Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in quadrivalent influenza vaccine vaccinated mice.

There are considerable avenues through which currently licensed influenza vaccines could be optimized. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus-derived defective interfering (SDI) RNA, a RIG-I agonist; and an amphiphilic imidazoquinoline (IMDQ-PEG-Chol), a TLR7/8 agonist. The negatively charged SDI RNA was formulated into lipid nanoparticles (LNPs) facilitating direct delivery of SDI RNA to the cytosol, where RIG-I sensing induces inflammatory and type I interferon responses. We previously tested SDI RNA and IMDQ-PEG-Chol as standalone and combination adjuvants for influenza and SARS-CoV-2 vaccines. Here, we tested two different ionizable lipids, K-Ac7-Dsa and S-Ac7-Dog, for LNP formulations. The LNPs were incorporated with SDI RNA to determine its potential as a combination adjuvant with IMDQ-PEG-Chol by evaluating the host immune response to vaccination and infection in immunized BALB/c mice. Adjuvanticity of IMDQ-PEG-Chol with and without empty or SDI-loaded LNPs was validated with quadrivalent inactivated influenza vaccine (QIV), showing robust induction of antibody titers and T-cell responses. Depending on the adjuvant combination and LNP formulation, humoral and cellular vaccine responses could be tailored towards type 1 or type 2 host responses with specific cytokine profiles that correlated with the protective responses to viral infection. The extent of protection conferred by different vaccine/LNP/adjuvant combinations was tested by challenging mice with a vaccine-matched strain of influenza A virus A/Singapore/gp1908/2015 IVR-180 (H1N1). Groups that received either LNP formulated with SDI or IMDQ-PEG-Chol, or both, showed very low levels of viral replication in their lungs at 5 days post-infection (DPI). These studies provide evidence that the combination of vaccines with LNPs and/or adjuvants promote antigen-specific cellular responses that can contribute to protection upon infection. Interestingly, we observed differences in humoral and cellular responses to vaccination between different groups receiving K-Ac7-Dsa or S-Ac7-Dog lipids in LNP formulations. The differences were also reflected in inflammatory responses in lungs of vaccinated animals to infection, depending on LNP formulations. Therefore, this study suggests that the composition of the LNPs, particularly the ionizable lipid, plays an important role in inducing inflammatory responses in vivo, which is important for vaccine safety and to prevent adverse effects upon viral exposure.

Melatonin application during cryopreservation improves the development and clinical outcomes of human vitrified-warmed oocytes.

In this clinical study, we investigated the potential of melatonin (MT) supplementation in the freeze-thaw medium used for cryopreserved human oocytes. In total, 152 patients who underwent in vitro fertilization between January 2020 and December 2022 were included and categorized into different groups as follows: the donor group, comprising 108 patients who donated their oocytes, with 34 patients using a vitrification and warming medium supplemented with MT (D-MT subgroup) and 74 patients using conventional medium without MT (D-0 subgroup); and the autologous group, comprising 38 patients who used their own oocytes, with 19 patients using medium supplemented with MT (A-MT subgroup) and 19 patients using medium without MT (A-0 subgroup). After thawing, the surviving oocytes in the D-MT and A-MT subgroups and D-0 and A-0 subgroups were cultured in a fertilization media with and without 10-9 MMT for 2.5 h, respectively, followed by intracytoplasmic sperm injection insemination, embryo culture, and transfer. The survival, cleavage, high-quality embryo, clinical pregnancy, ongoing pregnancy, and implantation rates were significantly higher in the D-MT subgroup than in the D-0 subgroup (all P < 0.05). Similarly, the survival, fertilization, high-quality embryo, and high-quality blastocyst rates were significantly higher in the A-MT subgroup than in the A-0 subgroup (all P < 0.05). These findings indicate that MT addition during cryopreservation can enhance the development of vitrified-warmed human oocytes and improve clinical outcomes.

Global, regional, and national burden of heatwave-related mortality from 1990 to 2019: A three-stage modelling study.

BACKGROUND: The regional disparity of heatwave-related mortality over a long period has not been sufficiently assessed across the globe, impeding the localisation of adaptation planning and risk management towards climate change. We quantified the global mortality burden associated with heatwaves at a spatial resolution of 0.5°×0.5° and the temporal change from 1990 to 2019. METHODS AND FINDINGS: We collected data on daily deaths and temperature from 750 locations of 43 countries or regions, and 5 meta-predictors in 0.5°×0.5° resolution across the world. Heatwaves were defined as location-specific daily mean temperature ≥95th percentiles of year-round temperature range with duration ≥2 days. We first estimated the location-specific heatwave-mortality association. Secondly, a multivariate meta-regression was fitted between location-specific associations and 5 meta-predictors, which was in the third stage used with grid cell-specific meta-predictors to predict grid cell-specific association. Heatwave-related excess deaths were calculated for each grid and aggregated. During 1990 to 2019, 0.94% (95% CI: 0.68-1.19) of deaths [i.e., 153,078 cases (95% eCI: 109,950-194,227)] per warm season were estimated to be from heatwaves, accounting for 236 (95% eCI: 170-300) deaths per 10 million residents. The ratio between heatwave-related excess deaths and all premature deaths per warm season remained relatively unchanged over the 30 years, while the number of heatwave-related excess deaths per 10 million residents per warm season declined by 7.2% per decade in comparison to the 30-year average. Locations with the highest heatwave-related death ratio and rate were in Southern and Eastern Europe or areas had polar and alpine climates, and/or their residents had high incomes. The temporal change of heatwave-related mortality burden showed geographic disparities, such that locations with tropical climate or low incomes were observed with the greatest decline. The main limitation of this study was the lack of data from certain regions, e.g., Arabian Peninsula and South Asia. CONCLUSIONS: Heatwaves were associated with substantial mortality burden that varied spatiotemporally over the globe in the past 30 years. The findings indicate the potential benefit of governmental actions to enhance health sector adaptation and resilience, accounting for inequalities across communities.

Associations between residential greenness and obesity phenotypes among adults in Southwest China.

BACKGROUND: Although exposure to greenness has generally benefited human metabolic health, the association between greenness exposure and metabolic obesity remains poorly studied. We aimed to investigate the associations between residential greenness and obesity phenotypes and the mediation effects of air pollutants and physical activity (PA) level on the associations. METHODS: We used the baseline of the China Multi-Ethnic Cohort (CMEC) study, which enrolled 87,613 adults. Obesity phenotypes were defined based on obesity and metabolic status, including metabolically unhealthy obesity (MUO), non-obesity (MUNO), metabolically healthy obesity (MHO), and non-obesity (MHNO). Greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 500-m buffer zones around the participants' residence. Multivariable logistic regression was used to estimate the associations between greenness and obesity phenotypes. Stratified analyses by age, sex, educational level, and urbanicity were performed to identify how the effect varies across different subgroups. Causal mediation analysis was used to examine the mediation effects of air pollutants and PA level. RESULTS: Compared with MHNO, each interquartile range (IQR) increase in greenness exposure was associated with reduced risks of MHO (ORNDVI [95% CI] = 0.87 [0.81, 0.93]; OREVI = 0.91 [0.86, 0.97]), MUO (ORNDVI = 0.83 [0.78, 0.88]; OREVI = 0.86 [0.81, 0.91]), and MUNO (ORNDVI = 0.88 [0.84, 0.91]; OREVI = 0.89 [0.86, 0.92]). For each IQR increase in both NDVI and EVI, the risks of MHO, MUO, and MUNO were reduced more in men, participants over 60 years, those with a higher level of education, and those living in urban areas, compared to their counterparts. Concentrations of particulate matter (PM) and PA level partially mediated the associations between greenness exposure and obesity phenotypes. CONCLUSIONS: Exposure to residential greenness was associated with decreased risks of MHO, MUO, and MUNO, which was mediated by concentrations of PM and PA level, and modified by sex, age, educational level, and urbanicity.

A Survey of Needle Steering Approaches in Minimally Invasive Surgery.

In virtue of a curved insertion path inside tissues, needle steering techniques have revealed the potential with the assistance of medical robots and images. The superiority of this technique has been preliminarily verified with several maneuvers: target realignment, obstacle circumvention, and multi-target access. However, the momentum of needle steering approaches in the past decade leads to an open question-"How to choose an applicable needle steering approach for a specific clinical application?" This survey discusses this question in terms of design choices and clinical considerations, respectively. In view of design choices, this survey proposes a hierarchical taxonomy of current needle steering approaches. Needle steering approaches of different manipulations and designs are classified to systematically review the design choices and their influences on clinical treatments. In view of clinical consideration, this survey discusses the steerability and acceptability of the current needle steering approaches. On this basis, the pros and cons of the current needle steering approaches are weighed and their suitable applications are summarized. At last, this survey concluded with an outlook of the needle steering techniques, including the potential clinical applications and future developments in mechanical design.

Cohort profile: China undergraduate cohort for environmental health study.

The China Undergraduate Cohort (CUC) is an ambispective cohort study with its major purpose to better understand the effects of lifetime environmental exposures on health outcomes. We recruited 5322 college students with an average age of 18.3 ± 0.7 years in China from August 23, 2019 to October 28, 2019. Follow-up surveys were conducted annually. The dataset comprises individual demographic data (e.g. age, sex, height, weight, birth date, race, home address, annual family income, contact information), health-related behavior data (smoking status, smoking cessation, passive smoking exposure, drinking habit, physical activity, dietary status), lifestyle data (physical exercise, dietary habit, length of time spent outdoors), disease history (respiratory disease history, cardiovascular disease history, urinary system disease history, etc.), mental health status data (sleep quality, self-reported stress, anxiety and depression symptoms), lung function and blood samples data. Preliminary results from our cohort have found the association between air pollution, summer heat and mercury exposure and lung function among young adults in China.

Estimates of global mortality burden associated with short-term exposure to fine particulate matter (PM2·5).

BACKGROUND: The acute health effects of short-term (hours to days) exposure to fine particulate matter (PM2·5) have been well documented; however, the global mortality burden attributable to this exposure has not been estimated. We aimed to estimate the global, regional, and urban mortality burden associated with short-term exposure to PM2·5 and the spatiotemporal variations in this burden from 2000 to 2019. METHODS: We combined estimated global daily PM2·5 concentrations, annual population counts, country-level mortality rates, and epidemiologically derived exposure-response functions to estimate the mortality attributable to short-term PM2·5 exposure from 2000 to 2019, in the continental regions and in 13 189 urban centres worldwide at a spatial resolution of 0·1°â€ˆ× 0·1°. We tested the robustness of our mortality estimates with different theoretical minimum risk exposure levels, lag effects, and exposure-response functions. FINDINGS: Approximately 1 million (95% CI 690 000-1·3 million) premature deaths per year from 2000 to 2019 were attributable to short-term PM2·5 exposure, representing 2·08% (1·41-2·75) of total global deaths or 17 (11-22) premature deaths per 100 000 population. Annually, 0·23 million (0·15 million-0·30 million) deaths attributable to short-term PM2·5 exposure were in urban areas, constituting 22·74% of the total global deaths attributable to this cause and accounting for 2·30% (1·56-3·05) of total global deaths in urban areas. The sensitivity analyses showed that our worldwide estimates of mortality attributed to short-term PM2·5 exposure were robust. INTERPRETATION: Short-term exposure to PM2·5 contributes a substantial global mortality burden, particularly in Asia and Africa, as well as in global urban areas. Our results highlight the importance of mitigation strategies to reduce short-term exposure to air pollution and its adverse effects on human health. FUNDING: Australian Research Council and the Australian National Health and Medical Research Council.

Heat Exposure, Preterm Birth, and the Role of Greenness in Australia.

Importance: Preterm birth (PTB) is associated with adverse health outcomes. The outcomes of heat exposure during pregnancy and the moderating association of greenness with PTB remain understudied. Objective: To investigate associations between heat exposure, greenness, and PTB, as well as interactions between these factors. Design, Setting, and Participants: Included in this cohort study were births occurring in Sydney, New South Wales, Australia, between 2000 and 2020, retrieved from New South Wales Midwives Data Collection. Participants with incomplete or missing data on their residential address or those who resided outside of New South Wales during their pregnancy were excluded. Data were analyzed from March to October 2023. Exposures: Greenness measured using normalized difference vegetation index (NDVI) and tree cover derived from satellite images. Daily extreme heat and nighttime extreme heat were defined as above the 95th percentile of community- and trimester-specific daily mean temperatures and nighttime temperatures. Main Outcomes and Measures: Logistic regression models estimated the independent association of extreme heat with PTB, adjusting for individual- and area-level covariates, season of conception, and long-term trend. An interaction term between extreme heat exposure and greenness was included to explore potential modification. With a significant interaction observed, the number of preventable heat-associated PTBs that were associated with greenness was estimated. Results: A total of 1 225 722 births (median [IQR] age, 39 [38-40] weeks; 631 005 male [51.5%]) were included in the analysis, including 63 144 PTBs (median [IQR] age, 35 [34-36] weeks; 34 822 male [55.1%]). Compared with those without heat exposure, exposure to daily extreme heat and nighttime extreme heat in the third trimester was associated with increased risks of PTB, with an adjusted odds ratio (OR) of 1.61 (95% CI, 1.55-1.67) and 1.51 (95% CI, 1.46-1.56]), respectively (PTB rates: exposed, 4615 of 61 338 [7.5%] vs unexposed, 56 440 of 1 162 295 [4.9%] for daily extreme heat and 4332 of 61 337 [7.1%] vs 56 723 of 1 162 296 [4.9%] for nighttime extreme heat). Disparities in associations between extreme heat exposure and PTB were observed, with lower odds of PTB among pregnant individuals residing in greener areas. The associations between extreme heat exposure and PTB could be mitigated significantly by higher greenness. Improving NDVI and tree cover could reduce daily extreme heat-associated PTB by 13.7% (95% CI, 2.3%-15.1%) and 20.9% (95% CI, 5.8%-31.5%), respectively. For nighttime extreme heat-associated PTB, reductions were 13.0% (0.2%-15.4%) and 17.2% (4.1%-27.0%), respectively. Conclusions and Relevance: Results of this large birth cohort study suggest that extreme heat exposure was adversely associated with PTB, with greenness playing a moderating role. Increasing greenness levels in residential communities could prevent heat-associated PTBs. These findings emphasize the importance of integrating heat mitigation strategies and improving green space in urban planning and public health interventions.

Ambient PM2.5 and productivity-adjusted life years lost in Brazil: a national population-based study.

Enormous health burden has been associated with air pollution and its effects continue to grow. However, the impact of air pollution on labour productivity at the population level is still unknown. This study assessed the association between premature death due to PM2.5 exposure and the loss of productivity-adjusted life years (PALYs), in Brazil. We applied a novel variant of the difference-in-difference (DID) approach to assess the association. Daily all-cause mortality data in Brazil were collected from 2000-2019. The PALYs lost increased by 5.11% (95% CI: 4.10-6.13%), for every 10 µg/m3 increase in the 2-day moving average of PM2.5. A total of 9,219,995 (95% CI: 7,491,634-10,921,141) PALYs lost and US$ 268.05 (95% CI: 217.82-317.50) billion economic costs were attributed to PM2.5 exposure, corresponding to 7.37% (95% CI: 5.99-8.73%) of the total PALYs lost due to premature death. This study also found that 5,005,306 PALYs could be avoided if the World Health Organization (WHO) air quality guideline (AQG) level was met. In conclusion, this study demonstrates that ambient PM2.5 exposure is associated with a considerable labour productivity burden relating to premature death in Brazil, while over half of the burden could be prevented if the WHO AQG was met. The findings highlight the need to reduce ambient PM2.5 levels and provide strong evidence for the development of strategies to mitigate the economic impacts of air pollution.

Use of pus metagenomic next-generation sequencing for efficient identification of pathogens in patients with sepsis.

The positive detection rate of blood metagenomic next-generation sequencing (mNGS) was still too low to meet clinical needs, while pus from the site of primary infection may be advantageous for identification of pathogens. To assess the value of mNGS using pus in patients with sepsis, thirty-five samples were collected. Pathogen identification and mixed infection diagnosis obtained by use of mNGS or cultivation methods were compared. Fifty-three aerobic or facultative anaerobes, 59 obligate anaerobes and 7 fungi were identified by the two methods. mNGS increased the accuracy rate of diagnosing aerobic or facultative anaerobic infections from 44.4% to 94.4%; mNGS also increased the sensitivity of diagnosing obligate anaerobic infections from 52.9% to 100.0%; however, mNGS did not show any advantage in terms of fungal infections. Culture and mNGS identified 1 and 24 patients with mixed infection, respectively. For obligate anaerobes, source of microorganisms was analyzed. The odontogenic bacteria all caused empyema (n = 7) or skin and soft tissue infections (n = 5), whereas the gut-derived microbes all caused intra-abdominal infections (n = 7). We also compared the clinical characteristics of non-obligate anaerobic and obligate anaerobic infection groups. The SOFA score [9.0 (7.5, 14.3) vs. 5.0 (3.0, 8.0), P = 0.005], procalcitonin value [4.7 (1.8, 39.9) vs. 2.50 (0.7, 8.0), P = 0.035], the proportion of septic shock (66.7% vs. 35.3%, P = 0.044) and acute liver injury (66.7% vs. 23.5%, P = 0.018) in the non-obligate anaerobic infection group were significantly higher than those in the obligate anaerobic infection group. In patients with sepsis caused by purulent infection, mNGS using pus from the primary lesion may yield more valuable microbiological information.

Spatiotemporal characteristics and influencing factors for joint events of air pollution wave and cold wave in China.

Climate change triggered more environmental extremes. The joint events of air pollution wave and cold wave showed higher health risks than independent events, but little evidence is available for the spatiotemporal features of their co-occurrence. To better understand and forecast the joint events, a method framework was developed in this study. The temporal trend and spatial distribution of count and duration for joint events were measured at each grid cell (0.5°×0.5°) by integrating the PM2.5 air pollution wave and cold wave. The generalized linear mixed model was used to screen influencing variables that took into account socioeconomic characteristics, meteorological variables, and annual PM2.5 levels. During 2000 and 2018, the average annual count of joint events was 4.1 ± 6.8 days and the average duration ranged from 1.0 to 9.7 days. High spatial heterogeneity was observed throughout China, with a significant increase in joint events observed in Xinjiang area (the largest province in China). The most average count of joint events was observed in Henan province (one of the most populous provinces), while the longest duration was in Chongqing (a municipality, one of the megacities). Areas with higher PM2.5 levels, prolonged air pollution wave, and cold wave durations would experience more joint events. These findings can assist China in locating vulnerable areas and establishing effective local early warning systems. The method framework offers broader perspectives on mitigating health risks associated with extreme events in other countries and regions.

Facile Synthesis of a Novel AgIO3/CTF Heterojunction and Its Adsorption-Photocatalytic Performance with Organic Pollutants.

With the development of modern industry, the issue of water pollution has garnered increasing attention. Photocatalysis, as a novel green environmental technology that is resource-efficient, environmentally friendly, and highly promising, has found extensive applications in the field of organic pollutant treatment. However, common semiconductor materials exhibit either a relatively low photocatalytic efficiency in the visible light range or an inefficient separation of photogenerated charges, resulting in their limited ability to harness solar energy effectively. Consequently, the development of new photocatalysts has become a pivotal focus in current photocatalysis research to enhance solar energy utilization. This research provides a brief explanation of the photocatalytic mechanism of the AgIO3/CTF heterojunction photocatalyst. Due to the localized surface plasmon resonance (LSPR) effect, the Ag nanoparticles demonstrate significant absorption in the visible light region, playing a crucial role in the highly efficient photocatalytic reduction of organic pollutants.

A Highly Selective Implantable Electrochemical Fiber Sensor for Real-Time Monitoring of Blood Homovanillic Acid.

Homovanillic acid (HVA) is a major dopamine metabolite, and blood HVA is considered as central nervous system (CNS) dopamine biomarker, which reflects the progression of dopamine-associated CNS diseases and the behavioral response to therapeutic drugs. However, facing blood various active substances interference, particularly structurally similar catecholamines and their metabolites, real-time and accurate monitoring of blood HVA remains a challenge. Herein, a highly selective implantable electrochemical fiber sensor based on a molecularly imprinted polymer is reported to accurately monitor HVA in vivo. The sensor exhibits high selectivity, with a response intensity to HVA 12.6 times greater than that of catecholamines and their metabolites, achieving 97.8% accuracy in vivo. The sensor injected into the rat caudal vein tracked the real-time changes of blood HVA, which paralleled the brain dopamine fluctuations and indicated the behavioral response to dopamine increase. This study provides a universal design strategy for improving the selectivity of implantable electrochemical sensors.

Effectiveness of a socioecological model-guided, smart device-based, self-management-oriented lifestyle intervention in community residents: protocol for a cluster-randomized controlled trial.

BACKGROUND: Healthy lifestyles are crucial for preventing chronic diseases. Nonetheless, approximately 90% of Chinese community residents regularly engage in at least one unhealthy lifestyle. Mobile smart devices-based health interventions (mHealth) that incorporate theoretical frameworks regarding behavioral change in interaction with the environment may provide an appealing and cost-effective approach for promoting sustainable adaptations of healthier lifestyles. We designed a randomized controlled trial (RCT) to evaluate the effectiveness of a socioecological model-guided, smart device-based, and self-management-oriented lifestyles (3SLIFE) intervention, to promote healthy lifestyles among Chinese community residents. METHODS: This two-arm, parallel, cluster-RCT with a 6-month intervention and 6-month follow-up period foresees to randomize a total of 20 communities/villages from 4 townships in a 1:1 ratio to either intervention or control. Within these communities, a total of at least 256 community residents will be enrolled. The experimental group will receive a multi-level intervention based on the socioecological model supplemented with a multi-dimensional empowerment approach. The control group will receive information only. The primary outcome is the reduction of modifiable unhealthy lifestyles at six months, including smoking, excess alcohol consumption, physical inactivity, unbalanced diet, and overweight/obesity. A reduction by one unhealthy behavior measured with the Healthy Lifestyle Index Score (HLIS) will be considered favorable. Secondary outcomes include reduction of specific unhealthy lifestyles at 3 months, 9 months, and 12 months, and mental health outcomes such as depression measured with PHQ-9, social outcomes such as social support measured with the modified Multidimensional Scale of Perceived Social Support, clinical outcomes such as obesity, and biomedical outcomes such as the development of gut microbiota. Data will be analyzed with mixed effects generalized linear models with family and link function determined by outcome distribution and accounting for clustering of participants in communities. DISCUSSION: This study will provide evidence concerning the effect of a mHealth intervention that incorporates a behavioral change theoretical framework on cultivating and maintaining healthy lifestyles in community residents. The study will provide insights into research on and application of similar mHealth intervention strategies to promote healthy lifestyles in community populations and settings. TRIAL REGISTRATION NUMBER: ChiCTR2300070575. Date of registration: April 17, 2023. https://www.chictr.org.cn/index.aspx .

Dual targeting of Mcl-1 and Bcl-2 to overcome chemoresistance in cervical and colon cancer.

After an initial positive response to chemotherapy, cancer patients often become resistant and experience relapse. Our previous research identified eukaryotic translation initiation factor 4E (eIF4E) as a crucial target to overcome chemoresistance. In this study, we delved further into the role and therapeutic potential of myeloid cell leukemia 1 (Mcl-1), an eIF4E-mediated target, in chemoresistance. We showed that the levels of phosphor and total eIF4E, as well as Mcl-1, were elevated in chemoresistant cervical but not colon cancer cells. Mcl-1 inhibitor S64315 decreased Mcl-1 levels in chemoresistant cancer cells, regardless of Mcl-1 upregulation, decreased viability in chemoresistant cancer cells and acted synergistically with chemotherapy drugs. The combined inhibition of Mcl-1 and B-cell lymphoma 2 (Bcl-2), employing both genetic and pharmacological approaches, led to a markedly more substantial decrease in viability compared with the inhibition of either target individually. The combination of S64315 and Bcl-2 inhibitors reduced tumor growth in chemoresistant cervical and colon cancer models without causing general toxicity in mice. This combination also prolonged overall survival compared with using S64315 or venetoclax alone. Our research highlights the therapeutic potential of inhibiting Mcl-1 and Bcl-2 simultaneously in chemoresistant cancers and provides a rationale for initiating clinical trials to investigate the combination of S64315 and venetoclax for the treatment of advanced colon and cervical cancer.

Efficacy and safety analysis of stereotactic body radiotherapy for brain multi-metastases in non-small cell lung cancer patients.

BACKGROUND: Lung cancer is prone to metastasize to the brain, which is difficult for surgery and leads to poor prognosis due to poor chemotherapy efficacy. OBJECTIVE: Our aim is to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for brain multi-metastases. METHODS: In the retrospective study, a total of 51 non-small cell lung cancer (NSCLC) patients with brain multi-metastases (3-5 metastases) receiving SBRT in the local hospital between 2016 and 2019 were enrolled for analyzing the efficacy and safety of SBRT. The primary endpoints included 1-year local control rate, radiotherapy toxicity, overall survival and progression-free survival. RESULTS: The median follow-up for the enrolled patients was 21 months, and the 1-year and 2-year OS rates were 82.4% and 45.1%, respectively. Demographic analysis showed no significant differences between SBRT alone and combination with whole brain radiotherapy in clinical characteristics including age, gender and Eastern Cooperative Oncology Group performance status. The 1-year local control rate was 77.3% (17/22) for SBRT alone, which was comparable to 79.3% (23/29) of combined radiotherapy. Cox proportional hazard regression demonstrated that the prognostic benefit of combining WBRT was not significantly superior to SBRT alone (HR = 0.851, P= 0.263). Their radiotherapy toxicity rate was lower in SBRT alone group (13.6%, vs. 44.8% for combination; P= 0.017). CONCLUSION: The current research suggested that SBRT alone could effectively relieve tumor burden and improve the prognosis and quality of life for NSCLC patients with brain multi-metastases, which should be validated in further prospective clinical trials.

Interface-Stabilized Fiber Sensor for Real-Time Monitoring of Amniotic Fluid During Pregnancy.

Diseases in pregnancy endanger millions of fetuses worldwide every year. The onset of these diseases can be early warned by the dynamic abnormalities of biochemicals in amniotic fluid, thus requiring real-time monitoring. However, when continuously penetrated by detection devices, the amnion is prone to loss of robustness and rupture, which is difficult to regenerate. Here, an interface-stabilized fiber sensor is presented for real-time monitoring of biochemical dynamics in amniotic fluid during pregnancy. The sensor is seamlessly integrated into the amnion through tissue adhesion, amniotic regeneration, and uniform stress distribution, posing no risk to the amniotic fluid environment. The sensor demonstrates a response performance of less than 0.3% fluctuation under complex dynamic conditions and an accuracy of more than 98% from the second to the third trimester. By applying it to early warning of diseases such as intrauterine hypoxia, intrauterine infection, and fetal growth restriction, fetal survival increases to 95% with timely intervention.

Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity.

Poly(I:C) is a synthetic analogue of dsRNA capable of activating both TLR3 and RLRs, such as MDA-5 and RIG-I, as pathogen recognition receptors. While poly(I:C) is known to provoke a robust type I IFN, type III IFN, and Th1 cytokine response, its therapeutic use as a vaccine adjuvant is limited due to its vulnerability to nucleases and poor uptake by immune cells. is encapsulated poly(I:C) into lipid nanoparticles (LNPs) containing an ionizable cationic lipid that can electrostatically interact with poly(I:C). LNP-formulated poly(I:C) triggered both lysosomal TLR3 and cytoplasmic RLRs, in vitro and in vivo, whereas poly(I:C) in an unformulated soluble form only triggered endosomal-localized TLR3. Administration of LNP-formulated poly(I:C) in mouse models led to efficient translocation to lymphoid tissue and concurrent innate immune activation following intramuscular (IM) administration, resulting in a significant increase in innate immune activation compared to unformulated soluble poly(I:C). When used as an adjuvant for recombinant full-length SARS-CoV-2 spike protein, LNP-formulated poly(I:C) elicited potent anti-spike antibody titers, surpassing those of unformulated soluble poly(I:C) by orders of magnitude and offered complete protection against a SARS-CoV-2 viral challenge in vivo, and serum from these mice are capable of significantly reducing viral infection in vitro.

Long-term effects of PM2.5 constituents on metabolic syndrome and mediation effects of serum uric acid.

Exposure to particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) was associated with the risk for metabolic syndrome (MetS) in the general population, but the contributions of individual PM2.5 constituents to this association and the potential pathway between PM2.5 constituents and MetS risk are not well elaborated. This study aimed to investigate associations between PM2.5 constituents and MetS in general populations, relative importance of PM2.5 constituents to and mediation effects of serum uric acid (SUA) on those associations. The 48,148 participants from a provincially representative cohort established in southwest China were included. The 3-year average concentrations of PM2.5 and its constituents (nitrate [NO3-], sulfate [SO42-], ammonium [NH4+], organic matter [OM], and black carbon [BC]) were estimated using a series of machine-learning models. Multivariate logistic regression and weighted quantile sum regression were used to estimate effects of independent PM2.5 constituents on MetS and their contributions to the joint effect. Mediation analysis examined the potential mediation effects of SUA on the associations between PM2.5 constituents and MetS. Each interquartile range (IQR) increase in the concentration of PM2.5 constituents was all positively associated with the increased MetS odds, including SO42- (OR = 1.15 [1.11, 1.19]]), NO3- (OR = 1.12 [1.08, 1.16]), NH4+ (OR = 1.13 [1.09, 1.17]), OM (OR = 1.09 [1.06, 1.13]), and BC (OR = 1.09 [1.06, 1.13]). Their joint associations on MetS were mainly attributed to SO42- (weight=46.1%) and NH4+ (44.0%). The associations of PM2.5 constituents with abnormal MetS components were mainly attributed to NH4+ for elevated BP (51.6%) and reduced HDL-C (97.0%), SO42- for elevated FG (68.9%), NO3- for elevated TG (51.0%), and OM for elevated WC (63.0%). Percentages mediated by SUA for the associations of PM2.5, SO42-, NO3-, and BC with MetS were 13.6%, 13.1%, 10.6%, and 11.1%, respectively. Long-term exposure to PM2.5 constituents, mainly NH4+ and SO42-, was positively associated with MetS odds, partially mediated by SUA.

Maternal greenness exposure and preterm birth in Brazil: A nationwide birth cohort study.

In the dynamic landscape of maternal and child health, understanding the intricate interplay between environmental factors and pregnancy outcomes is of paramount importance. This study investigates the relationship between maternal greenness exposure and preterm births in Brazil using data spanning from 2010 to 2019. Satellite-derived indices, including the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI), were employed to assess greenness exposure during whole pregnancy in maternal residential area. Employing Cox proportional hazard models, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) for changes in NDVI, while adjusting for individual and area-level covariates. In total, 24,010,250 live births were included. Prevalence of preterm birth was 11.5%, with a modest but statistically significant decreasing trend (p = 0.013) observed across the nation over the study period. The findings reveal a significant association between greenness exposure and a reduced risk of preterm birth. Specifically, for every 0.1 increase in NDVI, there was a 2.0% decrease in the risk of preterm birth (95%CI: 1.9%-2.2%). Stratified analyses based on maternal education and ethnicity indicated potential effect modifications, with stronger protective effects observed among younger mothers and those with less years of education. Sensitivity analyses using EVI yielded consistent results. In conclusion, this study suggests that higher maternal greenness exposure is linked to a decreased risk of preterm birth in Brazil. These findings imply that enhancing residential greenspaces could be a valuable public health strategy to promote maternal and child health in Brazil.