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Confirming the tumor origin is often a diagnostic challenge in pathology and carries significant therapeutic impacts. Cytokeratin 7, estrogen receptor, and GATA binding protein 3 (GATA3) are well-established diagnostic markers frequently used to support a tumor's breast origin. However, their specificities still have room to improve. Many nonbreast tumors express cytokeratin 7 and estrogen receptor, and urothelial tumors frequently express GATA3. There is a practical need for a new breast lineage marker that is sensitive and specific. Wnt family member proteins play critical roles in embryo development, tissue homeostasis and tumor development through β-catenin dependent and independent pathways. The current study evaluated Wnt9b and GATA3 expression in 163 primary breast cancers, 63 metastatic breast cancers, and 525 nonbreast epithelial tumors. The positive rates of Wnt9b and GATA3 in primary breast cancer were both 98.7%. The positive rates in metastatic breast cancer were 87.3% for Wnt9b and 96.8% for GATA3. For nonbreast tumors, including 64 cases of urothelial carcinoma, Wnt9b was negative in all except salivary gland carcinomas. The study demonstrated that Wnt9b is a breast cancer marker with similar sensitivity as GATA3 but with greater specificity than GATA3 and may ultimately become a useful diagnostic tool in routine surgical pathology practice.

Aqueous zinc (Zn)-ion batteries are considered very promising in grid-scale energy storage systems. However, the dendrite, corrosion, and H2 evolution issues of Zn anode have restricted their further applications. Herein, to solve these issues, a hydrophilic layer, consisting of a covalent organic polymer (COP) and carboxylmethyl cellulose (CMC), is designed to in situ construct a multifunctional quasi-gel (COP-CMC/QG) interface between Zn metal and the electrolyte. The COP-CMC/QG interface can significantly improve the rechargeability of the Zn anode through enhancing Zn2+ transport kinetics, guiding uniform nucleation, and suppressing Zn corrosion and H2 evolution. As a result, the COP-CMC-Zn anode exhibits a reduced overpotential (12 mV at 0.25 mA cm-2), prolonged cycle life (over 4000 h at 0.25 mA cm-2 and 2000 h at 5 mA cm-2 in symmetrical cells), and elevated full-cell (Zn/MnO2) performance. This work provides an efficient approach to achieve long-life Zn metal anodes and paves the way toward high-performance Zn-based and other metal-ion batteries.

sRecent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response. Single-cell RNA sequencing (scRNA-seq) can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine, analyze the characteristics of cells with the same phenotype, and provide new insights into the growth and development of intestinal organs, the clonal evolution of cells, and immune cell changes. These findings can provide new ideas for the diagnosis and treatment of intestinal diseases.To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC.Using the Gene Expression Omnibus (GEO) database, we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing (RNA-seq) to reveal the core genes of UC. We then combined weighted gene correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis to reveal diagnostic markers of UC.After processing the scRNA-seq data, we obtained data from approximately 24340 cells and identified 17 cell types. Through intercellular communication analysis, we selected monocyte marker genes as the candidate gene set for the prediction model. Construction of a WGCNA coexpression network identified RhoB, cathepsin D (CTSD) and zyxin (ZYX) as core genes. Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells. Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses, which are associated with many challenges in the diagnosis and treatment of UC.Through scRNA-seq analysis, LASSO diagnostic model building and WGCNA, we identified RhoB, CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.

This study aims to explore the toxicity mechanism of Rhododendri Mollis Flos(RMF) based on serum metabolomics and network toxicology. The toxic effect of RMF on normal rats was evaluated according to the symptoms, serum biochemical indexes, and histopathology. Serum metabolomics was combined with multivariate statistical analysis to search endogenous differential metabolites and related metabolic pathways. The toxic components, targets, and signaling pathways of RMF were screened by network toxicology technique, and the component-target-metabolite-metabolic pathway network was established with the help of serum metabolomics. The result suggested the neurotoxicity, hepatotoxicity, and cardiotoxicity of RMF. A total of 31 differential metabolites and 10 main metabolic pathways were identified by serum metabolomics, and 11 toxic components, 332 related target genes and 141 main signaling pathways were screened out by network toxicology. Further analysis yielded 7 key toxic components: grayanotoxin Ⅲ,grayanotoxinⅠ, rhodojaponin Ⅱ, rhodojaponin Ⅴ, rhodojaponin Ⅵ, rhodojaponin Ⅶ, and kalmanol, which acted on the following 12 key targets: androgen receptor(AR), albumin(ALB), estrogen receptor β(ESR2), sex-hormone binding globulin(SHBG), type 11 hydroxysteroid(17-beta) dehydrogenase(HSD17 B11), estrogen receptor α(ESR1), retinoic X receptor-gamma(RXRG), lactate dehydrogenase type C(LDHC), Aldo-keto reductase(AKR) 1 C family member 3(AKR1 C3), ATP binding cassette subfamily B member 1(ABCB1), UDP-glucuronosyltransferase 2 B7(UGT2 B7), and glutamate-ammonia ligase(GLUL). These targets interfered with the metabolism of gamma-aminobutyric acid, estriol, testosterone, retinoic acid, 2-oxobutyric acid, and affected 4 key metabolic pathways of alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism, steroid hormone biosynthesis, and retinol metabolism. RMF exerts toxic effect on multiple systems through multiple components, targets, and pathways. Through the analysis of key toxic components, target genes, metabolites, and metabolic pathways, this study unveiled the mechanism of potential neurotoxicity, cardiotoxicity, and hepatotoxicity of RMF, which is expected to provide a clue for the basic research on toxic Chinese medicinals.

To quantify the impacts of native vegetation on the spatial and temporal variations in hydraulic properties of bank gully concentrated flows, a series of in situ flume experiments in the bank gully were performed at the Yuanmou Gully Erosion and Collapse Experimental Station in the dry-hot valley region of the Jinsha River, Southwest China. This experiment involved upstream catchment areas with one- and two-year native grass (Heteropogon contortus) and bare land drained to bare gully headcuts, i.e., Gullies 1, 2 and 3. In Gully 4, Heteropogon contortus and Agave sisalana were planted in the upstream catchment area and gully bed, respectively. Among these experiments, the sediment concentration in runoff in Gully 3 was the highest and that in Gully 2 was the lowest, clearly indicating that the sediment concentration in runoff obviously decreased and the deposition of sediment obviously increased as the vegetation cover increased. The concentrated flows were turbulent in response to the flow discharge. The concentrated flows in the gully zones with native grass and bare land were sub- and supercritical, respectively. The flow rate and shear stress in Gully 3 upstream catchment area were highest among the four upstream catchment areas, while the flow rate and shear stress in the gully bed of Gully 4 were lowest among the four gully beds, indicating that native grass notably decreased the bank gully flow rate and shear stress. The Darcy-Weisbach friction factor (resistance f) and flow energy consumption in the gully bed of Gully 4 were notably higher than those in the other three gully beds, clearly indicating that native grass increased the bank gully surface resistance and flow energy consumption. The Reynolds number (Re), flow rate, shear stress, resistance f, and flow energy consumption in the gully beds and upstream areas increased over time, while the sediment concentration in runoff and Froude number (Fr) decreased. Overall, increasing vegetation cover in upstream catchment areas and downstream gully beds of the bank gully is essential for gully erosion mitigation.

With rapidly growing rates of prevalence, disability, and mortality, Parkinson’s disease (PD) has become a global healthcare burden. Increasing elderly population increases the incidence of neurodegenerative diseases in China. Hence, PD poses a huge burden to Chinese economic and healthcare system. PD is a movement disorder that affects the motor and nonmotor functions. Dopamine agonists are used in the management of PD. Piribedil is an antiparkinsonian drug and piperazine derivative, which acts as D2/D3 receptor agonist. Piribedil is one of the non-ergot dopamine receptor (DR) agonists and has been used in China for many years as monotherapy or in combination with levodopa. In this paper, we present a review of clinical application of piribedil, management of adverse events, and drug interactions, and discuss the results of clinical trials of piribedil on motor and non-motor symptoms of PD.

The photophysical and charge transport properties of five non-planar cyclopenta-fused polycyclic aromatic hydrocarbons including dibenzo[a,m]rubicene (molecule 1) and its derivatives are studied through density functional theory (DFT). The absorption and emission spectra (λab and λem) are calculated at the B3LYP/6-31+G(d,p), PBE0/6-31+G(d,p), BMK/6-31+G(d,p), M062X/6-31+G(d,p) and CAM-B3LYP/6-31+G(d,p) levels in dichloromethane solvent. The results show that the BMK and M062X functionals can reproduce experimental λab and λem more accurately than other functionals, respectively. The charge mobilities can be effectively tuned through introducing silyl groups of different sizes (molecules 2, 3 and 4) and the 1,3-dimethoxy benzene group (molecule 5) to dibenzo[a,m]rubicene. The relationship between the structures of five dibenzo[a,m]rubicene derivatives and a set of relevant electronic properties including the molecular geometries, frontier molecular orbitals, ionization potentials, electron affinities, reorganization energies and transfer integrals have been established. The results show that these molecules possess prominent charge carrier mobilities, although they all possess non-planar geometries. The charge transport properties could be effectively modulated via introducing different substituents to molecule 1. The high hole mobilities indicate that all five molecules facilitate hole transport, which is in accordance with the experimental results. Intriguingly, the electron mobility is enhanced maximally by five times through introducing silyl groups of different sizes from 0.06 cm2 V−1 s−1 (molecule 1) to 0.30 cm2 V−1 s−1 (molecule 4). Particularly, molecules 4 and 5 possess balanced electron and hole mobilities, which could be used as bipolar semiconductors and show promising use in optoelectronic devices.

Background Poliomyelitis is an acute infection caused by an enterovirus, which primarily infects the human gastrointestinal tract. In general, patients with polio have no association with the occurrence of cancer. The present case study presents a rare case of poliomyelitis combined with primary breast cancer. Case summary A 61-year-old woman who was diagnosed with poliomyelitis at 5 years old and confirmed invasive breast cancer by core needle biopsy (CNB) after hospitalization. The patient received a modified radical mastectomy and four cycles of chemotherapy with the TC (docetaxel and cyclophosphamide) regimen. The patient was also prescribed endocrine therapy without radiotherapy after chemotherapy. The patient had no evidence of lymphedema in the right upper extremities and no evidence of either regression or distant metastasis at the 1-year follow-up. Conclusion The pectoral muscles of patients with polio are easily damaged in traumatic procedures, such as CNB, local anesthesia for tumor excision, and general anesthesia for surgery. A CNB, modified radical mastectomy, and four cycles of TC chemotherapy were successfully completed for the present case and the adverse reactions were found to be tolerable. This case may indicate the relationship between breast cancer and polio, and the examination and treatment methods used could be used as a guide for similar cases in the future.

Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare and aggressive tumour, and the molecular features and staining profile with contemporary immunohistochemical (IHC) biomarkers are largely unexplored. We characterise the clinicopathological, molecular and IHC features of MM (n = 13) and mesothelial neoplasms of uncertain malignant potential (MUMP) (n = 4).Targeted next-generation sequencing was performed on seven MMs and two MUMPs. IHC was performed for methylthioadenosine phosphorylase (MTAP), BRCA1-associated protein 1 (BAP1) and SRY-box transcription factor 6 (SOX6). Thirteen adenomatoid tumours were also assessed with SOX6. MM were epithelioid (seven of 13) or biphasic (six of 13). In MM, NF2 (five of seven; 71%), CDKN2A (three of seven; 43%) and BAP1 (two of seven; 29%) were most frequently altered. Non-recurrent driver events were identified in PTCH1 and TSC1. In contrast, none of these alterations were identified in MUMPs; however, one MUMP harboured a TRAF7 missense mutation. By IHC, loss of MTAP (two of 12; 17%) and BAP1 (two of nine; 22%) was infrequent in MM, whereas both were retained in the MUMPs. SOX6 was positive in nine of 11 (82%) MMs and negative in all MUMPs and adenomatoid tumours.Testicular MM exhibit a similar mutational profile to those of the pleura/peritoneum; however, alterations in CDKN2A and BAP1 are less common. These findings suggest that although MTAP and BAP1 IHC are specific for MM, their sensitivity in testicular MMs appears lower. In addition, rare tumours may harbour targetable alterations in driver genes (PTCH1 and TSC1) that are unusual in MMs at other anatomical sites. SOX6 is sensitive for MM; accordingly, the presence of SOX6 expression argues against a benign neoplastic process.

Introduction: Physical activity is a key component of a healthy lifestyle for youths with visual impairments (i.e., blindness or low vision). This study aims to examine the habitual physical activity and sedentary time of Chinese children and adolescents with visual impairments and to determine whether age, gender, and body composition significantly influence their behavior. Methods: A purposeful sample method was utilized to recruit 137 Chinese youths with visual impairments from a special school for individuals with visual and hearing impairments. A total of 72 students with visual impairments (aged 7–17 years; M age = 13.4) participated in this study. ActiGraph GT3X accelerometers were used to measure the habitual physical activity and sedentary time. Results: Youths with visual impairments in this study spent an average of 287.86 (standard deviation [ SD] = 45.67) minutes of light physical activity, 146.79 ( SD = 56.95) minutes of moderate physical activity, 18.47 ( SD = 15.15) minutes of vigorous physical activity, 165.26 ( SD = 69.83) minutes of moderate-to-vigorous-intensity physical activity, and 979.51 ( SD = 109.10) minutes of sedentary time per day. Children with visual impairments in elementary school engaged in more habitual physical activity and had less sedentary time than did students in middle and high school. Differences in gender and body composition with regard to time spent being active or sedentary were insignificant. Discussion: Findings demonstrated that Chinese youths with visual impairments in this study had sufficient health-enhancing physical activity and were habitually active. Future research is needed to identify the factors that account for the high habitual physical activity levels of Chinese youths with visual impairments. Implications for practitioners: Transition planning for students with visual impairments to facilitate active habitual physical activity participation when children grow up is warranted.

The aim of this study was to reveal the effect of let‐7b on osteoporosis (OP). Synthetic let‐7b mimics or inhibitors were transfected into MC3T3‐E1 cells. The expression of let‐7b in MC3T3‐E1 and its effect on cell viability, apoptosis, and the apoptosis‐related proteins (Bcl‐2, Bax, and cleaved caspase‐9) were tested by CCK‐8 assay, flow cytometry and Western blot, severally. The osteogenic differentiation markers (Runx2 and Osterix) and Wnt/β‐catenin pathway related markers (β‐catenin and C‐myc) were detected by qRT‐PCR and Western blot. The relationships between let‐7b and cyclin D1 (CCND1) were confirmed by luciferase reporter assay. The differentiation and mineralization of MC3T3‐E1 cells were analyzed by alkaline phosphatase (ALP) activity assay and alizarin red staining. The outcomes indicated that overexpression/ablation of let‐7b repressed/facilitated MC3T3‐E1 cell viability and accelerated/suppressed MC3T3‐E1 cell apoptosis. Besides, a remarkable decrease/augment of Bcl‐2 protein expression and the distinct fortify/reduction of Bax and cleaved caspase‐9 expression levels were observed in let‐7b mimics/inhibitors group in MC3T3‐E1 cells. Moreover, we discovered that let‐7b overexpression/ablation retrained/facilitated the mRNA and protein expression of Runx2 and Osterix. It was confirmed that CCND1 was a downstream target of let‐7b and was negatively modulated by let‐7b. In addition, high‐expression/deficiency of let‐7b inhibited/increased the expression levels of β‐catenin and C‐myc in MC3T3‐E1 cells. Taken together, our study revealed that let‐7b overexpression/depletion repressed/accelerated MC3T3‐E1 cell proliferation, differentiation, and mineralization while promoted/suppressed MC3T3‐E1 cell apoptosis through targeting CCND1, which might be adjusted by Wnt/β‐catenin pathway. Our findings might offer a basis for developing novel targets for OP treatment.

Circulating miRNAs are a newly emerging class of noninvasive biomarkers, and the accurate quantification of their expression is essential to the biological research and early clinic diagnosis. Herein, we demonstrate the construction of a quencher-free cascade amplification system for highly sensitive detection of serum circulating miRNAs. The target miRNA can hybridize with the linear probe to induce the cyclic strand displacement amplification (SDA) (cycle I) for the production of the binding probes. The binding probe can subsequently react with the 2-aminopurine (2-AP)-hairpin probe to induce the recycling exonuclease cleavage of 2-AP-hairpin probes (cycle II), releasing the triggers and 2-AP molecules simultaneously. The released trigger can hybridize with the free linear probe to start new cycles I and II amplifications. Through multiple rounds of cascade amplifications, a large number of 2-AP molecules are released, generating an enhanced fluorescence signal. This method exhibits a large dynamic range of 8 orders of magnitude and a detection limit of 0.16 aM. It can differentiate a single-base mismatch in miR-486-5p, quantify miR-486-5p in lung cancer cells at various stages, and even discriminate the expressions of serum circulating miR-486-5p in healthy persons from that in nonsmall-cell lung carcinoma (NSCLC) patients. Moreover, this assay can be rapidly carried out in one step under isothermal condition in a label-free manner, holding promising applications in point-of-care diagnosis and prognosis of lung cancers.

Objective To study the use of Chinese medicine (CM) in cancer patients in southern China. Methods A total of 1,950 cancer patients finished questionnaires in four provinces in southern China. The survey included socio-demographic and clinical characteristics of participants, dosage forms, efficacy, and side effects. Results The study results showed that cancer patients with higher education (>12 years) were more likely to accept the treatment of Chinese herbs. There were 54.61% (1,065 cases) of patients chose Chinese herbs for the initial treatment and 14.46% (282 cases) chose Chinese herbs as monotherapy. Most patients (54.51%, 1,063 cases) continuously used CM for more than 6 months, and a few of them (212 cases) used CM for up to 3 years. All kinds of dosage forms of CM had been used, including CM decoction, CM patent prescription and CM injection. Concerning the efficacy in the view of patients, 40.31% (786 cases) believed that it would be effective to take Chinese herbs before they starting the anti-cancer treatment, and the percentage increased to 81.08% after 1-month CM treatment. The effect of Chinese herbs was mainly demonstrated by symptom relief and improvement of quality of life, and 8.31% (162 cases) of patients experienced control of tumor growth and decreased tumor markers. Furthermore, only 14.31% (279 cases) participants reported that they experienced side effects during CM treatment. Conclusion This large scale investigation reflects the current situation of domestic CM usage objectively and comprehensively, which might provide new ways for cancer treatment.

Background: MicroRNA-1258 ( miR-1258 ) has been shown to play an anti-cancer role in a variety of cancers, but its relationship with papillary thyroid cancer (PTC) has not been reported. The emphasis of this research was to reveal the biological function of miR-1258 in PTC and its potential mechanisms. Material and methods: We measured miR-1258 expression in PTC cells and the transfection efficiency of miR-1258 mimic and miR-1258 inhibitor by quantitative real-time PCR (qRT-PCR) assay. Cell Counting Kit-8 assay (CCK8) and Transwell experiments were conducted to examine the influences of altering miR-1258 expression on the viability, migration, and invasion of PTC cells. Bioinformatics prediction and dual-luciferase experiment were performed to verify the target gene of miR-1258 . Finally, we carried out a rescue assay to verify whether the regulation of miR-1258 on the biological behaviour of PTC cells needs to be achieved by regulating TMPRSS4 . Results: The outcomes revealed that miR-1258 was lowly expressed in PTC cell lines and miR-1258 showed the lowest expression in KTC-1 and the highest expression in B-CPAP among all tested PTC cell lines. Overexpression of miR-1258 inhibited KTC-1 cell viability and ability to migrate and invade, whereas inhibition of miR-1258 in B-CPAP cells has the opposite effect. Furthermore, we affirmed that miR-1258 can directly target TMPRSS4 , and miR-1258 can reduce the biological malignant behaviour of PTC cells via regulation of TMPRSS4 . Conclusion: Taken together, our research raised the possibility that miR-1258 was an anti-oncogene, which exerts its anti-cancer function by targeting TMPRSS4 . Hence, it may be possible to treat PTC by targeting the miR-1258/TMPRSS4 axis in the future.

Spatiotemporal information is essential for video salient object detection (VSOD) due to the highly attractive object motion for human's attention. Previous VSOD methods usually use Long Short-Term Memory (LSTM) or 3D ConvNet (C3D), which can only encode motion information through step-by-step propagation in the temporal domain. Recently, the non-local mechanism is proposed to capture long-range dependencies directly. However, it is not straightforward to apply the non-local mechanism into VSOD, because i) it fails to capture motion cues and tends to learn motion-independent global contexts; ii) its computation and memory costs are prohibitive for video dense prediction tasks such as VSOD. To address the above problems, we design a Constrained Self-Attention (CSA) operation to capture motion cues, based on the prior that objects always move in a continuous trajectory. We group a set of CSA operations in Pyramid structures (PCSA) to capture objects at various scales and speeds. Extensive experimental results demonstrate that our method outperforms previous state-of-the-art methods in both accuracy and speed (110 FPS on a single Titan Xp) on five challenge datasets. Our code is available at https://github.com/guyuchao/PyramidCSA.

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

We develop a new fluorescence method for the sensitive detection of protein tyrosine phosphatase 1B (PTP1B) based on dephosphorylation-directed tricyclic DNA amplification cascades. This method exhibits good specificity and high sensitivity with a detection limit of 0.24 pM. Moreover, it can be applied for kinetics analysis, inhibitor screening, and the accurate detection of PTP1B in a variety of cancer cells.

Three 9-substituted acridines, namely 9-carboxyacridine (CA), 9-methylacridine (MA), and 9-aminoacridine (AA), were designed and synthesized for the development of effective inhibitors for mild steel corrosion in a 15% HCl solution. The corrosion-resistance ability was tested by weight-loss tests, electrochemical techniques, surface-topography analyses (SEM, SECM, and XPS), and contact angle measurements. The results indicated the inhibition performance followed the order of η(AA) > η(MA) > η(CA), and these acridines acted as mixed type inhibitors with a predominant restrained cathode process. The adsorption of the three acridines on a mild steel surface obeyed the Langmuir adsorption isotherm and involved both physisorption and chemisorption modes. Surface analysis and characterization confirmed the existence of an adsorbed film. Quantum chemical calculations were performed to provide mechanistic insights into the roles of the different substituents (−COOH, −CH3, and −NH2) on the corrosion-inhibition behavior of the three acridines. Molecular dynamics (MD) simulations were carried out to explore the configurational adsorption behavior of these 9-substituted acridines on the Fe(110) surface.

Single nucleotide polymorphisms (SNPs) have been proven to be important biomarkers for disease diagnosis, prognosis and disease pathogenesis. Here, taking the advantages of a self-assembled oligonucleotide sandwich structure and robust chemical reactions, we have developed a simple, high-throughput and effective colorimetric analytical technique termed CuAAC-based ligation-assisted assays (CuAAC-LA) for SNP detection using a DNA-BIND 96-well plate. With the 5'-azide and 3'-alkyne groups labelled on two oligonucleotide probes, the target DNA can direct a Cu(i)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction. Since the small difference in duplex stability caused by a single-nucleotide mismatch was amplified by the steric effects of these reactive groups for the ligation reaction of an unstable duplex, CuAAC-LA exhibited an ultra-sensitive discrimination ability for a mutant type target in the presence of large amounts of wild type targets. As low as 0.05% SNP could be clearly detected, which was better than most previously reported methods by various DNA ligases, indicating that a simple and rapid synthetic method i.e., the DNA template-directed click reaction held the potential to replace the ligase for SNP detection.

Clinical guidelines state that neoadjuvant chemotherapy should be administered before surgery in muscle invasive urinary bladder small cell neuroendocrine carcinoma. Recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation, however, its efficacy in urinary tract small cell carcinoma is not well established. This study examines immunohistochemical expression of INSM1 on whole tissue sections of urinary tract small cell neuroendocrine carcinoma and compares INSM1 expression with established neuroendocrine markers. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed on 32 cases of small cell neuroendocrine carcinoma of the bladder. Staining was scored for intensity (0: no staining; 1: weak; 2: moderate; 3: strong) and proportion of cells stained (0: 0%; 1: >0% to ≤25%; 2: >25% to ≤50%; 3: >50% to ≤75%; 4: >75% to 100%). INSM1 was positive (intensity 1 to 3 or proportion 1 to 4) in 87% (28/32) of cases (20 with intensity 2 to 3, 17 with proportion 3 to 4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary tract. However, this study suggests that optimal utilization of INSM1 would be inclusion in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases.

BackgroundNeoadjuvant chemotherapy (NACT) is an important treatment option for patients with ovarian cancer. Although intravenous NACT can improve optimal resection rates and decrease surgical morbidity and mortality, these advantages do not translate into a survival benefit. Ovarian carcinoma is mainly confined to the peritoneal cavity, which makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Our previous study showed that HIPEC could be used in the neoadjuvant setting, which was named neoadjuvant HIPEC (NHIPEC). Since hyperthermia is an excellent chemosensitiser, we hypothesised that the combination of NHIPEC and intravenous NACT could show superior efficacy to intravenous NACT alone.MethodsThis study is a single-centre, open-label, randomised (1:1 allocation ratio) phase 2 trial. A total of 80 patients will be randomly assigned into an experimental group (NHIPEC+intravenous NACT) or a control group (intravenous NACT). Patients in the experimental group will receive NHIPEC following laparoscopic evaluation, and four tubes will be placed via the laparoscopic ports, which will be used to administer NHIPEC. Then, perfusion with docetaxel (60–75 mg/m2) will be performed (43°C for 60 min, Day 0) followed by cisplatin (75 mg/m2, Day 1) infusion (43°C for 60 min) 24 hours later. After NHIPEC, two cycles of intravenous NACT will be given. Patients in the control group will receive three cycles of intravenous NACT. The primary endpoint is the proportion of patients who achieve a Chemotherapy Response Score (CRS) of 3 according to the CRS system. The secondary endpoints include progression-free survival, overall survival and the rates of complete resection and NHIPEC-related adverse events.Ethics approval and disseminationThis study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital (approval number: 2020-ky-050). Results will be submitted to peer-reviewed journals and presented at national and international conferences.Trial registration numberChiCTR2000038173.

Industrial thiocyanate (SCN

Introduction: Dysregulation of spinal cord development can lead to serious neuronal damage and dysfunction, causing significant health problems in newborns. MiRNA-138 appears to be crucial for proliferation, differentiation, and apoptosis of cells. However, the regulation of miRNA-138 and downstream molecules in embryonic spinal cord development remain elusive. The aim of this experiment is to determine whether overexpression of miRNA-138 or RNA interference (RNAi) can regulate the development of spinal cord in fetal rats. Methods: Two plasmid vectors including pLenti-III-mico-GFP (miRNA-138 open reading frame [ORF]) and pLenti-III-miR-Off (miRNA-138 short hairpin) were constructed and injected into the tail vein of rats on the 14th day of pregnancy. Hematoxylin-eosin (HE) staining was used to observe the cell morphology. QRT-PCR, Western blot, and immunostaining confirmed the regulatory relationship between miRNA-138 and downstream molecules sonic hedgehog (Shh). Results: Overexpression of miRNA-138 increased neuron regeneration significantly and decreased neuronal apoptosis when compared with the control. Silencing of miRNA-138 increased neuronal apoptosis and spinal cord atrophy significantly. Furthermore, miRNA-138 ORF treatment effectively increased the expression level of miRNA-138 and also upregulated the level of Shh. Comparatively, knockdown of miRNA-138 downregulated Shh levels in myelodysplastic regions. Conclusion: These findings indicated that miRNA-138 overexpression could protect the spinal cord development of fetal rats, and the underlying mechanisms were associated with Shh expression. The present study provides a novel strategy to promote the molecular mechanism of embryonic spinal cord development.