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1.
J Affect Disord ; 368: 23-32, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39260575

ABSTRACT

BACKGROUND: While patients with major depressive disorder (MDD) and bipolar disorder (BD) exhibited default mode network (DMN) dysfunction revealed by aberrant resting-state functional connectivity (rsFC) patterns, previous findings have been inconsistent. Little is known about the similarities and differences in DMN rsFC between MDD and BD. METHODS: A voxel-wise meta-analysis of seed-based DMN rsFC studies on MDD or BD was performed using the Seed-based d Mapping software with permutation of subject images (SDM-PSI). Aberrant DMN rsFC in both disorders was investigated separately, followed by conjunction and between-disorder comparison analyses. Functional decoding was performed to implicate the psychophysiological underpinnings of derived brain abnormalities. RESULTS: Thirty-four studies comparing 1316 MDD patients with 1327 HC, and 22 studies comparing 1059 BD patients with 1396 HC were included. Compared to HC, MDD patients exhibited DMN hyperconnectivity with frontolimbic systems, and hypoconnectivity with temporal lobe and posterior cingulate cortex. BD patients displayed increased DMN connectivity with bilateral precuneus, and reduced connectivity with prefrontal cortex and middle temporal gyrus. No common patterns of DMN rsFC abnormalities were observed between MDD and BD. Compared to BD, MDD patients showed DMN hyperconnectivity with triangular part of the left inferior frontal gyrus and left fusiform gyrus. Functional decoding found that patterns of DMN rsFC alteration between MDD and BD were primarily related to action and perception domains. CONCLUSION: Distinct DMN dysfunction patterns in MDD and BD enhance current understanding of the neural substrates of mood disorders and may provide a potential biomarker for differentiation.

2.
Natl Sci Rev ; 11(10): nwae283, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39301071

ABSTRACT

Black carbon (BC) is a crucial air pollutant that contributes to short-lived climate forcing and adverse health impacts. BC emissions have rapidly declined over the past three decades and it is important to uncover the major factors behind this decline. Herein, the temporal trends in BC emissions were compiled from 146 detailed sources from 1960 to 2019. Results revealed that the major emission sources were residential solid fuel usage, coke production and brick production. Furthermore, 96.9% of the emission reduction from 3.03 Tg in 1995 to 1.02 Tg in 2019 was attributed to these three sources. It was determined that the transition in residential energy/stove usage, phasing-out of beehive coke ovens and brick kiln upgrading were the most important drivers leading to this reduction and will continue to play a key role in future emission mitigation. In addition, this study identified the need to address emissions from coal used in vegetable greenhouses and the commercial sector, and diesel consumption in on/off-road vehicles.

3.
Int Immunopharmacol ; 142(Pt A): 113053, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39260307

ABSTRACT

Abnormally elevated tumor necrosis factor-α (TNFα) levels at the maternal-fetal interface can lead to adverse pregnancy outcomes, including recurrent miscarriage (RM), but the mechanism underlying upregulated TNFα expression is not fully understood. We previously reported that the interaction between monoclonal nonspecific suppressor factor-ß (MNSFß) and RC3H1 upregulates TNFα expression, but the precise mechanisms are unknown. In this study, we found that MNSFß stimulated the LPS-induced TNFα expression by inactivating the promoting effect of RC3H1 on TNFα mRNA degradation rather than directly inhibiting the expression of RC3H1 in THP1-Mϕs. Mechanistically, the 81-326 aa region of the RC3H1 protein binds to the 101-133 aa region of the MNSFß protein, and MNSFß facilitated stress granules (SGs) formation and the translocation of RC3H1 to SGs by interacting with RC3H1 and fragile X mental retardation 1 (FMR1) in response to LPS-induced stress. The SGs-localization of RC3H1 reduced its inhibitory effect on TNFα expression in LPS-treated THP1-Mϕs. The designed HEPN2 peptide effectively reduced the LPS-induced expression of TNFα in THP1-Mϕs by interfering with the MNSFß-RC3H1 interaction. Treatment with the HEPN2 peptide significantly improved adverse pregnancy outcomes, including early pregnancy loss (EPL) and lower fetal weight (LFW), which are induced by LPS in mice. These data indicated that MNSFß promoted TNFα expression at least partially by increasing the localization of RC3H1 to SGs under inflammatory stimulation and that the HEPN2 peptide improved the adverse pregnancy outcomes induced by LPS in mice, suggesting that MNSFß is a potential pharmacological target for adverse pregnancy outcomes caused by abnormally increased inflammation at early pregnancy.

4.
Phys Chem Chem Phys ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39234768

ABSTRACT

In this paper, a kind of layered metastructure (LMS) is proposed by stacking multi-layer dielectric plates. By adjusting the dielectric constant of medium A (set as εi), the Brewster angle (BA) of incident electromagnetic waves (EMWs) has been directly selected. At the same time, the operating band of the above angle selection (AS) can be extended to the whole visible light band (VLB) which covers 400 nm to 700 nm according to Bragg reflection. After careful design, two ranges of BAs that cross 0° to 42° and 0° to 60° have been realized in the VLB, which is defined as privacy protection (PP) in this paper. Compared with previous reports, this accomplishment improves transmissivity at small angles and covers a large band. Also, the gradient thickness of the proposed LMS can be changed arbitrarily according to the needs of operating bands, which undoubtedly expands the actual operating scenarios. The obtained results can offer some help to the design of directional devices in industry production, the PP of daily life, and so on.

5.
Environ Int ; 190: 108936, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39146863

ABSTRACT

Electricity production is a significant source of air pollution. Various factors, including electricity demand, generation efficiency, energy mix, and end-of-pipe control measures, are responsible for the emission changes during electricity generation. Although electricity production more than doubled from 1990 to 2017, air pollutant emissions showed a moderate increase or decrease, which was attributed to mitigating drivers such as increased clean energy use, improved power generation efficiency, and widespread installation of end-of-pipe control facilities. The absence of these mitigating drivers would have increased CO2, fine particulate matter (PM2.5), black carbon, SO2, and NOx emissions in 2017 by 165 %, 403 %, 1070 %, 614 %, and 274 % than their actual levels, respectively. The improved electricity generation efficiency reduced potential CO2, PM2.5, SO2, and NOx emissions by 30 %, 295 %, 119 %, and 52 % compared to actual emissions, respectively. Meanwhile, the installation of end-of-pipe facilities reduced potential SO2 and PM2.5 emissions by 34.7 and 4.0 Tg, respectively. Considerable differences in emissions among countries were found to be attributable to their differences in electricity demand and the implementation of local mitigating polices.


Subject(s)
Air Pollutants , Air Pollution , Carbon Dioxide , Particulate Matter , Power Plants , Air Pollutants/analysis , Carbon Dioxide/analysis , Air Pollution/statistics & numerical data , Air Pollution/prevention & control , Particulate Matter/analysis , Environmental Monitoring , Sulfur Dioxide/analysis
6.
ACS Nano ; 18(34): 23289-23300, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39151414

ABSTRACT

mRNA vaccines have been revolutionizing disease prevention and treatment. However, their further application is hindered by inflammatory side effects, primarily caused by delivery systems such as lipid nanoparticles (LNPs). In response to this issue, we prepared cationic lipids (mLPs) derived from mildronate, a small-molecule drug, and subsequently developed the LNP (mLNP-69) comprising a low dose of mLP. Compared with the LNP (sLNP) based on SM-102, a commercially available ionizable lipid, mLNP-69 ensures effective mRNA delivery while significantly reducing local inflammation. In preclinical prophylactic and therapeutic B16-OVA melanoma models, mLNP-69 demonstrated successful mRNA cancer vaccine delivery in vivo, effectively preventing tumor occurrence or impeding tumor progression. The results suggest that the cationic lipids derived from mildronate, which exhibit efficient delivery capabilities and minimal inflammatory side effects, hold great promise for clinical application.


Subject(s)
Inflammation , Lipids , Animals , Mice , Lipids/chemistry , Inflammation/prevention & control , Nanoparticles/chemistry , Mice, Inbred C57BL , Cancer Vaccines/immunology , Cancer Vaccines/administration & dosage , Cancer Vaccines/chemistry , mRNA Vaccines , RNA, Messenger/genetics , Female , Melanoma, Experimental/pathology
7.
Nucleic Acids Res ; 52(17): 10255-10275, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39162221

ABSTRACT

Pachynema progression contributes to the completion of prophase I. Nevertheless, the regulation of this significant meiotic process remains poorly understood. In this study, we identified a novel testis-specific protein HSF5, which regulates pachynema progression during male meiosis in a manner dependent on chromatin-binding. Deficiency of HSF5 results in meiotic arrest and male infertility, characterized as unconventional pachynema arrested at the mid-to-late stage, with extensive spermatocyte apoptosis. Our scRNA-seq data confirmed consistent expressional alterations of certain driver genes (Sycp1, Msh4, Meiob, etc.) crucial for pachynema progression in Hsf5-/- individuals. HSF5 was revealed to primarily bind to promoter regions of such key divers by CUT&Tag analysis. Also, our results demonstrated that HSF5 biologically interacted with SMARCA5, SMARCA4 and SMARCE1, and it could function as a transcription factor for pachynema progression during meiosis. Therefore, our study underscores the importance of the chromatin-associated HSF5 for the differentiation of spermatocytes, improving the protein regulatory network of the pachynema progression.


Subject(s)
Chromatin , Infertility, Male , Meiosis , Spermatocytes , Transcription Factors , Male , Animals , Mice , Chromatin/metabolism , Chromatin/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Spermatocytes/metabolism , Meiosis/genetics , Infertility, Male/genetics , Pachytene Stage/genetics , Spermatogenesis/genetics , Testis/metabolism , Mice, Knockout , Fertility/genetics , Apoptosis/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , DNA Helicases/genetics , DNA Helicases/metabolism , Adenosine Triphosphatases , Chromosomal Proteins, Non-Histone
8.
Cell Mol Biol (Noisy-le-grand) ; 70(7): 174-179, 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39097877

ABSTRACT

AGO2 plays a vital role in small RNA-guided gene silencing, which has been implied in the tumorigenesis of different types of tumors. Fundamentally, increased expression of AGO2 protein is associated with cancer progression and metastasis. This study aims to investigate the molecular mechanism by which AGO2 promotes tumorigenesis in colorectal cancer (CRC). Databases were used to analyze the expression levels of AGO2 in CRC and confirmed by a quantitative reverse transcriptase-PCR (qRT-PCR) assay in CRC tissues and normal adjacent tissues collected from 25 CRC patients. CRISPR/Cas9-mediated genome editing was used to knockout the AGO2 in HCT116 cells as a model system for colorectal cancers. The cell proliferation, migration and invasion ability of HCT116 cells were detected by CCK-8 assay, Wound scratch assay and Transwell assay. Moreover, the quantities of miRNA binding with AGO2 were detected by RNA-Binding Protein Immunoprecipitation (RIP-Assay). We demonstrated that AGO2 was aberrantly high-expressed in 25 matched-tissue pairs of colorectal cancer and para-carcinoma tissue. The following functional experiments verified that knockout of AGO2 suppressed cell proliferation, migration and tumorigenesis to hamper the aggressiveness of CRC. Our study also suggests a possible link between AGO2 and miRNA in RISC. AGO2 was elevated in CRC and knockout of AGO2 suppressed proliferation and tumorigenicity of CRC cells. Moreover, RISC formation and the function of miRNAs are also subject to AGO2. AGO2 may be a meaningful target for CRC therapy.


Subject(s)
Argonaute Proteins , CRISPR-Cas Systems , Carcinogenesis , Cell Movement , Cell Proliferation , Colorectal Neoplasms , Gene Expression Regulation, Neoplastic , MicroRNAs , Humans , Argonaute Proteins/metabolism , Argonaute Proteins/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Cell Proliferation/genetics , CRISPR-Cas Systems/genetics , Cell Movement/genetics , Carcinogenesis/genetics , Carcinogenesis/pathology , HCT116 Cells , MicroRNAs/genetics , MicroRNAs/metabolism , Gene Knockout Techniques
9.
Int J Mol Sci ; 25(15)2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39125892

ABSTRACT

Boron (B) deficiency has been shown to inhibit root cell growth and division. However, the precise mechanism underlying B deficiency-mediated root tip growth inhibition remains unclear. In this study, we investigated the role of BnaA3.NIP5;1, a gene encoding a boric acid channel, in Brassica napus (B. napus). BnaA3.NIP5;1 is expressed in the lateral root cap and contributes to B acquisition in the root tip. Downregulation of BnaA3.NIP5;1 enhances B sensitivity in B. napus, resulting in reduced shoot biomass and impaired root tip development. Transcriptome analysis was conducted on root tips from wild-type B. napus (QY10) and BnaA3.NIP5;1 RNAi lines to assess the significance of B dynamics in meristematic cells during seedling growth. Differentially expressed genes (DEGs) were significantly enriched in plant circadian rhythm and nitrogen (N) metabolism pathways. Notably, the circadian-rhythm-related gene HY5 exhibited a similar B regulation pattern in Arabidopsis to that observed in B. napus. Furthermore, Arabidopsis mutants with disrupted circadian rhythm (hy5/cor27/toc1) displayed heightened sensitivity to low B compared to the wild type (Col-0). Consistent with expectations, B deficiency significantly disrupted N metabolism in B. napus roots, affecting nitrogen concentration, nitrate reductase enzyme activity, and glutamine synthesis. Interestingly, this disruption was exacerbated in BnaA3NIP5;1 RNAi lines. Overall, our findings highlight the critical role of B dynamics in root tip cells, impacting circadian rhythm and N metabolism, ultimately leading to retarded growth. This study provides novel insights into B regulation in root tip development and overall root growth in B. napus.


Subject(s)
Boron , Brassica napus , Circadian Rhythm , Gene Expression Regulation, Plant , Nitrogen , Plant Roots , Brassica napus/genetics , Brassica napus/metabolism , Brassica napus/growth & development , Boron/metabolism , Boron/deficiency , Nitrogen/metabolism , Nitrogen/deficiency , Plant Roots/metabolism , Plant Roots/growth & development , Plant Roots/genetics , Circadian Rhythm/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/growth & development , Seedlings/metabolism , Seedlings/growth & development , Seedlings/genetics , Gene Expression Profiling , Plant Proteins/genetics , Plant Proteins/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism
10.
Front Microbiol ; 15: 1419914, 2024.
Article in English | MEDLINE | ID: mdl-39144224

ABSTRACT

Microbiota in the reproductive tract of cattle play a vital role in maintaining normal reproduction. However, the information on microbiota in different parts of reproductive tracts with different genetic background is few. The aim of the present study was to describe and compare the microbiota in vagina, cervix and uterus of Yanbian cattle and Yanhuang cattle. The results showed that microbial diversity increases from the vagina to the uterus. The top three bacterial phyla in bovine reproductive tract were Proteobacteria, Firmicutes and Bacteroidetes, accounting for more than 85%. From the vagina to the uterus, the relative abundance of Proteobacteria gradually decreased, while that of Firmicutes gradually increased. Phylum-level Firmicutes and genus-level UCG_010 were significantly enriched in the uterus of Yanbian cattle and Yanhuang cattle. Comparing the same parts of the two breeds, it was found that there was no significant difference in alpha diversity, but significant differences in beta diversity. In addition, microbiota with significant differences in the relative abundance of the reproductive tract were found. These findings lay a foundation for a comprehensive understanding of the structure of the genital tract microbiota of cows and its regulatory mechanisms.

11.
Microbiol Spectr ; : e0069224, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39145626

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus that causes substantial economic loss to the global pig industry. The emergence of PEDV variants has increased the need for new vaccines, as commercial vaccines confer inferior protection against currently circulating strains. It is well established that the induction of mucosal immunity is crucial for PEDV vaccines to provide better protection against PEDV infection. In this study, we constructed a recombinant adenovirus expressing the core neutralization epitope (COE) of G2b PEDV based on human adenovirus serotype 5 (Ad5). We evaluated the effects of different administration routes and doses of vaccine immunogenicity in Balb/c mice. Both intramuscular (IM) and intranasal (IN) administration elicited significant humoral responses, including COE-specific IgG in serum and mucosal secretions, along with serum-neutralizing antibodies. Moreover, IN delivery was more potent than IM in stimulating IgA in serum and mucosal samples and in dampening the immune response to the Ad5 vector. The immune response was stronger after high versus low dose IM injection, whereas no significant difference was observed between high and low IN doses. In summary, our findings provide important insights for developing novel PEDV vaccines.IMPORTANCEPorcine epidemic diarrhea (PED) is a highly contagious disease that has severe economic implications for the pork industry. Developing an effective vaccine against PEDV remains a necessity. Here, we generated a recombinant adenovirus vaccine based on Ad5 to express the COE protein of PEDV (rAd5-PEDV-COE) and systematically evaluated the immunogenicity of the adenovirus-vectored vaccine using different administration routes (intramuscular and intranasal) and doses in a mouse model. Our results show that rAd5-PEDV-COE induced potent systemic humoral response regardless of the dose or immunization route. Notably, intranasal delivery was superior to induce peripheral and mucosal IgA antibodies compared with intramuscular injection. Our data provide valuable insights into designing novel PEDV vaccines.

12.
Front Bioeng Biotechnol ; 12: 1431988, 2024.
Article in English | MEDLINE | ID: mdl-39188374

ABSTRACT

Objective: This study aims to investigate the plantar biomechanics of healthy young males as they descend a single transition step from varying heights. Methods: Thirty healthy young males participated the experiment using the F-scan insole plantar pressure system in which participants made single transition steps descent from four step heights (5, 15, 25, and 35 cm), leading with their dominant or non-dominant foot. Plantar pressure data were collected for 5 s during the period between landing touchdown and standing on the ground. Landing at each step height was repeated three times, with a five-minute rest between different height trials. Results: At 5 cm and 15 cm steps, participants demonstrated a rearfoot landing strategy on both sides. However, forefoot contact was observed at heights of 25 cm and 35 cm. Parameters related to center of plantar pressure (COP) of the leading foot were significantly larger compared to the trailing foot (P < 0.001), increased with higher step heights. Vertical ground reaction forces for the biped, leading and trailing feet decreased with increasing step height (all P < 0.05). The leading foot had a higher proportion of overall and forefoot loads, and a lower proportion of rearfoot load compared to the trailing foot (P < 0.001). The overall load on the dominant side was lower than that on the non-dominant side for both the leading and trailing feet (P < 0.001). For the trailing foot, forefoot load on the dominant side was lower than that on the non-dominant side, however, the opposite result appeared in rearfoot load (P < 0.001). Upon the leading foot landing, forefoot load exceeded the rearfoot load for the dominant (P < 0.001) and non-dominant sides (P < 0.001). Upon the trailing foot landing, forefoot load was lower than the rearfoot load for the dominant (P < 0.001) and non-dominant sides (P = 0.019). Conclusion: When the characteristics of biomechanical stability are compromised by step height, landing foot, and footedness factors - due to altered foot landing strategies, changing COP, or uneven force distribution - ability to control motion efficiently and respond adaptively to the forces experienced during movement is challenged, increasing the likelihood of loss of dynamic balance, with a consequent increased risk of ankle sprains and falls.

13.
Sci Total Environ ; 951: 175694, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39173765

ABSTRACT

There is no evidence on the associations between persistent organic pollutants (POPs) and the incidence of chronic kidney disease (CKD) in the Chinese rural population. We aimed to investigate the individual and mixed effects of 22 POPs on the prevalence and incidence of CKD, and the joint effects of POPs and abnormal glucose metabolism as well as the modification effects of healthy lifestyle on these associations. A total of 2775 subjects, including 925 subjects with normal plasma glucose (NPG) and 925 subjects with prediabetes (PDM) and type 2 diabetes mellitus (T2DM), were enrolled from the Henan Rural Cohort Study. Logistic regression and quantile g-computation were performed to assess the individual and mixed effects of POPs on the risk of CKD. Joint effects of POPs and abnormal glucose metabolism status, as well as the modification effects of lifestyle on CKD were assessed. After 3-year follow-up, an increment of ln-o,p'-DDT was related to an elevated risk of CKD prevalence. Positive associations of p,p'-DDE and ß-BHC with CKD incidence were observed (P < 0.05). In addition, participants with high levels of ∑POPs were associated elevated incidence risk of CKD (OR: 1.217, 95%CI: 1.008-1.469). One quartile increase in POPs mixture was associated with the increased incidence of CKD among T2DM patients (P < 0.05). Further, a higher risk of CKD was observed among PDM and T2DM patients with high levels of o,p'-DDT, p,p'-DDE, ß-BHC, and ∑POPs than NPG subjects with low levels of pollutants. In addition, interactive effects of ∑POPs and lifestyle score on CKD incidence were found. Individual and mixed exposure to POPs increased the prevalence and incidence of CKD, and glucose metabolic status exacerbated the risk of CKD resulting from such exposures. Further, the modifying effects of lifestyle were observed, highlighting the importance of precision prevention for high-risk CKD population and healthy lifestyle intervention measures.


Subject(s)
Diabetes Mellitus, Type 2 , Environmental Exposure , Life Style , Persistent Organic Pollutants , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/epidemiology , Male , Female , Middle Aged , China/epidemiology , Prospective Studies , Environmental Exposure/statistics & numerical data , Diabetes Mellitus, Type 2/epidemiology , Incidence , Adult , Blood Glucose , Prediabetic State/epidemiology , Prevalence , Glucose/metabolism , Rural Population/statistics & numerical data
14.
Radiat Oncol ; 19(1): 93, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39049106

ABSTRACT

BACKGROUND: Conventional single-energy CT can only provide a raw estimation of electron density (ED) for dose calculation by developing a calibration curve that simply maps the HU values to ED values through their correlations. Spectral CT, also known as dual-energy CT (DECT) or multi-energy CT, can generate a series of quantitative maps, such as ED maps. Using spectral CT for radiotherapy simulations can directly acquire ED information without developing specific calibration curves. The purpose of this study is to assess the feasibility of utilizing electron density (ED) maps generated by a novel dual-layer detector spectral CT simulator for dose calculation in radiotherapy treatment plans. METHODS: 30 patients from head&neck, chest, and pelvic treatment sites were selected retrospectively, and all of them underwent spectral CT simulation. Treatment plans based on conventional CT images were transplanted to ED maps with the same structure set, including planning target volume (PTV) and organs at risk (OARs), and the dose distributions were then recalculated. The differences in dose and volume histogram (DVH) parameters of the PTV and OARs between the two types of plans were analyzed and compared. Besides, gamma analysis between these plans was performed by using MEPHYSTO Navigator software. RESULTS: In terms of PTV, the homogeneity index (HI), gradient index (GI), D2%, D98%, and Dmean showed no significant difference between conventional plans and ED plans. For OARs, statistically significant differences were observed in parotids D50%, brainstem in head&neck plans, spinal cord in chest plans and rectum D50% in pelvic plans, whereas the variance remained minor. For the rest, the DVH parameters exhibited no significant difference between conventional plans and ED plans. All of the mean gamma passing rates (GPRs) of gamma analysis were higher than 90%. CONCLUSION: Compared to conventional treatment plans relying on CT images, plans utilizing ED maps demonstrated similar dosimetric quality. However, the latter approach enables direct utilization in dose calculation without the requirements of establishing and selecting a specific Hounsfield unit (HU) to ED calibration curve, providing an advantage in clinical applications.


Subject(s)
Electrons , Feasibility Studies , Organs at Risk , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Tomography, X-Ray Computed , Humans , Radiotherapy Planning, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Retrospective Studies , Electrons/therapeutic use , Organs at Risk/radiation effects , Radiotherapy, Intensity-Modulated/methods , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/diagnostic imaging , Neoplasms/radiotherapy , Neoplasms/diagnostic imaging , Male , Female
15.
Proc Natl Acad Sci U S A ; 121(31): e2322025121, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39052827

ABSTRACT

Microbial communities such as biofilms are commonly found at interfaces. However, it is unclear how the physical environment of interfaces may contribute to the development and behavior of surface-associated microbial communities. Combining multimode imaging, single-cell tracking, and numerical simulations, here, we found that activity-induced interface bulging promotes colony biofilm formation in Bacillus subtilis swarms presumably via segregation and enrichment of sessile cells in the bulging area. Specifically, the diffusivity of passive particles is ~50% lower inside the bulging area than elsewhere, which enables a diffusion-trapping mechanism for self-assembly and may account for the enrichment of sessile cells. We also uncovered a quasilinear relation between cell speed and surface-packing density that underlies the process of active interface bulging. Guided by the speed-density relation, we demonstrated reversible formation of liquid bulges by manipulating the speed and local density of cells with light. Over the course of development, the active bulges turned into striped biofilm structures, which eventually give rise to a large-scale ridge pattern. Our findings reveal a unique physical mechanism of biofilm formation at air-solid interface, which is pertinent to engineering living materials and directed self-assembly in active fluids.


Subject(s)
Bacillus subtilis , Biofilms , Bacillus subtilis/physiology , Biofilms/growth & development
16.
Biomed Chromatogr ; 38(9): e5948, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38981997

ABSTRACT

Epimedium is a traditional Chinese medicine with a wide range of clinical applications; however, there have been numerous reports of adverse reactions in recent years. The most common side effect of Epimedium is liver injury. In this study, the liquid chromatography-mass spectrometry (LC-MS) method has been established to study the components of Epimedium and to identify the components absorbed into the blood of rats. Bioinformatics was used to screen out potential toxic components, and the integrating metabolomics method was used to explore the molecular mechanism of Epimedium-induced liver injury. The chemical constituents of Epimedium were identified by LC-MS, and 62 compounds were obtained, including 57 flavonoids, four organic acids and one alkaloid. The toxicity network of "Epimedium-component-target-liver injury" was constructed using bioinformatics research methods, and then the key hepatotoxic component icaritin was identified. Integrating metabolomics was used to investigate the changes in the metabolic profile of L-02 cells with different durations of icaritin administration compared with the control group, and 106 different metabolites were obtained. A total of 14 potential biomarkers significantly associated with cell survival were screened by Pearson correlation analysis combined with the L-02 cell survival rate. Our study preliminarily revealed the mechanism of hepatotoxicity induced by Epimedium.


Subject(s)
Chemical and Drug Induced Liver Injury , Computational Biology , Epimedium , Flavonoids , Metabolomics , Rats, Sprague-Dawley , Epimedium/chemistry , Metabolomics/methods , Animals , Chemical and Drug Induced Liver Injury/metabolism , Rats , Flavonoids/chemistry , Flavonoids/pharmacology , Male , Humans , Chromatography, Liquid/methods , Cell Line , Mass Spectrometry/methods , Drugs, Chinese Herbal/chemistry , Metabolome/drug effects , Cell Survival/drug effects
17.
Ecotoxicol Environ Saf ; 283: 116778, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39067072

ABSTRACT

BACKGROUND AND AIMS: There is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations. METHODS: A total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM. RESULTS: After 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR-P<0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P<0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients. CONCLUSIONS: Individual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure.


Subject(s)
Diabetes Mellitus, Type 2 , Exercise , Mendelian Randomization Analysis , Pesticides , Humans , Diabetes Mellitus, Type 2/epidemiology , Male , Middle Aged , Female , China/epidemiology , Cohort Studies , Adult , Incidence , Pyrethrins/toxicity , Environmental Exposure , Case-Control Studies , Aged , Blood Glucose/analysis , Environmental Pollutants
18.
J Med Chem ; 67(14): 12386-12398, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38995618

ABSTRACT

Breast cancer, globally the most common cancer in women, presents significant challenges in treatment. Breast-conserving surgery (BCS), a less traumatic and painful alternative to radical mastectomy, not only preserves the breast's appearance but also supports postsurgical functional recovery. However, accurately identifying tumors, precisely delineating margins, and thoroughly removing metastases remain complex surgical challenges, exacerbated by the limitations of current imaging techniques, including poor tumor uptake and low signal contrast. Addressing these challenges, our study developed a series of GnRHR-targeted probes (YQGN-n) for fluorescence imaging and surgical navigation of breast cancer through a drug repositioning strategy. Notably, YQGN-7, with its high cellular affinity (Kd of 217.8 nM), demonstrates exceptional selectivity and specificity for breast cancer tumors, surpassing traditional imaging agents like ICG in tumor uptake and pharmacokinetic properties. Furthermore, YQGN-7's effectiveness in surgical navigation, both for primary breast tumors and metastases, highlights its potential as a revolutionary tool in BCS.


Subject(s)
Breast Neoplasms , Fluorescent Dyes , Gonadotropin-Releasing Hormone , Female , Humans , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Fluorescent Dyes/chemistry , Animals , Gonadotropin-Releasing Hormone/chemistry , Mice , Optical Imaging , Drug Repositioning , Cell Line, Tumor , Mice, Nude , Receptors, LHRH/metabolism , Neoplasm Metastasis , Mice, Inbred BALB C
19.
Bioresour Technol ; 408: 131158, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39059589

ABSTRACT

Despite the promising potential of elemental sulfur-based denitrification (ESDeN) packed-bed progresses, challenges such as excessive biofilm growth and gas entrapment persist, leading to denitrification deterioration. Water flush (WF) is recognized as an effective strategy, yet its effects remain underexplored. To address this knowledge gap, this study systematically investigated WF effects on ESDeN packed-bed denitrification. Results demonstrated that controlling WF effectively regulated denitrification, achieving superior and stable rates. Compared to no WF (0.45 kgN·m-3·d-1), rates improved by 1.20 âˆ¼ 1.56 times under low-frequency (weekly WF, 0.54 kgN·m-3·d-1) and low-intensity WF (0.54 âˆ¼ 0.70 kgN·m-3·d-1). High-frequency (hours WF) and high-intensity WF (30 & 50 m/h) further amplified denitrification rates by 1.73 âˆ¼ 2.29 times. The enhanced denitrifications under low-frequency/intensity WF were mainly attributed to prolonged actual hydraulic retention time (AHRT), while high-frequency/intensity WF improved both AHRT prolonging and biofilm thinning, facilitating mass transfer. This study offers a promising avenue for fine-tuning denitrification rates via strategic WF adjustments.


Subject(s)
Biofilms , Denitrification , Sulfur , Water/chemistry , Bioreactors , Water Purification/methods , Waste Disposal, Fluid/methods
20.
Adv Mater ; 36(31): e2403848, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38837906

ABSTRACT

All-solid-state lithium batteries with polymer electrolytes suffer from electrolyte decomposition and lithium dendrites because of the unstable electrode/electrolyte interfaces. Herein, a molecule crowding strategy is proposed to modulate the Li+ coordinated structure, thus in situ constructing the stable interfaces. Since 15-crown-5 possesses superior compatibility with polymer and electrostatic repulsion for anion of lithium salt, the anions are forced to crowd into a Li+ coordinated structure to weaken the Li+ coordination with polymer and boost the Li+ transport. The coordinated anions prior decompose to form LiF-rich, thin, and tough interfacial passivation layers for stabilizing the electrode/electrolyte interfaces. Thus, the symmetric Li-Li cell can stably operate over 4360 h, the LiFePO4||Li full battery presents 97.18% capacity retention in 700 cycles at 2 C, and the NCM811||Li full battery possesses the capacity retention of 83.17% after 300 cycles. The assembled pouch cell shows excellent flexibility (stand for folding over 2000 times) and stability (89.42% capacity retention after 400 cycles). This work provides a promising strategy to regulate interfacial chemistry by modulating the ion environment to accommodate the interfacial issues and will inspire more effective approaches to general interface issues for polymer electrolytes.

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