Evidence for a single-layer van der Waals multiferroic.

Multiferroic materials have attracted wide interest because of their exceptional static1-3 and dynamical4-6 magnetoelectric properties. In particular, type-II multiferroics exhibit an inversion-symmetry-breaking magnetic order that directly induces ferroelectric polarization through various mechanisms, such as the spin-current or the inverse Dzyaloshinskii-Moriya effect3,7. This intrinsic coupling between the magnetic and dipolar order parameters results in high-strength magnetoelectric effects3,8. Two-dimensional materials possessing such intrinsic multiferroic properties have been long sought for to enable the harnessing of magnetoelectric coupling in nanoelectronic devices1,9,10. Here we report the discovery of type-II multiferroic order in a single atomic layer of the transition-metal-based van der Waals material NiI2. The multiferroic state of NiI2 is characterized by a proper-screw spin helix with given handedness, which couples to the charge degrees of freedom to produce a chirality-controlled electrical polarization. We use circular dichroic Raman measurements to directly probe the magneto-chiral ground state and its electromagnon modes originating from dynamic magnetoelectric coupling. Combining birefringence and second-harmonic-generation measurements with theoretical modelling and simulations, we detect a highly anisotropic electronic state that simultaneously breaks three-fold rotational and inversion symmetry, and supports polar order. The evolution of the optical signatures as a function of temperature and layer number surprisingly reveals an ordered magnetic polar state that persists down to the ultrathin limit of monolayer NiI2. These observations establish NiI2 and transition metal dihalides as a new platform for studying emergent multiferroic phenomena, chiral magnetic textures and ferroelectricity in the two-dimensional limit.

Structural insights into the transcription activation mechanism of the global regulator GlnR from actinobacteria.

In actinobacteria, an OmpR/PhoB subfamily protein called GlnR acts as an orphan response regulator and globally coordinates the expression of genes responsible for nitrogen, carbon, and phosphate metabolism in actinobacteria. Although many researchers have attempted to elucidate the mechanisms of GlnR-dependent transcription activation, progress is impeded by lacking of an overall structure of GlnR-dependent transcription activation complex (GlnR-TAC). Here, we report a co-crystal structure of the C-terminal DNA-binding domain of GlnR (GlnR_DBD) in complex with its regulatory cis-element DNA and a cryo-EM structure of GlnR-TAC which comprises Mycobacterium tuberculosis RNA polymerase, GlnR, and a promoter containing four well-characterized conserved GlnR binding sites. These structures illustrate how four GlnR protomers coordinate to engage promoter DNA in a head-to-tail manner, with four N-terminal receiver domains of GlnR (GlnR-RECs) bridging GlnR_DBDs and the RNAP core enzyme. Structural analysis also unravels that GlnR-TAC is stabilized by complex protein-protein interactions between GlnR and the conserved ß flap, σAR4, αCTD, and αNTD domains of RNAP, which are further confirmed by our biochemical assays. Taken together, these results reveal a global transcription activation mechanism for the master regulator GlnR and other OmpR/PhoB subfamily proteins and present a unique mode of bacterial transcription regulation.

Synaptotagmin-1 is a bidirectional Ca2+ sensor for neuronal endocytosis.

Exocytosis and endocytosis are tightly coupled. In addition to initiating exocytosis, Ca2+ plays critical roles in exocytosis­endocytosis coupling in neurons and nonneuronal cells. Both positive and negative roles of Ca2+ in endocytosis have been reported; however, Ca2+ inhibition in endocytosis remains debatable with unknown mechanisms. Here, we show that synaptotagmin-1 (Syt1), the primary Ca2+ sensor initiating exocytosis, plays bidirectional and opposite roles in exocytosis­endocytosis coupling by promoting slow, small-sized clathrin-mediated endocytosis but inhibiting fast, large-sized bulk endocytosis. Ca2+-binding ability is required for Syt1 to regulate both types of endocytic pathways, the disruption of which leads to inefficient vesicle recycling under mild stimulation and excessive membrane retrieval following intense stimulation. Ca2+-dependent membrane tubulation may explain the opposite endocytic roles of Syt1 and provides a general membrane-remodeling working model for endocytosis determination. Thus, Syt1 is a primary bidirectional Ca2+ sensor facilitating clathrin-mediated endocytosis but clamping bulk endocytosis, probably by manipulating membrane curvature to ensure both efficient and precise coupling of endocytosis to exocytosis.

A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Spontaneous orbital polarization in the nematic phase of FeSe.

The origin of nematicity in FeSe remains a critical outstanding question towards understanding unconventional superconductivity in proximity to nematic order. To understand what drives the nematicity, it is essential to determine which electronic degree of freedom admits a spontaneous order parameter independent from the structural distortion. Here we use X-ray linear dichroism at the Fe K pre-edge to measure the anisotropy of the 3d orbital occupation as a function of in situ applied stress and temperature across the nematic transition. Along with using X-ray diffraction to precisely quantify the strain state, we reveal a lattice-independent, spontaneously ordered orbital polarization within the nematic phase, as well as an orbital polarizability that diverges as the transition is approached from above. These results provide strong evidence that spontaneous orbital polarization serves as the primary order parameter of the nematic phase.

Profilin1 Regulates Trophoblast Invasion and Macrophage Differentiation.

Unexplained recurrent spontaneous abortion (URSA) has been associated with the dysfunction of trophoblasts and decidual macrophages. Current evidence suggests that profilin1 (PFN1) plays an important role in many biological processes. However, little is known about whether PFN1 is related to URSA. Herein, the location of PFN1 was detected by immunohistochemistry, and the level of PFN1 was detected by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. The proliferation of trophoblasts was detected by CCK8 and 5-ethynyl-2'-deoxyuridine assays, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays were used to detect apoptosis of trophoblasts. The migration and invasion ability of trophoblasts was assessed by using the wound-healing test and transwell test. Polarization of macrophages was detected in macrophages cultured in trophoblast conditioned medium. PFN1 expression was observed in cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts and was decreased in the villous tissue of patients with URSA. The migration and invasion ability and cell viability of trophoblastic cell lines that underwent PFN1 knockdown significantly decreased, and apoptosis increased. Opposite findings were observed after the overexpression of PFN1 in trophoblastic cells. In addition, PFN1 could regulate trophoblast function through phosphatidylinositol 3-kinase/AKT signal transduction rather than mitogen-activated protein kinase signaling pathways. Finally, knockdown of PFN1 in trophoblasts promoted tumor necrosis factor-α secretion to induce macrophage polarization to M1 phenotype, mediated by the NF-κB signaling pathway. These findings indicate that PFN1 has a broad therapeutic potential for patients with URSA.

Spatially and Temporally Differentiated NOx and VOCs Emission Abatement Could Effectively Gain O3-Related Health Benefits.

The increasing level of O3 pollution in China significantly exacerbates the long-term O3 health damage, and an optimized health-oriented strategy for NOx and VOCs emission abatement is needed. Here, we developed an integrated evaluation and optimization system for the O3 control strategy by merging a response surface model for the O3-related mortality and an optimization module. Applying this system to the Yangtze River Delta (YRD), we evaluated driving factors for mortality changes from 2013 to 2017, quantified spatial and temporal O3-related mortality responses to precursor emission abatement, and optimized a health-oriented control strategy. Results indicate that insufficient NOx emission abatement combined with deficient VOCs control from 2013 to 2017 aggravated O3-related mortality, particularly during spring and autumn. Northern YRD should promote VOCs control due to higher VOC-limited characteristics, whereas fastening NOx emission abatement is more favorable in southern YRD. Moreover, promotion of NOx mitigation in late spring and summer and facilitating VOCs control in spring and autumn could further reduce O3-related mortality by nearly 10% compared to the control strategy without seasonal differences. These findings highlight that a spatially and temporally differentiated NOx and VOCs emission control strategy could gain more O3-related health benefits, offering valuable insights to regions with severe ozone pollution all over the world.

Nod-like receptor protein 3 inflammasome-mediated pyroptosis contributes to chronic NaAsO2 exposure-induced fibrotic changes and dysfunction in the liver of SD rats.

The metalloid arsenic, known for its toxic properties, is widespread presence in the environment. Our previous research has confirmed that prolonged exposure to arsenic can lead to liver fibrosis injury in rats, while the precise pathogenic mechanism still requires further investigation. In the past few years, the Nod-like receptor protein 3 (NLRP3) inflammasome has been found to play a pivotal role in the occurrence and development of liver injury. In this study, we administered varying doses of sodium arsenite (NaAsO2) and 10 mg/kg.bw MCC950 (a particular tiny molecular inhibitor targeting NLRP3) to Sprague-Dawley (SD) rats for 36 weeks to explore the involvement of NLRP3 inflammasome in NaAsO2-induced liver injury. The findings suggested that prolonged exposure to NaAsO2 resulted in pyroptosis in liver tissue of SD rats, accompanied by the fibrotic injury, extracellular matrix (ECM) deposition and liver dysfunction. Moreover, long-term NaAsO2 exposure activated NLRP3 inflammasome, leading to the release of pro-inflammatory cytokines in liver tissue. After treatment with MCC950, the induction of NLRP3-mediated pyroptosis and release of pro-inflammatory cytokines were significantly attenuated, leading to a decrease in the severity of liver fibrosis and an improvement in liver function. To summarize, those results clearly indicate that hepatic fibrosis and liver dysfunction induced by NaAsO2 occur through the activation of NLRP3 inflammasome-mediated pyroptosis, shedding new light on the potential mechanisms underlying arsenic-induced liver damage.

Sensory impairment and depressive symptoms among older adults before and during the COVID-19 pandemic.

OBJECTIVES: This study examined the associations between sensory impairment (SI), lack of social contact during the COVID-19 pandemic, and depressive symptoms among Americans aged 50 and above. METHODS: We employed data from the 2018 and 2020 Health and Retirement Study (N = 13,460) to examine four SI groups: no SI, visual impairment (VI) only, hearing impairment (HI) only, and dual sensory impairment (DSI). First, multilevel models were employed to estimate the associations between SI and depressive symptoms before and during the pandemic using the full dataset (N = 13,460). Second, linear regression models were employed to estimate the moderation effect of lack of social contact during the pandemic using the 2020 wave data only (N = 4,133). RESULTS: Among older adults, 15.60% had VI only, 10.16% had HI only, and 9.66% had DSI. All SI groups reported significantly more depressive symptoms than the no SI group. The differences between older adults with VI and DSI and those without SI regarding depressive symptoms narrowed during the pandemic. There was no statistically significant moderation effect of lack of social contact for SI and depressive symptoms. CONCLUSION: Older adults with SI faced mental health challenges and demonstrated psychological resilience during the pandemic. Future research should examine other risk factors that may modify the relationship between SI and mental health during public health crises.

Physical Activity, Social Participation, and Pain Outcomes Among Community-Dwelling Older Adults.

BACKGROUND: Little is known regarding the effect of social participation (SP) and physical activity (PA) on pain outcomes among community-dwelling older adults in the United States. AIMS: To determine whether SP and PA are associated with pain outcomes (bothersome pain and number of pain sites). DESIGN: Guided by the biopsychosocial model of chronic pain for older adults, we analyzed data from 7,187 community dwelling participants in the National Health and Aging Trends Study. In cross-sectional analyses, we utilized logistic and negative binomial regressions. METHODS: We prospectively assessed the association between SP/ PA and new or worsening pain from baseline (2011) to 2021 using a discrete time survival analysis by logistic regression, controlling for sociodemographic and health characteristics. RESULTS: At baseline, participation in 5 SP activities per month versus no activities, and performing any PA compared with no PA were significantly associated with lower likelihood of bothersome pain. Although SP and PA were associated with reporting fewer pain sites at baseline, SP was not associated with developing new or worsening pain, prospectively. However, walking and vigorous exercise compared with no PA was significantly associated with a 10% lower risk of developing new or worsening pain (adj odds ratio 0.90, 95% confidence interval [CI] 0.82-0.98). CONCLUSIONS: Physical activity but not social participation may protect against development of new or worsening pain. More research is needed to determine whether social activity can be beneficial for pain prevention and management. Efforts to promote physical activity among older adults may reduce risk of new or worsening pain.

Gray mold disease on bottle gourd caused by Cladosporium tenuissimum in China.

Bottle gourd [Lagenaria siceraria (Mol.) Stand] is a widely cultivated succulent crop species. In December 2022, a serious bottle gourd disease occurred in the protected vegetable planting base of Xingguo County, Ganzhou City, Jiangxi Province, China, with 85% of the 2,100 plants having gray mold disease-like symptoms, including gray spots on the infected fruit. They quickly expanded at suitable temperature and humidity, forming a gray mold layer with inward depressions, which spread to the fruit stem causing watery rot, and the flesh turned black and started to rot. To isolate the pathogen, fruits of the diseased plants were surface-disinfected with 75% ethanol for 30 s, immersed in 0.1% HgCl2 for 1 min, rinsed thrice with sterile water, and cultured on a potato-dextrose agar (PDA) medium at 28°C. Mycelia from the diseased tissue were subcultured on fresh PDA medium to obtain pure cultures. After incubation at 25°C for 7 days, olive-green colonies (~2.5 mm·d-1) developed. Cultures developed numerous elliptical and limoniform conidia measuring 2.69~9.79 µm to 2.10~5.92 µm (average 5.62×3.12 µm) (n=20). The morphological characteristics of the pathogen resembled those of Cladosporium spp. Fungal genomic DNA was extracted, and the internal transcribed spacer (ITS), partial translation elongation factor-1 alpha (TEF-1α), and actin (ACT) regions were amplified with primers ITS1/4, TEF-728F/986R, and ACT-512F/783R, respectively, and sequenced (Bensch et al. 2012; Jo et al. 2018). Basic Local Alignment Search Tool analysis (BLAST) revealed that the ITS (accession no. OQ186729), ACT (OQ240962), and TEF-1α (OQ240963) sequences of isolate hjt4 shared the highest similarity (99-100%) with those of Cladosporium tenuissimum (accessions no. OM232068, OM256530, OM256526) (Duccio et al. 2015). A phylogenetic tree of the isolate hjt4 and its close relatives within Cladosporium was constructed using the MEGA X neighbor-joining method. The pathogen was identified as C. tenuissimum based on morphological and molecular characteristics. A specimen (JXAU-H2022982) was deposited at the Herbarium of the College of Agronomy, Jiangxi Agricultural University. To confirm its pathogenicity, seven-day-old healthy bottle gourd fruits were disinfected with 75% ethanol, 1 mm-deep wounds were made with sterilized scalpels, and the plants were inoculated with PDA plugs (0.8 cm in diameter) containing actively growing mycelia of isolate hjt4. Plants inoculated with sterile PDA plugs served as controls. Each group contained three fruits, and the experiment was performed in triplicate. All fruits were incubated in a biochemical incubator at 28°C. After 3 days, the fruit surface shrank, and the flesh turned to a black colour and rotten, which rapidly spread to the branches. Control fruits did not develop any symptoms. Reisolated colonies showed the same morphological traits as those of the inoculation isolates, whereas no target colonies were isolated from the control fruits. The pathogen was previously reported to cause leaf blight disease in Coriandrum sativum (Zhou et al. 2022) and sooty spots on Cape gooseberry (Miyake et al. 2022), among others. To our knowledge, this is the first report of gray mold disease caused by C. tenuissimum on bottle gourd in China. The findings provide an important foundation for monitoring and controlling the spread of this disease.

First report of Lasiodiplodia pseudotheobromae causing soft rot of plum in China.

Plum (Prunus salicina) is one of the most important fruit tree species worldwide (Valderrama-Soto et al. 2021). In June 2023, the postharvest soft rot symptoms were observed on plum fruits in several fruit markets of Guiyang city, Guizhou province, China. The disease incidence in these markets ranged from 20 to 25% with 70% disease severity. Plum fruits showed rotting, which was characterized by water soaked fruit tissue, softening and presence of whitish mycelia four days post inoculation. In severe conditions, whole fruits become rotted and were covered with white fungal mycelia. Small sections (5 × 3 mm) from 6 diseased plum fruits were surface sterilized by using 75% ethanol for 30 s followed by 0.1% mercuric chloride solution for 5 min, rinsed three times with ddH2O, and then transferred onto potato dextrose agar (PDA) and incubated at 25 ± 2°C for three days. Three pure cultures (GUCC23-0001 to GUCC23-0003) were obtained by transferring a single hyphal tip to new PDA plates. Colonies of these isolates were grayish-white initially, gradually turning to whitish brown with fluffy aerial mycelia and uneven edges and finally turned to a dark gray colony after five days of inoculation. The pseudoparaphyses were hyaline, cylindrical, aseptate, and rounded at apex. Conidia were ellipsoidal, hyaline, unicellular, and 24.2 to 28.6 × 12.3 to 15.5 µm in size (n = 30) (Fig. S1), which were similar to the morphology of Lasiodiplodia pseudotheobromae (Alves et al. 2008). Furthermore, fungal DNA was extracted from fresh mycelia of PDA after seven days by using fungus genomic DNA extraction kit (Biomiga, USA). Partial DNA sequences from four loci including internal transcribed spacer (ITS), translation elongation factor 1-alpha (tef1), beta-tubulin (tub2), and polymerase II second largest subunit (rpb2) were amplified with ITS1 and ITS4 (White et al. 1990), EF1-688F and EF1-1251R (Alves et al. 2008), Bt2a and Bt2b (Glass and Donaldson 1995), and RPB2-LasF and RPB2-LasR, respectively (Cruywagen et al. 2017). GenBank accession numbers are OR361680, OR361681, OR361682 for ITS, OR423394, OR423395, OR423396 for tef1, OR423397, OR423398, OR423399 for tub2, and OR423391, OR423392, OR423393 for rpb2, and gene sequencing showed 99.6 to 100% identity with ex-type strain of L. pseudotheobromae (CBS 116459). Phylogenetic analysis also placed our isolates in a highly supported clade with the reference isolate of L. pseudotheobromae (Fig. S2). Another experiment was designed to confirm the pathogenicity test for additional confirmation. Five mm mycelial plugs of L. pseudotheobromae from a three day old culture on PDA were placed on five surface-sterilized and non-wounded plum fruits for 12 hours and incubated at 25°C ± 2°C for four days. Sterilized fungus free PDA plugs were used as a negative control. Mycelial plugs were removed after 12 hours following which whole fruits were incubated in plastic boxes at 25°C ± 2°C. The experiment was repeated twice. The pathogenicity was evaluated under control conditions in laboratory (relative humidity, 70 ± 5% and temperature 25 ± 5˚C). Plum fruits showed rotting, which was characterized by water soaked fruit tissue, softening and presence of whitish mycelia four days post inoculation. These symptoms and signs were similar to the initially observed symptoms on plums in the markets. No disease symptoms were observed on the control fruits. The re-isolated fungus obtained from inoculated plum fruits was very similar to those isolated from diseased samples in morphology, fulfilling Koch's postulates. To the best of our knowledge, this is the first report of L. pseudotheobromae causing postharvest fruit rot of plum in China. In 2022, the total planting area of plum was 1946.5 thousand hectares, which produces approximately 6626300 tons of plum (Food and Agriculture Organization of the United Nations, 2022). Based on the disease incidence and severity reported in the current study, soft rot of plum may be responsible for nearly 35% of yield losses under severe. Therefore, our study laid a theoretical foundation for the prevention and control of this post-harvest disease of plum.

Cobalt oxyhydroxide nanosheet-modulated ratiometric fluorescence platform for the selective detection of malachite green in fish.

A ratiometric fluorescence platform was developed based on the cobalt oxyhydroxide (CoOOH) nanosheet-modulated fluorescence response of blue emissive copper nanoclusters (Cu NCs) and yellow emissive o-phenylenediamine (OPD). CoOOH nanosheets showed dual function of strong absorption and oxidation ability, which can effectively quench the blue fluorescence of Cu NCs, with an excitation and emission peak maximum at 390 and 450 nm, respectively , and transfer the OPD into yellow fluorescence products, with an excitation and emission peak maximum at 390 and 560 nm, respectively. Upon introducing butyrylcholinesterase (BChE) and its substrates, CoOOH nanosheets were decomposed into Co2+, and malachite green (MG) showed strong inhibition ability to this  process. This resulted in the obvious difference on the ratio of blue and yellow fluorescence recorded on the system in the presence and absence of MG, which was utilized for the quantitative detection of MG, with a limit of detection of 0.140 µM and a coefficient of variation of 3.5%. The fluorescence ratiometric assay showed excellent detection performances in practical sample analysis.

Efficient porphyrin integrated UiO-66 probes for ratiometric fluorescence sensing of antibiotic residues in milk.

Dual-emissive fluorescence probes were designed by integrating porphyrin into the frameworks of UiO-66 for ratiometric fluorescence sensing of amoxicillin (AMX). Porphyrin integrated UiO-66 showed dual emission in the blue and red region. AMX resulted in the quenching of blue fluorescence component, attributable to the charge neutralization and hydrogen bonds induced energy transfer. AMX was detected using (F438/F654) as output signals. Two linear relationships were observed (from 10 to 1000 nM and 1 to 100 µM), with a limit of detection of 27 nM. The porphyrin integrated UiO-66 probe was used to detect AMX in practical samples. This work widens the road for the development of dual/multiple emissive fluorescence sensors for analytical applications, providing materials and theoretical supporting for food, environmental, and human safety.

A case of cardiac tamponade occurred 1 day after transcatheter atrial septal defect closure.

Transesophageal echocardiography (TEE) shows pericardial effusion and a gap between the left atrium and the aortic sinus by atrial septal defect occluder.

Social Contact, Social Participation, and Emotional Well-Being Among Older Adults During the COVID-19 Pandemic: The Roles of Giving and Receiving Social Support.

This study examined whether social contact, social participation, and social support during the COVID-19 pandemic were associated with depression and anxiety. Data were taken from the 2020 COVID-19 Supplement of the National Health and Aging Trends Study (N = 2,778). Depression and anxiety were regressed on social contact frequency, social participation, and social support. Path analyses were also performed. The results showed that in-person contact was related to lower levels of depression, while in-person contact and attending religious services were related to lower levels of anxiety. Giving and receiving support were associated with higher levels of depression and anxiety. Giving support mediated the link between virtual contact, volunteering, and depression, while receiving support mediated the link between virtual contact and depression. Receiving and giving support mediated the association between virtual social contact, volunteering, and anxiety. During the pandemic, being socially connected provided some benefits in terms of emotional well-being, but in some cases being socially connected did not provide salubrious effects.

Bifidobacterium pseudolongum-generated acetate suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma.

BACKGROUND & AIMS: Recent studies have highlighted the role of the gut microbiota and their metabolites in non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). We aimed to identify specific beneficial bacterial species that could be used prophylactically to prevent NAFLD-HCC. METHODS: The role of Bifidobacterium pseudolongum was assessed in two mouse models of NAFLD-HCC: diethylnitrosamine + a high-fat/high-cholesterol diet or + a choline-deficient/high-fat diet. Germ-free mice were used for the metabolic study of B. pseudolongum. Stool, portal vein and liver tissues were collected from mice for non-targeted and targeted metabolomic profiles. Two human NAFLD-HCC cell lines (HKCI2 and HKCI10) were co-cultured with B. pseudolongum-conditioned media (B.p CM) or candidate metabolites. RESULTS: B. pseudolongum was the top depleted bacterium in mice with NAFLD-HCC. Oral gavage of B. pseudolongum significantly suppressed NAFLD-HCC formation in two mouse models (p < 0.01). Incubation of NAFLD-HCC cells with B.p CM significantly suppressed cell proliferation, inhibited the G1/S phase transition and induced apoptosis. Acetate was identified as the critical metabolite generated from B. pseudolongum in B.p CM, an observation that was confirmed in germ-free mice. Acetate inhibited cell proliferation and induced cell apoptosis in NAFLD-HCC cell lines and suppressed NAFLD-HCC tumor formation in vivo. B. pseudolongum restored heathy gut microbiome composition and improved gut barrier function. Mechanistically, B. pseudolongum-generated acetate reached the liver via the portal vein and bound to GPR43 (G coupled-protein receptor 43) on hepatocytes. GPR43 activation suppressed the IL-6/JAK1/STAT3 signaling pathway, thereby preventing NAFLD-HCC progression. CONCLUSIONS: B. pseudolongum protected against NAFLD-HCC by secreting the anti-tumor metabolite acetate, which reached the liver via the portal vein. B. pseudolongum holds potential as a probiotic for the prevention of NAFLD-HCC. IMPACT AND IMPLICATIONS: Non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) is an increasing healthcare burden worldwide. There is an urgent need to develop effective agents to prevent NAFLD-HCC progression. Herein, we show that the probiotic Bifidobacterium pseudolongum significantly suppressed NAFLD-HCC progression by secreting acetate, which bound to hepatic GPR43 (G coupled-protein receptor 43) via the gut-liver axis and suppressed the oncogenic IL-6/JAK1/STAT3 signaling pathway. Bifidobacterium pseudolongum holds potential as a novel probiotic for NAFLD-HCC prevention.

Long-Term Imaging of Cys in Cells and Tumor Mice by a Solid-State Fluorescence Probe.

Cysteine is an important biological thiol and is closely related to cancer. It remains a challenge to develop a probe that can provide long-term fluorescence detection and imaging of Cys in cells as well as in living organisms. Here, a solid-state fluorophore HTPQ is combined with an acrylate group to construct a solid-state fluorescent probe HTPQC for Cys recognition. The fluorescence of the probe is quenched when the photoinduced electron transfer (PET) process is turned on and the excited-state intramolecular proton transfer (ESIPT) process is turned off. In the presence of Cys, an obvious solid-state fluorescence signal can be observed. The double quenching mechanism makes the probe HTPQC have the advantages of high sensitivity, good selectivity, and high contrast of biological imaging. Due to low cytotoxicity, the probe HTPQC can be used to detect exogenous and endogenous Cys in living cells and is capable of imaging over long periods of time. By making full use of long wavelengths, the probe can be applied for the detection of Cys levels in tumor mice and equipped with the ability to conduct long-term imaging in vivo.

Endowing Covalent Organic Frameworks with Photoresponsive Active Sites for Controllable Propylene Adsorption.

Photoresponsive covalent organic frameworks (PCOFs) have emerged as attractive candidates for adsorption, but it is challenging to construct PCOF adsorbents due to structural order loss of covalent organic frameworks (COFs) after introducing photoresponsive motifs and/or tedious steps of postmodification. Here, a facile strategy is developed, by dispersing photoresponsive metal-organic polyhedra (PMOP) into COFs, to endow COFs with photoresponsive adsorption sites. As a proof-of-concept study, a COF with pore size of 4.5 nm and PMOP with suitable molecular size (4.0 and 3.1 nm for trans and cis configuration, respectively) are selected to meet the requirements of proper accommodation space, good guest dispersion, and free isomerization. The structure of COF is well preserved after introducing PMOPs. Interestingly, the obtained photoresponsive host-guest composite (PHGC) adsorbents exhibit photomodulated adsorption capacity on propylene (C3 H6 ) and the change in adsorption capacity can reach up to 43.3% and is stable during multiple cycles. Density functional theory calculations reveal that visible-light irradiation drives the azobenzene motifs in PHGCs to the trans configuration and the adsorption sites are fully open and interact with C3 H6 . UV-light irradiation makes the azobenzene motifs transform to the cis configuration, leading to the shield of the adsorption sites and the consequent release of C3 H6 .