Mechanisms of Yiai Fuzheng formula in the treatment of triple-negative breast cancer based on UPLC-Q-Orbitrap-HRMS, network pharmacology, and experimental validation.

Ethnopharmacological relevance: Yiai Fuzheng formula (YAFZF), as a Traditional Chinese Medicine (TCM) prescription, has been used widely at Zhongnan Hospital of Wuhan University for its therapeutic effects and high safety on triple-negative breast cancer (TNBC). Objective: In this study, we employed ultra-high-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS), network pharmacology, and experimental validation to elucidate the underlying action mechanism of YAFZF in the treatment of TNBC. Methods: The key active ingredients in YAFZF were analyzed using UPLC-Q-Orbitrap-HRMS, and then the potential components, target genes and signalling pathways of YAFZF were predicted using the network pharmacological method. We then used molecular docking to visualize the combination characteristics between major active components and macromolecules in the crucial pathway. In vitro experiments were conducted to investigate the inhibitory effects of YAFZF treatment on the cell viability, invasion, and migration of 4T1 and MDA-MB-231 cells. The xenograft TNBC models were constructed using female Balb/c mice, and their body weights, tumour volumes, and weights were monitored during YAFZF treatment. Quantitative real-time PCR (qRT-PCR), Hematoxylin-eosin (HE), immunohistochemistry (IHC) staining, Western blot (WB), and terminal deoxynucleotidyl transferase (TdT)-dUTP nick-end labeling (TUNEL) staining were used for further experimental validation. Results: Based on UPLC-Q-Orbitrap-HRMS and network pharmacology analysis, 6 major bioactive components and 153 intersecting genes were obtained for YAFZF against TNBC. Functional enrichment analysis identified that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway might be the mechanism of action of YAFZF in the treatment of TNBC. Molecular docking results suggested that the main active compounds in YAFZF had strong binding energies with the proteins in the PI3K/Akt pathway. In vitro experiments showed that YAFZF inhibited the cell viability, invasion, and migration abilities of TNBC cells. Animal experiments confirmed that YAFZF treatment suppressed tumour cell proliferation and increased apoptotic cells. PCR, HE, WB, and IHC results indicated that YAFZF could suppress xenograft tumour metastases by inhibiting the PI3K/AKT/mTOR pathway regulating the epithelial-mesenchymal transition (EMT) process. Conclusion: YAFZF therapy showed its potential for reducing proliferation, invasion, and migration abilities, increasing apoptosis of TNBC cells. Furthermore, YAFZF treated TNBC by inhibiting xenograft tumour distant metastases via the regulation of EMT by the PI3K/Akt/mTOR pathway, suggesting that it may be useful as an adjuvant treatment.

c-Myc alone is enough to reprogram fibroblasts into functional macrophages.

BACKGROUND: Macrophage-based cell therapy is promising in solid tumors, but the efficient acquisition of macrophages remains a challenge. Induced pluripotent stem cell (iPSC)-induced macrophages are a valuable source, but time-consuming and costly. The application of reprogramming technologies allows for the generation of macrophages from somatic cells, thereby facilitating the advancement of cell-based therapies for numerous malignant diseases. METHODS: The composition of CD45+ myeloid-like cell complex (MCC) and induced macrophage (iMac) were analyzed by flow cytometry and single-cell RNA sequencing. The engraftment capacity of CD45+ MCC was evaluated by two transplantation assays. Regulation of c-Myc on MafB was evaluated by ChIP-qPCR and promoter reporter and dual luciferase assays. The phenotype and phagocytosis of iMac were explored by flow cytometry and immunofluorescence. Leukemia, breast cancer, and patient-derived tumor xenograft models were used to explore the anti-tumor function of iMac. RESULTS: Here we report on the establishment of a novel methodology allowing for reprogramming fibroblasts into functional macrophages with phagocytic activity by c-Myc overexpression. Fibroblasts with ectopic expression of c-Myc in iPSC medium rapidly generated CD45+ MCC intermediates with engraftment capacity as well as the repopulation of distinct hematopoietic compartments. MCC intermediates were stably maintained in iPSC medium and continuously generated functional and highly pure iMac just by M-CSF cytokine stimulation. Single-cell transcriptomic analysis of MCC intermediates revealed that c-Myc up-regulated the expression of MafB, a major regulator of macrophage differentiation, to promote macrophage differentiation. Characterization of the iMac activity showed NF-κB signaling activation and a pro-inflammatory phenotype. iMac cells displayed significantly increased in vivo persistence and inhibition of tumor progression in leukemia, breast cancer, and patient-derived tumor xenograft models. CONCLUSIONS: Our findings demonstrate that c-Myc alone is enough to reprogram fibroblasts into functional macrophages, supporting that c-Myc reprogramming strategy of fibroblasts can help circumvent long-standing obstacles to gaining "off-the-shelf" macrophages for anti-cancer immunotherapy.

Identifying the pollution risk pattern from industrial production to rural settlements and its countermeasures in China.

Impacted by large-scale and rapid rural industrialization in the past few decades, China's rural settlements are confronted with the risk of heavy metal pollution stemming from industrial production, which might pose a significant threat to the rural habitat and the well-beings. This study devised a relative risk model for industrial heavy metal pollution to the rural settlements based on the source-pathway-receptor risk theory. Using this model, we assessed the risk magnitudes of heavy metal pollution from industrial production at a 10 km × 10 km grid scale and identified the characteristics of the risk pattern in China. Our finding reveals: (1) the relative risk values of wastewater, waste gas and total heavy metal pollution are notably concentrated within a confined spectrum, with only a small number of units are characterized by high-risk level; (2) Approximately 21.57 % of China's rural settlements contend with heavy metal pollution, with 4.17 %, 9.84 % and 7.55 % being subjected to high, medium and low risks, respectively; (3) The high-risk units mainly is concentrated in the developed areas such as Yangtze River Delta, Pearl River Delta, and the Beijing-Tianjin metropolitan area, also dispersed in the plain areas with high rural population density. Guided by these insights, this study puts forth regionally tailored prevention and control strategies, as well as distinct process prevention and control strategies.

TRIM24 Cooperates with Ras Mutation to Drive Glioma Progression through snoRNA Recruitment of PHAX and DNA-PKcs.

The factors driving glioma progression remain poorly understood. Here, the epigenetic regulator TRIM24 is identified as a driver of glioma progression, where TRIM24 overexpression promotes HRasV12 anaplastic astrocytoma (AA) progression into epithelioid GBM (Ep-GBM)-like tumors. Co-transfection of TRIM24 with HRasV12 also induces Ep-GBM-like transformation of human neural stem cells (hNSCs) with tumor protein p53 gene (TP53) knockdown. Furthermore, TRIM24 is highly expressed in clinical Ep-GBM specimens. Using single-cell RNA-sequencing (scRNA-Seq), the authors show that TRIM24 overexpression impacts both intratumoral heterogeneity and the tumor microenvironment. Mechanically, HRasV12 activates phosphorylated adaptor for RNA export (PHAX) and upregulates U3 small nucleolar RNAs (U3 snoRNAs) to recruit Ku-dependent DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Overexpressed TRIM24 is also recruited by PHAX to U3 snoRNAs, thereby facilitating DNA-PKcs phosphorylation of TRIM24 at S767/768 residues. Phosphorylated TRIM24 induces epigenome and transcription factor network reprogramming and promotes Ep-GBM-like transformation. Targeting DNA-PKcs with the small molecule inhibitor NU7441 synergizes with temozolomide to reduce Ep-GBM tumorigenicity and prolong animal survival. These findings provide new insights into the epigenetic regulation of Ep-GBM-like transformation and suggest a potential therapeutic strategy for patients with Ep-GBM.

Network pharmacology and experimental verification to decode the action of Qing Fei Hua Xian Decotion against pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion (QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification. METHODS: The candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding "herb-compound-target" network of QFHXD. The protein-protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments. RESULTS: A total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1ß, STAT3, MMP-9, and TGF-ß1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-ß1/Smad2/3. CONCLUSIONS: QFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-ß1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.

KAP1 stabilizes MYCN mRNA and promotes neuroblastoma tumorigenicity by protecting the RNA m6A reader YTHDC1 protein degradation.

BACKGROUND: Neuroblastoma (NB) patients with amplified MYCN often face a grim prognosis and are resistant to existing therapies, yet MYCN protein is considered undruggable. KAP1 (also named TRIM28) plays a crucial role in multiple biological activities. This study aimed to investigate the relationship between KAP1 and MYCN in NB. METHODS: Transcriptome analyses and luciferase reporter assay identified that KAP1 was a downstream target of MYCN. The effects of KAP1 on cancer cell proliferation and colony formation were explored using the loss-of-function assays in vitro and in vivo. RNA stability detection was used to examine the influence of KAP1 on MYCN expression. The mechanisms of KAP1 to maintain MYCN mRNA stabilization were mainly investigated by mass spectrum, immunoprecipitation, RIP-qPCR, and western blotting. In addition, a xenograft mouse model was used to reveal the antitumor effect of STM2457 on NB. RESULTS: Here we identified KAP1 as a critical regulator of MYCN mRNA stability by protecting the RNA N6-methyladenosine (m6A) reader YTHDC1 protein degradation. KAP1 was highly expressed in clinical MYCN-amplified NB and was upregulated by MYCN. Reciprocally, KAP1 knockdown reduced MYCN mRNA stability and inhibited MYCN-amplified NB progression. Mechanistically, KAP1 regulated the stability of MYCN mRNA in an m6A-dependent manner. KAP1 formed a complex with YTHDC1 and RNA m6A writer METTL3 to regulate m6A-modified MYCN mRNA stability. KAP1 depletion decreased YTHDC1 protein stability and promoted MYCN mRNA degradation. Inhibiting MYCN mRNA m6A modification synergized with chemotherapy to restrain tumor progression in MYCN-amplified NB. CONCLUSIONS: Our research demonstrates that KAP1, transcriptionally activated by MYCN, forms a complex with YTHDC1 and METTL3, which in turn maintain the stabilization of MYCN mRNA in an m6A-dependent manner. Targeting m6A modification by STM2457, a small-molecule inhibitor of METTL3, could downregulate MYCN expression and attenuate tumor proliferation. This finding provides a new alternative putative therapeutic strategy for MYCN-amplified NB.

LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling.

BACKGROUND: Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). METHODS: LncRNA microarray assay was performed to document abundance changes of lncRNAs in paclitaxel (PTX)-resistant MDA-MB-231 BCSC (ALDH+) and non-BCSC (ALDH-). RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to determine the binding proteins of LINC00115. The clinical significance of the LINC00115 pathway was examined in TNBC metastatic lymph node tissues. The biological function of LINC00115 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA sequencing, mass spectrometry, and the CRISPR/Cas9-knockout system. The therapeutic potential of LINC00115 was examined through xenograft animal models. RESULTS: LINC00115 functions as a scaffold lncRNA to link SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3 at both K106 and K200 in drug-resistant BCSC. PLK3 methylation decreases PLK3 phosphorylation of HIF1α and thereby increases HIF1α stability. HIF1α, in turn, upregulates ALKBH5 to reduce m6A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1α are prognostic for clinical triple-negative breast cancers. CONCLUSIONS: Our findings uncover LINC00115 as a critical regulator of BCSC and highlight targeting LINC00115 and SETDB1 as a potential therapeutic strategy for chemotherapeutic resistant breast cancer.

Full Spatial Characterization of Entangled Structured Photons.

Vector modes are fully polarized modes of light with spatially varying polarization distributions, and they have found widespread use in numerous applications such as microscopy, metrology, optical trapping, nanophotonics, and communications. The entanglement of such modes has attracted significant interest, and it has been shown to have tremendous potential in expanding existing applications and enabling new ones. However, due to the complex spatially varying polarization structure of entangled vector modes (EVMs), a complete entanglement characterization of these modes remains challenging and time consuming. Here, we have used a time-tagging event camera to demonstrate the ability to completely characterize the entanglement of EVMs. Leveraging the camera's capacity to provide independent measurements for each pixel, we simultaneously characterize the entanglement of approximately 2.6×10^{6} modes between a bipartite EVM through measuring only 16 observables in polarization. We reveal that EVMs can naturally generate various polarization-entangled Bell states. This achievement is an important milestone in high-dimensional entanglement characterization of structured light, and it could significantly impact the implementation of related quantum technologies. The potential applications of this technique are extensive, and it could pave the way for advancements in quantum communication, quantum imaging, and other areas where structured entangled photons play a crucial role.

Effects of Perilla Seed Meal on Productive Performance, Egg Quality, Antioxidant Capacity and Hepatic Lipid Metabolism of Wenchang Breeder Hens.

The aim of this study was to investigate the effects of adding perilla seed meal (PSM) to the diet on reproductive performance, egg quality, yolk fatty acids, antioxidant capacity and liver lipid metabolism in breeding hens. A total of 192 31-week-old yellow-feathered hens were randomly divided into 4 treatments with 6 replicates of 8 birds for 8 weeks. The chickens were fed a typical corn-soybean meal diet containing 0% (control), 0.3%, 0.6%, and 1% PSM. The results showed that PSM can change the productivity of laying hens. Adding 0.6% PSM to the feed reduced the mortality rate of chickens. Adding 1% PSM improved the fertilization rate and hatching rate of chickens. Regarding egg quality, the albumen height and Haugh unit were improved in the 0.6% PSM group. The content of MUFAs and PUFAs in the egg yolk was increased in all the PSM groups, while SFAs were only increased in the 0.6% PSM group. Among the indicators related to lipid metabolism, serum GLU decreased in all the PSM groups. The 0.6% PSM group had a reduction in serum and liver TG, as well as reductions in serum LDL-C and ALT. The same results were observed for the abdominal fat percentage in the 0.6% PSM group. Liver lipid metabolism-associated gene expression of FAS and LXRα was decreased in all the PSM groups, and the mRNA expression of ACC and SREBP-1c was significantly reduced in the 0.6% PSM group. HE staining showed that the vacuoles in the liver tissue gradually decreased with increasing PSM doses, especially the 1% PSM dose. Lipid droplets with a similar trend were observed using Oil Red O staining. In the results of the antioxidant capacity test, the serum T-AOC was increased in the 0.6% and 1% PSM groups, and the SOD in both the serum and liver was significantly increased in all the PSM groups. The expression of antioxidant-related genes such as Nrf2, NQO-1, HO-1, CAT and GSH-Px was significantly upregulated in the 1% PSM group. In conclusion, the PSM diet improved the lipid metabolism and antioxidant capacity of breeding hens. PSM reduces mortality and improves fertilization and hatchability in the late laying period of chickens, resulting in greater benefits. We recommend adding 0.6% PSM to layer feed, which improves the physical condition of the hens and brings higher economic benefits.

Toward the Achievable Rate-Distortion Bound of VVC Intra Coding: A Beam Search-Based Joint Optimization Scheme.

In this paper, we present the first attempt at determining where the achievable rate-distortion (R-D) performance bound in versatile video coding (VVC) intra coding is when considering the mutual dependency in the rate-distortion optimization (RDO) process. In particular, the abundant search space of encoding parameters in VVC intra coding is practically explored with a beam search-based joint rate-distortion optimization (BSJRDO) scheme. As such, the partitioning, prediction and transform decisions are jointly optimized across different coding units (CUs) with a customized search subset instead of the full space. To make the beam search process implementation-friendly for VVC, the dependencies among the CUs are truncated at different depths. To facilitate finer computational scalability, the beam size is flexibly adjusted based on the characteristics of the CUs, such that the operational points that satisfy different complexity demands for diverse applications can be practically obtained. The proposed BSJRDO approach, which fully conforms to the VVC decoding syntax, can serve as both the way toward the optimal RDO bound and a practical performance-boosting solution. BSJRDO is further implemented on a VVC coding platform (VVC Test model (VTM) 12.0), and extensive experiments show that BSJRDO can achieve 1.30% and 3.22% bit rate savings compared to the VTM anchor under the common test condition and low-bit-rate coding scenarios, respectively. Moreover, the performance gain can also be flexibly customized with different computational overheads.

Catalytic degradation of crystal violet and methyl orange in heterogeneous Fenton-like processes.

Metals-loaded (Fe3+, Cu2+ and Zn2+) activated carbons (M@AC) with different loading ratios (0.1%, 0.5%, 1%, 5% and 10%) were prepared and employed for catalytic degradation of dye model compounds (crystal violet (CV) and methyl orange (MO)) in wastewater by heterogeneous Fenton-like technique. Compared with Cu@AC and Zn@AC, 0.5% Fe3+ loaded AC (0.5Fe@AC) had better catalytic activity for dyes degradation. The effects of dyes initial concentration, catalyst dosage, pH and hydrogen peroxide (H2O2) volume on the catalytic degradation process were investigated. Cyclic performance, stability of 0.5Fe@AC and iron leaching were explored. Degradation kinetics were well fitted to the pseudo-second-order model (Langmuir-Hinshelwood). Almost complete decolorization (99.7%) of 400 mg L-1 CV was achieved after 30 min reaction under the conditions of CV volume (30 mL), catalyst dosage (0.05 g), H2O2 volume (1 mL) and pH (7.7). Decolorization of MO reached 98.2% under the same conditions. The abilities of pyrolysis char (PC) of dyeing sludge (DS) and metal loaded carbon to remove dye pollutants were compared. The intermediate products were analyzed and the possible degradation pathway was proposed. This study provided an insight into catalytic degradation of triphenylmethane- and aromatic azo-based substances, and utilization of sludge char.

Targeting TRIM24 promotes neuroblastoma differentiation and decreases tumorigenicity via LSD1/CoREST complex.

PURPOSE: High-risk neuroblastoma (NB) still has an unfavorable prognosis and inducing NB differentiation is a potential strategy in clinical treatment, yet underlying mechanisms are still elusive. Here we identify TRIM24 as an important regulator of NB differentiation. METHODS: Multiple datasets and clinical specimens were analyzed to define the role of TRIM24 in NB. The effects of TRIM24 on differentiation and growth of NB were determined by cell morphology, spheres formation, soft agar assay, and subcutaneous xenograft in nude mice. RNA-Seq and qRT-PCR were used to identify genes and pathways involved. Mass spectrometry and co-immunoprecipitation were used to explore the interaction of proteins. RESULTS: Trim24 is highly expressed in spontaneous NB in TH-MYCN transgenic mice and clinical NB specimens. It is associated with poor NB differentiation and unfavorable prognostic. Knockout of TRIM24 in neuroblastoma cells promotes cell differentiation, reduces cell stemness, and inhibits colony formation in soft agar and subcutaneous xenograft tumor growth in nude mice. Mechanistically, TRIM24 knockout alters genes and pathways related to neural differentiation and development by suppressing LSD1/CoREST complex formation. Besides, TRIM24 knockout activates the retinoic acid pathway. Targeting TRIM24 in combination with retinoic acid (RA) synergistically promotes NB cell differentiation and inhibits cell viability. CONCLUSION: Our findings demonstrate that TRIM24 is critical for NB differentiation and suggest that TRIM24 is a promising therapeutic target in combination with RA in NB differentiation therapy.

Intensity interferometry for holography with quantum and classical light.

As first demonstrated by Hanbury Brown and Twiss, it is possible to observe interference between independent light sources by measuring correlations in their intensities rather than their amplitudes. In this work, we apply this concept of intensity interferometry to holography. We combine a signal beam with a reference and measure their intensity cross-correlations using a time-tagging single-photon camera. These correlations reveal an interference pattern from which we reconstruct the signal wavefront in both intensity and phase. We demonstrate the principle with classical and quantum light, including a single photon. Since the signal and reference do not need to be phase-stable nor from the same light source, this technique can be used to generate holograms of self-luminous or remote objects using a local reference, thus opening the door to new holography applications.

All fabric and flexible wearable sensors for simultaneous sweat metabolite detection and high-efficiency collection.

Wearable sweat electrochemical sensors have attracted wide attention due to their advantages of non-invasive, portable, real-time monitoring, etc. However, existing sensors still have some problems with efficient sweat collection. Microfluidic channel technology and electrospinning technology are commonly used to collect sweat efficiently, but there are some limitations such as complex channel design and multiple spinning parameters. Besides, existing sensors are mostly based on flexible polymers, such as, PET, PDMS, PI and PI, which have limited wearability and permeability. Based on the above, all fabric and dual-function flexible wearable sweat electrochemical sensor is proposed in this paper. This sensor uses fabric as the raw material to implement the directional transport of sweat and the multi-component integrated detection dual functions. Meanwhile, the high-efficiency collection of sweat is obtained by a Janus fabric, wherein one side of the selected silk is superhydrophobic graft treated and the other side is hydrophilic plasma treated. Therefore, the resulting Janus fabric can effectively transfer sweat from the skin side to the electrode, and the minimum sweat droplet can reach 0.2 µL to achieve micro-volume collection. Besides, the patterned sensor, made of silk-based carbon cloth, is fabricated using a simple laser engraving, which could detect Na+, pH, and glucose instantaneously. As a result, these proposed sensors can achieve good sensing performance and high-efficiency sweat collection dual functionality; moreover, it has good flexibility and comfortable wearability.

Phytosterols Alleviate Hyperlipidemia by Regulating Gut Microbiota and Cholesterol Metabolism in Mice.

Phytosterols (PS) have been shown to regulate cholesterol metabolism and alleviate hyperlipidemia (HLP), but the mechanism is still unclear. In this study, we investigated the mechanism by which PS regulates cholesterol metabolism in high-fat diet (HFD) mice. The results showed that PS treatment reduced the accumulation of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the serum of HFD mice, while increasing the serum levels of high-density lipoprotein cholesterol (HDL-C). Compared with HFD mice, PS not only increased the antioxidant activity of the liver but also regulated the mRNA expression levels of enzymes and receptors related to cholesterol metabolism. The hypolipidemic effect of PS was abolished by antibiotic (Abx) intervention and reproduced by fecal transplantation (FMT) intervention. The results of 16S rRNA sequencing analysis showed that PS modulated the gut microbiota of mice. PS reduced the relative abundance of Lactobacillus and other bile salt hydrolase- (BSH-) producing gut microbiota in HFD mice, which are potentially related to cholesterol metabolism. These findings partially explain the mechanisms by which PS regulates cholesterol metabolism. This implies that regulation of the gut microbiota would be a potential target for the treatment of HLP.

Germline Neurofibromin 1 mutation enhances the anti-tumour immune response and decreases juvenile myelomonocytic leukaemia tumourigenicity.

Juvenile myelomonocytic leukaemia (JMML) is an aggressive paediatric leukaemia characterized by mutations in five canonical RAS pathway genes, including the NF1 gene. JMML is driven by germline NF1 gene mutations, with additional somatic aberrations resulting in the NF1 biallelic inactivation, leading to disease progression. Germline mutations in the NF1 gene alone primarily cause benign neurofibromatosis type 1 (NF1) tumours rather than malignant JMML, yet the underlying mechanism remains unclear. Here, we demonstrate that with reduced NF1 gene dose, immune cells are promoted in anti-tumour immune response. Comparing the biological properties of JMML and NF1 patients, we found that not only JMML but also NF1 patients driven by NF1 mutations could increase monocytes generation. But monocytes cannot further malignant development in NF1 patients. Utilizing haematopoietic and macrophage differentiation from iPSCs, we revealed that NF1 mutations or knockout (KO) recapitulated the classical haematopoietic pathological features of JMML with reduced NF1 gene dose. NF1 mutations or KO promoted the proliferation and immune function of NK cells and iMacs derived from iPSCs. Moreover, NF1-mutated iNKs had a high capacity to kill NF1-KO iMacs. NF1-mutated or KO iNKs administration delayed leukaemia progression in a xenograft animal model. Our findings demonstrate that germline NF1 mutations alone cannot directly drive JMML development and suggest a potential cell immunotherapy for JMML patients.

Co-pyrolysis of dyeing sludge and pine sawdust in a fluidized bed: Characterization and analysis of pyrolytic products and investigation of synergetic effects.

Co-pyrolysis of dyeing sludge (DS) and pine sawdust (PS) was carried out in a fluidized bed pyrolyser. The results revealed that addition of PS increased the yields of condensate and gas, and dramatically improved pore structure of co-pyrolysis char, enhancing immobilization of the metals, nutrient and pollution elements. Catalysts (Na-ZSM-5 and HZSM-5) significantly reduced tar and coke, strengthened the integrity of pore structure. Yield of nitrogen-containing compounds declined sharply from 88.66% to 8.14% when 25% of PS was added. Addition of 50% PS promoted ring opening to generate chain compounds and abundant oxygenates (such as ketones, aldehydes and carboxylic acids) in pyrolysis oil (PO) at 650 °C. Correspondingly, yield of gaseous products was inhibited except CO2 and H2 when PS content was dominant. The catalysts greatly increased yield of gaseous products by enhancing primary and secondary cracking depending on different feedstocks and catalysts (e.g., DS over Na-ZSM-5 and PS over HZSM-5). The maximum energy efficiency (69.75%) was obtained at 650 °C when 75% PS was added.

Effects of Lactobacillus plantarum fermented Shenling Baizhu San on gut microbiota, antioxidant capacity, and intestinal barrier function of yellow-plumed broilers.

The current study focused on the effects of Shenling Baizhu San (SLBZS) fermented by Lactobacillus plantarum (L. plantarum) on gut microbiota, antioxidant capacity, and intestinal barrier function of yellow-plumed broilers. Our results showed that the content of ginsenoside Rb1 was the highest when SLBZS were inoculated with 3% L. plantarum and fermented at 28°C for 24 h. One-day-old male broilers were divided into five treatment groups. Treatment consisted of a basal diet as a control (Con), 0.1% unfermented SLBZS (U-SLBZS), 0.05% fermented SLBZS (F-SLBZS-L), 0.1% fermented SLBZS (F-SLBZS-M), and 0.2% fermented SLBZS (F-SLBZS-H). On days 14, 28, and 42, six chickens from each group were randomly selected for blood collection and tissue sampling. The results showed that the addition of 0.1% fermented SLBZS could significantly increase average daily feed intake (ADFI) and average daily gain (ADG), and decrease feed conversion ratio (FCR) of broilers. The addition of 0.1 and 0.2% fermented SLBZS significantly increased the lymphoid organ index of broilers on day 28 and 42. The addition of 0.1 and 0.2% fermented SLBZS could improve the antioxidant capacity of broilers. Moreover, the addition of 0.1 and 0.2% fermented SLBZS could significantly increase the villus height/crypt depth of the ileum, and significantly increase the expression of tight junction. In addition, fermentation of SLBZS increase the abundance of Coprococcus, Bifidobacterium and Bilophila in the gut of broilers. These results indicate that the supplementation of fermented SLBZS in the diet could improve the growth performance, lymphoid organ index, antioxidant capacity, and positively affect the intestinal health of broilers.

Snapshot hyperspectral imaging with quantum correlated photons.

Hyperspectral imaging (HSI) has a wide range of applications from environmental monitoring to biotechnology. Conventional snapshot HSI techniques generally require a trade-off between spatial and spectral resolution and are thus limited in their ability to achieve high resolutions in both simultaneously. Most techniques are also resource inefficient with most of the photons lost through spectral filtering. Here, we demonstrate a proof-of-principle snapshot HSI technique utilizing the strong spectro-temporal correlations inherent in entangled photons using a modified quantum ghost spectroscopy system, where the target is directly imaged with one photon and the spectral information gained through ghost spectroscopy from the partner photon. As only a few rows of pixels near the edge of the camera are used for the spectrometer, effectively no spatial resolution is sacrificed for spectral. Also since no spectral filtering is required, all photons contribute to the HSI process making the technique much more resource efficient.