Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor.

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

Isolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice.

We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin1. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4.

Folate deficiency promotes cervical squamous carcinoma SiHa cells progression by targeting miR-375/FZD4/ß-catenin signaling.

Epidemiological studies suggest an association between folate deficiency (FD) and cervical squamous cell carcinoma (SCC) progression. However, the underlying mechanism is unclear. Our study showed that FD-driven downregulation of miR-375 promoted proliferation of SCC SiHa cells and progression of xenograft tumors developed from SiHa; however, the exact mechanism of this process remained unclear. The current study aimed to elucidate the underlying mechanisms by which FD promotes the progression of SiHa cells by downregulating miR-375 expression. The results showed that miR-375 acted as a suppressor of SCC and inhibited the proliferation, migration, and invasion of SiHa cells. The FZD4 gene was identified as a target gene of miR-375, which can reverse the anti-onco effect of miR-375 and promote the proliferation and migration of SiHa cells. Furthermore, the regulatory effects of miR-375 and FZD4 on SiHa cells may be achieved by activating the ß-catenin signaling pathway. Moreover, FD may regulate the expression of miR-375 by regulating its DNA methylation level in the promoter region. In conclusion, our study reveals that FD regulates the miR-375/FZD4 axis by increasing the methylation of the miR-375 promoter, thereby activating ß-catenin signaling to promote SiHa cells progression. This study may provide new insights into the role of folic acid in the prevention and treatment of SCC.

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

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

Role of Prognostic Marker PRR11 in Immune Infiltration for Facilitating Lung Adenocarcinoma Progression.

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.

Secondary hyperperfusion injury following surgical evacuation for acute isolated epidural hematoma with concurrent cerebral herniation.

Objective: Hemispherical cerebral swelling or even encephalocele after head trauma is a common complication and has been well elucidated previously. However, few studies have focused on the secondary brain hemorrhage or edema occurring regionally but not hemispherically in the cerebral parenchyma just underneath the surgically evacuated hematoma during or at a very early stage post-surgery. Methods: In order to explore the characteristics, hemodynamic mechanisms, and optimized treatment of a novel peri-operative complication in patients with isolated acute epidural hematoma (EDH), clinical data of 157 patients with acute-isolated EDH who underwent surgical intervention were reviewed retrospectively. Risk factors including demographic characteristics, admission Glasgow Coma Score, preoperative hemorrhagic shock, anatomical location, and morphological parameters of epidural hematoma, as well as the extent and duration of cerebral herniation on physical examination and radiographic evaluation were considered. Results: It suggested that secondary intracerebral hemorrhage or edema was determined in 12 of 157 patients within 6 h after surgical hematoma evacuation. It was featured by remarkable, regional hyperperfusion on the computed tomography (CT) perfusion images and associated with a relatively poor neurological prognosis. In addition to concurrent cerebral herniation, which was found to be a prerequisite for the development of this novel complication, multivariate logistic regression further showed four independent risk factors contributing to this type of secondary hyperperfusion injury: cerebral herniation that lasted longer than 2 h, hematomas that were located in the non-temporal region, hematomas that were thicker than 40 mm, and hematomas occurring in pediatric and elderly patients. Conclusion: Secondary brain hemorrhage or edema occurring within an early perioperative period of hematoma-evacuation craniotomy for acute-isolated EDH is a rarely described hyperperfusion injury. Because it plays an important prognostic influence on patients' neurological recovery, optimized treatment should be given to block or reduce the consequent secondary brain injuries.

Effects of Three Essential Oil Fumigation Treatments on the Postharvest Control of Botrytis cinerea and Their Efficacy as Preservatives of Cherry Tomatoes.

Cherry tomatoes (Solanum lycopersicum) are becoming increasingly popular due to their nutrition and delicious flavor. However, cherry tomatoes are highly perishable and susceptible to various pathogenic microorganisms after harvest, such as Botrytis cinerea. In the pretest experiment, we screened out three kinds of plant essential oils (EOs) (Torreya grandis oil, Eriobotrya japonica oil, and Citrus medica oil) that have strong fungicidal activity on B. cinerea from cherry tomatoes. To further evaluate the postharvest preservation application prospect of these three oils for cherry tomatoes, the oils were extracted from different parts of three plants by hydrodistillation, and their chemical constituents were analyzed by gas chromatography-mass spectrometry. The main representative components of T. grandis oil, E. japonica oil, and C. medica oil were δ-cadinene (11.76%), transnerolidol (9.70%), and 5,7-dimethoxycoumarin (23.22%), respectively. These three EOs effectively inhibited the mycelial growth of B. cinerea in vitro, with EC50 values of 81.672, 144.046, and 221.500 µl/liter, respectively. Compared with the blank control and other oil treatments, the T. grandis oil (at a concentration of 200 µl/liter) fumigation treatment was more effective at inhibiting the growth rate of the pathogen. In addition, the phenolic content and phenylalanine ammonia lyase, ß-1,3-glucanase, chitinase, and peroxidase activities of tomatoes significantly increased on the seventh day due to the T. grandis oil treatment. The present study shows that these three oils with high extraction rates have preservation potential for cherry tomatoes. Among these three EOs, T. grandis oil can be used to further develop preservative products as a fumigant.

Analysis of the Risk Factors for Massive Hemorrhage in Pernicious Placenta Previa and Evaluation of the Efficacy of Internal Iliac Artery Balloon Occlusion.

Objective: To investigate the risk factors of intraoperative massive hemorrhage in patients with pernicious placenta previa (PPP) and analyze the value of bilateral internal iliac artery balloon occlusion in Cesarean section for these patients. Methods: The clinical data of 134 patients with PPP admitted to the Second Hospital of Shanxi Medical University from January 2012 to January 2019 were analyzed. A logistic regression analysis was used to analyze the risk factors for intraoperative massive hemorrhage in PPP. The study subjects were divided into the intervention group (38 cases) and the routine group (96 cases) according to whether bilateral internal iliac artery balloon occlusion was conducted during the operation. The differences in some clinical indicators were compared between the two groups. Results: The risk factors for intraoperative massive hemorrhage in PPP were age ≥35 years, gestational age ≥34 weeks, complete placenta previa, and the presence of placenta accreta. The differences in the operation time, postoperative transfer to the intensive care unit, postoperative length of the hospital stay, and neonatal weight and score were not statistically significant between the intervention group and the routine group (P > 0.05 for all). While the intraoperative blood loss and the transfusion volume in the intervention group were lower than in the routine group, the hospitalization cost was higher in the former than in the latter, and the differences were statistically significant (P < 0.05 for all). Moreover, there was no case of hysterectomy in the intervention group, while there were two cases of hysterectomies in the routine group. Conclusion: The risk factors for intraoperative massive hemorrhage in PPP were age ≥35 years, gestational age ≥34 weeks, complete placenta previa, and the presence of placenta accreta. Internal iliac artery balloon occlusion during PPP could reduce intraoperative blood loss and the hysterectomy rate.

Regulating substrate preference of phosphatase by reshaping the "cap domain" for multi-enzymatic biosynthesis of high-purity monosaccharides.

Phosphatases are a class of enzymes catalyzing the cleavage of monophosphate ester bonds from the phosphorylated substrates. They have important applications in construction of in vitro multi-enzymatic system for monosaccharides. However, the enzymes generally show substrate ambiguity, which has become a bottleneck for efficient biosynthesis of target products with high purity. In this study, semirational design was performed on phosphatase from Thermosipho atlanticus (Ta-PST). The hotspot amino acid residues forming a "cap domain" were identified and selected for saturation mutagenesis. The mutant F179T and F179M showed improved substrate preference toward fructose-6-phosphate and mannose-6-phosphate, respectively. Coupling with other enzymes involved in the multi-enzymatic system under optimized conditions, the application of F179T led to fructose yield of 80% from 10 g/L maltodextrin and the ratio between the target product and by-product glucose was increased from 2:1 to 19:1. On the other hand, the application of F179M led to mannose yield of 59% with ratio of mannose to the by-products glucose and fructose increased from 1:1:1 to 14:2:1. Moreover, the molecular understanding of the beneficial substitution was gained by structural analysis and molecular dynamic simulations, giving important guidance to regulate the enzyme's substrate preference.

A new metal complex-templated silver iodobismuthate exhibiting photocurrent response and photocatalytic property.

An organic-inorganic hybrid silver iodobismuthate characteristic of the infrequent [Ag2BiI6L2] cluster (L = I or I3) and with a unique Ag/Bi molar ratio (2/1), namely, [Zn(bipy)3]2Ag2BiI6(I)1.355(I3)1.645 (bipy = 2,2'-bipyridine; 1), was solvothermally synthesized, and structurally, optically, and theoretically studied. Intriguingly, compound 1 exhibited semiconductor behavior with an optical band gap of 2.33 eV, which endowed it with excellent photoelectric and photocatalytic properties. Electronic structure calculations further revealed that the relative separate conduction band (CB) and valence band (VB) in compound 1 may be responsible for the good optical activity. This study also includes the Hirshfeld surface analyses, thermogravimetric measurements and X-ray photoelectron spectroscopy (XPS) characterization.

Potential HIV latency-reversing agents with STAT1-activating activity from the leaves of Wikstroemia chamaedaphne.

Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.

Synthesis and Growth Mechanism of SiS2 Rods.

The SiS2 rods exhibit a significant anisotropy property applied in a special field such as in the one of all-solid-state lithium-ion batteries and so on. In this work, the orthorhombic SiS2 rods with high chemical/phase purity were prepared by an elemental method, either through a boiling or a steaming process, at 1023-1073 K for 3 h and under the saturated S-vapor pressure (2.57-3.83 MPa) in a closed sealed-tube system. The composition, crystal structure, morphology, and growth mechanism were investigated. Results showed that the growth orientation of SiS2 along the <0 0 1> is intrinsically governed by the crystal structure motif. It could exist in both processes and the latter tends to show in macroscopic morphology. Using the pressure-temperature diagram, structure refinement, pole figures, image analyses, and so forth, factors influencing the purity and growth of SiS2 rods were concluded from the thermodynamics and kinetics viewpoints.

Consideration in Randomized Placebo-Controlled Trial on Neck Pain to Avoid the Placebo Effect in Analgesic Action.

Background: In neck pain treatment, many therapies are focused on etiology, while it is well-known that placebo analgesia is also present in these therapies. The specific efficacy for etiology may be underestimated by ignoring their actual placebo effect. In this study, a logistic regression analysis is used to explore the risk factors causing different placebo responses in patients with neck pain among two RCTs. The probability of the placebo effect is predicted based on these risk factors. Methods: Trial A and Trial B were similarly designed, randomized, double-/single-blind, placebo-controlled trials in patients treating neck pain with Qishe pill or Shi-style manipulation. Both studies set a placebo pill twice a day or traction for every other day as control. For further analyses on the placebo effect in neck pain management, logistic regression was used to assess subgroup-placebo interactions. The odds ratio assessed a significant influence on the placebo effect. Results: In this pooled analysis, the total number of patients recruited for these two studies was 284, of which 162 patients received placebo treatment (placebo drug or traction for every other day). No statistically significant differences are found at baseline between the participants with placebo effect and non-placebo effect in the gender, age, and disease duration except in VAS and NDI at the initial time. There are numerically more patients with placebo effect in the shorter disease duration subgroup (< 4 months [76%]), higher initial VAS subgroup (>60 mm [90%]), and worse initial NDI subgroup (>24 [72%]) compared with the gender and age subgroup. An ROC curve is established to assess the model-data fit, which shows an area under the curve of 0.755 and a 95% confidence interval of 0.677-0.830. Participants who show placebo effect after 2 weeks have significantly lower VAS scores after 4 weeks, while there is no significant difference in NDI improvement between the two groups after 4 weeks. Conclusion: Neck pain patients with shorter disease duration are more likely to overscore their pain severity, because of their less experience in pain perception, tolerance, and analgesia expectation.

Effect of Alteplase Thrombolysis on Coagulation Function and Nerve Function of Patients with Ischemic Stroke.

Objective: To investigate the effects of alteplase thrombolysis on coagulation function and nerve function of patients with ischemic stroke. Methods: 76 cases with ischemic stroke receiving thrombolytic therapy in Cangzhou Central Hospital from November 2018 to November 2019 were recruited. They were assigned via the random number table method at a ratio of 1 : 1 to receive alteplase thrombolysis either within 3h after the onset (observation group) or within 3-4.5 h after the onset (control group), followed by aspirin administration after no bleeding in cranial computed tomography (CT). Outcome measures included plasma fibrinogen (FIB), activated partial prothrombin time (APTT), platelet (PLT) levels, the National Institute of Health stroke scale (NIHSS) score, and adverse events. Results: Alteplase thrombolysis within 3 h was associated with better prothrombin time (PT), APTT, FIB, and PLT levels versus thrombolysis within 3-4.5 h (P < 0.05). Thrombolysis within 3 h showed significantly lower NIHSS scores versus within 3-4.5 h (P < 0.05). The two groups showed a similar incidence of adverse events (X 2 = 2.963, P=0.615). Conclusion: Alteplase thrombolysis showed benefits in mitigating the coagulation function and nerve function damage of patients with ischemic stroke, especially within 3 hours after the onset, with a high safety profile.

[Effects of heterogeneous habitats on the coexistence of aquatic ecotype Alternanthera philoxeroides and Paspalum paspaloides]. / 异质生境对水生型空心莲子草-åŒç©—é›€ç¨—å ±å­˜çš„å½±å“.

Species coexistence depends on the comprehensive effects of biological properties and habitat heterogeneity. Based on a large-scale field survey (21°-35° N), we compared the differences on morphological and stoichiometric characteristics between the invasive aquatic species Alternanthera philoxeroides and the native co-occurring species Paspalum paspaloides, and examined the effects of environmental factors on such differences. The results showed that the coverage and importance value (IV) of A. philoxeroides were all significantly greater than P. paspa-loides (34.3% and 104.0%, respectively), whereas the height of P. paspaloides was significantly greater than A. philoxeroides (13.8%). Moreover, the total nitrogen concentration (TN) and N:P of A. philoxeroides were significantly greater than those of P. paspaloides (55.1% and 55.8%, respectively), whereas the total carbon concentration (TC) and C:N of P. paspaloides were significantly greater than those of A. philoxeroides (4.1% and 83.8%, respectively). A. philoxeroides coverage increased with the increases of longitude, and its abundance increased with the increases of water nitrate concentration and longitude, while its IV increased with the increases of water ammonium concentration. However, the coverage, abundance, and IV of P. paspaloides decreased with the increases of ammonium concentration. C:N of A. philoxeroides decreased with the increase of ammonium concentration. Increased mean annual temperature and mean annual precipitation increased C:N but decreased N:P of P. paspa-loides. The C:P of both species decreased with the increases of ammonium concentration and electrical conductivity. N:P of A. philoxeroides was little affected by environment. These results indicated that A. philoxeroides had greater coverage and N absorption capacity than P. paspaloides, and that enriched water nitrogen would aggravate the invasion of A. philoxeroides. Meanwhile, P. paspaloides improved its C-assimilate reserves and chose the growth competition strategy for resisting A. philoxeroides invasion under the superior hydrothermal conditions. Different responses to environmental changes contributed to their coexistence in aquatic ecosystem.

p53 inhibits CTR1-mediated cisplatin absorption by suppressing SP1 nuclear translocation in osteosarcoma.

Background: Osteosarcoma (OS) is a malignant bone tumor mainly affecting children and young adolescents. Cisplatin is a first-line chemotherapy drug for OS, however, drug resistance severely limits the survival of OS. Nevertheless, cellular factors in cisplatin resistance for OS remain obscure. In this study, the function and potential mechanism of p53 in cisplatin absorption were explored in OS cells. Methods: The CRISPR-Cas9 gene editing technology was performed to obtain p53 gene knock-out U2OS cells. The p53 over-expression 143B cell line was established by lentivirus-mediated virus infection. Moreover, the functions of p53 and CTR1 in cisplatin absorption were assessed by inductively coupled plasma mass spectrometry (ICP-MS) through CTR1 over-expression and knock-down. Further, the DNA binding activity of SP1 on CTR1 gene promoter was determined by dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay. The functional regulation of p53 on SP1 was studied by nucleocytoplasmic separation assay and electrophoretic mobility shift assay (EMSA). The interaction between p53 and SP1 was verified by Co-Immunoprecipitation assay. Results: Under cisplatin treatment, p53 knock-out promoted CTR1 expression and cisplatin uptake, while p53 overexpression inhibited CTR1 expression and cisplatin uptake. Moreover, p53 regulated CTR1 level not by binding to CTR1 promoter directly but by suppressing the nuclear translocation of transcription factor specificity protein 1 (SP1). It was verified that SP1 is directly bound with CTR1 promoter. SP1 overexpression stimulated CTR1 expression, and SP1 knock-down attenuated CTR1 expression. Conclusion: The p53 might function as a negative regulator in CTR1 mediated cisplatin absorption, and the p53-SP1-CTR1 axis is a target for cisplatin resistance.

MUC13 promotes lung cancer development and progression by activating ERK signaling.

Mucin 13 (MUC13) is a glycoprotein that is expressed on the cell surface and participates in the tumorigenesis of multiple malignancies, including pancreatic cancer, colorectal cancer and renal cancer. However, to the best of our knowledge, the expression levels and function of MUC13 in lung cancer progression have not yet been demonstrated. Therefore, the present study examined the expression pattern and regulatory role of MUC13 in lung cancer tumorigenesis. The results demonstrated that MUC13 was highly expressed in lung cancer tissues and cell lines compared with that in normal tissues and cell lines. Functionally, knockdown of MUC13 inhibited cell proliferation and enhanced the apoptosis of A549 and NCI-H1650 lung cancer cells. Furthermore, silencing of MUC13 suppressed the migration and invasion of lung cancer cells. Additionally, a xenograft tumor model demonstrated that knockdown of MUC13 delayed the development of the lung cancer xenograft and suppressed the expression of proliferation marker Ki-67 in tumor tissues. Mechanistically, MUC13 activated the ERK signaling pathway by enhancing the phosphorylation of ERK, JNK and p38 in lung cancer tissues compared with that in normal tissues. Knockdown of MUC13 inhibited the phosphorylation of ERK/JNK/p38 in A549 and NCI-H1650 cells. Overall, these findings suggested that MUC13 could act as an oncogenic glycoprotein to accelerate the progression of lung cancer via abnormal activation of the ERK/JNK/p38 signaling pathway and might serve as a therapeutic target for lung cancer treatment.

Combined laparoscopic-endoscopic approach for gastric glomus tumor: A case report.

BACKGROUND: Gastric glomus tumor (GGT) is rare submucosal mesenchymal tumor that lacks specific clinical manifestations and is usually treated mainly by traditional surgical resection. This paper presents a case of a GGT, exhibited both intraluminally and extraluminally growth that was removed by laparoscopy-gastroscopy cooperative surgery. CASE SUMMARY: A 52-year-old male presented with epigastric discomfort accompanied by a sense of fullness for 3 mo. Upper gastrointestinal endoscopy identified a submucosal lump located in the gastric antrum. Endoscopic ultrasonography identified a 2.4 cm × 1.8 cm lump located in the gastric antrum. It originated from the muscularis propria and exhibited both intraluminally and extraluminally growth, with hypoechoicity on the periphery, hyperechoicity in the middle, and unclear boundaries. Computed tomography showed nodular thickening of 3.0 cm × 2.2 cm in the gastric wall of the gastric antrum, and after enhancement, the lesion exhibited obvious enhancement We suspected that it was a gastrointestinal stromal tumor (glomus tumor and schwannoma were not excluded) and planned to perform laparoscopy-gastroscopy cooperative surgery. Immunohistochemical staining after the operation revealed that spinal muscular atrophy (+), h-caldesmon (+), cluster of differentiation 34 (CD34) (+), 2% Ki-67-positive rate, CD56, melanoma antigen, CD117, discovered on GIST-1, leukocyte common antigen, caudal type homeobox 2, cytokeratin, and S-100 were all negative. The tumor was finally diagnosed as a GGT. CONCLUSION: GGTs are rare submucosal tumors of the stomach and should be considered in the differential diagnosis of gastric submucosal tumors. Laparoscopy-gastroscopy cooperative surgery is less invasive and more precise and could be an effective method for the treatment of GGTs.

Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis.

Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.

Monitoring atmospheric 85Kr by atom counting.

Radioactive 85Kr is a major gaseous fission product emitted into the air by the nuclear fuel reprocessing industry. Measuring atmospheric 85Kr has applications in environmental monitoring, atmospheric transport model validation and dating of environmental water samples, including groundwater, sea water and glacier ice. We present an ultra-sensitive method for fast analysis of atmospheric 85Kr at 10-5 parts per trillion level. This method is based on laser cooling and trapping and is capable of counting individual 85Kr atoms. Measurements at the 3% precision level can be made on krypton extracted from 1L STP of air with a turnaround time of 1.5 h. Moreover, we have realized a system for continuous air sampling over days to weeks. Based on this atom-counting technology and a portable air sample integrator we have realized atmospheric 85Kr baseline monitoring in Hefei, China, for over 20 months. The technological advances presented in this work lay the ground for a global atmospheric 85Kr monitoring network.