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1.
J Colloid Interface Sci ; 677(Pt A): 470-480, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39098280

ABSTRACT

Photocatalysis has emerged as a extremely promising green technology for the treatment of uranium-containing wastewater. This study focuses on the fabrication of Ti3C2Tx/Cd0.8Zn0.2S composites with Schottky junctions through the in-situ growth of Cd0.8Zn0.2S on Ti3C2Tx nanosheets, enabling efficient photoreduction of U(VI) without the requirement of sacrificial agents. The results demonstrate that the Ti3C2Tx/Cd0.8Zn0.2S composites achieve remarkable 99.48 % U(VI) reduction efficiency within 60 min in a 100 ppm uranium solution. Furthermore, the removal rate remains above 90 % after five cycles. The formation of Schottky heterojunctions by Ti3C2Tx and Cd0.8Zn0.2S leads to the generation of an internal electric field that significantly promotes the rapid separation and transfer of photogenerated carriers, thereby enhancing the photocatalytic reduction efficiency of Ti3C2Tx/Cd0.8Zn0.2S-3:100 (TC/CZS-3:100). A considerable amount of electrons accumulate on Ti3C2Tx via the Schottky barrier, effectively facilitating the reduction of U(VI) to U(IV). As a co-catalyst, Ti3C2Tx enhances the photocatalytic performance and stability of Cd0.8Zn0.2S. Moreover, the practical application in the waste liquid of rare earth tailings reveals that the removal rate can be as high as 91.24 %. This research is of significant value in the development of effective photocatalysts for the elimination of uranium from wastewater.

2.
J Inflamm Res ; 17: 5177-5195, 2024.
Article in English | MEDLINE | ID: mdl-39104909

ABSTRACT

Introduction: Both rheumatoid arthritis (RA) and rosacea represent common chronic systemic autoimmune conditions. Recent research indicates a heightened RA risk among individuals with rosacea. However, the molecular mechanisms linking these diseases remain largely unknown. This study aims to uncover shared molecular regulatory networks and immune cell infiltration patterns in both rosacea and RA. Methods: The gene expression profiles of RA (GSE12021, GSE55457), and the rosacea gene expression profile (GSE6591), were downloaded from Gene Expression Omnibus (GEO) databases, and obtained to screen differentially expressed genes (DEGs) by using "limma" package in R software. Various analyses including GO, KEGG, protein-protein interaction (PPI) network, and weighted gene co-expression network analyses (WGCNA) were conducted to explore potential biological functions and signaling pathways. CIBERSORT was used to assess the abundance of immune cells. Pearson coefficients were used to calculate the correlations between overlapped genes and the leukocyte gene signature matrix. Flow cytometry (FCM) analysis confirmed the most abundant immune cells detected in rheumatoid arthritis and rosacea. Receiver operator characteristic (ROC) analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to confirm biomarkers and functions. Results: Two hundred seventy-seven co-expressed DEGs were identified from these datasets. Functional enrichment analysis indicated that these DEGs were associated with immune processes and chemokine-mediated signaling pathways. Fourteen and 17 hub genes overlapped between cytoHubba and WGCNA were identified in RA and rosacea, respectively. Macrophages and dendritic cells were RA and rosacea's most abundant immune cells, respectively. The ROC curves demonstrated potential diagnostic values of CXCL10 and CCL27, showing higher levels in the serum of patients with RA or rosacea, and suggesting possible regulation in the densities and functions of macrophages and dendritic cells from RA and rosacea, which were validated by FCM and qRT-PCR. Conclusion: Importantly, our findings may contribute to the scientific basis for biomarkers and therapeutic targets for patients with RA and rosacea in the future.

3.
Angew Chem Int Ed Engl ; : e202412337, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39106111

ABSTRACT

A cascade Nazarov cyclization/dicycloexpansions reaction was developed for the precise synthesis of the angularly fused M/5/N (M = 5, 6; N = 4-9, 13) tricyclic skeletons. The prioritized expansion of the first ring played a critical role in the transformations, due to the release of ring strain, and the nature of the substituents present on the substrate is another influencing factor. This pioneering cascade reaction features broad substrates scope (33 examples), short reaction time, exceptional yields (up to 95%), and remarkable regioselectivities (> 20:1). Exploiting the synthetic application of this cascade reaction, we successfully executed a succinct total synthesis of nominal madreporanone for the first time.

4.
Pain Physician ; 27(5): E567-E577, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39087963

ABSTRACT

BACKGROUND: Fascial plane block techniques have evolved considerably in recent years. Unlike the conventional peripheral nerve block methods, the fascial plane block's effect can be predicted based on fascial anatomy and does not require a clear vision of the target nerves. The anatomy of the retroperitoneal interfascial space is complex, since it comprises multiple compartments, including the transversalis fascia (TF), the retroperitoneal fasciae (RF), and the peritoneum. For this reason, an in-depth, accurate understanding of the retroperitoneal interfascial space's anatomical characteristics is necessary for perceiving the related regional blocks and mechanisms that lie underlie the dissemination of local anesthetics (LAs) outside or within the various retroperitoneal compartments. OBJECTIVES: This review aims to summarize the retroperitoneum's anatomical characteristics and elucidate the various communications among different interfascial spaces as well as their clinical significance in regional blocks, including but not limited to the anterior quadratus lumborum block (QLB), the fascia iliaca compartment block (FICB), the transversalis fascia plane block (TFPB), and the preperitoneal compartment block (PCB). STUDY DESIGN: This is a narrative review of pertinent studies on the use of retroperitoneal spaces in regional anesthesia (RA). METHODS: We conducted searches in multiple databases, including PubMed, MEDLINE, and Embase, using "retroperitoneal space," "transversalis fascia," "renal fascia," "quadratus lumborum block," "nerve block," and "liquid diffusion" as some of the keywords. RESULTS: The anatomy of the retroperitoneal interfascial space has a significant influence on the injectate spread in numerous RA blocking techniques, particularly the QLB, FICB, and TFPB approaches. Furthermore, the TF is closely associated with the QLB, and the extension between the TF and iliac fascia offers a potential pathway for LAs. LIMITATIONS: The generalizability of our findings is limited by the insufficient number of randomized controlled trials (RCTs). CONCLUSIONS: Familiarity with the anatomy of the retroperitoneal fascial space could enhance our understanding of peripheral nerve blocks. By examining the circulation in the fascial space, we may gain a more comprehensive understanding of the direction and degree of injectate diffusion during RA as well as the block's plane and scope, possibly resulting in effective analgesia and fewer harmful clinical consequences.


Subject(s)
Anesthesia, Conduction , Nerve Block , Humans , Retroperitoneal Space/anatomy & histology , Anesthesia, Conduction/methods , Nerve Block/methods , Fascia/anatomy & histology , Anesthetics, Local/administration & dosage
5.
Int J Biol Macromol ; : 134457, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39111487

ABSTRACT

The optimization of hydrogel structure is crucial for adsorption capacity, mechanical stability, and reusability. Herein, a chitosan and laponite-XLS co-doped poly(acrylic acid-co-acrylamide) hydrogel (CXAA) with honeycomb-like porous structures is synthesized by cooperative cross-linking of 2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) and laponite-XLS in reticular frameworks of acrylic acid (AAc) and acrylamide (AM). The CXAA exhibits extraordinary mechanical performances including tough tensile strength (3.36 MPa) and elasticity (2756 %), which facilitates recycling in practical adsorption treatment and broadens potential applications. Since the regular porous structures can fully expose numerous adsorption sites and electronegative natures within polymer materials, CXAA displays efficient and selective adsorption properties for cationic dyes like methylene blue (MB) and malachite green (MG) from mixed pollutants and can reach record-high values (MB = 6886 mg g-1, MG = 11,381 mg g-1) compared with previously reported adsorbents. Therefore, CXAA exhibits promising potential for separating cationic and anionic dyes by their charge disparities. Mechanism studies show that the synergistic effects of HACC, laponite-XLS, and functional groups in monomers promote highly efficient adsorption. Besides, the adsorption capacity of CXAA remains stable even after undergoing five cycles of regeneration. The results confirm that CXAA is a promising adsorbent for effectively removing organic dyes in wastewater.

6.
Exp Ther Med ; 28(3): 353, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39071913

ABSTRACT

The present study aimed to determine the optimal posterior tibial plateau inclination for fixed-platform unicondylar knee arthroplasty (UKA) using finite element analysis (FEA). These findings provided a theoretical basis for selecting an appropriate posterior inclination of the tibial plateau during surgery. The present study utilized the FEA method to create models of fixed-platform UKA with tibial plateau posterior inclinations of 3, 6 and 9˚. The stress changes in the internal structures of each model after knee flexion motion were then compared. During knee flexion from 0 to 90˚, the contact and Von Mises equivalent stresses of the femoral condyle prosthesis and tibial platform pad revealed consistent trends of 3˚ posterior inclination, >6˚ posterior inclination and >9˚ posterior inclination. The present study established the first quasi-dynamic fixed-platform UKA model of the knee joint under load-bearing conditions. From a theoretical perspective, it was found that controlling the posterior inclination of UKA between 6 and 9˚ may be more beneficial for the survival of the tibial platform pad than between 3 and 6˚. It is also more effective in reducing pad wear.

7.
Chem Biodivers ; : e202401407, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39072979

ABSTRACT

Three uncommon isospongian diterpenoids including a new one, 3-epi-kravanhin A (2), were isolated from the leaves of Amomum tsao-ko. Compounds 2 and 3 dose-dependently promoted GLP-1 secretion on STC-1 cells with promotion ratios of 109.7% and 186.1% (60 µM). Mechanism study demonstrated that the GLP-1 stimulative effects of 2 and 3 were closely related with Ca2+/CaMKII and PKA pathways, but irrelevant to GPBAR1 and GPR119 receptors. Moreover, compound 1 showed moderate DPP-4 inhibitory activity with an IC50 value of 311.0 µM. Molecular docking verified the binding affinity of 1 with DPP-4 by hydrogen bonds between the γ-lactone carbonyl (C-15) and Arg61 residue. Bioinformatics study indicated that compound 1 exerted antidiabetic effects by improving inflammation, oxidative stress and insulin resistance. This study first disclosed the presence of isospongian diterpenoids in A. tsao-ko, which showed antidiabetic potency by promoting GLP-1 secretion and inhibiting DPP-4 activity.

8.
Proc Natl Acad Sci U S A ; 121(28): e2322972121, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38968116

ABSTRACT

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.


Subject(s)
DNA Repair , Ubiquitin-Protein Ligases , Humans , DNA Breaks, Double-Stranded , Histones/metabolism , Histones/genetics , Polyubiquitin/metabolism , Tumor Suppressor p53-Binding Protein 1/metabolism , Tumor Suppressor p53-Binding Protein 1/genetics , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitination
9.
Adv Skin Wound Care ; 37(8): 1-6, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39037102

ABSTRACT

OBJECTIVE: To explore the practical effect of the case management model in a comprehensive nursing clinic. METHODS: Based on the case management model, the authors constructed a comprehensive nursing clinic providing wound care, ostomy care, peripherally inserted central catheter care, drainage tube care, nursing consultations, and home care. They evaluated the practical effect of the comprehensive nursing clinic according to workload, economic benefits, and satisfaction of the medical staff and patients. RESULTS: Since the inception of the comprehensive nursing clinic, the number of visits has increased by 63.57%, and the satisfaction of patients and medical staff has also improved. CONCLUSIONS: This comprehensive nursing clinic based on the case management model meets the medical needs of patients, has improved the satisfaction of patients and the medical staff, and enhances the professional sense of value and comprehensive quality of specialized nurses.


Subject(s)
Case Management , Humans , Patient Satisfaction , Models, Nursing , Comprehensive Health Care/organization & administration , Ambulatory Care Facilities/organization & administration , Female , Male
10.
Dis Model Mech ; 17(8)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39056117

ABSTRACT

N-methyl-D-aspartate (NMDA)-induced retinal damage has been well studied in rodents, but the detailed mechanisms have not yet been characterized in nonhuman primates. Here, we characterized the retinal degenerative effects of NMDA on rhesus monkeys in vivo. NMDA saline or saline-only control was injected intravitreally to the randomly assigned eyes and contralateral eyes of four rhesus monkeys, respectively. The structural and functional changes of retina were characterized by optical coherence tomography and electroretinography on days 0, 4, 30 and 60 post injection. Both optic discs and macular areas of the NMDA-injected eyes initially presented with a transient retinal thickening, followed by continued retinal thinning. The initial, transient retinal thickening has also been observed in glaucoma patients, but this has not been reported in rodent NMDA models. This initial response was followed by loss of retina ganglion cells (RGCs), which is similar to glaucomatous optic neuropathy and other RGC-related retinal degenerations. The amplitudes of both the photopic negative response and pattern electroretinogram decreased significantly and remained low until the end of the study. Thus, the NMDA monkey model may serve as a more clinically relevant animal model of retinal damage.


Subject(s)
Disease Models, Animal , Electroretinography , Macaca mulatta , N-Methylaspartate , Retina , Tomography, Optical Coherence , Animals , Retina/pathology , Retina/drug effects , Retinal Ganglion Cells/pathology , Retinal Ganglion Cells/drug effects , Male
11.
Reprod Biomed Online ; 49(4): 104077, 2024 May 09.
Article in English | MEDLINE | ID: mdl-39047319

ABSTRACT

RESEARCH QUESTION: Does luteal phase support (LPS) with oral progesterone improve the live birth rate (LBR) in patients undergoing intrauterine insemination (IUI) cycles with letrozole? DESIGN: This retrospective cohort study included 1199 IUI cycles with letrozole between January 2017 and December 2021. A nearest neighbour random matching approach was employed to pair the LPS group and the control group in a 1:2 ratio. Eight variables were chosen for matching in the propensity score matching (PSM) model: age; body mass index; duration of infertility; cause(s) of infertility; antral follicle count; basal concentration of FSH; rank of IUI attempts; and leading follicle size. LBR was selected as the primary outcome. RESULTS: In total, 427 LPS cycles were matched with 772 non-LPS (control) cycles after PSM. The LBR was significantly higher in the LPS group compared with the control group (19.7% versus 14.5%; P = 0.0255). The clinical pregnancy rate (23.2% versus 17.6%; P = 0.0245) and ongoing pregnancy rate (20.6% versus 15.8%; P = 0.0437) were also significantly higher in the LPS group. The biochemical pregnancy rate, ectopic pregnancy rate and miscarriage rate were similar in the two groups (P > 0.05). The intergroup comparison revealed no significant variances in terms of gestational age, mode of delivery, ectopic pregnancy rate or abortion rate. Furthermore, there were no significant differences in birth weight or birth length between the two groups. CONCLUSIONS: Luteal support with oral progesterone significantly improved the LBR in IUI cycles with letrozole, but did not affect neonatal outcomes.

12.
bioRxiv ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39026774

ABSTRACT

Accumulating evidence indicates that coronary microvascular dysfunction (CMD) caused by hypercholesterolemia can lead to myocardial ischemia, with or without obstructive atherosclerotic coronary artery disease (CAD). However, the molecular pathways associated with compromised coronary microvascular function prior to the development of myocardial ischemic injury remain poorly defined. In this study, we investigated the effects of hypercholesterolemia on the function and integrity of the coronary microcirculation in mice and the underlying mechanisms. Mice were fed with a hypercholesterolemic Paigen's diet (PD) for 8 weeks. Echocardiography data showed that PD caused CMD, characterized by significant reductions in coronary blood flow and coronary flow reserve (CFR), but did not affect cardiac remodeling or dysfunction. Immunofluorescence studies revealed that PD-induced CMD was associated with activation of coronary arterioles inflammation and increased myocardial inflammatory cell infiltration. These pathological changes occurred in parallel with the upregulation of lysosomal signaling pathways in endothelial cells (ECs). Treating hypercholesterolemic mice with the cholesterol-lowering drug ezetimibe significantly ameliorated PD-induced adverse effects, including hypercholesterolemia, steatohepatitis, reduced CFR, coronary EC inflammation, and myocardial inflammatory cell infiltration. In cultured mouse cardiac endothelial cells (MCECs), 7-ketocholesterol (7K) increased mitochondrial reactive oxygen species (ROS) and inflammatory responses. Meanwhile, 7K induced the activation of TFEB and lysosomal signaling in MCECs, whereas the lysosome inhibitor bafilomycin A1 blocked 7K-induced TFEB activation and exacerbated 7K-induced inflammation and cell death. Interestingly, ezetimibe synergistically enhanced 7K-induced TFEB activation and attenuated 7K-induced mitochondrial ROS and inflammatory responses in MCECs. These results suggest that CMD can develop and precede detectable cardiac functional or structural changes in the setting of hypercholesterolemia, and that upregulation of TFEB-mediated lysosomal signaling in ECs plays a protective role against CMD.

13.
BMC Pulm Med ; 24(1): 354, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039507

ABSTRACT

BACKGROUND: miR-223-3p has been demonstrated as a Pseudomonas aeruginosa colonization-related miRNA in bronchiectasis (BE), but its clinical value in BE has not been revealed, which is of great significance for the clinical diagnosis and monitoring of BE. This study aimed to identify a reliable biomarker for screening BE and predicting patients' outcomes. METHODS: The serum expression of miR-223-3p was compared between healthy individuals (n = 101) and BE patients (n = 133) and evaluated its potential in distinguishing BE patients. The severity of BE patients was estimated by BSI and FACED score, and the correlation of miR-223-3p with inflammation and severity of BE patients was evaluated by Pearson correlation analysis. BE patients were followed up for 3 years, and the predictive value of miR-223-3p in prognosis was assessed by logistic regression analysis. RESULTS: Significant upregulation of miR-223-3p was observed in BE patients, which significantly distinguished BE patients and showed positive correlations with C-reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL-6), and neutrophil-to-lymphocyte ratio (NLR) of BE patients. Additionally, miR-223-3p was also positively correlated with BSI and FACED scores, indicating its correlation with inflammation and severity of BE. BE patients with adverse prognoses showed a higher serum miR-223-3p level, which was identified as an adverse prognostic factor and discriminated patients with different prognoses. CONCLUSION: Increasing serum miR-223-3p can be considered a biomarker for the onset, severity, and prognosis of BE.


Subject(s)
Biomarkers , Bronchiectasis , MicroRNAs , Severity of Illness Index , Humans , Bronchiectasis/blood , Bronchiectasis/diagnosis , MicroRNAs/blood , Male , Female , Middle Aged , Prognosis , Retrospective Studies , Biomarkers/blood , Adult , Aged , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Procalcitonin/blood , Case-Control Studies , Interleukin-6/blood
14.
Environ Sci Technol ; 58(28): 12390-12399, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38963915

ABSTRACT

Investigating the ternary relationship among nanoparticles (NPs), their immediate molecular environment, and test organisms rather than the direct interaction between pristine NPs and test organisms has been thrust into the mainstream of nanotoxicological research. Diverging from previous work that predominantly centered on surrounding molecules affecting the toxicity of NPs by modulating their nanoproperties, this study has unveiled a novel dimension: surrounding molecules altering bacterial susceptibility to NPs, consequently impacting the outcomes of nanobio interaction. The study found that adding nitrate as the surrounding molecules could alter bacterial respiratory pathways, resulting in an enhanced reduction of ceria NPs (nanoceria) on the bacterial surfaces. This, in turn, increased the ion-specific toxicity originating from the release of Ce3+ ions at the nanobio interface. Further transcriptome analysis revealed more mechanistic details underlying the nitrate-induced changes in the bacterial energy metabolism and subsequent toxicity patterns. These findings offer a new perspective for the deconstruction of nanobio interactions and contribute to a more comprehensive understanding of NPs' environmental fate and ecotoxicity.


Subject(s)
Cerium , Cerium/toxicity , Cerium/chemistry , Bacteria/metabolism , Nanoparticles/toxicity , Metal Nanoparticles/toxicity , Metal Nanoparticles/chemistry
15.
Exp Ther Med ; 28(3): 348, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39006452

ABSTRACT

Platycladi cacumen (PC) is derived from the dry twigs and leaves of Platycladi orientalis (L.) Franco and exerts anti-epileptic effects. However, its mechanism of action remains unknown. The present study explored the potential anti-epileptic components and mechanisms of PC. The primary active components and targets of PC were analyzed using network pharmacology and a lipopolysaccharide (LPS)-induced murine microglial cell line (BV2) was used to confirm anti-epileptic effects by detecting reactive oxygen species (ROS), apoptosis, inflammatory markers, cell migration and signaling pathways. A total of 13 core active components showed druggable properties, of which deoxypicrop odophyllotoxin, hinokinin and isopimaric acid (IPA) were predicted to cross the blood-brain barrier. In total, 255 potential targets of these three compounds were predicted using SwissTargetPrediction and Similarity Ensemble Approach websites and 150 were associated with epilepsy. In vitro experiments confirmed that IPA significantly inhibited LPS-induced microglial oxidative stress and inflammation by decreasing the migration area, cellular ROS content, lactate dehydrogenase release and early phase of apoptosis. IPA also increased the mRNA expression of anti-oxidative enzymes (superoxide dismutase-1 and -2) and suppressed inflammatory cytokines (interleukin-1ß and tumor necrosis factor-α). Furthermore, IPA phosphorylated AKT and mTOR proteins. Taken together, the present findings suggested that IPA is a potential anti-epileptic compound derived from PC.

16.
Front Plant Sci ; 15: 1392924, 2024.
Article in English | MEDLINE | ID: mdl-39006959

ABSTRACT

Roads are an increasingly prevalent form of human activity that drives the decrease in plant community functions and threatens global biodiversity. However, few studies have focused on the changes in the function and diversity of alpine meadows caused by road infrastructure in the Tibetan Plateau. In this study, the changes in species diversity, functional diversity, and community stability were examined at different distances from the Qinghai-Tibet highway. The results showed that the road intensified the degradation of vegetation, which significantly altered species diversity and community structure. This effect gradually decreased from near to far from the highway. Plant community cover and species diversity were highest at intermediate distances (50-100 m) from the roadway; species diversity and stability were lowest in the grassland most disturbed by the road (0 m), and species diversity and functional diversity tended to stabilize farther away from the road (250 m). Our findings indicate that changes in species diversity are synchronized with changes in functional diversity, which largely determines the outcome of degraded grassland community diversity and stability. Our results provide a reference point for restoring degraded alpine areas and mitigating the ecological impacts of roads.

17.
Eur J Med Res ; 29(1): 366, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014466

ABSTRACT

PURPOSE: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. METHODS AND MATERIALS: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. RESULTS: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005]). CONCLUSION: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.


Subject(s)
Algorithms , Anthracyclines , Breast Neoplasms , Neoadjuvant Therapy , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Female , Anthracyclines/therapeutic use , Anthracyclines/administration & dosage , Neoadjuvant Therapy/methods , Middle Aged , China/epidemiology , Adult , Homologous Recombination , Mutation , Aged , DNA Copy Number Variations , BRCA1 Protein/genetics
18.
Langmuir ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013598

ABSTRACT

In this paper, the bubble nucleation process of water was studied by molecular dynamics (MD) simulation. The nucleation mechanism of water on a grooved substrate was revealed from the perspective of hydrogen bond and energy change, and the effect of system pressure on nucleation was studied. The results show that the process of bubble nucleation of water molecules is essentially a process in which the thermal motion of water molecules gradually intensifies and the hydrogen bond continues to break with the increase in kinetic energy. As the hydrogen bond breaks, the kinetic energy of the water molecules is continuously converted to intermolecular potential energy. By analyzing the composition of the hydrogen bond energy, it is found that the electrostatic energy is much greater than the van der Waals energy, so the water nucleation process mainly overcomes the electrostatic force between molecules. With the gradual increase of pressure, although the kinetic energy distribution of molecules does not change significantly, it will cause the potential energy of water molecules to decrease significantly and then lead to the increase of the energy barrier that needs to be crossed for nucleation. Meanwhile, the rise of the nucleation barrier may result in the absence of obvious initial vapor nuclei inside the liquid so that the number of hydrogen bonds cannot be rapidly reduced, which is not conducive to boiling nucleation. The results of this study provide important implications for further understanding of the nucleate boiling process of water.

19.
Ann Surg Oncol ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014163

ABSTRACT

BACKGROUND: Lung cancer poses a global health threat necessitating early detection and precise staging for improved patient outcomes. This study focuses on developing and validating a machine learning-based risk model for early lung cancer screening and staging, using routine clinical data. METHODS: Two medical center, observational, retrospective studies were conducted, involving 2312 lung cancer patients and 653 patients with benign nodules. Machine learning techniques, including differential analysis and feature selection, were employed to identify key factors for modeling. The study focused on variables such as nodule density, carcinoembryonic antigen (CEA), age, and lifestyle habits. The Logistic Regression model was utilized for early diagnoses, and the XGBoost model was utilized for staging based on selected features. RESULTS: For early diagnoses, the Logistic Regression model achieved an area under the curve (AUC) of 0.716 (95% confidence interval [CI] 0.607-0.826), with 0.703 sensitivity and 0.654 specificity. The XGBoost model excelled in distinguishing late-stage from early-stage lung cancer, exhibiting an AUC of 0.913 (95% CI 0.862-0.963), with 0.909 sensitivity and 0.814 specificity. These findings highlight the model's potential for enhancing diagnostic accuracy and staging in lung cancer. CONCLUSION: This study introduces a novel machine learning-based risk model for early lung cancer screening and staging, leveraging routine clinical information and laboratory data. The model shows promise in enhancing accuracy, mitigating overdiagnosis, and improving patient outcomes.

20.
Sci Data ; 11(1): 780, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013888

ABSTRACT

Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.


Subject(s)
Euglena gracilis , Euglena gracilis/genetics , Chromosomes , Microalgae/genetics , Molecular Sequence Annotation , Glucans
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