Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.288
Filter
1.
Sci Rep ; 14(1): 10779, 2024 05 11.
Article in English | MEDLINE | ID: mdl-38734824

ABSTRACT

Health apps and wearables are touted to improve physical health and mental well-being. However, it is unclear from existing research the extent to which these health technologies are efficacious in improving physical and mental well-being at a population level, particularly for the underserved groups from the perspective of health equity and social determinants. Also, it is unclear if the relationship between health apps and wearables use and physical and mental well-being differs across individualistic, collectivistic, and a mix of individual-collectivistic cultures. A large-scale online survey was conducted in the U.S. (individualist culture), China (collectivist culture), and Singapore (mix of individual-collectivist culture) using quota sampling after obtaining ethical approval from the Institutional Review Board (IRB-2021-262) of Nanyang Technological University (NTU), Singapore. There was a total of 1004 respondents from the U.S., 1072 from China, and 1017 from Singapore. Data were analyzed using multiple regression and negative binomial regression. The study found that income consistently had the strongest relationship with physical and mental well-being measures in all three countries, while the use of health apps and wearables only had a moderate association with psychological well-being only in the US. Health apps and wearables were associated with the number of times people spent exercising and some mental health outcomes in China and Singapore, but they were only positively associated with psychological well-being in the US. The study emphasizes the importance of considering the social determinants, social-cultural context of the population, and the facilitating conditions for the effective use of digital health technologies. The study suggests that the combined use of both health apps and wearables is most strongly associated with better physical and mental health, though this association is less pronounced when individuals use only apps or wearables.


Subject(s)
Mental Health , Mobile Applications , Wearable Electronic Devices , Humans , Singapore , Male , China , Female , United States , Adult , Middle Aged , Surveys and Questionnaires , Young Adult , Adolescent , Aged
2.
J Med Internet Res ; 26: e44973, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739429

ABSTRACT

BACKGROUND: While text messaging has proven effective for smoking cessation (SC), engagement in the intervention remains suboptimal. OBJECTIVE: This study aims to evaluate whether using more interactive and adaptive instant messaging (IM) apps on smartphones, which enable personalization and chatting with SC advisors, can enhance SC outcomes beyond the provision of brief SC advice and active referral (AR) to SC services. METHODS: From December 2018 to November 2019, we proactively recruited 700 adult Chinese daily cigarette users in Hong Kong. Participants were randomized in a 1:1 ratio. At baseline, all participants received face-to-face brief advice on SC. Additionally, they were introduced to local SC services and assisted in selecting one. The intervention group received an additional 26 personalized regular messages and access to interactive chatting through IM apps for 3 months. The regular messages aimed to enhance self-efficacy, social support, and behavioral capacity for quitting, as well as to clarify outcome expectations related to cessation. We developed 3 sets of messages tailored to the planned quit date (within 30 days, 60 days, and undecided). Participants in the intervention group could initiate chatting with SC advisors on IM themselves or through prompts from regular messages or proactive inquiries from SC advisors. The control group received 26 SMS text messages focusing on general health. The primary outcomes were smoking abstinence validated by carbon monoxide levels of <4 parts per million at 6 and 12 months after the start of the intervention. RESULTS: Of the participants, 505/700 (72.1%) were male, and 450/648 (69.4%) were aged 40 or above. Planning to quit within 30 days was reported by 500/648 (77.2%) participants, with fewer intervention group members (124/332, 37.3%) reporting previous quit attempts compared with the control group (152/335, 45.4%; P=.04). At the 6- and 12-month follow-ups (with retention rates of 456/700, 65.1%, and 446/700, 63.7%, respectively), validated abstinence rates were comparable between the intervention (14/350, 4.0%, and 19/350, 5.4%) and control (11/350, 3.1% and 21/350, 6.0%) groups. Compared with the control group, the intervention group reported greater utilization of SC services at 12 months (RR 1.26, 95% CI 1.01-1.56). Within the intervention group, engaging in chat sessions with SC advisors predicted better validated abstinence at 6 months (RR 3.29, 95% CI 1.13-9.63) and any use of SC services (RR 1.66, 95% CI 1.14-2.43 at 6 months; RR 1.67, 95% CI 1.26-2.23 at 12 months). CONCLUSIONS: An IM-based intervention, providing support and assistance alongside brief SC advice and AR, did not yield further increases in quitting rates but did encourage the utilization of SC services. Future research could explore whether enhanced SC service utilization leads to improved long-term SC outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03800719; https://clinicaltrials.gov/ct2/show/NCT03800719.


Subject(s)
Mobile Applications , Smoking Cessation , Text Messaging , Humans , Smoking Cessation/methods , Smoking Cessation/psychology , Hong Kong , Male , Female , Adult , Middle Aged , Smokers/psychology , Smokers/statistics & numerical data , Smartphone
3.
Article in English | MEDLINE | ID: mdl-38718383

ABSTRACT

Polyurea has found applications in protective coatings. Yet, the too fast polymerization and lack of functions limit its application. Herein, we report a high-performance polyurea via the stepwise polymerization of an isocyanate (NCO)-terminated prepolymer consisting of poly(propylene glycol)-block-poly(ethylene glycol)-block-poly(propylene glycol) (PPG-b-PEG-b-PPG) with a nanocluster synthesized via the hydrolysis of N-phenylaminomethyltriethoxysilane. Such a nanocluster contains low-reactivity secondary amines, so the polymerization of polyurea can be slowed down (over 1 h), which improves its wetting and adhesion to a substrate. The residual silanol groups on the nanocluster further increase the adhesion. Such polyurea exhibits high adhesion on various substrates, including glass, ceramic, steel, copper, titanium, wood, and natural rubber (∼2.35-14.64 MPa). Besides, the nanoclusters can cross-link the prepolymer into a tough network, endowing the polyurea with a high mechanical strength of ∼25 MPa, much higher than the traditional polyaspartic ester polyurea. On the other hand, the PEG segments enable the polyurea to have good fouling resistance against proteins (fibrinogen absorption was reduced by over 90%), bacteria (RBA of S. aureusE. coli and Pseudomonas sp. was less than 10%), as well as diatom (diatom density was less than 100 cells/mm2). The polyurea is expected to find applications in biomedical engineering and marine antifouling.

4.
J Imaging Inform Med ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740662

ABSTRACT

Automatic retinal layer segmentation in optical coherence tomography (OCT) images is crucial for the diagnosis of ocular diseases. Currently, automatic retinal layer segmentation works well with normal OCT images. However, pigment epithelial detachment (PED) dramatically alters the retinal structure, causing blurred boundaries and partial disappearance of the Bruch's Membrane (BM), thus posing challenges to the segmentation. To tackle these problems, we propose a novel dual-path U-shaped network for simultaneous layer segmentation and boundary regression. This network first designs a feature interaction fusion (FIF) module to strengthen the boundary shape constraints in the layer path. To address the challenge posed by partial BM disappearance and boundary-blurring, we propose a layer boundary repair (LBR) module. This module aims to use contrastive loss to enhance the confidence of blurred boundary regions and refine the segmentation of layer boundaries through the re-prediction head. In addition, we introduce a novel bilateral threshold distance map (BTDM) designed for the boundary path. The BTDM serves to emphasize information within boundary regions. This map, combined with the updated probability map, culminates in topology-guaranteed segmentation results achieved through a topology correction (TC) module. We investigated the proposed network on two severely deformed datasets (i.e., OCTA-500 and Aier-PED) and one slightly deformed dataset (i.e., DUKE). The proposed method achieves an average Dice score of 94.26% on the OCTA-500 dataset, which was 1.5% higher than BAU-Net and outperformed other methods. In the DUKE and Aier-PED datasets, the proposed method achieved average Dice scores of 91.65% and 95.75%, respectively.

5.
Alzheimers Res Ther ; 16(1): 104, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730505

ABSTRACT

BACKGROUND: Optimal blood pressure (BP) levels to reduce the long-term risk of cognitive decline remains controversial. We aimed to investigate the association between BP and anti-hypertensive treatment status with cognitive decline in older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study. Cognitive function was assessed at year 2011, 2013, 2015, and 2018. Global cognitive Z-score was calculated as the average score of episodic memory and mental intactness. BP were measured at the first and second wave. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Cumulative BP was calculated as the area under the curve using BP measurements from 2011 to 2013. Linear mixed models were used to assess the longitudinal association between BP-related measurements and cognitive decline. RESULTS: We included 11,671 participants (47.3% men and mean age 58.6 years). Individual with BP > 140/90 mm Hg or taking anti-hypertensive medication were independently associated with accelerated cognitive decline (ß=-0.014, 95% CI: -0.020 to -0.007). Individuals with anti-hypertensive medication use, but with controlled SBP to less than 120 mm Hg did not have a significantly increased risk of cognitive decline compared with normotension (ß=-0.003, 95% CI: -0.021 to 0.014). Individuals on anti-hypertensive treatment with PP of more than 70 mm Hg had a significantly higher risk of cognitive decline (ß=-0.033, 95% CI: -0.045 to -0.020). Regardless of anti-hypertensive treatment status, both elevated baseline and cumulative SBP and PP were found to be independently associated with accelerated cognitive decline. CONCLUSIONS: Cumulatively elevated SBP, PP and uncontrolled BP were associated with subsequent cognitive decline. Effectively controlling BP with anti-hypertensive treatment may be able to preserve cognitive decline in older adults.


Subject(s)
Antihypertensive Agents , Blood Pressure , Cognitive Dysfunction , Hypertension , Independent Living , Humans , Male , Female , Cognitive Dysfunction/epidemiology , Longitudinal Studies , China/epidemiology , Middle Aged , Antihypertensive Agents/therapeutic use , Blood Pressure/physiology , Blood Pressure/drug effects , Aged , Hypertension/drug therapy , Hypertension/epidemiology
6.
J Gen Intern Med ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696026

ABSTRACT

BACKGROUND: Very brief advice (VBA; ≤ 3 min) on quitting is practical and scalable during brief medical interactions with patients who smoke. This study aims to synthesize the effectiveness of VBA for smoking cessation and summarize the implementation strategies. METHODS: We searched randomized controlled trials aiming at tobacco abstinence and comparing VBA versus no smoking advice or no contact from Medline, Embase, CINAHL, Cochrane Library, PsycInfo databases, six Chinese databases, two trial registries ClinicalTrials.gov and WHO-ICTRP from inception to September 30, 2023. Grading of Recommendations, Assessment, Development, and Evaluations framework was used to assess the certainty of the evidence of the meta-analytic findings. The outcomes were self-reported long-term tobacco abstinence at least 6 months after treatment initiation, earlier than 6 months after treatment initiation, and quit attempts. Effect sizes were computed as risk ratio (RR) with 95% CI using frequentist random-effect models. DATA SYNTHESIS: Thirteen randomized controlled trials from 15 articles (n = 26,437) were included. There was moderate-certainty evidence that VBA significantly increased self-reported tobacco abstinence at ≥ 6 months in the adjusted model (adjusted risk ratio ARR 1.17, 95% CI: 1.07-1.27) compared with controls. The sensitivity analysis showed similar results when abstinence was verified by biochemical validation (n = 6 studies, RR 1.53, 95% CI 0.98-2.40). There was high-certainty evidence that VBA significantly increased abstinence at < 6 months (ARR 1.22, 95% CI: 1.01-1.47). Evidence of effect on quit attempts (ARR 1.03, 95% CI 0.97-1.08) was of very low certainty. DISCUSSION: VBA delivered in a clinical setting is effective in increasing self-reported tobacco abstinence, which provides support for wider adoption in clinical practice.

7.
Plant Physiol Biochem ; 212: 108725, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38772164

ABSTRACT

Elevated CO2 concentrations may inhibit photosynthesis due to nitrogen deficiency, but legumes may be able to overcome this limitation and continue to grow. Our study confirms this conjecture well. First, we placed the two-year-old potted saplings of Ormosia hosiei (O. hosiei) (a leguminous tree species) in the open-top chamber (OTC) with three CO2 concentrations of 400 (CK), 600 (E1), and 800 µmol·mol-1 (E2) to simulate the elevated CO2 concentration environment. After 146 days, the light saturation point (LSP), light compensation point (LCP), apparent quantum efficiency (AQE), and dark respiration rate (Rd) of O. hosiei were increased under increasing CO2 concentration and obtain the maximum ribulose diphosphate (RuBP) carboxylation rate (Vc max) and RuBP regenerated photosynthetic electron transfer rate (Jmax) were also significantly increased under E2 treatment (P < 0.05). This results in a significant increase of the maximum assimilation rate (Amax) under elevated CO2 concentrations. Sucrose phosphate synthase (SPS) activity in sucrose metabolism increased in the leaves, more soluble sugars, starches, and sucrose was produced, but sucrose content only in leaves increased at E2, and more carbon flows to the roots. The activity of the NH4+ assimilating enzymes glutamine synthetase (GS), glutamate synthetase (GOGAT), and glutamate dehydrogenase (GDH) in the leaves of O. hosiei increases under elevated CO2 concentrations to promote nitrogen synthesis that reduces the content of ammonium nitrogen and increases the content of nitrate nitrogen. In addition, under E1 conditions, sucrose synthase (SS), direction of synthesis activity was highest and sucrose invertase (INV) activity was lowest, this means that the balance of C and N metabolism is maintained. While under E2 conditions SS activity decreased and INV activity increased, this increased C/N and nitrogen use efficiency. So, the elevated CO2 concentration promotes the accumulation of O. hosiei biomass, especially in the aboveground part, but did not have a significant effect on the accumulation of root biomass. This means that O. hosiei is able to cope under the elevated CO2 concentration without showing photosynthetic adaptation during the experimental period.

8.
Comput Methods Programs Biomed ; 251: 108229, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38761413

ABSTRACT

BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) is currently one of the most advanced retinal imaging methods. Retinal biomarkers in OCT images are of clinical significance and can assist ophthalmologists in diagnosing lesions. Compared with fundus images, OCT can provide higher resolution segmentation. However, image annotation at the bounding box level needs to be performed by ophthalmologists carefully and is difficult to obtain. In addition, the large variation in shape of different retinal markers and the inconspicuous appearance of biomarkers make it difficult for existing deep learning-based methods to effectively detect them. To overcome the above challenges, we propose a novel network for the detection of retinal biomarkers in OCT images. METHODS: We first address the issue of labeling cost using a novel weakly semi-supervised object detection method with point annotations which can reduce bounding box-level annotation efforts. To extend the method to the detection of biomarkers in OCT images, we propose multiple consistent regularizations for point-to-box regression network to deal with the shortage of supervision, which aims to learn more accurate regression mappings. Furthermore, in the subsequent fully supervised detection, we propose a cross-scale feature enhancement module to alleviate the detection problems caused by the large-scale variation of biomarkers. We also propose a dynamic label assignment strategy to distinguish samples of different importance more flexibly, thereby reducing detection errors due to the indistinguishable appearance of the biomarkers. RESULTS: When using our detection network, our regressor also achieves an AP value of 20.83 s when utilizing a 5 % fully labeled dataset partition, surpassing the performance of other comparative methods at 5 % and 10 %. Even coming close to the 20.87 % result achieved by Point DETR under 20 % full labeling conditions. When using Group R-CNN as the point-to-box regressor, our detector achieves 27.21 % AP in the 50 % fully labeled dataset experiment. 7.42 % AP improvement is achieved compared to our detection network baseline Faster R-CNN. CONCLUSIONS: The experimental findings not only demonstrate the effectiveness of our approach with minimal bounding box annotations but also highlight the enhanced biomarker detection performance of the proposed module. We have included a detailed algorithmic flow in the supplementary material.

9.
Tob Induc Dis ; 222024.
Article in English | MEDLINE | ID: mdl-38751548

ABSTRACT

INTRODUCTION: Smoke or aerosols from cigarettes, e-cigarettes (ECs), or heated tobacco products (HTPs) are harmful. Yet, there is little knowledge about the specific patterns of secondhand tobacco exposure by source within household settings and the socioeconomic status (SES) differences in adolescents. METHODS: We used territory-representative student data from a cross-sectional school-based survey in 2020-2021 to calculate the weighted prevalence of secondhand exposure to cigarettes, e-cigarettes, and HTPs in the past seven days. Parental education and perceived family affluence were used as indicators of socioeconomic status. Generalized linear mixed models were used to analyze associations. RESULTS: Among 22039 participants, 29.8% reported any secondhand tobacco exposure (SH-Any) at home, primarily from cigarettes (27.4%), followed by e-cigarettes (4.0%) and HTPs (0.9%). Tertiary parental education level was associated with lower SH-Any exposure (Adjusted odds ratio, AOR=0.49; 95% CI: 0.45-0.53, p<0.001), fewer exposure days (ß= -0.685, p<0.001), lower exposure to cigarettes (SH-CC) (AOR=0.49; 95% CI: 0.45-0.54, p<0.001) and to e-cigarettes or HTPs (SH-EC/HTP) (AOR=0.57; 95% CI: 0.45-0.71, p<0.001). 'Poor' family affluence was associated with higher exposures [AOR(SH-Any) =1.14; 95% CI: 1.06-1.22, p=0.001; ß(days)=0.160, p<0.001; AOR(SH-CC) =1.15; 95% CI: 1.07-1.24, p<0.001], except for SH-EC/HTP exposure, which was higher in students in an affluent family (AOR =1.66; 95% CI: 1.25-2.21, p<0.001). Significant SES differences in SH-EC/HTP exposure were found only in groups with low parental education level. Dose-response relationships were found between lower SH-Any and SH-CC and higher SES categories (p for trend<0.001). CONCLUSIONS: Adolescents experienced a high prevalence of tobacco smoke exposure at home, primarily from cigarettes. Higher SES was associated with lower tobacco exposure, except for SH-EC/HTP, which was higher among adolescents from affluent families. Additionally, high parental education level was protective against exposure to SH-EC/HTP. Comprehensive control measures to reduce the use of these tobacco products are needed to protect adolescents of diverse socioeconomic backgrounds.

10.
J Control Release ; 370: 438-452, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38701885

ABSTRACT

Triggering pyroptosis is a major new weathervane for activating tumor immune response. However, biodegradable pyroptosis inducers for the safe and efficient treatment of tumors are still scarce. Herein, a novel tumor microenvironment (TME)-responsive activation nanoneedle for pyroptosis induction, copper-tannic acid (CuTA), was synthesized and combined with the sonosensitizer Chlorin e6 (Ce6) to form a pyroptosis amplifier (CuTA-Ce6) for dual activation and amplification of pyroptosis by exogenous ultrasound (US) and TME. It was demonstrated that Ce6-triggered sonodynamic therapy (SDT) further enhanced the cellular pyroptosis caused by CuTA, activating the body to develop a powerful anti-tumor immune response. Concretely, CuTA nanoneedles with quadruple mimetic enzyme activity could be activated to an "active" state in the TME, destroying the antioxidant defense system of the tumor cells through self-destructive degradation, breaking the "immunosilent" TME, and thus realizing the pyroptosis-mediated immunotherapy with fewer systemic side effects. Considering the outstanding oxygen-producing capacity of CuTA and the distinctive advantages of US, the sonosensitizer Ce6 was attached to CuTA via an amide reaction, which further amplified the pyroptosis and sensitized pyroptosis-induced immunotherapy with the two-pronged strategy of CuTA enzyme-catalyzed cascade and US-driven SDT pathway to generate a "reactive oxygen species (ROS) storm". Conclusively, this work provided a representative paradigm for achieving safe, reliable and efficient pyroptosis, which was further enhanced by SDT for more robust immunotherapy.

11.
JAMA Intern Med ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587827

ABSTRACT

Importance: Alcohol use is prevalent among university students. Mobile instant messaging apps could enhance the effectiveness of an alcohol brief intervention (ABI), but the evidence is scarce. Objective: To evaluate the effectiveness of an ABI plus 3 months of mobile chat-based instant messaging support for alcohol reduction in university students at risk of alcohol use disorder. Design, Setting, and Participants: In this randomized clinical trial, 772 students at risk of alcohol use disorder (Alcohol Use Disorders Identification Test [AUDIT] score ≥8) were recruited from 8 universities in Hong Kong between October 15, 2020, and May 12, 2022. Participants were randomly assigned 1:1 to either the intervention or control group. Interventions: Both groups received the same ABI at baseline, which consisted of face-to-face or video conferencing with research nurses who delivered personalized feedback based on the participant's AUDIT risk level, along with a 12-page booklet describing the benefits of alcohol reduction and the harmful effects of alcohol on health and social well-being. The intervention group then received 3 months of chat-based instant messaging support on alcohol reduction guided by behavioral change techniques. The control group received 3 months of short message service (SMS) messaging on general health topics. Main Outcomes and Measures: All outcomes were self-reported. The primary outcome was alcohol consumption in grams per week at 6 months of follow-up. By definition, 1 alcohol unit contains 10 g of pure alcohol. Secondary outcomes at the 6-month follow-up included changes in AUDIT score, weekly alcohol consumption, intention to drink in the next 30 days, drinking frequency and any binge or heavy drinking in the past 30 days, and self-efficacy of quitting drinking. The primary analysis followed the intention-to-treat principle, and linear regression (reported as unstandardized coefficient B) and logistic regression (reported as odds ratios) were used to compare the primary and secondary outcomes between the intervention and control groups. Results: The study included 772 students (mean [SD] age, 21.1 [3.5] years; 395 females [51.2%]) who were randomly assigned to either the intervention (n = 386) or control (n = 386) group. In the intention-to-treat analysis, the intervention group had lower alcohol consumption in grams per week (B, -11.42 g [95% CI, -19.22 to -3.62 g]; P = .004), a lower AUDIT score (B, -1.19 [95% CI, -1.63 to -0.34]; P = .003), reduced weekly alcohol unit consumption (B, -1.14 [95% CI, -1.92 to -0.36]; P = .004), and less intention to drink (odds ratio, 0.66 [95% CI, 0.47 to 0.92]; P = .01) at the 6-month follow-up compared with the control group. In analyses adjusted for baseline characteristics, interacting at least once with the research nurse on the instant messaging application resulted in lower estimated alcohol consumption in grams per week (adjusted B, -17.87 g [95% CI, -32.55 to -3.20 g]; P = .01), lower weekly alcohol unit consumption (adjusted B, -1.79 [95% CI, -3.25 to -0.32]; P = .02), and a lower AUDIT score (adjusted B, -0.53 [95% CI, -1.87 to -0.44]; P = .01) at 6 months. Conclusions and Relevance: Results of this randomized clinical trial indicate that mobile chat-based instant messaging support for alcohol reduction in addition to an ABI was effective in reducing alcohol consumption in university students in Hong Kong at risk of alcohol use disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT04025151.

12.
Adv Healthc Mater ; : e2400606, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38683681

ABSTRACT

Emerging organic molecules with emissions in the second near-infrared (NIR-II) region are garnering significant attention. Unfortunately, achieving accountable organic emission intensity over the NIR-IIa (1300 nm) region faces challenges due to the intrinsic energy gap law. Up to the current stage, all reported organic NIR-IIa emitters belong to polymethine-based dyes with small Stokes shifts (<50 nm) and low quantum yield (QY; ≤0.015%). However, such polymethines have proved to cause self-absorption with constrained emission brightness, limiting advanced development in deep-tissue imaging. Here a new NIR-IIa scaffold based on rigid and highly conjugated dibenzofluoran core terminated by amino-containing moieties that reveal emission peaks of 1230-1305 nm is designed. The QY is at least 10 times higher than all synthesized or reported NIR-IIa polymethines with extraordinarily large Stokes shifts of 370-446 nm. DBF-BJ is further prepared as a polymer dot to demonstrate its in vivo 3D stereo imaging of mouse vasculature with a 1400 nm long-pass filter.

13.
Acta Biomater ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38663684

ABSTRACT

Ferroptosis induced by lipid peroxide (LPO) accumulation is an effective cell death pathway for cancer therapy. However, how to effectively induce ferroptosis at tumor sites and improve its therapeutic effectiveness remains challenging. Here, MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex with tumor-specific targeting and TME response is constructed to overcome immunosuppressive tumor microenvironment (TME) to potentiate the curative effect of ferroptosis by coupling the immune checkpoint indoleamine 2,3-dioxygenase (IDO) inhibitor, NLG919, and hyaluronic acid (HA) to novel ultra-small MnFe2O4@NaGdF4 (MG) nanoparticles with a Janus structure. Firstly, tumor site-precise delivery of MG and NLG919 is achieved with HA targeting. Secondly, MG acts as a magnetic resonance imaging contrast agent, which not only has a good photothermal effect to realize tumor photothermal therapy, but also depletes glutathione and catalyzes the production of reactive oxygen species from endogenous H2O2, which effectively promotes the accumulation of LPO and inhibits the expression of glutathione peroxidase 4, achieving enhanced ferroptosis. Thirdly, NLG919 inhibits the differentiation of Tregs by blocking the tryptophan/kynurenine immune escape pathway, thereby reversing immunosuppressive TME together with the Mn2+-activated cGAS-STING pathway. This work contributes new perspectives for the development of novel ultra-small Janus nanoparticles to reshape immunosuppressive TME and ferroptosis activation. STATEMENT OF SIGNIFICANCE: The Janus structured MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex was synthesized, which can realize the precise delivery of T1/T2 contrast agents MnFe2O4@NaGdF4 (MG) and NLG919 at the tumor site under the ultra-small Janus structural characteristics and targeted molecule HA. The production of ROS, consumption of GSH, and photothermal properties of MGNH make it possible for CDT/PTT activated ferroptosis, and synergistically disrupt and reprogram tumor growth and immunosuppressive tumor microenvironment with NLG919 and Mn2+-mediated activation of cGAS-STING pathway, achieving CDT/PTT/immunotherapy activated by ferroptosis. Meanwhile, ultra-small structural properties of MGNH facilitate subsequent metabolic clearance by the body, allowing for the minimization of potential biotoxicity associated with its prolonged retention.

14.
Org Lett ; 26(17): 3612-3616, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38656195

ABSTRACT

Switchable enantioselectivity was uncovered in the enantioselective catalytic conjugate addition of ß,γ-unsaturated α-keto esters with terminal alkynes to the chiral Lewis acid complex of In(BF4)3 and chiral phosphoric acid.

15.
Biomaterials ; 308: 122550, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38581762

ABSTRACT

Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1. The resultant fibrous glue is capable of normalizing tumoral vasculature as well as restricting immune escape. The pre-GP1 retains a 6-fold higher penetration depth than that of antibody in the multicellular spheroids (MCSs) model. It also shows remarkable tumor growth inhibition (TGI) from 19% to 61% in a murine advanced large tumor model compared to the clinical combination therapy. In addition, in the orthotopic renal tumor preclinical model, the lung metastatic nodules are reduced by 64% compared to the clinically used combination. This pre-GP1 provides a promising strategy to control the progression and metastasis of advanced renal carcinoma.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Animals , Kidney Neoplasms/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/therapy , Kidney Neoplasms/immunology , Humans , Mice , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/therapy , Carcinoma, Renal Cell/drug therapy , Cell Line, Tumor , Tumor Microenvironment/drug effects , Mice, Inbred BALB C , Female , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism
16.
Pest Manag Sci ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676556

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) are non-coding RNAs that play a pivotal role in antiviral infection. The miR184-3p has been identified to promote rice black streaked dwarf virus (RBSDV) infection in vector Laodelphax striatellus, whether it targets other genes of L. striatellus to modulate RBSDV propagation remains unknown. RESULTS: We first analyzed the expression profiles of miR184-3p and its role in regulating RBSDV infection in L. striatellus. Then the candidate genes expression of miR184-3p were systemically analyzed with gain and loss function of miR184-3p, and the interaction of candidate gene, ecdysone inducible protein 78 (Eip78) with miR184-3p was verified by dual luciferase reporter assay. We found Eip78 is evolutionary conserved among agricultural pests and predominantly expressed in the central nervous system (CNS) of L. striatellus. Knockdown of Eip78 effectively increased RBSDV propagation and transmission. Blockade with Eip78 antibody or injection with Eip78 protein could significantly regulate RBSDV infection. Further analysis revealed that knockdown of Eip78 specifically suppresses RBSDV infection in the head part but not in the body part of L. striatellus. Besides, knockdown of ecdysone receptor (EcR) notably restricted Eip78 expression and increased RBSDV accumulation in L. striatellus. CONCLUSIONS: Taken together, we identified a novel target gene of miR184-3p, Eip78, a member of the ecdysone signaling pathway, and revealed the anti-RBSDV role of Eip78 in the CNS of L. striatellus. These results shed light on the interaction mechanisms of miRNAs, virus and ecdysone signaling pathway in insect vector. © 2024 Society of Chemical Industry.

17.
Pest Manag Sci ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38567786

ABSTRACT

BACKGROUND: The important wood-boring pest Batocera horsfieldi has evolved a sensitive olfactory system to locate host plants. Odorant-binding proteins (OBPs) are thought to play key roles in olfactory recognition. Therefore, exploring the physiological function of OBPs could facilitate a better understanding of insect chemical communications. RESULTS: In this research, 36 BhorOBPs genes were identified via transcriptome sequencing of adults' antennae from B. horsfieldi, and most BhorOBPs were predominantly expressed in chemosensory body parts. Through fluorescence competitive binding and fluorescence quenching assays, the antenna-specific BhorOBP28 was investigated and displayed strong binding affinities forming stable complexes with five volatiles, including (+)-α-Pinene, (+)-Limonene, ß-Pinene, (-)-Limonene, and (+)-Longifolene, which could also elicit conformation changes when they were interacting with BhorOBP28. Batocera horsfieldi females exhibited a preference for (-)-Limonene, and a repellent response to (+)-Longifolene. Feeding dsOBP19 produced by a bacteria-expressed system with a newly constructed vector could lead to the knockdown of BhorOBP28, and could further impair B. horsfieldi attraction to (-)-Limonene and repellent activity of (+)-Longifolene. The analysis of site-directed mutagenesis revealed that Leu7, Leu72, and Phe121 play a vital role in selectively binding properties of BhorOBP28. CONCLUSION: By modeling the molecular mechanism of olfactory recognition, these results demonstrate that BhorOBP28 is involved in the chemoreception of B. horsfieldi. The bacterial-expressed dsRNA delivery system gains new insights into potential population management strategies. Through the olfactory process concluded that discovering novel behavioral regulation and environmentally friendly control options for B. horsfieldi in the future. © 2024 Society of Chemical Industry.

19.
Clin Cosmet Investig Dermatol ; 17: 513-528, 2024.
Article in English | MEDLINE | ID: mdl-38463558

ABSTRACT

Background: Overweight and obesity have become public health problems worldwide. An increasing number of research works are focusing on skin physiology and the manifestations of obesity-associated skin diseases, but little is known about the correlations between body mass index (BMI), facial skin physiological parameters, and the facial skin microbiome in healthy women. Objective: To investigate the correlations between BMI, facial skin physiological parameters and facial bacteria and fungi in 198 women aged 18 to 35 years in Shanghai. Methods: According to the international BMI standard and Chinese reference standard, subjects were divided into three groups, "lean" B1, "normal" B2 and "overweight" B3, and the physiological parameters of facial skin were measured by non-invasive instrumental methods, and the skin microbiota was analyzed by 16S rRNA and ITS high-throughput sequencing. Results: Compared with the skin physiological parameters of the normal group, those of the overweight group exhibited a significant increase in trans-epidermal water loss (TEWL), which indicated that the skin barrier was impaired. The skin haemoglobin content was significantly increased, and skin surface pH was significant decreased in those with a high BMI. Furthermore, α-diversity, analysed using the Shannon, Chao, Sobs, and Ace indexes, was increased in the overweight group, suggesting that the diversity and species abundance of facial bacterial and fungal microbiota were also increased. Moreover, the overweight group had higher abundances of Streptococcus, Corynebacterium, Malassezia, and Candida. Notably, skin surface pH was significantly and negatively correlated with the relative abundances of Malassezia, Candida, and Cladosporium. Besides, the abundance of Malassezia was positively associated with the abundances of Staphylococcus and Corynebacterium. Conclusion: These results indicate that BMI is associated with differences in the biophysical properties and microbiome of the facial skin. A high BMI affects the integrity of skin barrier and changes the skin flora diversity and species composition.

20.
Tob Control ; 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38458757

ABSTRACT

OBJECTIVES: To examine the associations between tobacco industry denormalisation (TID) beliefs and support for tobacco endgame policies. METHODS: A total of 2810 randomly selected adult respondents of population-based tobacco policy-related surveys (2018-2019) were included. TID beliefs (agree vs disagree/unsure) were measured by seven items: tobacco manufacturers ignore health, induce addiction, hide harm, spread false information, lure smoking, interfere with tobacco control policies and should be responsible for health problems. Score of each item was summed up and dichotomised (median=5, >5 strong beliefs; ≤5 weak beliefs). Support for tobacco endgame policies on total bans of tobacco sales (yes/no) and use (yes/no) was reported. Associations between TID beliefs and tobacco endgame policies support across various smoking status were analysed, adjusting for sociodemographics. RESULTS: Fewer smokers (23.3%) had strong beliefs of TID than ex-smokers (48.4%) and never smokers (48.5%) (p<0.001). Support for total bans on tobacco sales (74.6%) and use (76.9%) was lower in smokers (33.3% and 35.3%) than ex-smokers (74.3% and 77.9%) and never smokers (76.0% and 78.3%) (all p values<0.001). An increase in the number of TID beliefs supported was positively associated with support for a total ban on sales (adjusted risk ratio 1.06, 95% CI 1.05 to 1.08, p<0.001) and use (1.06, 95% CI 1.05 to 1.07, p<0.001). The corresponding associations were stronger in smokers than non-smokers (sales: 1.87 vs 1.25, p value for interaction=0.03; use: 1.78 vs 1.21, p value for interaction=0.03). CONCLUSION: Stronger TID belief was associated with greater support for total bans on tobacco sales and use. TID intervention may increase support for tobacco endgame, especially in current smokers.

SELECTION OF CITATIONS
SEARCH DETAIL
...