A single photoreceptor splits perception and entrainment by cotransmission.

Vision enables both image-forming perception, driven by a contrast-based pathway, and unconscious non-image-forming circadian photoentrainment, driven by an irradiance-based pathway1,2. Although two distinct photoreceptor populations are specialized for each visual task3-6, image-forming photoreceptors can additionally contribute to photoentrainment of the circadian clock in different species7-15. However, it is unknown how the image-forming photoreceptor pathway can functionally implement the segregation of irradiance signals required for circadian photoentrainment from contrast signals required for image perception. Here we report that the Drosophila R8 photoreceptor separates image-forming and irradiance signals by co-transmitting two neurotransmitters, histamine and acetylcholine. This segregation is further established postsynaptically by histamine-receptor-expressing unicolumnar retinotopic neurons and acetylcholine-receptor-expressing multicolumnar integration neurons. The acetylcholine transmission from R8 photoreceptors is sustained by an autocrine negative feedback of the cotransmitted histamine during the light phase of light-dark cycles. At the behavioural level, elimination of histamine and acetylcholine transmission impairs R8-driven motion detection and circadian photoentrainment, respectively. Thus, a single type of photoreceptor can achieve the dichotomy of visual perception and circadian photoentrainment as early as the first visual synapses, revealing a simple yet robust mechanism to segregate and translate distinct sensory features into different animal behaviours.

Tethered peptide activation mechanism of the adhesion GPCRs ADGRG2 and ADGRG4.

Adhesion G protein-coupled receptors (aGPCRs) constitute an evolutionarily ancient family of receptors that often undergo autoproteolysis to produce α and ß subunits1-3. A tethered agonism mediated by the 'Stachel sequence' of the ß subunit has been proposed to have central roles in aGPCR activation4-6. Here we present three cryo-electron microscopy structures of aGPCRs coupled to the Gs heterotrimer. Two of these aGPCRs are activated by tethered Stachel sequences-the ADGRG2-ß-Gs complex and the ADGRG4-ß-Gs complex (in which ß indicates the ß subunit of the aGPCR)-and the other is the full-length ADGRG2 in complex with the exogenous ADGRG2 Stachel-sequence-derived peptide agonist IP15 (ADGRG2(FL)-IP15-Gs). The Stachel sequences of both ADGRG2-ß and ADGRG4-ß assume a U shape and insert deeply into the seven-transmembrane bundles. Constituting the FXφφφXφ motif (in which φ represents a hydrophobic residue), five residues of ADGRG2-ß or ADGRG4-ß extend like fingers to mediate binding to the seven-transmembrane domain and activation of the receptor. The structure of the ADGRG2(FL)-IP15-Gs complex reveals the structural basis for the improved binding affinity of IP15 compared with VPM-p15 and indicates that rational design of peptidic agonists could be achieved by exploiting aGPCR-ß structures. By converting the 'finger residues' to acidic residues, we develop a method to generate peptidic antagonists towards several aGPCRs. Collectively, our study provides structural and biochemical insights into the tethered activation mechanism of aGPCRs.

Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility.

Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.

Domain Switching Characteristics in Ga-Doped HfO2 Ferroelectric Thin Films with Low Coercive Field.

The gallium-doped hafnium oxide (Ga-HfO2) films with different Ga doping concentrations were prepared by adjusting the HfO2/Ga2O3 atomic layer deposition cycle ratio for high-speed and low-voltage operation in HfO2-based ferroelectric memory. The Ga-HfO2 ferroelectric films reveal a finely modulated coercive field (Ec) from 1.1 (HfO2/Ga2O3 = 32:1) to an exceptionally low 0.6 MV/cm (HfO2/Ga2O3 = 11:1). This modulation arises from the competition between domain nucleation and propagation speed during polarization switching, influenced by the intrinsic domain density and phase dispersion in the film with specific Ga doping concentrations. Higher Ec samples exhibit a nucleation-dominant switching mechanism, while lower Ec samples undergo a transition from a nucleation-dominant to a propagation-dominant reversal mechanism as the electric field increases. This work introduces Ga as a viable dopant for low Ec and offers insights into material design strategies for HfO2-based ferroelectric memory applications.

Single-cell transcriptome analyses reveal critical regulators of spermatogonial stem cell fate transitions.

BACKGROUND: Spermatogonial stem cells (SSCs) are the foundation cells for continual spermatogenesis and germline regeneration in mammals. SSC activities reside in the undifferentiated spermatogonial population, and currently, the molecular identities of SSCs and their committed progenitors remain unclear. RESULTS: We performed single-cell transcriptome analysis on isolated undifferentiated spermatogonia from mice to decipher the molecular signatures of SSC fate transitions. Through comprehensive analysis, we delineated the developmental trajectory and identified candidate transcription factors (TFs) involved in the fate transitions of SSCs and their progenitors in distinct states. Specifically, we characterized the Asingle spermatogonial subtype marked by the expression of Eomes. Eomes+ cells contained enriched transplantable SSCs, and more than 90% of the cells remained in the quiescent state. Conditional deletion of Eomes in the germline did not impact steady-state spermatogenesis but enhanced SSC regeneration. Forced expression of Eomes in spermatogenic cells disrupted spermatogenesis mainly by affecting the cell cycle progression of undifferentiated spermatogonia. After injury, Eomes+ cells re-enter the cell cycle and divide to expand the SSC pool. Eomes+ cells consisted of 7 different subsets of cells at single-cell resolution, and genes enriched in glycolysis/gluconeogenesis and the PI3/Akt signaling pathway participated in the SSC regeneration process. CONCLUSIONS: In this study, we explored the molecular characteristics and critical regulators of subpopulations of undifferentiated spermatogonia. The findings of the present study described a quiescent SSC subpopulation, Eomes+ spermatogonia, and provided a dynamic transcriptional map of SSC fate determination.

Trans-complementation of the viral movement protein mediates efficient expression of large target genes via a tobacco mosaic virus vector.

The development of plant virus-based expression systems has expanded rapidly owing to their potential applications in gene functional and disease resistance research, and industrial production of pharmaceutical proteins. However, the low yield of certain proteins, especially high-molecular-mass proteins, restricts the production scale. In this study, we observed that the tobacco mosaic virus (TMV)-mediated expression of a foreign protein was correlated with the amount of the movement protein (MP) and developed a TMV-derived pAT-transMP vector system incorporating trans-complementation expression of MP. The system is capable of efficient expression of exogenous proteins, in particular those with a high molecular mass, and enables simultaneous expression of two target molecules. Furthermore, viral expression of competent CRISPR-Cas9 protein and construction of CRISPR-Cas9-mediated gene-editing system in a single pAT-transMP construct was achieved. The results demonstrated a novel role for TMV-MP in enhancing the accumulation of a foreign protein produced from the viral vector or a binary expression system. Further investigation of the mechanism underlying this role will be beneficial for optimization of plant viral vectors with broad applications.

Human umbilical cord-derived mesenchymal stem cell transplantation improves the long COVID.

No effective treatments can ameliorate symptoms of long COVID patients. Our study assessed the safety and efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in the treatment of long COVID patients. Ten long COVID patients were enrolled and received intravenous infusions of UC-MSCs on Days 0, 7, and 14. Adverse events and clinical symptoms were recorded, and chest-high-resolution CT (HRCT) images and laboratory parameters were analyzed. During UC-MSCs treatment and follow-up, we did not observe serious adverse events, the symptoms of long COVID patients were significantly relieved in a short time, especially sleep difficulty, depression or anxiety, memory issues, and so forth, and the lung lesions were also repaired. The routine laboratory parameters did not exhibit any significant abnormalities following UC-MSCs transplantation (UMSCT). The proportion of regulatory T cells gradually increased, but it was not statistically significant until 12 months. The proportion of naive B cells was elevated, while memory B cells, class-switched B-cells, and nonswitched B-cells decreased at 1 month after infusion. Additionally, we observed a transient elevation in circulating interleukin (IL)-6 after UMSCT, while tumor necrosis factor (TNF)-α, IL-17A, and IL-10 showed no significant changes. The levels of circulating immunoglobulin (Ig) M increased significantly at month 2, while IgA increased significantly at month 6. Furthermore, the SARS-CoV-2 IgG levels remained consistently high in all patients at Month 6, and there was no significant decrease during the subsequent 12-month follow-up. UMSCT was safe and tolerable in long COVID patients. It showed potential in alleviating long COVID symptoms and improving interstitial lung lesions.

Significant improvement of n-contact performance and wall plug efficiency of AlGaN-based deep ultraviolet light-emitting diodes by atomic layer etching.

The reactive ion etching (RIE) process is needed to fabricate deep ultraviolet (DUV) light-emitting diodes (LEDs). However, the n-contact performance deteriorates when the high-Al n-AlGaN surface undergoes RIE, leading to decreased LED performance. In this study, we employed an atomic layer etching (ALE) technology to eliminate surface damage generated during the mesa etching process, thus enhancing the n-Al0.65Ga0.35N ohmic contact. The improved contact performance reduced LED operation voltage and mitigated device heat generation. It was observed that DUV LEDs treated with 200 cycles of ALE showed a reduction in operating voltage from 8.3 to 5.2 V at 10 mA, with a knee voltage of 4.95 V. The peak wall plug efficiency (WPE) was approximately 1.74 times that of reference devices. The x-ray photoelectron spectroscopy (XPS) analysis revealed that ALE removed the surface damage layer induced by plasma etching, eliminating surface nitrogen vacancies and increasing surface electron concentration. Consequently, it facilitated better ohmic contact formation on n-Al0.65Ga0.35N. This study demonstrates that the ALE technology achieves etching with minor surface damage and is suitable for use in III-nitride materials and devices to remove surface defects and contaminations, leading to improved device performance.

Tumour necrosis factor α regulates the miR-27a-3p-Sfrp1 axis in a mouse model of osteoporosis.

Osteoporosis is a metabolic bone disease that involves gradual loss of bone density and mass, thus resulting in increased fragility and risk of fracture. Inflammatory cytokines, such as tumour necrosis factor α (TNF-α), inhibit osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and several microRNAs are implicated in osteoporosis development. This study aimed to explore the correlation between TNF-α treatment and miR-27a-3p expression in BMSC osteogenesis and further understand their roles in osteoporosis. An osteoporosis animal model was established using ovariectomized (OVX) mice. Compared with Sham mice, the OVX mice had a significantly elevated level of serum TNF-α and decreased level of bone miR-27a-3p, and in vitro TNF-α treatment inhibited miR-27a-3p expression in BMSCs. In addition, miR-27a-3p promoted osteogenic differentiation of mouse BMSCs in vitro, as evidenced by alkaline phosphatase staining and Alizarin Red-S staining, as well as enhanced expression of the osteogenic markers Runx2 and Osterix. Subsequent bioinformatics analysis combined with experimental validation identified secreted frizzled-related protein 1 (Sfrp1) as a downstream target of miR-27a-3p. Sfrp1 overexpression significantly inhibited the osteogenic differentiation of BMSCs in vitro and additional TNF-α treatment augmented this inhibition. Moreover, Sfrp1 overexpression abrogated the promotive effect of miR-27a-3p on the osteogenic differentiation of BMSCs. Furthermore, the miR-27a-3p-Sfrp1 axis was found to exert its regulatory function in BMSC osteogenic differentiation via regulating Wnt3a-ß-catenin signalling. In summary, this study revealed that TNF-α regulated a novel miR-27a-3p-Sfrp1 axis in osteogenic differentiation of BMSCs. The data provide new insights into the development of novel therapeutic strategies for osteoporosis.

Quality of childcare and delayed child development in left-behind children in China.

BACKGROUND: Inequalities in job opportunities and income prompts many Chinese parents to leave rural regions to work in urban regions. Their children are left behind in rural regions, subjected to worse quality of childcare that jeopardizes their development. This study aimed to examine the association between quality of childcare and delayed child development in under-three years children left behind in China. METHODS: Cross-sectional national survey was conducted in children left behind in rural China in 2017. Exploratory and confirmatory factor analysis was used to develop a quality of childcare index. Mutlilevel analyses determined factors associated with quality of childcare and child development on a province and individual level. RESULT: The largest population of at-risk children left behind were found in higher-GDP provinces. Children left behind had the lowest mean quality of childcare score. Multilevel analysis found that province level accounted for a great proportion of variance observed. CONCLUSIONS: While migration to urban regions for work may improve household income, a trade-off in worse quality of childcare and developmental delays exists. With improving household income often being the greatest contributing factor for parental migration, policies to reduce inequalities in job opportunities and wealth between rural and urban regions are required. IMPACT: Previous studies identified higher prevalence of developmental delays in children left behind in China. However, quality of childcare has not been examined. Based on WHO's Nurturing Care Framework, we developed a quality of childcare index to assess its association with child development in children left behind. Greatest proportion of children left behind at-risk of developmental delays resided in higher-GDP states, indicating a trade-off in worse quality of childcare and developmental delays. Since improving household income is the main factor for parental migration, policies to close inequalities in job opportunities and wealth between rural and urban regions are required.

TfOH-Catalyzed Reactions of Aryl Methyl Ketones with Ynamides: Synthesis of 1-Amino-1H-indenes and 2,4-Dienamides.

The efficient synthesis of 1-amino-1H-indenes and 2,4-dienamides was realized via TfOH-catalyzed reactions of aryl methyl ketones with terminal ynamides in two distinct pathways. Aromatic ketones with high electrophilicity underwent [3 + 2] annulation with ynamides to produce 1-amino-1H-indenes, while aromatic ketones with low electrophilicity proceeded under the same conditions to afford 2,4-dienamides. Furthermore, the obtained 1-amino-1H-indenes could be converted into the corresponding 1H-indenes and dihydro-1H-indenes in excellent yields.

TMSOTf-Catalyzed Reactions of N-Arylynamides with Sulfilimines To Construct 2-Aminoindoles and α-Arylated Amidines.

Here, we disclose an efficient TMSOTf-catalyzed C-H annulation of aryl-terminated N-arylynamides with sulfilimines, leading to the practical assembly of various valuable 2-aminoindoles in generally moderate to excellent yields with a broad range of functional groups, while nonaryl terminated N-arylynamides undergo TMSOTf-catalyzed aminative arylation with sulfilimines providing α-arylated amidines.

Simple and field-adapted species identification of biological specimens combining multiplex multienzyme isothermal rapid amplification, lateral flow dipsticks, and universal primers for initial rapid screening without standard PCR laboratory.

Species identification of biological specimens can provide the valuable clues and accelerate the speed of prosecution material processing for forensic investigation, especially when the case scene is inaccessible and the physical evidence is cumbersome. Thus, establishing a rapid, simple, and field-adapted species identification method is crucial for forensic scientists, particularly as first-line technology at the crime scene for initial rapid screening. In this study, we established a new field-adapted species identification method by combining multiplex multienzyme isothermal rapid amplification (MIRA), lateral flow dipstick (LFD) system, and universal primers. Universal primers targeting COX I and COX II genes were used in multiplex MIRA-LFD system for seven species identification, and a dedicated MIRA-LFD system primer targeting CYT B gene was used to detect the human material. DNA extraction was performed by collecting DNA directly from the centrifuged supernatant. Our study found that the entire amplification process took only 15 min at 37 °C and the results of LFDs could be visually observed after 10 min. The detection sensitivity of human material could reach 10 pg, which is equivalent to the detection of single cell. Different common animal samples mixed at the ratio of 1 ng:1 ng, 10 ng:1 ng, and 1 ng:10 ng could be detected successfully. Furthermore, the damaged and degraded samples could also be detected. Therefore, the convenient, feasible, and rapid approach for species identification is suitable for popularization as first-line technology at the crime scene for initial rapid screening and provides a great convenient for forensic application.

Brønsted acid catalyzed Ficini [2 + 2] cycloaddition of ynamides with enones.

Herein, we describe a novel metal-free Brønsted acid-catalyzed Ficini [2 + 2] cycloaddition of ynamides with enones under mild reaction conditions, leading to the formation of various cyclobutenamides in generally good to excellent yields within short reaction times. This work represents the first example of ynamides involved in a nonmetal-catalyzed [2 + 2] cycloaddition with enones.

Understanding Variations in Ferrate Detection through the ABTS Method in the Presence of Electron-Rich Organic Compounds.

The chromogenic reaction between 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and ferrate [Fe(VI)] has long been utilized for Fe(VI) content measurement. However, the presence of electron-rich organic compounds has been found to significantly impact Fe(VI) detection using the ABTS method, leading to relative errors ranging from ∼88 to 100%. Reducing substances consumed ABTS•+ and resulted in underestimated Fe(VI) levels. Moreover, the oxidation of electron-rich organics containing hydroxyl groups by Fe(VI) could generate a phenoxyl radical (Ph•), promoting the transformation of Fe(VI) → Fe(V) → Fe(IV). The in situ formation of Fe(IV) can then contribute to ABTS oxidation, altering the ABTS•+:Fe(VI) stoichiometry from 1:1 to 2:1. To overcome these challenges, we introduced Mn(II) as an activator and 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic agent for Fe(VI) detection. This Mn(II)/TMB method enables rapid completion of the chromogenic reaction within 2 s, with a low detection limit of approximately 4 nM and a wide detection range (0.01-10 µM). Importantly, the Mn(II)/TMB method exhibits superior resistance to reductive interference and effectively eliminates the impact of phenoxyl-radical-mediated intermediate valence iron transfer processes associated with electron-rich organic compounds. Furthermore, this method is resilient to particle interference and demonstrates practical applicability in authentic waters.

Prevalence and risk factors of sleep disorders in inflammatory bowel disease: a cross-sectional study.

BACKGROUND: Sleep disorders are one of the major public health problems, which can potentially induce inflammation and exacerbate disease activity, resulting in compromised sleep quality. This study aimed to investigate the prevalence and risk factors associated with sleep disorders among patients with inflammatory bowel disease (IBD). METHODS: Between March 2023 and February 2024, the Pittsburgh Sleep Quality Index was employed to assess sleep quality in both IBD patients and healthy control subjects. Univariate and multivariate analysis were performed to identify the risk factors associated with SD in IBD patients. RESULTS: Overall, 208 IBD patients [150 Crohn's disease (CD) and 58 ulcerative colitis (UC)] and 199 healthy individuals were included. Sleep disorders were observed in 59.6% of patients with IBD, with a higher prevalence among females (63.5%) compared to males (56.9%) (P = 0.476). The prevalence of sleep disorders in IBD patients was significantly higher than that found in healthy controls (37.7%) (all P < 0.01). The prevalence of sleep disorders  among CD and UC patients was 58% and 63.8%, respectively (P = 0.291). The multivariate analysis revealed that older age (OR, 1.070; 95% CI: 1.035-1.105, P = 0.000), smoking (OR, 2.698; 95% CI: 1.089-6.685, P = 0.032), and depression (OR, 4.779; 95% CI: 1.915-11.928, P = 0.001) were risk factors for sleep disorders in IBD patients. However, higher body mass index (OR, 0.879; 95% CI: 0.790-0.977, P = 0.017) was identified as a protective factor. CONCLUSION: Sleep disorders are common among IBD patients regardless of activity levels. Smoking and depression are the major risk factors.

CO Oxidation Promoted by NO Adsorption on RhMn2O3- Cluster Anions.

CO oxidation represents an important model reaction in the gas phase to provide a clear structure-reactivity relationship in related heterogeneous catalysis. Herein, in combination with mass spectrometry experiments and quantum-chemical calculations, we identified that the RhMn2O3- cluster cannot oxidize CO into gas-phase CO2 at room temperature, while the NO preadsorbed products RhMn2O3-[(NO)1,2] are highly reactive in CO oxidation. This discovery is helpful to get a fundamental understanding on the reaction behavior in real-world three-way catalytic conditions where different kinds of reactants coexist. Theoretical calculations were performed to rationalize the crucial roles of preadsorbed NO where the strongly attached NO on the Rh atom can greatly stabilize the products RhMn2O2-[(NO)1,2] during CO oxidation and at the same time works together with the Rh atom to store electrons that stay originally in the attached CO2- unit. The leading result is that the desorption of CO2, which is the rate-determining step of CO oxidation by RhMn2O3-, can be greatly facilitated on the reactions of RhMn2O3-[(NO)1,2] with CO.

Single-dose methamphetamine administration impairs ORM retrieval in mice via excessive DA-mediated inhibition of PrLGlu activity.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

SGLT2 inhibitors ameliorate NAFLD in mice via downregulating PFKFB3, suppressing glycolysis and modulating macrophage polarization.

Sodium-glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i) is a novel class of anti-diabetic drug, which has displayed a promising benefit for non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of SGLT2i against NAFLD and the underlying mechanisms. The db/db mice and western diet-induced NAFLD mice were treated with dapagliflozin (1 mg·kg-1·d-1, i.g.) or canagliflozin (10 mg·kg-1·d-1, i.g.) for 8 weeks. We showed that the SGLT2i significantly improved NAFLD-associated metabolic indexes, and attenuated hepatic steatosis and fibrosis. Notably, SGLT2i reduced the levels of pro-inflammatory cytokines and chemokines, downregulated M1 macrophage marker expression and upregulated M2 macrophage marker expression in liver tissues. In cultured mouse bone marrow-derived macrophages and human peripheral blood mononuclear cell-derived macrophages, the SGLT2i (10, 20 and 40 µmol/L) significantly promoted macrophage polarization from M1 to M2 phenotype. RNA sequencing, Seahorse analysis and liquid chromatography-tandem mass spectrometry analysis revealed that the SGLT2i suppressed glycolysis and triggered metabolic reprogramming in macrophages. By using genetic manipulation and pharmacological inhibition, we identified that the SGLT2i targeted PFKFB3, a key enzyme of glycolysis, to modulate the macrophage polarization of M1 to M2 phenotype. Using a co-culture of macrophages with hepatocytes, we demonstrated that the SGLT2i inhibited lipogenesis in hepatocytes via crosstalk with macrophages. In conclusion, this study highlights a potential therapeutic application for repurposing SGLT2i and identifying a potential target PFKFB3 for NAFLD treatment.

Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.