Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells.

Background: Cystic Fibrosis causing mutations in the gene CFTR , reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations. A pilot trial of Ivacaftor supported its potential efficacy for the treatment of mucus obstruction in COPD. These findings prompted the search for CFTR potentiators that are more effective in ameliorating cigarette-smoke (CS) induced mucostasis. Methods: A novel small molecule potentiator (SK-POT1), previously identified in CFTR binding studies, was tested for its activity in augmenting CFTR channel activity using patch clamp electrophysiology in HEK-293 cells, a fluorescence-based assay of membrane potential in Calu-3 cells and in Ussing chamber studies of primary bronchial epithelial cultures. Addition of cigarette smoke extract (CSE) to the solutions bathing the apical surface of Calu-3 cells and primary bronchial airway cultures was used to model COPD. Confocal studies of the velocity of fluorescent microsphere movement on the apical surface of CSE exposed airway epithelial cultures, were used to assess the effect of potentiators on CFTR-mediated mucociliary movement. Results: We showed that SK-POT1, like VX-770, was effective in augmenting the cyclic AMP-dependent channel activity of CFTR. SK-POT-1 enhanced CFTR channel activity in airway epithelial cells previously exposed to CSE and ameliorated mucostasis on the surface of primary airway cultures. Conclusion: Together, this evidence supports the further development of SK-POT1 as an intervention in the treatment of COPD.

Prime editing-mediated correction of the CFTR W1282X mutation in iPSCs and derived airway epithelial cells.

A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.

First report of four rare strongylid species infecting endangered Przewalski's horses (Equus ferus przewalskii) in Xinjiang, China.

BACKGROUND: The Przewalski's horse (Equus ferus przewalskii) is the only surviving wild horse species in the world. A significant population of Przewalski's horses resides in Xinjiang, China. Parasitosis poses a considerable threat to the conservation of this endangered species. Yet, there is limited information on the nematode parasites that infect these species. To deepen our understanding of parasitic fauna affecting wild horses, we identified the intestinal nematodes of Przewalski's horses in Xinjiang and added new barcode sequences to a public database. METHODS: Between 2018 and 2021, nematodes were collected from 104 dewormed Przewalski's horses in Xinjiang. Each nematode was morphologically identified to the species level, and selected species underwent DNA extraction. The extracted DNA was used for molecular identification through the internal transcribed spacer 2 (ITS2) genetic marker. RESULTS: A total of 3758 strongylids were identified. To the best of our knowledge, this is the first study to identify four specific parasitic nematodes (Oesophagodontus robustus, Bidentostomum ivashkini, Skrjabinodentus caragandicus, Petrovinema skrjabini) and to obtain the ITS2 genetic marker for P. skrjabini. CONCLUSIONS: The ITS2 genetic marker for P. skrjabini enriches our understanding of the genetic characteristics of this species and expands the body of knowledge on parasitic nematodes. Our findings extend the known host range of four strongylid species, thereby improving our understanding of the relationship between Przewalski's horses and strongylids. This, in turn, aids in the enhanced conservation of this endangered species. This study introduces new instances of parasitic infections in wild animals and offers the DNA sequence of P. skrjabini as a valuable resource for molecular techniques in nematode diagnosis among wildlife.

SIS-Based Electrostatic Spinning High-Safety Lithium-Ion Battery Separators.

As an important component, the properties of separators directly affect the capacity, life, and safety performance of lithium-ion batteries (LIBs). The high thermal stability and safety application value of the thermoplastic elastomer poly(styrene-b-isoprene-b-styrene) block copolymer (SIS) with different block ratios were explored to enhance the thermal stability and mechanical strength of the cross-linked polyacrylonitrile (PAN) membranes by vulcanization cross-linking and heat treatment. Among these membranes, the sample named the S/PAN/SIS-4019 separator was confirmed to be a self-closing separator that can cope with the thermal runaway, attributing to the continued fusion of the SIS soft and hard segments in the cross-linked structure under high-temperature heat treatment. Moreover, the tensile strength of S/PAN/SIS-4019 separator increased to 17.49 MPa, which was better than that of Celgard 2400, PAN, and other inlay separators. Using S/PAN/SIS-4019 as a battery separator, lithium-ion batteries showed a superior electrochemical performance compared to the usage of Celgard 2400. Owing to the stable pore structure and thermally protected self-shutdown mechanism, the overall properties of the obtained cross-linked separator were improved in terms of higher thermal stability, high ionic conductivity, and electrochemical properties.

Icariin as a potential anticancer agent: a review of its biological effects on various cancers.

Numerous chemical compounds used in cancer treatment have been isolated from natural herbs to address the ever-increasing cancer incidence worldwide. Therein is icariin, which has been extensively studied for its therapeutic potential due to its anti-inflammatory, antioxidant, antidepressant, and aphrodisiac properties. However, there is a lack of comprehensive and detailed review of studies on icariin in cancer treatment. Given this, this study reviews and examines the relevant literature on the chemopreventive and therapeutic potentials of icariin in cancer treatment and describes its mechanism of action. The review shows that icariin has the property of inhibiting cancer progression and reversing drug resistance. Therefore, icariin may be a valuable potential agent for the prevention and treatment of various cancers due to its natural origin, safety, and low cost compared to conventional anticancer drugs, while further research on this natural agent is needed.

Migration and transformation of Cd in four crop rotation systems and their potential for remediation of Cd-contaminated farmland in southern China.

A crop rotation system combining agricultural production with phytoremediation is an economical and sustainable method of remediation of cadmium (Cd)-contaminated farmland. This study focuses on migration and transformation of Cd in rotation systems and the influencing factors. In a two-year field experiment, four rotation systems were evaluated: traditional rice and oilseed rape (TRO), low-Cd rice and oilseed rape (LRO), maize and oilseed rape (MO), and soybean and oilseed rape (SO). Oilseed rape is a remediation plant in rotation systems. Compared to 2020, the grain Cd concentrations of traditional rice, low-Cd rice, and maize in 2021 decreased by 73.8%, 65.7%, and 24.0% (below the safety limits), respectively. However, soybean increased by 71.4%. The LRO system featured the highest oil content of rapeseed (about 50%) and economic output/input ratio (1.34). Removal efficiency of total Cd in soil was 10.03% (TRO) > 8.3% (LRO) > 5.32% (SO) > 3.21% (MO). Crop uptake of Cd was influenced by bioavailability of soil Cd, and soil environmental factors regulated the bioavailable Cd. Redundancy analysis (RDA) indicated that soil nitrate­nitrogen (NO3--N) had a dominant impact on bioavailable Cd in soil, with variance contributions of 56.7% for paddy-upland (TRO and LRO) and 53.5% for dryland (MO and SO) rotation systems. The difference reflected that ammonium N (NH4+-N) was a secondary factor in paddy-upland rotations, while it was the available phosphorus (P) in dryland rotations, with variance contributions of 10.4% and 24.3%, respectively. The comprehensive evaluation of crop safety, production, economic benefits, and remediation efficiency revealed that the LRO system was efficient and more acceptable to local farmers, providing a new direction for the utilization and remediation of Cd-contaminated farmland.

Four cases of reported adverse effects from black boletoi, Anthracoporus nigropurpureus (Boletaceae) mushroom ingestion.

In southwestern China, wild boletes are generally considered as safe and tasty edible mushrooms. However, in fact, significant adverse effects after ingestion of boletes is commonly reported in this region. In June 2022, four cases occurred in central and southwestern of China. In these case series, five adults and one child ingested wild boletoi mushrooms known locally as "Yanyoujun" (). This study carried out a detailed epidemiological investigation and mushroom identification. Based on morphological and phylogenetic analysis, the suspected mushrooms were identified as Anthracoporus nigropurpureus (Boletaceae). All five adult victims reported dizziness and blurred vision. Some of them also reported different symptoms, such as muscle weakness, red eyes, headache, muscle cramps, even tremors in the extremities. Reportedly, the symptoms began to subside about 4 to 8 h after ingestion. Among six victims, the child was asymptomatic possibly because a small amount of mushroom was ingested. This possible poisoning appears to be a self-limited illness with a short latency and a relatively short duration. Unfortunately, laboratory investigations of the victims were not performed. Further observations and formal medical examination of victims are required in the future. It is the first detailed report of possible poisoning the genus Anthracoporus.

Histological Analysis of Regenerative Properties in Human Glenoid Labral Regions.

BACKGROUND: The healing capacity of the human glenoid labrum varies by tear location. Current evidence suggests that the healing capacity of meniscal and cartilage injuries relates to cellular composition and vascularity. However, little is known about the histological characteristics of the glenoid labrum and how they may affect healing potential in specific anatomic regions. HYPOTHESIS: Regenerative characteristics of the glenoid labrum differ based on the anatomic region. STUDY DESIGN: Descriptive laboratory study. METHODS: Human glenoid labra from fresh unpreserved cadavers were transversely sectioned in different anatomic regions. Masson trichrome stain was used to determine dense and loose extracellular matrix regions and vessel densities. Hematoxylin and eosin, Ki-67+, and CD90+/CD105+ stains were performed to determine total, proliferative, and progenitor cell densities, respectively. Regression models demonstrated relationships between vascular area, progenitor cell quantity, and probability of successful operation. RESULTS: Among all labral aspects, the superior glenoid labrum had the highest percentage (56.8% ± 6.9%) of dense extracellular matrix or avascular tissue (P < .1). The vascular region of the superior labrum had the fewest total cells (321 ± 135 cells/mm2; P < .01) and progenitor cells (20 ± 4 cells/mm2; P < .001). Vascular area was directly correlated with progenitor cell quantity (P = .006002). An increase in probability of successful operation was associated with a linear increase in vascular area (R2 = 0.765) and an exponential increase in progenitor cell quantity (R2 = 0.795). Subsequently, quadratic models of vascularity and progenitor cell quantity around the labral clock were used to assess relative healing potential. Quadratic models for percentage vascular area (P = 6.35e-07) and weighted progenitor cell density (P = 3.03e-05) around the labral clock showed that percentage vascular area and progenitor cell quantity increased as labral tissue neared the inferior aspect and diminished near the superior aspect. CONCLUSION: Anatomic regions of the glenoid labrum differ in extracellular matrix composition, vascularity, and cell composition. The superior glenoid labrum is deficient in vascularity and progenitor cells, which may explain the high failure rates for repairs in this location. CLINICAL RELEVANCE: Improved understanding of the composition of distinct glenoid labral positions may help to improve therapeutic strategies for labral pathology.

The synthetic aminoglycoside ELX-02 induces readthrough of G550X-CFTR producing superfunctional protein that can be further enhanced by CFTR modulators.

Ten percent of cystic fibrosis (CF) patients carry a premature termination codon (PTC); no mutation-specific therapies exist for these individuals. ELX-02, a synthetic aminoglycoside, suppresses translation termination at PTCs (i.e., readthrough) by promoting the insertion of an amino acid at the PTC and restoring expression of full-length CFTR protein. The identity of amino acids inserted at PTCs affects the processing and function of the resulting full-length CFTR protein. We examined readthrough of the rare G550X-CFTR nonsense mutation due to its unique properties. We found that forskolin-induced swelling in G550X patient-derived intestinal organoids (PDOs) was significantly higher than in G542X PDOs (both UGA PTCs) with ELX-02 treatment, indicating greater CFTR function from the G550X allele. Using mass spectrometry, we identified tryptophan as the sole amino acid inserted in the G550X position during ELX-02- or G418-mediated readthrough, which differs from the three amino acids (cysteine, arginine, and tryptophan) inserted in the G542X position after treatment with G418. Compared with wild-type CFTR, Fischer rat thyroid (FRT) cells expressing the G550W-CFTR variant protein exhibited significantly increased forskolin-activated Cl- conductance, and G550W-CFTR channels showed increased PKA sensitivity and open probability. After treatment with ELX-02 and CFTR correctors, CFTR function rescued from the G550X allele in FRTs reached 20-40% of the wild-type level. These results suggest that readthrough of G550X produces greater CFTR function because of gain-of-function properties of the CFTR readthrough product that stem from its location in the signature LSGGQ motif found in ATP-binding cassette (ABC) transporters. G550X may be a particularly sensitive target for translational readthrough therapy.NEW & NOTEWORTHY We found that forskolin-induced swelling in G550X-CFTR patient-derived intestinal organoids (PDOs) was significantly higher than in G542X-CFTR PDOs after treatment with ELX-02. Tryptophan (W) was the sole amino acid inserted in the G550X position after readthrough. Resulting G550W-CFTR protein exhibited supernormal CFTR activity, PKA sensitivity, and open probability. These results show that aminoglycoside-induced readthrough of G550X produces greater CFTR function because of the gain-of-function properties of the CFTR readthrough product.

Mucociliary Clearance Augmenting Drugs Block SARS-Cov-2 Replication in Human Airway Epithelial Cells.

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve barrier function of the airway epithelium, reduce viral replication and, ultimately, COVID-19 outcomes. We tested five agents known to increase MCT through distinct mechanisms for activity against SARS-CoV-2 infection using a model of human respiratory epithelial cells terminally differentiated in an air/liquid interphase. Three of the five mucoactive compounds tested showed significant inhibitory activity against SARS-CoV-2 replication. An archetype mucoactive agent, ARINA-1, blocked viral replication and therefore epithelial cell injury, thus, it was further studied using biochemical, genetic and biophysical methods to ascertain mechanism of action via improvement of MCT. ARINA-1 antiviral activity was dependent on enhancing the MCT cellular response, since terminal differentiation, intact ciliary expression and motion was required for ARINA-1-mediated anti-SARS-CoV2 protection. Ultimately, we showed that improvement of cilia movement was caused by ARINA-1-mediated regulation of the redox state of the intracellular environment, which benefited MCT. Our study indicates that Intact MCT reduces SARS-CoV-2 infection, and its pharmacologic activation may be effective as an anti-COVID-19 treatment.

Application of metagenomic next-generation sequencing in the diagnosis of urinary tract infection in patients undergoing cutaneous ureterostomy.

Objective: Urinary tract infection (UTI) is an inflammatory response of the urothelium to bacterial invasion and is a common complication in patients with cutaneous ureterostomy (CU). For such patients, accurate and efficient identification of pathogens remains a challenge. The aim of this study included exploring utility of metagenomic next-generation sequencing (mNGS) in assisting microbiological diagnosis of UTI among patients undergoing CU, identifying promising cytokine or microorganism biomarkers, revealing microbiome diversity change and compare virulence factors (VFs) and antibiotic resistance genes (ARGs) after infection. Methods: We performed a case-control study of 50 consecutive CU patients from December 2020 to January 2021. According to the clinical diagnostic criteria, samples were divided into infected group and uninfected group and difference of urine culture, cytokines, microorganism, ARGs and VFs were compared between the two groups. Results: Inflammatory responses were more serious in infected group, as evidenced by a significant increase in IFN-α (p=0.031), IL-1ß (0.023) and IL-6 (p=0.018). Clinical culture shows that there is higher positive rate in infected group for most clinical pathogens like Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Candida auris etc. and the top three pathogens with positive frequencies were E. coli, K. pneumoniae, and Enterococcus faecalis. Benchmarking clinical culture, the total sensitivity is 91.4% and specificity is 76.3% for mNGS. As for mNGS, there was no significant difference in microbiome α- diversity between infected and uninfected group. Three species biomarkers including Citrobacter freundii, Klebsiella oxytoca, and Enterobacter cloacae are enriched in infected group based on Lefse. E. cloacae were significantly correlated with IL-6 and IL-10. K. oxytoca were significantly correlated with IL-1ß. Besides, the unweighted gene number and weighted gene abundance of VFs or ARGs are significantly higher in infected group. Notablely, ARGs belonging to fluoroquinolones, betalatmas, fosfomycin, phenicol, phenolic compound abundance is significantly higher in infected group which may have bad effect on clinical treatment for patients. Conclusion: mNGS, along with urine culture, will provide comprehensive and efficient reference for the diagnosis of UTI in patients with CU and allow us to monitor microbial changes in urine of these patients. Moreover, cytokines (IL-6, IL-1ß, and IFN-a) or microorganisms like C. freundii, K. oxytoca or E. cloacae are promising biomarkers for building effective UTI diagnostic model of patients with CU and seriously the VFs and ARGs abundance increase in infected group may play bad effect on clinical treatment.

Transcriptome analyses reveal the effects of mixed saline-alkali stress on indoleacetic acid and cytokinins in Malus hupehensis Rehd. leaves.

Saline-alkali stress is a universal abiotic stress factor limiting fruit tree cultivation worldwide. Apple (Malus×domestica Borkh.) is one of the fruits with the largest yields worldwide. Tea crabapple (Malus hupehensis Rehd. var. pingyiensis Jiang) is a type of common apple rootstock in China. Because facultative apomixis occurs in this species, it is often used in molecular research. The present study investigated the molecular mechanism of the response of indoleacetic acid (IAA) and cytokinins [zeatin, trans-zeatin riboside (tZR), isopentenyladenine (iP), and isopentenyladenosine (iPA)] to mixed saline-alkali stress (MSAS) in tea crabapple leaves. The endogenous hormone content of tea crabapple leaves under MSAS was measured, and the expression of stress response-related genes was analyzed by RNA sequencing. The results showed that the concentration of IAA was initially higher and then lower than that in the control, whereas the concentration of zeatin, tZR, iP, and iPA was higher than that in the control. A total of 1262 differentially expressed genes were identified in the three comparison groups. Further analyses suggested that IAA and cytokinin biosynthetic genes were mostly upregulated in tea crabapple leaves, indicating that auxin and cytokinin signaling pathway regulation occurred in response to MSAS. These findings suggest that IAA and cytokinins play an important role in the response of tea crabapple to MSAS. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01275-4.

Mucociliary clearance augmenting drugs block SARS-CoV-2 replication in human airway epithelial cells.

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve the barrier function of the airway epithelium and reduce viral replication and, ultimately, COVID-19 outcomes. We tested five agents known to increase MCT through distinct mechanisms for activity against SARS-CoV-2 infection using a model of human respiratory epithelial cells terminally differentiated in an air/liquid interphase. Three of the five mucoactive compounds tested showed significant inhibitory activity against SARS-CoV-2 replication. An archetype mucoactive agent, ARINA-1, blocked viral replication and therefore epithelial cell injury; thus, it was further studied using biochemical, genetic, and biophysical methods to ascertain the mechanism of action via the improvement of MCT. ARINA-1 antiviral activity was dependent on enhancing the MCT cellular response, since terminal differentiation, intact ciliary expression, and motion were required for ARINA-1-mediated anti-SARS-CoV2 protection. Ultimately, we showed that the improvement of cilia movement was caused by ARINA-1-mediated regulation of the redox state of the intracellular environment, which benefited MCT. Our study indicates that intact MCT reduces SARS-CoV-2 infection, and its pharmacologic activation may be effective as an anti-COVID-19 treatment.

Gut microbial community structure and function of Przewalski's horses varied across reintroduced sites in China.

Host-associated microbiota can significantly impact host fitness. Therefore, naturally occurring variations in microbiota may influence the health and persistence of their hosts. This finding is particularly important in reintroduced animals, as they typically experience habitat changes during translocations. However, little is known about how microbiomes are altered in response to conservation translocation. Here, we accessed the gut microbiome of Przewalski's horse (Equus przewalskii) populations in China from three nature reserves (i.e. Xinjiang Kalamaili Nature Reserve, KNR; Dunhuang Xihu National Nature Reserve, DXNNR; and Anxi Extreme-arid Desert Nature Reserve, AENR) using 16s rRNA gene and metagenome sequencing. The results showed that the microbial composition and function differed significantly across locations, while a subset of core taxa was consistently present in most of the samples. The abundance of genes encoding microbe-produced enzymes involved in the metabolism of carbohydrates, especially for glycoside hydrolases, was significantly higher in open-spaced KNR populations than in more confined AENR individuals. This study offers detailed and significant differential characters related to the microbial community and metabolic pathways in various reintroduced sites of Przewalski's horse, which might provide a basis for future microecological and conservation research on endangered reintroduced animals.

Biomolecule-releasing bioadhesive for glenoid labrum repair through induced host progenitor cell responses.

Glenoid labral tears occur with repetitive dislocation events and are common injuries observed in shoulder arthroscopic procedures. Although surgery can restore shoulder anatomy, repair is associated with poor clinical outcomes, which may be attributed to the poor regenerative capability of glenoid labral fibrocartilage. Thus, this study was designed to assess whether in situ tissue regeneration via biomolecule-stimulated recruitment of progenitor cells is a viable approach for the regeneration of labral tears. We developed a click chemistry-based bioadhesive to improve labral repair and reduce local inflammatory responses due to trauma. Additionally, we previously identified the presence of progenitor cells in the human labrum, which can be recruited by platelet-derived growth factor (PDGF). Thus, we hypothesized that PDGF-releasing adhesives could induce the regenerative responses of progenitor cells at the injury site to improve labral healing. In a rat glenoid labral tear model, we evaluated the effect of PDGF-releasing adhesives on promoting progenitor cells to participate in labral tear healing. After 3 and 6 weeks, the labrum was histologically analyzed for inflammatory responses, progenitor cell recruitment, proliferation, and extracellular matrix (ECM) production (collagen and glycosaminoglycan). Our results showed that adhesives alone considerably reduced local inflammatory responses and labral tissue dissolution. PDGF-releasing adhesives significantly increased progenitor cell recruitment, proliferation, and ECM production. These results demonstrate that by accelerating autologous progenitor cell responses, PDGF-releasing adhesives represent a novel clinically relevant strategy to improve the healing of glenoid labral tears.

A time-dependent survival analysis for early prognosis of chronic wounds by monitoring wound alkalinity.

The objective is to determine whether monitoring wound alkalinity between visits may help prognosticate chronic wound healing. The alkalinity of 167 wounds during the first 3 visits was assessed using disposable DETEC® pH. Wounds grouped by frequency of alkaline results were compared by % wound size reduction during each visit and 120-day healing probability. The Cox proportional hazards model for time-dependent variables was used to generate non-healing probability curves, where variables are binary (alkaline/non-alkaline, infection/no infection), categorical (wound type), and continuous (wound area); the response is time to complete wound healing; and the event of interest is complete wound healing in 120 days. Results show that wounds with frequent alkaline results have significantly smaller % size reduction per visit. Logistic regression shows an increase in 120-day healing probability with fewer alkaline results. Survival analysis shows that the instantaneous healing rate of non-alkaline or non-alkaline transitioning wounds is 1.785, 2.925, and 5.908 times that of alkaline or alkaline-transitioning wounds for 1, 2, and 3 alkalinity measurements, respectively. Furthermore, the concordance statistic of each survival model shows that goodness of fit increases with more alkalinity measurements. Overall, frequent wound alkalinity assessments may serve as a novel way to prognosticate wound healing outcomes.

A wound alkalinity measurement to predict non-healing wound outcomes.

OBJECTIVE: As wound pH could influence wound healing rates, this study examined the alkalinity of the entire wound during patients' follow-up visits to predict the final non-healing outcome. METHOD: Wound alkalinity of patients with diabetic foot ulcers (DFUs), venous leg ulcers, and other wounds during three follow-up visits within a four week period was recorded. All wounds were followed until 12 weeks to confirm that healed wounds did not relapse. The alkalinity of various wounds over multiple visits with varying durations was compared with final wound status to assess whether one-time wound alkalinity measurement could predict non-healing wounds. The effect of wound types, infection, age and sex on such determinations was also studied. RESULTS: A total of 96 patients were included in this study. Based on probability variations of pre- and post-test non-healing outcomes from multiple visits over 12 weeks, second visit assessment gave the highest increase in risk of non-healing for an alkaline test result (+8.0%) and decrease in risk of non-healing for a non-alkaline test result (-19.7%). Moreover, a second visit (7-21 days from first visit) showed a greater change in risk for non-healing based on alkaline and non-alkaline test results (+15.7% and -38.1% respectively), compared with a visit within seven days (+6.3% and -12.5%, respectively). Wound type, infection, age and sex did not affect the prognostic ability of wound alkalinity. CONCLUSION: The results of this study support that a single wound alkalinity measurement during the second visit (7-21 days from first visit) can be used to predict non-healing wounds. Wound alkalinity may be routinely assessed to predict non-healing wounds and to determine whether the wounds are healing as expected following initial treatment.

A deep eutectic solvent magnetic molecularly imprinted polymer for extraction of laminarin from seaweeds.

Magnetic molecular imprinted polymers (MIPs) based on 4-vinylbenzyltrimethylammonium chloride (VBTAC) and 4-vinylbenzoic acid (VBA) deep eutectic solvent as dual functional monomers was successfully synthesized for the specific recognition of laminarin. The MIPs were characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, thermal gravimetric analysis, and vibrating sample magnetometer analysis. The results showed that the MIPs were spheres of a uniform size, with the surface rich in cavities and excellent superparamagnetism properties. The adsorption experiments showed that MIPs conform to pseudo-second-order kinetics and Langmuir isotherm adsorption. The maximum adsorption capacity under optimal conditions was 322.58 µg·mg-1 and the imprinting factor was 2.13. Under the optimized conditions, the limit of detection (LOD) of the developed material was 6.6 µM. Linearity of the material was obtained within the range 20-800 µM with a coefficient of determination (r2) being better 0.999. Relative standard deviations (RSDs) were less than 3.96%, and satisfactory recoveries were between 94.55 and 97.39%. The actual sample analysis manifested that MIPs could effectively separate laminarin from Laminarin japonica Aiesch.

Clinical value and application of a novel nomogram containing inflammatory, nutritional and clinical markers in predicting overall survival of stage II/III gastric cancer patients after radical resection: a bi-centered retrospective study of 2,443 patients.

OBJECTIVES: We aimed to identify nutritional, inflammatory and clinical indicators associated with stage II/III gastric cancer in patients, and construct a nomogram model for accurate prediction of prognosis of patients. METHODS: We retrospectively recruited stage II/III gastric cancer (GC) patients who underwent radical gastrectomy at Fudan University Shanghai Cancer Center, from 2012 to 2019. The patients were randomly divided into training and internal validation sets, and then the Maximum log-rank statistic method was used to determine the optimal cut-off value. Next, we performed univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival (OS). These were subsequently used to develop a nomogram model. We validated this model in patients with stage II/III gastric cancer (from 2010 to 2019) at Guangxi Medical University Affiliated Tumor Hospital. RESULTS: A total of 2,443 patients met our inclusion criteria and were therefore included in our study. Patients from Fudan University Shanghai Cancer Center were randomly divided into training (n=1725) and internal validation (n=430) sets, while those from Guangxi Medical University Affiliated Tumor Hospital were used as the external validation set (n=288). Results from univariate and multivariate Cox regression analyses revealed that age (adjusted HR, 1.23; 95% CI, 1.05-1.44; P=0.012), TNM stage (adjusted HR, 3.62; 95% CI, 2.79-4.68; P<0.001), CEA (adjusted HR, 1.40; 95% CI, 1.14-1.71; P<0.001), CA199 (adjusted HR, 1.47; 95% CI, 1.21-1.79; P<0.001), and Prognostic Nutritional Index (PNI, adjusted HR, 0.81; 95% CI, 0.67-0.98; P=0.026) were independent prognostic factors for OS in the training set. The established nomogram model, with a C-index of 0.67, had 3- and 5-year Area under Curve (AUC) values of 0.719 and 0.714, respectively. Notably, the model effectively distinguished patients' OS in both the internal (P<0.001) and external (P<0.001) datasets. CONCLUSIONS: PNI is an independent prognostic factor for stage II/III GC patients after radical resection. The established novel nomogram model, based on nutritional, inflammatory and clinical indicators, can accurately and efficiently predict prognosis of stage II/III GC patients.

A Contribution to Knowledge of Craterellus (Hydnaceae, Cantharellales) in China: Three New Taxa and Amended Descriptions of Two Previous Species.

Species of Craterellus (Hydnaceae, Cantharellales) in China are investigated on the basis of morphological and molecular phylogenetic analyses of DNA sequences from nuc 28S rDNA D1-D2 domains (28S) and nuc rDNA internal transcribed spacer ITS1-5.8S-ITS2 region. Five species are recognized in China, of which three of them are described as new, viz. C. fulviceps, C. minor, and C. parvopullus, while two of them are previously described taxa, viz. C. aureus, and C. lutescens. A key to the known Chinese taxa of the genus is also provided.