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In this paper, a sensitive biomimetic enzyme-linked immunoassay (BELISA) method based on an Au@Pt@Au composite nanozyme label was developed for histamine (HA) detection. A molecular imprinted polymer prepared directly on the 96-well plate served as a biomimetic antibody. A BELISA method was developed for HA standard solutions at concentrations ranging from 0.01 to 100.00 mg/L. Under optimal conditions, the novel BELISA method had a low limit of detection (0.069 mg/L) and high sensitivity (7.20 mg/L). The HA spiked in yellow rice wine and liqueur samples were detected by this BELISA method with the recoveries ranging from 84.28% to 108.82%. There was no significant difference of the results between the BELISA method and HPLC for the detection of HA in the red and white grape wine samples.

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

It is well known that the difficulty of siRNA therapeutic application is the lack of safe and effective delivery vector. Virosome is a nano vesicle composed of lipid membrane and membrane protein. It retains fusion protein without virus genetic material, and therefore has the reduced immunogenicity compared with viral vector. Virosomes have the potential to deliver protein and nucleic acid drugs, but the traditional preparation method of virosomes is quite limited. In this study, we firstly proposed to synthesize influenza virus hemagglutinin HA2 virosomes by cell-free protein synthesis. In this study, liposomes provided the hydrophobic lipid bilayer environment for the formation of HA2 protein multimer, which inhibited the aggregation of hydrophobic HA2 and improved HA2 protein expression. Chitosan as a rigid core adsorbed siRNA and improved the encapsulation efficiency of siRNA. In conclusion, the cell-free protein synthesis was used to prepare HA2 virosomes, which paves the way for constructing a novel nano vector with high delivery efficiency and biosafety for the delivery of siRNA.

PurposeAtrial fibrillation (AF) is a common atrial arrhythmia. Quercetin (Que) has some advantages in the treatment of cardiovascular disease arrhythmias, but its specific drug mechanism of action needs further investigation. To explore the mechanism of action of Que in AF, core target speculation and analysis were performed using network pharmacology and molecular docking methods.MethodsQue chemical structures were obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank , STITCH, Binding DB, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF from normal tissues by GEO database differentially expressed genes. Then, the intersecting genes were obtained by online Wayne mapping tool. The intersection genes were introduced into the top five targets selected for molecular docking via protein-protein interaction (PPI) network to verify the binding activity between Que and the target proteins. GO and KEGG enrichment analysis of the intersected genes using program R was performed to further screen for key genes and key pathways.ResultsThere were 65 effective targets for Que and AF. Through further screening, the top 5 targets were IL6, VEGFA, JUN, MMP9 and EGFR. Que treatment of AF may involve signaling pathways such as lipid and atherosclerosis pathway, AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking suggests that Que has strong binding to key targets.ConclusionThis study systematically elucidates the key targets of Que treatment for AF and the specific mechanisms through network pharmacology as well as molecular docking, providing a new direction for further basic experimental exploration and clinical treatment.

Background Local recurrence is the main cause of death among patients with oral squamous cell carcinoma (OSCC). This study assessed near-infrared fluorescence (NIF) imaging and spectroscopy to monitor surgical margins intraoperatively for OSCC. Methods Cytological and animal experiments were first performed to confirm the feasibility of monitoring surgical margins with NIF imaging and spectroscopy. Then, 20 patients with OSCC were included in the clinical trials. At 6–8 h after 0.75 mg/kg indocyanine green (ICG) injection, all patients underwent surgery with NIF imaging. During the surgery, both NIF images and quantified fluorescence intensity were acquired to monitor the surgical margins. Results In cytological and animal experiments, the results showed it was feasible to monitor surgical margins with NIF imaging and spectroscopy. Fluorescence was detected in primary tumors in all patients. The fluorescence intensities of the tumor, peritumoral, and normal tissues were 398.863 ± 151.47, 278.52 ± 84.89, and 274.5 ± 100.93 arbitrary units (AUs), respectively (P < 0.05). The SBR of tumor to peritumoral tissue and normal tissues was computed to be 1.45 ± 0.36 and 1.56 ± 0.41, respectively. After primary tumor excision, the wounds showed abnormal fluorescence in four patients (4/20), and residual cancer cells were confirmed by pathological examination in two patients (2/20). Conclusion These findings confirmed the complementary value of NIF imaging during radical tumor resection of OSCC. Before tumor resection, we could utilize the fluorescence margin produced by ICG NIF imaging to determine the surgical margin. Moreover, after tumor blocks were removed, the status of surgical margin could also be evaluated rapidly by ICG NIF imaging of tumor bed and in vitro specimens.

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.

Piebaldism is a rare, autosomal dominant and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SNAI2 genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Herein, we report a 5-month-old Chinese girl with severe piebaldism but no family history thereof. She has white forelock and large patches of depigmentation in the jaw, central anterior trunk, perineum and extremities. We performed whole-exome and Sanger sequencing and identified a de novo KIT mutation (NM_000222.2: c.2657G>A, p.Gly886Val) in exon 18 of KIT in the proband. Currently, this mutation is located in the most extreme C-terminal of the tyrosine kinase domain 2 of the KIT gene amongst all reported mutations and causes a severe clinical phenotype. We further reviewed literature on piebaldism and summarized 79 KIT gene mutations that lead to this disease. Our study may expand knowledge on the genotype-phenotype correlation in piebaldism and serve as a reference for genetic counseling and prenatal diagnosis of affected families.

BackgroundAcrodermatitis enteropathica (AE) is a rare autosomal recessive hereditary skin disease caused by mutations in the SLC39A4 gene and is characterized by periorificial dermatitis, alopecia and diarrhoea due to insufficient zinc absorption. Only one of the three known sets of twins with AE has genetic information. This case reports the discovery of new mutation sites in rare twin patients and draws some interesting conclusions by analysing the relationship between genetic information and clinical manifestations.Case presentationHere, we report a pair of 16-month-old twin boys with AE exhibiting periorificial and acral erythema, scales and blisters, while subsequent laboratory examination showed normal plasma zinc and alkaline phosphatase levels. Further Sanger sequencing demonstrated that the patients were compound heterozygous for two unreportedSLC39A4mutations: a missense mutation in exon 5 (c.926G > T), which led to a substitution of the 309th amino acid residue cysteine with phenylalanine, a splice site mutation occurring in the consensus donor site of intron 5 (c.976 + 2 T > A). A family study revealed that the boys’ parents were heterozygous carriers of these two mutations.ConclusionWe identified a new compound heterozygous mutation in Chinese twins with AE, which consisted of two previous unreported variants in exon 5 and intron 5 of SLC39A4. We propose an up-to-date review that different mutations in SLC39A4 may exhibit different AE manifestations. In conjunction with future research, our work may shed light on genotype-phenotype correlations in AE patients and provide knowledge for genetic counselling and treatment for AE patients.

This study reports a fluorescence ratio immunosensor method for detecting dibutyl phthalate (DBP) sensitively and specifically using dual-emission carbon quantum dots labelled with amino-modified nucleic acid aptamers. Under optimal experimental conditions, the linearity range of the method for detecting DBP was from 12.5 to 1500 μg/L, with a limit of detection of 5.0 μg/L. Compared with detection results for two structural analogues, this method showed good specificity for DBP. Liquor samples spiked with DBP measured by this method exhibited a standard recovery of 93.2% to 112.4% with a relative standard deviation of 1.59% to 4.54%. The method was used to determine the DBP content in edible oil samples, providing results not significantly different from those obtained by gas chromatography. Compared with the single wavelength emission method, this method had a stronger anti-interference ability and provided more accurate results, so can be used for highly sensitive detection of DBP in food samples.

In this work, a novel ratiometric electrochemical sensor based on dual-functional poly-dopamine (PDA) and nickel sulfide@hollow carbon spheres (NiS@HCS) was successfully developed for sunset yellow (SY) detection. The NiS@HCS nanocomposite possessing a large specific surface area, good catalytic activity and excellent electrical conductivity was employed for signal amplification. PDA films prepared by electropolymerization acted as an internal reference probe and enhanced the sensitivity of the proposed sensor through electrostatic attraction between SY and PDA. Under optimized conditions, the developed PDA/NiS@HCS/GCE sensor allowed SY quantification over wide linear range (0.01-100 μM), with a low limit of detection of 0.003 μM. SY recovery tests were carried out in rice vinegar and cooking wine with satisfactory recoveries (83.50-112.80 %). Meanwhile, the content of SY in two kinds of carbonated drinks was determined using the constructed sensor and a UV-Vis spectrometry method, with no significant difference found in the results.

The coronavirus disease 2019 (COVID-19) may cause cytokine storm and respiratory illness such as pneumonia and progressive respiratory failure. Tocilizumab (TCZ), a monoclonal antibody that targets the interleukin-6 (IL-6) receptor, was approved as an alternative treatment for severe COVID-19 patients despite limited real-world clinical data in China. In the present study, we will discuss and evaluate the treatment response of TCZ therapy in patients with COVID-19. The clinical characteristics, treatment, laboratory parameters of IL-6, C-reactive protein (CRP), lymphocyte counts before and after TCZ therapy, and clinical outcomes in the 13 patients with COVID-19 were retrospectively evaluated according to the related medical records. The results showed that 13 patients with COVID-19 were totally included in this study. One of them was moderately ill, 8 were seriously ill, and 4 were critically ill. Eleven patients received TCZ administration once, while the other 2 patients received it twice. The median level of IL-6 before TCZ administration was 27.91 (7.42–210.90) pg/mL. Serum IL-6 level tended to further spike firstly and then gradually decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL-6 was observed in 2 patients who were finally dead. The CRP levels of 76.92% (10/13) of the patients were above the normal range before the start of TCZ therapy and gradually declined after the TCZ treatment. No. 1 and No. 10 patients finally died accompanied by the corresponding lymphocyte counts persistently dropping. No. 13 patient became exacerbated possibly due to inducing severe bacterial infection after TCZ treatment, while the other 10 patients showed clinical improvement. In summary, the study revealed that TCZ may have a certain therapeutic effect on severe COVID-19 patients with a risk of the cytokine storm. It is necessary to further evaluate the efficacy and safety of TCZ by rigorous randomized controlled trial in the next step.

To explore whether medication non-adherence experience, readiness for hospital discharge, financial toxicity and symptoms predicted oral chemotherapy adherence at home for Chinese cancer patients.Oral chemotherapy adherence is critical to determine the treatment efficacy among cancer patients. Identifying predictors before discharge from hospital based on transition theory could assist healthcare providers to improve oral chemotherapy adherence at home.An observational prospective study.Between October 2018 and December 2019, self-reported questionnaires were used to collect data among 151 cancer patients with oral chemotherapy at home. At discharge, baseline data of patient-perceived readiness for hospital discharge, financial toxicity and non-adherence experience were collected, while symptoms and adherence of oral chemotherapy at home were collected after finishing one cycle of oral chemotherapy at home (21 days, the first 14 days received oral chemotherapy). Regression analyses were performed for the predictors' explorations. The STROBE guidelines were followed.Among 151 participants with oral chemotherapy at home, 30.46% of patients reported medication non-adherence experience at discharge and 82.12% of patients reported adherence to oral chemotherapy at home. Patients with non-adherence experience at discharge were 5.4 times more likely to being non-adhered to oral chemotherapy at home. Numbness were the most frequent and severe symptoms during at home, patients with numbness were 6.6 times more likely to being non-adhered to oral chemotherapy. Although patients reported high level of readiness for discharge and financial toxicity at discharge, which did not predicted oral chemotherapy adherence at home.Patients with medication non-adherence experience at discharge and symptom of numbness from oral chemotherapy suggested a higher risk of oral chemotherapy non-adherence at home.Preventive interventions should focus on patients with previous medication non-adherence experience at discharge and experiencing numbness to promote oral chemotherapy adherence.

BACKGROUND Both healthcare provider-patient communication and self-care efficacy affect psychological distress, which is prevalent among patients with gastrointestinal (GI) cancers. It is essential to explore the underlying mechanism among them to relieve psychological distress. OBJECTIVE The aim of this study was to examine whether self-care efficacy mediated the association between healthcare provider-patient communication and psychological distress among patients with GI cancers. METHODS A cross-sectional study was conducted between March 2018 and May 2019 in China. In total, 219 patients with GI cancers were recruited before discharge from chemotherapy. Healthcare provider-patient communication was assessed by the revised Physician-Patient Communication Scale; patient self-care efficacy was assessed by the Strategies Used by People to Promote Health; and psychological distress was assessed by the Distress Thermometer and the Hospital Anxiety and Depression Scale. Mediation analyses were conducted to examine the mediating effect of self-care efficacy on the association between healthcare provider-patient communication and psychological distress. RESULTS A total of 54.34% of patients experienced psychological distress. Patients reported a mean score of 89.93 (SD, 13.81) for healthcare provider-patient communication and 93.91 (SD, 23.39) for self-care efficacy. Self-care efficacy completely mediated the association between healthcare provider-patient communication and psychological distress, and communication outcome was the only domain that significantly influenced self-care efficacy. CONCLUSION Psychological distress is prevalent among patients with GI cancers. Healthcare provider-patient communication, especially communication outcome, promoted patients' self-care efficacy to reduce psychological distress. IMPLICATIONS FOR PRACTICE Healthcare providers should design interventions to improve communication outcomes and eventually increase self-care efficacy to relieve psychological distress among patients with GI cancers.

An electrochemical sensor based on stearyl trimethyl ammonium bromide - functionalized niobium carbide@multi-walled carbon nanotubes (Nb

Real-life data on guselkumab in psoriasis are limited and not available in China hitherto. This study aimed to evaluate the short-term effectiveness and safety of guselkumab in patients with psoriasis under Chinese real-life conditions and to explore the effect of guselkumab on CD4+ CD25+ Foxp3+ regulatory T cells (Tregs). A Chinese prospective and real-life study involving patients with psoriasis in Dermatology Hospital of Southern Medical University, Guangzhou, China from April to September 2020 was conducted. A total of 45 patients with psoriasis were finally enrolled in the study. Psoriasis Area Severity Index (PASI) 90 and 100 responses at week 16 were achieved by 88.6% and 45.5% of patients, respectively. The analysis of PASI response in different subgroups showed no statistically significant difference. Univariate logistic regression analysis revealed that at week 16, none of the variables were associated with decreasing PASI 90 response, whereas age at onset of disease was a predictor of PASI 100 response. Dynamic detection of CD4+ CD25+ Foxp3+ Tregs frequency from peripheral blood suggested a stable maintained trend in terms of guselkumab treatment duration. No severe adverse events occurred during the follow-up period. This study confirmed the short-term effectiveness and safety of guselkumab, as well as its good tolerance against psoriasis, in the Chinese population. Guselkumab treatment maintains levels of Tregs in patients with psoriasis.

At present, there is limited research on pregnancy body image and no valid tool to measure body image in pregnant Chinese women. The purpose of this study was to translate the Body Understanding Measure Pregnancy Scale into Chinese to determine its reliability and validity in measuring body image in pregnant women.The translation of the Body Understanding Measure Pregnancy Scale (BUMPs) was carried out with a standardized procedure. This study was conducted from July to December 2020 in the outpatient department of three tertiary hospitals in China. There were 1069 pregnant women completed the questionnaire and 1057 of those women were included in the analysis. Internal consistency, test-retest reliability, content validity, and construct validity of the translation version were examined.The final Chinese version of the BUMPs (BUMPs-C) had four dimensions with 16 items. Exploratory factor analysis obtained a three-factor solution, which explained 50.26% of the total variances. Confirmatory factor analysis showed that the model fit of the four-factor model was better than the three-factor model, and the four-factor model also reached a satisfactory model fit after modifying: Minimum Discrepancy was 2.82; Comparative Fit Index was 0.939, and Tucker-Lewis Index was 0.92; Root Mean Square Error of Approximation was 0.059. The content validity index of the scale was 1.0; the Cronbach's alpha (α) coefficient was 0.82 for the total scale, the McDonald's omega (ω) coefficient was 0.829; the test-retest reliability was 0.796.The BUMPs-C showed good reliability and validity among pregnant Chinese women, which can be used as a simple and valid measurement tool to assess the feelings of pregnant Chinese women on body changes during pregnancy.

Long non‐coding RNAs (lncRNAs) play critical roles in regulating immune‐associated diseases and chronic inflammatory disorders. Here, we found that lncRNAs involve in the pathogenesis of psoriasis through integrative analysis of RNA‐seq data sets from a psoriasis cohort. Then, lncRNA‐protein‐coding genes (PCGs) co‐expression network analysis demonstrated that lncRNAs extensively interact with IFN‐γ signalling pathway‐associated genes. Further, we validated 3 lncRNAs associate with IFN‐γ signalling pathway activation upon IFN‐γ stimulated in HaCaT cells, and loss of function experiments indicate their functional roles in the activation of inflammatory cytokine genes. Additionally, microRNA target screening analysis showed that lncRNAs may regulate JAK/STAT pathway activity through complete endogenous RNA (ceRNA) mechanism. Further experimental validation of PRKCQ‐AS1/STAT1/miR‐545‐5p regulatory circuitry showed that lncRNAs regulate the expression of JAK/STAT signalling pathway genes through competing for miR‐545‐5p. In summary, our results demonstrated that dysregulation of lncRNA‐JAK/STAT pathway axis promotes the inflammation level in psoriasis and thus provide potential therapeutic targets for psoriasis treatments.

Psoriasis is a chronic inflammatory skin disease. Although miRNAs are reported to be associated with the pathogenesis of psoriasis, the contribution of individual microRNAs toward psoriasis remains unclear. The miR-17-92 cluster regulates cell growth and immune functions that are associated with psoriasis. miR-17-3p is a member of miR-17-92 cluster; however, its role in dermatological diseases remains unclear. Our study aims at investigating the effects of miR-17-3p and its potential target gene on keratinocytes proliferation and secretion of pro-inflammatory cytokine and their involvement in psoriasis. Initially, we found that miR-17-3p was upregulated in psoriatic skin lesions, and bioinformatic analyses suggested that CTR9 is likely to be a target gene of miR-17-3p. Quantitative reverse-transcriptase PCR and immunohistochemical analysis revealed that CTR9 expression was downregulated in psoriatic lesions. Using dual-luciferase reporter assays, we identified CTR9 as a direct target of miR-17-3p. Further functional experiments demonstrated that miR-17-3p promoted the proliferation and pro-inflammatory cytokine secretion of keratinocytes, whereas CTR9 exerted the opposite effects. Gain-of-function studies confirmed that CTR9 suppression partially accounted for the effects of miR-17-3p in keratinocytes. Furthermore, Western blot revealed that miR-17-3p activates the downstream STAT3 signaling pathway while CTR9 inactivates the STAT3 signaling pathway. Together, these findings indicate that miR-17-3p regulates keratinocyte proliferation and pro-inflammatory cytokine secretion partially by targeting the CTR9, which inactivates the downstream STAT3 protein, implying that miR-17-3p might be a novel therapeutic target for psoriasis.

An 80-year-old women complained of painful erythema, papules, nodules on her right wrist for 9 months. Granuloma and inflammatory infiltrates with septate fungal hyphae were observed in pathological sections. Growth of demaciatious fungus on SDA was confirmed to be Exophiala spinifera by microscopic appearance and ITS rDNA sequencing. The diagnosis of phaeohyphomycosis due to E. spinifera was established. The patient had a poor response to oral itraconazole (200 mg/d) combining with terbinafine (250 mg/d) for 6 weeks. Then, following three courses of ALA-PDT, used as adjuvant therapy, skin lesions greatly improved and remained stable after 3 months follow-up. The case suggests that ALA-PDT is an effective adjuvant treatment option for patients with recalcitrant local subcutaneous fungal infection.

Graphene has some outstanding properties in the photoelectric field, especially ultra fast response and broad spectrum absorption, which have led to strong attraction on graphene photodetector. However, the photoresponsivity of pure graphene device is below 10 mA W−1. It would limit the application of graphene photodetector. Here, we design a metamaterial structure with a broadband high absorption spectrum. And by integrating it into the graphene photodetector, the high photoresponsivity of a pure graphene photodetector in a broadband range could be acquired. The photoresponsivity of photodetector can achieve nearly 200 mA W−1, which is two orders higher than the one of pure monolayer graphene photodetector. Besides, the photodetector also keeps the broadband photoresponse. The hot carriers can be generated by coupling of multiple resonances and effectively transported to graphene with the advantage of ultrathin metal film. Based on this work, more potential applications of graphene photodetector could be developed in some related fields.

Transition metal dichalcogenides (TMDs) are a category of promising two-dimensional (2D) materials for the optoelectronic devices, and their unique characteristics include tunable band gap, nondang...

Graphene and other two-dimensional (2D) materials have emerged as promising materials for future optoelectric applications. However, low detectivity of two-dimensional materials based photodetector inhibits their application. Here, we report a lateral graphene/MoS2/graphene (GMG) heterostructure photodetector which was synthesized by chemical vapor disposition (CVD). Electrical measurement shows that on/off ratio is up to 10 6 and two opposing Schottky junctions are connected in a series. Photocurrent mapping indicates that the Schottky junctions formed by graphene and MoS2 are the core part of the device, where photoexcited electron-hole pairs are spontaneously and rapidly separated. The responsivity is more than 2 × 10 3 m A / W and the maximum specific detectivity is as high as 10 13 J o n e s , respectively. This special design for the 2D materials based photodetector with high detectivity gives great potential for future application in nano-optoelectronic devices.

Two-dimensional transition-metal dichalcogenides (TMDs) have attracted significant attention, owing to their excellent electrical and optoelectrical properties, especially MoS2. However, the photoresponse of pure MoSe2 is still unsatisfactory due to the absence of a photoresponse enhancement mechanism, which impedes its rapid development in optoelectronics. Here, we report a pure MoSe2 phototransistor with an in-plane lateral thickness-dependent MoSe2 homojunction in the channel perpendicular to the charge transfer direction as an enhancement scheme for the first time. An in-plane lateral built-in field is spontaneously formed due to the different electrical band structure of MoSe2 with different thickness, which facilitates the efficient separation of photo-excited carriers. Furthermore, with an increase in the applied negative back-gate voltage, separation could be further strengthened due to the increase of the built-in field in the homojunction resulting in optimization of the photoresponse performance. These results suggest a facile approach for the enhancement of photoresponse performance to materials which possesses a thickness-dependent energy band structure.

Alzheimer's disease (AD) is a progressive neurodegenerative disease of the brain. It cannot be cured currently, and those suffering from AD place a great burden on their caregivers and society. AD is characterized by high levels of iron ions in the brain, which catalyze radicals that damage the neurons. Knowing that the Aβ42 peptide precipitates iron by binding iron ions at amino acid residues D1, E3, H11, H13, and H14, we synthesized a 5-repeat (HAYED) sequence peptide. By treating iron-stressed SH-SY5Y cells with it and injecting it into the cerebrospinal fluid (CSF) of naturally senescence Kunming mouse, which displaying AD-similar symptoms such as learning and memory dysfunction, neuron degeneration and high level of iron in brain, we found that HAYED (5) decreased the iron and radical levels in the cell culture medium and in the CSF. Specially, the synthesized peptide prevented cell and brain damage. Furthermore, functional magnetic resonance imaging (fMRI), Morris water maze and passive avoidance tests demonstrated that the peptide ameliorated brain blood-oxygen metabolism and slowed cognitive loss in the experimental senescence mice, and clinical and blood tests showed that HAYED (5) was innoxious to the kidney, the liver and blood and offset the AD-associated inflammation and anemia.

Background Readiness for hospital discharge is associated with patients’ health outcomes after they return home. However, little is known about this association among cancer patients receiving oral chemotherapy at home. This study aimed to examine whether patients’ reported readiness for hospital discharge was associated with symptoms and non-routine utilization of post-discharge services among cancer patients receiving oral chemotherapy at home. Methods A prospective study was conducted, and 151 cancer patients receiving oral chemotherapy were recruited from a provincial level hospital in South China between October 2018 and December 2019. The primary outcome was readiness for hospital discharge assessed by the Readiness for Hospital Discharge Scale-Short Form on the day of discharge. The secondary endpoints were symptoms assessed by MD Anderson Symptom Inventory and non-routine utilization of post-discharge services within one cycle of chemotherapy at home (21 days). Results Among these 151 participants, 74.2% of them reported as ready for discharge. Patients who were employed, lived in suburban area or villages, had a higher Eastern Cooperative Oncology Group score, took Tegafur as oral chemotherapy, and took oral chemotherapy for the first time reported lower readiness for hospital discharge. These five factors explained 28.1% of variance in readiness for hospital discharge. Patients who were not ready for discharge were prone to report higher symptom severity ( p = 0.038). No differences in non-routine utilization of post-discharge services were found between the readiness versus non-readiness for discharge groups ( p = 0.891). Conclusions Most cancer patients receiving oral chemotherapy at home were ready for discharge, which was influenced by employment status, residence status, Eastern Cooperative Oncology Group score, type of oral chemotherapy drug, and the experience of taking oral chemotherapy at home. Patients with lower readiness reported worse symptom severity at home. Routine assessment was suggested to recognize unready patients, and more extensive preparations for discharge were recommended to help them manage symptoms at home.

Background Psoriasis is a chronic immune-mediated inflammatory dermatosis. Long noncoding RNAs (lncRNAs) play an important role in immune-related diseases. This study aimed to identify potential immune-related lncRNA biomarkers for psoriasis. Methods We screened differentially expressed immune-related lncRNAs biomarkers using GSE13355 (skin biopsy samples of 180 cases) from Gene Expression Omnibus (GEO). Moreover, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were performed to explore biological mechanisms in psoriasis. In addition, we performed LASSO logistic regression to identify potential diagnostic lncRNAs and further verify the diagnostic value and relationship with drug response using two validation sets: GSE30999 (skin biopsy samples of 170 cases) and GSE106992 (skin biopsy samples of 192 cases). Furthermore, we estimated the degree of infiltrated immune cells and investigated the correlation between infiltrated immune cells and diagnostic lncRNA biomarkers. Results A total of 394 differentially expressed genes (DEGs) were extracted from gene expression profile. GO and KEGG analysis of target genes found that immune-related lncRNAs were primarily associated with epidermis development, skin development, collagen-containing extracellular matrix, and glycosaminoglycan binding and mainly enriched in cytokine-cytokine receptor interaction and influenza A and chemokine signaling pathway. We found that LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1, CARMN, CCDC18-AS1, EPB41L4A-AS, and LINC01214 exhibited well diagnostic efficacy. The ROC and ROC CI were 0.944 (0.907–0.982), 0.953 (0.919–0.987), 0.822 (0.758–0.887), 0.854 (0.797–0.911), 0.957(0.929–0.985), 0.894 (0.846–0.942), and 0.964 (0.937–0.991) for LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1,CARMN, CCDC18-AS1, EPB41L4A-AS1, and LINC01214. LINC01137, LINC01215, and LINC01214 were correlated with drug response. LINC01137, CCDC18-AS1, and CARMN were positively correlated with activated memory CD4 T cell, activated myeloid dendritic cell (DC), neutrophils, macrophage M1, and T follicular helper (Tfh) cells, while negatively correlated with T regulatory cell (Treg). LINC01215, MAPKAPK5-AS1, TPT1-AS1, EPB41L4A-AS, and LINC01214 were negatively correlated with activated memory CD4 T cell, activated myeloid DC, neutrophils, macrophage M1, and Tfh, while positively correlated with Treg. Conclusions These findings indicated that these immune-related lncRNAs may be used as potential diagnostic and predictive biomarkers for psoriasis.

Wnt signaling is one of the key cascades regulating normal tissue development and has been tightly associated with cancer. The Wnt signaling can be subdivided into two categories: canonical & noncanonical. Noncanonical Wnt signaling pathways mainly include Wnt/PCP (planar cell polarity) signaling and Wnt-cGMP (cyclic guanosine monophosphate) /Ca2+ signaling. It has been well studied by previous researches that noncanonical Wnt signaling regulates multiple cell functions including proliferation, differentiation, adhesion, polarity, motility, and migration. The aberrant activation or inhibition of noncanonical Wnt signaling is crucial in cancer progression, exerting both oncogenic and tumor-suppressive effects. Recent studies show the involvement of noncanonical Wnt in regulating cancer cell invasion, metastasis, metabolism, and inflammation. Here, we review current insights into novel components of non-canonical signalings and describe their involvement in various cancer types. We also summarize recent biological and clinical discoveries that outline non-canonical Wnt signaling in tumorigenesis. Finally, we provide an overview of current strategies to target non-canonical Wnt signaling in cancer and challenges that are associated with such approaches.

Strain engineering is proposed to be an effective technology to tune the properties of two-dimensional (2D) transition metal dichalcogenides (TMDCs). Conventional strain engineering techniques (e.g., mechanical bending, heating) cannot conserve strain due to their dependence on external action, which thereby limits the application in electronics. In addition, the theoretically predicted strain-induced tuning of electrical performance of TMDCs has not been experimentally proved yet. Here, a facile but effective approach is proposed to retain and tune the biaxial tensile strain in monolayer MoS2 by adjusting the process of the chemical vapor deposition (CVD). To prove the feasibility of this method, the strain formation model of CVD grown MoS2 is proposed which is supported by the calculated strain dependence of band gap via the density functional theory (DFT). Next, the electrical properties tuning of strained monolayer MoS2 is demonstrated in experiment, where the carrier mobility of MoS2 was increased by two orders (∼ 0.15 to ∼ 23 cm2·V−1·s−1). The proposed pathway of strain preservation and regulation will open up the optics application of strain engineering and the fabrication of high performance electronic devices in 2D materials.

Objective To investigate the expression and clinical significance of phosphatase and tension homolog deleted on chromosome ten (PTEN) and stimulator of interferon genes (STING) in human tongue squamous cell carcinoma (TSCC). Methods The expression of PTEN and STING protein in 65 pairs of TSCC and paracancerous tissues was detected by immunohistochemical EnVision method, and the relationships between PTEN, STING and clinicopathological parameters, overall survival (OS) and prognosis were analyzed by statistical methods. Results Compared with the adjacent tissues, the expression of PTEN in TSCC significantly decreased, and the expression of STING significantly increased. PTEN was negatively correlated with STING. In TSCC, the expression of PTEN and STING were correlated with pathological grade, TNM stage and lymph node metastasis. There were no significant correlations between the expression intensity of PTEN, STING and the gender and age of patients. The low expression of PTEN and the high expression of STING in TSCC tissues were significantly associated with poor prognosis and significantly shortened overall survival of patients. Conclusion TSCC patients with low expression of PTEN and high expression of STING have poor prognosis and short survival time. Combined detection of PTEN and STING expression is helpful to evaluate the degree of tumor progression and patient prognosis.

Background: D-dimer is a small protein fragment and high levels of D-dimer have been associated with increased mortality in patients presenting to emergency departments with infection. Previous studies have reported increased levels of D-dimer in COVID-19; however, it is unclear whether an increased D-dimer level provides early warning of poor prognosis. Therefore, this study aimed to assess the usefulness of D-dimer as an early indicator of prognosis in patients with coronavirus disease (COVID-19).Methods: We conducted a retrospective study of patients with COVID-19 admitted to Leishenshan Hospital in Wuhan, China, from February 15 to March 30, 2020. The final date of follow-up was April 11, 2020.Results: Of the 1,643 patients with COVID-19, 691 had elevated D-dimer levels. Their median age was 65 years. Of the patients with elevated D-dimer levels, 45% had comorbidities, with cardiovascular disease (205 [29.7%]) being the most common. Patients with elevated D-dimer were more likely to require treatment with high-flow oxygen, anticoagulation, antibiotics, and admission to the intensive care unit They were also more likely to have increased interleukin-6, monocytes, and lymphocytes. Patients with elevated D-dimer levels had significantly higher mortality than those with normal or low D-dimer levels.Conclusion: In patients with COVID-19, elevated D-dimer was associated with abnormal immunity, underlying disease, increased disease severity, and increased mortality. Taken together, D-dimer may be a marker for the early warning of disease severity and increased risk of death. These findings provide insights into the potential risk of elevated D-dimer in patients with COVID-19.

Capsaicin is a chili pepper extract with multiple therapeutic properties including anti-liver fibrosis. However, the paucity of its underlying mechanisms limited its widely clinical application.In the present study, carbon tetrachloride (CClHere, we show that capsaicin attenuates liver fibrosis progression by mediating macrophage inflammatory response. Capsaicin inhibited M1 polarization of macrophage by regulating Notch signaling leading to the reduced secretion of inflammatory cytokine TNF-α that correspondingly attenuates myofibroblasts regeneration and fibrosis formation of hepatocyte stellate cells (HSCs).Taken together, capsaicin alleviates liver fibrosis by inactivation of Notch signaling and further inhibiting TNF-α secretion from M1 macrophage. Targeting TNF-α or Notch signaling in macrophage represents a promising strategy to combat liver fibrosis.

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

Background Shen-ling-bai-zhu-san (SLBZS) regulates inflammation and gut microbiota which are associated with Streptococcus pneumoniae (Spn)-induced pneumonia. So, we studied the therapeutic effect of SLBZS and evaluated whether gut microbiota is associated with the effects of SLBZS in improving Spn-induced pneumonia. Methods Spn-induced pneumonia NIH mice were treated by SLBZS and cefixime. A CT scan was performed and Myeloperoxidase (MPO) activity in lung homogenates was determined using the MPO Colorimetric Assay Kit. Inflammation levels in lung homogenates were measured using ELISA. Bacterial load was coated on a TSAII sheep blood agar. Intestinal gut microbiota information was analyzed according to sequencing libraries. Results SLBZS decreased bacterial load, reduced wet/dry weight ratio, inhibited myeloperoxidase activity, reduced the neutrophils count, and ameliorated lung injury. Furthermore, SLBZS inhibited interleukin (IL)-1β, IL-6, tumor necrosis factor-α, IL-2, IL-8, IL-12, and interferon-γ secretion and enhanced IL-10 secretion. These results suggest that SLBZS ameliorates lung injury in mice with Spn-induced pneumonia. Moreover, SLBZS reduced inflammatory cytokine levels in a concentration-dependent manner and increased gut microbiota abundance and diversity. After SLBZS treatment, bacteria such as Epsilonbacteraeota, Bacteroidetes, Actinobacteria, Proteobacteria, and Patescibacteria were significantly reduced, while Tenericutes and Firmicutes were significantly increased. Conclusion SLBZS ameliorates inflammation, lung injury, and gut microbiota in mice with S. pneumoniae-induced pneumonia.

ObjectiveTo investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity.MethodsWe retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT).ResultThe levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (pConclusionThe coagulation systems in COVID-19 patients are inordinate, and dynamic monitoring of them, might be a key in the control of COVID-19 death.

RationaleIn late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease.ObjectivesTo study the epidemiology, clinical features and outcomes of patients with COVID-19.Methodswe performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital.Measurements and Main ResultsThe median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%.ConclusionsThe COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.

Background: Since the end of 2019, coronavirus disease-2019 (COVID-19) outbreak spreads around the world We aimed to share the details of critically ill patien

Background: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China. We aimed to study the epidemiology and clinical features of patients diagnosed as coronavirus disease 2019 (COVID-19) and their treatment and outcome in Wuhan, China. Methods: We did a single center, retrospective case series study in patients from Zhongnan Hospital of Wuhan University, Wuhan, China. 221 admitted patients with laboratory confirmed SARS-CoV-2 infection, including 55 severe patients and 166 non-severe patients, were recruited from January 2, 2020 to February 10, 2020. Data of epidemiology, clinic, laboratory exams, radiology and treatment were collected from standardized case report forms and compared between the severe and non-severe patients with COVID-19. Specifically, the outcome of corticosteroid therapy was analyzed in the severe patients in intensive care unit (ICU). Findings: Of the 221 patients with COVID-19, 108 (48.9%) of them were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe patients, the median age of the severe patients was significantly older (62.0 vs 51.0 years), and they were more likely to have chronic comorbidities, including hypertension, cardiovascular disease and cerebrovascular disease. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 73 (33.0%) of the 221 patients showed leukopenia and 163 (73.8%) showed lymphopenia. The laboratory results showed more severity of aberrant coagulation pathway, hepatic injury, myocardial injury and kidney injury in the severe patients. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications, including acute respiratory distress syndrome (ARDS), arrhythmia, acute cardiac injury, shock and acute kidney injury. As of Feb 15, 2020, a total of 42 (19.0%) patients had been discharged and 12 (5.4%) patients died. In the 55 severe patients, 44 (80%) of them received ICU care, and 23 of them transferred to the general wards due to relieved symptoms, and the mortality rate was 21.8%. Interpretation: In this single-center case series of 221 hospitalized patients with confirmed COVID-19 in Wuhan, China, 55 severe patients with elder age and chronic comorbidities, developed more than one complication. The mortality rate was significantly higher in the severe patients compared to that in the non-severe patients (21.8% vs 0.0%). Older and male patients with higher APACHE II & SOFA scores, elevated PCT level, excessive fluid volume input, as well as the delayed use of corticosteroid might increase the risk of death in ICU. Funding Statement: This work was supported by the National Natural Science Foundation of China (grant no. 81700493 to Dr. Pan; grant no. 81971816 to Dr. Peng). Declaration of Interests: The authors declared no conflicts. Ethics Approval Statement: This study was approved by the National Health Commission of China and Ethics Commission of Zhongnan Hospital. Written informed consent was waived by the Ethics Commission for emerging infectious disease.