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1.
Water Environ Res ; 96(6): e11054, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828755

ABSTRACT

The land application of sewage sludge from wastewater treatment plants has been recognized as a major source of microplastic contamination in soil. Nevertheless, the fate and behavior of microplastics in soil remain uncertain, particularly their distribution and transport, which are poorly understood. This study does a bibliometric analysis and visualization of relevant research publications using the CiteSpace software. It explores the limited research available on the topic, highlighting the potential for it to emerge as a research hotspot in the future. Chinese researchers and institutions are paying great attention to this field and are promoting close academic cooperation among international organizations. Current research hot topics mainly involve microplastic pollution caused by the land application of sewage sludge, as well as the detection, environmental fate, and removal of microplastics in soil. The presence of microplastics in sludge, typically ranging from tens of thousands to hundreds of thousands of particles (p)/kg, inevitably leads to their introduction into soil upon land application. In China, the estimated annual accumulation of microplastics in the soil due to sludge use is approximately 1.7 × 1013 p. In European countries, the accumulation ranges from 8.6 to 71 × 1013 p. Sludge application has significantly elevated soil microplastic concentrations, with higher application rates and frequencies resulting in up to several-fold increases. The primary forms of microplastics found in soils treated with sludge are fragments and fibers, primarily in white color. These microplastics consist primarily of components such as polyamide, polyethylene, and polypropylene. The vertical transport behavior of microplastics is influenced by factors such as tillage, wind, rainfall, bioturbation, microplastic characteristics (e.g., fraction, particle size, and shape), and soil physicochemical properties (e.g., organic matter, porosity, electrical conductivity, and pH). Research indicates that microplastics can penetrate up to 90 cm into the soil profile and persist for decades. Microplastics in sewage sludge-amended soils pose potential long-term threats to soil ecosystems and even human health. Future research should focus on expanding the theoretical understanding of microplastic behavior in these soils, enabling the development of comprehensive risk assessments and informed decision-making for sludge management practices. PRACTITIONER POINTS: Microplastics in sewage sludge range from tens to hundreds of thousands per kilogram. Sludge land application contributes significantly to soil microplastic pollution. The main forms of microplastics in sludge-amended soils are fragments and fibers. Microplastics are mainly composed of polyamide, polyethylene, and polypropylene. Microplastics can penetrate up to 90 cm into the soil profile and persist for decades.


Subject(s)
Microplastics , Sewage , Soil Pollutants , Soil , Sewage/chemistry , Microplastics/analysis , Soil Pollutants/analysis , Soil/chemistry , Bibliometrics , Environmental Monitoring
2.
Acta Biomater ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838909

ABSTRACT

Although vaccination with inactivated vaccines is a popular preventive method against pseudorabies virus (PRV) infection, inactivated vaccines have poor protection efficiency because of their weak immunogenicity. The development of an effective adjuvant is urgently needed to improve the efficacy of inactivated PRV vaccines. In this study, a promising nanocomposite adjuvant named as MIL@A-SW01-C was developed by combining polyacrylic acid-coated metal-organic framework MIL-53(Al) (MIL@A) and squalene (oil)-in-water emulsion (SW01) and then mixing it with a carbomer solution. One part of the MIL@A was loaded onto the oil/water interface of SW01 emulsion via hydrophobic interaction and coordination, while another part was dispersed in the continuous water phase using carbomer. MIL@A-SW01-C showed good biocompatibility, high PRV (antigen)-loading capability, and sustained antigen release. Furthermore, the MIL@A-SW01-C adjuvanted PRV vaccine induced high specific serum antibody titers, increased splenocyte proliferation and cytokine secretion, and a more balanced Th1/Th2 immune response compared with commercial adjuvants, such as alum and biphasic 201. In the mouse challenge experiment, two- and one-shot vaccinations resulted in survival rates of 73.3% and 86.7%, respectively. After one-shot vaccination, the host animal pigs were also challenged with wild PRV. A protection rate of 100% was achieved, which was much higher than that observed with commercial adjuvants. This study not only establishes the superiority of MIL@A-SW01-C composite nanoadjuvant for inactivated PRV vaccine in mice and pigs but also presents an effective method for developing promising nanoadjuvants. STATEMENT OF SIGNIFICANCE: We have developed a nanocomposite of MIL-53(Al) and oil-in-water emulsion (MIL@A-SW01-C) as a promising adjuvant for the inactivated PRV vaccines. MIL@A-SW01-C has good biocompatibility, high PRV (antigen) loading capability, and a good property of sustained antigen release. The developed nanoadjuvant induced much higher specific IgG antibody titers, increased splenocyte proliferation and cytokine secretion, and a more balanced Th1/Th2 immune response than commercial adjuvants alum and biphasic 201. In challenge experiments with mice, survival rates of 73.3% and 86.7% were achieved from two-shot vaccination and one-shot vaccination, respectively. At the same time, a protection rate of 100% was achieved with the host animal pigs challenged with wild PRV.

3.
ACS Nano ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833666

ABSTRACT

The property of being stubborn and degradation resistant makes nanoplastic (NP) pollution a long-standing remaining challenge. Here, we apply a designed top-down strategy to leverage the natural hierarchical structure of waste crayfish shells with exposed functional groups for efficient NP capture. The crayfish shell-based organic skeleton with improved flexibility, strength (14.37 to 60.13 MPa), and toughness (24.61 to 278.98 MJ m-3) was prepared by purposefully removing the inorganic components of crayfish shells through a simple two-step acid-alkali treatment. Due to the activated functional groups (e.g., -NH2, -CONH-, and -OH) and ordered architectures with macropores and nanofibers, this porous crayfish shell exhibited effective removal capability of NPs (72.92 mg g-1) by physical interception and hydrogen bond/electrostatic interactions. Moreover, the sustainability and stability of this porous crayfish shell were demonstrated by the maintained high-capture performance after five cycles. Finally, we provided a postprocessing approach that could convert both porous crayfish shell and NPs into a tough flat sheet. Thus, our feasible top-down engineering strategy combined with promising posttreatment is a powerful contender for a recycling approach with broad application scenarios and clear economic advantages for simultaneously addressing both waste biomass and NP pollutants.

4.
J Am Chem Soc ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842530

ABSTRACT

Photocatalytic C2H6-to-C2H4 conversion is very promising, yet it remains a long-lasting challenge due to the high C-H bond dissociation energy of 420 kJ mol-1. Herein, partially oxidized Pdδ+ species anchored on ZnO nanosheets are designed to weaken the C-H bond by the electron interaction between Pdδ+ species and H atoms, with efforts to achieve high-rate and selective C2H6-to-C2H4 conversion. X-ray photoelectron spectra, Bader charge calculations, and electronic localization function demonstrate the presence of partially oxidized Pdδ+ sites, while quasi-in situ X-ray photoelectron spectra disclose the Pdδ+ sites initially adopt and then donate the photoexcited electrons for C2H6 dehydrogenation. In situ electron paramagnetic resonance spectra, in situ Fourier transform infrared spectra, and trapping agent experiments verify C2H6 initially converts to CH3CH2OH via ·OH radicals, then dehydroxylates to CH3CH2· and finally to C2H4, accompanied by H2 production. Density-functional theory calculations elucidate that loading Pd site can lengthen the C-H bond of C2H6 from 1.10 to 1.12 Å, which favors the C-H bond breakage, affirmed by a lowered energy barrier of 0.04 eV. As a result, the optimized 5.87% Pd-ZnO nanosheets achieve a high C2H4 yield of 16.32 mmol g-1 with a 94.83% selectivity as well as a H2 yield of 14.49 mmol g-1 from C2H6 dehydrogenation in 4 h, outperforming all the previously reported photocatalysts under similar conditions.

5.
J Electrocardiol ; 85: 39-45, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38843738

ABSTRACT

Ventricular premature beats (VPBs) can potentially lead to life-threatening arrhythmias, especially in patients with structural heart disease (SHD). However, identifying dangerous VPBs has always been a topic and challenge in clinical research. This study aimed to evaluate the relationship of postextrasystolic repolarization changes of VPBs with SHD and its possible additional prognostic value. 125 cases of frequent VPBs with SHD and 156 cases without SHD were included. VPBs were stratified selected from 24 h Holter recording according to the scale of heart rate. Average QTDV (difference value of QT interval between the first beat follow VPB with beats preceding VPB) and max QTDV were significantly longer in SHD group than that in the non-SHD group. For identifying patients with SHD, the best cutoff value were 19 ms for average QTDV (AUC = 0.931) and 29 ms for max QTDV (AUC = 0.910) respectively. For Tu morphology analysis, PT2 (postextrasystolic T wave amplitude change ≥2 mV), reversed T wave, and Pu (postextrasystolic u wave) change were all highly specific, but low sensitive as identification of SHD. Compared with average QTDV < 19 ms patients, average QTDV ≥ 19 ms patients had significantly larger left heart size and wores left cardiac function. The presence of non-persistent ventricular tachycardia runs was higher in average QTDV ≥ 19 ms group and positive Pu change group than that in control groups. The findings indicated that postextrasystolic repolarization changes of VPBs correlated with SHD and suggested potential value in prognosis asssessment.

6.
Mater Today Bio ; 26: 101098, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38840795

ABSTRACT

Developing patches that effectively merge intrinsic deformation characteristics of cardiac with superior tunable mechanical properties remains a crucial biomedical pursuit. Currently used traditional block-shaped or mesh patches, typically incorporating a positive Poisson's ratio, often fall short of matching the deformation characteristics of cardiac tissue satisfactorily, thus often diminishing their repairing capability. By introducing auxeticity into the cardiac patches, this study is trying to present a beneficial approach to address these shortcomings of the traditional patches. The patches, featuring the auxetic effect, offer unparalleled conformity to the cardiac complex mechanical challenges. Initially, scaffolds demonstrating the auxetic effect were designed by merging chiral rotation and concave angle units, followed by integrating scaffolds with a composite hydrogel through thermally triggering, ensuring excellent biocompatibility closely mirroring heart tissue. Tensile tests revealed that auxetic patches possessed superior elasticity and strain capacity exceeding cardiac tissue's physiological activity. Notably, Model III showed an equivalent modulus ratio and Poisson's ratio closely toward cardiac tissue, underscoring its outstanding mechanical potential as cardiac patches. Cyclic tensile loading tests demonstrated that Model III withstood continuous heartbeats, showcasing outstanding cyclic loading and recovery capabilities. Numerical simulations further elucidated the deformation and failure mechanisms of these patches, leading to an exploration of influence on mechanical properties with alternative design parameters, which enabled the customization of mechanical strength and Poisson's ratio. Therefore, this research presents substantial potential for designing cardiac auxetic patches that can emulate the deformation properties of cardiac tissue and possess adjustable mechanical parameters.

7.
Front Psychol ; 15: 1361878, 2024.
Article in English | MEDLINE | ID: mdl-38694438

ABSTRACT

This paper explored the training methods to improve the level of deaf college students' ToM. Eighty deaf college students were selected as participants and randomly divided into experimental group and control group. The ToM training group received ToM training; The non-ToM training group received physical-conversation training. Cognitive ToM task and affective ToM task were used to investigate the training effect. After training, the level of ToM of deaf college students who received ToM training was significantly improved. The results show that ToM training can effectively promote the level of deaf college students' ToM.

8.
Mol Oncol ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750006

ABSTRACT

Bladder cancer poses a significant challenge to chemotherapy due to its resistance to cisplatin, especially at advanced stages. Understanding the mechanisms behind cisplatin resistance is crucial for improving cancer therapy. The enzyme glutathione S-transferase omega class 1 (GSTO1) is known to be involved in cisplatin resistance in colon cancer. This study focused on its role in cisplatin resistance in bladder cancer. Our analysis of protein expression in bladder cancer cells stimulated by secretions from tumor-associated macrophages (TAMs) showed a significant increase in GSTO1. This prompted further investigation into the role of GSTO1 in bladder cancer. We found a strong correlation between GSTO1 expression and cisplatin resistance. Mechanistically, GSTO1 triggered the release of large extracellular vesicles (EVs) that promoted cisplatin efflux, thereby reducing cisplatin-DNA adduct formation and enhancing cisplatin resistance. Inhibition of EV release effectively counteracted the cisplatin resistance associated with GSTO1. In conclusion, GSTO1-mediated EV release may contribute to cisplatin resistance caused by TAMs in bladder cancer. Strategies to target GSTO1 could potentially improve the efficacy of cisplatin in treating bladder cancer.

9.
Entropy (Basel) ; 26(5)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38785627

ABSTRACT

Tree-like structures, characterized by hierarchical relationships and power-law distributions, are prevalent in a multitude of real-world networks, ranging from social networks to citation networks and protein-protein interaction networks. Recently, there has been significant interest in utilizing hyperbolic space to model these structures, owing to its capability to represent them with diminished distortions compared to flat Euclidean space. However, real-world networks often display a blend of flat, tree-like, and circular substructures, resulting in heterophily. To address this diversity of substructures, this study aims to investigate the reconstruction of graph neural networks on the symmetric manifold, which offers a comprehensive geometric space for more effective modeling of tree-like heterophily. To achieve this objective, we propose a graph convolutional neural network operating on the symmetric positive-definite matrix manifold, leveraging Riemannian metrics to facilitate the scheme of information propagation. Extensive experiments conducted on semi-supervised node classification tasks validate the superiority of the proposed approach, demonstrating that it outperforms comparative models based on Euclidean and hyperbolic geometries.

10.
J Phys Chem A ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819200

ABSTRACT

As an ambident nucleophile, CN- has both C and N atoms that can act as the reactive center to facilitate substitution reactions. We investigate in detail the potential energy profiles of CN-(H2O)0-3 with CH3CH2X (X = Cl, Br, I) to explore the influence of solvent molecules on competition between the different nucleophilic atoms C and N involving the SN2 and E2 pathways. The energy barrier sequence for the transition states follows C@inv-SN2 < N@inv-SN2 < C@anti-E2 < N@anti-E2. When two different atoms act as nucleophilic atoms, the SN2 reaction is always preferred over the E2 reaction, and this preference increases with microsolvation. For the ambident nucleophiles CN-(H2O)0-3, C as the reactive center always has stronger nucleophilicity and basicity than N acting as the reactive center. Regarding the leaving group, the height of the energy barrier is positively correlated with the acidity of the CH3CH2X substrate for the E2 pathway and with X-heterolysis for the SN2 pathway. Furthermore, we found that in the gas phase, the energy barrier for different leaving group systems decreases gradually in the order Cl > Br > I, while in the SMD solution, the energy barrier and product energy increase slightly in the system from X = Cl to Br; this change may be due to the significantly weakened transition-state interaction for the X = Br system. Our activation strain, quantitative molecular orbital, and charge analyses reveal the physical mechanisms underlying the various computed trends. In addition, we also demonstrate the two points recently proposed by Vermeeren, P. . Chem. Eur. J. 2020, 26, 15538-15548.

11.
PLoS One ; 19(5): e0304379, 2024.
Article in English | MEDLINE | ID: mdl-38809848

ABSTRACT

OBJECTIVE: To determine whether a bidirectional causal relationship exists between major depressive disorder (MDD) and heart failure (HF). METHODS: Our two-sample bidirectional Mendelian randomization (MR) study consisted of two parts. In the first part, we conducted a forward MR analysis where MDD was considered as the exposure and HF as the outcome. In the second part, a reverse MR analysis was performed, treating HF as the exposure and MDD as the outcome. Summary data on MDD and HF were obtained from the IEU Open GWAS database. RESULTS: Based on the results of the MR-Egger regression intercept test, there was no evidence of horizontal pleiotropy in this study. Furthermore, the IVW results consistently suggested estimates of causal effect values. The findings revealed that individuals with MDD had a 16.9% increased risk of HF compared to those without MDD (OR = 1.169, 95%CI: 1.044-1.308, P = 0.007). However, there was no evidence to support that HF would increase the risk of MDD (OR = 1.012, 95%CI: 0.932-1.099, P = 0.773). Heterogeneity in SNPs of MDD and HF was observed through the heterogeneity test and funnel plot. Additionally, the leave-one-out method did not identify any instances where a single SNP was biased toward or dependent on causation. CONCLUSION: Our study provides evidence supporting a one-way causal relationship between MDD and HF. Specifically, MDD increases the risk of developing HF. However, our findings did not provide any evidence suggesting that HF increases the risk of developing MDD.


Subject(s)
Depressive Disorder, Major , Heart Failure , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Humans , Depressive Disorder, Major/genetics , Heart Failure/genetics , Genome-Wide Association Study , Genetic Predisposition to Disease , Risk Factors
12.
Adv Healthc Mater ; : e2304196, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712598

ABSTRACT

For many clinically prevalent severe injuries, the inherent regenerative capacity of skeletal muscle remains inadequate. Skeletal muscle tissue engineering (SMTE) seeks to meet this clinical demand. With continuous progress in biomedicine and related technologies including micro/nanotechnology and 3D printing, numerous studies have uncovered various intrinsic mechanisms regulating skeletal muscle regeneration and developed tailored biomaterial systems based on these understandings. Here, the skeletal muscle structure and regeneration process are discussed and the diverse biomaterial systems derived from various technologies are explored in detail. Biomaterials serve not merely as local niches for cell growth, but also as scaffolds endowed with structural or physicochemical properties that provide tissue regenerative cues such as topographical, electrical, and mechanical signals. They can also act as delivery systems for stem cells and bioactive molecules that have been shown as key participants in endogenous repair cascades. To achieve bench-to-bedside translation, the typical effect enabled by biomaterial systems and the potential underlying molecular mechanisms are also summarized. Insights into the roles of biomaterials in SMTE from cellular and molecular perspectives are provided. Finally, perspectives on the advancement of SMTE are provided, for which gene therapy, exosomes, and hybrid biomaterials may hold promise to make important contributions.

13.
Langmuir ; 40(20): 10792-10803, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38728598

ABSTRACT

To achieve the green, sustainable, and controllable recovery of oil-water resources and to address the limited functionality of single superwet materials in oil-water separation, this study reports a multifunctional oil-water separation strategy by compositing the underwater superoleophobic and underoil superhydrophobic materials (HS). The underwater superoleophobic quartz sands with an oil contact angle of 152.68° were prepared by adjusting the particle size. This material demonstrated a water flux of 4688 L m-2 h-1 and a low-density oil and water mixture separation efficiency of 98.6%, which remained above 97.9% over 50 cycles. It was effective in separating oil-in-water emulsions with a separation efficiency of >99%. For HS, quartz sands were modified with dodecyltrimethoxysilane. The optimized HS-4 exhibited superhydrophobic properties with a water contact angle of 157.06°. It achieved an oil flux of 5775 L m-2 h-1 and a water and dichloromethane mixture separation efficiency of 98.4%. Additionally, they exhibited significant potential in the separation of water-in-oil emulsions. Furthermore, by placing the underwater superoleophobic and underoil superhydrophobic units at the bottom of the filter, we achieved cyclic separation of high-density oil and water mixtures, low-density oil and water mixtures, water-in-oil emulsions, and oil-in-water emulsions. The separation efficiency consistently exceeded 96.5% over 10 cycles. In addition, the oil-water separation mechanism of underwater oleophobic and underoil hydrophobic materials was demonstrated by the relative concentration distribution of water and oil with molecular dynamics simulations. This intelligent oil-water separation method marks a significant advancement in the sustainable separation of diverse oil-water mixtures.

14.
Cancer Invest ; 42(4): 333-344, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38712480

ABSTRACT

BACKGROUND: There is a controversy about whether surgery should proceed among metastatic pancreatic cancer (mPC) patients. A survival benefit was observed in mPC patients who underwent primary tumor resection; however, determining which patients would benefit from surgery is complex. For this purpose, we created a model to identify mPC patients who may benefit from primary tumor excision. METHODS: Patients with mPC were extracted from the Surveillance, Epidemiology, and End Results database, and separated into surgery and nonsurgery groups based on whether the primary tumor was resected. Propensity score matching (PSM) was applied to balance confounding factors between the two groups. A nomogram was developed using multivariable logistic regression to estimate surgical benefit. Our model is evaluated using multiple methods. RESULTS: About 662 of 14,183 mPC patients had primary tumor surgery. Kaplan-Meier analyses showed that the surgery group had a better prognosis. After PSM, a survival benefit was still observed in the surgery group. Among the surgery cohort, 202 patients survived longer than 4 months (surgery-beneficial group). The nomogram discriminated better in training and validation sets under the receiver operating characteristic (ROC) curve (AUC), and calibration curves were consistent. Decision curve analysis (DCA) revealed that it was clinically valuable. This model is better at identifying candidates for primary tumor excision. CONCLUSION: A helpful prediction model was developed and validated to identify ideal candidates who may benefit from primary tumor resection in mPC.


Subject(s)
Nomograms , Pancreatic Neoplasms , SEER Program , Humans , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/mortality , Female , Male , Aged , Middle Aged , Propensity Score , Kaplan-Meier Estimate , Prognosis , ROC Curve , Patient Selection , Neoplasm Metastasis
15.
Int J Biol Macromol ; 269(Pt 2): 132172, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38719009

ABSTRACT

Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccines to improve their performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn2+) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn2+-loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn2+-loaded nanoadjuvant for veterinary vaccines.


Subject(s)
Adjuvants, Immunologic , Herpesvirus 1, Suid , Immunity, Cellular , Immunity, Humoral , Manganese , Nanoparticles , Polysaccharides, Bacterial , Tannins , Animals , Mice , Adjuvants, Immunologic/pharmacology , Nanoparticles/chemistry , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Tannins/chemistry , Tannins/pharmacology , Manganese/chemistry , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/pharmacology , Polysaccharides, Bacterial/immunology , Herpesvirus 1, Suid/immunology , Pseudorabies Vaccines/immunology , Vaccines, Inactivated/immunology , Pseudorabies/prevention & control , Pseudorabies/immunology , Female , Cytokines/metabolism , Mice, Inbred BALB C , Antibodies, Viral/blood , Antibodies, Viral/immunology , Polyphenols
16.
Reprod Biol ; 24(2): 100891, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38733656

ABSTRACT

Azoospermia constitutes a significant factor in male infertility, defined by the absence of spermatozoa in the ejaculate, afflicting 15% of infertile men. However, a subset of azoospermic cases remains unattributed to known genetic variants. Prior investigations have identified the chibby family member 2 (CBY2) as prominently and specifically expressed in the testes of both humans and mice, implicating its potential involvement in spermatogenesis. In this study, we conducted whole exome sequencing (WES) on an infertile family to uncover novel genetic factors contributing to azoospermia. Our analysis revealed a homozygous c .355 C>A variant of CBY2 in a non-obstructive azoospermic patient. This deleterious variant significantly diminished the protein expression of CBY2 both in vivo and in vitro, leading to a pronounced disruption of spermatogenesis at the early round spermatid stage post-meiosis. This disruption was characterized by a nearly complete loss of elongating and elongated spermatids. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation assays demonstrated the interaction between CBY2 and Piwi-like protein 1 (PIWIL1). Immunofluorescence staining further confirmed the co-localization of CBY2 and PIWIL1 in the testes during the spermatogenic process in both humans and mice. Additionally, diminished PIWIL1 expression was observed in the testicular tissue from the affected patient. Our findings suggest that the homozygous c .355 C>A variant of CBY2 compromises CBY2 function, contributing to defective spermatogenesis at the round spermiogenic stage and implicating its role in the pathogenesis of azoospermia.


Subject(s)
Azoospermia , Spermatogenesis , Male , Azoospermia/genetics , Humans , Spermatogenesis/genetics , Mutation , Animals , Mice , Testis/metabolism , Testis/pathology , Adult , Exome Sequencing , Pedigree , Argonaute Proteins/genetics , Argonaute Proteins/metabolism
17.
Cell Death Dis ; 15(5): 364, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802337

ABSTRACT

Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.


Subject(s)
Apoptosis , Brain Injuries, Traumatic , Fibronectins , Mice, Knockout , Mitochondria , Neurons , Oxidative Stress , Sirtuin 3 , Animals , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/pathology , Brain Injuries, Traumatic/genetics , Sirtuin 3/metabolism , Sirtuin 3/genetics , Fibronectins/metabolism , Mitochondria/metabolism , Neurons/metabolism , Neurons/pathology , Mice , Humans , Male , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , Mitochondrial Dynamics
18.
Front Genet ; 15: 1380746, 2024.
Article in English | MEDLINE | ID: mdl-38798700

ABSTRACT

The increasing incidence and mortality of prostate cancer worldwide significantly impact the life span of male patients, emphasizing the urgency of understanding its pathogenic mechanism and associated molecular changes that regulate tumor progression for effective prevention and treatment. RNA modification, an important post-transcriptional regulatory process, profoundly influences tumor cell growth and metabolism, shaping cell fate. Over 170 RNA modification methods are known, with prominent research focusing on N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, 5-methylcytidine, pseudouridine, and N4-acetylcytidine modifications. These alterations intricately regulate coding and non-coding RNA post-transcriptionally, affecting the stability of RNA and protein expression levels. This article delves into the latest advancements and challenges associated with various RNA modifications in prostate cancer tumor cells, tumor microenvironment, and core signaling molecule androgen receptors. It aims to provide new research targets and avenues for molecular diagnosis, treatment strategies, and improvement of the prognosis in prostate cancer.

19.
Sci Rep ; 14(1): 8132, 2024 04 07.
Article in English | MEDLINE | ID: mdl-38584153

ABSTRACT

To figure out how does SARS-CoV-2 affect sperm parameters and what influencing factors affect the recovery of sperm quality after infection? We conducted a prospective cohort study and initially included 122 men with SARS-CoV-2 infection. The longest time to track semen quality after infection is 112 days and 58 eligible patients were included in our study eventually. We subsequently exploited a linear mixed-effects model to statistically analyze their semen parameters at different time points before and after SARS-CoV-2 infection. Semen parameters were significantly reduced after SARS-CoV-2 infection, including total sperm count (211 [147; 347] to 167 [65.0; 258], P < 0.001), sperm concentration (69.0 [38.8; 97.0] to 51.0 [25.5; 71.5], P < 0.001), total sperm motility (57.5 [52.3; 65.0] to 51.0 [38.5; 56.8], P < 0.001), progressive motility (50.0 [46.2; 58.0] to 45.0 [31.5; 52.8], P < 0.001). The parameters displayed the greatest diminution within 30 days after SARS-CoV-2 infection, gradually recovered thereafter, and exhibited no significant difference after 90 days compared with prior to COVID-19 infection. In addition, the patients in the group with a low-grade fever showed a declining tendency in semen parameters, but not to a significant degree, whereas those men with a moderate or high fever produced a significant drop in the same parameters. Semen parameters were significantly reduced after SARS-CoV-2 infection, and fever severity during SARS-CoV-2 infection may constitute the main influencing factor in reducing semen parameters in patients after recovery, but the effect is reversible and the semen parameters gradually return to normal with the realization of a new spermatogenic cycle.


Subject(s)
COVID-19 , Infertility, Male , Humans , Male , Semen Analysis , Semen , Prospective Studies , Sperm Motility , SARS-CoV-2 , Spermatozoa , Sperm Count
20.
RSC Adv ; 14(16): 11217-11231, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38590351

ABSTRACT

The present investigation delves into the adverse environmental impact of atmospheric pollutant gases, specifically nitrogen dioxide (NO2) and sulfur dioxide (SO2), which necessitates the identification and implementation of effective control measures. The central objective of this study is to explore the eradication of these pollutants through the utilization of aluminum Al13 and Al15 metal clusters, distinguished by their unique properties. The comprehensive evaluation of gas/cluster interactions is undertaken employing density functional theory (DFT). Geometric optimization calculations for all structures are executed using the ωB97XD functional and the Def2-svp basis set. To probe various interaction modalities, gas molecule distribution around the metal clusters is sampled using the bee colony algorithm. Frequency calculations employing identical model chemistry validate the precision of the optimization calculations. The quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) methodologies are applied for the analysis of intermolecular interactions. This research establishes the robust formation of van der Waals attractions between the investigated gas molecules, affirming aluminum metal clusters as viable candidates for the removal and control of these gases.

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