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1.
Zookeys ; 1210: 133-142, 2024.
Article in English | MEDLINE | ID: mdl-39220721

ABSTRACT

Altimella Wang & Zhang, gen. nov., a new genus belonging to Cicurinidae, is established, and two new species are described, Altimellanedong Wang & Zhang, sp. nov. (♂♀, type species) and A.ngamring Wang & Zhang, sp. nov. (♂♀), from Xizang, China. Detailed descriptions of somatic features and genital characteristics, photos of the habitus, photos and drawings of the copulatory organs, and a distribution map are provided.

2.
J Am Chem Soc ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235150

ABSTRACT

To date, it remains challenging to precisely and efficiently construct structurally intriguing polycarbocycles with densely packed stereocenters in organic synthesis. Niduterpenoid B, a naturally occurring ERα inhibitor, exemplifies this complexity with its intricate polycyclic network comprising 5 cyclopentane and 1 cyclopropane rings, featuring 13 contiguous stereocenters, including 4 all-carbon quaternary centers. In this work, we describe the first total synthesis of niduterpenoid B using a structural reorganization strategy. Key features include the following: (1) an efficient methoxy-controlled cascade reaction that precisely forges a highly functionalized tetraquinane (A-D rings) bearing sterically hindered contiguous quaternary stereocenters; (2) a rhodium-catalyzed [1 + 2] cycloaddition that facilitates the construction of a strained 3/5 bicycle (E-F rings) angularly fused with ring D.

3.
BMC Musculoskelet Disord ; 25(1): 703, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227806

ABSTRACT

BACKGROUND: Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. PURPOSE: Investigate the effects of tDCS on pain and physical function in patients with KOA. METHODS: Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. RESULTS: Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. CONCLUSIONS: The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.


Subject(s)
Osteoarthritis, Knee , Pain Measurement , Randomized Controlled Trials as Topic , Transcranial Direct Current Stimulation , Humans , Transcranial Direct Current Stimulation/methods , Osteoarthritis, Knee/therapy , Osteoarthritis, Knee/physiopathology , Treatment Outcome , Pain Measurement/methods , Arthralgia/therapy , Arthralgia/diagnosis , Arthralgia/physiopathology , Arthralgia/etiology , Pain Threshold , Pain Management/methods , Quality of Life , Knee Joint/physiopathology
4.
J Hazard Mater ; 478: 135494, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39141940

ABSTRACT

The widespread use of organophosphate flame retardants (OPFRs), a serious type of pervasive environmental contaminants, has led to a global concern regarding their diverse toxicities to living beings. Using a combination of experimental and theoretical approaches, we systematically studied the adsorption, accumulation, and influence of a series of OPFRs on the lipid membranes of bacteria and cells. Our results revealed that OPFRs can aggregate in lipid membranes, leading to the destruction of membrane integrity. During this process, the molecular structure of the OPFRs is a dominant factor that significantly influences the strength of their interaction with the lipid membrane, resulting in varying degrees of biotoxicity. Triphenyl phosphate (TPHP), owing to its large molecular size and strong hydrophobicity, causes severe membrane disruption through the formation of nanoclusters. The corresponding severe toxicity originates from the phase transitions of the lipid membranes. In contrast, smaller OPFRs such as triethyl phosphate (TEP) and tris(2-chloroethyl) phosphate (TCEP) have weaker hydrophobicity and induce minimal membrane disturbance and ineffective damage. In vivo, gavage of TPHP induced more severe barrier damage and inflammatory infiltration in mice than TEP or TCEP, confirming the higher toxicity of TPHP. Overall, our study elucidates the structure-dependent adsorption of OPFRs onto lipid membranes, highlighting their destructive interactions with membranes as the origin of OPFR toxicity.

5.
Neuromolecular Med ; 26(1): 33, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138706

ABSTRACT

The newly identified estrogen receptor, G protein-coupled receptor 30 (GPR30), is prevalent in the brain and has been shown to provide significant neuroprotection. Recent studies have linked ferroptosis, a newly characterized form of programmed cell death, closely with cerebral ischemia-reperfusion injury (CIRI), highlighting it as a major contributing factor. Consequently, our research aimed to explore the potential of GPR30 targeting in controlling neuronal ferroptosis and lessening CIRI impacts. Results indicated that GPR30 activation not only improved neurological outcomes and decreased infarct size in a mouse model but also lessened iron accumulation and malondialdehyde formation post-middle cerebral artery occlusion (MCAO). This protective effect extended to increased levels of Nrf2 and GPX4 proteins. Similar protective results were replicated in PC12 cells subjected to Oxygen Glucose Deprivation and Reoxygenation (OGD/R) using the GPR30-specific agonist G1. Importantly, inhibition of Nrf2 with ML385 curtailed the neuroprotective effects of GPR30 activation, suggesting that GPR30 mitigates CIRI primarily through inhibition of neuronal ferroptosis via upregulation of Nrf2 and GPX4.


Subject(s)
Ferroptosis , Infarction, Middle Cerebral Artery , Mice, Inbred C57BL , NF-E2-Related Factor 2 , Phospholipid Hydroperoxide Glutathione Peroxidase , Receptors, Estrogen , Receptors, G-Protein-Coupled , Reperfusion Injury , Signal Transduction , Animals , NF-E2-Related Factor 2/metabolism , Reperfusion Injury/prevention & control , Reperfusion Injury/metabolism , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/physiology , Ferroptosis/drug effects , Ferroptosis/physiology , Signal Transduction/drug effects , Mice , PC12 Cells , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Rats , Male , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Disease Models, Animal
6.
World J Clin Cases ; 12(22): 4905-4912, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39109002

ABSTRACT

BACKGROUND: Spastic pelvic floor syndrome (SPFS) is a refractory pelvic floor disease characterized by abnormal (uncoordinated) contractions of the external anal sphincter and puborectalis muscle during defecation, resulting in rectal emptation and obstructive constipation. The clinical manifestations of SPFS are mainly characterized by difficult defecation, often accompanied by a sense of anal blockage and drooping. Manual defecation is usually needed during defecation. From physical examination, it is commonly observed that the patient's anal muscle tension is high, and it is difficult or even impossible to enter with his fingers. AIM: To investigate the characteristics of anorectal pressure and botulinum toxin A injection combined with biofeedback in treating pelvic floor muscle spasm syndrome. METHODS: Retrospective analysis of 50 patients diagnosed with pelvic floor spasm syndrome. All patients underwent pelvic floor surface electromyography assessment, anorectal dynamics examination, botulinum toxin type A injection 100 U intramuscular injection, and two cycles of biofeedback therapy. RESULTS: After the botulinum toxin A injection combined with two cycles of biofeedback therapy, the patient's postoperative resting and systolic blood pressure were significantly lower than before surgery (P < 0.05). Moreover, the electromyography index of the patients in the resting stage and post-resting stages was significantly lower than before surgery (P < 0.05). CONCLUSION: Botulinum toxin A injection combined with biofeedback can significantly reduce pelvic floor muscle tension in treating pelvic floor muscle spasm syndrome. Anorectal manometry is an effective method to evaluate the efficacy of treatment objectively. However, randomized controlled trials are needed.

7.
Chem Commun (Camb) ; 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39177032

ABSTRACT

A catalytic asymmetric α-hydroxylation of pyridinone-fused lactones, containing the core structure of camptothecin, is described. Development of a novel spiropyrrolidine amide (SPA) derived triazolium bromide organo-cation catalyst is crucial for a highly enantioselective oxidation, which also accommodates a wide array of lactones with various substituents. The resulting tricyclic tertiary alcohol with an oxa-quaternary carbon center can be further applied in the synthesis of SN-38 and irinotecan, two anti-cancer drugs derived from camptothecin.

8.
Front Bioeng Biotechnol ; 12: 1461343, 2024.
Article in English | MEDLINE | ID: mdl-39170060

ABSTRACT

The arabinogalactan in the representative softwood biomass of larch was degraded using an environmentally friendly hydrogen peroxide and vitamin C (H2O2-VC) system to improve its immunomodulatory activity. Through the H2O2-VC degradation mechanism, hydroxyl radicals are generated, which then target the hydrogen atoms within polysaccharides, resulting in the breaking of glycosidic bonds. Given the impact of oxidative degradation on polysaccharides, we identified three specific arabinogalactan degradation products distinguished by their arabinosyl side chain compositions. The primary structures of the degradation products were investigated using Fourier-transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. Congo red staining showed that the degradation products were absent in the triple-helix structure. The results of the in vitro immunological experiments indicated that an appropriate reduction in the molar ratio of arabinose to galactose enhanced the immunostimulatory effects on RAW 264.7 cells. In addition, the immunostimulatory pathway mediated by arabinogalactan was explored by toll-like receptor 4 (TLR4) inhibitor (TAK-242) These findings provide novel insights into the understanding of the relationship between the structure of arabinogalactan and its biological activity.

9.
Zhongguo Gu Shang ; 37(8): 808-13, 2024 Aug 25.
Article in Chinese | MEDLINE | ID: mdl-39183006

ABSTRACT

OBJECTIVE: To investigate the clinical efficacy of the placement of the main mechanical support points in the early and middle stages of mechanical repair of femoral head necrosis in preventing collapse of the femoral head. METHODS: A retrospective analysis was performed for 17 cases 22 hips of non-traumatic femoral head necrosis in the early and middle stages from June 2018 to June 2019, including 14 males 18 hips and 3 females 4 hips, aged 34 to 47 years old. Among them, 6 cases were hormonal, 8 were alcoholic and 3 were idiopathic. According to China-Japan Friendship Hospital(CJFH) classification, 9 hip were type L1, 8 were L2, 5 were L3. All cases were given dead bone scraping, autologous iliac granules pressed bone grafting, and allogeneic fibula column support treatment. After surgery, Sanqi Jiegu Pill() was administered orally for 3 months. X-rays of both hips were performed after surgery and follow-up, and the clinical efficacy was evaluated by hip Harris score before and after surgery. RESULTS: All cases were followed up for 24 to 38 months. The Harris score of 22 hips increased from 58 to 77 preoperative to 68 to 94 at the final follow-up. At the final follow-up, 3 hips were excellent, 11 hips were good, 3 hips were acceptable, 5 hips were poor. Two hips of L2 type progressed to ARCO ⅢB stage and continued to be observed, 2 hips of L2 type and 2 hips of L3 type progressed to ARCO Ⅳ stage, and received total hip replacement, and 1 hip infection at 3 months after surgery was given a cement spacer. CONCLUSION: Based on CJFH classification, collapse can be predicted to a certain extent according to the area, volume, location and human biological characteristics of osteonecrosis, and the main mechanical support points are found on this basis to prevent collapse.


Subject(s)
Femur Head Necrosis , Humans , Femur Head Necrosis/surgery , Male , Female , Middle Aged , Adult , Retrospective Studies , Bone Transplantation/methods
10.
J Invest Surg ; 37(1): 2387524, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39191411

ABSTRACT

BACKGROUND: Superior mesenteric artery syndrome (SMAS) is a rare condition, for which laparoscopic surgery was successfully performed safely and with long-term efficacy. METHODS: This single center retrospective clinical study comprised 66 patients with SMAS, surgically treated between January 2010 and January 2020, who were allocated to three different surgical groups according to their medical history and symptoms (Laparoscopic duodenojejunostomy, n = 35; Gastrojejunostomy, n = 16; Duodenojejunostomy plus gastrojejunostomy, n = 15). Patient demographics, surgical data and postoperative outcomes were retrieved from the medical records. RESULTS: All operations were successfully completed laparoscopically, and with a median follow-up of 65 months, the overall symptom score was significantly reduced from 32 to 8 (p < 0.0001) and the BMI was increased from 17.2 kg/m2 to 21.8 kg/m2 (p < 0.0001). CONCLUSIONS: When conservative measures failed in the treatment of SMAS, laparoscopic surgery proved to be a safe and effective method. The specific surgical technique was selected according to the history and symptoms of each individual patient. To our knowledge, this study represents the largest number of laparoscopic procedures at a single center for the treatment of superior mesenteric artery syndrome.


Subject(s)
Laparoscopy , Superior Mesenteric Artery Syndrome , Humans , Superior Mesenteric Artery Syndrome/surgery , Superior Mesenteric Artery Syndrome/etiology , Superior Mesenteric Artery Syndrome/diagnosis , Laparoscopy/methods , Laparoscopy/adverse effects , Female , Male , Retrospective Studies , Middle Aged , Adult , Treatment Outcome , Aged , Gastric Bypass/methods , Gastric Bypass/adverse effects , Duodenostomy/methods , Follow-Up Studies , Postoperative Complications/etiology , Postoperative Complications/epidemiology
11.
Dalton Trans ; 53(34): 14451-14456, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39145540

ABSTRACT

The mechanical properties of halide perovskites have been attracting ever-increasing interest for their significant importance in future industrial applications. However, studies focused on the effect of B-site substitution of molecular perovskites on their mechanical properties are rare, which makes it favorable to shed light on their fundamental structure-mechanical property relationships. Here, using isostructural halide perovskites, [C4H12N2][BCl3]·H2O (B = NH4+; K+), constructed by ionic bonds and hydrogen bonds, respectively, as the model systems, we investigate their mechanical properties through high-pressure synchrotron X-ray diffraction experiments and density functional theory calculations. Owing to the similar sizes of NH4+ and K+, the two compounds possess almost identical cell parameters and frameworks. Upon compression, the two perovskites exhibit analogous behavior except for slight differences in the shrinkage ratio of principal axes and the onset pressure of amorphization. The fitted bulk moduli of [C4H12N2][KCl3]·H2O and [C4H12N2][NH4Cl3]·H2O are 43.89 and 27.28 GPa, respectively. These results demonstrate that the simple replacement of K+ by NH4+ can significantly reduce the structural rigidity of the corresponding compounds, which is ascribed to the weaker strength of NH4⋯Cl hydrogen bonds than that of K-Cl bonds.

12.
Int J Biol Macromol ; 279(Pt 2): 135170, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39214225

ABSTRACT

As the most important phenolic biopolymer in nature, lignin shows promising application potentialities in various bioactivities in vivo and in vitro, mainly including antioxidant, anti-inflammatory, hypolipidemic, and antidiabetic control. In this work, several carbon-based solid acids were synthesized to catalyze the fragmentation of organosolv lignin (OL). The generated lignin fragments, with controllable molecular weight and functional groups, were further evaluated for their application in the prevention and treatment of type 2 diabetes mellitus (T2DM). The results suggested that the urea-doped catalyst (SUPC) showed a more excellent catalytic performance in producing diethyl ether insoluble lignin (DEIL) and diethyl ether soluble lignin (DESL). In addition, the lignin fragments have a good therapeutic effect on the cell model of T2DM. Compared with the insulin resistance model, DEIL obtained by catalytic depolymerization of OL with SUPC could improve the glucose consumption of insulin-resistant cells. Moreover, low-concentration samples (50 µg/mL) can promote glucose consumption (19.7 mM) more than the traditional drug rosiglitazone (17.5 mM). This work demonstrates the prospect of depolymerized lignin for the prevention and treatment of T2DM and provides a new application field for lignin degradation products.

13.
J Dig Dis ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39211938

ABSTRACT

OBJECTIVE: We aimed to investigate the role of forkhead box O1 (FoxO1) inhibitor AS1842856 (AS) in nonalcoholic steatohepatitis (NASH) mice and the potential mechanisms. METHODS: Mice were given methionine-choline-sufficient (MCS), or methionine- and choline-deficient (MCD) diet for 5 weeks, along with AS (60 mg/kg) or vehicle gavage treatment (0.2 mL/day). Body and liver weight, serum triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose and insulin levels were measured. Liver macrophage infiltration and ileal ZO-1 protein expression were also detected. Interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α, sterol regulatory element binding protein (SREBP)-1c, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase), α-smooth muscle actin (SMA), recombinant collagen type III α1 (Col3a1), and connective tissue growth factor (Ctgf) expressions were measured. Stool samples were collected for 16S rDNA sequencing. RESULTS: Compared to the MCD group, AS attenuated liver weight, reduced serum TG, ALT, and AST levels, increased HDL-C levels, mitigated hepatic steatosis, decreased macrophage infiltration, and augmented ileal ZO-1 proteins in NASH mice. It also reduced the levels of IL-6, IL-1ß, and TNF-α, alongside with the Srebp-1c mRNA expression. However, no significant effects on Pepck, G6Pase, α-SMA, Col3a1, or Ctgf were observed. Furthermore, AS promoted diversity and altered gut microbiota composition in NASH mice, causing increased beneficial bacteria like Akkermansia muciniphila, Parabacteroides distasonis, and Prevotellamassilia, which were associated with metabolic functions. CONCLUSION: FoxO1 inhibitor AS ameliorated hepatic steatosis, inflammation, and intestinal dysbiosis in NASH mice, making it a potentially promising treatment for NASH.

14.
J Am Heart Assoc ; 13(17): e033059, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39190571

ABSTRACT

BACKGROUND: Left atrial (LA) fibrosis is a marker of atrial cardiomyopathy and has been reported to be associated with both atrial fibrillation and ischemic stroke. Elucidating this relationship is clinically important as LA fibrosis could serve as a surrogate biomarker of LA cardiomyopathy. The objective of this study is to investigate the association of LA fibrosis and embolic stroke of undetermined source (ESUS) using cardiac magnetic resonance imaging. METHODS AND RESULTS: Following an International Prospective Register of Systematic Reviews-registered protocol, 3 blinded reviewers performed a systematic review for studies that quantified the degree of LA fibrosis in patients with ESUS as compared with healthy patients from inception to February 2024. A meta-analysis was conducted in the mean difference. From 7 studies (705 patients), there was a significantly higher degree of LA fibrosis in patients with ESUS compared with healthy controls (MD, 5.71% [95% CI, 3.55%-7.87%], P<0.01). The degree of LA fibrosis was significantly higher in patients with atrial fibrillation than healthy controls (MD, 8.22% [95% CI, 5.62%-10.83%], P<0.01). A similar degree of LA fibrosis was observed in patients with ESUS compared with patients with atrial fibrillation (MD, -0.92% [95% CI, -2.29% to 0.44%], P=0.35). CONCLUSIONS: A significantly higher degree of LA fibrosis was found in patients with ESUS as compared with healthy controls. This suggests that LA fibrosis may play a significant role in the pathogenesis of ESUS. Further research is warranted to investigate LA fibrosis as a surrogate biomarker of atrial cardiomyopathy and recurrent stroke risk in patients with ESUS.


Subject(s)
Atrial Fibrillation , Fibrosis , Heart Atria , Ischemic Stroke , Humans , Heart Atria/diagnostic imaging , Heart Atria/pathology , Heart Atria/physiopathology , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/etiology , Magnetic Resonance Imaging , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/etiology , Atrial Function, Left , Magnetic Resonance Imaging, Cine/methods
15.
Biomed Mater ; 19(6)2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39208838

ABSTRACT

The invasion and metastasis of tumors pose significant challenges in the treatment of ovarian cancer (OC), making it difficult to cure. One potential treatment approach that has gained attention is the use of matrix metalloproteinase reactive controlled release micelle preparations. In this study, we developed a novel PEG5000-PVGLIG-hyaluronic acid docetaxel/bakuchiol (PP-HA-DTX/BAK) micelles formulation with desirable characteristics such as particle size, narrow polydispersity index, and a ZETA potential of approximately -5 mV. The surface modification with HA facilitates tumor penetration into the tumor interior, while the incorporation of DSPE-PEG2000-PVGLIG-PEG5000helps conceal DSPE-PEG2000-HA, reducing off-target effects and prolonging drug circulation timein vivo. Bothin vitroandin vivoexperiments demonstrated that these micelles effectively inhibit proliferation, invasion, and metastasis of OC cells while promoting apoptosis. Therefore, our findings suggest that PP-HA-DTX/BAK micelles represent a safe and effective therapeutic strategy for treating OC.


Subject(s)
Docetaxel , Micelles , Neoplasm Invasiveness , Ovarian Neoplasms , Phenols , Polyethylene Glycols , Docetaxel/chemistry , Docetaxel/pharmacology , Docetaxel/administration & dosage , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Humans , Animals , Cell Line, Tumor , Polyethylene Glycols/chemistry , Phenols/chemistry , Phenols/pharmacology , Mice , Apoptosis/drug effects , Hyaluronic Acid/chemistry , Taxoids/chemistry , Taxoids/pharmacology , Taxoids/administration & dosage , Cell Proliferation/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Mice, Nude , Particle Size , Mice, Inbred BALB C , Neoplasm Metastasis , Drug Carriers/chemistry
16.
Vaccines (Basel) ; 12(8)2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39203982

ABSTRACT

Yellow fever (YF), caused by the yellow fever virus (YFV), continually spreads and causes epidemics worldwide, posing a great threat to human health. The live-attenuated YF 17D vaccine (YF-17D) has been licensed for preventing YFV infection and administrated via the intramuscular (i.m.) route. In this study, we sought to determine the immunogenicity and protective efficacy of aerosolized YF-17D via the intratracheal (i.t.) route in mice. YF-17D stocks in liquids were successfully aerosolized into particles of 6 µm. Further in vitro phenotype results showed the aerosolization process did not abolish the infectivity of YF-17D. Meanwhile, a single i.t. immunization with aerosolized YF-17D induced robust humoral and cellular immune responses in A129 mice, which is comparable to that received i.p. immunization. Notably, the aerosolized YF-17D also triggered specific secretory IgA (SIgA) production in bronchoalveolar lavage. Additionally, all immunized animals survived a lethal dose of YFV challenge in mice. In conclusion, our results support further development of aerosolized YF-17D in the future.

17.
Liver Int ; 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39037193

ABSTRACT

BACKGROUND AND AIMS: Distinctive gut microbial profiles have been observed between patients with Wilson disease (WD) and healthy individuals. Despite this, the exact relationship and influence of gut microbiota on the advancement of WD-related liver damage remain ambiguous. This research seeks to clarify the gut microbiota characteristics in both human patients and mouse models of WD, as well as their impact on liver injury. METHODS: Gut microbial features in healthy individuals, patients with WD, healthy mice and mice with early- and late-stage WD were analysed using 16S rRNA gene sequencing. Additionally, WD-afflicted mice underwent treatment with either an antibiotic cocktail (with normal saline as a control) or healthy microbiota (using disease microbiota as a control). The study assessed gut microbiota composition, hepatic transcriptome profiles, liver copper concentrations and hepatic pathological injuries. RESULTS: Patients with hepatic WD and mice with WD-related liver injury displayed altered gut microbiota composition, notably with a significant reduction in Lactobacillus abundance. Additionally, the abundances of several gut genera, including Lactobacillus, Veillonella and Eubacterium coprostanoligenes, showed significant correlations with the severity of liver injury in patients with WD. In WD mice, antibiotic treatment or transplantation of healthy microbiota altered the gut microbial structure, increased Lactobacillus abundance and modified the hepatic transcriptional profile. These interventions resulted in reduced hepatic copper concentration and alleviation of WD-related liver injury. CONCLUSIONS: Individuals and mice with pronounced WD-related liver injury exhibited shifts in gut microbial composition. Regulating gut microbiota through healthy microbiota transplantation emerges as a promising therapeutic approach for treating WD-related liver injury.

19.
Plant Genome ; : e20493, 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39073025

ABSTRACT

Powdery mildew, caused by the fungal pathogen Blumeria graminis (DC.) E. O. Speer f. sp. tritici Em. Marchal (Bgt), is a constant threat to global wheat (Triticum aestivum L.) production. Although ∼100 powdery mildew (Pm) resistance genes and alleles have been identified in wheat and its relatives, more is needed to minimize Bgt's fast evolving virulence. In tetraploid wheat (Triticum turgidum L.), wild emmer wheat [T. turgidum ssp. dicoccoides (Körn. ex Asch. & Graebn.) Thell.] accessions from Israel have contributed many Pm resistance genes. However, the diverse genetic reservoirs of cultivated emmer wheat [T. turgidum ssp. dicoccum (Schrank ex Schübl.) Thell.] have not been fully exploited. In the present study, we evaluated a diverse panel of 174 cultivated emmer accessions for their reaction to Bgt isolate OKS(14)-B-3-1 and found that 66% of accessions, particularly those of Ethiopian (30.5%) and Indian (6.3%) origins, exhibited high resistance. To determine the genetic basis of Bgt resistance in the panel, genome-wide association studies were performed using 46,383 single nucleotide polymorphisms (SNPs) from genotype-by-sequencing and 4331 SNPs from the 9K SNP Infinium array. Twenty-five significant SNP markers were identified to be associated with Bgt resistance, of which 21 SNPs are likely novel loci, whereas four possibly represent emmer derived Pm4a, Pm5a, PmG16, and Pm64. Most novel loci exhibited minor effects, whereas three novel loci on chromosome arms 2AS, 3BS, and 5AL had major effect on the phenotypic variance. This study demonstrates cultivated emmer as a rich source of powdery mildew resistance, and the resistant accessions and novel loci found herein can be utilized in wheat breeding programs to enhance Bgt resistance in wheat.

20.
J Pineal Res ; 76(5): e12995, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39073181

ABSTRACT

Melatonin (MT) has been implicated in the plant response to phosphorus (P) stress; however, the precise molecular mechanisms involved remain unclear. This study investigated whether MT controls internal P distribution and root cell wall P remobilization in rice. Rice was treated with varying MT and P levels and analyzed using biochemical and molecular techniques to study phosphorus utilization. The results demonstrated that low P levels lead to a rapid increase in endogenous MT levels in rice roots. Furthermore, the exogenous application of MT significantly improved rice tolerance to P deficiency, as evidenced by the increased biomass and reduced proportion of roots to shoots under P-deficient conditions. MT application also mitigated the decrease in P content regardless in both the roots and shoots. Mechanistically, MT accelerated the reutilization of P, particularly in the root pectin fraction, leading to increased soluble P liberation. In addition, MT enhanced the expression of OsPT8, a gene involved in root-to-shoot P translocation. Furthermore, we observed that MT induced the production of nitric oxide (NO) in P-deficient rice roots and that the mitigating effect of MT on P deficiency was compromised in the presence of the NO inhibitor, c-PTIO, implying that NO is involved in the MT-facilitated mitigation of P deficiency in rice. Overall, our findings highlight the potential of MT as a promising strategy for enhancing rice tolerance to P deficiency and improving P use efficiency in agricultural practices.


Subject(s)
Cell Wall , Melatonin , Nitric Oxide , Oryza , Phosphorus , Plant Roots , Oryza/metabolism , Phosphorus/metabolism , Melatonin/metabolism , Melatonin/pharmacology , Plant Roots/metabolism , Plant Roots/drug effects , Cell Wall/metabolism , Cell Wall/drug effects , Nitric Oxide/metabolism
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