Boosting of Redox-Active Polyimide Porous Organic Polymers with Multi-Walled Carbon Nanotubes towards Pseudocapacitive Energy Storage.

Redox-active porous organic polymers (POPs) demonstrate significant potential in supercapacitors. However, their intrinsic low electrical conductivity and stacking tendencies often lead to low utilization rates of redox-active sites within their structural units. Herein, polyimide POPs (donated as PMTA) are synthesized in situ on multi-walled carbon nanotubes (MWCNTs) from tetramino-benzoquinone (TABQ) and 1,4,5,8-naphthalene tetracarboxylic dianhydride (PMDA) monomers. The strong π-π stacking interactions drive the PMTA POPs and the MWCNTs together to form a PMTA/MWCNT composite. With the assistance of MWCNTs, the stacking issue and low conductivity of PMTA POPs are well addressed, leading to the obvious activation and enhanced utilization of the redox-active groups in the PMTA POPs. PMTA/MWCNT then achieves a high capacitance of 375.2 F g-1 at 1 A g-1 as compared to the pristine PMTA POPs (5.7 F g-1) and excellent cycling stability of 89.7% after 8000 cycles at 5 A g-1. Cyclic voltammetry (CV) and in situ Fourier-Transform Infrared (FT-IR) results reveal that the electrode reactions involve the reversible structural evolution of carbonyl groups, which are activated to provide rich pseudocapacitance. Asymmetric supercapacitors (ASCs) assembled with PMTA/MWCNTs and activated carbon (AC) offer a high energy density of 15.4 Wh kg-1 at 980.4 W kg-1 and maintain a capacitance retention of 125% after 10,000 cycles at 5 A g-1, indicating their good potential for practical applications.

Waterborne polyurethane nanoparticles incorporating linoleic acid as a potential strategy for controlling antibiotic resistance spread in the mammalian intestine.

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

Distinguishing Quantum Phases through Cusps in Full Counting Statistics.

Measuring physical observables requires averaging experimental outcomes over numerous identical measurements. The complete distribution function of possible outcomes or its Fourier transform, known as the full counting statistics, provides a more detailed description. This method captures the fundamental quantum fluctuations in many-body systems and has gained significant attention in quantum transport research. In this Letter, we propose that cusp singularities in the full counting statistics are a novel tool for distinguishing between ordered and disordered phases. As a specific example, we focus on the superfluid-to-Mott transition in the Bose-Hubbard model. Through both analytical analysis and numerical simulations, we demonstrate that the full counting statistics exhibit a cusp singularity as a function of the phase angle in the superfluid phase when the subsystem size is sufficiently large, while it remains smooth in the Mott phase. This discontinuity can be interpreted as a first-order transition between different semiclassical configurations of vortices. We anticipate that our discoveries can be readily tested using state-of-the-art ultracold atom and superconducting qubit platforms.

Arthrocentesis for temporomandibular joint disorders: a network meta-analysis of randomised controlled trials.

OBJECTIVE: Clinical studies have demonstrated the effectiveness of arthrocentesis in managing temporomandibular joint disorders (TMDs). However, there is a lack of consensus among these studies regarding the selection of injectables. Furthermore, an increasing number of drugs have been tested for TMDs in recent years, complicating the decision-making process for clinicians. This study conducted a network meta-analysis of randomized controlled trials (RCTs) to compare the clinical efficacy of different arthrocentesis treatment regimens. METHODS: We conducted a comprehensive search of Embase, PubMed, Cochrane Library, and Web of Science to gather articles on RCTs pertaining to the management of TMDs using arthrocentesis. This search spanned from inception of these databases up to July 29, 2024. We then performed a network meta-analysis using Stata 17.0 software. The outcome indicators used were VAS scores and changes in unassisted maximum opening. To determine the efficacy of each regimen, we employed surface-under the cumulative ranking curve (SUCRA) ranking. RESULT: Forty RCTs were included, encompassing 1904 temporomandibular joints (TMJs) cases. Treatment options encompass platelet-rich plasma (PRP), hyaluronic acid (HA), corticosteroids (CS), bone marrow concentrate (BMAC), injectable platelet-rich fibrin (i-PRF), concentrated growth factor (CGF), Tenoxicam (TX), microfragmented adipose tissue (FAT), and their combination regimens. The SUCRA ranking revealed that the most effective treatment options at 1-, 3-, and 6-months post-arthrocentesis were HA + PRP, i-PRF, and BMAC, respectively. CONCLUSION: HA + PRP, i-PRF and BMAC may represent the optimal arthrocentesis agents for the management of TMDs symptoms and restoration of TMJ function in the short, medium, and long term, respectively. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024563975.

The diagnostic value of a nomogram based on enhanced CT radiomics for differentiating between intrahepatic cholangiocarcinoma and early hepatic abscess.

Objective: This study aimed to investigate the value of a CT-enhanced scanning radiomics nomogram in distinguishing between early hepatic abscess (EHA) and intrahepatic cholangiocarcinoma (ICC) and to validate its diagnostic efficacy. Materials and Methods: Clinical and imaging data on 112 patients diagnosed with EHA and ICC who underwent double-phase CT-enhanced scanning at our hospital were collected. The contours of the lesions were delineated layer by layer across the three phases of CT scanning and enhancement using 3D Slicer software to define the region of interest (ROI). Subsequently, the contours were merged into 3D models, and radiomics features were extracted using the Radiomics plug-in. The data were randomly divided into training (n = 78) and validation (n = 34) cohorts at a 7:3 ratio, using the R programming language. Standardization was performed using the Z-score method, and LASSO regression was used to select the best λ-value for screening variables, which were then used to establish prediction models. The rad-score was calculated using the best radiomics model, and a joint model was constructed based on the rad-score and clinical scores. A nomogram was developed based on the joint model. The diagnostic efficacy of the models for distinguishing ICC and EHA was assessed using receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses. Calibration curves were used to evaluate the reliability and accuracy of the nomograms, while decision curves and clinical impact curves were utilized to assess their clinical value. Results: Compared with the ICC group, significant differences were observed in clinical data and imaging characteristics in the EHA group, including age, centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement (p < 0.05). Logistic regression analysis identified centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement as independent influencing factors. Three, five, and four radiomics features were retained in the scanning, arterial, and venous phases, respectively. Single-phase models were constructed, with the radiomics model from the arterial phase demonstrating the best diagnostic efficacy. The rad-score was calculated using the arterial-phase radiomics model, and nomograms were drawn in conjunction with the clinical model. The nomogram based on the combined model exhibited the highest differential diagnostic efficacy between EHA and ICC (training cohort: AUC of 0.972; validation cohort: AUC of 0.868). The calibration curves indicated good agreement between the predicted and pathological results, while decision curves and clinical impact curves demonstrated higher clinical utility of the nomograms. Conclusion: The CT-enhanced scanning radiomics nomogram demonstrates high clinical value in distinguishing between EHA and ICC, thereby enhancing the accuracy of preoperative diagnosis.

Hfq-binding small RNA PqsS regulates Pseudomonas aeruginosa pqs quorum sensing system and virulence.

Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.

Ultrasound targeted microbubble destruction assisted exosomal delivery of siHmox1 effectively inhibits doxorubicin-induced cardiomyocyte ferroptosis.

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region. UTMD greatly facilitated exosome delivery into heart. Consistently, UTMD assisted exosomal delivery of siHomox1 nearly blocked the ferroptosis and the subsequent cardiotoxicity induced by doxorubicin. In summary, our findings reveal that the upregulation of HMOX1 induces ferroptosis in cardiomyocytes and UTMD-assisted exosomal delivery of siHmox1 can be used as a potential therapeutic strategy for DIC.

Anisotropic SmFe10V2 Bulk Magnets with Enhanced Coercivity via Ball Milling Process.

Anisotropic bulk magnets of ThMn12-type SmFe10V2 with a high coercivity (Hc) were successfully fabricated. Powders with varying particle sizes were prepared using the ball milling process, where the particle size was controlled with milling time. A decrease in Hc occurred in the heat-treated bulk pressed from large-sized powders, while heavy oxidation excessively occurred in small powders, leading to the decomposition of the SmFe10V2 (1-12) phase. The highest Hc of 8.9 kOe was achieved with powders ball-milled for 5 h due to the formation of the grain boundary phase. To improve the maximum energy product ((BH)max), which is only 2.15 MGOe in the isotropic bulk, anisotropic bulks were prepared using the same powders. The easy alignment direction, confirmed by XRD and EBSD measurements, was <002>. Significant enhancements were observed, with saturation magnetization (Ms) increasing from 59 to 79 emu/g and a remanence ratio (Mr/Ms) of 83.7%. (BH)max reaching 7.85 MGOe. For further improvement of magnetic properties, controlling oxidation is essential to form a uniform grain boundary phase and achieve perfect alignment with small grain size.

Gamma-type immunoglobulin enhances phagocytosis of amyloid-beta fibrils by microglia.

The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer's disease. Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system, though the mechanisms are unclear. Here, we found that gamma-type immunoglobulin, a product originating from peripheral blood B cells, localized in the brain parenchyma of multiple mouse models with amyloid pathology, and was enriched on microglia but not on other brain cell types. Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes, including upregulation of pathways related to phagocytosis and immunity. Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc, but not Fab, fragment. Our data indicate that microglia, when exposed to gamma-type immunoglobulin, exhibit an enhanced capacity for clearing amyloid-beta fibrils, potentially via the gamma-type immunoglobulin Fc fragment signaling pathway. This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer's disease by enhancing microglial function.

Compressible Hollow Microlasers in Organoids for High-Throughput and Real-Time Mechanical Screening.

Mechanical stress within organoids is a pivotal indicator in disease modeling and pharmacokinetics, yet current tools lack the ability to rapidly and dynamically screen these mechanics. Here, we introduce biocompatible and compressible hollow microlasers that realize all-optical assessment of cellular stress within organoids. The laser spectroscopy yields identification of cellular deformation at the nanometer scale, corresponding to tens of pascals stress sensitivity. The compressibility enables the investigation of the isotropic component, which is the fundamental mechanics of multicellular models. By integrating with a microwell array, we demonstrate the high-throughput screening of mechanical cues in tumoroids, establishing a platform for mechano-responsive drug screening. Furthermore, we showcase the monitoring and mapping of dynamic contractile stress within human embryonic stem cell-derived cardiac organoids, revealing the internal mechanical inhomogeneity within a single organoid. This method eliminates time-consuming scanning and sample damage, providing insights into organoid mechanobiology.

Physician Associate/Assistant Program Medical Directors Are Important Advocates for the Physician Associate/Assistant Profession: Results From a National Pilot Study.

INTRODUCTION: This pilot study aimed to evaluate whether and how physician associate/assistant (PA) program medical directors play a role in advocating on behalf of PAs and what factors correlate with this. METHODS: The study used a mixed-methods grounded theory approach and was deemed institutional review board exempt. After literature review, a survey was developed and piloted by study personnel and faculty to affirm validity. Recruits with known email addresses were sent a link to a survey that included demographic information and 10 Likert scale questions. There were 69 respondents, and the response rate was 26%. Fisher's exact test and analysis of variance were performed using the R program. A P-value <.05 indicated significance. Thematic analysis of qualitative data was performed using ChatGPT, followed by iterative analysis by the research team. Consensus was achieved for each response. RESULTS: Most of the respondents had the following characteristics: MD degree, male, White, practicing clinically, and worked as PA medical directors 8 to 12 hours per week. Participants did not support PA title change, nor had they engaged in legislative efforts to support optimal team practice. Participants were strong PA advocates by promoting PA leadership positions, PA employment, improved attitudes in health care organizations toward PAs, and securing clinical rotations. Many respondents (41%) felt that none of their professional organizations supported them in their role as PA program medical director. DISCUSSION: Exploring ways to support continued advocacy by our valued PA program medical directors within PA professional organizations could be advantageous to PA program medical directors' professional growth and the PA profession.

PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson's disease.

TFE3 and TFEB, as the master regulators of lysosome biogenesis and autophagy, are well characterized to enhance the synaptic protein α-synuclein degradation in protecting against Parkinson's disease (PD) and their levels are significantly decreased in the brain of PD patients. However, how TFE3 and TFEB are regulated during PD pathogenesis remains largely vague. Herein, we identified that programmed cell death 4 (PDCD4) promoted pathologic α-synuclein accumulation to facilitate PD development via suppressing both TFE3 and TFEB translation. Conversely, PDCD4 deficiency significantly augmented global and nuclear TFE3 and TFEB distributions to alleviate neurodegeneration in a mouse model of PD with overexpressing α-synuclein in the striatum. Mechanistically, like TFEB as we reported before, PDCD4 also suppressed TFE3 translation, rather than influencing its transcription and protein stability, to restrain its nuclear translocation and lysosomal functions, eventually leading to α-synuclein aggregation. We proved that the two MA3 domains of PDCD4 mediated the translational suppression of TFE3 through binding to its 5'-UTR of mRNA in an eIF-4A dependent manner. Based on this, we developed a blood-brain barrier penetrating RVG polypeptide modified small RNA drug against pdcd4 to efficiently prevent α-synuclein neurodegeneration in improving PD symptoms by intraperitoneal injections. Together, we suggest PDCD4 as a PD-risk protein to facilitate α-synuclein neurodegeneration via suppressing TFE3 and TFEB translation and further provide a potential small RNA drug against pdcd4 to treat PD by intraperitoneal injections.

IL-23 Priming Enhances the Neuroprotective Effects of MSC-Derived Exosomes in Treating Retinal Degeneration.

Purpose: Neuroinflammation is a characteristic feature of neurodegenerative diseases. Mesenchymal stem cell-derived exosomes (MSC-exo) have shown neuroprotective effects through immunoregulation, but the therapeutic efficacy remains unsatisfactory. This study aims to enhance the neuroprotective capacity of MSC-exo through IL-23 priming for treating retinal degeneration in mice. Methods: MSC were primed with IL-23 stimulation in vitro, and subsequently, exosomes (MSC-exo and IL-23-MSC-exo) were isolated and characterized. Two retinal degenerative disease models (NaIO3-induced mice and rd10 mice) received intravitreal injections of these exosomes. The efficacy of exosomes was assessed by examining retinal structural and functional recovery. Furthermore, exosomal microRNA (miRNA) sequencing was conducted, and the effects of exosomes on the M1 and M2 microglial phenotype shift were evaluated. Results: IL-23-primed MSC-derived exosomes (IL-23-MSC-exo) exhibited enhanced capability in protecting photoreceptor cells and retinal pigment epithelium (RPE) cells against degenerative damage and fostering the restoration of retinal neural function in both NaIO3-induced retinal degeneration mice and rd10 mice when compared with MSC-exo. The exosomal miRNA suppression via Drosha knockdown in IL-23-primed MSC would abolish the neuroprotective role of IL-23-MSC-exo, highlighting the miRNA-dependent mechanism. Bioinformatic analysis, along with further in vivo biological studies, revealed that IL-23 priming induced a set of anti-inflammatory miRNAs in MSC-exo, prompting the transition of M1 to M2 microglial polarization. Conclusions: IL-23 priming presents as a potential avenue for amplifying the immunomodulatory and neuroprotective effects of MSC-exo in treating retinal degeneration.

Single-cell laser emitting cytometry for label-free nucleolus fingerprinting.

The nucleolus, a recognized biomolecular condensate, serves as the hub for ribosome biogenesis within the cell nucleus. Its quantity and morphology are discernible indicators of cellular functional states. However, precise identification and quantification of nucleoli remain challenging without specific labeling, particularly for suspended cells, tissue-level analysis and high-throughput applications. Here we introduce a single-cell laser emitting cytometry (SLEC) for label-free nucleolus differentiation through light-matter interactions within a Fabry-Perot resonator. The separated gain medium enhances the threshold difference by 36-fold between nucleolus and its surroundings, enabling selective laser emissions at nucleolar area while maintaining lower-order mode. The laser emission image provides insights into structural inhomogeneity, temporal fluid-like dynamics, and pathological application. Lasing spectral fingerprint depicts the quantity and size of nucleoli within a single cell, showcasing the label-free flow cytometry for nucleolus. This approach holds promise for nucleolus-guided cell screening and drug evaluation, advancing the study of diseases such as cancer and neurodegenerative disorders.

Multiparametric simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) incorporating intratumoral and peritumoral regions for grading of glioma.

Background: Preoperative grading gliomas is essential for therapeutic clinical decision-making. Current non-invasive imaging modality for glioma grading were primarily focused on magnetic resonance imaging (MRI) or positron emission tomography (PET) of the tumor region. However, these methods overlook the peritumoral region (PTR) of tumor and cannot take full advantage of the biological information derived from hybrid-imaging. Therefore, we aimed to combine multiparameter from hybrid 18F-fluorodeoxyglucose (18F-FDG) PET/MRI of the solid component and PTR were combined for differentiating high-grade glioma (HGG) from low-grade glioma (LGG). Methods: A total of 76 patients with pathologically confirmed glioma (41 HGG and 35 LGG) who underwent simultaneous 18F-FDG PET, arterial spin labelling (ASL), and diffusion-weighted imaging (DWI) with hybrid PET/MRI were retrospectively enrolled. The relative maximum standardized uptake value (rSUVmax), relative cerebral blood flow (rCBF), and relative minimum apparent diffusion coefficient (rADCmin) for the solid component and PTR at different distances outside tumoral border were compared. Receiver operating characteristic (ROC) curves were applied to assess the grading performance. A nomogram for HGG prediction was constructed. Results: HGGs displayed higher rSUVmax and rCBF but lower rADCmin in the solid component and 5 mm-adjacent PTR, lower rADCmin in 10 mm-adjacent PTR, and higher rCBF in 15- and 20-mm-adjacent PTR. rSUVmax in solid component performed best [area under the curve (AUC) =0.865] as a single parameter for grading. Combination of rSUVmax in the solid component and adjacent 20 mm performed better (AUC =0.881). Integration of all 3 indicators in the solid component and adjacent 20 mm performed the best (AUC =0.928). The nomogram including rSUVmax, rCBF, and rADCmin in the solid component and 5-mm-adjacent PTR predicted HGG with a concordance index (C-index) of 0.906. Conclusions: Multiparametric 18F-FDG PET/MRI from the solid component and PTR performed excellently in differentiating HGGs from LGGs. It can be used as a non-invasive and effective tool for preoperative grade stratification of patients with glioma, and can be considered in clinical practice.

High-purity La3-xTe4 Material with Superior Thermoelectric Performance Synthesized via Te-vapor Transport and Solid-State Diffusion.

La3-xTe4 is a very promising high-temperature candidate applied in next-generation Radioisotope Thermoelectric Generators (RTGs). Conventional synthesis of such materials is based on the mechanochemical method, which makes the sample difficult to purify due to the high-energy ball milling. In this report, a novel synthetic method is developed, which utilizes Te-vapor transport and solid-phase diffusion to efficiently produce the RE3-xTe4 phases (RE = La, Ce, Pr, Nd). Notably, this method obviates the requirement for high-energy ball-milling instruments, conventionally indispensable in the mechanochemical syntheses. For as-synthesized La2.74Te4 material, a high figure of merit of 1.5 is achieved at 1073 K, owning to the reduced electronic thermal conductivity with metal impurities well eliminated.

Brain Short-Chain Fatty Acids Induce ACSS2 to Ameliorate Depressive-Like Behavior via PPARγ-TPH2 Axis.

Short-chain fatty acids (SCFAs) have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiota-gut-brain axis. However, the precise mechanism by which brain SCFAs extert multiple beneficial effects is not completely understood. Our previous research has demonstrated that the acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is a novel target of the rapid and long-lasting antidepressant responses. Here, we show that micromolar SCFAs significantly augment both total cellular and nuclear ACSS2 to trigger tryptophan hydroxylase 2 (TPH2) promoter histone acetylation and its transcription in SH-SY5Y cells. In chronic-restraint-stress-induced depression mice, neuronal ACSS2 knockdown by stereotaxic injection of adeno-associated virus in the hippocampus abolished SCFA-mediated improvements in depressive-like behaviors of mice, supporting that ACSS2 is required for SCFA-mediated antidepressant responses. Mechanistically, the peroxisome-proliferator-activated receptor gamma (PPARγ) is identified as a novel partner of ACSS2 to activate TPH2 transcription. Importantly, PPARγ is also responsible for SCFA-mediated antidepressant-like effects via ACSS2-TPH2 axis. To further support brain SCFAs as a therapeutic target for antidepressant effects, d-mannose, which is a naturally present hexose, can significantly reverse the dysbiosis of gut microbiota in the chronic-restraint-stress-exposure mice and augment brain SCFAs to protect against the depressive-like behaviors via ACSS2-PPARγ-TPH2 axis. In summary, brain SCFAs can activate ACSS2-PPARγ-TPH2 axis to play the antidepressive-like effects, and d-mannose is suggested to be an inducer of brain SCFAs in resisting depression.

Therapeutic intervention in neuroinflammation for neovascular ocular diseases through targeting the cGAS-STING-necroptosis pathway.

The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.

Self-assembled Au-CQDs nanofluids with excellent solar absorption and medium-high temperature stability for solar energy harvesting.

Nanofluids-based direct absorption solar collectors are promising candidates for medium-high-temperature solar energy harvesting. However, nanofluids' complicated preparation process and undesirable high-temperature stability have hindered their practical applications. Herein, we propose a facile method for synthesizing gold/carbon quantum dots (Au-CQDs) nanofluids by directly carbonizing the base fluid and spontaneously assembling with Au nanoparticles (AuNPs) triggered by high temperatures. The results indicate that the self-assembled Au-CQDs nanofluids can maintain high stability at 110 °C for 100 h without precipitation and keep excellent photothermal conversion performance under 10 sun irradiation. The concentration and particle size of AuNPs are crucial factors affecting the self-assembly process. By modulating the microscopic morphologies of the self-assembled nanoparticles, the extinction coefficient of the prepared nanofluids is up to 88.7 % at a low loading of 30 ppm. The nanofluids can reach an equilibrium temperature of 50 °C under 1 sun irradiation, 10.4 °C higher than the base fluid due to the enhanced plasmonic effects and stability resulting from the CQDs dotted AuNPs. This work offers a new strategy to fabricate highly stable nanofluids with excellent light absorption properties for efficient solar thermal applications.

The Relationship Between Alcohol Consumption and Frailty Among Older Adults in China: Results From the Chinese Longitudinal Healthy Longevity Survey.

INTRODUCTION: Alcohol consumption has an impact on the frailty, but current research in China lacks a detailed classification of alcohol use. This study aimed to explore the relationship between different drinking patterns and frailty in older adults. METHODOLOGY: The data came from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) study, which included older adults (aged ≧ 60). Their demographic data, drinking status, and frailty index were collected in CLHLS. Through logistic regression models to analyze the correlation between alcohol consumption and frailty. RESULTS: A total of 14,931 participants were included in the analysis. The prevalence of frailty was 29.1%, 35.2%, and 14.9% among risk-free, past risky, and now risky drinkers, respectively. After adjusting for covariates, past risky drinking was a risk factor for frailty (p = .003). DISCUSSION: High-risk alcohol consumption is positively correlated with frailty. Prevention and reduction of risky drinking in older adults may help protect them from developing frailty.