Alkyl effects on charge recombination in copper electrolyte-based dye-sensitized solar cells: Insights for targeted molecular design towards high performance.

Two quinoxaline dyes utilized in copper-electrolyte-based dye-sensitized solar cells (Cu-DSSCs) are theoretically investigated to analyze the impact of alkyl chains on dye performance. The investigation shows that ZS4, known for its record efficiency of up to 13.2 %, exhibits higher electron coupling and fewer binding sites for dye-[Cu(tmby)2]2+ interaction compared to ZS5. Contrary to common belief, alkyl chains are found to not only provide shielding but also hinder the interaction between dye and [Cu(tmby)2]2+ by influencing the optimal conformation of dyes, thereby impeding the charge recombination process. It is crucial to consider the influence of alkyl chains on dye conformation when discussing the relationship between dye structure and performance, rather than oversimplifying it as often done traditionally. Building on these findings, eight dyes are strategically designed by adjusting the position of the alkyl chain to further decrease charge recombination compared to ZS4. Theoretical evaluation of these dyes reveals that changing the alkyl chain on the nitrogen atom from 2-ethylhexyl (ZS4) to 1-hexylheptyl (D3-2) not only reduces the charge recombination rate but also enhances light harvesting ability. Therefore, D3-2 shows potential as a candidate for experimental synthesis of high-performance Cu-DSSCs with improved efficiency.

Observation of multiple topological bound states in the continuum in the photonic bilayer trimer lattice.

A topological bound state in the continuum (TBIC) is a novel topological phase that has attracted significant attention. Different from conventional topological insulators (TIs), where boundary states reside within gaps, TBICs can support unconventional boundary states that remain isolated from the surrounding bulk states. In this work, we experimentally demonstrate multiple TBICs in photonic bilayer trimer lattices using femtosecond laser writing technology. By modulating the interlayer coupling between two trimer chains, we observe the emergence of two distinct types of TBICs. Moreover, we experimentally achieve the coexistence of in-gap topological states and TBICs and demonstrate the transformation between them. Our work unveils new insights into the flexible construction of TBICs, and this method can be easily applied to other one-dimensional topological structures, offering promising avenues for further research.

Restricting Linker Rotation in Nanocages of ZIF-8 Membranes using Crown Ether "Molecular Locks" for Enhanced Propylene/Propane Separation.

ZIF-8 membranes have long been prized for their exceptional C3H6/C3H8 separation performance. On the other hand, ZIF-8 has structural flexibility, where the external pressure triggers channel expansion, potentially deteriorating the molecular sieving ability. Here, we demonstrate a reliable strategy to fine-tune the flexible pore structure of ZIF-8 by embedding crown ether within a ZIF-8 membrane. Benzo-15-crown-5 (15C5) was selected as the cavity occupant and perfectly confined in the sodalite (SOD) cage of ZIF-8. The 15C5 molecules, which have a size comparable to the nanocage, impose a spatial constraint on linker rotation, enabling the phase transition to a rigid structure in the flexible ZIF-8. The corresponding 15C5@ZIF-8 membranes achieve an ultrahigh C3H6/C3H8 selectivity of 220, outperforming that of most membranes. Unlike their flexible counterparts, the resulting membranes manifest a positive increase in the C3H6/C3H8 separation factor with elevated pressure, securing a record-high C3H6/C3H8 separation factor of 331 under 7 bar. More importantly, extraordinary separation stability was demonstrated with continuous measurement, which is highly desirable for practical applications.

Divergent roles of ADP-ribosylation factor GTPase-activating proteins in lignocellulose utilization of Trichoderma guizhouense NJAU4742.

BACKGROUND: The ability of lignocellulose degradation for filamentous fungi is always attributed to their efficient CAZymes system with broader applications in bioenergy development. ADP-ribosylation factor GTPase-activating proteins (Arf-GAPs), pivotal in fungal morphogenesis, lack comprehensive studies on their regulatory mechanisms in lignocellulose utilization. RESULTS: Here, the orthologs (TgGlo3 and TgGcs1) of Arf-GAPs in S. cerevisiae were characterized in Trichoderma guizhouense NJAU4742. The results indicated that overexpression of Tggcs1 (OE-Tggcs1) enhanced the lignocellulose utilization, whereas increased expression of Tgglo3 (OE-Tgglo3) elicited antithetical responses. On the fourth day of fermentation with rice straw as the sole carbon source, the activities of endoglucanase, cellobiohydrolase, xylanase, and filter paper of the wild-type strain (WT) reached 8.20 U mL-1, 4.42 U mL-1, 14.10 U mL-1, and 3.56 U mL-1, respectively. Compared to WT, the four enzymes activities of OE-Tggcs1 increased by 7.93%, 6.11%, 9.08%, and 12.92%, respectively, while those decreased to varying degrees of OE-Tgglo3. During the nutritional growth, OE-Tgglo3 resulted in the hyphal morphology characterized by sparsity and constriction, while OE-Tggcs1 led to a notable increase in vacuole volume. In addition, OE-Tggcs1 exhibited higher transport efficiencies for glucose and cellobiose thereby sustaining robust cellular metabolic rates. Further investigations revealed that Tgglo3 and Tggcs1 differentially regulated the transcription level of a dynamin-like GTPase gene (Tggtp), eliciting distinct redox states and apoptotic reaction, thus orchestrating the cellular response to lignocellulose utilization. CONCLUSIONS: Overall, these findings underscored the significance of TgArf-GAPs as pivotal regulators in lignocellulose utilization and provided initial insights into their differential modulation of downstream targets.

Nonplanar Nanographene with a Large Conjugated π-Surface.

Conjugated π-surfaces are ubiquitous in molecules and materials. However, large π-surfaces up to a few nanometers in size are difficult to construct in an atomically precise manner. They tend to aggregate because of strong π-π interactions, resulting in notorious problems for both purification and spectroscopic investigations. Here, by contrast, we report the design, synthesis, and full characterizations of a nonplanar nanographene 1, which has a large, precise, and nonstacked π-surface. It is soluble in common organic solvents and allows for thorough investigations. The structure of 1, comprising 85 fused rings with an extended π-surface of 3 nm in size, is unambiguously confirmed by single-crystal X-ray diffraction. Unusual electronic structures, record-high near-infrared absorption, pronounced magnetic shielding, and ultrastrong heteromolecular van der Waals complexations are demonstrated, enabling us to establish a clear structure-property relationship, which has been elusive for decades. These results have broad implications for studying and understanding various phenomena and processes relevant to both discrete and interacting π-surfaces.

In Vivo Self-Sorting of Peptides via In Situ Assembly Evolution.

Despite significant progress achieved in artificial self-sorting in solution, operating self-sorting in the body remains a considerable challenge. Here, we report an in vivo self-sorting peptide system via an in situ assembly evolution for combined cancer therapy. The peptide E3C16-SS-EIY consists of two disulfide-connected segments, E3C16SH and SHEIY, capable of independent assembly into twisted or flat nanoribbons. While E3C16-SS-EIY assembles into nanorods, exposure to glutathione (GSH) leads to the conversion of the peptide into E3C16SH and SHEIY, thus promoting in situ evolution from the nanorods into self-sorted nanoribbons. Furthermore, incorporation of two ligand moieties targeting antiapoptotic protein XIAP and organellar endoplasmic reticulum (ER) into the self-sorted nanoribbons allows for simultaneous inhibition of XIAP and accumulation surrounding ER. This leads to the cytotoxicity toward the cancer cells with elevated GSH levels, through activating caspase-dependent apoptosis and inducing ER dysfunction. In vivo self-sorting of E3C16-SS-EIY decorated with ligand moieties is thoroughly validated by tissue studies. Tumor-bearing mouse experiments confirm the therapeutic efficacy of the self-sorted assemblies for inhibiting tumor growth, with excellent biosafety. Our findings demonstrate an efficient approach to develop in vivo self-sorting systems and thereby facilitating in situ formulation of biomedical agents.

Phase separation of phospho-HDAC6 drives aberrant chromatin architecture in triple-negative breast cancer.

How dysregulated liquid-liquid phase separation (LLPS) contributes to the oncogenesis of female triple-negative breast cancer (TNBC) remains unknown. Here we demonstrate that phosphorylated histone deacetylase 6 (phospho-HDAC6) forms LLPS condensates in the nuclei of TNBC cells that are essential for establishing aberrant chromatin architecture. The disordered N-terminal domain and phosphorylated residue of HDAC6 facilitate effective LLPS, whereas nuclear export regions exert a negative dominant effect. Through phase-separation-based screening, we identified Nexturastat A as a specific disruptor of phospho-HDAC6 condensates, which effectively suppresses tumor growth. Mechanistically, importin-ß interacts with phospho-HDAC6, promoting its translocation to the nucleus, where 14-3-3θ mediates the condensate formation. Disruption of phospho-HDAC6 LLPS re-established chromatin compartments and topologically associating domain boundaries, leading to disturbed chromatin loops. The phospho-HDAC6-induced aberrant chromatin architecture affects chromatin accessibility, histone acetylation, RNA polymerase II elongation and transcriptional profiles in TNBC. This study demonstrates phospho-HDAC6 LLPS as an emerging mechanism underlying the dysregulation of chromatin architecture in TNBC.

Fludarabine, busulfan, and melphalan conditioning regimen in allogeneic hematopoietic stem cell transplantation for adult patients with myeloid malignancies: A multicenter retrospective study.

Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS-IB-1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05-60.03, p = 0.045; HR = 3.64, 95%CI 1.40-9.44, p = 0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11-0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.

Transcriptomic Analysis Reveals the Effect of Urea on Metabolism of Nannochloropsis oceanica.

The eukaryotic microalga Nannochloropsis oceanica represents a promising bioresource for the production of biofuels and pharmaceuticals. Urea, a crucial nutrient for the photosynthetic N. oceanica, stimulates the accumulation of substances such as lipids, which influence growth and physiology. However, the specific mechanisms by which N. oceanica responds and adapts to urea addition remain unknown. High-throughput mRNA sequencing and differential gene expression analysis under control and urea-added conditions revealed significant metabolic changes. This involved the differential expression of 2104 genes, with 1354 being upregulated and 750 downregulated, resulting in the reprogramming of crucial pathways such as carbon and nitrogen metabolism, photosynthesis, and lipid metabolism. The results specifically showed that genes associated with photosynthesis in N. oceanica were significantly downregulated, particularly those related to light-harvesting proteins. Interestingly, urea absorption and transport may depend not only on specialized transport channels such as urease but also on alternative transport channels such as the ABC transporter family and the CLC protein family. In addition, urea caused specific changes in carbon and lipid metabolism. Genes associated with the Calvin cycle and carbon concentration mechanisms were significantly upregulated. In lipid metabolism, the expression of genes associated with lipases and polyunsaturated fatty acid synthesis was highly activated. Furthermore, the expression of several genes involved in the tricarboxylic acid cycle and folate metabolism was enhanced, making important contributions to energy supply and the synthesis and modification of genes and macromolecules. Our observations indicate that N. oceanica actively and dynamically regulates the redistribution of carbon and nitrogen after urea addition, providing references for further research on the effects of urea on N. oceanica.

Ultrafast Laser Manipulation of In-Lattice Plasmonic Nanoparticles.

Plasmonic nanoparticles enable manipulation and enhancement of light fields at deep subwavelength scales, leading to structures and devices for diverse applications in optics. Despite hybrid plasmonic materials display remarkable optical properties due to interactions between components in nanoproximity, scalable production of plasmonic nanostructures within a single-crystalline matrix to achieve an ideal plasmon-crystal interface remains challenging. Here, a novel approach is presented to realize efficient manipulation of in-lattice plasmonic nanoparticles. Employing ultrafast-laser-driven plasmonic nanolithography, metallic nanoparticles with controllable morphology are precisely defined in the crystalline lattice of yttrium aluminum garnet (YAG) crystal. Through direct ion implantation, hybrid plasmonic material composed of nanoparticles embedded in a sub-surface amorphous YAG layer is created. Subsequently, femtosecond laser pulses guide formation and reshaping of plasmonic nanoparticles from the amorphous layer into the single-crystalline matrix along direction of light propagation, facilitated by a plasmon-mediated evolution of laser energy deposition. By tailoring resonance modes and optimizing the coupling between structured particle assemblies, a range of applications including polarization-dependent absorption and nonlinearity, controllable photoluminescence, and structural color generation is demonstrated. This research introduces a new approach for fabricating advanced optical materials featuring in-lattice plasmonic nanostructures, paving the way for the development of diverse functional photonic devices.

Assessment of Global Antibiotic Exposure Risk for Crops: Incorporating Soil Adsorption via Machine Learning.

The overuse and misuse of antibiotics could significantly increase their accumulation in soils. Consequently, antibiotics possibly enter food chain through crop uptake, posing a threat to global food security. Assessing the exposure risks of antibiotics for crops is crucial for addressing this global issue. In this study, we assessed global antibiotic exposure risk for crops, incorporating a machine learning adsorption model based on 4893 data sets from nine antibiotics. The optimized machine learning adsorption model, using the eXtreme Gradient Boosting algorithm and the class-specific modeling strategy, demonstrated relatively good performance. Notably, we introduced unsaturated soil conditions and considered spatiotemporal variations in soil moisture and temperature for the first time in such a risk assessment. Global distributions of antibiotic exposure risk for crops were predicted for March, June, September, and December. The results indicate that soil moisture significantly influences the exposure risk assessment. Relatively high exposure risk for crops was observed during months with colder local temperatures: generally June for the Southern Hemisphere and December for the Northern Hemisphere. The resulting map highlights high-risk agricultural regions, including southern Canada, western Russia, and southern Australia.

Targeting the transmembrane cytokine co-receptor neuropilin-1 in distal tubules improves renal injury and fibrosis.

Neuropilin-1 (NRP1), a co-receptor for various cytokines, including TGF-ß, has been identified as a potential therapeutic target for fibrosis. However, its role and mechanism in renal fibrosis remains elusive. Here, we show that NRP1 is upregulated in distal tubular (DT) cells of patients with transplant renal insufficiency and mice with renal ischemia-reperfusion (I-R) injury. Knockout of Nrp1 reduces multiple endpoints of renal injury and fibrosis. We find that Nrp1 facilitates the binding of TNF-α to its receptor in DT cells after renal injury. This signaling results in a downregulation of lysine crotonylation of the metabolic enzyme Cox4i1, decreases cellular energetics and exacerbation of renal injury. Furthermore, by single-cell RNA-sequencing we find that Nrp1-positive DT cells secrete collagen and communicate with myofibroblasts, exacerbating acute kidney injury (AKI)-induced renal fibrosis by activating Smad3. Dual genetic deletion of Nrp1 and Tgfbr1 in DT cells better improves renal injury and fibrosis than either single knockout. Together, these results reveal that targeting of NRP1 represents a promising strategy for the treatment of AKI and subsequent chronic kidney disease.

Protonated Z-scheme CdS-covalent organic framework heterojunction with highly efficient photocatalytic hydrogen evolution.

The low efficiency of photocatalytic hydrogen production from water is mainly suffer from limited light absorption, charge separation and water delivery to the active centers. Herein, an inorganic-organic Z-scheme heterojunction (CdS-COF-Ni) is constructed by in-situ growth of CdS nanosheets on the porphyrin-based covalent organic framework with nickel ions (COF-Ni) in the porphyrin centers. A built-in electric field is formed at the interface, which accelerates the separation and transfer of photogenerated charges. Moreover, through the surface protonation treatment in ascorbic acid (AC) solution, the hydrophilicity of the obtained composite is obviously increased and facilitates the transport of water molecules to the photocatalytic centers. Under the synergistic effect of the interfacial interaction and surface protonation treatment, the photocatalytic hydrogen production rate is optimized to be 18.23 mmol h-1 g-1 without adding any cocatalysts, which is 21 times that of CdS. After a series of photoelectrochemical measurements, in situ X-ray photoelectron spectroscopy (XPS) analysis, and density functional theory (DFT) calculations, it is found that the photocatalytic charge transfer pathway conforms to the Z-scheme mechanism, which not only greatly accelerates the separation and transfer of photogenerated charges, but also retains a high reduction capacity for water splitting. This work offers a good strategy for constructing highly efficient organic-inorganic heterojunctions for water splitting.

Atypical KCNQ1/Kv7 channel function in a neonatal diabetes patient: Hypersecretion preceded the failure of pancreatic ß-cells.

KCNQ1/Kv7, a low-voltage-gated K+ channel, regulates cardiac rhythm and glucose homeostasis. While KCNQ1 mutations are associated with long-QT syndrome and type2 diabetes, its function in human pancreatic cells remains controversial. We identified a homozygous KCNQ1 mutation (R397W) in an individual with permanent neonatal diabetes melitus (PNDM) without cardiovascular symptoms. To decipher the potential mechanism(s), we introduced the mutation into human embryonic stem cells and generated islet-like organoids (SC-islets) using CRISPR-mediated homology-repair. The mutation did not affect pancreatic differentiation, but affected channel function by increasing spike frequency and Ca2+ flux, leading to insulin hypersecretion. With prolonged culturing, the mutant islets decreased their secretion and gradually deteriorated, modeling a diabetic state, which accelerated by high glucose levels. The molecular basis was the downregulated expression of voltage-activated Ca2+ channels and oxidative phosphorylation. Our study provides a better understanding of the role of KCNQ1 in regulating insulin secretion and ß-cell survival in hereditary diabetes pathology.

Recent Progresses in the Multimodality Imaging Assessment of Myocardial Fibrosis.

Myocardial fibrosis, a common pathophysiological consequence of various cardiovascular diseases, is characterized by fibroblast activation and excessive deposition of extracellular matrix (ECM) collagen. Accumulating evidence indicates that myocardial fibrosis contributes to ventricular stiffness, systolic and diastolic dysfunction, and ultimately leads to the development of heart failure (HF). Early detection and targeted treatment of myocardial fibrosis is critical to reverse ventricular remodeling and improve clinical outcomes in patients with cardiovascular diseases. However, despite considerable progresses made in understanding molecular mechanisms of myocardial fibrosis, non-invasive imaging to assess myocardial fibrosis and guide clinical treatment is still not widely available, limiting the development of innovative treatment strategies. This review summarizes recent progresses of imaging modalities for detecting myocardial fibrosis, with a focus on nuclear medicine, echocardiography and cardiac magnetic resonance (CMR).

Bond Strength Assessment of Normal Strength Concrete-Ultra-High-Performance Fiber Reinforced Concrete Using Repeated Drop-Weight Impact Test: Experimental and Machine Learning Technique.

Ultra-high-performance concrete (UHPC) has been used in building joints due to its increased strength, crack resistance, and durability, serving as a repair material. However, efficient repair depends on whether the interfacial substrate can provide adequate bond strength under various loading scenarios. The objective of this study is to investigate the bonding behavior of composite U-shaped normal strength concrete-ultra-high-performance fiber reinforced concrete (NSC-UHPFRC) specimens using multiple drop-weight impact testing techniques. The composite interface was treated using grooving (Gst), natural fracture (Nst), and smoothing (Sst) techniques. Ensemble machine learning (ML) algorithms comprising XGBoost and CatBoost, support vector machine (SVM), and generalized linear machine (GLM) were employed to train and test the simulation dataset to forecast the impact failure strength (N2) composite U-shaped NSC-UHPFRC specimen. The results indicate that the reference NSC samples had the highest impact strength and surface treatment played a substantial role in ensuring the adequate bond strength of NSC-UHPFRC. NSC-UHPFRC-Nst can provide sufficient bond strength at the interface, resulting in a monolithic structure that can resist repeated drop-weight impact loads. NSC-UHPFRC-Sst and NSC-UHPFRC-Gst exhibit significant reductions in impact strength properties. The ensemble ML correctly predicts the failure strength of the NSC-UHPFRC composite. The XGBoost ensemble model gave coefficient of determination (R2) values of approximately 0.99 and 0.9643 at the training and testing stages. The highest predictions were obtained using the GLM model, with an R2 value of 0.9805 at the testing stage.

Integration of Epigenome and Lactylome Reveals the Regulation of Lipid Production in Nannochloropsis oceanica.

Lysine lactylation (Kla) is a kind of novel post-translational modification (PTM) that participates in gene expression and various metabolic processes. Nannochloropsis has a remarkable capacity for triacylglycerol (TAG) production under nitrogen stress. To elucidate the involvement of lactylation in lipid synthesis, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) and mRNA-seq analyses to monitor lactylation modifications and transcriptome alterations in Nannochloropsis oceanica. In all, 2057 genes showed considerable variation between nitrogen deprivation (ND) and nitrogen repletion (NR) conditions. Moreover, a total of 5375 differential Kla peaks were identified, including 5331 gain peaks and 44 loss peaks under ND vs NR. The differential Kla peaks were primarily distributed in the promoter (≤1 kb) (71.07%), 5'UTR (22.64%), and exon (4.25%). Integrative analysis of ChIP-seq, transcriptome, and previous proteome and lactylome data elucidates the potential mechanism by which lactylation promotes lipid accumulation under ND. Lactylation facilitates autophagy and protein degradation, leading to the recycling of carbon into the tricarboxylic acid (TCA) cycle, thereby providing carbon precursors for lipid synthesis. Additionally, lactylation induces the redirection of carbon from membrane lipids to TAG by upregulating lipases and enhancing the TCA cycle and ß-oxidation pathways. This research offers a new perspective for the investigation of lipid biosynthesis in Nannochloropsis.

Inhibiting the self-discharging process of quantum batteries in non-Markovian noises.

One of the main challenges in developing high-performance quantum batteries is the self-discharging process, where energy is dissipated from a quantum battery into the environment. In this work, we investigate the influence of non-Markovian noises on the performance of a quantum battery. Our results demonstrate that adding auxiliary qubits to a quantum battery system can effectively suppress the self-discharging process, leading to an improvement in both the steady-state energy and extractable work. We reveal that the physical mechanism inhibiting the self-discharging process is the formation of system-environment bound states, rather than an increase in non-Markovianity. Our results could be of both theoretical and experimental interest in exploring the ability of quantum batteries to maintain long stored energy in the environment.

Revealing the gut microbiome mystery: A meta-analysis revealing differences between individuals with autism spectrum disorder and neurotypical children.

The brain-gut axis intricately links gut microbiota (GM) dysbiosis to the development or worsening of autism spectrum disorder (ASD). However, the precise GM composition in ASD and the effectiveness of probiotics are unclear. To address this, we performed a thorough meta-analysis of 28 studies spanning PubMed, PsycINFO, Web of Science, Scopus, and MEDLINE, involving 1,256 children with ASD and 1042 neurotypical children, up to February 2024. Using Revman 5.3, we analyzed the relative abundance of 8 phyla and 64 genera. While individuals with ASD did not exhibit significant differences in included phyla, they exhibited elevated levels of Parabacteroides, Anaerostipes, Faecalibacterium, Clostridium, Dorea, Phascolarctobacterium, Lachnoclostridium, Catenibacterium, and Collinsella along with reduced percentages of Barnesiella, Odoribacter, Paraprevotella, Blautia, Turicibacter, Lachnospira, Pseudomonas, Parasutterella, Haemophilus, and Bifidobacterium. Notably, discrepancies in Faecalibacterium, Clostridium, Dorea, Phascolarctobacterium, Catenibacterium, Odoribacter, and Bifidobacterium persisted even upon systematic exclusion of individual studies. Consequently, the GM of individuals with ASD demonstrates an imbalance, with potential increases or decreases in both beneficial and harmful bacteria. Therefore, personalized probiotic interventions tailored to ASD specifics are imperative, rather than a one-size-fits-all approach.

Phlorizin from Lithocarpus litseifolius [Hance] Chun ameliorates FFA-induced insulin resistance by regulating AMPK/PI3K/AKT signaling pathway.

BACKGROUND: Insulin resistance (IR) is the central pathophysiological feature in the pathogenesis of metabolic syndrome, obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia. As the main active ingredient in Lithocarpus litseifolius [Hance] Chun, previous studies have shown that phlorizin (PHZ) can reduce insulin resistance in the liver. However, the effect of phlorizin on attenuating hepatic insulin resistance has not been fully investigated, and whether this effect is related to AMPK remains unclear. PURPOSE: The present study aimed to further investigate the effect of phlorizin on attenuating insulin resistance and the potential action mechanism. METHODS: Free fatty acids (FFA) were used to induce insulin resistance in HepG2 cells. The effects of phlorizin and FFA on cell viability were detected by MTT analysis. Glucose consumption, glycogen synthesis, intracellular malondialdehyde (MDA), superoxide dismutase (SOD), total cholesterol (TC), and triglyceride (TG) contents were quantified after phlorizin treatment. Glucose uptake and reactive oxygen species (ROS) levels in HepG2 cells were assayed by flow cytometry. Potential targets and signaling pathways for attenuating insulin resistance by phlorizin were predicted by network pharmacological analysis. Moreover, the expression levels of proteins related to the AMPK/PI3K/AKT signaling pathway were detected by western blot. RESULTS: Insulin resistance was successfully induced in HepG2 cells by co-treatment of 1 mM sodium oleate (OA) and 0.5 mM sodium palmitate (PA) for 24 h. Treatment with phlorizin promoted glucose consumption, glucose uptake, and glycogen synthesis and inhibited gluconeogenesis in IR-HepG2 cells. In addition, phlorizin inhibited oxidative stress and lipid accumulation in IR-HepG2 cells. Network pharmacological analysis showed that AKT1 was the active target of phlorizin, and the PI3K/AKT signaling pathway may be the potential action mechanism of phlorizin. Furthermore, western blot results showed that phlorizin ameliorated FFA-induced insulin resistance by activating the AMPK/PI3K/AKT signaling pathway. CONCLUSION: Phlorizin inhibited oxidative stress and lipid accumulation in IR-HepG2 cells and ameliorated hepatic insulin resistance by activating the AMPK/PI3K/AKT signaling pathway. Our study proved that phlorizin played a role in alleviating hepatic insulin resistance by activating AMPK, which provided experimental evidence for the use of phlorizin as a potential drug to improve insulin resistance.