The ARK2N-CK2 complex initiates transcription-coupled repair through enhancing the interaction of CSB with lesion-stalled RNAPII.

Transcription is extremely important for cellular processes but can be hindered by RNA polymerase II (RNAPII) pausing and stalling. Cockayne syndrome protein B (CSB) promotes the progression of paused RNAPII or initiates transcription-coupled nucleotide excision repair (TC-NER) to remove stalled RNAPII. However, the specific mechanism by which CSB initiates TC-NER upon damage remains unclear. In this study, we identified the indispensable role of the ARK2N-CK2 complex in the CSB-mediated initiation of TC-NER. The ARK2N-CK2 complex is recruited to damage sites through CSB and then phosphorylates CSB. Phosphorylation of CSB enhances its binding to stalled RNAPII, prolonging the association of CSB with chromatin and promoting CSA-mediated ubiquitination of stalled RNAPII. Consistent with this finding, Ark2n-/- mice exhibit a phenotype resembling Cockayne syndrome. These findings shed light on the pivotal role of the ARK2N-CK2 complex in governing the fate of RNAPII through CSB, bridging a critical gap necessary for initiating TC-NER.

A meta-analysis of the value of serum TSH concentration in the diagnosis of differentiated thyroid cancer in patients with thyroid nodules.

Background: In recent years, most studies believe that high TSH level is positively correlated with the incidence of thyroid cancer, but it is still controversial. For this reason, the purpose of this study is to analyze the correlation between preoperative TSH level and thyroid malignant nodules using pathological diagnosis as the gold standard. To evaluate the role of serum TSH in predicting malignancy of thyroid nodules with uncertain cytology.As an important member of the hypothalamus-pituitary-thyroid axis in the endocrine system, TSH plays a crucial role in regulating the growth, differentiation, and function of thyroid cells (Zhang et al., 2023) [1]. Therefore, it has always been considered closely related to TC. Currently, most studies have compared the TSH levels of TC patients and individuals with benign thyroid disease or healthy controls. These findings from various studies indicated that TC patients often demonstrate elevated TSH levels, even when their TSH falls within the normal range. However, it is important to highlight that the current evidence primarily relies on cross-sectional studies, which mainly describe a phenomenon without establishing causal relationships. The involvement of TSH in the early onset or late progression of TC remains unknown, the interaction between TSH and other factors and how it affects TC is not well understood (Gubbi et al., 2020) [2].Symptoms of thyroid cancer are usually insidious, and early thyroid cancer often has no obvious clinical symptoms. Therefore, early detection and early treatment are particularly important, and how to improve the preoperative diagnosis rate of thyroid nodules is also a problem that clinicians pay close attention to. Objective: To evaluate the value of serum TSH concentration in the diagnosis of differentiated thyroid carcinoma in patients with thyroid nodules. Methods: Our study searched databases in both Chinese and English.China Academic Journals FULL-text Database (CNKI), China Online Journals, Chinese Scientific Journals database and Chinese Biomedical Literature Database (CBM) were searched by computer. The English literature was established by PubMed, Embase, Cochrane Library, Web of Science and other databases until June 2022 to search for relevant literatures on the diagnostic test of serum TSH concentration in patients with thyroid nodule. The literatures that met the criteria were screened, the data were extracted, and the literature quality was evaluated. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the method for the diagnosis of differentiated thyroid carcinoma were calculated and summarized. The receiver operating characteristic (SROC) curve was drawn and the area under the curve was obtained. Results: A total of 23 diagnostic tests were included (5348 lesions). Meta-analysis showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of serum TSH concentration in the diagnosis of differentiated thyroid carcinoma were 0.64, 0.72, 2.511, 0.386 and 7.14, respectively. The area under SROC curve (AUC) was 0.79, and the Q index was 0.7283, indicating no statistically significant difference. Conclusion: Based on current evidence, detection of serum TSH concentration in thyroid nodule patients has high sensitivity and specificity for the diagnosis of differentiated thyroid cancer, which has good clinical application value. However, other auxiliary examinations are still needed to improve the diagnosis rate.

MBD1 protects replication fork stability by recruiting PARP1 and controlling transcription-replication conflicts.

The replication-stress response is essential to ensure the faithful transmission of genetic information to daughter cells. Although several stress-resolution pathways have been identified to deal with replication stress, the precise regulatory mechanisms for replication fork stability are not fully understood. Our study identified Methyl-CpG Binding Domain 1 (MBD1) as essential for the maintaining genomic stability and protecting stalled replication forks in mammalian cells. Depletion of MBD1 increases DNA lesions and sensitivity to replication stress. Mechanistically, we found that loss of MBD1 leads to the dissociation of Poly(ADP-ribose) polymerase 1 (PARP1) from the replication fork, potentially accelerating fork progression and resulting in higher levels of transcription-replication conflicts (T-R conflicts). Using a proximity ligation assay combined with 5-ethynyl-2'-deoxyuridine, we revealed that the MBD1 and PARP1 proteins were recruited to stalled forks under hydroxyurea (HU) treatment. In addition, our study showed that the level of R-loops also increased in MBD1-delated cells. Without MBD1, stalled replication forks resulting from T-R conflicts were primarily degraded by the DNA2 nuclease. Our findings shed light on a new aspect of MBD1 in maintaining genome stability and providing insights into the mechanisms underlying replication stress response.

CircDLGAP4 overexpression ameliorates neuronal injury in Parkinson's disease by binding to EIF4A3 and increasing HMGA2 expression.

Parkinson's disease (PD) is a prevalent neurodegenerative disease, and its prevalence increases steadily with age. Circular RNAs (circRNAs) are involved in various neurodegenerative diseases. Here, we aimed to explore the role of circRNA DLG-associated protein 4 (circDLGAP4) in 1-methyl-4-phenylpyridinium ion (MPP+ )-induced neuronal injury in PD. SH-SY5Y cells were treated with MPP+ to establish PD cell models. The levels of circDLGAP4 and high mobility group AT-hook 2 (HMGA2) in SH-SY5Y cells were detected. SH-SY5Y cell viability and apoptosis were detected. The levels of inflammatory damage (IL-1ß, IL-6, TNF-α) and oxidative stress (reactive oxygen species, lactate dehydrogenase, superoxide dismutase, and malondialdehyde)-related factors were measured. The binding of eukaryotic initiation factor 4A3 (EIF4A3) to circDLGAP4 and HMGA2 was analyzed using RNA pull-down or RNA immunoprecipitation. The stability of HMGA2 was detected after actinomycin D treatment, and its effects on neuronal injury were tested. CircDLGAP4 expression was decreased in MPP+ -induced SH-SY5Y cells. CircDLGAP4 upregulation restored cell activity, decreased apoptosis, and reduced inflammatory damage and oxidative stress in PD cell models. CircDLGAP4 bound to EIF4A3 to increase HMGA2 expression and stability. Silencing HMGA2 attenuated the protective effect of circDLGAP4 overexpression. Overall, circDLGAP4 upregulated HMGA2 by recruiting EIF4A3, thus increasing the mRNA stability of HMGA2 and alleviating neuronal injury in PD.

Inverse design of metasurfaces with customized transmission characteristics of frequency band based on generative adversarial networks.

In recent years, deep learning (DL) has demonstrated significant potential in the inverse design of metasurfaces, and the generation of metasurfaces with customized transmission characteristics of frequency band remains a challenging and underexplored area. In this study, we propose a DL-assisted method for the inverse design of transmissive metasurfaces. The method consists of a generative adversarial network (GAN)-based graph generator, an electromagnetic response predictor, and a genetic algorithm optimizer. By integrating these components, we can obtain customized metasurfaces with desired transmission characteristics of frequency band. We demonstrate the effectiveness of the proposed method through examples of inverse-designed three-layer cascaded transmissive metasurfaces with wideband, dual-band, and stopband responses in the 8∼12 GHz frequency range. Specifically, we realize three different types of dual-band metasurfaces, namely double-wide, front-wide and rear-narrow, and front-narrow and rear-wide configurations. Additionally, we analyze the accuracy and reliability of the inverse design method by employing data from the training dataset, self-defined objectives, and bandwidth-reduced target responses scaled from the wideband type as design inputs. Quantitative evaluation is performed using metrics such as mean absolute error and average precision. The proposed method successfully achieves the desired effect as intended.

Hsa_circ_0054220 Upregulates HMGA1 by the Competitive RNA Pattern to Promote Neural Impairment in MPTP Model of Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease. Circular RNAs (circRNAs) have been confirmed to regulate neurodegenerative diseases. This study was aimed to explore hsa_circ_0054220 functions in PD. MPP-stimulated SH-SY5Y cells were established as the PD cell model. PD mouse model was established by MPTP. Gene expression in cells and tissues was tested by RT-qPCR. Cell viability and apoptosis were evaluated through CCK-8 and TUNEL assays. The interactions of RNAs were determined by RNA pull-down assay, RIP assay, and luciferase reporter assay. Circ_0054220 expressed at a high level in MPP-treated SH-SY5Y cells. Circ_0054220 inhibition promoted viability and suppressed apoptosis in MPP-stimulated cells. Furthermore, we found that circ_0054220 can competitively bind to miR-145 and miR-625 to upregulate high mobility group A1 (HMGA1) expression. HMGA1 was positively regulated by circ_0054220 and overexpressed in MPP-treated cells as well as the striatum (STR), substantia nigra pars compacta (SNpc), and serum of MPTP-induced mouse model of PD. HMGA1 overexpression counteracted the function of circ_0054220 silencing on cell apoptosis. Furthermore, HMGA1 inhibition notably alleviated motor dysfunction and increased the quantity of neurons in mice resembling PD. Circ_0054220 upregulates HMGA1 by the competitive endogenous RNAs (ceRNA) pattern to promote neural impairment in PD.

Monolithic 3D integration of 2D transistors and vertical RRAMs in 1T-4R structure for high-density memory.

Emerging data-intensive computation has driven the advanced packaging and vertical stacking of integrated circuits, for minimized latency and energy consumption. Yet a monolithic three-dimensional (3D) integrated structure with interleaved logic and high-density memory layers has been difficult to achieve due to challenges in managing the thermal budget. Here we experimentally demonstrate a monolithic 3D integration of atomically-thin molybdenum disulfide (MoS2) transistors and 3D vertical resistive random-access memories (VRRAMs), with the MoS2 transistors stacked between the bottom-plane and top-plane VRRAMs. The whole fabrication process is integration-friendly (below 300 °C), and the measurement results confirm that the top-plane fabrication does not affect the bottom-plane devices. The MoS2 transistor can drive each layer of VRRAM into four resistance states. Circuit-level modeling of the monolithic 3D structure demonstrates smaller area, faster data transfer, and lower energy consumption than a planar memory. Such platform holds a high potential for energy-efficient 3D on-chip memory systems.

A transcription-independent mechanism determines rapid periodic fluctuations of BRCA1 expression.

BRCA1 expression is highly regulated to prevent genomic instability and tumorigenesis. Dysregulation of BRCA1 expression correlates closely with sporadic basal-like breast cancer and ovarian cancer. The most significant characteristic of BRCA1 regulation is periodic expression fluctuation throughout the cell cycle, which is important for the orderly progression of different DNA repair pathways throughout the various cell cycle phases and for further genomic stability. However, the underlying mechanism driving this phenomenon is poorly understood. Here, we demonstrate that RBM10-mediated RNA alternative splicing coupled to nonsense-mediated mRNA decay (AS-NMD), rather than transcription, determines the periodic fluctuations in G1/S-phase BRCA1 expression. Furthermore, AS-NMD broadly regulates the expression of period genes, such as DNA replication-related genes, in an uneconomical but more rapid manner. In summary, we identified an unexpected posttranscriptional mechanism distinct from canonical processes that mediates the rapid regulation of BRCA1 as well as other period gene expression during the G1/S-phase transition and provided insights into potential targets for cancer therapy.

A Photopatternable Conjugated Polymer with Thermal-Annealing-Promoted Interchain Stacking for Highly Stable Anti-Counterfeiting Materials.

Photoresponsive polymers can be conveniently used to fabricate anti-counterfeiting materials through photopatterning. However, an unsolved problem is that ambient light and heat can damage anti-counterfeiting patterns on photoresponsive polymers. Herein, photo- and thermostable anti-counterfeiting materials are developed by photopatterning and thermal annealing of a photoresponsive conjugated polymer (MC-Azo). MC-Azo contains alternating azobenzene and fluorene units in the polymer backbone. To prepare an anti-counterfeiting material, an MC-Azo film is irradiated with polarized blue light through a photomask, and then thermally annealed under the pressure of a photonic stamp. This strategy generates a highly secure anti-counterfeiting material with dual patterns, which is stable to sunlight and heat over 200 °C. A key for the stability is that thermal annealing promotes interchain stacking, which converts photoresponsive MC-Azo to a photostable material. Another key for the stability is that the conjugated structure endows MC-Azo with desirable thermal properties. This study shows that the design of photopatternable conjugated polymers with thermal-annealing-promoted interchain stacking provides a new strategy for the development of highly stable and secure anti-counterfeiting materials.

The efficacy of targeted therapy combined with radiotherapy and temozolomide-based chemotherapy in the treatment of glioma: A systemic review and meta-analysis of phase II/III randomized controlled trials.

Background: Glioma is the most common intracranial tumor, accounting for about half of the primary intracranial tumors, with the characteristics of hidden onset and high mortality. Even after surgery, radiotherapy and chemotherapy, the prognosis of glioma is not ideal. Targeted therapy has developed rapidly in the treatment of other malignant tumors, which is also an important direction in the research and development of new therapies for glioma. So far, targeting combined with radiotherapy and chemotherapy have been used as the treatment of glioma in many clinical trials, but the role of targeted combined radiotherapy and chemotherapy in the treatment of glioma is still controversial. The purpose of this study was to evaluate the efficacy of targeted therapy combined with radiotherapy and temozolomide (TMZ)-based chemotherapy in the treatment of glioma. Methods: Phase II or phase III clinical trials involving targeted therapy combined with radiotherapy and chemotherapy and temozolomide-based radiotherapy and chemotherapy for gliomas were searched using PubMed, Embase and Web of Science databases, and a comprehensive meta-analysis was conducted. The primary outcome was overall survival time (OS) and progression-free survival time (PFS), and the secondary outcome was adverse reaction. The time-to-event data is summarized as hazard ratio (HR), and the binary results are summarized as odds ratio (OR). Two researchers conducted literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria. Stata16.0 software was used for analysis, random effect model was used for data merging, and forest map was used for display. Results: A total of 11 eligible literatures and 12 prospective randomized controlled clinical trials of 1284 cases were included in the meta-analysis. The results showed that compared with radiotherapy and chemotherapy alone, targeted drugs combined with temozolomide-based radiotherapy and chemotherapy could significantly improve OS in phase II trial, but there was no improvement in Phase III trial, and PFS of newly diagnosed glioma patients was improved (HR=0.82(0.71-0.94) 95%CI, p =0.005). The PFS of the third phase of the experiment also improved. Compared with radiotherapy and chemotherapy alone, there was no statistically significant increase in adverse events in targeted combined radiotherapy and chemotherapy group. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022326012.

Organic‒inorganic semi-interpenetrating networks with orthogonal light- and magnetic-responsiveness for smart photonic gels.

Living matter has the ability to perceive multiple stimuli and respond accordingly. However, the integration of multiple stimuli-responsiveness in artificial materials usually causes mutual interference, which makes artificial materials work improperly. Herein, we design composite gels with organic‒inorganic semi-interpenetrating network structures, which are orthogonally responsive to light and magnetic fields. The composite gels are prepared by the co-assembly of a photoswitchable organogelator (Azo-Ch) and superparamagnetic inorganic nanoparticles (Fe3O4@SiO2). Azo-Ch assembles into an organogel network, which shows photoinduced reversible sol-gel transitions. In gel or sol state, Fe3O4@SiO2 nanoparticles reversibly form photonic nanochains via magnetic control. Light and magnetic fields can orthogonally control the composite gel because Azo-Ch and Fe3O4@SiO2 form a unique semi-interpenetrating network, which allows them to work independently. The orthogonal photo- and magnetic-responsiveness enables the fabrication of smart windows, anti-counterfeiting labels, and reconfigurable materials using the composite gel. Our work presents a method to design orthogonally stimuli-responsive materials.

Circ_0008784 activates Wnt/ß-catenin pathway to affect the proliferation and apoptosis of triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC), as a subtype of breast tumors with aggressive nature, threatens the health of females across the globe. It's urgent to explore novel therapeutic targets for the improvement of TNBC treatments. Bioinformatics was used to identify circular RNA (circRNA) differentially expressed in TNBC tissues. The circular structure and expression in TNBC cells was subjected to analysis of quantitative polymerase chain reaction (qPCR) and PCR-agarose gel electrophoresis. Functional experiments and qPCR assays were carried out to probe the biological functions of circ_0008784 and microRNA-506-3p (miR-506-3p). It was verified by the assays that circ_0008784 propels proliferation and inhibit apoptosis of TNBC cells; and miR-506-3p was found to suppress proliferation and facilitate apoptosis of TNBC cells. TOP/FOP-Flash reporter, luciferase reporter, RNA-binding protein immunoprecipitation (RIP), RNA pulldown and rescue assays were implemented for exploring the underlying mechanisms of circ_0008784. It was found that circ_0008784 regulates Wnt/ß-catenin signaling pathway, and augments TNBC cell progression via sponging miR-506-3p to modulate catenin beta 1 (CTNNB1). Circ_0008784 activates Wnt/ß-catenin pathway to affect the proliferation and apoptosis of TNBC cells. Elucidating the mechanism of circ_0008784 underlying TNBC is of great significance to TNBC treatment.

GeO2-doped ring-core photonic crystal fiber for supporting robust orbital angular momentum modes.

Orbital angular momentum (OAM)-mode-supported photonic crystal fibers (PCFs) have inspired intensive research in modern fiber optics due to the robust propagation and theoretically unlimited signal-carried channels. In this paper, a dual-cladding GeO2-doped ring-core PCF is designed, and a strategy for optimizing OAM mode properties is analyzed by structure parameters and GeO2-doping concentration. Numeric results show that high structural degrees of freedom are available to improve the effective refractive index separation (within the vector modes), chromatic dispersion, effective mode field area, nonlinear coefficient, and OAM mode purity in terms of inner cladding, outer cladding, and ring-core. In particular, the effective refractive index separation and chromatic dispersion can exhibit a high order magnitude of 10-3 and a low value in the broad band from 1.3 µm to 1.7 µm, respectively. In addition to structural optimization, doping high index material into the ring-core is another way to regulate the fiber performance by controlling the doping concentration. A systematic investigation shows that as the doping concentration increases, the effective refractive index separation and mode purity increase obviously, while the dispersion and mode field area gradually decrease. This flexible manipulation offers a method for customizing the optical properties of OAM-supported PCFs in communication and sensor systems.

Bibliometric analysis: Research trends of acupuncture treatment to cognitive impairment in recent 15 years.

Objectives: Acupuncture therapy has been used for cognitive impairment-related diseases, however, there are still few studies on the overall trend of acupuncture therapy on cognitive impairment based on bibliometric analysis. The purpose of this study was to explore the research trend of the impact of acupuncture on cognitive impairment in the past 15 years, analyze the research trends and hotspots, and provide new ideas and theoretical basis for future research directions. Methods: From the Web of Science Core Collection (WoSCC), the relevant literature on the treatment of cognitive impairment with acupuncture from 2007 to 2022 was retrieved. Then, based on the CiteSpace and VOSviewer software of the Java platform, the cooperation between countries and institutions in this field, the co-citation of journals and documents, and the cooperation between authors and authors, etc. were analyzed. In addition, the co-occurrence and burst analysis of keywords are also carried out, and a visual knowledge map is drawn. Results: As of August 08, 2022, a total of 394 records related to the treatment of cognitive impairment with acupuncture were identified. The analysis results show: The number and rate of annual publications have steadily increased, with some fluctuations from year to year. The countries that contribute the most to this field are China and the USA. Among them, Beijing University of Chinese Medicine and Capital Medical University are tied for first place in terms of the number of published papers. Tao Jing is the most prolific author and the number one cited author. Conclusions: The number of publications on acupuncture for cognitive impairment is expected to increase rapidly in future research, suggesting a bright future for the field. Future research hotspots will focus on pain, injury, protocol, diagnosis, guidelines, etc. It is also necessary to strengthen cross-regional and cross-country cooperation among various academic groups.

Melatonin intervention to prevent delirium in hospitalized patients: A meta-analysis.

BACKGROUND: Evaluation of the effectiveness of melatonin is necessary to prevent the development of delirium in hospitalized patients. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland of the brain from the amino acid tryptophan. Synthetic melatonin supplements have been used for various medical conditions, especially sleep-related diseases, and have proved to be successful. AIM: To determine the effect of melatonin on the prevention of delirium in hospitalized patients. METHODS: A literature search of the CNKI, Wanfang Database, VIP Database, China Biomedical Literature Database, PubMed, Embase, Cochrane Library, Web of Science, and other databases was conducted. The CNKI, Wanfang Database, VIP Database (VIP), and China Biomedical Literature Database were searched for Chinese studies, and PubMed, Embase, Cochrane Library, Web of Science and other databases were searched for international studies. It will be established in June 2021 in a randomized controlled trial (RCT) whether melatonin treatment for 6 mo prevents delirium in hospitalized patients. Literature screening, quality review, and data extraction were carried out using the Cochrane Manual 5.1.0 systematic evaluation method, and Stata 15.0 software and Review Manager 5.3 were used for meta-analysis and processing. RESULTS: A total of 18 new RCT articles and 18 experimental subjects were identified. The results of the meta-analysis showed that following the occurrence of delirium, melatonin reduced the incidence of delirium in patients (RR = 0.69, 95%CI: 0.60-0.80), which is of significance, but heterogeneity was significant I 2 = 62%. Subgroup analysis was performed to examine the source of heterogeneity, and it was found that different patient types were the source of heterogeneity; the research on subgroup analysis was of high quality and homogeneous. To determine the reliability and robustness of the research results, a sensitivity analysis was carried out. The results showed that after excluding individual studies one by one, the effect size was still within 95%CI, which strengthened the reliability of the original meta-analysis results. Melatonin has a significant preventive effect on delirium in hospitalized medical patients [RR = 0.60, 95%CI: 0.47-0.76), P < 0.001]. CONCLUSION: Melatonin can reduce the rate of delirium in medical patients, and the role of melatonin in reducing the incidence of delirium in surgical patients and critical care unit patients requires further study.

Association of 'Klotho' gene polymorphism with cerebral infarction.

Background: We aimed to investigate the expression of Klotho gene in peripheral blood of patients with cerebral infarction (CI) and the association of its polymorphisms with the occurrence of CI. Methods: A total of 60 CI patients (CI group) and 20 healthy people receiving physical examination (control group) were enrolled as the research subjects. The expression of Klotho gene in CI group and control group was determined using enzyme-linked immunosorbent assay kit. Single nucleotide polymorphisms (rs192031, rs200131 and rs102312) in the promoter region of the Klotho gene were typed via conformational difference gel electrophoresis. Besides, whether the distribution frequencies of Klotho genotypes conformed to Hardy-Weinberg equilibrium was evaluated by chi-square test. Meanwhile, the associations of Klotho alleles and gene polymorphisms with CI occurrence were analyzed. Results: The protein expression level of Klotho in the peripheral blood was remarkably lower in patients in CI group than that in control group (P<0.05).HardyWeinberg equilibrium analysis revealed that Klotho gene polymorphisms (rs192031, rs200131 and rs102312) conformed to the genetic equilibrium distribution (P>0.05). Gene-based association analysis manifested that only rs192031 polymorphism and alleles were correlated with CI occurrence (P<0.05). Systolic blood pressure and highdensity lipoprotein cholesterol were notably higher in CI patients with TT genotype of Klotho gene polymorphism rs192031 than those in control group (P<0.05). Furthermore, there were no associations of rs200131 and rs102312 polymorphisms and alleles with the occurrence of CI (P>0.05). Conclusions: The expression level of Klotho is evidently reduced in the peripheral blood of CI patients. Rs192031 in the promoter region of the Klotho gene is associated with the occurrence of CI, while rs200131 and rs102312 have no relations with CI.

Fully Convolutional Neural Network Deep Learning Model Fully in Patients with Type 2 Diabetes Complicated with Peripheral Neuropathy by High-Frequency Ultrasound Image.

This study was aimed at exploring the diagnostic value of high-frequency ultrasound imaging based on a fully convolutional neural network (FCN) for peripheral neuropathy in patients with type 2 diabetes (T2D). A total of 70 patients with T2D mellitus were selected and divided into a lesion group (n = 31) and a nonlesion group (n = 39) according to the type of peripheral neuropathy. In addition, 30 healthy people were used as controls. Hypervoxel-based and FCN-based high-frequency ultrasound images were used to examine the three groups of patients to evaluate their diagnostic performance and to compare the changes of peripheral nerves and ultrasound characteristics. The results showed that the Dice coefficient (92.7) and mean intersection over union (mIOU) (82.6) of the proposed algorithm after image segmentation were the largest, and the Hausdorff distance (7.6) and absolute volume difference (AVD) (8.9) were the smallest. The high-frequency ultrasound based on the segmentation algorithm showed higher diagnostic accuracy (94.0% vs. 86.0%), sensitivity (87.1% vs. 67.7%), specificity (97.1% vs. 94.2%), positive predictive value (93.1% vs. 86.7%), and negative predictive value (94.4% vs. 84.0%) (P < 0.05). There were significant differences in the detection values of the three major nerve segments of the upper limbs in the control group, the lesion group, and the nonlesion group (P < 0.05). Compared with the nonlesion group, the patients in the lesion group were more likely to have reduced nerve bundle echo, blurred reticular structure, thickened epineurium, and unclear borders of adjacent tissues (P < 0.05). In summary, the high-frequency ultrasound processed by the algorithm proposed in this study showed a high diagnostic value for peripheral neuropathy in T2D patients, and high-frequency ultrasound can be used to evaluate the morphological changes of peripheral nerves in T2D patients.

Bioresource-derived tannic acid-supported immuno-network in lateral flow immunoassay for sensitive clenbuterol monitoring.

Although lateral flow immunoassay (LFIA) as a point-of-care (POC) diagnostic tool has been widely used because of numerous merits, it remains challenging to realize higher sensitivity, easier labeling, and fewer antibodies consumption. Herein, a bioresource-derived tannic acid (TA)-supported immuno-network based LFIA for clenbuterol (CLE) monitoring was proposed by employing poly TA nanospheres (PTAN) as the new tracer. Attributing to the effective protein-enrichment ability of TA, plenty of goat anti-mouse immunoglobulins (GAMI) were first absorbed on the surface of PTAN and then monoclonal antibodies (AbCLE) were added to form immuno-network. Compared with directly coupling antibodies, the utilization efficiency of AbCLE was significantly improved. Thus, the detection sensitivity (take the cut-off value as an example) was enhanced 5-fold and 10-fold at least compared with PTAN-AbCLE and colloidal gold-based LFIA, respectively. Additionally, the proposed method was successfully verified in beef and pork liver and provided an effective strategy for food safety monitoring.

IL-39 increases ROS production and promotes the phosphorylation of p38 MAPK in the apoptotic cardiomyocytes.

INTRODUCTION: The cytokine interleukin (IL)-39 is a novel member of the IL-12 family. Our previous study found that the serum level of IL-39 significantly increased in patients with acute myocardial infarction. However, the role of IL-39 in cardiomyocyte apoptosis remains unclear. MATERIAL AND METHODS: In this study, the cultured mouse HL-1 cardiomyocytes were incubated with PBS, 0-100 ng/mL IL-39, 200 µM H2O2 or 20 µM Trolox. RESULTS: IL-39 promoted the production of intracellular reactive oxygen species (ROS) in a concentration dependent manner in HL-1 cardiomyocytes. IL-39 and H2O2 both significantly promoted the production of intracellular ROS, increased the level of intracellular CCL2, stimulated the apoptotic progress of cardiomyocytes, increased the mRNA and protein expression levels of Bax, caspase-3, and p-p38 MAPK, and decreased the mRNA and protein expression levels of Bcl-2. ROS production, CCL2 level, cardiomyocyte apoptosis, and expression of Bax, caspase-3, and p-p38 MAPK were significantly amplified by the administration of IL-39 combined with H2O2, and these processes were significantly alleviated by an antioxidant Trolox. CONCLUSION: This study was novel in revealing that IL-39 promoted apoptosis by stimulating the phosphorylation of p38 MAPK in mouse HL-1 cardiomyocytes.

Prognostic value of initial chest CT findings for clinical outcomes in patients with COVID-19.

Rationale: To identify whether the initial chest computed tomography (CT) findings of patients with coronavirus disease 2019 (COVID-19) are helpful for predicting the clinical outcome. Methods: A total of 224 patients with laboratory-confirmed COVID-19 who underwent chest CT examination within the first day of admission were enrolled. CT findings, including the pattern and distribution of opacities, the number of lung lobes involved and the chest CT scores of lung involvement, were assessed. Independent predictors of adverse clinical outcomes were determined by multivariate regression analysis. Adverse outcome were defined as the need for mechanical ventilation or death. Results: Of 224 patients, 74 (33%) had adverse outcomes and 150 (67%) had good outcomes. There were higher frequencies of more than four lung zones involved (73% vs 32%), both central and peripheral distribution (57% vs 42%), consolidation (27% vs 17%), and air bronchogram (24% vs 13%) and higher initial chest CT scores (8.6±3.4 vs 5.4±2.1) (P < 0.05 for all) in the patients with poor outcomes. Multivariate analysis demonstrated that more than four lung zones (odds ratio [OR] 3.93; 95% confidence interval [CI]: 1.44 to 12.89), age above 65 (OR 3.65; 95% CI: 1.11 to 10.59), the presence of comorbidity (OR 5.21; 95% CI: 1.64 to 19.22) and dyspnea on admission (OR 3.19; 95% CI: 1.35 to 8.46) were independent predictors of poor outcome. Conclusions: Involvement of more than four lung zones and a higher CT score on the initial chest CT were significantly associated with adverse clinical outcome. Initial chest CT findings may be helpful for predicting clinical outcome in patients with COVID-19.