Signal amplification in molecular sensing by imprinted polymers.

In the field of sensing, the development of sensors with high sensitivity, accuracy, selectivity, sustainability, simplicity, and low cost remains a key focus. Over the past decades, optical and electrochemical sensors based on molecular imprinting techniques have garnered significant attention due to the above advantages. Molecular imprinting technology utilizes molecularly imprinted polymers (MIPs) to mimic the specific recognition capabilities of enzymes or antibodies for target molecules. Recently, MIP-based sensors rooting in signal amplification techniques have been employed to enhance molecular detection level and the quantitative ability for environmental pollutants, biomolecules, therapeutic compounds, bacteria, and viruses. The signal amplification techniques involved in MIP-based sensors mainly cover nucleic acid chain amplification, enzyme-catalyzed cascade, introduction of high-performance nanomaterials, and rapid chemical reactions. The amplified analytical signals are centered around electrochemical, fluorescence, colorimetric, and surface-enhanced Raman techniques, which can effectively realize the determination of some low-abundance targets in biological samples. This review highlights the recent advancements of electrochemical/optical sensors based on molecular imprinting integrated with various signal amplification strategies and their dedication to the study of trace biomolecules. Finally, future research directions on developing multidimensional output signals of MIP-based sensors and introducing multiple signal amplification strategies are proposed.

Fluorescent/colorimetric probe for the detection of Cr(â ¥) based on MIL-101(Fe)-NH2 with peroxidase-like activity.

In the present research, Fe-based metal-organic frameworks (MIL-101(Fe)-NH2) nanoparticles were synthesized by simple solvothermal methods and used to assay Cr(Ⅵ). The MIL-101(Fe)-NH2 performs dual functions: the 2-aminoterephthalic acid (NH2-BDC) ligand endows a strong fluorescence emission, and the Fe metal nodes are able to facilitate the oxidation of 3,3',5,5'- tetramethylbenzidine (TMB) directly, resulting in the generation of oxidized-TMB (ox-TMB). Our research results showed that reducing agents such as ascorbic acid (AA) can collapse the structures of MIL-101(Fe)-NH2 because of the reduction of Fe3+ by AA, resulting in release of NH2-BDC. In the presence of Cr(Ⅵ), the fluorescence intensity of the MIL-101(Fe)-NH2 + AA system will be decreased due to the competitive reduction of Fe3+ and Cr(Ⅵ). Nevertheless, Cr(Ⅵ) can significantly accelerate the oxidation of TMB by MIL-101(Fe)-NH2 as it boosts the electron transfer rate between Fe3+ and Fe2+. Therefore, a fluorescent/colorimetric dual-mode platform was developed for the detection of Cr(Ⅵ) with an extensive linear range (7.5-750 µg/L and 13.3-1000 µg/L) as well as a remarkably low detection limit (0.99 µg/L and 1.98 µg/L). This MOF with the ability to release ligands not only provides inspiration for the design of new luminescent materials, but also offers a novel and reliable solution for the detection of Cr(Ⅵ).

Migration of naphthalene in a biochar-amended bioretention facility based on HYDRUS-1D analysis.

Biochar has been proved as a promising and efficient filler in bioretention facilities for enhancing the stormwater pollutants removal. However, the migration behaviors of stormwater pollutants in biochar filled bioretention facilities is unclear. In this study, as one of the most typical stormwater pollutants, naphthalene was selected as an example and a HYDRUS-1D model was first used to understand the migration behavior of naphthalene in a bioretention facility. In comparison with the conventional bioretention soil media (sandy loam), the amended biochar filled bioretention cell showed that the naphthalene removal rate was enhanced by up to 10.1%. Meanwhile, the experimental data was well-fitted by the "two-site sorption model" in HYDRUS-1D model. Another, the effect of rainfall intensity on the naphthalene migration in both bioretention columns was further investigated. The HYDRUS-1D model fitting indicated that the increase in rainfall intensity promoted naphthalene migration by increasing hydraulic conductivity and water flux. In addition, static batch experiments revealed that the biochar filled fillers achieved about 50% higher adsorption capacity than sandy loam. The sensitivity analysis from the HYDRUS-1D model data verified adsorption coefficient Kd and longitudinal dispersivity λ are the main factors affecting naphthalene migration. Finally, the model simulation displays that the proportion of naphthalene retained by the fillers was highest during high rainfall intensities, indicating that the fillers remain the most important fate for naphthalene. This study presents research on the behavior and mechanisms of stormwater pollutant transport through improved bioretention facilities.

Randomized trial of influence of vitamin D on the prevention and improvement of symptomatic COVID-19.

We aimed to investigate the preventive effect of vitamin D2 on COVID-19 and the improvement of symptoms after COVID-19 infection. The study recruited 228 health care workers who tested negative PCR or antigen for COVID-19. Subjects were randomly allocated to vitamin D2 or non-intervention at a ratio 1:1. Subjects recorded PCR or antigen tests and the symptoms of COVID-19 twice a week during the follow-up visit. The concentration of serum 25-hydroxyvitamin D (25(OH)D), C-reaction protein (CRP), complement component C1q and inflammatory cytokines were measured. The rates of COVID-19 infection were 50.5% in the vitamin D2 group and 52.4% in the non-intervention group (P = 0.785). There was no difference in the COVID-19 symptoms between the two groups. The mean 25(OH)D level significantly increased from 14.1 to 31.1 ng/mL after administration (P < 0.001). The difference between the two groups was not significant for the concentrations of CRP, C1q and inflammatory cytokines on the thirtieth day of the trial. According to the second level of vitamin D, there was a 14.3% difference in positive infection rates between the vitamin D adequate (> 30 ng/mL) and deficient groups (< 20 ng/mL). Adequate vitamin D had a tendency to prevent COVID-19.Trial registration: ClinicalTrials.gov NCT05673980, dated: 12/2022.

Characterization, enrichment, and computational modeling of cross-linked actin networks in trabecular meshwork cells.

Purpose: Cross-linked actin networks (CLANs) are prevalent in the glaucomatous trabecular meshwork (TM), yet their role in ocular hypertension remains unclear. We used a human TM cell line that spontaneously forms fluorescently-labeled CLANs (GTM3L) to explore the origin of CLANs, developed techniques to increase CLAN incidence in GMT3L cells, and computationally studied the biomechanical properties of CLAN-containing cells. Methods: GTM3L cells were fluorescently sorted for viral copy number analysis. CLAN incidence was increased by (i) differential sorting of cells by adhesion, (ii) cell deswelling, and (iii) cell selection based on cell stiffness. GTM3L cells were also cultured on glass or soft hydrogel to determine substrate stiffness effects on CLAN incidence. Computational models were constructed to mimic and study the biomechanical properties of CLANs. Results: All GTM3L cells had an average of 1 viral copy per cell. LifeAct-GFP expression level did not affect CLAN incidence rate, but CLAN rate was increased from ∼0.28% to ∼50% by a combination of adhesion selection, cell deswelling, and cell stiffness-based sorting. Further, GTM3L cells formed more CLANs on a stiff vs. a soft substrate. Computational modeling predicted that CLANs contribute to higher cell stiffness, including increased resistance of the nucleus to tensile stress when CLANs are physically linked to the nucleus. Conclusions: It is possible to greatly enhance CLAN incidence in GTM3L cells. CLANs are mechanosensitive structures that affect cell biomechanical properties. Further research is needed to determine the effect of CLANs on TM biomechanics and mechanobiology as well as the etiology of CLAN formation in the TM.

Contributions of individual qSOFA elements to assessment of severity and for prediction of mortality.

BACKGROUND: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.

Respiratory rate ≥22/min demonstrated the most superior diagnostic value.Respiratory rate ≥22/min showed the strongest association with severity.Respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg predicted mortality well, adequately and poorly, respectively.

Light-Controlled Regulation of Dual-Enzyme Properties in YbGd-Carbon Quantum Dots Nano-Hybrid for Advanced Biosensing.

Compared to nanozymes with single enzyme activity, those with multiple enzyme activities possess broader application potential due to their diversified enzymatic functionalities. However, the multienzyme nanozymes currently face challenges of interference among different enzymatic activities during practical applications. In this study, we report the synthesis of a light-responsive YbGd-carbon quantum dots nano-hybrid, termed YbGd-CDs, which exhibits controllable enzyme-mimicking activities. This light-responsive behavior enables selective control of the enzymatic activities. Under visible light irradiation, YbGd-CDs demonstrate robust oxidase-like activity. Conversely, under dark conditions, they primarily exhibit peroxidase-like activity. Leveraging the dual-enzyme-mimicking capabilities of YbGd-CDs, we developed colorimetric assays for sensitive detection of total antioxidant capacity (TAC) in both normal and cancer cells as well as d-amino acids in human saliva. This study not only advances the synthesis of carbon-based nanozymes but also highlights their potential in biosensing applications.

Seed endophytes and rhizosphere microbiome of Imperata cylindrica, a pioneer plant of abandoned mine lands.

Some plant-associated microorganisms could improve host plants biotic and abiotic stress tolerance. Imperata cylindrica is a dominant pioneer plant in some abandoned mine lands with higher concentrations of heavy metal (HM). To discover the specific microbiome of I. cylindrica in this extreme environment and evaluate its role, the microbiome of I. cylindrica's seeds and rhizosphere soils from HM heavily contaminated (H) and lightly contaminated (L) sites were studied. It was found that HM-contamination significantly reduced the richness of endophytic bacteria in seeds, but increased the abundance of resistant species, such as Massilia sp. and Duganella sp. Spearman's rank correlation coefficient analysis showed that both Massilia sp. and Duganella sp. showed a significant positive correlation with Zn concentration, indicating that it may have a strong tolerance to Zn. A comparison of the microbiome of rhizosphere soils (RS) and adjacent bare soils (BS) of site H showed that I. cylindrica colonization significantly increased the diversity of fungi in rhizosphere soil and the abundance of Ascomycota associated with soil nutrient cycling. Spearman's rank correlation coefficient analysis showed that Ascomycota was positively correlated with the total nitrogen. Combined with the fact that the total nitrogen content of RS was significantly higher than that of BS, we suppose that Ascomycota may enhance the nitrogen fixation of I. cylindrica, thereby promoting its growth in such an extreme environment. In conclusion, the concentration of HM and nutrient contents in the soil significantly affected the microbial community of rhizosphere soils and seeds of I. cylindrica, in turn, the different microbiomes further affected soil HM concentration and nutrient contents. The survival of I. cylindrica in HM severely contaminated environment may mainly be through recruiting more microorganisms that can enhance its nutrition supply.

Glucose activated synergistic cascade therapy of diabetic wound by platinum and glucose oxidase decorated camelina lipid droplets.

Hyperglycemia provides a favorable breeding ground for bacteria, resulting in repeated and persistent inflammation of wounds and prolonged healing processes. In this study, platinum (Pt) nanoparticles (NPs) and glucose oxidase (GOx) were decorated on the surface of camelina lipid droplets (OB) linked with hFGF2, forming PGOB through in situ reduction of Pt ions and electrostatic adsorption, respectively. PGOB exhibits cascade enzyme catalytic activity, which can be activated by glucose in diabetic wound tissues. Specifically, GOx on PGOB catalyzes glucose into hydrogen peroxide, which can further decompose into hydroxyl radicals that have higher toxicity for bacterial inactivation. Additionally, glucose decomposition creates a low pH microenvironment, facilitating the cascade catalytic activity that ensures better bacterial suppression within the wound tissues. Furthermore, hFGF2 promotes the proliferation and migration of fibroblasts. Both in vitro and in vivo experiments confirm that PGOB effectively accelerates wound healing processes through bacteria inactivation and tissue regeneration. This study has developed an alternative strategy for glucose-triggered synergistic cascade therapy for diabetic wounds.

Circadian Rhythm-Regulated ADSC-Derived sEVs and a Triphasic Microneedle Delivery System to Enhance Tendon-to-Bone Healing.

Modulating the inflammatory microenvironment to reconstruct the fibrocartilaginous layer while promoting tendon repair is crucial for enhancing tendon-to-bone healing in rotator cuff repair (RCR), a persistent challenge in orthopedics. Small extracellular vesicles (sEVs) hold significant potential to modulate inflammation, yet the efficient production of highly bioactive sEVs remains a substantial barrier to their clinical application. Moreover, achieving minimally invasive local delivery of sEVs to the tendon-to-bone interface presents significant technical difficulties. Herein, the circadian rhythm of adipose-derived stem cells is modulated to increase the yield and enhance the inflammatory regulatory capacity of sEVs. Circadian rhythm-regulated sEVs (CR-sEVs) enhance the cyclic adenosine monophosphate signaling pathway in macrophage (Mφ) via platelet factor 4 delivery, thereby inhibiting Mφ M1 polarization. Subsequently, a triphasic microneedle (MN) scaffold with a tip, stem, and base is designed for the local delivery of CR-sEVs (CR-sEVs/MN) at the tendon-to-bone junction, incorporating tendon-derived decellularized extracellular matrix in the base to facilitate tendon repair. CR-sEVs/MN mitigates inflammation, promotes fibrocartilage regeneration, and enhances tendon healing, thereby improving biomechanical strength and shoulder joint function in a rat RCR model. Combining CR-sEVs with this triphasic microneedle delivery system presents a promising strategy for enhancing tendon-to-bone healing in clinical settings.

Analysis of histomorphology and SERNINA5 gene expression in different regions of epididymis of cattleyak.

The molecular mechanism of sterility in cattleyak is still unresolved. The related factors of infertility in cattleyak were studied by tissue section, SERPINA5 gene cloning and bioinformatics technology. Tissue sections of the epididymis showed poorly structured and disorganized epithelial cells in the corpus of the epididymis compared to the caput of the epididymis, while in the cauda part of the epididymis, the extra basal smooth muscle was thinner, the surface of the epithelial lumen was discontinuous and the epithelium was markedly degenerated. The results of gene cloning showed that the coding sequence (CDS) region of the SERPINA5 gene in cattleyak was 1215 bp in length, encoding a total of 404 amino acids, of which the isoleucine content was the highest, accounting for a total of 49 amino acids (12.1%). The results of real-time fluorescence quantitative PCR (qPCR) showed that the expression of the SERPINA5 gene in the epididymis caput in cattleyak was significantly higher than that in the corpus and cauda (P < 0.05), but there were no significant differences between the corpus and cauda. In the current study, histological and bioinformatics analysis, physicochemical properties, and the expression analysis of the SERPINA5 gene in different regions of the epididymis in cattleyak were carried out to explore the biological complications of cattleyak infertility.

Association between serum ß2-microglobulin and left ventricular hypertrophy in patients with type 2 diabetes mellitus: A cross-sectional study.

BACKGROUND: Beta 2-microglobulin (ß2-MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of ß2-MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum ß2-MG and LVH in T2DM patients. METHODS: The retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non-LVH groups based on echocardiography results. Serum ß2-MG levels were measured, and participants were categorized into four groups (Q1-Q4) by their serum ß2-MG quartile. The relationship of serum ß2-MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning. RESULTS: The prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum ß2-MG level corresponded to a 1.17-fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05-1.31); p = 0.006]. When considering ß2-MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09-1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36-2.31); p < 0.001] had a significantly higher prevalence of LVH than Q1. RCS analysis found a nonlinear association between ß2-MG and LVH prevalence (p for nonlinearity <0.05). Additionally, machine learning results confirmed the importance of ß2-MG for LVH in T2DM patients. CONCLUSION: Elevated serum ß2-MG levels were likely to be associated with an increased prevalence of LVH in T2DM patients, suggesting its potential role in LVH development.

[Research advance on the interaction between gut microbes and cytokines in inflammatory bowel disease].

Dysregulation of interaction between the gut microbiota and the host immune system leads to the development of chronic inflammation, such as inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Numerous studies have shown that the host-microbiota of IBD can directly or indirectly affect the homeostasis of the immune system. Furthermore, the balance between pro-inflammatory and anti-inflammatory cytokines involves in maintaining a healthy microbiota community and enhances epithelial barrier functions. Understanding the interactions between gut microbiota and cytokines (IL-10, IL-17, IL-18, TNF-α) provides crucial insights into the pathogenesis of inflammatory bowel disease.

Transport Pathways of Nitrate in Stormwater Runoff Inferred from High-Frequency Sampling and Stable Water Isotopes.

Storm events can mobilize nitrogen species from landscapes into streams, exacerbating eutrophication and threatening aquatic ecosystems as well as human health. However, the transport pathways and storm responses of different nitrogen forms remain elusive. We used high-frequency chemical and isotopic sampling to partition sources of stormwater runoff and determine transport pathways of multiple nitrogen forms in an agricultural catchment. Bayesian mixing modeling reveals shallow subsurface water as the dominant source of stormwater runoff, contributing 74% of the water flux and 72, 71, and 79% of total nitrogen (TN), total dissolved nitrogen (TDN), and nitrate (NO3-N), respectively. Groundwater, by contrast, contributed 11% of stormwater runoff and 21, 22, and 17% of TN, TDN, and NO3-N, respectively. The remaining 14% of stormwater runoff can be attributed to rainwater, which contains much less TN, TDN, and NO3-N. Surprisingly, during storm events, the dominant nitrogen form was NO3-N rather than dissolved organic nitrogen. Antecedent conditions and runoff characteristics have an important influence on nitrogen loads during storm events. Our results provide insight into hydrological mechanisms driving nitrogen transport during storm events and may help in developing catchment management practices for reducing nitrogen pollution in aquatic ecosystems.

The application of methylene blue location technique in deep-seated benign breast tumor resection under endoscopy: a retrospective, single-institution analysis.

Background: Endoscopic curative excision of benign breast diseases (BBDs) can preserve the cosmetic appearance of the breast. However, endoscopic surgery is not feasible, and some challenges still need to be addressed. Traditional line marker localization methods cannot visualize tumors, and the exploration of deep tumors may lead to certain risks of accidental injury. This study aimed to investigate the value of the methylene blue location (MBL) technique in endoscopic resection of deep-seated benign breast tumors. Methods: A total of 217 patients with benign deep breast tumors admitted to the Sixth Affiliated Hospital of Sun Yat-sen University between November 2017 and June 2023 met the inclusion criteria. Among them, 107 patients underwent endoscopic resection with a MBL, in which methylene blue was injected to guide the tumor resection endoscopically, whereas 110 patients underwent endoscopic resection with a skin mark location (SML), in which the tumor was located by a marking line on the skin. We compared patient characteristics, surgery-related data, complications, and cosmetic outcomes between the two groups. Results: Endoscopic breast tumor resection was successfully performed in 217 patients, none of whom had undergone open surgery. The mean operation time was significantly different between the MBL and SML groups (45.70±12.508 and 49.59±10.997 min, respectively; P=0.008<0.05), and blood loss in the MBL group was significantly reduced compared with that in the SML group (11.07±5.665 and 13.83±7.918 mL, respectively; P=0.004<0.05). There were no significant differences in drainage volume, length of hospital stay, or postoperative complications between the MBL and SML groups (P>0.05). The postoperative cosmetic outcomes of the patients were noteworthy, with no statistically significant differences between the two groups. Conclusions: The methylene blue positioning technique is safe and effective for the endoscopic treatment of deep breast tumors. It shortens operation time, reduces surgical complications, and is worthy of clinical promotion.

Palladium-Catalyzed Denitrative α-Arylation of Heteroarenes with Nitroarenes via C-H and C-NO2 Bond Activations.

A general approach for the α-arylation of heteroarenes with nitroarenes via denitrative coupling is reported for the first time. Various heteroarenes, including derivatives of furan, benzofuran, pyrrole, indole, thiophene, and benzothiophene, can be arylated at the α-position in moderate to good yields. Mechanistic studies demonstrate that the reaction proceeds via a CMD pathway, with C-H bond activation as the rate-determining step. Furthermore, the scalability and applicability in the synthesis of a drug molecule exemplify the utility of this protocol.

The value of multiparametric MRI-based habitat imaging for differentiating uterine sarcomas from atypical leiomyomas: a multicentre study.

PURPOSE: To explore the feasibility of multiparametric MRI-based habitat imaging for distinguishing uterine sarcoma (US) from atypical leiomyoma (ALM). METHODS: This retrospective study included the clinical and preoperative MRI data of 69 patients with US and 225 patients with ALM from three hospitals. At both the individual and cohort levels, the K-means and Gaussian mixture model (GMM) algorithms were utilized to perform habitat imaging on MR images, respectively. Specifically, T2-weighted images (T2WI) and contrast-enhanced T1-weighted images (CE-T1WI) were clustered to generate structural habitats, while apparent diffusion coefficient (ADC) maps and CE-T1WI were clustered to create functional habitats. Parameters of each habitat subregion were extracted to construct distinct habitat models. The integrated models were constructed by combining habitat and clinical independent predictors. Model performance was assessed using the area under the curve (AUC). RESULTS: Abnormal vaginal bleeding, lactate dehydrogenase (LDH), and white blood cell (WBC) counts can serve as clinical independent predictors of US. The GMM-based functional habitat model at the cohort level had the highest mean AUC (0.766) in both the training and validation cohorts, followed by the GMM-based structural habitat model at the cohort level (AUC = 0.760). Within the integrated models, the K-means functional habitat model based on the cohort level achieved the highest mean AUC (0.905) in both the training and validation cohorts. CONCLUSION: Habitat imaging based on multiparametric MRI has the potential to distinguish US from ALM. The combination of clinical independent predictors with the habitat models can effectively improve the performance.

No QTc prolongation with CDK 4/6 inhibitor FCN-437c: results of a concentration-QTc analysis from a dedicated study in adult healthy subjects.

Cardiotoxicity and QT interval prolongation have been a common cause of withdrawal of drugs from the market. FCN-437c is an oral, second-generation, potent, and selective CDK4/6 inhibitor for the treatment of patients with HR+/HER2- metastatic breast cancer. A single-center, double-blind, randomized, and placebo-controlled clinical study in healthy subjects was conducted to investigate the QTc prolongation potential of FCN-437c utilizing Concentration-QTc (C-QTc) modeling approach. FCN-437c was administered at doses of 300, and 400 mg with single oral administration, along with placebo, in 18 healthy subjects. Electrocardiograms (ECGs) through 24 h holter monitor and blood samples were collected. The Cmax of 400 mg single dose in healthy subjects is similar to that from therapeutic dose 200 mg QD at steady state in patients with cancer. The 90% CI upper limit of ΔΔQTcF at the Cmax geometric mean in both dose groups were <10 ms. It is concluded that FCN-437c has low risk of prolonging the QT interval at therapeutic dose. Systematic Review Registration: https://clinicaltrials.gov/study/NCT06290466?term=NCT06290466&rank=1, identifier [NCT06290466].

The Mechanisms of Cadmium Stress Mitigation by Fungal Endophytes from Maize Grains.

Maize is a crucial staple crop that ensures global food security by supplying essential nutrients. However, heavy metal (HM) contamination inhibits maize growth, reduces output, and affects food security. Some endophytic fungi (EFs) in maize seeds have the potential to enhance growth and increase dry biomass, offering a solution to mitigate the negative effect of HM contamination. Using these functional EFs could help maintain crop production and ensure food safety in HM-contaminated areas. In the present study, the diversity of EFs in corn grains from various HM-contaminated areas in China was studied through culture-dependent and culture-independent methods. We tested the plant growth-promoting (PGP) traits of several dominant culturable isolates and evaluated the growth-promoting effects of these twenty-one isolates through pot experiments. Both studies showed that HM contamination increased the diversity and richness of corn grain EFs and affected the most dominant endophytes. Nigrospora and Fusarium were the most prevalent culturable endophytes in HM-contaminated areas. Conversely, Cladosporium spp. were the most isolated endophytes in non-contaminated areas. Different from this, Saccharomycopsis and Fusarium were the dominant EFs in HM-contaminated sites, while Neofusicoccum and Sarocladium were dominant in non-contaminated sites, according to a culture-independent analysis. PGP trait tests indicated that 70% of the tested isolates (forty-two) exhibited phosphorus solubilization, IAA production, or siderophore production activity. Specifically, 90% of the tested isolates from HM-contaminated sites showed better PGP results than 45% of the isolates from non-contaminated sites. The benefit of the twenty-one isolates on host plant growth was further studied through pot experiments, which showed that all the isolates could improve host plant growth. Among them, strains derived from HM-contaminated sites, including AK18 (Nigrospora), AK32 (Beauveria), SD93 (Gibberellia), and SD64 (Fusarium), had notable effects on enhancing the dry biomass of shoots and roots of maize under Cd stress. We speculate that the higher ratio of PGP EFs in corn grains from HM-contaminated areas may explain their competitiveness in such extreme environments. Fusarium and Cladosporium isolates show high PGP properties, but they can also be phytopathogenic. Therefore, it is essential to evaluate their pathogenic properties and safety for crops before considering their practical use in agriculture.

Effects of vitamin D supplementation on diabetic foot ulcer healing: a meta-analysis.

PURPOSE: To systematically review the effect of vitamin D supplementation on diabetic foot ulcer (DFU) healing. METHODS: The PubMed, Web of Science, Science direct, Ebsco host, CNKI, WanFang, VIP, and CBM databases were electronically searched to collect randomized controlled trials (RCTs) on the impact of vitamin D supplementation on DFUs from inception to 19 November 2022. Two researchers independently screened the literature, extracted the data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software. RESULTS: A total of seven studies involving 580 patients were included. The results of meta-analysis showed that compared with control group, the wound healing efficiency rate (RR = 1.42, 95%CI 1.03 to 1.95, P = 0.03) and wound reduction rate (MD = 13.11, 95%CI 4.65 to 21.56, P < 0.01) of the experimental group were higher; the change values of the wound area (MD = -3.29, 95%CI -4.89 to 1.70, P < 0.01) and 25 (OH) D (MD = 9.63, 95%CI 6.96 to 12.31, P < 0.01) were larger. Supplementation of vitamin D on DFU patients can improve glucose metabolism and insulin indexes: hemoglobin A1c (MD = -0.44, 95%CI -0.62 to -0.26, P < 0.01), fasting insulin (MD = -3.75, 95%CI -5.83 to -1.67, P < 0.01), HOMA - ß (MD = -5.14, 95%CI -8.74 to -1.54, P < 0.01), and quantitative insulin sensitivity check index (MD = 0.02, 95%CI 0.01 to 0.02, P < 0.01). It can also improve inflammation and oxidative stress markers: high sensitivity C-reactive protein (MD = -0.83, 95%CI -1.06 to -0.59, P < 0.01), erythrocyte sedimentation rate (MD = -15.74, 95%CI -21.78 to -9.71, P<0.01), nitric oxide (MD = 1.81, 95%CI 0.07 to 3.55, P = 0.04), and malondialdehyde (MD = -0.43, 95%CI -0.61 to -0.24, P<0.01). There was no statistically significant difference in changes of fasting plasma glucose, homeostasis model of assessment-insulin resistance, total antioxidant capacity, glutathione, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol (P>0.05). CONCLUSION: The current evidence suggests that vitamin D supplementation can significantly promote DFU healing by lowering blood sugar and alleviating inflammation and oxidative stress. Key messages What is already known on this topic  Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, with high morbidity, mortality and resource utilization. Vitamin D has the effect of lowering blood sugar, improving insulin sensitivity, and increasing anti-inflammatory response. Clinical research on vitamin D supplementation for the treatment of DFU is increasing, but due to the lack of combing and integration, the actual efficacy of vitamin D in patients is unclear. What this study adds  This meta-analysis has shown that vitamin D supplementation can significantly promote DFU healing by lowering blood glucose and alleviating inflammation and oxidative stress. How this study might affect research, practice or policy  This study preliminarily found the effectiveness of vitamin D supplementation on the healing of DFU, which can provide a reference for the treatment of DFU by medical staff.