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Wuling capsule has been used in treatment of insomnia disorder in China for decades, but the reported treatment efficacy of different studies was not consistent. This study intended to evaluate the efficacy and safety of Wuling capsule for insomnia disorder, so as to provide evidence for clinical application.Eight databases (MEDLINE, EMBASE, Ovid, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, Chinese Biomedical Database and Wanfang) were searched from inception to September 14, 2021. Randomized controlled trials (RCTs) comparing Wuling capsule with controls in adults with insomnia disorder were eligible. The primary outcome was sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI), and the secondary outcomes were severity of insomnia disorder measured by Sleep Dysfunction Rating Scale (SDRS) and adverse events. This study was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.Nineteen RCTs with a total of 1850 participants were included. In terms of sleep quality assessed by PSQI, Wuling capsule significantly lowered PSQI score (MD: -1.92, 95% CI: [-2.34, -1.50], P 0.00001, IWuling capsule can safely and effectively improve sleep quality in patients with insomnia disorder. However, these findings require careful recommendation due to the high heterogeneity and high risk of bias in the included trials. Clinical trials with higher quality designs are needed.

Four dinuclear osmium complexes have been constructed for antitumor phototherapy. The most potent Os4 has extremely high photothermal conversion capability under irradiation of an 808 nm low-power laser, targets mitochondria in human melanoma cells without nucleus affinity, and acts as an antitumor photothermal therapy agent

A series of dinuclear Ru

Objective The clinical importance of aberrantly expressed microRNAs (miRNAs) in diagnosing inflammatory bowel disease (IBD) has not been well established, so was investigated in this systematic review and meta-analysis. Methods Articles in online databases from inception to March 17, 2021 were retrieved. Random effects meta-analysis was used to obtain sensitivity, specificity, positive (PLRs) and negative likelihood ratios (NLRs), diagnostic odds ratios (DORs), and areas under the curve (AUC) with 95% confidence intervals (CI) for IBD diagnosis. Results Of 117 studies reporting altered miRNA expression in IBD included in the systematic review, 15 involving 937 patients with IBD and 707 controls, 22 miRNAs, and two miRNA panels were eligible for meta-analysis. Pooled analyses showed a moderate diagnostic accuracy for miRNAs in the IBD diagnosis, with a sensitivity of 0.80 (95% CI: 0.79–0.82), specificity of 0.84 (95% CI: 0.82–0.86), DOR of 21.19 (95% CI: 13.90–32.31), and AUC of 0.89. Subgroup analyses revealed a better performance in patients with ulcerative colitis (AUC, 0.93) than Crohn’s disease (AUC, 0.84). Consistent upregulation of miR-21, miR-16, and miR-192 in blood with a high-moderate diagnostic accuracy was found in at least two studies. Conclusions These findings suggest miRNAs are credible diagnostic biomarkers in IBD.

Background Coronary artery disease (CAD) is a common comorbidity of chronic obstructive pulmonary disease (COPD). However, data related to the impact of CAD on outcomes of acute exacerbation of COPD (AECOPD) are limited and whether the relationship depends on sex remains unknown. Our aim was to determine the impact of comorbid CAD on clinical outcomes among men and women with AECOPD. Methods We used data from the acute exacerbation of chronic obstructive pulmonary disease inpatient registry (ACURE) study, which is a nationwide observational real-world study conducted between September 2017 and February 2020 at 163 centers in patients admitted with AECOPD as their primary diagnosis. Patients were stratified according to the presence or absence of CAD in men and women. The primary outcomes were the length of hospital stay and economic burden during hospitalization. Results Among 3906 patients included in our study, the prevalence of CAD was 17.0%, and it was higher in women than in men (19.5% vs. 16.3%; P = 0.034). Age and other cardiovascular diseases were common factors associated with comorbid CAD in men and women, while body-mass index, cerebrovascular disease, and diabetes were determinants in men and pre-admission use of long-acting beta-adrenoceptor agonist and home oxygen therapy were protective factors in women. Only in men, patients with CAD had a longer length of hospital stay (median 10.0 vs. 9.0 days, P Conclusions In hospitalized AECOPD patients, comorbid CAD was significantly associated with poorer short-term outcomes in men. Clinicians should have heightened attention for men with comorbid CAD to achieve an optimal management of AECOPD patients.

Objectives To develop and validate a model for predicting the risk of early diabetic foot ulcer (DFU) based on systematic review and meta-analysis. Methods Data were analyzed from the risk factors of DFU with their corresponding risk ratio (RR) by meta-analysis. The DFU prediction model included statistically significant risk factors from the meta-analysis, all of which were scored by its weightings, and the prediction model was externally validated using a validation cohort from China. The occurrence of early DFU was defined as patients with type 2 diabetes who were free of DFU at baseline and diagnosed with DFU at follow-up. Evaluation of model performance was based on the area under the discrimination receiver operating characteristic curve (ROC), with optimal cutoff point determined by calculation of sensitivity and specificity. Kaplan–Meier curve were performed to compare the cumulative risk of different groups. Results Our meta-analysis confirmed a cumulative incidence of approximately 6.0% in 46,521 patients with diabetes. The final risk prediction model included Sex, BMI, HbA1c, Smoker, DN, DR, DPN, Intermittent Claudication, Foot care, and their RRs were 1.87, 1.08, 1.21, 1.77, 2.97, 2.98, 2.76, 3.77, 0.38, respectively. The total score of all risk factors was 80 points according to their weightings. The prediction model showed good discrimination with AUC = 0.798 (95 %CI 0.738–0.858). At the optimal cut-off value of 46.5 points, the sensitivity, specificity and Youden index were 0.769, 0.798 and 0.567, respectively. The final model stratified the validation cohort into low, low-intermediate, high-intermediate and high-risk groups; Compared with low-risk group, the RR with 95 %CI of developing DFU in high-intermediate and high-risk group were 17.23 (5.12–58.02), p Conclusion We have developed a simple tool to facilitates early identification of patients with diabetes at high risk of developing DFU based on scores. This simple tool may improve clinical decision-making and potentially guide early intervention.

ObjectivesTo identify factors associated with length of stay (LOS) in chronic obstructive pulmonary disease (COPD) hospitalised patients, which may help shorten LOS and reduce economic burden accrued over hospital stay.DesignA retrospective cohort study.SettingThis study was performed in a tertiary hospital in China.ParticipantsPatients with COPD who were aged ≥40 years and newly admitted between 2016 and 2017.Primary and secondary outcome measuresLOS at initial admission was the primary outcome and health expenditures were the secondary outcome. To identify factors associated with LOS, we collected information at index hospitalisation and constructed a conceptual model using directed acyclic graph. Potential factors were classified into five groups: demographic information, disease severity, comorbidities, hospital admission and environmental factors. Negative binomial regression model was fitted for each block of factors and a parsimonious analysis was performed.ResultsIn total, we analysed 565 patients with COPD. The mean age was 69±11 years old and 69.4% were men. The median LOS was 10 (interquartile range 8–14) days. LOS was significantly longer in patients with venous thromboembolism (VTE) (16 vs 10 days, p=0.0002) or with osteoporosis (15 vs 10 days, p=0.0228). VTE ((rate ratio) RR 1.38, 95% CI 1.07 to 1.76), hypoxic–hypercarbic encephalopathy (RR 1.53, 95% CI 1.06 to 2.20), respiratory infection (RR 1.12, 95% CI 1.01 to 1.24), osteoporosis (RR 1.45, 95% CI 1.07 to 1.96) and emergence admission (RR 1.08, 95% CI 1.01 to 1.16) were associated with longer LOS. In parsimonious analysis, all these factors remained significant except emergency admission, highlighting the important role of concomitant morbidities in patients’ hospital stay. Total hospitalisation cost and patients’ out-of-pocket cost increased monotonically with LOS (both ptrend ConclusionPatients’ concomitant morbidities predicted excessive LOS in patients with COPD. Healthcare cost increased over the LOS. Quality improvement initiatives may need to identify patients at high risk for lengthy stay and implement early interventions to reduce COPD economic burden.

This study introduces the feasibility study experience of intensive care clinical information management system in order to provide reference for the construction of intensive care clinical information management system in other hospitals.Four kinds of mainstream intensive care clinical information management system software were used to evaluate the implementation effect of each software such as equipment integration, information integration and application function module, so as to explore the construction scheme of intensive care clinical information management system.The optimized construction scheme and comprehensive feasibility study report of intensive care clinical information management system were formed, which provided an objective basis for the final scheme design, demonstration, procurement and decision-making of the hospital.The trial and feasibility study of intensive care clinical information management system contribute to optimize the construction scheme.

MicroRNA (miRNA) biogenesis is finely controlled by complex layers of post-transcriptional regulators, including RNA-binding proteins (RBPs). Here, we show that an RBP, QKI5, activates the processing of primary miR-124-1 (pri-124-1) during erythropoiesis. QKI5 recognizes a distal QKI response element and recruits Microprocessor through interaction with DGCR8. Furthermore, the recruited Microprocessor is brought to pri-124-1 stem loops by a spatial RNA-RNA interaction between two complementary sequences. Thus, mutations disrupting their base-pairing affect the strength of QKI5 activation. When erythropoiesis proceeds, the concomitant decrease of QKI5 releases Microprocessor from pri-124-1 and reduces mature miR-124 levels to facilitate erythrocyte maturation. Mechanistically, miR-124 targets TAL1 and c-MYB, two transcription factors involved in normal erythropoiesis. Importantly, this QKI5-mediated regulation also gives rise to a unique miRNA signature, which is required for erythroid differentiation. Taken together, these results demonstrate the pivotal role of QKI5 in primary miRNA processing during erythropoiesis and provide new insights into how a distal element on primary transcripts affects miRNA biogenesis.

Transcriptional activity is repressed due to the packaging of sperm chromatins during spermiogenesis. The detection of numerous transcripts in sperm, however, raises the question whether transcriptional events exist in sperm, which has been the central focus of the recent studies. To summarize the transcriptional activity during spermiogenesis and in sperm, we reviewed the documents on transcript differences during spermiogenesis, in sperm with differential motility, before and after capacitation and cryopreservation. This will lay a theoretical foundation for studying the mechanism(s) of gene expression in sperm, and would be invaluable in making better use of animal sires and developing reproductive control technologies.

Peroral endoscopic myotomy (POEM) has shown excellent results for the treatment of achalasia in adults, but studies for children are limited. The study was aimed to analyze outcomes of peroral endoscopic myotomy (POEM) in children and compared with those in adults in a large multi-center study.Records of consecutive patients with achalasia who underwent POEM at three tertiary centers were reviewed. A total of 130 children were included in this study. The primary outcomes of perioperative outcomes and clinical follow-up data were analyzed.One child (0.8%) experienced technical failure. Five children (3.8%) had major adverse events, including one with pneumothorax requiring drainage, two with delayed mucosa barrier failure, one with readmission, and one with vital-sign instability. Both post-POEM Eckardt score and median LES pressure were significantly lower than their pre-POEM reference values in children (0.7 vs 7.4; 7.0 vs 27.1 mmHg; both P 0.001). During a median follow-up time of 40 months, clinical reflux rate was 27.0% and clinical failure rates at 1, 3, and 5 years were 1.8%, 3.5%, and 4.4% for children. The technical failure, major adverse events, and postoperative clinical reflux were comparable between children and adults (all P 0.05). Kaplan-Meier analysis showed that the risk of clinical failure was lower in children than adults (log-rank test, hazard ratio = 0.37, 95% confidence interval 0.15-0.91, P = 0.023).POEM can be safely performed in children with achalasia, and produce a better clinical response during long-term follow-up compared with that in adults.

Genome-wide sequencing technologies have led to the identification of many non-coding RNAs and revealed an important role for these molecules in cancer. Although there have been many studies on the role of short non-coding RNAs in cancer, much work remains to characterize the functions of long non-coding RNAs. PVT1, a long non-coding RNA encoded by the human PVT1 gene, is located in the well-known cancer-related region 8q24, also known as the 8q24 'gene desert.' PVT1 has three main molecular mechanisms of action: participating in DNA rearrangements, encoding microRNAs, and interacting with MYC. Studies on the association between PVT1 and cancer have shown that PVT1 is a potential oncogene in a variety of cancer types. However, the underlying molecular mechanisms of PVT1 in cancer remain unknown. Further studies of PVT1 will be required to test the utility of this molecule as a target for cancer diagnosis and therapy, and they should also increase our understanding of the role of long non-coding RNAs in tumorigenesis.

We and others previously reported that the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 significantly accumulate with age in mouse lung. This is accompanied by elevated phosphorylation of p38. Here, we further investigate whether aging affects activation of p38 signaling and the inflammatory reaction after exposure to lipopolysaccharide (LPS) in the lungs of mice in vivo and humans ex vivo. The data showed that activation of p38 peaked at 0.5 h and then rapidly declined in young (2-month-old) mouse lung, after intranasal inhalation challenge with LPS. In contract, activation of p38 peaked at 24 h and was sustained longer in aged (20-month-old) mice. As well as altered p38, activations of its upstream activator MKK and downstream substrate NF-κB were also changed in the lungs of aged mice, which corresponded with the absence in the early phase but delayed increases in concentrations of TNF-α, IL-1β and IL-6. Consistent with the above observations in mice, similar patterns of p38 signaling also occurred in human lungs. Compared with younger lungs from adult–middle aged subjects, the activation of p38, MKK and NF-κB, as well as the production of pro-inflammatory cytokines were significantly increased in the lungs of older subjects ex vivo. Exposure of human lung cells to LPS induced rapid activation of p38, MKK and NF-κB in these cells from adult–middle aged subjects, but not older subjects, with increases in the production of the pro-inflammatory cytokines. The LPS-induced rapid activation in the lung cells from adult–middle aged subjects occurred as early as 0.25 h after exposure, and then declined. Compared with adult–middle aged subjects, the LPS exposure did not induce marked changes in the early phase, either in the activation of p38, MKK and NF-κB, or in the production of TNF-α, IL-1β or IL-6 in the lung cells from older subjects. In contrast, these changes occurred relatively late, peaked at 16 h and were sustained longer in the lungs of older subjects. These data support the hypothesis that the sustained activation of the p38 signaling pathway at baseline and the absence in the early phase but delayed of p38 signaling pathway response to LPS in the elderly may play important roles in increased susceptibility of aged lungs to inflammatory injury.

The use of prophylactic central neck dissection (pCND) for papillary thyroid cancer (PTC) without clinical evidence of nodal metastasis (cN0) remains controversial. This study was designed to examine whether pCND for PTC affected locoregional recurrence (LRR).A systematic review was performed to compare the LRR between patients with PTC who underwent total thyroidectomy (TT) and pCND and those who underwent TT alone. The primary outcome was LRR. Other outcomes, including postoperative radioiodine (RAI) ablation and surgically related complications, were evaluated. A meta-analysis was performed using the random-effects model.We included 17 studies, which comprised 4437 patients. Patients in the TT+pCND group had a significantly reduced risk of LRR (risk ratio [RR] = 0.66; 95% confidence interval [CI]: 0.49-0.90; P = 0.008). The LRR in the central neck compartment (RR = 0.35; 95% CI 0.18-0.68; P = 0.002) was significantly lower in the TT+pCND group, whereas the LRR in the lateral neck compartment was similar between the two groups. Compared with the TT alone group, patients in the TT+pCND group tended to receive higher RAI (74.6% vs. 59.9%) and experience temporary hypocalcemia (odds ratio [OR] = 2.37; 95% CI 1.89-2.96; P 0.00001), permanent hypocalcemia (OR = 1.93; 95% CI 1.05-3.57; P = 0.03), and increased overall morbidity (OR = 2.56; 95% CI 1.75-3.74; P 0.00001).This meta-analysis suggested that although pCND reduced the LRR in PTC-specifically in the central neck compartment-it was accompanied by an increased rate of postoperative hypocalcemia. However, the evidence is limited and randomized, controlled trials are needed to clarify this role further.

Previous studies that investigated the association between body mass index (BMI) and pancreatectomy outcomes have produced conflicting conclusions. We conducted this meta-analysis to assess the association between them.We searched PubMed, EMBASE, and Cochrane Library databases up to December 28, 2014. Patients were divided into high-BMI group (BMI ≥ 25 kg/m) and normal-BMI group (BMI25 kg/m). Postoperative and intraoperative outcomes were evaluated. Meta-regression and subgroup analysis were performed to evaluate any factors accountable for the heterogeneity. Meta-analysis was performed using a random-effect model.We included 22 studies involving 8994 patients. Patients in the high-BMI group had significantly increased postoperative pancreatic fistula rate (odds ratio [OR],1.96; 95% confidence interval [CI], 1.43-2.67), delayed gastric emptying rate (OR, 1.62; 95% CI, 1.15-2.29), wound infection rate (OR, 1.43; 95% CI, 1.07-1.93), operation time (mean difference [MD],15; 95% CI, 13.40-16.60), blood loss (MD, 270.71; 95% CI, 248.93-292.49), and length of hospital stay (MD, 2.87; 95% CI, 1.51-4.24). For modest heterogeneity in postoperative pancreatic fistula, regional distribution tended to be the contributor.High BMI not only increased the surgical difficulty but also decreased the surgical safety for pancreatectomy.

Pathogenesis of pancreatic ductal adenocarcinoma (PDAC) is thought to develop through the progression of precursor lesions, known as pancreatic intraepithelial neoplasias (PanIN). In the present study, we showed that c-Fos promoted proliferation, cell cycle and migration in pancreatic cancer cells. Caerulein was used to accelerate the pathogenesis of Pdx-cre; KrasG12D mice. During PanIN formation and development of PDAC, the expression of ERK and c-Fos increased concomitantly. When ERK activity was inhibited by U0126, the expression of c-Fos also decreased. Inactivation of ERK/c-Fos suppressed pancreatic lesions concurrently through proliferation, inflammation and apoptosis. Our findings suggest that the ERK/c-Fos pathway is required for PDAC initiation and progression.

Objective: In order to explore the relevance of SOCS3 gene polymorphisms with infantile asthma and provide evidence for the ethology of infantile asthma, we conducted this case-control study. Methods: A total of 273 children were enrolled for study in this article, including 119 children with asthma and 154 healthy controls frequency-matched with the former in sex and age. The genotyping of SOCS3 rs4969170, rs4969168 polymorphisms in all subjects were performed using TaqMan probe method. Odds ratio (OR) with 95% confidence interval (CI) was used to represent the association strength between SOCS3 polymorphisms and infantile asthma and calculated by χ² test which was conducted to check the Hardy-Weinberg equilibrium (HWE) in the control group. Results: The genotypes distributions of SOCS3 polymorphisms in controls conformed to HWE. Compared with GG/GA genotype in SOCS3 rs4969170, AA genotype obviously increased the susceptibility to asthma in children (OR=2.556, 95% CI=1.377-4.744) and A allele also made the same conclusion (OR=2.287, 95% CI=1.311-3.991). Differently in rs4969168, AG and AG/GG genotypes distributions had significant differences in two groups (P=0.036, 0.043). This two polymorphisms existed the linkage disequilibrium and the haplotype analysis showed that A-G and A-A haplotypes in rs4969170-rs4969168 increased 1.855 and 0.863 times risk of asthma development in children, respectively. Conclusions: A significant relevance involved in SOCS3 gene polymorphisms and infantile asthma development based on a Chinese Han population.

Rhomboid proteins perform a wide range of important functions in a variety of organisms. Recent studies have revealed that rhomboid proteins are involved in human cancer progression; however, the underlying molecular mechanism remains largely unclear. Here we show that RHBDD1, a rhomboid intramembrane serine protease, is highly expressed and closely associated with survival in patients with colorectal cancer. We observe that inactivation of RHBDD1 decreases tumor cell growth. Further studies show that RHBDD1 interacts with proTGFα and induces the ADAM-independent cleavage and secretion of proTGFα. The secreted TGFα further triggers the activation of the EGFR/Raf/MEK/ERK signalling pathway. Finally, the positive correlation of RHBDD1 expression with the EGFR/Raf/MEK/ERK signalling pathway is further corroborated in a murine model of colitis-associated colorectal cancer. These findings provide evidence of a growth-promoting role for RHBDD1 in colorectal cancer and may aid the development of tumor biomarkers or antitumor therapeutics., Rhomboid proteins are involved in human cancer progression. Here, the authors show that RHBDD1, a rhomboid intramembrane serine protease, promotes tumor growth in colorectal cancer via cleavage and secretion of TGFα, and activation of the EGFR/Raf/MEK/ERK signalling pathway.

It is not known whether patients with chronic obstructive pulmonary disease (COPD) have a different exercise capacity with (CB(+) ) or without accompanying chronic bronchitis (CB(-) ).We conducted spirometry, a 6-min walk distance test and cardiopulmonary exercise test in 50 age-matched healthy control subjects, 45 COPD patients without CB (CB(-) ) and 37 COPD patients with CB (CB(+) ). A multiple regression model was established to identify factors independently associated with peak oxygen consumption ( V ˙ O 2 ).Patients with and without CB had similar forced expiratory volume in 1 s (FEV1 ). CB(+) patients had a lower V ˙ O 2 . CB(+) and CB(-) participants had similar increases in tidal volume at peak exercise; however, CB(+) patients had an increased respiratory rate (RR). These patients reached the peak value for ratio of end-expiratory lung volume to total lung capacity (TLC) at a lower work load. A stepwise multiple linear regression analysis identified chronic bronchitis, FEV1 , diffusing capacity for carbon monoxide, the ratio of residual volume to TLC and serum tumour necrosis factor-α as independent predictors of peak V ˙ O 2 .CB significantly lowers exercise capacity in COPD patients because of dynamic hyperinflation during exercise. The accelerated dynamic hyperinflation may contribute to increased airway and systemic inflammation in COPD patients.

Amblyomma americanum (the lone star tick) is a broadly distributed tick that transmits multiple pathogens of humans and domestic animals. ‘ Candidatus Rickettsia amblyommii’ is a spotted-fever group rickettsial species that is potentially associated with human disease. In 2008 and 2009, we assayed over 500 unfed adult ticks from 19 Maryland populations for the presence of ‘ Candidatus R. amblyommii’. Infection frequencies ranged from 33% to 100%, with an average infection rate of 60% in 2008 and 69% in 2009. Infection frequencies did not differ statistically between sexes. To develop a system in which to study ‘ Candidatus R. amblyommii’ in the laboratory, we used a cell line developed from Anopheles gambiae mosquitoes (Sua5B) to isolate and culture ‘ Candidatus R. amblyommii’ from field-collected A. americanum ticks from 2 localities in Maryland. After infection, Sua5B cells were infected for more than 40 passages. Infection was confirmed by Rickettsia -specific PCR, gene sequencing, and Rickettsia -specific fluorescence in situ hybridization (FISH). These data show that ‘ Candidatus R. amblyommii’ is widespread in Maryland A. americanum populations and that Sua5B cells are a useful tool for culturing Rickettsia infections from wild ticks.

The endosymbiotic bacterium Wolbachia is being investigated as a potential control agent in several important vector insect species. Recent studies have shown that Wolbachia can protect the insect host against a wide variety of pathogens, resulting in reduced transmission of parasites and viruses. It has been proposed that compromised vector competence of Wolbachia-infected insects is due to up-regulation of the host innate immune system or metabolic competition. Anopheles mosquitoes, which transmit human malaria parasites, have never been found to harbor Wolbachia in nature. While transient somatic infections can be established in Anopheles, no stable artificially-transinfected Anopheles line has been developed despite numerous attempts. However, cultured Anopheles cells can be stably infected with multiple Wolbachia strains such as wAlbB from Aedes albopictus, wRi from Drosophila simulans and wMelPop from Drosophila melanogaster. Infected cell lines provide an amenable system to investigate Wolbachia-Anopheles interactions in the absence of an infected mosquito strain. We used Affymetrix GeneChip microarrays to investigate the effect of wAlbB and wRi infection on the transcriptome of cultured Anopheles Sua5B cells, and for a subset of genes used quantitative PCR to validate results in somatically-infected Anopheles mosquitoes. Wolbachia infection had a dramatic strain-specific effect on gene expression in this cell line, with almost 700 genes in total regulated representing a diverse array of functional classes. Very strikingly, infection resulted in a significant down-regulation of many immune, stress and detoxification-related transcripts. This is in stark contrast to the induction of immune genes observed in other insect hosts. We also identified genes that may be potentially involved in Wolbachia-induced reproductive and pathogenic phenotypes. Somatically-infected mosquitoes had similar responses to cultured cells. The data show that Wolbachia has a profound and unique effect on Anopheles gene expression in cultured cells, and has important implications for mechanistic understanding of Wolbachia-induced phenotypes and potential novel strategies to control malaria., Author Summary Wolbachia are bacteria that infect many insect species, but do not infect Anopheles mosquitoes. These mosquitoes transmit Plasmodium parasites, which cause malaria in humans. Wolbachia infection in Aedes aegypti mosquitoes reduces their ability to transmit diverse pathogens including viruses, nematodes and bird malaria parasites. Wolbachia-induced stimulation of the mosquito's innate immune system has been suggested as a mechanism conferring this pathogen interference. Since no Wolbachia-infected Anopheles mosquito strain exists, we used infected cultured Anopheles cells to examine the effect of infection on Anopheles gene expression. Wolbachia had a profound influence on Anopheles gene expression. Many of the genes regulated by Wolbachia have been seen in other studies to influence Plasmodium levels in mosquitoes, but interestingly and in contrast to other mosquitoes, many of the host genes were suppressed rather than induced.

We have previously reported that rhomboid domain containing 1 (RHBDD1), a new member of the Rhomboid family, is highly expressed in testis. In the present work, luciferase analyses showed that RHBDD1 enhanced the AP-1 activity in a dose- and activity-dependent manner. RHBDD1 overexpression increased c-Jun activity, and the activity was visibly inhibited when RHBDD1 was knocked down. The suppression of c-Jun by inactivation of RHBDD1 was rescued by overexpressing RHBDD1. However, c-Jun overexpression did not alter the expression level of RHBDD1. Furthermore, knockdown of RHBDD1 led to increased cell apoptosis and reduced expression of Bcl-3. Our findings indicate that RHBDD1 could inhibit cell apoptosis by activating and upregulating c-Jun and its downstream target, Bcl-3.