, it was discovered that DHRS4-AS1 was significantly down-regulated in HCC tissues compared to normal tissues based on the database TCGA. It was also detected in a lower-than-usual expression quantity in HCC tissues we collected and HCC cell lines. Kaplan-Meier survival analysis revealed that high expression of DHRS4-AS1 contributed to higher overall survival rate of HCC patients. DHRS4-AS1 expression was significantly correlated to tumor size (P = 0.02) and TNM stage (P = 0.045). CCK-8, BrdU and colony-forming assays collectively demonstrated that overexpression of DHRS4-AS1 significantly restrained HCC cell proliferation. In vivo xenograft animal experiment showed that DHRS4-AS1 could efficiently preclude the tumor growth of HCC. Further investigation performed using flow cytometry and western blot showed that DHRS4-AS1 exerted its effects by accelerating cell apoptosis and capturing cell cycle in G0/G1 phase. Our study subsequently lucubrated that miR-522-3p was a negative target of DHRS4-AS1. Increased expression level of miR-522-3p was examined in HCC tissues and cell lines. Similarly, miR-522-3p mimics could reverse the inhibitory effect on HCC brought by DHRS4-AS1. SOCS5 was then discovered as a down-stream target of miR-522-3p, which suggested that SOCS5 participated in DHRS4-AS1/miR-522-3p axis to collectively mediate the development of HCC. Our study provides lncRNA DHRS4-AS1/miR-522-3p/SOCS5 axis as a novel target for HCC therapeutic strategy with potentiality.

The robust cell-in-shell structure is highly desirable for endowing living cells with an artificial exoskeleton to defend them from many environmental factors such as osmotic pressure, shear force, heat, UV radiation, and enzymes. Cell encapsulation has shown potential applications in many fields and attracted increasing interest. However, the influences of the precursors on the cell viability during the shell formation process are not clear and seldom investigated. Here, zinc nitrite, zinc acetate and zinc sulfate were applied individually to synthesize zeolitic imidazolate framework-8 (ZIF-8) shells on living cells. All the zinc salt precursors could convert to a ZIF-8 layer on the living cell surface. The zinc salts and organic ligand did not exhibit obvious toxicity to yeast cells when applied individually. However, dead cells were observed during the living cell encapsulation process using different zinc precursors. Compared with zinc nitrate and zinc acetate, ZIF-8 formed by zinc sulfate led to a higher percentage of cell death, especially under high concentrations of zinc sulfate. Cell division was suppressed by the ZIF-8 shell but restored fully upon shell removal by EDTA solution or pH 4.0 buffer. Escherichia coli (E. coli) cells showed a lower percentage of cell death, indicating excellent tolerance to the ZIF-8 encapsulation process. This work illustrates the cell toxicity during the formation of ZIF-8 cell shells by different zinc salts and engineering of the cell growth by MOF coating, which could provide a foundation for further quantitative analysis and potential applications in biomedicine and bioengineering.

Cellulose nanocrystal (CNC) composite filter papers were fabricated by a facile method, which consists of the bleaching and hydrolysis of fibers, and drop coating of filter papers with CNC solution. The filter properties of the composite filter papers were applied for the removal of bacteria from aqueous solutions. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were used to evaluate the bacteria removal performance of the CNC composite filter papers. It is indicated that the nanopores formed by nanoscale rod-like crystals contribute to the bacteria removal capacity of porous CNC nanocomposite filter papers. Overlapped five layers of the CNC composite filter papers displayed a rapid (0.12 L/min) and highly efficient removal (remove rate at ~ 100%) of bacteria from aqueous solutions. Due to their advantages of convenient preparation, sustainable materials and low cost, the CNC composite filter papers have promising prospects and potential applications in many fields concerning bacteria removal and water purification.

How to obtain sufficient functional olfactory receptors and coupled to transducers with high efficiency are crucial to biomimetic olfactory-based biosensors. In this study, a cell-free expression system was employed to prepare functional olfactory receptors that were utilized as sensitive elements for biomimetic olfactory receptor-based biosensors. A nematode olfactory receptor, ODR-10, was used as a model of olfactory receptors and expressed in Escherichia coli (E. coli) cell-free expression system. To improve the coupling efficiency and obtain the on-chip purification, a His6-tag was expressed as a fusion to ODR-10, which makes the expressed ODR-10 capable of selectively binding to the sensor surface modified with anti-His6-tag aptamers. Electrolyte-insulator-semiconductor (EIS) sensors were utilized as the transducer to measure the capacitance changes induced by the ODR-10 responding to its natural ligand, diacetyl. The results show that ODR-10 was successfully expressed using E. coli cell-free expression system and the expression could be promoted by adding 0.5% Brij58 as the detergent. Capacitance measurement results indicate that this olfactory receptor-based biosensor can detect diacetyl with high specificity and sensitivity. Concentration-dependent linear response to diacetyl ranging from 0.01 nM to 1 nM was obtained. The detection limit was as low as 0.01 nM. All the results demonstrated that the cell-free expression system provides a new approach for the preparation of functional olfactory receptors, which have great potential to be applied in biomimetic sensors towards chemical sensing.

The decomposition of hydrogen peroxide was determined in the neutral solution of ZIF-67 crystals. The fast decomposition of H2O2 can be observed by naked eyes in seconds after mixing the reactants. A crumpled surface was observed for ZIF-67 crystals after the decomposition reaction. The decomposition reaction was found to follow the first-order kinetics. Temperature-dependent studies calculated that the activation energy was 37 kJ mol−1. Based on the obtained results, a possible mechanism was proposed.

The tumor immune microenvironment (TIME) is comprised of a complex milieu that contributes to stunting antitumor immune responses by restricting T cells to accumulate in the vicinity of the tumor. Nanomedicine-based strategies are being proposed as a salvage effort to reinvigorate antitumor immunity. Various strategies, however, often fail to unleash the antitumor immune response because of the paucity of appropriate therapeutic targets in the complex TIME, invigorating a fervor of investigation into mechanisms underlying the TIME to resist nanomedicines. In this review article, effective nano/biomaterial-based delivery and TIME normalization approaches that promote T cell-mediated antitumor immune response will be discussed, with a focus on emerging preclinical and clinical strategies for immune normalization. Based on currently available evidence, it seems as if the ultimate success of cancer immunotherapy and nanomedicine hinges on the capacity to normalize the TIME. Here, how nanomedicines target immunosuppressive cells and signaling pathways to broaden the impact of cancer immunotherapy are explored. Acquisition of the urgently needed knowledge of nanomedicine-mediated immune normalization will guide researchers and scientists towards clinical applications of cancer immunotherapy.

Objectives To develop a radiomics signature for predicting surgical portal vein-superior mesenteric vein (PV-SMV) in patients with pancreatic ductal adenocarcinoma (PDAC) and measure the effect of providing the predictions of radiomics signature to radiologists with different diagnostic experiences during imaging interpretation. Methods Between February 2008 and June 2020, 146 patients with PDAC in pancreatic head or uncinate process from two institutions were retrospectively included and randomly split into a training (n = 88) and a validation (n =58) cohort. Intraoperative vascular exploration findings were used to identify surgical PV-SMV invasion. Radiomics features were extracted from the portal venous phase CT images. Radiomics signature was built with a linear elastic-net regression model. Area under receiver operating characteristic curve (AUC) of the radiomics signature was calculated. A senior and a junior radiologist independently review CT scans and made the diagnosis for PV-SMV invasion both with and without radiomics score (Radscore) assistance. A 2-sided Pearson's chi-squared test was conducted to evaluate whether there was a difference in sensitivity, specificity, and accuracy between the radiomics signature and the unassisted radiologists. To assess the incremental value of providing Radscore predictions to the radiologists, we compared the performance between unassisted evaluation and Radscore-assisted evaluation by using the McNemar test. Results Numbers of patients identified as presence of surgical PV-SMV invasion were 33 (37.5%) and 19 (32.8%) in the training and validation cohort, respectively. The radiomics signature achieved an AUC of 0.848 (95% confidence interval, 0.724-0.971) in the validation cohort and had a comparable sensitivity, specificity, and accuracy as the senior radiologist in predicting PV-SMV invasion (all p-values > 0.05). Providing predictions of radiomics signature increased both radiologists' sensitivity in identifying PV-SMV invasion, while only the increase of the junior radiologist was significant (63.2 vs 89.5%, p-value = 0.025) instead of the senior radiologist (73.7 vs 89.5%, p-value = 0.08). Both radiologists' accuracy had no significant increase when provided radiomics signature assistance (both p-values > 0.05). Conclusions The radiomics signature can predict surgical PV-SMV invasion in patients with PDAC and may have incremental value to the diagnostic performance of radiologists during imaging interpretation.

Background: Multiple researches have revealed that long non-coding RNA (lncRNAs) served as regulatory factor in modulating tumorigenesis of hepatocellular carcinoma (HCC). In this study, we demonstrated that lncRNA HCP5 was a tumor promoting factor of HCC, and the molecular mechanism of HCP5 has been elucidated at length.Methods: BrdU, transwell assay and flow cytometry were exerted to estimate cell growth, metastasis, invasion and apoptosis of HCC in vitro. Animal studies were performed the effect of HCP5 in vivo. Furthermore, we identified that miR-29b-3p interacted with HCP5 or DNA methyltransferase 3A (DNMT3A) using dual luciferase assay. qRT-PCR, western blot, BrdU, tanswell and flow cytometry assays were used to investigate the correlation of HCP5/miR-29b-3p/DNMT3A axis. Results: In present research, we elaborated that HCP5 was overexpressed in HCC tissues and cell lines, and this phenomenon was even obvious in metastatic and recurrent cases. Knockdown of HCP5 significantly alleviated cell growth, metastasis and invasion through preventing apoptosis and activating EMT progress. Moreover, miR-29b-3p has been identified as a negatively regulatory target gene of HCP5, which served as tumor suppressor of HCC to prevent cell proliferation, migration and invasion. Subsequently, DNMT3A was found as a downstream regulatory factor of miR-29b-3p, of which study found that a participated element of HCC progression by activating AKT phosphorylation.Conclusion: Generally, our study elucidated for the first time that HCP5 plays a crucial role in HCC via HCP5/ miR-29b-3p/DNMT3A/AKT axis and demonstrated a novel diagnostic and therapeutic strategy with potentiality.

Objective. To evaluate the therapeutic effect of epigallocatechin gallate (EGCG) on precancerous lesions of gastric carcinoma (PLGC) and to determine whether EGCG protects against PLGC by regulating PI3K/Akt/mTOR pathway. Methods. Twenty-four male Wistar rats were randomly divided into 3 groups: normal control group (NC), PLGC model group (MC), and group of PLGC rats treated with EGCG (MC + EGCG). 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) and sodium salicylate were combined and used to establish the PLGC rat animal model. The therapeutic effect of EGCG on PLGC was evaluated by body weight and pathological lesions of gastric mucosa in PLGC rats. Quantitative polymerase chain reaction (qPCR) was applied to measure the mRNA expressions of PI3K, Akt, and mTOR. The protein expressions of cleaved caspase-3, PTEN, PI3K, p-PI3K, Akt, p-Akt, p-mTOR, and mTOR were determined by automated western immunoblotting. Results. The body weight decreased in PLGC rats while EGCG significantly increased body weight. The gastric mucosa of PLGC rats exhibited the pathological lesions of atrophy, intestinal metaplasia, and atypical hyperplasia while EGCG could ameliorate the pathological lesions. EGCG could upregulate the expressions of cleaved caspase-3 and PTEN and reduce the expressions of PI3K, Akt, and mTOR. Conclusions. EGCG ameliorated pathological lesions of PLGC and exerted the effect of apoptosis promotion in PLGC rats. The apoptotic pathway triggered by EGCG may be related to inhibition of PI3K/Akt/mTOR pathway. It provided a theoretical basis for the PLGC treatment and gastric cancer prevention.

A new photoelectrochemical imaging method termed scanning electrochemical photometric sensor (SEPS) is proposed in this work. It was derived from light-addressable potentiometric sensor (LAPS) and scanning photoinduced impedance microscopy (SPIM) using a front-side laser illumination at a field-effect structure. When the laser beam scans across the sensor substrate, local photocurrent changes at inversion due to the light absorption of analytes can be recorded. It will be shown that SEPS could be used for label-free living cell imaging with micro-resolution as well as real-time quantitative absorption analysis, which would broaden the applications of traditional LAPS/SPIM from potentiometric/impedance measurements to local optical analysis.

Lycorine, an natural isoquinoline alkaloid has reportedly that possesses multi-anticancer activity. However, to date, the anticancer feature of lycorine in non-small cell lung carcinoma (NSCLC) has still not fully been spelled out. The present study mainly focused on the molecular mechanism of lycorine against NSCLC in vitro and vivo. The results showed that lycorine evidently inhibited proliferation of A549 and H460 with IC50 values were 10.83 ± 1.14 μM and 12.35 ± 1.13 μM, while caused slight cytotoxicity in normal pulmonary epithelial Beas-2B cells, and arrested cell cycle in G0/G1 phase. Hoechst DNA-binding staining showed that typical characteristics of nuclear morphology apoptosis, AnnexinV-FITC/PI staining revealed the early-period apoptosis and the dissipation of mitochondrial membrane potential (Δψm) were also captured after lycorine treatment. Moreover, lycorine effectively repressed the Wnt/β-catenin signaling and reversed epithelial-mesenchymal transition (EMT). In addition, lycorine also intervened the caspase-mediated mitochondrial apoptosis pathway. Furthermore, A549/Luc tumor xenograft model was also corroborated that lycorine significantly suppressed the growth and metastasis of the lung tumor. These data highlight the significance of lycorine as potential anti-neoplastic agents to combat NSCLC.

In this study, we developed a novel bioelectronic taste sensor for the detection of specific bitter substances. A human bitter taste receptor, hT2R4, was efficiently expressed in Escherichia coli (E. coli), which was used as the primary recognition element. A simple and low-cost electrochemical device based on ITO-based electrolyte-semiconductor (ES) structure was innovatively employed as the transducer to assess bacterial metabolic consequences of receptor activation in real time. An apparent increase in extracellular acidification rate was observed, which was resulted from the triggering of hT2R4 receptors by their target ligand of denatonium. The sensor showed dose-dependent responses to denatonuim ranging from 50 nM to 500 nM, while non-bioengineered bacteria without hT2R4 receptors exhibited negligible responses to the same stimulus. In addition, the specificity of the proposed taste biosensor was verified using other typical bitter substances such as quinine and alpha-naphthylthiourea (ANTU). This research provides a simple and inexpensive approach for the construction of bioelectronic taste sensors.

A miniaturized platform combining integrated microelectrode (IME) and functional nucleic acids was developed for homogeneous label-free electrochemical biosensing. IME was constructed with a carbon fiber microelectrode and a platinum wire in a θ type glass tube as a two-electrode system for electrochemical monitoring at microliter level. A newly reported G-triplex/methylene blue (G3/MB) complex was used as the signal generator in the homogeneous label-free electrochemical biosensor. G3 has strong affinity with MB and it can cause significant decrease of the diffusion current of MB after binding. Melamine was chosen as the model target. Since melamine can interact with nucleobase thymine (T) to form T-melamine-T structure through complementary hydrogen bonds, a single-strand functional DNA hairpin structure with poly T and G3 elaborately blocked via base pairing was designed. The presence of melamine can trigger the conformation switching of the DNA hairpin to release the G3. The released G3 combined with MB could therefore change the diffusion current, leading to a simple and rapid detection of melamine. The combination of functional DNA hairpin as target recognition element, G3/MB as signal generator, and IME as transducer provided a "Mix and Measure" miniaturized platform for the construction of homogeneous label-free electrochemical biosensors.

UV irradiation is a threat to the living cells which could damage the DNA and lead to the death of cells. In this study, delaminated Ti3C2Tx flake was applied as a novel UV-protective material for living cells. Compared with naked yeasts, the cell viability of coated yeasts could be obviously increased after exposing to the UV light. Besides yeasts, this material could be applied in the protection of mammalian cell under UV irradiation. Thus, the delaminated MXene flake has potential applications in cells storage, cell transportation, and UV-resistant fields.

Platelet lysate (PL) contains a cocktail of growth factors that actively participates in cartilage repair. This study was designed to determine the effect and mechanism of PL on osteoarthritis (OA). An arthritis model was established to mimic human OA by intra-articular injection of monoiodoacetate (MIA) to Sprague Dawley (SD) rats. The model was weekly treated with PL by intra-articular injection. Thermal withdrawal latency, mechanical withdrawal threshold, and treadmill gait were tested for pain behavior observation. Histopathological and immunohistochemical analyses were conducted for evaluating cartilage degradation. Real time PCRs and Western blots were conducted to elucidate the mechanism of PL on primary chondrocytes. Results showed that, in vivo, PL significantly attenuated pain symptoms and exerted chondrocyte-protective and extracellular matrix (ECM)-modifying effect on the arthritic cartilage in a dose-dependent manner. The in situ expressions of type II Collagen (Col2) and matrix metalloproteinase 13 (Mmp13) in the arthritic cartilage was abnormal and was restored by PL. In vitro, PL significantly restored tumor necrosis factor α (TNF-α)-suppressed anabolic gene expression (Col2 and aggrecan) and TNF-α-increased catabolic gene expression (Col10, Mmp13, Adamts5, and Adamts9) in chondrocytes. The effects were mediated by TNF-α downstream signaling, including inhibition of NF-κB and c-Jun activities. This study provides certain knowledge of anti-OA effect and TNF signaling-related mechanism of PL, placing it as a promising and alternative option for OA therapy in the future.

Hirsutella sinensis fungus (HSF) is an artificial substitute of the well-known medicine Cordyceps sinensis with similar beneficial effects in humans. We previously found that HSF can regulate immune function and inhibit tumor growth; however, the mechanisms involved in these effects were still unclear. Accordingly, in this study, we investigated the effects of HSF on immune cell subsets in the tumor microenvironment in mice. The results showed that HSF inhibited Lewis lung cancer growth, alleviated abnormalities in routine blood tests, and enhanced tumor-infiltrating T cells, particularly the proportion of effector CD8[Formula: see text] T cells. In addition, HSF also ameliorated the immune-suppressive microenvironment and decreased the proportions of regulatory T cell and myeloid-derived suppressor cell populations. To confirm the effects of HSF on promotion of effector CD8[Formula: see text] T-cell production, we further evaluated changes in postoperative metastasis following treatment with HSF. Indeed, orthotopic lung metastasis was significantly suppressed, and survival times were increased in HSF-treated mice. Taken together, our findings suggested that HSF inhibited Lewis lung cancer by enhancing the population of effective CD8[Formula: see text] T cells.

Following the publication of the original article [1], it was reported that the accession number given in the ‘Data accessibility’ declaration, GSE65696, is incorrect.