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1.
World J Diabetes ; 15(6): 1317-1339, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38983802

ABSTRACT

BACKGROUND: Diabetic retinopathy (DR) is the primary cause of visual problems in patients with diabetes. The Heyingwuzi formulation (HYWZF) is effective against DR. AIM: To determine the HYWZF prevention mechanisms, especially those underlying mitophagy. METHODS: Human retinal capillary endothelial cells (HRCECs) were treated with high glucose (hg), HYWZF serum, PX-478, or Mdivi-1 in vitro. Then, cell counting kit-8, transwell, and tube formation assays were used to evaluate HRCEC proliferation, invasion, and tube formation, respectively. Transmission electron microscopy was used to assess mitochondrial morphology, and Western blotting was used to determine the protein levels. Flow cytometry was used to assess cell apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential. Moreover, C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks. Blood glucose levels and body weight were monitored continuously. Changes in retinal characteristics were evaluated using hematoxylin and eosin, tar violet, and periodic acid-Schiff staining. Protein levels in retinal tissues were determined via Western blotting, immunohistochemistry, and immunostaining. RESULTS: HYWZF inhibited excessive ROS production, apoptosis, tube formation, and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro. It increased the mRNA expression levels of BCL2-interacting protein 3 (BNIP3), FUN14 domain-containing 1, BNIP3-like (BNIP3L, also known as NIX), PARKIN, PTEN-induced kinase 1, and hypoxia-inducible factor (HIF)-1α. Moreover, it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio. However, PX-478 and Mdivi-1 reversed these effects. Additionally, PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy. HYWZF intervention improved the symptoms of diabetes, tissue damage, number of acellular capillaries, and oxidative stress in vivo. Furthermore, in vivo experiments confirmed the results of in vitro experiments. CONCLUSION: HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.

2.
Front Neurol ; 15: 1407418, 2024.
Article in English | MEDLINE | ID: mdl-38966082

ABSTRACT

Background: Despite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG). Methods: This is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10 mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3 weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod's therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4 weeks. MG-ADL responder was defined as a ≥ 2-point improvement that persisted for 4 weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study. Results: Between 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7 years, with a mean MG-ADL score of 10.86 ± 3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported. Discussion: A single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients.

3.
J Am Chem Soc ; 146(27): 18427-18439, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38946080

ABSTRACT

Pseudomonas aeruginosa bacteria are becoming increasingly resistant against multiple antibiotics. Therefore, the development of vaccines to prevent infections with these bacteria is an urgent medical need. While the immunological activity of lipopolysaccharide O-antigens in P. aeruginosa is well-known, the specific protective epitopes remain unidentified. Herein, we present the first chemical synthesis of highly functionalized aminoglycoside trisaccharide 1 and its acetamido derivative 2 found in the P. aeruginosa serotype O5 O-antigen. The synthesis of the trisaccharide targets is based on balancing the reactivity of disaccharide acceptors and monosaccharide donors. Glycosylations were analyzed by quantifying the reactivity of the hydroxyl group of the disaccharide acceptor using the orbital-weighted Fukui function and dual descriptor. The stereoselective formation of 1,2-cis-α-fucosylamine linkages was achieved through a combination of remote acyl participation and reagent modulation. The simultaneous SN2 substitution of azide groups at C2' and C2″ enabled the efficient synthesis of 1,2-cis-ß-linkages for both 2,3-diamino-D-mannuronic acids. Through a strategic orthogonal modification, the five amino groups on target trisaccharide 1 were equipped with a rare acetamidino (Am) and four acetyl (Ac) groups. Glycan microarray analyses of sera from patients infected with P. aeruginosa indicated that trisaccharides 1 and 2 are key antigenic epitopes of the serotype O5 O-antigen. The acetamidino group is not an essential determinant of antibody binding. The ß-D-ManpNAc3NAcA residue is a key motif for the antigenicity of serotype O5 O-antigen. These findings serve as a foundation for the development of glycoconjugate vaccines targeting P. aeruginosa serotype O5.


Subject(s)
Aminoglycosides , O Antigens , Pseudomonas aeruginosa , Trisaccharides , Pseudomonas aeruginosa/immunology , O Antigens/chemistry , O Antigens/immunology , Trisaccharides/chemistry , Trisaccharides/immunology , Trisaccharides/chemical synthesis , Aminoglycosides/chemistry , Aminoglycosides/chemical synthesis , Aminoglycosides/immunology
4.
Cell ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39013470

ABSTRACT

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

5.
Nanoscale ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39011858

ABSTRACT

Sulfuration reactions dominate the synthesis of transition-metal dichalcogenides via chemical vapor deposition. A neglected critical issue is the evolution of crystal domain morphology and growth models caused by boundary layer development. In this study, we propose two growth models within a laminar flow field to investigate the kinetic mechanism of uniformly grown MoS2. We used supercritical fluid pre-deposition to obtain a well-distributed and low-crystallinity Mo precursor on the surface of a substrate to avoid non-stoichiometric supply in sulfuration. The development of the boundary layer was suppressed through mainstream force by adjusting the substrate slope angle. For growth within the underdeveloped laminar boundary layer, monolayer MoS2 with a size of 50 µm uniformly distributed on the full substrate with R = 85% (relative change in boundary layer thickness). Moreover, the growth constrained by surface chemical reactions tended to promote spatially uniform growth. However, within the fully developed laminar flow, the crystal domains preferentially grew vertically, which was attributed to the excessive crystal growth rate (g). Our results provide new insights into the controllable preparation of two-dimensional materials.

6.
Biosens Bioelectron ; 261: 116475, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38852324

ABSTRACT

Rapid and accurate identification of tumor boundaries is critical for the cure of glioma, but it is difficult due to the invasive nature of glioma cells. This paper aimed to explore a rapid diagnostic strategy based on a label-free surface-enhanced Raman scattering (SERS) technique for the quantitative detection of glioma cell proportion intraoperatively. With silver nanoparticles as substrate, an in-depth SERS analysis was performed on simulated clinical samples containing normal brain tissue and different concentrations of patient-derived glioma cells. The results revealed two universal characteristic peaks of 655 and 717 cm-1, which strongly correlated with glioma cell proportion regardless of individual differences. Based on the intensity ratio of the two peaks, a ratiometric SERS strategy for the quantification of glioma cells was established by employing an artificial neuron network model and a polynomial regression model. Such a strategy accurately estimated the proportion of glioma cells in simulated clinical samples (R2 = 0.98) and frozen samples (R2 = 0.85). More importantly, it accurately facilitated the delineation of tumor margins in freshly obtained samples. Taken together, this SERS-based method ensured a rapid and more detailed identification of tumor margins during surgical resection, which could be beneficial for intraoperative decision-making and pathological evaluation.


Subject(s)
Brain Neoplasms , Glioma , Metal Nanoparticles , Silver , Spectrum Analysis, Raman , Glioma/surgery , Glioma/pathology , Glioma/diagnostic imaging , Humans , Spectrum Analysis, Raman/methods , Metal Nanoparticles/chemistry , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Brain Neoplasms/diagnostic imaging , Silver/chemistry , Biosensing Techniques/methods
7.
Bioengineering (Basel) ; 11(6)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38927831

ABSTRACT

This paper presents an eye image segmentation-based computer-aided system for automatic diagnosis of ocular myasthenia gravis (OMG), called OMGMed. It provides great potential to effectively liberate the diagnostic efficiency of expert doctors (the scarce resources) and reduces the cost of healthcare treatment for diagnosed patients, making it possible to disseminate high-quality myasthenia gravis healthcare to under-developed areas. The system is composed of data pre-processing, indicator calculation, and automatic OMG scoring. Building upon this framework, an empirical study on the eye segmentation algorithm is conducted. It further optimizes the algorithm from the perspectives of "network structure" and "loss function", and experimentally verifies the effectiveness of the hybrid loss function. The results show that the combination of "nnUNet" network structure and "Cross-Entropy + Iou + Boundary" hybrid loss function can achieve the best segmentation performance, and its MIOU on the public and private myasthenia gravis datasets reaches 82.1% and 83.7%, respectively. The research has been used in expert centers. The pilot study demonstrates that our research on eye image segmentation for OMG diagnosis is very helpful in improving the healthcare quality of expert doctors. We believe that this work can serve as an important reference for the development of a similar auxiliary diagnosis system and contribute to the healthy development of proactive healthcare services.

8.
Bioorg Chem ; 150: 107560, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38878752

ABSTRACT

Leveraging the elevated hydrogen peroxide (H2O2) levels in cancer cells, H2O2-activated prodrugs have emerged as promising candidates for anticancer therapy. Notably, the efficacy of these prodrugs is influenced by the varying H2O2 levels across different cancer cell types. In this context, we have developed a novel H2O2-activated prodrug, PBE-AMF, which incorporates a phenylboronic ester (PBE) motif. Upon H2O2 exposure, PBE-AMF liberates the fluorescent and cytotoxic molecule amonafide (AMF), functioning as a theranostic agent. Our studies with PBE-AMF have demonstrated a positive correlation between intracellular H2O2 concentration and anticancer activity. The breast cancer cell line MDA-MB-231, characterized by high H2O2 content, showed the greatest susceptibility to this prodrug. Subsequently, we replaced the PBE structure with phenylboronic acid (PBA) to obtain the prodrug PBA-AMF, which exhibited enhanced stability, aqueous solubility, and tumor cell selectivity. This selectivity is attributed to its affinity for sialic acid, which is overexpressed on the surfaces of cancer cells. In vitro assays confirmed that PBA-AMF potently and selectively inhibited the proliferation of MDA-MB-231 cells, while sparing non-cancerous MCF-10A cells. Mechanistic investigations indicated that PBA-AMF impedes tumor proliferation by inhibiting DNA synthesis, reducing ATP levels, inducing apoptosis, and arresting the cell cycle. Our work broadens the range of small molecule H2O2-activated anticancer theranostic prodrugs, which are currently limited in number. We anticipate that the applications of PBA-AMF will extend to a wider spectrum of tumors and other diseases associated with increased H2O2 levels, thereby offering new horizons in cancer diagnostics and treatment.

9.
Org Lett ; 26(24): 5215-5219, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38861677

ABSTRACT

Bacterial nonulosonic acids (NulOs), which feature a nine-carbon backbone, are associated with the biological functions of bacterial glycans. Here, an orthogonally protected 5-amino-7-azido-3,5,7,9-tetradeoxy-d-glycero-l-gluco-2-nonulosonic acid related to Fusobacterium nucleatum ATCC 23726 NulO was synthesized from N-acetylneuraminic acid with sequential performance of C5,7 azidation, C9 deoxygenation, C4 epimerization, and N5,7 differentiation. The C5 azido group in the obtained 5,7-diazido-NulO can be regioselectively reduced to differentiate the two amino groups.


Subject(s)
N-Acetylneuraminic Acid , Sugar Acids , N-Acetylneuraminic Acid/chemistry , N-Acetylneuraminic Acid/chemical synthesis , Molecular Structure , Sugar Acids/chemistry , Sugar Acids/chemical synthesis , Fusobacterium nucleatum/chemistry , Azides/chemistry
10.
Mol Biotechnol ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38852121

ABSTRACT

Myocardial ischemia-reperfusion injury (MIRI) is fatal to patients, leading to cardiomyocyte death and myocardial remodeling. Reactive oxygen species (ROS) and oxidative stress play important roles in MIRI. There is a complex crosstalk between ROS and regulatory cell deaths (RCD) in cardiomyocytes, such as apoptosis, pyroptosis, autophagy, and ferroptosis. ROS is a double-edged sword. A reasonable level of ROS maintains the normal physiological activity of myocardial cells. However, during myocardial ischemia-reperfusion, excessive ROS generation accelerates myocardial damage through a variety of biological pathways. ROS regulates cardiomyocyte RCD through various molecular mechanisms. Targeting the removal of excess ROS has been considered an effective way to reverse myocardial damage. Many studies have applied antioxidant drugs or new advanced materials to reduce ROS levels to alleviate MIRI. Although the road from laboratory to clinic has been difficult, many scholars still persevere. This article reviews the molecular mechanisms of ROS inhibition to regulate cardiomyocyte RCD, with a view to providing new insights into prevention and treatment strategies for MIRI.

11.
Eur J Neurol ; 31(8): e16322, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38726639

ABSTRACT

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.


Subject(s)
Myasthenia Gravis , Humans , Myasthenia Gravis/drug therapy , Female , Male , Middle Aged , Adult , Aged , Treatment Outcome , Receptors, Cholinergic/immunology
12.
Int J Biol Macromol ; 271(Pt 1): 131980, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38821790

ABSTRACT

The mass proliferation of seed cells and imitation of meat structures remain challenging for cell-cultured meat production. With excellent biocompatibility, high water content and porosity, hydrogels are frequently-studied materials for anchorage-dependent cell scaffolds in biotechnology applications. Herein, a scaffold based on gelatin/alginate/ε-Poly-l-lysine (GAL) hydrogel is developed for skeletal muscle cells, which has a great prospect in cell-cultured meat production. In this work, the hydrogel GAL-4:1, composed of gelatin (5 %, w/v), alginate (5 %, w/v) and ε-Poly-l-lysine (molar ratio vs. alginate: 4:1) is selected as cell scaffold based on Young's modulus of 11.29 ± 1.94 kPa, satisfactory shear-thinning property and suitable porous organized structure. The commercially available C2C12 mouse skeletal myoblasts and porcine muscle stem cells (PMuSCs), are cultured in the 3D-printed scaffold. The cells show strong ability of attachment, proliferation and differentiation after induction, showing high biocompatibility. Furthermore, the cellular bioprinting is performed with GAL-4:1 hydrogel and freshly extracted PMuSCs. The extracted PMuSCs exhibit high viability and display early myogenesis (desmin) on the 3D scaffold, suggesting the great potential of GAL hydrogel as 3D cellular constructs scaffolds. Overall, we develop a novel GAL hydrogel as a 3D-printed bioactive platform for cultured meat research.


Subject(s)
Alginates , Cell Differentiation , Cell Proliferation , Gelatin , Hydrogels , Polylysine , Printing, Three-Dimensional , Tissue Scaffolds , Animals , Alginates/chemistry , Gelatin/chemistry , Polylysine/chemistry , Cell Differentiation/drug effects , Tissue Scaffolds/chemistry , Swine , Cell Proliferation/drug effects , Mice , Hydrogels/chemistry , Stem Cells/cytology , Meat , Muscle Development , Tissue Engineering/methods , Cell Line , Bioprinting/methods , In Vitro Meat
13.
Org Lett ; 26(19): 4142-4146, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38717147

ABSTRACT

Fusobacterium nucleatum, a colorectal-cancer-associated oncomicrobe, can trigger or accelerate numerous pathologies. We report the first synthesis of a conjugation-ready disaccharide containing six amino groups from F. nucleatum ATCC 23726 O-antigen. Rare 2,3-diamido-d-glucuronic acid amide and 2-acetamido-4-amino-d-fucose were synthesized from d-glucosamine through configuration inversion, nucleophilic substitution, C6 oxidation, and C6 deoxygenation. A judicious choice of protecting groups and reaction conditions enabled the selective installation of N-acetyl, N-propanoyl, N-formyl, and carboxamido groups.


Subject(s)
Fusobacterium nucleatum , O Antigens , Fusobacterium nucleatum/chemistry , O Antigens/chemistry , Molecular Structure , Disaccharides/chemistry , Disaccharides/chemical synthesis
14.
World J Psychiatry ; 14(5): 678-685, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38808091

ABSTRACT

BACKGROUND: Rectus abdominis separation (DRA) affects pelvic stability and body image. No studies have explored the effects of manual massage on early postpartum DRA and postpartum depression. AIM: To analyze the curative effect of massage on early postpartum DRA and its impact on postpartum depression and thus its ability promote the overall psychosomatic rehabilitation of postpartum women. METHODS: Data were retrospectively collected on 70 primiparous women with postpartum DRA who underwent rehabilitation at the Postpartum Rehabilitation Center of Huzhou Maternal and Child Health Hospital from October 2022 to September 2023. The patients were divided into the Group S (35 cases, biomimetic electrical stimulation treatment) and Group L (35 cases, biomimetic electrical stimulation combined with manual massage treatment). Baseline data, the edinburgh postpartum depression scale (EPDS) score, and the visual analog scale (VAS) scores for rectus abdominis distance, waist circumference, and lower back pain before and after treatment were compared. RESULTS: No significant differences were found in the baseline data, rectus abdominis distance, waist circumference, and VAS and EPDS scores between the two groups before treatment (P > 0.05). After treatment, the distance between rectus abdominis and waist circumference in Group L were significantly smaller than those in Group S (P < 0.05). Furthermore, lower back pain (VAS score) and the EPDS score in Group L were significantly lower than those in Group S (P < 0.05). CONCLUSION: Manual massage can significantly reduce early postpartum DRA, waist circumference, and back pain and improve the patient's mental state and postpartum depression.

15.
Nat Prod Res ; : 1-5, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813681

ABSTRACT

The phenomena of intramolecular self-assembly of bidesmosidic kalopanaxsaponins was identified for the first time in this paper. NMR (1H-NMR, NOESY), transmission electron microscopy (TEM), and molecular dynamics (MD) simulation techniques were used to compare the spatial structures of bidesmosidic kalopanaxsaponins and monodesmosidic kalopanaxsaponins. The results showed that the bidesmosidic kalopanaxsaponins formed a clustered and twisted structure in space, whereas the monodesmosidic kalopanaxsaponins were in an extended state. This discovery confirmed the presence of intramolecular self-assembly in bidesmosidic kalopanaxsaponins.

16.
J Med Virol ; 96(6): e29716, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38818787

ABSTRACT

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16ink4a immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16ink4a, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.


Subject(s)
DNA, Viral , Genotype , Oncogene Proteins, Viral , Oropharyngeal Neoplasms , Papillomavirus Infections , Paraffin Embedding , Humans , Oropharyngeal Neoplasms/virology , Retrospective Studies , Papillomavirus Infections/virology , Papillomavirus Infections/diagnosis , Middle Aged , Male , Female , Oncogene Proteins, Viral/genetics , Aged , DNA, Viral/genetics , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomaviridae/classification , Polymerase Chain Reaction/methods , Genotyping Techniques/methods , China , Adult , Formaldehyde , Human Papillomavirus Viruses
17.
Genomics ; 116(3): 110849, 2024 05.
Article in English | MEDLINE | ID: mdl-38679345

ABSTRACT

Paulownia fortunei is an ecologically and economically valuable tree cultivated for its rapid growth and high-quality timber. To enhance Paulownia germplasm, we have developed the elite variety QingT with patented advantages in growth rate and apical dominance. To illuminate the genetic basis of QingT's superior traits, here we harness comparative population genomics to analyze genomic variation patterns between QingT and common Paulownia. We performed whole-genome re-sequencing of 30 QingT and 30 common samples, detecting 15.6 million SNPs and 2.6 million indels. Phylogeny and population structure analyses robustly partitioned common and QingT into distinct groups which indicate robust genome stabilization. QingT exhibited reduced heterozygosity and linkage disequilibrium decay compared to common Paulownia, reflecting high recombination, indicating hybridizing effects with common white-flowered string is the source of its patented advantages. Genome selection scans uncovered 25 regions of 169 genes with elevated nucleotide diversity, indicating selection sweeps among groups. Functional analysis of sweep genes revealed upregulation of ribosomal, biosynthesis, and growth pathways in QingT, implicating enhanced protein production and developmental processes in its rapid growth phenotype. This study's insights comprehensively chart genomic variation during Paulownia breeding, localizing candidate loci governing agronomic traits, and underpinnings of future molecular breeding efforts to boost productivity.


Subject(s)
Genome, Plant , Polymorphism, Single Nucleotide , Selective Breeding , Selection, Genetic , Plant Breeding , Linkage Disequilibrium , Phylogeny
18.
Adv Sci (Weinh) ; 11(24): e2307830, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38588016

ABSTRACT

Reconfiguration of architected structures has great significance for achieving new topologies and functions of engineering materials. Existing reconfigurable strategies have been reported, including approaches based on heat, mechanical instability, swelling, origami/kirigami designs, and electromagnetic actuation. However, these approaches mainly involve physical interactions between the host materials and the relevant stimuli. Herein, a novel, easy-manipulated, and controllable reconfiguration strategy for polymer architectures is proposed by using a chemical reaction of host material within a hydrogel reactive microenvironment. 3D printed polycaprolactone (PCL) lattices transformed in an aqueous polyacrylamide (PAAm) hydrogel precursor solution, in which ultraviolet (UV) light triggered heterogeneous grafting polymerization between PCL and AAm. In situ microscopy shows that PCL beams go through volumetric expansion and cooperative buckling, resulting in transformation of PCL lattices into sinusoidal patterns. The transformation process can be tuned easily and patterned through the adjustment of the PCL beam diameter, unit cell width, and UV light on-off state. Controlling domain formation is achieved by using UV masks. This framework enables the design, fabrication, and programming of architected materials and inspires the development of novel 4D printing approaches.

19.
Bioresour Technol ; 401: 130704, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636879

ABSTRACT

In this study, a SNAD-SBBR process was implemented to achieve ammonia removal and carbon reduction of mature landfill leachate under extremely low dissolved oxygen conditions (0.051 mg/L) for a continuous operation of 266 days. The process demonstrated excellent removal performance, with ammonia nitrogen removal efficiency reaching 100 %, total nitrogen removal efficiency reaching 87.56 %, and an average removal rate of 0.180 kg/(m3·d). The recalcitrant organic compound removal efficiency reached 34.96 %. Nitrogen mass balance analysis revealed that the Anammox process contributed to approximately 98.1 % of the nitrogen removal. Candidatus Kuenenia achieved a relative abundance of 1.49 % in the inner layer of the carrier. In the SNAD-SBBR system, the extremely low DO environment created by the highly efficient partial nitrification stage enabled the coexistence of AnAOB, denitrifying bacteria, and Nitrosomonas, synergistically achieving ammonia removal and carbon reduction. Overall, the SNAD-SBBR process exhibits low-cost and high-efficiency characteristics, holding tremendous potential for landfill leachate treatment.


Subject(s)
Carbon , Denitrification , Nitrification , Nitrogen , Oxygen , Water Pollutants, Chemical , Oxygen/metabolism , Water Pollutants, Chemical/metabolism , Ammonia/metabolism , Bioreactors , Oxidation-Reduction , Biodegradation, Environmental , Water Purification/methods , Bacteria/metabolism , Anaerobiosis
20.
Discov Nano ; 19(1): 68, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38625606

ABSTRACT

The green synthesis of metallic nanoparticles is attributable towards diverse applications in various fields, recently. In this research, we report simple and eco-friendly synthesis of chromium oxide (Cr2O3) nanoparticles using the fruit extract of Phyllanthus emblica as a reducing and capping agent. The absorbance peaks at 350 nm and 450 nm validated the nanoparticle formation in UV-visible spectrum. FTIR spectrum revealed the nature of functional groups. The crystalline properties of nanoparticles were ascertained by XRD analysis. EDX spectrum corroborated the elemental composition of nanoparticles in which chromium and oxygen constituted 68% of total weight. SEM images demonstrated agglomeration of nanoparticles resulting in the formation of large irregularly shaped flakes. Cr2O3 nanoparticles demonstrated excellent antimicrobial properties against 11 bacterial isolates and 1 fungal isolate. The largest inhibition zone (53 mm) was measured against A. baumannii while the smallest inhibition zone (26 mm) was recorded against S. aureus. Minimum inhibitory concentration (MIC) values were < 1 µg/ml for all microbes. However, the synthesized nanoparticles did not reveal synergism with any of the selected antibiotics (FICI values > 1). Nanoparticles possessed potent anti-biofilm powers with maximum (77%) inhibition of E. coli biofilms and minimum (45%) inhibition of S. enterica biofilms. Photocatalytic activity of Cr2O3 nanoparticles was evaluated to determine their efficacy in environmental bioremediation. Outcomes demonstrated degradation of methyl red (84%) but not of methylene blue dye. Furthermore, the Cr2O3 nanoparticles displayed considerable antioxidant (43%) as well as anti-inflammatory (44%) potentials. Hence, the present study accounts for the versatile applications of P. emblica-mediated Cr2O3 nanoparticles which could be pursued for future biomedical and environmental applications.

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