Optical controlled and nuclear targeted CECR2 competitor to downregulate CSF-1 for metastatic breast cancer immunotherapy.

The crosstalk between breast cancer cells and tumor associated macrophages (TAMs) greatly contributes to tumor progression and immunosuppression. In this work, cat eye syndrome chromosome region candidate 2 (CECR2) is identified to overexpress in breast cancer patients, which can recognize v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) and activate nuclear factor κB (NF-κB) to release colony stimulating factor-1 (CSF-1). Pharmacological inhibition of CECR2 by the bromodomain competitor (Bromosporine, Bro) can downregulate CSF-1 to inhibit M2 type TAMs. To amplify the immunotherapeutic effect, a chimeric peptide-based and optical controlled CECR2 competitor (designated as N-PB) is constructed to enhance the nuclear targeted delivery of Bro and initiate an immunogenic cell death (ICD). In vivo results indicate a favorable breast cancer targeting ability and primary tumor suppression effect of N-PB under optical irradiation. Importantly, N-PB downregulates CSF-1 by competitive inhibition of CECR2 and NF-κB(RelA) interactions, thus inhibiting immunosuppressive M2-like TAMs while improving the antitumorigenic M1-like phenotype. Ultimately, the systemic anti-tumor immunity is activated to suppress the metastatic breast cancer in an optical controlled manner. This study provides a promising therapeutic target and reliable strategy for metastatic breast cancer treatment by interrupting immunosuppressive crosstalk between tumor cells and macrophages.

Health risk assessment and potential sources of metals in riparian soils of the Wujiang River, China.

In order to understand the pollution status of metals in the riparian soils along the Wujiang River, 26 sampling sites in the mainstream and tributary streams were selected for investigation. The geo-accumulation index (Igeo), Nemerow integrated pollution index, and potential ecological risk index were applied to evaluate the contamination status and ecological risks of metals. Results revealed that the average concentrations of As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn were 12.20, 0.51, 84.01, 57.42, 922.57, 38.37, 38.06, and 127.82 mg/kg, respectively. The metal contamination degree and ecological risks in the upper reaches were significantly higher than those in the middle and lower reaches of the Wujiang River. Cd was the dominant contamination metal. Significant non-carcinogenic and carcinogenic risks of metals were found in children based on the hazard index and carcinogenic risk. As was the main non-carcinogenic and carcinogenic pollutant metal in both adults and children. According to principal component analysis, hierarchical clustering analysis, and absolute principal component scores-multiple linear regression, anthropogenic sources (mining and agricultural activities) contributed most to Zn, Pb, Cr, Cd, Cu, and Ni, with contribution rates of 89.14, 82.32, 74.46, 72.12, 68.52, and 61.02%, respectively. Natural sources contributed most to Mn, with a contribution rate of 83.07%. Unidentified sources contributed most to As, with a contribution rate of 47.27%.

Chimeric Peptide-Engineered Self-Delivery Nanomedicine for Photodynamic-Triggered Breast Cancer Immunotherapy by Macrophage Polarization.

A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG8 -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.

Silencing HOXC13 exerts anti-prostate cancer effects by inducing DNA damage and activating cGAS/STING/IRF3 pathway.

BACKGROUND: Advanced prostate cancer (PCa) will develop into castration-resistant prostate cancer (CRPC) and lead to poor prognosis. As the primary subtype of CRPC, CRPC-AR accounts for the major induction of PCa heterogeneity. CRPC-AR is mainly driven by 25 transcription factors (TFs), which we speculate may be the key factors driving PCa toward CRPC. Therefore, it is necessary to clarify the key regulator and its molecular mechanism mediating PCa progression. METHODS: Firstly, we downloaded transcriptomic data and clinical information from TCGA-PRAD. The characteristic gene cluster was identified by PPI clustering, GO enrichment, co-expression correlation and clinical feature analyses for 25 TFs. Then, the effects of 25 TFs expression on prognosis of PCa patients was analyzed using univariate Cox regression, and the target gene was identified. The expression properties of the target gene in PCa tissues were verified using tissue microarray. Meanwhile, the related mechanistic pathway of the target gene was mined based on its function. Next, the target gene was silenced by small interfering RNAs (siRNAs) for cellular function and mechanistic pathway validation. Finally, CIBERSORT algorithm was used to analyze the infiltration levels of 22 immune cells in PCa patients with low and high expression of target gene, and validated by assaying the expression of related immunomodulatory factor. RESULTS: We found that HOX family existed independently in 25 TFs, among which HOXC10, HOXC12 and HOXC13 had unique clinical features and the PCa patients with high HOXC13 expression had the worst prognosis. In addition, HOXC13 was highly expressed in tumor tissues and correlated with Gleason score and pathological grade. In vitro experiments demonstrated that silencing HOXC13 inhibited 22RV1 and DU145 cell function by inducing cellular DNA damage and activating cGAS/STING/IRF3 pathway. Immune infiltration analysis revealed that high HOXC13 expression suppressed infiltration of γδ T cells and plasma cells and recruited M2 macrophages. Consistent with these results, silencing HOXC13 up-regulated the transcriptional expression of IFN-ß, CCL2, CCL5 and CXCL10. CONCLUSION: HOXC13 regulates PCa progression by mediating the DNA damage-induced cGAS/STING/IRF3 pathway and remodels TIME through regulation of the transcription of the immune factors IFN-ß, CCL2, CCL5 and CXCL10.

Spatio-temporal fusion of meteorological factors for multi-site PM2.5 prediction: A deep learning and time-variant graph approach.

In the field of environmental science, traditional methods for predicting PM2.5 concentrations primarily focus on singular temporal or spatial dimensions. This approach presents certain limitations when it comes to deeply mining the joint influence of multiple monitoring sites and their inherent connections with meteorological factors. To address this issue, we introduce an innovative deep-learning-based multi-graph model using Beijing as the study case. This model consists of two key modules: firstly, the 'Meteorological Factor Spatio-Temporal Feature Extraction Module'. This module deeply integrates spatio-temporal features of hourly meteorological data by employing Graph Convolutional Networks (GCN) and Long Short-Term Memory (LSTM) for spatial and temporal encoding respectively. Subsequently, through an attention mechanism, it retrieves a feature tensor associated with air pollutants. Secondly, these features are amalgamated with PM2.5 concentration values, allowing the 'PM2.5 Concentration Prediction Module' to predict with enhanced accuracy the joint influence across multiple monitoring sites. Our model exhibits significant advantages over traditional methods in processing the joint impact of multiple sites and their associated meteorological factors. By providing new perspectives and tools for the in-depth understanding of urban air pollutant distribution and optimization of air quality management, this model propels us towards a more comprehensive approach in tackling air pollution issues.

Chimeric Peptide Engineered Bioregulator for Metastatic Tumor Immunotherapy through Macrophage Polarization and Phagocytosis Restoration.

Tumor-associated macrophages (TAMs) are the most abundant immune cells in solid tumor tissues, which restrict antitumor immunity by releasing tumor-supporting cytokines and attenuating phagocytosis behaviors. In this work, a chimeric peptide engineered bioregulator (ChiP-RS) is constructed for tumor immunotherapy through macrophage polarization and phagocytosis restoration. ChiP-RS is fabricated by utilizing macrophage-targeting chimeric peptide (ChiP) to load Toll-like receptor agonists (R848) and Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP-2) inhibitor (SHP099). Among which, ChiP-RS prefers to be internalized by TAMs, repolarizing M2 macrophages into M1 macrophages to reverse the immunosuppressive microenvironment. In addition, SHP-2 can be downregulated to promote phagocytotic elimination behaviors of M1 macrophages, which will also activate T cell-based antitumor immunity for metastatic tumor therapy. In vitro and in vivo findings demonstrate a superior suppression effect of ChiP-RS against metastatic tumors without systemic side effects. Such a simple but effective nanoplatform provides sophisticated synergism for immunotherapy, which may facilitate the development of translational nanomedicine for metastatic tumor treatment.

Blood typing and transfusion therapy in a patient with A2 subtype acute myeloid leukemia M2: A case report.

BACKGROUND: Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. However, AML is relatively rare in the population overall, accounting for only about 1 percent of all cancers. Treatment for AML can be very effective for some patients, yet it leaves others with serious and even life-threatening side effects. Chemotherapy is still the primary treatment for most AML, but over time, leukemia cells become resistant to chemotherapy drugs. In addition, stem cell transplantation, targeted therapy, and immunotherapy are currently available. At the same time, with the progression of the disease, the patient may have corresponding complications, such as coagulation dysfunction, anemia, granulocytopenia, and repeated infection, so transfusion supportive therapy will be involved in the overall treatment regime. To date, few articles have reported on blood transfusion treatment options for patients with ABO subtypes AML-M2. Blood transfusion therapy is an important supportive treatment for AML-M2, and accurate determination of patients' blood type is one of the most important steps in the treatment process. In this study, we explored blood typing and supportive treatment strategies for a patient with A2 subtype AML-M2 to provide the basis for treatment for all patients. CASE SUMMARY: In order to determine the blood type of the patient, serological and molecular biological methods were used for reference tests, and the genetic background was studied to determine the patient's final blood type and select the appropriate blood products for infusion treatment. According to the results obtained by serological and molecular biological methods, the blood type of the patient was A2 subtype; the genotype was A02/001; the irregular antibody screening was negative, and anti-A1 was found in the plasma. According to the overall treatment plan, active anti-infection, elevated cells, component blood transfusion support, and other rescue and supportive treatments were given, and the patient successfully passed the stage of myelosuppression after chemotherapy. Re-examination of bone marrow smears showed that AL was in complete remission of bone marrow signs, and minimal residual leukemia lesions suggested no cells with obvious abnormal immunophenotype (residual leukemia cells < 10-4). CONCLUSION: The infusion of patients with A2 subtype AML-M2 with A irradiated platelets and O washing red blood cells can meet the needs of clinical treatment.

Drug induced mitochondria dysfunction to enhance photodynamic therapy of hypoxic tumors.

As most solid tumors are characterized by a hypoxic microenvironment, enormous efforts have been made to develop strategies to fight hypoxia. This study shows that ivermectin (IVM), an antiparasitic drug, is able to alleviate tumor hypoxia by inhibiting mitochondrial respiration. We explore this to strengthen oxygen-dependent photodynamic therapy (PDT) using chlorin e6 (Ce6) as a photosensitizer. To synergize their pharmacological behaviors, Ce6 and IVM are encapsulated into stable Pluronic F127 micelles. The micelles are uniform in size and seem well-suited for the co-delivery of Ce6 and IVM. The micelles could passively target the drugs into tumors and enhance their cellular internalization. Most importantly, through mitochondrial dysfunction, the micelles reduce the oxygen consumption (making the tumor less hypoxic). Consequently, the production of reactive oxygen species would be increase which, in turn, improves the efficacy of PDT against hypoxic tumors.

Recent Progress in Carrier-Free Nanomedicine for Tumor Phototherapy.

Safe and effective strategies are urgently needed to fight against the life-threatening diseases of various cancers. However, traditional therapeutic modalities, such as radiotherapy, chemotherapy and surgery, exhibit suboptimal efficacy for malignant tumors owing to the serious side effects, drug resistance and even relapse. Phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), are emerging therapeutic strategies for localized tumor inhibition, which can produce a large amount of reactive oxygen species (ROS) or elevate the temperature to initiate cell death by non-invasive irradiation. In consideration of the poor bioavailability of phototherapy agents (PTAs), lots of drug delivery systems have been developed to enhance the tumor targeted delivery. Nevertheless, the carriers of drug delivery systems inevitably bring biosafety concerns on account of their metabolism, degradation, and accumulation. Of note, carrier-free nanomedicine attracts great attention for clinical translation with synergistic antitumor effect, which is characterized by high drug loading, simplified synthetic method and good biocompatibility. In this review, the latest advances of phototherapy with various carrier-free nanomedicines are summarized, which may provide a new paradigm for the future development of nanomedicine and tumor precision therapy.

High Endogenously Synthesized N-3 Polyunsaturated Fatty Acids in Fat-1 Mice Attenuate High-Fat Diet-Induced Insulin Resistance by Inhibiting NLRP3 Inflammasome Activation via Akt/GSK-3ß/TXNIP Pathway.

High-fat (HF) diets and low-grade chronic inflammation contribute to the development of insulin resistance and type 2 diabetes (T2D), whereas n-3 polyunsaturated fatty acids (PUFAs), due to their anti-inflammatory effects, protect against insulin resistance. Interleukin (IL)-1ß is implicated in insulin resistance, yet how n-3 PUFAs modulate IL-1ß secretion and attenuate HF diet-induced insulin resistance remains elusive. In this study, a HF diet activated NLRP3 inflammasome via inducing reactive oxygen species (ROS) generation and promoted IL-1ß production primarily from adipose tissue preadipocytes, but not from adipocytes and induced insulin resistance in wild type (WT) mice. Interestingly, endogenous synthesized n-3 polyunsaturated fatty acids (PUFAs) reversed this process in HF diet-fed fat-1 transgenic mice although the HF diet induced higher weight gain in fat-1 mice, compared with the control diet. Mechanistically, palmitic acid (PA), the main saturated fatty acid in an HF diet inactivated AMPK and led to decreased GSK-3ß phosphorylation, at least partially through reducing Akt activity, which ultimately blocked the Nrf2/Trx1 antioxidant pathway and induced TXNIP cytoplasm translocation and NLRP3 inflammasome activation, whereas docosahexaenoic acid (DHA), the most abundant n-3 PUFA in fat-1 adipose tissue, reversed this process via inducing Akt activation. Our GSK-3ß shRNA knockdown study further revealed that GSK-3ß played a pivot role between the upstream AMPK/Akt pathway and downstream Nrf2/Trx1/TXNIP pathway. Given that NLRP3 inflammasome is implicated in the development of most inflammatory diseases, our results suggest the potential of n-3 PUFAs in the prevention or adjuvant treatment of NLRP3 inflammasome-driven diseases.

Small RNA sequencing reveals various microRNAs involved in piperine biosynthesis in black pepper (Piper nigrum L.).

BACKGROUND: Black pepper (Piper nigrum L.), an important and long-cultivated spice crop, is native to South India and grown in the tropics. Piperine is the main pungent and bioactive alkaloid in the berries of black pepper, but the molecular mechanism for piperine biosynthesis has not been determined. MicroRNAs (miRNAs), which are classical endogenous noncoding small RNAs, play important roles in regulating secondary metabolism in many species, but less is known regarding black pepper or piperine biosynthesis. RESULTS: To dissect the functions of miRNAs in secondary metabolism especially in piperine biosynthesis, 110 known miRNAs, 18 novel miRNAs and 1007 individual targets were identified from different tissues of black pepper by small RNA sequencing. qRT-PCR and 5'-RLM-RACE experiments were conducted to validate the reliability of the sequencing data and predicted targets. We found 3 miRNAs along with their targets including miR166-4CL, miR396-PER and miR397-CCR modules that are involved in piperine biosynthesis. CONCLUSION: MiRNA regulation of secondary metabolism is a common phenomenon in plants. Our study revealed new miRNAs that regulate piperine biosynthesis, which are special alkaloids in the piper genus, and they might be useful for future piperine genetic improvement of black pepper.

Evaluation of analytic and clinical performance of two immunoassays for detecting thyroid-stimulating receptor antibody in the diagnosis of Graves' disease.

OBJECTIVE: To evaluate the analytical and clinical performance of two immunoassays for diagnosis of Graves' disease (GD), the Immulite thyroid-stimulating immunoglobulin (TSI), and Elecsys Anti-TSH receptor (TSHR) assay. METHODS: Precision and analytical measurement range were assessed using pooled samples of patients. The comparison between the two methods was evaluated using 579 clinical samples, and receiver operating characteristic (ROC) curves were drawn using the final diagnosis as reference. Clinical sensitivity and specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the two tests. RESULTS: The repeatability and intermediate imprecision coefficient of variation (CV%) of the TSI assay were 3.8% and 4.1% at 0.95 IU/L, and 3.5% and3.6% at 19.5 IU/L, respectively. The assays were linear over a range 0.27-38.5 IU/L. There was a high correlation between the quantitative results of the two methods (correlation coefficient r = 0.930). The cut-off value obtained by ROC analysis for TSI assay was 0.7 IU/L with sensitivity of 93.7% and specificity of 85.1%. An overall qualitative agreement of 91.5% between two methods was observed. Among 44 patients with discordant qualitative results, the TSI assay provided more satisfactory results consistent with clinical diagnoses. CONCLUSION: The TSI assay showed excellent analytical performance and provided a high PPV for GD.

Development of a novel ssDNA aptamer targeting cardiac troponin I and its clinical applications.

Cardiac troponin I (cTnI) is a specific biomarker of acute myocardial infarction (AMI). However, cTnI detection kits prepared with antibodies have many defects. Nucleic acid aptamers are sequences of single-strand DNA or RNA that can overcome the deficiency of antibodies. Herein, sandwich ELONA methods were established based on aptamers. Two selected ssDNA aptamers (Apt3 and Apt6) showed high binding affinity and sensibility (Apt3: Kd = 1.01 ± 0.07 nM, Apt6: k = 0.68 ± 0.05) and did not bind to the same domain of cTnI. Therefore, these two aptamers can be applied to the ELONA methods. The detection range of cTnI using the dual-aptamer sandwich ELONA method was 0.05-200 ng/mL, and the bioanalytical method verification results can meet the national standard of Chinese Pharmacopoeia (2020 Edition). There was no difference between results of the dual-aptamer sandwich ELONA method and the diagnostic results of serum obtained from 243 people (P = 0.39, P ˃ 0.05). The sensitivity and specificity of the ELONA with cTnI in serum were 96.46% and 93.85%, respectively. Compared with the FICA kit, which is clinically used, the consequences of ELONA method are closer to the diagnostic results. This study suggests that the aptamers Apt3 and Apt6 have high affinity and strong specificity and that the dual-aptamer sandwich ELONA method has a wide detection range and can be used to determine cTnI in serum, with potential applications in the diagnosis of AMIs.

Necrostatin-1 prolongs latency to convulsion in mice exposed to high oxygen partial pressure.

INTRODUCTION: Exposure to very high oxygen partial pressure may cause central nervous system oxygen toxicity (CNS-OT). The role of necroptosis in the pathogenesis of CNS-OT is still unclear. METHODS: In experiment one, male C57BL/6 mice in the oxygen toxicity (OT) group (n = 5) and necrostatin-1 (Nec-1; a necroptosis inhibitor) (1.5 mg·kg-1, intraperitoneal) group (n = 5) were exposed to pure oxygen at 600 kPa, and the latency to tonic-clonic seizure was recorded. In experiment two, mice were divided into three groups: control group (n = 11), OT group (n = 12) and Nec-1 group (n = 12). Nec-1 was intraperitoneally administered 30 min before oxygen exposure. Mice in the OT group and Nec-1 group were exposed to pure oxygen at 400 kPa for 30 min, and then sacrificed; the brain was harvested for the assessment of inflammation, oxidative stress and necroptosis. RESULTS: Experiment one. Nec-1 pre-treatment significantly prolonged the latency to seizure (245 [SD 18] seconds in the OT group versus 336 (34) seconds in the Nec-1 group). Experiment two. Nec-1 pre-treatment markedly reduced inflammatory cytokines and inhibited cerebral necroptosis, but failed to significantly suppress cerebral oxidative stress. CONCLUSIONS: These findings indicate necroptosis is involved in the pathogenesis of CNS-OT, and inhibition of necroptosis may prolong seizure latency, but the specific mechanisms should be investigated further.

An oncolytic vaccinia virus armed with anti-human-PD-1 antibody and anti-human-4-1BB antibody double genes for cancer-targeted therapy.

Oncolytic virus can selectively recognize cancer cells, target tumors, and stimulate an oncolytic and immune response. Recombinant armed oncolytic vaccinia virus has emerged as an attractive tool in oncolytic virotherapy because it has tumor-specific cytotoxicity and serves as a vector to express immune genes. A novel thymidine kinase (TK) gene-deleted oncolytic vaccinia virus (named ΔTK-Armed-VACV) armed with anti-human-programed cell death-1 protein (PD-1) antibody and anti-human-tumor necrosis factor receptor superfamily, member 9 (4-1BB) antibody genes was constructed based on Western Reserve in our previous study. The present study evaluated the ability of this virus for cancer-targeted therapy both in vitro and in vivo. A complete morphological structure of ΔTK-Armed-VACV was verified using transmission electron microscopy. The antibody was co-expressed with the replication of ΔTK-Armed-VACV in vitro assessed by Western blot analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-rboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay showed that the ΔTK-Armed-VACV exhibited significant tumor-specific cytotoxicity in vitro. The ΔTK-Armed-VACV inhibited the tumor growth in a 4T1 or A549 tumor-bearing mouse model. ELISpot assay showed that ΔTK-Armed-VACV-treated mice induced the expression of interferon-gamma, and lactate dehydrogenase-dependent cytotoxicity assay revealed that the ΔTK-Armed-VACV treatment activated tumor-specific cytotoxic T lymphocytes. The results indicated that oncolytic VACV with Western Reserve-mediated anti-human-PD-1 and anti-human-4-1BB antibody co-expression exerted a significant antitumor effect, indicating that the combination of oncolytic virotherapy and immunotherapy by the oncolytic VACV expressing one or more immune checkpoint genes might have satisfactory clinical expectations.

Double-Scale Adaptive Transmission in Time-Varying Channel for Underwater Acoustic Sensor Networks.

The communication channel in underwater acoustic sensor networks (UASNs) is time-varying due to the dynamic environmental factors, such as ocean current, wind speed, and temperature profile. Generally, these phenomena occur with a certain regularity, resulting in a similar variation pattern inherited in the communication channels. Based on these observations, the energy efficiency of data transmission can be improved by controlling the modulation method, coding rate, and transmission power according to the channel dynamics. Given the limited computational capacity and energy in underwater nodes, we propose a double-scale adaptive transmission mechanism for the UASNs, where the transmission configuration will be determined by the predicted channel states adaptively. In particular, the historical channel state series will first be decomposed into large-scale and small-scale series and then be predicted by a novel k-nearest neighbor search algorithm with sliding window. Next, an energy-efficient transmission algorithm is designed to solve the problem of long-term modulation and coding optimization. In particular, a quantitative model is constructed to describe the relationship between data transmission and the buffer threshold used in this mechanism, which can then analyze the influence of buffer threshold under different channel states or data arrival rates theoretically. Finally, numerical simulations are conducted to verify the proposed schemes, and results show that they can achieve good performance in terms of channel prediction and energy consumption with moderate buffer length.

Advances in the treatment of neuropathic pain with hyperbaric oxygen.

Neuropathic pain (NPP) refers to the pain caused by primary or secondary injury or dysfunction of the peripheral or central nervous system, and usually requires multidisciplinary treatment. However, most pharmacological and non-pharmacological interventions can only temporarily and/or moderately improve pain-related symptoms, and they often produce unbearable adverse reactions or cause drug resistance. Hyperbaric oxygen (HBO2) therapy has been widely used in the clinical treatment of some diseases due to its advantages of safety, few side effects, no resistance, and non-invasiveness. In recent years, increasing numbers of basic and clinical studies have been conducted to investigate the efficacy and mechanism of HBO2 in the treatment of NPP, and great progress has been made in this field. In this paper, we briefly introduce the pathogenesis of NPP and therapeutic effects of HBO2 and summarize the mechanisms underlying the effects of HBO2 in treating NPP, which may provide reference for the clinical treatment of pain with HBO2.

Zero-Shot Learning to Index on Semantic Trees for Scalable Image Retrieval.

In this study, we develop a new approach, called zero-shot learning to index on semantic trees (LTI-ST), for efficient image indexing and scalable image retrieval. Our method learns to model the inherent correlation structure between visual representations using a binary semantic tree from training images which can be effectively transferred to new test images from unknown classes. Based on predicted correlation structure, we construct an efficient indexing scheme for the whole test image set. Unlike existing image index methods, our proposed LTI-ST method has the following two unique characteristics. First, it does not need to analyze the test images in the query database to construct the index structure. Instead, it is directly predicted by a network learnt from the training set. This zero-shot capability is critical for flexible, distributed, and scalable implementation and deployment of the image indexing and retrieval services at large scales. Second, unlike the existing distance-based index methods, our index structure is learnt using the LTI-ST deep neural network with binary encoding and decoding on a hierarchical semantic tree. Our extensive experimental results on benchmark datasets and ablation studies demonstrate that the proposed LTI-ST method outperforms existing index methods by a large margin while providing the above new capabilities which are highly desirable in practice.

[Regulatory roles of microRNAs in sarcopenia and exercise intervention].

Sarcopenia is an age-related degenerative disease, in which skeletal muscle mass and function are reduced during aging process. Physical intervention is one of the most effective strategies available for the treatment of sarcopenia. Studies have shown that microRNAs (miRNAs), as important regulators of gene expression, play an important role in maintaining the homeostasis of senescent skeletal muscle cells by regulating skeletal muscle cell development (proliferation and differentiation), mitochondrial biogenesis, protein synthesis and degradation, inflammatory response and metabolic pathways. Furthermore, exercise can combat age-related changes in muscle mass, composition and function, which is associated with the changes in the expression and biological functions of miRNAs in skeletal muscle cells. In this article, we systematically review the regulatory mechanisms of miRNAs in skeletal muscle aging, and discuss the regulatory roles and molecular targets of exercise-mediated miRNAs in muscular atrophy during aging process, which may provide novel insights into the prevention and treatment of sarcopenia.

Regulatory roles of microRNAs in sarcopenia and exercise intervention / 生理学报

Sarcopenia is an age-related degenerative disease, in which skeletal muscle mass and function are reduced during aging process. Physical intervention is one of the most effective strategies available for the treatment of sarcopenia. Studies have shown that microRNAs (miRNAs), as important regulators of gene expression, play an important role in maintaining the homeostasis of senescent skeletal muscle cells by regulating skeletal muscle cell development (proliferation and differentiation), mitochondrial biogenesis, protein synthesis and degradation, inflammatory response and metabolic pathways. Furthermore, exercise can combat age-related changes in muscle mass, composition and function, which is associated with the changes in the expression and biological functions of miRNAs in skeletal muscle cells. In this article, we systematically review the regulatory mechanisms of miRNAs in skeletal muscle aging, and discuss the regulatory roles and molecular targets of exercise-mediated miRNAs in muscular atrophy during aging process, which may provide novel insights into the prevention and treatment of sarcopenia.