Rational modification of Neisseria meningitidis ß1,3-N-acetylglucosaminyltransferase for lacto-N-neotetraose synthesis with reduced long-chain derivatives.

Lacto-N-neotetraose (LNnT), as a neutral core structure within human milk oligosaccharides (HMOs), has garnered widespread attention due to its exceptional physiological functions. In the process of LNnT synthesis using cellular factory approaches, substrate promiscuity of glycosyltransferases leads to the production of longer oligosaccharide derivatives. Here, rational modification of ß1,3-N-acetylglucosaminyltransferase from Neisseria meningitidis (LgtA) effectively decreased the concentration of long-chain LNnT derivatives. Specifically, the optimal ß1,4-galactosyltransferase (ß1,4-GalT) was selected from seven known candidates, enabling the efficient synthesis of LNnT in Escherichia coli BL21(DE3). Furthermore, the influence of lactose concentration on the distribution patterns of LNnT and its longer derivatives was investigated. The modification of LgtA was conducted with computational assistance, involving alanine scanning based on molecular docking to identify the substrate binding pocket and implementing large steric hindrance on crucial amino acids to obstruct LNnT entry. The implementation of saturation mutagenesis at positions 223 and 228 of LgtA yielded advantageous mutant variants that did not affect LNnT synthesis while significantly reducing the production of longer oligosaccharide derivatives. The most effective mutant, N223I, reduced the molar ratio of long derivatives by nearly 70 %, showcasing promising prospects for LNnT production with diminished byproducts.

Intracellular Construction of Organelle-like Compartments Facilitates Metabolic Flux in Escherichia coli.

The formation of well-designed synthetic compartments or membraneless organelles for applications in synthetic biology and cellular engineering has aroused enormous interest. However, establishing stable and robust intracellular compartments in bacteria remains a challenge. Here, we use the structured DIX domains derived from Wnt signaling pathway components, more specifically, Dvl2 and Axin1, as building blocks to generate intracellular synthetic compartments in Escherichia coli. Moreover, the aggregation behaviors and physical properties of the DIX-based compartments can be tailored by genetically embedding a specific dimeric domain into the DIX domains. Then, a pair of interacting motifs, consisting of the aforementioned dimeric domain and its corresponding binding ligand, was incorporated to modify the client recruitment pattern of the synthetic compartments. As a proof of concept, the human milk oligosaccharide lacto-N-tetraose (LNT) biosynthesis pathway was selected as a model metabolic pathway. The fermentation results demonstrated that the co-compartmentalization of sequential pathway enzymes into intracellular compartments created by DIX domain, or by the DIX domain in conjunction with interacting motifs, prominently enhanced the metabolic flux and increased LNT production. These synthetic protein compartments may provide a feasible and effective tool to develop versatile organelle-like compartments in bacteria for applications in cellular engineering and synthetic biology.

Harsh Environment-Tolerant, High Performance Soft Pressure Sensors Enabled by Fiber-Segment Structure and Plasma Treatment.

As the demand for specialized and diversified pressure sensors continues to increase, excellent performance and multi-applicability have become necessary for pressure sensors. Currently, flexible pressure sensors are primarily utilized in fields such as health monitoring and human-computer interaction. However, numerous complex extreme environments in reality, including deep sea, corrosive conditions, extreme cold, and high temperatures, urgently require the services of flexible devices. Here, a piezoresistive flexible pressure sensor based on expanded polytetrafluoroethylene/functionalized carbon nanotubes (EPTFE/FCNT) is proposed. Benefiting from the unique fiber-segment architecture, chemical stability, and strong chemical binding force between EPTFE and FCNT, the fabricated sensor exhibits remarkable sensing capabilities and can be employed in multifarious extreme environments. It demonstrates a sensitivity of 862.28 kPa-1, a response time of 6-7 ms, and a detection limit below 1 Pa. Furthermore, it possesses a pressure resolution of 0.0018% under 111 kPa and can withstand over 10,000 loading and unloading cycles under 1 MPa. Additionally, the EPTFE/FCNT sensor retains its outstanding pressure response and work efficiency in extreme conditions such as an ultra-low temperature of -80 °C, high temperature (200 °C), acidic and alkaline corrosion, and underwater. These notable attributes enormously broaden the sensors' real-world application range.

GALNT9 enrichment attenuates MPP+-induced cytotoxicity by ameliorating protein aggregations containing α-synuclein and mitochondrial dysfunction.

BACKGROUND: GALNTs (UDP-GalNAc; polypeptide N-acetylgalactosaminyltransferases) initiate mucin-type O-GalNAc glycosylation by adding N-GalNAc to protein serine/threonine residues. Abnormalities in O-GalNAc glycosylation are involved in various disorders such as Parkinson's disease (PD), a neurodegenerative disorder. GALNT9 is potentially downregulated in PD patients. METHODS: To determine whether GALNT9 enrichment ameliorates cytotoxicity related to PD-like variations, a pcDNA3.1-GALNT9 plasmid was constructed and transfected into SH-SY5Y cells to establish a GALNT9-overexpressing cell model. RESULTS: Downregulation of GALNT9 and O-GalNAc glycosylation was confirmed in our animal and cellular models of PD-like variations. GALNT9 supplementation greatly attenuated cytotoxicity induced by MPP+ (1-Methyl-4-phenylpyridinium iodide) since it led to increased levels of tyrosine hydroxylase and dopamine, reduced rates of apoptosis, and significantly ameliorated MPP+-induced mitochondrial dysfunction by alleviating abnormal levels of mitochondrial membrane potential and reactive oxygen species. A long-lasting mPTP (mitochondrial permeability transition pores) opening and calcium efflux resulted in significantly lower activity in the cytochrome C-associated apoptotic pathway and mitophagy process, signifying that GALNT9 supplementation maintained neuronal cell health under MPP+ exposure. Additionally, it was found that glycans linked to proteins influenced the formation of protein aggregates containing α-synuclein, and GALNT9 supplement dramatically reduced such insoluble protein aggregations under MPP+ treatment. Glial GALNT9 predominantly appears under pathological conditions like PD-like variations. CONCLUSIONS: GALNT9 enrichment improved cell survival, and glial GALNT9 potentially represents a pathogenic index for PD patients. This study provides insights into the development of therapeutic strategies for the treatment of PD.

Correlative Effects of Carbon Support Structures and Surface Properties on ORR Catalytic Activities of Loaded Catalysts.

As a complex three-phase heterogeneous catalyst, the oxygen reduction reaction (ORR) catalyst activity is determined by the interfacial and surface structures and chemical state of the catalyst support. As a typical biomass carbon-based support, rice husk-based porous carbon (RHPC) has natural unique hierarchical porous structures, which easily regulate the microstructure and surface properties. This study explored the correlative effects of RHPC structure and surface properties on ORR catalytic activity through the typical modification methods, namely, alkali etching, high temperature, oxidation, and ball milling. The various factors for the joint effects are defined as the specific surface area, oxygen-containing functional groups, graphite edge defects, resistivity, and contact angle. The analysis of such joint influences is difficult to quantitatively evaluate due to the large number of experimental factors and small sample sizes. Partial least-squares (PLS) can better deal with such problems. Therefore, a PLS regression model was established to evaluate the relative weight of each factor on the catalytic activity for the RHPC-based support catalysts. The results reveal that the regression coefficients of four factors yield similar magnitude for the effect of the half-wave potential (E1/2). However, graphite edge defects had a more significant impact on the limiting diffusion current density (J) and electron transfer number (n). Furthermore, an optimal support named BM-RHPC-3 was prepared with more defects and oxygen-containing functional groups, which prepared Fe-NS/BM-RHPC-3 presenting the best ORR catalytic activity (E1/2 = 0.880 V, J of 5.15 mA cm-2), superior to Pt/C (E1/2 = 0.844 V, J of 4.99 mA cm-2). The statistical regression model is validated with a relative error of less than 5% between predicted and true values for analyzing RHPC-based ORR catalysts' catalytic performance. It shows the feasibility of experiment-informed learning for data-driven material discovery and design.

TRMT10C gene polymorphisms confer hepatoblastoma susceptibility: evidence from a seven-center case-control study.

N1-methyladenosine (m1A) is a reversible epigenetic modification of RNAs. Aberrant m1A modification levels due to dysregulation of m1A regulators have been observed in multiple cancers. tRNA methyltransferase 10C (TRMT10C) can install m1A in RNAs; however, its role in hepatoblastoma remains unknown. We conducted this study to identify causal polymorphisms in the TRMT10C gene for hepatoblastoma susceptibility in a cohort of Chinese children (313 cases vs. 1446 controls). The genotypes of four potential functional polymorphisms (rs7641261 C>T, rs2303476 T>C, rs4257518 A>G, and rs3762735 C>G) were determined in participants using TaqMan real-time PCR. The associations of these polymorphisms with hepatoblastoma susceptibility were estimated by logistic regression analysis adjusted for age and sex. All four polymorphisms were significantly associated with hepatoblastoma risk. In particular, under the recessive genetic model, these polymorphisms conferred an increased risk of hepatoblastoma: rs7641261 C>T [adjusted odds ratio (OR)=1.64, 95% confidence interval (CI)=1.04-2.58, P=0.033], rs2303476 T>C (adjusted OR=1.87, 95% CI=1.16-3.02, P=0.010), rs4257518 A>G (adjusted OR=1.45, 95% CI=1.09-1.94, P=0.012), and rs3762735 C>G (adjusted OR=3.83, 95% CI=2.15-6.82, P<0.0001). Combined analysis revealed that kids had an increased risk of developing hepatoblastoma if they harbored at least one risk genotype (adjusted OR=1.94, 95% CI=1.48-2.54, P<0.0001). In addition, the combined risk effects of the four SNPs persisted across all the subgroups. We identified four hepatoblastoma susceptibility loci in the TRMT10C gene. Identifying more disease-causing loci may facilitate the development of genetic marker panels to predict individuals' hepatoblastoma predisposition.

Multistrategy Engineering of an Inulosucrase to Enhance the Activity and Thermostability for Efficient Production of Microbial Inulin.

Inulin has found commercial applications in the pharmaceutical, nutraceutical, and food industries due to its beneficial health effects. The enzymatic biosynthesis of microbial inulin has garnered increasing attention. In this study, molecular modification was applied to Lactobacillus mulieris UMB7800 inulosucrase, an enzyme that specifically produces high-molecular weight inulin, to enhance its catalytic activity and thermostability. Among the 18 variable regions, R5 was identified as a crucial region significantly impacting enzymatic activity by replacing it with more conserved sequences. Site-directed mutagenesis combined with saturated mutagenesis revealed that the mutant A250 V increased activity by 68%. Additionally, after screening candidate mutants by rational design, four single-point mutants, S344D, H434P, E526D, and G531P, were shown to enhance thermostability. The final combinational mutant, M5, exhibited a 66% increase in activity and a 5-fold enhancement in half-life at 55 °C. These findings are significant for understanding the catalytic activity and thermostability of inulosucrase and are promising for the development of microbial inulin biosynthesis platforms.

Bacterial Degradation of Antinutrients in Foods: The Genomic Insight.

Antinutrients, also known as anti-nutritional factors (ANFs), are compounds found in many plant-based foods that can limit the bioavailability of nutrients or can act as precursors to toxic substances. ANFs have controversial effects on human health, depending mainly on their concentration. While the positive effects of these compounds are well documented, the dangers they pose and the approaches to avoid them have not been discussed to the same extent. There is no dispute that many ANFs negatively alter the absorption of vitamins, minerals, and proteins in addition to inhibiting some enzyme activities, thus negatively affecting the bioavailability of nutrients in the human body. This review discusses the chemical properties, plant bioavailability, and deleterious effects of anti-minerals (phytates and oxalates), glycosides (cyanogenic glycosides and saponins), polyphenols (tannins), and proteinaceous ANFs (enzyme inhibitors and lectins). The focus of this study is on the possibility of controlling the amount of ANF in food through fermentation. An overview of the most common biochemical pathways for their microbial reduction is provided, showing the genetic basis of these phenomena, including the active enzymes, the optimal conditions of action, and some data on the regulation of their synthesis.

Compartmentalization of pathway sequential enzymes into synthetic protein compartments for metabolic flux optimization in Escherichia coli.

Advancing the formation of artificial membraneless compartments with organizational complexity and diverse functionality remains a challenge. Typically, synthetic compartments or membraneless organelles are made up of intrinsically disordered proteins featuring low-complexity sequences or polypeptides with repeated distinctive short linear motifs. In order to expand the repertoire of tools available for the formation of synthetic membraneless compartments, here, a range of DIshevelled and aXin (DIX) or DIX-like domains undergoing head-to-tail polymerization were demonstrated to self-assemble into aggregates and generate synthetic compartments within E. coli cells. Then, synthetic complex compartments with diverse intracellular morphologies were generated by coexpressing different DIX domains. Further, we genetically incorporated a pair of interacting motifs, comprising a homo-dimeric domain and its anchoring peptide, into the DIX domain and cargo proteins, respectively, resulting in the alteration of both material properties and client recruitment of synthetic compartments. As a proof-of-concept, several human milk oligosaccharide biosynthesis pathways were chosen as model systems. The findings indicated that the recruitment of pathway sequential enzymes into synthetic compartments formed by DIX-DIX heterotypic interactions or by DIX domains embedded with specific interacting motifs efficiently boosted metabolic pathway flux and improved the production of desired chemicals. We propose that these synthetic compartment systems present a potent and adaptable toolkit for controlling metabolic flux and facilitating cellular engineering.

Discovery of a Thermostable Tagatose 4-Epimerase Powered by Structure- and Sequence-Based Protein Clustering.

d-Tagatose is a highly promising functional sweetener known for its various physiological functions. In this study, a novel tagatose 4-epimerase from Thermoprotei archaeon (Thar-T4Ease), with the ability to convert d-fructose to d-tagatose, was discovered through a combination of structure similarity search and sequence-based protein clustering. The recombinant Thar-T4Ease exhibited optimal activity at pH 8.5 and 85 °C, in the presence of 1 mM Ni2+. Its kcat and kcat/Km values toward d-fructose were measured to be 248.5 min-1 and 2.117 mM-1·min-1, respectively. Notably, Thar-T4Ease exhibited remarkable thermostability, with a t1/2 value of 198 h at 80 °C. Moreover, it achieved a conversion ratio of 18.9% using 100 g/L d-fructose as the substrate. Finally, based on sequence and structure analysis, crucial residues for the catalytic activity of Thar-T4Ease were identified by molecular docking and site-directed mutagenesis. This research expands the repertoire of enzymes with C4-epimerization activity and opens up new possibilities for the cost-effective production of d-tagatose from d-fructose.

Association of Thallium Exposure with Decreased Renal Function among Chinese Adults - China, 2017-2018.

What is already known about this topic?: Thallium (Tl) is significantly more toxic than heavy metals such as lead, cadmium, and mercury. However, previous studies examining the relationship between Tl exposure and the risk of chronic kidney disease (CKD) have yielded inconsistent results. What is added by this report?: The study demonstrated that elevated urinary Tl levels were associated with a higher prevalence of CKD and a reduced estimated glomerular filtration rate (eGFR), particularly among older adults. These findings were consistent in the restricted cubic spline (RCS) analyses. What are the implications for public health practice?: This study identified Tl as a risk factor for decreased renal function, underscoring the need to enhance surveillance of Tl to mitigate the disease burden of CKD.

The impact of molecular configuration on the bond breaking rates of hydrocarbons: a computational study.

The dissociation of hydrocarbon bonds plays a pivotal role in their utilization, whether through fuel combustion or the thermo-cracking of large hydrocarbons in petroleum refinement. Previous studies have primarily focused on the effects of temperature, pressure, and chemical environment on hydrocarbon reactions. However, the influence of molecular configuration on bond breaking rates has not been thoroughly explored. In this study, we propose an approach to compute bond dissociation rates, and apply it to the reactive molecular dynamics simulation (ReaxFF) trajectories of three molecules: n-tridecane, n-pentane, and 1,3-propanediol. Our results reveal that the bond dissociation rate depends not only on the bond position in the chain, but also on the molecular configuration. Stretched configurations exhibit higher dissociation rates, particularly favoring the breaking of central bonds. Conversely, when the molecule is coiled, resulting in a reduced size, terminal bonds exhibit higher dissociation rates. This research contributes to a deeper understanding of molecular dissociation properties in the oxidation of hydrocarbons, and provides a way to explore the bond breaking properties of other molecules.

A quantitative computational framework for allopolyploid single-cell data integration and core gene ranking in development.

Polyploidization drives regulatory and phenotypic innovation. How the merger of different genomes contributes to polyploid development is a fundamental issue in evolutionary developmental biology and breeding research. Clarifying this issue is challenging because of genome complexity and the difficulty in tracking stochastic subgenome divergence during development. Recent single-cell sequencing techniques enabled probing subgenome divergent regulation in the context of cellular differentiation. However, analyzing single-cell data suffers from high error rates due to high-dimensionality, noise, and sparsity, and the errors stack up in polyploid analysis due to the increased dimensionality of comparisons between subgenomes of each cell, hindering deeper mechanistic understandings. Here, we developed a quantitative computational framework, pseudo-genome divergence quantification (pgDQ), for quantifying and tracking subgenome divergence directly at the cellular level. Further comparing with cellular differentiation trajectories derived from scRNA-seq data allowed for an examination of the relationship between subgenome divergence and the progression of development. pgDQ produces robust results and is insensitive to data dropout and noise, avoiding high error rates due to multiple comparisons of genes, cells, and subgenomes. A statistical diagonostic approach is proposed to identify genes that are central to subgenome divergence during development, which facilitates the integration of different data modalities, enabling the identification of factors and pathways that mediate subgenome-divergent activity during development. Case studies demonstrated that applying pgDQ to single cell and bulk tissue transcriptome data promotes a systematic and deeper understanding of how dynamic subgenome divergence contributes to developmental trajectories in polyploid evolution.

The effect of dual antioxidant modification on oxidative stress resistance and anti-dysfunction of non-split HDL and recombinant HDL.

Recombinant high-density lipoprotein (rHDL) as anti-atherosclerosis (AS) vehicle has unique advantages including multiple anti-atherogenic functions and homing features to plaques. However, rHDL may be converted into dysfunctional forms due to complex treatment during preparation. Herein, oxidation-induced dysfunction of non-split HDL and rHDL was initially investigated. It was found that although both non-split HDL and rHDL showed oxidative dysfunction behavior, non-split HDL demonstrated superior oxidation defense compared to rHDL due to its intact composition and avoidance of overprocessing such as split and recombination. Unfortunately, in vivo oxidative stress could compromise the functionality of HDL. Therefore, surface engineering of non-split HDL and rHDL with cascade antioxidant enzyme analogues Ebselen and mitochondrial-targeted TPGS-Tempo was conducted to construct a dual-line defense HDL nano system (i.e., T@E-HDLs/rHDL), aiming to restore plaque redox balance and preserving the physiological function of HDL. Results indicated that both T@E-HDLs and rHDLs performed without distinction and exhibited greater resistance to oxidative stress damage as well as better functions than unmodified HDLs in macrophage foam cells. Overall, the modification of dual antioxidants strategy bridges the gap between non-split HDL and rHDL, and provides a promising resolution for the dilemmas of oxidative stress in plaques and HDL self dysfunction.

Establishment of patient-derived organoids and a characterization based drug discovery platform for treatment of gastric cancer.

BACKGROUND: Gastric cancer (GC) encompasses many different histological and molecular subtypes. It is a major driver of cancer mortality because of poor survival and limited treatment options. Personalised medicine in the form of patient-derived organoids (PDOs) represents a promising approach for improving therapeutic outcomes. The goal of this study was to overcome the limitations of current models by ameliorating organoid cultivation. METHODS: Organoids derived from cancer tissue were evaluated by haematoxylin and eosin staining, immunohistochemistry, mRNA, and whole-exome sequencing. Three representative chemotherapy drugs, 5-fluorouracil, docetaxel, and oxaliplatin, were compared for their efficacy against different subtypes of gastric organoids by ATP assay and apoptosis staining. In addition, drug sensitivity screening results from two publicly available databases, the Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopaedia, were pooled and applied to organoid lines. Once key targeting genes were confirmed, chemotherapy was used in combination with poly (ADP ribose) polymerase (PARP)-targeted therapy. RESULTS: We successfully constructed GC PDOs surgically resected from GC patient tissue. PDOs closely reflected the histopathological and genomic features of the corresponding primary tumours. Whole-exosome sequencing and mRNA analysis revealed that changes to the original tumour genome were maintained during long-term culture. The drugs caused divergent responses in intestinal, poorly differentiated intestinal, and diffuse gastric cancer organoids, which were confirmed in organoid lines. Poorly differentiated intestinal GC patients benefited from a combination of 5-fluorouracil and veliparib. CONCLUSION: The present study demonstrates that combining chemotherapy with PARP targeting may improve the treatment of chemotherapy-resistant tumours.

Bright green cellulose-based fluorescent probe toward Au3+ smartphone technology recognition and its visualization application.

In this study, a novel fluorescent probe, MAC-2, for the detection of Au3+ was designed and synthesised using cellulose as a carrier combined with benzothiazole derivatives. The structure of the probe was confirmed by SEM, XRD, FTIR, and 1H NMR, also the optical properties of the product were investigated. MAC-2 showed bright green fluorescence under a 365 nm UV lamp and exhibited significant quenching behaviour toward Au3+. MAC-2 utilises more sustainable biomass resources, featuring green and biodegradable characteristics that meet environmental requirements. Compared with most reported probes, it exhibits notable fluorescence properties. The limit of detection (LOD) is as low as 0.057 µM, and the response time is 1 min. It also demonstrates good specific recognition and anti-interference abilities. In addition, a smartphone was used as a portable signal processing device to achieve rapid detection of Au3+ concentration. Meanwhile, MAC-2 was successfully prepared as a fluorescent test strip, providing a potential application for the convenient detection of Au3+. The high sensitivity and selectivity exhibited by cellulose-based fluorescent probes in detecting Au3+ offer valuable insights and new ideas for the detection of other metal ions and biomolecules. These inspirations will help promote the continuous development of research and applications in related fields.

Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children: A five-center case-control study.

Objective: Nucleotide excision repair (NER) plays a vital role in maintaining genome stability, and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation. This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children. Methods: In this five-center case-control study, we enrolled 966 subjects from East China (193 hepatoblastoma patients and 773 healthy controls). The TaqMan method was used to genotype 19 single nucleotide polymorphisms (SNPs) in NER pathway genes, including ERCC1, XPA, XPC, XPD, XPF, and XPG. Then, multivariate logistic regression analysis was performed, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to assess the strength of associations. Results: Three SNPs were related to hepatoblastoma risk. XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model (adjusted OR=1.49, 95% CI=1.07-2.08, P=0.019; adjusted OR=1.66, 95% CI=1.12-2.45, P=0.012, respectively). However, XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model (adjusted OR=0.68, 95% CI=0.49-0.95; P=0.024). Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups. Moreover, there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) analysis. Conclusions: In summary, NER pathway gene polymorphisms (XPC rs2229090, XPD rs3810366, and XPD rs238406) are significantly associated with hepatoblastoma risk, and further research is required to verify these findings.

Associations of Serum Per- and Polyfluoroalkyl Substances with Hyperuricemia in Adults: A Nationwide Cross-Sectional Study.

There has been widespread concern about the health hazards of per- and polyfluoroalkyl substances (PFAS), which may be the risk factor for hyperuricemia with evidence still insufficient in the general population in China. Here, we conducted a nationwide study involving 9,580 adults aged 18 years or older from 2017 to 2018, measured serum concentrations of uric acid and PFAS (PFOA, PFOS, 6:2 Cl-PFESA, PFNA, PFHxS) in participants, to assess the associations of individual PFAS with hyperuricemia, and estimated a joint effect of PFAS mixtures. We found positive associations of higher serum PFAS with elevated odds of hyperuricemia in Chinese adults, with the greatest contribution from PFOA (69.37%). The nonmonotonic dose-response (NMDR) relationships were observed for 6:2 Cl-PFESA and PFHxS with hyperuricemia. Participants with less marine fish consumption, overweight, and obesity may be the sensitive groups to the effects of PFAS on hyperuricemia. We highlight the potential health hazards of legacy long-chain PFAS (PFOA) once again because of the higher weights of joint effects. This study also provides more evidence about the NMDR relationships in PFAS with hyperuricemia and emphasizes a theoretical basis for public health planning to reduce the health hazards of PFAS in sensitive groups.

Shale Gas Nanofluid in the Curved Carbon Nanotube: A Molecular Dynamics Simulation Study.

Curved nanochannels are prevalent in porous and tortuous materials, with shale matrices being a noteworthy example. The tortuosity of shale matrices significantly influences the behavior of shale gas, holding crucial implications for gas recovery engineering. In this study, we employ molecular dynamics simulation (MD) to investigate the impact of curvature and radius in tortuous nanochannel formed by a curved single-walled carbon nanotube (SWCNT) on the adsorption and transport properties of methane gas fluid. Our findings reveal that the inner half surface of the SWCNT, characterized by negative curvature, exhibits enhanced methane adsorption. Methane in straighter and narrower channels displays higher flow velocities, while wider channels exhibit higher flow flux. The nonzero flow velocity alters adsorption strength, causing the outer half to surpass the inner half. Tangent and vertical velocities of the flow are heterogeneously distributed in the channel, with the outer half having higher tangent velocities. Additionally, a vertical velocity pulse near the entrance induces turbulent vortex flow, slowing down the tangent flow velocity. This research contributes to a deeper understanding of shale gas properties in matrices with bent and curved channels, offering insights into nanofluids in carbon nanotubes and porous media featuring curved nanochannels.