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1.
Nat Commun ; 15(1): 4155, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806467

ABSTRACT

The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma metabolomic signatures between combined IF-P (n = 21) versus a heart-healthy, calorie-restricted (CR, n = 20) diet matched for overall energy intake in free-living human participants (women = 27; men = 14) with overweight/obesity for 8 weeks. Gut symptomatology improves and abundance of Christensenellaceae microbes and circulating cytokines and amino acid metabolites favoring fat oxidation increase with IF-P (p < 0.05), whereas metabolites associated with a longevity-related metabolic pathway increase with CR (p < 0.05). Differences indicate GM and metabolomic factors play a role in WL maintenance and body composition. This novel work provides insight into the GM and metabolomic profile of participants following an IF-P or CR diet and highlights important differences in microbial assembly associated with WL and body composition responsiveness. These data may inform future GM-focused precision nutrition recommendations using larger sample sizes of longer duration. Trial registration, March 6, 2020 (ClinicalTrials.gov as NCT04327141), based on a previous randomized intervention trial.


Subject(s)
Body Composition , Caloric Restriction , Fasting , Gastrointestinal Microbiome , Metabolomics , Humans , Gastrointestinal Microbiome/physiology , Caloric Restriction/methods , Male , Female , Fasting/blood , Adult , Middle Aged , Metabolomics/methods , Feces/microbiology , Feces/chemistry , Metabolome , Weight Loss/physiology , Obesity/metabolism , Obesity/therapy , Obesity/diet therapy , Obesity/microbiology , Dietary Proteins/metabolism , Dietary Proteins/administration & dosage , Intermittent Fasting
2.
Food Funct ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809131

ABSTRACT

Metabolic Syndrome (MetS) during pregnancy can lead to complications such as gestational diabetes mellitus (GDM) and hypertensive disorders. In this study, we sought to examine the influence of dietary fiber, from both food sources and soluble fiber supplementation, on the metabolic health and overall pregnancy outcomes of women at high risk of MetS. We conducted a randomized controlled trial involving 376 women between 11 and 13 weeks of gestation. To evaluate dietary fiber intake, we performed an exhaustive dietary component analysis using a food frequency questionnaire. Additionally, the participants in the intervention group received daily soluble fiber supplements until delivery. All participants underwent nutritional consultations and metabolic health assessments at three distinct stages of pregnancy (GW 11-13, GW 24-26, and GW 32-34). Our findings revealed a significant correlation between insufficient dietary fiber intake and an increased risk of GDM, even after adjusting for variables such as maternal age and pre-pregnancy BMI. We also noted that a high total dietary fiber intake was associated with reduced changes in triglyceride levels. In addition, the intervention group showed lower need for constipation medication, and soluble fiber supplementation may offer potential benefits for GDM patients. Importantly, our study verified the safety of long-term soluble fiber supplementation during pregnancy. Our results underscore the importance of adequate fiber intake, particularly from dietary sources, for the metabolic health of pregnant women. Moreover, our findings suggest that early fiber supplementation may benefit pregnant women experiencing constipation or those diagnosed with GDM.

3.
Int J Surg ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38781043

ABSTRACT

BACKGROUND: The aim of this study is to assess the diagnostic accuracy of intraoperative frozen section (FS) in determining the pathological subtypes among patients diagnosed with cT1N0M0 invasive lung adenocarcinoma. MATERIALS AND METHODS: This was a prospective, multi-center (7 centers in China) clinical trial of Eastern Cooperative Thoracic Oncology Projects (ECTOP-1015). Patients with cT1N0M0 invasive lung adenocarcinoma were enrolled in the study. Pathological images obtained from FS and final pathology (FP) were reviewed by at least two pathologists. The primary endpoint was the concordance between FS and FP diagnoses. The inter-observer agreement for identifying pathological subtypes on FS was evaluated among three pathologists. RESULTS: A total of 935 patients were enrolled. The best sensitivity of diagnosing the predominant subtype was 78.2% in the evaluation of acinar pattern. Presence of acinar pattern diagnosed by FS was an independent factor for the concordance between FS and FP (P=0.007, 95% CI: 2.332-4.736). Patients with tumor size >2 cm measured by pathology showed a better concordance rate for the predominant subtype (81.6% vs 74.6%, P=0.023). The presence of radiological ground glass opacity (GGO) component did not affect the diagnosis accuracy of FS for predominant subtype (concordance rate: 76.4% vs 75.2%, P=0.687). Patients with GGO component showed better accuracy of the identification in the presence of LPA (82.1% vs 71.0%, P= 0.026). Substantial agreement between the FS diagnosis from 3 pathologists for the predominant pathological pattern was revealed with κ = 0.846. CONCLUSIONS: This is the largest prospective trial evaluating FS diagnosing pathological subtype in cT1N0M0 invasive lung adenocarcinoma. A favorable concordance in the assessment of the pathological subtypes between FS and FP was observed, indicating the feasibility of utilizing accurate intraoperative pathological diagnoses from FS in guiding surgical strategies. And combination of radiology could improve the precision of FS.

4.
Accid Anal Prev ; 203: 107639, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38763064

ABSTRACT

The interactions between vehicles and pedestrians are complex due to their interdependence and coupling. Understanding these interactions is crucial for the development of autonomous vehicles, as it enables accurate prediction of pedestrian crossing intentions, more reasonable decision-making, and human-like motion planning at unsignalized intersections. Previous studies have devoted considerable effort to analyzing vehicle and pedestrian behavior and developing models to forecast pedestrian crossing intentions. However, these studies have two limitations. First, they mainly focus on investigating variables that explain pedestrian crossing behavior rather than predicting pedestrian crossing intentions. Moreover, some factors such as age, sensation seeking and social value orientation, used to establish decision-making models in these studies are not easily accessible in real-world scenarios. In this paper, we explored the critical factors influencing the decision-making processes of human drivers and pedestrians respectively by using virtual reality technology. To do this, we considered available kinematic variables and analyzed the internal relationship between motion parameters and pedestrian behavior. The analysis results indicate that longitudinal distance and vehicle acceleration are the most influential factors in pedestrian decision-making, while pedestrian speed and longitudinal distance also play a crucial role in determining whether the vehicle yields or not. Furthermore, a mathematical relationship between a pedestrian's intention and kinematic variables is established for the first time, which can help dynamically assess when pedestrians desire to cross. Finally, the results obtained in driver-yielding behavior analysis provide valuable insights for autonomous vehicle decision-making and motion planning.

5.
BMC Public Health ; 24(1): 1378, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778312

ABSTRACT

BACKGROUND: Understanding the intricate influences of risk factors contributing to suicide among young individuals remains a challenge. The current study employed interpretable machine learning and network analysis to unravel critical suicide-associated factors in Chinese university students. METHODS: A total of 68,071 students were recruited between Sep 2016 and Sep 2020 in China. Students reported their lifetime experiences with suicidal thoughts and behaviors, categorized as suicide ideation (SI), suicide plan (SP), and suicide attempt (SA). We assessed 36 suicide-associated factors including psychopathology, family environment, life events, and stigma. Local interpretations were provided using Shapley additive explanation (SHAP) interaction values, while a mixed graphical model facilitated a global understanding of their interplay. RESULTS: Local explanations based on SHAP interaction values suggested that psychoticism and depression severity emerged as pivotal factors for SI, while paranoid ideation strongly correlated with SP and SA. In addition, childhood neglect significantly predicted SA. Regarding the mixed graphical model, a hierarchical structure emerged, suggesting that family factors preceded proximal psychopathological factors, with abuse and neglect retaining unique effects. Centrality indices derived from the network highlighted the importance of subjective socioeconomic status and education in connecting various risk factors. CONCLUSIONS: The proximity of psychopathological factors to suicidality underscores their significance. The global structures of the network suggested that co-occurring factors influence suicidal behavior in a hierarchical manner. Therefore, prospective prevention strategies should take into account the hierarchical structure and unique trajectories of factors.


Subject(s)
Students , Suicidal Ideation , Humans , Male , Risk Factors , Female , Cross-Sectional Studies , Young Adult , China/epidemiology , Students/psychology , Students/statistics & numerical data , Suicide, Attempted/statistics & numerical data , Suicide, Attempted/psychology , Adolescent , Universities , Adult , Suicide/psychology , Suicide/statistics & numerical data , Machine Learning
6.
Nat Commun ; 15(1): 3789, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38710693

ABSTRACT

The CUL3-RING E3 ubiquitin ligases (CRL3s) play an essential role in response to extracellular nutrition and stress stimuli. The ubiquitin ligase function of CRL3s is activated through dimerization. However, how and why such a dimeric assembly is required for its ligase activity remains elusive. Here, we report the cryo-EM structure of the dimeric CRL3KLHL22 complex and reveal a conserved N-terminal motif in CUL3 that contributes to the dimerization assembly and the E3 ligase activity of CRL3KLHL22. We show that deletion of the CUL3 N-terminal motif impairs dimeric assembly and the E3 ligase activity of both CRL3KLHL22 and several other CRL3s. In addition, we found that the dynamics of dimeric assembly of CRL3KLHL22 generates a variable ubiquitination zone, potentially facilitating substrate recognition and ubiquitination. These findings demonstrate that a CUL3 N-terminal motif participates in the assembly process and provide insights into the assembly and activation of CRL3s.


Subject(s)
Amino Acid Motifs , Cryoelectron Microscopy , Cullin Proteins , Receptors, Interleukin-17 , Ubiquitin-Protein Ligases , Ubiquitination , Cullin Proteins/metabolism , Cullin Proteins/chemistry , Cullin Proteins/genetics , Humans , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/chemistry , Ubiquitin-Protein Ligases/genetics , HEK293 Cells , Protein Multimerization , Conserved Sequence , Protein Binding , Models, Molecular
7.
Angew Chem Int Ed Engl ; : e202401724, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691401

ABSTRACT

The dual emission (DE) characteristics of atomically precise copper nanoclusters (Cu NCs) are of significant theoretical and practical interest. Despite this, the underlying mechanism driving DE in Cu NCs remains elusive, primarily due to the complexities of excited state processes. Herein, a novel [Cu4(PPh3)4(C≡C-p-NH2C6H4)3]PF6 (Cu4) NC, shielded by alkynyl and exhibiting DE, was synthesized. Hydrostatic pressure was applied to Cu4, for the first time, to investigate the mechanism of DE. With increasing pressure, the higher-energy emission peak of Cu4 gradually disappeared, leaving the lower-energy emission peak as the dominant emission. Additionally, the Cu4 crystal exhibited notable piezochromism transitioning from cyan to orange. Angle-dispersive synchrotron X-ray diffraction results revealed that the reduced inter-cluster distances under pressure brought the peripheral ligands closer, leading to the formation of new C-H···N and N-H···N hydrogen bonds in Cu4. It is proposed that these strengthened hydrogen bond interactions limit the ligands´ vibration, resulting in the vanishing of the higher-energy peak. In situ high-pressure Raman and vibrationally resolved emission spectra demonstrated that the benzene ring C=C stretching vibration is the structural source of the DE in Cu4.

8.
Anal Chem ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758012

ABSTRACT

Oxygen vacancy (Ov) is known to act as an active center of the metal oxide. Quantification of surface Ov is vital for understanding the quantitative structure-activity relationship. Facile quantification characterization of surface Ov is highly desirable but still challenging. In this study, we presented a simple colorimetric method for rapidly quantifying surface Ov. As an example of metal oxide nanoparticles, Co3O4 was used to catalyze the 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2 colorimetric reaction. It was found that the absorbance of the TMB-H2O2 system was dependent on the surface Ov amount in Co3O4. The investigation of the mechanism showed that the Ov-dependent absorbance would be attributed to the activity of surface Ov to easily adsorb and dissociate H2O2 into a hydroxyl radical (•OH). The absorbance signal of the TMB-H2O2 system acted as a probe to estimate the surface Ov. This colorimetric measurement could be completed in less than 20 min. The Ov concentrations obtained by the proposed colorimetric method matched well with those obtained by X-ray photoelectron spectroscopy. This method does not require any complex operation and expensive equipment and can be performed in any ordinary chemical laboratory. So, this colorimetric method is expected to become an alternative approach for quantifying the surface Ov in metal oxide nanoparticles. This method will provide essential insights into the rational design and application of Ov.

9.
Article in English | MEDLINE | ID: mdl-38740078

ABSTRACT

PURPOSE: Left ventricular assist devices (LVADs) are well-established for treating end-stage heart failure, but this therapy is only available to Chinese patients in recent years. The CH-VAD is the first used fully magnetically levitated pump and the most widely used device in China. This study reports the long-term outcomes of a cohort supported by the CH-VAD for the first time. METHODS: From June 2017 to August 2023, 50 consecutive patients received CH-VAD implantation in Fuwai Hospital. Clinical data were collected during follow-up and retrospectively analyzed. RESULTS: Baseline characteristics included a mean age of 47.9±13.9 years, 90% male, and 26% ischemic etiology. The INTERMACS profile revealed 12% Profile 1, 56% Profile 2, 26% Profile 3 and 6% Profile 4. Mean support duration was 868 ± 630 days (range 33 days-6.4 years). Kaplan-Meier survival rate was 96% (95% confidence interval [CI], 85 to 99) at 6 months, 93% (95% CI, 79-98) at 1 year, 93% (95% CI, 79-98) at 2 years and 89% (95% CI, 71-96) at 3 years. 40 patients (80%) currently remain on support, 3 were bridged to recovery, 2 received transplant, and 5 expired during support. Major adverse events included right heart failure (10%), surgical related bleeding (8%), arrhythmia (8%) and driveline infection (16%). Major hemocompatibility-related adverse events were limited to 3 non-disabling strokes and 1 gastrointestinal bleeding. There was no major device malfunction during the follow-up period. CONCLUSIONS: The largest single-center experience with the leading LVAD in China shows high survival with low complication rates, demonstrating the CH-VAD is safe and efficient in providing long-term support for end-stage heart failure patients.

10.
Int Immunopharmacol ; 133: 112145, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38691920

ABSTRACT

Treatment strategies for paediatric neuroblastoma as well as many other cancers are limited by the unfavourable tumour microenvironment (TME). In this study, the TMEs of neuroblastoma were grouped by their genetic signatures into four distinct subtypes: immune enriched, immune desert, non-proliferative and fibrotic. An Immune Score and a Proliferation Score were constructed based on the molecular features of the subtypes to quantify the immune microenvironment or malignancy degree of cancer cells in neuroblastoma, respectively. The Immune Score correlated with a patient's response to immunotherapy; the Proliferation Score was an independent prognostic biomarker for neuroblastoma and proved to be more accurate than the existing clinical predictors. This double scoring system was further validated and the conserved molecular pattern associated with immune landscape and malignancy degree was confirmed. Axitinib and BI-2536 were confirmed as candidate drugs for neuroblastoma by the double scoring system. Both in vivo and in vitro experiments demonstrated that axitinib-induced pyroptosis of neuroblastoma cells activated anti-tumour immunity and inhibited tumour growth; BI-2536 induced cell cycle arrest at the S phase in neuroblastoma cells. The comprehensive double scoring system of neuroblastoma may predict prognosis and screen for therapeutic strategies which could provide personalized treatments.


Subject(s)
Axitinib , Immunotherapy , Neuroblastoma , Tumor Microenvironment , Neuroblastoma/immunology , Neuroblastoma/therapy , Neuroblastoma/pathology , Neuroblastoma/drug therapy , Humans , Tumor Microenvironment/immunology , Prognosis , Animals , Immunotherapy/methods , Cell Line, Tumor , Axitinib/therapeutic use , Child , Male , Female , Child, Preschool , Mice , Infant , Xenograft Model Antitumor Assays , Cell Proliferation/drug effects
11.
J Environ Manage ; 359: 121075, 2024 May.
Article in English | MEDLINE | ID: mdl-38723502

ABSTRACT

Sequencing batch biofilm reactor (SBBR) has the potential to treat hypersaline high-strength nitrogen wastewater by simultaneous nitrification-denitrification (SND). Dissolved oxygen (DO) and aeration modes are major factors affecting pollutant removal. Low DO (0.35-3.5 mg/L) and alternative anoxic/aerobic (A/O) mode are commonly used for municipal wastewater treatment, however, the appropriate DO concentration and operation mode are still unknown under hypersaline environment because of the restricted oxygen transfer in denser extracellular polymeric substances (EPS) barrier and the decreased carbon source consumption during the anoxic phase. Herein, two SBBRs (R1, fully aerobic mode; R2, A/O mode) were used for the treatment of hypersaline high-strength nitrogen wastewater (200 mg/L NH4+-N, COD/N of 3 and 3% salinity). The results showed that the relatively low DO (2 mg/L) could not realize effective nitrification, while high DO (4.5 mg/L) evidently increased nitrification efficiency by enhancing oxygen transfer in denser biofilm that was stimulated by high salinity. A stable SND was reached 16 days faster with a ∼10% increase of TN removal under A/O mode. Mechanism analysis found that denser biofilm with coccus and bacillus were present in A/O mode instead of filamentous microorganisms, with the secretion of more EPS. Corynebacterium and Halomonas were the dominant genera in both SBBRs, and HN-AD process might assist partial nitrification-denitrification (PND) for highly efficient TN removal in biofilm systems. By using the appropriate operation mode and parameters, the average NH4+-N and TN removal efficiency could respectively reach 100% and 70.8% under the NLR of 0.2 kg N·m-3·d-1 (COD/N of 3), which was the highest among the published works using SND-based SBBRs in treatment of saline high-strength ammonia nitrogen (low COD/N) wastewater. This study provided new insights in biofilm under hypersaline stress and provided a solution for the treatment of hypersaline high-strength nitrogen (low COD/N) water.


Subject(s)
Biofilms , Bioreactors , Denitrification , Nitrification , Nitrogen , Wastewater , Nitrogen/metabolism , Waste Disposal, Fluid/methods , Salinity , Oxygen/metabolism
12.
Small ; : e2402256, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38794863

ABSTRACT

Sodium (Na)-metal batteries (SMBs) are considered one of the most promising candidates for the large-scale energy storage market owing to their high theoretical capacity (1,166 mAh g-1) and the abundance of Na raw material. However, the limited stability of electrolytes still hindered the application of SMBs. Herein, sulfolane (Sul) and vinylene carbonate (VC) are identified as effective dual additives that can largely stabilize propylene carbonate (PC)-based electrolytes, prevent dendrite growth, and extend the cycle life of SMBs. The cycling stability of the Na/NaNi0.68Mn0.22Co0.1O2 (NaNMC) cell with this dual-additive electrolyte is remarkably enhanced, with a capacity retention of 94% and a Coulombic efficiency (CE) of 99.9% over 600 cycles at a 5 C (750 mA g-1) rate. The superior cycling performance of the cells can be attributed to the homogenous, dense, and thin hybrid solid electrolyte interphase consisting of F- and S-containing species on the surface of both the Na metal anode and the NaNMC cathode by adding dual additives. Such unique interphases can effectively facilitate Na-ion transport kinetics and avoid electrolyte depletion during repeated cycling at a very high rate of 5 C. This electrolyte design is believed to result in further improvements in the performance of SMBs.

13.
Int J Biol Macromol ; 269(Pt 2): 131879, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692527

ABSTRACT

Multifunctional polysaccharide hydrogels with strong tissue adhesion, and antimicrobial and hemostatic properties are attractive wound healing materials. In this study, a chitosan-based hydrogel (HCS) was designed, and its properties were enhanced by incorporating oxidized eggshell membrane (OEM). Hydrogel characterization and testing results showed that the hydrogel had excellent antimicrobial properties, cytocompatibility, satisfactory adhesion properties on common substrates, and wet-state adhesion capacity. A rat liver injury model confirmed the significant hemostatic effect of the hydrogel. Finally, the ability of the hydrogel to promote wound healing was verified using rat skin wound repair experiments. Our findings indicate that HCS/OEM hydrogels with added eggshell membrane fibers have better self-healing properties, mechanical strength, adhesion, hemostatic properties, and biocompatibility than HCS hydrogels, in addition to having superior repair performance in wound repair experiments. Overall, the multifunctional polysaccharide hydrogels fabricated in this study are ideal for wound repair.


Subject(s)
Egg Shell , Hydrogels , Polysaccharides , Wound Healing , Wound Healing/drug effects , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Egg Shell/chemistry , Rats , Polysaccharides/chemistry , Polysaccharides/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Powders , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Rats, Sprague-Dawley
14.
Int J Biol Macromol ; 270(Pt 2): 132338, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38763237

ABSTRACT

Extracellular polymeric substances (EPSs) in excess sludge of wastewater treatment plants are valuable biopolymers that can act as recovery materials. However, effectively concentrating EPSs consumes a significant amount of energy. This study employed novel energy-saving pressure-free dead-end forward osmosis (DEFO) technology to concentrate various biopolymers, including EPSs and model biopolymers [sodium alginate (SA), bovine serum albumin (BSA), and a mixture of both (denoted as BSA-SA)]. The feasibility of the DEFO technology was proven and the largest concentration ratios for these biopolymers were 94.8 % for EPSs, 97.1 % for SA, 97.8 % for BSA, and 98.4 % for BSA-SA solutions. An evaluation model was proposed, incorporating the FO membrane's water permeability coefficient and the concentrated substances' osmotic resistance, to describe biopolymers' concentration properties. Irrespective of biopolymer type, the water permeability coefficient decreased with increasing osmotic pressure, remained constant with increasing feed solution (FS) concentration, increased with increasing crossing velocity in the draw side, and showed little dependence on draw salt type. In the EPS DEFO concentration process, osmotic resistance was minimally impacted by osmotic pressure, FS concentration, and crossing velocity, and monovalent metal salts were proposed as draw solutes. The interaction between reverse diffusion metal cations and EPSs affected the structure of the concentrated substances on the FO membrane, thus changing the osmotic resistance in the DEFO process. These findings offer insights into the efficient concentration of biopolymers using DEFO.

15.
Psychol Res Behav Manag ; 17: 1975-1989, 2024.
Article in English | MEDLINE | ID: mdl-38766317

ABSTRACT

Aim: Stressful life events have a significant impact on the mental health of college students. Depression, as a prevalent psychological issue, has garnered attention in the field of college student mental health and is closely linked to it. Additionally, parenting style is identified as an important factor influencing the development of college students' mental health. Therefore, this study aims to explore the relationship between these three factors. Methods: A total of 8079 first-year college students from two medical universities in Shandong Province, China were surveyed. The Beck Depression Inventory was utilized to evaluate depressive symptoms among the college students, while the Adolescent Self-rating Life Events Checklist and the Egna Minnen Beträfande Uppfostran were employed to gather data. Subsequently, the SPSS macro program PROCESS was utilized to analyze both the mediating and moderating effects. All statistical analyses were conducted using SPSS 26.0. Results: The study found a detection rate of 6.3% for depressive symptoms among college students. The correlation analysis of this study showed that the stressful life events of college students were significantly positively correlated with depressive symptoms (r=0.261, p< 0.01). Each dimension of parenting style was associated with depressive symptoms in different degrees and directions. At the same time, parenting styles of all sizes play a partial mediating role between stressful life events and depressive symptoms in college students, gender plays a crucial regulatory role in this mediation. Conclusion: Stressful life events experienced by college students have a significant impact on their mental health. Early intervention through positive parenting styles from parents may prove to be beneficial in promoting the development of good mental health among college students.

16.
Acta Biomater ; 180: 407-422, 2024 May.
Article in English | MEDLINE | ID: mdl-38614414

ABSTRACT

Facile construction of a fully biodegradable spherical nucleic acid (SNA) nanoplatform is highly desirable for clinical translations but remains rarely explored. We developed herein the first polycarbonate-based biodegradable SNA nanoplatform for self-codelivery of a chemotherapeutic drug, doxorubicin (DOX), and a human liver-specific miR122 for synergistic chemo-gene therapy of hepatocellular carcinoma (HCC). Ring-opening polymerization (ROP) of a carbonate monomer leads to a well-defined polycarbonate backbone for subsequent DOX conjugation to the pendant side chains via acidic pH-cleavage Schiff base links and miR122 incorporation to the chain termini via click coupling, affording an amphiphilic polycarbonate-DOX-miR122 conjugate, PBis-Mpa30-DOX-miR122 that can self-assemble into stabilized SNA. Besides the desired biodegradability, another notable merit of this nanoplatform is the use of miR122 not only for gene therapy but also for enhanced innate immune response. Together with the ICD-triggering effect of DOX, PBis-Mpa30-DOX-miR122 SNA-mediated DOX and miR122 codelivery leads to synergistic immunogenicity enhancement, resulting in tumor growth inhibition value (TGI) of 98.1 % significantly higher than those of the groups treated with only drug or gene in a Hepa1-6-tumor-bearing mice model. Overall, this study develops a useful strategy toward biodegradable SNA construction, and presents a drug and gene-based self-codelivery SNA with synergistic immunogenicity enhancement for efficient HCC therapy. STATEMENT OF SIGNIFICANCE: Facile construction of a fully biodegradable SNA nanoplatform is useful for in vivo applications but remains relatively unexplored likely due to the synthetic challenge. We report herein construction of a polycarbonate-based SNA nanoplatform for co-delivering a chemotherapeutic drug, DOX, and a human liver-specific miR-122 for synergistic HCC treatment. In addition to the desired biodegradability properties, this SNA nanoplatform integrates DOX-triggered ICD and miR-122-enhanced innate immunity for simultaneously activating adaptive and innate immunities, which leads to potent antitumor efficiency with a TGI value of 98.1 % in a Hepa1-6-tumor-bearing mice model.


Subject(s)
Adaptive Immunity , Doxorubicin , Immunity, Innate , MicroRNAs , Doxorubicin/pharmacology , Doxorubicin/chemistry , MicroRNAs/genetics , Animals , Immunity, Innate/drug effects , Humans , Adaptive Immunity/drug effects , Mice , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/immunology , Nanoparticles/chemistry , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Mice, Nude , Mice, Inbred BALB C
17.
Int J Biol Macromol ; 268(Pt 2): 131941, 2024 May.
Article in English | MEDLINE | ID: mdl-38685545

ABSTRACT

The inherent functional fractions (gelation and ice-affinitive fractions) of gelatin enable it as a promising cryoprotectant alternative. However, the composition-antifreeze property relationships of gelatin remain to be investigated. In this study, the HW-PSG and LW-PSG fractions of gelatin from fish scales were obtained, according to the critical gelation conditions and ice-binding measurements, respectively. Thermal hysteresis (THA) value, associated with ice nucleation, of LW-PSG was higher than that of HW-PSG. Besides, the relatively low-sized ice crystals (210-550 µm2) indicated that HW-PSG showed strong ice recrystallization inhibition (IRI) ability, compared to other groups. These results suggested that LW-PSG inhibited ice nucleation, while HW-PSG displayed the strong IRI ability. Furthermore, the antifreeze mechanisms were clarified through IRI measurements and molecular dynamics simulation. The minimum size of ice crystals was found for HW-PSG gels with dense microstructure, suggesting the HW-PSG retarded the growth of ice crystals by restricting the migration and phase transformation of water molecules. The hydrogen bond interactions between the ice crystal surface and ASN1294 and PRO1433 residues of LW-PSG, and hydrophobic interactions contributed to inhibiting the nucleation of ice crystals. This study provided some references to further enhance antifreeze performance of gelatin by modulating fragment composition.


Subject(s)
Gelatin , Molecular Dynamics Simulation , Gelatin/chemistry , Animals , Ice , Crystallization , Hydrogen Bonding , Cryoprotective Agents/chemistry , Cryoprotective Agents/pharmacology , Hydrophobic and Hydrophilic Interactions , Fishes
18.
Int J Gen Med ; 17: 1521-1531, 2024.
Article in English | MEDLINE | ID: mdl-38680193

ABSTRACT

Purpose: Investigating the therapeutic efficacy of Laparoscopic Sleeve Gastrectomy (LSG) in low BMI (30-35 kg/m2) patients with obesity, and exploring the correlation between patients' preoperative BMI and postoperative weight loss. Methods: Comparing the weight loss, remission of comorbidities, occurrence of complications, and quality of life among the different BMI patients who underwent LSG. Analyzing the relationship between BMI and percentage of excess weight loss (%EWL) by using Spearman correlation analysis and linear regression analysis. Results: The %EWL at 12 months after the surgical procedure was (104.26±16.41)%, (90.36±9.98)%, and (78.30±14.64)% for patients with Class I, II, and III obesity, respectively, P<0.05. Spearman correlation coefficients between %EWL and BMI at 1, 3, 6, and 12 months after surgery were R=-0.334 (P<0.001), R=-0.389 (P<0.001), and R=-0.442 (P<0.001), R=-0.641 (P<0.001), respectively. The remission of hypertension, diabetes and dyslipidaemia did not differ significantly between groups (P>0.05). Conclusion: Individuals with obesity for varying BMI can experience favorable outcomes following LSG surgery. It is advisable to consider LSG treatment for patients with Class I obesity.

19.
Front Microbiol ; 15: 1355069, 2024.
Article in English | MEDLINE | ID: mdl-38680915

ABSTRACT

Objective: Infections caused by Carbapenem-resistant Enterobacterales (CRE) have high treatment costs, high mortality and few effective therapeutic agents. This study aimed to determine the risk factors for progression from intestinal colonization to infection in hematological patients and the risk factors for 30-day mortality in infected patients. Methods: A retrospective case-control study was conducted in the Department of Hematology at Shandong Provincial Hospital affiliated to Shandong First Medical University from April 2018 to April 2022. Patients who developed subsequent infections were identified as the case group by electronic medical record query of patients with a positive rectal screen for CRE colonization, and patients who did not develop subsequent infections were identified as the control group by stratified random sampling. Univariate analysis and logistic regression analysis determined risk factors for developing CRE infection and risk factors for mortality in CRE-infected patients. Results: Eleven hematological patients in the study developed subsequent infections. The overall 30-day mortality rate for the 44 hematological patients in the case-control study was 11.4% (5/44). Mortality was higher in the case group than in the control group (36.5 vs. 3.0%, P = 0.0026), and septic shock was an independent risk factor for death (P = 0.024). Univariate analysis showed that risk factors for developing infections were non-steroidal immunosuppressants, serum albumin levels, and days of hospitalization. In multivariable logistic regression analysis, immunosuppressants [odds ratio (OR), 19.132; 95% confidence interval (CI), 1.349-271.420; P = 0.029] and serum albumin levels (OR, 0.817; 95% CI, 0.668-0.999; P = 0.049) were independent risk factors for developing infections. Conclusion: Our findings suggest that septic shock increases mortality in CRE-infected hematological patients. Hematological patients with CRE colonization using immunosuppressive agents and reduced serum albumin are more likely to progress to CRE infection. This study may help clinicians prevent the onset of infection early and take measures to reduce mortality rates.

20.
Nat Prod Res ; : 1-4, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684008

ABSTRACT

A new glycoside (1) along with six known analogues (1-7) were isolated from Codonopsis pilosula collected at Shanxi in China. The structure of 1 was established based on comprehensive spectroscopic data and literature comparison. The anti-inflammatory effects of isolated compounds were further investigated in LPS-induced RAW264.7 macrophage.

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