Clinical Analysis of Pediatric Acute Megakaryocytic Leukemia With CBFA2T3-GLIS2 Fusion Gene.

CBFA2T3-GLIS2 is the most frequent chimeric oncogene identified to date in non-Down syndrome acute megakaryocytic leukemia (AMKL), which is associated with extremely poor clinical outcome. The presence of this fusion gene is associated with resistance to high-intensity chemotherapy, including hematopoietic stem cell transplantation (HSCT), and a high cumulative incidence of relapse frequency. The clinical features and clinical effects of China Children's Leukemia Group-acute myeloid leukemia (AML) 2015/2019 regimens and haploidentical HSCT (haplo-HSCT) for treatment of 6 children harboring the CBFA2T3-GLIS2 fusion gene between January 2019 and December 2021 were retrospectively analyzed. The 6 patients included 4 boys and 2 girls with a median disease-onset age of 19.5 months (range: 6-67 mo) who were diagnosed with AMKL. Flow cytometry demonstrated CD41a, CD42b, and CD56 expression and lack of HLA-DR expression in all 6 patients. All the children were negative for common leukemia fusion genes by reverse transcription polymerase chain reaction, but positive for the CBFA2T3-GLIS2 fusion gene by next-generation sequencing and RNA sequencing. All patients received chemotherapy according to China Children's Leukemia Group-AML 2015/2019 regimens, and 4 achieved complete remission. Four children underwent haplo-HSCT with posttransplant cyclophosphamide-based conditioning; 3 had minimal residual disease negative (minimal residual disease <0.1%) confirmed by flow cytometry at the end of the follow-up, with the remaining patient experiencing relapse at 12 months after transplantation. Transcriptome RNA sequencing is required for the detection of the CBFA2T3-GLIS2 fusion gene and for proper risk-based allocation of pediatric patients with AML in future clinical strategies. Haplo-HSCT with posttransplant cyclophosphamide-based conditioning may improve survival in children with AMKL harboring the fusion gene.

Thermosensitive hydrogel with emodin-loaded triple-targeted nanoparticles for a rectal drug delivery system in the treatment of chronic non-bacterial prostatitis.

BACKGROUND: The complex etiology and pathogenesis underlying Chronic Non-Bacterial Prostatitis (CNP), coupled with the existence of a Blood Prostate Barrier (BPB), contribute to a lack of specificity and poor penetration of most drugs. Emodin (EMO), a potential natural compound for CNP treatment, exhibits commendable anti-inflammatory, anti-oxidant, and anti-fibrosis properties but suffers from the same problems as other drugs. METHODS: By exploiting the recognition properties of lactoferrin (LF) receptors that target intestinal epithelial cells (NCM-460) and prostate epithelial cells (RWPE-1), a pathway is established for the transrectal absorption of EMO to effectively reach the prostate. Additionally, hyaluronic acid (HA) is employed, recognizing CD44 receptors which target macrophages within the inflamed prostate. This interaction facilitates the intraprostatic delivery of EMO, leading to its pronounced anti-inflammatory effects. A thermosensitive hydrogel (CS-Gel) prepared from chitosan (CS) and ß-glycerophosphate disodium salt (ß-GP) was used for rectal drug delivery with strong adhesion to achieve effective drug retention and sustained slow release. Thus, we developed a triple-targeted nanoparticle (NPs)/thermosensitive hydrogel (Gel) rectal drug delivery system. In this process, LF, with its positive charge, was utilized to load EMO through dialysis, producing LF@EMO-NPs. Subsequently, HA was employed to encapsulate EMO-loaded LF nanoparticles via electrostatic adsorption, yielding HA/LF@EMO-NPs. Finally, HA/LF@EMO-NPs lyophilized powder was added to CS-Gel (HA/LF@EMO-NPs Gel). RESULTS: Cellular assays indicated that NCM-460 and RWPE-1 cells showed high uptake of both LF@EMO-NPs and HA/LF@EMO-NPs, while Raw 264.7 cells exhibited substantial uptake of HA/LF@EMO-NPs. For LPS-induced Raw 264.7 cells, HA/LF@EMO-NPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways. Tissue imaging corroborated the capacity of HA/LF-modified formulations to breach the BPB, accumulating within the gland's lumen. Animal experiments showed that rectal administration of HA/LF@EMO-NPs Gel significantly reduced inflammatory cytokine expression, oxidative stress levels and fibrosis in the CNP rats, in addition to exerting anti-inflammatory effects by inhibiting the NF-κB signaling pathway without obvious toxicity. CONCLUSION: This triple-targeted NPs/Gel rectal delivery system with slow-release anti-inflammatory, anti-oxidant, and anti-fibrosis properties shows great potential for the effective treatment of CNP.

Clinical characteristics and outcomes of overt gastrointestinal bleeding in children undergoing haploidentical hematopoietic stem cell transplantation: a single-center retrospective analysis.

BACKGROUND: Overt gastrointestinal bleeding (GIB) is a potentially serious and life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, relatively little information is available regarding overt GIB in children. OBJECTIVES: To assess the prevalence, clinical patterns, and outcomes of overt GIB in children undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: A total of 123 consecutive patients with malignant or non-malignant blood disorders who received haplo-HSCT were reviewed in our hospital between October 2017 and October 2022. Overt GIB was determined as hematemesis, melena or hematochezia. Continuous variables were compared by Mann Whitney U test. Categorical parameters were compared by the χ2 test or Fisher's exact test. Kaplan-Meier curves and log-rank tests were used to assess overall survival (OS), non-relapse mortality (NRM) and relapse. Univariate and multivariate analyses were performed to identify potential risk factors of overt GIB development. RESULTS: The median follow-up was 26.3 (range,1.7-74.8) months. Overt GIB occurred in 31 patients (25.2% incidence), with a median time elapsed after haplo-HSCT of 376 days (range, 58-1275 days). Compared with the non-GIB group, patients with overt GIB had reduced OS and increased NRM. In multivariate analysis, grade III-IV gut acute graft versus-host disease (aGvHD), thrombotic microangiopathy (TMA) and cytomegalovirus (CMV) viremia were significant risk factors for the occurrence of overt GIB after haplo-HSCT. CONCLUSIONS: Overt GIB is a frequent complication after haplo-HSCT in pediatric patients, and associated with worse survival. Grade III-IV gut aGvHD, TMA and CMV viremia were associated with its development.

Chromium Picolinate Regulates Bone Metabolism and Prevents Bone Loss in Diabetic Rats.

Diabetic osteoporosis (DOP) is an abnormal metabolic disease caused by long-term hyperglycemia. In this study, a model rat of streptozotocin (STZ)-induced diabetes was established, and chromium picolinate (5 mg·kg-1) was given; the changes in blood glucose and body weight were detected before and after administration; and bone mineral density (BMD), bone morphology, bone turnover markers, inflammatory cytokines, and oxidative stress indicators were observed in each group. We found that after chromium picolinate (CP) intervention for 8 weeks, the blood glucose level was decreased; the BMD, the bone histomorphology parameters, and the pathological structure were improved; the expression of bone resorption-related proteins was downregulated; and the expression of bone formation-related proteins was upregulated. Meanwhile, serum antioxidant activity was increased, and inflammatory cytokine levels were decreased. In conclusion, CP could alleviate DOP by anti-oxidation, inhibition of bone turnover, anti-inflammation, and regulation of the OPG/RANKL/RANK signaling pathway. Therefore, CP has important application values for further development as a functional food or active medicine in DOP treatment.

Nanoscale Local Contacts Enable Inverted Inorganic Perovskite Solar Cells with 20.8 % Efficiency.

Inorganic perovskite solar cells (IPSCs) have gained significant attention due to their excellent thermal stability and suitable band gap (~1.7 eV) for tandem solar cell applications. However, the defect-induced non-radiative recombination losses, low charge extraction efficiency, energy level mismatches, and so on render the fabrication of high-efficiency inverted IPSCs remains challenging. Here, the use of 3-amino-5-bromopyridine-2-formamide (ABF) in methanol was dynamically spin-coated on the surface of CsPbI2.85Br0.15 film, which facilitates the limited etching of defect-rich subsurface layer, resulting in the formation of vertical PbI2 nanosheet structures. This enabled localized contacts between the perovskite film and the electron transport layer, suppress the recombination of electron-hole and beneficial to electron extraction. Additionally, the C=O and C=N groups in ABF effectively passivated the undercoordinated Pb2+ at grain boundaries and on the surface of CsPbI2.85Br0.15 film. Eventually, we achieved a champion efficiency of 20.80 % (certified efficiency of 20.02 %) for inverted IPSCs with enhanced stability, which is the highest value ever reported to date. Furthermore, we successfully prepared p-i-n type monolithic inorganic perovskite/silicon tandem solar cells (IPSTSCs) with an efficiency of 26.26 %. This strategy provided both fast extraction and efficient passivation at the electron-selective interface.

A Survey of Airborne Fungi and Their Sensitization Profile in Wuhan, China.

INTRODUCTION: Airborne fungi induce allergic symptoms in 3-10% of the population worldwide. To better prevent and manage fungi-related allergic diseases, it is essential to identify the genus and the distribution profile of airborne fungi. METHODS: With this purpose in mind, we carried out a 12-month volumetric sampling study to monitor the airborne fungi and retrospectively analyzed the sensitization profile of four dominant fungi (Cladosporium, Alternaria, Aspergillus, and Penicillium) among respiratory allergies during the same study period in Wuhan, China. RESULTS: A total of 29 different fungal genuses were identified, and the peak fungal concentration period was found to be in September and October, followed by May and June. The most prevalent fungi in this area were Cladosporium (36.36%), Ustilago (20.12%), and Alternaria (13.87%). In addition, the skin prick test data from 1,365 respiratory allergies patients showed that 202 (14.80%) of them were sensitized to fungi. The sensitization rates to Cladosporium, Alternaria, Aspergillus, and Penicillium were 11.72%, 4.69%, 1.98%, and 4.76%, respectively. The seasonal fluctuation of Alternaria and Aspergillus correlated with their sensitization rates. Among the fungal sensitized patients, 76 (37.62%) were sensitized to two or more kinds of fungi. The serum-specific IgE tests suggested low to high correlations existed between these fungi; however, these correlations were not found between fungi and other allergens. CONCLUSION: Our study provides the distribution profile and reveals the clinical significance of the airborne fungi in Wuhan, which will facilitate the precise management of fungal allergy.

Prophylactic donor lymphocyte infusion after haploidentical hematopoietic cell transplantation and post-transplant cyclophosphamide for treatment of high-risk myeloid neoplasms in children: A retrospective study.

BACKGROUND: Post-transplant cyclophosphamide (PTCy) has been recommended for prevention of graft-versus-host disease (GvHD) following haploidentical hematopoietic cell transplantation (haplo-HCT) for treatment of malignant blood diseases, but disease relapse remains a problem. Although donor lymphocyte infusion (DLI) is reported to be effective for treating post-transplantation relapse, the efficacy and safety of prophylactic-DLI (pro-DLI) post haplo-HCT, and PTCy in pediatric patients with hematological malignancies is unknown. METHODS: We retrospectively analyzed the outcomes of 54 pediatric patients with high-risk myeloid neoplasms who received a PTCy regimen for GvHD prophylaxis and pro-DLI after haploidentical peripheral blood stem cell transplantation. The high-risk myeloid neoplasms in this cohort included acute myeloid leukemia (n = 46) and myelodysplastic syndromes (n = 8). RESULTS: Median follow-up was for 19.7 (range: 3.4-46.6) months. The cumulative incidences of grade II-IV and III-IV acute GvHD were 37.0% (95% CI: 22.7%-48.7%) and 16.7% (95% CI: 6.1%-26.0%), respectively. There were no graft-failure events, and the 2-year rate of moderate/severe chronic GvHD was 8.1% (95% CI: 0%-16.7%). The 2-year non-relapse mortality, relapse, disease-free survival, GvHD-free relapse-free survival, and overall survival rates were 5.1% (95% CI: 0%-11.7%), 16.6% (95% CI: 5.3%-26.6%), 78.9% (95% CI: 68.0%-91.6%), 62.2% (95% CI: 49.4%-78.3%), and 87.3% (95% CI: 78.3%-97.4%), respectively. CONCLUSIONS: Prophylactic donor lymphocyte infusion in the setting of haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide appears to be effective and safe in pediatric patients with high-risk myeloid neoplasms.

"Dual sensitive supramolecular curcumin nanoparticles" in "advanced yeast particles" mediate macrophage reprogramming, ROS scavenging and inflammation resolution for ulcerative colitis treatment.

Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on ß-cyclodextrin (ß-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for "supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects" in "advanced yeast particles", but also provided strong theoretical support multi-effect therapy for UC.

Dose dependent effect of nitrogen on the phyto extractability of Cd in metal contaminated soil using Wedelia trilobata.

Cadmium (Cd) is one of the toxic heavy metal that negatively affect plant growth and compromise food safety for human consumption. Nitrogen (N) is an essential macronutrient for plant growth and development. It may enhance Cd tolerance of invasive plant species by maintaining biochemical and physiological characteristics during phytoextraction of Cd. A comparative study was conducted to evaluate the phenotypical and physiological responses of invasive W. trilobata and native W. chinensis under low Cd (10 µM) and high Cd (80 µM) stress, along with different N levels (i.e., normal 91.05 mg kg-1 and low 0.9105 mg kg-1). Under low-N and Cd stress, the growth of leaves, stem and roots in W. trilobata was significantly increased by 35-23%, 25-28%, and 35-35%, respectively, compared to W. chinensis. Wedelia trilobata exhibited heightened antioxidant activities of catalase and peroxidase were significantly increased under Cd stress to alleviate oxidative stress. Similarly, flavonoid content was significantly increased by 40-50% in W. trilobata to promote Cd tolerance via activation of the secondary metabolites. An adverse effect of Cd in the leaves of W. chinensis was further verified by a novel hyperspectral imaging technology in the form of normalized differential vegetation index (NDVI) and photochemical reflectance index (PRI) compared to W. trilobata. Additionally, W. trilobata increased the Cd tolerance by regulating Cd accumulation in the shoots and roots, bolstering its potential for phytoextraction potential. This study demonstrated that W. trilobata positively responds to Cd with enhanced growth and antioxidant capabilities, providing a new platform for phytoremediation in agricultural lands to protect the environment from heavy metals pollution.

Effect of Antecedent Hypertension on Mortality After Acute Coronary Syndromes in the Coronary Intervention Era: A Meta-analysis.

BACKGROUND: The effect of antecedent hypertension on mortality after acute coronary syndromes (ACS) in the percutaneous coronary intervention era is unclear. Therefore, this meta-analysis aimed to assess the effect of antecedent hypertension on short-term and long-term mortality after ACS in the coronary intervention era. METHODS: PubMed, Medline, EMBASE, and the Cochrane library were systematically searched up to July 2023. Ten studies with a total of 64,989 of patients met the inclusion criteria. The outcomes of interest were all-cause in-hospital mortality and long-term all-cause mortality. RESULTS: No significant difference was observed in in-hospital mortality between the antecedent hypertension and non-antecedent hypertension groups in the ACS patients (pooled OR 1.07; 95% CI 0.79-1.45; I2=82%), which was the same as the ST elevation myocardial infarction group (pooled OR 1.01; 95% CI 0.73-1.39; I2=66%). However, the result was statistically significant for non-ST elevation myocardial infarction patients (pooled OR 0.67; 95% CI 0.55-0.82; p=0.0001; I2=0%). Antecedent hypertension was related to increased long-term mortality in patients with ACS (pooled OR 1.28; 95% CI 1.16-1.40; p=0.0001; I2=0%), which was the same as the ST elevation myocardial infarction subgroup. CONCLUSION: In the percutaneous coronary intervention era, antecedent hypertension is associated with higher long-term mortality in ACS patients. This meta-analysis found no significant difference in in-hospital mortality between the hypertension and non-hypertension groups. However, antecedent hypertension may be a protective factor related to in-hospital mortality for non-ST elevation myocardial infarction patients.

Chromium Picolinate Protects against Testicular Damage in STZ-Induced Diabetic Rats via Anti-Inflammation, Anti-Oxidation, Inhibiting Apoptosis, and Regulating the TGF-ß1/Smad Pathway.

Chromium picolinate (CP) is an organic compound that has long been used to treat diabetes. Our previous studies found CP could relieve diabetic nephropathy. Thus, we speculate that it might have a positive effect on diabetic testicular injury. In this study, a diabetic rat model was established, and then the rats were treated with CP for 8 weeks. We found that the levels of blood glucose, food, and water intake were reduced, and body weight was enhanced in diabetic rats after CP supplementation. Meanwhile, in CP treatment groups, the levels of male hormone and sperm parameters were improved, the pathological structure of the testicular tissue was repaired, and testicular fibrosis was inhibited. In addition, CP reduced the levels of serum inflammatory cytokines, and decreased oxidative stress and apoptosis in the testicular tissue. In conclusion, CP could ameliorate testicular damage in diabetic rats, as well as being a potential testicle-protective nutrient in the future to prevent the testicular damage caused by diabetes.

The hepatoprotective effect of Sophora viciifolia fruit extract against acetaminophen-induced liver injury in mice.

This research demonstrated the protective effect and possible mechanism of the Sophora viciifolia extract (SVE) against acetaminophen-induced liver injury in mice. The levels of ALT and AST in the serum and antioxidant enzyme activity in the liver were measured. We used immunohistochemistry to detect CYP2E1, Nrf2, and Keap1 protein expression in the liver. The mRNA expression in the liver of TNF-α, NF-κB, and IL-6, Nrf2 and its downstream genes HO-1 and GCLC were measured by qRT-PCR. We found that SVE could decrease the ALT and AST levels, promote the activities of SOD, CAT, GSH-Px, and GSH, and ameliorate pathological liver lesions. SVE could down-regulate the mRNA expression of inflammatory factors and up-regulate Nrf2, HO-1 and GCLC. SVE reduced the protein expression of the CYP2E1 and increased the Nrf2 and Keap1. SVE has been shown to have a protective effect against APAP-induced liver injury, possibly through activation of the Keap1-Nrf2 pathway.

Coronavirus Porcine Epidemic Diarrhea Virus Nucleocapsid Protein Interacts with p53 To Induce Cell Cycle Arrest in S-Phase and Promotes Viral Replication.

Subversion of the host cell cycle to facilitate viral replication is a common feature of coronavirus infections. Coronavirus nucleocapsid (N) protein can modulate the host cell cycle, but the mechanistic details remain largely unknown. Here, we investigated the effects of manipulation of porcine epidemic diarrhea virus (PEDV) N protein on the cell cycle and the influence on viral replication. Results indicated that PEDV N induced Vero E6 cell cycle arrest at S-phase, which promoted viral replication (P < 0.05). S-phase arrest was dependent on the N protein nuclear localization signal S71NWHFYYLGTGPHADLRYRT90 and the interaction between N protein and p53. In the nucleus, the binding of N protein to p53 maintained consistently high-level expression of p53, which activated the p53-DREAM pathway. The key domain of the N protein interacting with p53 was revealed to be S171RGNSQNRGNNQGRGASQNRGGNN194 (NS171-N194), in which G183RG185 are core residues. NS171-N194 and G183RG185 were essential for N-induced S-phase arrest. Moreover, small molecular drugs targeting the NS171-N194 domain of the PEDV N protein were screened through molecular docking. Hyperoside could antagonize N protein-induced S-phase arrest by interfering with interaction between N protein and p53 and inhibit viral replication (P < 0.05). The above-described experiments were also validated in porcine intestinal cells, and data were in line with results in Vero E6 cells. Therefore, these results reveal the PEDV N protein interacts with p53 to activate the p53-DREAM pathway, and subsequently induces S-phase arrest to create a favorable environment for virus replication. These findings provide new insight into the PEDV-host interaction and the design of novel antiviral strategies against PEDV. IMPORTANCE Many viruses subvert the host cell cycle to create a cellular environment that promotes viral growth. PEDV, an emerging and reemerging coronavirus, has led to substantial economic loss in the global swine industry. Our study is the first to demonstrate that PEDV N-induced cell cycle arrest during the S-phase promotes viral replication. We identified a novel mechanism of PEDV N-induced S-phase arrest, where the binding of PEDV N protein to p53 maintains consistently high levels of p53 expression in the nucleus to mediate S-phase arrest by activating the p53-DREAM pathway. Furthermore, a small molecular compound, hyperoside, targeted the PEDV N protein, interfering with the interaction between the N protein and p53 and, importantly, inhibited PEDV replication by antagonizing cell cycle arrest. This study reveals a new mechanism of PEDV-host interaction and also provides a novel antiviral strategy for PEDV. These data provide a foundation for further research into coronavirus-host interactions.

Pathogen resistance in Sphagneticola trilobata (Singapore daisy): molecular associations and differentially expressed genes in response to disease from a widespread fungus.

Understanding the molecular associations underlying pathogen resistance in invasive plant species is likely to provide useful insights into the effective control of alien plants, thereby facilitating the conservation of native biodiversity. In the current study, we investigated pathogen resistance in an invasive clonal plant, Sphagneticola trilobata, at the molecular level. Sphagneticola trilobata (i.e., Singapore daisy) is a noxious weed that affects both terrestrial and aquatic ecosystems, and is less affected by pathogens in the wild than co-occurring native species. We used Illumina sequencing to investigate the transcriptome of S. trilobata following infection by a globally distributed generalist pathogen (Rhizoctonia solani). RNA was extracted from leaves of inoculated and un-inoculated control plants, and a draft transcriptome of S. trilobata was generated to examine the molecular response of this species following infection. We obtained a total of 49,961,014 (94.3%) clean reads for control (un-inoculated plants) and 54,182,844 (94.5%) for the infected treatment (inoculated with R. solani). Our analyses facilitated the discovery of 117,768 de novo assembled contigs and 78,916 unigenes. Of these, we identified 3506 differentially expressed genes and 60 hormones associated with pathogen resistance. Numerous genes, including candidate genes, were associated with plant-pathogen interactions and stress response in S. trilobata. Many recognitions, signaling, and defense genes were differentially regulated between treatments, which were confirmed by qRT-PCR. Overall, our findings improve our understanding of the genes and molecular associations involved in plant defense of a rapidly spreading invasive clonal weed, and serve as a valuable resource for further work on mechanism of disease resistance and managing invasive plants.

The relationship between the neutrophil-to-lymphocyte ratio and diabetic retinopathy in adults from the United States: results from the National Health and nutrition examination survey.

BACKGROUND: Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM). Systemic inflammation is intimately associated with DR. The neutrophil-to-lymphocyte ratio (NLR) index is a relatively new indicator of inflammation. METHODS: This cross-sectional study was carried out among adults with DM based on the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2016. NLR was presented as absolute neutrophil counts/ absolute lymphocyte counts. The relationship of NLR levels to DR was analyzed using multivariable logistic regression. RESULTS: There were 2772 eligible subjects extracted from the NHANES. In the multivariate analysis, NLR was related to the risk of DR after adjustment for potential confounders. The association between NLR levels and DR was nonlinear, with an inflection point of 4.778. Compared with the baseline values, NLR was not statistically significant on the right side of the inflection point (1.000, 0.914 to 1.094, 0.9974) but was positively associated with DR on the left side (1.236, 1.132 to 1.349, < 0.0001). CONCLUSIONS: NLR reflects systemic inflammation that may increase the risk of DR. NLR positively correlates with DR when its value is less than 4.778.

pH/ROS dual-sensitive and chondroitin sulfate wrapped poly (ß-amino ester)-SA-PAPE copolymer nanoparticles for macrophage-targeted oral therapy for ulcerative colitis.

An oral nanoparticle (NPs) encapsulated in chitosan/alginate hydrogel (CA-Gel) with dual-sensitive in pH and reactive oxygen species (ROS) was developed to load curcumin (CUR) based on the intracellular-specific characteristics of macrophages. Chondroitin sulfate (CS) wrapped PBAE-SA-PAPE with intracellular pH/ROS dual-sensitive characteristics and CUR via a simple nanoprecipitation method to form NPs (CS-CUR-NPs), and mixed CA-Gel to acquire the final preparation (CS-CUR-NPs-Gel). CS-CUR-NPs displayed an ideal average particle size (179.19±5.61nm) and high encapsulating efficiency (94.74±1.15%). CS showed a good targeting ability on macrophages and the CA-Gel contribution in protecting NPs from being destroyed in the upper gastrointestinal tract. As expected, CS-CUR-NPs-Gel could significantly alleviate inflammation in DSS-induced UC mice via TLR4-MAPK/NF-κB pathway. This study is the first to attempt to design a novel pH/ROS dual-stimulated release strategy in helping intracellular CUR delivery and anticipated for efficient anti-UC therapy.

Transcriptome profiling of Arabidopsis thaliana roots in response to allelopathic effects of Conyza canadensis.

The molecular mechanisms underlying allelopathy and their role in the interactions between invasive weeds and native species remain unclear. In this study, we aimed to explore the physiological and molecular response of plant roots of a native species to allelopathy from an invasive weed. We examined the growth and development of roots of native Arabidopsis thaliana for a 2-week period after being treated with aqueous extracts at different concentrations from invasive Conyza canadensis. Extracts with higher concentration in the Murashige and Skoog (MS) media (i.e., 4 mg of extract/mL of MS) significantly affected the root growth of A. thaliana. Roots of A. thaliana displayed weakened root tip activity and an accumulation of reactive oxygen species (ROS) in response to extracts from C. canadensis. The transcriptome analysis of A. thaliana roots exposed to phytotoxicity revealed differentially expressed genes (DEGs) involved in cell wall formation, abiotic stress, transporter genes and signal transduction. We found that genes associated with nutrient transport, such as major facilitator superfamily (MFS) and amino acid permease (AAP3) transporters as well as genes involved in stress response, including leucine-rich repeat receptor-like protein kinases (LRR-RLKs) were down-regulated. In addition, we found that many transcription factors associated with plant stress (such as APETALA2/ethylene response factors) were up-regulated while others (e.g., zinc-finger proteins) were down-regulated. Allelochemicals from C. canadensis also induced the up-regulation of detoxification (DTX) genes, ROS related genes, calcineurin B-like interacting protein kinases (CIPKs) and calmodulin. Overall, our findings provided insights into allelopathy in C. canadensis at the molecular level, and contributes to our understanding of invasion mechanisms of alien plant species. CLINICAL TRIALS REGISTRATION: This study does not contain any studies with clinical trials performed by any of the authors.

CRISPR/Cas9 technology as an innovative approach to enhancing the phytoremediation: Concepts and implications.

Phytoremediation is currently an active field of research focusing chiefly on identifying and characterizing novel and high chelation action super-accumulators. In the last few years, molecular tools have been widely exploited to understand better metal absorption, translocation, cation, and tolerance mechanisms in plants. Recently more advanced CRISPR-Cas9 genome engineering technology is also employed to enhance detoxification efficiency. Further, advances in molecular science will trigger the understanding of adaptive phytoremediation ability plant production in current global warming conditions. The enhanced abilities of nucleases for genome modification can improve plant repair capabilities by modifying the genome, thereby achieving a sustainable ecosystem. The purpose of this manuscript focuses on biotechnology's fundamental principles and application to promote climate-resistant metal plants, especially the CRISPR-Cas9 genome editing system for enhancing the phytoremediation of harmful contamination and pollutants.

The soil pH and heavy metals revealed their impact on soil microbial community.

Soil microbial community is the main indicator having a crucial role in the remediation of polluted soils. These microbes can alter soil pH, organic matter in soils (SOM), soil physic-chemical properties, and potential soil respiration rate via their enzymatic activities. Similarly, heavy metals also have a crucial role in soil enzymatic activities. For this purpose, a number of methods are studied to evaluate the impact of soil pH (a key factor in the formation of biogeographic microbial patterns in bacteria) on bacterial diversity. The effects of pH on microbial activity are glamorous but still unclear. Whereas, some studies also indicate that soil pH alone is not the single key player in the diversity of soil bacteria. Ecological stability is achieved in a pollution-free environment and pH value. The pH factor has a significant impact on the dynamics of microbes' communities. Here, we try to discuss factors that directly or indirectly affect soil pH and the impact of pH on microbial activity. It is also discussed the environmental factors that contribute to establishing a specific bacterial community structure that must be determined. From this, it can be concluded that the environmental impact on soil pH, reducing soil pH and interaction with this factor, and reducing the effect of soil pH on soil microbial community.

Entrapment of Macrophage-Target Nanoparticles by Yeast Microparticles for Rhein Delivery in Ulcerative Colitis Treatment.

In this study, we developed an advanced colitis-targeted nanoparticles (NPs)-into-yeast cell wall microparticles (YPs) drug delivery system for ulcerative colitis (UC) therapy. In brief, YPs entrap hyaluronic acid (HA), and polyethylenimine (PEI) modified rhein (RH)-loaded ovalbumin NPs (HA/PEI-RH NPs) to form HA/PEI-RH NYPs. YPs can make HA/PEI-RH NPs pass through gastric environment stably and be degraded by ß-glucanase to promote drug release from HA/PEI-RH NYPs in the colon. Cellular uptake evaluation confirmed that HA/PEI-RH NPs could specifically target and enhance the uptake rate via HA ligands. In biodistribution studies, HA/PEI-RH NYPs were able to efficiently accumulate in the inflammed colon in mice. In vivo experiments revealed that the HA/PEI-RH NYPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, HA/PEI-RH NYPs have advantages of good gastric stability, ß-glucanase-sensitive release ability, macrophage-targeted ability, and anti-UC effects. These advantages indicate YPs-entrapped multifunctional NPs are a promising oral drug delivery system for UC therapy.