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1.
Front Cell Dev Biol ; 12: 1415258, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144255

RESUMEN

Background: Tuberous sclerosis is a multi-system disorder caused by mutations in either TSC1 or TSC2. The majority of affected patients (85%-90%) have heterozygous variants, and a smaller number (around 5%) have mosaic variants. Despite using various techniques, some patients still have "no mutation identified" (NMI). Methods: We hypothesized that the causal variants of patients with NMI may be structural variants or deep intronic variants. To investigate this, we sequenced the DNA of 26 tuberous sclerosis patients with NMI using targeted long-read sequencing. Results: We identified likely pathogenic/pathogenic variants in 13 of the cases, of which 6 were large deletions, four were InDels, two were deep intronic variants, one had retrotransposon insertion in either TSC1 or TSC2, and one was complex rearrangement. Furthermore, there was a de novo Alu element insertion with a high suspicion of pathogenicity that was classified as a variant of unknown significance. Conclusion: Our findings expand the current knowledge of known pathogenic variants related to tuberous sclerosis, particularly uncovering mosaic complex structural variations and retrotransposon insertions that have not been previously reported in tuberous sclerosis. Our findings suggest a higher prevalence of mosaicism among tuberous sclerosis patients than previously recognized. Our results indicate that long-read sequencing is a valuable approach for tuberous sclerosis cases with no mutation identified (NMI).

2.
Org Biomol Chem ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39143911

RESUMEN

A visible light-induced difluoroalkylation/heteroarylation of [1.1.1]propellane with nitrogen containing heterocycles and difluoroiodane(III) reagents was achieved. Various heteroarenes and difluoroiodane(III) reagents exhibited good compatibility, yielding the desired products in moderate to good yields. The accessibility of the reagents and the mild reaction conditions establish this method as an alternative and practical strategy for accessing diverse 1-difluoroalkyl-3-heteroaryl bicyclo[1.1.1]pentanes (BCPs).

3.
Front Genet ; 15: 1421565, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39130747

RESUMEN

Accurate haplotyping facilitates distinguishing allele-specific expression, identifying cis-regulatory elements, and characterizing genomic variations, which enables more precise investigations into the relationship between genotype and phenotype. Recent advances in third-generation single-molecule long read and synthetic co-barcoded read sequencing techniques have harnessed long-range information to simplify the assembly graph and improve assembly genomic sequence. However, it remains methodologically challenging to reconstruct the complete haplotypes due to high sequencing error rates of long reads and limited capturing efficiency of co-barcoded reads. We here present a pipeline, AsmMix, for generating both contiguous and accurate diploid genomes. It first assembles co-barcoded reads to generate accurate haplotype-resolved assemblies that may contain many gaps, while the long-read assembly is contiguous but susceptible to errors. Then two assembly sets are integrated into haplotype-resolved assemblies with reduced misassembles. Through extensive evaluation on multiple synthetic datasets, AsmMix consistently demonstrates high precision and recall rates for haplotyping across diverse sequencing platforms, coverage depths, read lengths, and read accuracies, significantly outperforming other existing tools in the field. Furthermore, we validate the effectiveness of our pipeline using a human whole genome dataset (HG002), and produce highly contiguous, accurate, and haplotype-resolved assemblies. These assemblies are evaluated using the GIAB benchmarks, confirming the accuracy of variant calling. Our results demonstrate that AsmMix offers a straightforward yet highly efficient approach that effectively leverages both long reads and co-barcoded reads for haplotype-resolved assembly.

4.
Bioact Mater ; 41: 46-60, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39101027

RESUMEN

Hydrogels are promising materials for wound protection, but in wet, or underwater environments, the hydration layer and swelling of hydrogels can seriously reduce adhesion and limit their application. In this study, inspired by the structural characteristics of strong barnacle wet adhesion and combined with solvent exchange, a robust wet adhesive hydrogel (CP-Gel) based on chitosan and 2-phenoxyethyl acrylate was obtained by breaking the hydration layer and resisting swelling. As a result, CP-Gel exhibited strong wet adhesion to various interfaces even underwater, adapted to joint movement and skin twisting, resisted sustained rushing water, and sealed damaged organs. More importantly, on-demand detachment and controllable adhesion were achieved by promoting swelling. In addition, CP-Gel with good biosafety significantly promotes seawater-immersed wound healing and is promising for use in water-contact wound care, organ sealing, and marine emergency rescue.

5.
Microbiol Spectr ; : e0100424, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101825

RESUMEN

Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = -0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = -0.4451) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = -0.3868) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.

6.
J Colloid Interface Sci ; 677(Pt A): 873-882, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39126805

RESUMEN

The construction of S-scheme heterojunctions, which offers a promising approach for spatially separating photogenerated charge carriers with high redox potentials and multimolecular activation, represents a viable modification strategy in photocatalytic applications. However, the prevalent insufficient contact areas between two components result in low interface charge transfer efficiency, thereby impeding the photocatalytic performance of such heterostructures. Herein, we address this limitation by introducing a unique mCN@mPDIP molecular heterojunction through a pH-triggered molecule self-assembly eutectoid technique, enabling intimate interface contact and promoting highly efficient interfacial charge transfer following an S-scheme mechanism. Consequently, the mCN@mPDIP molecular heterojunction achieves significantly improved charge separation efficiency and higher concentration of active carriers compared to typical bCN-bPDIP bulk heterojunction and nCN/nPDIP nano heterojunction. Combined with the effective sulfide activation on mPDIP sites and O2 activation on mCN sites, the resulting mCN@mPDIP demonstrates outstanding activity in the photocatalytic aerobic oxidation of sulfides into sulfoxides without any redox mediators.

7.
Org Biomol Chem ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39105651

RESUMEN

A visible-light-induced tandem reaction involving quinoxalin-2(1H)-ones, alkenes, and sulfonyl chlorides, catalyzed by 4CzIPN, was developed. The utilization of easily accessible sulfonyl chlorides, metal-free conditions, and a wide substrate scope established this protocol as an efficient and alternative method for obtaining sulfonated quinoxalin-2(1H)-ones.

8.
Traffic ; 25(7): e12952, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39073202

RESUMEN

SNX32 is a member of the evolutionarily conserved Phox (PX) homology domain- and Bin/Amphiphysin/Rvs (BAR) domain- containing sorting nexin (SNX-BAR) family of proteins, which play important roles in sorting and membrane trafficking of endosomal cargoes. Although SNX32 shares the highest amino acid sequence homology with SNX6, and has been believed to function redundantly with SNX5 and SNX6 in retrieval of the cation-independent mannose-6-phosphate receptor (CI-MPR) from endosomes to the trans-Golgi network (TGN), its role(s) in intracellular protein trafficking remains largely unexplored. Here, we report that it functions in parallel with SNX1 in mediating epidermal growth factor (EGF)-stimulated postendocytic trafficking of the epidermal growth factor receptor (EGFR). Moreover, SNX32 interacts directly with EGFR, and recruits SNX5 to promote sorting of EGF-EGFR into multivesicular bodies (MVBs) for lysosomal degradation. Thus, SNX32 functions distinctively from other SNX-BAR proteins to mediate signaling-coupled endolysosomal trafficking of EGFR.


Asunto(s)
Factor de Crecimiento Epidérmico , Receptores ErbB , Lisosomas , Transporte de Proteínas , Nexinas de Clasificación , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genética , Receptores ErbB/metabolismo , Lisosomas/metabolismo , Humanos , Transporte de Proteínas/fisiología , Factor de Crecimiento Epidérmico/metabolismo , Células HeLa , Endosomas/metabolismo , Red trans-Golgi/metabolismo , Cuerpos Multivesiculares/metabolismo
9.
Int J Ophthalmol ; 17(7): 1193-1204, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39026925

RESUMEN

AIM: To address the challenges of data labeling difficulties, data privacy, and necessary large amount of labeled data for deep learning methods in diabetic retinopathy (DR) identification, the aim of this study is to develop a source-free domain adaptation (SFDA) method for efficient and effective DR identification from unlabeled data. METHODS: A multi-SFDA method was proposed for DR identification. This method integrates multiple source models, which are trained from the same source domain, to generate synthetic pseudo labels for the unlabeled target domain. Besides, a softmax-consistence minimization term is utilized to minimize the intra-class distances between the source and target domains and maximize the inter-class distances. Validation is performed using three color fundus photograph datasets (APTOS2019, DDR, and EyePACS). RESULTS: The proposed model was evaluated and provided promising results with respectively 0.8917 and 0.9795 F1-scores on referable and normal/abnormal DR identification tasks. It demonstrated effective DR identification through minimizing intra-class distances and maximizing inter-class distances between source and target domains. CONCLUSION: The multi-SFDA method provides an effective approach to overcome the challenges in DR identification. The method not only addresses difficulties in data labeling and privacy issues, but also reduces the need for large amounts of labeled data required by deep learning methods, making it a practical tool for early detection and preservation of vision in diabetic patients.

10.
Heliyon ; 10(13): e33693, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39040267

RESUMEN

The prevention of chronic wound formation has already been a primary subject in wound management, particularly for deep wounds. The electrospun nanofiber membranes hold tremendous potential in the prevention of chronic wounds due to their micro/nano pore structures. Currently, many natural and synthetic materials have been utilized in the fabrication of nanofiber membranes. However, striking a balance between the structural stability and the biocompatibility remains challenging. It is necessary not only to ensure the long-term durability of nanofiber membranes but also to enhance their biocompatibility for alleviating patients' suffering. In this study, we reported a nanofiber membrane dressing with excellent biocompatibility and mechanical properties, which is potential for the treatment of deep wounds. The basal material chosen for the preparation of the nanofiber membrane was a co-polyester (NI-LPGD5) synthesized by non-isocyanate polyurethane (NIPU) and polyglycolic acid with a dihydroxy structure (LPGD-synthesized from glycolic acid and neopentyl glycol). Moreover, curcumin was also added as a bioactive substance to enhance the pro-healing effect of dressings. The physicochemical properties of the prepared nanofiber membranes were characterized through various physicochemical tools. Our results demonstrated that the NI-LPGD5 co-polymer can be electrospun into smooth fibers. Meanwhile, curcumin-loaded nanofiber membranes (Cur/NI-LPGD5) also exhibited a favorable microscopic morphology. The fabricated membranes exhibited suitable mechanical properties, outstanding hygroscopic-swelling rate and water vapor transmittance. Besides, in vitro cell culturing, the cells on the NI-LPGD5 membrane maintained their maximum viability. The potential of in vivo wound healing was further demonstrated through animal experiments. The experimental results showed that the nanofiber membranes effectively prevented chronic wounds from forming and promoted granulation tissue growth without replacing the dressing throughout the healing process. We also found that these nanofiber membranes could effectively promote the expression of related biomarkers to accelerate wound healing, particularly the Cur/NI-LPGD5 membrane. In conclusion, the fabricated membranes possess suitable physicochemical properties and promising bioactivity. As a result, it effectively prevented the formation of chronic wounds and demonstrated significant potential in reducing the frequency of dressing changes.

11.
Artículo en Inglés | MEDLINE | ID: mdl-39031849

RESUMEN

GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator (class I) that is co-administered with ritonavir to maintain the anticipated concentration required for the effective antiviral activity of GLS4. In this study, the first physiologically-based pharmacokinetic (PBPK) model for GLS4/ritonavir was successfully developed. The predictive performance of the PBPK model was verified using data from 39 clinical studies, including single-dose, multiple-dose, food effects, and drug-drug interactions (DDI). The PBPK model accurately described the PK profiles of GLS4 and ritonavir, with predicted values closely aligning with observed data. Based on the verified GLS4/ritonavir model, it prospectively predicts the effect of hepatic impairment (HI) and DDI on its pharmacokinetics (PK). Notably, CYP3A4 inducers significantly influenced GLS4 exposure when co-administered with ritonavir; co-administered GLS4 and ritonavir significantly influenced the exposure of CYP3A4 substrates. Additionally, with the severity of HI increased, there was a corresponding increase in the exposure to GLS4 when co-administered with ritonavir. The GLS4/ritonavir PBPK model can potentially be used as an alternative to clinical studies or guide the design of clinical trial protocols.

12.
Cytokine ; 182: 156718, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39084067

RESUMEN

OBJECTIVE: To investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters. METHODS: The remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated. RESULTS: The r2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1ß and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05). CONCLUSION: There are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches.

13.
Clin Lab ; 70(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38965951

RESUMEN

BACKGROUND: Sexually transmitted infections (STIs) increase gradually and have become a public health problem in the world. UU, CT, NG, and MG are four common STI pathogens. Our retrospective study analyzed the clinical situation and the laboratory data of patients infected with the four pathogens. The prevalence of the four pathogens, detected in urine and genital tract secretion, was studied in Hangzhou, China. METHODS: A total of 3,168 male and female patients were randomly selected from February 2023 to February 2024. Urine and genital secretions were collected, and four STI pathogens were controlled for detection. Data were collected from the hospital's electronic medical records, and SPSS 25.0 software was used to perform a statistical analysis. RESULTS: Among 3,168 patients, a total of 1,527 were detected as positive, and the positive rate was 48.20%. The age of patients ranged from 13 - 98 years, with an average age of 45.6. The total of patients consisted of 2,191 males and 977 females, which had a significant difference (p < 0.05). Specimens were mainly collected from the Department of Dermatovenerology, Urological Surgery, Obstetrics and Gynecology, and so on. The positive rate was statistically different between male and female patients (p < 0.05). Single infection performed a main role and accounted for 79.57% of all of the positive patients. In the ≤ 20 age group, the positive rate was the highest and was as high as 77.65%. In detail, single infection caused by UU dominated, especially in the 21 - 30 age group. Double infection caused by UU and CT and triple infection caused by UU, CT, and NG were the majority, both especially in the 21 - 30 age group. There were significant differences in the positive rates in the different age groups and in the four pathogens (p < 0.05). Quadruple infection was very rare and had only been detected in one patient. CONCLUSIONS: The prevalence of the four pathogens in Hangzhou was different from other regions. More male than female patients, more single than multiple infections, and more single and multiple infections occurring in young people were the features in Hangzhou. The study would provide reference for prevention, diagnosis, and treatment of STI.


Asunto(s)
Enfermedades de Transmisión Sexual , Humanos , Masculino , Femenino , China/epidemiología , Adulto , Persona de Mediana Edad , Adolescente , Prevalencia , Adulto Joven , Estudios Retrospectivos , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/orina , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/microbiología , Anciano , Anciano de 80 o más Años , Gonorrea/epidemiología , Gonorrea/diagnóstico , Gonorrea/orina , Gonorrea/microbiología , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/orina , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/microbiología
14.
Artículo en Inglés | MEDLINE | ID: mdl-38969588

RESUMEN

Castleman disease (CD) is characterized by the proliferation of lymphoid tissue and encompasses a range of disorders that vary in clinical presentation, histopathological features, and therapeutic approaches. This article presents a comprehensive review of the current state of CD research, emphasizing the etiology, pathogenesis, clinical manifestations, diagnostic criteria, treatment options, and prognostic factors. CD is a relatively rare condition infrequently encountered in clinical practice. Certain subtypes of CD progress rapidly and pose a significant threat to patient health. Consequently, a timely and accurate diagnosis is crucial. This article aimed to equip clinicians and researchers with an updated and detailed understanding of CD, thereby enhancing the management of this complex condition.

15.
BMC Musculoskelet Disord ; 25(1): 518, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970062

RESUMEN

OBJECTIVE: The practice of simultaneous bilateral unicompartmental knee arthroplasty (SBUKA) remains a topic of debate, particularly in patients with obesity. Thus, the purpose of this study was to assess the impact of body mass index (BMI) on the 30-day complication rate and the survival rate of the implant following SBUKA. METHODS: We retrospectively examined the clinical records of 245 patients (490 knees) who underwent SBUKA at the Affiliated Hospital of Qingdao University and the Third Hospital of Hebei Medical University between January 2010 and December 2020. Patients were categorised based on their BMI at the time of surgery into four groups: normal weight (BMI 18.5 to 22.9 kg/m2), overweight (BMI 23.0 to 24.9 kg/m2), obese (BMI 25.0 to 29.9 kg/m2), and severely obese (BMI ≥30 kg/m2). Variables such as length of hospital stay, duration of surgery, and costs of hospitalisation were compared across all groups. Additionally, we recorded the 30-day postoperative complication rate and the time from surgery to any required revision. The Kaplan-Meier survival analysis was employed to evaluate and compare the implant survival rates. RESULTS: The follow-up period for the 245 patients ranged from 39 to 114 months, with an average of 77.05±18.71 months. The incidence of complications within 30 days post-surgery did not significantly differ across the groups (χ2 = 1.102, p = 0.777). The implant survival rates from the lowest to the highest BMI groups were 97.14%, 93.9%, 94.44%, and 96.43%, respectively. Both the rate of implant revision (χ2 =1.612, p = 0.657) and the survival curves of the implants (p = 0.639) showed no statistically significant differences among the groups. CONCLUSIONS: BMI did not influence the 30-day complication rate nor the survival rate of implants following SBUKA, suggesting that SBUKA should not be contraindicated based on BMI alone.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Índice de Masa Corporal , Prótesis de la Rodilla , Complicaciones Posoperatorias , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/instrumentación , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Prótesis de la Rodilla/efectos adversos , Falla de Prótesis , Obesidad/complicaciones , Obesidad/cirugía , Osteoartritis de la Rodilla/cirugía , Reoperación/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Factores de Riesgo , Resultado del Tratamiento
16.
Int J Cardiol ; 412: 132338, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38964551

RESUMEN

BACKGROUND: Surprisingly, despite the high prevalence of metformin use in type 2 diabetes (T2D) patients with heart disease, limited safety data is available regarding metformin use in patients with acute and critical heart disease. METHODS: In this single-center retrospective study, patients admitted to the cardiology department for heart failure (HF) or acute coronary syndrome (ACS) between December 2013 and December 2021 and who underwent arterial blood gas analysis at admission with an estimated glomerular clearance rate of ≥45 ml/min/1.73 m2 were identified. The incidences of hyperlactatemia, acidosis, and 30-day in-hospital mortality were compared between preadmission metformin users and nonusers. RESULTS: Of 526 admissions, 193/193 metformin users/nonusers were selected in a propensity score-matched model. Metformin users had greater lactate levels (2.55 ± 2.07 mmol/l vs. 2.00 ± 1.80 mmol/l P < 0.01), a greater incidence of hyperlactatemia [odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.63-3.98; P < 0.01] and acidosis (OR = 1.78; 95% CI, 1.00-3.16; P < 0.05) at admission and a greater incidence of in-hospital mortality (OR = 3.83; 95% CI, 1.05-13.94; P < 0.05), especially those with HF/acute myocardial infarction, elderly age, or without preadmission insulin use. CONCLUSIONS: Our results suggest that, compared to metformin nonusers, preadmission use of metformin may be associated with a greater incidence of hyperlactatemia and acidosis at admission and greater 30-day in-hospital mortality among T2D patients with HF or ACS at high risk of hypoxia, particularly those without preadmission insulin use. The safety of metformin in this population needs to be confirmed in prospective controlled trials.


Asunto(s)
Diabetes Mellitus Tipo 2 , Mortalidad Hospitalaria , Hiperlactatemia , Hipoglucemiantes , Metformina , Humanos , Metformina/uso terapéutico , Metformina/efectos adversos , Masculino , Femenino , Mortalidad Hospitalaria/tendencias , Estudios Retrospectivos , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Hiperlactatemia/epidemiología , Hiperlactatemia/sangre , Hiperlactatemia/inducido químicamente , Incidencia , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Persona de Mediana Edad , Hipoxia/epidemiología , Hipoxia/mortalidad , Hipoxia/sangre , Admisión del Paciente/tendencias , Cardiopatías/epidemiología , Cardiopatías/mortalidad , Cardiopatías/sangre , Anciano de 80 o más Años , Factores de Riesgo
17.
Int J Biol Macromol ; 276(Pt 2): 133942, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39025181

RESUMEN

The immune-suppressive microenvironment of solid tumors is a key factor limiting the effectiveness of immunotherapy, which seriously threatens human life and health. Ferroptosis and apoptosis are key cell-death pathways implicated in cancers, which can synergistically activate tumor immune responses. Here, we developed a multifunctional composite hydrogel (CE-Fc-Gel) based on the self-assembly of poloxamer 407, cystamine-linked ιota-carrageenan (CA)-eicosapentaenoic acid (EPA), and ferrocene (Fc). CE-Fc-Gel improved targeting in tumor microenvironment due to its disulfide bonds. Moreover, CE-Fc-Gel promoted lipid peroxidation, enhanced reactive oxygen species (ROS) production, and decreased glutathione peroxidase 4 (GPX4), inducing ferroptosis by the synergistic effect of Fc and EPA. CE-Fc-Gel induced apoptosis and immunogenic cell death (ICD), thereby promoting dendritic cells (DCs) maturation and T cell infiltration. As a result, CE-Fc-Gel significantly inhibited primary and metastatic tumors in vivo. Our findings provide a novel strategy for enhancing tumor immunotherapy by combining apoptosis, ferroptosis, and ICD.


Asunto(s)
Apoptosis , Carragenina , Ácido Eicosapentaenoico , Ferroptosis , Compuestos Ferrosos , Hidrogeles , Metalocenos , Ferroptosis/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Metalocenos/química , Metalocenos/farmacología , Apoptosis/efectos de los fármacos , Ratones , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Carragenina/farmacología , Ácido Eicosapentaenoico/farmacología , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/química , Humanos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Metástasis de la Neoplasia , Microambiente Tumoral/efectos de los fármacos , Femenino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos
18.
Microbiol Res ; 287: 127855, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39079269

RESUMEN

Potato is an important crop due to its high contents of starch, protein, and various vitamins and minerals. Biofertilizers are composed of plant growth promoting microbes (PGPMs) which are essential for improving the growth and resistance of potato. However, little information has focused on the modes of inoculation of biofertilizers on plant growth and microecology. This study aims to reveal the response mechanism of the potato to three modes of inoculation of biofertilizers all containing PGPM Bacillus amyloliquefaciens EZ99, i.e. scattered mode of 5 kg/ha biofertilizer (M5), soaking seed tubers with dissolved 5 kg/ha biofertilizer (MZG), and scattered mode of 3 kg/ha biofertilizer + 2 kg/ha sucrose (MY34) in alkaline loess field through multi-omics analysis of transcriptome, metabolome and microbiome. The physiological result revealed that two application modes of equal amount of biofertilizer M5 and MZG significantly improved the growth and yield of potatoes. Furthermore, the transcriptome of potato exhibited sets of differentially expressed genes enriched in photosynthesis, sugar metabolism, and phenylpropanoid biosynthesis among the three modes, with the M5 mode exhibiting overall up-regulation of 828 genes. Based on the untargeted metabolomic analysis of potato tuber, M5 mode significantly accumulated sucrose, while MZG and MY34 mode significantly accumulated the stress metabolites euchrenone b6 and mannobiose, respectively. Besides, the microbial structure of potato rhizosphere showed that the diversity of bacteria and fungi was similar in all soils, but their abundances varied significantly. Specifically, beneficial Penicillium was enriched in M5 and MZG soils, whereas MY34 soil accumulated potential pathogens Plectosphaerella and saccharophilic Mortierella. Collectively, these e findings highlight that MZG is the most effective mode to promote potato growth and stimulate rhizosphere effect. The present study not only encourages sustainable agriculture through agroecological practices, but also provides broad prospects for the application of PGPM biofertilizer in staple foods.


Asunto(s)
Fertilizantes , Microbiología del Suelo , Solanum tuberosum , Solanum tuberosum/microbiología , Solanum tuberosum/crecimiento & desarrollo , Fertilizantes/análisis , Bacillus amyloliquefaciens/crecimiento & desarrollo , Transcriptoma , Tubérculos de la Planta/microbiología , Tubérculos de la Planta/crecimiento & desarrollo , Microbiota , Suelo/química , Metaboloma , Rizosfera , Sacarosa/metabolismo , Desarrollo de la Planta , Metabolómica/métodos , Multiómica
19.
Pharmaceutics ; 16(7)2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39065615

RESUMEN

The encapsulation of sodium sulfobutylether-ß-cyclodextrin (SBE-ß-CD) is influenced not only by the degree of substitution (DS) but also by the presence of strong-bonded water (SBW). Guests compete with SBW for positions within the cavity of SBE-ß-CD. However, the correlation between DS and SBW was not clear. This study revealed a positive correlation between DS and SBW utilizing Karl Fischer titration. The mechanism may be attributed to molecular polarizability. To explore the impact of SBW inside SBE-ß-CD with different DS on encapsulation, density functional theory was employed. Throughout the release process, an increase in enthalpy is unfavorable, while an increase in entropy favors spontaneous reaction occurrence. For SBE-ß-CD (DS = 2, 3), enthalpy increase is the primary factor, leading to the retention of SBW within the cavities and consequently hindering guest entry. In contrast, for SBE-ß-CD (DS = 4, 7), the situation differs. For SBE10-ß-CD, the influence of SBW is minimal. This study aims to elucidate the relationship between DS and SBW, as well as the effect of SBW inside SBE-ß-CD with different DS on encapsulation. It is crucial for a comprehensive understanding of the factors affecting the encapsulation of SBE-ß-CD, thereby promoting quality control and functional development of SBE-ß-CD.

20.
Foods ; 13(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39063326

RESUMEN

Chinese farmers, especially small ones, always sell their food at low prices during harvest season rather than storing it for a better price. Based on a theoretical framework of expected utility, this paper examines the mechanism by which risk perception affects farmers' timing choices of food sales and the role played by risk preference, utilizing data from the 2019 China Family Database and the China Household Finance Survey of farmers in six provinces of the main wheat-producing regions. This study shows that farmers with a high risk perception are more likely to choose current sales compared with intertemporal sales. The channel and mechanism analysis finds that increased risk perception leads to risky returns from intertemporal sales lower than certain returns from current sales in utility comparisons. It is further found that risk preference has a substitution effect on risk perception in farmers' intertemporal food sales.

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