Enhanced Mechanical Strength and Sustained Drug Release in Carrier-Free Silver-Coordinated Anthraquinone Natural Antibacterial Anti-Inflammatory Hydrogel for Infectious Wound Healing.

The persistent challenge of healing infectious wounds and the rise of bacterial resistance represent significant hurdles in contemporary medicine. In this study, based on the natural small molecule drug Rhein self-assembly to form hydrogels and coordinate assembly with silver ions (Ag+), a sustained-release carrier-free hydrogel with compact structure is constructed to promote the repair of bacterial-infected wounds. As a broad-spectrum antimicrobial agent, Ag+ can avoid the problem of bacterial resistance caused by the abuse of traditional antibiotics. In addition, due to the slow-release properties of Rhein hydrogel, continuous effective concentration of Ag+ at the wound site can be ensured. The assembly of Ag+ and Rhein makes the hydrogel system with enhanced mechanical stability. More importantly, it is found that Rhein effectively promotes skin tissue regeneration and wound healing by reprogramming M1 macrophages into M2 macrophages. Further mechanism studies show that Rhein realizes its powerful anti-inflammatory activity through NRF2/HO-1 activation and NF-κB inhibition. Thus, the hydrogel system combines the excellent antibacterial properties of Ag+ with the excellent anti-inflammatory and tissue regeneration ability of Rhein, providing a new strategy for wound management with dual roles.

An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,ß-Unsaturated Aldehydes-Design and Evolution.

The introduction of an abiological catalytic group into the binding pocket of a protein host allows for the expansion of enzyme chemistries. Here, we report the generation of an artificial enzyme by genetic encoding of a non-canonical amino acid that contains a secondary amine side chain. The non-canonical amino acid and the binding pocket function synergistically to catalyze the asymmetric nitrocyclopropanation of α,ß-unsaturated aldehydes by the iminium activation mechanism. The designer enzyme was evolved to an optimal variant that catalyzes the reaction at high conversions with high diastereo- and enantioselectivity. This work demonstrates the application of genetic code expansion in enzyme design and expands the scope of enzyme-catalyzed abiological reactions.

Rethinking Sweetener Discovering: Multiparameter Modeling of Molecular Docking Results between the T1R2-T1R3 Receptor and Compounds with Different Tastes.

Molecular docking has been widely applied in the discovery of new sweeteners, yet the interpretation of computational results sometimes remains difficult. Here, the interaction between the T1R2-T1R3 sweet taste receptor and 66 tasting compounds, including 26 sweet, 19 bitter, and 21 sour substances was investigated by batch molecular docking processes. Statistical analysis of the docking results generated two novel methods of interpreting taste properties. Quantitative correlation between relative sweetness (RS) and docking results created a multiparameter model to predict sweetness intensity, whose correlation coefficient r = 0.74 is much higher than r = 0.17 for the linear correlation model between sweetness and binding energy. The improved correlation indicated that docking results besides binding energy contain undiscovered information about the ligand-protein interaction. Qualitative discriminant analysis of different tasting molecules generated an uncorrelated linear discriminant analysis (UDLA) model, which achieved an overall 93.1% accuracy in discriminating the taste of molecules, with specific accuracy for verifying sweet, bitter, and sour compounds reaching 88.0%, 92.1%, and 100%. These unprecedented models provide a unique perspective for interpreting computational results and may inspire future research on sweetener discovery.

Electrochemically Driven para-Selective C(sp2)-H Alkylation Enabled by Activation of Alkyl Halides without Sacrificial Anodes.

With alkyl halides (I, Br, Cl) as a coupling partner, an electrochemically driven strategy for para-selective C(sp2)-H alkylation of electron-deficient arenes (aryl esters, aldehydes, nitriles, and ketones) has been achieved to access diverse alkylated arenes in one step. The reaction enables the activation of alkyl halides in the absence of sacrificial anodes, achieving the formation of C(sp2)-C(sp3) bonds under mild electrolytic conditions. The utility of this protocol is reflected in high site selectivity, broad substrate scope, and scalable.

Electrochemically Driven C4-Selective Decyanoalkylation of Cyanopyridines with Unactivated Alkyl Bromides Enabling C(sp3)-C(sp2) Coupling.

With cyanopyridines and alkyl bromides as coupling partners, an electrochemically driven C4-selective decyanoalkylation has been established to access diverse 4-alkylpyridines in one step. The reaction proceeds through the single electron reduction/radical-radical coupling tandem process under mild electrolytic conditions, achieving the cleavage of the C(sp2)-CN bond and the formation of C(sp3)-C(sp2). The practicality of this protocol is illustrated by no sacrificial anodes, a broad substrate scope, and gram-scale synthesis.

Short-Term Ambient Air Pollution and Urticaria in Guangzhou, China: Estimating the Association and Population Attributable Fraction.

Limited evidence is available regarding the association between acute exposure to ambient air pollutants and the risk of urticaria, even though the skin is an organ with direct contact with the external environment. This study utilized generalized additive models to investigate the association between particulate matter with an aerodynamic diameter smaller than 10 µm (PM10) and 2.5 µm (PM2.5), nitrogen dioxide (NO2) and sulfur dioxide (SO2), and daily outpatient visits for urticaria in Guangzhou, China from 2013 to 2017. We also estimated the attributable fraction of urticaria outpatient visits due to air pollution. A total of 216,648 outpatient visits due to urticaria occurred during the study period. All air pollutants were significantly associated with an increased excess risk of urticaria. Each 10 µg/m3 increase in PM2.5, PM10, NO2, and SO2 was associated with an increase of 1.23% (95% CI: 0.42%, 2.06%), 0.88% (95% CI: 0.28%, 1.49%), 3.09% (95% CI: 2.16%, 4.03%), and 2.82% (95% CI: 0.93%, 4.74%) in hospital visits for urticaria at lag05, respectively. It was estimated that 3.77% (95% CI: 1.26%, 6.38%), 1.91% (95% CI: 0.60%, 3.26%), 6.36% (95% CI: 4.38%, 8.41%), and 0.08% (95% CI: 0.03%, 0.14%) of urticaria outpatient visits were attributable to PM2.5, PM10, NO2, and SO2 using the World Health Organization's air quality guideline as the reference. Relatively stronger associations were observed during the cold season. This study indicates that short-term air pollution may play a significant role in outpatient visits for urticaria, and that such relationships could be modified by season.

Electrodeposition of paracetamol oxide for intelligent portable ratiometric detection of nicotine and ethyl vanillin ß-D-glucoside.

Herein, the electrodeposition of paracetamol oxide (PA ox) for the intelligent portable ratiometric detection of nicotine (NIC) and ethyl vanillin ß-D-glucoside (EVG) is reported. PA ox electrodeposited on a screen-printed carbon electrode (SPCE) was used as a new fixed state ratiometric reference probe. A portable electrochemical workstation combined with a smart phone was applied as an intelligent portable electrochemical sensing platform. The sensor was studied by scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FT-IR), ultraviolet-visible spectrophotometry (UV-vis), theoretical calculation, chronoamperometry, cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV). Under optimized conditions, the detection range of NIC is 10-200 µmol L-1, and the detection limit is 0.256 µmol L-1. The detection range of EVG was 10-180 µmol L-1, and the detection limit was 0.058 µmol L-1. The sensor can realize the real-time detection of NIC and EVG concentration in cigarette samples quickly and accurately, and has good anti-interference, repeatability and stability.

Extraction and characterization of anti-virus anthraquinones from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220.

In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.

Few-Atomic Zero-Valent Palladium Ensembles for Efficient Reductive Dehydrogenation and Dehalogenation Catalysis.

Single-atom catalysts (SACs) offer immense potential in heterogeneous catalysis due to their maximized atomic utilization and high selectivity but suffer the problem of low reactivity in catalytic reductive reactions due to their high-valent state. Here, we demonstrate that supported palladium (Pd) ensembles consisting of a few zero-valent Pd atoms (Pd1+c-red/CN) exhibit exceptional reactivity in formic acid (FA) dehydrogenation and 4-chlorophenol (4-CP) dechlorination. The initial FA dehydrogenation and 4-CP dechlorination rates of Pd1+c-red/CN are 42-104 and 16-210 times higher than that of supported Pd SACs (Pd1-ox/CN), respectively. Experimental results and density functional theory (DFT) calculations reveal that optimal adsorption sites of Pd1+c-red/CN stimulate the formation of H*, which is indispensable for 4-CP dechlorination. Moreover, direct electron transfer from Pd atoms to FA with a high electron density on Pd1+c-red/CN also contributes to the rapid 4-CP dechlorination. The superior dehalogenation capability of Pd1+c-red/CN for organohalides of great environmental and health concerns suggested its immense application potential in environmental remediation. This work highlights the pivotal roles of the structure and valence state of Pd ensembles in catalytic reductive reactions and provides a strategy to broaden the application of Pd-based catalysts for dehydrogenation and dehalogenation.

Review of two-dimensional nanomaterials in tribology: Recent developments, challenges and prospects.

From our ordinary lives to various mechanical systems, friction and wear are often unavoidable phenomena that are heavily responsible for excessive expenditures of nonrenewable energy, the damages and failures of system movement components, as well as immense economic losses. Thus, achieving low friction and high anti-wear performance is critical for minimization of these adverse factors. Two-dimensional (2D) nanomaterials, including transition metal dichalcogenides, single elements, transition metal carbides, nitrides and carbonitrides, hexagonal boron nitride, and metal-organic frameworks have attracted remarkable interests in friction and wear reduction of various applications, owing to their atomic-thin planar morphologies and tribological potential. In this paper, we systematically review the current tribological progress on 2D nanomaterials when used as lubricant additives, reinforcement phases in the coatings and bulk materials, or a major component of superlubricity system. Additionally, the conclusions and prospects on 2D nanomaterials with the existing drawbacks, challenges and future direction in such tribological fields are briefly provided. Finally, we sincerely hope such a review will offer valuable lights for 2D nanomaterial-related researches dedicated on tribology in the future.

A novel integrated time-resolved array avalanche photodiode detection system for nuclear resonant scattering measurements.

The nuclear resonant scattering (NRS) experiment requires photon-counting detectors with high time resolution, short dead time, large dynamic range, low noise, and large detection area. An 8-channel avalanche photodiode (APD) array detector system with high integrity, flexibility, and reliability has been developed to adapt to the demands of NRS experiments. The detector system mainly consists of four key parts: (i) an array-APD sensor, (ii) 8-channel integrated fast preamplifiers, (iii) the time-to-digital converter readout electronics, and (iv) a data acquisition system and EPICS support software. Remarkably, the system exhibits a time resolution of better than 500 ps and has a sufficiently low noise level, allowing for the lowest detection energy threshold of 4 keV. The performance of the new array-APD system as well as its real application in nuclear forward scattering (NFS) and nuclear resonant inelastic x-ray scattering (NRIXS) experiments was tested in two synchrotron facilities. With the new system, the NFS signal very close to the prompt electronic scattering signal can be extracted. Thanks to the customized EPICS-areaDetector-based control software, NRIXS spectra can be readily measured with time and energy information of the NRIXS signal stored in the raw data, which is promising for developing NRIXS data analysis in the time domain. The array-APD detector can be deployed for nuclear resonant scattering experiments at various synchrotron radiation facilities.

Development of a MOF-based SPE method combined with GC-MS for simultaneous determination of alachlor, acetochlor and pretilachlor in field soil.

In this work, a rapid, highly selective, reusable and effective method was developed for simultaneous determination of alachlor, acetochlor and pretilachlor in field soil by GC-MS coupled with MIL-101 based SPE. Main factors affecting the SPE by using MIL-101 were optimized. Moreover, by comparing with the other commercial materials such as C18, PSA and Florisil, the MIL-101(Cr) exhibited excellent adsorption performance, which aimed at amide herbicides. On the other hand, method validation displayed excellent method performance, achieving good linearities with r2 ≥ 0.9921, limits of detection between 0.25-0.45 µg kg-1, enrichment factors ≥ 89, matrix effect in the range of ± 20%, recoveries between 86.3% and 102.4%, and RSD lower than 4.38%. The developed method was successfully applied to the determination of amide herbicides in soil taken from the wheat, corn and soybean field at different depths, where the concentration of alachlor, acetochlor and pretilachlor were in the range of 0.62-8.04 µg kg-1. It was demonstrated that the more depth of soil, the lower of three amide herbicides. This finding could be proposed a novel method to detect the amide herbicides in the agriculture and food industry.

Tofacitinib combined with melanocyte protector α-MSH to treat vitiligo through dextran based hydrogel microneedles.

Vitiligo can cause serious damage to the appearance of patients and affect physical and mental health, but there is currently no simple and effective treatment. According to the theory of autoimmune disorder, the separable hydrogel microneedles delivering alpha-melanocyte-stimulating hormone (α-MSH) and tofacitinib were designed to treat vitiligo. This hydrogel microneedles were formed by dextran methacrylate (DexMA) and cyclodextrin-adamantane based host-guest supramolecules (HGSM) through CC double bond polymerization and host-guest assembly. The microneedle tips formed by the double cross-linked hydrogel can pierce the stratum corneum and deliver melanocyte protector α-MSH and JAK inhibitor tofacitinib directly to the epidermis and dermis. Under the treatment of α-MSH/tofacitinib microneedles, massive deposition of melanin in epidermis and hair follicles significantly accelerated skin and hair pigmentation.

Temperature controlled microcapsule loaded with Perilla essential oil and its application in preservation of peaches.

In this study, Perilla frutescens essential oil (PEO) loaded microcapsules (PEOM) were successfully prepared and their thermal stability, temperature-responsive releasing effect, antioxidant activity, antibacterial activity, and preservation of peach were systematically investigated. PEOM showed excellent encapsulation efficiency (91.5%) with a core-shell ratio of 1.4:1 and exhibited high thermal stability, indicating that PEOM could effectively maintain PEO release rate. In vitro assays indicated that the optimal kinetic model for PEO release fitted well with first order with a diffusion mechanism. A high level of antioxidant and antibacterial activity of PEOM was maintained. In addition, owing to its sustained release, PEOM could prolong the shelf life of peaches significantly. Therefore, PEOM has potential application and development prospects in the field of food preservation.

Mechanisms of action of Lycium barbarum polysaccharide in protecting against vitiligo mice through modulation of the STAT3-Hsp70-CXCL9/CXCL10 pathway.

CONTEXT: Vitiligo is a common skin disease with a complex pathogenesis, and so far, no effective treatment is available. Lycium barbarum L. (Solanaceae) polysaccharide (LBP), the main active ingredient of goji berries, has been demonstrated to protect keratinocytes and fibroblasts against oxidative stress. OBJECTIVE: This study explored the effects and mechanism of LBP on monobenzone-induced vitiligo in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into five groups (n = 6): negative control that received vaseline, vitiligo model group induced by monobenzone that treated with vaseline, positive control that received tacrolimus (TAC), LBP groups that received 0.3 and 0.6 g/kg LBP, respectively. We quantified the depigmentation by visual examination and scores, detected the expression of CD8+ T cells, pro-inflammatory cytokines and analysed the STAT3-Hsp70-CXCL9/CXCL10 pathway. RESULTS: LBP 0.3 and 0.6 g/kg groups can significantly reduce depigmentation scores and the infiltration of local inflammatory cells in the skin lesions. Moreover, the expression of CXCL9, CXCL3, CXCL10 and HSP70 decreased by 54.3, 20.3, 48.5 and 27.2% in 0.3 g/kg LBP group, which decreased by 62.1, 26.6, 58.2 and 34.5% in 0.6 g/kg LBP group. In addition, 0.3 and 0.6 g/kg LBP decreased the release of IL-8 (9.7%, 22.8%), IL-6 (40.8%, 42.5%), TNF-α (25.7%, 35%), IFN-γ (25.1%, 27.6%) and IL-1ß (23.7%, 33.7%) and inhibited the phosphorylation expression of STAT3 by 63.2 and 67.9%, respectively. CONCLUSION: These findings indicated LBP might be recommended as a new approach for vitiligo which provide a theoretical basis for the clinical application of LBP in treating vitiligo patients.

Diterpenes from oriental tobacco Nicotiana tabacum 'YNOTBS1' and their bioactivities.

Seven diterpenes including two new seco-cembranoid basmanoids A (1) and B (2), and two new labdane basmadanes A (3) and B (4), and three known compounds (-)-dehydro-nor-ambreinolid (5), (13E)-8-hydroxy-13-labden-12-one (6), and 14,15,16-dinor-7-oxolabda-8-ene-13-oic acid (7) were isolated from oriental tobacco Nicotiana tabacum 'YNOTBS1'. Compounds 1-3 and 5 showed anti-tobacco mosaic virus (TMV) activity with inhibition rates in the range of 30-69% at the concentration of 1 mg/mL. However, none of them exhibited any inhibitory effects against nitric oxide (NO) production in LPS and IFN-γ-induced RAW 264.7 murine macrophages and anti-proliferative activities against cancer cell lines SMMC-7721 and A-549.

The anti-TMV potency of the tobacco-derived fungus Aspergillus versicolor and its active alkaloids, as anti-TMV activity inhibitors.

Nicotiana tabacum (tobacco) has attracted interest as one of the most economically important industrial crops widely cultivated in China, whose dried leaves are popularly consumed medicinally and recreationally by human societies. In this study, five undescribed alkaloids derivatives, isoaspergillines A-E, together with eight known alkaloids, notoamide D, (1R,4S)-4-benzyl-1-isopropyl-2,4-dihydro-1H-pyrazino-[2,1-b]quinazoline-3,6-dione, protuboxepin K, notoamide C, notoamide M, deoxybrevianamide E, cyclo (D-Pro-L-Trp), and versicolamide B, were obtained from the culture of the Nicotiana tabacum-derived fungus Aspergillus versicolor. Their structures were mainly elucidated through comprehensive analyses of spectroscopic data. Bioactivity evaluation of all isolated compounds revealed that isoaspergilline A and notoamide M exhibited anti-TMV activities with IC50 values of 20.0 and 22.8 µM, respectively. Molecular docking suggested that isoaspergilline A and notoamide M were well located into the active site of anti-TMV by interacting with SER138, SER143, and ASN73 residues. This study enlightens the therapeutic potential of the endophytic fungus A. versicolor and it is helpful to find undescribed anti-TMV activity inhibitors, as well as searching for new anti-TMV candidates from natural sources.

All-Loop Four-Point Aharony-Bergman-Jafferis-Maldacena Amplitudes from Dimensional Reduction of the Amplituhedron.

We define a new geometry obtained from the all-loop amplituhedron in N=4 SYM by reducing its four-dimensional external and loop momenta to three dimensions. Focusing on the simplest four-point case, we provide strong evidence that the canonical form of this "reduced amplituhedron" gives the all-loop integrand of the Aharony-Bergman-Jafferis-Maldacena four-point amplitude. In addition to various all-loop cuts manifested by the geometry, we present explicitly new results for the integrand up to five loops, which are much simpler than results in N=4 SYM. One of the reasons for such all-loop simplifications is that only a very small fraction of the so-called negative geometries survives the dimensional reduction, which corresponds to bipartite graphs. Our results suggest an unexpected relation between four-point amplitudes in these two theories.

The prognostic significance of prognostic nutritional index in gastrointestinal stromal tumors: A systematic review and meta-analysis.

BACKGROUND: Risk assessment before treatment is important for gastrointestinal stromal tumors (GISTs), which will determine the priority of surgery or preoperative treatment. The prognostic nutritional index (PNI) is an integrated parameter consisting of serum albumin and lymphocyte count. Immunonutritional status defined in this manner is well-known to be closely linked to the prognosis of several other cancers. Nevertheless, the prognostic value of PNI specifically in GISTs has not been well-established. This study aimed to verify the prognostic role of PNI in patients with GISTs. METHODS: A comprehensive literature search was conducted on medical databases up to June, 2022, and the raw data (hazard ratios and 95% confidence intervals [CIs]) focusing on the prognostic value of PNI in patients with GISTs regarding recurrence-free survival were extracted and synthesized adopting the random-effects model. This review was registered in the PROSPERO database (CRD42022345440). RESULTS: A total of 8 eligible studies including 2627 patients with GISTs was analyzed and the pooled results confirmed that an elevated PNI was associated with a better recurrence-free survival (hazard ratio: 0.52, 95% CI: 0.40-0.68), with a moderate heterogeneity (I-square, 38%). The findings from subgroup analysis were consistent with the overall pooled results, and a sensitivity analysis, not the subgroup analysis, identified the source of heterogeneity. CONCLUSION: Elevated pretreatment PNI may be a useful indicator for assessing risk of recurrence in patients from China with GISTs. Studies in other countries and regions are needed to further verify the prognostic value of PNI in GISTs.

Direct adsorption sampling and ambient mass spectrometry analysis of tobacco smoke with porous paper strips.

Chemical analysis of atmospheric aerosols by conventional analytical methods is usually required to perform complicated and time-consuming sample preparation processes. In recent decades, ambient ionization mass spectrometry (AI-MS) methods have been proven to be simple, rapid, and effective analytical tools for direct analysis of various complex samples. In this work, we applied porous paper filters for direct adsorptive sampling of tobacco smoke, and then the sampled paper filters were performed the emitters of the paper spray ionization (PSI) device. An auto-sampling device was made to control the generation and collection of tobacco smoke. Nicotine, the typical compound of tobacco smoke, was used to optimize the key conditions of auto-sampling. Moreover, different types of tobacco smoke were also compared with multivariate variable analysis, and the makers of tobacco smoke from different sources of tobacco smoke were investigated. By using this method, direct sampling and analysis of a single tobacco sample can be completed within minutes. Overall, our results show that PSI-MS is a powerful tool that integrates collection, extraction, ionization, and identification analytes in smoke.