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1.
Emerg Microbes Infect ; 13(1): 2409319, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39315943

ABSTRACT

Cluster analysis of HIV sequence can provide insights into viral transmission patterns in border regions. This study aims to illuminate the HIV-1 subtype distribution and transmission dynamics among newly diagnosed individuals in Dehong prefecture, a region along the China-Myanmar border. Among 948 participants with pol gene sequences, 36 HIV-1 subtypes were identified, with URFs (18.8%, 178/948) being the dominant strain, followed by CRF01_AE (18.5%, 175/948) and CRF07_BC (10.9%, 103/948). Additionally, 287 sequences (30.3%, 287/948) were grouped into 91 clusters, 31 of which contained both Chinese and Burmese individuals. Multivariable logistic regression indicated that men who have sex with men (MSM), CD4 + cell count of 200∼499, and 500 cells/µl and above, and CRF01_AE were risk factors for entering the network. Through the Chord diagram, we found frequent transmission relationships among heterosexual China male group, especially those over 35 years of age. Additionally, the correlation between heterosexual Myanmar female group and heterosexual China male group among cross-risk groups deserved to be emphasized. Furthermore, the network exhibited a growing trend over time, with the largest active transmission cluster identified in Ruili county. In conclusion, the HIV-1 subtype landscape in Dehong has become increasingly complex, and the region has faced risks of transmission from both domestic and international sources. Targeted intervention strategies should be implemented for MSM, heterosexual Chinese middle-aged and elderly men, and heterosexual Burmese young adults to mitigate these risks. These findings provided evidence-based insights for local government to formulate coordinated transnational intervention approaches.


Subject(s)
HIV Infections , HIV-1 , Humans , HIV-1/genetics , HIV-1/classification , Male , HIV Infections/transmission , HIV Infections/epidemiology , HIV Infections/virology , Myanmar/epidemiology , China/epidemiology , Female , Adult , Cluster Analysis , Middle Aged , Young Adult , Phylogeny , Adolescent , Risk Factors , Homosexuality, Male , Genotype , CD4 Lymphocyte Count
2.
Oncogene ; 43(39): 2914-2926, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39164524

ABSTRACT

Interest in the use of proteolysis-targeting chimeras (PROTACs) in cancer therapy has increased in recent years. Targeting bromodomain and extra terminal domain (BET) proteins, especially bromodomain-containing protein 4 (BRD4), has shown inhibitory effects on basal-like breast cancer (BLBC). However, the bioavailability of BRD4 PROTACs is restricted by their non-selective biodegradability and low tumor-targeting ability. We demonstrated that 6b (BRD4 PROTAC) suppresses BLBC cell growth by targeting BRD4, but not BRD2 and BRD3, for cereblon (CRBN)-mediated ubiquitination and proteasomal degradation. Compound 6b also inhibited expression of Krüppel-like factor 5 (KLF5) transcription factor, a key oncoprotein in BLBC, controlled by BRD4-mediated super-enhancers. Moreover, 6b inhibited HCC1806 tumor growth in a xenograft mouse model. The combination of 6b and KLF5 inhibitors showed additive effects on BLBC. These results suggest that BRD4-specific PROTAC can effectively inhibit BLBC by downregulating KLF5, and that 6b has potential as a novel therapeutic drug for BLBC.


Subject(s)
Breast Neoplasms , Cell Cycle Proteins , Kruppel-Like Transcription Factors , Proteolysis , Transcription Factors , Xenograft Model Antitumor Assays , Humans , Kruppel-Like Transcription Factors/metabolism , Kruppel-Like Transcription Factors/genetics , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Mice , Female , Transcription Factors/antagonists & inhibitors , Transcription Factors/metabolism , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/antagonists & inhibitors , Proteolysis/drug effects , Cell Line, Tumor , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Cell Proliferation/drug effects , Ubiquitination/drug effects , Mice, Nude , Bromodomain Containing Proteins
3.
Angew Chem Int Ed Engl ; : e202407921, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39175097

ABSTRACT

Fatty acids produced by the type-II fatty acid biosynthesis pathway (FAS-II) are essential biomaterials for bacterial membrane construction and numerous metabolic routes. The ß-ketoacyl-ACP synthase FabF catalyzes the key C-C bond formation step for fatty acid extension in FAS-II. Here, we revealed the substrate recognition and catalytic mechanisms of FabF by determining FabF-ACP complexes. FabF displays a distinctive bimodal catalytic pattern specifically on C6 and C10 acyl-ACP substrates. It utilizes positively charged residues located on the η3-helix and loop1 regions near the catalytic tunnel entrance to bind ACP, and two hydrophobic cavities as well as "front", "middle", and "back" door residues to specifically stabilize C6 and C10 acyl substrates for preferential catalysis. Further quantum chemistry calculations suggest that the FabF catalytic residues Lys336 and His304 facilitate proton transfer during condensation catalysis and C-C bond formation. Our results provide key mechanistic insights into the biosynthesis of molecular carbon skeletons based on ketosynthases that are highly conserved through the FAS and polyketide synthase (PKS) analogous biosynthetic routes, broaden the understanding of the tricarboxylic acid cycle that utilizes lipoic acid derived from C8-ACP accumulated due to the FabF distinctive catalytic pattern for oxidative decarboxylations, and may facilitate the development of narrow-spectrum antibacterial drugs.

4.
Neuroimage ; 298: 120787, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39147293

ABSTRACT

Evidence from epidemiological studies suggests that hearing loss is associated with an accelerated decline in cognitive function, but the underlying pathophysiological mechanism remains poorly understood. Studies using auditory tasks have suggested that degraded auditory input increases the cognitive load for auditory perceptual processing and thereby reduces the resources available for other cognitive tasks. Attention-related networks are among the systems overrecruited to support degraded auditory perception, but it is unclear how they function when no excessive recruitment of cognitive resources for auditory processing is needed. Here, we implemented an EEG study using a nonauditory visual attentional selection task in 30 individuals with age-related hearing loss (ARHLs, 60-73 years) and compared them with aged (N = 30, 60-70 years) and young (N = 35, 22-29 years) normal-hearing controls. Compared with their normal-hearing peers, ARHLs demonstrated a significant amplitude reduction for the posterior contralateral N2 component, which is a well-validated index of the allocation of selective visual attention, despite the comparable behavioral performance. Furthermore, the amplitudes were observed to correlate significantly with hearing acuities (pure tone audiometry thresholds) and higher-order hearing abilities (speech-in-noise thresholds) in aged individuals. The target-elicited alpha lateralization, another mechanism of visuospatial attention, demonstrated in control groups was not observed in ARHLs. Although behavioral performance is comparable, the significant decrease in N2pc amplitude in ARHLs provides neurophysiologic evidence that may suggest a visual attentional deficit in ARHLs even without extra-recruitment of cognitive resources by auditory processing. It supports the hypothesis that constant degraded auditory input in ARHLs has an adverse impact on the function of cognitive control systems, which is a possible mechanism mediating the relationship between hearing loss and cognitive decline.


Subject(s)
Attention , Electroencephalography , Presbycusis , Visual Perception , Humans , Middle Aged , Attention/physiology , Male , Female , Aged , Adult , Visual Perception/physiology , Young Adult , Presbycusis/physiopathology , Aging/physiology , Auditory Perception/physiology
5.
Chembiochem ; : e202400466, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955950

ABSTRACT

The human fatty acid synthase (hFASN) produces fatty acids for cellar membrane construction, energy storage, biomolecule modifications and signal transduction. Abnormal expression and functions of hFASN highly associate with numerous human diseases such as obesity, diabetes, and cancers, and thereby it has been considered as a valuable potential drug target. So far, the structural and catalytic mechanisms of most of the hFASN enzymatic modules have been extensively studied, except the key dehydratase module (hDH). Here we presented the enzymatic characterization and the high-resolution crystal structure of hDH. We demonstrated that the hDH preferentially catalyzes the acyl substrates with short lengths between 4 to 8-carbons, and exhibits much lower enzymatic activity on longer substrates. Subsequent structural study showed that hDH displays a pseudo-dimeric organization with a single L-shaped composite hydrophobic catalytic tunnel as well as an atypical ACP binding site nearby, indicating that hDH achieves distinct substrate recognition and dehydration mechanisms compared to the conventional bacterial fatty acid dehydratases identified. Our findings laid the foundation for understanding the biological and pathogenic functions of hFASN, and may facilitate therapeutical drug development against diseases with abnormal functionality of hFASN.

6.
Int J Antimicrob Agents ; 64(3): 107251, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38906487

ABSTRACT

Antimicrobial resistance (AMR) has emerged as a critical global health challenge. However, the significance of AMR is not limited to humans and domestic animals but extends to wildlife and the environment. Based on the analysis of > 200 peer-reviewed papers, this review provides comprehensive and current insights into the detection of clinically significant antimicrobial resistant bacteria and resistance genes in wild mammals, birds and reptiles worldwide. The review also examines the overlooked roles of wildlife in AMR emergence and transmission. In wildlife, AMR is potentially driven by anthropogenic activity, agricultural and environmental factors, and natural evolution. This review highlights the significance of AMR surveillance in wildlife, identifies species and geographical foci and gaps, and demonstrates the value of multifaceted One Health strategies if further escalation of AMR globally is to be curtailed.


Subject(s)
Animals, Wild , Anti-Bacterial Agents , Bacteria , Drug Resistance, Bacterial , One Health , Animals , Animals, Wild/microbiology , Drug Resistance, Bacterial/genetics , Bacteria/drug effects , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Anti-Bacterial Agents/pharmacology , Birds/microbiology , Humans , Mammals/microbiology , Reptiles/microbiology , Bacterial Infections/microbiology , Bacterial Infections/veterinary , Bacterial Infections/drug therapy , Global Health
7.
Biomed Environ Sci ; 37(4): 399-405, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38727162

ABSTRACT

Objective: This study aimed to determine the current epidemiological status of PLWHA aged ≥ 50 years in China from 2018 to 2021. It also aimed to recommend targeted interventions for the prevention and treatment of HIV/AIDS in elderly patients. Methods: Data on newly reported cases of PLWHA, aged ≥ 50 years in China from 2018 to 2021, were collected using the CRIMS. Trend tests and spatial analyses were also conducted. Results: Between 2018 and 2021, 237,724 HIV/AIDS cases were reported among patients aged ≥ 50 years in China. The main transmission route was heterosexual transmission (91.24%). Commercial heterosexual transmission (CHC) was the primary mode of transmission among males, while non-marital non-CHC ([NMNCHC]; 60.59%) was the prevalent route in women. The proportion of patients with CHC decreased over time ( Z = 67.716, P < 0.01), while that of patients with NMNCHC increased ( Z = 153.05, P < 0.01). The sex ratio varied among the different modes of infection, and it peaked at 17.65 for CHC. The spatial analysis indicated spatial clustering, and the high-high clustering areas were mainly distributed in the southwestern and central-southern provinces. Conclusion: In China, PLWHA, aged ≥ 50 years, were predominantly infected through heterosexual transmission. The primary modes of infection were CHC and NMNCHC. There were variations in the sex ratio among different age groups, infected through various sexual behaviors. HIV/AIDS cases exhibited spatial clustering. Based on these results, the expansion of HIV testing, treatment, and integrated behavioral interventions in high-risk populations is recommended to enhance disease detection in key regions.


Subject(s)
Acquired Immunodeficiency Syndrome , Epidemics , HIV Infections , Humans , China/epidemiology , Male , Female , Middle Aged , Aged , HIV Infections/epidemiology , HIV Infections/transmission , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/transmission , Aged, 80 and over , Prevalence
8.
Chin J Traumatol ; 27(4): 187-199, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38631945

ABSTRACT

PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the total human model for safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities were conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized. RESULTS: There is a significant correlation observed between each criterion of skull and brain injury (p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F-test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. CONCLUSION: The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.


Subject(s)
Accidents, Traffic , Craniocerebral Trauma , Finite Element Analysis , Pedestrians , Humans , Biomechanical Phenomena , Stress, Mechanical
9.
Lancet Glob Health ; 12(5): e744-e755, 2024 May.
Article in English | MEDLINE | ID: mdl-38614628

ABSTRACT

BACKGROUND: Expanding universal health coverage (UHC) might not be inherently beneficial to poorer populations without the explicit targeting and prioritising of low-income populations. This study examines whether the expansion of UHC between 2000 and 2019 is associated with reduced socioeconomic inequalities in infant mortality in low-income and middle-income countries (LMICs). METHODS: We did a retrospective analysis of birth data compiled from Demographic and Health Surveys (DHSs). We analysed all births between 2000 and 2019 from all DHSs available for this period. The primary outcome was infant mortality, defined as death within 1 year of birth. Logistic regression models with country and year fixed effects assessed associations between country-level progress to UHC (using WHO's UHC service coverage index) and infant mortality (overall and by wealth quintile), adjusting for infant-level, mother-level, and country-level variables. FINDINGS: A total of 4 065 868 births to 1 833 011 mothers were analysed from 177 DHSs covering 60 LMICs between 2000 and 2019. A one unit increase in the UHC index was associated with a 1·2% reduction in the risk of infant death (AOR 0·988, 95% CI 0·981-0·995; absolute measure of association, 0·57 deaths per 1000 livebirths). An estimated 15·5 million infant deaths were averted between 2000 and 2019 because of increases in UHC. However, richer wealth quintiles had larger associated reductions in infant mortality from UHC (quintile 5 AOR 0·983, 95% CI 0·973-0·993) than poorer quintiles (quintile 1 0·991, 0·985-0·998). In the early stages of UHC, UHC expansion was generally beneficial to poorer populations (ie, larger reductions in infant mortality for poorer households [infant deaths per 1000 per one unit increase in UHC coverage: quintile 1 0·84 vs quintile 5 0·59]), but became less so as overall coverage increased (quintile 1 0·64 vs quintile 5 0·57). INTERPRETATION: Since UHC expansion in LMICs appears to become less beneficial to poorer populations as coverage increases, UHC policies should be explicitly designed to ensure lower income groups continue to benefit as coverage expands. FUNDING: UK National Institute for Health and Care Research.


Subject(s)
Carboplatin/analogs & derivatives , Developing Countries , Succinates , Universal Health Insurance , Infant , Humans , Retrospective Studies , Infant Mortality , Infant Death , Health Policy
10.
Alzheimers Res Ther ; 16(1): 62, 2024 03 19.
Article in English | MEDLINE | ID: mdl-38504361

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia, progressively impairing cognitive abilities. While neuroimaging studies have revealed functional abnormalities in AD, how these relate to aberrant neuronal circuit mechanisms remains unclear. Using magnetoencephalography imaging we documented abnormal local neural synchrony patterns in patients with AD. To identify global abnormal biophysical mechanisms underlying the spatial and spectral electrophysiological patterns in AD, we estimated the parameters of a biophysical spectral graph model (SGM). METHODS: SGM is an analytic neural mass model that describes how long-range fiber projections in the brain mediate the excitatory and inhibitory activity of local neuronal subpopulations. Unlike other coupled neuronal mass models, the SGM is linear, available in closed-form, and parameterized by a small set of biophysical interpretable global parameters. This facilitates their rapid and unambiguous inference which we performed here on a well-characterized clinical population of patients with AD (N = 88, age = 62.73 +/- 8.64 years) and a cohort of age-matched controls (N = 88, age = 65.07 +/- 9.92 years). RESULTS: Patients with AD showed significantly elevated long-range excitatory neuronal time scales, local excitatory neuronal time scales and local inhibitory neural synaptic strength. The long-range excitatory time scale had a larger effect size, compared to local excitatory time scale and inhibitory synaptic strength and contributed highest for the accurate classification of patients with AD from controls. Furthermore, increased long-range time scale was associated with greater deficits in global cognition. CONCLUSIONS: These results demonstrate that long-range excitatory time scale of neuronal activity, despite being a global measure, is a key determinant in the local spectral signatures and cognition in the human brain, and how it might be a parsimonious factor underlying altered neuronal activity in AD. Our findings provide new insights into mechanistic links between abnormal local spectral signatures and global connectivity measures in AD.


Subject(s)
Alzheimer Disease , Cognition Disorders , Cognitive Dysfunction , Humans , Middle Aged , Aged , Alzheimer Disease/complications , Alzheimer Disease/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Brain/diagnostic imaging , Cognition
11.
Planta ; 259(5): 104, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38551672

ABSTRACT

MAIN CONCLUSION: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron.


Subject(s)
MicroRNAs , Rhododendron , Transcriptome/genetics , Rhododendron/genetics , Rhododendron/metabolism , Ecosystem , Heat-Shock Response/genetics , MicroRNAs/genetics , Gene Expression Profiling
12.
JAC Antimicrob Resist ; 6(2): dlad119, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38455378

ABSTRACT

Objectives: The wide spread of tet(X4) gene orthologues in the environment, food, poultry and humans is causing serious tigecycline resistance. Consequently, developing a fast and universal method to detect tigecycline resistance has become increasingly important. Methods: During 2019-2022, 116 Escherichia coli isolates were obtained from nine provinces in China. All isolates were tested for their susceptibility to antimicrobial agents by the microdilution broth method and for the tet(X4) gene by PCR. Ten tet(X4)-positive E. coli isolates were used to confirm certain conditions, including the optimal incubation time, the optimal concentration of tigecycline, and the cut-off of the relative growth (RG) value. Results: The optimal time and concentration of tigecycline for separation of susceptible and resistant isolates was 2 h and 4 mg/L, and the RG cut-off value was 0.4. We validated whether the experiment was feasible using 116 isolates of E. coli. The method yielded a susceptibility of 94.9% (95% CI: 81.4%-99.1%) and a specificity of 96.1% (95% CI: 88.3%-99.0%). Conclusions: This research has shown that this optical antimicrobial susceptibility testing method can rapidly differentiate between susceptible and resistant phenotypes in isolates of E. coli. In the same range as the current gold-standard methods, the clinical turnaround time is reduced from 48 h to 2.5 h. The above results suggest that the method has splendid specificity and operationality.

13.
Microbiome ; 12(1): 52, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38481333

ABSTRACT

BACKGROUND: The rise of linezolid resistance has been widely observed both in clinical and non-clinical settings. However, there were still data gaps regarding the comprehensive prevalence and interconnections of linezolid resistance genes across various niches. RESULTS: We screened for potential linezolid resistance gene reservoirs in the intestines of both humans and animals, in meat samples, as well as in water sources. A total of 796 bacteria strains out of 1538 non-duplicated samples were identified to be positive for at least one linezolid resistance gene, optrA, poxtA, cfr, and cfr(D). The prevalence of optrA reached 100% (95% CI 96.3-100%) in the intestines of pigs, followed by fish, ducks, and chicken at 77.5% (95% CI 67.2-85.3%), 62.0% (95% CI 52.2-70.9%), and 61.0% (95% CI 51.2-70.0%), respectively. The meat and water samples presented prevalences of 80.0% (95% CI 70.6-87.0%) and 38.0% (95% CI 25.9-51.9%), respectively. The unreported prevalence of the cfr(D) gene was also relatively higher at 13.0% (95% CI 7.8-21.0%) and 19.0% (95% CI 10.9-25.6%) for the feces samples of ducks and pigs, respectively. Enterococci were the predominant hosts for all genes, while several non-enterococcal species were also identified. Phylogenetic analysis revealed a significant genetic distance among linezolid resistance gene reservoirs, with polyclonal structures observed in strains within the same niche. Similar genetic arrays harboring assorted insertion sequences or transposons were shared by reservoirs displaying heterogeneous backgrounds, though large diversity in the genetic environment of linezolid resistance genes was also observed. CONCLUSIONS: The linezolid resistance genes were widespread among various niches. The horizontal transfer played a crucial role in driving the circulation of linezolid resistance reservoirs at the human-animal-environment interfaces. Video Abstract.


Subject(s)
Anti-Bacterial Agents , Enterococcus faecium , Humans , Animals , Swine , Linezolid/pharmacology , Anti-Bacterial Agents/pharmacology , Phylogeny , Enterococcus faecalis/genetics , Enterococcus faecium/genetics , Drug Resistance, Bacterial/genetics , Ducks , Water , Microbial Sensitivity Tests
14.
Nanomedicine (Lond) ; 19(7): 597-613, 2024 03.
Article in English | MEDLINE | ID: mdl-38299352

ABSTRACT

Background: Copper oxide nanoparticles (CuO NPs) exhibit antitumor activity; however, their potential as an antiangiogenesis agent is unknown. Materials & methods: The antiangiogenesis properties of CuO NPs were evaluated in vitro and in vivo and the underlying mechanism was examined using RNA sequencing and metabolomic analyses. Results: CuO NPs inhibited endothelial cell function in vitro. They also mitigated retinal vasculature development and alleviated pathological retinal angiogenesis in vivo. RNA sequencing and metabolomic analyses revealed that CuO NPs disrupt the tricarboxylic acid cycle and induce cuproptosis, which was further supported by evaluating cuproptosis-related metabolites and proteins. Conclusion: CuO NPs may be an effective antiangiogenic agent for the treatment of retinal angiogenesis.


Subject(s)
Metal Nanoparticles , Nanoparticles , Copper/pharmacology , Angiogenesis , Nanoparticles/metabolism , Endothelial Cells/metabolism , Oxides
15.
J Nanobiotechnology ; 22(1): 80, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38418972

ABSTRACT

The advancement of biomaterials with antimicrobial and wound healing properties continues to present challenges. Macrophages are recognized for their significant role in the repair of infection-related wounds. However, the interaction between biomaterials and macrophages remains complex and requires further investigation. In this research, we propose a new sequential immunomodulation method to enhance and expedite wound healing by leveraging the immune properties of bacteria-related wounds, utilizing a novel mixed hydrogel dressing. The hydrogel matrix is derived from porcine acellular dermal matrix (PADM) and is loaded with a new type of bioactive glass nanoparticles (MBG) doped with magnesium (Mg-MBG) and loaded with Curcumin (Cur). This hybrid hydrogel demonstrates controlled release of Cur, effectively eradicating bacterial infection in the early stage of wound infection, and the subsequent release of Mg ions (Mg2+) synergistically inhibits the activation of inflammation-related pathways (such as MAPK pathway, NF-κB pathway, TNF-α pathway, etc.), suppressing the inflammatory response caused by infection. Therefore, this innovative hydrogel can safely and effectively expedite wound healing during infection. Our design strategy explores novel immunomodulatory biomaterials, offering a fresh approach to tackle current clinical challenges associated with wound infection treatment.


Subject(s)
Anti-Infective Agents , Curcumin , Wound Infection , Animals , Swine , Hydrogels/pharmacology , Wound Healing , Biomimetics , Bandages , Anti-Bacterial Agents/therapeutic use , Biocompatible Materials , Immunotherapy , Wound Infection/drug therapy
16.
ACS Nano ; 18(10): 7644-7655, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38412252

ABSTRACT

Engineering exosomes with nanomaterials usually leads to the damage of exosomal membrane and bioactive molecules. Here, pathological angiogenesis targeting exosomes with magnetic imaging, ferroptosis inducing, and immunotherapeutic properties is fabricated using a simple coincubation method with macrophages being the bioreactor. Extremely small iron oxide nanoparticle (ESIONPs) incorporated exosomes (ESIONPs@EXO) are acquired by sorting the secreted exosomes from M1-polarized macrophages induced by ESIONPs. ESIONPs@EXO suppress pathological angiogenesis in vitro and in vivo without toxicity. Furthermore, ESIONPs@EXO target pathological angiogenesis and exhibit an excellent T1-weighted contrast property for magnetic resonance imaging. Mechanistically, ESIONPs@EXO induce ferroptosis and exhibit immunotherapeutic ability toward pathological angiogenesis. These findings demonstrate that a pure biological method engineered ESIONPs@EXO using macrophages shows potential for targeted pathological angiogenesis therapy.


Subject(s)
Exosomes , Humans , Angiogenesis , Macrophages , Neovascularization, Pathologic/therapy , Magnetic Iron Oxide Nanoparticles
18.
Commun Med (Lond) ; 4(1): 25, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383740

ABSTRACT

BACKGROUND: IMP-producing Klebsiella spp. (IMPKsp) strains have spread globally, including in China. Currently, the prevalence and genomic characterization of IMPKsp is largely unknown nationwide. Here we aimed to provide a general overview of the phenotypic and genomic characteristics of IMPKsp strains. METHODS: 61 IMPKsp strains were obtained from 13 provinces in China during 2016-2021. All strains were tested for their susceptibility to antimicrobial agents by the microdilution broth method and sequenced with Illumina next-generation sequencing. We performed conjugation experiments on thirteen representative strains which were also sequenced by Oxford nanopore sequencing technology to characterize blaIMP-encoding plasmids. RESULTS: We find that all IMPKsp strains display multidrug-resistant (MDR) phenotypes. All strains belong to 27 different STs. ST307 emerges as a principal IMP-producing sublineage. blaIMP-4 is found to be the major isoform, followed by blaIMP-38. Seven incompatibility types of blaIMP-encoding plasmids are identified, including IncHI5 (32/61, 52.5%), IncN-IncR (10/61, 16.4%), IncFIB(K)-HI1B (7/61, 11.5%), IncN (5/61, 8.2%), IncN-IncFII (2/61, 3.3%), IncFII (1/61, 1.6%) and IncP (1/61, 1.6%). The strains carrying IncHI5 and IncN plasmids belong to diverse ST types, indicating that these two plasmids may play an important role in the transmission of blaIMP genes among Klebsiella spp. strains. CONCLUSIONS: Our results highlight that multi-clonal transmission, multiple genetic environments and plasmid types play a major role in the dissemination process of blaIMP genes among Klebsiella spp. IncHI5 type plasmids have the potential to be the main vectors mediating the spread of the blaIMP genes in Klebsiella spp.


Antibiotic resistance occurs when bacteria evolve to withstand antibiotic drugs. We are aware that a bacteria called Klebsiella is rapidly becoming resistant to carbapenems, a class of broad-spectrum antibiotics. In this study, we conducted a genetic and microbiological surveillance study across 13 provinces of China to understand factors that contribute to the growing bacterial drug resistance. We find that the way the multiple bacterial types interact with each other and swap certain genetic material may be the main cause of growing resistance. These findings call for close monitoring of genetic evolution as a matter of public health management strategy.

19.
Sci Rep ; 14(1): 2568, 2024 01 31.
Article in English | MEDLINE | ID: mdl-38297076

ABSTRACT

The freshness of vegetable soybean (VS) is an important indicator for quality evaluation. Currently, deep learning-based image recognition technology provides a fast, efficient, and low-cost method for analyzing the freshness of food. The RGB (red, green, and blue) image recognition technology is widely used in the study of food appearance evaluation. In addition, the hyperspectral image has outstanding performance in predicting the nutrient content of samples. However, there are few reports on the research of classification models based on the fusion data of these two sources of images. We collected RGB and hyperspectral images at four different storage times of VS. The ENVI software was adopted to extract the hyperspectral information, and the RGB images were reconstructed based on the downsampling technology. Then, the one-dimensional hyperspectral data was transformed into a two-dimensional space, which allows it to be overlaid and concatenated with the RGB image data in the channel direction, thereby generating fused data. Compared with four commonly used machine learning models, the deep learning model ResNet18 has higher classification accuracy and computational efficiency. Based on the above results, a novel classification model named ResNet-R &H, which is based on the residual networks (ResNet) structure and incorporates the fusion data of RGB and hyperspectral images, was proposed. The ResNet-R &H can achieve a testing accuracy of 97.6%, which demonstrates a significant enhancement of 4.0% and 7.2% compared to the distinct utilization of hyperspectral data and RGB data, respectively. Overall, this research is significant in providing a unique, efficient, and more accurate classification approach in evaluating the freshness of vegetable soybean. The method proposed in this study can provide a theoretical reference for classifying the freshness of fruits and vegetables to improve classification accuracy and reduce human error and variability.


Subject(s)
Glycine max , Vegetables , Humans , Fruit , Machine Learning , Nutrients
20.
BMC Infect Dis ; 24(1): 49, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178011

ABSTRACT

INTRODUCTION: The dynamic HIV/AIDS epidemic significantly impacts China, particularly affecting injection drug users (IDUs), former plasma donors (FPDs), men who have sex with men (MSM), and those engaging in high-risk heterosexual behavior (HRHB). This study specifically focuses on identifying the risk factors and influences that drive the spread of HIV among these population groups by performing a comprehensive analysis of contact histories of individuals diagnosed with HIV. METHODS: Data for this research were gathered from China's HIV/AIDS Comprehensive Response Information Management System (CRIMS). Contact histories were described using bar and venn diagram. Trend in engaging in HBRB among MSM were identify potential change using the Cochran-Armitage test. Logistic regression was employed to analyze the factors influencing HBRB in MSM. RESULTS: From 1989 through to 2022, a total of 1,457,218 individuals aged 15 years or older in China, who reported being infected with HIV, indicated they had one or more types of contact histories including injecting drug use, male homosexual behavior, commercial plasma donation, and high-risk heterosexual behavior. Among these, 97.0% reported a single type of contact history, while 3.0% reported having multiple contact histories. Of those with multiple contact histories, 98.0% (42,258 individuals) had engaged in HRHB. Among all HIV-infected IDUs, MSM, and FPDs, their respective proportions of engagement in HRHB were 11.8%, 5.7% and 6.2%. Prior to 2012, most were reported to be IDUs; however, subsequent to this, most reported being MSM. Factors that heightened the risk of engaging in HRHB among HIV-infected MSM included being of age between 25-34 years [adjusted odds ratio (AOR) = 1.29] or 35-44 years (AOR = 1.22), marital status such as being married (AOR = 1.23) or being divorced/widowed (AOR = 1.17), belonging to an ethnic minority (AOR = 1.29), receiving diagnosis in hospitals (AOR = 1.81), residing in rural areas (AOR = 1.12), among others. However, the risk of HRHB decreased when age ≥ 55 years (55-64 years: AOR = 0.82; ≥ 65 years: AOR = 0.64). CONCLUSION: The potential for HIV transmission among diverse populations is substantial. As such, it is imperative that strategies are implemented to mitigate the propagation of HIV to the general populace via heterosexual intercourse.


Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Sexual and Gender Minorities , Male , Humans , Adult , Homosexuality, Male , Sexual Behavior , HIV Infections/diagnosis , Ethnicity , Minority Groups , Risk Factors , China/epidemiology
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