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Abstract: Staphylococcus aureus (S. aureus), a prominent, highly contagious nosocomial and com-munity-acquired bacterial pathogen, can cause a broad spectrum of diseases. Antibiotic-resistant S. aureus strains, which pose potential causes of morbidity and mortality, have continuously emerged in recent years, calling for novel anti-S. aureus agents. 1,2,3-Triazole and 1,2,4-triazole, the bioisostere of amides, esters, and carboxylic acids, are potent inhibitors of DNA gyrase, topoisomerase IV, efflux pumps, filamentous temperature-sensitive protein Z, and penicillin-binding protein. In particular, 1,2,3-triazole- and 1,2,4-triazole-containing hybrids have the potential to exert dual or multiple anti-bacterial mechanisms of action. Moreover, 1,2,3-triazole-cephalosporin hybrid cefatrizine, 1,2,3-triazole-oxazolidinone hybrid radezolid, and 1,2,4-triazolo[1,5-a]pyrimidine hybrid essramycin, have already been used in clinical practice to treat bacterial infections. Hence, 1,2,3-triazole- and 1,2,4-triazole-containing hybrids possess promising broad-spectrum antibacterial activity against diverse clinically significant organisms, including drug-resistant forms. This review is an update on the latest development of 1,2,3-triazole- and 1,2,4-triazole-containing hybrids with anti-S. aureus activity, cov-ering articles published between January 2020 and July 2021.

Pressure losses from pipe and perforation friction control the relation between wellhead pressure and pressure at the mouth (entrance) of hydraulic fractures. Because both pipe and perforation friction are proportional to flow rate squared, standard step-down tests that rely on the steady pressure response at a set of injection rates cannot uniquely determine pipe and perforation friction. We introduce a novel method to resolve this nonuniqueness by analyzing the water hammer response, measured by high-rate pressure sensors at the wellhead, following abrupt rate steps during shut-in following a stimulation treatment. Constraints on perforation friction permit quantification of the number of active perforations connecting to fractures and hence perforation cluster efficiency.Our method requires a shut-in procedure with abrupt drops in injection rate to produce water hammer oscillations (tube waves propagating between the wellhead and current stage). The rate drop is accompanied by a drop in wellhead pressure as a tube wave propagates away from the wellhead, decelerating the fluid behind it. Pipe friction attenuates this wave, such that the local flow rate remains higher at depth than near the wellhead. This expands the fluid, causing additional depressurization at the wellhead until the arrival of the reflected wave from the stage. The Darcy-Weisbach pipe friction factor is determined from the depressurization rate. At high background flow rates, the reflected wave amplitude is controlled by perforation friction with minimal sensitivity to fracture properties.The claims above are substantiated by numerical simulations of tube wave propagation and reflection from perforation clusters connected to hydraulic fractures. We then present two case studies in which the method is applied data from hydraulic fracturing treatments in two stages in different wells targeting the Wolfcamp and Bone Spring Formations, Permian Basin. The inferred pipe friction factor is 2×10−3, an order of magnitude smaller than for turbulent water flow, but consistent with the use of friction reducers and pumping company pressure loss tables. The measured perforation friction is higher than predictions based on a standard formula involving fluid density, discharge coefficient, entry hole diameter, and design number of holes. This suggests not all clusters connect to fractures; the inferred cluster efficiency is 67% (Case-A, Wolfcamp) and 84% (Case-B, Bone Spring).This work extends simulation and inversion capabilities utilizing wellhead data to nonlinear problems involving tube wave interactions with hydraulic fractures and perforations. The ability to independently constrain pipe and perforation friction resolves nonuniqueness of step rate tests. Rapid inversion enables us to deliver real-time measurements of perforation cluster efficiency, pipe and perforation friction that complement traditional fracture diagnostics. Combined with acoustic pulsing to quantify near-well flow resistance, the method provides a noninvasive, cost-effective means of monitoring of the critical connection between the well and fractures during simulation treatment. The method can be used to diagnose and treat problems such as uneven fluid distribution across clusters.

The transmission of 84 OAM modes with spectral efficiency of 241.92 bit/s/Hz over 14 km 7-core ring core fiber whose cladding diameter is 180μm is demonstrated, using 4 × 4 MIMO equalizations.

Rechargeable aqueous metal-sulfur batteries have received high attention due to their low cost, reliable security, and environmental friendliness. However, poor cycle performance impedes their development. Herein, a nitrogen-doped hierarchical porous...

Protein glycosylation is one of the ubiquitous post-translational modifications in eukaryotic cells, which play important roles in plant growth and adverse response. In this study, we performed the first comprehensive wheat plasma membrane N-glycoproteome analysis under drought stress via glycopeptide HILIC enrichment and LC-MS/MS identification. In total, 414 glycosylated sites corresponding to 407 glycopeptides and 312 unique glycoproteins were identified, of which 173 plasma membrane glycoproteins with 215 N-glycosylation sites were significantly regulated by drought stress. Functional enrichment analysis reveals that the significantly regulated N-glycosylation proteins were particularly related to protein kinase activity involved in the reception and transduction of extracellular signal and plant cell wall remolding. The motifs and sequence structures analysis showed that the significantly regulated N-glycosylation sites were concentrated within [NxT] motif, and 79.5% of them were located on the random coil that is always on the protein surface and flexible regions, which could facilitate protein glycosylated modification and enhance protein structural stability via reducing protein flexibility. PNGase F enzyme digestion and glycosylation site mutation further indicated that N-glycosylated modification could increase protein stability. Therefore, N-glycosylated modification is involved in plant adaptation to drought stress by improving the stability of cell wall remodeling related plasma membrane proteins.

In order to efficiently extract natural medicines, response surface methodology (RSM)were used for the modeling and optimization of flash extraction of total flavonoids to determine the antioxidant activity of the extracts obtained from Edgeworthia gardneri (Wall). For the optimal combination of the comprehensive yield of total flavonoids (Y), the Box-Behnken design (BBD) was used to improve extract voltage (X1), extraction time (X2), ethanol concentration (X3), and liquid-solid ratio (X4). Based on the results of single factor test, the amount of total flavonoids extracted from Edgeworthia gardneri (Wall) Meissn was used as the evaluation index. The Box-Behnken experimental design was used to optimize the flash extraction process and to investigate the antioxidant activity in vitro. The results showed that the optimal extraction conditions were as follows: extraction voltage 150 V, flash extraction time 100 s, ethanol volume fraction 70%, solid-liquid ratio 1:30 mL/g, and total flavonoids extraction amount of 18.91 (mg/g). The total flavonoids of Edgeworthia gardneri (Wall) Meissn had significant scavenging ability against 2,2-diphenyl-1-picrylhydrazyl (DPPH), O2- and OH free radicals, and had good antioxidant activity. Furthermore, the HPLC separation conditions of total flavonoids of Edgeworthia gardneri (Wall) were explored. Under the set HPLC conditions (Hanbon benatach C18 250 mm × 4.6 mm, 5 μm, A: acetonitrile-B: 0.2% formic acid aqueous solution, 0→10→50→65→85 min, 5%→10%→30%→45%→90% A gradient elution, 1 mL/min, 314 nm, Column temperature: 25 ℃), the main components of total flavonoids of Edgeworthia gardneri (Wall) could achieve a good separation, which provide the separation conditions and basis for the identification of total flavonoids from Edgeworthia gardneri (Wall) Meissn.

In order to repair an osteochondral defect, it is critical to advance a bi-lineage constructive scaffold with gradient transition. In this study, we developed a simple and straightforward approach for fabricating a multidomain gel scaffold through the assembly/disassembly of low-molecular-weight gels (LMWGs) inside a stable PEGDA network by photopolymerization. The versatility of this technology enabled to vary biological, topological, and mechanical properties through material selection and to generate a chondrogenic-osteogenic gradient transition. The multidomain gel exhibited an increasing stiffness gradient along the longitudinal direction from the cartilage layer at approximately 20 kPa to the bone layer at approximately 300 kPa as well as spatial variation at the gradient interface. Moreover, the transitional layer with a condensed structure and intermediate stiffness prevented delamination of the contrasting layers and maintained microenvironmental differences in the upper and lower layers. The in vitro results indicated that each domain had an individual capacity to spatially control the differentiation of MSCs toward osteoblastic lineage and chondrocytic lineage. This was mainly because the mechanical and topographical cues from the respective domains played an important role in modulating the Rho-ROCK signaling pathway, whereas the blockage of ROCK signals significantly impaired domain-modulated osteogenesis and enhanced chondrogenesis. Additionally, the quantity and quality of osteochondral repair were evaluated at 4 and 8 weeks through histological analysis and micro-computed tomography (micro-CT). The results indicated that the multidomain gels distinctly improved the regeneration of subchondral bone and cartilage tissues. Overall, the outcomes of this study can motivate future bioinspired gradient and heterogeneity strategies for osteochondral tissue regeneration. Statement of significance The regeneration of osteochondral defects remains a major challenge due to the complexity of osteochondral structure and the limited self-repair capacity of cartilage. The gradient designs to mimic the transition between the calcified cartilage and subchondral bone plate as well as the zones of cartilage are an effective strategy. In this study, the controlled multi-domain gels were fabricated though the assembly/disassembly of low molecular weight gels inside the stable PEGDA network by photopolymerization. The prepared multi-domain gels presented a chondrogenic-osteogenic gradient transition, which decreased the possibility of delamination and stimulated the osteochondral tissue regeneration in vivo. Overall, our study can inspire new strategies of bioinspired gradients and heterogeneities for more challenging applications.

Heterogeneous Information Network (HIN) is a natural and general representation of data in recommender systems. Combining HIN and recommender systems can not only help model user behaviors but also make the recommendation results explainable by aligning the users/items with various types of entities in the network. Over the past few years, path-based reasoning models have shown great capacity in HIN-based recommendation. The basic idea of these models is to explore HIN with predefined path schemes. Despite their effectiveness, these models are often confronted with the following limitations: (1) Most prior path-based reasoning models only consider the influence of the predecessors on the subsequent nodes when modeling the sequences, and ignore the reciprocity between the nodes in a path; (2) The weights of nodes in the same path instance are usually assumed to be constant, whereas varied weights of nodes can bring more flexibility and lead to expressive modeling; (3) User-item interactions are noisy, but they are often indiscriminately exploited. To overcome the aforementioned issues, in this paper, we propose a novel path-based reasoning approach for recommendation over HIN. Concretely, we use a bidirectional LSTM to enable the two-way modeling of paths and capture the reciprocity between nodes. Then an attention mechanism is employed to learn the dynamical influence of nodes in different contexts. Finally, the adversarial regularization terms are imposed on the loss function of the model to mitigate the effects of noise and enhance HIN-based recommendation. Extensive experiments conducted on three public datasets show that our model outperforms the state-of-the-art baselines. The case study further demonstrates the feasibility of our model on the explainable recommendation task., 11 pages, 5 figures, Neurocomputing

Zinc biology, featuring intertwining signaling networks and of critical importance to human health, witnesses exciting opportunities in the big data era of physiology. Here, we report a class of red- and far-red-emitting Zn 2+ probes with K d values ranging from 190 nM to 74 μM, which are particularly suitable for real-time monitoring the high concentration of Zn 2+ /insulin co-released during vesicular secretory events. Compared to the prototypical rhodamine-based Zn 2+ probes, the new class exploits morpholino auxochromes which eliminates phototoxicity during long-term live recording from isolated islets. A Si-rhodamine-based Zn 2+ probe with high turn-on ratio (> 100), whose synthesis was enabled by a new route featuring late-stage N-alkylation, allowed simultaneous recording of Ca 2+ influx, mitochondrial signal, and insulin secretion in isolated mouse islets. The time-lapse multicolor fluorescence movies and their analysis, enabled by red-shifted Zn 2+ and other orthogonal physiological probes, highlight the potential impact of biocompatible fluorophores on the fields of islet endocrinology and system biology.

Rheumatoid arthritis (RA) could be a common autoimmune disease that involves severe joint deformation. The main off-target medicines unable to cure RA, that permits associate in nursing infection with the unwellness. The nanomaterials-based RA medical aid is an excellent strategy to enhance the treatment efficaciousness within the inflammatory region. Specifically, metal-based nanomaterials are a wonderful choice for a delivery vehicle for inflammatory disease agents, because of their novel properties. We have got developed a small-sized Polyethylenimine (PEI) coated gold nanoparticles (AuNPs) with an average diameter of 80 nm, that area unit used for top loading of carboxylic acid (MA). Various microscopic and qualitative analysis tools like high-resolution transmission microscopy (HR-TEM), Field-emission scanning microscope (FE-SEM), and Fourier-transform infrared (FTIR) spectroscopic analysis studies were accustomed to make sure as-made PEI-AuNPs. The invented PEI-coated AuNPs (PEI-AuNPs) exhibited higher contrast with an extended expanse that's promising to store giant amounts of MA medicine. MA is attributed to reducing the inflammatory response by inhibiting the pro-inflammatory cytokines and averting undesirable ancient drug aspect effects in Collagen-induced inflammatory disease (CIA). Many organic chemistry parameters like weight, hind paw volume, protein estimation, anti-serum protein analysis, and microscopic anatomy examination were conducted in Collagen-induced arthritis mice treated at a dose (10 µg) of MA packed PEI-AuNPs. The obtained results showed the MA-PEI-AuNPs were used with success within the treatment of Collagen-induced arthritis, relative to PEI-AuNPs and MA. Therefore, MA loaded PEI-AuNPs as a stimulating candidate in future RA applications.

Cu2Nb37O87 exhibits excellent electrochemical properties, high theoretical capacity (401 mAh g−1), safe working voltage (~1.7 V) and outstanding rate performance for lithium-ion batteries. However, poor electrical conductivity inhibits its further development. In this study, Cu2Nb37O87@C nano-wires are prepared by combining electrospinning and carbon-coating techniques to mitigate this issue, which breaks through the barrier of low conductivity, improves the ion diffusion rate and relieves the change of crystal volume. Besides, the sample is tested by scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy and most importantly, the mechanism of lithium-ion storage is explored by an in-situ X-ray diffraction analysis. Moreover, according to a sequence of electrochemical tests, it is clarified that the electronic conductivity and electrochemical activity of Cu2Nb37O87 are enhanced significantly. All these are inseparable from the synergistic effect of the nano-crystallisation and carbon coating. Therefore, nano-structures and surface cladding provide effective tactics to construct effective ion-migration interfaces and enhance conductivity for the further study of Cu2Nb37O87 and other electrode materials.

The nonlinearity of the light-emitting diode (LED) in underwater wireless optical communication (UWOC) systems is considered the one major limiting factor that degrades the system’s performance. Volterra series-based nonlinear equalization is widely employed to mitigate such nonlinearity in communication systems. However, the conventional Volterra series-based model is of high complexity, especially for the nonlinearity of higher-order terms or longer memory lengths. In this paper, by pruning away some negligible beating terms and adaptively picking out some of the dominant terms while discarding the trivial ones, we propose and experimentally demonstrate a sparse pruned-term-based nonlinear decision-feedback equalization (SPT-NDFE) scheme for the LED-based UWOC system with an inappreciable performance degradation as compared to systems without the pruning strategy. Meanwhile, by replacing the self/cross beating terms with the terms formed by the absolute operation of a sum of two input samples instead of the product operation terms, a sparse pruned-term-based absolute operation nonlinear decision-feedback equalization (SPT-ANDFE) scheme is also introduced to further reduce complexity. The experimental results show that the SPT-NDFE scheme exhibits comparable performance as compared to the conventional NDFE (nonlinear decision-feedback equalization) scheme with lower complexity (the nonlinear coefficients are reduced by 63.63% as compared to the conventional NDFE scheme). While the SPT-ANDFE scheme yields suboptimal performance with further reduced complexity at the expense of a slight performance degradation, the robustness of the proposed schemes in different turbidity waters is experimentally verified. The proposed channel equalization schemes with low complexity and high performance are promising for power/energy-sensitive UWOC systems.

Electro-optic (EO) modulators with a high modulation bandwidth are indispensable parts of an optical interconnect system. A key requirement for an energy-efficient EO modulator is the low drive voltage, which can be provided using a standard complementary metal oxide semiconductor circuity without an amplifying driver. Thin-film lithium niobate has emerged as a new promising platform, and shown its capable of achieving driverless and high-speed EO modulators. In this paper, we report a compact high-performance modulator based on the thin-film lithium niobate platform on a silicon substrate. The periodic capacitively loaded travelling-wave electrode is employed to achieve a large modulation bandwidth and a low drive voltage, which can support a driverless single-lane 100Gbaud operation. The folded modulation section design also helps to reduce the device length by almost two thirds. The fabricated device represents a large EO bandwidth of 45GHz with a half-wave voltage of 0.7V. The driverless transmission of a 100Gbaud 4-level pulse amplitude modulation signal is demonstrated with a power consumption of 4.49fj/bit and a bit-error rate below the KP4 forward-error correction threshold of 2.4×10−4.

A successful transmission of 14 multiplexed orbital angular momentum (OAM) channels each carrying 80 wavelengths over a 100-km single-span ring-core fiber (RCF) is experimentally demonstrated. Each transmission channel is modulated by a 20-GBaud quadrature phase-shift keying (QPSK) signal, achieving a record spectral-efficiency-distance product of 1870 (bit/s/Hz)·km for the single-core RCF based mode division multiplexing (MDM) transmissions. In addition, only low-complexity 2×2 or 4×4 multiple-input multiple-output (MIMO) equalization with time-domain equalization tap number no more than 25 is required to deal with the crosstalk among the highly degenerate intra-MG modes at the receiving end of the demonstrated OAM-MDM-WDM system, showing great potential in large-capacity and relatively long-distance MDM transmission with low digital signal processing (DSP) complexity.

Air infiltration significantly impacts building energy consumption and the indoor thermal environment. The proportion of infiltration load in large-space buildings is higher than in normal buildings. Due to the particularity of building structure and function, the existing building infiltration load calculation methods are unsuitable for large-space buildings. This paper proposed a new method for analyzing the building infiltration process from a thermodynamic perspective, enabling large-space buildings' infiltration load to be calculated more accurately and quickly. Compared with the existing method, it was found that a fixed proportional difference existed, and the proposed method relied on certain assumptions. The correction factor η was introduced to correct these limitations. The proposed method was verified to be accurate and universal in actual buildings. The paper also presents the results of η in different building scenarios and discusses the influence of mechanical ventilation and ideal gas assumption on η. Compared with the air change method and the gap method, the correction factor is stable in the range of 0.257–0.278 and 0.327–0.353, respectively. Furthermore, the correction factor for a monatomic ideal gas is 40% higher than that for a diatomic ideal gas. The new method provides a more accurate and efficient way to calculate the infiltration load, which can help improve the energy efficiency of buildings and the indoor thermal environment. Post-print / Final draft