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1.
Environ Sci Technol ; 58(19): 8432-8443, 2024 May 14.
Article En | MEDLINE | ID: mdl-38699990

Sea salt (ss) aerosols in PM2.5 are often quantified through source apportionment by applying sodium (Na+) and chloride (Cl-) as the markers, but both markers can be substantially emitted from anthropogenic sources. In this study, we differentiate ss from nonss (nss) portions of Na+ and Cl- to better apportion PM2.5 in a coastal tropical urban environment. Size-resolved ionic profiles accounting for Cl- depletion of aged ss were applied to 162-day measurements during 2012 and 2018-2019. Results show that the nss (likely anthropogenic) portions, on average, account for 50-80% of total Na+ and Cl- in submicron aerosols (PM1). This corresponds to up to 2.5 µg/m3 of ss in submicron aerosols that can be ∼10 times overestimated if one attributes all Na+ and Cl- in PM1 to ss. Employing the newly speciated ss- and nss-portions of Na+ and Cl- to source apportionment of urban PM2.5 via positive matrix factorization uncovers a new source of transported anthropogenic emissions during the southwest monsoon, contributing to 12-15% of PM2.5. This increases anthropogenic PM2.5 by ≥19% and reduces ss-related PM2.5 by >30%. In addition to demonstrating Cl- depletion (aging) in submicron aerosols and quantifying ssNa+, nssNa+, ssCl-, as well as nssCl- therein, the refined PM2.5 apportionment resolves new insights on PM2.5 of anthropogenic origins in urban environments, useful to facilitate policy making.


Aerosols , Air Pollutants , Cities , Environmental Monitoring , Particulate Matter , Environmental Monitoring/methods , Air Pollutants/analysis
2.
Bioresour Technol ; 402: 130784, 2024 Jun.
Article En | MEDLINE | ID: mdl-38701976

Thermoanaerobacterium aotearoense SCUT27 is a prominent producer of biofuels from lignocellulosic materials. To provide sufficient NAD(P)H for ethanol production, redox-related genes, including lactate dehydrogenase (ldh), redox-sensing transcriptional repressor (rex), and hydrogenase (hfsB), were knocked out. However, the growth of strain PRH (Δldh/Δrex/ΔhfsB) was suppressed due to the intracellular redox state imbalance with the increased NADH concentration. Coincidentally, when the Bcd-EtfAB (BCD) complex was overexpressed, the resulting strain PRH-B3 (Δldh/Δrex/ΔhfsB::BCD) grew rapidly and produced ethanol with a high yield. With lignocellulosic hydrolysates, PRH-BA (Δldh/Δrex/ΔhfsB::BCD::adhE) demonstrated high ethanol productivity and yield, reaching levels of 0.45-0.51 g/L/h and 0.46-0.53 g/g sugars, respectively. The study results shed light on the cofactor balance for cell stability and the high ferredoxin-NAD+ reductase activity of the BCD complex under an intracellular low redox state. They also provide an essential reference for developing strains for improved biofuel production.


Ethanol , Thermoanaerobacterium , Ethanol/metabolism , Thermoanaerobacterium/metabolism , Thermoanaerobacterium/genetics , Thermoanaerobacterium/enzymology , Fermentation , NAD/metabolism , Oxidation-Reduction
3.
Environ Int ; 185: 108533, 2024 Mar.
Article En | MEDLINE | ID: mdl-38430585

BACKGROUND: The potential effects of short-term exposure to major ambient gaseous pollutants (ozone: O3, carbon monoxide: CO, and sulfur dioxide: SO2) on platelet mitochondrial DNA (mtDNA) methylation have been uncertain and no studies have examined whether platelet mtDNA methylation levels could modify the associations between ambient gaseous pollutants and the risks of ST-segment depression (STDE) and T-wave inversion events (TIE), two indicators of myocardial ischemia. METHODS: This study used data from a randomized, double-blind, placebo-controlled intervention study with a standardized 24-hour exposure protocol among 110 participants in Beijing. Absolute changes in platelet mtDNA methylation (ACmtDNAm) levels were determined by two repeated measurements on platelet mtDNA methylation levels in blood samples collected before and after the 24-hour exposure period. A multivariable linear regression model and a generalized linear model with a Poisson link function were used to investigate the associations of ambient gaseous pollutants with platelet mtDNA methylation levels, STDE, and TIE, respectively. RESULTS: Short-term O3 exposure was significantly associated with decreased ACmtDNAm at ATP6_P1 but increased ACmtDNAm at mt12sRNA, MT-COX1, and MT-COX1_P2; short-term CO and SO2 exposures were significantly associated with decreased ACmtDNAm at D-loop, MT-COX3- and ATP-related genes. Moreover, short-term O3 exposure was significantly associated with increased risks of STDE and TIE, and ACmtDNAm at MT-COX1 and MT-COX1_P2 modified the association between short-term O3 exposure and STDE events. L-Arg supplementation attenuated the effects of ambient gaseous pollutants, particularly O3, on ACmtDNAm and STDE. CONCLUSIONS: Platelet mtDNA methylation levels are promising biomarkers of short-term exposure to ambient gaseous air pollution, and are likely implicated in the mechanism behind the association of ambient O3 pollution with adverse cardiovascular effects. L-Arg supplementation showed the potential to mitigate the adverse effects of ambient O3 pollution.


Air Pollutants , Air Pollution , Myocardial Ischemia , Ozone , Humans , Air Pollutants/toxicity , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Blood Platelets , DNA, Mitochondrial , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Methylation , Nitrogen Dioxide/analysis , Ozone/analysis , Particulate Matter/analysis , Randomized Controlled Trials as Topic
4.
World J Gastroenterol ; 30(2): 115-127, 2024 Jan 14.
Article En | MEDLINE | ID: mdl-38312115

Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification, thereby contributing significantly to the maintenance of cellular functions related to protein synthesis. SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression, holding immense potential in controlling human diseases. It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types, stages, metastasis, treatment response and/or prognosis in patients. On the other hand, colorectal cancer (CRC), a prevalent malignancy of the digestive system, is characterized by high incidence and mortality rates, ranking as the third most common cancer type. Recent research indicates that snoRNA dysregulation is associated with CRC, as snoRNA expression significantly differs between normal and cancerous conditions. Consequently, assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC. Nevertheless, current comprehension of the potential roles of snoRNAs in CRC remains limited. This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC, providing valuable insights into the discovery of novel biomarkers, therapeutic targets, and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.


Colorectal Neoplasms , RNA, Small Nucleolar , Humans , RNA, Small Nucleolar/genetics , RNA, Small Nucleolar/metabolism , Carcinogenesis/genetics , Cell Transformation, Neoplastic/genetics , Prognosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology
5.
Eur Heart J Case Rep ; 8(2): ytad581, 2024 Feb.
Article En | MEDLINE | ID: mdl-38328600

Background: Isolated arrhythmogenic left ventricular cardiomyopathy (IALVC) is a hereditary cardiomyopathy that is characterized by the replacement of left ventricular (LV) cardiomyocytes with fibrous and adipose tissue. Case summary: A 55-year-old male patient presented with recurrent chest pain and palpitations characterized by episodes of monomorphic ventricular tachycardia and T-wave inversion. Coronary angiography was conducted to rule out myocardial ischaemia as the cause of chest pain. Echocardiography results revealed ventricular aneurysm formation at the apex of the left ventricle. Structural alterations of the cardiac magnetic resonance were consistent with the diagnosis of arrhythmogenic left ventricular cardiomyopathy with LV alterations without right ventricular involvement. Pathological staining of the lesion area further confirmed the diagnosis of IALVC. The TTN1 c.17617 C>A mutation in arrhythmogenic cardiomyopathy was identified using whole exome sequencing. His symptoms improved by the treatments including implantable cardioverter defibrillator (ICD) implantation, radiofrequency ablation, and ventricular aneurysm resection. Discussion: The patient presented with IALVC with apical fibrofatty displacement and underwent surgical management, highlighting the importance of multimodal imaging, gene analysis, and histopathological findings for timely diagnosis, and emphasizing the benefits of life-saving therapy, including ICD implantation, radiofrequency ablation, and ventricular aneurysm resection. These findings contribute to a deeper understanding of the clinical presentation and outcome of IALVC.

6.
Ann Hematol ; 103(4): 1345-1351, 2024 Apr.
Article En | MEDLINE | ID: mdl-38316642

Myelodysplastic syndrome (MDS) is a rare clonal hematopoietic disorder in children. The risk stratification system and treatment strategy for adults are unfit for children. The role of hypomethylating agents (HMAs) in higher-risk childhood MDS has not been identified. This study aimed to investigate the outcomes of hematopoietic stem cell transplantation (HSCT) in children with higher-risk MDS at one single center. A retrospective study was conducted in children with higher-risk MDS undergoing HSCT between September 2019 and March 2023 at Blood Diseases Hospital CAMS. The clinical characteristics and transplantation information were reviewed and analyzed. A total of 27 patients were analyzed, including 11 with MDS with excess blasts (MDS-EB), 14 with MDS-EB in transformation (MDS-EBt) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 2 with therapy-related MDS/AML (t-MDS/AML). Eight patients harbored monosomy 7. Before transplantation, induction therapy was administered to 25 patients, and 19 of them achieved bone marrow blasts <5% before HSCT. The stem cell source was unmanipulated-related bone marrow or peripheral blood stem cells for nineteen patients and unrelated cord blood for eight. All patients received decitabine-containing and Bu/Cy-based myeloablative conditioning; 26 patients achieved initial engraftment. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GvHD) at 100 days were 65.4% and 42.3%, respectively. The incidence of cGvHD was 38.5%. The median follow-up was 26 (range 4-49) months after transplantation. By the end of follow-up, two patients died of complications and two died of disease progression. The probability of 3-year overall survival (OS) was 84.8% (95%CI, 71.1 to 98.5%). In summary, decitabine-containing myeloablative conditioning resulted in excellent outcomes for children with higher-risk MDS undergoing allogeneic HSCT.


Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Adult , Child , Humans , Decitabine/therapeutic use , Retrospective Studies , Transplantation, Homologous , Hematopoietic Stem Cell Transplantation/methods , Myelodysplastic Syndromes/drug therapy , Transplantation Conditioning/methods , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/drug therapy , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control
7.
Front Biosci (Landmark Ed) ; 29(2): 90, 2024 Feb 23.
Article En | MEDLINE | ID: mdl-38420791

BACKGROUND: Deguelin (DGL) is a natural flavonoid reported to exhibit antitumor effects in breast cancer (BC). PEG-PCL (Polyethylene Glycol- Polycaprolactone), as polymeric micelles, has biodegradability and biocompatibility. The aim of this study was to investigate whether the nanoparticular delivery system, PEG-PCL could improve the bioavailability of DGL for suppressing proliferation of BC cells. METHODS: PEG-PCL polymers were first prepared by ring-opening polymerization, and DGL and paclitaxel (PTX)-loaded PEG-PCL nano-micelles were formulated via the film dispersion method. The composition and molecular weight of PEG-PCL were analyzed by nuclear magnetic resonance and fourier Transform infrared spectroscopy (FTIR) spectra. Particle size, surface potential and hemolytic activity of micelles were assessed by dynamic light scattering, transmission electron microscopy and hemolysis assay, respectively. Then proliferation and apoptosis of MDA-MB-231 and MDA-MB-468 cells were tested with Edu staining, CCK-8, TUNEL staining, and Flow cytometer. Caspase 3 expression was also assessed by Western blot. RESULTS: Our results first indicated that PEG2000-PCL2000 was successfully synthesized. DGL and PTX-loaded PEG-PCL nano-micelles were rounded in shape with a particle size of 35.78 ± 0.35 nm and a surface potential of 2.84 ± 0.27 mV. The micelles had minimal hemolytic activity. Besides, we proved that DGL and PTX-loaded PEG-PCL nano-micelles could suppress proliferation and induce apoptosis in BC cells. The DGL and PTX-loaded PEG-PCL nano-micelles constructed in this study had a prominent inhibitory role on proliferation and a remarkable promotional role on apoptosis in BC cells. CONCLUSIONS: This study proposes that nano-micelles formed by PEG-PCL can enhance the cytotoxicity of Paclitaxel against breast cancer cells, and concurrently, the loading of Deguelin may further inhibit cell proliferation. This presents a potential for the development of a novel therapeutic strategy.


Breast Neoplasms , Paclitaxel , Rotenone/analogs & derivatives , Humans , Female , Paclitaxel/pharmacology , Breast Neoplasms/drug therapy , Micelles , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Polyethylene Glycols/therapeutic use , Polymers , Apoptosis , Cell Line, Tumor
8.
Yi Chuan ; 46(2): 149-167, 2024 Feb 20.
Article En | MEDLINE | ID: mdl-38340005

The Han populations represent the largest ethnic group in China. Previous studies have primarily focused on investigating their genetic origins, migration and integration, as well as paternal genetic relationships within specific regional Han populations. However, a comprehensive analysis of the global paternal genetic structure of Han populations is lacking. In this study, we performed Y-chromosome sequencing on 362 unrelated male samples from Chinese Han individuals collected from Qinghai, Sichuan and Liaoning provinces. We then integrated relevant data from reported studies. Our final dataset comprised 1830 samples from 16 Han populations across 15 provinces in China, encompassing information on 89 Y-SNPs and 16 Y-STRs. Statistical analyses were conducted to assess Y-STR haplotype diversity (HD) and Y-SNP haplogroup frequencies. Additionally, we employed principal component analysis (PCA), phylogenetic tree and haplotype network to explore genetic differentiation within Han populations and the genetic relationships between Han populations and ethnic minorities surrounding them. Our results demonstrated that the O-M175 haplogroup represents the predominant paternal lineage in Han populations, with frequencies ranging from 60.53% (Qinghai Han) to 92.7% (Guangdong Han). Moreover, the subclades downstream of O-M175 showed distinct regional variations in their distribution patterns. The O2-M122 haplogroup was prevalent in all Han populations and demonstrated a gradual decline in frequency from north to south. Conversely, the distribution frequency of the O1b-M268 haplogroup decreased from south to north, particularly showed significant presence among Han populations in the Lingnan region. Haplogroup O1a-M119 distributed more frequently in the central Han populations. Our findings revealed that Chinese Han populations can be categorized into three subgroups: northern, central, and southern. Notably, there were significant differences among Han in Qinghai and other regions. Regarding the genetic relationships between Han populations and surrounding ethnic minorities, we observed a closer genetic affinity between different Han populations, but northern Han demonstrated a stronger relationship with the Hui ethnic group, while southern Han exhibited a closer connection with the Gelao and Li ethnic groups. In summary, this study presented a systematic analysis of haplogroup distribution, genetic substructure of Han populations and genetic relationships between Han populations and surrounding ethnic minorities based on 89 Y-SNPs and 16 Y-STRs systematically. Our research supplemented valuable insights into population genetics and forensic genetics, and provided data support for the forensic application of Y chromosome. The integration of Y-SNP haplogroups with Y-STR haplotypes offers enhanced understanding of the genetic substructure within Han populations, which holds significance for both population genetics research and forensic science applications.


Microsatellite Repeats , Polymorphism, Single Nucleotide , Humans , Phylogeny , Genetics, Population , Ethnicity/genetics , Haplotypes , Chromosomes, Human, Y/genetics , China
9.
Inorg Chem ; 63(5): 2814-2820, 2024 Feb 05.
Article En | MEDLINE | ID: mdl-38265337

In the present work, we have successfully obtained two new UV antimony-based sulfates, NH4Sb(SO4)2 and Ca2Sb2O(SO4)4, by a conventional hydrothermal method. Interestingly, both compounds share similar structural building blocks, such as SbO4 seesaws and SO4 tetrahedra, yet they endow discrepant birefringence values measured at 546 nm with values of 0.150 and 0.114, respectively, owing to the different distortions of the SbO4 groups with SCALP electrons. Moreover, both compounds display large band gaps (4.32 and 4.43 eV, respectively), so they can be used as short-wavelength UV birefringent materials. Moreover, NH4Sb(SO4)2 is a noncentrosymmetric compound, showing a frequency doubling effect of 0.2 × KDP. Detailed structural analyses and calculations confirm the source of superior optical performance and the reasons for the different birefringence of the two compounds. This work provides ideas for the following discovery of antimony-based optical materials with excellent properties.

10.
World J Clin Oncol ; 15(1): 9-22, 2024 Jan 24.
Article En | MEDLINE | ID: mdl-38292664

Chronic inflammation is known to increase the risk of gastrointestinal cancers (GICs), the common solid tumors worldwide. Precancerous lesions, such as chronic atrophic inflammation and ulcers, are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis. Unfortunately, due to the lack of effective therapeutic targets, the prognosis of patients with GICs is still unsatisfactory. Interestingly, it is found that six transmembrane epithelial antigens of the prostate (STEAPs), a group of metal reductases, are significantly associated with the progression of malignancies, playing a crucial role in systemic metabolic homeostasis and inflammatory responses. The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress, responding to inflammatory reactions. Under the imbalance status of abnormal oxidative stress, STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process. This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms, with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

11.
Toxics ; 12(1)2024 Jan 15.
Article En | MEDLINE | ID: mdl-38251031

BACKGROUND: The burden of cardiovascular diseases caused by ambient particulate air pollution is universal. An increasing number of studies have investigated the potential effects of exposure to particulate air pollution on endothelial function, which is one of the important mechanisms for the onset and development of cardiovascular disease. However, no previous study has conducted a summary analysis of the potential effects of particulate air pollution on endothelial function. OBJECTIVES: To summarize the evidence for the potential effects of short-term exposure to ambient particulate air pollution on endothelial function based on existing studies. METHODS: A systematic literature search on the relationship between ambient particulate air pollution and biomarkers of endothelial function including endothelin-1 (ET-1), E-selectin, intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was conducted in PubMed, Scopus, EMBASE, and Web of Science up to 20 May 2023. Subsequently, a meta-analysis was conducted using a random effects model. RESULTS: A total of 18 studies were included in this meta-analysis. A 10 µg/m3 increase in short-term exposure to ambient PM2.5 was associated with a 1.55% (95% CI: 0.89%, 2.22%) increase in ICAM-1 and a 1.97% (95% CI: 0.86%, 3.08%) increase in VCAM-1. The associations of ET-1 (0.22%, 95% CI: -4.94%, 5.65%) and E-selectin (3.21%, 95% CI: -0.90% 7.49%) with short-term exposure to ambient PM2.5 were statistically insignificant. CONCLUSION: Short-term exposure to ambient PM2.5 pollution may significantly increase the levels of typical markers of endothelial function, including ICAM-1 and VCAM-1, suggesting potential endothelial dysfunction following ambient air pollution exposure.

12.
Blood ; 143(4): 320-335, 2024 Jan 25.
Article En | MEDLINE | ID: mdl-37801708

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with resistant clonal propagation in recurrence. We performed high-throughput droplet-based 5' single-cell RNA with paired T-cell receptor (TCR) sequencing of paired diagnosis-relapse (Dx_Rel) T-ALL samples to dissect the clonal diversities. Two leukemic evolutionary patterns, "clonal shift" and "clonal drift" were unveiled. Targeted single-cell DNA sequencing of paired Dx_Rel T-ALL samples further corroborated the existence of the 2 contrasting clonal evolution patterns, revealing that dynamic transcriptional variation might cause the mutationally static clones to evolve chemotherapy resistance. Analysis of commonly enriched drifted gene signatures showed expression of the RNA-binding protein MSI2 was significantly upregulated in the persistent TCR clonotypes at relapse. Integrated in vitro and in vivo functional studies suggested that MSI2 contributed to the proliferation of T-ALL and promoted chemotherapy resistance through the posttranscriptional regulation of MYC, pinpointing MSI2 as an informative biomarker and novel therapeutic target in T-ALL.


Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , RNA-Binding Proteins , Humans , Clonal Evolution/genetics , Drug Resistance, Neoplasm/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Receptors, Antigen, T-Cell/genetics , Recurrence , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , T-Lymphocytes/metabolism
13.
China Pharmacy ; (12): 925-930, 2024.
Article Zh | WPRIM | ID: wpr-1016713

OBJECTIVE To prepare tetrandrine (TET)-loaded chitosan(CS)-stearic acid (SA) nano micelles modified with folic acid (FA)( FA-CS-SA/TET nano micelles), characterize them and study the anti-inflammatory effect in vitro. METHODS FA- CS-SA/TET nano micelles were prepared by ultrasonic method; the preparation technology was optimized by orthogonal test and validation test was also performed with the mass ratio of FA-CS-SA to TET, ultrasound power and ultrasound times as the factors, using the comprehensive score of entrapment efficiency (EE), drug loading (DL) and particle size as evaluation index. FA-CS-SA/ TET nano micelles prepared by the optimal technology were characterized, and their release performance in vitro was investigated. RAW264.7 cells were used as subjects to investigate their anti-inflammatory activity in vitro. RESULTS The optimal preparation technology included that the mass ratio of FA-CS-SA to TET was 2∶1, ultrasonic power was 200 W, and the ultrasonic frequency was 200 times. The parameters of FA-CS-SA/TET nano micelles prepared by optimized technology included that EE was (98.86± 0.30)%, DL was (28.57±0.34)%, the average particle size was (227.0±9.4) nm, polydispersity index was 0.42±0.04, and the Zeta potential was(12.6±2.3)mV, respectively. The nano micelles were uniform in appearance and round in shape. The nano micelles were released quickly in 0.5% sodium dodecyl sulfate solution, with a cumulative release rate of (79.49±3.43)% within 72 hours, and its anti-inflammatory effect was stronger than that of TET raw materials. CONCLUSIONS FA-CS-SA/TET nano micelles are prepared successfully in the study, with good drug loading performance, uniform particle size, and good in vitro anti-inflammatory activity.

14.
Acta Pharmaceutica Sinica B ; (6): 350-364, 2024.
Article En | WPRIM | ID: wpr-1011241

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

15.
Article En | WPRIM | ID: wpr-1011012

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.


Mice , Rats , Animals , Myeloid Differentiation Factor 88/metabolism , Vascular Remodeling , Cell Proliferation , Vascular System Injuries/pathology , Carotid Artery Injuries/pathology , Molecular Docking Simulation , Muscle, Smooth, Vascular , Cell Movement , Mice, Inbred C57BL , Signal Transduction , Succinates/pharmacology , Potassium/pharmacology , Cells, Cultured , Diterpenes , Cadherins
16.
Environ Pollut ; 343: 123230, 2024 Feb 15.
Article En | MEDLINE | ID: mdl-38158011

Air pollution control protocols and policies formulated for PM2.5 and PM10 (particulate matter [PM] with an aerodynamic diameter of ≤2.5 and 10 µm), however, such protocols and policies have not been available for black carbon (BC). A growing number of studies have evaluated the association between long-term exposure to ambient air pollution with BC and PM and pre-eclampsia. We applied a meta-analysis to estimate pooled odds ratios (ORs) and 95 % confidence intervals (CIs) based on four exposure windows (first/second/third trimester and entire pregnancy). 24 studies meeting our selection criteria (8 for BC, 21 and 15 for PM2.5 and PM10) were finally included after screening studies published up to June 22, 2023. An increase of 1 µg/m3 BC during the second trimester and entire pregnancy were associated with a 16 % (OR: 1.16, 95 % CI: [1.02, 1.32]) and a 15 % (OR: 1.15, 95 % CI: [1.03, 1.29]) increased risk of pre-eclampsia, respectively. A 10 µg/m3 increase in second-trimester exposure to PM2.5 and PM10 was associated with a 1 % (OR: 1.01, 95 % CI: [1.00, 1.03]) and a 5 % (OR: 1.05, 95 % CI: [1.01, 1.10]) increased risk of pre-eclampsia. An 11 % (OR: 1.11, 95 % CI: [1.03, 1.21]) increased risk of pre-eclampsia was found to be associated with a 10 µg/m3 increase in PM10 exposure during the entire pregnancy. The results support the potential effect of exposure to ambient particulate pollutants on risk of pre-eclampsia and emphasize the necessity of strategies and protocols for controlling BC. Greater efforts in controlling ambient particulate pollution and especially BC are needed in order to prevent pregnant women from developing pre-eclampsia.


Air Pollutants , Air Pollution , Pre-Eclampsia , Humans , Female , Pregnancy , Particulate Matter/analysis , Air Pollutants/analysis , Pre-Eclampsia/epidemiology , Pre-Eclampsia/chemically induced , Air Pollution/adverse effects , Air Pollution/analysis , Dust , Carbon , Environmental Exposure
17.
Pathol Res Pract ; 252: 154920, 2023 Dec.
Article En | MEDLINE | ID: mdl-37948998

Clinical data indicates that SARS-CoV-2 infection-induced respiratory failure is a fatal condition for severe COVID-19 patients. However, the pathological alterations of different types of respiratory failure remained unknown for severe COVID-19 patients. This study aims to evaluate whether there are differences in the performance of various types of respiratory failure in severe COVID-19 patients and investigate the pathological basis for these differences. The lung tissue sections of severe COVID-19 patients were assessed for the degree of injury and immune responses. Transcriptome data were used to analyze the molecular basis in severe COVID-19 patients. Severe COVID-19 patients with combined oxygenation and ventilatory failure presented more severe pulmonary fibrosis, airway obstruction, and prolonged disease course. The number of M2 macrophages increased with the degree of fibrosis in patients, suggesting that it may be closely related to the development of pulmonary fibrosis. The co-existence of pro-inflammatory and anti-inflammatory cytokines in the pulmonary environment could also participate in the progression of pulmonary fibrosis. Furthermore, the increased apoptosis in the lungs of COVID-19 patients with severe pulmonary fibrosis may represent a critical factor linking sustained inflammatory responses to fibrosis. Our findings indicate that during the extended phase of COVID-19, antifibrotic and antiapoptotic treatments should be considered in conjunction with the progression of the disease.


COVID-19 , Pulmonary Fibrosis , Respiratory Insufficiency , Humans , COVID-19/complications , COVID-19/pathology , Pulmonary Fibrosis/pathology , Autopsy , SARS-CoV-2 , Lung/pathology , Macrophages/pathology , Respiratory Insufficiency/pathology , Apoptosis
18.
NPJ Precis Oncol ; 7(1): 110, 2023 Oct 31.
Article En | MEDLINE | ID: mdl-37907595

The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its relationship with genomic features, clinicopathological characteristics and prognosis in lung cancer is poorly understood, which could lead to population bias in prospective studies. We retrospectively analyzed 1011 lung cancer patients whose tumor samples were successfully profiled by high-throughput sequencing panel including GI/HRD score. Alterations of many cancer suppressor genes were associated with higher GI/HRD scores, biallelic inactivation of TP53 was correlated with a high GI/HRD score. A combination of two gene alterations exhibited a higher GI/HRD scores than single gene alterations. The GI/HRD score was associated with advanced stages in lung adenocarcinoma but not in lung squamous cell carcinoma. Furthermore, patients with higher GI/HRD scores had significantly shorter overall survival and progression-free survival than patients with lower GI/HRD scores. Finally, patients with a combination of a higher GI/HRD scores and TP53 alteration exhibited an extremely poor prognosis compared with patients with a lower GI/HRD scores and wild-type TP53 (overall survival, training cohort, hazard ratio (HR) = 8.56, P < 0.001; validation cohort, HR = 6.47, P < 0.001; progression-free survival, HR = 4.76, P < 0.001). Our study revealed the prognostic value of the GI/HRD score in lung adenocarcinoma, but not for all lung cancer. Moreover, the combination of the GI/HRD score and TP53 status could be a promising strategy to predict the prognosis of patients with lung adenocarcinoma.

19.
Foods ; 12(22)2023 Nov 18.
Article En | MEDLINE | ID: mdl-38002225

The conflict between economic growth and the arable land demand poses a significant challenge to maintaining food security and achieving the Sustainable Development Goals. Meanwhile, substantial regional disparities in food consumption contribute to variations in land demand, further exacerbating constraints on food security. However, few studies have delved into regional differences in land demand related to food consumption. To bridge these gaps, this study estimated the arable land demand and associated pressures, considering food consumption patterns and the land footprint across 31 provincial districts in China. The findings reveal that grains remain the primary crop consumed by Chinese residents. Notably, the food consumption pattern exhibits substantial disparities among provincial districts, particularly concerning livestock products. Given China's vast population and escalating consumption of livestock, the country demonstrates heightened land demands. While China does not face a national-level food security threat, regional disparities are evident, with eight provincial districts facing potential food security risks. This study explored the challenges and pathways in maintaining food security and the visions to achieve it, emphasizing the importance of sustaining a balanced food consumption pattern, reducing food waste, improving environmentally friendly agriculture practices, formulating effective and continuous laws and regulations, and exploring potential land resource development to alleviate the pressure on arable land and ensure food security.

20.
Ibrain ; 9(2): 236-242, 2023.
Article En | MEDLINE | ID: mdl-37786554

Decubitus ulcers are a common spinal cord injury (SCI) complication that puts patients' lives in danger and has emerged as a more prevalent issue in modern clinical rehabilitation and care. Decubitus ulcers in humans can currently be treated in a number of different ways, but there are fewer studies on how to treat and care for decubitus ulcers in macaques. To treat a 20-year-old adult male macaque monkey with SCI and decubitus ulcers after a quarter transection of the thoracic spinal cord, a number of scientific care procedures and pharmaceutical treatments, such as dietary changes and topical or intravenous administration of medication, were carried out and continuously monitored in real-time. In comparison to the untreated group, we observed a significant improvement in decubitus wound healing in the macaques. In this article, we provide a good protocol for decubitus ulcer care after SCI and suggest that future experimental animal modeling needs to focus on issues such as care for postoperative complications.

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