Dual-Region Computed Tomography Radiomics-Based Machine Learning Predicts Subcarinal Lymph Node Metastasis in Patients with Non-small Cell Lung Cancer.

BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.

Effectiveness of Very Brief Advice on Tobacco Cessation: A Systematic Review and Meta-Analysis.

BACKGROUND: Very brief advice (VBA; ≤ 3 min) on quitting is practical and scalable during brief medical interactions with patients who smoke. This study aims to synthesize the effectiveness of VBA for smoking cessation and summarize the implementation strategies. METHODS: We searched randomized controlled trials aiming at tobacco abstinence and comparing VBA versus no smoking advice or no contact from Medline, Embase, CINAHL, Cochrane Library, PsycInfo databases, six Chinese databases, two trial registries ClinicalTrials.gov and WHO-ICTRP from inception to September 30, 2023. Grading of Recommendations, Assessment, Development, and Evaluations framework was used to assess the certainty of the evidence of the meta-analytic findings. The outcomes were self-reported long-term tobacco abstinence at least 6 months after treatment initiation, earlier than 6 months after treatment initiation, and quit attempts. Effect sizes were computed as risk ratio (RR) with 95% CI using frequentist random-effect models. DATA SYNTHESIS: Thirteen randomized controlled trials from 15 articles (n = 26,437) were included. There was moderate-certainty evidence that VBA significantly increased self-reported tobacco abstinence at ≥ 6 months in the adjusted model (adjusted risk ratio ARR 1.17, 95% CI: 1.07-1.27) compared with controls. The sensitivity analysis showed similar results when abstinence was verified by biochemical validation (n = 6 studies, RR 1.53, 95% CI 0.98-2.40). There was high-certainty evidence that VBA significantly increased abstinence at < 6 months (ARR 1.22, 95% CI: 1.01-1.47). Evidence of effect on quit attempts (ARR 1.03, 95% CI 0.97-1.08) was of very low certainty. DISCUSSION: VBA delivered in a clinical setting is effective in increasing self-reported tobacco abstinence, which provides support for wider adoption in clinical practice.

Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment.

Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1ß). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods.

Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review.

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy.

Short-chain fatty acids mitigate Methamphetamine-induced hepatic injuries in a Sigma-1 receptor-dependent manner.

Methamphetamine (Meth) is a potent psychostimulant with well-established hepatotoxicity. Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to yield beneficial effects on the liver. In this study, we aim to further reveal the mechanisms of Meth-induced hepatic injuries and investigate the potential protective effects of SCFAs. Herein, mice were intraperitoneally injected with 15 mg/kg Meth to induce hepatic injuries. The composition of fecal microbiota and SCFAs was profiled using 16 S rRNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) analysis, respectively. Subsequently, SCFAs supplementation was performed to evaluate the protective effects against hepatic injuries. Additionally, Sigma-1 receptor knockout (S1R-/-) mice and fluvoxamine (Flu), an agonist of S1R, were introduced to investigate the mechanisms underlying the protective effects of SCFAs. Our results showed that Meth activated S1R and induced hepatic autophagy, inflammation, and oxidative stress by stimulating the MAPK/ERK pathway. Meanwhile, Meth disrupted SCFAs product-related microbiota, leading to a reduction in fecal SCFAs (especially Acetic acid and Propanoic acid). Accompanied by the optimization of gut microbiota, SCFAs supplementation normalized S1R expression and ameliorated Meth-induced hepatic injuries by repressing the MAPK/ERK pathway. Effectively, S1R knockout repressed Meth-induced activation of the MAPK/ERK pathway and further ameliorated hepatic injuries. Finally, the overexpression of S1R stimulated the MAPK/ERK pathway and yielded comparable adverse phenotypes to Meth administration. These findings suggest that Meth-induced hepatic injuries relied on the activation of S1R, which could be alleviated by SCFAs supplementation. Our study confirms the crucial role of S1R in Meth-induced hepatic injuries for the first time and provides a potential preemptive therapy.

lncRNA ANRIL accelerates wound healing in diabetic foot ulcers via modulating HIF1A/VEGFA signaling through interacting with FUS.

BACKGROUND: Diabetic foot ulcer (DFU) is a frequently diagnosed complication of diabetes, and remains a heathcare burden worldwide. However, the pathogenesis of DFU is still largely unclear. The objective of this study is to delineate the function and underlying mechanism of lncRNA antisense non coding RNA in the INK4 locus (ANRIL) in endothelial progenitor cells (EPCs) and DFU mice. METHODS: The DFU mouse model was established, and EPCs were subjected to high glucose (HG) treatment to mimic diabetes. qRT-PCR or western blot was employed to detected the expression of ANRIL, HIF1A, FUS and VEGFA. CCK-8 and Annexin V/PI staining were used to monitor cell proliferation and apoptosis. Wound healing, Transwell invasion and tube formation assays were conducted to assess cell migration, invasion and angiogenesis, respectively. The association between ANRIL and FUS was verified by RNA pull-down and RIP assays. Luciferase and ChIP assays were employed to investigate HIF1A-mediated transcriptional regulation of VEGFA and ANRIL. The histological alterations of DFU wound healing were observed by H&E and Masson staining. RESULTS: ANRIL was downregulated in peripheral blood samples of DFU patients, DFU mice and HG-treated EPCs. Mechanistically, ANRIL regulated HIFA mRNA stability via recruiting FUS. VEGFA and ANRIL were transcriptionally regulated by HIF1A. Functional experiments revealed that HG suppressed EPC proliferation, migration, invasion and tube formation, but promoted apoptosis via ANRIL/HIF1A axis. ANRIL accelerated DFU wound healing via modulating HIF1A expression in vivo. CONCLUSION: ANRIL accelerated wound healing in DFU via modulating HIF1A/VEGFA signaling in a FUS-dependent manner.

Large-scale forward genetic screening of zebrafish affecting thyroid development.

The thyroid follicular cells originate from the foregut endoderm and elucidating which genes and signaling pathways regulate their development is crucial for understanding developmental disorders as well as diseases in adulthood. We exploited unique advantages of the zebrafish model to carry an ENU-based forward mutagenesis screen aiming at identifying genes involved in the development and function of the thyroid follicular cells. ENU is an excellent chemical mutagen due to its high mutation efficiency and an indiscriminate selection of genes. A total of 1606 F2 families from 36 ENU treated founders was raised and embryos from F3 generation were collected at 5dpf to perform the whole embryo in situ hybridization with a cocktail probe of thyroid marker thyroglobulin(tg), pituitary marker thyroid stimulating hormone (tshba) to determine the mutagenic phenotype. Among the 1606 F2 families, 112 F2 mutant families with normal development stages except for thyroid dysfunction were identified and divided into three different groups according to their phenotypic characteristics. Further studies of the mutants are likely to shed more insights into the molecular basis of both the thyroid development and function in the zebrafish and vertebrate.

The increased expression of cytokeratin 13 leads to an increase in radiosensitivity of nasopharyngeal carcinoma HNE-3 cells by upregulating ERRFI1.

The main factors contributing to the unfavorable outcome in the clinical treatment of patients with nasopharyngeal carcinoma (NPC) patients are radiation resistance and recurrence. This study aimed to investigate the sensitivity and molecular foundation of cytokeratin 13 (CK13) in the radiotherapy of NPC. To achieve this, a human NPC cell line overexpressing CK13, HNE-3-CK13, was constructed. The effects of CK13 overexpression on cell viability and apoptosis under radiotherapy conditions were evaluated using the CCK-8 assay, immunofluorescence, and western blotting (WB). Next-generation sequencing was performed to identify the downstream genes and signaling pathways of CK13 that mediate radiotherapy response. The potential role of the candidate gene ERRFI1 in CK13-induced enhancement of radiosensitivity was investigated through rescue experiments using clone formation and WB. The effects of ERRFI1 on cell viability, cell apoptosis, cell cycle, and the related key genes were further evaluated using CCK-8, immunofluorescence, flow cytometry, quantitative polymerase chain reaction and WB. The results showed that CK13 overexpression in HNE-3 significantly inhibited cell survival under radiotherapy and promoted apoptosis marker γH2AX expression, leading to a significant increase of ERRFI1. Knockdown of ERRFI1 rescued the decreased cell viability and proliferation and the increased cell apoptosis that were caused by CK13 overexpression-mediated radiotherapy sensitization of NPC cells. In this process, EGFR, AKT, and GSK-3ß were found involved. In the end, ERRFI1 was proven to inhibit expression levels of CDK1, CDK2, cyclin B1, and cyclin D1, resulting an increased G2/M cell ratio. Overexpression of CK13 enhances the radiosensitivity of NPC cells, which is characterized by decreased cell viability and proliferation and increased apoptosis. This regulation may affect the survival of HNE-3 cells by increasing the expression of ERRFI1 and activating the EGFR/Akt/GSK-3ß signaling pathway, providing new potential therapeutic targets for the treatment of NPC.

Hydrogen sulfide inhibits human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG4B.

Hydrogen sulfide (H2 S) is a redox gasotransmitter. It has been shown that H2 S has a key role in host antiviral defense by inhibiting interleukin production and S-sulfhydrating Keap1 lead to Nrf2/ARE pathway activation. However, it is yet unclear whether H2 S can play an antiviral role by regulating autophagy. In this study, we found that exogenous H2 S decreased the expression of human T-cell leukemia virus type-1 (HTLV-1) protein and HTLV-1 induced autophagosomes accumulation. Transmission electron microscope assays indicated that autophagosomes accumulation decreased after H2 S administration. HTLV-1-transformed T-cell lines had a high level of CSE (H2 S endogenous enzyme) which could be induced in Hela by HTLV-1 infection. Immunoblot demonstrated that overexpression of CSE inhibited HTLV-1 protein expression and autophagy. And we got the opposite after CSE knockdown. Meanwhile, H2 S could not restrain the autophagy when ATG4B had a mutant at its site of 89. In a word, these results suggested that H2 S modulated HTLV-1 protein expression via ATG4B. Therefore, our findings suggested a new mechanism by which H2 S defended against virus infection.

Complete genome sequence of Aquitalea pelogenes USM4 (JCM19919), a polyhydroxyalkanoate producer.

Polyhydroxyalkanoate (PHA) is a type of biopolymer produced by most bacteria and archaea, resembling thermoplastic with biodegradability and biocompatibility features. Here, we report the complete genome of a PHA producer, Aquitalea sp. USM4, isolated from Perak, Malaysia. This bacterium possessed a 4.2 Mb circular chromosome and a 54,370 bp plasmid. A total of 4067 predicted protein-coding sequences, 87 tRNA genes, and 25 rRNA operons were identified using PGAP. Based on ANI and dDDH analysis, the Aquitalea sp. USM4 is highly similar to Aquitalea pelogenes. We also identified genes, including acetyl-CoA (phaA), acetoacetyl-CoA (phaB), PHA synthase (phaC), enoyl-CoA hydratase (phaJ), and phasin (phaP), which play an important role in PHA production in Aquitalea sp. USM4. The heterologous expression of phaC1 from Aquitalea sp. USM4 in Cupriavidus necator PHB-4 was able to incorporate six different types of PHA monomers, which are 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), 4-hydroxybutyrate (4HB), 5-hydroxyvalerate (5HV), 3-hydroxyhexanoate (3HHx) and isocaproic acid (3H4MV) with suitable precursor substrates. This is the first complete genome sequence of the genus Aquitalea among the 22 genome sequences from 4 Aquitalea species listed in the GOLD database, which provides an insight into its genome evolution and molecular machinery responsible for PHA biosynthesis.

Investigation of the anchoring and electrocatalytic properties of pristine and doped borophosphene for Na-S batteries.

Designing an anchoring layer on the sulfur electrode has been considered one of the effective approaches to promoting the real application of room-temperature sodium-sulfur (RT-Na-S) batteries. In this work, based on the first-principles calculation method, the potential of pristine and doped borophosphene (BP) as anchoring materials for Na-S batteries has been investigated. The calculated adsorption energies of sodium polysulfides (NaPSs) adsorbed on pristine and doped substrates are higher than those of NaPSs adsorbed with the electrolytes (DOL&DME), indicating that the shuttle effect could be well alleviated. Meanwhile, the projected density of states (PDOS) suggests that the metallic characteristics of the adsorption systems are still well preserved, which is in favor of improving the electronic conductivity. More importantly, excellent electrocatalytic properties of the substrates are exhibited by reducing the catalytic decomposition energy barriers of Na2S, in which 0.27/0.79/1.02 eV is found on the pristine/N-doped/C-doped BP, indicating that the electrochemical processes could be improved smoothly. Therefore, it could be expected that pristine and doped BP are excellent anchoring materials for sodium-sulfur batteries.

Exploration of Damage Identification Method for a Large-Span Timber Lattice Shell Structure in Taiyuan Botanical Garden based on Structural Health Monitoring.

Large-span spatial lattice structures generally have characteristics such as incomplete modal information, high modal density, and high degrees of freedom. To address the problem of misjudgment in the damage detection of large-span spatial structures caused by these characteristics, this paper proposed a damage identification method based on time series models. Firstly, the order of the autoregressive moving average (ARMA) model was selected based on the Akaike information criterion (AIC). Then, the long autoregressive method was used to estimate the parameters of the ARMA model and extract the residual sequence of the autocorrelation part of the model. Furthermore, principal component analysis (PCA) was introduced to reduce the dimensionality of the model while retaining the characteristic values. Finally, the Mahalanobis distance (MD) was used to construct the damage sensitive feature (DSF). The dome of Taiyuan Botanical Garden in China is one of the largest non-triangular timber lattice shells worldwide. Relying on the structural health monitoring (SHM) project of this structure, this paper verified the effectiveness of the damage identification model through numerical simulation and determined the damage degree of the dome structure through SHM measurement data. The results demonstrated that the proposed damage identification method can effectively identify the damage of large-span timber lattice structures, locate the damage position, and estimate the degree of damage. The constructed DSF had relatively strong robustness to small damage and environmental noise and has practical application value for SHM in engineering.

Bamboo Weaving Inspired Design of a Carbonaceous Electrode with Exceptionally High Volumetric Capacity.

A highly densified electrode material is desirable to achieve large volumetric capacity. However, pores acting as ion transport channels are critical for high utilization of active material. Achieving a balance between high volume density and pore utilization remains a challenge particularly for hollow materials. Herein, capillary force is employed to convert hollow fibers to a bamboo-weaving-like flexible electrode (BWFE), in which the shrinkage of hollow space results in high compactness of the electrode. The volume of the electrode can be decreased by 96% without sacrificing the gravimetric capacity. Importantly, the conductivity of BWFE after thermal treatment can reach up to 50,500 S/m which exceeds that for most other carbon materials. Detailed mechanical analysis reveals that, due to the strong interaction between nanoribbons, Young's modulus of the electrode increases by 105 times. After SnO2 active materials is impregnated, the BWFE/SnO2 electrode exhibits an exceptionally ultrahigh volumetric capacity of 2000 mAh/cm3.

Quassinoids from Twigs of Harrisonia perforata (Blanco) Merr and Their Anti-Parkinson's Disease Effect.

Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1-7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer-Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson's disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson's disease model of PINK1B9. Perforalactones G and I (2 and 4) showed a 10-15% increase in cell viability of the model cells at 50 µM, while compounds 2 and 4 (100 µM) significantly improved the climbing ability of PINK1B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.

Cytokeratin 13 promotes radiotherapy sensitivity of nasopharyngeal carcinoma by downregulating the MEK/ERK pathway.

BACKGROUND: Radiation therapy is the first treatment choice for nasopharyngeal carcinoma (NPC), while radiation resistance and recurrence have become the primary factors and are associated with poor prognosis in the clinical treatment of NPC patients. The purpose of the present study was to explore the sensitivity and molecular basis of cytokeratin 13 (CK13) that regulates NPC radiotherapy. METHODS: HNE-3 or C666-1 cell line was used for overexpression and knockdown tests. Under radiotherapy conditions, CCK-8 assay, clone formation assay, and flow cytometry analyzed the effects of CK13 overexpression on cell proliferation, apoptosis, and cell cycle, respectively. In addition, Western blotting detected CK13-mediated downregulation of cell cycle-related genes. The mouse subcutaneous tumor-bearing experiment identified the effects of CK13 overexpression on the treatment of NPC in vivo. Further, Western blotting, CCK-8 assay, and flow cytometry investigated whether the CK13-mediated cell apoptosis involves the MEK/ERK signaling pathway. RESULTS: Overexpression of CK13 significantly inhibited the survival of HNE-3 cells under radiotherapy in vitro and in vivo, and there was a substantial decrease in cyclin-dependent kinase 4 and 6 (CDK4/6) levels promoting the cell percentage number in the G2/M phase and, subsequently, the ratio of the apoptotic cells. In contrast, the knockdown of CK13 showed the opposite partial regulatory effect. Interestingly, CK13 overexpression also showed a reduction in the survival of C666-1 cells and an increased ratio of the apoptotic cells under radiotherapy treatment. Furthermore, higher levels of CK13 downregulated the MEK/ERK signaling pathway, resulting in decreased HNE-3 cell proliferation and increased apoptosis. However, ERK activators were able to rescue the process partially. CONCLUSIONS: Together, these results showed that CK13 promoted the radiosensitivity of NPC cells by downregulating the MEK/ERK signaling pathway. Thus, targeting CK13 provided insights into the treatment of NPC radiotherapy.

Translation-invariant context-retentive wavelet reflection removal network.

It has been widely investigated for images taken through glass to remove unwanted reflections in deep learning. However, none of these methods have bad effects, but they all remove reflections in specific situations, and validate the results with their own datasets, e.g., several local places with strong reflections. These limitations will result in situations where real reflections in the world cannot be effectively eliminated. In this study, a novel Translation-invariant Context-retentive Wavelet Reflection Removal Network is proposed to address this issue. In addition to context and background, low-frequency sub-images still have a small amount of reflections. To enable background context retention and reflection removal, the low-frequency sub-images at each level are performed on the Context Retention Subnetwork (CRSn) after wavelet transform. Novel context level blending and inverse wavelet transform are proposed to remove reflections in low frequencies and retain background context recursively, which is of great help in restoring clean images. High-frequency sub-images with reflections are performed on the Detail-enhanced Reflection layer removal Subnetwork to complete reflection removal. In addition, in order to further separate the reflection layer and the transmission layer better, we also propose Detail-enhanced Reflection Information Transmission, through which the extracted features of reflection layer in high-frequency images can help the CRSn effectively separate the transmission layer and the reflection layer, so as to achieve the effects of removing reflection. The quantitative and visual experimental results on benchmark datasets demonstrate that the proposed method performs better than the state-of-the-art approaches.

Spontaneous chiral resolution of pentahelicene molecules on Cd(0001).

Chiral resolution is of fundamental importance to conglomerate or racemate crystallization. Here we demonstrate that the spontaneous chiral resolution of pentahelicene racemates occurred in the monolayer domains. When deposited on a Cd(0001) surface, pentahelicene molecules crystallize into a commensurate (6 × 6)R0° structure built mainly from homochiral trimers. Spontaneous chirality separation takes place in the form of opposite mirror domains, where 2D enantiomorphism is not expressed by the oblique adlattice, but by the supramolecular chirality of the pentahelicene trimers. Furthermore, annealing the sample or extreme close-packing lead to the presence of lattice handedness through the formation of a porous network structure or an edge-on phase. These results provide valuable insight for 2D conglomerate crystallization and stereochemical recognition.

Geraniol enhances peroxiredoxin-1, and prevents isoproterenol-induced oxidative stress and inflammation associated with myocardial infarction in experimental animal models.

This study has explored the fact that geraniol prevents isoproterenol (ISO)-induced oxidative stress and inflammation-mediated myocardial infarction (MI) through enhanced expression of peroxiredoxin-1 (Prdx-1) in experimental animal models. The experimental strategies of MI were stimulated through the subcutaneous direction of ISO (85 mg/kg body weight) for 14 days. ISO-directed models showed elevated heart rate levels and cardiac markers (serum creatine kinase [CK], serum CK-myocardial band, serum C-reactive proteins, and plasma homocysteine); increased cardiac-troponins-T, and troponin-I levels in both serum and myocardium. Moreover, we perceived that a higher level of lipid peroxidation molecules (thiobarbituric acid reactive substances and lipid hydroperoxides) reduced the antioxidant enzyme levels in plasma and heart tissue of ISO-directed rats. However, geraniol treatment prevents ISO-directed enhancement of the heart rate, cardiac and lipid peroxidative genes; reverted the blood pressure, and antioxidant status in ISO-directed rats. Furthermore, gene expression results revealed that geraniol treatment inhibited the mitogen-activated protein kinase (MAPK) proteins, inflammatory responder (tumor necrosis factor-α, interleukin 6, nuclear factor-κB), and cardiac fibrotic proteins (matrix metalloproteinase-2[MMP-2], MMP-9) in ISO directed rats. Prdx-1 is an antioxidant response element, and it can regulate all the antioxidant proteins and it scavenges harmful radicals. Therefore, enhanced Prdx-1 expression is considered to have a pivotal role in preventing cardiac infarction. In this study, an elevated expression of Prdx1 was noticed in geraniol treated with ISO-directed rats. Hence, we concluded that geraniol is considered a potential phytodrug, and it prevents ISO-directed MAPKs, inflammation, and cardiac markers by enhancing the expression of Prdx1.

Tpo knockout in zebrafish partially recapitulates clinical manifestations of congenital hypothyroidism and reveals the involvement of TH in proper development of glucose homeostasis.

Congenital hypothyroidism (CH) is a highly prevalent but treatable neonatal endocrine disorder. Thyroid peroxidase (TPO) catalyzes key reactions in thyroid hormone (TH) synthesis. TPO mutations have been found to underlie approximately 5% of congenital hypothyroidism in Chinese patients with more severe phenotypes, the treatment of whom usually requires a higher dose of L-thyroxine. The Tpo gene of zebrafish has 66% homology with the human TPO gene, and synteny analysis has indicated that it is likely a human TPO ortholog. In this study, we generated a tpo-/- mutant zebrafish line through knockout of tpo with CRISPR/Cas9 and investigated the associated phenotypes. Tpo-/- mutant zebrafish displayed growth retardation; an increased number of thyroid follicular cells; and abnormal extrathyroidal phenotypes including pigmentation defects, erythema in the thoracic region, delayed scale development and failure of swim bladder secondary lobe formation. All these abnormal phenotypes were reversed by 30 nM thyroxine (T4) treatment starting at 1 month of age. Tpo-/- mutants also showed increased glucose levels during larval stages, and the increases were induced at least in part by increasing glucagon and decreasing insulin expression. Our work indicates that tpo-mutant zebrafish may serve as a human congenital hypothyroidism model for studying TPO- and TH-related disease mechanisms.

Retrospective Study from a Single Center on the Efficacy of Pulsed Lavage Following Excision of Burns ≥30% of the Total Body Surface Area in 63 Patients.

BACKGROUND Ensuring the take rate of skin grafting and reducing the mortality of patients with severe burns have remained big challenges worldwide. This retrospective study from a single center aimed to evaluate the efficacy of pulsed lavage following excision of burns ≥30% of the total body surface area (TBSA) in 63 patients. MATERIAL AND METHODS Among 63 patients, the types of burns sustained were severe burns and extremely severe burns (≥30% TBSA). The degrees of the burns were second degree and third degree, and the causes were thermal, chemical, and electric. Patients with early aggressive excision were divided into a pulsed lavage group and control group. The constituent of the lavage fluid was 0.9% physiological saline. The evaluation of wound healing and complications was based on the wound healing rate and time, clinical symptoms, and examination. We determined the take rate of skin grafting, positive rate of postoperative bacterial cultures, changes in perioperative serum C-reactive protein (CRP) and procalcitonin (PCT) levels, and incidence of secondary grafting. RESULTS The take rate of skin grafting and the decreased rates of perioperative serum CRP and PCT levels were significantly higher in the pulsed lavage group than in the control group (P<0.05). Moreover, the positive rate of wound postoperative bacterial cultures and mortality in the pulsed lavage group showed remarkably lower levels (P<0.05). CONCLUSIONS Pulsed lavage following excision of burns ≥30% TBSA increased the take rate of skin grafting, alleviated the positive rate of postoperative bacterial cultures, decreased serum CRP and PCT levels, and reduced mortality.