Search

Lupus anticoagulants (LA) increase the risk of thrombotic and obstetric events in patients with antiphospholipid syndrome than in those with other antiphospholipid antibodies. Anti-phosphatidylserine/prothrombin (aPS/PT) complex antibodies are thought to cause LA positivity. Therefore, we aimed to explore whether aPS/PT antibodies could prolong phospholipid (PL)-dependent clotting time and increase the risk of thrombosis or pregnancy complications based on LA positivity.We recruited 222 patients with positive LA and estimated their aPS/PT, anticardiolipin (aCL), anti-β2-glycoprotein I (aβ2GPI), and anti-β2GPI domain I (anti-D1) antibody (IgM and IgG) titers and PL-dependent clotting time.PT was longer in aPS/PT IgG-positive patients than in aPS/PT IgM-negative patients (P0.001), while there was no significant difference between aPS/PT IgM-positive and IgM-negative patients (P = 0.100). Both SCT-S and dRVVT-S were prolonged in aPS/PT (IgG and IgM)-positive patients compared to aPS/PT-negative patients (P0.001, P = 0.010, P0.001, P = 0.002, respectively). Similarly, the associations between aPS/PT IgG or IgM antibody titers and SCT-S or dRVVT-S were significant. SCT-C and dRVVT-C did not show any significant differences. The incidence of thrombosis in the aPS/PT IgG-positive group was much higher than that in the IgG-negative group (P = 0.012). Likewise, the incidence of thrombosis was higher in the anti-D1- and aPS/PT IgG-positive patients than in the negative controls (40% vs. 14.3%, χThe aPS/PT antibodies prolonged PL-dependent clotting time, especially SCT-S and dRVVT-S. In addition, the presence of aPS/PT IgG antibodies increased the risk of thrombosis in LA positivity.

Luteolin can affect multiple biological functions, such as anti-inflammatory, antioxidant and immune enhancement processes. Luteolin can inhibit inflammation of T2-high asthma, but its role in neutrophilic asthma has been insufficently studied.This study determines the effect of luteolin on IL-36γ secretion-mediated MAPK pathway signalling in neutrophilic asthma.The asthma model was established by using ovalbumin/lipopolysaccharide (OVA/LPS). Female 6-8-week-old C57BL/6 mice were divided into control, asthma, luteolin (20 mg/kg) and asthma + luteolin (20 mg/kg) groups. To explore the mechanism of anti-inflammatory effects of luteolin in neutrophilic asthma, Beas-2B cells were treated with luteolin (20 µmol/L), LPS (100 ng/mL), recombinant human IL-36γ protein (rhIL-36γ; 100 ng/mL) or IL-36γ siRNA.IL-36γ secretion and MAPK/IL-1β signalling were significantly increased in the asthma mouse model compared with the control (Luteolin alleviated neutrophilic asthma by inhibiting IL-36γ secretion-mediated MAPK pathways. These findings provided a theoretical basis for the application of luteolin in the treatment of neutrophilic asthma.

The DArk Matter Particle Explorer (DAMPE) is well suitable for searching for monochromatic and sharp $\gamma$-ray structures in the GeV$-$TeV range thanks to its unprecedented high energy resolution. In this work, we search for $\gamma$-ray line structures using five years of DAMPE data. To improve the sensitivity, we develop two types of dedicated data sets (including the BgoOnly data which is the first time to be used in the data analysis for the calorimeter-based gamma-ray observatories) and adopt the signal-to-noise ratio optimized regions of interest (ROIs) for different DM density profiles. No line signals or candidates are found between 10 and 300 GeV in the Galaxy. The constraints on the velocity-averaged cross section for $\chi\chi \to \gamma\gamma$ and the decay lifetime for $\chi \to \gamma\nu$, both at 95% confidence level, have been calculated and the systematic uncertainties have been taken into account. Comparing to the previous Fermi-LAT results, though DAMPE has an acceptance smaller by a factor of $\sim 10$, similar constraints on the DM parameters are achieved and below 100 GeV the lower limits on the decay lifetime are even stronger by a factor of a few. Our results demonstrate the potential of high-energy-resolution observations on dark matter detection., Comment: 14 pages, 8 figures. Update the content to keep up with the published version

The mononuclear phagocyte system (MPS) consists of monocytes, dendritic cells and macrophages, which play vital roles in innate immune defense against cancer. Hepatocellular carcinoma (HCC) is a complex disease that is affected or initiated by many factors, including chronic hepatitis B virus infection, hepatitis C virus infection, metabolic disorders or alcohol consumption. Liver function, tumor stage and the performance status of patients affect HCC clinical outcomes. Studies have shown that targeted treatment of tumor microenvironment disorders may improve the efficacy of HCC treatments. Cytokines derived from the innate immune response can regulate T-cell differentiation, thereby shaping adaptive immunity, which is associated with the prognosis of HCC. Therefore, it is important to elucidate the function of the MPS in the progression of HCC. In this review, we outline the impact of HCC on the MPS. We illustrate how HCC reshapes MPS cell phenotype remodeling and the production of associated cytokines and characterize the function and impairment of the MPS in HCC.

There are many commercially available glycogen particles in the market due to their bioactive functions as food additive, drug carrier and natural moisturizer, etc. It would be beneficial to rapidly determine the origins of commercially-available glycogen particles, which could facilitate the establishment of quality control methodology for glycogen-containing products. With its non-destructive, label-free and low-cost features, surface enhanced Raman spectroscopy (SERS) is an attractive technique with high potential to discriminate chemical compounds in a rapid mode. In this study, we applied the combination of SERS technique and machine leaning algorithms on glycogen analysis, which successfully predicted the origins of glycogen particles from a variety of organisms with convolutional neural network (CNN) algorithm plus attention mechanism having the best computational performance (5-fold cross validation accuracy = 96.97 %). In sum, this is the first study focusing on the discrimination of commercial glycogen particles originated from different organisms, which holds the application potential in quality control of glycogen-containing products.

Preeclampsia (PE) is characterized by placenta-mediated pregnancy complication. The only effective treatment for PE is the delivery of the placenta. However, this treatment may cause preterm birth and neonatal death. Therefore, preventing PE is needed. The mechanism of PE involves abnormal placentation, which leads to the release of anti-angiogenic and inflammatory mediators into maternal circulation. These mediators contribute to systemic vascular dysfunction, inflammatory responses, and excessive thrombin generation. Microparticles (MPs) are reportedly involved in PE by promoting the thromboinflammatory response. This study describes a strategy to prevent PE by reducing MP release using the recombinant protein, diannexin. Results showed that the patients with PE had elevated MP number and procoagulant activity and increased NLRP3 inflammasome activation. Additionally, diannexin remarkably reduced the release of MPs from activated cells by binding to phosphatidylserine exposed on the surface of activated cells. Moreover, in vivo results showed that diannexin could prevent PE-like symptoms by decreasing MPs and NLRP3 inflammasome activation in pregnant mice. Furthermore, diannexin effectively inhibited trophoblast cell activation and NLRP3 inflammasome activation in vitro. These findings suggested that diannexin inhibited MP release and might be an effective therapeutic strategy for preventing PE.

Since FRB 200428 has been found to be associated with an X-ray burst from the Galactic magnetar SGR J1935+2154, it is interesting to explore whether the magnetar bursts also follow the similar active periodic behaviour as some repeating FRBs. Previous studies show that there is possible period of about 230 days in SGR J1935+2154 bursts. Here, we collected an updated burst sample from SGR J1935+2154, including all bursts reported by Fermi/GBM and GECAM till 2022 January. We also developed a targeted search pipeline to reveal more bursts from SGR J1935+2154 in the Fermi/GBM data from 2008 August to 2014 December (i.e. before the first burst detected by Swift/BAT). With this burst sample, we re-analysed the possible periodicity of SGR J1935+2154 bursts using the Period Folding and Lomb–Scargle Periodogram methods. Our results show that the periodicity ∼238 days reported in literature is probably fake and the observation effects may introduce false periods (i.e. 55 days) according to simulation tests. We find that, for the current burst sample, the most probable period is 126.88 ± 2.05 days, which could be interpreted as the precession of the magnetar. However, we note that the whole burst history is very complicated and difficult to be perfectly accommodated with any period reported thus far, therefore more monitoring observations of SGR J1935+2154 are required to test any periodicity hypothesis.

Since the insulation performance of air is not as good as that of SF6 and other gases, it is necessary to conduct an in-depth study on the insulation characteristics of the fuse tube in order to meet the requirements of normal breaking and to design a structural improvement scheme for a 12 kV environmental protection cabinet fuse tube that is suitable for using air as the insulating medium. In this study, the insulation performance of the fuse tube before improvement was studied, and the electric-field distribution of the 12 kV fuse tube placed in the air-insulated switchgear was analyzed. The results showed that the electric-field was heavily concentrated in the air gap of the fuse tube plug and around the ground rod. In this study, the structure of the fuse tube was specifically designed. By spraying conductive paint on the intersection surface of different media, equipotentiality was achieved, and a reasonable metal shielding structure was added to the site where the field intensity was concentrated so as to improve the distribution of the electric-field and avoid the breakdown caused by the concentration of field intensity. Through several improved designs, the maximum electric-field strength of the fuse tube of an environmental protection cabinet can be effectively reduced, and the insulation requirements of relevant standards can be met. A partial discharge test for the improved fuse tube was carried out, and the local discharge quantity of the improved fuse tube met the industry requirements, which verified the rationality of the fuse-tube-improvement scheme.

Background Polymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms. Methods A case–control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining. Results The miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000–1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017–1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018–1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele. Conclusion The variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3′UTR of IKBA and activating NF-κB inflammatory pathways.

S1. TAp73 activates the expression of 6PGD

S2. TAp73 enhances PPP via 6PGD

Cancer cells frequently alter their metabolism to support biogenesis and proliferation and survive specific metabolic stressors. The glucose-associated pentose phosphate pathway (PPP) is crucial for cancer cell proliferation. In particular, 6-phosphogluconate dehydrogenase (6PGD), the second dehydrogenase in the PPP, catalyzes the decarboxylation of 6-phosphogluconate into ribulose 5-phosphate (Ru5P). However, the mechanisms controlling 6PGD expression in cancer cells remain unclear. Herein, we show that TAp73 increases Ru5P and NADPH production through 6PGD activation to counteract reactive oxygen species and protects cells from apoptosis. Moreover, 6PGD overexpression rescues the proliferation and tumorigenic ability of TAp73-deficient cells. These findings further establish the critical role of TAp73 on glucose metabolism regulation, demonstrating that TAp73 can activate 6PGD expression to support oncogenic cell growth.Implications:By transcriptional upregulation of 6PGD, TAp73 promotes the generation of Ru5P and NADPH, and enhances tumor cell proliferation.

Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) is a dedicated mission, launched in December 2020, for gamma-ray transients, including gamma-ray bursts (GRBs) and soft gamma repeater (SGR) bursts in the multimessenger and multiwavelength astronomy era. Since GECAM consists of two independent spacecrafts (or say instruments), and the framework of data analysis for multiple spacecrafts is distinctive from that for only one spacecraft, which is the case for most GRB missions, we developed a dedicated pipeline called Energetic Transients Joint Analysis System for Multi-INstrument (ETJASMIN) for GECAM mission. This pipeline has been naturally extended to incorporate data from other gamma-ray instruments, including the operating missions, such as Insight-HXMT/HE, Fermi/GBM, Swift/BAT, INTEGRAL/SPI-ACS, Konus-Wind, and GRID, as well as the forthcoming missions, such as SVOM/GRM and HEBS. In this paper, we present this pipeline with a focus on the data analysis procedures, methodology, and results in terms of the localization, verification (classification), spectral, and temporal analyses of gamma-ray transients. We show that this pipeline could provide more accurate, reliable, and comprehensive results than that of individual spacecraft, which is beneficial for gamma-ray transients observation.

Objective: To study the clinical efficacy of Dapagliflozin in patients with coronary heart disease (CHD) combined with Heart Failure with Reduced Ejection Fraction (HFrEF) and type 2 diabetes mellitus (T2DM) who have CHD. Methods: A retrospective analysis of 202 patients with CHD and T2DM who were hospitalized in our department of cardiovascular medicine and underwent PCI treatment from November 2019 to November 2022 was conducted. Patients were divided into two groups according to whether they received Dapagliflozin treatment: the Dapagliflozin group (n=100) and the control group (n=102). A subgroup analysis was performed on the 80 HFrEF patients in the total population, which was also divided into two groups: the Dapagliflozin group (n=44) and the control group (n=36). The incidence of major adverse cardiovascular events (MACE) during hospitalization and the median follow-up period (224.5 days) was recorded and analyzed in both the total population and the subgroup. Results: The results of the analysis of the total patient population showed no statistical differences between the two groups in baseline data and related clinical treatment conditions (P>0.05). The follow-up period event analysis showed that the overall MACE event rate in the Dapagliflozin group was lower than that in the control group (6.00% vs. 17.65%), but not statistically significant (P=0.071). The COX regression analysis of MACE events showed that the use of Dapagliflozin was an independent protective factor for MACE events [HR=0.166, 95% CI (0.026-0.953), P=0.047]. In the HFrEF subgroup analysis, there was no significant difference between the two groups in the baseline data analysis (P>0.05). The COX regression analysis in the subgroup analysis showed that the use of Dapagliflozin was a strong protective factor for the HFrEF subgroup during the follow-up period [HR=0.250, 95% CI (0.017-0.518), P Conclusion: The use of Dapagliflozin in patients with CHD combined with HFrEF and T2DM may be effective in reducing the incidence of MACE.

Objective To explore the role of PD-L1/PD-1 blockage in the cytotoxicity of natural killer cell in NSCLC. Methods Two NSCLC cell lines, Calu-1 and H460, were tested for susceptibility to the cytolytic activity of freshly isolated healthy donor NK cells by a non-radioactive cellular cytotoxicity assay kit. Western blot analysis, FACS, ELISA and antibody blockage experiments were conducted to determine the mechanisms. NK cells isolated from NSCLC patients were also collected for functional assays. Results Calu-1 and H460 cells were lysed by NK cells in a dose-dependent manner. H460 cells showed less susceptibility to NK cell-mediated lysis than Calu-1 cells at all ratios. The expression of PD-L1 on H460 cells was higher than that on Calu-1 cells, as determined by FACS and western blot analysis. The specific lysis of H460 cells by NK cells was enhanced when the PD-L1/PD-1 interaction was blocked by anti-PD-L1 antibody. This finding was also demonstrated in NK cells isolated from NSCLC patients. Conclusions The present study revealed that PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cells in NSCLC via granzyme B secretion. This study will greatly facilitate the precise treatment of lung cancer through determination of PD-L1 expression in tumors.

SARS-CoV-2 is continuing to evolve and diversify, with an array of various Omicron sub-lineages, including BA.5, BA.2.75, BN.1, BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5, now circulating globally at recent time. In this study, we evaluated the neutralization sensitivity of a comprehensive panel of Omicron subvariants to sera from different clinical cohorts, including individuals who received homologous or heterologous booster vaccinations, vaccinated people who had Delta or BA.2 breakthrough infection in previous waves, and patients who had BA.5 or BF.7 breakthrough infection in the current wave in China. All the Omicron subvariants exhibited substantial neutralization evasion, with BQ.1, BQ.1.1, XBB.1, and XBB.1.5 being the strongest escaped subvariants. Sera from Omicron breakthrough infection, especially the recent BA.5 or BF.7 breakthrough infection, exhibited higher neutralizing activity against all Omicron sub-lineages, indicating the chance of BA.5 and BF.7 being entirely replaced by BQ or XBB subvariants in China in a short-term might be low. We also demonstrated that the BQ and XBB subvariants were the most resistant viruses to monoclonal antibodies. Continuing to monitor the immune escape of SARS-CoV-2 emerging variants and developing novel broad-spectrum vaccines and antibodies are still crucial.

A charged particle detector (CPD) is one of two main detectors on the GECAM satellite. It was designed to detect charged particles. Electrons and protons are space’s mainly charged particles. So, a research on the proton detection ability of a CPD and deriving the energy response to charged particles of the CPD in the two designed operating modes is important. The proton calibration tests of the CPD under different working modes were carried out at the Heavy Ion Research Facility in Lanzhou. Through testing and analysis, it was concluded that when CPD works in semi-component mode, it can detect the maximum energy, and when working in full-component mode, it can provide better energy resolution.