Ts2O Promoted Deoxygenative C-H Dithiocarbonation of Quinoline N-Oxides with Potassium O-Alkyl Xanthates.

A simple, efficient, and practical method for the synthesis of S-quinolyl xanthates was developed via Ts2O-promoted deoxygenative C-H dithiocarbonation of quinoline N-oxides with various potassium O-alkyl xanthates. The reaction performed well under transition-metal-free, base-free, and room-temperature conditions with wide substrate tolerance. Employing potassium O-tert-butyl xanthate (tBuOCS2K) as a nucleophile, some valuable quinoline-2-thiones were unexpectedly obtained in a one-pot reaction without any additional base.

Persulfate-Promoted Carbamoylation/Cyclization of Alkenes: Synthesis of Amide-Containing Quinazolinones.

The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3H)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH4)2S2O8.

Identification of the domestication gene GmCYP82C4 underlying the major quantitative trait locus for the seed weight in soybean.

KEY MESSAGE: A major quantitative trait locus (QTL) for the hundred-seed weight (HSW) was identified and confirmed in the two distinct soybean populations, and the target gene GmCYP82C4 underlying this locus was identified that significantly associated with soybean seed weight, and it was selected during the soybean domestication and improvement process. Soybean is a major oil crop for human beings and the seed weight is a crucial goal of soybean breeding. However, only a limited number of target genes underlying the quantitative trait loci (QTLs) controlling seed weight in soybean are known so far. In the present study, six loci associated with hundred-seed weight (HSW) were detected in the first population of 573 soybean breeding lines by genome-wide association study (GWAS), and 64 gene models were predicted in these candidate QTL regions. The QTL qHSW_1 exhibits continuous association signals on chromosome four and was also validated by region association study (RAS) in the second soybean population (409 accessions) with wild, landrace, and cultivar soybean accessions. There were seven genes in qHSW_1 candidate region by linkage disequilibrium (LD) block analysis, and only Glyma.04G035500 (GmCYP82C4) showed specifically higher expression in flowers, pods, and seeds, indicating its crucial role in the soybean seed development. Significant differences in HSW trait were detected when the association panels are genotyped by single-nucleotide polymorphisms (SNPs) in putative GmCYP82C4 promoter region. Eight haplotypes were generated by six SNPs in GmCYP82C4 in the second soybean population, and two superior haplotypes (Hap2 and Hap4) of GmCYP82C4 were detected with average HSW of 18.27 g and 18.38 g, respectively. The genetic diversity of GmCYP82C4 was analyzed in the second soybean population, and GmCYP82C4 was most likely selected during the soybean domestication and improvement process, leading to the highest proportion of Hap2 of GmCYP82C4 both in landrace and cultivar subpopulations. The QTLs and GmCYP82C4 identified in this study provide novel genetic resources for soybean seed weight trait, and the GmCYP82C4 could be used for soybean molecular breeding to develop desirable seed weight in the future.

Omental coating attenuates implant-induced foreign body reaction in rats.

The objective of this study is to clarify whether the omental coating can effectively attenuate foreign body reaction (FBR) induced by implanted materials. Male Sprague-Dawley rats were injected with polydextran particle slurry intraperitoneally to activate the omentum. 7 days later, polyether polyurethane sponge discs were implanted subcutaneously on each side of the rat's back as the foreign implants to induce FBR. The next day, omental transposition were performed. The disc on the left side of each rat's back was wrapped with omental flap (omental group); the disc on the right side was untreated (control group). All discs were removed 21 days after implantation and assessed by determining the components of the fibrovascular tissue (angiogenesis, inflammation, foreign body giant cells (FBGCs) aggregation and fibrogenesis). In implants in omental group, micro vessel density (MVD), Hemoglobin (Hb) content and VEGF levels (pro-angiogenic cytokine) were increased when compared with implants from control group. Inflammatory parameters (IL-1ß; macrophage accumulation-NAG activity; neutrophil accumulation- MPO levels) were decreased in implants after omental coating. Also, collagen deposition, fibrous capsule thickness, and FBGCs decreased in implants from omental group. However, intra-implant levels of TNF-α and TGF-ß1 were not different after omental coating. Our findings showed for the first time that the omental coating around the implants attenuate the adverse FBR, it may be critical in developing new strategies to control FBR and improve the function and performance of the implanted materials.

Nitrogen removal characteristics of novel bacterium Klebsiella sp. TSH15 by assimilatory/dissimilatory nitrate reduction and ammonia assimilation.

A novel strain with heterotrophic nitrification and aerobic denitrification was screened and identified as Klebsiella sp. TSH15 by 16S rRNA. The results demonstrated that the ammonia-N and nitrate-N removal rates were 2.99 mg/L/h and 2.53 mg/L/h under optimal conditions, respectively. The analysis of the whole genome indicated that strain TSH15 contained the key genes involved in assimilatory/dissimilatory nitrate reduction and ammonia assimilation, including nas, nar, nir, nor, glnA, gltB, gdhA, and amt. The relative expression levels of key nitrogen removal genes were further detected by RT-qPCR. The results indicated that the N metabolic pathways of strain TSH15 were the conversion of nitrate or nitrite to ammonia by assimilatory/dissimilatory nitrate reduction (NO3-→NO2-→NH4+) and further conversion of ammonia to glutamate (NH4+-N â†’ Glutamate) by ammonia assimilation. These results indicated that the strain TSH15 had the potential to be applied to practical sewage treatment in the future.

Influence of friction on the packing efficiency and short-to-intermediate range structure of hard-sphere systems.

Using particle-resolved computer simulations, we investigate the effect of friction on the packing structure of hard-sphere mixtures with two kinds of particles under external compression. We first show that increasing friction between the particles results in a more disordered and less efficient packing of the local structure on the nearest neighbor scale. It is also found that standard two-point correlation functions, i.e., radial distribution function and static structure factor, show basically no detectable changes beyond short-range distances upon varying inter-particle friction. Further analysis of the structure using a four-point correlation method reveals that these systems have on the intermediate-range scale a three-dimensional structure with an icosahedral/dodecahedral symmetry that exhibits a pronounced dependence on friction: small friction gives rise to an orientational order that extends to larger distances. Our results also demonstrate that composition plays a role in that the degree of structural order and the structural correlation length are mainly affected by the friction coefficients associated with the more abundant species.

Ball milling synthesis of S-quinolyl xanthates via coupling of haloquinolines with potassium O-alkyl xanthates.

An environmentally benign protocol that provides various S-quinolyl xanthates via a ball milling enabled cross coupling reaction of haloquinolines and readily available potassium O-alkyl xanthates is first reported. The reaction proceeded well under mild, transition metal- and solvent-free conditions, making it an attractive method for the introduction of xanthates into the quinoline scaffold.

Circ_072697 knockdown promotes advanced glycation end products-induced cell proliferation and migration in HaCaT cells via miR-3150a-3p/KDM2A axis.

OBJECTIVE: Diabetes foot ulcer (DFU) is a serious complication of diabetes, which can lead to significant mortality and amputation rate. Our previous study found circ_072697 was highly expressed in DFU tissues, but the regulatory mechanism of circ_072697 in DFU remains unclear. METHODS: The relative expressions of circ_072697, miR-3150a-3p, and KDM2A in DFU patients or advanced glycation end products (AGEs)-treated HaCaT cells (used as DFU cell model) were determined by using qRT-PCR. Cell proliferation and migration abilities were determined by using CCK-8 and Transwell assays. The interaction between miR-3150a-3p with circ_072697 or KDM2A were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. Furthermore, the protein expression of genes involved in MAPK signaling pathway was detected by western blot. RESULTS: The expression of circ_072697 was significantly upregulated in DFU tissues, while the expression of miR-3150a-3p was downregulated. Circ_072697 knockdown promoted the proliferation and migration of AGEs-treated HaCaT cells. miR-3150a-3p was confirmed as a target of circ_072697 and its inhibitor reversed the promotion effects of circ_072697 knockdown on biological behavior of cells. In addition, KDM2A was considered as a target of miR-3150a-3p and it was highly expressed in DFU samples. Importantly, circ_072697 could regulate KDM2A expression through sponging miR-3150a-3p, and this axis had effect on the MAPK signaling pathway. CONCLUSIONS: Overall, circ_072697 regulated the biological behaviors of keratinocytes in DFU via miR-3150a-3p/KDM2A axis and MAPK signaling pathway, revealing a new insight into the pathogenesis and potential therapeutic targets of DFU.

Single-cell analysis reveals melanocytes may promote inflammation in chronic wounds through cathepsin G.

During acute wound (AW) healing, a series of proper communications will occur between different epidermal cells at precise temporal stages to restore the integrity of the skin. However, it is still unclear what variation happened in epidermal cell interaction in the chronic wound environment. To provide new insights into chronic wound healing, we reconstructed the variations in the epidermal cell-cell communication network that occur in chronic wound healing via single-cell RNA-seq (scRNA-seq) data analysis. We found that the intricate cellular and molecular interactions increased in pressure ulcer (PU) compared to AW, especially the PARs signaling pathways were significantly upregulated. It shows that the PARs signaling pathways' main source was melanocytes and the CTSG-F2RL1 ligand-receptor pairs were its main contributor. Cathepsin G (CatG or CTSG) is a serine protease mainly with trypsin- and chymotrypsin-like specificity. It is synthesized and secreted by some immune or non-immune cells. Whereas, it has not been reported that melanocytes can synthesize and secrete the CTSG. F2R Like Trypsin Receptor 1 (F2RL1) is a member of proteinase-activated receptors (PARs) that are irreversibly activated by proteolytic cleavage and its stimulation can promote inflammation and inflammatory cell infiltration. In this study, we found that melanocytes increased in pressure ulcers, melanocytes can synthesize and secrete the CTSG and may promote inflammation in chronic wounds through CTSG-F2RL1 pairs, which may be a novel potential target and a therapeutic strategy in the treatment of chronic wounds.

Single-polymer dynamics of starch-like branched ring polymers in steady shear flow.

The stretching dynamics and dynamical behaviors of individual branched ring polymer (BRP), a coarse-grained model for some types of the starch, in steady shear flow are studied by using a hybrid mesoscale simulation approach that combines multiparticle collision dynamics with standard molecular dynamics. By analyzing the stretched configuration of BRPs, we find the polymer size increases nonmonotonically with increasing branch length. Meanwhile, the decrease of the alignment angle of the stretched configuration of BRPs follows a universal power law during the first downward phase as the shear rate increases. Constructing the three-dimensional surface of the polymer's ring backbone and tracing the temporal fluctuations of the surface's normal vector along the simulation trajectory, the tumbling and tank-treading motion are clearly reflected by periodic and non-periodic changes of the normal vector. Interestingly, these temporal changes are much more regular than that of the gyration tensor. Thus, a novel cross-correlation function, which is the correlation between fluctuations of the normal vector along the flow direction and the velocity-gradient direction, is proposed to analyze the tumbling motion that usually coexists with the tank-treading motion. This function can naturally address the fails of traditional method that analyzing the tumbling motion by determining the correlation of temporal fluctuations of the gyration tensor Gαα. By analyzing the dynamical behaviors of BRPs, diverse dependences of the tumbling frequency ωTB and tank-treading frequency ωTT on the shear rate γ̇ are observed at a wide range of shear rates and polymer sizes. Furthermore, our simulations also reveal that the tank-treading motion is more stable than the tumbling motion for small-branch-size BRPs but the tumbling motion is more stable than the tank-treading motion for large-branch-size BRPs.

Theoretical study on the stability, ferroelectricity and photocatalytic properties of CaBiO3.

Materials with high ferroelectric polarization strength and sufficient absorption of visible light have unique advantages in photocatalysis. Based on the results of structure search, phonon frequency, and elasticity coefficient calculations, CaBiO3 has a stable R3 polar structure. First-principles calculations indicate that R3-CaBiO3 is a potentially efficient ferroelectric visible-light photocatalytic material for hydrogen production. CaBiO3 under slight strain can maintain high ferroelectric polarization strength, strong visible light absorption capacity and small effective mass. CaBiO3 under tensile strain has potentially ferroelectric photogeneration of hydrogen with a band edge position that crosses the redox potential of water. These results can expand the application of Bi-based materials in photocatalytic hydrogen production.

Theoretical study on the ferroelectric and light absorption properties of Li2SbBiO6 for harvesting visible light.

Ferroelectric oxides with large bandgaps have restricted applications in photovoltaic and photocatalytic fields. Based on recent experiments with the ferroelectric compound, LiSbO3, the stability and optoelectronic properties of a new ferroelectric compound, namely Li2SbBiO6, are investigated in this study. The calculated results demonstrate that Li2SbBiO6 satisfies the stability conditions of the elastic coefficients and phonon dynamics. Li2SbBiO6 maintains the ferroelectric polarization strength of LiSbO3 and significantly reduces the bandgap, and thus has been explored for applications in photovoltaic and photocatalytic fields. Li2SbBiO6 is a new potential ferroelectric oxide for harvesting visible light owing to its suitable bandgap and a large hole-electron effective mass ratio.

Theoretical study on ferroelectric nitrides with super-wurtzite structures for solar energy conversion applications.

Polarized structured nitride semiconductors are attractive due to their unique and environment-friendly electronic properties. The stability, ferroelectricity and photocatalytic and photovoltaic properties of super-wurtzite Mg2XN3 (X = Bi, Mo, Nb, Sb, Ta, Tc and W) were determined based on first principles calculations in this study. The calculated results indicate that Mg2XN3 (X = Sb, Ta, Bi and Nb) are stable polar nitrides by phonon frequencies, elastic coefficients and ferroelectric analysis. Mg2XN3 (X = Sb, Ta and Nb) with large ferroelectric polarization strength could absorb ultraviolet light to promote photocatalytic water splitting for hydrogen production. Mg2BiN3 is a new excellent photovoltaic candidate due to its ideal energy band, high electron mobility, high absorption coefficient and large ferroelectric polarization strength.

Prevalence and prognosis of hard-to-heal wounds with comorbidities in China.

OBJECTIVE: Regular retrospective analysis is necessary for potential improvement in clinical practice for the treatment of hard-to-heal wounds. Comorbidities and outcomes have demonstrated spatial and temporal diversity, emphasising the importance of updates in epidemiology. The complexity of healing hard-to-heal wounds has long been known, and so we sought evidence-based improvement on the current principles of treatment. METHOD: Demographic and clinical information of patients from the WoundCareLog database was collected. Patients who met the inclusion criteria and completed follow-up after treatment were included. Comorbidities were diagnosed and classified into eight categories based on ICD-10. We compared the demographic and aetiological characteristics between patients with and without comorbidities by t-test and Chi-squared test. The impact of comorbidities on wound healing were evaluated with a multivariate Cox model. RESULTS: A total of 2163 patients met the inclusion criteria and were enrolled, of whom 37.0% were aged 61-80 years, 36.0% were aged 41-60 years and 60.8% were male. The lower extremities and buttocks were the most commonly affected areas with hard-to-heal wounds. Non-traumatic wounds accounted for 66.6% of cases, and infection, pressure and diabetes were the most common causes. Paralysis and diabetes were the most important factors which led to a prolonged healing process and inferior clinical outcomes. CONCLUSION: Comorbidities of hard-to-heal wounds were treated as separate contributors and their weighted effect on outcome was calculated through correlation analysis. Paralysis and diabetes were the most unfavourable comorbidities affecting the treatment of non-traumatic hard-to-heal wounds. Our study highlighted the priority of comorbidity treatment through data-driven approaches. It provides potential value in developing better public health strategies and preventive medicine.

Dynamical and Structural Properties of Comb Long-Chain Branched Polymer in Shear Flow.

Using hybrid multi-particle collision dynamics (MPCD) and a molecular dynamics (MD) method, we investigate the effect of arms and shear flow on dynamical and structural properties of the comb long-chain branched (LCB) polymer with dense arms. Firstly, we analyze dynamical properties of the LCB polymer by tracking the temporal changes on the end-to-end distance of both backbones and arms as well as the orientations of the backbone in the flow-gradient plane. Simultaneously, the rotation and tumbling behaviors with stable frequencies are observed. In other words, the LCB polymer undergoes a process of periodic stretched-folded-stretched state transition and rotation, whose period is obtained by fitting temporal changes on the orientation to a periodic function. In addition, the impact induced by random and fast motions of arms and the backbone will descend as the shear rate increases. By analyzing the period of rotation behavior of LCB polymers, we find that arms have a function in keeping the LCB polymer's motion stable. Meanwhile, we find that the rotation period of the LCB polymer is mainly determined by the conformational distribution and the non-shrinkable state of the structure along the velocity-gradient direction. Secondly, structural properties are numerically characterized by the average gyration tensor of the LCB polymer. The changes in gyration are in accordance with the LCB polymer rolling when varying the shear rate. By analyzing the alignment of the LCB polymer and comparing with its linear and star counterparts, we find that the LCB polymer with very long arms, like the corresponding linear chain, has a high speed to reach its configuration expansion limit in the flow direction. However, the comb polymer with shorter arms has stronger resistance on configuration expansion against the imposed flow field. Moreover, with increasing arm length, the comb polymer in shear flow follows change from linear-polymer-like to capsule-like behavior.

CT-Angiography-Based Outcome Prediction on Diabetic Foot Ulcer Patients: A Statistical Learning Approach.

The purpose of our study is to predict the occurrence and prognosis of diabetic foot ulcers (DFUs) by clinical and lower extremity computed tomography angiography (CTA) data of patients using the artificial neural networks (ANN) model. DFU is a common complication of diabetes that severely affects the quality of life of patients, leading to amputation and even death. There are a lack of valid predictive techniques for the prognosis of DFU. In clinical practice, the use of scales alone has a large subjective component, leading to significant bias and heterogeneity. Currently, there is a lack of evidence-based support for patients to develop clinical strategies before reaching end-stage outcomes. The present study provides a novel technical tool for predicting the prognosis of DFU. After screening the data, 203 patients with diabetic foot ulcers (DFUs) were analyzed and divided into two subgroups based on their Wagner Score (138 patients in the low Wagner Score group and 65 patients in the high Wagner Score group). Based on clinical and lower extremity CTA data, 10 predictive factors were selected for inclusion in the model. The total dataset was randomly divided into the training sample, testing sample and holdout sample in ratio of 3:1:1. After the training sample and testing sample developing the ANN model, the holdout sample was utilized to assess the accuracy of the model. ANN model analysis shows that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of the overall ANN model were 92.3%, 93.5%, 87.0%, 94.2% and 0.955, respectively. We observed that the proposed model performed superbly on the prediction of DFU with a 91.6% accuracy. Evaluated with the holdout sample, the model accuracy, sensitivity, specificity, PPV and NPV were 88.9%, 90.0%, 88.5%, 75.0% and 95.8%, respectively. By contrast, the logistic regression model was inferior to the ANN model. The ANN model can accurately and reliably predict the occurrence and prognosis of a DFU according to clinical and lower extremity CTA data. We provided clinicians with a novel technical tool to develop clinical strategies before end-stage outcomes.

A Trefoil Knot Polymer Chain Translocates through a Funnel-like Channel: A Multi-Particle Collision Dynamics Study.

With combining multi-particle collision dynamics (MPCD) for the solvent and molecular dynamics (MD) for the polymer chains, we have studied the conformation and untying behaviors of a trefoil knot polymer chain translocated through a confined funnel-like channel. For the trefoil knot chain, we found that the untying knot behavior mostly happens during the translocation process, and the translocation behavior of linear chains is also simulated as a comparison. Some characteristics of the trefoil knot chain during translocation process, such as average gyration radius and the average end-to-end distances are discussed, and we statistic the scale relations of the translocation time versus the chain length, and that of the chain rigidity. This study may help to understand translocation behaviors of the knotted linear polymer chain in the capillary flow field.

Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to facilitate tissue repair in diabetic wounds.

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO-induced dysfunction. We observed that the accumulation of MGO-derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO-derived AGEs in the wound tissue of type-2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1-like macrophages induced by lipopolysaccharide (LPS), but not those of M0-like macrophages induced by PMA or of M2-like macrophages induced by interleukins 4 (IL-4) and 13 (IL-13); the impaired phagocytosis of M1-like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non-healing diabetic wounds.

CO2 Laser Debridement and Negative Pressure Wound Therapy With Endoscopic Support for Treatment of Sinus Wound at the Ischial Tuberosity: Case Report.

The sinus tract of the ischial tuberosity is often caused by pressure injury. It has the characteristics of difficult treatment and high cost, which increases the anxiety of patients and reduces the quality of life of patients. This case report is to describe an effective method to treat sinus wound at the ischial tuberosity. A 53-year-old male suffered pressure ulcer with sinus wound at the left ischial tuberosity due to inadequate walking and sedentary activity. On the basis of pressure relief and immobilization, the patient was treated with CO2 laser debridement and negative pressure wound therapy under endoscope support 3 times, the deep of the sinus wound was completely closed, and then the residual superficial wound was treated by skin grafting. Follow-up of 1 year after healing showed no recurrence of wound.

Application of Compound Polymyxin B Ointment in the Treatment of Chronic Refractory Wounds.

The purpose of this study was to investigate the clinical efficacy of compound polymyxin B ointment for treating chronic refractory wounds. A retrospective analysis was performed on 111 patients who underwent chronic refractory wound treatment. Patients were divided into 2 groups, with 45 patients included in the experimental group (compound polymyxin B group) and 66 patients included in the control group (silver sulfadiazine group). After thorough debridement in both groups, either compound polymyxin B ointment or silver sulfadiazine cream was evenly applied to the patient's wound and covered with sterile gauze. In both groups, dressing changes were dependent on the wound's condition and secretions. Using the Bates-Jensen Wound Assessment Tool (BWAT), patients in both groups were scored, after which wound healing, infection, and healing time were compared. There was no significant difference in BWAT scores between the 2 groups on the 7th or 14th day; however, on the 21st day, the BWAT score in the experimental group was significantly lower than that of the control group. The difference was statistically significant (P < .05). There was no significant difference in the BWAT-I scores between the 2 groups on the seventh day. The healing time in the experimental group was significantly shorter than that of the control group, and the difference was statistically significant (P < .05). For the treatment of chronic refractory wounds, thorough debridement followed by compound polymyxin B ointment topical application can reduce and control wound infection effectively and accelerate the process of wound repair.