Obesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. There is growing recognition that food motivation is altered in people with ...obesity. However, it remains unclear how brain circuits that control food motivation are altered in obese animals.
Using a novel behavioral assay that quantifies work during food seeking, in vivo and ex vivo cell-specific recordings, and a synaptic blocking technique, we tested the hypothesis that activity of circuits promoting appetitive behavior in the core of the nucleus accumbens (NAc) is enhanced in the obese state, particularly during food seeking.
We first confirmed that mice made obese with ad libitum exposure to a high fat diet work harder than lean mice to obtain food, consistent with an increase in food motivation in obese mice. We observed greater activation of D
receptor-expressing NAc spiny projection neurons (NAc D1
) during food seeking in obese mice relative to lean mice. This enhanced activity was not observed in D
receptor-expressing neurons (D2
). Consistent with these in vivo findings, both intrinsic excitability and excitatory drive onto D1
were enhanced in obese mice relative to lean mice, and these measures were selective for D1
. Finally, blocking synaptic transmission from D1
, but not D2
, in the NAc core decreased physical work during food seeking and, critically, attenuated high fat diet-induced weight gain.
These experiments demonstrate the necessity of NAc core D1
in food motivation and the development of diet-induced obesity, establishing these neurons as a potential therapeutic target for preventing obesity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Carbon nanofiber (CNF) papers have been widely used in many renewable energy systems, and the development of its catalytic function is of great significance and a major challenge. In this work, we ...pioneer a time- and cost-efficient strategy for the preparation of large-area flexible CNF films with uniformly distributed diatomic FeN3-CoN3 sites (Fe1Co1-CNF). Due to the excellent compatibility and similar functionality of the pre-designed ZnFeCo-NC precursors (ZnFeCo-pre) with the electrospun polymer polyacrylonitrile (PAN), the mixture of ZnFeCo-pre and PAN can be co-electrospun and subject to a standard CNF fabrication process. The resulting Fe1Co1-CNF exhibits excellent bifunctional catalytic performance for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), attributing to the abundant dual catalytic FeN3-CoN3 sites which are mutually beneficial for attaining optimal electronic properties for the adsorption/desorption of reaction intermediates. The assembled liquid-electrolyte ZAB provides a high specific power of 201.7 mW cm−2 and excellent cycling stability. More importantly, due to the good mechanical strength and flexibility of Fe1Co1-CNF, portable ZAB with exceptional shape deformability and stability can be demonstrated, in which Fe1Co1-CNF utility as an integrated free-standing membrane electrode. These findings provide a facile strategy for manufacturing flexible multi-functional catalytic electrodes with high production.
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•Large-area self-standing flexible CNF film with diatomic Fe-Co sites was developed.•The diatomic Fe-Co sites render optimized adsorption of O-containing intermediates.•The Fe1Co1-CNF exhibits superior bifunctional ORR/OER performance.•The Fe1Co1-CNF shows great potential in liquid/flexible Zn-air battery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
T cell exhaustion in the tumor microenvironment has been demonstrated as a substantial contributor to tumor immunosuppression and progression. However, the correlation between T cell exhaustion and ...osteosarcoma (OS) remains unclear.
In our present study, single-cell RNA-seq data for OS from the GEO database was analysed to identify CD8+ T cells and discern CD8+ T cell subsets objectively. Subgroup differentiation trajectory was then used to pinpoint genes altered in response to T cell exhaustion. Subsequently, six machine learning algorithms were applied to develop a prognostic model linked with T cell exhaustion. This model was subsequently validated in the TARGETs and Meta cohorts. Finally, we examined disparities in immune cell infiltration, immune checkpoints, immune-related pathways, and the efficacy of immunotherapy between high and low TEX score groups.
The findings unveiled differential exhaustion in CD8+ T cells within the OS microenvironment. Three genes related to T cell exhaustion (RAD23A, SAC3D1, PSIP1) were identified and employed to formulate a T cell exhaustion model. This model exhibited robust predictive capabilities for OS prognosis, with patients in the low TEX score group demonstrating a more favorable prognosis, increased immune cell infiltration, and heightened responsiveness to treatment compared to those in the high TEX score group.
In summary, our research elucidates the role of T cell exhaustion in the immunotherapy and progression of OS, the prognostic model constructed based on T cell exhaustion-related genes holds promise as a potential method for prognostication in the management and treatment of OS patients.
•The paper empirically investigates the impact of enterprises' participation in targeted poverty alleviation on the cost of debt financing.•We verify the mechanisms are information asymmetry effect, ...brand value and reputation effect and ESG investment effect.•Furthermore, we find that private enterprises' participation in targeted poverty alleviation is more effective in reducing their debt financing costs compared with state-owned enterprises.
Poverty reduction is a hot topic in current academic research. Using a sample of Shanghai and Shenzhen A-share listed enterprises in China, this paper investigates whether firms participate in targeted poverty relief project can reduce debt financing costs. The study finds that enterprises' participation in targeted poverty alleviation effectively reduces debt financing costs. Mechanism tests further demonstrate that such participation diminishes the information asymmetry between internal and external enterprises, enhances brand value and reputation, attracts ESG investors to invest, and ultimately results in reduced debt financing costs. Furthermore, private enterprises' participation in targeted poverty alleviation is more effective in reducing their debt financing costs compared with state-owned enterprises. These findings highlight the win-win nature of enterprises' involvement in targeted poverty alleviation, offering valuable insights for developing countries to sustainably eliminate poverty.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Antimicrobial transformation products (ATPs) in the environment have raised extensive concerns in recent years due to their potential health risks. However, only a few ATPs have been investigated, ...and most of the transformation pathways of antimicrobials have not been completely elucidated. In this study, we developed a nontarget screening strategy based on molecular networks to detect and identify ATPs in pharmaceutical wastewater. We identified 52 antimicrobials and 49 transformation products (TPs) with a confidence level of three or above. Thirty of the TPs had not been previously reported in the environment. We assessed whether TPs could be classified as persistent, mobile, and toxic (PMT) substances based on recent European criteria for industrial substances. Owing to poor experimental data, definitive PMT classifications could not be established for novel ATPs. PMT assessment based on structurally predictive physicochemical properties revealed that 47 TPs were potential PMT substances. These results provide evidence that novel ATPs should be the focus of future research.
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IJS, KILJ, NUK, PNG, UL, UM
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•We synthesize TiO2-COOH and TiO2-NH2 nanoparticles with improved dispersibility.•TiO2-COOH and TiO2-NH2 show low cytotoxicity compare to bare TiO2.•TiO2-NH2 shows higher cellular ...uptake efficiency than TiO2-COOH.•Early exocytosis of TiO2-NH2 from HeLa cell is found after 6h incubation.•Clathrin-endocytic pathway dominates in the intracellular process of TiO2-NH2.
Titanium dioxide nanoparticles (TiO2 NPs) have a potential in the field of biological application. However, its poor dispersibility in water hampered its applications. In this study, 3-phosphonopropionic acid and 3-aminopropyl-triethoxysilane were respectively used for surface modification on TiO2 NPs with negative and positive surface charges (denoted as TiO2-COOH and TiO2-NH2). Zeta potentials of the prepared samples with high absolute value demonstrate the great improvement in their dispersibility. In terms of viability experiment, both TiO2-COOH and TiO2-NH2 showed low cytotoxicity. The cellular uptake efficiency and the uptake pathways of TiO2-COOH and TiO2-NH2 for cancer cells were studied. The exocytosis of TiO2-NH2 was also observed in the experiment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Layered double hydroxides (LDHs) have been recognized to have great potential for the treatment of heavy metals in wastewater and soil through various mechanisms. Isomorphic substitution is an ...important mechanism for the sorption of heavy metal cations with LDH reconstruction and highly stable product formation. However, sorption performance, structure-related relationships, and, more importantly, stability are still poorly understood. In this study, a series of LDHs with different structures were synthesized to evaluate their cadmium (Cd) sorption performance and stability concerning the isomorphic substitution mechanism. Divalent cation types in the LDH lattice determined the Cd sorption capacity as well as the isomorphic substitution possibility, following the order of hydroxide solubility of divalent cations (MII): Ca2+>Mg2+>(Cd2+) > Ni2+>Zn2+. In addition, CaAl-LDH exhibited a super-high Cd sorption capacity of 625.0 mg g−1. Cd sorption by LDHs with different interlayer anion types and divalent/trivalent cation molar ratios varied due to crystallite size-related MII release through cation-exchange/isomorphic substitution. Coexisting cations (e.g., Zn2+, Ni2+, Mg2+) influence the sorption performance of MII-LDH mainly through isomorphic substitution mechanism, largely depending on the solubility of MII(OH)2 with a trend of stable product formation. Furthermore, Mg2.9Cd0.1AlCl-LDH was fabricated, and limited Cd dissolution without destruction of the LDH structure was observed under various conditions. For example, only 7.69%, 2.16% and 0.96% of Cd was released from as-prepared Mg2.9Cd0.1AlCl-LDH in NaCl solution (0.02 mol L−1, pH 5), soil extract, and soil matrix, respectively. The very low leaching of Cd from Cd-containing LDHs indicated the high stability of LDH-sorbed Cd via isomorphic substitution and feasible practical application in Cd sequestration in wastewater treatment and soil remediation.
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•Eleven LDHs were synthesized to evaluate Cd sorption performance.•Ca3AlCl-LDH shows super high Cd sorption capacity of 625 mg g−1•Cd-bearing MgAlCl-LDH was fabricated to assess Cd sorption stability.•Low Cd leaching from Mg2.9Cd0.1Al-LDH was observed ranging from 7.7% to 0.96%.•Isomorphic substitution facilitated Cd sorption and induced super stable products.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Curcuminoids are functional food additives, and the effect on gonadal hormone biosynthesis remains unclear. Gonads contain 3β-hydroxysteroid dehydrogenase isoforms, h3β-HSD2 (humans) and r3β-HSD1 ...(rats), which catalyse pregnenolone into progesterone. The potency and mechanisms of curcuminoids to inhibit 3β-HSD activity were explored. The inhibitory potency was bisdemethoxycurcumin (IC
50
, 1.68 µM) >demethoxycurcumin (3.27 µM) > curcumin (13.87 µM) > tetrahydrocurcumin (109.0 µM) > dihydrocurcumin and octahydrocurcumin on KGN cell h3β-HSD2, while that was bisdemethoxycurcumin (1.22 µM) >demethoxycurcumin (2.18 µM) > curcumin (4.12 µM) > tetrahydrocurcumin (102.61 µM) > dihydrocurcumin and octahydrocurcumin on testicular r3β-HSD1. All curcuminoids inhibited progesterone secretion by KGN cells under basal and forskolin-stimulated conditions at >10 µM. Docking analysis showed that curcuminoids bind steroid-active site with mixed or competitive mode. In conclusion, curcuminoids inhibit gonadal 3β-HSD activity and de-methoxylation of curcumin increases inhibitory potency and metabolism of curcumin by saturation of carbon chain losses inhibitory potency.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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