Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.940
Filter
1.
Ultrason Sonochem ; 107: 106932, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38824698

ABSTRACT

Artemisia argyi leaf polysaccharide (AALPs) were prepared through ultrasound-assisted extraction (UAE), and their antifatigue activities were evaluated. Extraction was optimized using response surface methodology (RSM), which yielded the following optimal UAE conditions: ultrasonication power of 300 W, extraction temperature of 51 °C, liquid:solid ratio of 20 mL/g, and ultrasonication time of 47 mins. The above optimal conditions resulted in the maximum extraction rate of 10.49 %. Compared with hot water extraction (HWE), UAE supported higher yields and total sugar, uronic acid, and sulfate contents of AALPs. Meanwhile, AALP prepared through UAE (AALP-U) exhibited higher stability due to its smaller particle size and higher absolute value of zeta potential than AALP prepared through HWE (AALP-H). In addition, AALP-U demonstrated stronger antioxidant activity than AALP-H. In forced swimming tests on mice, AALP-U could significantly prolong swimming time with a dose-dependent effect, increase liver and muscle glycogen levels, and improve other biochemical indices, thus showing great potential for application in functional food.

2.
PeerJ ; 12: e17453, 2024.
Article in English | MEDLINE | ID: mdl-38827294

ABSTRACT

Sown mixed grassland is rarely used for livestock raising and grazing; however, different forages can provide various nutrients for livestock, which may be beneficial to animal health and welfare. We established a sown mixed grassland and adopted a rotational grazing system, monitored the changes in aboveground biomass and sheep weights during the summer grazing period, measured the nutrients of forage by near-infrared spectroscopy, tested the contents of medium- and long-chain fatty acids by gas chromatography, and explored an efficient sheep fattening system that is suitable for agro-pastoral interlacing areas. The results showed that the maximum forage supply in a single grazing paddock was 4.6 kg DM/d, the highest dry matter intake (DMI) was 1.80 kg DM/ewe/d, the average daily weight gain (ADG) was 193.3 g, the DMI and ADG were significantly correlated (P < 0.05), and the average feed weight gain ratio (F/G) reached 8.02. The average crude protein and metabolizable energy intake by sheep were 286 g/ewe/d and 18.5 MJ/ewe/d respectively, and the n-6/n-3 ratio of polyunsaturated fatty acids in mutton was 2.84. The results indicated that the sheep fattening system had high feed conversion efficiency, could improve the yield and quality of sheep, and could be promoted in suitable regions.


Subject(s)
Animal Feed , Animal Husbandry , Grassland , Animals , Sheep , Animal Husbandry/methods , Animal Feed/analysis , Weight Gain/physiology , Biomass , Animal Nutritional Physiological Phenomena/physiology
3.
HIV Med ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38812289

ABSTRACT

INTRODUCTION: Direct-acting antivirals (DAAs) are key to eliminating hepatitis C virus (HCV). In men who have sex with men (MSM) with HIV co-infection, recently acquired HCV infection is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates. METHODS: The cohort included MSM with recently acquired HCV infection from 2014 to 2021. The patients' demographic, clinical, behavioural, and laboratory data and treatment and reinfection outcomes were documented. RESULTS: A total of 237 men with recently acquired HCV infection were included: 216 (91%) had HIV. The median age was 46 years (interquartile range [IQR] 39-52), and the median CD4 count was 660/mm3 (IQR 527-835). The annual incidence of recently acquired HCV remained between 0.28% and 0.43% but dropped to 0.02% in 2021 during the COVID pandemic, almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95% confidence interval 12.6-18.8), and reinfection was associated with the use of crystal methamphetamine (p = 0.032) and ketamine (p = 0.042). In total, 31.3% had multiple reinfections, and four reinfections occurred in users of pre-exposure prophylaxis. CONCLUSIONS: High treatment and cure rates did not lead to HCV elimination. A change in sexual behaviour, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As recently acquired HCV is prevalent in MSM with and without HIV, surveillance is necessary to consolidate elimination goals.

4.
ACS Appl Mater Interfaces ; 16(21): 27463-27469, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38743927

ABSTRACT

Chlorine substitution, as an effective and low-cost modification strategy, has been applied in the design of donor and acceptor structures in organic solar cells. We synthesized a series of chlorinated dimerized acceptors to investigate the effect of chlorine numbers and locations on the photovoltaic properties. The results show that the planarity and morphology of DYV-γ-2Cl are greatly improved due to the appropriate numbers and positions of the substituted chlorine atoms. Therefore, the device based on PM6:DYV-γ-2Cl achieves a superior power conversion efficiency (PCE) of 15.54% among the three oligomeric acceptors with optimized molecular planarity and film morphology. This work demonstrated the positive effect of suitable numbers and the substitution positions of chlorines on the molecular arrangement and photovoltaic properties of the corresponding dimerized acceptors.

5.
Nat Commun ; 15(1): 4316, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773095

ABSTRACT

As signalling organelles, cilia regulate their G protein-coupled receptor content by ectocytosis, a process requiring localised actin dynamics to alter membrane shape. Photoreceptor outer segments comprise an expanse of folded membranes (discs) at the tip of highly-specialised connecting cilia, into which photosensitive GPCRs are concentrated. Discs are shed and remade daily. Defects in this process, due to mutations, cause retinitis pigmentosa (RP). Whilst fundamental for vision, the mechanism of photoreceptor disc generation is poorly understood. Here, we show membrane deformation required for disc genesis is driven by dynamic actin changes in a process akin to ectocytosis. We show RPGR, a leading RP gene, regulates actin-binding protein activity central to this process. Actin dynamics, required for disc formation, are perturbed in Rpgr mouse models, leading to aborted membrane shedding as ectosome-like vesicles, photoreceptor death and visual loss. Actin manipulation partially rescues this, suggesting the pathway could be targeted therapeutically. These findings help define how actin-mediated dynamics control outer segment turnover.


Subject(s)
Actins , Eye Proteins , Retinitis Pigmentosa , Animals , Actins/metabolism , Mice , Retinitis Pigmentosa/metabolism , Retinitis Pigmentosa/genetics , Eye Proteins/metabolism , Eye Proteins/genetics , Cilia/metabolism , Humans , Retinal Photoreceptor Cell Outer Segment/metabolism , Mice, Knockout , Mice, Inbred C57BL , Cell Membrane/metabolism
6.
Dev Cell ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38781974

ABSTRACT

Broad-spectrum disease resistance (BSR) is crucial for controlling plant diseases and relies on immune signals that are subject to transcriptional and post-translational regulation. How plants integrate and coordinate these signals remains unclear. We show here that the rice really interesting new gene (RING)-type E3 ubiquitin ligase OsRING113 targets APIP5, a negative regulator of plant immunity and programmed cell death (PCD), for 26S proteasomal degradation. The osring113 mutants in Nipponbare exhibited decreased BSR, while the overexpressing OsRING113 plants showed enhanced BSR against Magnaporthe oryzae (M. oryzae) and Xanthomonas oryzae pv. oryzae (Xoo). Furthermore, APIP5 directly suppressed the transcription of the Bowman-Birk trypsin inhibitor genes OsBBTI5 and AvrPiz-t-interacting protein 4 (APIP4). Overexpression of these two genes, which are partially required for APIP5-mediated PCD and disease resistance, conferred BSR. OsBBTI5 and APIP4 associated with and stabilized the pathogenesis-related protein OsPR1aL, which promotes M. oryzae resistance. Our results identify an immune module with integrated and coordinated hierarchical regulations that confer BSR in plants.

7.
Water Res ; 257: 121693, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38728785

ABSTRACT

Cyanobacterial harmful algal blooms (cyanoHABs) are becoming increasingly common in aquatic ecosystems worldwide. However, their heterogeneous distributions make it difficult to accurately estimate the total algae biomass and forecast the occurrence of surface cyanoHABs by using traditional monitoring methods. Although various optical instruments and remote sensing methods have been employed to monitor the dynamics of cyanoHABs at the water surface (i.e., bloom area, chlorophyll a), there is no effective in-situ methodology to monitor the dynamic change of cell density and integrated biovolume of algae throughout the water column. In this study, we propose a quantitative protocol for simultaneously measurements of multiple indicators (i.e., biovolume concentration, size distribution, cell density, and column-integrated biovolume) of cyanoHABs in water bodies by using the laser in-situ scattering and transmissometry (LISST) instrument. The accuracy of measurements of the biovolume and colony size of algae was evaluated and exceeded 95% when the water bloom was dominated by cyanobacteria. Furthermore, the cell density of cyanobacteria was well estimated based on total biovolume and mean cell volume measured by the instrument. Therefore, this methodology has the potential to be used for broader applications, not only to monitor the spatial and temporal distribution of algal biovolume concentration but also monitor the vertical distribution of cell density, biomass and their relationship with size distribution patterns. This provides new technical means for the monitoring and analysis of algae migration and early warning of the formation of cyanoHABs in lakes and reservoirs.


Subject(s)
Cyanobacteria , Environmental Monitoring , Environmental Monitoring/methods , Harmful Algal Bloom , Biomass , Eutrophication , Chlorophyll/analysis
8.
Asia Pac J Ophthalmol (Phila) ; 13(3): 100070, 2024.
Article in English | MEDLINE | ID: mdl-38777093

ABSTRACT

PURPOSE: To evaluate the dynamic transitions in diabetic retinopathy (DR) severity over time and associated risk factors in an Asian population with diabetes. DESIGN: Longitudinal cohort study METHODS: We analyzed data from 9481 adults in the Singapore Integrated Diabetic Retinopathy Screening Program (2010-2015) with linkage to death registry. A multistate Markov model adjusted for age, sex, systolic blood pressure (SBP), diabetes duration, HbA1c, and body mass index (BMI) was applied to estimate annual transition probabilities between four DR states (no, mild, moderate, and severe/proliferative) and death, and the mean sojourn time in each state. RESULTS: The median assessment interval was 12 months, with most patients having 3 assessments. Annual probabilities for DR progression (no-to-mild, mild-to-moderate and moderate-to-severe/proliferative) were 6.1 %, 7.0 % and 19.3 %, respectively; and for regression (mild-to-no, moderate-to-mild and severe-to-moderate) were 55.4 %, 17.3 % and 4.4 %, respectively. Annual mortality rates from each DR state were 1.2 %, 2.0 %, 18.7 %, and 30.0 %. The sojourn time in each state were 8.2, 0.8, 0.8 and 2.2 years. Higher HbA1c and SBP levels were associated with progression of no-mild and mild-moderate DR, and diabetes duration with no-to-mild and moderate-to-severe/proliferative DR. Lower HbA1c levels were associated with regression from mild-to-no and moderate-to-mild, and higher BMI with mild-to-no DR. CONCLUSIONS: Our results suggest a prolonged duration (∼8 years) in developing mild DR, with faster transitions (within a year) from mild or moderate states. Moderate/above DR greatly increases the probability of progression and death as compared to mild DR/below. HbA1c was associated with both progression as well as regression.


Subject(s)
Diabetic Retinopathy , Disease Progression , Humans , Diabetic Retinopathy/mortality , Male , Female , Middle Aged , Singapore/epidemiology , Risk Factors , Aged , Glycated Hemoglobin/metabolism , Adult , Follow-Up Studies , Diabetes Mellitus, Type 2/complications , Asian People , Longitudinal Studies
9.
Zhongguo Zhong Yao Za Zhi ; 49(3): 809-818, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38621885

ABSTRACT

Scutellariae Radix extract is one of the important components in Shuganning Injection. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was established for simultaneously determining five components in Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats, so as to reveal the difference in the excretion process of Shuganning Injection and Scutellariae Radix extract in rats and explore the law of the excretion process of the five components in vivo before and after the compatibility of Scutellariae Radix. Rats were injected with Shuganning Injection and Scutellariae Radix extract(4.2 mL·kg~(-1)), respectively, and the excretion of baicalin, baicalein, oroxylin A, oroxylin A-7-O-ß-D-glucuronide, and scutellarin in bile, urine, and feces of rats in 24 h was observed. The results showed that except for baicalin, the other four index components were excreted as prototype components in a high proportion after intravenous injection of Shuganning Injection and Scutellariae Radix extract in rats, respectively. The excretion of each component was relatively high in urine and less in feces and bile. After the compatibility of Scutellariae Radix extract, the accumulative excretion of five index components in rats all decreased. Among them, the cumulative excretion of baicalein in bile, urine, and feces significantly decreased by 26.67%, 48.11%, and 31.01%. The cumulative excretion of baicalin in bile, urine, and feces decreased significantly by 70.69%, 19.43%, and 31.22%. The result showed that the five index components in Scutellariae Radix extract were mainly excreted by the kidneys, and other components in Shuganning Injection delayed the excretion process and prolonged the residence time. This study is of great significance for elucidating the compatibility rationality of Shuganning Injection.


Subject(s)
Bile , Scutellaria baicalensis , Rats , Animals , Chromatography, Liquid , Tandem Mass Spectrometry , Flavonoids , Feces , Chromatography, High Pressure Liquid
10.
Stress Biol ; 4(1): 24, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38668992

ABSTRACT

As one of the most important food and feed crops worldwide, maize suffers much more tremendous damages under heat stress compared to other plants, which seriously inhibits plant growth and reduces productivity. To mitigate the heat-induced damages and adapt to high temperature environment, plants have evolved a series of molecular mechanisms to sense, respond and adapt high temperatures and heat stress. In this review, we summarized recent advances in molecular regulations underlying high temperature sensing, heat stress response and memory in maize, especially focusing on several important pathways and signals in high temperature sensing, and the complex transcriptional regulation of ZmHSFs (Heat Shock Factors) in heat stress response. In addition, we highlighted interactions between ZmHSFs and several epigenetic regulation factors in coordinately regulating heat stress response and memory. Finally, we laid out strategies to systematically elucidate the regulatory network of maize heat stress response, and discussed approaches for breeding future heat-tolerance maize.

11.
Health Res Policy Syst ; 22(1): 49, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637888

ABSTRACT

Cardiovascular diseases (CVDs) are the major cause of death among Malaysians. Reduction of salt intake in populations is one of the most cost-effective strategies in the prevention of CVDs. It is very feasible as it requires low cost for implementation and yet could produce a positive impact on health. Thus, salt reduction initiatives have been initiated since 2010, and two series of strategies have been launched. However, there are issues on its delivery and outreach to the target audience. Further, strategies targeting out of home sectors are yet to be emphasized. Our recent findings on the perceptions, barriers and enablers towards salt reduction among various stakeholders including policy-makers, food industries, food operators, consumers and schools showed that eating outside of the home contributed to high salt intake. Foods sold outside the home generally contain a high amount of salt. Thus, this supplementary document is being proposed to strengthen the Salt Reduction Strategy to Prevent and Control Non-communicable Diseases (NCDs) for Malaysia 2021-2025 by focussing on the strategy for the out-of-home sectors. In this supplementary document, the Monitoring, Awareness and Product (M-A-P) strategies being used by the Ministry of Health (MOH) are adopted with a defined outline of the plan of action and indicators to ensure that targets could be achieved. The strategies will involve inter-sectoral and multi-disciplinary approaches, including monitoring of salt intake and educating consumers, strengthening the current enforcement of legislation on salt/sodium labelling and promoting research on reformulation. Other strategies included in this supplementary document included reformulation through proposing maximum salt targets for 14 food categories. It is hoped that this supplementary document could strengthen the current the Salt Reduction Strategy to Prevent and Control NCDs for Malaysia 2021-2025 particularly, for the out-of-home sector, to achieve a reduction in mean salt intake of the population to 6.0 g per day by 2025.


Subject(s)
Cardiovascular Diseases , Noncommunicable Diseases , Southeast Asian People , Humans , Sodium Chloride, Dietary , Noncommunicable Diseases/prevention & control , Malaysia , Health Policy , Cardiovascular Diseases/prevention & control
12.
Water Res ; 256: 121573, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38608618

ABSTRACT

Sulfidated zero valent iron (ZVI) is a popular material for the reductive degradation of halogenated organic pollutants. Simple and economic synthesis of this material is highly demanded. In this study, sulfidated micro/nanostructured ZVI (MNZVI) particles were prepared by simply heating MNZVI particles and sulfur elements (S0) in pure water (50℃). The iron oxides on the surface of MNZVI particles were conducive to sulfidation reaction, indicating the formation of iron-sulphide minerals (FeSx) on the surface of MNZVI particles might not be from the direct reaction of Fe0 with S0 (Fe0 and S0 acted as reductant and oxidant, respectively). As an important reductant, hydrogen atom (H•) can be generated from the reduction of H+ by MNZVI particles and participate in the formation of FeSx. Quenching experiment and cyclic voltammetry analysis proved the existence of H• on the surface of MNZVI particles. DFT calculation found that the potential barrier of H•/S0 and Fe0/S0 were 1.91 and 7.24 eV, respectively, indicating that S0 would preferentially react with H• instead of Fe0. The formed H• can quickly react with S0 to generate hydrogen sulfide (H2S), which can further react with iron oxides such as α-Fe2O3 on the surface of MNZVI particles to form FeSx. In addition, the H2 partial pressure in water significantly affected the amount of H• generated, thereby affecting the sulfidation efficiency. For TCE degradation, as the sulfur loading of sulfidated MNZVI particles increased, the contribution of H• significantly decreased while the contribution of direct electron transfer increased. This study provided new insights into the synthesis mechanism of sulfidated ZVI in water.


Subject(s)
Hydrogen , Iron , Hydrogen/chemistry , Iron/chemistry , Oxidation-Reduction
13.
J Org Chem ; 89(9): 6607-6614, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38624206

ABSTRACT

The trivalent phosphine-catalyzed [4+1] spiro-annulation reaction of allenyl imide and activated methylene cyclocompounds has been developed for the construction of various spiro-2-cyclopenten-1-ones. Oxindoles, 3-isochromanones, and 2-indanones are selected as 1C synthons to capture the in situ-generated bis-electrophilic α,ß-unsaturated ketenyl phosphonium intermediate, affording the corresponding monospiro- and bispiro-cyclopentenones in good to excellent yields (≤91%) under mild conditions. The primary attempt at asymmetric catalysis using monophosphine (R)-SITCP provides promising enantioselectivity (45% ee). A plausible reaction mechanism is also proposed.

14.
Cancer Cell Int ; 24(1): 144, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654350

ABSTRACT

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Toxoplasma gondii (T. gondii) has shown anticancer activity in breast cancer mouse models, and exerted beneficial effect on the survival of breast cancer patients, but the mechanism was unclear. METHODS: The effect of tachyzoites of T. gondii (RH and ME49 strains) on human breast cancer cells (MCF-7 and MDA-MB-231 cells) proliferation and migration was assessed using cell growth curve and wound healing assays. Dual RNA-seq was performed for T. gondii-infected and non-infected cells to determine the differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction Networks analysis (PPI) were performed to explore the related signaling pathway and hub genes. Hub genes were validated using the Kaplan-Meier plotter database, and Pathogen Host Interaction (PHI-base) database. The results were verified by qRT-PCR. RESULTS: The tachyzoites of T. gondii decreased the expression of Ki67 and increased the expression of E-cadherin, resulting in suppressing the proliferation and migration of infected human breast cancer cells. The inhibitory effect of T. gondii on breast cancer cells showed a significant dose-response relationship. Compared with the control group, 2321 genes were transcriptionally regulated in MCF-7 cells infected with T. gondii, while 169 genes were transcriptionally regulated in infected MDA-MB-231 cells. Among these genes, 698 genes in infected MCF-7 cells and 67 genes in infected MDA-MB-231 cells were validated by the publicly available database. GO and KEGG analyses suggested that several pathways were involved in anticancer function of T. gondii, such as ribosome, interleukin-17 signaling, coronavirus disease pathway, and breast cancer pathway. BRCA1, MYC and IL-6 were identified as the top three hub genes in infected-breast cancer cells based on the connectivity of PPI analysis. In addition, after interacting with breast cancer cells, the expression of ROP16 and ROP18 in T. gondii increased, while the expression of crt, TgIST, GRA15, GRA24 and MIC13 decreased. CONCLUSIONS: T. gondii transcriptionally regulates several signaling pathways by altering the hub genes such as BRCA1, MYC and IL-6, which can inhibit the breast tumor growth and migration, hinting at a potential therapeutic strategy.

15.
J Environ Manage ; 357: 120707, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38554455

ABSTRACT

Water diversion has been widely utilized to enhance lake water quality and mitigate cyanobacterial blooms. However, previous studies have mainly focused on investigating the effects of water diversion on water quality or aquatic ecological health. Consequently, there is limited research investigating the combined impact of water diversion on the water quality and the ecological health of eutrophic lakes, and whether the WQI and phytoplankton assemblages demonstrate similar patterns following water diversion. In this study, the effects of water diversion on the ecosystem health of eutrophic lakes were comprehensively evaluated based on the WQI indices and phytoplankton assemblages during the NWDP-21 and WDP-22. The results showed that the annual mean of WQI increased from 52.02 to 54.36 after water diversion, which improved the water quality of the lake, especially NH3-N and TN decreased by 58.6% and 15.2%, respectively. The phytoplankton assemblages changed significantly before and after water diversion, and we observed that the total biomass of phytoplankton decreased by 12.3% and phytoplankton diversity indices (Shannon-Wiener diversity, Pielou evenness, and Simpson index) increased by 8.6%-8.9% after water diversion, with an improvement in the connectivity and stability of the phytoplankton. Notably, enhanced adaptations of rare sub-communities for resource use in water diversion environments, and water diversion inhibited the dispersal ability of dominant functional groups, and the effects of hydrological disturbances on the structure of phytoplankton assemblage favored the ecological health of eutrophic lakes. VPA analysis further reveals that water diversion alters the drivers of phytoplankton functional group biomass and phytoplankton diversity. The results of the PLS-PM analysis clarify that water diversion indirectly impacts the total phytoplankton biomass and phytoplankton diversity primarily by modifying light availability. Significant correlations are observed between the dominant functional groups biomass and diversity indices of WQI. The trends in changes observed in water quality indices and phytoplankton following water diversion align with the evaluation of water ecological health. This study provides valuable guidance for the ecological management of the diversion project in Yilong Lake and serves as a reference for similar projects in other lakes.


Subject(s)
Phytoplankton , Water Quality , Lakes/chemistry , Ecosystem , Eutrophication , China
16.
Cancer Manag Res ; 16: 225-243, 2024.
Article in English | MEDLINE | ID: mdl-38525373

ABSTRACT

Purpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases. Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the "CMS classifier" and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected. Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting "seed" of tumor cells of different CMS groups had a preference for metastasis to "soil" of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases. Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.

17.
J Med Chem ; 67(7): 5924-5934, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38507820

ABSTRACT

Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated ß-galactosidase (SA-ß-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]Ga-BGal displayed high sensitivity and specificity for ß-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the ß-Gal concentration and reaction time. In PET imaging, high ß-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [68Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.


Subject(s)
Gallium Radioisotopes , Positron-Emission Tomography , Humans , Positron-Emission Tomography/methods , HeLa Cells , Doxorubicin , Cell Line, Tumor
18.
J Med Internet Res ; 26: e41065, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546730

ABSTRACT

BACKGROUND: Diabetic kidney disease (DKD) and diabetic retinopathy (DR) are major diabetic microvascular complications, contributing significantly to morbidity, disability, and mortality worldwide. The kidney and the eye, having similar microvascular structures and physiological and pathogenic features, may experience similar metabolic changes in diabetes. OBJECTIVE: This study aimed to use machine learning (ML) methods integrated with metabolic data to identify biomarkers associated with DKD and DR in a multiethnic Asian population with diabetes, as well as to improve the performance of DKD and DR detection models beyond traditional risk factors. METHODS: We used ML algorithms (logistic regression [LR] with Least Absolute Shrinkage and Selection Operator and gradient-boosting decision tree) to analyze 2772 adults with diabetes from the Singapore Epidemiology of Eye Diseases study, a population-based cross-sectional study conducted in Singapore (2004-2011). From 220 circulating metabolites and 19 risk factors, we selected the most important variables associated with DKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2) and DR (defined as an Early Treatment Diabetic Retinopathy Study severity level ≥20). DKD and DR detection models were developed based on the variable selection results and externally validated on a sample of 5843 participants with diabetes from the UK biobank (2007-2010). Machine-learned model performance (area under the receiver operating characteristic curve [AUC] with 95% CI, sensitivity, and specificity) was compared to that of traditional LR adjusted for age, sex, diabetes duration, hemoglobin A1c, systolic blood pressure, and BMI. RESULTS: Singapore Epidemiology of Eye Diseases participants had a median age of 61.7 (IQR 53.5-69.4) years, with 49.1% (1361/2772) being women, 20.2% (555/2753) having DKD, and 25.4% (685/2693) having DR. UK biobank participants had a median age of 61.0 (IQR 55.0-65.0) years, with 35.8% (2090/5843) being women, 6.7% (374/5570) having DKD, and 6.1% (355/5843) having DR. The ML algorithms identified diabetes duration, insulin usage, age, and tyrosine as the most important factors of both DKD and DR. DKD was additionally associated with cardiovascular disease history, antihypertensive medication use, and 3 metabolites (lactate, citrate, and cholesterol esters to total lipids ratio in intermediate-density lipoprotein), while DR was additionally associated with hemoglobin A1c, blood glucose, pulse pressure, and alanine. Machine-learned models for DKD and DR detection outperformed traditional LR models in both internal (AUC 0.838 vs 0.743 for DKD and 0.790 vs 0.764 for DR) and external validation (AUC 0.791 vs 0.691 for DKD and 0.778 vs 0.760 for DR). CONCLUSIONS: This study highlighted diabetes duration, insulin usage, age, and circulating tyrosine as important factors in detecting DKD and DR. The integration of ML with biomedical big data enables biomarker discovery and improves disease detection beyond traditional risk factors.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Adult , Female , Humans , Middle Aged , Aged , Male , Diabetic Retinopathy/epidemiology , Cross-Sectional Studies , Insulin , Risk Factors , Tyrosine
19.
Chemosphere ; 355: 141726, 2024 May.
Article in English | MEDLINE | ID: mdl-38521105

ABSTRACT

Polymer stabilization, exemplified by carboxymethyl cellulose (CMC), has demonstrated effectiveness in enhancing the transport of nanoscale zero-valent iron (nZVI). And, sulfidation is recognized for enhancing the reactivity and selectivity of nZVI in dechlorination processes. The influence of polymer stabilization on sulfidated nZVI (S-nZVI) with various sulfur precursors remains unclear. In this study, CMC-stabilized S-nZVI (CMC-S-nZVI) was synthesized using three distinct sulfur precursors (S2-, S2O42-, and S2O32-) through one-step approach. The antioxidant properties of CMC significantly elevated the concentration of reduced sulfur species (S2-) on CMC-S-nZVIs, marking a 3.1-7.0-fold increase compared to S-nZVIs. The rate of trichloroethylene degradation (km) by CMC-S-nZVIs was observed to be 2.2-9.0 times higher than that achieved by their non-stabilized counterparts. Among the three CMC-S-nZVIs, CMC-S-nZVINa2S exhibited the highest km. Interesting, while the electron efficiency of CMC-S-nZVIs surged by 7.9-12 times relative to nZVI, it experienced a reduction of 7.0-34% when compared with S-nZVIs. This phenomenon is attributed to the increased hydrophilicity of S-nZVI particles due to CMC stabilization, which inadvertently promotes the hydrogen evolution reaction (HER). In conclusion, the findings of this study underscores the impact of CMC stabilization on the properties and dechlorination performance of S-nZVI sulfidated using different sulfur precursors, offering guidance for engineering CMC-S-nZVIs with desirable properties for contaminated groundwater remediation.


Subject(s)
Groundwater , Trichloroethylene , Water Pollutants, Chemical , Carboxymethylcellulose Sodium , Iron , Sulfur , Polymers
20.
Proc Natl Acad Sci U S A ; 121(14): e2318777121, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38547057

ABSTRACT

A concept of solar energy convertible zinc-air battery (SZAB) is demonstrated through rational design of an electrode coupled with multifunction. The multifunctional electrode is fabricated using nitrogen-substituted graphdiyne (N-GDY) with large π-conjugated carbonous network, which can work as photoresponsive bifunctional electrocatalyst, enabling a sunlight-promoted process through efficient injection of photoelectrons into the conduction band of N-GDY. SZAB enables direct conversion and storage of solar energy during the charging process. Such a battery exhibits a lowered charge voltage under illumination, corresponding to a high energy efficiency of 90.4% and electric energy saving of 30.3%. The battery can display a power conversion efficiency as high as 1.02%. Density functional theory calculations reveal that the photopromoted oxygen evolution reaction kinetics originates from the transition from the alkyne bonds to double bonds caused by the transfer of excited electrons, which changes the position of highest occupied molecular orbital and lowest unoccupied molecular orbital, thus greatly promoting the formation of intermediates to the conversion process. Our findings provide conceptual and experimental confirmation that batteries are charged directly from solar energy without the external solar cells, providing a way to manufacture future energy devices.

SELECTION OF CITATIONS
SEARCH DETAIL
...