Affinity-based protein profiling-driven discovery of myricanol as a Nampt activator.

Herein, we synthesized an affinity-based probe of myricanol (pMY) with a photo-affinity cross-linker to initiate a bioconjugation reaction, which was applied for target identification in live C2C12 myotubes. Pull-down of biotinylated pMY coupled with mass spectroscopy and Western blotting revealed that pMY can bind with nicotinamide phosphoribosyltransferase (Nampt), a rate-limiting enzyme in the nicotinamide adenine dinucleotide salvage pathway. Cellular thermal shift assay, drug affinity responsive target stability assay and recombinant protein labeling further validated the direct interaction between myricanol and Nampt. Myricanol did not affect the protein expression of Nampt, but enhanced its activity. Knock-down of Nampt totally abolished the promoting effect of myricanol on insulin-stimulated glucose uptake in C2C12 myotubes. Taken together, myricanol sensitizes insulin action in myotubes through binding with and activating Nampt.

Effect of three aging processes on physicochemical and As(V) adsorption properties of Ce/Mn-modified biochar.

Modified biochar used for soil remediation is affected by exposure to the environment and aging process results in changes in its physicochemical properties and As(V) adsorption and immobilization in soil. Herein, the Ce/Mn-modified wheat straw-biochar (MBC) was manufactured and then aged through three artificial aging processes by exposure to soil with additional natural, freeze-thaw, and dry-wet cycles involved. It revealed that the specific surface areas of freeze-thaw-aged MBC reached 214.98 m2/g and was increased more than those of other two aging treatments. In addition, the pH values and C contents of MBC all decreased after aging while the H and O contents increased. Correspondingly, the contents of O-containing functional groups like C-O, -OH, and CO all increased by >16% with aging. The freeze-thaw cycling and alternating dry-wet aging treatments improved adsorption capacities of As(V) onto MBC and were increased by 16.2 and 10.6% at pH 5, respectively and these samples exhibited the best recyclability and adsorption selectivity for As(V). However, natural aging exerted a lower effect for As(V) adsorption by MBC due to its few changes on physicochemical properties. Causally, the freeze-thaw and dry-wet aging activated the Ce/Mn-oxides to generate Mn2+/3+ species and a new mono-Ce that exerted a strong bonding complexation with As(V) to form Ce/Mn-O-As ligands and increased CeAsO4 precipitation. Our results offer a new insight into the alterations expected for modified biochars with aging treatment in terms of As(V) adsorption for its long-term utilization in As contaminated soil.

Phosphorus-modified biochar cross-linked Mg-Al layered double-hydroxide stabilizer reduced U and Pb uptake by Indian mustard (Brassica juncea L.) in uranium contaminated soil.

The decommissioning of uranium tailings (UMT) is usually accompanied by uranium (U) contamination in soil, which poses a serious threat to human health and ecological security. Therefore, the remediation of uranium pollution in soil is imminent from ecological and environmental points of view. In recent years, the use of biochar stabilizers to repair uranium tailings (UMT) soil has become a research hotspot. In this study, a novel phosphorus-modified bamboo biochar (PBC) cross-linked Mg-Al layered double-hydroxide composite (PBC@LDH) was prepared. The hyperaccumulator plant Indian mustard (Brassica juncea L.) was selected as the test plant for outdoor pot experiments, and the stabilizers were added to the UMT soil at the dosage ratio of 15 g kg-1, which verified the bioconcentrate and translocate of U and associated heavy metal Pb in the UMT soil by Indian mustard after stabilizer remediated. The results shown that, after 50 days of growth, compared with the untreated sample (CK), the Indian mustard in PBC@LDH treatment possessed a better growth and its biomass weight of whole plant was increased by 52.7%. Meanwhile, the bioconcentration factors (BF) of U and Pb for PBC@LDH treatment were significantly decreased by 73.4% and 34.2%, respectively; and the translocation factors (TF) were also commendable reduced by 15.1% and 2.4%, respectively. Furthermore, the Tessier available forms of U and Pb in rhizosphere soil showed a remarkably decrease compared with CK, which reached by 55.97% and 14.1% after PBC@LDH stabilization, respectively. Complexation, precipitation, and reduction of functional groups released by PBC@LDH with U and Pb described the immobilization mechanisms of biochar stabilizer preventing U and Pb enrichment in Indian mustard. As well as, the formation of U-containing vesicles was prevented by the precipitation of -OH functional groups with free U and Pb ions around the cell tissue fluids and vascular bundle structure of plant roots, thereby reducing the migration risk of toxic heavy metals to above-ground parts. In conclusion, this research demonstrates that the PBC@LDH stabilizer offers a potentially effective amendment for the remediation of U contaminated soil.

Boronate ester bond-based potentiometric aptasensor for screening carcinoembryonic antigen-glycoprotein using nanometer-sized CaCO3 with ion-selective electrode.

Phenylboronic acid-functionalized nanometer-sized CaCO3 particles (PBA-CaCO3) were designed to determine the carcinoembryonic antigen (CEA) glycoprotein with a portable Ca2+ ion-selective electrode (Ca-ISE) through a typical boronate ester bond. CaCO3 nanospheres were conjugated to 3-aminophenylboronic acid by amine-epoxy reaction, whereas target CEA was captured into the aptasensing interface by the immobilized thiolated aptamer on gold substrate. Upon PBA-CaCO3 introduction, 3-aminophenylboronic acid labeled to CaCO3 microsphere specifically recognized with CEA glycoprotein based on sugar-boronic acid interaction to form a sandwiched complex. The carried CaCO3 was dissolved under acidic conditions to release Ca2+ ion with a portable Ca-ISE readout. Thanks to the specific boronate ester bond between PBA and 1,2-diols, the synthesized PBA-CaCO3 exhibited good conjugation properties for CEA glycoprotein. Under optimum conditions, Ca-ISE-based aptasensing platform exhibited good electrode potential response for evaluation of target CEA, and allowed detection of CEA at a concentration as low as 7.3 pg mL-1. Importantly, Ca-ISE-based aptasensing system is readily extended to detect other disease-related glycoproteins by controlling the corresponding aptamer.

Unveiling the transcriptome alteration of POMC neuron in diet-induced obesity.

Loss of neuron homeostasis in the arcuate nucleus (ARC) is responsible for diet-induced-obesity (DIO). We previously reported that loss of Rb1 gene compromised the homeostasis of anorexigenic POMC neurons in ARC and induced obesity in mice. To evaluate the development of DIO, we propose to analyze the transcriptomic alteration of POMC neurons in mice following high fat diet (HFD) feeding. We isolated these neurons from established DIO mice and performed transcriptomic profiling using RNA-seq. In total, 1066 genes (628 upregulated and 438 downregulated) were identified as differentially expressed genes (DEGs). Pathway enrichment analysis with these DEGs further revealed that "cell cycle," "apoptosis," "chemokine signaling," and "sphingolipid metabolism" pathways were correlated with DIO development. Moreover, we validated that the pRb protein, a key regulator of "cell cycle pathway," was inactivated by phosphorylation in POMC neurons by HFD feeding. Importantly, the reversal of deregulated cell cycle by stereotaxic delivering of the unphosphorylated pRbΔP in ARC significantly meliorated the DIO. Collectively, our study provides insights into the mechanisms related to the loss of homeostasis of POMC neurons in DIO, and suggests pRb phosphorylation as a potential intervention target to treat DIO.

Handheld pH meter-assisted immunoassay for C-reactive protein using glucose oxidase-conjugated dendrimer loaded with platinum nanozymes.

A simple and feasible pH meter-based immunoassay is reported for detection of C-reactive protein (CRP) using glucose oxidase (GOD)-conjugated dendrimer loaded with platinum nanozyme. Initially, platinum nanozymes were loaded into the dendrimers through an in situ synthetic method. Then, GOD and monoclonal anti-CRP antibody with a high molar ratio were covalently conjugated onto carboxylated dendrimers via typical carbodiimide coupling. The immunoreaction was carried out with a competitive mode in a CRP-coated microplate. Along with formation of immunocomplex, the added glucose was oxidized into gluconic acid and hydrogen peroxide by GOD, and the latter was further decomposed by platinum nanozyme, thus accelerating chemical reaction in the positive direction. The produced gluconic acid changed the pH of detection solution, which was determined using a handheld pH meter. Under optimum conditions, the pH meter-based immunoassay gave a good signal toward target CRP from 0.01 to 100 ng mL-1. The limit of detection was 5.9 pg mL-1. An intermediate precision ≤ 11.2% was acquired with batch-to-batch identification. No nonspecific adsorption was observed during a series of procedures to detect target CRP, and the cross-reaction against other biomarkers was very low. Importantly, our system gave well-matched results for analysis of human serum samples relative to a referenced ELISA kit.Graphical abstract.

[A study on KIF1A gene missense variant analysis and its protein expression and structure profiles of an autism spectrum disorder family trio].

OBJECTIVE: To analyze the pathogenic variants of the KIF1A gene and its corresponding protein structure in an autism spectrum disorder (ASD) family trio carrying harmful missense variants in the KIF1A gene. METHODS: The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant. RESULTS: The WES sequencing revealed a missense variant c.664A>C (p.Asn222His) in the child's KIF1A gene, and this variant was a de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of KIF1A gene in the brain. It is found that KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of KIF1A will cause many changes in the secondary structure of protein, such as alpha-helix, beta-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function. CONCLUSION: The KIF1A gene may be a risk gene for ASD.

Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide-Gonearrestide.

In this study, a novel scorpion venom-derived peptide named Gonearrestide was identified in an in-house constructed scorpion venom library through a combination of high-throughput NGS transcriptome and MS/MS proteome platform. In total, 238 novel peptides were discovered from two scorpion species; and 22 peptides were selected for further study after a battery of functional prediction analysis. Following a series of bioinformatics analysis alongside with in vitro biological functional screenings, Gonearrestide was found to be a highly potent anticancer peptide which acts on a broad spectrum of human cancer cells while causing few if any observed cytotoxic effects on epithelial cells and erythrocytes. We further investigated the precise anticancer mechanism of Gonearrestide by focusing on its effects on the colorectal cancer cell line, HCT116. NGS RNA sequencing was employed to obtain full gene expression profiles in HCT116 cells, cultured in the presence and absence of Gonearrestide, to dissect signalling pathway differences. Taken together the in vitro, in vivo and ex vivo validation studies, it was proven that Gonearrestide could inhibit the growth of primary colon cancer cells and solid tumours by triggering cell cycle arrest in G1 phase through inhibition of cyclin-dependent kinases 4 (CDK4) and up-regulate the expression of cell cycle regulators/inhibitors-cyclin D3, p27, and p21. Furthermore, prediction of signalling pathways and potential binding sites used by Gonearrestide are also presented in this study.

In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer.

Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progression; however, the mechanism of OPN-induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage-independent growth, cell migration and invasion in KRAS gene mutant cells but to a lesser extent in KRAS wild-type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E-cadherin in KRAS mutant cells. In human CRC specimens, a high-level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E-cadherin expression. Furthermore, we have found that 15 genes were co-upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene signature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer.

Hylaranins: prototypes of a new class of amphibian antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii.

Amphibian skin secretions contain a broad spectrum of biologically active compounds, particularly antimicrobial peptides, which are considered to constitute a first line of defence against bacterial infection. Here we describe the identification of two prototype peptides representing a novel structural class of antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii. Named hylaranin-L1 (GVLSAFKNALPGIMKIIVamide) and hylaranin-L2 (GVLSVIKNALPGIMRFIAamide), both peptides consist of 18 amino acid residues, are C-terminally amidated and are of unique primary structures. Their primary structures were initially deduced by MS/MS fragmentation sequencing from reverse-phase HPLC fractions of skin secretion that demonstrated antimicrobial activity. Subsequently, their precursor-encoding cDNAs were cloned from a skin secretion-derived cDNA library and their primary structures were confirmed unequivocally. Synthetic replicates of both peptides exhibited broad-spectrum antimicrobial activity with mean inhibitory concentrations (MICs) of 34 µM against Gram-negative Escherichia coli, 4.3 µM against Gram-positive Staphylococcus aureus and 4-9 µM against the yeast, Candida albicans. Both peptides exhibited little haemolytic activity (<6%) at the MICs for S. aureus and C. albicans. Amphibian skin secretions thus continue to provide novel antimicrobial peptide structures that may prove to be lead compounds in the design of new classes of anti-infection therapeutics.

Ornithokinin (avian bradykinin) from the skin of the Chinese bamboo odorous frog, Odorrana versabilis.

One of the most widespread and abundant families of pharmacologically active peptides in amphibian defensive skin secretions is the bradykinins and related peptides. Despite retaining certain primary structural attributes that assign them to this peptide family, bradykinins and related peptides are unique among amphibian skin peptides in that they exhibit a wide range of primary structural variations, post-translational modifications and/or N-terminal or C-terminal extensions. Initially it was believed that their high degree of primary structural heterogeneity was reflective of random gene mutations within species, but latterly, there is an increasing body of evidence that the spectrum of structural modifications found within this peptide family is reflective of the vertebrate predator spectrum of individual species. Here we report the discovery of ornithokinin (avian bradykinin - Thr(6) , Leu(8) -bradykinin) in the skin secretion of the Chinese bamboo odorous frog, Odorrana versabilis. Molecular cloning of its biosynthetic precursor-encoding cDNA from a skin secretion-derived cDNA library revealed a deduced open-reading frame of 86 amino acid residues, encoding a single copy of ornithokinin towards its C-terminus. The domain architecture of this ornithokinin precursor protein was consistent with that of a typical amphibian skin peptide and quite different to that of the ornithokininogen from chicken plasma. Ornithokinin was reported to induce hypotension in the chicken and to contract the chicken oviduct but to have no obvious effect on the rat uterus. However, in this study, synthetic ornithokinin was found to contract the rat ileum (EC50 = 539 nM) and to increase contraction frequency in the rat uterus (EC50 = 1.87 µM).

Scientometric trends and knowledge maps of global health systems research.

BACKGROUND: In the last few decades, health systems research (HSR) has garnered much attention with a rapid increase in the related literature. This study aims to review and evaluate the global progress in HSR and assess the current quantitative trends. METHODS: Based on data from the Web of Science database, scientometric methods and knowledge visualization techniques were applied to evaluate global scientific production and develop trends of HSR from 1900 to 2012. RESULTS: HSR has increased rapidly over the past 20 years. Currently, there are 28,787 research articles published in 3,674 journals that are listed in 140 Web of Science subject categories. The research in this field has mainly focused on public, environmental and occupational health (6,178, 21.46%), health care sciences and services (5,840, 20.29%), and general and internal medicine (3,783, 13.14%). The top 10 journals had published 2,969 (10.31%) articles and received 5,229 local citations and 40,271 global citations. The top 20 authors together contributed 628 papers, which accounted for a 2.18% share in the cumulative worldwide publications. The most productive author was McKee, from the London School of Hygiene & Tropical Medicine, with 48 articles. In addition, USA and American institutions ranked the first in health system research productivity, with high citation times, followed by the UK and Canada. CONCLUSIONS: HSR is an interdisciplinary area. Organization for Economic Co-operation and Development countries showed they are the leading nations in HSR. Meanwhile, American and Canadian institutions and the World Health Organization play a dominant role in the production, collaboration, and citation of high quality articles. Moreover, health policy and analysis research, health systems and sub-systems research, healthcare and services research, health, epidemiology and economics of communicable and non-communicable diseases, primary care research, health economics and health costs, and pharmacy of hospital have been identified as the mainstream topics in HSR fields. These findings will provide evidence of the current status and trends in HSR all over the world, as well as clues to the impact of this popular topic; thus, helping scientific researchers and policy makers understand the panorama of HSR and predict the dynamic directions of research.

AcT-2: a novel myotropic and antimicrobial type 2 tryptophyllin from the skin secretion of the Central American red-eyed leaf frog, Agalychnis callidryas.

Tryptophyllins are a diverse family of amphibian peptides originally found in extracts of phyllomedusine frog skin by chemical means. Their biological activities remain obscure. Here we describe the isolation and preliminary pharmacological characterization of a novel type 2 tryptophyllin, named AcT-2, from the skin secretion of the red-eyed leaf frog, Agalychnis callidryas. The peptide was initially identified during smooth muscle pharmacological screening of skin secretion HPLC fractions and the unique primary structure--GMRPPWF-NH2--was established by both Edman degradation and electrospray MS/MS fragmentation sequencing. A. cDNA encoding the biosynthetic precursor of AcT-2 was successfully cloned from a skin secretion-derived cDNA library by means of RACE PCR and this contained an open-reading frame consisting of 62 amino acid residues with a single AcT-2 encoding sequence located towards the C-terminus. A synthetic replicate of AcT-2 was found to relax arterial smooth muscle (EC50 = 5.1 nM) and to contract rat urinary bladder smooth muscle (EC50 = 9.3 µ M). The peptide could also inhibit the growth of the microorganisms, Staphylococcus aureus, (MIC = 256 mg/L) Escherichia coli (MIC = 512 mg/L), and Candida albicans (128 mg/L). AcT-2 is thus the first amphibian skin tryptophyllin found to possess both myotropic and antimicrobial activities.

Myricanol prevents aging-related sarcopenia by rescuing mitochondrial dysfunction via targeting peroxiredoxin 5.

Aging is a process that represents the accumulation of changes in organism overtime. In biological level, accumulations of molecular and cellular damage in aging lead to an increasing risk of diseases like sarcopenia. Sarcopenia reduces mobility, leads to fall-related injuries, and diminishes life quality. Thus, it is meaningful to find out novel therapeutic strategies for sarcopenia intervention that may help the elderly maintain their functional ability. Oxidative damage-induced dysfunctional mitochondria are considered as a culprit of muscle wasting during aging. Herein, we aimed to demonstrate whether myricanol (MY) protects aged mice against muscle wasting through alleviating oxidative damage in mitochondria and identify the direct protein target and its underlying mechanism. We discovered that MY protects aged mice against the loss of muscle mass and strength through scavenging reactive oxygen species accumulation to rebuild the redox homeostasis. Taking advantage of biophysical assays, peroxiredoxin 5 was discovered and validated as the direct target of MY. Through activating peroxiredoxin 5, MY reduced reactive oxygen species accumulation and damaged mitochondrial DNA in C2C12 myotubes. Our findings provide an insight for therapy against sarcopenia through alleviating oxidative damage-induced dysfunctional mitochondria by targeting peroxiredoxin 5, which may contribute an insight for healthy aging.

Lnc-PIK3R1, transcriptionally suppressed by YY1, inhibits hepatocellular carcinoma progression via the Lnc-PIK3R1/miR-1286/GSK3ß axis.

Hepatocellular carcinoma (HCC) poses a significant threat due to its highly aggressive and high recurrence characteristics, necessitating urgent advances in diagnostic and therapeutic approaches. Long non-coding RNAs exert vital roles in HCC tumorigenesis, however the mechanisms of their expression regulation and functions are not fully elucidated yet. Herein, we identify that a novel tumor suppressor 'lnc-PIK3R1' was significantly downregulated in HCC tissues, which was correlated with poor prognosis. Functionally, lnc-PIK3R1 played tumor suppressor roles to inhibit the proliferation and mobility of HCC cells, and to impede the distant implantation of xenograft in mice. Mechanistic studies revealed that lnc-PIK3R1 interacted with miR-1286 and alleviated the repression on GSK3B by miR-1286. Notably, pharmacological inhibition of GSK3ß compromised the tumor suppression effect by lnc-PIK3R1, confirming their functional relevance. Moreover, we identified that oncogenic YY1 acts as a specific transcriptional repressor to downregulate the expression of lnc-PIK3R1 in HCC. In summary, this study highlights the tumor-suppressive effect of lnc-PIK3R1, and provides new insights into the regulation of GSK3ß expression in HCC, which would benefit the development of innovative intervention strategies for HCC.

Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2.

Soft-tissue sarcomas (STS) emerges as formidable challenges in clinics due to the complex genetic heterogeneity, high rates of local recurrence and metastasis. Exploring specific targets and biomarkers would benefit the prognosis and treatment of STS. Here, we identified RCC1, a guanine-nucleotide exchange factor for Ran, as an oncogene and a potential intervention target in STS. Bioinformatics analysis indicated that RCC1 is highly expressed and correlated with poor prognosis in STS. Functional studies showed that RCC1 knockdown significantly inhibited the cell cycle transition, proliferation and migration of STS cells in vitro, and the growth of STS xenografts in mice. Mechanistically, we identified Skp2 as a downstream target of RCC1 in STS. Loss of RCC1 substantially diminished Skp2 abundance by compromising its protein stability, resulting in the upregulation of p27Kip1 and G1/S transition arrest. Specifically, RCC1 might facilitate the nucleo-cytoplasmic trafficking of Skp2 via direct interaction. As a result, the cytoplasmic retention of Skp2 would further protect it from ubiquitination and degradation. Notably, recovery of Skp2 expression largely reversed the phenotypes induced by RCC1 knockdown in STS cells. Collectively, this study unveils a novel RCC1-Skp2-p27Kip1 axis in STS oncogenesis, which holds promise for improving prognosis and treatment of this formidable malignancy.

Functional Characterization of the Soybean Glycine max Actin Depolymerization Factor GmADF13 for Plant Resistance to Drought Stress.

Abiotic stress significantly affects plant growth and has devastating effects on crop production. Drought stress is one of the main abiotic stressors. Actin is a major component of the cytoskeleton, and actin-depolymerizing factors (ADFs) are conserved actin-binding proteins in eukaryotes that play critical roles in plant responses to various stresses. In this study, we found that GmADF13, an ADF gene from the soybean Glycine max, showed drastic upregulation under drought stress. Subcellular localization experiments in tobacco epidermal cells and tobacco protoplasts showed that GmADF13 was localized in the nucleus and cytoplasm. We characterized its biological function in transgenic Arabidopsis and hairy root composite soybean plants. Arabidopsis plants transformed with GmADF13 displayed a more robust drought tolerance than wild-type plants, including having a higher seed germination rate, longer roots, and healthy leaves under drought conditions. Similarly, GmADF13-overexpressing (OE) soybean plants generated via the Agrobacterium rhizogenes-mediated transformation of the hairy roots showed an improved drought tolerance. Leaves from OE plants showed higher relative water, chlorophyll, and proline contents, had a higher antioxidant enzyme activity, and had decreased malondialdehyde, hydrogen peroxide, and superoxide anion levels compared to those of control plants. Furthermore, under drought stress, GmADF13 OE activated the transcription of several drought-stress-related genes, such as GmbZIP1, GmDREB1A, GmDREB2, GmWRKY13, and GmANK114. Thus, GmADF13 is a positive regulator of the drought stress response, and it may play an essential role in plant growth under drought stress conditions. These results provide new insights into the functional elucidation of soybean ADFs. They may be helpful for breeding new soybean cultivars with a strong drought tolerance and further understanding how ADFs help plants adapt to abiotic stress.

Global informetric perspective studies on translational medical research.

BACKGROUND: Translational medical research literature has increased rapidly in the last few decades and played a more and more important role during the development of medicine science. The main aim of this study is to evaluate the global performance of translational medical research during the past few decades. METHODS: Bibliometric, social network analysis, and visualization technologies were used for analyzing translational medical research performance from the aspects of subject categories, journals, countries, institutes, keywords, and MeSH terms. Meanwhile, the co-author, co-words and cluster analysis methods were also used to trace popular topics in translational medical research related work. RESULTS: Research output suggested a solid development in translational medical research, in terms of increasing scientific production and research collaboration. We identified the core journals, mainstream subject categories, leading countries, and institutions in translational medical research. There was an uneven distribution of publications at authorial, institutional, and national levels. The most commonly used keywords that appeared in the articles were "translational research", "translational medicine", "biomarkers", "stroke", "inflammation", "cancer", and "breast cancer". CONCLUSIONS: The subject categories of "Research & Experimental Medicine", "Medical Laboratory Technology", and "General & Internal Medicine" play a key role in translational medical research both in production and in its networks. Translational medical research and CTS, etc. are core journals of translational research. G7 countries are the leading nations for translational medical research. Some developing countries, such as P.R China, also play an important role in the communication of translational research. The USA and its institutions play a dominant role in the production, collaboration, citations and high quality articles. The research trends in translational medical research involve drug design and development, pathogenesis and treatment of disease, disease model research, evidence-based research, and stem and progenitor cells.

Survival benefit of active surveillance for papillary thyroid carcinoma: a propensity score matching analysis based on SEER database.

Background: Over-treatment of papillary thyroid microcarcinoma (PTMC) has become a common issue. Although active surveillance (AS) has been proposed as an alternative treatment to immediate surgery for PTMC, its inclusion criteria and mortality risk have not been clearly defined. The purpose of this study was to investigate whether surgery can achieve significant survival benefits in patients with larger tumor diameter of papillary thyroid carcinoma (PTC), in order to evaluate the feasibility of expanding the threshold for active surveillance. Methods: This study retrospectively collected data of patients with papillary thyroid carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The propensity score matching (PSM) method was used to minimize confounding factors and selection bias between the surgery and non-surgery groups, and to compare the clinical and pathological characteristics between the two groups based on the SEER cohort. Meanwhile, the impact of surgery on prognosis was compared using Kaplan-Meier estimates and Cox proportional hazard models. Results: A total of 175,195 patients were extracted from the database, including 686 patients who received non-surgical treatment, and were matched 1:1 with patients who received surgical treatment using propensity score matching. The Cox proportional hazard forest plot showed that age was the most important factor affecting overall survival (OS) of patients, while tumor size was the most important factor affecting disease-specific survival (DSS) of patients. In terms of tumor size, there was no significant difference in DSS between PTC patients with tumor size of 0-1.0cm who underwent surgical treatment and those who underwent non-surgical treatment, and the relative survival risk began to increase after the tumor size exceeded 2.0cm. Additionally, the Cox proportional hazard forest plot showed that chemotherapy, radioactive iodine, and multifocality were negative factors affecting DSS. Moreover, the risk of death increased over time, and no plateau phase was observed. Conclusion: For patients with papillary thyroid carcinoma (PTC) staged as T1N0M0, AS is a feasible management strategy. As the tumor diameter increases, the risk of death without surgical treatment gradually increases, but there may be a threshold. Within this range, a non-surgical approach may be a potentially viable management strategy. However, beyond this range, surgery may be more beneficial for patient survival. Therefore, it is necessary to conduct more large-scale prospective randomized controlled trials to further confirm these findings.

Efficient Dehazing with Recursive Gated Convolution in U-Net: A Novel Approach for Image Dehazing.

Image dehazing, a fundamental problem in computer vision, involves the recovery of clear visual cues from images marred by haze. Over recent years, deploying deep learning paradigms has spurred significant strides in image dehazing tasks. However, many dehazing networks aim to enhance performance by adopting intricate network architectures, complicating training, inference, and deployment procedures. This study proposes an end-to-end U-Net dehazing network model with recursive gated convolution and attention mechanisms to improve performance while maintaining a lean network structure. In our approach, we leverage an improved recursive gated convolution mechanism to substitute the original U-Net's convolution blocks with residual blocks and apply the SK fusion module to revamp the skip connection method. We designate this novel U-Net variant as the Dehaze Recursive Gated U-Net (DRGNet). Comprehensive testing across public datasets demonstrates the DRGNet's superior performance in dehazing quality, detail retrieval, and objective evaluation metrics. Ablation studies further confirm the effectiveness of the key design elements.