A novel hydrogel with inherent antibacterial and hemostatic properties for burn wound healing.

The skin is the immune system's first line of defense. Extensive skin burns can lead to tissue necrosis, sepsis, and even death. Anti-infectious care of burn wounds is a major challenge in clinical medicine. However, the extensive use of antibiotics led to the emergence of multi-drug-resistant bacteria and silver dressings with antibacterial effects are also cytotoxic. We used the natural cationic antibacterial agent ε-polylysine (EPL) to graft Epigallocatechin-3-gallate (EGCG) to synthesize EPL-EGCG. Then, we used methacrylated gelatin (GelMA) with arginine-glycine-aspartate-rich acid (RGD) sequence and EPL-EGCG form interpenetrating polymer network hydrogels with excellent swelling properties. The hydrogel's inherent antibacterial properties and photo-cross-linking properties can cover irregular burn wounds and isolate bacteria to prevent infection. In addition, we used polydopamine (PDA) to coat GelMA microspheres with excellent hemostatic efficacy and load platelet-rich plasma (PRP) to enhance the hemostatic efficacy of the microspheres and impart inflammation-regulating functions. The hydrogel showed excellent hemostatic efficacy in rat liver injury and tail vein injury models. In the rat infected burn model, the hydrogel exhibited favorable antimicrobial, pro-angiogenic, and anti-inflammatory phenotype polarization of macrophages. Our study shows that GelMA/EPL-EGCG/GM-PDA@PRP hydrogel application has excellent antibacterial, hemostatic and anti-inflammatory effects, providing a new treatment strategy for wound care before burn skin grafting.

Fabrication and characterization of tea seed starch-tea polyphenol complexes.

This study investigates the complexation between tea seed starch (TSS) and tea polyphenols (TPs) at varying concentrations (2.5, 5.0, 7.5, and 10.0 %). The objectives can expand the knowledge of TSS, which is a novel starch, and to examine how TPs influence the structure and physicochemical properties of the complexes. Results indicate that TPs interact with TSS through hydrogen bonding, altering granule morphology and disrupting ordered structure of starch. Depending on the concentration, TPs induce either V-type or non-V-type crystal structures within TSS, which had bearing on iodine binding capacity, swelling, pasting, gelatinization, retrogradation, rheology, and gel structure. In vitro digestibility analysis reveals that TSS-TPs complexes tend to reduce readily digestible starch while increasing resistant starch fractions with higher TP concentrations. Thus, TSS-TPs complexes physicochemical and digestibility properties can be modulated, providing a wide range of potential applications in the food industry.

A Novel Shunt Zigzag Double-Tap Low-Harmonic Multi-Pulse Rectifier Based on a Three-Stage Power Electronic Phase-Shifting Transformer.

To solve the problem of the large size of traditional industrial frequency phase-shift transformers and the harmonic distortion of multi-pulse wave rectifier systems, this paper proposes a three-stage shunt zigzag power electronic phase-shift transformer based on a double-tap multi-pulse wave rectifier, which combines the power factor correction (PFC) converter with the voltage-type SPWM inverter circuit to form a power electronic converter to realize the frequency boost and power factor correction. Through AC-DC-AC conversion, the frequency of the three-phase AC input voltage is increased, the number of core and coil turns in the transformer is reduced to reduce the size of the phase-shifter transformer, a zigzag structure of the phase-shifter transformer is used to solve the unbalanced distribution of current between the diode bridges, and a passive harmonic suppression method on the DC side is used to generate a loop current by using a group of single-phase rectifier bridges to regulate the input line current of the phase-shifter transformer. The phase-shifted voltage is input into two three-phase diode rectifier bridges to rectify and supply power to the load. Simulation and semi-physical test results show that the proposed method reduces the total harmonic distortion (THD) value of the input current of the phase-shifted transformer to 7.17%, and the THD value of the grid-side input current is further reduced to 2.49%, which meets the harmonic standard and realizes the purpose of power factor correction as well as being more suitable for high-power applications.

TMEM16 proteins: Ca2+­activated chloride channels and phospholipid scramblases as potential drug targets (Review).

TMEM16 proteins, which function as Ca2+­activated Cl­ channels are involved in regulating a wide variety of cellular pathways and functions. The modulators of Cl­ channels can be used for the molecule­based treatment of respiratory diseases, cystic fibrosis, tumors, cancer, osteoporosis and coronavirus disease 2019. The TMEM16 proteins link Ca2+ signaling, cellular electrical activity and lipid transport. Thus, deciphering these complex regulatory mechanisms may enable a more comprehensive understanding of the physiological functions of the TMEM16 proteins and assist in ascertaining the applicability of these proteins as potential pharmacological targets for the treatment of a range of diseases. The present review examined the structures, functions and characteristics of the different types of TMEM16 proteins, their association with the pathogenesis of various diseases and the applicability of TMEM16 modulator­based treatment methods.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Rational design of a dual-mode fluorescent probe for portable detection of pyriproxyfen in the environment and food.

The development of a fluorescent probe for pyriproxyfen (PPF) is crucial due to its potential threat to human health. However, the chemical inertness and low solubility of PPF present significant challenges for the detection of PPF in aqueous solutions using fluorescent probes. Herein, we have originally proposed a complex based on 2-(4-(dimethylamino)phenyl)-3-hydroxy-6,7-dimethoxy-4 H-chromen-4-one (HOF) and serum albumin (SA) as a dual-mode fluorescent probe, HOF@SA. This probe utilizes an indicator displacement assay (IDA) to release the dye HOF from the probe at low PPF concentrations (< 10 µM) and embeds the free dye HOF into the micelle of PPF at high concentrations (> 10 µM). This results in dual-mode fluorescent response characteristics for PPF: a turn-off response at low concentrations and a ratiometric response at high concentrations. An investigation of sensing behavior of HOF@SA for PPF detection exhibits rapid response (< 60 s), high sensitivity (LOD ∼4.7 ppb), high selectivity, and excellent visual detection capability (from cyan to yellow). Moreover, with the aid of a portable device, this method enables to analyze PPF in environmental and food samples. These results promote the advancement of a fluorescent probe approach for PPF analysis in environment and food.

Pyrazolone-Protein Interaction Enables Long-Term Retention Staining and Facile Artificial Biorecognition on Cell Membranes.

Cell membrane genetic engineering has been utilized to confer cell membranes with functionalities for diagnostic and therapeutic purposes but concerns over cost and variable modification results. Although nongenetic chemical modification and phospholipid insertion strategies are more convenient, they still face bottlenecks in either biosafety or stability of the modifications. Herein, we show that pyrazolone-bearing molecules can bind to proteins with high stability, which is mainly contributed to by the multiple interactions between pyrazolone and basic amino acids. This new binding model offers a simple and versatile noncovalent approach for cell membrane functionalization. By binding to cell membrane proteins, pyrazolone-bearing dyes enabled precise cell tracking in vitro (>96 h) and in vivo (>21 days) without interfering with the protein function or causing cell death. Furthermore, the convenient anchor of pyrazolone-bearing biotin on cell membranes rendered the biorecognition to avidin, showing the potential for artificially creating cell targetability.

Arthroscopy-Assisted Closed Reduction and Percutaneous Internal Fixation for Medial Malleolus Fracture.

BACKGROUND: Arthroscopy-assisted closed reduction and percutaneous internal fixation is a minimally invasive technique for medial malleolus fracture treatment. The purpose of the study was to assess the quality and functional outcomes of this technique. METHODS: Seventy-eight patients with combined medial malleolus fractures were treated with arthroscopy-assisted closed reduction and percutaneous screw fixation technique. The surgical procedure was described in detail; the clinical efficacy of this method was evaluated in terms of time of operation, postoperative complications, and fracture healing time; and functional outcomes were analyzed. RESULTS: All of the patients were followed up for a minimum of 12 months without complications of the medial malleolus wound, and all of the medial malleolus fractures healed within 6 to 8 weeks. At the last follow-up, the visual analog scale scores ranged from 0 to 3 and the American Orthopaedic Foot and Ankle Society ankle and hindfoot function scores ranged from 75 to 95. CONCLUSIONS: Arthroscopy-assisted closed reduction and percutaneous internal fixation makes the treatment of medial malleolus fractures less invasive compared with traditional surgical methods and allows simultaneous exploration and management of the articular surface.

Benzorhodol derived far-red/near-infrared fluorescent probes for selective and sensitive detection of butyrylcholinesterase activity in living cells and the non-alcoholic fatty liver of zebrafish.

Liver diseases are a growing public health concern and the development of non-alcoholic fatty liver disease (NAFLD) has a significant impact on human metabolism. Butyrylcholinesterase (BChE) is a vital biomarker for NAFLD, making it crucial to monitor BChE activity with high sensitivity and selectivity. In this study, we designed and synthesized a range of benzorhodol-derived far-red/near-infrared fluorescent probes, FRBN-B, NF-SB, and NF-B, for the quantitative detection and imaging of BChE. These probes differed in the size of their conjugated systems and in the number of incorporated cyclopropanecarboxylates, acting as the recognition site for BChE. Comprehensive characterization showed that FRBN-B and NF-SB fluorescence was triggered by BChE-mediated hydrolysis, while an additional cyclopropanecarboxylate in NF-B impeded the fluorescence release. High selectivity towards BChE was observed for FRBN-B and NF-SB, with a detection limit of 7.2 × 10-3 U mL-1 for FRBN-B and 1.9 × 10-3 U mL-1 for NF-SB. The probes were further employed in the evaluation of BChE inhibitor efficacy and imaging of intracellular BChE activity. Additionally, FRBN-B was utilized for imaging the BChE activity level in liver tissues in zebrafish, demonstrating its potential as a diagnostic tool for NAFLD.

A fluorescent NBD "turn-on" probe for the rapid and on-site analysis of fructose in food.

High fructose intake is an important cause of metabolic disease. Due to the increasing prevalence of metabolic diseases worldwide, the development of an accurate and efficient tool for monitoring fructose in food is urgently needed to control the intake of fructose. Herein, a new fluorescent probe NBD-PQ-B with 7-nitrobenz-2-oxa-1, 3-diazole (NBD) as the fluorophore, piperazine (PQ) as the bridging group and phenylboronic acid (B) as the recognition receptor, was synthesized to detect fructose. The fluorescence of NBD-PQ-B increased linearly at 550 nm at an excitation wavelength of 497 nm with increasing fructose concentration from 0.1 to 20 mM. The limit of detection (LOD) of fructose was 40 µM. The pKa values of NBD-PQ-B and its fructose complexes were 4.1 and 10.0, respectively. In addition, NBD-PQ-B bound to fructose in a few seconds. The present technique was applied to determine the fructose content in beverages, honey, and watermelon with satisfactory results. Finally, the system could not only be applied in an aqueous solution with a spectrophotometer, but also be fabricated as a NBD-PQ-B/polyvinyl oxide (PEO) film by electrospinning for on-site food analysis simply with the assistance of a smartphone.

Harnessing a simple ratiometric fluorescent probe for albumin recognition and beyond.

A commercially available naphthalene fluorophore serves as a ratiometric indicator for albumin, showcasing its applications in albumin-based supramolecular recognition.

Efficacy of salvage surgery versus re-irradiation for isolated regional lymph node recurrence in patients with nasopharyngeal carcinoma.

BACKGROUND: To compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment. METHODS: We retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors. RESULTS: The median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group. CONCLUSIONS: For NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.

Formation, physicochemical properties, and biological activities of theabrownins.

Theabrownins (TBs) are heterogeneous mixtures of water-soluble brown tea pigments, and important constituents to evaluate the quality of dark tea. TBs have numerous hydroxyl and carboxyl groups and are formed by the oxidative polymerization of tea polyphenols. Many biological activities attributed to TBs, including antioxidant, anti-obesity, and lipid-regulating, have been demonstrated. This review summarizes the research progress made on the formation mechanism and physicochemical properties of TBs. It also discusses their protective effects against various diseases and associated potential molecular mechanisms. Additionally, it examines the signaling pathways mediating the bioactivities of TBs and highlights the difficulties and challenges of TBs research as well as their research prospects and applications.

Ratiometric determination of etomidate based on an albumin-based indicator displacement assay (IDA).

The first fluorescent sensor based on the indicator displacement assay (IDA) for on-site determination of etomidate.

Gram-negative bacteria recognition and photodynamic elimination by Zn-DPA based sensitizers.

The abuse and overuse of antibiotics let drug-resistant bacteria emerges. Antibacterial photodynamic therapy (APDT) has shown outstanding merits to eliminate the drug-resistant bacteria via cytotoxic reactive oxygen species produced by irradiating photosensitizer. However, most of photosensitizers are not effective for Gram-negative bacteria elimination. Herein conjugates of NBS, a photosensitizer, linked with one (NBS-DPA-Zn) or two (NBS-2DPA-Zn) equivalents of zinc-dipicolylamine (Zn-DPA) have been designed to achieve the functional recognition of different bacteria. Due to the cationic character of NBS and metal transfer channel effect of Zn-DPA, NBS-DPA-Zn exhibited the first regent to distinguish P. aeruginosa from other Gram-negative bacteria. Whereas NBS-2DPA-Zn showed broad-spectrum antibacterial effect because the two arm of double Zn-DPA enhanced interactions with anionic membranes of bacteria, led the bacteria aggregation and thus provided the efficacy of APDT to bacteria and corresponding biofilm. In combination with a hydrogel of Pluronic, NBS-2DPA-Zn@gel shows promising clinical application in mixed bacterial diabetic mouse model infection. This might propose a new method that can realize functional identification and elimination of bacteria through intelligent regulation of Zn-DPA, and shows excellent potential for antibacterial application.

Theabrownins in dark tea form complexes with tea polysaccharide conjugates.

BACKGROUND: Theabrownins (TBs) are one of most important quality components in dark tea, but have not been produced industrially. In this study, the aqueous extract was obtained from Pu-erh ripe tea, one kind of dark tea. Caffeine, theaflavin, catechin and saponin were removed by trichloromethane, ethyl acetate and n-butanol in turn to obtain a TB isolate. The TB isolate was subjected to column chromatography using a macroporous resin HPD-750 and eluted with a gradient of 0-700 g kg-1 ethanol aqueous solution. Four fractions were obtained, and named as TBs-FC1, TBs-FC2, TBs-FC3 and TBs-FC4. RESULTS: These four fractions contained polysaccharides and no small molecules such as catechins, caffeine and theaflavins as well as average molecular weights of 123.000 kDa, 23.380 kDa, 89.870 kDa and 106.600 kDa. It was revealed that they were complexes of TBs and tea polysaccharide conjugates (TPCs). Ultraviolet-visible (UV-visible) and infrared (IR) spectra showed the properties of TBs and TPCs. Their zeta potentials ranged from -13.40 mV to -38.80 mV in aqueous solutions at pH 3.0-9.0. CONCLUSION: This study reveals that TBs do not exist in free state but in combined state in dark tea, which provide the theoretical basis for the industrialization of TBs. © 2024 Society of Chemical Industry.

Antidiabetic drug administration prevents bone mineral density loss: Evidence from a two-sample Mendelian randomization study.

The aim of this study was to investigate the effect of common antidiabetic drugs on BMD by two-sample Mendelian randomization (MR). The single nucleotide polymorphisms that were strongly associated with insulin, metformin, rosiglitazone and gliclazide were extracted as instrumental variables (IVs) for MR analysis. The inverse variance weighted (IVW) method was used as the primary MR method to assess the causal effect of antidiabetic drugs on BMD, and other MR methods, including Weighted median, MR Egger and Weighted mode, were used for complementary analysis. Reliability and stability were assessed by the leave-one-out test. In the present work, IVW estimation of the causal effect of insulin on heel BMD demonstrated that there was a null effect of insulin on heel BMD (ß = 0.765; se = 0.971; P = 0.430), while metformin treatment had a positive effect on heel BMD (ß = 1.414; se = 0.460; P = 2.118*10-3). The causal relationship between rosiglitazone and heel BMD analysed by IVW suggested that there was a null effect of rosiglitazone on heel BMD (ß = -0.526; se = 1.744; P = 0.763), but the causal effect of gliclazide on heel BMD evaluated by IVW demonstrated that there was a positive effect of gliclazide on heel BMD (ß = 2.671; se = 1.340; P = 0.046). In summary, the present work showed that metformin and gliclazide have a role in reducing BMD loss in patients with diabetes and are recommended for BMD loss prevention in diabetes.

Structurally Modified Polysaccharides: Physicochemical Properties, Biological Activities, Structure-Activity Relationship, and Applications.

Polysaccharides are an important class of biomolecules derived from several sources. However, the inherent structure of polysaccharides prevents them from exhibiting favorable physicochemical properties, which restricts their development in agriculture, industry, food, and biomedicine. This paper systematically summarizes the changes in the primary and advanced structures of modified polysaccharides, and focuses on the effects of various modification methods on the hydrophobicity, rheological properties, emulsifying properties, antioxidant activity, hypoglycemic, and hypolipidemic activities of polysaccharides. Then there is a list the applications of modified polysaccharides in treating heavy metal pollutants, purifying water resources, improving beverage stability and bread quality, and precisely delivering the drug. When summarized and reviewed, the information above can shed further light on the relationship between polysaccharide structure and function. Determining the structure-activity relationship provides a scientific basis for the direction of molecular modifications of polysaccharides.

Early-stage neutralizing antibody level associated with the re-positive risk of Omicron SARS-CoV-2 RNA in patients recovered from COVID-19.

Post-discharge re-positivity of Omicron SARS-CoV-2 is challenging for the sufficient control of this pandemic. However, there are few studies about the risk of re-positivity. We aimed to explore the association of neutralizing antibodies (nAbs, AU/mL) with the incidence of re-positivity among patients recovered from COVID-19. A retrospective cohort study selected 318 Omicron-infected patients was conducted in China between December 2021 and April 2022. The peak value of nAb levels (nAb-peak) within 14 days of disease onset was defined as the baseline and was mainly used for the subsequent analyses. In the unadjusted, minimally adjusted, fully adjusted, and additionally adjusted for IgG models, a per-standard deviation (SD) increase in the nAb-peak values was significantly associated with a 59 %, 59 %, 50 %, and 75 % decreased risk of Omicron SARS-CoV-2 re-positivity during post-discharge surveillance, respectively. Stratified analyses showed no significant changes in the relationship between nAbs and re-positivity. Our study suggested that the increase in baseline nAb levels independently associated with a low risk of re-positivity in patients recovered from COVID-19.