Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins.

TAX1BP1, a multifunctional autophagy adaptor, plays critical roles in different autophagy processes. As an autophagy receptor, TAX1BP1 can interact with RB1CC1, NAP1, and mammalian ATG8 family proteins to drive selective autophagy for relevant substrates. However, the mechanistic bases underpinning the specific interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins remain elusive. Here, we find that there are two distinct binding sites between TAX1BP1 and RB1CC1. In addition to the previously reported TAX1BP1 SKICH (skeletal muscle and kidney enriched inositol phosphatase (SKIP) carboxyl homology)/RB1CC1 coiled-coil interaction, the first coiled-coil domain of TAX1BP1 can directly bind to the extreme C-terminal coiled-coil and Claw region of RB1CC1. We determine the crystal structure of the TAX1BP1 SKICH/RB1CC1 coiled-coil complex and unravel the detailed binding mechanism of TAX1BP1 SKICH with RB1CC1. Moreover, we demonstrate that RB1CC1 and NAP1 are competitive in binding to the TAX1BP1 SKICH domain, but the presence of NAP1's FIP200-interacting region (FIR) motif can stabilize the ternary TAX1BP1/NAP1/RB1CC1 complex formation. Finally, we elucidate the molecular mechanism governing the selective interactions of TAX1BP1 with ATG8 family members by solving the structure of GABARAP in complex with the non-canonical LIR (LC3-interacting region) motif of TAX1BP1, which unveils a unique binding mode between LIR and ATG8 family protein. Collectively, our findings provide mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins and are valuable for further understanding the working mode and function of TAX1BP1 in autophagy.

Deep learning in pulmonary nodule detection and segmentation: a systematic review.

OBJECTIVES: The accurate detection and precise segmentation of lung nodules on computed tomography are key prerequisites for early diagnosis and appropriate treatment of lung cancer. This study was designed to compare detection and segmentation methods for pulmonary nodules using deep-learning techniques to fill methodological gaps and biases in the existing literature. METHODS: This study utilized a systematic review with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching PubMed, Embase, Web of Science Core Collection, and the Cochrane Library databases up to May 10, 2023. The Quality Assessment of Diagnostic Accuracy Studies 2 criteria was used to assess the risk of bias and was adjusted with the Checklist for Artificial Intelligence in Medical Imaging. The study analyzed and extracted model performance, data sources, and task-focus information. RESULTS: After screening, we included nine studies meeting our inclusion criteria. These studies were published between 2019 and 2023 and predominantly used public datasets, with the Lung Image Database Consortium Image Collection and Image Database Resource Initiative and Lung Nodule Analysis 2016 being the most common. The studies focused on detection, segmentation, and other tasks, primarily utilizing Convolutional Neural Networks for model development. Performance evaluation covered multiple metrics, including sensitivity and the Dice coefficient. CONCLUSIONS: This study highlights the potential power of deep learning in lung nodule detection and segmentation. It underscores the importance of standardized data processing, code and data sharing, the value of external test datasets, and the need to balance model complexity and efficiency in future research. CLINICAL RELEVANCE STATEMENT: Deep learning demonstrates significant promise in autonomously detecting and segmenting pulmonary nodules. Future research should address methodological shortcomings and variability to enhance its clinical utility. KEY POINTS: Deep learning shows potential in the detection and segmentation of pulmonary nodules. There are methodological gaps and biases present in the existing literature. Factors such as external validation and transparency affect the clinical application.

PFASs in Cerebrospinal Fluids and Blood-CSF Barrier Permeability in Patients with Cognitive Impairment.

Attention has been drawn to the associations between PFASs and human cognitive decline. However, knowledge on the occurrence and permeability of PFASs in the brains of patients with cognitive impairment has not been reported. Here, we determined 30 PFASs in paired sera and cerebrospinal fluids (CSFs) from patients with cognitive impairment (n = 41) and controls without cognitive decline (n = 18). We revealed similar serum PFAS levels but different CSF PFAS levels, with lower CSF PFOA (median: 0.125 vs 0.303 ng/mL, p < 0.05), yet higher CSF PFOS (0.100 vs 0.052 ng/mL, p < 0.05) in patients than in controls. Blood-brain transfer rates also showed lower RCSF/Serum values for PFOA and higher RCSF/Serum values for PFOS in patients, implying potential heterogeneous associations with cognitive function. The RCSF/Serum values for C4-C14 perfluoroalkyl carboxylates exhibited a U-shape trend with increasing chain length. Logistic regression analyses demonstrated that CSF PFOS levels were linked to the heightened risk of cognitive impairment [odds ratio: 3.22 (1.18-11.8)] but not for serum PFOS. Toxicity inference results based on the Comparative Toxicogenomics Database suggested that PFOS in CSF may have a greater potential to impair human cognition than other PFASs. Our results contribute to a better understanding of brain PFAS exposure and its potential impact on cognitive function.

Ionomer structure and component transport in the cathode catalyst layer of PEM fuel cells: A molecular dynamics study.

The transport of water and protons in the cathode catalyst layer (CCL) of proton exchange membrane (PEM) fuel cells is critical for cell performance, but the underlying mechanism is still unclear. Herein, the ionomer structure and the distribution/transport characteristics of water and protons in CCLs are investigated via all-atom molecular dynamics simulations. The results show that at low water contents, isolated water clusters form in ionomer pores, while proton transport is mainly via the charged sites of the ionomer side chains and the Grotthuss mechanism. Moreover, with increasing water content, water clusters are interconnected to form continuous water channels, which provide effective paths for proton transfer via the vehicular and Grotthuss mechanisms. Increasing the ionomer mass content can enhance the dense arrangement of the ionomer, which, in turn, increases the density of charge sites and improves the proton transport efficiency. When the ionomer mass content is high, the clustering effect reduces the space for water diffusion, increases the proton transport path, and finally decreases the proton transport efficiency. By providing physics insights into the proton transport mechanism, this study is helpful for the structural design and performance improvement of CCLs of PEM fuel cells.

Comparing the Outcomes of Suture Anchor Repair and Rein-Type Capsular Suture for Triangular Fibrocartilage Complex Foveal Tears With a Minimum 2-Year Follow-Up.

PURPOSE: Recent biomechanical studies have highlighted the importance of foveal reinsertion when repairing triangular fibrocartilage complex (TFCC) injury with foveal tears. However, clinical studies comparing different repair techniques are scarce. We compared the clinical outcomes of suture anchor repair and rein-type capsular suture in patients with TFCC palmer 1B foveal tears with a minimum of 2-year follow-up. METHODS: This was a single-surgeon, single-center, retrospective, comparative study. We included patients who underwent TFCC repair surgery due to a foveal tear from December 2013 to October 2018 with a minimum follow-up of 24 months. Postoperative Quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, Modified Mayo Wrist Score, visual analogue scale for pain, wrist range of motion, and grip strength were compared. We also measured the maximal ulnar head displacement with dynamic ultrasound to quantify distal radioulnar joint stability. RESULTS: In total, 103 patients were in the suture anchor group (group A) and 84 patients in the rein-type capsular suture group (group B). The mean follow-up time exceeded three years for both groups. There was a minimal difference regarding QuickDASH score, visual analogue scale for pain, and grip strength ratio between the two groups. The rein-type group had significantly better Modified Mayo Wrist Score. The suture anchor group showed better distal radioulnar joint stability with dynamic ultrasound, but was more limited in ulnar deviation. However, these differences are most likely clinically insignificant. CONCLUSIONS: Both suture anchor repair and rein-type capsular suture yielded satisfactory results for TFCC 1B foveal tear in a minimum of 2-year follow-up. The functional scores were similar, and no major complications or recurrent instability were noted in either group. TYPE OF STUDY/LEVEL OF EVIDENCE: Retrospective Therapeutic Comparative Investigation IV.

Liver biomarkers, lipid metabolites, and risk of gestational diabetes mellitus in a prospective study among Chinese pregnant women.

BACKGROUND: Liver plays an important role in maintaining glucose homeostasis. We aimed to examine the associations of liver enzymes and hepatic steatosis index (HSI, a reliable biomarker for non-alcoholic fatty liver disease) in early pregnancy with subsequent GDM risk, as well as the potential mediation effects of lipid metabolites on the association between HSI and GDM. METHODS: In a birth cohort, liver enzymes were measured in early pregnancy (6-15 gestational weeks, mean 10) among 6,860 Chinese women. Multivariable logistic regression was performed to examine the association between liver biomarkers and risk of GDM. Pearson partial correlation and least absolute shrinkage and selection operator (LASSO) regression were conducted to identify lipid metabolites that were significantly associated with HSI in a subset of 948 women. Mediation analyses were performed to estimate the mediating roles of lipid metabolites on the association of HSI with GDM. RESULTS: Liver enzymes and HSI were associated with higher risks of GDM after adjustment for potential confounders, with ORs ranging from 1.42 to 2.24 for extreme-quartile comparisons (false discovery rate-adjusted P-trend ≤0.005). On the natural log scale, each SD increment of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and HSI was associated with a 1.15-fold (95% CI: 1.05, 1.26), 1.10-fold (1.01, 1.20), 1.21-fold (1.10, 1.32), 1.15-fold (1.04, 1.27), and 1.33-fold (1.18, 1.51) increased risk of GDM, respectively. Pearson partial correlation and LASSO regression identified 15 specific lipid metabolites in relation to HSI. Up to 52.6% of the association between HSI and GDM risk was attributed to the indirect effect of the HSI-related lipid score composed of lipid metabolites predominantly from phospholipids (e.g., lysophosphatidylcholine and ceramides) and triacylglycerol. CONCLUSIONS: Elevated liver enzymes and HSI in early pregnancy, even within a normal range, were associated with higher risks of GDM among Chinese pregnant women. The association of HSI with GDM was largely mediated by altered lipid metabolism.

Coordination Engineering of Defective Cobalt-Nitrogen-Carbon Electrocatalysts with Graphene Quantum Dots for Boosting Oxygen Reduction Reaction.

Developing efficient and robust metal-nitrogen-carbon electrocatalysts for oxygen reduction reaction (ORR) is of great significance for the application of hydrogen-oxygen fuel cells and metal-air batteries. Herein, a coordination engineering strategy is developed to improve the ORR kinetics and stability of cobalt-nitrogen-carbon (Co-N-C) electrocatalysts by grafting the oxygen-rich graphene quantum dots (GQDs) onto the zeolite imidazole frameworks (ZIFs) precursors. The optimized oxygen-rich GQDs-functionalized Co-N-C (G-CoNOC) electrocatalyst demonstrates an increased mass activity, nearly two times higher than that of pristine defective Co-N-C electrocatalyst, and retains a stability of 90.0% after 200 h, even superior to the commercial Pt/C. Comprehensive investigations demonstrate that the GQDs coordination can not only decrease carbon defects of Co-N-C electrocatalysts, improving the electron transfer efficiency and resistance to the destructive free radicals from H2 O2 , but also optimize the electronic structure of atomic Co active site to achieve a desired adsorption energy of OOH- , leading to enhanced ORR kinetics and stability by promoting further H2 O2 reduction, as confirmed by theoretical calculations and experimental results. Such a coordination engineering strategy provides a new perspective for the development of highly active noble-metal-free electrocatalysts for ORR.

Mitoquinone protects against acetaminophen-induced liver injury in an FSP1-dependent and GPX4-independent manner.

Mitochondrial oxidative stress has been a crucial mediator in acetaminophen (APAP)-induced hepatotoxicity. MitoQ, an analog of coenzyme Q10, is targeted towards mitochondria and acts as a potent antioxidant. This study aimed to explore the effect of MitoQ on APAP-induced liver injury and its possible mechanisms. To investigate this, CD-1 mice and AML-12 cells were treated with APAP. Hepatic MDA and 4-HNE, two markers of lipid peroxidation (LPO), were elevated as early as 2 h after APAP. Oxidized lipids were rapidly upregulated in APAP-exposed AML-12 cells. Hepatocyte death and mitochondrial ultrastructure alterations were observed in APAP-induced acute liver injury. The in vitro experiments showed that mitochondrial membrane potentials and OXPHOS subunits were downregulated in APAP-exposed hepatocytes. MtROS and oxidized lipids were elevated in APAP-exposed hepatocytes. We discovered that APAP-induced hepatocyte death and liver injury were ameliorated by attenuation of protein nitration and LPO in MitoQ-pretreated mice. Mechanistically, knockdown of GPX4, a key enzyme for LPO defense systems, exacerbated APAP-induced oxidized lipids, but did not influence the protective effect of MitoQ on APAP-induced LPO and hepatocyte death. Whereas knockdown of FSP1, another key enzyme for LPO defense systems, had little effect on APAP-induced lipid oxidation but partially weakened the protection of MitoQ on APAP-induced LPO and hepatocyte death. These results suggest that MitoQ may alleviate APAP-evoked hepatotoxicity by eliminating protein nitration and suppressing hepatic LPO. MitoQ prevents APAP-induced liver injury partially dependent of FSP1 and independent of GPX4.

Mutation of CsARC6 affects fruit color and increases fruit nutrition in cucumber.

KEY MESSAGE: A mutation of CsARC6 not only causes white fruit color in cucumber, but also affects plant growth and fruit quality. Fruit color of cucumber is a very important agronomic trait, but most of the genes affecting cucumber white fruit color are still unknow, and no further studies were reported on the effect of cucumber fruit quality caused by white fruit color genes. Here, we obtained a white fruit mutant em41 in cucumber by EMS mutagenesis. The mutant gene was mapped to a 548 kb region of chromosome 2. Through mutation site analysis, it was found to be a null allele of CsARC6 (CsaV3_2G029290). The Csarc6 mutant has a typical phenotype of arc6 mutant that mesophyll cells contained only one or two giant chloroplasts. ARC6 protein was not detected in em41, and the level of FtsZ1 and FtsZ2 was also reduced. In addition, FtsZ2 could not form FtsZ ring-like structures in em41. Although these are typical arc6 mutant phenotypes, some special phenotypes occur in Csarc6 mutant, such as dwarfness with shortened internodes, enlarged fruit epidermal cells, decreased carotenoid contents, smaller fruits, and increased fruit nutrient contents. This study discovered a new gene, CsARC6, which not only controls the white fruit color, but also affects plant growth and fruit quality in cucumber.

Polycyclic aromatic hydrocarbon exposure burden: Individual and mixture analyses of associations with chronic obstructive pulmonary disease risk.

Accumulating data demonstrate that polycyclic aromatic hydrocarbons (PAH) exposure is linked to compromised respiratory diseases. This study aimed to analyze urinary PAH metabolites and their associations with chronic obstructive pulmonary disease (COPD) in a sample size of 3015 subjects from a total population of 50,588 from the National Health and Nutrition Examination Survey (NHANES) in 2007-2016. Results showed that the most predominant metabolite was 1-Hydroxynaphthalene (1-NAP, 84%) with a geometric mean concentration of 50,265 ng/L, followed by its homologue 2-NAP (10%), both of which arose from sources including road emission, smoking and cooking. Multiple logistic regression showed that seven of the ten major PAH metabolites were correlated with increased COPD risk: including 1-NAP (OR: 1.83, 95%CI: 1.25, 2.69), 2-Hydroxyfluorene (2-FLU, OR: 2.29, 95%CI: 1.42, 3.68) and 1-Hydroxyphenanthrene (1-PHE, OR: 2.79, 95%CI: 1.85, 4.21), when compared to the lowest tertile after adjusted for covariates. Total exposure burden per PAH congener sub-group demonstrated persistent positive correlation with COPD for ∑PHE (OR: 1.80, 95%CI: 1.34, 2.43) and ∑FLU (OR: 2.74, 95%CI: 1.77, 4.23) after adjusted for covariates. To address the contribution of PAH exposure as mixture towards COPD, weighted quantile sum (WQS) regression analyses revealed that 1-NAP, 9-Hydroxyfluorene (9-FLU), 3-Hydroxyfluorene (3-FLU) and 1-PHE were among the top contributors in the associations with COPD. Our results demonstrate the contemporary yet ongoing exposure burden of PAH exposure for over a decade, particularly towards NAPs and FLUs that contribute significantly to COPD risk, calling for more timely environmental regulation.

High quality diet attenuated the positive association between polychlorinated biphenyls and premature mortality among middle-aged and older adults.

OBJECTIVE: Polychlorinated biphenyls (PCBs) have been reported to be a risk factor for premature death, while a high diet quality is thought to lower mortality risk. We aimed to examine whether PCBs were associated with higher all-cause and cause-specific mortality risk and whether such associations could be modified by the diet quality among US middle-aged and older adults. METHODS: Included were 1259 participants aged 40 years or older from the 1999-2004 National Health and Nutrition Examination surveys. Exposure to PCBs was assessed in non-fasting serum samples, and mortality status was ascertained through December 31, 2019 using the public-use, linked mortality files. Diet quality was assessed using the Healthy Eating Index-2015 based on 24-h dietary recalls. Cox proportional hazard regression was applied to assess the associations of different PCB congener groups with mortality and the modifying effect by the diet quality. RESULTS: During a median follow-up of 17.75 years, 419 deaths occurred, including 131 from cardiovascular disease (CVD) and 102 from cancer. Serum concentrations of dioxin-like PCBs and non-dioxin-like PCBs were significantly associated with all-cause mortality, with hazard ratios (HRs) of 1.84 (95% confidence interval [CI], 1.10, 2.99) and 1.82 (1.09, 3.03) for extreme-tertile comparisons. A significant interaction was noted between dioxin-like PCBs and diet quality (P for interaction: 0.012), with a substantially more pronounced association among participants with a low diet quality (HR, 3.47; 95% CI: 1.29, 9.32), compared to those with a high diet quality (HR, 0.98; 95% CI: 0.40, 2.43). A similar weaker association was observed for total PCBs in participants with a high diet quality (P for interaction: 0.032). However, effect modifications by diet quality were not noted for the associations between different PCB groups and CVD mortality. CONCLUSIONS: While our findings need to be validated in other populations and mechanistic studies, they may suggest that a high quality diet could potentially attenuate the harmful effects of chronic PCB exposure.

Brain-targeted nanoreactors prevent the development of organophosphate-induced delayed neurological damage.

BACKGROUND: Organophosphate (OP)-induced delayed neurological damage is attributed to permanent neuropathological lesions caused by irreversible OP-neurocyte interactions, without potent brain-targeted etiological antidotes to date. The development of alternative therapies to achieve intracerebral OP detoxification is urgently needed. METHODS: We designed a brain-targeted nanoreactor by integrating enzyme immobilization and biomimetic membrane camouflaging protocols with careful characterization, and then examined its blood-brain barrier (BBB) permeability both in vitro and in vivo. Subsequently, the oxidative stress parameters, neuroinflammatory factors, apoptotic proteins and histopathological changes were measured and neurobehavioral tests were performed. RESULTS: The well-characterized nanoreactors exerted favourable BBB penetration capability both in vitro and in vivo, significantly inhibiting OP-induced intracerebral damage. At the cellular and tissue levels, nanoreactors obviously blocked oxidative stress, cellular apoptosis, inflammatory reactions and brain histopathological damage. Furthermore, nanoreactors radically prevented the occurrence of OP-induced delayed cognitive deficits and psychiatric abnormality. CONCLUSION: The nanoreactors significantly prevented the development of OP-induced delayed neurological damage, suggesting a potential brain-targeted etiological strategy to attenuate OP-related delayed neurological and neurobehavioral disorders.

Sorption of representative organic contaminants on microplastics: Effects of chemical physicochemical properties, particle size, and biofilm presence.

Microplastic pollution has attracted mounting concerns worldwide. Microplastics may concentrate organic and metallic contaminants; thus, affecting their transport, fate and organismal exposure. To better understand organic contaminant-microplastic interactions, our study explored the sorption of selected polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), α-hexabromocyclododecane (α-HBCDD), and organophosphate flame retardants (OPFRs) on high-density polyethylene (HDPE) and polyvinylchloride (PVC) microplastics under saline conditions. Sorption isotherms determined varied between chemicals and between HDPE and PVC microplastics. Log Freundlich sorption coefficients (Log KF) for the targeted chemicals ranged from 2.01 to 5.27 L kg-1 for HDPE, but were significantly lower for PVC, i.e., ranging from Log KF data (2.84 - 8.58 L kg-1). Significant correlations between chemicals' Log KF and Log Kow (octanol-water partition coefficient) indicate that chemical-dependent sorption was largely influenced by their hydrophobicity. Sorption was evaluated using three size classes (< 53, 53 - 300, and 300 - 1000 µm) of lab-fragmented microplastics. Particle size did not significantly affect sorption isotherms, but influenced the time to reach equilibrium and the predicted maximum sorption, likely related to microplastic surface areas. The presence of biofilms on HDPE particles significantly enhanced contaminant sorption capacity, indicating more complex sorption dynamics in the chemical-biofilm-microplastic system. Our findings offer new insights into the chemical-microplastic interactions in marine environment.

Chinese herbal medicine compound of flavonoids adjunctive treatment for oral cancer.

Oral cancer is a prevalent global issue, with oral squamous cell carcinoma constituting the majority of cases. Standard treatments like surgery, radiotherapy, and chemotherapy are available but may have adverse effects. Molecular gene therapy, focusing on genetic mutations linked to oral cancer, presents a promising alternative.In this study, we evaluated 27 chemotherapeutic drugs and 63 Chinese herbal medicines for their effectiveness, categorized them by their cellular mechanisms, and identified potential adjuvant therapy candidates for oral cancer. Our findings highlight the impact of natural flavonoids on oral cancer cells, inducing apoptosis, and confirming their potential in molecular genetic analysis. In conclusion, the natural compounds present in Chinese herbal medicine, particularly flavonoids, offer a promising avenue to target specific genetic mutations in oral cancer cells. This approach may reduce the risks associated with oral cancer treatment and pave the way for innovative adjuvant therapies.

Molecular Mechanism Biomarkers Predict Diagnosis in Schizophrenia and Schizoaffective Psychosis, with Implications for Treatment.

Diagnostic uncertainty and relapse rates in schizophrenia and schizoaffective disorder are relatively high, indicating the potential involvement of other pathological mechanisms that could serve as diagnostic indicators to be targeted for adjunctive treatment. This study aimed to seek objective evidence of methylenetetrahydrofolate reductase MTHFR C677T genotype-related bio markers in blood and urine. Vitamin and mineral cofactors related to methylation and indolamine-catecholamine metabolism were investigated. Biomarker status for 67 symptomatically well-defined cases and 67 asymptomatic control participants was determined using receiver operating characteristics, Spearman's correlation, and logistic regression. The 5.2%-prevalent MTHFR 677 TT genotype demonstrated a 100% sensitive and specific case-predictive biomarkers of increased riboflavin (vitamin B2) excretion. This was accompanied by low plasma zinc and indicators of a shift from low methylation to high methylation state. The 48.5% prevalent MTHFR 677 CC genotype model demonstrated a low-methylation phenotype with 93% sensitivity and 92% specificity and a negative predictive value of 100%. This model related to lower vitamin cofactors, high histamine, and HPLC urine indicators of lower vitamin B2 and restricted indole-catecholamine metabolism. The 46.3%-prevalent CT genotype achieved high predictive strength for a mixed methylation phenotype. Determination of MTHFR C677T genotype dependent functional biomarker phenotypes can advance diagnostic certainty and inform therapeutic intervention.

Rice ACID PHOSPHATASE 1 regulates Pi stress adaptation by maintaining intracellular Pi homeostasis.

The concentration and homeostasis of intracellular phosphate (Pi) are crucial for sustaining cell metabolism and growth. During short-term Pi starvation, intracellular Pi is maintained relatively constant at the expense of vacuolar Pi. After the vacuolar stored Pi is exhausted, the plant cells induce the synthesis of intracellular acid phosphatase (APase) to recycle Pi from expendable organic phosphate (Po). In this study, the expression, enzymatic activity and subcellular localization of ACID PHOSPHATASE 1 (OsACP1) were determined. OsACP1 expression is specifically induced in almost all cell types of leaves and roots under Pi stress conditions. OsACP1 encodes an acid phosphatase with broad Po substrates and localizes in the endoplasmic reticulum (ER) and Golgi apparatus (GA). The phylogenic analysis demonstrates that OsACP1 has a similar structure with human acid phosphatase PHOSPHO1. Overexpression or mutation of OsACP1 affected Po degradation and utilization, which further influenced plant growth and productivity under both Pi-sufficient and Pi-deficient conditions. Moreover, overexpression of OsACP1 significantly affected intracellular Pi homeostasis and Pi starvation signalling. We concluded that OsACP1 is an active acid phosphatase that regulates rice growth under Pi stress conditions by recycling Pi from Po in the ER and GA.

Hepatic Fatty Acid Profiles Associated with Exposure to Emerging and Legacy Halogenated Contaminants in Two Harbor Seal Populations across the North Atlantic.

Fatty acids (FAs) have been extensively used as indicators of foraging ecology in marine mammals, yet their association with exposure to contaminants has rarely been investigated. The present study provided the first characterization of the relationship between hepatic FA profiles and exposure to a suite of contaminants in a sentinel species─the harbor seal (Phoca vitulina)─from the Gulf of Maine and the south coast of Sweden. FA profiles differed in the two seal populations, and the levels of legacy and alternative brominated flame retardants and polyhalogenated carbazoles were significantly elevated in Maine seals. Correlations between individual FAs and multiple flame retardants (FRs) and poly- and perfluoroalkyl substances (PFASs) were found in seals from both populations. Moreover, several FR and PFAS chemicals were significantly associated with the estimated desaturating enzyme activity inferred from the FA profiles. The ratios of poly to monounsaturated FAs (∑PUFAs/∑MUFAs) and those of unsaturated to saturated FAs (∑UFAs/∑SFAs) were significantly associated with HBBZ, PFHxS, or BDE 47 in seals from Maine and Sweden, whereas ∑n - 6/∑n - 3 PUFAs was significantly associated with BDE 154 and 36-CCZ in Swedish and Maine seals, respectively. Our results suggest the lipid metabolism-disrupting potential of these contaminants in marine mammals and warrant continuous biomonitoring and risk assessment, considering the critical role of PUFAs in vital biological processes.

Long-Term Exposure to Environmentally Relevant Doses of Large Polystyrene Microplastics Disturbs Lipid Homeostasis via Bowel Function Interference.

The question of whether long-term chronic exposure to microplastics (MPs) could induce dose- and size-dependent adverse effects in mammals remains controversial and poorly understood. Our study explored potential health risks from dietary exposure to environmentally relevant doses of polystyrene (PS) MPs, through a mouse model and integrated analyses of the interruptions of fecal microbial metagenomes and plasma lipidomes. After 21 weeks of exposure to the MPs (40-100 µm), mice mainly exhibited gut microbiota dysbiosis, tissue inflammation, and plasma lipid metabolism disorder, although no notable accumulation of MPs was observed in the gut or liver. The change of the relative abundance of microbiota was strongly associated with the exposure dose and size of MPs while less significant effects were observed in gut damage and abnormal lipid metabolism. Moreover, multiomics data suggested that the host abnormal lipid metabolism was closely related to bowel function disruptions, including gut microbiota dysbiosis, increased gut permeability, and inflammation induced by MPs. We revealed for the first time that even without notable accumulation in mouse tissues, long-term exposure to MPs at environmentally relevant doses could still induce widespread health risks. This raises concern on the health risks from the exposure of humans and other mammals to environmentally relevant dose MPs.

Radial distraction may reduce the incidence of ulnar-sided wrist pain in ulna-plus morphology intraoperatively following distal radius fractures fixation.

INTRODUCTION: Fixed-angle plate fixation can be an effective treatment for distal radius fractures (DRFs). However, patients with existing ulnar positive variance might be at risk of developing symptoms of ulnar-sided wrist pain (USWP). Ulnar shortening osteotomy (USO) is one of the main treatment options for USWP. We hypothesized that a limited radial distraction at the fracture site at the time of surgery for DRF would be functionally equivalent to an indirect USO and that if this were done in a patient with an ulnar plus morphology it could potentially decrease the risk of USWP. METHODS: This retrospective study was conducted at a single institution and all the surgeries were performed by single surgeon. A total of 136 patients (92 women and 44 men) with a mean age of 55 years were enrolled with 57 patients in the distraction group (from 2014 to 2017) and 79 patients (from 2011 to 2013) in the non-distraction group. Patients were assessed USWP. Functional outcomes were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Visual Analogue Scale (VAS) for pain, grip strength, and range of motion for the wrist. RESULTS: The mean follow-up was 37.9 months (range, 28-61 months). The radiographs at postoperative 2-year follow-ups showed the mean ulnar positive variance was 1.3 mm (range, 1-2 mm) in the distraction group and 3.5 mm (range, 2-5 mm) in the non-distraction group. The average of the distraction length was 2.32 mm (range, 2-3 mm). At the 2-year follow-ups, USWP presented in 7% (four patients) in the distraction group, which was significantly less than the incidence of 28% (22 patients) in the non-distraction group. The distraction group exhibited significantly better DASH scores and grip strength and less subsequent ulnar-shortening osteotomy for ulnar-sided wrist pain. CONCLUSIONS: The radial distraction procedure performed during DRFs fixation could possibly reduce the occurrence of postoperative USWP and improve the functional outcomes. LEVEL OF EVIDENCE: Level III, Therapeutic.

Arthroscopic-assisted radiocarpal ligaments tensioning for dynamic radiocarpal instability.

BACKGROUND: Dynamic radiocarpal instability is one of the causes of post-trauma radial-sided wrist pain. It is not easy to diagnose and may possibly be overlooked. The key ligaments responsible for dynamic radiocarpal instability are the radioscaphocapitate (RSC) and long radiolunate (LRL) ligaments. Tensioning of these 2 ligaments could be a method of treatment for dynamic carpal instability. We proposed a method for arthroscopic thermal shrinkage of these 2 ligaments, and for setting a landmark arthroscopically to facilitate identification of these 2 ligaments during the combined open suture tensioning procedure. METHODS: Between January 2016 and May 2020, 12 patients treated with this method were enrolled. The mean age was 33.3 years (range, 18-57 years), and the mean duration from injury to operation was 7.8 months (range, 3-25 months). The diagnosis was mainly depended on the physical examinations and confirmed under arthroscopy. The mean follow-up was 17.7 months (range, 12-26 months). RESULTS: All the patients had marked improvement of pain, grip strength, the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), and the radiocarpal stability. The wrist range of motion showed significant decrease around 5o in both flexion and extension and around 4o in the ulnar deviation at the final follow-ups. All patients were able to return to their previous full level of work and activities. CONCLUSIONS: We conclude that arthroscopic thermal shrinkage combined with open suture tensioning can be effective in treating dynamic carpal instability, while the arthroscopic-assisted landmark setting can help identify the accurate location of the RSC and LRL ligaments without dissecting too much soft tissue.