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BACKGROUND: Alzheimer's disease (AD), characterized by the ongoing deterioration of neural function, often presents alongside depressive features and greatly affects the quality of life of individuals living with the condition. Although several treatment methods exist, their efficacy is limited. In recent years, repetitive transcranial magnetic stimulation (rTMS) utilizing the theta burst stimulation (TBS) mode, specifically the intermittent TBS (iTBS), has demonstrated promising therapeutic potential in the management of neuropsychiatric disorders. AIM: To examine the therapeutic efficacy of iTBS mode of rTMS for treating depressive symptoms in patients with AD. METHODS: This retrospective study enrolled 105 individuals diagnosed with AD with depressive symptoms at Huzhou Third Municipal Hospital, affiliated with Huzhou University, between January 2020 and December 2023. Participants received standard pharmacological interventions and were categorized into control (n = 53) and observation (n = 52) groups based on treatment protocols. The observation group received iTBS mode of rTMS, while the control group received pseudo-stimulation. A comparative analysis evaluated psychological well-being, adverse events, and therapeutic at initiation of hospitalization (T0) and 15 days post-treatment (T1). RESULTS: At T1, both groups exhibited a marked reduction in self-rating depression scale and Hamilton depression scale scores compared to T0. Furthermore, the observation group showed a more pronounced decrease than the control group. By T1, the Mini-mental state examination scores for both groups had increased markedly from their initial T0 assessments. Importantly, the increase was particularly more substantial in the observation group than in the control group. Fourteen patients in the control group had ineffective treatment effects, while five patients in the observation group experienced the same. Additionally, the observation group experienced a substantially reduced incidence of ineffective treatment as compared to the control group (both P < 0.05); there were no recorded serious adverse events in either group. CONCLUSION: The iTBS model of rTMS effectively treated AD with depression, improving depressive symptoms and cognitive function in patients without serious adverse reactions, warranting clinical consideration.
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Aluminium nitride (AlN) materials are widely used in heat-dissipation substrates and electronic device packages. However, the application of aluminium nitride ceramics is hindered by the obvious anisotropy and high brittleness of its crystals, leading to poor material surface integrity and high grinding force. With the rapid development of microelectronics, the requirements for the material's dimensional accuracy, machining efficiency, and surface accuracy are increasing. Therefore, a new machining process is proposed, combining laser and ultrasonic vibration with grinding. The laser-ultrasonic-assisted grinding (LUAG) of aluminium nitride is simulated by molecular dynamics (MD). Meanwhile, the effects of different processing techniques on grinding force, stress distribution, matrix damage mechanism, and subsurface damage depth are systematically investigated and verified by experiments. The results show that laser-ultrasonic-assisted grinding produces 50% lower grinding forces compared to traditional grinding (TG). The microhardness of AlN can reach more than 1200 HV, and the coefficient of friction and wear is reduced by 42.6%. The dislocation lines of the AlN substrate under this process are short but interlaced, making the material prone to phase transformation. Moreover, the subsurface damage depth is low, realising the substrate's material hardening and wear resistance. These studies not only enhance the comprehension of material build-up and stress damage under the synergistic impact of laser, ultrasonic, and abrasive processing but also indicate that the proposed method can facilitate and realise high-performance machining of aluminium nitride substrate surfaces.
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Two Gram-stain-negative, rod-shaped, non-motile, aerobic and carotenoid-producing strains, belonging to the family Erythrobacteraceae, designated as H149T and Z2T, were isolated from tidal flat sediment samples collected in Hainan and Zhejiang, PR China, respectively. Growth of strain H149T occurred at 15-42 °C, 0-10.0â% (w/v) NaCl, and pH 6.0-8.5, with the optima at 35-37 °C, 3.0-3.5â% (w/v) NaCl and pH 7.0. Strain Z2T grew at 15-37 °C, 0-6.0â% (w/v) NaCl, and pH 6.0-9.5, with the optima at 25-30 °C, 0.5-1.0â% (w/v) NaCl and pH 6.0-6.5. Ubiquinone-10 was the sole ubiquinone in two strains. The predominant cellular fatty acids of strain H149T were C16â:â0, summed feature 3 and summed feature 8, while those of strain Z2T were C17â:â1 ω6c, summed feature 3 and summed feature 8. Strains H149T and Z2T shared diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and sphingoglycolipid as major polar lipids. The 16S rRNA gene sequence identity analysis indicated that strain H149T had the highest sequence identity of 98.4â% with Aurantiacibacter odishensis KCTC 23981T, and strain Z2T had that of 98.2â% with Qipengyuania pacifica NZ-96T. Phylogenetic trees based on 16S rRNA gene and core-genome sequences revealed that strains H149T and Z2T formed two independent clades in the genera Aurantiacibacter and Qipengyuania, respectively. Strain H149T had average nucleotide identity values of 74.0-81.3â% and in silico DNA-DNA hybridization values of 18.5-23.1â% with Aurantiacibacter type strains, while strain Z2T had values of 73.3-78.7â% and 14.5-33.3â% with Qipengyuania type strains. The genomic DNA G+C contents of strains H149T and Z2T were 64.3 and 61.8â%, respectively. Based on the genetic, genomic, phylogenetic, physiological and chemotaxonomic results, strains H149T (=KCTC 8397T=MCCC 1K08920T) and Z2T (=KCTC 8396T=MCCC 1K08946T) are concluded to represent two novel Erythrobacteraceae species for which the names Aurantiacibacter hainanensis sp. nov. and Qipengyuania zhejiangensis sp. nov. are proposed, respectively.
Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Ubiquinone , RNA, Ribosomal, 16S/genetics , Geologic Sediments/microbiology , China , DNA, Bacterial/genetics , Seawater/microbiology , PhospholipidsABSTRACT
Owing to the contradiction between agricultural production and environmental development, the issues of food security and carbon mitigation cannot be isolated, and achieving coupled and coordinated development is the key to agricultural sustainability. This study adopted the coupled coordination model and dynamic qualitative comparative analysis (dynamic QCA) method to measure the coupled coordination degree (CCD) of the food security index (FSI) and agricultural carbon emission efficiency (ACEE) in 31 provinces of China from 2010 to 2021, seeking paths to achieve high coupled coordination from Climate-Smart Agriculture technology, external environment, and incentive dimensions, and simulating path selection differences under various CSA priority scenarios. The results indicated that the CCD of the FSI and ACEE in China significantly increased year-on-year increase, with significant regional differences primarily reflected in the Northeast > East > West > Central regions. Based on the CSA orientation, the "technology-environmental safeguard" linkage path and the "technology-environment-incentive" hybrid path are proposed. There are differences in CSA practices across regions, which require customization based on their unique socioeconomic, ecological, and political landscapes. When priorities favour food security, the "technology-environment-incentive" hybrid pathway supports high CCD, and as priorities increase, the contribution of CSA technologies, centred on water-saving irrigation, increases and the role of the external environment diminishes. When the priority tendency is to mitigate emissions, both paths can achieve high CCD. As the priority tendency for carbon emissions increases, urbanisation and CSA technologies such as water-saving irrigation and straw return become essential factors contributing to higher coupling coordination, and the role of agriculture-related financial expenditures diminishes. These findings provide policy support for safeguarding food security and low-carbon agriculture.
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BACKGROUND: In recent years, compression therapy has attracted gradually increasing clinical attention in lower extremity venous diseases. However, basic concepts and clear nomenclature, standard treatment methods, and consistent product standards for pressure equipment are lacking. Therefore, developing clinical guidelines for compression therapy is essential to improving the treatment of venous diseases. METHODS: Our panel generated strong (Grade I), moderate (Grade IIa and IIb), and weak (Grade III) recommendations based on high quality (Class A), moderate quality (Class B), and low quality (Class C) evidence, using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach and the European Society of Cardiology (ESC) grading system. RESULTS: The panels made 30 recommendations from current evidence, focusing on seven fields of lower extremity venous disease (venous thromboembolism, post-thrombotic syndrome, chronic venous insufficiency, varicose veins, hemangioma and vascular malformations, lymphedema, and venous ulcers) and 18 topics. CONCLUSIONS: Of the 30 recommendations made across the 18 topics, 7 were strong (Grade I) and 17 were based on high quality (Class A) evidence, highlighting the need for further research of the use of compression therapy for .
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During the second-to-third trimester, the neuronal pathways of the fetal brain experience rapid development, resulting in the complex architecture of the interwired network at birth. While diffusion MRI-based tractography has been employed to study the prenatal development of structural connectivity network (SCN) in preterm neonatal and postmortem fetal brains, the in utero development of SCN in the normal fetal brain remains largely unknown. In this study, we utilized in utero dMRI data from human fetuses of both sexes between 26 and 38 gestational weeks to investigate the developmental trajectories of the fetal brain SCN, focusing on intrahemispheric connections. Our analysis revealed significant increases in global efficiency, mean local efficiency, and clustering coefficient, along with significant decrease in shortest path length, while small-worldness persisted during the studied period, revealing balanced network integration and segregation. Widespread short-ranged connectivity strengthened significantly. The nodal strength developed in a posterior-to-anterior and medial-to-lateral order, reflecting a spatiotemporal gradient in cortical network connectivity development. Moreover, we observed distinct lateralization patterns in the fetal brain SCN. Globally, there was a leftward lateralization in network efficiency, clustering coefficient, and small-worldness. The regional lateralization patterns in most language, motor, and visual-related areas were consistent with prior knowledge, except for Wernicke's area, indicating lateralized brain wiring is an innate property of the human brain starting from the fetal period. Our findings provided a comprehensive view of the development of the fetal brain SCN and its lateralization, as a normative template that may be used to characterize atypical development.
Subject(s)
Diffusion Magnetic Resonance Imaging , Nerve Net , Pregnancy Trimester, Third , Humans , Female , Male , Pregnancy , Diffusion Magnetic Resonance Imaging/methods , Nerve Net/diagnostic imaging , Nerve Net/embryology , Nerve Net/physiology , Nerve Net/growth & development , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/embryology , Pregnancy Trimester, Second , Neural Pathways/embryology , Neural Pathways/diagnostic imaging , Neural Pathways/physiology , Fetus/diagnostic imaging , Fetal Development/physiology , Diffusion Tensor Imaging/methodsABSTRACT
KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.
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ABSTRACT: Imaging plates can measure isotopes with alpha decay (such as radon and its progeny, americium, and so on). However, the detection efficiency of imaging plates is affected by alpha particle energy, types of imaging plates, and the overlapping effect. In this study, simulations were performed to analyze the relationship between detection efficiency and these three influence factors. The research findings suggest that BAS-TR and BAS-MS are well-suited for the detection of alpha particles with energy levels below 6.83 MeV and above, respectively. The track overlap effect correction method proposed in this study is applicable to both BAS-TR and BAS-MS image plates. The measurement results of radon progeny demonstrate that the correction method enhances the detection efficiency from 0.203 to 0.288. This study presents a valuable approach for selecting the appropriate image plate and correcting the track overlap effect in the measurement of alpha radioactive material concentration and other related information.
Subject(s)
Alpha Particles , Radiometry/methods , Radiometry/instrumentation , Radon/analysis , Computer SimulationABSTRACT
Importance: The incidence of melanoma in situ (MIS) has increased significantly over the past decades, and traditional guidelines for treatment of MIS have been excision with a 5-mm clinical margin; however, current Australian and other guidelines now recommend 5- to 10-mm margins. This changed recommendation was largely driven by the outcomes of studies using Mohs micrographic surgery, and recent studies using Mohs micrographic surgery are advocating for even wider excisions up to 18 mm for clearance. Objective: To assess the rate of recurrence of MIS excised with a 5-mm margin. Design, Setting, and Participants: This case series studied all MIS lesions from a single private dermatology clinic between January 1, 2011, and November 30, 2018. The criteria for inclusion were a documented 5-mm excisional margin on operation report and more than 5 years of site-specific follow-up after wide local excision. Lesions were excluded if the excisional margin was more than 5 mm or undocumented, there was less than 5 years of follow-up, or they required more than 1 wide local excision. Data analysis was performed January 30 to February 25, 2024. Intervention: Wide local excision with 5-mm margin. Results: A total of 351 MISs were identified from 292 patients (mean [SD] age, 60.3 [11.8] years; 162 females [55.5%]). Superficial spreading melanoma was the most common subtype diagnosed (177 lesions [50.4%]), followed by lentigo maligna (107 lesions [30.5%]) and lentiginous MIS (67 lesions [19.1%]). The trunk was the most common location of lesions (168 lesions [47.9%]), followed by upper limb (96 lesions [27.4%]) and lower limb (59 lesions [16.8%]). Scalp was the least common location (2 lesions [0.6%]). Most of the lesions were small, with 274 lesions (78.1%) having a length less than 10 mm and 312 lesions (88.9%) having a width less than 10 mm. A total of 348 lesions (99.1%) did not have clinical recurrence after excision with a 5-mm clinical margin following then current guidelines. A total of 3 lesions (0.9%) experienced local recurrence with no metastatic spread. Conclusions and Relevance: This case series found that excision with a 5-mm margin for MIS of smaller size (<10 mm) on low-risk body sites had a low rate of recurrence. Conservative 5-mm excisional margin is likely to be suitable for small MIS on lower-risk body sites.
Subject(s)
Margins of Excision , Melanoma , Neoplasm Recurrence, Local , Skin Neoplasms , Humans , Skin Neoplasms/surgery , Skin Neoplasms/pathology , Melanoma/surgery , Melanoma/pathology , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/prevention & control , Female , Male , Middle Aged , Aged , Mohs Surgery/statistics & numerical data , Mohs Surgery/methods , Adult , Aged, 80 and over , Retrospective Studies , Follow-Up Studies , Australia/epidemiologyABSTRACT
Monolithic textured perovskite/silicon tandem solar cells (TSCs) are expected to achieve maximum light capture at the lowest cost, potentially exhibiting the best power conversion efficiency. However, it is challenging to fabricate high-quality perovskite films and preferred crystal orientation on commercially textured silicon substrates with micrometer-size pyramids. Here, we introduced a bulky organic molecule (4-fluorobenzylamine hydroiodide (F-PMAI)) as a perovskite additive. It is found that F-PMAI can retard the crystallization process of perovskite film through hydrogen bond interaction between F- and FA+ and reduce (111) facet surface energy due to enhanced adsorption energy of F-PMAI on the (111) facet. Besides, the bulky molecular is extruded to the bottom and top of perovskite film after crystal growth, which can passivate interface defects through strong interaction between F-PMA+ and undercoordinated Pb2+/I-. As a result, the additive facilitates the formation of large perovskite grains and (111) preferred orientation with a reduced trap-state density, thereby promoting charge carrier transportation, and enhancing device performance and stability. The perovskite/silicon TSCs achieved a champion efficiency of 30.05% based on a silicon thin film tunneling junction. In addition, the devices exhibit excellent long-term thermal and light stability without encapsulation. This work provides an effective strategy for achieving efficient and stable TSCs.
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OBJECTIVES: Medical research faces substantial challenges from noisy labels attributed to factors like inter-expert variability and machine-extracted labels. Despite this, the adoption of label noise management remains limited, and label noise is largely ignored. To this end, there is a critical need to conduct a scoping review focusing on the problem space. This scoping review aims to comprehensively review label noise management in deep learning-based medical prediction problems, which includes label noise detection, label noise handling, and evaluation. Research involving label uncertainty is also included. METHODS: Our scoping review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched 4 databases, including PubMed, IEEE Xplore, Google Scholar, and Semantic Scholar. Our search terms include "noisy label AND medical/healthcare/clinical," "uncertainty AND medical/healthcare/clinical," and "noise AND medical/healthcare/clinical." RESULTS: A total of 60 papers met inclusion criteria between 2016 and 2023. A series of practical questions in medical research are investigated. These include the sources of label noise, the impact of label noise, the detection of label noise, label noise handling techniques, and their evaluation. Categorization of both label noise detection methods and handling techniques are provided. DISCUSSION: From a methodological perspective, we observe that the medical community has been up to date with the broader deep-learning community, given that most techniques have been evaluated on medical data. We recommend considering label noise as a standard element in medical research, even if it is not dedicated to handling noisy labels. Initial experiments can start with easy-to-implement methods, such as noise-robust loss functions, weighting, and curriculum learning.
Subject(s)
Deep Learning , Humans , Biomedical ResearchABSTRACT
Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.
Subject(s)
Antibodies, Monoclonal , Epitopes , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Humans , Herpesvirus 4, Human/immunology , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/virology , Antibodies, Monoclonal/immunology , Epitopes/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Mice , Histocompatibility Antigens Class II/immunology , Histocompatibility Antigens Class II/metabolism , Viral Proteins/immunology , B-Lymphocytes/immunologyABSTRACT
Although the treatment of ovarian cancer has made great progress, there are still many patients who are not timely detected and given targeted therapy due to unknown pathogenesis. Recent studies have found that hsa_circ_0015326 is upregulated in ovarian cancer and is involved in the proliferation, invasion, and migration of ovarian cancer cells. However, whether hsa_circ_0015326 can be used as a new target of ovarian cancer needs further investigation. Therefore, the effect of hsa_circ_0015326 on epithelial ovarian cancer was investigated in this study. At first, si-hsa_circ_0015326 lentivirus was transfected into epithelial ovarian cancer cells. Then real-time fluorescence quantitative PCR (qRT-PCR) was used to detect hsa_circ_0015326 level. The proliferation of ovarian cancer cells was detected by CCK-8 assay. The horizontal and vertical migration abilities of the cells were detected by wound-healing assay and Transwell assay, respectively. Transwell assay was also used to determine the invasion rate. As for the apoptosis rate, it was assessed by flow cytometry. As a result, the expression level of hsa_circ_0015326 in A2780 and SKOV3 was found to be higher than that in IOSE-80. However, after transfecting si-hsa_circ_0015326 and si-NC into the cells, the proliferation, migration, and invasion abilities of A2780 and SKOV3 cells in the si-hsa_circ_0015326 group were significantly reduced in comparison to those in the si-NC and mock groups, while their apoptosis rates were elevated. Collectively, silencing hsa_circ_0015326 bears the capability of inhibiting the proliferation, migration, and invasion of ovarian cancer cells while increasing apoptosis rate. It can be concluded that hsa_circ_0015326 promotes the malignant biological activities of epithelial ovarian cancer cells.
Subject(s)
MicroRNAs , Ovarian Neoplasms , Humans , Female , RNA/metabolism , Carcinoma, Ovarian Epithelial/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , Cell Line, Tumor , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Cell Proliferation , Apoptosis , MicroRNAs/metabolism , Cell MovementABSTRACT
BACKGROUND: Rapid cycling bipolar disorder (RCBD), characterized by four or more episodes per year, is a complex subtype of bipolar disorder (BD) with poorly understood characteristics. METHOD: This multicenter, observational, longitudinal cohort study enrolled 520 BD patients across seven psychiatric institutions in China from January 2013 to January 2014. Participants were divided into RCBD and non-RCBD (NRCBD) groups based on the frequency of mood episodes in the preceding year. Data collection utilized a standardized form, supplemented by a medical record review, focusing on sociodemographic, clinical, and treatment characteristics. Statistical analysis involved independent samples t-tests, Kruskal-Wallis H tests, Chi-square or Fisher's exact tests, with Bonferroni correction applied to account for multiple comparisons, and multivariable logistic regression to identify characteristics associated with RCBD. RESULTS: Among the BD cohort, 9.4% were identified as current RCBD. Compared to NRCBD, RCBD patients had a shorter duration from the first psychiatric consultation to the diagnosis of BD, a reduced duration of their longest period of euthymia, a lower proportion of lifetime hospitalization history due to BD, and less use of electroconvulsive therapy (ECT) within the last 12 months. Additionally, they presented higher baseline scores on the Mood Disorder Questionnaire (MDQ) and the Brief 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). However, after applying the Bonferroni correction, these differences were not statistically significant. Multivariable logistic regression analysis identified three factors that were independently associated with RCBD: time from first psychiatric consultation to BD diagnosis (Odds Ratio [OR] = 0.512, P = 0.0416), lifetime hospitalization history due to BD (OR = 0.516, P = 0.0476), and ECT treatment within the past 12 months (OR = 0.293, P = 0.0472). CONCLUSION: This study revealed that the duration from first psychiatric consultation to BD diagnosis, lifetime hospitalization history due to BD, and ECT treatment in the past year were associated with RCBD. Recognizing these factors could contribute to enhance the early identification and clinical outcomes of RCBD. Trial Registration Number Registry ClinicalTrials.gov NCT01770704. Date of Registration: First posted on January 18, 2013.
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BACKGROUND: Neuromedin B (Nmb) plays a pivotal role in the transmission of neuroinflammation, particularly during spinal cord ischemia-reperfusion injury (SCII). However, the detailed molecular mechanisms underlying this process remain elusive. METHODS: The SCII model was established by clamping the abdominal aorta of male Sprague-Dawley (SD) rats for 60 min. The protein expression levels of Nmb, Cav3.2, and IL-1ß were detected by Western blotting, while miR-214-3p expression was quantified by qRT-PCR. The targeted regulation between miR-214-3p and Nmb was investigated using a dual-luciferase reporter gene assay. The cellular localization of Nmb and Cav3.2 with cell-specific markers was visualized by immunofluorescence staining. The specific roles of miR-214-3p on the Nmb/Cav3.2 interactions in SCII-injured rats were explored by intrathecal injection of Cav3.2-siRNA, PD168368 (a specific NmbR inhibitor) and synthetic miR-214-3p agomir and antagomir in separate experiments. Additionally, hind-limb motor function was evaluated using the modified Tarlov scores. RESULTS: Compared to the Sham group, the protein expression levels of Nmb, Cav3.2, and the proinflammatory factor Interleukin(IL)-1ß were significantly elevated at 24 h post-SCII. Intrathecal injection of PD168368 and Cav3.2-siRNA significantly suppressed the expression of Cav3.2 and IL-1ß compared to the SCII group. The miRDB database and dual-luciferase reporter gene assay identified Nmb as a direct target of miR-214-3p. As expected, in vivo overexpression of miR-214-3p by agomir-214-3p pretreatment significantly inhibited the increases in Nmb, Cav3.2 and IL-1ß expression and improved lower limb motor function in SCII-injured rats, while antagomiR-214-3p pretreatment reversed these effects. CONCLUSIONS: Nmb protein levels positively correlated with Cav3.2 expression in SCII rats. Upregulating miR-214-3p ameliorated hind-limb motor function and protected against neuroinflammation via inhibiting the aberrant Nmb/Cav3.2 interactions and downstream IL-1ß release. These findings provide novel therapeutic targets for clinical prevention and treatment of SCII.
Subject(s)
Calcium Channels, T-Type , MicroRNAs , Neuroinflammatory Diseases , Reperfusion Injury , Spinal Cord Ischemia , Animals , Male , Rats , Calcium Channels, T-Type/genetics , Calcium Channels, T-Type/metabolism , Disease Models, Animal , Interleukin-1beta/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/drug therapy , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Signal Transduction , Spinal Cord/metabolism , Spinal Cord Ischemia/metabolism , Spinal Cord Ischemia/geneticsABSTRACT
A Gram-stain-negative bacterium with a rod-to-ovoid shape, named strain M216T, was isolated from sand sediment from the coastal intertidal zone of Huludao, Liaoning Province, China. Growth was observed at 8-40 °C (optimal, 30 °C), pH 5.5-9.5 (optimal, pH 6.5) and 0.5-14.0% (w/v) NaCl (optimal, 6%). Strain M216T possessed ubiquinone-9 as its sole respiratory quinone and phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophosphoglycolipid, one unidentified aminophospholipid, two unidentified phosphoglycolipids, three unidentified phospholipids and three unidentified glycolipids as the main polar lipids. C12:0, C16:0, C12:0 3-OH, C16:1 ω9c, C18:1 ω9c and summed features 3 (C16:1 ω7c and/or C16:1 ω6c) were the major fatty acids (> 5%). The 16S rRNA gene sequence of strain M216T exhibited high similarity to those of 'Marinobacter arenosus' CAU 1620T and Marinobacter adhaerens HP15T (99.3% and 98.5%, respectively) and less than 98.5% similarity to those of the other type strains. The ANI and dDDH values between the strain M216T and 'Marinobacter arenosus' CAU 1620T were 87.4% and 33.3%, respectively; these values were the highest among the other type strains but lower than the species threshold. The G+C content of strain M216T was 58.3%. Genomic analysis revealed that strain M216T harbors the major CAZymes of GH13, GH23, GH73, and PL5, which are responsible for polysaccharide degradation and the potential ability to reduce nitrate to ammonia. Through phenotypic, genotypic, and chemotaxonomic analyses, we proposed the name Marinobacter albus sp. nov., a novel species in the genus Marinobacter, with its type strain M216T (= MCCC 1K08600T = KCTC 82894T).
Subject(s)
Marinobacter , Marinobacter/genetics , RNA, Ribosomal, 16S/genetics , Sand , Ammonia , ChinaABSTRACT
A Gram-stain-negative, aerobic, motile with flagella and rod- or ovoid-shaped bacterium, designated GG15T, was isolated from tidal flat sediment sampled in Zhoushan, Zhejiang Province. Strain GG15T grew at 20-40â°C (optimum, 30â°C), at pH 5.5-9.5 (optimum, pH 7.0-8.0) and with 1.0-10.0â% (w/v) NaCl (optimum, 1.5â%). Colony diameters ranged from 1 to 3 mm within the first week, reaching a maximum of 6-7 mm after 15 days of cultivation. Strain GG15T exhibited highest 16S rRNA gene sequence similarity to Microbulbifer taiwanensis CCM 7856T (98.1 %), with similarity to other species within the genus Microbulbifer ranging from 97.8 to 93.8â%. Similarity values to other genera were below 93.8â%. Strain GG15T exhibited positive activity for ß-glucosidase, trypsin and chymotrypsin, whereas the reference strain showed negative activity. Chemotaxonomic analyses indicated that strain GG15T contained Q-8 as the sole respiratory quinone, C16â:â0 (9.1â%), iso-C15â:â0 (30.9â%) and iso-C11â:â0 3-OH (7.2â%) as the predominant fatty acids, and phosphatidylethanolamine, phosphatidylglycerol, three unidentified lipids, four unidentified glycolipids, one unidentified phospholipid, two unidentified aminolipids and two unidentified aminophospholipids as the main polar lipids. The genome of strain GG15T was 4â307â641 bp long, comprising 3861 protein-coding genes. The G+C content of strain GG15T was 61.5âmol% based on its genomic sequence. Strain GG15T showed low digital DNA-DNA hybridization (<70â%) and average nucleotide identity values (<95â%) with other Microbulbifer species. As a result, a novel species within the genus Microbulbifer, named Microbulbifer magnicolonia sp. nov., is proposed. The type strain is GG15T (MCCC 1K08802T=KCTC 8210T).
Subject(s)
Alteromonadaceae , Fatty Acids , Base Composition , Fatty Acids/chemistry , RNA, Ribosomal, 16S/genetics , Phylogeny , Sequence Analysis, DNA , DNA, Bacterial/genetics , Bacterial Typing Techniques , ChinaABSTRACT
Key Clinical Message: CHARGE syndrome is a rare genetic disorder characterized by several distinct features. The presence of fetal ear abnormalities could be the early indicator of CHARGE syndrome. Subsequent prenatal diagnosis is essential to confirm the disorder. This is significant because the patient may receive genetic counseling and appropriate disposal based on the accurate diagnosis. Abstract: CHARGE syndrome is a rare genetic disorder with multiple specific clinical features. The prenatal diagnosis is crucial but rarely achieved. We report a fetus with fetal external ear abnormality detected by ultrasound at 22nd week of gestation. Postnatal examination revealed an external ear abnormality, a mild atrial septal defect, and other clinical signs of CHARGE syndrome. A de novo pathogenic nonsense mutation in the CHD7 gene (c.406C > T, p.Q136X in exon 2) was identified to cause the disorder. Our study demonstrated that prenatal diagnosis and genetic testing were recommended to obtain a solid diagnosis of CHARGE syndrome when fetal external ear abnormality was detected by ultrasound examination.
ABSTRACT
Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.