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Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes severe infections in humans and the swine industry. Acquisition and utilization of available carbon sources from challenging host environments is necessary for bacterial pathogens to ensure growth and proliferation. Glycogen is abundant in mammalian body and may support the growth of SS2 during infection in hosts. However, limited information is known about the mechanism between the glycogen utilization and host adaptation of SS2. Here, the pleiotropic effects of exogenous glycogen on SS2 were investigated through transcriptome sequencing. Analysis of transcriptome data showed that the main basic metabolic pathways, especially the core carbon metabolism pathways and virulence-associated factors, of SS2 responded actively to glycogen induction. Glycogen induction led to the perturbation of the glycolysis pathway and citrate cycle, but promoted the pentose phosphate pathway and carbohydrate transport systems. Extracellular glycogen utilization also promoted the mixed-acid fermentation in SS2 rather than homolactic fermentation. Subsequently, apuA, a gene encoding the unique bifunctional amylopullulanase for glycogen degradation, was deleted from the wild type and generated the mutant strain ΔapuA. The pathogenicity details of the wild type and ΔapuA cultured in glucose and glycogen were investigated and compared. Results revealed that the capsule synthesis or bacterial morphology were not affected by glycogen incubation or apuA deletion. However, extracellular glycogen utilization significantly enhanced the hemolytic activity, adhesion and invasion ability, and lethality of SS2. The deletion of apuA also impaired the pathogenicity of bacteria cultured in glucose, indicating that ApuA is indeed an important virulence factor. Our results revealed that exogenous glycogen utilization extensively influenced the expression profile of the S. suis genome. Based on the transcriptome response, exogenous glycogen utilization promoted the carbon adaption and pathogenicity of SS2.

Objective: To analyze the prescription rules of traditional Chinese medicine for patients with COVID-19 in Wuhan Third Hospital, and summarize the disease characteristics and clinical treatment ideas, in order to learn from the treatment of this disease by traditional Chinese medicine. Methods: This study established a cloud database based on the ancient and modern medical cases to mine the rules of medication with analyses of frequency of drug used, association analysis, cluster analysis, complex network and other methods. Results: Of 340 COVID-19 patients discharged from our hospital, 143 males and 197 females with male: female = 0.73: 1, and there were 167 patients over 60 years old, and the majority of clinical illnesses were mainly middle-aged and elderly people. Most of them had dry cough, anorexia, fatigue, etc. The traditional Chinese medicine for the treatment of COVID-19 involves a total of 204 flavors. The most frequent use is Fuling of 225 times. The treatment of traditional Chinese medicines is mainly involved with flavors such as warm, spicy and sweet. Mainly detoxification, dampness and phlegm, Qingfei Paidu Decoction is a common clinical prescription, of which the core drugs are Huoxiang, Fabanxia, Chenpi, Baizhu, Cangzhu, Fuling, Chaihu, Huangqin, Xingren, and Gancao.Conclusion: Through this study, the patients with COVID-19 in our hospital are mainly middle-aged and elderly people, and the etiology is characterized by "cold, wet, poisonous, and epidemic". Wetness is the most important core of the disease.

PIK3R2 encodes the p85β regulatory subunit of phosphatidylinositol 3-kinase and is frequently amplified in cancers. The signaling mechanism and therapeutic implication of p85β are poorly understood. Here we report that p85β upregulates the protein level of the receptor tyrosine kinase AXL to induce oncogenic signaling in ovarian cancer. p85β activates p110 activity and AKT-independent PDK1/SGK3 signaling to promote tumorigenic phenotypes, which are all abolished upon inhibition of AXL. At the molecular level, p85β alters the phosphorylation of TRIM2 (an E3 ligase) and optineurin (an autophagy receptor), which mediate the selective regulation of AXL by p85β, thereby disrupting the autophagic degradation of the AXL protein. Therapeutically, p85β expression renders ovarian cancer cells vulnerable to inhibitors of AXL, p110, or PDK1. Conversely, p85β-depleted cells are less sensitive to these inhibitors. Together, our findings provide a rationale for pharmacological blockade of the AXL signaling axis in PIK3R2-amplified ovarian cancer., p85β (PIK3R2), a regulatory subunit of PI3K, has oncogenic properties. Here the authors show that p85β promotes AXL protein stability, which in turn activates p110 to induce PDK1/SGK3 signaling, and therapeutically, p85β-expressing ovarian cancer cells are sensitive to AXL inhibition.

The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is dysregulated in a broad spectrum of human cancers. Genomic alterations of the pathway members can cause cell transformation and tumorigenesis. The class IA PI3K is a dimeric enzyme composed of a catalytic subunit and a regulatory subunit to initiate AKT activation, with the two major regulatory subunits being p85α and p85β. Apart from sharing a canonical function in binding to and stabilizing p110α, we and the others have demonstrated that p85α and p85β carry distinct activities. We have recently reported an oncogenic role of p85β in ovarian cancer cells. In this study, we analyzed multiple omics data to further explore the oncogenic mechanism of p85β. BCL2 Associated Transcription Factor 1 (BCLAF1) was identified as a downstream effector of p85β. We found that the protein level of BCLAF1 was consistently decreased upon PIK3R2 silencing in ovarian cancer cell lines, and that the decrease could be reversed after PIK3R2 overexpression. Importantly, knockdown of BCLAF1 reduced the oncogenicity of p85β, whereas BCLAF1 overexpression promoted cell viability, cell invasion and migration. Accompanied with the increase in total protein level was enhanced phosphorylation of multiple serine residues of BCLAF1. Functional analysis of the serine residues by expressing the phosphorylation-defective mutants suggested that Ser161, Ser512 and Ser531 are critical for BCLAF1 oncogenic functions in ovarian cancer. Together, the findings reveal a new downstream effector by which p85β exerts its oncogenic effects in ovarian cancer. Citation Format: Panpan Wang, Ling Rao, Victor CY Mak, Lydia WT Cheung. Identifying BCLAF1 as a downstream effector of p85β in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2563.

In this paper, we report a self-sacrificing route for fabrication of the Ce/Tb co-doped GdPO

To investigate the association of clinical and histological characteristics and the development of ESRD in T2DM patients with renal involvement.We conducted a retrospective analysis of clinical and pathologic data from T2DM patients who underwent renal biopsy (n = 120).The mean age, duration of diabetes, and eGFR were 50.9 ± 11.2 years, 92.8 ± 41.3 months, 55.1 ± 42.3 mL/min/1.73 mThe prognosis of DN patients is significantly worse than that of NDRD patients. Compared with glomerular lesions, tubulointerstitial lesions were associated with higher risk for renal death in DN patients.

Small-sized BaLaF

Ammonia inhibition easily affects the performance of anaerobic digestion (AD) for municipal sludge and the oxidization of volatile fatty acids (VFAs) is the rate-limiting step of this process. Bioaugmentation is considered to be an effective method to alleviate ammonia inhibition of AD, but most study used the hydrogenotrophic methanogens as the bioaugmentation culture. In this study, bioaugmentation of mesophilic AD (MAD) and thermophilic AD (TAD) under ammonia inhibition with syntrophic acetate and propionate oxidizing consortia was investigated. The results showed that the bioaugmented reactors recovered earlier than control reactors with 20 (MAD) and 8 (TAD) days, respectively. The high-throughput 16S rRNA gene sequencing indicated that the relative abundance of carbohydrates fermenter (Lentimicrobium), syntrophic VFAs-oxidizing bacteria (Rikenellaceae_DMER64, Smithella and Syntrophobacter) and acetoclastic and hydrogenotrophic methanogens (Methanosaeta, Methanolinea and Methanospirillum) increased in MAD after bioaugmentation. However, part of the bioaugmentation culture could not adapt to the high free ammonia (FAN) concentration in MAD and the effect was weakened. In TAD, proteolytic bacteria (Keratinibaculum and Tepidimicrobium), syntrophic VFAs-oxidizing bacteria (Syntrophomonas) and hydrogenotrophic methanogen (Methanosarcina) were strengthened. The effect of bioaugmentation in TAD was durable even at higher organic loading rate (OLR), due to its positive influence on microbial community. These results suggested that the different bioaugmentation mechanism occurred in MAD and TAD, which are derived from the synergetic effects of ammonia tolerance and microbial interactions. Our study revealed the VFAs-oxidizing consortia as bioaugmented culture could be the potential strategy to alleviate the ammonia stress of AD.

Three 2-phenyl-1,3-diazaazulene derivatives were synthesized and their protonation behaviours were investigated systematically via UV–vis absorption titration and 1H NMR titration, as well as theoretical calculations. One of them exhibited a monoprotonation process while the others displayed prominent halochromic diprotonation responses. Interestingly, upon protonation of 2-phenyl-1,3-diazaazulene derivatives, the coplanarity and conjugation of the 16-π-conjugated backbones were well kept, while the electronic structures were controllably adjusted. The response mechanism of 1,3-diazaazulene derivatives towards acid is through the attachment of acid proton to the nitrogen atom in the diazaazulene ring, resulting in the change of the hybridization of protonated-N from sp2 to sp3, which differed from that of the well-known azulene (analogue of 1,3-diazaazulene, protonation at carbon atom). This work would provide a new insight into the protonation research of the organic functional molecules.

We present a numerical method based on genetic algorithm combined with a fictitious domain method for a shape optimization problem governed by an elliptic equation with Dirichlet boundary condition. The technique of the immersed boundary method is incorporated into the framework of the fictitious domain method for solving the state equations. Contrary to the conventional methods, our method does not make use of the finite element discretization with obstacle fitted meshes. It conduces to overcoming difficulties arising from re-meshing operations in the optimization process. The method can lead to a reduction in computational effort and is easily programmable. It is applied to a shape reconstruction problem in the airfoil design. Numerical experiments demonstrate the efficiency of the proposed approach.

In this paper, a series of Tb 3+ /Dy 3+ /Mn 2+ doped CePO 4 downconversion nanophosphors (DCNPs) were prepared by a one-pot hydrothermal process. The obtained DCNPs presented monoclinic and hexagonal phase structure with wire-like shape. The photoluminescence (PL) properties and the energy transfer (ET) mechanism of these DCNPs were investigated in detail. The ET mechanism of Ce 3+ /Tb 3+ in CePO 4 host was calculated by means of concentration quenching and spectral overlapping, and calculation results revealed that dipole–dipole interactions should be more responsible. The maximum value of ET efficiency was measured to 87.4% for Tb 3+ doped CePO 4 system. In addition, owing to the efficient ET between Ce 3+ and Tb 3+ /Dy 3+ /Mn 2+ , these as-prepared DCNPs exhibit tunable multi-color output under ultra-violet (UV) light excitation. More importantly, the intense cold and warm white emissions can be realized by singly doping 2%Dy 3+ and 20%Mn 2+ in CePO 4 host under UV irradiation, respectively. The corresponding CIE 1931 coordinates were calculated to be (0.30, 0.30) and (0.30, 0.32), respectively, which are closed to the standard white emission (0.33, 0.33). These findings demonstrate the efficient white light emission by singly doped Dy 3+ or Mn 2+ in CePO 4 system for the first time, which is different from commonly used co-doped or tri-doped system. The multicolor tuning and white emission make these Tb 3+ /Dy 3+ /Mn 2+ doped CePO 4 DCNPs potential phosphors in the fields of displays, lighting, and field-emission devices.

In this study, sub-10 nm BaLuF 5 nanocrystals with cubic phase structure were synthesized by a solvothermal method using oleic acid as the stabilizing agent. The as-prepared BaLuF 5 nanocrystals were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and analyzed by the upconversion (UC) spectra. The TEM results reveal that these samples present high uniformity. Compared with Gd-free samples, the size of BaLuF 5 :Yb/Er doped with 10% Gd 3+ decreased to 5.6 nm. In addition, BaLuF 5 :Yb/Tm/Gd upconversion nanoparticles (UCNPs) presented efficient near-infrared (NIR)-NIR UC luminescence. Therefore, it is expected that these ultra-small BaLuF 5 nanocrystals with well-controlled shape, size, and UC emission have potential applications in biomedical imaging fields.

In this paper, the monodispersed NaErF 4 :Yb, Mn nanoparticles (NPs) were successfully synthesized by a simple and mild solvothermal method. The as-prepared NPs were characterized by X-ray diffraction, transmission electron microscopy, and spectrophotometer. The crystal phase, size, morphology, and upconversion (UC) properties of these NPs can be readily tuned by doping Mn 2+ . With increasing Mn 2+ contents, the crystal phase of NaErF 4 :Yb NPs was transferred from hexagonal to cubic, and then a new orthorhombic phase NaMn 3 F 10 appeared. The morphology of NaErF 4 :Yb was tuned from nanodisks to nanocubes and then to large nanoflakes with increasing Mn 2+ dopant contents. Moreover, the UC luminescence (UCL) intensity can be enhanced by increasing Mn 2+ content. Interestingly, single-band red emission can be achieved when the Mn 2+ content reaches 20%. This is mainly ascribed to the efficient energy transfer between Er 3+ and Mn 2+ . The enhanced UCL intensity and single-band red UCL make these NaErF 4 :Yb/Mn NPs ideal probes for optical bioimaging owing to the low tissue absorption and deep tissue penetration of red light.