TERT activates endogenous retroviruses to promote an immunosuppressive tumour microenvironment.

Telomerase plays a pivotal role in tumorigenesis by both telomere-dependent and telomere-independent activities, although the underlying mechanisms are not completely understood. Using single-sample gene set enrichment analysis (ssGSEA) across 9,264 tumour samples, we observe that expression of telomerase reverse transcriptase (TERT) is closely associated with immunosuppressive signatures. We demonstrate that TERT can activate a subclass of endogenous retroviruses (ERVs) independent of its telomerase activity to form double-stranded RNAs (dsRNAs), which are sensed by the RIG-1/MDA5-MAVS signalling pathway and trigger interferon signalling in cancer cells. Furthermore, we show that TERT-induced ERV/interferon signalling stimulates the expression of chemokines, including CXCL10, which induces the infiltration of suppressive T-cell populations with increased percentage of CD4+ and FOXP3+ cells. These data reveal an unanticipated role for telomerase as a transcriptional activator of ERVs and provide strong evidence that TERT-mediated ERV/interferon signalling contributes to immune suppression in tumours.

Optimized gas pressure of an Rb vapor cell in a single-beam SERF magnetometer.

We present a theoretical and experimental study of a single-beam spin-exchange relaxation-free magnetometer in 87Rb vapor cells under different nitrogen gas pressures. The spin relaxation rate is a key component to limit the magnetic sensitivity, and the zero-field resonance method was used to measure the spin relaxation rates of different alkali metal cells. Simultaneously, in a single-beam spin-exchange-relaxation-free (SERF) magnetometer, we demonstrated that the fundamental magnetic field sensitivity was also limited by the pumping light intensity. Based on our theoretical analysis and experimental results, we determined the optimal pumping light intensity and optimal gas pressure. We experimentally demonstrated that the magnetic field sensitivity was 8.89 fT/Hz in the single-beam configuration, with an active measurement volume of 3 × 3 × 3~mm3.

Evaluation of optical parameters for a microminiature Rb vapor cell in a dual-beam SERF magnetometer.

In the spin-exchange relaxation-free (SERF) magnetometer of a perpendicular pump-probe configuration, the pump and probe beam characteristics significantly affect the performance. In this paper, an efficient evaluation of optical parameters to improve the sensitivity of a miniature magnetometer has been presented. We have determined the pump light's optimal intensity and wavelength through theoretical analysis and the zero-field resonance experiments. Chirp signals are applied to measure the optical rotations at different probe intensities and frequencies. Through theoretical and experimental analysis of noise source characterization under different beam intensities and wavelengths, we demonstrate that dual-beam magnetometer performance is mainly limited by photon shot noise. Based on the optimum pump and probe beam parameters, we demonstrate magnetic field sensitivity of 6.3 fT/Hz in an 87Rb vapor cell filled with nitrogen gas, with an active measurement volume of 3 × 3 × 3 mm3.

Rabi oscillation of spin-polarized rubidium in the spin-exchange relaxation-free regime.

The transient dynamics of atomic spins under oscillating and static magnetic fields have been studied in the spin-exchange relaxation-free (SERF) regime with a dual-beam configuration. The spin-relaxation rate can be accurately measured by detecting the transient response signal of the free induction decay (FID) process within several milliseconds. Leveraging this convenient method for measuring a large relaxation rate in a small cell volume, the dependence of the spin-relaxation rate on the probe intensity and ambient magnetic field was studied in the limit of low spin polarization. Moreover, by theoretical analysis of the dynamic evolution of the Rabi oscillation generated by a consecutive oscillating field and a small static magnetic field, we experimentally demonstrate that the amplitude of the Rabi oscillation is affected by the amplitude of the oscillating field in the SERF regime. According to the retrieved frequency of the FID signal and amplitude of relevant Rabi oscillation, the coil constants were 75.55 ± 0.78~nT/mA, 151.5 ± 0.9~nT/mA, and 116.6 ± 0.3~nT/mA along the x-, y-, and z-axes, respectively.

Adaptive Neural Network Control of Time Delay Teleoperation System Based on Model Approximation.

A bilateral neural network adaptive controller is designed for a class of teleoperation systems with constant time delay, external disturbance and internal friction. The stability of the teleoperation force feedback system with constant communication channel delay and nonlinear, complex, and uncertain constant time delay is guaranteed, and its tracking performance is improved. In the controller design process, the neural network method is used to approximate the system model, and the unknown internal friction and external disturbance of the system are estimated by the adaptive method, so as to avoid the influence of nonlinear uncertainties on the system.

Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones.

BACKGROUND: Sex hormones play important roles in the estrus return of post-weaning sows. Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota. However, the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown. RESULTS: In this study, we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows. Using metagenomic sequencing data from 85 fecal samples, we identified 37 bacterial species that were significantly associated with estrus return. Normally returning sows were characterized by increased abundances of L. reuteri and P. copri and decreased abundances of B. fragilis, S. suis, and B. pseudolongum. The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome. The results were confirmed in a validation cohort. Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis. An integrated analysis of differential bacterial species, metagenome, and fecal metabolome provided evidence that normal return-associated bacterial species L. reuteri and Prevotella spp. participated in the degradation of pregnenolone, progesterone, and testosterone, thereby promoting estrogen biosynthesis. Furthermore, the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return. CONCLUSIONS: An integrated analysis of differentially abundant bacterial species, metagenome, and fecal metabolome revealed the involvement of L. reuteri and Prevotella spp. in sow estrus return. These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones, suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.

The influence of modulated magnetic field on light absorption in SERF atomic magnetometer.

A single-beam spin-exchange relaxation-free atomic magnetometer is ultra-sensitive in the zero field, which has great potential for the detection of a magnetoencephalogram. The addition of a modulated magnetic field is an important approach to achieve high sensitivity for devices of this kind. In this study, we discovered that the amplitude and frequency of the modulated magnetic field (modulation index 0-3) both influence the light absorption. We defined this effect into a function by combining theoretical analysis and the results of experiments. It is discovered that the transmission intensity decreases with an increase in the modulation index. This effect is weakened under the application of a high modulation index. In addition, the transmission intensity and bias magnetic field no longer follow a strict Lorentz curve, while a high degree of fit can be achieved by applying the numerical solution of the Bloch function. A compact magnetometer with a volume of 10 cm3 and a sensitivity of 20 fT/Hz is developed based on the single beam scheme for the proof of concept. Our study is crucial in two aspects: (1) Obtaining high sensitivity through a short measurement period and (2) alignment of the scale factor of the individual magnetometer in a detection array, which further pave the way for improvement in a magnetometer's performance under a variety of optics platforms.

Gut bacterial species in late trimester of pregnant sows influence the occurrence of stillborn piglet through pro-inflammation response.

Maternal gut microbiota is an important regulator for the metabolism and immunity of the fetus during pregnancy. Recent studies have indicated that maternal intestinal microbiota is closely linked to the development of fetus and infant health. Some bacterial metabolites are considered to be directly involved in immunoregulation of fetus during pregnancy. However, the detailed mechanisms are largely unknown. In this study, we exploited the potential correlation between the gut microbiota of pregnant sows and the occurrence of stillborn piglets by combining the 16S rRNA gene and metagenomic sequencing data, and fecal metabolome in different cohorts. The results showed that several bacterial species from Bacteroides, potential pathogens, and LPS-producing bacteria exhibited significantly higher abundances in the gut of sows giving birth to stillborn piglets. Especially, Bacteroides fragilis stood out as the key driver in both tested cohorts and showed the most significant association with the occurrence of stillborn piglets in the DN1 cohort. However, several species producing short-chain fatty acids (SCFAs), such as Prevotella copri, Clostridium butyricum and Faecalibacterium prausnitzii were enriched in the gut of normal sows. Functional capacity analysis of gut microbiome revealed that the pathways associated with infectious diseases and immune diseases were enriched in sows giving birth to stillborn piglets. However, energy metabolism had higher abundance in normal sows. Fecal metabolome profiling analysis found that Lysophosphatidylethanolamine and phosphatidylethanolamine which are the main components of cell membrane of Gram-negative bacteria showed significantly higher concentration in stillbirth sows, while SCFAs had higher concentration in normal sows. These metabolites were significantly associated with the stillborn-associated bacterial species including Bacteroides fragilis. Lipopolysaccharide (LPS), IL-1ß, IL-6, FABP2, and zonulin had higher concentration in the serum of stillbirth sows, indicating increased intestinal permeability and pro-inflammatory response. The results from this study suggested that certain sow gut bacterial species in late trimester of pregnancy, e.g., an excess abundance of Bacteroides fragilis, produced high concentration of LPS which induced sow pro-inflammatory response and might cause the death of the relatively weak piglets in a farrow. This study provided novel evidences about the effect of maternal gut microbiota on the fetus development and health.

Induction of heat shock protein 27 by bicyclol attenuates d-galactosamine/lipopolysaccharide-induced liver injury.

Heat shock proteins (Hsps) are critical for cell survival under adverse environmental conditions. Bicyclol is a novel hepatoprotectant that has been shown to protect against liver injury by inducing Hsps, including Hsp27 and Hsp70. Although the role of Hsp70 in protecting against acute hepatic failure has been clearly explored, the precise function of Hsp27 in this setting is poorly defined. This study was undertaken to evaluate the role of Hsp27 in bicyclol-mediated hepatoprotection. Both primary hepatocytes and bone marrow-derived macrophages were subjected to bicyclol treatment, followed by detection of Hsp27 expression. Adenoviruses containing the mouse Hsp27 coding sequence or shRNA interference sequence targeting Hsp27 were used to manipulate Hsp27 expression in the liver before the mice were treated with bicyclol and/or confronted with D-galactosamine/lipopolysaccharide (Galn/LPS)-induced acute liver damage. Only hepatocytes increased their Hsp27 expression after bicyclol treatment and the time course of bicyclol-induced Hsp27 expression in hepatocytes was in line with the in vivo results. Although high-dose bicyclol could protect against liver failure without Hsp27, the effect of bicyclol given at a low dose was dependent on Hsp27 induction. Adenovirus-mediated transduction of Hsp27 protected against acute liver damage and partially replicated the protective effect afforded by bicyclol. These results demonstrated that bicyclol induced Hsp27 expression in hepatocytes, which was essential to bicyclol-mediated hepatoprotection. Overexpression of Hsp27 in hepatocytes could confer remarkable protection against acute liver damage.