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DEP domain containing protein 1B (DEPDC1B) is overexpressed in a variety of malignant tissues and cells. As an oncoprotein, it participates in the occurrence and development of many kinds of cancers and regulates different malignant biological forms, including promoting tumor cell invasion, migration, proliferation and inhibiting apoptosis, which is closely related to the function of DEP, Rho GAP and other domains. This paper mainly combines the domain composition of oncoprotein DEPDC1B to explore the relationship between oncoprotein DEPDC1B and the occurrence, development and treatment of cancer, in order to provide a reference basis for further study of the mechanism of DEPDC1B in cancer and potential anticancer therapy.

For silicon-based epitaxial quantum dot lasers (QDLs), the mismatches of the lattice constants and the thermal expansion coefficients lead to the generation of threaded dislocations (TDs), which act as the non-radiative recombination centers through the Shockley–Read–Hall (SRH) recombination. Based on a three-level model including the SRH recombination, the nonlinear properties of the silicon-based epitaxial QDLs under optical injection have been investigated theoretically. The simulated results show that, through adjusting the injection parameters including injection strength and frequency detuning, the silicon-based epitaxial QDLs can display rich nonlinear dynamical states such as period one (P1), period two (P2), multi-period (MP), chaos (C), and injection locking (IL). Relatively speaking, for a negative frequency detuning, the evolution of the dynamical state with the injection strength is more abundant, and an evolution path P1-P2-MP-C-MP-IL has been observed. Via mapping the dynamical state in the parameter space of injection strength and frequency detuning under different SRH recombination lifetime, the effects of SRH recombination lifetime on the nonlinear dynamical state of silicon-based epitaxial QDLs have been analyzed.

Introduction: Risk of adverse effects and exacerbation in autoimmune neurological conditions (ANC)are frequently cited reasons for COVID-19 vaccine hesitancy. This study evaluates the ANC safety of COVID-19 vaccines in the real world. Methods: Electronic databases were searched to identify studies reporting the use of the COVID-19 vaccine in ANC. We selected studies that provided data on adverse effects and worsening conditions related to ANC after vaccination. The pooled incidence rates for various adverse effects, stratified for the disease category, dosage, and type of vaccine, were estimated. Results: Twenty-eight studies (31 vaccination cohorts) were included. The pooled incidence rate of general adverse events was 0.35 (95%CI, 0.27–0.43, I2 = 100 %). The pooled incidence rates of local injection reaction, fatigue, weakness, myalgia, fever, headache, and chills were 0.27 (0.18–0.36, I2 = 98 %), 0.16(0.11–0.21, I2 = 93 %), 0.15(0.00–0.31, I2 = 97 %), 0.13(0.08–0.19, I2 = 97 %), 0.11(0.07–0.15, I2 = 95 %), 0.11(0.07–0.16, I2 = 97 %), and 0.09 (0.03–0.16, I2 = 96 %), respectively. The pooled incidence rate of exacerbation adverse events was 0.05 (95%CI, 0.04–0.07, I2 = 84 %). Conclusion: According to available evidence, the administration of COVID-19 vaccines in individuals with autoimmune neurological disorders seems well-tolerated, with few reports of adverse events. Furthermore, exacerbation of autoimmune neurological conditions following vaccination appears to be infrequent.

Purpose: To evaluate the ability of computer-aided diagnosis (CAD) system (S-Detect) to identify malignancy in ultrasound (US) -detected BI-RADS 3 breast lesions. Materials and methods: 148 patients with 148 breast lesions categorized as BI-RADS 3 were included in the study between January 2021 and September 2022. The malignancy rate, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were calculated. Results: In this study, 143 breast lesions were found to be benign, and 5 breast lesions were malignant (malignancy rate, 3.4 %, 95 % confidence interval (CI): 0.5–6.3). The malignancy rate rose significantly to 18.2 % (4/22, 95 % CI: 2.1–34.3) in the high-risk group with a “possibly malignant” CAD result (p = 0.017). With a “possibly benign” CAD result, the malignancy rate decreased to 0.8 % (1/126, 95 % CI: 0–2.2) in the low-risk group (p = 0.297). The AUC, sensitivity, specificity, accuracy, PPV, and NPV of the CAD system in BI-RADS 3 breast lesions were 0.837 (95 % CI: 77.7–89.6), 80.0 % (95 % CI: 73.6–86.4), 87.4 % (95 % CI: 82.0–92.7), 87.2 % (95 % CI: 81.8–92.6), 18.2 % (95 % CI: 2.1–34.3) and 99.2 % (95 % CI: 97.8–100.0), respectively. Conclusions: CAD system (S-Detect) enables radiologists to distinguish a high-risk group and a low-risk group among US-detected BI-RADS 3 breast lesions, so that patients in the low-risk group can receive follow-up without anxiety, while those in the high-risk group with a significantly increased malignancy rate should actively receive biopsy to avoid delayed diagnosis of breast cancer.

Abstract Background Problem-based learning (PBL) is a widely adopted educational approach in medical education that aims to promote critical thinking and problem-solving in authentic learning situations. However, the impact of PBL educational mode on undergraduate medical students’ clinical thinking ability has been limitedly investigated. This study aimed to assess the influence of an integrated PBL curriculum on clinical thinking ability of medical students prior to clinical practice. Methods Two hundred and sixty-seven third-year undergraduate medical students at Nantong University were recruited in this study and were independently assigned to either the PBL or control group. The Chinese version of the Clinical Thinking Ability Evaluation Scale was used to assess clinical thinking ability, and the students’ performance in the PBL tutorials was assessed by tutors. All participants in both groups were required to complete the pre-test and post-test questionnaires to self-report their clinical thinking ability. A paired sample t-test, independent sample t-test and one-way analysis of variance test (ANOVA) were used to compare the difference in clinical thinking scores among different groups. Multiple linear regression was conducted to analyze the influencing factors correlated with clinical thinking ability. Results The clinical thinking ability of most third-year undergraduate medical students at Nantong University was at a high level. The PBL group had a higher proportion of students with high-level clinical thinking ability in the post-test compared to the control group. The pre-test scores of clinical thinking ability were similar between the PBL and control groups, but the post-test scores of clinical thinking ability in the PBL group were significantly higher than those in the control group. Additionally, there was a significant difference in clinical thinking ability between the pre-test and post-test in the PBL group. The post-test scores of sub-scales of critical thinking ability were significantly higher than the pre-test in the PBL group. Furthermore, the frequency of reading literature, time of PBL self-directed learning, and PBL performance score ranking were influencing factors on the clinical thinking ability of medical students in the PBL group. Moreover, there was a positive correlation between clinical thinking ability and the frequency of reading literature, as well as the scores of the PBL performance. Conclusions The integrated PBL curriculum model has an active impact on improving undergraduate medical students' clinical thinking ability. This improvement in clinical thinking ability may be correlated with the frequency of reading literature, as well as the performance of the PBL curriculum.

Abstract T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

Glucosinolates (GSLs) are not only a unique flavor substance from leaf B. juncea but also a major secondary metabolite produced in response to abiotic stresses. Cold stress is one of the most common abiotic stresses in leaf B. juncea; however, the metabolic response pattern of GSLs in leaf B. juncea under cold stress has not yet been reported. In the present study, we analyzed the GSLs content of leaf B. juncea under cold stress and found that it increased and subsequently decreased. According to RNA-seq data, genes related to the synthesis of aliphatic GSLs were significantly upregulated following 24 h of cold stress; genes related to the synthesis of indole GSLs were significantly upregulated following 48 h of cold stress; and BjBGLU25 and BjBGLU27 were significantly upregulated. Further analysis of the correlation between transcription factors and GSLs content revealed that MYB, ERF, IQD, and bHLH may be involved in regulating the GSLs response pattern in leaf B. juncea under cold stress. In particular, an unreported transcription factor, BjMYBS3 (BjuVA05G33250), was found to play a possible role in the synthesis of aliphatic GSLs. And the external application of GSLs increased the ability of leaf B. juncea to cope with cold stress.

The complete mitogenome sequence of Micromys erythrotis was determined using long PCR. The genome was 16,238 bp in length and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, 1 origin of L strand replication and 1 control region. The overall base composition of the heavy strand is A (33.7%), C (24.8%), T (29.1%) and G (12.4%). The base compositions present clearly the A–T skew, which is most obviously in the control region and protein-coding genes. Mitochondrial genome analyses based on MP, ML, NJ and Bayesian analyses yielded identical phylogenetic trees. This study verifies the evolutionary status of Micromys erythrotis in Muridae at the molecular level. The mitochondrial genome would be a significant supplement for the Micromys erythrotis genetic background.

Image-guided tumor ablation eliminates tumor cells by physical or chemical stimulation, which shows less invasive and more precise in local tumor treatment. Tumor ablation provides a treatment option for medically inoperable patients. Currently, clinical ablation techniques are widely used in clinical practice, including cryoablation, radiofrequency ablation (RFA), and microwave ablation (MWA). Previous clinical studies indicated that ablation treatment activated immune responses besides killing tumor cells directly, such as short-term anti-tumor response, immunosuppression reduction, specific and non-specific immune enhancement, and the reduction or disappearance of distant tumor foci. However, tumor ablation transiently induced immune response. The combination of ablation and immunotherapy is expected to achieve better therapeutic results in clinical application. In this paper, we provided a summary of the principle, clinical application status, and immune effects of tumor ablation technologies for tumor treatment. Moreover, we discussed the clinical application of different combination of ablation techniques with immunotherapy and proposed possible solutions for the challenges encountered by combined therapy. It is hoped to provide a new idea and reference for the clinical application of combinate treatment of tumor ablation and immunotherapy.

This paper studies the large time behavior of solutions to the 2D micropolar equations with linear damping velocity. It is proven that the global solutions have rapid time decay rates ∥∇ω∥L2+∥∇u∥L2≤C(1+t)−32 and ∥u∥L2≤C(1+t)−32,∥ω∥L2≤C(1+t)−1. The findings are mainly based on the new observation that linear damping actually improves the low-frequency effect of the system. The methods here are also available for complex fluid models with linear damping structures.

The objective of this study was to retrieve daily composite soil moisture by jointly using brightness temperature observations from multiple operating satellites for near real-time application with better coverage and higher accuracy. Our approach was to first apply the single-channel brightness radiometric algorithm to estimate soil moisture from the respective brightness temperature observations of the SMAP, SMOS, AMSR2, FY3B, and FY3C satellites on the same day and then produce a daily composite dataset by averaging the individual satellite-retrieved soil moisture. We further evaluated our product, the official soil moisture products of the five satellites, and the ensemble mean (i.e., arithmetic mean) of the five official satellite soil moisture products against ground observations from two networks in Central Tibet and Anhui Province, China. The results show that our product outperforms the individual released products of the five satellites and their ensemble means in the two validation areas. The root mean square error (RMSE) values of our product were 0.06 and 0.09 m3/m3 in Central Tibet and Anhui Province, respectively. Relative to the ensemble mean of the five satellite products, our product improves the accuracy by 9.1% and 57.7% in Central Tibet and Anhui Province, respectively. This demonstrates that jointly using brightness temperature observations from multiple satellites to retrieve soil moisture not only improves the spatial coverage of daily observations but also produces better daily composite products. Keywords: Soil moisture retrieval, Passive microwave remote sensing, Multiple satellites, Surface hydrology, SMAP, SMOS, AMSR2, FY3B, FY3C

Abstract Background Innate immune dysfunction contributes to the development and progression of nonalcoholic fatty liver disease (NAFLD), however, its pathogenesis is still incompletely understood. Identifying the key innate immune component responsible for the pathogenesis of NAFLD and clarifying the underlying mechanisms may provide therapeutic targets for NAFLD. Recently, F-box- and WD repeat domain-containing 7 (FBXW7) exhibits a regulatory role in hepatic glucose and lipid metabolism. This study aims to investigate whether FBXW7 controls high-mobility group box 1 protein (HMGB1)-mediated innate immune signaling to improve NAFLD and the mechanism underlying this action. Methods Mice were fed a high-fat diet (HFD) for 12 or 20 weeks to establish NAFLD model. Hepatic overexpression or knockdown of FBXW7 was induced by tail-vein injection of recombinant adenovirus. Some Ad-FBXW7-injected mice fed a HFD were injected intraperitoneally with recombinant mouse HMGB1 to confirm the protective role of FBXW7 in NAFLD via inhibition of HMGB1. Results FBXW7 improves NAFLD and related metabolic parameters without remarkable influence of body weight and food intake. Moreover, FBXW7 markedly ameliorated hepatic inflammation and insulin resistance in the HFD-fed mice. Furthermore, FBXW7 dramatically attenuated the expression and release of HMGB1 in the livers of HFD-fed mice, which is associated with inhibition of protein kinase R (PKR) signaling. Thereby, FBXW7 restrains Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) signaling in HFD-fed mouse livers. In addition, exogenous HMGB1 treatment abolished FBXW7-mediated inhibition of hepatic inflammation and insulin resistance in HFD-fed mouse livers. Conclusions Our results demonstrate a protective role of FBXW7 in NAFLD by abating HMGB1-mediated innate immune signaling to suppress inflammation and consequent insulin resistance, suggesting that FBXW7 is a potential target for therapeutic intervention in NAFLD development.

The shape of the leaf is the primary phenotype which determines the commercial value of leaf mustard (Brassica juncea). However, there arefew reports on the lobed-leaf gene of B. juncea, and the molecular regulatory mechanisms underlying leaf margin formation are unknown. In this study, an F2 population derived from ‘MN001’ and ‘MU056’ was constructed. Genetic analysis revealed that the lobed-leaf trait is controlled by a major gene, and lobed leavesare dominant compared to round leaves. The GradedPool-Seq analysis combined with the re-sequencing results of parents identified a major interval on chromosome 10 of B. juncea’s genome A. The BjLMI1 gene (BjuA040054) was confirmed to be a candidate gene by gene ontology (GO) analysis, and it is homologous with LMI1 and encodes HD-Zip protein ATHB-51. A base substitution was observed in the conserved domain, and a 63 bp fragment deletion was found in the exon region between the two parents in the CDs region. The expression of BjLMI1 was significantly higher in the lobed-leaf parent than in the round-leaf parent. These findings provide insights into the molecular mechanism underlying leaf margin formation and will be valuable in the development of an ideal leaf shape in B. juncea.

Objective: Dentin hypersensitivity (DH) is a common oral disease with approximately 41.9% prevalence. Reconstruction of dental hard tissues is the preferred treatment for relieving DH. Here, we applied biomineralization method using oligopeptide simulating cementum protein 1 (CEMP1) to regenerate hard tissues on demineralized dentin. Methods: The self-assembly and biomineralization property of the oligopeptide were detected by scanning electron microscopy (SEM), circular dichroism spectroscopy, and transmission electron microscopy. Oligopeptide’s binding capacity to demineralized dentin was evaluated by SEM and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Remineralization was characterized using SEM, ATR-FTIR, X-ray diffraction, and nanoindentation. Oligopeptide’s biocompatibility was evaluated using periodontal ligament cells. Results: Oligopeptides self-assembled into nano-matrix and templated mineral precursor formation within 24 h. Moreover, oligopeptide nano-matrix bound firmly on demineralized dentin and resisted water rinsing. Then, bound nano-matrix served as a template to initiate nucleation and transformation of hydroxyapatite on demineralized dentin. After 96 h, oligopeptide nano-matrix regenerated an enamel-like tissue layer with a thickness of 15.35 μm, and regenerated crystals occluded dentin tubules with a depth of 31.27 μm. Furthermore, the oligopeptide nano-matrix had good biocompatibility when co-cultured with periodontal ligament cells. Conclusions: This biomimetic oligopeptide simulating CEMP1 effectively induced remineralization and reconstructed hard tissues on demineralized dentin, providing a potential biomaterial for DH treatment.

Background: Alkylating agents are critical therapeutic options for melanoma, while dacarbazine (DTIC)-based chemotherapy showed poor sensitivity in clinical trials. Long non-coding RNAs (lncRNAs) were highlighted in the progression of malignant tumors in recent years, whereas little was known about their involvement in melanoma.Methods: The functional role and molecular mechanism of lncRNA POU3F3 were evaluated on DTIC-resistant melanoma cells. Further studies analyzed its clinical role in the disease progression of melanoma.Results: We observed elevated the expression of lncRNA POU3F3 in the DTIC-resistant melanoma cells. Gain-of-function assays showed that the overexpression of lncRNA POU3F3 maintained cell survival with DTIC treatment, while the knockdown of lncRNA POU3F3 restored cell sensitivity to DTIC. A positive correlation of the expression O6-methylguanine-DNA-methyltransferase (MGMT) was observed with lncRNA POU3F3 in vitro and in vivo. Bioinformatic analyses predicted that miR-650 was involved in the lncRNA POU3F3-regulated MGMT expression. Molecular analysis indicated that lncRNA POU3F3 worked as a competitive endogenous RNA to regulate the levels of miR-650, and the lncRNA POU3F3/miR-650 axis determined the transcription of MGMT in melanoma cells to a greater extent. Further clinical studies supported that lncRNA POU3F3 was a risk factor for the disease progression of melanoma.Conclusion: LncRNA POU3F3 upregulated the expression of MGMT by sponging miR-650, which is a crucial way for DTIC resistance in melanoma. Our results indicated that lncRNA POU3F3 was a valuable biomarker for the disease progression of melanoma.

Background Clear cell renal cell carcinoma (ccRCC) is a common urological disease. Expression of the protein tyrosine phosphatase 12 gene ( PTPN12 ) is decreased in many cancers; however, the relationship between PTPN12 gene function and renal cancer remains unclear. Methods We detected PTPN12 protein expression in ccRCC and corresponding normal tissues from 64 patients with ccRCC by immunohistochemistry, and relative PTPN12 mRNA levels by real-time quantitative polymerase chain reaction. The relationships between the relative expression levels of PTPN12 mRNA and the patients’ clinical data were analyzed. Results PTPN12 protein and mRNA expression levels were significantly lower in ccRCC compared with the corresponding normal tissues. The mRNA expression levels in the ccRCC and corresponding normal tissues from the 64 patients with ccRCC were 0.459±0.445 and 1.001±0.128, respectively, compared with the control (glyceraldehyde 3-phosphate dehydrogenase). There was a significant correlation between relative expression of PTPN12 mRNA in ccRCC tissues and tumor diameter and clinical stage. Conclusion The expression levels of PTPN12 protein and mRNA were significantly lower in ccRCC tissues compared with normal tissues. The role of PTPN12 may provide new insights and evidence to aid the diagnosis and targeted therapy of ccRCC.

Objective To investigate the mitochondrial DNA (mtDNA) mutation load in hair follicles from different scalp regions of patients with mitochondrial, encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), compare the mutation load in different scalp regions, and analyze the difference in mutation load between scalp regions with lesion site in the brain and scalp regions without lesion site in the brain. Methods Seven MELAS patients with m.3243A > G mutations were studied. Hair follicles were obtained from 8 scalp regions (bilateral frontal, temporal, parietal and occipital lobes) of all patients and DNA was extracted. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to detect the m.3243A > G mutation. Results The mean value of m.3243A > G mutation load in hair follicles from all patients was (60.57 ± 7.71)%. In different scalp regions, the mean mutation load was (61.30 ± 7.32)% in left frontal, (65.41 ± 5.85)% in right frontal, (59.80 ± 5.58)% in left temporal, (57.59 ± 14.47)% in right temporal, (62.46 ± 5.02)% in left parietal, (60.11 ± 7.11)% in right parietal, (59.70 ± 8.68)% in left occipital and (59.42 ± 6.28)% in right occipital regions, respectively. There was no significant difference in the m.3243A > G mutation load among different scalp regions (F = 0.537, P = 0.802). There was no significant difference in the mutation load between scalp regions corresponding lesion site of the brain and scalp regions incorresponding lesion site of the brain [(60.33 ± 8.70)% vs. (61.02 ± 6.52)%; t = 0.319, P = 0.751)]. Conclusions Hair follicles are convenient and noninvasive sampled tissue for detecting mtDNA mutations. There is no difference in the mutation load among different scalp regions. Furthermore, there is no difference between scalp regions corresponding lesion site of the brain and scalp regions incorresponding lesion site of the brain.

DOI: 10.3969/j.issn.1672-6731.2017.11.014

Abstract Purpose: To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis. Methods: 90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology. Results: Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group. Conclusion: Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-a, -ß, and -1, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response. [ABSTRACT FROM AUTHOR]

Myostatin, a member of the transforming growth factor beta (TGF-β) superfamily, is a dominant inhibitor that acts to limit skeletal muscle growth and development. In this study, we generated transgenic mice that express porcine myostatin containg mutations at its cleavage site (RSRR) to evaluate its effect on muscle mass. Results showed that the weight of four skeletal muscles including gastrocnemius, rectus femoris, tibialis anterior, and pectoralis increased by 17.83 and 28.39%, 21.76 and 28.70%, 34.31 and 41.62%, 53.21 and 27.54% in transgenic male and female mice, respectively, compared to their corresponding non-transgenic control mice. Measurement of muscle fiber size and number indicated that the mean myofiber size increased by 50.73 and 61.30% in transgenic male and female mice respectively compared to the non-transgenic controls. However, there was no difference in the number of myofiber between transgenic and non-transgenic male mice. These results clearly demonstrated that the increase in skeletal muscle mass in transgenic mice is caused by hypertrophy instead of hyperplasia.

A series of fluorinated 7-hydroxycoumarin derivatives containing an oxime ether moiety have been designed, synthesized and evaluated for their antifungal activity. All the target compounds were determined by 1H-NMR, 13C-NMR, FTIR and HR-MS spectra. The single-crystal structures of compounds 4e, 4h, 5h and 6c were further confirmed using X-ray diffraction. The antifungal activities against Botrytis cinerea (B. cinerea), Alternariasolani (A. solani), Gibberella zeae (G. zeae), Rhizoctorzia solani (R. solani), Colletotrichum orbiculare (C. orbiculare) and Alternaria alternata (A. alternata) were evaluated in vitro. The preliminary bioassays showed that some of the designed compounds displayed the promising antifungal activities against the above tested fungi. Strikingly, the target compounds 5f and 6h exhibited outstanding antifungal activity against B. cinerea at 100 μg/mL, with the corresponding inhibition rates reached 90.1 and 85.0%, which were better than the positive control Osthole (83.6%) and Azoxystrobin (46.5%). The compound 5f was identified as the promising fungicide candidate against B. cinerea with the EC50 values of 5.75 μg/mL, which was obviously better than Osthole (33.20 μg/mL) and Azoxystrobin (64.95 μg/mL). Meanwhile, the compound 5f showed remarkable antifungal activities against R. solani with the EC50 values of 28.96 μg/mL, which was better than Osthole (67.18 μg/mL) and equivalent to Azoxystrobin (21.34 μg/mL). The results provide a significant foundation for the search of novel fluorinated 7-hydroxycoumarin derivatives with good antifungal activity.

Background: Kearns-Sayre syndrome (KSS) is a mitochondrial DNA (mtDNA) deletion disorder characterized by a triad of onset before 20 years of age, ophthalmoplegia, and pigmentary retinopathy. The heart and central nervous system are commonly involved. We summarized clinical and brain magnetic resonance imaging (MRI) features of a cohort of Chinese KSS patients. Methods: Nineteen patients confirmed by muscle biopsy and mtDNA analysis were enrolled. We examined clinical profiles, mainly focusing on changes in electrocardiogram (ECG) and brain MRI. The correlation between genotype and phenotype was statistically analyzed. Results: The mean age of onset was 9.6 ± 4.3 years, with all developing the classic triad at the time of diagnosis. Heart conduction block was detected in 63.2%, with four initially presenting as bundle branch block and developing into complete atrioventricular block over 3–72 months. Brain MRI showed symmetric high-T2 signals in 100% of cerebral and cerebellar white matter, as well as brainstem, 46.7% of basal ganglia, and 53.3% of thalamus. There were two patterns of cerebral white matter involvements, one with selective subcortical U-fibers and the other with periventricular white matter. The size of mtDNA deletion did not significantly correlate with age of onset or percentage of ragged blue fibers on muscle pathology. Conclusions: The clinical features of KSS evolve dynamically, affecting the cardiac conduction system predominantly, highlighting the significance of ECG monitoring. Brain MRI showed changes involving both the white matter and deep gray nuclei. Clinical presentation or severity of muscle pathological changes is not related to the size of mtDNA deletions.

Background Treatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs) and applied microRNA biochips to screen differentially expressed miRNAs that were related to radiation tolerance in irradiated human laryngeal CSCs. According to the predicted genes and pathways of differential miRNAs target, down-regulated expression of hsa-miR-138-2-3p under radiation was thought to play a key role in enhancing the radio-sensitivity in human laryngeal squamous cancer stem cells. Method To investigate the radiational enhancement of hsa-miR-138-2-3p, we transfected hsa-miR-138-2-3p mimics that were synthesized based on the sequences of hsa-miR-138-2-3p in vitrointo human laryngeal CSCs (Hep-2, M2e, and TU212 cell lines) to make hsa-miR-138-2-3p overexpressed, and the tumorous specialities of CSCs, like cell proliferation, invasion, apoptosis, cell cycle arrest, and DNA damage were evaluated by CCK-8 assay, clone formation assay, invasion assay, flow cytometry, and comet assay. Furthermore, we explored the signal transduction pathways that regulated the cancer stem cell initiation, development, invasion, apoptosis and cell cycle arrest, which were controlled by hsa-miR-138-2-3p. Result Overexpressed hsa-miR-138-2-3p played a key role in many anti-cancer biological processes in human laryngeal CSCs: (1) it decreased laryngeal CSCs proliferation and invasion in response to radiotherapy; (2) it increased the proportion of early and late apoptosis in laryngeal CSCs after radiation, raised G1 phase arrest in laryngeal CSCs after radiation, and decreased the proportion of S stage cells of cell cycle that were related to radio-resistance in laryngeal CSCs; (3) it down-regulated the expression of β-catenin in Wnt signal pathway that was related to the tolerance of laryngeal CSCs to radiotherapy; (4) it down-regulated the expression of YAP1 in Hippo signal pathway that regulated cell proliferation, invasion and apoptosis; (5) it up-regulated the expression of p38 and JNK1 in MAPK signal pathway that was concerned to radio-sensitivity. Conclusion In the present study, it was found that hsa-miR-138-2-3p regulated the Wnt/β-catenin pathways, the Hippo/YAP1 pathways, and the MAPK/p38/JNK1 pathways that were involved in cell proliferation, invasion, apoptosis, cell cycle arrest, radio-resistance and radio-sensitivity in laryngeal CSCs. These results will be useful for a better understanding of the cell biology of hsa-miR-138-2-3p in laryngeal CSCs, and for serving hsa-miR-138-2-3p as a promising biomarker and as a target for diagnosis and for novel anti-cancer therapies for laryngeal cancers.

This review aims to compare peri-implant tissue changes in terms of clinical and radiographic aspects of implant restoration protocol using one-time abutment to repeated abutment connection in platform switched implant.A structured search strategy was applied to three electronic databases, namely, Pubmed, Embase and Web of Science. Eight eligible studies, including seven randomised controlled studies and one controlled clinical study, were identified in accordance with inclusion/exclusion criteria. Outcome measures included peri-implant bone changes (mm), peri-implant soft tissue changes (mm), probing depth (mm) and postsurgical complications.Six studies were pooled for meta-analysis on bone tissue, three for soft tissue, two for probing depth and four for postsurgical complications. A total of 197 implants were placed in one-time abutment group, whereas 214 implants were included in repeated abutment group. The implant systems included Global implants, Ankylos, JDEvolution (JdentalCare), Straumann Bone level and Conelog-Screwline. One-time abutment group showed significantly better outcomes than repeated abutment group, as measured in the standardised differences in mean values (fixed- and random-effect model): vertical bone change (0.41, 3.23) in 6 months, (1.51, 14.81) in 12 months and (2.47, 2.47) in 3 years and soft tissue change (0.21, 0.23). No significant difference was observed in terms of probing depth and complications.Our meta-analysis revealed that implant restoration protocol using one-time abutment is superior to repeated abutment for platform switched implant because of less bone resorption and soft tissue shifts in former. However, future randomised clinical trials should be conducted to further confirm these findings because of the small samples and the limited quality of the original research.

Our laboratory recently produced genetically engineered (GE) Meishan pigs containing a ZFN-edited myostatin loss-of-function mutant. These GE pigs develop and grow as normal as wild type pigs but produce pork with greater lean yield and lower fat mass. To assess any potential subchronic toxicity risks of this GE pork, a 90-day feeding study was conducted in Sprague-Dawley rats. Rats were randomly divided into five groups, and fed for 90 days with basic diet and basic diets formulated with low dose and high dose pork prepared from wild type pigs and GE pigs, respectively. Animal behaviors and clinical signs were monitored twice daily, and body weight and food consumption were measured and recorded weekly. At days 45 and 90, blood tests (lipid panel, electrolytes, parameters related to liver and kidney functions, and complete blood counts) were performed. Additionally, gross pathology and histopathological analyses were performed for major organs in each group. Data analysis shows that there were no significant differences in growth rate, food consumption, and blood test parameters between rat groups fed with GE pork and wild type pork. Although differences in some liver function parameters (such as aspartate aminotransferase, total proteins, albumin, and alkaline phosphatase) and white blood cell counts (such as lymphocyte percentage and monocyte percentage) were observed between rats fed with high dose GE pork and basic diet, all test results in rats fed with GE pork are in the normal range. Additionally, there are no apparent lesions noted in all organs isolated from rats in all five feeding groups on days 45 and 90. Overall, our results clearly indicate that food consumption of GE pork produced by ZFN-edited myostatin loss-of-function mutant pigs did not have any long-term adverse effects on the health status in rats.

Graphene based 2D nanomaterials have attracted increasing attention in biosensing application due to the outstanding physicochemical properties of graphene. In this work, palladium nanoparticles (Pd) loaded reduced graphene oxide (rGO) hybrid (rGO-Pd) was synthesized through a facile method. Laccase (Lac) was immobilized on rGO-Pd by utilizing the self-polymerization of dopamine, which generated polydopamine (PDA). The PDA-Lac-rGO-Pd nanocomposites were further modified on electrode surface to construct novel biosensing platform. The obtained electrochemical biosensor was applied in the detection of catechol, achieving excellent analytic results. Under the optimum condition, this biosensor possessed a linear range from 0.1 µM to 263 µM for catechol detection, the sensitivity reached 18.4 µA mM−1, and the detection limit was as low as 0.03 µM. In addition, the biosensor also showed good repeatability, reproducibility, anti-interference, and stability. Moreover, the novel Lac based biosensor was successfully used in the trace detection of catechol existing in real water environment.