2D/2D Co3O4/BiOCl nanocomposite with enhanced antibacterial activity under full spectrum: Synergism of mesoporous structure, photothermal effect and photocatalytic reactive oxygen species.

The overuse of antibiotics has caused the emergence of drug-resistant bacteria and even superbugs, which makes it imperative to develop promising antibiotic-free alternatives. Herein, a multimodal antibacterial nanoplatform of two dimensional/two dimensional (2D/2D) mesoporous Co3O4/BiOCl nanocomposite is constructed, which possesses the effect of "kill three birds with one stone": (1) the use of mesoporous Co3O4 can enlarge the surface area of the nanocomposite and promote the adsorption of bacteria; (2) Co3O4 displays remarkable full-spectrum absorption and photo-induced self-heating effect, which can raise the temperature of Co3O4/BiOCl and help to kill bacteria; (3) the p-type Co3O4 and n-type BiOCl form a p-n heterojunction, which promotes the separation of photoelectrons and holes, thus producing more reactive oxygen species (ROS) for killing bacteria. The synergism of mesoporous structure, photothermal effect and photocatalytic ROS makes the developed Co3O4/BiOCl a promising antibacterial material, which shows outstanding antibacterial activity with an inhibition rate of nearly 100 % against Escherichia coli (E. coli) within 8 min. This work provides inspiration for designing multimodal synergistic nanoplatform for antibacterial applications.

Apple polyphenols prevent patulin-induced intestinal damage by modulating the gut microbiota and metabolism of the gut-liver axis.

Patulin (PAT), a foodborne toxin, causes severe intestinal damage. To mitigate this health threat, mice were pretreated with apple polyphenols (AP) in their drinking water (0.01 % and 0.05 %) for eight weeks, followed by exposure to PAT during the last two weeks. Subsequently, histopathological and biochemical evaluations of intestinal tissues were conducted, alongside assessments of alterations in gut microbiota, colonic content metabolome, and hepatic metabolome. Consequently, AP alleviated PAT-induced villus and crypt injury, mucus depletion, GSH level decline, GSH-Px and SOD activity reduction, and MPO activity elevation. Notably, AP counteracted PAT-mediated microbiota disruptions and promoted the abundance of beneficial bacteria (Dubosiella, Akkermansia, Lachnospiraceae, and Lactobacillus). Furthermore, AP counteracted PAT-induced metabolic disorders in the colonic contents and liver. Ultimately, AP prevented intestinal injury by regulating the gut microbiota and amino acid, purine, butanoate, and glycerophospholipid metabolism in the gut-liver axis. These results underscore the potential of AP to prevent foodborne toxin-induced intestinal damage.

Passive activity enhances residual control ability in patients with complete spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202508000-00024/figure1/v/2024-09-30T120553Z/r/image-tiff Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level. However, because of prolonged inactivity, initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway. A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation, as measured by surface electromyography. In this study, we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury. Eleven patients with chronic complete thoracic spinal cord injury were recruited. Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol. The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation. Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity, the difference was not statistically significant. These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

Flavopiridol induces cell cycle arrest and apoptosis by interfering with CDK1 signaling pathway in human ovarian granulosa cells.

Several clinical trials have been conducted to evaluate the use of flavopiridol (FP) to treat a variety of cancers, and almost all cancer drugs were found to be associated with toxicity and side effects. It is not clear whether the use of FP will affect the female reproductive system. Granulosa cells, as the important cells that constitute the follicle, play a crucial role in determining the reproductive ability of females. In this study, we investigated whether different concentrations of FP have a toxic effect on the growth of immortalized human ovarian granulosa cells. The results showed that FP had an inhibitory effect on cell proliferation at a level of nanomole concentration. FP reduced cell proliferation and induced apoptosis by inducing mitochondrial dysfunction and oxidative stress, as well as increasing BAX/BCL2 and pCDK1 levels. These results suggest that toxicity to the reproductive system should be considered when FP is used in clinical applications.

Identifying effects of volatile organic compounds exposure on kidney stone prevalence in U.S. adults: a cross-sectional analysis of NHANES 2007-2020.

OBJECTIVE: Our aim was to comprehensively investigate the relationship between blood volatile organic compounds (VOCs) and kidney stone prevalence for U.S. adults. METHODS: In this cross-sectional study, 10,052 participants from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) were included. Multivariate logistic regression model was employed to investigate the association between 9 blood VOCs and kidney stones. We explored the dose-response relationship between blood VOCs and kidney stones using restricted cubic spline (RCS) analysis. Additionally, weighted quantile sum (WQS) regression model was performed to assess the overall association of 9 blood VOCs with kidney stones. Finally, subgroup analyses were conducted to identify the findings in different populations at high prevalence. RESULTS: Logistic regression analysis and dose-response risk curves revealed that blood benzene (aOR = 1.308, 95% CI: 1.118-1.530, P = 0.001), blood ethylbenzene (aOR = 1.280, 95% CI: 1.054-1.554, P = 0.013), blood m-/p-xylene (aOR = 1.187, 95% CI: 1.008-1.398, P = 0.040), blood 2,5-dimethylfuran (aOR = 1.319, 95% CI: 1.135-1.533, P < 0.001) and blood furan (aOR = 1.698, 95% CI: 1.305-2.209, P < 0.001) were positively associated with the prevalence of kidney stones. WQS regression analysis revealed that exposure to mixed blood VOCs was positively correlated with kidney stone prevalence (OR = 1.34, 95% CI: 1.14-1.57), with furans carrying the greatest weight. Subgroup analyses suggested that kidney stones were more susceptible to the effects of blood VOCs in young and middle-aged, female, overweight and obese, non-hypertensive, and non-diabetic populations. CONCLUSIONS: In this study, the results indicated that high VOC exposure was positively and independently associated with kidney stones in U.S. adults. This finding highlighted the need for public health strategies to reduce VOC exposure and its role in kidney stone prevention and treatment.

Rhodium-Catalyzed Asymmetric Cyclopropanation of Indoles with N-Triftosylhydrazones.

Here we report a general rhodium-catalyzed asymmetric intermolecular dearomative cyclopropanation of indoles using trifluoromethyl N-triftosylhydrazones as carbene precursors. The reaction enables the rapid construction of diverse cyclopropane fused indolines bearing a trifluoromethylated quaternary stereocenter in high enantioselectivities (up to 99% ee). This mild method exhibits a broad substrate scope, is compatible with various functional groups, and can even be utilized for the late-stage diversification of complex bioactive molecules. DFT calculations suggest that the formation of a key zwitterionic intermediate is responsible for the chiral induction. Overall, this approach opens up new possibilities for asymmetric cyclopropanation of challenging aromatic heterocyclic compounds.

A Tricyclic Framework with Integrated B←N and Cyano Dual Functionalization for Superior n-Type Organic Electronics.

n-Type conjugated polymers featuring low-lying lowest unoccupied molecular orbital (LUMO) energy levels are essential for achieving high-performance n-type organic thin-film transistors (OTFTs) and organic thermoelectrics (OTEs). However, the synthesis of acceptors with strong electron-withdrawing characteristics presents a significant challenge. Herein, a peripheral functionalization strategy is employed on the widely used tricyclic framework anthracene by introducing dual N,O-bidentate BF2/B(CN)2 groups to enhance its electron-withdrawing capability. This approach successfully navigates synthetic challenges, leading to the development of two novel acceptor building blocks: DBNF and DBNCN. Compared to the counterparts with a single N,O-bidentate BF2/B(CN)2 moiety, DBNF and DBNCN exhibit an extended π-backbone, enhanced molecular packing, and improved electron-withdrawing properties. Utilizing these innovative acceptor monomers, copolymers, PDBNF and PDBNCN, are synthesized, which exhibit considerably suppressed LUMO ≈ -4.0 eV. The deep LUMO of PDBNF together with its favourable bimodal packing orientation leads to remarkable electron mobility of 3.04 cm² V⁻¹ s⁻¹ with improved stability in OTFTs. Importantly, efficient n-doping in OTEs is achieved with PDBNCN, exhibiting exceptional conductivity of 95.5 S cm⁻¹ and a maximum power factor of 147.8 µW m⁻¹ K⁻²-among the highest reported for solution-processed n-type polymers.

On the contribution of atmospheric reactive nitrogen deposition to nitrogen burden in a eutrophic Lake in eastern China.

Although it has been demonstrated that atmospheric reactive nitrogen (i.e., Nr mainly including NH3, NH4+, NOx, NO3- and etc.) deposition has substantial impacts on nitrogen pools in remote and/or sensitive lakes, there is a scarcity of systematic evaluations regarding the impact on nitrogen burden in eutrophic lakes with riverine input as primary nitrogen source. Utilizing a regional atmospheric chemical transport model, combined with observation-based estimates of atmospheric nitrogen deposition fluxes and riverine nitrogen inputs, we investigate the contribution of atmospheric Nr deposition to the fifth largest freshwater lake located in eastern China, i.e., the Chaohu Lake which is facing frequent outbreaks of algal bloom. The results indicate that in the studied year of 2022, riverine total nitrogen (TN) input to the lake was 11553.3 t N yr-1 and atmospheric TN deposition was 2326.0 t N yr-1. For Nr species which are directly available for the biosphere supporting algae and plant growth, riverine NH4+ input was 1856.1 t N yr-1 and atmospheric NHx (NH3 and NH4+) deposition was 824.5 t N yr-1. The latter accounts for 30.8% of total NHx input to the lake. For NOy (HNO3 and NO3-), riverine NO3- input was estimated as 2621.7 t N yr-1, while atmospheric NOy deposition was 629.3 t N yr-1, accounting for 19.4%. In all, atmospheric Nr deposition accounts for 24.5 % of total Nr input to the lake. Our results suggest that even in regions with dense human activities with primary riverine N input, atmospheric deposition of Nr could also contribute significantly to the bio-available nitrogen in lake systems, and addressing eutrophication in Lake Chaohu and other eutrophic lakes will also need to consider the influence of atmospheric Nr deposition which is related to NH3 and NOx (i.e., NO + NO2, the precursor of NOy) emissions, in addition to the mitigation of riverine N input.

Gut microbiota as a prognostic biomarker for unresectable hepatocellular carcinoma treated with anti-PD-1 therapy.

Objective: To investigate the relationship between the gut microbiome and the response to anti-PD-1-based combination therapy in unresectable hepatocellular carcinoma (HCC). We aimed to identify potential non-invasive biomarkers and new strategies to modulate immunotherapy in HCC. Methods: In this study, fresh stool samples and clinical data were collected from unresectable HCC patients treated with anti-PD-1-based combination therapy at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2020 and December 2021. The patients were divided into two groups based on their response to treatment: the treatment responder group (R group) and the treatment non-responder group (NR group). The composition and diversity of the gut microbiome were bioinformatically analyzed by using the Whole Genome Shotgun strategy, including taxonomic composition analysis, Alpha diversity analysis, Beta diversity analysis, and differentially enriched bacterial taxa analysis. Differentially enriched bacterial taxa between R and NR groups were identified based on the magnitude of the linear discriminant analysis effect size (LEfSe) and analyzed for their impact on the survival of the patient. Results: A total of 45 eligible patients with unresectable HCC treated with anti-PD-1-based combination therapy participated in this study. The gut microbiological composition and Alpha diversity of patients were not statistically different, but there was a statistically significant difference in Beta diversity between the R and NR groups. (PERMANOVA tests, P = 0.006). We further identified 56 enriched bacterial taxa in the R group and 44 enriched bacterial taxa in the NR group based on the LEfSe analysis (LDA >2.66, P< 0.05). Patients with a high abundance of Collinsella genus, Ruminococcus_AM4211, and Ruminococcus_AF25_28AC had a longer median PFS and median OS compared to those with low abundance (P < 0.05). On the contrary, the median PFS and OS of patients with a high abundance of Bacteroides_AF20_13LB and Veillonella_atypica were significantly shorter than those of patients with low abundance (P < 0.05). The multivariate analysis showed that the abundance of Bacteroides_AF20_13LB and Ruminococcus_ AF25_28AC was independent related factors for PFS, and the abundance of Bacteroides_AF20_13LB was an independent related factor of OS. Conclusion: The enrichment of specific gut microbiota affected clinical efficacy and survival benefits in HCC treated with anti-PD-1 therapy and may be a promising non-invasive gut microbial biomarker and a new strategy for modulating immunotherapy in HCC.

Sustainable Processing of Ultralow-Cost Petroleum Cokes Into Ultrastable Self-Doped Fe3C@CNT Catalysts for High-Efficiency HER.

Petroleum cokes are largely used as low-cost anodes in aluminum industries and general fuels in cement industries, where large amounts of CO2 are generated. To reduce CO2 release, it is challenging to develop green strategies for processing abundant petroleum cokes into high-value products, because there are abundant hetero-atoms in petroleum cokes. To overcome such issues, a sustainable electrochemical approach is proposed to convert ultralow-cost high sulfur petroleum coke and iron powders into high-efficiency catalysts for hydrogen evolution reaction (HER). During molten-salt electrolysis, raw petroleum cokes are converted into CNTs via heteroatom removal and the catalytic effect of Fe, forming Fe3C nanoparticles on the sulfur and nitrogen co-dopped carbon nanotubes (Fe3C@S, N-CNTs). The electrochemical reaction analysis using the continuum model suggested that the rate-determining step referred to the slow transport of mobile ions inside the porous cathode. Because the self-doped S and N atoms massively alleviated the energy barrier for H* absorption and H2 desorption (i.e., promoting HER kinetics), the as-prepared Fe3C@S, N-CNTs exhibited low overpotentials at 10 mA cm-2 in acidic (96 mV) and alkaline (106 mV) solutions with ultralong-term duration (200 h). This study offers a sustainable approach to convert ultralow-cost petroleum cokes into ultrastable catalysts for high-efficiency HER.

Is Working Memory Necessary for Both Selection and Calculation in Level 1 Visual Perspective Taking? Evidence from Children and Adults.

Previous research has suggested that there are two modular processes of perspective selection and calculation in level 1 perspective taking. Evidence further showed that verbal working memory is associated with both processes in adults. However, research has not tested whether verbal working memory may be associated with working memory in children. Moreover, since perspective taking is associated with spatial working memory, it is necessary to investigate whether spatial working memory links to both processes. By recruiting 9-year-old children and college students in the single-task paradigm and the dual-task paradigm, we conducted two experiments to answer these questions. Results in experiment 1 suggested that verbal working memory correlated with adults' perspective calculation, but with both processes in children's perspective taking. Results in experiment 2 showed that spatial working memory is associated with adults' perspective calculation and children's perspective selection. These findings suggest that different components of working memory play distinct roles in the processing of perspective taking, which is moderated by age.

SEC14L3 knockdown inhibited clear cell renal cell carcinoma proliferation, metastasis and sunitinib resistance through an SEC14L3/RPS3/NFκB positive feedback loop.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) arises from the renal parenchymal epithelium and is the predominant malignant entity of renal cancer, exhibiting increasing incidence and mortality rates over time. SEC14-like 3 (SEC14L3) has emerged as a compelling target for cancer intervention; nevertheless, the precise clinical implications and molecular underpinnings of SEC14L3 in ccRCC remain elusive. METHODS: By leveraging clinical data and data from the TCGA-ccRCC and GEO datasets, we investigated the association between SEC14L3 expression levels and overall survival rates in ccRCC patients. The biological role and mechanism of SEC14L3 in ccRCC were investigated via in vivo and in vitro experiments. Moreover, siRNA-SEC14L3@PDA@MUC12 nanoparticles (SSPM-NPs) were synthesized and assessed for their therapeutic potential against SEC14L3 through in vivo and in vitro assays. RESULTS: Our investigation revealed upregulated SEC14L3 expression in ccRCC tissues, and exogenous downregulation of SEC14L3 robustly suppressed the malignant traits of ccRCC cells. Mechanistically, knocking down SEC14L3 facilitated the ubiquitination-mediated degradation of ribosomal protein S3 (RPS3) and augmented IκBα accumulation in ccRCC. This concerted action thwarted the nuclear translocation of P65, thereby abrogating the activation of the nuclear factor kappa B (NFκB) signaling pathway and impeding ccRCC cell proliferation and metastasis. Furthermore, diminished SEC14L3 levels exerted a suppressive effect on NFKB1 expression within the NFκB signaling cascade. NFKB1 functions as a transcriptional regulator capable of binding to the SEC14L3 enhancer and promoter, thereby promoting SEC14L3 expression. Consequently, the inhibition of SEC14L3 expression was further potentiated, thus forming a positive feedback loop. Additionally, we observed that downregulation of SEC14L3 significantly increased the sensitivity of ccRCC cells to sunitinib. The evaluation of SSPM-NPs nanotherapy highlighted its effectiveness in combination with sunitinib for inhibiting ccRCC growth. CONCLUSION: Our findings not only underscore the promise of SEC14L3 as a therapeutic target but also unveil an SEC14L3/RPS3/NFκB positive feedback loop that curtails ccRCC progression. Modulating SEC14L3 expression to engage this positive feedback loop might herald novel avenues for ccRCC treatment.

The prevalence of developmental coordination disorder in children: a systematic review and meta-analysis.

Purpose: The aim of the study was to synthesize previous evidence and clarify the prevalence of developmental coordination disorder (DCD) in children by meta-analysis. Methods: A comprehensive computerized search of databases, including PubMed, Embase, Web of Science, The Cochrane Library, CINAHL, and PsycINFO databases, was conducted to identify relevant national and international articles published before 18 December 2023 on DCD prevalence in children. The meta-analysis of prevalence was conducted using Stata 18.0. Results: A total of 18 papers involving 31,203 patients were included. The prevalence of children with DCD was found to be 5%. A subgroup analysis showed that prevalence was 7% [95% confidence interval (CI) 4%-10%] and 4% (95% CI 3%-7%) for boys and girls, respectively; 4% (95% CI 2%-8%), 2% (95% CI 2%-2%), and 6% (95% CI 3%-10%) in Asia, Europe, and North America, respectively; and 18% (95% CI 8%-31%) and 6% (95% CI 4%-7%) for preterm (<37 weeks) and term infants (≥37 weeks), respectively. The prevalence of very low birth weight children (<1,250 g) with DCD was found to be 31%. Conclusion: In this study, we found that the prevalence of children with DCD in the general population was 5% and that preterm infants (<37 weeks) and very low birth weight infants (<1,250 g) have a higher prevalence of DCD and require early screening and regular follow-up. Systematic Review Registration: https://www.crd.york.ac.uk/, Identifier (CRD42024503320).

Low temperature alleviated the adverse effects of simulated transport stress on the intestinal health in Chinese soft-shelled turtle Pelodiscus sinensis.

Transport stress always poses a threat to aquatic animals. Transportation under low temperatures was often used to relieve transport stress in practical production of Chinese soft-shelled turtle Pelodiscus sinensis, but their effect on the turtle's intestinal barrier remains unclear. In this study, P. sinensis (initial weight 200 ± 20 g) were exposed to simulated transport stress for 12 h at control (30 °C) and low (20 °C) temperature, and then recovery for 24 h, and each treatment had 4 replicates with each replicate containing 4 turtles. The results showed that transportation induced obvious morphological and histological damages in intestinal villus, with a down-regulated expression of the tight junction related genes. Besides turtles in transport group showed an oxidative stress in intestine, which stimulated a physiological detoxification response together with apoptosis. Low temperature transport plays a mitigative effect on the transport stress of turtle intestine via relieved stress response. Specifically, the intestinal villus/crypt (V/C) ratio and the expression of tight junction genes in the low-temperature group were significantly higher compared to the control temperature group, while stress response parameters such as intestinal cortisol levels and hsp expression were significantly lower in the low-temperature group. Additionally, low temperature alleviated oxidative damage and apoptosis caused by transport stress relative to the control temperature group. However, the protective effect of low temperature on P. sinensis intestine was limited, especially after the temperature recovery stage. Overall, the findings of the present study demonstrated that transport stress would induce the disruption of intestinal integrity and oxidative damage, also activated the mucosal immunity and antioxidant enzyme system response of turtles. It was also suggested that low temperature could alleviate the adverse effects of transport stress on intestinal integrity through modulation of oxidative status and apoptosis, whereas much less impact after temperature recovery.

Finite element study on the mechanism of the influence of pretension force and block strength on the shear resistance of the anchor cable with C-shaped tube.

To prevent the early breakage of anchor cables under shear loads in support engineering, a combined structure of Anchor Cable with C-shaped Tube (ACC) has been proposed. The shear resistance enhancement mechanism of this structure and the mechanisms of various influencing factors have yet to be fully revealed. A refined nonlinear finite element model of ACC was original established using ABAQUS software, taking into account the actual structure of the steel strands and the interactions, such as contact and failure between the various components. Various anchor cable pretension forces and block strengths were set to investigate their effects on the shear mechanical response of ACC. The results successfully demonstrated a high correlation between peak shear load and pretension force. The results demonstrate that an increase in pretension force reduces the ACC's peak shear load and break displacement. Additionally, the structure exhibited higher flexural stiffness, the block strength was mobilized earlier, and the block failed locally more quickly. Under high pretension forces, the system exhibited higher shear stiffness in the early stages of shearing due to the influence of the axial force component. With low pretension forces, the ACC exhibited a larger break displacement due to the minor tensile deformation at the shear plane position for the same shear displacement. At low pretension forces, the structure's bending angle increased more rapidly during the middle and later stages of shearing, accompanied by a larger break displacement. Both of these factors led to a greater bending angle at the shear plane position at the point of failure. The results reveal the characteristic of the peak shear load initially increasing and then decreasing with the increase in test block strength, along with its underlying mechanism. As the block strength increased, the bending angle of the structure at the shear plane position increased more rapidly, resulting in higher shear stiffness. With high block strength, the combination of smaller break displacement and greater shear stiffness led to an initial increase followed by a decrease in peak shear load. A comprehensive RSSB (Relative Stiffness between Structure and Test Block) that considers both structural and test block stiffness was proposed. The deformation pattern of the structure was controlled by the RSSB. The higher the RSSB, the wider the plastic hinge extension range for the same shear displacement, the smaller the bending angle at the shear plane position, and the smaller the maximum curvature of the structure. The contact force of the C-shaped tube generally exhibited a "single peak" distribution. As the shear displacement increased, the peak position of the contact force moved away from the shear plane, and the maximum contact force increased rapidly and remained relatively stable. At the end of the shearing process, the contact force of the C-shaped tube exhibited a "double peak" distribution.

Isomalto-Oligosaccharide Potentiates Alleviating Effects of Intermittent Fasting on Obesity-Related Cognitive Impairment during Weight Loss and the Rebound Weight Gain.

Obesity-related cognitive dysfunction poses a significant threat to public health. The present study demonstrated mitigating effects of intermittent fasting (IF) and its combination with isomalto-oligosaccharides and IF (IF + IMO) on cognitive impairments induced by a high-fat-high-fructose (HFHF) diet in mice, with IF + IMO exhibiting superior effects. Transcriptomic analysis of the hippocampus revealed that the protective effects on cognition might be attributed to the suppression of toll-like receptor 4 (TLR4)/NFκB signaling, oxidative phosphorylation, and neuroinflammation. Moreover, both IF and IF + IMO modulated the gut microbiome and promoted the production of short-chain fatty acids, with IF + IMO displaying more pronounced effects. IF + IMO-modulated gut microbiota, metabolites, and molecular targets associated with cognitive impairments were further corroborated using human data from public databases Gmrepo and gutMgene. Furthermore, the fecal microbiome transplantation confirmed the direct impacts of IF + IMO-derived microbiota on improving cognition functions by suppressing TLR4/NFκB signaling and increasing BDNF levels. Notably, prior exposure to IF + IMO prevented weight-regain-induced cognitive decline, suppressed TLR4/NFκB signaling and inflammatory cytokines in the hippocampus, and mitigated weight regain-caused gut dysbacteriosis without altering body weight. Our study underscores that IMO-augmented alleviating effects of IF on obesity-related cognitive impairment particularly during weight-loss and weight-regain periods, presenting a novel nutritional strategy to tackle obesity-related neurodegenerative disorders.

New insights and investigation: Morphomolecular notes on the infraciliature, taxonomy, and systematics of pleurostomatid ciliates (Protozoa, Ciliophora), with establishment of a new suborder, two new genera, and three new species.

Pleurostomatid ciliates, as a highly diverse and widely distributed unicellular eukaryote group, play a crucial role in the cycling of nutrients and energy in microbial food webs. However, research on pleurostomatids remains insufficient, resulting in a paucity of molecular information and substantial gaps in knowledge of their phylogenetic relationships. In recent years, we investigated pleurostomatid diversity in various Chinese habitats, including their systematic relationships and taxonomic circumscriptions, which were comprehensively analyzed using an integrative morphomolecular approach. Results revealed that: (1) pleurostomatids can be categorized into two suborders, Protolitonotina subord. nov. and Amphileptina Jankowski, 1967; (2) Protolitonotina subord. nov. represents the ancestral pleurostomatid group and includes two genera, Protolitonotus and Heterolitonotus gen. nov., characterized by right kineties progressively shortened along rightmost full kineties and absence of a left dorsolateral kinety; (3) Heterolitonotus gen. nov. represents an orphan lineage and is defined by an oral slit extending to its dorsal margin; (4) " Protolitonotus clampi" does not group with congeners but instead represents an orphan lineage, thus Novilitonotus gen. nov. is established to which P. clampi is transferred as Novilitonotus clampi comb. nov.; (5) three new species, Apoamphileptus paraclaparedii sp. nov., Heterolitonotus rex gen. nov., sp. nov., and Loxophyllum apohelus sp. nov., are described; and (6) helices 21es6a to 21es6d within the V4 region of small subunit ribosomal RNA (SSU rRNA) may serve as a useful tool for discriminating pleurostomatids. The evolutionary relationships among all main lineages of pleurostomatids are discussed and a key to the identification of pleurostomatid genera is provided.

High glucose-induced senescence contributes to tubular epithelial cell damage in diabetic nephropathy.

Dysfunctional renal tubular epithelial cells, induced by high glucose, are commonly observed in the kidney tissues of diabetic nephropathy (DN) patients. The epithelial-mesenchymal transition (EMT) of these cells often leads to renal interstitial fibrosis and kidney damage in DN. High glucose also triggers mitochondrial damage and apoptosis, contributing further to the dysfunction of renal tubular epithelial cells. Cellular senescence, a recognized characteristic of DN, is primarily caused by high glucose. However, it remains unclear whether high glucose-induced cellular senescence in DN exacerbates the functional impairment of tubular epithelial cells. In this study, we examined the relationship between EMT and cellular senescence in kidney tissues from streptozotocin (STZ)-induced DN and HK-2 cells treated with high glucose (HG). We also investigated the impact of HG concentrations on tubular epithelial cells, specifically mitochondrial dysfunction, cellular senescence and apoptosis. These damages were primarily associated with the secretion of cytokines (such as IL-6, and TNF-α), production of reactive oxygen species (ROS), and an increase of intracellular Ca2+. Notably, resveratrol, an anti-aging agent, could effectively attenuate the occurrence of EMT, mitochondrial dysfunction, and apoptosis induced by HG. Mechanistically, anti-aging treatment leads to a reduction in cytokine secretion, ROS production, and intracellular Ca2+ levels.

Rational and Semirational Approaches for Engineering Salicylate Production in Escherichia coli.

Salicylate plays a pivotal role as a pharmaceutical intermediate in drugs, such as aspirin and lamivudine. The low catalytic efficiency of key enzymes and the inherent toxicity of salicylates to cells pose significant challenges to large-scale microbial production. In this study, we introduced the salicylate synthase Irp9 into an l-phenylalanine-producing Escherichia coli, constructing the shortest salicylate biosynthetic pathway. Subsequent protein engineering increased the catalytic efficiency of Irp9 by 33.5%. Furthermore, by integrating adaptive evolution with transcriptome analysis, we elucidated the crucial mechanism of efflux proteins in salicylate tolerance. The elucidation of this mechanism guided us in the targeted modification of these transport proteins, achieving a reported maximum level of 3.72 g/L of salicylate in a shake flask. This study highlights the importance of efflux proteins for enhancing the productivity of microbial cell factories in salicylate production, which also holds potential for application in the green synthesis of other phenolic acids.

Highland Barley Alleviates High-Fat Diet-Induced Obesity and Liver Injury Through the IRS2/PI3K/AKT Signaling Pathway in Rats.

Objectives: Highland barley (HB) consumption offers numerous health benefits; however, its impact on glycolipid metabolism abnormalities induced by a high-fat diet remains unclear. Consequently, this study aimed to investigate the therapeutic effects and underlying molecular mechanisms of HB in the context of obesity; Methods: Rats were fed either a high-fat diet (HFD) to induce obesity or a standard diet (SD) for six weeks. The rats in the HFD group were randomly assigned into five groups: HFD+HFD, HFD+SD, and low (30%), medium (45%), and high (60%) doses of the HB diet for an additional ten weeks. Analyses of serum lipid profiles, liver histology, transcriptomes, and untargeted metabolomes were conducted; Results: HB intake resulted in decreased weight gain, reduced feed intake, lower serum triglyceride and cholesterol levels, and diminished hepatic lipid accumulation. It also improved insulin and fasting blood glucose levels, and antioxidant capacity in the HFD-fed rats. Transcriptome analysis revealed that HB supplementation significantly suppressed the HFD-induced increase in the expression of Angptl8, Apof, CYP7A1, GDF15, Marveld1, and Nr0b2. Furthermore, HB supplementation reversed the HFD-induced decrease in Pex11a expression. Untargeted metabolome analysis indicated that HB primarily influenced the pentose phosphate pathway, the Warburg effect, and tryptophan metabolism. Additionally, integrated transcriptome and metabolome analyses demonstrated that the treatments affected the expression of genes associated with glycolipid metabolism, specifically ABCG8, CYP2C12, CYP2C24, CYP7A1, and IRS2. Western blotting confirmed that HB supplementation impacted the IRS2/PI3K/AKT signaling pathway; Conclusions: HB alleviates HFD-induced obesity and liver injury in an obese rat model possibly through the IRS2/PI3K/Akt signaling pathway.