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1.
Skin Res Technol ; 30(7): e13785, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38932455

RESUMO

PURPOSE: The etiology of alopecia areata (AA) in relation to serum lipids remains unclear, thereby prompting our intention to do Mendelian study on this subject. DESIGN: Two-sample Mendelian randomization (MR) analysis was performed in the study. The inverse variance-weighted method was used as the primary method. METHODS: In our study, we integrated a set of 123 single-nucleotide polymorphisms (SNPs) into our analysis. These SNPs have been extensively studied and are known to exhibit associations with serum lipids. We sourced these SNPs from a variety of relevant studies and consortia that specifically focus on lipid-related research, such as the MRC Integrative Epidemiology Unit. These carefully curated SNPs were then utilized as instrumental variables in our analysis, allowing us to explore and evaluate the causal relationships between these genetic variants and serum lipids. By incorporating this comprehensive set of SNPs, we aimed to enhance the precision and robustness of our findings, shedding light on the intricate interplay between genetics and serum lipids. RESULTS: In the MR analysis, a higher total lipid concentration in large low-density lipoprotein (LDL) particles (odds ratio [OR] = 1.502; 95% confidence interval [CI] = 1.086-1.953; p = 0.006), a greater ratio of cholesteryl esters to total lipids in chylomicrons and extremely large very LDL (VLDL) particles (OR = 2.174; 95% CI = 1.300-2.500; p = 0.010), and a greater ratio of cholesterol to total lipids in chylomicrons and extremely large VLDL particles (OR = 2.363;95% CI = 1.556-4.438; p = 0.004), were genetically predicted to be causally associated with an increased risk of AA, while patients with a higher triglyceride to total lipids ratio in chylomicrons and extremely large VLDL particles had a lower risk of AA (OR = 0.481; 95% CI = 0.191-1.270; p = 0.002). CONCLUSION: This study found that serum lipids may be causally implicated in AA.


Assuntos
Alopecia em Áreas , Lipídeos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Alopecia em Áreas/genética , Alopecia em Áreas/sangue , Alopecia em Áreas/epidemiologia , Humanos , Lipídeos/sangue , Predisposição Genética para Doença/genética
2.
Front Nutr ; 11: 1402328, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38938670

RESUMO

Objective: The controlling nutritional status score (CONUT) has been widely used for ascertaining the prognosis of various cancers. However, its use in patients with hematological malignancies remains unclear. This review examined evidence on the utility of CONUT as a prognostic marker for patients with hematological malignancies. Methods: All cohort studies that examined the association between CONUT and outcomes of hematological malignancies and were published on the databases of Embase, Scopus, CENTRAL, Web of Science, and PubMed were searched from the inception of the databases to 30 January 2024. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Results: A total of 23 studies were available for review. A meta-analysis of 22 studies showed that high CONUT was significantly associated with poor OS in patients with hematological malignancies (HR: 1.95 95% CI: 1.62, 2.35 I 2 = 89%). The results remained unchanged on sensitivity and subgroup analyses based on study location, sample size, diagnosis, CONUT cutoff, and the Newcastle-Ottawa Scale score. Only six studies reported data on PFS, and the pooled analysis found that high CONUT was a significant marker for poor PFS in patients with hematological malignancies [hazards ratio (HR): 1.64 95% CI: 1.21, 2.20 I 2 = 70%]. These results, too, maintained significance in the sensitivity analysis. Conclusion: CONUT is an independent predictor of poor OS in patients with hematological malignancies. The results appear to be valid across different cancer types and with different CONUT cutoffs. Scarce data also suggest that CONUT could predict PFS.

3.
Fundam Res ; 4(1): 188-198, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38933843

RESUMO

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

4.
J Hazard Mater ; 476: 134951, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38917628

RESUMO

Mesotrione is a herbicide used in agricultural production; however, its stability and long-term residues pose ecological risks to soil health and subsequent crops. In this research, the strain Amycolatopsis nivea La24 was identified as capable of completely degrading 50 mg∙L-1 mesotrione within 48 h. It exhibited a broad adaptability to various environment and could degrade three sulfonylurea herbicides (nicosulfuron, chlorimuron-methyl, and cinosulfuron). Non-target metabonomic and mass spectrometry demonstrated that La24 strain broke down the mesotrione parent molecule by targeting the ß-diketone bond and nitro group, resulting in the production of five possible degradation products. The differentially expressed genes were significantly enriched in fatty acid degradation, amino acid metabolism, and other pathways, and the differentially metabolites in glutathione metabolism, arginine/proline metabolism, cysteine/methionine metabolism, and other pathways. Additionally, it was confirmed by heterologous expression that nitroreductase was directly involved in the mesotrione degradation, and NDMA-dependent methanol dehydrogenase would increase the resistance to mesotrione. Finally, the intracellular response of La24 during mesotrione degradation was proposed. This work provides insight for a comprehensive understanding of the mesotrione biodegradation mechanism, significantly expands the resources for pollutant degradation, and offers the potential for a more sustainable solution to address herbicide pollution in soil.

5.
Nanoscale Horiz ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38919145

RESUMO

The design and synthesis of highly durable and active electrocatalysts are crucial for improving the hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs). In this work, we present a novel dealloyed nanoporous PtCuNiCoMn multicomponent alloy with ligaments/pores ranging from 2-3 nm, which is in situ encapsulated in a three-dimensional, free-standing nanoporous nanotubular graphene network featuring a pore/tube diameter of ∼200 to 300 nm. This method allows precise control over the noble metal loading and alloy composition while preventing noble metal loss throughout the preparation process. The innovative bimodal nanoporous graphene/alloy structure, coupled with an open 3D spongy morphology, and optimized surface Pt electronic structure through multicomponent interaction, significantly enhances the activity for the HER/ORR, outperforming commercial Pt/C. Moreover, this design addresses the issues of Pt nanoparticle aggregation and detachment from carbon supports that typically exist in Pt/C-type catalysts, thereby substantially improving the catalytic durability, even under intense gas bubbling conditions.

6.
Glia ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899731

RESUMO

Spinal cord injury (SCI) can result in severe motor and sensory deficits, for which currently no effective cure exists. The pathological process underlying this injury is extremely complex and involves many cell types in the central nervous system. In this study, we have uncovered a novel function for macrophage G protein-coupled receptor kinase-interactor 1 (GIT1) in promoting remyelination and functional repair after SCI. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we identified that GIT1 deficiency in macrophages led to an increased generation of tumor necrosis factor-alpha (TNFα), reduced proportion of mature oligodendrocytes (mOLs), impaired remyelination, and compromised functional recovery in vivo. These effects in GIT1 CKO mice were reversed with the administration of soluble TNF inhibitor. Moreover, bone marrow transplantation from GIT1 CWT mice reversed adverse outcomes in GIT1 CKO mice, further indicating the role of macrophage GIT1 in modulating spinal cord injury repair. Our in vitro experiments showed that macrophage GIT1 plays a critical role in secreting TNFα and influences the differentiation of oligodendrocyte precursor cells (OPCs) after stimulation with myelin debris. Collectively, our data uncovered a new role of macrophage GIT1 in regulating the transformation of OPCs into mOLs, essential for functional remyelination after SCI, suggesting that macrophage GIT1 could be a promising treatment target of SCI.

7.
Int Microbiol ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900217

RESUMO

Chlorobenzene (CB), extensively used in industrial processes, has emerged as a significant contaminant in soil and groundwater. The eco-friendly and cost-effective microbial remediation has been increasingly favored to address this environmental challenge. In this study, a degrading bacterium was isolated from CB-contaminated soil at a pesticide plant, identified as Pandoraea sp. XJJ-1 (CCTCC M 2021057). This strain completely degraded 100 mg·L-1 CB and showed extensive degradability across a range of pH (5.0-9.0), temperature (10-37 °C), and CB concentrations (100-600 mg·L-1). Notably, the degradation efficiency was 85.2% at 15 °C, and the strain could also degrade six other aromatic hydrocarbons, including benzene, toluene, ethylbenzene, and xylene (o-, m-, p-). The metabolic pathway of CB was inferred using ultraperformance liquid chromatography, gas chromatography-mass spectrometry, and genomic analysis. In strain XJJ-1, CB was metabolized to o-chlorophenol and 3-chloroxychol by CB monooxygenase, followed by ortho-cleavage by the action of 3-chlorocatechol 1,2-dioxygenase. Moreover, the presence of the chlorobenzene monooxygenation pathway metabolism in strain XJJ-1 is reported for the first time in Pandoraea. As a bacterium with low-temperature resistance and composite pollutant degradation capacity, strain XJJ-1 has the potential application prospects in the in-situ bioremediation of CB-contaminated sites.

8.
Medicine (Baltimore) ; 103(25): e38336, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905383

RESUMO

This study aimed to characterize the risk factors, etiology, clinical manifestations, anatomical characteristics, stroke mechanisms, imaging features, and prognosis of bilateral medial medullary infarction (BMMI). A retrospective analysis was conducted on 11 patients with BMMI who met the inclusion criteria at the Affiliated Hospital of Xuzhou Medical University from January 2013 to January 2023. The patients' imaging and clinical features were analyzed and summarized. Eleven patients (7 male, 4 female), aged 46 to 62 years, met the inclusion criteria. Common clinical presentations included dysarthria (90.9%), dysphagia (90.9%), quadriplegia (81.8%), and so on. Within 72 hours of onset, 8 cases presented with quadriplegia, 2 cases with hemiplegia, and 1 case without limb paralysis. The main risk factor for BMMI was hypertension, followed by diabetes. "Heart appearance" infarcts occurred in 4 cases (36.4%), while "Y appearance" infarcts occurred in 7 cases (63.6%). Among the patients, 3 had unilateral vertebral artery stenosis or occlusion, 5 had bilateral vertebral artery stenosis or occlusion, 2 had normal vertebral basilar artery, and 1 did not undergo cerebrovascular examination. All patients received standardized treatment for cerebral infarction. The prognosis was poor, with 81.8% of patients having an unfavorable outcome, including 1 death, 9 cases of disability, and only 1 patient achieving self-care ability after recovery. BMMI is more prevalent in males aged 45 to 60 years. The main risk factors are hypertension and diabetes. Atherosclerosis is the primary etiological subtype. The main clinical manifestations are dyskinesia, dizziness, quadriplegia, and dysarthria. The prognosis of BMMI is poor. The specific imaging features of "heart appearance" or "Y appearance" infarcts aid in the diagnosis of BMMI.


Assuntos
Infartos do Tronco Encefálico , Bulbo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Bulbo/irrigação sanguínea , Bulbo/patologia , Bulbo/diagnóstico por imagem , Infartos do Tronco Encefálico/diagnóstico por imagem , Fatores de Risco , Prognóstico , Quadriplegia/etiologia , Hipertensão/complicações , Hipertensão/epidemiologia
9.
Angew Chem Int Ed Engl ; : e202408792, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850105

RESUMO

The abnormal fluctuation of temperature in vivo usually reflects the progression of inflammatory diseases. Noninvasive, real-time, and accurate monitoring and imaging of temperature variation in vivo is advantageous for guiding the early diagnosis and treatment of disease, but it remains difficult to achieve. Herein, we developed a temperature-activated near-infrared-II fluorescence (NIR-II FL) and surface-enhanced Raman scattering (SERS) nanoprobe for long-term monitoring of temperature changes in rat arthritis and timely assessment of the status of osteoarthritis. The thermosensitive polymer bearing NIR-II FL dye was grafted onto the surface of nanoporous core-satellite gold nanostructures to form the nanoprobe, wherein the nanoprobe contains NIR-II FL and Raman reference signals that are independent of temperature change. The ratiometric FL1150/FL1550 and S1528/S2226 values of the nanoprobe exhibited a reversible conversion with temperature changes. The nanoprobe accurately distinguishes the temperature variations in the inflamed joint versus the normal joint in vivo by ratiometric FL and SERS imaging, allowing for an accurate diagnosis of inflammation. Meanwhile, it can continuously monitor fluctuations in temperature over an extended period during the onset and treatment of inflammation. The tested temperature change trend could be used as an indicator for early diagnosis of inflammation and real-time evaluation of therapeutic effects.

10.
J Oleo Sci ; 73(7): 943-952, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38945923

RESUMO

Eleven kinds of Camellia oleifera seed oils (CSOs) were evaluated in terms of chemical constituents, antioxidant activities, acid value (AV) as well as peroxide value (POV). These CSOs contained abundant ß-sitosterol, squalene, α-tocopherol and phenolics, in which the squalene was the distinct constituent with the content between 45.8±0.8 and 184.1±5.5 mg/kg. The ß-sitosterol ranging from 143.7±4.8 to 1704.6±72.0 mg/kg contributed a considerable content to total accompaniments. Palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid were present in these CSOs, in which the dominant fatty acid was oleic acid with the content between 59.66±0.72 and 82.89±2.16 g/100 g. The AV ranged from 0.1±0.0 to 1.3±0.0 mg KOH/g, and the POV was between 0.1±0.0 and 1.0±0.0 g/100 g. These CSOs showed antioxidant activity based on DPPH and ABTS radical scavenging assay. Both α-tocopherol and ß-sitosterol contents showed a positive correlation with DPPH and ABTS values, respectively, while the α-tocopherol content showed a negative correlation with AV. These results suggested that CSO can be categorized into high oleic acid vegetable oil with abundant active constituents, of which the quality presented variation among different origins. These accompaniments may contribute to the delay of its quality deterioration.


Assuntos
Antioxidantes , Camellia , Ácido Oleico , Óleos de Plantas , Sementes , Sitosteroides , Esqualeno , alfa-Tocoferol , Camellia/química , Antioxidantes/análise , Óleos de Plantas/química , Óleos de Plantas/análise , Sitosteroides/análise , Sementes/química , Esqualeno/análise , China , alfa-Tocoferol/análise , Ácido Oleico/análise , Fenômenos Químicos , Ácidos Graxos/análise , Ácido Palmítico/análise , Fenóis/análise , Ácido Linoleico/análise , Peróxidos/análise
11.
Heliyon ; 10(10): e31560, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38826722

RESUMO

Background: Elderly patients with multimorbidity are at higher risk of greater healthcare costs and poor outcomes due to decreased physical function. The aim of this study was to investigate the impact of infection on healthcare costs and poor outcomes in elderly hospitalized patients with multimorbidity. Methods: We retrospectively enrolled 264 patients who met the inclusion criteria from the department of geriatrics of a large public hospital in Shanghai, China between January 2020 and December 2020. Patients were divided into two groups based on whether they had infection [infection present on admission (IPOA) or healthcare-associated infection(HAI)]. We recorded the basic information and follow-up information of all patients. The follow-up information included 30-day and 1-year all-cause readmission and mortality. Then we analyzed the association between infection and healthcare costs and clinical outcomes. Results: Among 264 subjects, 47.73 % of them achieved IPOA or HAI. The 30-day poor outcomes rate was 45.45 %, and the 1-year poor outcomes rate was 78.41 %. Compared with subjects without infection, the number of drugs and the disease burden were greater in subjects with infection(P < 0.001). Subjects with infection had longer length of hospital stay(P < 0.001) and had greater healthcare cost(P < 0.001). Moreover, subjects with infection had higher poor outcomes rates of 30-day and 1-year(P < 0.001). Infection could predict greater total cost [odds ratio (OR): 1.32, 95 % CI: 1.18,1.49,P < 0.001], nursing cost(OR: 11.45, 95 % CI: 3.49,37.63,P < 0.001), and medicine cost (OR: 2.37, 95 % CI: 1.70,3.31,P < 0.001). In addition, infection was also independently associated with the 30-day poor outcomes rate(OR:3.07, 95%CI: 1.80,5.24,P < 0.001), but we found no association between infection and 1-year poor outcomes rate(OR:1.43, 95 % CI:0.73,2.79,P = 0.300) after adjustment. Conclusions: Infection was a risk factor for higher healthcare cost and 30-day poor outcome rate in elderly hospitalized patients with multimorbidity.

12.
Poult Sci ; 103(7): 103814, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38718538

RESUMO

Yolk Peritonitis can lead to a rapid decline in egg production, which seriously affects the health of laying hens and the profitability of chicken farms. Escherichia coli (E. coli) is the most common cause of yolk peritonitis in laying hens. In this study, bacterial samples were collected from the ovaries and fallopian tubes of laying hens with suspected yolk peritonitis from a laying farm in Jiangsu Province, and their pathogenicity and drug resistance were investigated. Initially, morphological and biochemical detection methods were employed to isolate and identify the pathogenic bacteria. The results showed that a total of 16 strains of E. coli were isolated from laying hens with yolk peritonitis. Subsequently, the drug resistance and pathogenicity of a randomly selected E. coli strain were analyzed and predicted by genome sequencing technology, and the drug resistance of E. coli was verified by drug sensitivity test and PCR. Finally, the virulence was verified by infection experiment in mice. The study revealed that the egg-yolk peritonitis in laying hens was caused by E. coli infection, and the genome sequencing analysis revealed that the bacteria had multidrug resistance and high virulence. The drug susceptibility testing indicates that E. coli exhibited resistance to aminoglycosides, ß-lactam, macrolides, fluoroquinolones, and sulfonamides. In this study, resistance genes including KdpE, aadA5, APH(3 ")-ID, APH(6)-ID, and TEM-1 were identified, and their expression levels varied across different stages of bacterial growth. The results of virulence analysis indicated a mortality rate of 50% in mice infected with E. coli at a concentration of 2.985 × 107 CFU/mL. E. coli infection resulted in damage to various tissues and organs in mice, with the intestinal tissue structure being the most severely affected. This study provides a reference for the study of drug resistance mechanisms in E. coli and provides valuable insights into the selection of drugs for the treatment of vitelline peritonitis.


Assuntos
Antibacterianos , Galinhas , Infecções por Escherichia coli , Escherichia coli , Peritonite , Doenças das Aves Domésticas , Animais , Peritonite/microbiologia , Peritonite/veterinária , Peritonite/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/fisiologia , Escherichia coli/patogenicidade , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/microbiologia , Doenças das Aves Domésticas/microbiologia , Feminino , Antibacterianos/farmacologia , Virulência , Camundongos , Farmacorresistência Bacteriana , Gema de Ovo
13.
Int J Med Sci ; 21(6): 1103-1116, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774759

RESUMO

Background: Colorectal cancer (CRC) has a high morbidity and mortality. Ferroptosis is a phenomenon in which metabolism and cell death are closely related. The role of ferroptosis-related genes in the progression of CRC is still not clear. Therefore, we screened and validated the ferroptosis-related genes which could determine the prevalence, risk and prognosis of patients with CRC. Methods: We firstly screened differentially expressed ferroptosis-related genes by The Cancer Genome Atlas (TCGA) database. Then, these genes were used to construct a risk-score model using the least absolute shrinkage and selection operator (LASSO) regression algorithm. The function and prognosis of the ferroptosis-related genes were confirmed using multi-omics analysis. The gene expression results were validated using publicly available databases and qPCR. We also used publicly available data and ferroptosis-related genes to construct a prognostic prediction nomogram. Results: A total of 24 differential expressed genes associated with ferroptosis were screened in this study. A three-gene risk score model was then established based on these 24 genes and GPX3, CDKN2A and SLC7A11 were selected. The significant prognostic value of this novel three-gene signature was also assessed. Furthermore, we conducted RT-qPCR analysis on cell lines and tissues, and validated the high expression of CDKN2A, GPX3 and low expression of SLC7A11 in CRC cells. The observed mRNA expression of GPX3, CDKN2A and SLC7A11 was consistent with the predicted outcomes. Besides, eight variables including selected ferroptosis related genes were included to establish the prognostic prediction nomogram for patients with CRC. The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations. Also, the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the nomogram. Conclusions: The present study constructed and validated a novel ferroptosis-related three-gene risk score signature and a prognostic prediction nomogram for patients with CRC. Also, we screened and validated the ferroptosis-related genes GPX3, CDKN2A, and SLC7A11 which could serve as novel biomarkers for patients with CRC.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Biomarcadores Tumorais , Neoplasias Colorretais , Ferroptose , Regulação Neoplásica da Expressão Gênica , Nomogramas , Humanos , Ferroptose/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Prognóstico , Biomarcadores Tumorais/genética , Sistema y+ de Transporte de Aminoácidos/genética , Masculino , Feminino , Inibidor p16 de Quinase Dependente de Ciclina/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Idoso
14.
Inorg Chem ; 63(23): 10585-10593, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38798023

RESUMO

Solid electrolytes with high ionic conductivity and satisfactory electrochemical stability are essential for the development of solid-state batteries. However, current strategies, including polymer (and polymer-based composite) electrolytes, still face challenges in meeting the bar set by real operations. We seek to improve the Li-ion conduction of the electrolytes by incorporating mesoporous metal-organic frameworks (MOFs) into the polymer matrix. Specifically, MOFs with pores larger than 3.0 nm are constructed by three-component reactions that involve the construction of both coordinative and dynamic imine linkages. The MOFs allow polymer penetration and amorphization and efficient lithium salt dissociation in the confined channels. Numerous metal sites and organic functionalities in the MOF backbone further assist the ion migration by providing strong interactions with the fluorinated polymer and the Li+. Remarkable ionic conductivity (0.95 mS cm-1) and a large lithium transference number (0.64) are achieved. Overall, the study fully utilizes both the MOF structural units with atomic precision and the encompassed space at the mesoscale for solid-state electrolyte development.

15.
Mol Ther ; 32(7): 2248-2263, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38796708

RESUMO

Acute kidney injury (AKI) is a major worldwide health concern that currently lacks effective medical treatments. PSMP is a damage-induced chemotactic cytokine that acts as a ligand of CCR2 and has an unknown role in AKI. We have observed a significant increase in PSMP levels in the renal tissue, urine, and plasma of patients with AKI. PSMP deficiency improved kidney function and decreased tubular damage and inflammation in AKI mouse models induced by kidney ischemia-reperfusion injury, glycerol, and cisplatin. Single-cell RNA sequencing analysis revealed that Ly6Chi or F4/80lo infiltrated macrophages (IMs) were a major group of proinflammatory macrophages with strong CCR2 expression in AKI. We observed that PSMP deficiency decreased CCR2+Ly6Chi or F4/80lo IMs and inhibited M1 polarization in the AKI mouse model. Moreover, overexpressed human PSMP in the mouse kidney could reverse the attenuation of kidney injury in a CCR2-dependent manner, and this effect could be achieved without CCL2 involvement. Extracellular PSMP played a crucial role, and treatment with a PSMP-neutralizing antibody significantly reduced kidney injury in vivo. Therefore, PSMP might be a therapeutic target for AKI, and its antibody is a promising therapeutic drug for the treatment of AKI.


Assuntos
Injúria Renal Aguda , Modelos Animais de Doenças , Macrófagos , Receptores CCR2 , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Receptores CCR2/metabolismo , Receptores CCR2/genética , Animais , Camundongos , Humanos , Macrófagos/metabolismo , Masculino , Rim/metabolismo , Rim/patologia , Camundongos Knockout , Traumatismo por Reperfusão/metabolismo
16.
Oral Oncol ; 154: 106867, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797001

RESUMO

OBJECTIVE: To investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with anti-PD-1 immunotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: A total of 217 patients diagnosed with LA-NPC at the First Affiliated Hospital of Nanchang University, including 67 who received IC combined with anti-PD-1 and 150 who received IC, were retrospectively enrolled. Efficacy was evaluated at the end of the IC cycles and one month after radiotherapy based on RECIST v1.1 criteria. Acute toxicities were graded based on the CTCAE v5.0 criteria. Quantitative variables were compared by unpaired t-tests, and categorical variables were evaluated by Fisher Freeman-Halton test or Pearson Chi-square test. RESULTS: At the end of all induction therapy cycles, the objective response rate (ORR) of the IC + anti-PD-1 group was 88.1 % (59/67) as opposed to 70.0 % (105/150) in the IC group. Subgroup analysis showed that patients in both stage Ⅲ and ⅣA achieved a significant improvement in ORR with the inclusion of anti-PD-1 therapy. Patients with T3-4 or N2-3 category appeared to benefit more from anti-PD-1 compared to patients with T1-2 or N0-1 category. However, neither ORR nor the complete response (CR) rate was significantly different between the two treatment groups one month after the end of radiotherapy. In addition, the frequency of Grade 3-4 adverse events were also similar in both groups. CONCLUSIONS: IC combined with anti-PD-1 immunotherapy significantly improved the ORR of LA-NPC patients after induction therapy compared to IC alone.


Assuntos
Quimioterapia de Indução , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Receptor de Morte Celular Programada 1 , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Quimioterapia de Indução/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/terapia , Adulto , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Resultado do Tratamento , Adulto Jovem
17.
Data Brief ; 54: 110441, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38708295

RESUMO

The Diptera insects have important ecological functions. Many plants rely on Diptera insects for pollination, and they play an important role in Co-evolution with plants. We described the detailed characteristics across the complete mitogenome sequences of Desmometopa sabroskyi Brake, 2003 (Diptera: Milichiidae) and an unidentified species of Gampsocera (Diptera: Chloropidae), which are pollinators of orchid species. Sequences were assembled and annotated using the reference genomes of Phyllomyza sp. (OP612805) and Elachiptera insignis (OP612812) available in Genbank. The complete mitogenomes of D. sabroskyi and Gampsocera sp. are 15,841 bp and 16,036 bp in length, respectively. Both mitogenomes include 37 genes consisting of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and one noncoding region (NCR). The mitogenome data would better contribute to species identification, taxonomy, phylogenetics, and evolutionary analysis of Diptera insects. .

18.
Nat Commun ; 15(1): 4296, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769295

RESUMO

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Ferroptose , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transporte de Elétrons/efeitos dos fármacos , Simulação de Acoplamento Molecular , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Animais , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Camundongos
19.
Plants (Basel) ; 13(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732443

RESUMO

Research on Satyrium nepalense var. ciliatum (Lindl.) Hook. f. has primarily focused on populations in Northwestern Yunnan, with limited studies on pollination syndromes and insect behavior. In addition, it is geographically limited in its breeding system studies. Here, pollination syndromes, florivory, and breeding systems of S. nepalense var. ciliatum from Liangwang Mountain (Central Yunnan, China) were investigated through field work, microscope, scanning electron microscope (SEM), and parafin section. It was revealed that the pollination syndrome was possessing out-crossing, such as bright color, a developed rostellum, nectar glands in the spur, and food hairs at the lip base. The color and nectar attracted flower visitors, and florivory was observed. Some flower visitors pollinated their companion species. Ants were identified as floral visitors for the first time in Satyrium, although substantial pollination was not observed. Ants might be potential pollinators. S. nepalense var. ciliatum possessed a mixed breeding system, including selfing, out-crossing, and apomixis, with apomixis being predominant in nature. It is suggested that the pollination syndrome, florivory, and pollination competition would contribute to its mixed breeding systems, particularly leading to the occurrence of apomixis.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38729032

RESUMO

Body color is an important visual indicator of crustacean quality and plays a major role in consumer acceptability, perceived quality, and the market price of crustaceans. The freshwater prawn (Macrobrachium rosenbergii) has two distinct phenotypic variations, characterized by dark blue and light yellow body colors. However, the underlying mechanisms regulating the body color of M. rosenbergii remain unclear. In this study, the composition of shell color parameters and pigment cells of raw and cooked dark blue and light yellow M. rosenbergii was investigated and the mechanisms associated with body color were elucidated by transcriptome analysis. The results showed significant differences in the raw shells of the dark blue and light yellow M. rosenbergii (L: 26.20 ± 0.53 vs. 29.25 ± 0.45; a: -0.88 ± 0.19 vs. 0.35 ± 0.18; b: 1.73 ± 0.20 vs. 3.46 ± 0.37; dE: 70.33 ± 0.53 vs. 67.34 ± 0.45, respectively, p = 0.000) as well as the cooked shells (L: 58.14 ± 0.81 vs. 55.78 ± 0.55; a: 19.30 ± 0.56 vs. 16.42 ± 0.40; b: 23.60 ± 0.66 vs. 20.30 ± 0.40, respectively, p < 0.05). Transcriptome differential gene analysis obtained 39.02 Gb of raw data and 158,026 unigenes. Comprehensive searches of the SwissProt, Nr, KEGG, Pfam, and KOG databases resulted in successful annotations of 23,902 (33 %), 40,436 (25.59 %), 32,015 (20.26 %), 26,139 (16.54 %), and 22,155 (14.02 %) proteins, respectively. By KEGG pathway analysis, numerous differentially expressed genes were related to pigmentation-related pathways (MAPK signaling pathway, Wnt signaling pathway, melanin production, tyrosine metabolism, and cell-cell communication process). Candidate DEGs that may be involved in body color included apolipoprotein D, crustacyanin, cytochrome P450, and tyrosinase, as verified by quantitative real-time PCR. The results of this study provide useful references to further elucidate the molecular mechanisms of color formation of M. rosenbergii and other crustaceans.


Assuntos
Perfilação da Expressão Gênica , Palaemonidae , Pigmentação , Transcriptoma , Animais , Palaemonidae/genética , Pigmentação/genética , Proteínas de Artrópodes/genética , Exoesqueleto/metabolismo , Cor
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