Copper-Catalyzed Enantioconvergent Radical C(sp3)-N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions.

The enantioconvergent C(sp3)-N cross-coupling of racemic alkyl halides with (hetero)aromatic amines represents an ideal means to afford enantioenriched N-alkyl (hetero)aromatic amines yet has remained unexplored due to the catalyst poisoning specifically for strong-coordinating heteroaromatic amines. Here, we demonstrate a copper-catalyzed enantioconvergent radical C(sp3)-N cross-coupling of activated racemic alkyl halides with (hetero)aromatic amines under ambient conditions. The key to success is the judicious selection of appropriate multidentate anionic ligands through readily fine-tuning both electronic and steric properties for the formation of a stable and rigid chelating Cu complex. Thus, this kind of ligand could not only enhance the reducing capability of a copper catalyst to provide an enantioconvergent radical pathway but also avoid the coordination with other coordinating heteroatoms, thereby overcoming catalyst poisoning and/or chiral ligand displacement. This protocol covers a wide range of coupling partners (89 examples for activated racemic secondary/tertiary alkyl bromides/chlorides and (hetero)aromatic amines) with high functional group compatibility. When allied with follow-up transformations, it provides a highly flexible platform to access synthetically useful enantioenriched amine building blocks.

Review and Thinking on Forensic Pathological Changes of Coronavirus-Infected Diseases.

Since the beginning of this century, three types of coronavirus have widely transmitted and caused severe diseases and deaths, which strongly indicates that severe infectious diseases caused by coronavirus infection are not accidental events. Coronavirus-infected diseases are mainly manifested by respiratory symptoms, with multiple organ dysfunctions. Precisely investigating the pathological process, characteristics and pathogenesis of coronavirus-infected diseases will be beneficial for us to understand clinical manifestations and provide targeted suggestions on prophylaxis and treatment. This paper briefly reviews the pathological findings of three known coronavirus-infected diseases, and attempts to construct the pathological spectrum of coronavirus-infected diseases, aiming to provide reference and thinking for autopsy, histopathological examination and animal infection model study of coronavirus-infected diseases.

Thermal transport properties of monolayer MoSe2 with defects.

Two-dimensional (2D) molybdenum diselenide (MoSe2) as one of the ultrathin transition metal dichalcogenides (TMDs) has attracted considerable attention because of its potential applications in thermoelectric and nano-electronic devices. Here, the thermal conductivity of monolayer MoSe2 and its responses to simulated size and defects are studied by nonequilibrium molecular dynamics simulations. With the increase of sample length, the thermal conductivity of monolayer MoSe2 nanoribbons exhibits an enhancement whereas it is insensitive to the width. At room temperature, the thermal conductivities of monolayer MoSe2 along armchair and zigzag directions are 17.758 and 18.932 W (m K)-1, respectively, which are consistent with previous results. The impact of defects on thermal conductivity has also been studied by varying the concentration of the vacancy from 0.1% to 0.5%. The results show that an increase of the defect concentration will greatly suppress the thermal conductivity. The 0.5% defect concentration with a Mo vacancy can result in a thermal conductivity reduction of ∼43%. Such a study would provide a good insight into the tunable thermal transport for potential applications of not only monolayer MoSe2, but also many other TMDs.

First-principles calculations of thermal transport properties in MoS2/MoSe2 bilayer heterostructure.

Bilayer transition metal dichalcogenide heterostructures obtained by vertical stacking have attracted considerable attention because of their potential applications in thermoelectric and optoelectronics devices. The thermal transport behavior plays a pivotal role in assessing their functional performance. Here, we systematically investigate the thermal transport properties of the MoS2/MoSe2 bilayer heterostructure (MoS2/MoSe2-BH) by combining first-principles calculations and Boltzmann transport theory (BTE). The results show that the thermal conductivity of MoS2/MoSe2-BH at room temperature is 25.39 W m-1 K-1, which is in-between those of monolayer MoSe2 and MoS2. According to our calculated orbital-resolved phonon dispersion curves, Grüneisen parameters, phonon group velocity and relaxation time, we find that the acoustic and low-frequency optical branches below 172.65 cm-1 have strong coupling and contribute mainly to the lattice thermal conductivity. Compared with free standing monolayer MoS2 and MoSe2, the lattice thermal conductivity of MoS2/MoSe2-BH is influenced by the weak van der Waals interlayer interactions.

Difference in vaginal microecology, local immunity and HPV infection among childbearing-age women with different degrees of cervical lesions in Inner Mongolia.

BACKGROUND: This study aims to investigate the difference in vaginal microecology, local immunity and HPV infection among childbearing-age women with different degrees of cervical lesions. METHODS: A total of 432 patients were included in this study. Among these patients, 136 patients had LSIL, 263 patients had HSIL and 33 patients had CSCC. These patients were assigned as the research groups. In addition, 100 healthy females were enrolled and assigned as the control group. RESULTS: The microbiological indexes of vaginal secretions were evaluated. Furthermore, the concentrations of SIgA, IgG, IL-2 and IL-10 in vaginal lavage fluid, as well as the presence of HPV, mycoplasma and Chlamydia in cervical secretions, were detected. The results is that: (1) Differences in evaluation indexes of vaginal microecology among all research groups and the control group were statistically significant (P < 0.0001). As the degree of cervical lesions increased, the number of Lactobacillus decreased, and there was an increase in prevalence of bacterial imbalance, and the diversity, density and normal proportion of bacteria was reduced. Furthermore, the incidence of HPV, trichomonads, clue cell and Chlamydia infection increased. Moreover, the positive rate of H2O2 decreased, while the positive rates of SNa and GADP increased. (2) Differences in the ratio of IL-2 and IL-10 in the female genital tract among all research groups and the control group were statistically significant (P < 0.0001). CONCLUSIONS: As the degree of cervical lesions increased, IL-2 decreased, IL-10 increased and IL-2/IL-10 decreased, while SIgA and IgG were elevated. The reduction of dominant Lactobacillus in the vagina, impairment of H2O2 function, flora ratio imbalance, pathogen infections, reduction in IL-2/IL-10 ratio, and changes in SIgA and IgG levels could all be potential factors that influenced the pathogenicity of HPV infection and the occurrence and development of cervical lesions.

Correlation between replicative senescence of endometrial gland epithelial cells in shedding and non-shedding endometria and endometriosis cyst during menstruation.

To investigate correlation between abnormal replicative senescence of endometrial gland epithelial cells (EGECs) in shedding and non-shedding endometria and endometriosis cyst during menstruation. Musashi-1 expression, ß-catenin expression, and EGECs ultrastructure in shedding and non-shedding endometrium when menstruation were observed through real-time PCR and transmission electron microscopy technologies. (1) Musashi-1 and ß-catenin exhibited a high expression in shedding and non-shedding endometria in experimental group, showing a positive correlation between each other; and were significantly higher than that in control group. However; there was no correlation between these two in control group. (2) Transmission electron microscopy results: In experimental group, organelles in EGECs in shedding endometrium obtained were abundant on the first day of menstruation, nuclei were irregular, double nucleoli could be observed, and chromatin was rich. Furthermore, morphology of EGECs in non-shedding endometrium was irregular, organelles were abundant, basement membrane was irregular with abnormal curvature, and a large amount of collagenic fibers were found in intercellular spaces. On the fifth day of menstruation, the cilia and microvilli on secretory cells in endometrium increased and prolongated, and organelles became extremely rich. EGECs have potentials of division, proliferation, invasion and migration; and is associated with formation of endometriosis cysts.

A novel mutation in the STK11 gene causes heritable Peutz-Jeghers syndrome - a case report.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. STK11 has been identified as a causative gene for this disease. CASE PRESENTATION: Herein we report a Chinese Han kindred with PJS. Onset for the PJS signs in three of the patients was rarely as early as at birth. We identified a novel heterozygous mutation (c.440_441delGT, p.Arg147Leufs*15) in the gene STK11, causing a short frameshift followed by a deletion of 63% of the amino acids in the STK protein. This mutation co-segregated with the PJS phenotype, and was absent in two hundred of unrelated ethnicity-matched controls. The mutation led to expression decrease of unaffected STK11 protein in patients than in controls, as well in PJ polyps than in circulating leucocytes from the patients. Phosphorylation levels of the downstream kinase AMPKα altered according with the expression of STK11. These results indicated the possibility that haploinsufficiency and epigenetic reduction of STK11 contributed to the pathogenesis of the disease. CONCLUSION: This study identifies a novel mutation in the pathogenic gene STK11 leading to PJS.

Effect of acupuncture on tic disorder: a randomized controlled clinical trial based on energy metabolomics and infrared thermography.

BACKGROUND: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. METHODS: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. DISCUSSION: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).

N-cadherin-dependent neuron-neuron interaction is required for the maintenance of activity-induced dendrite growth.

Formation of neural circuits depends on stable contacts between neuronal processes, mediated by interaction of cell adhesion molecules, including N-cadherin. In the present study, we found that activity-dependent dendrite arborization specifically requires N-cadherin-mediated extracellular neuron-neuron interaction, because the enhancement did not occur for neurons cultured in isolation or plated on an astrocyte monolayer and was abolished by a recombinant soluble N-cadherin ectodomain. Furthermore, depolarization elevated the level of membrane-associated cadherin/catenin complexes and surface N-cadherin. Importantly, surface N-cadherin elevation is specifically required for the maintenance of nascent dendrite arbors. Through loss- and gain-of-function approaches, we showed that N-cadherin-mediated dendrite growth requires association of the cadherin/catenin complex with the actin cytoskeleton. In summary, these results identify a previously unexplored and specific function for activity-induced, N-cadherin-mediated neuron-neuron contacts in the maintenance of dendrite arbors.

Intragastric fish bones migrate into the liver: A case report.

BACKGROUND: A foreign body in the digestive tract is a common disease in the clinic. However, it is rare for a foreign body to migrate into the liver. Most patients are diagnosed before or after perforation of the digestive tract. Laparoscopic removal of intrahepatic foreign bodies is an effective treatment method. CASE SUMMARY: A 55-year-old male patient was admitted to the hospital due to fever for 3 d, in addition to pain and discomfort in the right side of his waist. After admission, abdominal computed tomography showed a foreign body in the liver, and gastroscopy did not indicate obvious erosion or ulcers. The patient then underwent laparoscopic surgery. During the operation, an abscess was seen near the gastric antrum and between the caudate lobes of the liver. It was approximately 30 mm × 31 mm × 23 mm in size. The abscess was cut open, and a fish bone was found inside. The fish bone had penetrated the liver and was successfully removed. It was confirmed that the fish bone migrated from the stomach to the liver. CONCLUSION: Although intrahepatic foreign bodies are rare, they should be diagnosed and treated as early as possible to avoid serious complications such as intrahepatic abscess, which may lead to liver resection and even life-threatening events.

Aqueous two-phase systems coupled with chemometrics-enhanced HPLC-DAD for simultaneous extraction and determination of flavonoids in honey.

In this study, an accurate, rapid, green, and environment friendly method for the extraction and quantitative analysis of flavonoids in honey was established by using the aqueous two-phase extraction combined with the chemometrics-assisted HPLC-DAD. The first purpose of this study was to extract seven flavonoids in five different types of honey using alcohol/salt aqueous two-phase system (ATPS). The system with 2.82 mL sodium citrate (30%), 1.58 mL water, and 3.10 mL isopropanol, showed the highest flavonoids extraction yields in the top phase (87.66-101.50%). Additionally, the three-way array of honey samples based on HPLC-DAD was decomposed mathematically by the alternating trilinear decomposition (ATLD) algorithm to obtain reasonable chromatograms, spectra, and concentration profiles for each analyte. Compared with the traditional solid-phase extraction method, the ATPS-ATLD-based method showed satisfactory spiked recoveries, lower limit of detection, and higher sensitivity, further verifying its accuracy and stability.

Discrimination of the harvesting season of green tea by alcohol/salt-based aqueous two-phase systems combined with chemometric analysis.

The flavor and aroma quality of green tea are closely related to the harvest season. The aim of this study was to identify the harvesting season of green tea by alcohol/salt-based aqueous two-phase system (ATPS) combined with chemometric analysis. In this paper, the single factor experiments (SFM) and response surface methodology (RSM) optimization were designed to investigate and select the optimal ATPS. A total of 180 green tea samples were studied in this work, including 86 spring tea and 94 autumn tea. After the active components in green tea samples were extracted by the optimal ethanol/(NH4)2SO4 ATPS, the qualitative and quantitative analysis was realized based on HPLC-DAD combined with alternating trilinear decomposition-assisted multivariate curve resolution (ATLD-MCR) algorithm, with satisfactory spiked recoveries (86.00 %-112.45 %). The quantitative results obtained from ATLD-MCR model were subjected to chemometric pattern recognition analysis. The constructed partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) models showed better results than the principal component analysis (PCA) model, and the R2Xcum values (>0.835) and R2Ycum (>0.937) were close to 1, the Q2cum values were greater than 0.75 (>0.933), and the differences between R2Ycum and Q2cum were not larger than 0.2, indicating excellent cross-validation prediction performance of the models. Furthermore, the classification results based on the hierarchical clustering analysis (HCA) were consistent with the PCA, PLS-DA and OPLS-DA results, establishing a good correlation between tea active components and the harvesting seasons of green tea. Overall, the combination of ATPS and chemometric methods is accurate, sensitive, fast and reliable for the qualitative and quantitative determination of tea active components, providing guidance for the quality control of green tea.

Bioinformatics analysis of SOXF family genes reveals potential regulatory mechanism and diagnostic value in cancers.

Background: SOXF family genes (SOX7, SOX17, SOX18) have been reported to involved in tumorigenesis and development in previous articles, separately. But data sources, analysis contents and criteria are not same. Here, we focused on SOXF genes to analyze the regulatory mechanisms and diagnostic value at the same standards. Methods: This study analyzed functions, expressions, methylations, and mutations of SOXF genes through public databases including Metascape, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, Tumor IMmune Estimation Resource (TIMER), and Kaplan-Meier Plotter. TIMER applies a deconvolution method to infer the abundance of tumor-infiltrating immune cells (TIICs) from gene expression profiles. Metascape combines several biological functions and over 40 independent knowledge bases within one integrated portal. GEPIA analyses RNA sequencing expression data from the The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. The cBioPortal visualizes and analyses genetic data from cancer studies. Results: This study found that SOXF genes had low expressions in multiple types of cancer, such as lung cancer and breast cancer (ANOVA differential methods, |log2FC| cutoff: 1, q value cutoff: 0.01). The lung adenocarcinoma (LUAD) patients with high expression of SOX7 [HR =0.72 (0.61-0.85), logrank P=8.1e-05) and SOX17 [HR =0.54 (0.45-0.64), logrank P=1.7e-12] had a higher overall survival (OS) rate. Expression of SOX7 was significantly related to the copy number variation (CNV) (P=3.02e-8) and promoter methylation level (P=5.33e-14), while SOX17 was only related to the promoter methylation level (P=3.32e-12). The expression of SOXF genes was positively correlated with CD4+ T cell infiltration (SOX7: P=8.32e-07, SOX17: P=4.93e-06, SOX18: P=1.61e-11). The AUC for cg07660671 site of SOX7, cg15377283 site of SOX17, and cg24199599 site of SOX18 in distinguishing between normal and tumor in LUAD, intestinal cancer, and breast cancer reached 0.9. SOXF genes were mainly involved in transcriptional regulation, and the Wnt signaling pathway and low expression of SOXF genes in tumor tissue had a strong negative correlation with tumor hypoxia (correlation: -0.35, P≤0.001). Conclusions: This study implied that the expression of SOX7 and SOX17 are potential prognosis markers for patients with Lung cancer and the SOXF genes methylation is potential biomarkers for pan-cancer screening. The SOX7 and SOX17 might modulate the Wnt signaling pathway and the expression of SOXF family genes was significantly negatively correlated with tumor hypoxia.

[Identification and analysis of vaginal lactobacilli in patients with bacterial vaginosis patients and healthy women in nationality of Pastoral area].

OBJECTIVE: To identify and analyze the species of vaginal lactobacilli between patients with bacterial vaginosis (BV) and healthy women at childbearing age in Inner Mongolia. METHODS: From Jun. 2008 to Dec. 2008, 203 Mongolian healthy women, 74 Han healthy women and 102 Mongolian patients with BV from 3 pastoral areas were enrolled in this study. Isolation and culture of lactobacilli from vaginal wall were performed by modified culture medium. DNA of lactobacilli were extracted and sequenced. H2O2 were detected by TMB-HRP-MRS. RESULTS: (1) The rate of lactobacilli identification were 76.8% (156/203) in Mongolian healthy women and 21.6% (22/102) in Mongolian patients with BV, which reached statistical difference (P < 0.01). Lactobacilli identification in Han healthy women [82.4% (61/74)] did not show significant difference with that of Mongolian healthy women (P > 0.05). (2) The total of 193 strains and 11 species of Lactobacillus were detected in 203 Mongolian healthy women. Meanwhile, 22 strains and 4 species of Lactobacillus were found in 102 Mongolian BV cases. (3) The rate of H2O2 generating Lactobacilli was 27.3% (6/22) in Mongolian BV patients and 75.7% (56/74) in Mongolian healthy women, which showed statistical difference (P < 0.05). CONCLUSIONS: The rate of Lactobacillus was not related with the race of women in pastoral area in Inner Mongolian. The amount of lactobacilli and H2O2 generating Lactobacilli in the vagina of BV patients was remarkably lower than those of healthy women at childbearing age.

Oxytocin Regulates Synaptic Transmission in the Sensory Cortices in a Developmentally Dynamic Manner.

The development and stabilization of neuronal circuits are critical to proper brain function. Synapses are the building blocks of neural circuits. Here we examine the effects of the neuropeptide oxytocin on synaptic transmission in L2/3 pyramidal neurons of the barrel field of the primary somatosensory cortex (S1BF). We find that perfusion of oxytocin onto acute brain slices significantly increases the frequency of miniature excitatory postsynaptic currents (mEPSC) of S1BF L2/3 pyramidal neurons at P10 and P14, but reduces it at the later ages of P22 and P28; the transition occurs at around P18. Since oxytocin expression is itself regulated by sensory experience, we also examine whether the effects of oxytocin on excitatory synaptic transmission correlate with that of sensory experience. We find that, indeed, the effects of sensory experience and oxytocin on excitatory synaptic transmission of L2/3 pyramidal neurons both peak at around P14 and plateau around P18, suggesting that they regulate a specific form of synaptic plasticity in L2/3 pyramidal neurons, with a sensitive/critical period ending around P18. Consistently, oxytocin receptor (Oxtr) expression in glutamatergic neurons of the upper layers of the cerebral cortex peaks around P14. By P28, however, Oxtr expression becomes more prominent in GABAergic neurons, especially somatostatin (SST) neurons. At P28, oxytocin perfusion increases inhibitory synaptic transmission and reduces excitatory synaptic transmission, effects that result in a net reduction of neuronal excitation, in contrast to increased excitation at P14. Using oxytocin knockout mice and Oxtr conditional knockout mice, we show that loss-of-function of oxytocin affects baseline excitatory synaptic transmission, while Oxtr is required for oxytocin-induced changes in excitatory synaptic transmission, at both P14 and P28. Together, these results demonstrate that oxytocin has complex and dynamic functions in regulating synaptic transmission in cortical L2/3 pyramidal neurons. These findings add to existing knowledge of the function of oxytocin in regulating neural circuit development and plasticity.

CHNQD-00603 Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by the miR-452-3p-Mediated Autophagy Pathway.

Background: Periodontitis is a chronic and progressive disease accompanied by bone loss. It is still a challenge to restore the bone structure. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a decisive role in bone restoration and regeneration. Marine natural products (MNPs) have multiple biological activities, including anti-tumor and anti-inflammatory properties. However, the exploration of MNPs in osteogenesis is far from sufficient. Methods: We obtained a series of derivatives through structural optimization from 4-phenyl-3,4-dihydroquinolin-2(1H)-one alkaloid isolated from Scopulariopsis sp. Some preliminary cytological experiments showed that CHNQD-00603, obtained by adding a methoxy group to the position C3 and a hydroxyl group to the position C4 of 4-phenyl-3,4-dihydroquinolin-2(1H)-one, might promote the osteogenic differentiation of BMSCs. To further investigate the effects of CHNQD-00603 on BMSCs, we performed a CCK-8 assay and qRT-PCR, alkaline phosphatase staining (ALP), and alizarin red S staining to assess the cytotoxicity and the ability of osteogenic differentiation of CHNQD-00603. The autophagy level was assessed and validated by WB, qRT-PCR, and transmission electron microscopy. Then, 3-methyladenine (3-MA) was added to further examine the role of autophagy. Based on the expression of autophagy-related genes, we predicted and examined the potential miRNAs by bioinformatics. Results: CCK-8 assay showed that CHNQD-00603 at 1 µg/ml did not influence BMSCs activity. However, the proliferation rate decreased from the seventh day. qRT-PCR, ALP staining, ALP activity assay, and Alizarin red S staining showed that the best concentration of CHNQD-00603 to promote osteogenic differentiation was 1 µg/ml. Further investigations indicated that CHNQD-00603 activated autophagy, and the inhibition of autophagy by 3-MA attenuated CHNQD-00603-enhanced osteogenic differentiation. Subsequently, the findings from bioinformatics and qRT-PCR indicated that miR-452-3p might be a regulator of autophagy and osteogenesis. Furthermore, we transfected BMSCs with miR-452-3p NC and mimics separately to further determine the function of miR-452-3p. The data showed that the overexpression of miR-452-3p moderated the level of autophagy and osteogenic differentiation of CHNQD-00603-treated BMSCs. Conclusion: Our data suggested that CHNQD-00603 promoted the osteogenic differentiation of BMSCs by enhancing autophagy. Meanwhile, miR-452-3p played a regulatory role in this process.

Upregulation of XRN2 acts as an oncogene in oral squamous cell carcinoma and correlates with poor prognosis.

BACKGROUD: The 5'-3' exoribonuclease 2 (XRN2) has been reported involved in several tumors. However, the clinical significance and molecular mechanism of XRN2 in oral squamous cell carcinoma (OSCC) have not been elucidated. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to investigate the expression of XRN2 in OSCC and adjacent noncancerous tissues, which was further identified by western blot and GEPIA2 database analysis. Moreover, the relationship between XRN2 expression and the clinicopathological characteristics and prognosis of OSCC patients was evaluated. In addition, in vitro, the effects of XRN2 on OSCC cells were evaluated by Cell Counting Kit-8 (CCK8) assay, colony formation assay, apoptosis assay, wound healing assay, and transwell assays. RESULTS: XRN2 was overexpressed in 44 of 77 (57.1 %) OSCC tissues. High expression of XRN2 was significantly associated with tumor differentiation (P=0.003), pathological clinical stage (P=0.045), lymph node metastasis (P=0.041), and poor overall survival (P=0.0013). Furthermore, the multivariate analysis suggested that XRN2 expression(P=0.002) was determined as an independent prognostic factor for patients with OSCC. Additionally, with functional assays in vitro, we found that downregulation of XRN2 inhibited cell proliferation, migration, and invasion, while promoted apoptosis of OSCC cells. Furthermore, knockdown of XRN2 in OSCC cells could increase the expression of E-cadherin but reduce the expression of Vimentin, which changes the characteristic of epithelial-mesenchymal transition (EMT). CONCLUSION: XRN2 is significantly overexpressed in OSCC tissues and its upregulation was closely associated with poor prognosis of OSCC patients. XRN2 could be a useful prognostic biomarker and a potential therapeutic target for OSCC.

Patterns of endoscopy during COVID-19 pandemic: a global survey of interventional inflammatory bowel disease practice.

BACKGROUND/AIMS: Performance of diagnostic or therapeutic endoscopic procedures in inflammatory bowel disease (IBD) patients can be challenging during a viral pandemic; the main concerns being the safety and protection of patients and health care providers (HCP). The aim of this study is to identify endoscopic practice patterns and outcomes of IBD and coronavirus disease 19 (COVID-19) with a worldwide survey of HCP. METHODS: The 20-item survey questionnaire was sent to physician members of the American Society for Gastrointestinal Endoscopy Special Interest Group in Interventional IBD, Chinese IBD Society Endoscopy Interest Group, and the China Crohn's and Colitis Foundation. RESULTS: A total of 141 respondents submitted valid responses. Nighty-five respondents (67.9%) reported that at least 25% of their scheduled emergent endoscopic procedures were canceled or postponed during the pandemic. Fifty-six respondents (40.0%) have performed emergent endoscopy during the pandemic. A few respondents (9/140, 6.4%) estimated that more than 25% of their patients had worsened disease due to delayed or canceled emergent endoscopy procedures. More than 80% of respondents believed that personal protective equipment (PPE) for the endoscopy team, room sterilization, and pre-procedure screening of patients for COVID-19 were necessary. Out of 140 respondents, 16 (11.4%) reported that several of their patients had COVID-19. Eight clinicians (5.7%) reported that they or their endoscopy colleagues developed work-related COVID-19. CONCLUSIONS: Cancellation of elective and emergent endoscopy in IBD care during the pandemic was common. Few respondents reported that their patients' disease conditions worsened due to the cancellation of the endoscopy procedure. Most respondents voiced the need for proper PPE during the procedure regardless of patients' COVID-19 status and screening the patients for COVID-19.

On-chip rapid drug screening of leukemia cells by acoustic streaming.

Rapid and personalized single-cell drug screening testing plays an essential role in acute myeloid leukemia drug combination chemotherapy. Conventional chemotherapeutic drug screening is a time-consuming process because of the natural resistance of cell membranes to drugs, and there are still great challenges related to using technologies that change membrane permeability such as sonoporation in high-throughput and precise single-cell drug screening with minimal damage. In this study, we proposed an acoustic streaming-based non-invasive single-cell drug screening acceleration method, using high-frequency acoustic waves (>10 MHz) in a concentration gradient microfluidic device. High-frequency acoustics leads to increased difficulties in inducing cavitation and generates acoustic streaming around each single cell. Therefore, single-cell membrane permeability is non-invasively increased by the acoustic pressure and acoustic streaming-induced shear force, which significantly improves the drug uptake process. In the experiment, single human myeloid leukemia mononuclear (THP-1) cells were trapped by triangle cell traps in concentration gradient chips with different cytarabine (Ara-C) drug concentrations. Due to this dual acoustic effect, the drugs affect cell viability in less than 30 min, which is faster than traditional methods (usually more than 24 h). This dual acoustic effect-based drug delivery strategy has the potential to save time and reduce the cost of drug screening, when combined with microfluidic technology for multi-concentration drug screening. This strategy offers enormous potential for use in multiple drug screening or efficient drug combination screening in individualized/personalized treatments, which can greatly improve efficiency and reduce costs.

Serum tumor markers for the prediction of concordance between genomic profiles from liquid and tissue biopsy in patients with advanced lung adenocarcinoma.

BACKGROUND: The concordance between mutations detected from plasma and tissue is critical for treatment choices of patients with advanced lung adenocarcinoma. METHODS: We prospectively analyzed the association of the serum tumor markers with the concordance between blood and tissue genomic profiles from 185 patients with advanced lung adenocarcinoma. The concordance was defined according to 3 criteria. Class 1 included all targetable driver mutations in 8 genes; class 2 included class 1 mutations plus mutations in KRAS, STK11, and TP53; class 3 included class 2 mutations plus tumor mutation burden (TMB) status. RESULTS: Collectively, 150 out of 185 patients had mutations in both tissue and plasma samples, while one patient was mutation-negative for both, resulting a concordance of 81.6%. The concordance rate for class 1 mutations was 80%, and 65% and 69% for class 2 and class 3, respectively. Carbohydrate antigen 19-9 (CA19-9) or cytokeratin 19 (CYFRA21-1) levels higher than the normal upper limit predicted the concordance of tissue and blood results in class 1 (P=0.005, P=0.011), class 2 (P=0.011, P<0.001), and class 3 (P=0.001, P=0.014). In class 1, the cutoff values of CA19-9 were 30, 36, and 284 U/mL to reach the concordance thresholds of 90%, 95%, and 100%, respectively (P=0.032, P=0.003, P=0.043). For CYFRA21-1, the cutoff values were 6, 18, and 52 µg/L (P=0.005, P=0.051, P=0.354). In class 2, the cutoff values for CYFRA21-1 were 18, 22, and 52 µg/L (P=0.001, P=0.001, P=0.052). In class 3, the cutoff values for CA19-9 were 36, 39, and 85 U/mL (P=0.003, P=0.001, P=0.008). For CYFRA21-1, the cutoff values were 22, 52, and 52 µg/L (P=0.900, P>0.99, P>0.99). When the sum score for 4 serum tumor markers was greater than 35, both class 1, class 2, and class 3 reached a predictive threshold of 90%. CONCLUSIONS: Serum tumor markers can be used as easy and practical clinical predictors of concordance in mutation profiles between blood and tissue samples from patients with advanced lung adenocarcinoma.