Association of TNFRSF19 with a TNF family-based prognostic model and subtypes in gliomas using machine learning.

Purpose: TNF family members (TFMs) play a crucial role in different types of cancers, with TNF Receptor Superfamily Member 19 (TNFRSF19) standing out as a particularly important member in this category. Further research is necessary to investigate the potential impact of TFMs on prognosis prediction and to elucidate the function and potential therapeutic targets linked to TNFRSF19 expression in gliomas. Methods: Three databases provided the data on gene expression and clinical information. Fourteen prognostic members were found through univariate Cox analysis and subsequently utilized to construct TFMs-based model in LASSO and multivariate Cox analyses. TFMs-based subtypes based on the expression profile were identified using an unsupervised clustering method. Machine learning algorithm identified key genes linked to prognostic model and subtype. A sequence of immune infiltrations was evaluated using the ssGSEA and ESTIMATE algorithms. Immunohistochemistry was used to examine the patterns of expression and the clinical significance of TNFRSF19. Results: Our development of a prognostic model and subtypes based on the TNF family was successful, resulting in accurate predictions of prognosis. The findings indicate that TNFRSF19 exhibited strong performance. Upregulation of TNFRSF19 was correlated with malignant phenotypes and poor prognosis, which was confirmed through immunohistochemistry. TNFRSF19 played a role in reshaping the immunosuppressive microenvironment in gliomas, and multiple drug-targeted TNFRSF19 molecules were identified. Conclusions: The TMF-based prognostic model and subtype can facilitate treatment decisions for glioma. TNFRSF19 is an outstanding representative of a predictor of prognosis and immunotherapy effect in gliomas.

Simultaneous Detection of Ochratoxin A and Aflatoxin B1 Based on Stable Tuning Fork-shaped DNA Fluorescent Aptasensor.

Tuning fork, consisting of two fork arms and a fork handle, has a stable and rigid structure. Inspired by this structure, a tuning fork-shaped DNA (TF-DNA) fluorescence aptasensor was constructed to detect ochratoxin A (OTA) and aflatoxin B1 (AFB1). A TF-DNA double-stranded structure capable of attaching both OTA aptamer labeled with the FAM fluorescent group (FAM-Apt) and AFB1 aptamer labeled with the ROX fluorescent group (ROX-Apt) was designed and linked to magnetic beads. This TF-DNA double-stranded structure can provide a stable platform for dual-target detection. In the presence of OTA and AFB1, FAM-Apt and ROX-Apt preferentially bound to them and detached from the TF-DNA double-stranded structure. Dual-signal fluorescent probes were collected from the supernatant by magnetic separation, and achieved fluorescence enhancement at 520 nm and 607 nm, respectively. The linear ranges are 0.05 ng/mL to 100 ng/mL for OTA and 0.1 ng/mL to 100 ng/mL for AFB1, and the detection limits are 0.015 ng/mL and 0.045 ng/mL, respectively. The developed sensor has the advantages of simple and fast preparation, good specificity and reproducibility, which is promising for the simultaneous determination of multiple hazardous substances in food.

Differential diagnosis of Crohn's disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning.

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Biodegradation of various grades of polyethylene microplastics by Tenebrio molitor and Tenebrio obscurus larvae: Effects on their physiology.

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 µm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae-1⋅day-1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics.

A retrospective study comparing pharmacomechanical thrombectomy with catheter-directed thrombolysis for acute deep venous thrombosis.

PURPOSE: This study aims to conduct a comparative analysis of the clinical efficacy and safety between pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) in the context of acute lower-extremity deep venous thrombosis (LEDVT). MATERIALS AND METHODS: A retrospective review of our institution's patient database spanning from February 2011 to December 2019 was performed to identify cases of acute LEDVT. The patients were categorized into two distinct groups based on the thrombolytic interventions administered: the PMT group, specifically denoting PMT with AngioJet in our investigation, and the CDT group. Comprehensive data sets encompassing patient demographics, risk factors, procedural specifics, thrombolysis grading, and complications were collected. Subsequent follow-up evaluations at the two-year mark post-treatment included assessments of post-thrombotic syndrome (PTS) and the quality of life (QOL). RESULTS: Among the 348 patients identified (mean age: 50.12 ± 15.87 years; 194 females), 200 underwent catheter-directed thrombolysis (CDT) during the early stage (2011 to 2017), while 148 received pharmacomechanical thrombectomy (PMT) between 2017 and 2019. Baseline data between the two groups exhibited no statistically significant differences. Thrombus scores significantly decreased in both cohorts post-therapy (each p < 0.001).Patients subjected to PMT demonstrated higher thrombolysis rates (77.35±9.44% vs 50.85±6.72%), reduced administration of the thrombolytic agent urokinase [20(20-20) vs 350(263-416), p < 0.001], larger limb circumference differences (above the knee: 6.03±1.76cm vs 4.51±1.82cm, p < 0.001; below the knee: 2.90±1.16cm vs 2.51±0.90cm, p < 0.001), and shorter lengths of stay (7.19±3.11 days vs 12.33±4.77 days, p < 0.001). However, the PMT group exhibited a higher decline in hemoglobin levels (13.41±10.59 g/L vs 10.88±11.41 g/L, p = 0.038) and an increase in creatinine levels [9.58(2.32-15.82) umol/L vs 4.53(2.87-6.08) umol/L, p < 0.001] compared to the CDT group. No statistically significant differences were observed in the numbers of balloon angioplasty, stent implantation (each p > 0.050), and minor and major complications between the two groups. At the 1-year follow-up, post-thrombotic syndrome (PTS) occurred in 13.51% of the PMT group compared to 26% of the CDT group (p = 0.025), with a higher incidence of moderate-severe PTS in the CDT group (8% vs 2.7%, p = 0.036). At the 2-year follow-up, PTS was observed in 16.2% of the PMT group and 31.5% in the CDT group, p = 0.004. Preoperative and postoperative D-values of SF-36 PCS and SF-36 MCS showed no statistically significant between-group differences. CONCLUSION: In our institutional experience, both pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) have proven to be effective and safe therapeutic approaches for managing acute lower-extremity deep venous thrombosis (LEDVT). PMT, in particular, demonstrated superior efficacy in achieving thrombosis resolution and mitigating the risk of post-thrombotic syndrome, affirming its role as a favorable intervention in this clinical context.

Rational Design and Precise Synthesis of Single-Atom Alloy Catalysts for the Selective Hydrogenation of Nitroarenes.

Single-atom alloys (SAAs) have gained increasing prominence in the field of selective hydrogenation reactions due to their uniform distribution of active sites and the unique host-guest metal interactions. Herein, 15 SAAs are constructed to comprehensively elucidate the relationship between host-guest metal interaction and catalytic performance in the selective hydrogenation of 4-nitrostyrene (4-NS) by density functional theory (DFT) calculations. The results demonstrate that the SAAs with strong host-guest metal interactions exhibit a preference for N─O bond cleavage, and the reaction energy barrier of the hydrogenation process is primarily influenced by the host metal. Among them, Ir1Ni SAA stands out as the prime catalyst candidate, showcasing exceptional activity and selectivity. Furthermore, the Ir1Ni SAA is subsequently prepared through precise synthesis techniques and evaluated in the selective hydrogenation of 4-NS to 4-aminostyrene (4-AS). As anticipated, the Ir1Ni SAA demonstrates extraordinary catalytic performance (yield > 96%). In situ FT-IR experiments and DFT calculations further confirmed that the unique host-guest metal interaction at the Ir-Ni interface site of Ir1Ni SAA endows it with excellent 4-NS selective hydrogenation ability. This work provides valuable insights into enhancing the performance of SAAs catalysts in selective hydrogenation reactions by modulating the host-guest metal interactions.

A dual-signal ratiometric electrochemical aptasensor based on Thi/Au/ZIF-8 and catalytic hairpin assembly for ultra-sensitive detection of aflatoxin B1.

A dual-signal ratiometric electrochemical aptasensor has been developed  for AFB1 detection using thionine/Au/zeolitic imidazolate framework-8 (Thi/Au/ZIF-8) nanomaterials and catalytic hairpin assembly (CHA) reaction. Thi/Au/ZIF-8 combined with DNA hairpin 2 (H2) was used as a signal probe. [Fe(CN)6]3-/4- was served as another signal probe, and the IThi/Au/ZIF-8/I[Fe(CN)6]3-/4- ratio was for the first time utilized to quantify AFB1. AFB1-induced CHA was used to expand the ratio of electrical signals. In the presence of AFB1, H2/Thi/Au/ZIF-8 bound to the electrode via CHA, enhanced  the current signal of Thi/Au/ZIF-8. H2 contained the DNA phosphate backbone hindered [Fe(CN)6]3-/4- redox reaction and resulted in a lower [Fe(CN)6]3-/4- current signal. This aptasensor exhibited high specificity for AFB1, a linear range of 0.1 pg mL-1 to 100 ng mL-1, and a detection limit of 0.089 pg mL-1. It demonstrated favorable sensitivity, selectivity, stability, and repeatability. The aptasensor was suitable for detecting AFB1 in peanuts and black tea and holds potential for real sample applications.

The impact of COVID-19 restrictions on motorcycle crashes in Taiwan.

Taiwan is one of the countries with the highest motorcycle per capita globally, and motorcycle crashes are predominant among traffic crashes. This study examines the impact of coronavirus disease 2019 restrictions on motorcycle crashes. We analyzed the trend of motorcycle crashes in Taipei City from 2019 to 2020 using the dataset provided by the Department of Transportation, Taipei City Government, Taiwan. We found 47,108 and 51,441 motorcycle crashes in 2019 and 2020, involving 61,141 and 67,093 motorcycles, respectively. Mopeds had the highest risk in 2020, followed by heavy motorcycles [≥550 cubic capacity (cc)] and scooters compared to 2019. Food delivery motorcycle crashes increased for scooters (0.93% in 2019 to 3.45% in 2020, P < .0001) and heavy motorcycles (250 < cc < 550) (0.90% in 2019 to 3.38% in 2020, P < .0001). While fatalities remained under 1%, 30% to 51% of motorcyclists sustained injuries. Food delivery with scooters or heavy motorcycles (250 < cc < 550) was significantly associated with motorcyclist injuries and deaths. Compared with 2019, the adjusted odds ratios of motorcyclist injuries and deaths in 2020 were 1.43 (95% confidence interval = 1.05-1.94) for heavy motorcycles (≥550 cc) and 1.07 (95% confidence interval = 1.04-1.09) for scooters. This study shows that coronavirus disease 2019 restrictions was associated with elevated risks of crashes, injuries, and deaths among motorcyclists, reflecting the general preference for private transport over public transport. The popularity of food delivery services also contributed to increased motorcycle crashes.

TEMPO/O2 Synergistically Mediated BiBrO-Photocatalyzed Decarboxylative Phosphorylation of N-Arylglycines.

With both TEMPO and O2 (in air) as the homogeneous redox mediators, BiBrO as the heterogeneous semiconductor photocatalyst, the first example of semi-heterogeneous photocatalytic decarboxylative phosphorylation of N-arylglycines with diarylphosphine oxides was established. A series of α-amino phosphinoxides were efficiently synthesized.

Stereoregular poly(2-phenylthiirane) via cationic ring-opening polymerization.

Herein, we describe an effective strategy for synthesizing polythioethers with a well-defined structure through the cationic polymerization of thiirane with electron-withdrawing substituents. This strategy allows for precisely controlling the regio- and stereochemistry of the ring-opening polymerization of 2-phenylthiirane, thus allowing for producing poly(2-phenylthiirane) with high stereoregularity using enantiomeric pure thiirane.

One Health-based management for sustainably mitigating tetracycline-resistant Aeromonas hydrophila-induced health risk.

Aeromonas hydrophila has ability to spread tetracycline resistance (tetR) under stresses of oxytetracycline (OTC), one of the most important antibiotics in aquaculture industry. Even though environmental reservoir of Aeromonas allows it to be at interfaces across One Health components, a robust modelling framework for rigorously assessing health risks is currently lacking. We proposed a One Health-based approach and leveraged recent advances in quantitative microbial risk assessment appraised by available dataset to interpret interactions at the human-animal-environment interfaces in various exposure scenarios. The dose-response models were constructed considering the effects on mortality for aquaculture species and tetR genes transfer for humans. A scenario-specific risk assessment on pond species-associated A. hydrophila infection and human gut-associated tetR genes transfer was examined. Risk-based control strategies were involved to test their effectiveness. We showed that farmed shrimp exposed to tetracycline-resistant A. hydrophila in OTC-contaminated water experienced higher infection risk (relative risk: 1.25-1.34). The tetR genes transfer risk for farmers in shrimp ponds (∼2 × 10-4) and swimmers in coastal areas (∼4 × 10-6) during autumn exceeded acceptable risk (10-6). This cautionary finding underscores the importance of accounting for monitoring, assessing, and mitigating occupational health hazards among workers in shrimp farming sectors within future One Health-based strategies for managing water infection risks. We recommend that OTC emission rate together with A. hydrophila concentration should be reduced by up to 70-99% to protect human, farmed shrimp, and environmental health. Our predictive framework can be adopted for other systems and be used as a "risk detector" for assessing tetR-related health risks that invoke potential risk management on addressing sustainable mitigation on offsetting residual OTC emission and tetR genes spread in a species-human-environmental health system.

Molecular-Weight-Dependent Degradation of Plastics: Deciphering Host-Microbiome Synergy Biodegradation of High-Purity Polypropylene Microplastics by Mealworms.

The biodegradation of polypropylene (PP), a highly persistent nonhydrolyzable polymer, by Tenebrio molitor has been confirmed using commercial PP microplastics (MPs) (Mn 26.59 and Mw 187.12 kDa). This confirmation was based on the reduction of the PP mass, change in molecular weight (MW), and a positive Δδ13C in the residual PP. A MW-dependent biodegradation mechanism was investigated using five high-purity PP MPs, classified into low (0.83 and 6.20 kDa), medium (50.40 and 108.0 kDa), and high (575.0 kDa) MW categories to access the impact of MW on the depolymerization pattern and associated gene expression of gut bacteria and the larval host. The larvae can depolymerize/biodegrade PP polymers with high MW although the consumption rate and weight losses increased, and survival rates declined with increasing PP MW. This pattern is similar to observations with polystyrene (PS) and polyethylene (PE), i.e., both Mn and Mw decreased after being fed low MW PP, while Mn and/or Mw increased after high MW PP was fed. The gut microbiota exhibited specific bacteria associations, such as Kluyvera sp. and Pediococcus sp. for high MW PP degradation, Acinetobacter sp. for medium MW PP, and Bacillus sp. alongside three other bacteria for low MW PP metabolism. In the host transcriptome, digestive enzymes and plastic degradation-related bacterial enzymes were up-regulated after feeding on PP depending on different MWs. The T. molitor host exhibited both defensive function and degradation capability during the biodegradation of plastics, with high MW PP showing a relatively negative impact on the larvae.

Design, synthesis, and biological evaluation of first-in-class FABP1 inhibitors for the treatment of NASH.

The fatty acid-binding protein 1 (FABP1) is a fatty acid transporter protein that is considered as an emerging target for metabolic diseases. Despite forceful evidence that the inhibition of FABP1 is essential for ameliorating NASH, pharmacological control and validation of FABP1 are hindered by a lack of relevant inhibitors as pharmacological tool. Therefore, the development of effective FABP1 inhibitors is a current focus of research. Herein, we firstly reported the comprehensive structure-activity relationship (SAR) study of novel FABP1 inhibitors derived from high throughput screening of our in-house library, which resulting in the identification of the optimal compound 44 (IC50 = 4.46 ± 0.54 µM). Molecular docking studies revealed that 44 forms stable hydrogen bonds with amino acids around the active pocket of FABP1. Moreover, 44 alleviated the typical histological features of fatty liver in NASH mice, including steatosis, lobular inflammation, ballooning and fibrosis. Additionally, 44 has been demonstrated to have lipid metabolism regulating, anti-oxidative stress and hepatoprotective properties. This study might be provided a promising insight into the field of NASH and inspiration for the development of FABP1 inhibitors.

Dynamic flyer in barrel imaging via high intensity short-pulse laser.

The thin flyer is a small-scale flying object, which is well known as the core functional element of the initiator. Understanding how flyers perform has been a long-standing issue in detonator science. However, it remains a significant challenge to explore how the flyer is formed and functions in the barrel of the initiator via tabletop devices. In this study, we present dynamic and unprecedented images of flyer in barrel via high intensity short-pulse laser. Advanced radiography, coupled with a high-intensity picosecond laser X-ray source, has enabled the provision of state-of-the-art radiographs in a single-shot experiment for observing micron-scale flyer formation in a hollow cylinder in nanoseconds. The flyer was clearly visible in the barrel and was accelerated and restricted differently from that without the barrel. This first implementation of a tabletop X-ray source provided a new approach for capturing dynamic photographs of small-scale flying objects, which were previously reported to be accessible only via an X-ray phase-contrast imaging system at the advanced photon source. These efforts have led to a significant improvement of radiographic capability and a greater understanding of the mechanisms of "burst" of exploding foil initiators for this application.

Incidence and Risk Factors of Mental Illnesses Among Patients with Systemic Autoimmune Rheumatic Diseases: An 18-year population-based study.

OBJECTIVE: This study aimed to assess the incidence and risk factors surrounding mental illnesses in patients diagnosed with systemic autoimmune rheumatic diseases (SARDs). METHODS: This retrospective cohort study used nationwide, population-based claim data taken from Taiwan's National Health Insurance Research Database (NHIRD) to identify patients certified as having a catastrophic illness for Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), Systemic sclerosis (SSc), Dermatomyositis (DM), Polymyositis (PM) or Sjogren's syndrome (SS) from the years 2002-2020. We furthermore calculated the incidence of mental illness in patients diagnosed with SARDs while exploring factors associated with the development of mental illness using multivariable Cox regression analysis shown as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among the 28 588 participants, the average age was 47.4 (SD 14.9) years, with most participants being female (76.4%). When compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.20, 95% CI: 1.10-1.32), SS (HR: 1.29, 95% CI: 1.19-1.39), and DM (HR: 1.28, 95% CI: 1.04-1.32) showed a significantly increased risk of developing mental illness. Additionally, when compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.32, 95% CI: 1.21-1.44), SSc (HR: 1.20, 95% CI: 1.02-1.41), SS (HR: 1.17, 95% CI: 1.08-1.26), DM (HR: 1.73, 95% CI: 1.44-2.07), and PM (HR: 1.64, 95% CI: 1.32-2.03) showed a significantly increased risk of antidepressant use. CONCLUSIONS: This population-based cohort study revealed that patients diagnosed with SLE, SS and DM had significantly higher risks of developing mental illness when compared with patients with RA.

Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

The Association between Glymphatic System and Perivascular Macrophages in Brain Waste Clearance.

The glymphatic system suggests the convective bulk flow of cerebrospinal fluid (CSF) through perivascular spaces and the interstitial spaces of the brain parenchyma for the rapid removal of toxic waste solutes from the brain. However, the presence of convective bulk flow within the brain interstitial spaces is still under debate. We first addressed this argument to determine the involvement of the glymphatic system in brain waste clearance utilizing contrast-enhanced 3D T1-weighted imaging (T1WI), diffusion tensor imaging (DTI), and confocal microscopy imaging. Furthermore, perivascular macrophages (PVMs), which are immune cells located within perivascular spaces, have not been thoroughly explored for their association with the glymphatic system. Therefore, we investigated tracer uptake by PVMs in the perivascular spaces of both the arteries/arterioles and veins/venules and the potential association of PVMs in assisting the glymphatic system for interstitial waste clearance. Our findings demonstrated that both convective bulk flow and diffusion are responsible for the clearance of interstitial waste solutes from the brain parenchyma. Furthermore, our results suggested that PVMs may play an important function in glymphatic system-mediated interstitial waste clearance. The glymphatic system and PVMs could be targeted to enhance interstitial waste clearance in patients with waste-associated neurological conditions and aging.

Targeting Moonlighting Enzymes in Cancer.

Moonlighting enzymes are multifunctional proteins that perform multiple functions beyond their primary role as catalytic enzymes. Extensive research and clinical practice have demonstrated their pivotal roles in the development and progression of cancer, making them promising targets for drug development. This article delves into multiple notable moonlighting enzymes, including GSK-3, GAPDH, and ENO1, and with a particular emphasis on an enigmatic phosphatase, PTP4A3. We scrutinize their distinct roles in cancer and the mechanisms that dictate their ability to switch roles. Lastly, we discuss the potential of an innovative approach to develop drugs targeting these moonlighting enzymes: target protein degradation. This strategy holds promise for effectively tackling moonlighting enzymes in the context of cancer therapy.

Closed-loop recycling of sulfur-rich polymers with tunable properties spanning thermoplastics, elastomers, and vitrimers.

The development of closed-loop recycling polymers that exhibit excellent performance is of great significance. Sulfur-rich polymers possessing excellent optical, thermal, and mechanical properties are promising candidates for chemical recycling but lack efficient synthetic strategies for achieving diverse structures. Herein, we report a universal synthetic strategy for producing polytrithiocarbonates, a class of sulfur-rich polymers, via the polycondensation of dithiols and dimethyl trithiocarbonate. This strategy has excellent compatibility with a wide range of monomers, including aliphatic, heteroatomic, and aromatic dithiols enabling the synthesis of polytrithiocarbonates with diverse structures. The present synthesis strategy offers a versatile platform for the construction of thermoplastics, elastomers, and vitrimers. Notably, these polytrithiocarbonates can be easily depolymerized via solvolysis into the corresponding monomers, which can be repolymerized to virgin polymers without changing the material properties.

In vitro inhibition of α-Synuclein aggregation and disaggregation of preformed fibers by polyphenol hybrids with 2-conjugated benzothiazole.

The misfolding and aggregation of α-Syn play a pivotal role in connecting diverse pathological pathways in Parkinson's disease (PD). Preserving α-Syn proteostasis and functionality by inhibiting its aggregation or disaggregating existing aggregates using suitable inhibitors represents a promising strategy for PD prevention and treatment. In this study, a series of benzothiazole-polyphenol hybrids was designed and synthesized. Three identified compounds exhibited notable inhibitory activities against α-Syn aggregation in vitro, with IC50 values in the low micromolar range. These inhibitors demonstrated sustained inhibitory effects throughout the entire aggregation process, stabilizing α-Syn proteostasis conformation. Moreover, the compounds effectively disintegrated preformed α-Syn oligomers and fibers, potentially by binding to specific domains within the fibers, inducing fibril instability, collapse, and ultimately resulting in smaller-sized aggregates and monomers. These findings offer valuable insights into the therapeutic potential of polyphenol hybrids with 2-conjugated benzothiazole targeting α-Syn aggregation in the treatment of PD.