Prognostic and Diagnostic Values of Semaphorin 5B and Its Correlation With Tumor-Infiltrating Immune Cells in Kidney Renal Clear-Cell Carcinoma.

Background: Semaphorin 5B (SEMA5B) has been described to be involved in the development and progression of cancer. However, the potential diagnostic and prognosis roles and its correlation with tumor-infiltrating immune cells in KIRC have not been clearly reported yet. Methods: The mRNA level of SEMA5B was analyzed via the TCGA and GTEx database as well as the CCLE dataset and verified by GSE53757 and GSE40435 datasets. Meanwhile, the protein level of SEMA5B was analyzed by CPTAC and validated by HPA. The diagnostic value of SEMA5B was analyzed according to the TCGA database and validated by GSE53757, GSE46699, and GSE11024 + GSE46699 datasets. Then, the survival analysis was conducted using GEPIA2. R software (v3.6.3) was applied to investigate the relevance between SEMA5B and immune checkpoints and m6A RNA methylation regulator expression. The correlation between SEMA5B and MMRs and DNMT expression and tumor-infiltrating immune cells was explored via TIMER2. Co-expressed genes of SEMA5B were assessed by cBioPortal, and enrichment analysis was conducted by Metascape. The methylation analysis was conducted with MEXPRESS and MethSurv online tools. Gene set enrichment analysis (GSEA) was applied to annotate the biological function of SEMA5B. Results: SEMA5B was significantly upregulated at both the mRNA and protein levels in KIRC. Further analysis demonstrated that the mRNA expression of SEMA5B was significantly correlated with gender, age, T stage, pathologic stage, and histologic grade. High levels of SEMA5B were found to be a favorable prognostic factor and novel diagnostic biomarker for KIRC. SEMA5B expression was shown to be significantly associated with the abundance of immune cells in KIRC. Also, SEMA5B expression was significantly correlated with the abundance of MMR genes, DNMTs, and m6A regulators in KIRC. Enrichment analysis indicated that the co-expressed genes may involve in crosslinking in the extracellular matrix (ECM). GSEA disclosed that SYSTEMIC_LUPUS_ERYTHEMATOSUS and NABA_ECM_REGULATORS were prominently enriched in the SEMA5B low-expression phenotype. Finally, the methylation analysis demonstrated a correlation between hypermethylation of the SEMA5B gene and a poor prognosis in KIRC. Conclusion: Increased SEMA5B expression correlated with immune cell infiltration, which can be served as a favorable prognostic factor and a novel diagnostic biomarker for KIRC.

Addressing Label Sparsity With Class-Level Common Sense for Google Maps.

Successful knowledge graphs (KGs) solved the historical knowledge acquisition bottleneck by supplanting the previous expert focus with a simple, crowd-friendly one: KG nodes represent popular people, places, organizations, etc., and the graph arcs represent common sense relations like affiliations, locations, etc. Techniques for more general, categorical, KG curation do not seem to have made the same transition: the KG research community is still largely focused on logic-based methods that belie the common-sense characteristics of successful KGs. In this paper, we propose a simple yet novel three-tier crowd approach to acquiring class-level attributes that represent broad common sense associations between categories, and can be used with the classic knowledge-base default & override technique, to address the early label sparsity problem faced by machine learning systems for problems that lack data for training. We demonstrate the effectiveness of our acquisition and reasoning approach on a pair of very real industrial-scale problems: how to augment an existing KG of places and offerings (e.g. stores and products, restaurants and dishes) with associations between them indicating the availability of the offerings at those places. Label sparsity is a general problem, and not specific to these use cases, that prevents modern AI and machine learning techniques from applying to many applications for which labeled data is not readily available. As a result, the study of how to acquire the knowledge and data needed for AI to work is as much a problem today as it was in the 1970s and 80s during the advent of expert systems. Our approach was a critical part of enabling a worldwide local search capability on Google Maps, with which users can find products and dishes that are available in most places on earth.

Statin pretreatment combined with intravenous thrombolysis for ischemic stroke patients: A meta-analysis.

PURPOSE: For ischemic stroke patients, thrombolysis therapy combined statins might have a better benefit. But difference studies had a debate. The meta-analysis wants to make clear about whether statins could increase effect of therapy or decrease side effect for these patients. METHODS OBJECTIVES: To evaluate the effect and safety about using statins in ischemic stroke patients receiving thrombolysis. DATA SOURCES: Databases including PubMed, Web of Science, Embase and Cochrane Library. ELIGIBILITY CRITERIA: original observational cohort studies. PARTICIPANTS: ischemic stroke patients receiving thrombolysis. INTERVENTIONS: pretreatment statins. APPRAISAL AND SYNTHESIS METHODS: forest plot to show pooled results; I-squared test to evaluate the heterogeneity. RESULTS: Of 87 selected, 8 were eligible. The 8 studies included 10,344 patients (with statins: 2048; without statins: 8296). For clinical recovery at 24 h, pooled OR (odds ratios) was 1.82 (95% CI: 1.49-2.21). For excellent outcome, pooled OR was 1.03 (95% CI: 0.80-1.12). For favorable outcome, pooled OR was 0.99 (95% CI: 0.85-1.16). For ICH (intracranial hemorrhage), pooled OR was 1.16 (95% CI: 0.97-1.40). For sICH (symptomatic intracranial hemorrhage), pooled OR was 1.40 (95% CI: 1.02-1.91). For mortality, overall pooled OR was 0.96 (95% CI: 0.74-1.25). CONCLUSION: In conclusion, the meta-analysis found that for ischemic stroke patients receiving thrombolysis, pretreatment statins were related to a better clinical recovery and a lower short-term mortality. Pretreatment statins had no significant relationship with mRS at 90 days and ICH. Pretreatment high dose statins may be related to the occurrence of sICH.

Formaldehyde as Tethering Organocatalyst: Highly Diastereoselective Hydroaminations of Allylic Amines.

Catalysts possessing sufficient activity to achieve intermolecular alkene hydroaminations under mild conditions are rare, and this likely accounts for the scarcity of asymmetric variants of this reaction. Herein, highly diastereoselective hydroaminations of allylic amines utilizing hydroxylamines as reagents and formaldehyde as catalyst are reported. This catalyst induces temporary intramolecularity, which results in high rate accelerations, and high diastereocontrol with either chiral allylic amines or chiral hydroxylamines. The reaction scope includes internal alkenes. Overall this work provides a new, stereocontrolled route to form complex vicinal diamines.

Hydrogen bonding directed intermolecular Cope-type hydroamination of alkenes.

Intermolecular hydroamination of unactivated alkenes represents a significant synthetic challenge. An efficient Cope-type hydroamination is achieved under mild conditions for reactions of N-alkylhydroxylamines with allylic amines, using hydrogen bonding to achieve increased reactivity and high regioselectivity. This approach provides a number of highly functionalized vicinal diamine motifs as Markovnikov addition products.

Electrophilic fluorination of cationic Pt-aryl complexes.

The electrophilic fluorination of several (triphos)Pt-aryl(+) establishes the first example of aryl-F coupling from a Pt center.

{Bis[2-(diphenyl-phosphan-yl)eth-yl]phenyl-phosphane-κP,P',P''}[(Z)-8-mesityl-cyclo-oct-4-en-1-yl]platinum(II) tetra-fluorido-borate dichloro-methane disolvate.

In the title ionic compound, [Pt(C(17)H(23))(C(34)H(33)P(3))](BF(4))·2CH(2)Cl(2), the Pt(II) atom adopts a square-planar coordination geometry with the large (Z)-8-mesityl-cyclo-oct-4-en-1-yl group occupying the fourth coordination site. The (triphos)Pt moiety and the mesityl group are attached to the cyclo-oct-4-ene motif at the 1- and 8-position in a syn configuration. The (BF(4))(-) anion and one of the dichloromethane solvate molecules each are disordered over two sets of sites.

Steric Crowding Makes Challenging C(sp3)-F Reductive Eliminations Feasible.

A high-yielding fluorination of (triphos)Pt-R(+) has been achieved using an array of F(+) sources, with XeF(2) yielding R-F in minutes. The C-F coupling proved to be a stereoretentive process that proceeds via a concerted reductive elimination from a putative dicationic Pt(IV) center. The larger the steric congestion of the (triphos)Pt-C(sp3) (+) complexes, the more efficient the fluorination, seemingly a result of sterically accelerated C-F reductive elimination along with simultaneous deceleration of its competing processes (ß-H elimination).

Luminescence and reactivity of 7-azaindole derivatives and complexes.

7-Azaindole and its derivatives have been extensively investigated for uses in biological probes and imaging. In contrast, there have been very limited studies on the coordination chemistry and the applications of 7-azaindole and derivatives in materials science and in chemical bond activation. Our recent research has shown that 7-azaindolyl and derivatives are excellent blue emitters for organic light emitting diodes, they have rich coordination chemistry with both main group elements and transition metal ions, and their metal complexes display not only phosphorescence but also unusual and often unprecedented reactivity toward C-H and C-X bonds. This critical review discusses recent advances in these fields with focuses on new 7-azaindolyl derivatives and their metal complexes developed by our group. The luminescent properties and applications of 7-azaindolyl-based compounds will be presented. The reactivity of Pt(II) complexes toward C-H and C-X bonds, especially the steric impact of the bis(7-azaindolyl) chelate ligands and bimetallic cooperativity will be discussed (86 references).

Switchable ambient-temperature singlet-triplet dual emission in nonconjugated donor-acceptor triarylboron-Pt(II) complexes.

A triarylboron compound Si-BNPA (1) containing a BMes(2) acceptor and an N-(2'-pyridyl)-7-azaindolyl (NPA) donor linked by a tetrahedral silane group has been synthesised. This molecule displays unusual white singlet-triplet dual emission at 77 K, with an exceptionally long phosphorescent decay time (2.2 s). Fluoride titration experiments established that the singlet and triplet emission peaks are due to acceptor-based Mes-->B charge transfer and donor-based 3pi-->pi* transitions, respectively. This dual emission was found to be persistent and observable at ambient temperature in its Pt(II) complex [Pt(N,N-Si-BNPA)Ph2] (2a). Furthermore, 2a was found to undergo intramolecular "roll-over" C-H activation to produce the N,C-chelate complex [Pt(N,C-Si-BNPA)(SMe2)Ph] (2b). This compound also displays ambient temperature singlet-triplet dual emission, but with a much greater phosphorescent efficiency than 2a due to the formation of a more stable chelate ring. Addition of fluoride was found to have little impact on the phosphorescent emission of 2a, but resulted in a large enhancement of the phosphorescent emission intensity of 2b. To establish the impact of donor-acceptor geometry on this singlet-triplet dual emission, the properties of linearly conjugated donor-acceptor complexes [Pt(N,N-BNPA)Ph2] (3a) and [Pt(N,C-BNPA)Ph2] (3b) were also examined. Consistent with 2a and 2b, the N,C-chelate complex 3b has a much higher phosphorescent efficiency than the N,N-chelate 3a. Although 3a and 3b show bright and fluoride-switchable phosphorescence at ambient temperature, they are not dual emissive and show only metal-to-ligand chage-transfer-based phosphorescence. The non-conjugated donor-acceptor geometry and the overlap of the donor and acceptor singlet and triplet excitation bands in Si-BNPA and its Pt(II) complexes may thus be the key for achieving singlet-triplet dual emission on two separated chromophores in a single molecule.

Impact of the linker groups in bis(7-azaindol-1-yl) chelate ligands on structures and stability of Pt(N,N-L)R(2) complexes.

New organoplatinum(II) complexes with the general formula of Pt(N,N-L)R(2), where L is a bis(7-azaindol-1-yl) chelate ligand, R is a methyl or a phenyl, have been synthesized and investigated with the aim to understand the impact of the linker group in the L ligand on the structure and the stability of the Pt(II) complexes. The L ligands used in our investigation belong to two classes: class I with an aliphatic linker between two 7-azaindolyl groups such as -CH(2)- (BAM), -(CH(2))(3)- (1,3-BAPr), and -(CH(2))(4)- (1,4-BABu), class II with an aromatic linker such as 1,2-phenyl (1,2-BAB) 1,3-phenyl (1,3-BAB) and 1,4-dihydronaphthalene-1,4-epoxide (BAHE). The structures of these new mononuclear Pt(II) complexes have been determined by single-crystal X-ray diffraction analyses. For the 1,3-BAPr ligand, a dinuclear complex with the formula of [Pt(SMe(2))Ph(2)](2)(1,3-BAPr) was also obtained and its structure was established by X-ray diffraction analysis. The linker group's impact on the N-Pt-N bite angle and the relative orientation of the two 7-azaindolyl rings was examined by using the crystal structural data. Intramolecular three-center four-electron Pt(II) ... H-C interactions have been established for all Pt(II) complexes with class I ligands by single-crystal X-ray diffraction and (1)H NMR spectroscopic analyses. Complexes Pt(1,3-BAPr)Me(2) and Pt(1,4-BABu)Me(2) have been found to have a poor stability, compared to the 1,2-BAB and BAM analogues. Two geometric isomers of the Pt(BAHE)Ph(2) complex have been identified by NMR spectra and the structure of one of the isomers has been determined by X-ray diffraction analysis, establishing that the BAHE ligand is most effective in blocking the 5th coordination site of the Pt(II) center.

Reversible intramolecular C-C bond formation/breaking and color switching mediated by a N,C-chelate in (2-ph-py)BMes2 and (5-BMes2-2-ph-py)BMes2.

A diboron compound with both 3-coordinate boron and 4-coordinate boron centers, (5-BMes2-2-ph-py)BMes2 (1) and its monoboron analogue, (2-ph-py)BMes2 (2) have been synthesized. Both compounds are luminescent but have a high sensitivity toward light. UV and ambient light cause both compounds to isomerize to 1a and 2a, respectively, via the formation of a C-C bond between a mesityl and the phenyl group, accompanied by a drastic color change from yellow or colorless to dark olive green or dark blue. The structures of 1a and 2a were established by 2D NMR experiments and geometry optimization by DFT calculations. Both 1a and 2a can thermally reverse back to 1 and 2 via the breaking of a C-C bond, with the activation barrier being 107 and 110 kJ/mol, respectively. The N,C-chelate ligands in 1 and 2 were found to play a key role in promoting this unusual and reversible photo-thermal isomerization process on a tetrahedral boron center. Reactions with oxygen molecules convert 1a and 2a to 5-BMes2-2-[(2-Mes)-ph]-pyridine (1b) and 2-(2-Mes)-ph-pyridine (2b), respectively.

Ambient-temperature metal-to-ligand charge-transfer phosphorescence facilitated by triarylboron: Bnpa and its metal complexes.

A Cu(I) complex, 1, and a Pt(II) complex, 2a, of a triarylboron ligand, Bnpa, with bright ambient-temperature phosphorescence have been obtained. The phosphorescence of these complexes is highly sensitive toward molecular oxygen and has a distinct response to fluoride ions. For 1, the fluoride ion causes phosphorescent quenching and Bnpa dissociation, and for 2a, it switches phosphorescent color from yellow to green. The Cu(I) complex has an exceptionally high emission quantum yield (0.88) in the solid state.

Dinuclear Cu(I) complexes of 1,2,4,5-tetra(7-azaindolyl)benzene: persistent 3-coordinate geometry, luminescence, and reactivity.

Five Cu(I) complexes [Cu2(ttab)(CH3CN)2][BF4]2 (1), [Cu(2)(ttab)(PPh3)2][BF4]2 (2), [Cu2(ttab)I2] (3), [Cu2(ttab)(I3)2] (4), and [Cu2(ttab)(I)BF4]n (5) with 1,2,4,5-tetra(7-azaindolyl)benzene (ttab) have been synthesized and characterized. The structures of compound 1, 2, 4, and 5 have been determined by single-crystal X-ray diffraction analyses, which established that 1, 2, and 4 are discrete dinuclear Cu2 compounds while compound 5 is a 1D coordination polymer with the I- ligand bridging two dinuclear Cu2 units. The ttab ligand in all four complexes adopts a 1,3-chelation mode. The Cu(I) center in all complexes is three-coordinate. Close contact between the Cu(I) center and the benzene ring in the ttab ligand was observed in all four structures, which is believed to play a role in stabilizing the three-coordinate geometry of the Cu(I) center. The crystals of 1, 2, and 5 contain channels in the lattice that host solvent molecules such as CH2Cl2 and toluene. Fluorescent measurements established that, in solution, compounds 1-3 display weak blue luminescence which originates from the ttab but is significantly red-shifted and has a much lower emission intensity, compared to the free ttab ligand. The application of compound 1 in C-N cross-coupling reactions was examined by using the reaction of phenyl halides with imidazole as a model system. For the reaction with phenyl iodide, 1 was found to be as effective a catalyst as the CuI/1,10-phenanthroline system. For the reaction with phenyl bromide, 1 is less effective than the CuI/1,10-phenanthroline system. Compound 1 reacts with O2 gas, as established by UV-vis spectra, but the oxidized products have not been characterized.