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Developing artificial enzyme mimetics for the detection of small biomolecules are a current research interest because natural enzymes bear some serious disadvantages, such as their catalytic activity can be easily inhibited and they can be digested by proteases. Herein, a heteropoly acids (HPA) encapsulating metal–organic framework (MOF) with metal-carbene structure, [Cu10(H3trz)4(Htrz)4][PMo12VO41] (PMA-MOF) as bifunctional enzyme-mimetic catalyst for colorimetric detection of hydrogen peroxide (H2O2) and ascorbic acid (AA) was designed and synthesized. Thanks to the good stability and the synergistic effect of PMA and MOF, PMA-MOF exhibits the lower limit of detection (0.222 μM towards H2O2 and 0.0046 μM to AA), and the smaller Km value (0.0138 mM for H2O2 and 0.136 mM for o-phenylenediamine) compared to most reported MOF- and HPA-based enzyme-mimetic catalyst, to the best our knowledge. [ABSTRACT FROM AUTHOR]

Background: Tumor mutation burden (TMB) predicts immunotherapy efficacy in solid tumors. However, the biomarker role of TMB is still conflicting in resected tumors. We aimed to examine the association of TMB with prognosis and postoperative chemotherapy (CT) or radiochemotherapy (RCT) efficacy in resected gastric cancer (GC). Methods: Whole-exome sequencing (WES) was performed in 73 resected GC specimens. Validation cohorts included 352 patients from The Cancer Genome Atlas (TCGA) and 222 patients from the Asian Cancer Research Group (ACRG). Immune infiltration and hypoxia were evaluated by transcriptome data and immunohistochemistry assay. Results: TMB-high GC had favorable overall survival (OS) and disease-free survival (DFS), but the OS and DFS benefits with postoperative CT/RCT were more pronounced in TMB-low GC. These findings were consistent among all three cohorts and were maintained in the pooled cohort. Stratified by stages in the pooled cohort, stage III GC benefited from postoperative CT/RCT regardless of TMB level while stage Ib/II GC benefited from postoperative CT/RCT in TMB-low but not in TMB-high subgroup. TMB positively correlated with immune infiltration which was characterized by NK cell rather than CD8 + T cell enrichment. TMB-high GC was more hypoxic than TMB-low GC, and TMB-high stage Ib/II GC was the most hypoxic. Conclusions: High TMB may predict favorable prognosis in resected GC but poor response to postoperative CT/RCT in stage Ib/II subgroup, which may be determined by TMB-associated immune infiltration and hypoxia, respectively. [ABSTRACT FROM AUTHOR]

The Lewis base supported terminal uranium phosphinidene metallocene [η5-1,3-(Me3C)2C5H3]2U(＝P-2,4,6-iPr3C6H2)(OPMe3) (2) could be isolated from a salt metathesis reaction in toluene at ambient temperature between [η5-1,3-(Me3C)2C5H3]2U(Cl)Me (1) and 2,4,6-iPr3C6H2PHK in the presence of Me3PO, and its structure and reactivity were probed in detail. No reaction of 2 with internal alkynes was observed, but it reacts in the presence of various heterounsaturated molecules such as CS2, isothiocyanates, aldehydes, imines, diazenes, carbodiimides, nitriles, isonitriles, diazoalkane, and organic azides, forming carbodithioates, sulfidos, oxidos, metallaheterocycles, and imido complexes, in good yields. Moreover, on reaction with the diazoalkane derivative Me3SiCHN2 the pseudophosphinimido uranium(III) complex [η5-1,3-(Me3C)2C5H3]2U(N＝P-2,4,6-iPr3C6H2)(OPMe3) (20) can be isolated in good yield. [ABSTRACT FROM AUTHOR]

The synthesis, electronic structure, and reactivity of a uranium metallacyclopropene were comprehensively studied. Addition of diphenylacetylene (PhC≡CPh) to the uranium phosphinidene metallocene [η5‐1,2,4‐(Me3C)3C5H2]2U=P‐2,4,6‐tBu3C6H2 (1) yields the stable uranium metallacyclopropene, [η5‐1,2,4‐(Me3C)3C5H2]2U[η2‐C2Ph2] (2). Based on density functional theory (DFT) results the 5f orbital contributions to the bonding within the metallacyclopropene U‐(η2‐C=C) moiety increases significantly compared to the related ThIV compound [η5‐1,2,4‐(Me3C)3C5H2]2Th[η2‐C2Ph2], which also results in more covalent bonds between the [η5‐1,2,4‐(Me3C)3C5H2]2U2+ and [η2‐C2Ph2]2− fragments. Although the thorium and uranium complexes are structurally closely related, different reaction patterns are therefore observed. For example, 2 reacts as a masked synthon for the low‐valent uranium(II) metallocene [η5‐1,2,4‐(Me3C)3C5H2]2UII when reacted with Ph2E2 (E=S, Se), alkynes and a variety of hetero‐unsaturated molecules such as imines, ketazine, bipy, nitriles, organic azides, and azo derivatives. In contrast, five‐membered metallaheterocycles are accessible when 2 is treated with isothiocyanate, aldehydes, and ketones. [ABSTRACT FROM AUTHOR]

Background: In addition to ovarian and breast cancers, loss-of-function mutations in BRCA1 and BRCA2 genes are also linked to an increased risk of pancreatic cancer, with ~ 4 to 7% of pancreatic cancer patients harboring germline BRCA mutations. Most BRCA alterations in pancreatic cancer are frame-shifting indels, stop-gain, and splice-site mutations, but single nucleotide substitutions are rare. Recent studies demonstrated a significant progression-free survival (PFS) benefit from maintenance olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor administered to patients with germline BRCA mutations and metastatic pancreatic cancer. Case presentation: Here, we report a metastatic pancreatic cancer case who harbored a novel somatic BRCA2 c.6944T > C (p. I2315T) point mutation. After 6 weeks first-line chemotherapy, the patient was refractory to treatment and had a progressive disease. Due to the novel nonsynonymous BRCA2 point mutation, we decided to change the strategy by administering olaparib. The patient benefited from olaparib therapy and achieved a PFS of ~ 6.5 months. Conclusions: We describe a patient carrying a novel somatic BRCA2 p. I2315T point mutation, which is first reported in metastatic pancreatic cancer. This case report indicates that a gene mutation-based strategy should be considered in the clinic to provide more effective treatment. [ABSTRACT FROM AUTHOR]

The first stable base‐free terminal uranium phosphinidene metallocene is presented; and its structure and reactivity have been studied in detail and compared to that of the corresponding thorium derivative. Salt metathesis reaction of the methyl iodide uranium metallocene Cp"'2U(I)Me (2, Cp"'=η5‐1,2,4‐(Me3C)3C5H2) with Mes*PHK (Mes*=2,4,6‐(Me3C)3C6H2) in THF yields the base‐free terminal uranium phosphinidene metallocene, Cp"'2U=PMes* (3). In addition, density functional theory (DFT) studies suggest substantial 5f orbital contributions to the bonding within the uranium phosphinidene [U]=PAr moiety, which results in a more covalent bonding between the [Cp"'2U]2+ and [Mes*P]2− fragments than that for the related thorium derivative. This difference in bonding besides steric reasons causes different reactivity patterns for both molecules. Therefore, the uranium derivative 3 may act as a Cp"'2U(II) synthon releasing the phosphinidene moiety (Mes*P:) when treated with alkynes or a variety of hetero‐unsaturated molecules such as imines, thiazoles, ketazines, bipy, organic azides, diazene derivatives, ketones, and carbodiimides. [ABSTRACT FROM AUTHOR]

Two-stage isolated battery-driven grid interface (IBDGI) with front-end three-phase dual active bridge (DAB) dc–dc converter is promising to be applied in the residential battery energy storage system for supporting photovoltaic (PV) integration, load shifting, and backup power purposes. However, the second harmonic current (SHC) caused by the pulsating power of the downstream single-phase inverter will increase the battery's degradation and the component stress of the front-end converter. In this paper, a reduction method is proposed for the IBDGI with three-phase DAB converter using a load current feedforward control. The proposed idea is to incorporate virtual impedance to the output impedance of the front-end converter. The easy-to-be-implemented method does not need to modify the original voltage closed-loop controller but suppress SHC while keeping good dynamic performance. As the first step, the small-signal model of the three-phase DAB converter is provided. The parameter sensitivity analysis is proposed to demonstrate that the SHC can be well-suppressed within $\pm \text{20}\%$ parameter error of the feedforward control. Finally, a 1 kW experiment setup is built to verify the performance of the proposed SHC reduction method. [ABSTRACT FROM AUTHOR]

Polysaccharides from fungi are good free radical scavengers. However, there are no enzymes digesting these polysaccharides in the human body, which limits the use of fungal polysaccharides. Therefore, it is of great significance to study the preparation methods of fungal polysaccharides to improve the utilization rate of fungal polysaccharides. In this paper, the acidic polysaccharide of Tremella fuciformis was extracted by boiling and precipitated by ethanol. The total sugar content obtained by freeze-drying after ion exchange chromatography purification was 93.6%. It is mainly composed of mannose, glucuronic acid, xylose and fucose. According to the peak area, the mass ratio of the substance is about 6.8:1:1.5:0.6, which indicates that TFP is a polysaccharide with mannose as its main chain and glucuronic acid, fucose and xylose as well as a small amount of glucose as the branch chain. Molecular weight is 1.86 × 106 Da. The existence of glucuronic acid endows polysaccharides with negative charge in aqueous solution and can be assembled into nanostructures with chitosan. By measuring the swelling property in aqueous, it shows the TFP separated from Tremella fuciformis fruits is suitable for drug controlled release. • The polysaccharide extracted from Tremella Fuciformis Fruiting body, and characterized by HPLC, FTIR, HPGPC, 1H NMR/13C NMR. • Methods of nanostructures assembly of Tremella Fuciformis polysaccharide with chitosan were reported. • The nanostructures were characterized by FTIR, SEM and DLS. • The properties of medicine encapsulation and heavy metal ions absorption of the nanostructures were investigated [ABSTRACT FROM AUTHOR]

Abstract Application of multi-fractured horizontal wells has led to significant progress in the development of tight oil reservoirs. However, oil production rapidly decreases and the estimated ultimate recovery is still low when the well is in production and approaching depletion. Water huff-n-puff is regarded as a useful measure to improve oil recovery due to oil-water imbibition and drainage. Additionally, complex fracture networks consisting of natural fractures (NF) and hydraulic fractures can significantly enhance oil recovery in the process of water huff-n-puff after multi-stage hydraulic fracturing. However, there is a non-flowing thin film on the solid-liquid wall surface in the pore-throats of the matrix, and the so-called boundary layer effect (BLE) is quite significant at the nano-scale. This effect reduces the effective flow space and effective permeability of the reservoir, leading to production damage. To date, few numerical simulation studies have considered the impact of the BLE and complex fracture networks in water huff-n-puff process simulation studies. In this study, the process of water huff-n-puff is evaluated considering complex fracture networks and formation damage in a matrix. The embedded discrete fracture model (EDMF), validated by local grid refinement (LGR), is applied to describe the distribution of hydraulic fractures and NF. The well performance considering the BLE is analyzed by a vectorization programming. The results show that the BLE reduces production and accelerates the production decline, so the BLE should be considered in reservoir simulations and productivity evaluations of water huff-n-puff processes. A certain degree of natural fracture development is conducive to improving the sweep efficiency of the water huff-n-puff, which could significantly improve oil recovery compared to depletion. By considering the impact of the BLE in water huff-n-puff simulations in tight oil reservoirs, it is possible to accurately evaluate the well performance and provide a theoretical basis for the optimization of water huff-n-puff. Highlights • Natural fractures network is described by EDFM using the random function. • The permeability is modified considering boundary layer effect in the matrix. • The water huff-n-puff with the formation damage is evaluated. [ABSTRACT FROM AUTHOR]

Abstract The aim of the present work was to prepare high loading capacity carriers for immobilizing glucoamylase. Different sizes of chitosan based particles were successfully prepared by different methods to evaluate the performance in immobilization. Chitosan particles on millimeter size were prepared by dripping granulation method, chitosan covered magnetic nanoparticles and chitosan mixted graphene oxide nanosheets covered magnetic nanoparticles were synthesized by one-step method, chitosan-glucoamylase nanoparticles were synthesized by ionic cross linking method with Sodium tripolyphosphate. These particles were characterized by SEM, TEM, FTIR and DLS analysis. The performance of the immobilized enzyme was also investigated. The results showed that the loading capacity was greatly increased on chitosan based nanoparticles. The reaction conditions of immobilized enzyme were optimized, the reusability and storage stability was also investigated. The results showed the pH durance and storage stability of the immobilized enzyme on nanosize particles were enhanced. [ABSTRACT FROM AUTHOR]

Purpose: Several studies have proved that single nucleotide polymorphisms (SNPs) of mismatch repair system genes are closely related to the development of colorectal cancer (CRC) by causing microsatellite instability, while effects of the SNPs of MMR system-related genes on the clinical outcomes of cytotoxic chemotherapy are less understood. The aim of this study explored the influence of MLH1 SNPs on clinical outcomes of first-line irinotecan-based chemotherapy in CRC.Patients and methods: A total of 125 metastatic colorectal cancer (mCRC) patients who received first-line irinotecan-based chemotherapy (none of them combined with bevacizumab or cetuximab) were enrolled in this study. Blood samples or formalin-fixed paraffin-embedded tissues of study population were taken. DNA isolation and genotyping analyzed were obtained for potential functional polymorphisms of MLH1 rs1800734 by real-time PCR. Progression-free survival (PFS) was the primary endpoint and tumor response rate (RR) was the secondary endpoint of this study.Results: Of all the assessable population, the result showed no statistical difference among the three types SNPs of MLH1 rs1800734 (AA, AG, GG) for RR (P=0.859), and also without significant difference for AA + AG combined variants vs GG variant (P=0.849). The median PFS for AA, AG, and GG variants of MLH1 rs1800734 SNPs were 9.4 months, 7.0 months, and 6.9 months, respectively (log-rank P=0.031). Interestingly, compared with AA variant of MLH1 rs1800734 SNPs, GG variant showed a shorter PFS (HR: 3.49; 95 CI: 1.02–11.94; P=0.046). Furthermore, the median PFS of AA + AG combined variants and GG variant were 8.3 months and 6.9 months (log-rank P=0.037), and GG variant have a decreased trend with no significant difference (HR: 1.57; 95 CI: 0.98–2.53; P=0.061).Conclusion: The AA variant of MLH1 rs1800734 SNPs has a longer PFS in first-line irinotecan-based chemotherapy for mCRC patients, and the result needs to be further confirmed by prospective studies in the future. [ABSTRACT FROM AUTHOR]

In a recent paper, we proposed group-by-group bit filling (GBF) and group-by-group bit removal (GBR) to boost the efficiency of bit loading. Generally, GBF/GBR converges to a suboptimal bit-allocation profile (BAP), and thus, a supplementary greedy bit-filling/bit-removal procedure is required to converge to the optimal BAP. In this correspondence, we propose refined GBF (r-GBF) and refined GBR (r-GBR) to overcome the imperfection of GBF and GBR. The key idea is to adjust the group size dynamically such that the optimal BAP can be directly achieved for any available target data rate. Based on r-GBF and r-GBR, a couple of bit-loading algorithms, which are named iterative GBF and iterative GBR, are presented. Numerical results show that the newly presented algorithms converge to the optimal BAP properly and outperform existing optimal algorithms in computational cost. [ABSTRACT FROM PUBLISHER]

Abstract: Tm3+–Yb3+ co-doped titania–zirconia composites were synthesized by co-precipitation method with aqueous ammonia as precipitator. Time evolution of upconverted emission of thulium in ZT0.4–Tm0.01Yb0.04 (40%ZrO2–60%TiO2–1%Tm3+–4%Yb3+) demonstrated ZT0.4 to be a promising matrix in the field of upconversion luminescence. Raman spectrum shows low phonon energy (800cm−1) of ZT0.4 ensuring a fluent phonon transition process. The luminescent properties were investigated by photoluminescence spectra. Strong blue and red upconversion emissions could be observed which were attributed to 1G4–3H6, 3F2–3H6, 1G4–3F4 transitions, respectively. [Copyright &y& Elsevier]

Summary: Purpose: To assess the risk/benefit profiles of EGFR TKIs monotherapy using erlotinib or gefitinib in comparison with single-agent chemotherapy using third-generation cytotoxics (gemcitabine, vinorelbine, taxanes) as the first-line treatment for chemonaÏve patients with advanced non-small cell lung cancer (ANSCLC) and poor performance status (PS). Methods: A pooled analysis and systematic review was performed using trials identified through MEDLINE, EMBASE, Cochrane Library, and the Clinical-Trials.gov. Data were collected from randomized and non-randomized phase II or III clinical trials of EGFR TKIs monotherapy or single-agent chemotherapy using third-generation cytotoxics published before 3/1/2010, and the pooled estimates for efficacy and safety outcomes of interest were calculated. Results: Fifteen eligible trials (1425 patients) were selected from 323 studies that initially were identified. In 5 of the selected single-agent chemotherapy studies, the elderly were included together with poor PS patients. Outcomes from these studies still were employed for a thorough analysis. Targeting poor PS patients, we found that the pooled response rate (95% confidence interval) to EGFR TKIs for unselected population was 6% (3–8%), not substantially different from 9% (6–13%) reported by single-agent chemotherapy trials using third-generation cytotoxics. However, EGFR TKIs had better disease control rates with a pooled estimate of 40% (33–47%), significantly higher than 30% (20–41%) of the cytotoxics. Single-agent chemotherapy trials enrolling both elderly and poor PS patients had better results with the pooled response rate and the pooled disease control rate was 13% (11–16%) and 41% (36–46%) respectively. For safety information, despite both treatments were well-tolerated, the toxicity profile of EGFR TKIs was clearly more favorable than that reported by chemotherapy. The severe hematological adverse events related to EGFR TKIs treatment were rare. EGFR TKIs also tended to be more effective in improvement of symptoms or quality-of-life (QOL). Conclusion: Although, both of the treatments had low response rates, EGFR TKIs tended to be more effective in control of tumor progression, reduction of therapy-related toxicities, improvement of symptoms or quality-of-life in the first-line treatments of ANSCLC patients with poor PS. Moreover, our data also suggest that the elderly patients without selection carefully according their PS should be separated from this population. Further investigations with valid comparison groups are necessary. [Copyright &y& Elsevier]

Abstract: High dielectric CaCu3Ti4O12 (CCTO) ceramics have been successfully prepared by a novel basic co-precipitation (BCP) method. Compared with the conventional solid-state and/or soft chemistry methods, the BCP method has many advantages such as relatively lower sintering temperature, shorter sintering time and lower costs. The XRD patterns confirm the formation of CCTO crystal phase in the as-prepared samples. Influences of initial ingredients and sintering condition on phase composition, microstructure and dielectric property have been investigated through series of trials. The correlation between the process of the grain growth and dielectric properties of final products has been explored. The final products exhibit the dielectric constants higher than 10,000 and the dielectric losses lower than 0.15 at 1KHz. [ABSTRACT FROM AUTHOR]

Aiming at minimizing the transmit power of orthogonal frequency-division multiplexing (OFDM) systems subject to the target data rate, the target bit error rate (BER), the maximum allowable power per subcarrier, and the maximum allowable size of constellations, we present a couple of new discrete bit-loading algorithms, named efficient bit filling (EBF) and efficient bit removal (EBR), which are based on our new idea of group-by-group bit filling. Both EBF and EBR perform bit loading in two stages and are able to converge to the optimal bit-allocation profile. In the first stage, an intermediate bit-allocation profile, which is tightly close to the final bit-allocation profile, is obtained by using our proposed group-by-group bit filling (for EBF) or group-by-group bit removal (for EBR). In the second stage, the well-known greedy bit filling (for EBF) or greedy bit removal (for EBR) is performed for the remaining bits (usually of a small size). Analytical and numerical results reveal that the proposed algorithms converge to the optimal bit allocation with much lower computational complexities than existing optimal algorithms. It is also shown that the proposed algorithms outperform typical suboptimal algorithms in power efficiency with relatively higher computational complexities. [ABSTRACT FROM PUBLISHER]

Abstract: We report a stochastic nanopore sensing method for the detection of organophosphorus nerve agent hydrolysis products. By employing an engineered α-hemolysin single pore embedded in a planar lipid bilayer as the stochastic sensing element and β-cyclodextrin as a host molecule, trace amounts of soman and cyclosarin hydrolytes could be detected, with detection limits of 53nM and 102nM, respectively. Importantly, sarin, tabun, and VX hydrolysis products, as well as other common pesticides, do not interfere with detection of the analytes. The method offers the potential as a rapid and sensitive sensing technique for use in on-site analysis of nerve agents in environmental monitoring applications at the single-molecule level. [Copyright &y& Elsevier]

Abstract: The synthesis of new triphenylamine-branching chromophores with dibenzofuran-core and dibenzothiophene-core was reported and the molecular two-photon absorption (TPA) enhancement via core effect and generation effect was investigated. Comparatively, the core effect shows more significant contribution to TPA enhancement than the generation effect. This is of greatly valuable since optimizing dendritic core is laborsaving in comparison with synthesizing dendrimers with high generation. [Copyright &y& Elsevier]

Abstract: A novel four-branched chromophore TOZ-4 with starburst linker was synthesized and showed two-photon absorption cross-section (δ) as large as 5254GM, which was principally resulted from vibronic coupling enhancement. [Copyright &y& Elsevier]

Abstract: S-Adenosyl-l-methionine: uroporphyrinogen III methyltransferase (SUMT), a key regulatory enzyme, converts uroporphyrinogen III to precorrin-2 in the porphinoids biosynthesis. In this study, the mature SUMT was signified that the maize SUMT precursor encoded by the open reading frame of maize SUMT cDNA was deleted the first 91 amino acids constituting the postulated signal peptide. Several mature SUMT fusion and deletion mutants were conducted. It actively expressed in Escherichia coli that the mature SUMT, or the truncated one deleting the C-terminal extra 52 amino acids based on SUMT sequence comparisons. On the contrary, it expressed as an inclusion body in E. coli that the mature SUMT fusion mutant, the SUMT precursor, or the mature SUMT deleting the N-terminal 36 amino acids including glycine-rich region involved directly in SAM binding. The purified His6-tagged mature SUMT was homodimer with a molecular weight of 34kDa, as shown by SDS–PAGE, 52kDa using gel-filtration chromatography, and 79kDa by dynamic light scattering assay. Red fluorescent compounds were associated with the recombinant mature SUMT which were identified as sirohydrochlorin and trimethylpyrrocorphin by spectroscopic analysis. This association slightly altered the protein secondary structure confirmed by circular dichroism assay. [Copyright &y& Elsevier]

Objective. Immunotherapy has proven effective in treating advanced gastric cancer (AGC), yet its benefits are limited to a subset of patients. Our aim is to swiftly identify prognostic biomarkers using cytokines to improve the precision of clinical guidance and decision-making for PD-1 inhibitor-based cancer immunotherapy in AGC. Materials and Methods. The retrospective study compared 36 patients with AGC who received combined anti-PD-1 immunotherapy and chemotherapy (immunochemotherapy) with a control group of 20 patients who received chemotherapy alone. The concentrations of TNF-α, IL-1β, IL-2R, IL-6, IL-8, IL-10, and IL-17 in the serum were assessed using chemiluminescence immunoassay at three distinct time intervals following the commencement of immunochemotherapy. Results. When compared to controls, patients undergoing immunochemotherapy demonstrated a generalized rise in cytokine levels after the start of treatment. However, patients who benefited from immunochemotherapy showed a decrease in IL-6 or IL-8 concentrations throughout treatment (with varied trends observed for IL-1β, IL-2R, IL-10, IL-17, and TNF-α) was evident in patients benefiting from immunochemotherapy but not in those who did not benefit. Among these markers, the combination of IL-6, IL-8, and CEA showed optimal predictive performance for short-term efficacy of immunochemotherapy in AGC patients. Conclusion. Reductions in IL-6/IL-8 levels observed during immunochemotherapy correlated with increased responsiveness to treatment effectiveness. These easily accessible blood-based biomarkers are predictive and rapid and may play a crucial role in identifying individuals likely to derive benefits from PD-1 blockade immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The detection rate of Salmonella enterica serovar 1,4,[5], 12: i: - (S. 1,4,[5], 12: i: -) has increased as the most common serotype globally. A S. 1,4,[5], 12: i: - strain named ST3606 (sequence type 34), isolated from a fecal specimen of a child with acute diarrhea hospitalized in a tertiary hospital in China, was firstly reported to be resistant to carbapenem and ceftazidime-avibactam. The aim of this study was to characterize the whole-genome sequence of S. 1,4,[5], 12: i: - isolate, ST3606, and explore its antibiotic resistance genes and their genetic environments. Methods: The genomic DNA of S. 1,4,[5], 12: i: - ST3606 was extracted and performed with single-molecule real-time sequencing. Resistance genes, plasmid replicon type, mobile elements, and multilocus sequence types (STs) of ST3606 were identified by ResFinder 3.2, PlasmidFinder, OriTfinder database, ISfinder database, and MLST 2.0, respectively. The conjugation experiment was utilized to evaluate the conjugation frequency of pST3606-2. Protein expression and enzyme kinetics experiments of CTX-M were performed to analyze hydrolytic activity of a novel CTX-M-261 enzyme toward several antibiotics. Results: Single-molecule real-time sequencing revealed the coexistence of a 109-kb IncI1-Iα plasmid pST3606-1 and a 70.5-kb IncFII plasmid pST3606-2. The isolate carried resistance genes, including blaNDM-5, sul1, qacE, aadA2, and dfrA12 in pST3606-1, blaTEM-1B, aac(3)-lld, and blaCTX-M-261, a novel blaCTX-M-1 family member, in pST3606-2, and aac(6')-Iaa in chromosome. The blaCTX-M-261 was derived from blaCTX-M-55 by a single-nucleotide mutation 751G>A leading to amino acid substitution of Val for Met at position 251 (Val251Met), which conferred CTX-M increasing resistance to ceftazidime verified by antibiotics susceptibility testing of transconjugants carrying pST3606-2 and steady-state kinetic parameters of CTX-M-261. pST3606-1 is an IncI1-α incompatibility type that shares homology with plasmids of pC-F-164_A-OXA140, pE-T654-NDM-5, p_dm760b_NDM-5, and p_dmcr749c_NDM-5. The conjugation experiment demonstrated that pST3606-2 was successfully transferred to the Escherichia coli recipient C600 with four modules of OriTfinder. Conclusion: Plasmid-mediated horizontal transfer plays an important role in blaNDM-5 and blaCTX-M-261 dissemination, which increases the threat to public health due to the resistance to most β-lactam antibiotics. This is the first report of blaCTX-M-261 and blaNDM-5 in S. 1,4,[5], 12: i: -. The work provides insights into the enzymatic function and demonstrates the ongoing evolution of CTX-M enzymes and confirms urgency to control resistance of S. 1,4,[5], 12: i: -. [ABSTRACT FROM AUTHOR]

• The fluorogen with aggregation-induced emission has been designed and synthesized. • The AIEgen could be used for selective detection of hypochlorite. • The AIEgen could self-assemble in aqueous solution. • The AIEgen could be used for cell imaging and sensing hypochlorite in living cells. Fluorescent sensors have attracted great research attention for detection of various target substrates in environment and living organisms. However, there are still of some issues when using traditional organic probes owing to their poor water dispersibility and aggregation caused quenching effect. In this paper, we designed and synthesized an ionic fluorescent probe (named as TPY) with aggregation-induced emission (AIE) feature and explored its potential sensor performance towards hypochlorite in aqueous solution and living organisms. The results demonstrated that TPY can detect hypochlorite with excellent selectivity, outstanding sensitivity and fast response time. The reaction mechanism should be ascribed to the reaction between hypochlorite and TPY, that was evidenced by a number of characterization techniques, such as UV–vis/fluorescence spectroscopy, 1H NMR and mass spectroscopy. Most importantly, owing to its amphiphilicity and AIE feature, the probe could be well dispersed in aqueous solution and showed enhanced fluorescence, which endow it good sensor performance in both aqueous solution and living organisms. Finally, the biological assays confirmed that TPY has low toxicity and good biocompatibility, which could be used to detect hypochlorite in living cells. We trust this work will provide some new ideas for designing fluorescent probes with better performance for chemo/biosensors. [ABSTRACT FROM AUTHOR]

The use of multi-fractured horizontal wells has helped to develop tight oil reservoirs, but, if oil depletion occurs, the estimated ultimate recovery is low. Water flooding can be regarded as an easily applied method for improving oil recovery. This study aimed to optimize the scale of the stimulated reservoir volume (SRV) by conducting an experiment to verify the water injection capacity of the Chang 7 Formation, which is situated within in a typical tight oilfield. A one-dimensional long core displacement experiment was designed based on injecting formation water into a tight matrix core and fractured cores with different fracture lengths. Results were then verified and analyzed using core flood simulation and targeted field tests, and they clarified the feasibility of injecting water into a tight oil formation when the injection well is fractured, or when fractures exist near the injection well. It was also verified that although fractures increase the equivalent permeability in the fractured core and promote pressure propagation, they can also lead to rapid water breakthrough if they communicate with the producer well. It is thus considered that optimization of the SRV extent would enhance the recovery of oil and decrease the risk of water breakthrough. • The influence of hydraulic fracture length for the tight oil formation is evaluated. • A one-dimensional core displacement experiment and simulation are investigated in fractured cores. • The injectivity and oil displacement efficiency are evaluated in the experiments of matrix core and fractured core. [ABSTRACT FROM AUTHOR]

Outcome in adjuvant chemotherapy of gastric cancer (GC) has considerable stage-independent variability, which underscores the need for prognostic or predictive molecular markers. CHAF1A promotes tumor growth while its impact on chemotherapy outcome remains unknown. CHAF1A protein expression was measured in independent discovery and validation sets that included 86 and 325 patients respectively who received fluoropyrimidines-based adjuvant chemotherapy after radical gastrectomy. The chemosensitizing effect of CHAF1A knockdown was investigated in vitro. Bioinformatics analysis based on RNA-seq and proteome data from public database was performed to investigate the potential mechanisms and further validation was conducted. In both the discovery and validation sets, CHAF1A expression level was an independent predictor for disease-free survival (HR = 4.25; 95% CI: 2.31–7.79; P < 0.001; and HR = 1.91; 95% CI: 1.03–3.54; P = 0.039, respectively) and overall survival (HR = 3.25; 95% CI: 1.75–6.05; P < 0.001; and HR = 2.42; 95% CI: 1.12–5.20; P = 0.024, respectively) in patients with non-cardia GC but not in those with cardia GC. In GC cells, CHAF1A knockdown significantly decreased the IC 50 of 5-FU. Bioinformatics analyses indicated that CHAF1A correlated with folate metabolism and the expression of thymidylate synthetase (TS). Furthermore, CHAF1A knockdown significantly reduced TS expression in GC cells and CHAF1A positively correlated with TS protein expression in tumor tissues. Finally, ten proteins potentially relevant to the regulation of TS expression by CHAF1A were identified using online tools based on RNA-seq and proteome data. CHAF1A may impact adjuvant chemotherapy outcome of GC by regulating the expression of TS. • CHAF1A predicts adjuvant chemotherapy outcome in non-cardia gastric cancer. • CHAF1A induces 5-fluoropyrimidine resistance. • CHAF1A regulates the expression of thymidylate synthetase. [ABSTRACT FROM AUTHOR]

Throughout the wireless communication network planning process, efficient signal reception power estimation is of great significance for accurate 5 G network deployment. The wireless propagation model predicts the radio wave propagation characteristics within the target communication coverage area, making it possible to estimate cell coverage, inter-cell network interference, and communication rates, etc. In this paper, we develop a series of features by considering various factors in the signal transmission process, including the shadow coefficient, absorption coefficient in test area and base station area, distance attenuation coefficient, density, azimuth angle, relative height and ground feature index coefficient. Then we design a quantile regression neural network to predict reference signal receiving power (RSRP) by feeding the above features. The network structure is specially constructed to be generalized on various complex real environments. To prove the effectiveness of proposed features and deep learning model, extensive comparative ablation experiments are applied. Finally, we have achieved the precision rate (PR), recall rate (RR), and inadequate coverage recognition rate (PCRR) of 84.3%, 78.4%, and 81.2% on the public dataset, respectively. The comparison with a series of state-of-the-art machine learning methods illustrates the superiority of the proposed method. [ABSTRACT FROM AUTHOR]

Bilobalide has shown strong anti-inflammatory activity. Colorectal cancer (CRC) is closely associated with inflammation. However, no studies have reported on the use of bilobalide for treating CRC. This study aims to evaluate the effect of bilobalide on CRC prevention. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, and immunofluorescence showed that bilobalide significantly inhibits the M2 polarization of macrophages dependent on phorbol 12-myristate 13-acetate (PMA) and interleukin-4 (IL-4). Analysis of signaling pathways showed that the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT3) was regulated. In particular, human CRC organoids were established. Western blotting, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), and analysis of cell viability and morphology further supported the hypothesis that the anti-CRC effects of bilobalide could be explained by its ability to suppress M2 macrophage polarization and promote M1 transformation. C57BL/6 mice treated with azoxymethane (AOM)/dextran sodium sulfate (DSS) were divided into three groups, i.e., control, AOM/DSS, low (2.5 mg/kg), and high (5 mg/kg). High-dose bilobalide markedly inhibited the progression of CRC, as evidenced by the increased body weight, decrease in disease activity index (DAI) death rate, and alleviation of colon length reduction and tumorigenesis. According to the in vivo results, reduced levels of inflammatory cytokines in the serum included tumor necrosis factor (TNF-α), IL-6, IL-1β, and IL-10. Bilobalide reduced oxidative stress indices, lipid peroxide (LPO), and malondialdehyde (MDA) and increased reduced glutathione (GSH). In addition, the expression of proliferating cell nuclear antigen (PCNA), Ki67, cellular Myc (c-Myc), and CD206 was downregulated in the drug-treated groups, as confirmed by the immunohistochemical staining. Collectively, these results indicated that bilobalide administration improve experimental CRC by inhibiting M2 macrophage polarization and oxidative stress. Thus, bilobalide may prevent CRC and serve as a potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

The sensitivity and accuracy of nanopore sensors are severely hindered by the high noise associated with solid-state nanopores. To mitigate this issue, the deposition of organic polymer materials onto silicon nitride ( S i N x ) membranes has been effective in obtaining low-noise measurements. Nonetheless, the fabrication of nanopores sub-10 nm on thin polymer membranes remains a significant challenge. This work proposes a method for fabricating nanopores on polymethyl methacrylate (PMMA) membrane by the local high electrical field controlled breakdown, exploring the impact of voltage and current on the breakdown of PMMA membranes and discussing the mechanism underlying the breakdown voltage and current during the formation of nanopores. By improving the electric field application method, transient high electric fields that are one–seven times higher than the breakdown electric field can be utilized to fabricate nanopores. A comparative analysis was performed on the current noise levels of nanopores in PMMA- S i N x composite membranes and S i N x nanopores with a 5 nm diameter. The results demonstrated that the fast fabrication of nanopores on PMMA- S i N x membranes exhibited reduced current noise compared to S i N x nanopores. This finding provides evidence supporting the feasibility of utilizing this technology for efficiently fabricating low-noise nanopores on polymer composite membranes. [ABSTRACT FROM AUTHOR]

Recent evidence has shed light on the significant role of FANCD2 in cancer initiation, development, and progression. However, a comprehensive pan-cancer analysis of FANCD2 has been lacking. In this study, we have conducted a thorough investigation into the expression profiles and prognostic significance of FANCD2, as well as its correlation with clinicopathological parameters and immune cell infiltration, using advanced bioinformatic techniques. The results demonstrate that FANCD2 is significantly upregulated in various common cancers and is associated with prognosis. Notably, higher expression levels of FANCD2 are linked to poor overall survival, as indicated by Cox regression and Kaplan-Meier analyses. Additionally, we have observed a decrease in the methylation of FANCD2 DNA in some cancers, and this decrease is inversely correlated with FANCD2 expression. Genetic alterations in FANCD2 predominantly manifest as mutations, which are associated with overall survival, disease-specific survival, disease-free survival, and progression-free survival in certain tumor types. Moreover, FANCD2 exhibits a strong correlation with infiltrating cell levels, immune checkpoint genes, tumor mutation burden (TMB), and microsatellite instability (MSI). Enrichment analysis further highlights the potential impact of FANCD2 on Fanconi anemia (FA) pathway and cell cycle regulation. Through this comprehensive pan-cancer analysis, we have gained a deeper understanding of the functions of FANCD2 in oncogenesis and metastasis across different types of cancer. [ABSTRACT FROM AUTHOR]

Despite numerous efforts, the accurate determination of trace biomolecules with zeptomolar sensitivity remains elusive. Here, a 3D carbon nanomaze (CAM) electrode for the ultrasensitive detection of trace biomolecules such as nucleic acids, proteins, and extracellular vesicles is reported. The CAM electrode consists of an interlaced carbon fiber array on which intercrossed graphene sheets are vertically tethered in situ, permitting local confinement of trace molecules to increase molecular hybridization efficiency. Furthermore, a self‐assembled DNA tetrahedron array adopts a rigid spatial conformation to guarantee the controllable arrangement of immobilized biological probes, facilitating analytical sensitivity and reproducibility. In a proof‐of‐concept experiment on detecting microRNA‐155, a linearity of 0.1 aM to 100 nM and a sensitivity of 0.023 aM (23 zM) are achieved. With the optimal parameters, the proposed nanoelectrode demonstrates encouraging consistency with quantitative real‐time polymerase chain reaction during clinical sample detection. Through simple functionalization by appending various biomolecular probes of interest, the developed CAM platform with ultrahigh sensitivity can be exploited as a versatile tool in environmental, chemistry, biology, and healthcare fields. [ABSTRACT FROM AUTHOR]

Background: Novel biomarkers are required in gastric cancer (GC) treated by immunotherapy. Epstein-Barr virus (EBV) infection induces an immune-active tumor microenvironment, while its association with immunotherapy response is still controversial. Genes underlying EBV infection may determine the response heterogeneity of EBV + GC. Thus, we screened hub genes associated with EBV infection to predict the response to immunotherapy in GC. Methods: Prognostic hub genes associated with EBV infection were screened using multi-omic data of GC. EBV + GC cells were established and confirmed by EBV-encoded small RNA in situ hybridization (EBER-ISH). Immunohistochemistry (IHC) staining of the hub genes was conducted in GC samples with EBER-ISH assay. Infiltrating immune cells were stained using immunofluorescence. Results: CHAF1A was identified as a hub gene in EBV + GC, and its expression was an independent predictor of overall survival (OS). EBV infection up-regulated CHAF1A expression which also predicted EBV infection well. CHAF1A expression also predicted microsatellite instability (MSI) and a high tumor mutation burden (TMB). The combined score (CS) of CHAF1A expression with MSI or TMB further improved prognostic stratification. CHAF1A IHC score positively correlated with the infiltration of NK cells and macrophages M1. CHAF1A expression alone could predict the immunotherapy response, but its CS with EBV infection, MSI, TMB, or PD-L1 expression showed better effects and improved response stratification based on current biomarkers. Conclusions: CHAF1A could be a novel biomarker for immunotherapy of GC, with the potential to improve the efficacy of existing biomarkers. [ABSTRACT FROM AUTHOR]

Supratentorial spontaneous intracerebral hemorrhage (SICH) can be treated with endoscopic surgery, but the optimal timing remains uncertain. We retrospectively analyzed data from 46 patients who underwent endoscopic surgery for supratentorial SICH. We examined the relationship between time to evacuation and functional outcome at 3 months, adjusting for prognostic factors. Surgical outcomes and complications were compared between patients with early (≤ 12 h) or late (> 12 h) evacuation. Median time to evacuation was 12 h, and the rate of unfavorable outcome (modified Rankin Scale > 3 at 3 months) was 32.6%. Longer time to evacuation was independently associated with unfavorable outcome (odds ratio per hour delay: 1.26). Late evacuation carried a 7.25-fold higher risk of unfavorable outcome compared to early evacuation. This association held across subgroups based on hematoma volume, location, and intraventricular extension (P for interaction > 0.05). Patients with late evacuation had fewer spot signs (24% vs. 4.8%, P = 0.035) and markers of hemorrhagic expansion (36% vs. 9.5%, P = 0.018), longer neurosurgical intensive care unit (NSICU) stay (3.2 vs. 1.9 days, P = 0.011) and hospital stay (15.7 vs. 11.9 days, P = 0.014), and higher 30-day mortality (28.6 vs. 4%, P = 0.036) and complication rates (57.1% vs. 28.0%, P = 0.023). This study suggests a potential association between early endoscopic evacuation of supratentorial SICH and improved functional outcomes, lower 30-day mortality and reduced complications. The need for timely intervention in managing supratentorial SICH is highlighted, yet further validation through multi-center prospective studies is essential to substantiate these findings and provide a higher level of evidence. [ABSTRACT FROM AUTHOR]

There is no clear evidence on the indication and surgical approaches on evacuating basal ganglia hemorrhage caused by hypertensive bleeding. Some studies have shown that minimally invasive approaches have therapeutic potentials, but its benefits remain inconclusive. We describe an endoport assisted endoscopic transsylvian approach for basal ganglia hemorrhage evacuation. We evaluate the safety and efficacy of this approach in a cohort study. We included 19 patients (mean age 57 years) who underwent the surgery at a single county-level hospital in Yunan Province, China. The majority had a Glasgow coma scale between 9 and 12 on admission. The midline shift ranged from 16-29 mm (mean 19 mm). Hematoma volume ranged from 46 to 106 ml (mean 67 ml). Six patients (31.6%) presented with intraventricular hemorrhage. All patients achieved greater than 90% decrease in hematoma volume at postoperative computed tomography scan. The average operative time was 115 minutes and average blood loss of 44 ml. The most common postoperative complication was pulmonary infection (63.2%). No rebleeding, seizure, infectious meningitis, or postoperative mortality was observed. A total of 17 patients (89.5%) achieved good functional recovery at follow up within 90 days after surgery (Glasgow outcome scale 4–5) and 2 patients had severe disability (Glasgow outcome scale 3). Endoport assisted endoscopic surgery through transsylvian approach is safe and effective treatment for hypertensive basal ganglia hemorrhage. The majority of patients have good functional recovery and the rate of severe complications is low. [ABSTRACT FROM AUTHOR]

Background: Studies have found that toe-in gait reduced the peak knee adduction moment (KAM) during early stance, while toe-out gait reduced the peak KAM during late stance. However, some other studies found that toe-in or toe-out gait could reduce the KAM throughout stance phase. There is still a divergence of opinion on the use of toe-in or toe-out gait for reducing the KAM.Research Question: This study aimed to investigate whether static foot posture affected participants' biomechanical responses to three self-selected foot progression angles (FPA): neutral, toe-out and toe-in.Methods: Twenty-seven healthy participants were recruited for this FPA gait modification experiment and classified into three groups: neutral (n = 8), supination (n = 9) and pronation (n = 10), based on the Foot Posture Index (FPI). The kinematic and kinetic data were recorded with Vicon motion capture system and three force plates. The knee adduction moment and ankle eversion moment were calculated using an inverse dynamics model. The effect of the FPA modification on the knee loading parameters was analysed by the Friedman non-parametric test.Results: The KAM results in the neutral group showed that the toe-in gait modification reduced the first peak of the KAM (KAM1), while the KAM1 was increased in the supination group. The effect of the FPA modification on the KAM1 did not reach significance in the pronation group. The toe-out gait modification reduced the second peak (KAM2) regardless of the static posture.Significance: Different static foot postures were correlated with different peak KAM during the early stance phase due to FPA modification. These data suggest that the assessment of static foot posture provides a reference on how to offer adequate FPA modification for knee OA patients with different foot postures. [ABSTRACT FROM AUTHOR]

Efficient vessel scheduling through a channel can improve the operational efficiency of ports. Additionally, many large vessels with deep drafts may have delays due to the tidal cycles when transiting tidal channels. Therefore, it is of great significance to study the vessel scheduling through a channel in which the depth is affected by the tide. This paper presents a model and an algorithm to solve the vessel scheduling problem through a two-way traffic channel in which the depth is affected by tides. The vessels passing through the tidal channel from the inbound and outbound directions are ordered under the condition that the channel depth considering tide meets the requirements of vessels' drafts. The optimization objective is to minimize the total waiting time of all vessels to be scheduled. Next, the model and algorithm are verified using actual data from the north channel of the Yangtze River estuary. The results show that the scheduling efficiency is higher than other scheduling modes of first come first served (FCFS), random scheduling (RS), large draft vessel first (LDVF) and manual scheduling. Additionally, the proposed model and algorithm can be modified slightly and used for vessel scheduling through other two-way channels with tide-affected depth. [ABSTRACT FROM AUTHOR]

Background: Anti-PD-1 immunotherapy has emerged as an important therapeutic modality in advanced gastric cancer (GC). However, drug resistance frequently develops, limiting its effectiveness. Methods: The role of gastric cancer mesenchymal stem cells (GCMSCs) in anti-PD-1 resistance was evaluated in vivo in NPGCD34+ or NCGPBMC xenograft mouse model. In addition, we investigated CD8+T cell infiltration and effector function by spectral cytometry and IHC. The effects of GCMSCs conditional medium (GCMSC-CM) on GC cell lines were characterized at the level of the proteome, secretome using western blot, and ELISA assays. Results: We reported that GCMSCs mediated tolerance mechanisms contribute to tumor immunotherapy tolerance. GCMSC-CM attenuated the antitumor activity of PD-1 antibody and inhibited immune response in humanized mouse model. In GC cells under serum deprivation and hypoxia, GCMSC-CM promoted GC cells proliferation via upregulating PD-L1 expression. Mechanistically, GCMSC-derived IL-8 and AKT-mediated phosphorylation facilitated HK2 nuclear localization. Phosphorylated-HK2 promoted PD-L1 transcription by binding to HIF-1α. What is more, GCMSC-CM also induced lactate overproduction in GC cells in vitro and xenograft tumors in vivo, leading to impaired function of CD8+ T cells. Furthermore, CXCR1/2 receptor depletion, CXCR2 receptor antagonist AZD5069 and IL-8 neutralizing antibody application also significantly reversed GCMSCs mediated immunosuppression, restoring the antitumor capacity of PD-1 antibody. Conclusions: Our findings reveal that blocking GCMSCs-derived IL-8/CXCR2 pathway decreasing PD-L1 expression and lactate production, improving antitumor efficacy of anti-PD-1 immunotherapy, may be of value for the treatment of advanced gastric carcinoma. [ABSTRACT FROM AUTHOR]

We point out that the model in (3) of [1] is not accurate enough to characterize the energy captured by realistic ultra-wideband (UWB) receivers and hence the average bit error rate (ABER) evaluated by using the framework in [1] can be remarkably far from the actual ABER of realistic UWB receivers. We also show that good performance can be achieved by using the framework in [1] if models tailored for realistic receivers are employed instead of the original model in (3) of [1]. [ABSTRACT FROM AUTHOR]

A stable, efficient, and low-cost oxygen evolution reaction catalyst is very momentous to deal with energy crisis and achieve sustainable energy conversion and storage. Herein, the composite of Ni(OH)2 and reduced graphene oxide were obtained by a hydrothermal method at a high temperature and high pressure in a one-step hydrothermal process. SEM images showed that a multilayer sandwich structure with reduced graphene oxide in the middle of two layers of Ni(OH)2 was achieved for the electrode. This unique hierarchical catalyst exhibited remarkable oxygen evolution reaction (OER) electrochemical activity in 1 M KOH media: a 313-mV overpotential at 10 mA cm−2, a small Tafel slope of 46 mV dec−1, and excellent stability for a 22-h chronopotentiometry test. In addition, the overpotential of our catalyst is much lower than that of RuO2, i.e., 20 mV lower at 50 mA cm−2. This work demonstrates a new type of excellent OER catalyst with a hierarchical structure. [ABSTRACT FROM AUTHOR]

Highlights • Heat transfer, pressure loss and turbulent flow structure of miniature structured ribs are presented. • Experiments and numerical simulations have been done. • W-shaped miniature ribs have the best thermal performance by vortex flow. • Miniature structured ribs can achieve high heat transfer performance while having relatively low pressure losses. Abstract This paper presents an experimental and numerical study of turbulent flow heat transfer and pressure loss in channels with structured miniature ribs on one wall with the aim to improve the internal cooling performance of gas turbine blades and combustor liners. Miniature transverse, angled, V-shaped and W-shaped ribs are investigated respectively in the study, and the aspect ratio of the channels is kept to be 6:1, and the rib pitch to height ratio is 10 and the rib height to mean hydraulic diameter ratio is 0.029. The experiments were carried out at the Reynolds numbers ranging from 10,000 to 60,000, and a low-Reynolds number k -ε turbulence model was also adopted to simulate the turbulent flow and heat transfer in the channels. Both experimental and numerical results have shown that the shapes of miniature ribs have appreciable influences on the heat transfer and pressure loss performance in the channels. The experiments showed that the W ribs have the highest heat transfer and pressure loss performance in the channel, and the angled ribs have the lowest heat transfer and pressure loss performance in the channel. The W-ribbed channel shows respectively the globally averaged Nusselt numbers and overall Nusselt numbers of 2.2–2.6 and 2.9–3.3 times those of a smooth channel, and the friction factors of 2.5–3.7 times those of the smooth channel, which are higher than those of the V-ribbed channel and the transverse-ribbed channel. The miniature structured ribs show appreciable higher thermal performance than the conventional sized ribs. Furthermore, the numerical simulations show different vortex flow structures near the wall induced by the structured miniature ribs on the wall, which are responsible for the high-performance heat transfer enhancement. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance in advanced gastric cancer (GC) patients has largely limited the effectiveness of therapy, resulting in disease recurrence and poor prognosis. Gastric cancer derived mesenchymal stem cells (GCMSC) are widely believed to promote GC invasion, metastasis and immune escape via up-regulating programmed death ligand 1 (PD-L1). However, the mechanism by which PD-L1 mediated by GCMSC might regulate the chemoresistance is unknown in GC. Herein, higher half maximal inhibitory concentrations (IC50) and less apoptotic rate were observed in GCMSC conditioned medium (GCMSC-CM) treated GC cells exposed to cisplatin (DDP), along with high expression of multi-drug resistance 1 (MDR1) and DNA repair related genes such as Rad51. The knockdown of PD-L1 reversed the increase of Rad51 mediated by GCMSC-CM, resulting in the increased sensitivity of GC cells to DDP. In addition, inhibition of heat shock protein 90 (HSP90) regulated the expression of PD-L1 and Rad51, revealing the important role of HSP90 in GCMSC-CM mediated DDP resistance. Consistent with the observations in vitro, analysis of patient samples and xenograft models further confirmed that reduction of PD-L1 or HSP90 weakened DDP tolerance mediated by GCMSC-CM, along with decrease of Rad51 and MDR1. In conclusion, we demonstrated that GCMSC-CM enhanced DDP resistance in GC cells through regulating PD-L1-Rad51. It is the first to report this particular mechanism of DDP resistance induced by GCMSC in GC, suggesting a potential therapeutic targets for DDP resistant GC cells. [Display omitted] • GCMSC-CM enhanced the DDP resistance of GC cells. • GCMSC-CM decreased DNA damage induced by DDP by regulating Rad51-mediated DNA repair. • GCMSC-CM promoted DDP resistance via up-regulating HSP90/PD-L1 axis. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Xylan is the most abundant hemicellulose in nature. As a new type of green organic solvent, ionic liquid shows good preservation ability for the functional groups of hemicellulose. In this paper, a single molecule detection technology based on glass nanopore was established to analyze xylan dissolved in ionic liquid. Arabino‐xylan (AX) and beech xylan (BX) are respectively taken as the representatives of heterogeneous xylan and homogeneous xylan. Firstly, unmodified glass nanopore was used to detect the dissolved xylan in ionic liquid, and then poly(ethylene imine) (PEI) was used to modify the nanopore to change the surface charge in the nanopore and further enhance the interaction between the nanopore and the xylan molecule. It was found that before and after nanopore modification, at negative voltage and low positive voltage, AX didn't generate current blocking signal. On the contrary, BX didn't generate current blocking signal at positive voltage. This phenomenon may be due to the current disturbance driven by electrophoresis and electroosmosis of xylan molecules with weak negative charge. After statistics analysis, the current blocking signal of AX showed that the modified nanopore showed multiple peaks. It indicates that heterogeneous xylan and PEI modified nanopore had stronger interaction. The results show that the nanopore detection technology can show the structural difference of heterogenous branched chain and homogeneous straight chain based on the single characteristic current blocking signal and statistical information, providing a research basis for the structural analysis of water insoluble polysaccharides. [ABSTRACT FROM AUTHOR]

The small current detection circuit is the core component of the accurate detection of the nanopore sensor. In this paper, a compact, low-noise, and high-speed trans-impedance amplifier is built for the nanopore detection system. The amplifier consists of two amplification stages. The first stage performs low-noise trans-impedance amplification by using ADA4530-1, which is a high-performance FET operational amplifier, and a high-ohm feedback resistor of 1 GΩ. The high pass shelf filter in the second stage recovers the higher frequency above the 3 dB cutoff in the first stage to extend the maximum bandwidth up to 50 kHz. The amplifier shows a low noise below sub-2 pA rms when tuned to have a bandwidth of around 5 kHz. It also guarantees a stable frequency response in the nanopore sensor. [ABSTRACT FROM AUTHOR]

Uniformly dispersed nano‐sized aluminum nitride powders were prepared by the sol–gel foaming method using aluminum nitrate as the aluminum source, sucrose as the carbon source, and ammonium chloride as the foaming agent. The effects of ammonium chloride content on the particle size and the sintering properties of aluminum nitride were investigated. The results showed that when the molar ratio of ammonium chloride to aluminum nitrate was.5, the colloidal foams were uniform, large, and fluffy, and amorphous alumina precursors with uniform particles could be prepared. Aluminum nitride powder with a particle size of 22–27 nm can be obtained by calcining these precursors in nitrogen atmosphere at 1400°C for 2 h. At the same time, aluminum nitride bulk material with a relative density of 95% can be obtained by sintering the compact samples in nitrogen atmosphere at 1700°C for 2 h. [ABSTRACT FROM AUTHOR]

Deceptive behaviour is a common phenomenon in human society. Research has shown that humans are not good at distinguishing deception, so studying automated deception detection techniques is a critical task. Most of the relevant technologies are susceptible to personal and environmental influences: EEG-based technologies need large and expensive equipment, facial-based technologies are sensitive with the camera's perspective, and these reasons have somewhat limited the development of applications for deception detection technologies. In contrast, the equipment required for speech deception detection is cheap and easy to use, and the capture of speech is highly covert. Based on the application of signal decomposition algorithms in other fields such as EEG signals and speech emotion recognition, this paper proposed a signal decomposition and reconstruction method based on EMD to process the speech signal and a better deception detection performance was obtained by improving the speech quality. The comparison results with other decomposition algorithms showed that the EMD decomposition algorithm is the most suitable for our method. Across many different classification algorithms, accuracy improved by an average of 2.05% and the F1 score improved by an average of 1.7%. In addition, a new deception detector, called the TCN-LSTM network, was proposed in this paper. Experiments showed that this network organically combines the processing capability of TCN and LSTM for time series data; the recognition rate of deception detection was greatly improved, with the highest accuracy and F1 score reaching 86.2% and 86.0% under the EMD-based signal decomposition reconstruction method. Based on the research in this paper, the signal decomposition algorithms need to be further optimised for speech signals and more classification algorithms not used for this task should be tried. [ABSTRACT FROM AUTHOR]

Lactate extensively involves in gastric cancer (GC) progression, such as suppressing immune cells function and facilitating tumor angiogenesis. However, it remains unclear whether lactate promotes tumor progression by interacting with mesenchymal stem cells (MSCs), one of the major stroma components in GC. Here, we investigated the influence of lactate on the phenotype and function of MSCs. The migration of MSCs and the expression of several CAF markers in MSCs after lactate treatment were detected. We also evaluated the effect of lactate-primed MSCs on GC cells migration, proliferation, and programmed death ligand 1 (PD-L1) expression. It was found that lactate significantly activated MSCs, and increased fibroblast activation protein (FAP) expression via monocarboxylate transporter 1 (MCT1)/transforming growth factor-beta 1 (TGF-β1) signaling. In addition, lactate-primed MSCs promoted GC cells migration and proliferation via PD-L1. Inhibiting MCT1 by AZD3965 abrogated lactate induced FAP expression and tumor-promoting potential of MSCs. Therefore, targeting MCT1/TGF-β1/FAP axis in MSCs may serve as a potential strategy to restrain GC development. • Lactate induced the activation of both BMMSCs and GCMSCs. • Lactate-primed GCMSCs promoted the migration and proliferation of gastric cells by enhancing tumor cells intrinsic PD-L1. • Lactate enhanced FAP expression in GCMSCs via MCT1/TGF-β1 axis. • MCT1 inhibitor AZD3965 attenuated gastric cancer cells migration and proliferation induced by lactate-primed GCMSCs. [ABSTRACT FROM AUTHOR]

A practical solution to the power allocation problem in ultra-dense small cell networks can be achieved by using deep reinforcement learning (DRL) methods. Unlike traditional algorithms, DRL methods are capable of achieving low latency and operating without the need for global real-time channel state information (CSI). Based on the actor–critic framework, we propose a policy optimization of the power allocation algorithm (POPA) for small cell networks in this paper. The POPA adopts the proximal policy optimization (PPO) algorithm to update the policy, which has been shown to have stable exploration and convergence effects in our simulations. Thanks to our proposed actor–critic architecture with distributed execution and centralized exploration training, the POPA can meet real-time requirements and has multi-dimensional scalability. Through simulations, we demonstrate that the POPA outperforms existing methods in terms of spectral efficiency. Our findings suggest that the POPA can be of practical value for power allocation in small cell networks. [ABSTRACT FROM AUTHOR]

The tumormicroenvironment (TME) plays a key role in tumor progression. Tumor-associated macrophages (TAMs), which are natural immune cells abundantin the TME, are mainly divided into the anti-tumor M1 subtype and pro-tumor M2 subtype. Due to the high plasticity of TAMs, the conversion of the M1 to M2 phenotype in hypoxic and hypoglycemic TME promotes cancer progression, which is closely related to lipid metabolism. Key factors of lipid metabolism in TAMs, including peroxisome proliferator-activated receptor and lipoxygenase, promote the formation of a tumor immunosuppressive microenvironment and facilitate immune escape. In addition, tumor cells promote lipid accumulation in TAMs, causing TAMs to polarize to the M2 phenotype. Moreover, other factors of lipid metabolism, such as abhydrolase domain containing 5 and fatty acid binding protein, have both promoting and inhibiting effects on tumor cells. Therefore, further research on lipid metabolism in tumors is still required. In addition, statins, as core drugs regulating cholesterol metabolism, can inhibit lipid rafts and adhesion of tumor cells, which can sensitize them to chemotherapeutic drugs. Clinical studies on simvastatin and lovastatin in a variety of tumors are underway. This article provides a comprehensive review of the role of lipid metabolism in TAMs in tumor progression, and provides new ideas for targeting lipid metabolism in tumor therapy. [ABSTRACT FROM AUTHOR]

Nanopore-based technologies have attracted much attention recently for their promising use in low-cost and high-throughput genome sequencing. To achieve single-base resolution of DNA sequencing, it is critical to slow and control the translocation of DNA, which has been achieved in a protein nanopore but not yet in a solid-state nanopore. Using all-atom molecular dynamics simulations, we investigated the dynamics of a single-stranded DNA (ssDNA) molecule in an aqueous glycerol solution confined in a SiO2 nanopore. The friction coefficient ξ of the ssDNA molecule is found to be approximately 18 times larger in glycerol than in water, which can dramatically slow the motion of ssDNA. The electrophoretic mobility μ of ssDNA in glycerol, however, decreases by almost the same factor, yielding the effective charge (ξμ) of ssDNA being roughly the same as in water. This is counterintuitive since the ssDNA effective charge predicted from the counterion condensation theory varies with the dielectric constant of a solvent. Due to the larger friction coefficient of ssDNA in glycerol, we further show that glycerol can improve trapping of ssDNA in the DNA transistor, a nanodevice that can be used to control the motion of ssDNA in a solid-state nanopore. Simulation results of slowing ssDNA translocation were confirmed in our nanopore experiment. [ABSTRACT FROM AUTHOR]

Regenerating codes (RCs) are efficient at both storage cost and repair bandwidth, and thus are regarded as preferable candidates for distributed storage systems (DSSs). For DSSs with RCs, a file stored across n distributed nodes can be reconstructed from k (< n) nodes. The collection of the k nodes is called the reconstruction set. A failed node can be regenerated (i.e., repaired) from d (< n) remaining nodes. The collection of the d nodes is called the regeneration set. In traditional RCs, the numbers of reconstruction sets and regeneration sets are fixed to some specific values. In this paper, we introduce the concept of generalised RCs, in which the value ranges of the numbers of both reconstruction sets and regeneration sets are extended. Compared to traditional RCs, the generalised RCs possess more coding schemes and better system security level in terms of the probability of revealing original data file. An explicit construction of generalised RCs is provided, in which the numbers of both reconstruction sets and regeneration sets can be designed flexibly. Furthermore, based on the generalised RCs, an intruder model where an eavesdropper can access to some nodes is considered and a general upper bound on secrecy capacity is derived. The relationship between the obtained upper bound and existing ones achieved by traditional RCs is discussed in detail. The provided explicit construction is the first optimal construction of generalised RCs, which achieves the upper bound on secrecy capacity and has the flexibility in designing the numbers of reconstruction sets and regeneration sets. [ABSTRACT FROM AUTHOR]

With microplate-immobilized polyclonal antibodies against a starting enzyme or its active mutant bearing consistent accessible epitopes, the maximum activity of an adsorbed enzyme/mutant ( Vs) was predicted for comparison to recognize weakly-positive mutants. Rabbit antisera against Escherichia coli alkaline phosphatase (ECAP) were fractionated with 33% ammonium sulfate to yield crude polyclonal antibodies for conventional immobilization in 96-well microplates. The response curve of the activities of ECAP/mutant adsorbed by the immobilized polyclonal antibodies to protein quantities from a cell lysate was fit to an approximation model to predict Vs. With 0.4 μg crude polyclonal antibody for immobilization, Vs was consistent for ECAP in cell lysates bearing fourfold differences in its apparent specific activities when its abundance was greater than 0.9%. The ratio of Vs of the mutant R168K to that of ECAP was 1.5 ± 0.1 ( n = 2), consistent with that of their specific activities after affinity purification. Unfortunately, the prediction of Vs with polyclonal antibodies that saturated microplate wells was ineffective to Pseudomonas aeruginosa arylsulfatase bearing less than 2% specific activity of ECAP. Therefore, with microplate-immobilized polyclonal antibodies to adsorb enzyme/mutants from cell lysates, high-throughput prediction of Vs was practical to recognize weakly-positive mutants of starting enzymes bearing fairly-high activities. [ABSTRACT FROM AUTHOR]