Adipose Tissue Targeting Ultra-Small Hybrid Nanoparticles for Synergistic Photodynamic Therapy and Browning Induction in Obesity Treatment.

Photodynamic therapy (PDT), as a means of locally and rapidly inducing adipocyte death via light illumination, in combination with adipose browning induction, a more gradual and widespread effect that could transform white adipose tissue into thermogenic adipose tissue, manifests a promising approach to combat obesity. Herein, adipose-targeting ultra-small hybrid nanoparticles (Pep-PPIX-Baic NPs) composed of an adipose-targeting peptide, Fe3+, a photosensitizer (protoporphyrin IX), and a browning agent (baicalin) are introduced. Pep-PPIX-Baic NPs have been designed to simultaneously enhance the photodynamic effect and induce browning. After intravenous injection in obese mice, the hybrid nanoparticles can specifically accumulate in white adipose tissues, especially those rich in blood supply, and drive adipose reduction owing to the synergy of the PDT effect and baicalin browning induction. Overall, Pep-PPIX-Baic NPs exhibited superior anti-obesity potential through PDT synergistic with adipose browning induction. The designed multifunctional adipose-targeting hybrid nanoparticles present a prospective nanoplatform for obesity treatment.

Global, regional, and national burden of ischemic heart disease attributable to ambient PM2.5 from 1990 to 2019: An analysis for the global burden of disease study 2019.

Information on the spatio-temporal patterns of the burden of ischemic heart disease (IHD) caused by ambient ambient fine particulate matter (PM2.5) in the global level is needed to prioritize the control of ambient air pollution and prevent the burden of IHD. The Global Burden of Disease Study (GBD) 2019 provides data on IHD attributable to ambient PM2.5. The IHD burden and mortality attributable to ambient PM2.5 were analyzed by year, age, gender, socio-demographic index (SDI) level, geographical region and country. Estimated annual percentage change (EAPC) was calculated to estimate the temporal trends of age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) from 1990 to 2019. Globally, the ASMR and ASDR for ambient PM2.5-related IHD tended to level off generally, with EAPC of -0.03 (95% CI: -0.06, 0.12) and 0.3 (95% CI: 0.22, 0.37), respectively. In the past 30 years, there were obvious differences in the trend of burden change among different regions. A highest increased burden was estimated in low-middle SDI region (EAPC of ASMR: 3.73 [95% CI: 3.56, 3.9], EAPC of ASDR: 3.83 [95% CI: 3.64, 4.02]). In contrast, the burden in high SDI region (EAPC of ASMR: -4.48 [95% CI: -4.6, -4.35], EAPC of ASDR: -3.98 [95% CI: -4.12, -3.85]) has declined most significantly. Moreover, this burden was higher among men and older populations. EAPCs of the ASMR (R = -0.776, p < 0.001) and ASDR (R = -0.781, p < 0.001) of this burden had significant negative correlations with the countries' SDI level. In summary, although trends in the global burden of IHD attributable to ambient PM2.5 are stabilizing, but this burden has shifted from high SDI countries to middle and low SDI countries, especially among men and elderly populations. To reduce this burden, the air pollution management prevention need to be further strengthened, especially among males, older populations, and middle and low SDI countries.

Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Quantitative determination of flow rate variations in reservoir Eco-scheduling: A case study of Yangqu dam in the upper yellow river.

Accurate quantification of flow dynamics during reservoir ecological scheduling hinders the maintenance of normal reproductive activities in downstream riverine fish. This study proposed a quantitative method for determining the flow rate changes in reservoir ecological scheduling. The approach utilized the daily flow rate and daily flow-rate increment to characterize the flow process. Adopting the perspective of shifting spawning grounds of adhesive egg-laying fish species in response to flow rate variations, we introduced the Spawning Ground Overlap Rate as an indicator and utilized it to determine flow rate changes. Focusing on the downstream area of the Yangqu Hydropower Station in the upper reaches of the Yellow River, we calculated the distribution of spawning grounds and the Spawning Ground Overlap Rate in the region. We set a threshold for the Spawning Ground Overlap Rate to restrict the flow rate changes. The results indicated that during the fish spawning period, the ecological flow range in the downstream area of the Yangqu Dam was 480-1200 m3/s. It was required to maintain a daily flow rate change of less than 49.45 m3/(s·d) and a maximum seven-day flow difference of less than 227.76 m3/s to maintain the optimal level of spawning ground overlap rate. Additionally, it was necessary to keep the daily flow rate change below 123.83 m3/(s·d) and the maximum seven-day flow difference below 368.84 m3/s to maintain the minimum spawning ground overlap rate. The findings provide foundational data for determining flow dynamics during the ecological scheduling of the spawning period for viscous-spawning fish.

Discovery of dolutegravir-1,2,3-triazole derivatives against prostate cancer via inducing DNA damage.

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men, causing a huge number of deaths each year. Traditional chemotherapy for PCa mostly focused on targeting androgen receptors. However, some of the patients would develop resistance to hormonal therapy. In these cases, it is suggested for these patients to administer treatments in combination with other chemotherapeutics. Current chemotherapeutics for metastatic castration-resistant PCa could hardly reach satisfying effects, therefore it is crucial to explore novel agents with low cytotoxicity. Herein, a common drug against the human immunodeficiency virus (HIV), the dolutegravir (DTG) was modified to become a series of dolutegravir-1,2,3-triazole derivatives. Among these compounds, the 4d and 4q derivatives were verified with high anti-tumor efficiency, suppressing the proliferation of the prostate cancer cells PC3 and DU145. These compounds function by binding to the poly (adenosine diphosphate-ribose) polymerase (PARP), inactivating the PARP and inducing DNA damage in cancer cells. It is noteworthy that the 4d and 4q derivatives showed almost no impact on normal cells and mice. Thereby, the results reveal that these dolutegravir-1,2,3-triazole compounds are potential chemotherapeutics for PCa treatment.

A carrier-free supramolecular nano-twin-drug for overcoming irinotecan-resistance and enhancing efficacy against colorectal cancer.

Irinotecan (Ir) is commonly employed as a first-line chemotherapeutic treatment for colorectal cancer (CRC). However, tremendous impediments remain to be addressed to surmount drug resistance and ameliorate adverse events. Poly-ADP-Ribose Polymerase (PARP) participates in the maintenance of genome stability and the repair of DNA damage, thus playing a critical role in chemotherapy resistance. In this work, we introduce a novel curative strategy that utilizes nanoparticles (NPs) prepared by dynamic supramolecular co-assembly of Ir and a PARP inhibitor (PARPi) niraparib (Nir) through π-π stacking and hydrogen bond interactions. The Ir and Nir self-assembled Nano-Twin-Drug of (Nir-Ir NPs) could enhance the therapeutic effect on CRC by synergistically inhibiting the DNA damage repair pathway and activating the tumor cell apoptosis process without obvious toxicity. In addition, the Nir-Ir NPs could effectively reverse irinotecan-resistance by inhibiting the expression of multiple resistance protein-1 (MRP-1). Overall, our study underscores the distinctive advantages and potential of Nir-Ir NPs as a complementary strategy to chemotherapy by simultaneously overcoming the Ir resistance and improving the anti-tumor efficacy against CRC.

Smart Wearable Systems for Health Monitoring.

Smart wearable systems for health monitoring are highly desired in personal wisdom medicine and telemedicine. These systems make the detecting, monitoring, and recording of biosignals portable, long-term, and comfortable. The development and optimization of wearable health-monitoring systems have focused on advanced materials and system integration, and the number of high-performance wearable systems has been gradually increasing in recent years. However, there are still many challenges in these fields, such as balancing the trade-off between flexibility/stretchability, sensing performance, and the robustness of systems. For this reason, more evolution is required to promote the development of wearable health-monitoring systems. In this regard, this review summarizes some representative achievements and recent progress of wearable systems for health monitoring. Meanwhile, a strategy overview is presented about selecting materials, integrating systems, and monitoring biosignals. The next generation of wearable systems for accurate, portable, continuous, and long-term health monitoring will offer more opportunities for disease diagnosis and treatment.

Remote Effect from Boron Cluster: Tunable Photophysical Properties of o-Carborane-Based Luminogens.

We proposed a new molecular design strategy that the o-carboranyl group is attached as "an innocent unit" to the remote side of luminogens to tune photophysical properties. To verify this strategy, two o-carborane-based compounds with asymmetric molecular geometry were designed and synthesized. Photophysical properties of o-carborane-based luminogens were investigated on the basis of UV-Vis spectra, photoluminescence spectra, crystal structure analysis and theoretical calculations. The results indicate that the o-carboranyl group has a slight effect on the energy gap between the ground state (S0 ) and the first excited state (S1 ) in the solution state but a significant effect on the energy gap between S0 and S1 in the solid state. Besides, the radiative and non-radiative transition processes are modulated by the o-carboranyl unit. This leads to emission quenching in the solution state but an enhanced luminous efficiency in the aggregate state with a typical aggregation-induced emission (AIE) property.

MoS2/MXene pillared nanocomposite for ultrafast photonics applications.

In this work, we used nanocomposite saturable absorbers (SAs) in order to precisely design and modulate the process of compositing the light absorption by band gap engineering. Due to the higher absorption intensity of our MoS2/MXene nanocomposite, we have successfully shortened the pulse duration (1.2µs) of SA with enhancing saturable absorption intensity (7.22 MW cm-2), and the ultra-fast fiber laser based on this nanocomposite SA has shown wider Q-switching stable range in the case of high pump power. This strategy can efficiently improve the performance of SA and shows the potential application prospect of nanocomposites in nonlinear optics.

Removal efficiencies and risk assessment of endocrine-disrupting chemicals at two wastewater treatment plants in South China.

Endocrine-disrupting chemicals (EDCs) in the effluent from wastewater treatment plants (WWTPs) are an important pollutant sources of the aquatic system. In this study, the removal efficiencies of eight typical EDCs at two domestic WWTPs in Dongguan City, China, are reported based on instrumental analysis and bioassay results. Bioactivities, including steroidogenesis-disrupting effects, estrogen receptor (ER)-binding activity, and aryl hydrocarbon receptor (AhR)-binding activity were evaluated using the H295R, MVLN, and H4IIE cell bioassays, respectively. The potential environmental risks of these residual EDCs were also evaluated. The results of instrumental analysis showed that nonylphenol was the major chemical type present among the eight tested EDCs. Meanwhile, concentrations of estrogen compounds including estrone, 17ß-estradiol (E2), estriol, 17α-ethinyl estradiol, and diethylstilbestrol were relatively low. The removal rates of all eight EDCs were relatively high. Although the chemical analysis indicated high removal efficiency, the bioassay results showed that steroidogenesis-disrupting effects as well as ER-binding and AhR-binding activities remained, with E2-equivalent values of effluent samples ranging from 0.16 to 0.9 ng·L-1, and 2,3,7,8-tetrachlorodibenzo-p-dioxin-equivalent values ranging from 0.61 to 4.09 ng L-1. Principal component analysis combined with regression analysis suggests that the chemicals analyzed in this study were partly responsible for these ER and AhR activities. Ecological risk assessment of the residual EDCs showed that estrone was the most hazardous chemical among the eight EDCs tested, with a risk quotient of 1.44-5.50. Overall, this study suggests that, despite high apparent removal efficiencies of typical EDCs, their bioactivities and potential ecological risks cannot be ignored.

Live-Cell Sensing of Telomerase Activity by Using Hybridization-Sensitive Fluorescent Oligonucleotide Probes.

Live-cell sensing of telomerase activity with simple and efficient strategies remains a challenging target. In this work, a strategy for telomerase sensing by using hybridization-sensitive fluorescent oligonucleotide probes is reported. In the presence of telomerase and dNTPs, the designed supporting strand was extended and generated the hairpin structure that catalyzed the next telomerase extending reaction. The special extension mechanism increased the local concentration of another supporting strand and telomerase, which resulted in enhanced telomerase activity. The hybridization-sensitive oligonucleotide probes bound to the hairpin catalyst and generated turn-on fluorescence. This method realized the sensing of telomerase activity in HeLa cell extract with a detection limit below 1.6×10-6  IU µL-1 . The real-time in situ observation of telomerase extension was achieved in living HeLa cells. This strategy has been applied to monitor the efficiency of telomerase-targeting anticancer drugs in situ.

Protocol for induction of human kidney cell fibrosis.

Here, we present a protocol for inducing fibrosis in human kidney-2 (HK2) cells followed by quantitative real-time PCR analysis of fibrosis-related genes. We describe steps for growing and expanding cells, inducing HK2 fibrosis, and collecting cells for downstream applications. Given the limited cell quantity in culture flasks and the challenges of cell collection, we utilized 10-cm Petri dishes for cell harvesting, with each experimental group comprising five replicate samples. For complete details on the use and execution of this protocol, please refer to Zhang et al.1.

Exposure to Neighborhood Greenness and Hypertension Incidence in Adults: A Longitudinal Cohort Study in Taiwan.

BACKGROUND: There are few studies on the health effects of long-term exposure to neighborhood greenness in a longitudinal setting, especially in Asian countries with high population densities. OBJECTIVES: This study investigates the association between long-term exposure to neighborhood greenness and hypertension among adults in Taiwan. METHODS: We selected 125,537 participants (≥18 years of age) without hypertension from Taiwan who had joined the standard medical examination program between 2001 and 2016. Neighborhood greenness was estimated using the normalized difference vegetation index (NDVI), derived from satellite images at a resolution of 250 m2. The 2-y average NDVI value within a 500-m circular buffer around participants' residences was calculated. A time-varying Cox regression model was used to investigate the association between neighborhood greenness and incident hypertension. Mediation analyses were performed to examine whether the association was explained by air pollution, leisure-time physical exercise, or body mass index (BMI). RESULTS: Compared with living in areas within the first quartile of neighborhood greenness, living in areas within the second, third, and fourth quartiles of neighborhood greenness was found to be associated with a lower risk of hypertension, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.95 (95% CI: 0.91, 1.00), 0.95 (95% CI: 0.90, 0.99), and 0.93 (95% CI: 0.88, 0.97), respectively. Each 0.1-unit increase in the NDVI was associated with a 24% lower risk of developing hypertension (HR=0.76; 95% CI: 0.66, 0.87), with this associations being stronger among males and those with higher education levels. This association was slightly mediated by BMI but not by air pollution or leisure-time physical exercise. DISCUSSION: Our findings suggest the protective effects of neighborhood greenness on hypertension development, especially in males and well-educated individuals. Our results reinforced the importance of neighborhood greenness for supporting health. https://doi.org/10.1289/EHP13071.

Novel Carrier-Free Nanodrug Enhances Photodynamic Effects by Blocking the Autophagy Pathway and Synergistically Triggers Immunogenic Cell Death for the Efficient Treatment of Breast Cancer.

Photosensitizers have been widely used to cause intratumoral generation of reactive oxygen species (ROS) for cancer therapy, but they are easily disturbed by the autophagy pathway, a self-protective mechanism by mitigating oxidative damage. Hereby, we reported a simple and effective strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided the unexpected toxicity caused by the regular nanocarrier and also ameliorated its stability in different conditions. Light-activated Ce6 generated cytotoxic ROS and elicited part of the immunogenic cell death (ICD). Moreover, CQ induced autophagy dysfunction, which hindered self-healing in tumor cells and enhanced photodynamic therapy (PDT) to exert a more potent killing effect and more efficient ICD. Also, Ce6@CQ could effectively accumulate in the xenograft breast tumor site in a mouse model through the enhanced permeability and retention (EPR) effect, and the growth of breast tumors was effectively inhibited by Ce6@CQ with light. Such a carrier-free nanodrug provided a new strategy to improve the efficacy of PDT via the suppression of autophagy to digest ROS-induced toxic substances.

Consolidated bioprocessing of highly concentrated Jerusalem artichoke tubers for simultaneous saccharification and ethanol fermentation.

Consolidated bioprocessing (CBP) of Jerusalem artichoke tuber (Jat) for ethanol production is one of the most promising options for an alternate biofuel technology development. The technical barriers include the weak saccharolytic enzyme (inulinase) activity of the fermentation strain, and the well mixing of the high viscous fermentation slurry at the highly concentrated Jat loading. In this study, Saccharomyces cerevisiae DQ1 was found to produce relatively large amount of inulinase for hydrolysis of inulin in Jat, and the helical ribbon stirring bioreactor used provided well mixing performance under the high Jat loading. Even a highly concentrated Jat loading up to 35% (w/w) in the helical ribbon bioreactor for CBP was allowed. The results obtained from this study have demonstrated a feasibility of developing a CBP process technology in the helical ribbon bioreactor for ethanol production at a high yield 128.7 g/L and the theoretical yield 73.5%, respectively. This level of ethanol yield from Jat is relatively higher than others reported so far. The results of this study could provide a practical CBP process technology in the helical ribbon bioreactor for economically sustainable alternate biofuel production using highly concentrated inulin containing biomass feedstock such as Jat, at least 35%.

Cortical Pyramidal and Parvalbumin Cells Exhibit Distinct Spatiotemporal Extracellular Electric Potentials.

Highlighted Research Paper: L. J. Sukman and E. Stark, "Cortical pyramidal and parvalbumin cells exhibit distinct spatiotemporal extracellular electric potentials." eNeuro (2022).

Role of interneuron subtypes in controlling trial-by-trial output variability in the neocortex.

Trial-by-trial variability is a ubiquitous property of neuronal activity in vivo which shapes the stimulus response. Computational models have revealed how local network structure and feedforward inputs shape the trial-by-trial variability. However, the role of input statistics and different interneuron subtypes in this process is less understood. To address this, we investigate the dynamics of stimulus response in a cortical microcircuit model with one excitatory and three inhibitory interneuron populations (PV, SST, VIP). Our findings demonstrate that the balance of inputs to different neuron populations and input covariances are the primary determinants of output trial-by-trial variability. The effect of input covariances is contingent on the input balances. In general, the network exhibits smaller output trial-by-trial variability in a PV-dominated regime than in an SST-dominated regime. Importantly, our work reveals mechanisms by which output trial-by-trial variability can be controlled in a context, state, and task-dependent manner.

An ultrasmall PVP-Fe-Cu-Ni-S nano-agent for synergistic cancer therapy through triggering ferroptosis and autophagy.

Photothermal therapy (PTT) is an emerging field where photothermal agents could convert visible or near-infrared (NIR) radiation into heat to kill tumor cells. However, the low photothermal conversion efficiency of photothermal agents and their limited antitumor activities hinder the development of these agents into monotherapies for cancer. Herein, we have fabricated an ultrasmall polyvinylpyrrolidone (PVP)-Fe-Cu-Ni-S (PVP-NP) nano-agent via a simple hot injection method with excellent photothermal conversion efficiency (∼96%). Photothermal therapy with this nano-agent effectively inhibits tumor growth without apparent toxic side-effects. Mechanistically, our results demonstrated that, after NIR irradiation, PVP-NPs can induce ROS/singlet oxygen generation, decrease the mitochondrial membrane potential, release extracellular Fe2+, and consume glutathione, triggering autophagy and ferroptosis of cancer cells. Moreover, PVP-NPs exhibit excellent contrast enhancement according to magnetic resonance imaging (MRI) analysis. In summary, PVP-NPs have a high photothermal conversion efficiency and can be applied for MRI-guided synergistic photothermal/photodynamic/chemodynamic cancer therapy, resolving the bottleneck of existing phototherapeutic agents.

Comprehensive analysis of the relationship between xanthine oxidoreductase activity and chronic kidney disease.

Chronic kidney disease (CKD) is a common disease that seriously endangers human health. However, the potential relationship between xanthine oxidoreductase (XOR) activity and CKD remains unclear. In this study, we used clinical data, CKD datasets from the Gene Expression Omnibus database, and untargeted metabolomics to explain the relationship between XOR activity and CKD. First, XOR activity showed high correlation with the biomarkers of CKD, such as serum creatinine, blood urea nitrogen, uric acid, and estimated glomerular filtration rate. Then, we used least absolute shrinkage and selection operator logical regression algorithm and random forest algorithm to screen CKD molecular markers from differentially expressed genes, and the results of qRT-PCR of XDH, KOX-1, and ROMO1 were in accordance with the results of bioinformatics analyses. In addition, untargeted metabolomics analysis revealed that the purine metabolism pathway was significantly enriched in CKD patients in the simulated models of kidney fibrosis.

Nanodrugs systems for therapy and diagnosis of esophageal cancer.

With the increasing incidence of esophageal cancer, its diagnosis and treatment have become one of the key issues in medical research today. However, the current diagnostic and treatment methods face many unresolved issues, such as low accuracy of early diagnosis, painful treatment process for patients, and high recurrence rate after recovery. Therefore, new methods for the diagnosis and treatment of esophageal cancer need to be further explored, and the rapid development of nanomaterials has brought new ideas for solving this problem. Nanomaterials used as drugs or drug delivery systems possess several advantages, such as high drug capacity, adjustably specific targeting capability, and stable structure, which endow nanomaterials great application potential in cancer therapy. However, even though the nanomaterials have been widely used in cancer therapy, there are still few reviews on their application in esophageal cancer, and systematical overview and analysis are deficient. Herein, we overviewed the application of nanodrug systems in therapy and diagnosis of esophageal cancer and summarized some representative case of their application in diagnosis, chemotherapy, targeted drug, radiotherapy, immunity, surgery and new therapeutic method of esophageal cancer. In addition, the nanomaterials used for therapy of esophageal cancer complications, esophageal stenosis or obstruction and oesophagitis, are also listed here. Finally, the challenge and the future of nanomaterials used in cancer therapy were discussed.