Combination of Human Leukocyte Antigen and Killer Cell Immunoglobulin-Like Receptor Genetic Background Influences the Onset Age of Hepatocellular Carcinoma in Male Patients with Hepatitis B Virus Infection

To investigate whether killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) genetic background could influence the onset age of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection, one hundred and seventy-one males with HBV-related HCC were enrolled. The presence of 12 loci of KIR was detected individually. HLA-A, -B, and -C loci were genotyped with high resolution by a routine sequence-based typing method. The effect of each KIR locus, HLA ligand, and HLA-KIR combination was examined individually by Kaplan-Meier (KM) analysis. Multivariate Cox hazard regression model was also applied. We identified C1C1-KIR2DS2/2DL2 as an independent risk factor for earlier onset age of HCC (median onset age was 44 for C1C1-KIR2DS2/2DL2 positive patients compared to 50 for negative patients, P=0.04 for KM analysis; HR = 1.70, P=0.004 for multivariate Cox model). We conclude that KIR and HLA genetic background can influence the onset age of HCC in male patients with HBV infection. This study may be useful to improve the current HCC surveillance program in HBV-infected patients. Our findings also suggest an important role of natural killer cells (or other KIR-expressing cells) in the progress of HBV-related HCC development

KIR and HLA Loci Are Associated with Hepatocellular Carcinoma Development in Patients with Hepatitis B Virus Infection: A Case-Control Study

BACKGROUND: Natural killer (NK) cells activation has been reported to contribute to inflammation and liver injury during hepatitis B virus (HBV) infection both in transgenic mice and in patients. However, the role of NK cells in the process of HBV-associated hepatocellular carcinoma (HCC) development has not been addressed. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating NK cell activation through recognition of specific human leukocyte antigen (HLA) class I allotypes. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether KIR and HLA genes could influence the risk of HBV-associated HCC development, 144 HBV-infected patients with HCC and 189 well-matched HBV infectors with chronic hepatitis or cirrhosis as non-HCC controls were enrolled in this study. The presence of 12 loci of KIR was detected individually. HLA-A, -B, -C loci were genotyped with high-resolution. HLA-C group 1 homozygote (OR = 2.02; p = 0.005), HLA-Bw4-80I (OR = 2.67; p = 2.0E-04) and combination of full-length form and 22 bp-deleted form of KIR2DS4 (KIR2DS4/1D) (OR = 1.89; p = 0.017) were found associated with HCC incidence. When the combined effects of these three genetic factors were evaluated, more risk factors were observed correlating with higher odds ratios for HCC incidence (P trend = 7.4E-05). Because all the risk factors we found have been reported to result in high NK cell functional potential by previous studies, our observations suggest that NK cell activation may contribute to HBV-associated HCC development. CONCLUSIONS/SIGNIFICANCE: In conclusion, this study has identified significant associations that suggest an important role for NK cells in HCC incidence in HBV-infected patients. Our study is useful for HCC surveillance and has implications for novel personalized therapy strategy development aiming at HCC prevention in HBV-infected patients

A heterozygous moth genome provides insights into herbivory and detoxification

How an insect evolves to become a successful herbivore is of profound biological and practical importance. Herbivores are often adapted to feed on a specific group of evolutionarily and biochemically related host plants1, but the genetic and molecular bases for adaptation to plant defense compounds remain poorly understood2. We report the first whole-genome sequence of a basal lepidopteran species, Plutella xylostella, which contains 18,071 protein-coding and 1,412 unique genes with an expansion of gene families associated with perception and the detoxification of plant defense compounds. A recent expansion of retrotransposons near detoxification-related genes and a wider system used in the metabolism of plant defense compounds are shown to also be involved in the development of insecticide resistance. This work shows the genetic and molecular bases for the evolutionary success of this worldwide herbivore and offers wider insights into insect adaptation to plant feeding, as well as opening avenues for more sustainable pest management.Minsheng You … Simon W Baxter … et al

Dynamic Operation Loss Minimization for Permanent Magnet Synchronous Generator Based on Improved Model Predictive Direct Torque Control

During permanent magnet synchronous generator (PMSG) operation, aside from improving the rapid response of torque and reducing the rippling of torque and flux to guarantee the operational reliability, the loss of the PMSG itself cannot be ignored either. Aiming at this problem, an improved model predictive direct torque control (MPDTC) method is proposed, which suppresses the torque ripple and achieves PMSG efficiency optimization. Firstly, based on the conventional MPDTC and the loss model of PMSG, the predicted stator active current is determined, which is utilized for obtaining the predicted torque. Secondly, combined with the generator loss model, the set value of the stator energetic current is obtained; combined with the wind power system maximum power point tracking method, the set value of generator torque is obtained. Thirdly, by converting the torque control error and current control error into a per unit value, the influence of the weight coefficient in the cost function on the control effect is reduced. Finally, the key results verified the effectiveness and superiority of the proposed control scheme by simulation and experiment

Dynamic Operation Loss Minimization for Permanent Magnet Synchronous Generator Based on Improved Model Predictive Direct Torque Control

During permanent magnet synchronous generator (PMSG) operation, aside from improving the rapid response of torque and reducing the rippling of torque and flux to guarantee the operational reliability, the loss of the PMSG itself cannot be ignored either. Aiming at this problem, an improved model predictive direct torque control (MPDTC) method is proposed, which suppresses the torque ripple and achieves PMSG efficiency optimization. Firstly, based on the conventional MPDTC and the loss model of PMSG, the predicted stator active current is determined, which is utilized for obtaining the predicted torque. Secondly, combined with the generator loss model, the set value of the stator energetic current is obtained; combined with the wind power system maximum power point tracking method, the set value of generator torque is obtained. Thirdly, by converting the torque control error and current control error into a per unit value, the influence of the weight coefficient in the cost function on the control effect is reduced. Finally, the key results verified the effectiveness and superiority of the proposed control scheme by simulation and experiment

Association of Human Leukocyte Antigen Class I Polymorphism with Spontaneous Clearance of Hepatitis B Surface Antigen in Qidong Han Population

Aim. To investigate whether HLA class I polymorphisms could influence the clearance of hepatitis B surface antigen (HBsAg) in Qidong Han population. Methods. We genotyped HLA-A, -B, and -C loci of 448 individuals with HBV persistent infection and 140 persons with spontaneous clearance of HBsAg by polymerase chain reaction with sequencing based typing (PCR/SBT). All the individuals were unrelated males enrolled from Qidong Han population and were followed up for 10 years. Results. The frequency of HLA-A * 33:03:01G was increased in persistent HBV infection group ( value is 0.028), while frequency of HLA-B * 13:01:01G was increased in HBsAg clearance group ( value is 0.0004). Conclusion. These findings suggested that the host HLA class I polymorphism is an important factor in determining the outcomes of HBV infection

Efficacy and Safety of Different Courses of Tongxinluo Capsule as Adjuvant Therapy for Coronary Heart Disease after Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Tongxinluo capsule (TXLC) is a widely used traditional Chinese medicine for coronary heart disease (CHD). However, the efficacy and safety of different courses of TXLC for CHD after percutaneous coronary intervention (PCI) have not been systematically evaluated yet. The Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database were searched from the inception to 26 August 2021. A meta-analysis was performed using a fixed- or random-effects model. The risk of adverse cardiovascular events, mortality, or adverse effects was evaluated by risk ratio (RR) with 95% confidence interval (CI). Thirty-four studies involving 3652 patients were finally included. After the 6-month treatment, compared with conventional treatment alone, TXLC combined with conventional treatment achieved better efficacy in lowering the risk of angiographic restenosis (RR = 0.37, 95% CI = 0.28–0.48, p p p p p p = 0.001), and mortality due to any cardiovascular event (RR = 0.27, 95% CI = 0.09–0.80, p = 0.018). After the 12-month treatment, TXLC reduced the recurrence risk of angina (RR = 0.40, 95% CI = 0.20–0.80, p = 0.009). However, there was no difference in any outcomes after the 3-month treatment. Besides, no difference was found in the incidence of adverse effects after the 3-month and 6-month treatments (3 months: RR = 0.73, 95% CI = 0.35–1.56, p = 0.418; 6 months: RR = 1.71, 95% CI = 0.74–3.93, p = 0.209). The certainty of evidence ranged from very low to moderate due to the risk of bias, inconsistency, and imprecision. TXLC showed beneficial effects on reducing the adverse cardiovascular events without compromising safety for CHD patients after PCI on the 6-month course. However, due to the unavoidable risk of bias, more high-quality and long-term studies are still needed to further evaluate the efficacy and safety of TXLC in many countries, not only in China

Involvement of NF-κB, CREB and IRF-1 in neuronal MHC-I expression.

<p>(A) Western blot analysis of time-dependent activation of NF-κB p65, CREB as well as the increased expression of IRF-1 by adding 100μM KA to 8 div hippocampal neurons for 30min. (B) The densitometric analyses of p-p65/p65, p-CREB/CREB, and IRF-1/Tuj1 from three separate experiments were taken, and the data was shown as ratio compared to control. All the data are indicated as mean±SD. (C) Western blot analysis of the expression level of of NF-κB p65, CREB as well as the expression of IRF-1 during the development stages of mouse hippocampus. (D) The densitometric analyses of p-p65/p65, p-CREB/CREB, and IRF-1/Tuj1 from four separate experiments were taken, and the data was shown as ratio compared to P4. All the data are indicated as mean±SD.</p