High-Entropy Strategy to Achieve Electronic Band Convergence for High-Performance Thermoelectrics.

Multiband convergence has attracted significant interest due to its positive effects on further improving thermoelectric performance. However, the current research mainly focuses on two- or three-band convergence in lead chalcogenides through doping and alloying. Therefore, exploring a new strategy to facilitate more-band convergence has instructive significance and practical value in thermoelectric research. Herein, we first propose a high-entropy strategy to achieve four-band convergence for optimizing thermoelectric performance. Taking high-entropy AgSbPbSnGeTe5 as an example, we found that the emergence of more-band convergence occurs as the configuration entropy increases; in particular, the four-band convergence occurs in high-entropy AgSbPbSnGeTe5. The overlap of multiatom orbitals in the high-entropy sample contributes to the convergence of four valence bands, promoting the improvement of electrical performance. Meanwhile, due to large lattice distortion and disordered atoms, the phonon mean free path is effectively compressed, resulting in low lattice thermal conductivity of high-entropy AgSbPbSnGeTe5. Consequently, AgSbPbSnGeTe5 achieved an intrinsically high ZT value of 1.22 at 673 K, providing a cornerstone for further optimizing thermoelectric performance. For example, by generally optimizing the carrier concentration, a peak ZT value of ∼1.75 at 723 K is achieved. These insights offer a comprehensive understanding of the band structure affected by unique structures of high-entropy materials and also shed useful light on innovation mechanisms and functionalities for future improvement of thermoelectric performance.

NUS1 Variants Cause Lennox-Gastaut Syndrome Related to Unfolded Protein Reaction Activation.

NUS1 encodes the Nogo-B receptor, a critical regulator for unfolded protein reaction (UPR) signaling. Although several loss-of-function variants of NUS1 have been identified in patients with developmental and epileptic encephalopathy (DEE), the role of the NUS1 variant in Lennox-Gastaut syndrome (LGS), a severe child-onset DEE, remains unknown. In this study, we identified two de novo variants of NUS1, a missense variant (c.868 C > T/p.R290C) and a splice site variant (c.792-2 A > G), in two unrelated LGS patients using trio-based whole-exome sequencing performed in a cohort of 165 LGS patients. Both variants were absent in the gnomAD population and showed a significantly higher observed number of variants than expected genome-wide. The R290C variant was predicted to damage NUS1 and decrease its protein stability. The c.792-2 A > G variant caused premature termination of the protein. Knockdown of NUS1 activated the UPR pathway, resulting in apoptosis of HEK293T cells. Supplementing cells with expression of wild-type NUS1, but not the mutant (R290C), rescued UPR activation and apoptosis in NUS1 knockdown cells. Compared to wild-type Drosophila, seizure-like behaviors and excitability in projection neurons were significantly increased in Tango14 (homolog of human NUS1) knockdown and Tango14R290C/+ knock-in Drosophila. Additionally, abnormal development and a small body size were observed in both mutants. Activated UPR signaling was also detected in both mutants. Thus, NUS1 is a causative gene for LGS with dominant inheritance. The pathogenicity of these variants is related to the UPR signaling activation, which may be a common pathogenic mechanism of DEE.

Sex differences in colorectal cancer: with a focus on sex hormone-gut microbiome axis.

Sexual dimorphism has been observed in the incidence and prognosis of colorectal cancer (CRC), with men generally exhibiting a slightly higher incidence than women. Research suggests that this difference may be attributed to variations in sex steroid hormone levels and the gut microbiome. The gut microbiome in CRC shows variations in composition and function between the sexes, leading to the concept of 'microgenderome' and 'sex hormone-gut microbiome axis.' Conventional research indicates that estrogens, by promoting a more favorable gut microbiota, may reduce the risk of CRC. Conversely, androgens may have a direct pro-tumorigenic effect by increasing the proportion of opportunistic pathogens. The gut microbiota may also influence sex hormone levels by expressing specific enzymes or directly affecting gonadal function. However, this area remains controversial. This review aims to explore the differences in sex hormone in CRC incidence, the phenomenon of sexual dimorphism within the gut microbiome, and the intricate interplay of the sex hormone-gut microbiome axis in CRC. The objective is to gain a better understanding of these interactions and their potential clinical implications, as well as to introduce innovative approaches to CRC treatment.

Mitochondrial dynamics and colorectal cancer biology: mechanisms and potential targets.

Colorectal cancer (CRC) is a significant public health concern, and its development is associated with mitochondrial dysfunction. Mitochondria can adapt to the high metabolic demands of cancer cells owing to their plasticity and dynamic nature. The fusion-fission dynamics of mitochondria play a crucial role in signal transduction and metabolic functions of CRC cells. Enhanced mitochondrial fission promotes the metabolic reprogramming of CRC cells, leading to cell proliferation, metastasis, and chemoresistance. Excessive fission can also trigger mitochondria-mediated apoptosis. In contrast, excessive mitochondrial fusion leads to adenosine triphosphate (ATP) overproduction and abnormal tumor proliferation, whereas moderate fusion protects intestinal epithelial cells from oxidative stress-induced mitochondrial damage, thus preventing colitis-associated cancer (CAC). Therefore, an imbalance in mitochondrial dynamics can either promote or inhibit CRC progression. This review provides an overview of the mechanism underlying mitochondrial fusion-fission dynamics and their impact on CRC biology. This revealed the dual role of mitochondrial fusion-fission dynamics in CRC development and identified potential drug targets. Additionally, this study partially explored mitochondrial dynamics in immune and vascular endothelial cells in the tumor microenvironment, suggesting promising prospects for targeting key fusion/fission effector proteins against CRC.

Causal linkage between type 2 diabetes mellitus and inflammatory bowel disease: an integrated Mendelian randomization study and bioinformatics analysis.

Background: Observational studies have indicated associations between type 2 diabetes mellitus (T2DM) and both colorectal cancer (CRC) and inflammatory bowel disease (IBD). However, the underlying causality and biological mechanisms between these associations remains unclear. Methods: We conducted a bidirectional Mendelian randomization (MR) analysis employing summary statistics from genome-wide association studies involving European individuals. The inverse variance weighting (IVW) method was the primary method used to assess causality. Additionally, we applied MR Egger, Weighted median, Simple mode, and Weighted mode to evaluate the robustness of the results. Outliers were identified and eliminated using the MR-PRESSO, while the MR-Egger intercept was used to assess the horizontal pleiotropic effects of single nucleotide polymorphisms (SNPs). The heterogeneity was evaluated using the Cochrane Q test, and sensitivity analysis was performed using leave-one-out method. The F statistic was calculated to evaluate weak instrumental variable bias. Finally, a pilot bioinformatics analysis was conducted to explore the underlying biological mechanisms between T2DM and IBD/UC. Results: The IVW results demonstrated that T2DM significantly reduced risks of IBD (OR=0.885, 95% CI: 0.818-0.958, P=0.002) and ulcerative colitis (UC) (OR=0.887, 95% CI: 0.812-0.968, P=0.007). Although the 95% CIs of MR Egger, Weighted median, Simple mode, and Weighted mode were broad, the majority of their estimates were consistent with the direction of IVW. Despite significant heterogeneity among SNPs, no horizontal pleiotropy was observed. The leave-one-out analysis showed that the causality remained consistent after each SNP was removed, underscoring the reliability of the results. Reverse MR analysis indicated that genetic susceptibility to both CRC and IBD had no significant effect on the relative risk of T2DM. Ten hub genes were identified, which mainly enriched in pathways including maturity onset diabetes of the young, thyroid cancer, gastric acid secretion, longevity regulating pathway, melanogenesis, and pancreatic secretion. Conclusion: The presence of T2DM does not increase the risk of CRC or IBD. Moreover, T2DM might reduce risk of IBD, including UC. Conversely, the occurrence of CRC or IBD does not influence the risk of T2DM. The association between T2DM and IBD/UC may be related to the changes in multiple metabolic pathways and CTLA-4-mediated immune response.

Integrated network pharmacology, metabolomics, and transcriptomics of Huanglian-Hongqu herb pair in non-alcoholic fatty liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: The Huanglian-Hongqu herb pair (HH) is a synergistic drug combination used to treat non-alcoholic fatty liver disease (NAFLD). However, the molecular mechanism underlying the therapeuticeffects of HH requires further elucidation. AIM OF THE STUDY: The present study explored the potential mechanism of HH in treating NAFLD. MATERIALS AND METHODS: UPLC-Q-TOF-MS was employed to identify the drug constituents in HH. A NAFLD rat model was induced by a high-fat diet (HFD) and treated with different doses of HH. The functional mechanism of HH in NAFLD rats was predicted using network pharmacology, metabolomics and transcriptomics. Immunohistochemistry, real-time PCR, and Western blot were performed to validate the key mechanisms. RESULTS: Pharmacodynamic assessment demonstrated that HH exhibited improvements in lipid deposition and reduced hepatic oxidative stress in NAFLD rats. Hepatic wide-target metabolomics revealed that HH primarily modulated amino acids and their metabolites, fatty acids, organic acids and their derivatives, bile acids, and other liver metabolites. The enriched pathways included metabolic pathways, primary bile acid biosynthesis, and bile secretion. Network pharmacology analysis indicated that HH regulated the key pathways in NAFLD, notably PPAR, AMPK, NF-κB and other signaling pathways. Furthermore, hepatic transcriptomics, based on Illumina RNA-Seq sequencing analyses, suggested that HH improved NAFLD through metabolic pathways, the PPAR signaling pathway, primary bile acid biosynthesis, and fatty acid metabolism. Further mechanistic studies indicated that HH could regulate the genes and proteins associated with the PPAR signaling pathway. CONCLUSION: Our findings demonstrated that the potential therapeutic benefits of HH in ameliorating NAFLD by targeting the PPAR signaling pathway, thereby facilitating a more extensive use of HH in NAFLD.

Herbal medicine for the prevention of chemotherapy-induced nausea and vomiting in patients with advanced colorectal cancer: A prospective randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine is increasingly used as complementary therapy to manage nausea and vomiting in different cultures. One such herbal recipe is the Hezhong granules, which contain classical antiemetic formulations, and are commonly used to prevent chemotherapy-induced nausea and vomiting (CINV). Modern pharmacological studies have shown that the key components of Hezhong granules, including Pinellia ternata (Thunb.), Evodia rutaecarpa (Juss.), and Zingiber officinale exhibit significant antiemetic and antitumor properties. Despite this promising evidence, controlling CINV remains a significant challenge in cancer treatment. Moreover, there is a lack of scientifically designed clinical trials to validate the efficacy and safety of classical antiemetic formulas for CINV interventions. AIMS OF THE STUDY: To investigate the efficacy and safety of Hezhong granules in preventing CINV in patients with advanced colorectal cancer (CRC). METHODS: This study was conducted between October 2020 and February 2022 in 12 hospital wards in Southwest China. In this multicenter, randomized controlled trial, we enrolled patients with advanced CRC who received fluorouracil-based chemotherapy. The patients were randomly assigned in a 1:1 ratio to either the Hezhong granule group (receiving a 5-HT3-receptor antagonist, dexamethasone, and Hezhong granules) or the placebo group (receiving a 5-HT3-receptor antagonist, dexamethasone, and placebo) during the first and second courses of chemotherapy. A 5-day diary was provided to all patients. Acute and delayed CINV were defined as CINV occurring within 24 h or between 24 and 120 h after the start of treatment. The primary endpoints were complete response rate (CRR, defined as the proportion of patients without nausea/vomiting) and objective response rate (ORR, defined as the proportion of patients without nausea/vomiting plus mild nausea/vomiting) for both acute and delayed CINV. Secondary endpoints were the daily rates of CINV events and Functional Living Index-Emesis (FLIE). To identify the predictors of CINV, we conducted multivariate ordered logistic regression analysis. This study was registered with the Chinese Clinical Trial, number ChiCTR2100041643. RESULTS: A total of 120 participants were randomly assigned, of whom 112 (56/56) completed two cycles and were included in the full analysis. In the acute phase, there were minor improvements in the Hezhong granule group, but there were no significant differences in the CRRs for nausea and vomiting (mean difference:10.7 %, P = 0.318, 0.324), while the ORRs increased by approximately 17.5 % (mean difference:16.1 %, P = 0.051; 17.9 %, P = 0.037, respectively). In the delayed phase, significant improvements of approximately 20 % were observed in both the CRRs (mean difference:19.6 %, P = 0.053; 21.4 %, P = 0.035) and ORRs (mean difference:17.9 %, P = 0.037, 0.043) for nausea and vomiting. Additionally, the daily rate of CINV events showed a mean difference of 19 % (P < 0.05). According to FLIE scores, approximately 70 % of patients who received Hezhong granules reported an improvement in their quality of life, with CINV symptoms having"no impact on daily life (NIDL)". No serious adverse events were attributed to herbal medicine. CONCLUSIONS: Hezhong granules proved to be both effective and well-tolerated in preventing CINV in patients with advanced CRC, with notable benefits in preventing delayed CINV. These promising results set the stage for subsequent phase III clinical trials and experimental research on Hezhong Granules.

Multiple roles of baicalin and baicalein in the regulation of colorectal cancer.

The prevalence of colorectal cancer is increasing worldwide, and despite advances in treatment, colorectal cancer (CRC) remains in the top three for mortality due to several issues, including drug resistance and low efficiency. There is increasing evidence that baicalin and baicalein, novel small molecule inhibitor extracts of the Chinese herb Scutellaria baicalensis, have better anti-colorectal cancer effects and are less likely to induce drug resistance in cancer cells. The present review article explains the anti-proliferative properties of baicalin and baicalein in the context of against CRC. Additionally, it explores the underlying mechanisms by which these compounds modulate diverse signaling pathways associated with apoptosis, cell proliferation, tumor angiogenesis, invasion, metastasis, and tumor microenvironment. Moreover, this review article highlights the inhibitory effect of colorectal inflammatory-cancer transformation and the near-term therapeutic strategy of using them as adjuvant agents in chemotherapy.

Efficacy and safety of traditional plant-based medicines for preventing chronic oxaliplatin-induced peripheral neurotoxicity in patients with colorectal cancer: A systematic review and meta-analysis with core herb contribution.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional plant-based medicines (TMs) have been widely used to prevent chronic oxaliplatin-induced peripheral neurotoxicity (OIPN). However, the prevention and safety of TMs for chronic OIPN remain ambiguous. Furthermore, diverse TM prescriptions and complicated components limit in-depth research on the mechanisms of TMs. AIM OF THIS STUDY: To determine core TMs and potential pharmacological pathways on the basis of a thorough investigation into the preventive benefits and safety of oral TMs for chronic OIPN in colorectal cancer (CRC). METHODS: A search of the PubMed, Cochrane, Embase, CNKI, VIP, and Wanfang databases for RCTs reporting on TMs for chronic OIPN was conducted through December 1, 2022. Subgroup analysis, sensitivity analysis and meta-regression were applied to assess the impacts of influencing variables. The assessment of Risk of Bias was relied on Cochrane Risk of Bias tool. The funnel plot, Egger's test, and the Trim and Fill method were applied to identify potential publication bias. Trial sequential analyses (TSA) were carried out by the TSA tool to increase the robustness. The assessment of the quality of evidence was according to the GRADE system. System pharmacology analysis was employed to screen core herbal combinations to elucidate possible mechanisms for preventing chronic OIPN in CRC. RESULTS: The pooled effect estimate with robustness increased by TSA analysis demonstrated that oral TMs appeared to significantly decrease the incidence of chronic OIPN (RR = 0.66, 95% CI (0.56, 0.78); P＜0.00001), leukocytopenia (RR = 0.65, 95% CI (0.54,0.79); P＜0.00001), and nausea and vomiting (RR = 0.72, 95% CI (0.61,0.84); P＜0.0001) as well as improve the Objective Response Rate (ORR) (RR = 1.31, 95% CI (1.09,1.56); P = 0.003). The incidence of severe chronic OIPN was revealed a significant reduction, particularly when chemotherapy was administered for periods of time shorter than six months (RR = 0.33, 95% CI (0.15,0.71); P = 0.005; actuation duration＜3 months; RR = 0.33, 95% CI (0.17,0.62); P = 0.0007; actuation duration≥3 months, ＜6 months). The considerable heterogeneity among studies may be attributable to the severity of dysfunction categorized by grade and accumulated dosage. Using core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf. To regulate nuclear factor-kappa B against inflammation caused by activation of microglia might be an approach to preventing chronic OIPN. CONCLUSIONS: TMs appear to be effective and safe in the prevention of chronic OIPN, especially severe chronic OIPN. Additionally, core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf were presumably responsible for reducing the incidence of chronic OIPN, and the mechanism may be related to relieving inflammation. However, quality-assured trials with long-term follow-up for exploring inflammatory factors and preliminary research on core TMs and pharmacological pathways are needed.

Recent Advancements in Electrochemical Hydrogen Production via Hybrid Water Splitting.

As one of the most promising approaches to producing high-purity hydrogen (H2 ), electrochemical water splitting powered by the renewable energy sources such as solar, wind, and hydroelectric power has attracted considerable interest over the past decade. However, the water electrolysis process is seriously hampered by the sluggish electrode reaction kinetics, especially the four-electron oxygen evolution reaction at the anode side, which induces a high reaction overpotential. Currently, the emerging hybrid electrochemical water splitting strategy is proposed by integrating thermodynamically favorable electro-oxidation reactions with hydrogen evolution reaction at the cathode, providing a new opportunity for energy-efficient H2 production. To achieve highly efficient and cost-effective hybrid water splitting toward large-scale practical H2 production, much work has been continuously done to exploit the alternative anodic oxidation reactions and cutting-edge electrocatalysts. This review will focus on recent developments on electrochemical H2 production coupled with alternative oxidation reactions, including the choice of anodic substrates, the investigation on electrocatalytic materials, and the deep understanding of the underlying reaction mechanisms. Finally, some insights into the scientific challenges now standing in the way of future advancement of the hybrid water electrolysis technique are shared, in the hope of inspiring further innovative efforts in this rapidly growing field.

Mitochondrial fusion-fission dynamics and its involvement in colorectal cancer.

The incidence and mortality rates of colorectal cancer have elevated its status as a significant public health concern. Recent research has elucidated the crucial role of mitochondrial fusion-fission dynamics in the initiation and progression of colorectal cancer. Elevated mitochondrial fission or fusion activity can contribute to the metabolic reprogramming of tumor cells, thereby activating oncogenic pathways that drive cell proliferation, invasion, migration, and drug resistance. Nevertheless, excessive mitochondrial fission can induce apoptosis, whereas moderate mitochondrial fusion can protect cells from oxidative stress. This imbalance in mitochondrial dynamics can exert dual roles as both promoters and inhibitors of colorectal cancer progression. This review provides an in-depth analysis of the fusion-fission dynamics and the underlying pathological mechanisms in colorectal cancer cells. Additionally, it offers partial insights into the mitochondrial kinetics in colorectal cancer-associated cells, such as immune and endothelial cells. This review is aimed at identifying key molecular events involved in colorectal cancer progression and highlighting the potential of mitochondrial dynamic proteins as emerging targets for pharmacological intervention.

Interlayer Phonon Coupling from Heavy and Light Sublayers in a Natural Van der Waals Superlattice.

Layered compounds characterized by van der Waals gaps are often associated with relatively weak interlayer particle interactions. However, in specific scenarios, these seemingly feeble forces can exert an impact on interlayer interactions through subtle energy fluctuations, which can give rise to a diverse range of physical and chemical properties, particularly intriguing in the context of thermal transport. In this study, taking a natural superlattice composed of alternately stacked PbS and SnS2 sublayers as a model, we proposed that in a superlattice, there is strong hybridization between acoustic phonons of heavy sublayers and optical phonons of light sublayers. We identified newly generated vibration modes in the superlattice, such as interlayer shear and breathing, which exhibit lower sound velocity and contribute less to heat transport compared to their parent materials, which significantly alters the thermal behaviors of the superlattice compared to its bulk counterparts. Our findings on the behavior of interlayer phonons in superlattices not only can shed light on developing functional materials with enhanced thermal dissipation capabilities but also contribute to the broader field of condensed matter physics, offering insights into various fields, including thermoelectrics and phononic devices, and may pave the way for technological advancements in these areas.

Dual-Plasmon Resonance Coupling Promoting Directional Photosynthesis of Nitrate from Air.

Photocatalysis, particularly plasmon-mediated photocatalysis, offers a green and sustainable approach for direct nitrogen oxidation into nitrate under ambient conditions. However, the unsatisfactory photocatalytic efficiency caused by the limited localized electromagnetic field enhancement and short hot carrier lifetime of traditional plasmonic catalysts is a stumbling block to the large-scale application of plasmon photocatalytic technology. Herein, we design and demonstrate the dual-plasmonic heterojunction (Bi/Csx WO3 ) achieves efficient and selective photocatalytic N2 oxidation. The yield of NO3 - over Bi/Csx WO3 (694.32 µg g-1 h-1 ) are 2.4 times that over Csx WO3 (292.12 µg g-1 h-1 ) under full-spectrum irradiation. The surface dual-plasmon resonance coupling effect generates a surge of localized electromagnetic field intensity to boost the formation efficiency and delay the self-thermalization of energetic hot carriers. Ultimately, electrons participate in the formation of ⋅O2 - , while holes involve in the generation of ⋅OH and the activation of N2 . The synergistic effect of multiple reactive oxygen species drives the direct photosynthesis of NO3 - , which achieves the overall-utilization of photoexcited electrons and holes in photocatalytic reaction. The concept that the dual-plasmon resonance coupling effect facilitates the directional overall-utilization of photoexcited carriers will pave a new way for the rational design of efficient photocatalytic systems.

Electron transfer bridge inducing polarization of nitrogen molecules for enhanced photocatalytic nitrogen fixation.

Ammonia (NH3) plays a crucial role in the production of fertilizers, medicines, fibers, etc., which are closely relevant to the development of human society. However, the inert and nonpolar properties of NN seriously hinder artificial nitrogen fixation under mild conditions. Herein, we introduce a novel strategy to enhance the photocatalytic efficiency of N2 fixation through the directional polarization of N2 by rare earth metal atoms, which act as a local "electron transfer bridge." This bridge facilitates the transfer of delocalized electrons to the distal N atom and redirects the polarization of adsorbed N2 molecules. Taking cerium doped BiOCl (Ce-BiOCl) as an example, our results reveal that the electrons transfer to the distal N atom through the cerium atom, resulting in absorbed nitrogen molecular polarization. Consequently, the polarized nitrogen molecules exhibit an easier trend for NN cleavage and the subsequent hydrogenation process, and exhibit a greatly enhanced photocatalytic ammonia production rate of 46.7 µmol g-1 h-1 in cerium doped BiOCl, nearly 4 times higher than that of pure BiOCl. The original concept of directional polarization of N2 presented in this work not only deepens our understanding of the N2 molecular activation mechanism but also broadens our horizons for designing highly efficient catalysts for N2 fixation.

Telmisartan inhibits microglia-induced neurotoxic A1 astrocyte conversion via PPARγ-mediated NF-κB/p65 degradation.

Astrocytes are crucially involved in neuroinflammation. Activated astrocytes exhibit at least two phenotypes, A1 (neurotoxic) and A2 (neuroprotective). The A1 phenotype is the major reactive astrocyte phenotype involved in aging and neurodegenerative diseases. Telmisartan, which is an antihypertensive agent, is a promising neuroprotective agent. This study aimed to investigate the effects of telmisartan on the phenotype of reactive astrocytes. Astrocytes were activated by culturing with the conditioned medium derived from lipopolysaccharide-stimulated microglia. This conditioned medium induced early, transient A2 astrocyte conversion (within 24 h) and late, sustained A1 conversion (beginning at 24 h and lasting up to 7 days), with a concomitant increase in the production of pro-inflammatory cytokines (interleukin [IL]-1ß, tumor necrosis factor [TNF]α, and IL-6) and phosphorylation of nuclear factor-κB (NF-κB)/p65. Telmisartan treatment promoted and inhibited A2 and A1 conversion, respectively. Telmisartan reduced total and phosphorylated p65 protein levels. Losartan, a specific angiotensin II type-1 receptor (AT1R) blocker, did not influence the reactive state of astrocytes. Additionally, AT1R activation by angiotensin II did not induce the expression of pro-inflammatory cytokines and A1/A2 markers, indicating that the AT1R signaling pathway is not involved in the astrocyte-mediated inflammatory response. A peroxisome proliferator-activated receptor γ (PPARγ) antagonist reversed the effects of telmisartan. Moreover, telmisartan-induced p65 downregulation was reversed by the proteasome inhibitor MG132. These results indicate that telmisartan suppresses activated microglia-induced neurotoxic A1 astrocyte conversion through p65 degradation. Our findings contribute towards the elucidation of the anti-inflammatory activity of telmisartan in brain disorders.

Directional Shunting of Photogenerated Carriers in POM@MOF for Promoting Nitrogen Adsorption and Oxidation.

The efficient catalysis of nitrogen (N2 ) into high-value N-containing products plays a crucial role in the N economic cycle. However, weak N2 adsorption and invalid N2 activation remain two major bottlenecks in rate-determining steps, leading to low N2 fixation performance. Herein, an effective dual active sites photocatalyst of polyoxometalates (POMs)-based metal-organic frameworks (MOFs) is highlighted via altering coordination microenvironment and inducing directional shunting of photogenerated carriers to facilitate N2 /catalyst interaction and enhance oxidation performance. MOFs create more open unsaturated metal cluster sites with unoccupied d orbital possessing Lewis acidity to accept electrons from the 3σg bonding orbital of N2 for storage by combining with POMs to replace bidentate linkers. POMs act as electron sponges donating electrons to MOFs, while the holes directional flow to POMs. The hole-rich POMs with strong oxidation capacity are easily involved in oxidizing adsorbed N2 . Taking UiO-66 (C48 H28 O32 Zr6 ) and Mo72 Fe30 ([Mo72 Fe30 O252 (CH3 COO)12 {Mo2 O7 (H2 O)}2 {H2 Mo2 O8 (H2 O)}(H2 O)91 ]·150H2 O) as an example, Mo72 Fe30 @UiO-66 shows twofold enhanced adsorption of N2 (250.5 cm3  g-1 ) than UiO-66 (122.9 cm3 g-1 ) at P/P0  = 1. And, the HNO3 yield of Mo72 Fe30 @UiO-66 is 702.4 µg g-1  h-1 , ≈7 times and 24 times higher than UiO-66 and Mo72 Fe30 . This work provides reliable value for the storage and relaying artificial N2 fixation.

Realizing Plain Optimization of the Thermoelectric Properties in BiCuSeO Oxide via Self-Substitution-Induced Lattice Dislocations.

Seeking new strategies to tune the intrinsic defect and optimize the thermoelectric performance via no or less use of external doped elements (i.e., plain optimization) is an important method to realize the sustainable development of thermoelectric materials. Meanwhile, creating dislocation defects in oxide systems is quite challenging because the rigid and stiff ionic/covalent bonds can hardly tolerate the large strain energy associated with dislocations. Herein, taking BiCuSeO oxide as an example, the present work reports a successful construction of dense lattice dislocations in BiCuSeO by self-doping of Se at the O site (i.e., SeO self-substitution), and achieves plain optimization of the thermoelectric properties with only external Pb doping. Owing to the self-substitution-induced large lattice distortion and the potential reinforcement effect by Pb doping, high-density (about 3.0 × 1014 m-2) dislocations form in the grains, which enhances the scattering strength of mid-frequency phonon and results in a substantial low lattice thermal conductivity of 0.38 W m-1 K-1 at 823 K in Pb-doped BiCuSeO. Meanwhile, PbBi doping and Cu vacancy markedly improve the electrical conductivity while maintaining a competitively high Seebeck coefficient, thereby contributing to a highest power factor of 942 µW m-1 K-2. Finally, a remarkably enhanced zT value of 1.32 is obtained at 823 K in Bi0.94Pb0.06Cu0.97Se1.05O0.95 with almost compositional plainification. The high-density dislocation structure reported in this work will also provide a good inspiration for the design and construction of dislocations in other oxide systems.

Local cation-tuned reversible single-molecule switch in electric double layer.

The nature of molecule-electrode interface is critical for the integration of atomically precise molecules as functional components into circuits. Herein, we demonstrate that the electric field localized metal cations in outer Helmholtz plane can modulate interfacial Au-carboxyl contacts, realizing a reversible single-molecule switch. STM break junction and I-V measurements show the electrochemical gating of aliphatic and aromatic carboxylic acids have a conductance ON/OFF behavior in electrolyte solution containing metal cations (i.e., Na+, K+, Mg2+ and Ca2+), compared to almost no change in conductance without metal cations. In situ Raman spectra reveal strong molecular carboxyl-metal cation coordination at the negatively charged electrode surface, hindering the formation of molecular junctions for electron tunnelling. This work validates the critical role of localized cations in the electric double layer to regulate electron transport at the single-molecule level.

Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in the Drosophila model.

Introduction: With the advent of trio-based whole-exome sequencing, the identification of epilepsy candidate genes has become easier, resulting in a large number of potential genes that need to be validated in a whole-organism context. However, conducting animal experiments systematically and efficiently remains a challenge due to their laborious and time-consuming nature. This study aims to develop optimized strategies for validating epilepsy candidate genes using the Drosophila model. Methods: This study incorporate behavior, morphology, and electrophysiology for genetic manipulation and phenotypic examination. We utilized the Gal4/UAS system in combination with RNAi techniques to generate loss-of-function models. We performed a range of behavioral tests, including two previously unreported seizure phenotypes, to evaluate the seizure behavior of mutant and wild-type flies. We used Gal4/UAS-mGFP flies to observe the morphological alterations in the brain under a confocal microscope. We also implemented patch-clamp recordings, including a novel electrophysiological method for studying synapse function and improved methods for recording action potential currents and spontaneous EPSCs on targeted neurons. Results: We applied different techniques or methods mentioned above to investigate four epilepsy-associated genes, namely Tango14, Klp3A, Cac, and Sbf, based on their genotype-phenotype correlation. Our findings showcase the feasibility and efficiency of our screening system for confirming epilepsy candidate genes in the Drosophila model. Discussion: This efficient screening system holds the potential to significantly accelerate and optimize the process of identifying epilepsy candidate genes, particularly in conjunction with trio-based whole-exome sequencing.

Construction of Asymmetrical Dual Jahn-Teller Sites for Photocatalytic CO2 Reduction.

Photocatalytic CO2 reduction (PCR) expresses great attraction to convert useless greenhouse gas into valuable chemical feedstock. However, the weak interactions between catalytic sites and PCR intermediates constrains the PCR activity and selectivity. Herein, we proposed a new strategy to match the intermediates due to the maximum orbital overlap of catalytic sites and C1 intermediates by establishing dual Jahn-Teller (J-T) sites, in which, the strongly asymmetric J-T sites can break the nonpolar CO2 molecules and self-adapt the different structure of C1 intermediates. Taking cobalt carbonate hydroxide as an example, the weakly symmetric dual cobalt (Co2 ) dual J-T sites, weakly asymmetric Fe&Co sites and strongly asymmetric Cu&Co sites were assembled. After illumination, the interaction between dual J-T sites and the CO2 molecules enhances J-T distortion, which further modulates the PCR activity and selectivity. As a result, the Cu&Co sites exhibited CO yield of 8137.9 µmol g-1 , about 2.3-fold and 4.2-fold higher than that of the Fe&Co and Co2 sites within 5-hour photoreaction, respectively. In addition, the selectivity achieved as high as 92.62 % than Fe&Co (88.67 %) and Co2 sites (55.33 %). This work provides a novel design concept for the construction of dual J-T sites to regulate the catalytic activity and selectivity.