Mechanistic Insights into the Folding Mechanism of Region V in Ice-Binding Protein Secreted by Marinomonas primoryensis Revealed by Single-Molecule Force Spectroscopy.

The Gram-negative bacteria Marinomonas primoryensis secrete an ice-binding protein (MpIBP), which is a vital bacterial adhesin facilitating the adaptation and survival of the bacteria in the harsh Antarctic environment. The C-terminal region of MpIBP, known as region V (RV), is the first domain to be exported into the Ca2+-rich extracellular environment and acts as a folding nucleus for the entire adhesin. However, the mechanisms underlying the secretion and folding of RV remain poorly understood. Here, we used optical tweezers (OT) to investigate the secretion and folding mechanisms of RV at the single-molecule level. In the absence of Ca2+, apo-RV remains unstructured, while Ca2+-bound RV folds into a mechanically stable structure. The folding of RV could occur via the formation of an intermediate state. Even though this folding intermediate is "hidden" during the folding process of wild type RV in vitro, it likely forms in vivo and plays an important role in facilitating protein secretion. Additionally, our results revealed that the N-terminal part of the RV can significantly stabilize its C-terminal structure. Our study paves the way for further investigations into the structure and functions of MpIBP that help bacteria survive in challenging environments.

Cancer-associated fibroblasts subtypes and role in invasion and metastasis of gastric cancer.

Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs), an important cell type in the tumor microenvironment, play an important role in GC development. In this review, we describe the current knowledge of CAFs' heterogeneity and their role in GC invasion and metastasis. Currently, CAF-targeted cancer therapies are being rapidly explored and developed. However, the heterogeneity of CAFs limits the application of this therapy, so it is urgent to find specific markers and divide them into different subpopulations. With the development of single-cell RNA sequencing technology, researchers have used this technology to classify CAFs in many tumors, but whether it is applicable to GC and other tumors needs further study. And we believe that this technology will be in the near future utilized to sort CAFs on the basis of different cell markers and functions, so as to target tumor-promoting CAFs and inhibit tumor progression. Targeting CAFs by cell surface markers or normalizing the activated CAFs subsets may be an effective therapy, alone or in combination with other therapeutic approaches for GC treatment. Therefore, in the coming decades, the interaction between CAFs and GC cells will be still the focus of our research.

The Nrf2 inhibitor brusatol has a protective role in a rat model of oxygen-induced retinopathy of prematurity.

Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been testified to be involved in the development of retinopathy of prematurity (ROP), which can cause childhood visual impairment. Whether brusatol, an Nrf2 inhibitor, could be utilized to treat ROP was unknown. The oxygen-induced retinopathy rat model was established to mimic ROP, which was further intravitreal administrated with brusatol. Vessel morphology and microglial activation in the retina were assessed with histology analysis. The relative expression levels of angiogenesis and inflammation-related molecules were detected with Western blot and real-time polymerase chain reaction methods. Intravitreal brusatol administration could alleviate both angiogenesis and microgliosis induced by hyperoxia, along with down-regulation of vascular endothelial growth factor, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, cluster of differentiation molecule 11B, tumor necrosis factor alpha, inducible nitric oxide synthase, glial fibrillary acidic protein, and IBA-1 expression. It was further revealed that Nrf2 and heme oxygenease-1 were diminished by brusatol administration. The results demonstrate the potential of intravitreal brusatol deliver to treat ROP with down-regulation of angiogenesis and microgliosis.

Neonatal Inhibition of Connexin 36 Ameliorates Fetal Brain Injury Induced by Maternal Noninfectious Fever in Mice.

Prenatal fever could result in brain function impairments in the offspring. The present study investigated the effect of interleukin-6 (IL-6)-induced maternal fever on the offspring and the involvement of connexin 36 in this process. Pregnant C57BL/6J mice were injected with IL-6 on gestational day 15. The levels of iNOS and COX-2 were measured as an index of neuroinflammation in the brain of newborn pups. Offspring were treated with the connexin 36 (Cx36) inhibitor mefloquine at postnatal day (P)1-P3 or at P40-P42. Rotarod, grip traction, and foot fault tests were carried out to evaluate the motor behavior of adult offspring. Injection of IL-6 led to an elevation of the core temperature in the pregnant dams. Offspring of these dams showed significantly increased COX-2 and iNOS mRNA expression and protein levels in the whole-brain samples and significantly increased Cx36 in the cerebellum. Moreover, offspring of these dams showed motor deficits at an adult age. Neonatal administration of the Cx36 inhibitor mefloquine could prevent these motor deficits. Maternal fever during pregnancy induced by IL-6 injection could lead to neuroinflammation and motor deficits in the offspring. Neonatal inhibition of Cx36 could ameliorate the motor deficits in the offspring, indicating an involvement of Cx36 in the IL-6-induced maternal fever.

Cancer associated fibroblasts tailored tumor microenvironment of therapy resistance in gastrointestinal cancers.

Gastrointestinal cancers (GI), are a group of highly aggressive malignancies with heavy cancer-related mortalities. Even if continued development of therapy methods, therapy resistance has been a great obstruction for cancer treatment and thereby inevitably leads to depressed final mortality. Peritumoral cancer associated fibroblasts (CAFs), a versatile population assisting cancer cells to build a facilitated tumor microenvironment (TME), has been demonstrated exerting a promotion influence on cancer proliferation, migration, invasion, metastasis, and also therapy resistance. In this review, we provide an update progress in describing how CAFs mediate therapy resistance in GI by various means, meanwhile highlight the crosstalk between CAFs and cancer cells and present some vital signaling pathways activated by CAFs in this resistant process. Furthermore, we discuss the current advances in adopting novel drugs against CAFs and how the knowledge contributing to improved therapy efficacy in clinical practice. In sum, CAFs create a therapy-resistant TME in several aspects of GI progression, although some key problems about distinguishing CAFs subpopulations and controversial issues on pleiotropic CAFs in medication need to be solved for subsequent clinical application. Predictably, targeting therapy-resistant CAFs is a promising adjunctive treatment to benefit GI patients.

Correlation between conventional MR imaging combined with diffusion-weighted imaging and histopathologic findings in eyes primarily enucleated for advanced retinoblastoma: a retrospective study.

OBJECTIVES: To determine the diagnostic accuracy of conventional MRI in detecting tumour invasion of advanced intraocular retinoblastoma and to correlate ADC values with high-risk prognostic parameters. METHOD: The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV) and accuracies of MRI in detecting tumour-extent parameters of 63 retinoblastomas were determined. Furthermore, ADC values were correlated with high-risk prognostic parameters. RESULTS: MRI detected postlaminar optic nerve with a sensitivity of 73.3% (95% CI 44.9-92.2%) and a specificity of 89.6% (77.3-96.5%), while the specificity for choroidal invasion was only 31.8% (13.9-54.9%). Likewise, MRI failed to predicted early optic nerve invasion in terms of low sensitivity and PPV. In contrast, scleral and ciliary body invasion could be correctly excluded with high NPV. ADC values were significantly lower in patients with undifferentiated tumours, large tumour size, as with optic nerve and scleral invasion (all p < 0.05). However, no correlation was found between ADC values and the degree of choroidal or ciliary body infiltration. Additionally, ADC values were negatively correlated with Ki-67 index (r = -0.62, P = 0.002). CONCLUSIONS: Conventional MRI has some limitations in reliably predicting microscopic infiltration, with the diagnostic efficiency showing room for improvement, whereas ADC values correlated well with certain high-risk prognostic parameters for retinoblastoma. KEY POINTS: • Conventional MRI failed to predicted microscopic infiltration of the retinoblastoma. • Scleral and ciliary body invasion could be excluded with high NPV. • ADC values correlated well with some high-risk pathological prognostic parameters.

Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers.

Predicting lymph node metastasis (LNM) accurately is very important to decide treatment strategies preoperatively. The aim of this study was to explore risk factors that predict the presence of LNM in early gastric cancer (EGC). A total of 230 patients with EGC who underwent curative gastrectomy with lymph adenectomy at Xinhua Hospital from January 2006 to July 2014 were retrospectively reviewed. We studied the relationship between clinicopathological factors, biological markers (p53, ki67, nm23, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), E-cadherin (E-cad), beta-catenin (b-catenin), glutathione S-transferase (GST), and topoisomerase II (Topo II)), and LNM of EGC patients by chi-square test and logistic regression analysis. Meta-analyses were further conducted to review the effects of the proteins (P53, ki67, E-cad, and b-catenin) on LNM in ECG patients. LNM was detected in 42 (18.3 %) of 230 patients. Incidences of LNM was distinct in different tumor size (p = 0.044), depth of submucosal invasion (p < 0.0001), and P53 overexpression (p = 0.004). Multivariate analysis further indentified that large tumor size (≥20 mm, odds ratio (OR) = 2.168, p = 0.041), submucosa (OR = 4.000, p = 0.0005), and P53 overexpression (OR = 3.010, p = 0.022) were independent risk factors of LNM in EGC patients. The meta-analysis revealed a significantly statistical association of P53, ki67, and b-catenin with an increased risk of LNM in EGC patients (P53, OR = 1.81, p = 0.017; ki67, OR = 2.53, p = 0.0003; b-catenin, OR = 0.53, p = 0.01). Tumor size (≥20 mm), the depth of invasion (submucosa), and P53 overexpression may be helpful predictors of LNM in EGC patients. Furthermore, the results of meta-analysis revealed that P53, ki67 overexpression, and abnormal expression of b-catenin may be associated with LNM in EGC. The results need further validation in single large studies.

[Primitive neuroectodermal tumor of central nervous system with features of ependymoblastoma and neuroblastoma: a clinicopathologic study of 4 cases].

OBJECTIVE: To study clinicopathologic features, immunohistochemical profile, diagnosis and differential diagnosis of childhood central nervous system primitive neuroectodermal tumors (CNS PNETs) with the features of ependymoblastoma and neuroblastoma. METHODS: The clinical data, morphologic and immunohistochemical features were analyzed in 4 cases of pediatric CNS PNETs with features of ependymoblastoma and neuroblastoma. EnVision method immunohistochemistry was applied. RESULTS: Four patients including three boys and one girl presented at the age from 12 month to 4 years and three tumors located in cerebrum, one in brain stem. All tumors showed typical combined histological patterns of ependymoblastoma and neuroblastoma, demonstrating zones of true rosettes, occasional pseudovascular rosettes, and undifferentiated neuroepithelial cells in a prominent background of mature neuropils. There was focal expression of glial fibrillary acidic protein (GFAP) consistent with glial differentiation and epithelial membrane antigen (EMA) consistent with ependymal differentiation. Necrosis was seen in three cases and calcification was present in one case. Immunohistochemically, the rosettes and undifferentiated neuroepithelial cells were positive for vimentin, partially positive for GFAP and EMA but negative for synaptophysin. The tumor cells were also positive for synaptophysin in neuropils. The Ki-67 label index ranged from 20% to 60%. CONCLUSIONS: CNS PNETs with the features of ependymoblastoma and neuroblastoma is a rare tumor with poor prognosis. The tumor primarily occurs in childhood, especially infant and belongs to the family of embryonal tumors of the CNS. The morphologic, immunohistochemical and genetic features are important in differential diagnosis from other tumors of the CNS.

ZIF-8/g-C3N4 photocatalysts: enhancing CO2 reduction through improved adsorption and photocatalytic performance.

Nowadays, the widespread concern over controlling CO2 emissions and mitigating the adverse effects of greenhouse gases on global climate has attracted significant attention. In this study, g-C3N4 was synthesized by thermopolymerizing urea. Subsequently, ZIF-8 was combined with g-C3N4 using an in situ deposition method, resulting in the fabrication of ZIF-8/g-C3N4 composite photocatalysts at various molar ratios. Effective incorporation of ZIF-8 into g-C3N4 suppressed the recombination of photogenerated electrons and holes, thereby enhancing CO2 capture capacity and preserving light absorption capabilities. The ZIF-8/g-C3N4 composite demonstrates excellent photocatalytic performance for CO2 reduction, where the optimized material exhibited a CO2 adsorption capacity 1.52 times that of pure g-C3N4 and increased the conversion of CO2 to CH4 by more than sevenfold. This study harnesses the superior CO2 adsorption properties of metal-organic frameworks to develop more efficient photocatalysts, enhancing CO2 conversion efficacy and offering insights for developing efficient photocatalysts that utilize CO2.

Intense interaction between biochar/g-C3N4 promotes the photocatalytic performance of heterojunction catalysts.

In recent decades, environmental protection and energy issues have gained significant attention, and the development of efficient, environmentally friendly catalysts has become especially crucial for the advancement of photocatalytic technology. This study employs the sintering method to produce biochar. A hybrid photocatalyst for the degradation of RHB under visible light was prepared by loading varying proportions of biochar onto g-C3N4 using ultrasonic technology. Among them, 2% CGCD (2% biochar/g-C3N4) achieved a degradation rate of 91.3% for RHB after 30 minutes of visible light exposure, which was more than 25% higher than GCD (g-C3N4), and exhibited a higher photocurrent intensity and lower impedance value. The enhancement in photocatalytic activity is primarily attributed to the increased utilization efficiency of visible light and the electron transfer channel effect from a minor amount of biochar, effectively reducing the recombination of photo-generated charge carriers on the g-C3N4 surface, thereby significantly improving photocatalytic activity. The degradation of RHB is synergistically mediated by O2 -, h+ (photo-generated holes), and ˙OH. The free radical capture experiment indicates that O2 - and ˙OH are the primary active components, followed by h+.

Rapid discovery of natural skin-lightening ingredients based on an integrated screening strategy based on molecular docking and zebrafish model.

BACKGROUND: Natural herbs have been widely considered a reservoir for skin-lightening ingredients, but discovery of the effective ingredients from herbs remains a large challenge. AIM: This research aimed to rapidly identify compounds with skin-lightening activity in Chinese herbs. METHODS: The structure information of herbal compounds was collected and selected from the open-source data. High throughput virtual screening (HTVS) and Extra precision (XP) docking modes were used to screen for compounds that could bind to the mushroom tyrosinase involved in melanin synthesis. Furthermore, molecular dynamics (MD) simulations were introduced to assess the binding stability of those compounds with the key target protein. The candidate compounds found by this kind of multidimensional molecular screening were finally tested for their ability to inhibit pigmentation and potential toxicity using an in vivo zebrafish animal model. RESULTS: A Natural Compounds Database was established with 5616 natural compounds. Fourteen compounds with favorable binding capability were screened by the XP docking mode with mushroom tyrosinase and five compounds among them were found to have superior dynamic binding performance through MD simulations. Then the Zebrafish animal experiments revealed that two components, sennoside B (SB) and sennoside C (SC), could significantly inhibit melanogenesis rather than the other three compounds. Meanwhile, there were no obvious side effects observed in SB and SC about the morphology, heart rate, or body length of zebrafish. CONCLUSION: A strategy for rapid screening of compounds with whitening activity has been established, and two potent skin-lightening compounds, SB and SC, have been identified from a vast library of herbal compounds. This study revealed that SB and SC have potential for topical use in skin lightening for the first time. The findings of this study would provide an important theoretical basis for the application of these two compounds in the cosmetic field in the future.

Synergistic therapeutic effect of ginsenoside Rg3 modified minoxidil transfersomes (MXD-Rg3@TFs) on androgenic alopecia in C57BL/6 mice.

Inflammation in hair follicles will reduce the effectiveness of minoxidil (MXD) in the treatment of androgen alopecia (AGA) caused by elevated androgen levels. To target multiple physiological and pathological processes in AGA, a novel natural bioactive compound modified transfersomes (MXD-Rg3@TFs) was prepared to replace cholesterol that may disrupt hair growth, with ginsenosides Rg3 (Rg3) that have anti-inflammatory effects on AGA. The effects of MXD, Rg3 and their combination on AGA were evaluated using dihydrotestosterone (DHT) induced human dermal papilla cells (DPCs), and the results showed that the combination of MXD and Rg3 can significantly promote the proliferation, reduce the level of intracellular ROS and inflammatory factors, and inhibit the aging of DHT induced DPCs. Compared with cholesterol membrane transfersomes (MXD-Ch@TFs), MXD-Rg3@TFs has similar deformability, smaller particle size and better stability. MXD-Rg3@TFs has also significant advantages in shortening telogen phase and prolonging the growth period of hair follicles in C57BL/6 mice than MXD-Ch@TFs and commercial MXD tincture. The prominent ability of MXD-Rg3@TFs to inhibit the conversion of testosterone to DHT and reduce the level of inflammatory factors suggested that Rg3 and MXD in MXD-Rg3@TFs have synergistic effect on AGA therapy. MXD-Ch@TFs with no irritation to C57BL/6 mice skin is expected to reduce the dose of MXD and shorten the treatment time, which would undoubtedly provide a promising therapeutic option for treatment of AGA.

Effects of the fibroblast activation protein on the invasion and migration of gastric cancer.

OBJECTIVE: Cancer-associated fibroblasts (CAFs) are one of the most important components of tumor microenvironment. CAFs are believed to play an important role in tumor invasion and metastasis. Recently, fibroblast activation protein (FAP), a type II integral membrane glycoprotein belonging to the serine protease family, has emerged as a specific marker of CAFs. FAP was overexpressed in stromal fibroblasts of solid malignancies, however, the role of FAP on the process of invasion and metastasis of gastric carcinomas is still unknown. METHODS: Expression of FAP level was detected by immunohistochemistry in 60 gastric cancer surgical specimens (28 with omentum metastasis and 32 without), 20 normal human gastric tissues and omentum of 10 nonneoplastic gastric diseases. Fibroblasts were isolated from patient's tissues in the distal normal zones and tumor zones respectively, which were correspondingly designated as normal zone fibroblasts (NFs) and cancer-associated fibroblasts (CAFs). To explore the effects of FAP on NFs or CAFs, fibroblasts were co-cultured with human gastric cancer cell line MGC-803 cells. The ability of invasion and migration of MGC-803 cells was evaluated after transfecting FAP siRNA into CAFs of gastric carcinomas. RESULTS: We investigated the level of expression of FAP in surgical specimens, and found overexpressed in CAFs and non-expressed in NFs. Expression of FAP level in CAFs is significantly associated with Lauren classification,the degree of differentiation, depth of tumor invasion and TNM stage, but it is not correlated to age and gender in gastric carcinoma patients. There was positive correlation between the FAP level with metastasis to the omentum(p < 0.05, R(2) = 0.2736, p < 0.05, R(2) = 0.1479). In addition, the invasion and migration abilities of MGC-803 cells were significantly increased when cells were co-cultured with CAFs. On the other hand, invasion and migration abilities were significantly decreased by 46.9 and 50.3%, respectively, after knocking down FAP in CAFs.Further, NFs did not have appreciable effect on the invasion and migration of MGC-803 cells. CONCLUSIONS: Our findings showed that FAP was overexpressed in CAFs of gastric carcinomas, and siRNA-mediated knock down of FAP significantly suppressed invasion and migration of MGC-803 cells. FAP may be an important regulator in the invasion and migration of gastric cancer and may provide a novel therapeutic target in gastric carcinomas.

Parental detection of neonatal jaundice using a low-cost colour card: a multicentre prospective study.

BACKGROUND: Since most infants are usually discharged before age 48-72 hours, peak bilirubin levels will almost always occur after discharge. Parents may be the first to observe the onset of jaundice after discharge, but visual assessment is unreliable. The jaundice colour card (JCard) is a low-cost icterometer designed for the assessment of neonatal jaundice. The objective of this study was to evaluate parental use of JCard to detect jaundice in neonates. METHODS: We conducted a multicentre, prospective, observational cohort study in nine sites across China. A total of 1161 newborns ≥35 weeks of gestation were enrolled in the study. Measurements of total serum bilirubin (TSB) levels were based on clinical indications. The JCard measurements by parents and paediatricians were compared with the TSB. RESULTS: JCard values of parents and paediatricians were correlated with TSB (r=0.754 and 0.788, respectively). The parents' and paediatricians' JCard values 9 had sensitivities of 95.2% vs 97.6% and specificities of 84.5% vs 71.7% for identifying neonates with TSB ≥153.9 µmol/L. The parents' and paediatricians' JCard values 15 had sensitivities of 79.9% vs 89.0% and specificities of 66.7% vs 64.9% for identifying neonates with TSB ≥256.5 µmol/L. Areas under the receiver operating characteristic curves of parents for identifying TSB ≥119.7, ≥153.9, ≥205.2, and ≥256.5 µmol/L were 0.967, 0.960, 0.915, and 0.813, respectively, and those of paediatricians were 0.966, 0.961, 0.926 and 0.840, respectively. The intraclass correlation coefficient was 0.933 between parents and paediatricians. CONCLUSION: The JCard can be used to classify different levels of bilirubin, but it is less accurate with high bilirubin levels. The JCard diagnostic performance of parents was slightly lower than that of paediatricians.

CNS tumor with BCOR internal tandem duplication: Clinicopathologic, molecular characteristics and prognosis factors.

The central nervous system tumor with BCOR internal tandem duplication (CNS tumor with BCOR ITD) is a recently identified rare tumor entity, the complete morphologic characteristic, genetic alteration, classification, clinical outcomes and optimal treatment for this tumor entity have not been fully clarified. Here, two new cases of CNS tumor with BCOR ITD were reported and the clinicopathologic, molecular characteristics, and prognosis were analyzed through reviewing of the reported literature. The histological features included a clear border with adjacent brain parenchyma, an extensively microcystic background, and the cells with round to oval nuclei containing delicate chromatin, ependymoma-like perivascular pseudorosettes, and palisading necrosis. Immunohistochemical features showed strong and diffuse positive expression for BCOR, scattered positive expression for OLIG2, and negative expression for GFAP, Syn, and EMA. PCR and direct DNA sequencing analysis identified exon 15 ITD of the BCOR gene in both cases. Interestingly, both cases revealed two duplication segments, which had not been reported in the literature. A review of the literature shows that CNS tumor with BCOR ITD has a poor prognosis with a median survival of 1.7 years; surgical gross total resection is a good prognostic factor. A combination of radiation treatment and chemotherapy, while trending towards significance, does not reach statistical significance. On the contrary, the OS is not associated with age, gender, and tumor location. In conclusion, CNS tumor with BCOR ITD is a rare tumor entity with characteristic morphologic and molecular features and a poor prognosis. The optimal treatment strategies need further studies.

Nasal metastases from neuroblastoma-a rare entity: Two case reports.

BACKGROUND: Neuroblastoma (NB) is one of the most common malignancies in children. Metastasis in NB is not uncommon. However, nasal metastases are rare. Here, we reported two pediatric cases of nasal metastases. CASE SUMMARY: Case 1 was a 3-year-old boy without a history of NB. Case 2 was a 10-year-old girl who had a history of NB for 6 years. Both of them presented with symptoms of nasal and sinus masses such as epistaxis or discharge from the nose. The radiologic imaging results revealed masses in the nasal cavity or nasopharynx in both cases and a mass in the right adrenal gland of case 1. The pathologic examination of biopsy samples of their nasal masses revealed "small round blue-cell tumor" along with abundant vascular fibrous septa. The tumor cells expressed synaptophysin, cluster of differentiation 56, chromogranin A, paired like homeobox protein 2B and a very high Ki67 index in both case but were negative for vimentin, desmin, leucocyte common antigen and cytokeratin. Myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) amplification was detected in both cases. Finally, the two cases were diagnosed as nasal metastases from NB based on the clinical and pathologic findings. The two patients affected by NB were > 18 mo old, the primary tumor location was adrenal gland, and they presented with multiple metastases. CONCLUSION: It is difficult to differentiate between metastatic NB in the nose and olfactory neuroblastoma in the absence of a history of NB. Paired like homeobox protein 2B can play an important role in the diagnosis and differential diagnosis of this disease.

The Better Survival of MSI Subtype Is Associated With the Oxidative Stress Related Pathways in Gastric Cancer.

Background: Gastric cancer (GC) is the third leading fatal cancer in the world and its incidence ranked second among all malignant tumors in China. The molecular classification of GC, proposed by the The Cancer Genome Atlas (TCGA), was added to the updated edition (2019) of WHO classification for digestive system tumor. Although MSI and EBV subtypes appeared as ever-increasingly significant roles in immune checkpoint inhibitor therapy, the underlying mechanisms are still unclear. Methods: We systematically summarized the relationship between EBV, d-MMR/MSI-H subtypes and clinicopathological parameters in 271 GC cases. Furthermore, GSE62254/ACRG and TCGA-STAD datasets, originated from Gene Expression Omnibus (GEO) and TCGA respectively, were analyzed to figure out the prognosis related molecular characteristics by bioinformatics methods. Results: Patients with MSI subtype had better prognosis than the MSS subtype (P = 0.013) and considered as an independent biomarker by the univariate analysis (P = 0.017) and multivariate analysis (P = 0.050). While there was no significant difference between EBV positive and negative tissues (P = 0.533). The positive prognostic value conferred by MSI in different cohorts was revalidated via the clinical analysis of GSE62254/ACRG and TCGA-STAD datasets regardless of race. Then key gene module that tightly associated with better status and longer OS time for MSI cases was obtained from weighted gene co-expression network analysis(WGCNA). NUBP2 and ENDOG were screened from the gene cluster and oxidative phosphorylation, reactive oxygen species(ROS) and glutathione metabolism were analyzed to be the differential pathways in their highly expressed groups. Conclusions: Our results manifested the significant prognostic value of MSI in Chinese GC cohort and comparisons with other populations. More opportunities to induce apoptosis of cancer cells, led by the unbalance between antioxidant system and ROS accumulation, lay foundations for unveiling the better prognosis in MSI phenotype through the bioinformatics analysis.

Tetra-kis(µ-4-methoxy-benzoato)bis-[(4-methoxy-benzoato)(1,10-phenan-throline)terbium(III)].

In the title dinuclear complex, [Tb(2)(C(8)H(7)O(3))(6)(C(12)H(8)N(2))(2)], each Tb(III) ion is eight-coordinated by two N atoms from a 1,10-phenanthroline ligand and six O atoms from the carboxyl-ate groups of five 4-methoxy-benzoate ligands in a distorted square-anti-prismatic geometry. All six 4-methoxy-benzoate ligands act in a bidentate mode, two coordinating to one Tb center each and the other four bridging two Tb centers [Tb⋯Tb separation = 4.3144 (6) Å]. In the crystal, inter-molecular π-π inter-actions between the aromatic rings of 1,10-phenanthroline and 4-methoxy-benzoate ligands [centroid-centroid distance = 3.742 (9) Å] link two mol-ecules into a centrosymmetric dimer. Weak inter-molecular C-H⋯O hydrogen bonds help to consolidate the crystal packing.

Synthesis and degradation kinetics of TiO2/GO composites with highly efficient activity for adsorption and photocatalytic degradation of MB.

Poriferous TiO2/GO (denoted as TGO-x%) photocatalysts with ultrathin grapheme oxide (GO) layer were prepared by a hydrothermal method, the adsorption and photocatalytic degradation and its kinetics about Methylene blue(MB) were studied systematically. All the TGO-x% showed improved adsorption and photodegradation performance. TGO-25% had excellent adsorptivity while TGO-20% exhibit the highest visible light photocatalytic degradation activity. The adsorption capacity for TGO-25% was 20.25 mg/gcatalyst along with the k1 was about 0.03393 min·gcatalyst/mg, this enhancement was mainly owing to the strong adsorption capacity of GO and the stacking structure of sheets and nanoparticles. GO sheets prevented the agglomeration of TiO2 particles and TiO2 nanoparticles also prevented the agglomeration of GO sheets, which could provides greater surface area. Besides, the remarkably superior photodegradation activity of TiO2/GO composites is mainly attribute to the strong absorption of visible light and the effective charge separation revealed by the photoluminescence, the total removal rate of MB is 97.5% after 35 min adsorption and 140 min degradation, which is 3.5 times higher than that of TiO2.

Integrated assessment of PD-L1 expression and molecular classification facilitates therapy selection and prognosis prediction in gastric cancer.

PURPOSE: Targeting the PD-1/PD-L1 pathway has emerged as a novel therapy for cancer. To identify rational candidates for anti-PD-1/PD-L1 immunotherapy in gastric cancer (GC), the abundance of PD-L1 expression was evaluated on a kind of biomarker-based molecular classification for shaping prognosis and treatment planning. METHODS: One hundred and sixty-five GCs were classified into five subgroups using immunohistochemistry (IHC) and in situ hybridization (ISH) methods, based on a panel of seven markers (MLH1, PMS2, MSH2, MSH6, E-cadherin, P53, and Epstein-Barr virus mRNA). The expression of PD-L1 in GC tissues was analyzed immunohistochemically. RESULTS: The five categories (Epstein-Barr virus positivity, microsatellite instability, aberrant E-cadherin, aberrant P53 expression, and normal P53 expression) correspond to the reported molecular subgroups for similar proportions and clinicopathologic characteristics. Survival analysis indicated that subgroups with aberrant E-cadherin expression independently predicted a worse prognosis in GC patients (HR=2.51, P=0.010). The clinical and prognostic profiles produced by this stratification in nonintestinal-type GC were distinguishable from those in intestinal-type. Although PD-L1 was not a significant prognostic factor, that more frequent presence of PD-L1-positive in microsatellite instability tumors than other subtypes (P<0.010) hinted at a prolonged clinical course. Moreover, the lowest level of PD-L1 but the highest of Her2 was observed in the group of aberrant P53, namely it was suggested that there was a negative correlation between PD-L1 and Her2 overexpression. CONCLUSION: Different molecular subtypes in GC may have a tendency to react differently to anti-PD-L1/PD-1 immunotherapy or anti-Her2 therapy. A combination of PD-L1 expression and this cost-effective classification strategy would be helpful for predicting prognosis and promoting personalized therapy in clinical practice.