C2 pedicle screw insertion assisted by mobilization of the vertebral artery in cases with high-riding vertebral artery.

Objective: To describe the feasibility, safety and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with the high-riding vertebral artery (HRVA).. Methods: During the period January 2020 to September 2022, fifteen patients underwent posterior occipitocervical fixation in our department. All patients had unilateral HRVA on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 13 females aged 47 ± 11.9 years (range: 17-64 years). After the correction of the vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. A routine three-dimensional reconstructed CT examination was executed to confirm the trajectory of C2 pedicle screws post-operation, and a CT angiography examination was performed when necessary. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including anterior atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line, and clivus-canal angle (CCA), were collected and compared by paired t-test. Results: All 15 patients had atlas assimilation, among which 12 patients had C2-C3 fusion (Klippel-Feil syndrome). Mobilization of the HRVA was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were reached in all 15 patients. All the patients achieved bone fusion 6 months after surgery. No looseness and shift of internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative JOA score and the main radiological measurements were remarkably improved and statistically significant. Conclusions: C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

Structural basis of bifunctional CTP/dCTP synthase.

The final step in the de novo synthesis of cytidine 5'-triphosphate (CTP) is catalyzed by CTP synthase (CTPS), which can form cytoophidia in all three domains of life. Recently, we have discovered that CTPS binds to ribonucleotides (NTPs) to form filaments, and have successfully solved the structures of Drosophila melanogaster CTPS bound with NTPs. Previous biochemical studies have shown that CTPS can bind to deoxyribonucleotides (dNTPs) to produce 2'-deoxycytidine-5'-triphosphate (dCTP). However, the structural basis of CTPS binding to dNTPs is still unclear. In this study, we find that Drosophila CTPS can also form filaments with dNTPs. Using cryo-electron microscopy, we are able to solve the structure of Drosophila melanogaster CTPS bound to dNTPs with a resolution of up to 2.7 Å. By combining these structural findings with biochemical analysis, we compare the binding and reaction characteristics of NTPs and dNTPs with CTPS. Our results indicate that the same enzyme can act bifunctionally as CTP/dCTP synthase in vitro, and provide a structural basis for these activities.

Development and Validation of a Stromal-Immune Signature to Predict Prognosis in Intrahepatic Cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion: We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Glymphatic function and its influencing factors in different glucose metabolism states.

BACKGROUND: Dysfunction of the glymphatic system in the brain in different stages of altered glucose metabolism and its influencing factors are not well characterized. AIM: To investigate the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states, the present study employed diffusion tensor imaging along the perivascular space (DTI-ALPS) index. METHODS: Sample size was calculated using the pwr package in R software. This cross-sectional study enrolled 22 patients with normal glucose metabolism (NGM), 20 patients with prediabetes, and 22 patients with type 2 diabetes mellitus (T2DM). A 3.0T magnetic resonance imaging was used to evaluate the function of the glymphatic system. The mini-mental state examination (MMSE) was used to assess general cognitive function. The DTI-ALPS index of bilateral basal ganglia and the mean DTI-ALPS index was calculated. Further, the correlation between DTI-ALPS and clinical features was assessed. RESULTS: The left-side, right-side, and mean DTI-ALPS index in the T2DM group were significantly lower than that in the NGM group. The right-side DTI-ALPS and mean DTI-ALPS index in the T2DM group were significantly lower than those in the prediabetes group. DTI-ALPS index lateralization was not observed. The MMSE score in the T2DM group was significantly lower than that in the NGM and prediabetes group. After controlling for sex, the left-side DTI-ALPS and mean DTI-ALPS index in the prediabetes group were positively correlated with 2-hour postprandial blood glucose level; the left-side DTI-ALPS index was negatively correlated with total cholesterol and low-density lipoprotein level. The right-side DTI-ALPS and mean DTI-ALPS index were negatively correlated with the glycosylated hemoglobin level and waist-to-hip ratio in the prediabetes group. The left-side, right-side, and mean DTI-ALPS index in the T2DM group were positively correlated with height. The left-side and mean DTI-ALPS index in the T2DM group were negatively correlated with high-density lipoprotein levels. CONCLUSION: Cerebral glymphatic system dysfunction may mainly occur in the T2DM stage. Various clinical variables were found to affect the DTI-ALPS index in different glucose metabolism states. This study enhances our understanding of the pathophysiology of diabetic brain damage and provides some potential biological evidence for its early diagnosis.

Meta-analysis of postoperative incision infection risk factors in colorectal cancer surgery.

Objective: To evaluate the risk factors for postoperative incision infection in colorectal cancer, this meta-analysis aimed to identify key variables impacting infection incidence following colorectal cancer surgery. Methods: Utilizing a meta-analytical approach, studies published from January 2015 to December 2022 were systematically collected and analyzed through the assessment of factors like body mass index, diabetes, albumin levels, malnutrition, and surgical duration. Results: The meta-analysis of eleven high-quality studies revealed that elevated BMI, diabetes, low albumin levels, malnutrition, and extended surgical duration were associated with increased infection risk, while laparoscopic procedures showed potential for risk reduction. Conclusions: This study underscores the significance of preoperative risk assessment and management in mitigating postoperative incision infections in colorectal cancer patients. The findings present actionable insights for clinicians to enhance patient prognoses and overall quality of life.

Tocilizumab Treatment in a Patient of Refractory Anti-EJ Positive ASyS: A Case Report.

Anti-synthetase syndrome (ASyS) is an autoimmune disease characterized by the presence of autoantibodies to aminoacyl-tRNA synthetases accompanied with various organ involvements, including the lung, joints, and skin. The ASyS-related interstitial lung disease (ILD) can be seen in the vast majority of patients. The extent of lung involvement has a significant impact on patient prognosis; the occurrence of rapid-progressive ILD could prominently increase mortality. The mainstay of treatment is prednisone in combination with conventional synthetic disease-modifying anti-rheumatic drugs or some biologic disease-modifying anti-rheumatic drugs (DMARDs). Tocilizumab (TCZ), a recombinant humanized anti-interleukin (IL)-6 receptor monoclonal antibody, has also been used to treat some systemic autoimmune rheumatic diseases associated with ILD. Although the most recent American College of Rheumatology (ACR) Guideline for the Treatment of Interstitial Lung Disease conditionally recommends against the use of TCZ as a treatment option for people with idiopathic inflammatory myopathy (IIM)-ILD progression despite initial ILD treatment, the treatment effect of TCZ in ASyS patients remains obscure, particularly for refractory cases with anti-non-Jo1 antibodies. This report describes a case of Chinese ASyS patients with anti-EJ-positive antibodies who presented with typical proximal muscle weakness, elevated creatine kinase, and ILD with non-specific interstitial pneumonia (NSIP) pattern, along with typical skin involvement such as mechanic's hand. The patients were resistant to various treatments, including rituximab (RTX), but benefited from TCZ. In this case, TCZ shows good therapeutic efficacy in a fatal acute exacerbation of ILD with a hyperinflammatory status, resulting in a relative remission of the disease flare and full preservation of lung function with a positive long-term treatment outcome.

Impact of low-to moderate-intensity exercise training on the mRNA expression of purine receptors across various vessels in SHR.

OBJECTIVE: In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. METHODS: Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. RESULTS: In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. CONCLUSION: Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

Visible-Light-Induced Metal- and Photosensitizer-Free C(sp3)-H Phosphorylation of 3,4-Dihydroquinoxalin-2(1H)-ones with Diphenylphosphine Oxide.

Herein, we report a direct phosphorylation of the C(sp3)-H bond of 3,4-dihydroquinoxalin-2(1H)-ones using oxygen as a green oxidant under visible light at room temperature. This transformation was readily accomplished in the absence of metal and photosensitizer to construct new C(sp3)-P bonds and provide a series of phosphonylated dihydroquinoxalin-2-ones in good to excellent yields. This approach opens straightforward and environmentally friendly access to 3-phosphoryl quinoxalin-2-ones derivatives.

Diels-Alder Reaction Mechanisms of La@C60 and Gd@C60 Studied Using Density Functional Theory.

Encapsulation of transition metals represents a crucial method for modifying the electronic structure and regulating the reactivity of fullerene, thereby expanding its applications. Herein, we present calculations with density functional theory methods to investigate the mechanisms of the Diels-Alder (DA) reactions of cyclopentadiene and La@C60 or Gd@C60 as well as their tricationic derivatives. Our findings indicate that the encapsulation of La and Gd into the C60 cage is thermodynamically favorable. The DA reactions are favored by the presence of La and Gd, with lower barriers, though the regioselectivity, favoring 6-6 bonds in the fullerene, is not affected. The effect of external electric fields has been also considered.

Osteoporosis treatment: current drugs and future developments.

Osteoporosis is a common systemic metabolic disease characterized by a decrease in bone density and bone mass, destruction of bone tissue microstructure, and increased bone fragility leading to fracture susceptibility. Pharmacological treatment of osteoporosis is the focus of current research, and anti-osteoporosis drugs usually play a role in inhibiting bone resorption, promoting bone formation, and having a dual role. However, most of the drugs have the disadvantages of single target and high toxic and side effects. There are many types of traditional Chinese medicines (TCM), from a wide range of sources and mostly plants. Herbal plants have unique advantages in regulating the relationship between osteoporosis and the immune system, acupuncture therapy has significant therapeutic effects in combination with medicine for osteoporosis. The target cells and specific molecular mechanisms of TCM in preventing and treating osteoporosis have not been fully elucidated. At present, there is a lack of comprehensive understanding of the pathological mechanism of the disease. Therefore, a better understanding of the pathological signaling pathways and key molecules involved in the pathogenesis of osteoporosis is crucial for the design of therapeutic targets and drug development. In this paper, we review the development and current status of anti-osteoporosis drugs currently in clinical application and under development to provide relevant basis and reference for drug prevention and treatment of osteoporosis, with the aim of promoting pharmacological research and new drug development.

Membrane separation assisted colorimetric/fluorescent detection of ß-galactosidase-positive bacteria in milk and milk powder based on the oxidase-like activity of CoOOH nanosheets.

Species-specific enzymes provide a substantial boost to the precision and selectivity of identifying dairy products contaminated with foodborne pathogens, due to their specificity for target organisms. In this study, we developed cobalt oxyhydroxide nanosheets (CoOOH NSs) for a dual-mode biosensor capable of detecting ß-galactosidase (ß-Gal)-positive bacteria in milk and milk powder. The sensor exploits the oxidase-mimicking activity of CoOOH NSs, where ß-Gal converts the substrate ß-D-galactopyranoside to p-aminophenol, reducing CoOOH NSs to Co2+ and inhibiting the formation of the blue product from 3,3',5,5'-tetramethylben-zidine. Sensitivity was enhanced through membrane filtration and ß-Gal induction by isopropyl ß-D-thiogalactoside. The assay achieved a detection limit of 5 cfu mL-1 and demonstrated recoveries (90.7 % to 103 %) and relative standard deviations <5.7 % in milk and milk powder samples. These findings underscore the potential of the sensor for detecting ß-Gal-positive bacteria in dairy products.

Isobavachin induces autophagy-mediated cytotoxicity in AML12 cells via AMPK and PI3K/Akt/mTOR pathways.

Isobavachin (IBA) is a dihydroflavonoid compound with various pharmacological effects. However, further investigation into the hepatotoxicity of IBA is necessary. This study aims to identify the hepatotoxic effects of IBA and explore its potential mechanisms. The study assessed the impact of IBA on the viability of AML12, HepG2, LO2, rat, and mouse primary hepatocytes using MTT and LDH assays. Autophagy was detected in AML12 cells after IBA treatment using electron microscopy, MDC, and Ad-mCherry-GFP-LC3B fluorescence. The effect of IBA on autophagy-related proteins was examined using Western blot. The results showed that IBA had dose-dependent inhibitory effects on five cells, induced autophagy in AML12 cells, and promoted autophagic flux. The study found that IBA treatment inhibited phosphorylation of PI3K, Akt, and mTOR, while increasing phosphorylation levels of AMPK and ULK1. Treatment with both AMPK and PI3K inhibitors reversed the expression of AMPK and PI3K-Akt-mTOR signaling pathway proteins. These results suggest that IBA may have hepatocytotoxic effects but can also prevent IBA hepatotoxicity by inhibiting the AMPK and PI3K/Akt/mTOR signaling pathways. This provides a theoretical basis for preventing and treating IBA hepatotoxicity in clinical settings.

Purification and immobilization of ß-glucosidase using surface modified mesoporous silica Santa Barbara Amorphous 15 for eco-friendly preparation of sagittatoside A.

Functionalized mesoporous materials have become a promising carrier for enzyme immobilization. In this study, Santa Barbara Amorphous 15 (SBA-15) was modified by N-aminoethyl-γ-aminopropyl trimethoxy (R). R-SBA-15 was employed to purify and immobilize recombinant ß-glucosidase from Terrabacter ginsenosidimutans (BgpA) in one step for the first time. Optimum pH of the constructed R-SBA-15@BgpA were 7.0, and it has 20 â„ƒ higher optimal temperature than free enzyme. Relative activity of R-SBA-15@BgpA still retained > 70% at 42 â„ƒ after 8-h incubation. The investigation on organic reagent resistance revealed that the immobilized enzyme can maintain strong stability in 15% DMSO. In leaching test and evaluation of storage stability, only trace amount of protein was detected in buffer of the immobilized enzyme after storage at 4 â„ƒ for 33 days, and the immobilized BgpA still maintained > 50% relative activity. It also demonstrated good reusability, with 76.1% relative activity remaining after fourteen successive enzymatic hydrolyses of epimedin A to sagittatoside A. The newly proposed strategy is an effective approach for the purification and immobilization of BgpA concurrently. In addition, R-SBA-15@BgpA was demonstrated to have high efficiency and stability in this application, suggesting its great feasibility and potential to produce bioactive compounds such as secondary glycosides or aglycones from natural products.

Ameliorating the detrimental effects of chromium in wheat by silicon nanoparticles and its enriched biochar.

Increased anthropogenic activities over the last decades have led to a gradual increase in chromium (Cr) content in the soil, which, due to its high mobility in soil, makes Cr accumulation in plants a serious threat to the health of animals and humans. The present study investigated the ameliorative effect of foliar-applied Si nanoparticles (SiF) and soil-applied SiNPs enriched biochar (SiBc) on the growth of wheat in Cr-polluted soil (CPS). Two levels of CPS were prepared, including 12.5 % and 25 % by adding Cr-polluted wastewater in the soil as soil 1 (S1) and soil 2 (S2), respectively for the pot experiment with a duration of 40 days. Cr stress significantly reduced wheat growth, however, combined application of SiF and SiBc improved root and shoot biomass production under Cr stress by (i) reducing Cr accumulation, (ii) increasing activities of antioxidant enzymes (ascorbate peroxidase and catalase), and (iii) increasing protein and total phenolic contents in both root and shoot respectively. Nonetheless, separate applications of SiF and SiBc effectively reduced Cr toxicity in shoot and root respectively, indicating a tissue-specific regulation of wheat growth under Cr. Later, the Langmuir and Freundlich adsorption isotherm analysis showed a maximum soil Cr adsorption capacity ∼ Q(max) of 40.6 mg g-1 and 59 mg g-1 at S1 and S2 respectively, while the life cycle impact assessment showed scores of -1 mg kg-1 and -211 mg kg-1 for Cr in agricultural soil and - 0.184 and - 38.7 for human health at S1 and S2 respectively in response to combined SiF + SiBC application, thus indicating the environment implication of Si nanoparticles and its biochar in ameliorating Cr toxicity in different environmental perspectives.

Correlation between Anterior Mitral Annular Plane Systolic Excursion and Left Atrial Appendage Stasis in Patients with Nonvalvular Atrial Fibrillation.

Background: Atrial fibrillation (AF) can lead to a decline in left atrial appendage (LAA) function, potentially increasing the likelihood of LAA thrombus (LAAT) and spontaneous echo contrast (SEC). Measuring LAA flow velocity through transesophageal echocardiography (TEE) is currently the primary method for evaluating LAA function. This study aims to explore the potential correlation between anterior mitral annular plane systolic excursion (aMAPSE) and LAA stasis in patients with non-valvular atrial fibrillation (NVAF). Methods: A total of 465 patients with NVAF were enrolled between October 2018 and November 2021. Transthoracic echocardiography (TTE) and TEE were performed before scheduled electrical cardioversion. Propensity score matching (PSM) was used to balance confounders between the groups with and without LAAT/dense SEC. Results: Patients in the LAAT/dense SEC group showed increased left atrial (LA) diameter, LAA area, alongside reduced left ventricular ejection fraction (LVEF), LAA velocity, conjunction thickening ratio, aMAPSE, and LAA fraction area change (FAC) compared to those in the non-LAAT/dense SEC group. Multivariate logistic regression analysis identified aMAPSE and LAA FAC as independent predictors for LAAT/dense SEC. Specifically, an aMAPSE of < 6.76 mm and an LAA FAC of < 29.65% predicted LAAT/dense SEC with high diagnostic accuracy, demonstrated by an area under the curve (AUC) of 0.81 (sensitivity 0.81, specificity 0.80) for aMAPSE, and an AUC of 0.80 (sensitivity 0.70, specificity 0.84) for LAA FAC. Conclusions: Both aMAPSE and LAA FAC independently correlated with and accurately predict LAAT/dense SEC. Incorporating aMAPSE into routine TEE evaluations for LAA function alongside LAA flow velocity is recommended.

Biochemical Characterization of Recombinant Enterococcus faecalis EntV Peptide to Elucidate Its Antihyphal and Antifungal Mechanisms against Candida albicans.

Candida albicans is a common opportunistic fungus in humans, whose morphological switch between yeast and hyphae forms represents a key virulence trait. Developing strategies to inhibit C. albicans hyphal growth may provide insights into designs of novel antivirulent therapeutics. Importantly, the gut commensal bacterium, Enterococcus faecalis, secretes a bacteriocin EntV which has potent antivirulent and antifungal effects against C. albicans in infection models; however, hampered by the challenges to access large quantities of bioactive EntV, the detailed understanding of its mechanisms on C. albicans has remained elusive. In this work, we biochemically reconstituted the proteolytic cleavage reaction to obtain recombinant EntV88-His6 on a large preparative scale, providing facile access to the C-terminal EntV construct. Under in vitro C. albicans hyphal assay with specific inducers, we demonstrated that EntV88-His6 exhibits potent bioactivity against GlcNAc-triggered hyphal growth. Moreover, with fluorescent FITC-EntV88-His6, we revealed that EntV88-His6 enters C. albicans via endocytosis and perturbs the proper localization of the polarisome scaffolding Spa2 protein. Our findings provide important clues on EntV's mechanism of action. Surprisingly, we showed that EntV88-His6 does not affect C. albicans yeast cell growth but potently exerts cytotoxicity against C. albicans under hyphal-inducing conditions in vitro. The combination of EntV88-His6 and GlcNAc displays rapid killing of C. albicans, rendering it a promising antivirulent and antifungal agent.

Precipitation contributes to alleviating pollution of rubber-derived chemicals in receiving watersheds: Combining confluent stormwater runoff from different functional areas.

The release of rubber-derived chemicals (RDCs) in road surface runoff has received significant attention. Urban surface runoff is often the confluence of stormwater runoff from specific areas. However, the impact of precipitation on RDCs contamination in confluent stormwater runoff and receiving watersheds remains poorly understood. Herein, we investigated the profiles of RDCs and their transformation products in confluent stormwater runoff and receiving rivers affected by precipitation events. The results showed that 34 RDCs are ubiquitously present in confluent stormwater runoff and surface water, with mean concentrations of 1.03-2749 and 0.28-436 ng/L, respectively. The most dominant target compounds in each category were N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, 2-benzothiazolol, and 1,3-diphenylguanidine. Total RDCs concentrations in confluent stormwater runoff decreased spatially from industrial areas to business districts to college towns. A significant decrease in RDCs levels in surface water after rainfall was observed (P < 0.01), indicating that precipitation contributes to alleviating RDCs pollution in receiving watersheds. To our knowledge, this is the first report of N,N'-ditolyl-p-phenylenediamine quinone (DTPD-Q) levels in surface waters in China. The annual mass load of ∑RDCs reached 72,818 kg/y in confluent stormwater runoff, while 38,799 kg/y in surface water. The monitoring of confluent stormwater runoff is an efficient measure for predicting contamination loads from RDCs in rivers. Risk assessment suggested that most RDCs posed at least medium risks to aquatic organisms, especially 6PPD-quinone. The findings help to understand the environmental fate and risks of RDCs in the confluent stormwater runoff and receiving environments after precipitation events.

Poly(3,4-dihydroxyphenylalanine)-modified cellulose paper for the extraction of deoxyribonucleic acid by a laboratory-built automated extraction device.

The success of polymerase chain reaction (PCR) depends on the quality of deoxyribonucleic acid (DNA) templates. This study developed a cost-effective and eco-friendly DNA extraction system utilizing poly(3,4-dihydroxyphenylalanine)-modified cellulose paper (polyDOPA@paper). PolyDOPA@paper was prepared by oxidatively self-polymerizing DOPA under weak alkaline conditions and utilizing the adhesive property of polyDOPA on different materials. Compared to the uncoated cellulose paper, polyDOPA coating significantly enhances DNA adsorption owing to its abundant amino, carboxyl, and hydroxyl moieties. The DNA extraction mechanism using polyDOPA@paper was discussed. The maximum adsorption capacity of polyDOPA@paper for DNA was 20.7 µg cm-2. Moreover, an automated extraction system was designed and fabricated using 3D printing technology. The device simplifies the operation and ensures the reproducibility and consistency of the results. More importantly, it eliminates the need for specialized training of operators. The feasibility of the polyDOPA@paper-based automated extraction system was evaluated by quantitatively detecting Escherichia coli in spiked milk samples via a real-time PCR. The detection limit was 102 cfu mL-1. The results suggest that the system would have significant potential in detecting pathogens.

Selective fluorescence detection of acetylsalicylic acid, succinic acid and ascorbic acid based on a responsive lanthanide metal fluorescent coordination polymer.

A fluorescent sensor for highly selective and ultrasensitive detection of acetylsalicylic acid (ASA), succinic acid (SA), and ascorbic acid (AA) was reported. The water-soluble fluorescent ligand salicylic acid (Sal) was generated through catalyzing ASA by the hydrolase activity of zeolitic-imidazolate framework-8 (ZIF-8) or natural esterase (Est). The Sal can coordinate with 2-methylimidazole (2-MIm) and Ln(III) to form a fluorescent lanthanide coordination polymer (LCP), which has a fluorescence emission peak with the maximum wavelength at 412 nm (the excitation wavelength at 300 nm). Therefore, the detection of ASA can be achieved through the fluorescence intensity changes of LCPs in the system, which has comparable sensitivity and good selectivity (linear range of 0.031-1.00 mM and LODs of 11.72 and 3.22 µM) as compared to a direct reaction between Est/ZIF-8 and ASA for detecting ASA (linear range of 0.05-1.20 mM and limits of detection (LODs) of 4.43 and 4.58 µM). Furthermore, upon the addition of SA and AA, the fluorescence intensity of the reaction system can be enhanced and weakened through changing the energy resonance transfer pathways and affecting the enzymatic reaction process, respectively, realizing their sensitive and selective fluorescence detection. The established fluorescent sensors can work well in a wide linear range of SA concentrations from 0 to 2.50 mM (Est-based reaction system) and 0 to 1.50 mM (ZIF-8-based reaction system) with the LODs of 0.032 and 0.028 mM, respectively. The linear ranges of AA concentrations are from 0.0078 to 0.25 mM (Est-based reaction system) and 0.0078 to 0.13 mM (ZIF-8-based reaction system) with the LODs of 2.54 and 3.80 µM, respectively. The established sensors were successfully used in the detection of SA in rabbit plasma, with a recovery of 84.0%-98.7%. Additionally, the contents of ASA in Aspirin Enteric-Coated tablets and AA in vitamin C tablets were also determined by the developed methods.

TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.