Subarachnoid hemorrhage misdiagnosed as acute coronary syndrome leading to catastrophic neurologic injury: A case report.

BACKGROUND: Elevated levels of cardiac troponin and abnormal electrocardiogram changes are the primary basis for clinical diagnosis of acute coronary syndrome (ACS). Troponin levels in ACS patients can often be more than 50 times the upper reference limit. Some patients with subarachnoid hemorrhage (SAH) also show electrocardiogram abnormalities, myocardial damage, and elevated cardiac biomarkers. Unlike ACS patients, patients with SAH only have a slight increase in troponin, and the use of anticoagulants or antiplatelet drugs is prohibited. Because of the opposite treatment modalities, it is essential for clinicians to distinguish between SAH and ACS. CASE SUMMARY: A 56-year-old female patient was admitted to the emergency department at night with a sudden onset of severe back pain. The final diagnosis was intraspinal hematoma in the thoracic spine. We performed an emergency thoracic spinal canal hematoma evacuation procedure with the assistance of a microscope. Intraoperatively, diffuse hematoma formation was found in the T7-T10 spinal canal, and no obvious spinal vascular malformation changes were observed. Postoperative head and spinal magnetic resonance imaging (MRI) showed a small amount of SAH in the skull, no obvious abnormalities in the cervical and thoracic spinal canals, and no abnormal signals in the lumbar spinal canal. Thoracoabdominal aorta computed tomography angiography showed no vascular malformation. Postoperative motor system examination showed Medical Research Council Scale grade 1/5 strength in both lower extremities, and the patient experienced decreased sensation below the T12 rib margin and reported a Visual Analog Scale score of 3. CONCLUSION: Extremely elevated troponin levels (more than 50 times the normal range) are not unique to coronary artery disease. SAH can also result in extremely high troponin levels, and antiplatelet drugs are contraindicated in such cases. Emergency MRI can help in the early differential diagnosis, as a misdiagnosis of ACS can lead to catastrophic neurological damage in patients with spontaneous spinal SAH.

A Comparative Study on Microstructure, Segregation, and Mechanical Properties of Al-Si-Mg Alloy Parts Processed by GISS-HPDC and SEED-HPDC.

There are multiple routes to prepare semi-solid slurries with a globular microstructure for semi-solid forming. The variations in the microstructure of semi-solid slurries prepared using different routes may lead to significant differences in the flow behavior and mechanical properties of rheo-diecasting parts. Therefore, it is crucial to have a comprehensive understanding of the microstructure evolution associated with different slurry preparation routes and their resulting effects. In this study, the gas-induced semi-solid process (GISS) and the swirl enthalpy equilibrium device (SEED) routes were employed to prepare semi-solid Al-Si-Mg slurries for their simplicity and productivity in potential industrial applications. The prepared slurries were then injected into the shoot sleeves of a high-pressure die casting (HPDC) machine to produce tensile test bars. Subsequently, the bars underwent T6 treatment to enhance their mechanical properties. The microstructure, segregation, and mechanical properties of the samples were investigated and compared with those of conventional HPDC. The results indicated that the GISS and SEED can produce semi-solid slurries containing a spherical α-Al primary phase, as opposed to the dendritic structure commonly found in conventional castings. The liquid fraction had a significant effect on the flow behavior, resulting in variations in liquid segregation and mechanical properties. It was observed that a higher solid fraction (>75%) had a suppressing effect on surface liquid segregation. In addition, the tendency for liquid segregation gradually increased along the filling direction due to the special flow behavior of the semi-solid slurry with a low solid fraction. Furthermore, under the same die-casting process parameters, the conventional HPDC samples exhibit higher yield stress (139 ± 3 MPa) compared to SEED-HPDC and GISS-HPDC samples, which may be attributed to the small grain size and the distribution of eutectic phases. After undergoing the T6 treatment, both SEED-HPDC and GISS-HPDC samples showed a significant improvement in yield and tensile strength. These improvements are a result of solution and precipitation strengthening effects as well as the spheroidization of the eutectic Si phase. Moreover, the heat-treated SEED-HPDC samples demonstrate higher ultimate strength (336 ± 5 MPa) and elongation (13.7 ± 0.3%) in comparison to the GISS-HPDC samples (307 ± 4 MPa, 8.8 ± 0.2%) after heat treatment, mainly due to their low porosity density. These findings suggest that both GISS-HPDC and SEED-HPDC processes can be utilized to produce parts with favorable mechanical properties by implementing appropriate heat treatments. However, further investigation is required to control the porosities of GISS-HPDC samples during heat treatment.

Use of metagenomic next-generation sequencing in diagnosing lung abscesses caused by oral bacteria.

Lung abscesses are one of the most common lower respiratory tract infections worldwide and can seriously endanger life. However, pathogens associated with lung abscesses still cannot be detected quickly and accurately with the current microbial detection technology. Here, the case of a 53-year-old male with a lung abscess caused by oral bacteria is reported. After metagenomic next-generation sequencing was applied to identify the pathogenic microorganism, the patient recovered with precision medicine. Metagenomic next-generation sequencing is an important tool for the clinical diagnosis of infectious diseases caused by microorganisms and in guiding precision medicine.

Insufficient Dose of ERCC8 Protein Caused by a Frameshift Mutation Is Associated With Keratoconus With Congenital Cataracts.

Purpose: The purpose of this study was to identify a new candidate gene for keratoconus and congenital cataracts and further investigate its underlying pathogenic mechanisms. Methods: This study, using a Chinese family with keratoconus and congenital cataracts, 262 patients with sporadic keratoconus, and 20 patients with sporadic congenital cataract as subjects, used clinical and genetic analysis and in vitro cell experiments to detect genetic mutations and further investigate the underlying pathogenic mechanisms. Results: We found that a novel frameshift mutation of ERCC8 (NM_000082.3: c.394-398del, p. L132Nfs*6) is responsible for familial keratoconus with congenital cataracts. This mutation showed co-segregation with the phenotype in the family. This was revealed in another patient with sporadic keratoconus, absent in the 210 unrelated health controls, and considered to be "disease-causing." ERCC8 was expressed both in the cornea and lens. Through an in vitro cell experiment, we further demonstrated that the mutant proteins of ERCC8 were degraded and could lead to an insufficient dose of the ERCC8 protein. An insufficient dose reduced the DNA damage repair ability of human corneal fibroblast (HTK) and lens epithelial cells (HLEC) treated with hydrogen peroxide, leading to both cells showing higher DNA damage levels. In addition, it decreased cell viability, resulting in decreased collagen expression in HTK and increased apoptosis in HLEC via aberrant activation of the unfolded protein response. All these results suggested that ERCC8 plays an important role in the normal function of corneal stromal and lens epithelial cells. Conclusions: Our study showed that ERCC8 is a new gene associated with keratoconus and congenital cataracts.Chinese Abstract.

[Anti-oxidative and anti-apoptotic effects and molecular mechanisms of catalpol against H_2O_2-induced oxidative damage in pancreatic ß cells (INS-1 cells)].

The present study investigated the anti-oxidative and anti-apoptotic effects and molecular mechanisms of catalpol on the H_2O_2-induced pancreatic ß-cells(INS-1 cells).The oxidative damage model of INS-1 cells was induced and optimized by the stimulation of H_2O_2 of different concentrations for different time.CCK-8 assay was used to detect cell viability after catalpol intervention(1, 5, 10, 20, 40, 80, and 160 µmol·L~(-1)) for 24 h.Intracellular reactive oxygen species(ROS), superoxide dismutase(SOD), and lipid peroxide malondialdehyde(MDA) were measured by DCFH-DA fluorescent probe, WST-1, and TBA respectively.Moreover, the apo-ptotic effect was detected by AO-EB and Annexin V-FITC/PI staining.In addition, the protein expression levels were detected by Wes-tern blot, and intracellular insulin concentration was measured by ELISA.The results showed that the oxidative damage model of INS-1 cells was stably induced by 50 µmol·L~(-1) H_2O_2 treatment for 2 h, and catalpol at 1-80 µmol·L~(-1) did not affect cell viability of INS-1 cells.Compared with the conditions in the model group, 1, 5, and 10 µmol·L~(-1) catalpol intervention for 2 h could protect INS-1 cells from oxidative damage(P<0.001), reduce ROS and MDA, increase SOD, and inhibit excessive cell apoptosis.Moreover, 1, 5, and 10 µmol·L~(-1) catalpol could also up-regulate the phosphorylation of nuclear transcription factor NF-E2 related factors, negatively regulate Kelch-like ECH-associated protein 1(Keap1), phosphorylation of extracellular signal-regulated kinase(ERK), and heme oxyge-nase 1(HO-1), and promote the protein expression of pancreatic-duodenal homeobox factor-1(PDX-1) and glucose transporter 2(GLUT2).In addition, 1, 5, and 10 µmol·L~(-1) catalpol increased insulin secretion of INS-1 cells under oxidative damage in the high-glucose culture medium, indicating function recovery of pancreatic ß cells.PDX-1 is a key nuclear transcription factor of pancreatic ß cell function that directly regulates GLUT2 and insulin synthesis, and affects glucose homeostasis.In conclusion, catalpol can reduce the oxidative damage and apoptosis of INS-1 cells, activate antioxidant pathway, protect the function of pancreatic ß cells, and improve insulin synthesis and secretion.

Does Waldenstrom's macroglobulinemia also cause bone destruction? A rare case report.

Waldenstrom's macroglobulinemia (WM) is a rare type of malignant B-cell lymphoma. The main feature of WM is elevated serum monoclonal immunoglobulin M, similar to multiple myeloma (MM). Unlike in MM, the rarity of destructive bone lesions in WM has been repeatedly emphasized. We report a unique case of WM with a vertebral compression fracture as the first symptom. This case highlights that the presence or absence of bone destruction may not clearly distinguish between WM and MM. The possibility of WM should be considered in patients with vertebral fracture and destruction as the first presentation. Performing vertebral bone marrow aspiration biopsy during percutaneous vertebroplasty is a convenient and effective method to assist in the diagnosis of WM.

Cost-Effective Fabrication of Micro-Nanostructured Superhydrophobic Polyethylene/Graphene Foam with Self-Floating, Optical Trapping, Acid-/Alkali Resistance for Efficient Photothermal Deicing and Interfacial Evaporation.

Solar evaporation is one of the most attractive and sustainable approaches to address worldwide freshwater scarcity. Unfortunately, it is still a crucial challenge that needs to be confronted when the solar evaporator faces harsh application environments. Herein, a promising polymer molding method that combines melt blending and compression molding, namely micro extrusion compression molding, is proposed for the cost-effective fabrication of lightweight polyethylene/graphene nanosheets (PE/GNs) foam with interconnected vapor escape channels and surface micro-nanostructures. A contact angle of 155 ± 2°, a rolling angle of 5 ± 1° and reflectance of ≈1.6% in the wavelength range of 300-2500 nm appears on the micro-nanostructured PE/GNs foam surface. More interestingly, the micro-nanostructured PE/GNs foam surface can maintain a robust superhydrophobic state under dynamic impacting, high temperature and acid-/alkali solutions. These results mean that the micro-nanostructured PE/GNs foam surface possesses self-cleaning, anti-icing and photothermal deicing properties at the same time. Importantly, the foam exhibits an evaporation rate of 1.83 kg m-2 h-1 under 1 Sun illumination and excellent salt rejecting performance when it is used as a self-floating solar evaporator. The proposed method provides an ideal and industrialized approach for the mass production of solar evaporators suitable for practical application environments.

Real-time parametric estimation of periodic wake-foil interactions using bioinspired pressure sensing and machine learning.

Periodic wake-foil interactions occur in the collective swimming of bio-inspired robots. Wake interaction pattern estimation (and control) is crucial to thrust enhancement and propulsive efficiency optimization. In this paper, we study the wake interaction pattern estimation of two flapping foils in tandem configurations. The experiments are conducted at a Reynolds number of 1.41 × 104in a water channel. A modified wake-foil phase parameter Φ, which unifies the influences of inter-foil distanceLx, motion phase difference Δφand wake convection velocityUv, is introduced to describe the wake interaction patterns parametrically. We use a differential pressure sensor on the downstream foil to capture wake interaction characteristics. Data sets at different tandem configurations are collected. The wake-foil phase Φ is used to label the pressure signals. A one-dimensional convolutional neural networks (1D-CNN) model is used to learn an end-to-end mapping between the raw pressure measurements and the wake-foil phase Φ. The trained 1D-CNN model shows accurate estimations (average error 3.5%) on random wake interaction patterns and is fast enough (within 40 ms). Then the trained 1D-CNN model is applied to online thrust enhancement control of a downstream foil swimming in a periodic wake. Synchronous force monitoring and flow visualization demonstrate the effectiveness of the 1D-CNN model. The limitations of the model are discussed. The proposed approach can be applied to the online estimation and control of wake interactions in the collective swimming and flying of biomimetic robots.

A case of giant Ewing's sarcoma (EES)/primitive neuroectodermal tumor (PNET) of the cervicothoracic junction in children with incomplete paralysis of both lower limbs: Case report and literature review.

Background: Extraosseous Ewing's sarcoma/primary neuroectodermal tumor (EES/PNET) is a rare, malignant, small round blue cell tumor, which usually involves the larynx, kidneys, and esophagus. The most common metastatic sites are lung and bone. The incidence of epidural EES/PNET was 0.9%, and a detailed search of the PubMed literature found only 7 case reports of epidural ESS/PNET at the cervicothoracic junction in children. Case description: We report a case of epidural ESS/PNET at the cervicothoracic junction in a child with chest and back pain as the first symptom, which worsened after half a year and developed incomplete paralysis of both lower extremities and urinary incontinence. She underwent emergency surgery, chemotherapy and radiotherapy, and died of lung metastases 8 months after surgery. Conclusion: Primary epidural tumors are mostly benign, such as spinal meningiomas and neuromas. Contrary to what has been previously thought, we report a case of malignant epidural EES/PNET at the cervicothoracic junction without bone destruction; The rarity of epidural EES/PNET at the cervicothoracic junction in children has led to a lack of data, particularly on prognostic factors and recurrence patterns. Due to the difficulty of early diagnosis and high mortality, spine surgeons must explore and increase their awareness of this disease.

Role and mechanism of intraflagellar transport in mammalian spermiogenesis.

Eukaryotic cilia and flagella are evolutionarily conserved organelles that protrude from the cell surface. The unique location and properties of cilia allow them to function in vital processes such as motility and signaling. Ciliary assembly and maintenance rely on intraflagellar transport (IFT). Bidirectional movement of IFT particles composed of IFT-A and IFT-B complexes is powered by kinesin-2 and dynein-2 motors. IFT delivers building blocks between their site of synthesis in the cell body and the ciliary assembly site at the tip of the cilium. The integrity of the flagellum, a specialized organelle of mammalian sperm to generate the motility, is critical for normal sperm function. Recent findings suggest that IFT is indispensable for sperm flagellum formation and male fertility in mice and human. In this review, we summarize the role and mechanisms of IFT proteins during enflagellation in spermiogenesis, thereby discussing the pathological mechanisms of male infertility and providing theoretical basis for the diagnosis and treatment of male infertility.

The membrane-associated E3 ubiquitin ligase MARCH3 downregulates the IL-6 receptor and suppresses colitis-associated carcinogenesis.

The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis (IAC). How this axis is regulated to modulate IAC remains unknown. Here, we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6, as well as another IL-6 subfamily member, Oncostatin M (OSM). MARCH3 is associated with the IL-6 receptor α-chain (IL-6Rα) and its coreceptor gp130. Biochemical experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rα at K401 and gp130 at K849 following IL-6 stimulation, leading to their translocation to and degradation in lysosomes. MARCH3 deficiency increases IL-6- and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell types. MARCH3 deficiency enhances dextran sulfate sodium (DSS)-induced STAT3 activation, increases the expression of inflammatory cytokines, and exacerbates colitis, as well as azoxymethane (AOM)/DSS-induced colitis-associated cancer in mice. In addition, MARCH3 is downregulated in human colorectal cancer tissues and associated with poor survival across different cancer types. Our findings suggest that MARCH3 is a pivotal negative regulator of IL-6-induced STAT3 activation, inflammation, and inflammation-associated carcinogenesis.

Synthesis of Aporphine Analogues via Palladium-Catalyzed Intramolecular Aryl-Aryl Dehydrogenative Coupling.

Reported herein is an intramolecular dehydrogenative coupling of two inert aryl C-H bonds for the synthesis of aporphine analogues. The process represents a novel tool for the preparation of aporphines via palladiun-catalyzed C-H bond activation. The present reaction is compatible with various functional groups, and the coupling products have been further applied for the synthesis of natural products aporphine and zenkerine.

[Molecular mechanism of Gegen Qinlian Decoction in promoting differentiation of brown adipose tissue to improve glucose and lipid metabolism disorders in diabetic rats].

This study explored the molecular mechanism underlying the Gegen Qinlian Decoction(GQD) promoting the differentiation of brown adipose tissue(BAT) to improve glucose and lipid metabolism disorders in diabetic rats. After the hypoglycemic effect of GQD on diabetic rats induced by high-fat diet combined with a low dose of streptozotocin was confirmed, the total RNA of rat BAT around scapula was extracted. Nuclear transcription genes Prdm16, Pparγc1α, Pparα, Pparγ and Sirt1, BAT marker genes Ucp1, Cidea and Dio2, energy expenditure gene Ampkα2 as well as BAT secretion factors Adpn, Fndc5, Angptl8, IL-6 and Rbp4 were detected by qPCR, then were analyzed by IPA software. Afterward, the total protein from rat BAT was extracted, and PRDM16, PGC1α, PPARγ, PPARα, SIRT1, ChREBP, AMPKα, UCP1, ADPN, NRG4, GLUT1 and GLUT4 were detected by Western blot. The mRNA expression levels of Pparγc1α, Pparα, Pparγ, Ucp1, Cidea, Ampkα2, Dio2, Fndc5, Rbp4 and Angptl8 were significantly increased(P<0.05) and those of Adpn and IL-6 were significantly decreased(P<0.05) in the GQD group compared with the diabetic group. In addition, Sirt1 showed a downward trend(P=0.104), whereas Prdm16 tended to be up-regulated(P=0.182) in the GQD group. IPA canonical pathway analysis and diseases-and-functions analysis suggested that GQD activated PPARα/RXRα and SIRT1 signaling pathways to promote the differentiation of BAT and reduce the excessive lipid accumulation. Moreover, the protein expression levels of PRDM16, PGC1α, PPARα, PPARγ, SIRT1, ChREBP, AMPKα, UCP1, GLUT1, GLUT4 and NRG4 were significantly decreased in the diabetic group(P<0.01), which were elevated after GQD intervention(P<0.05). Unexpectedly, the expression of ADPN protein in the diabetic group was up-regulated(P<0.01) as compared with the control group, which was down-regulated after the administration with GQD(P<0.01). This study indicated that GQD promoted BAT differentiation and maturity to increase energy consumption, which reduced the glucose and lipid metabolism disorders and thereby improved diabetes symptoms.

Tunable fabrication of biomimetic polypropylene nanopillars with robust superhydrophobicity and antireflectivity.

The fine nanopillars on the natural cicada wing, which exhibits outstanding superhydrophobicity and anti-reflectivity, are carefully observed and analyzed. Here, a promising strategy by combining anodic aluminum oxide template and hot embossing is proposed for rapidly and efficiently mimicking the orderly and densely arranged nanopillars on the cicada wing surface to polypropylene (PP) surfaces. By adjusting the compression pressure, the nanostructures on the PP replica surface gradually evolve from nanoprotrusion-like features to nanopillar-like features so that a gradient wetting behavior from hydrophilicity to hydrophobicity and further to superhydrophobicity appears on the PP replica surfaces. Specifically, the biomimetic PP replica surface exhibits a contact angle of 159 ± 3° and a rolling angle of 8 ± 3° at a compression pressure of 15 MPa. Moreover, the biomimetic PP replica surface can stabilize its superhydrophobic state under a 1.96 kPa external pressure during the dynamic droplet impact. Besides robust dynamic superhydrophobicity, the biomimetic PP replica surface also demonstrated excellent anti-reflectivity because of the gradually changed effective refractive index. Therefore, the biomimetic PP replica inherits both the superhydrophobicity and anti-reflectivity of the natural cicada wing, which makes the products can effectively reduce the external damage when applied to agricultural films, dustproof films, and packaging materials.

Ultrafast Fabrication of Graphene-Reinforced Nanocomposites via Synergy of Steam Explosion and Alternating Convergent-Divergent Flow.

Producing high-quality graphene and polymer/graphene nanocomposite is facing the problems of complex procedure, low efficiency, and serious resource waste. To explore a new fabrication approach with high efficiency and low cost is crucial for solving these technical issues, which becomes a current research hotspot and also a great challenge. Herein, a one-step melt mixing strategy based on the synergy of steam explosion and alternating convergent-divergent flow, is innovatively developed to fabricate high-density polyethylene (HDPE)/graphene nanocomposites using industrial-grade expanded graphite (EG) without chemical agents and complex procedures. The co-action of the external force derived from elongational melts and the internal force generated by steam explosion make EG ultrafastly exfoliate into few-layer graphene nanosheets (GNS) and simultaneously disperse in melts within 4 min. The as-produced GNS have a lateral size of over 5 µm and a minimum thickness of 1.4 nm, can introduce super heterogeneous nucleation to HDPE macromolecules and greatly increases nanocomposite crystallinity up to 86.5%. Moreover, plentiful HDPE crystallites and well-dispersed GNS jointly form an improved thermally-conductive network, making nanocomposites with a rapid-respond ability in solar-to-thermal conversion and heat dissipation. This facile strategy will facilitate the development of scalable production and wide application of high-performance graphene and highly-filled nanocomposites.

Study on the action mechanism of Wuling Powder on treating osteoporosis based on network pharmacology.

Osteoporosis is a health problem to cause global concern. A lot of methods have been used to prevent and treat osteoporosis, but there is still a lack of effective treatment for osteoporosis owing to limited understanding of its mechanism. Therefore, the aim of this present study is to explore the underlying mechanism of Wuling Powder, a traditional Chinese medicine on treating osteoporosis. In this study, we firstly screened and identified the common targets between Wuling Powder and osteoporosis through the related databases, and then explored the relationships among these targets, Wuling Powder and osteoporosis by using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and network analyses. Subsequently, the molecular docking was performed by using systemsDock to evaluate the potential binding relationships between the active components of Wuling Powder and their related targets. The results showed that in total of 14 common targets including CREBBP, ADAM17, GOT1, GAPDH, USP8, ERBB2, EEF1A1, MTOR, RAC1, ETS1, DDX58, GCK, EGF and S100A8 were screened. EGF, ERBB2, MTOR and HIF-1 were the potential therapeutic targets for osteoporosis, and they were also the related targets for predicting active components in Wuling Powder. Taken together, we concluded that Wuling Powder might be used to treat osteoporosis through above these targets.

Efficient and economical approach for flexible photothermal icephobic copper mesh with robust superhydrophobicity and active deicing property.

Facing various problems caused by icing in daily life, preparing photothermal deicing materials with wide applicability in high efficiency and low cost is not only a current research hotspot but also a great challenge. Herein, an economical spray-coating method is applied to prepare high-efficiency flexible photothermal icephobic copper mesh using micro silicon carbide (SiC) particles as photothermal conversion material and nano silica (SiO2) particles as a surface superhydrophobic modifier. Owing to the excellent hierarchical micro-nanostructures, the SiC/SiO2 coated copper mesh exhibits a water contact angle (CA) of 162 ± 2° and a sliding angle (SA) of 3 ± 2°. Interestingly, the coated copper mesh exhibits exceptional mechanical durability against water droplet and water flow impact, repeated bending-twisting and tape-peeling. Benefitting from the robust superhydrophobicity, the SiC/SiO2 coating on the copper mesh can significantly delay the freezing time of the droplets and reduce the ice adhesion strength. Furthermore, the coated copper mesh well retains the good photothermal conversion and thermal conductivity properties of the micro SiC particles. Under NIR irradiation, the surface temperature of the coated copper mesh placed on the ice layer can increase by 35.3 °C in 220 s, so that it can rapidly melt the accumulated frost and ice layer on the inner wall of the refrigerator. The presented flexible photothermal icephobic copper mesh exhibits enormous potential when applied to remove ice from apparatus that is accessible, such as road, overhead transmission lines and power networks owing to its flexibility, economy, and high energy efficiency.

Systematically Displaying the Pathogenesis of Keratoconus via Multi-Level Related Gene Enrichment-Based Review.

Keratoconus (KC) is an etiologically heterogeneous corneal ectatic disorder. To systematically display the pathogenesis of keratoconus (KC), this study reviewed all the reported genes involved in KC, and performed an enrichment analysis of genes identified at the genome, transcription, and protein levels respectively. Combined analysis of multi-level results revealed their shared genes, gene ontology (GO), and pathway terms, to explore the possible pathogenesis of KC. After an initial search, 80 candidate genes, 2,933 transcriptional differential genes, and 947 differential proteins were collected. The candidate genes were significantly enriched in extracellular matrix (ECM) related terms, Wnt signaling pathway and cytokine activities. The enriched GO/pathway terms of transcription and protein levels highlight the importance of ECM, cell adhesion, and inflammatory once again. Combined analysis of multi-levels identified 13 genes, 43 GOs, and 12 pathways. The pathogenic relationships among these overlapping factors maybe as follows. The gene mutations/variants caused insufficient protein dosage or abnormal function, together with environmental stimulation, leading to the related functions and pathways changes in the corneal cells. These included response to the glucocorticoid and reactive oxygen species; regulation of various signaling (P13K-AKT, MAPK and NF-kappaB), apoptosis and aging; upregulation of cytokines and collagen-related enzymes; and downregulation of collagen and other ECM-related proteins. These undoubtedly lead to a reduction of extracellular components and induction of cell apoptosis, resulting in the loosening and thinning of corneal tissue structure. This study, in addition to providing information about the genes involved, also provides an integrated insight into the gene-based etiology and pathogenesis of KC.

Gordian Knot: Gastrointestinal lesions caused by three highly pathogenic coronaviruses from SARS-CoV and MERS-CoV to SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of 2019 novel coronavirus disease (COVID-19), is currently spreading around the world. The WHO declared on January 31 that the outbreak of SARS-CoV-2 was a public health emergency. SARS-Cov-2 is a member of highly pathogenic coronavirus group that also consists of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Although respiratory tract lesions were regarded as main manifestation of SARS-Cov-2 infection, gastrointestinal lesions were also reported. Similarly, patients with SARS-CoV and MERS-CoV were also observed. Common gastrointestinal symptoms of patients mainly included diarrhea, vomiting and abdominal pain. Gastrointestinal lesions could be used as basis for early diagnosis of patients, and at the same time, controlling gastrointestinal lesions better facilitated to cut off the route of fecal-oral transmission. Hence, this review summarizes the characteristics and mechanism of gastrointestinal lesions caused by three highly pathogenic human coronavirus infections including SARS-CoV, MERS-CoV, as well as SARS-CoV-2. Furthermore, it is expected to gain experience from gastrointestinal lesions caused by SARS-CoV and MERS-CoV infections in order to be able to better relieve SARS-CoV-2 epidemic. Targetin gut microbiota to regulate the process of SARS-CoV-2 infection should be a concern. Especially, the application of nanotechnology may provide help for further controlling COVID-19.

Liquid biopsy in head and neck squamous cell carcinoma: circulating tumor cells, circulating tumor DNA, and exosomes.

Introduction: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. Due to a lack of reliable markers, HNSCC patients are usually diagnosed at a late stage, which will lead to a worse outcome. Therefore, it is critical to improve the clinical management of cancer patients. Nowadays, the development of liquid biopsy enables a minimally invasive manner to extract molecular information from HNSCCs. Thus, this review aims to outline the clinical value of liquid biopsy in early detection, real-time monitoring, and prognostic evaluation of HNSCC. Areas covered: This comprehensive review focused on the characteristics as well as clinical applications of three liquid biopsy markers (CTCs, ctDNA, and exosomes) in HNSCC. What is more, it is promising to incorporate machine learning and 3D organoid models in the liquid biopsy of HNSCC. Expert opinion: Liquid biopsy provides a noninvasive technique to reflect the inter and intra-lesional heterogeneity through the detection of tumor cells or materials released from the primary and secondary tumors. Recently, some evolving technologies have the potential to combine with liquid biopsy to improve clinical management of HNSCC patients.