The Full Cytosine-Cytosine Base Paring: Self-Assembly and Crystal Structure.

The synthesis of self-assembly systems that can mimic partial biological behaviours require ingenious and delicate design. For decades, scientists are committed to exploring new base pairing patterns using hydrogen bonds directed self-assembly of nucleotides. A fundamental question is the adaptive circumstance of the recognition between base pairs, namely, how solvent conditions affect the domain of base pairs. Towards this question, three nucleotide complexes based on 2'-deoxycytidine-5'-monophosphate (dCMP) and cytidine-5'-monophosphate (CMP) were synthesized in different solvents and pH values, and an unusual cytosine-cytosine base paring pattern (named full C : C base pairing) has been successfully obtained. Systematic single crystal analysis and 1 H NMR titration spectra have been performed to explore factors influencing the formation of base paring patterns. Moreover, supramolecular chirality of three complexes were studied using circular dichroism (CD) spectroscopy in solution and solid-state combined with crystal structure analysis.

The Electronic Properties of Cadmium Naphthalene Diimide Coordination Complex.

The computational simulations for electronic properties of cadmium (Cd) coordinated L-alanine NDI ligand (H2-l-ala NDI) based complex are the focus of this research. For the first time, the Cd-NDI complex (monomer) has been produced using water as the solvent; this is a new approach to synthesizing the Cd-NDI complex that has not been reported yet. Along with crystallography and Hirsch field analysis, CAM-B3LYP/LANL2DZ and B3LYP/LANL2MB basis sets were used, and in-depth characterisation of the Cd-NDI complex by following DFT and TD-DFT hypothetical simulations. Hyperpolarizabilities, frontier molecular orbitals (FMOs), the density of states (DOS), dipole moment (µ), electron density distribution map (EDDM), transition density matrix (TDM), molecular electrostatic potential (MEP), electron-hole analysis (EHA), and electrical conductivity (σ) have all been studied regarding the Cd-NDI complex. The vibrational frequencies and types of interaction are studied using infrared (IR) and non-covalent interaction (NCI) analysis with iso-surface. In comparison to the Cd-NDI complex with 2.61, 2.42 eV Eg (using CAM-B3LYP/LANL2DZ and B3LYP/LANL2MB basis sets, respectively) and 376 nm λmax, (in case of B3LYP/LANL2MB λmax is higher), H2-l-ala NDI have 3.387 eV Eg and 375 nm λmax, metal-ligand coordination in complex dramatically altered charge transfer properties, such as narrowing band gap (Eg). Based on the electronic properties analysis of Cd-NDI complex, it is predicted that the Cd-NDI complex will have a spectacular (nonlinear optical) NLO response. The Cd-NDI complex is discovered to be advantageous for the creation of future nanoscale devices due to the harmony between the Cd metal and H2-l-ala NDI, in addition to their influences on NLO characteristics.

Conformation Locking of the Pentose Ring in Nucleotide Monophosphate Coordination Polymers via π-π Stacking and Metal-Ion Coordination.

The conformation of the pentose ring in nucleotides is extremely important and a basic problem in biochemistry and pharmaceutical chemistry. In this study, we used a strategy to regulate the conformation of pentose rings of nucleotides via the synergistic effect of metal-ion coordination and π-π stacking. Seven types of coordination complexes were developed and characterized using Fourier transform infrared spectroscopy, elemental analysis, thermogravimetric analysis, powder X-ray diffraction, ultraviolet-visible spectroscopy, 1H nuclear magnetic resonance spectroscopy, electrospray ionization mass spectrometry, and single-crystal X-ray diffraction. On the basis of two conformational parameters obtained from single-crystal structure analysis, i.e., the pseudorotation phase angle and degree of puckering, the exact conformation of the furanose ring in these coordination polymers was unequivocally determined. Crystallographic studies demonstrate that a short bridging ligand (4,4'-bipyridine) is conducive to the formation of a twist form, and long auxiliary ligands [1,2-bis(4-pyridyl)ethene and 4,4'-azopyridine] induce the formation of an envelope conformation. However, the longest auxiliary ligands [1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene] cannot limit the flexibility of a nucleotide. Our results demonstrated that the proposed strategy is universal and controllable. Moreover, the chirality of these coordination polymers was examined by combining the explanation of their crystal structures with solid-state circular dichroism spectroscopy measurements.

Coordination Patterns of the Diphosphate in IDP Coordination Complexes: Crystal Structure and Chirality.

The knowledge of accurate geometrical parameters from X-ray diffraction studies in the solid state of metal nucleotide is very important for understanding the relationship between structures and properties, including biochemical processes and even enzyme-metal-substrate interactions. The research is also very necessary to precisely and controllably design the functional materials. Here, seven types of coordination polymers of inosine 5'-diphosphate nucleotide (IDP) with transition metals, {[Zn(HIDP)(azpy)(H2O)2]·4H2O}n (1), {[Cd2(IDP)2(bpda)2]·[Cd(H2O)6]·11H2O}n (2), {[Cd3(IDP)2(4,4'-bipy)2(H2O)3]·6H2O}n (3), {[Cd2(IDP)2(bpe)2(H2O)2]·(H2bpe)·26H2O}n (4), {[Cu3(IDP)2(azpy)2(H2O)5]·5H2O}n (5), {[Cu3(IDP)2(bpe)2(H2O)5]·9H2O}n (6), and {[Co(HIDP)(azpy)(H2O)2]·7H2O}n (7) [4,4'-bipy = 4,4'-bipyridine, azpy = 4,4'-azopyridine, bpe = 1,2-bis(4-pyridyl)ethene, and bpda = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene], were designed, synthesized, and firmly characterized using single-crystal X-ray diffraction. The coordination patterns of the diphosphate group of IDP in these complexes were studied by crystallographic analysis, namely, open, close, and open-close hybrid types. We have investigated the diverse coordination patterns of the diphosphate group and its spatial relationship relative to the pentose ring on the basis of two conformational parameters, the pseudorotation phase angle and the degree of puckering. Crystallographic studies clearly reveal the correlation between the backbone torsion angle (ω' and φ) of the sugar-diphosphate and the conformational preference of the pentose ring, i.e., the signs of the backbone torsion angles ω' and φ are both plus (+) or minus (-), the conformation of the pentose ring is envelope form (E), while when one of the two signs is plus (+) and the other is minus (-), the pentose ring is in the twist form (T). This is the first time elucidation of the coordination pattern of diphosphate relative to the conformation of the pentose ring in nucleotide metal complexes, which are different from the other inorganic or organic diphosphate compounds. The chirality of these coordination polymers was examined by combining solid-state circular dichroism spectroscopy measurements with the explanation of their crystal structures. The results presented in this paper are very important for understanding their nucleotide coordination chemistry, their supramolecular chemistry, and even their biochemistry.

Effects of Biocontrol Agents Application on Soil Bacterial Community and the Quality of Tobacco.

In this study, to evaluate the effect of different biocontrol agents (BCAs) on the soil bacterial community, we investigated the effects of Bacillus amyloliquefaciens, synthetic bacterial community (Aspergillus niger:Bacillus subtilis:Bacillus licheniformis:Streptomyces microflavus = 3:3:3:1, SynCom), and BCAs combined with lime-nitrogen on soil bacterial community by utilizing 16S rRNA sequencing technology. The sequencing shows that BCAs application can improve the value of Shannon and Sobs index of bacterial community during tobacco rosette and vigorous growing period. With the growth of tobacco, the effect of BCAs on the composition and difference of soil bacterial community structure becomes more and more obvious. In terms of average relative richness, the top six phyla of soil bacterial community are Proteobacteria, Actinobacteria, Chloroflexi, Acidobacteria, Gemmatimonadetes, and Bacteroidetes. Bacillus amyloliquefaciens application can increase the relative richness of Proteobacteria and Bacteroidetes. And the combination between BCAs and lime-nitrogen can increase the relative richness of Gemmatimonadetes and Bacteroidetes. The SynCom also can increase the relative richness of Bacteroidetes, whereas it decreases the relative richness of Acidobacteria. Proteobacteria, Acidobacteria, Gemmatimonadetes, and Bacteroidetes showing an extremely significant correlation with pH and exchangeable magnesium (EMg). BCAs application can improve the tobacco yield, effective leaves, and reducing sugar content that also has extremely significant positive correlation with pH and EMg. In conclusion, the results of our field experiments clearly show that BCAs application can significantly affect the soil pH and EMg by changing most of the dominant soil bacterial species. The richness of Bacteroidetes can serve as an indicator of the changes in soil pH and EMg caused by BCAs application.

Enhanced bioproduction of fucosylated oligosaccharide 3-fucosyllactose in engineered Escherichia coli with an improved de novo pathway.

3-fucosyllactose (3-FL) and 2'-fucosyllactose (2'-FL), are two important fucosylated oligosaccharides in human milk. Extensive studies on 2'-FL enabled its official approval for use in infant formula. However, development of 3-FL has been somewhat sluggish due to its low content in human milk and poor yield in enlarged production. Here, an α-1,3-fucosyltransferase mutant was introduced into an engineered Escherichia coli (E. coli) capable of producing GDP-L-fucose, leading to a promising 3-FL titer in a 5.0-L bioreactor. To increase the availability of cofactors (NADPH and GTP) for optimized 3-FL production, zwf, pntAB, and gsk genes were successively overexpressed, finally resulting in a higher 3-FL level with a titer of 35.72 g/L and a yield of 0.82 mol 3-FL/mol lactose. Unexpectedly, the deletion of pfkA gene led to a much lower performance of 3-FL production than the control strain. Still, our strategy achieved the highest 3-FL level in E. coli to date.

LncRNA HOXA-AS3 Promotes the Progression of Pulmonary Arterial Hypertension through Mediation of miR-675-3p/PDE5A Axis.

Pulmonary arterial hypertension (PAH) seriously threatens the elder people. Long non-coding RNAs (lncRNAs) are involved in multiple diseases. However, the study of the lncRNAs in the occurrence of PAH is just beginning. For this, we sought to explore the biological function of lncRNA HOXA cluster antisense RNA 3 (HOXA-AS3) in PAH. Hypoxia (HYP) was used to mimic in vitro model of PAH. Gene and protein expressions in cells were detected by q-PCR and Western blotting, respectively. In addition, cell proliferation and viability were tested by CCK-8 and MTT assay. Cell apoptosis was measured by flow cytometry. Wound healing was used to detect cell migration. Furthermore, the connection of HOXA-AS3, miR-675-3p, and phosphodiesterase 5A (PDE5A) was verified by dual-luciferase report assay. HOXA-AS3 and PDE5A were upregulated in human pulmonary artery smooth muscle cells (HPASMCs) in the presence of HYP, while miR-675-3p was downregulated. Moreover, knockdown of HOXA-AS3 suppressed the growth and migration of HPASMCs, but induced the apoptosis. Overexpression of miR-675-3p achieved the same effect. MiR-675-3p inhibitor or overexpression of PDE5A notably reversed the inhibitory effect of HOXA-AS3 knockdown on PAH. Finally, HOXA-AS3 could sponge miR-675-3p, and PDE5A was directly targeted by miR-675-3p. HOXA-AS3 increased the development of PAH via regulation of miR-675-3p/PDE5 axis, which could be the potential biomarker for treatment of PAH.

Multi-Enzymatic Cascade One-Pot Biosynthesis of 3'-Sialyllactose Using Engineered Escherichia coli.

Among the human milk oligosaccharides (HMOs), one of the most abundant oligosaccharides and has great benefits for human health is 3'-sialyllactose (3'-SL). Given its important physiological functions and the lack of cost-effective production processes, we constructed an in vitro multi-enzymatic cofactor recycling system for the biosynthesis of 3'-SL from a low-cost substrate. First, we constructed the biosynthetic pathway and increased the solubility of cytidine monophosphate kinase (CMK) with chaperones. We subsequently identified that ß-galactosidase (lacZ) affects the yield of 3'-SL, and hence with the lacZ gene knocked out, a 3.3-fold increase in the production of 3'-SL was observed. Further, temperature, pH, polyphosphate concentration, and concentration of divalent metal ions for 3'-SL production were optimized. Finally, an efficient biotransformation system was established under the optimized conditions. The maximum production of 3'-SL reached 38.7 mM, and a molar yield of 97.1% from N-acetylneuraminic acid (NeuAc, sialic acid, SA) was obtained. The results demonstrate that the multi-enzymatic cascade biosynthetic pathway with cofactor regeneration holds promise as an industrial strategy for producing 3'-SL.

Complementation of Cobalamin Auxotrophy in Synechococcus sp. Strain PCC 7002 and Validation of a Putative Cobalamin Riboswitch In Vivo.

UNLABELLED: The euryhaline cyanobacterium Synechococcus sp. strain PCC 7002 has an obligate requirement for exogenous vitamin B12 (cobalamin), but little is known about the roles of this compound in cyanobacteria. Bioinformatic analyses suggest that only the terminal enzyme in methionine biosynthesis, methionine synthase, requires cobalamin as a coenzyme in Synechococcus sp. strain PCC 7002. Methionine synthase (MetH) catalyzes the transfer of a methyl group from N(5)-methyl-5,6,7,8-tetrahydrofolate to l-homocysteine during l-methionine synthesis and uses methylcobalamin as an intermediate methyl donor. Numerous bacteria and plants alternatively employ a cobalamin-independent methionine synthase isozyme, MetE, that catalyzes the same methyl transfer reaction as MetH but uses N(5)-methyl-5,6,7,8-tetrahydrofolate directly as the methyl donor. The cobalamin auxotrophy of Synechococcus sp. strain PCC 7002 was complemented by using the metE gene from the closely related cyanobacterium Synechococcus sp. strain PCC 73109, which possesses genes for both methionine synthases. This result suggests that methionine biosynthesis is probably the sole use of cobalamin in Synechococcus sp. strain PCC 7002. Furthermore, a cobalamin-repressible gene expression system was developed in Synechococcus sp. strain PCC 7002 that was used to validate the presence of a cobalamin riboswitch in the promoter region of metE from Synechococcus sp. strain PCC 73109. This riboswitch acts as a cobalamin-dependent transcriptional attenuator for metE in that organism. IMPORTANCE: Synechococcus sp. strain PCC 7002 is a cobalamin auxotroph because, like eukaryotic marine algae, it uses a cobalamin-dependent methionine synthase (MetH) for the final step of l-methionine biosynthesis but cannot synthesize cobalamin de novo Heterologous expression of metE, encoding cobalamin-independent methionine synthase, from Synechococcus sp. strain PCC 73109, relieved this auxotrophy and enabled the construction of a truly autotrophic Synechococcus sp. strain PCC 7002 more suitable for large-scale industrial applications. Characterization of a cobalamin riboswitch expands the genetic toolbox for Synechococcus sp. strain PCC 7002 by providing a cobalamin-repressible expression system.

Vipp1 is essential for the biogenesis of Photosystem I but not thylakoid membranes in Synechococcus sp. PCC 7002.

The biogenesis of thylakoid membranes in cyanobacteria is presently not well understood, but the vipp1 gene product has been suggested to play an important role in this process. Previous studies in Synechocystis sp. PCC 6803 reported that vipp1 (sll0617) was essential. By constructing a fully segregated null mutant in vipp1 (SynPCC7002_A0294) in Synechococcus sp. PCC 7002, we show that Vipp1 is not essential. Spectroscopic studies revealed that Photosystem I (PS I) was below detection limits in the vipp1 mutant, but Photosystem II (PS II) was still assembled and was active. Thylakoid membranes were still observed in vipp1 mutant cells and resembled those in a psaAB mutant that completely lacks PS I. When the vipp1 mutation was complemented with the orthologous vipp1 gene from Synechocystis sp. PCC 6803 that was expressed from the strong P(cpcBA) promoter, PS I content and activities were restored to normal levels, and cells again produced thylakoids that were indistinguishable from those of wild type. Transcription profiling showed that psaAB transcripts were lower in abundance in the vipp1 mutant. However, when the yfp gene was expressed from the P(psaAB) promoter in the presence and the absence of Vipp1, no difference in YFP expression was observed, which shows that Vipp1 is not a transcription factor for the psaAB genes. This study shows that thylakoids are still produced in the absence of Vipp1 and that normal thylakoid biogenesis in Synechococcus sp. PCC 7002 requires expression and biogenesis of PS I, which in turn requires Vipp1.

Targeted expression of BikDD eradicates pancreatic tumors in noninvasive imaging models.

Pancreatic cancer is an aggressive malignancy with morbidity rates almost equal to mortality rates because of the current lack of effective treatment options. Here, we describe a targeted approach to treating pancreatic cancer with effective therapeutic efficacy and safety in noninvasive imaging models. We developed a versatile expression vector "VISA" (VP16-GAL4-WPRE integrated systemic amplifier) and a CCKAR (cholecystokinin type A receptor) gene-based, pancreatic-cancer-specific promoter VISA (CCKAR-VISA) composite to target transgene expression in pancreatic tumors in vivo. Targeted expression of BikDD, a potent proapoptotic gene driven by CCKAR-VISA, exhibited significant antitumor effects on pancreatic cancer and prolonged survival in multiple xenograft and syngeneic orthotopic mouse models of pancreatic tumors with virtually no toxicity.

Homology modeling and function of trehalose synthase from Pseudomonas putida P06.

Trehalose is a non-reducing disaccharide that has wide applications in the food industry and pharmaceutical manufacturing. Trehalose synthase (TreS) from Pseudomonas putida P06 catalyzes the reversible interconversion of maltose and trehalose and may have applications in the food industry. However, the catalytic mechanism of TreS is not well understood. Here, we investigated the structural characteristics of this enzyme by homology modeling. The highly conserved Asp294 residue was identified to be critical for catalytic activity. In addition, flexible docking studies of the enzyme-substrate system were performed to predict the interactions between TreS and its substrate, maltose. Amino acids that interact extensively with the substrate and stabilize the substrate in an orientation suitable for enzyme catalysis were identified. The importance of these residues for catalytic activity was confirmed by the biochemical characterization of the relevant mutants generated by site-directed mutagenesis.

Altered carbohydrate metabolism in glycogen synthase mutants of Synechococcus sp. strain PCC 7002: Cell factories for soluble sugars.

Glycogen and compatible solutes are the major polymeric and soluble carbohydrates in cyanobacteria and function as energy reserves and osmoprotectants, respectively. Glycogen synthase null mutants (glgA-I glgA-II) were constructed in the cyanobacterium Synechococcus sp. strain PCC 7002. Under standard conditions the double mutant produced no glycogen and more soluble sugars. When grown under hypersaline conditions, the glgA-I glgA-II mutant accumulated 1.8-fold more soluble sugars (sucrose and glucosylglycer-(ol/ate)) than WT, and these cells spontaneously excreted soluble sugars into the medium at high levels without the need for additional transporters. An average of 27% more soluble sugars was released from the glgA-I glgA-II mutant than WT by hypo-osmotic shock. Extracellular vesicles budding from the outer membrane were observed by transmission electron microscopy in glgA-I glgA-II cells grown under hypersaline conditions. The glgA-I glgA-II mutant serves as a starting point for developing cell factories for photosynthetic production and excretion of sugars.

Maximum Correntropy Filtering for Complex Networks With Uncertain Dynamical Bias: Enabling Componentwise Event-Triggered Transmission.

This article is concerned with the maximum correntropy filtering (MCF) problem for a class of nonlinear complex networks subject to non-Gaussian noises and uncertain dynamical bias. With aim to utilize the constrained network bandwidth and energy resources in an efficient way, a componentwise dynamic event-triggered transmission (DETT) protocol is adopted to ensure that each sensor component independently determines the time instant for transmitting data according to the individual triggering condition. The principal purpose of the addressed problem is to put forward a dynamic event-triggered recursive filtering scheme under the maximum correntropy criterion, such that the effects of the non-Gaussian noises can be attenuated. In doing so, a novel correntropy-based performance index (CBPI) is first proposed to reflect the impacts from the componentwise DETT mechanism, the system nonlinearity, and the uncertain dynamical bias. The CBPI is parameterized by deriving upper bounds on the one-step prediction error covariance and the equivalent noise covariance. Subsequently, the filter gain matrix is designed by means of maximizing the proposed CBPI. Finally, an illustrative example is provided to substantiate the feasibility and effectiveness of the developed MCF scheme.

Preferential Enrichment of Enantiomer from Amino Acid Schiff Bases by Coordination Interaction and Crystallization.

In this paper, preferential enrichment (PE) is described for three pairs of novel amino acid Schiff base Cu(II)/Cu(I) complexes. Single crystal X-ray diffraction indicated that 1-S/R are one-dimensional coordination polymers (CPs) with helical structures, and 2-S/R and 3-S/R are one-dimensional CPs with auxiliary ligands. By tuning the pH, the solvent and second ligands, the 1-S/R, 3-S/R underwent polymorphic transitions, resulting in enantioselective liberation of excess enantiomers into solution, until the deposited crystals were slightly enriched with the opposite enantiomer, thereby successfully exhibiting PE. However, under the effects of Cu(II), the solvent and low pH, 2-S/R did not exhibit PE and resulted in enrichment of racemic compounds, which was attributed to amino acid Schiff base chiral complex mechanisms of PE. The three pairs of Cu complex structures were characterized by UV-vis, MS and X-ray photoelectron spectroscopy (XPS). All chiral properties were studied by circular dichroism (CD) in the solid and liquid.

Metabolic Engineering of Escherichia coli for High-Level Production of Lacto-N-neotetraose and Lacto-N-tetraose.

Lacto-N-neotetraose (LNnT) and lacto-N-tetraose (LNT) are important oligosaccharides found in breast milk and are commonly used as nutritional supplements in infant formula. We used metabolic engineering techniques to optimize the modified Escherichia coli BL21 star (DE3) strain for efficient synthesis of LNnT and LNT using ß-1,4-galactosyltransferase (HpgalT) from Helicobacter pylori and ß-1,3-galactosyltransferase (SewbdO) from Salmonella enterica subsp. salamae serovar, respectively. Further, we optimized the expression of three key genes, lgtA, galE, and HpgalT (SewbdO), to synthesize LNnT or LNT and deleted several genes (ugd, ushA, agp, wcaJ, otsA, and wcaC) to block competition in the UDP-galactose synthesis pathway. The optimized strain produced LNnT or LNT with a titer of 22.07 or 48.41 g/L, respectively, in a supplemented batch culture, producing 0.41 or 0.73 g/L/h, respectively. The strategies used in this study contribute to the development of cell factories for high-level LNnT and LNT and their derivatives.

Lineage-specific fragmentation and nuclear relocation of the mitochondrial cox2 gene in chlorophycean green algae (Chlorophyta).

In most eukaryotes the subunit 2 of cytochrome c oxidase (COX2) is encoded in intact mitochondrial genes. Some green algae, however, exhibit split cox2 genes (cox2a and cox2b) encoding two polypeptides (COX2A and COX2B) that form a heterodimeric COX2 subunit. Here, we analyzed the distribution of intact and split cox2 gene sequences in 39 phylogenetically diverse green algae in phylum Chlorophyta obtained from databases (28 sequences from 22 taxa) and from new cox2 data generated in this work (23 sequences from 18 taxa). Our results support previous observations based on a smaller number of taxa, indicating that algae in classes Prasinophyceae, Ulvophyceae, and Trebouxiophyceae contain orthodox, intact mitochondrial cox2 genes. In contrast, all of the algae in Chlorophyceae that we examined exhibited split cox2 genes, and could be separated into two groups: one that has a mitochondrion-localized cox2a gene and a nucleus-localized cox2b gene ("Scenedesmus-like"), and another that has both cox2a and cox2b genes in the nucleus ("Chlamydomonas-like"). The location of the split cox2a and cox2b genes was inferred using five different criteria: differences in amino acid sequences, codon usage (mitochondrial vs. nuclear), codon preference (third position frequencies), presence of nucleotide sequences encoding mitochondrial targeting sequences and presence of spliceosomal introns. Distinct green algae could be grouped according to the form of cox2 gene they contain: intact or fragmented, mitochondrion- or nucleus-localized, and intron-containing or intron-less. We present a model describing the events that led to mitochondrial cox2 gene fragmentation and the independent and sequential migration of cox2a and cox2b genes to the nucleus in chlorophycean green algae. We also suggest that the distribution of the different forms of the cox2 gene provides important insights into the phylogenetic relationships among major groups of Chlorophyceae.

Distributed Robust Optimization Algorithms Over Uncertain Network Graphs.

This article investigates the robustness issues of a set of distributed optimization algorithms, which aim to approach the optimal solution to a sum of local cost functions over an uncertain network. The uncertain communication network consists of transmission channels perturbed by additive deterministic uncertainties, which can describe quantization and transmission errors. A new robust initialization-free algorithm is proposed for the distributed optimization problem of multiple Euler-Lagrange systems, and the explicit relationship of the feedback gain of the algorithm, the communication topology, the properties of the cost function, and the radius of the channel uncertainties is established in order to reach the optimal solution. This result provides a sufficient condition for the selection of the feedback gain when the uncertainty size is less than the unity. As a special case, we discuss the impact of communication uncertainties on the distributed optimization algorithms for first-order integrator networks.

Particle-Filter-Based State Estimation for Delayed Artificial Neural Networks: When Probabilistic Saturation Constraints Meet Redundant Channels.

In this brief, the state estimation problem is investigated for a class of randomly delayed artificial neural networks (ANNs) subject to probabilistic saturation constraints (PSCs) and non-Gaussian noises under the redundant communication channels. A series of mutually independent Bernoulli distributed white sequences are introduced to govern the random occurrence of the time delays, the saturation constraints, and the transmission channel failures. A comprehensive redundant-channel-based communication mechanism is constructed to attenuate the phenomenon of packet dropouts so as to enhance the quality of data transmission. To compensate for the influence of randomly occurring time delays, the corresponding occurrence probability is exploited in the process of particle generation. In addition, an explicit expression of the likelihood function is established based on the statistical information to account for the impact of PSCs and redundant channels. By virtue of the modified operations of particle propagation and weight update, a particle-filter-based state estimation algorithm is proposed with mild restriction on the system type. Finally, an illustrative example with Monte Carlo simulations is provided to demonstrate the effectiveness of the developed state estimation scheme.

Efficacy comparison of immune treating strategies for NSCLC patients with negative PD-L1 expression.

BACKGROUND: We intended to compare and grade the proposed immune treating strategies for non-small cell lung cancer (NSCLC) with negative Programmed Cell Death Ligand 1(PD-L1). METHODS: We compared the efficacy of single immune checkpoint inhibitor (ICI), single ICI plus chemotherapy, and doublet ICIs with chemotherapy alone, as well as single ICI plus radiotherapy with single ICI for negative PD-L1 (<1%) NSCLC patients. Hazard Ratio (HR) and 95% confidence interval (CI) of progression-free survival (PFS) and overall survival (OS) were used as outcomes. RESULTS: We included 23 randomized control trials with 4665 patients. Compared with chemotherapy alone, single ICI, single ICI plus chemotherapy and doublet ICIs all showed a better OS (0.84 [0.71, 0.99] ; 0.77 [0.69, 0.85] ; 0.64 [0.53, 0.77])), while single ICI plus chemotherapy and doublet ICIs showed a better PFS (0.68 [0.61, 0.75] ; 0.69 [0.56, 0.85]). Additionally, single ICI plus radiotherapy obtained a greater pooled PFS (0.49 [0.28-0.87]) than single ICI. CONCLUSIONS: Both single ICI plus chemotherapy and doublet ICIs were probably better treatment decisions than chemotherapy alone for negative PD-L1 NSCLC patients. Also, single ICI plus radiotherapy carved out a new strategy.