Integrated Metagenomic and Transcriptomic Analyses Reveal the Dietary Dependent Recovery of Host Metabolism From Antibiotic Exposure

The balance of gut microbiome is essential for maintaining host metabolism homeostasis. Despite widespread antibiotic use, the potential long-term detrimental consequences of antibiotics for host health are getting more and more attention. However, it remains unclear whether diet affects the post-antibiotic recovery of gut microbiome and host metabolism. In this study, through metagenomic sequencing and hepatic transcriptome analysis, we investigated the divergent impacts of short-term vancomycin (Vac), or combination of ciprofloxacin and metronidazole (CM) treatment on gut microbiome and host metabolism, as well as their recovery extent from antibiotic exposure on chow diet (CD) and high-fat diet (HFD). Our results showed that short-term Vac intervention affected insulin signaling, while CM induced more functional changes in the microbiome. However, Vac-induced long-term (45 days) changes of species were more apparent when recovered on CD than HFD. The effects of antibiotic intervention on host metabolism were long-lasting, antibiotic-specific, and diet-dependent. The number of differentially expressed gene was doubled by Vac than CM, but was comparable after recovery on CD as revealed by the hepatic transcriptomic analysis. In contrast, HFD intake during recovery could worsen the extent of post-antibiotic recovery by altering infection, immunity, and cancer-related pathways in short-term Vac-exposed rats and by shifting endocrine system-associated pathways in CM-exposed rats. Together, the presented data demonstrated the long-term recovery extent after different antibiotic exposure was diet-related, highlighting the importance of dietary management during post-antibiotic recovery

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Ubiquitin-Specific Peptidase 8 Modulates Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis in Breast Cancer by Stabilizing Estrogen Receptor Alpha

Breast cancer (BC) is the most common neoplastic and lethal malignancy in women. Although antiendocrine therapy is the main treatment for estrogen receptor alpha (ERα)-positive BC, the development of resistance is a major clinical complication. In this study, we aimed to explore the role of ubiquitin-specific peptidase 8 (USP8) in ERα signaling and identify potential targets for endocrine resistance. Public databases were used to analyze USP8 expression, prognosis, clinical characteristics, and immune cell infiltration. Immunohistochemistry and western blot assays were used to detect protein levels and ERα signaling. Quantitative reverse transcription-PCR was used to measure ERα target gene expression. The cell counting kit-8, wound-healing, clone formation, and Transwell assays were used to investigate the effects of USP8 depletion or inhibition on cell proliferation, migration, and invasion. An immunofluorescence assay was used for localizing USP8 and ERα, and a protein stability assay was performed for detecting the degradation of ERα protein. The cell cycle and apoptosis were assessed using flow cytometry. USP8 was highly expressed in the luminal subtype of BC and was associated with poor prognosis. The infiltration levels of many immune cells were positively correlated with USP8 expression. Depletion of USP8 dramatically decreased the ERα signaling activity and weakened the proliferation, migration, and invasion capabilities of BC cells. USP8 knockdown markedly induced apoptosis and cell cycle arrest (G0/G1). Colocalization analysis and protein stability assays indicated a probable mechanism by which USP8 regulates ERα. Our study demonstrates that USP8 might be crucial in BC development and may be considered a potential target for treating ER-positive BC malignancies in vitro

OK-432 (Sapylin) Reduces Seroma Formation After Axillary Lymphadenectomy in Breast Cancer

Purpose/aim: Modified radical mastectomy is the standard surgery for breast cancer in developing countries. However, seroma formation regarded as the most frequent postoperative complication limits the therapeutic benefit of mastectomy and axillary surgery. The purpose of this study was to evaluate the efficacy of OK-432 in reducing seroma formation after axillary dissection. Methods: This prospective cohort study included 80 patients with advanced breast cancer who underwent modified radical mastectomy. Patients were randomized into two groups, which differed with the OK-432 administration. N = 40 patients per group were treated with either OK-432 plus closed suction drainage or drainage-only. Result: In comparison with the drainage-only group, we found that patients in the OK-432 group had a lower drainage volume (p = .030) and a shorter duration of axillary drainage (p < .01). Besides, the use of OK-432 could reduce the incidence of seroma formation (p < .01) and the volume of seroma (p = .040). There were also significant differences in reducing the chance of evacuative punctures (p = .036) and the healing time (p < .01) between control and OK-432 group. Conclusion: OK-432 not only shortened the suction drainage duration, but also significantly reduced seroma formation as well as the needs for aspiration punctures after modified radical mastectomy

Effect of the Annealing Process on the Microstructure and Performance of 5056 Aluminum Alloy Wires

Recrystallization can affect the mechanical properties of aluminum alloys by changing the grain structure, and even the secondary recrystallization will cause a sudden change in the grain size in the alloy. In this work, by choosing different annealing treatments on the cold-drawn 5056 aluminum wire, the microstructure evolution in the alloy homogenized at different annealing processes was discussed, and its influence on the mechanical properties was tested. The results demonstrated that the different annealing treatments had a great effect on the recrystallized structure in the 5056 aluminum alloy. During the annealing, it was observed that the recrystallization started at 250 °C and completed at 310 °C, leading to a significant decrease in the mechanical properties. When the temperature was further increased to 530 °C, the secondary recrystallization occurred, and the grain size of the secondary recrystallization was larger than that when the annealing temperature was 560 °C. However, there was only a minor decrease in the mechanical properties. The reasons and laws of the secondary recrystallization are analyzed and discussed in this paper

Cold exposure promotes coronavirus infection by altering the gut microbiota and lipid metabolism to reduce host immunity

Cold exposure has been suggested to be advantageous for the spread and infection of the coronavirus, and the gut microbiota influences the severity of the infection by modulating host inflammatory and immune responses. However, it remains unclear whether the promotion of viral infection through cold exposure is linked to the gut microbiota

A Fully Integrated Solid-State Charge Detector with through Fused Silica Glass via Process

A charge detector is a vital component in neutrino and dark matter detection. The integration of a charge collector in the form of flat pads and readout modules has been proposed as an optimization method as it can reduce noise and installation complexity. As a substrate, fused silica glass has attracted considerable attention due to its low radioactive background properties. In this research, based on the application requirements of a high charge collection rate and low noise, the structure of the charge detector was designed using calculation and simulation methods. The entire manufacturing process is described. In addition, a novel through glass via (TGV) structure composed of a conformal metal layer and a photosensitive material that is easy to fabricate and has high morphological compatibility with via filling is proposed. The curing property of the new material was characterized. A fully integrated solid-state charge detector with 32 groups of TGVs was realized. Additionally, the electrical properties of key structures were tested and analyzed

Optimizing ex vivo culture conditions to study human gut microbiome

Abstract The inter-individual variations of gut microbiome contribute to the different responses toward drug therapy among populations, developing a reliable ex vivo culture method for mixed bacteria is the urgent need for predicting personal reaction to drug therapy. Unfortunately, very few attentions have been paid to the bias that could be introduced during the culture process for mixed bacteria. Here we systemically evaluated the factors that may affect the outcomes of cultured bacteria from human feces. We demonstrated that inter-individual difference of host gut microbiome was the main factor affecting the outcomes of cultured bacteria, followed by the culture medium and time point. We further optimized a new medium termed GB based on our established multi-dimensional evaluation method, which could mimic the status of in situ host gut microbiome to the highest extent. Finally, we assessed the inter-individual metabolism by host gut microbiome from 10 donors on three frequently used clinical drugs (aspirin, levodopa and doxifluridine) based on the optimized GB medium. Our results revealed obvious variation in drug metabolism by microbiome from different donors, especially levodopa and doxifluridine. This work suggested the optimized culture medium had the potential for exploring the inter-individual impacts of host gut microbiome on drug metabolism

Parathyroid autotransplantation at a novel site for better evaluation of the grafted gland function: study protocol for a prospective, randomized controlled trial

Abstract Background Hypoparathyroidism is one of the most common complications encountered in thyroidectomy. In addition to parathyroid in-situ preservation, parathyroid autotransplantation (PA) is another important remedial method for patients whose parathyroid glands have been removed. However, an accurate evaluation method for the function of a transplanted parathyroid is lacking. Our preliminary study indicated that patients with PA at novel sites near antecubital veins had higher serum concentrations of parathyroid hormone (PTH). Therefore, the main hypothesis is that a grafted site closer to the cephalic vein is more useful for better evaluation of transplanted parathyroid function. This study aims to confirm the more efficient and accurate evaluation system through a prospective, randomized controlled trial. Methods In total, 280 patients will be enrolled in this study and randomly divided into two groups: 140 patients with transplanted parathyroid glands in the traditional sites (group A) and the other 140 transplanted in the novel sites (group B), close to the antecubital veins. The serum concentration of PTH and calcium ion from both forearms will be measured and monitored regularly for 12 months. The primary outcome of this trial will be the survival of grafted glands, defined as the ratio of PTH between the grafted vs. the non-grafted forearms being no less than 1.5. The secondary outcome is hypoparathyroidism, defined as the PTH level from the non-grafted forearms being less than 15 pg/ml (normal range 15–65 pg/ml). Discussion Our results from this study should provide a more accurate method to evaluate the function of transplanted parathyroid glands by comparing PTH concentrations in both the grafted and non-grafted forearms following PA at novel sites. A better PTH measurement is helpful not only for the management of postoperative patients, but also for further identification of factors affecting PA success. Trial registration ClinicalTrials.gov, ID: NCT02906748. Registered on 16 March 2016

Chiral 1D perovskite microwire arrays for circularly polarized light detection

Detection of circularly polarized light (CPL) accelerates the development of various optical technologies, but the additional quarter-wave plate and linear polarizer are required for conventional polarized light detectors, resulting in tremendous difficulty in integration and miniaturization of the devices. Herein, we fabricate pure (010)-orientated chiral one-dimensional (1D) perovskite microwire arrays with high crystallinity, strict alignment, and homogeneous size by a capillary-bridge-manipulated method. By the synergy of the excellent crystallinity and pure crystallographic orientation, high-performance CPL photodetectors are fabricated, with a maximum anisotropy factor of 0.23, responsivity exceeding 26 mA W −1, and detectivity exceeding 2.2 × 1011 Jones. Furthermore, the CPL photodetectors based on microwire arrays also exhibit impressive environmental stability under ambient conditions.Published versionThis work was supported by Ji Hua Laboratory Science Program (grant no. X190251UZ190), the Ministry of Science and Technology (MOST) of China (2017YFA0204504, 2018YFA0208502, and 2018YFA0704803), the National Natural Science Foundation (51922012, 52103238 and 21633014), Youth Innovation Promotion Association CAS (2018034), and Project funded by China Postdoctoral Science Foundation (2021TQ0289 and 2021M700128)