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Background: Mobile health (mHealth) is a promising intervention mode for HIV prevention, but little is known about its feasibility and effects in promoting pre-exposure prophylaxis (PrEP) uptake among Chinese gay, bisexual and other men who have sex with men (GBMSM). Methods: We evaluated an instant messaging application using a WeChat-based mini-app to promote PrEP uptake among GBMSM via a mixed-methods design that includes a 12-week, two-arm randomized controlled pilot trial and in-depth progress interviews in Guangzhou, China. Primary outcomes include the number of PrEP initiations, individual-level psychosocial variables related to PrEP initiation, and usability of the PrEP mini-app. Results: Between November 2020 and April 2021, 70 GBMSM were successfully enrolled and randomized into two arms at 2:1 ratio (46 to the intervention arm, 24 to the control arm). By the end of 12-week follow-up, 22 (31.4%) participants completed the initial consultation and lab tests for PrEP, and 13 (18.6%) filled their initial PrEP prescription. We observed modest but non-significant improvements in participants' intention to use PrEP, actual PrEP initiation, PrEP-related self-efficacy, stigma, and attitudes over 12 weeks when comparing the mini-app and the control arms. Qualitative interviews revealed the key barriers to PrEP uptake include anticipated stigma and discrimination in clinical settings, burden of PrEP care, and limited operating hours of the PrEP clinic. In-person clinic navigation support was highly valued. Conclusions: This pilot trial of a mobile phone-based PrEP mini-app demonstrated feasibility and identified limitations in facilitating PrEP uptake among Chinese GBMSM. Future improvements may include diversifying the content presentation in engaging media formats, adding user engagement features, and providing off-line in-clinic navigation support during initial PrEP visit. More efforts are needed to understand optimal strategies to identify and implement alternative PrEP provision models especially in highly stigmatized settings with diverse needs. Trial registration: Trial registration: The study was prospectively registered on clinicaltrials.gov (NCT04426656) on 11 June, 2020. [ABSTRACT FROM AUTHOR]

Humans beings decide to trust others selectively, often based on the appearance of a face. But how do observers deal with the wide variety of facial morphologies and, in particular, those outside their own familiar cultural group? Using reverse correlation, a data-driven approach to explore how individuals create internal representations without external biases, we studied the generation of trustworthy faces by French and Chinese participants (N = 160) within and outside their own cultural group. Participants selected the most trustworthy or attractive (control condition) face from two identical European or Asian descent faces that had been modified by different noise masks. A conjunction analysis to reveal facial features common to both cultures showed that Chinese and French participants unconsciously increased the contrast of the "pupil-iris area" to make the face appear more trustworthy. No significant effects common to both groups were found for the attraction condition suggesting that attraction judgements are dependent on cultural processes. These results suggest the presence of universal cross-cultural mechanisms for the construction of implicit first impressions of trust, and highlight the importance of the eyes area in this process. [ABSTRACT FROM AUTHOR]

The cultivation of walnuts (Juglans sp.) in Europe retains high economic, social, and environmental value. The recent reporting of the Thousand Cankers Disease (TCD) fungus, Geosmithia morbida, and of its vector, Pityophthorus juglandis, in walnut trees in Italy is alarming the whole of Europe. Although Italy is at present the only foothold of the disease outside North America, given the difficulties inherent in traditional identification of both members of this beetle/fungus complex, a rapid and effective protocol for the early detection and identification of TCD organisms is an absolute priority for Europe. Here we report the development of an effective and sensitive molecular tool based on simplex/duplex qPCR assays for the rapid, accurate and highly specific detection of both the bionectriaceous fungal pathogen and its bark-beetle vector. Our assay performed excellently, detecting minute amounts of target DNA without any non-specific amplification. Detection limits from various and heterogeneous matrices were lower than other reported assays. Our molecular protocol could assist in TCD organism interception at entry points, territory monitoring for the early identification and eradication of outbreaks, delineation of quarantine areas, and tracing back TCD entry and dispersal pathways. [ABSTRACT FROM AUTHOR]

Background: Inflammation is an important risk factor in atherosclerosis, the underlying cause of coronary artery disease (CAD). Unresolved inflammation may result in maladaptive immune responses and lead to immune reactivity to self-antigens. We hypothesized that inflammation in CAD patients would manifest in immune reactivity to self-antigens detectable in soluble HLA-I/peptide complexes in the plasma. Methods: Soluble HLA-I/peptide complexes were immuno-precipitated from plasma of male acute coronary syndrome (ACS) patients or age-matched controls and eluted peptides were subjected to mass spectrometry to generate the immunopeptidome. Self-peptides were ranked according to frequency and signal intensity, then mouse homologs of selected peptides were used to test immunologic recall in spleens of male apoE-/- mice fed either normal chow or high fat diet. The peptide detected with highest frequency in patient plasma samples and provoked T cell responses in mouse studies was selected for use as a self-antigen to stimulate CAD patient peripheral blood mononuclear cells (PBMCs). Results: The immunopeptidome profile identified self-peptides unique to the CAD patients. The mouse homologs tested showed immune responses in apoE-/- mice. Keratin 8 was selected for further study in patient PBMCs which elicited T Effector cell responses in CAD patients compared to controls, associated with reduced PD-1 mRNA expression. Conclusion: An immunopeptidomic strategy to search for self-antigens potentially involved in CAD identified Keratin 8. Self-reactive immune response to Keratin 8 may be an important factor in the inflammatory response in CAD. [ABSTRACT FROM AUTHOR]

Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t) form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/-) mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/-) mice, differentially activated by feeding with normal chow or high fat diet. Immunization of ApoE(-/-) with different doses of the shortened peptide (Cramp) resulted in differential outcomes with a lower dose reducing atherosclerosis whereas a higher dose exacerbating the disease with increased neutrophil infiltration of the atherosclerotic plaques. Low dose Cramp immunization also resulted in increased splenic CD8+ T cell degranulation and reduced CD11b+CD11c+ conventional dendritic cells (cDCs), whereas high dose increased CD11b+CD11c+ cDCs. Our results identified CRAMP, the mouse homolog of hCAP-18, as a potential self-antigen involved in the immune response to atherosclerosis in the ApoE(-/-) mouse model. [ABSTRACT FROM AUTHOR]

Objectives: The risk of herpes zoster (HZ) between patients with psoriasis receiving and not receiving systemic therapy has received increasing attention. This study investigated the association of psoriasis with the risk of HZ. Methods: We conducted a population-based retrospective cohort study by using the Taiwan National Health Insurance Research Database. The psoriasis cohort consisted of 4077 patients with newly diagnosed psoriasis between 2000 and 2006. Each patient with psoriasis was frequency-matched with four people without psoriasis, by sex, age and index year. (nonpsoriasis cohort; 16308 subjects). Patients who received systemic therapy were classified as having severe psoriasis, whereas those who did not receive systemic therapy were classified as having mild psoriasis. The Cox proportional hazards regression analysis was conducted to estimate the association between psoriasis and HZ risk. Results: The overall incidence density rate of HZ in the psoriasis cohort than in the nonpsoriasis cohort (4.50 vs. 3.44 per 1,000 person-years), with a multivariable Cox proportional hazards model measured adjusted HR of 1.29 [95% confidence interval (CI) = 1.07–1.56]. In additional, compared with the nonpsoriasis cohort, the risk of HZ was higher in the severe psoriasis cohort than in the nonpsoriasis cohort (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.15–2.27). The comparison between psoriasis and nonpsoriasis cohorts revealed a greatest magnitude risk of HZ in women (adjusted HR, 1.36; 95% CI, 1.04–1.79), study participants in the age group of 20–39 years (adjusted HR, 1.77; 95% CI, 1.17–2.66), and study participants without any comorbidities (adjusted HR, 1.37; 95% CI, 1.02–1.84). Conclusions: Our results suggest that psoriasis is associated with an increased risk of HZ, which involves differences in sex and age. Although systemic therapy may have a major role in the risk of HZ, the intrinsic factors of psoriasis cannot be excluded. [ABSTRACT FROM AUTHOR]

Salmonella enterica are a threat to public health. Current vaccines are not fully effective. The ability to grow in infected tissues within phagocytes is required for S. enterica virulence in systemic disease. As the infection progresses the bacteria are exposed to a complex host immune response. Consequently, in order to continue growing in the tissues, S. enterica requires the coordinated regulation of fitness genes. Bacterial gene regulation has so far been investigated largely using exposure to artificial environmental conditions or to in vitro cultured cells, and little information is available on how S. enterica adapts in vivo to sustain cell division and survival. We have studied the transcriptome, proteome and metabolic flux of Salmonella, and the transcriptome of the host during infection of wild type C57BL/6 and immune-deficient gp91-/-phox mice. Our analyses advance the understanding of how S. enterica and the host behaves during infection to a more sophisticated level than has previously been reported. [ABSTRACT FROM AUTHOR]

The study of action selection in humans can present challenges of task design since our actions are usually defined by many degrees of freedom and therefore occupy a large action-space. While saccadic eye-movement offers a more constrained paradigm for investigating action selection, the study of reach-and-grasp in upper limbs has often been defined by more complex scenarios, not easily interpretable in terms of such selection. Here we present a novel motor behaviour task which addresses this by limiting the action space to a single degree of freedom in which subjects have to track (using a stylus) a vertical coloured target line displayed on a tablet computer, whilst ignoring a similarly oriented distractor line in a different colour. We ran this task with 55 subjects and showed that, in agreement with previous studies, the presence of the distractor generally increases the movement latency and directional error rate. Further, we used two distractor conditions according to whether the distractor’s location changes asynchronously or synchronously with the location of the target. We found that the asynchronous distractor yielded poorer performance than its synchronous counterpart, with significantly higher movement latencies and higher error rates. We interpret these results in an action selection framework with two actions (move left or right) and competing ‘action requests’ offered by the target and distractor. As such, the results provide insights into action selection performance in humans and supply data for directly constraining future computational models therein. [ABSTRACT FROM AUTHOR]

Two distinct Phytophthora taxa were found to be associated with brown rot of pomelo (Citrus grandis), a new disease of this ancestral Citrus species, in the Vinh Long province, Mekong River Delta area, southern Vietnam. On the basis of morphological characters and using the ITS1-5.8S-ITS2 region of the rDNA and the cytochrome oxidase subunit 1 (COI) as barcode genes, one of the two taxa was provisionally named as Phytophthora sp. prodigiosa, being closely related to but distinct from P. insolita, a species in Phytophthora Clade 9, while the other one, was closely related to but distinct from the Clade 2 species P. meadii and was informally designated as Phytophthora sp. mekongensis. Isolates of P. sp. prodigiosa and P. sp. mekongensis were also obtained from necrotic fibrous roots of Volkamer lemon (C. volkameriana) rootstocks grafted with ‘King’ mandarin (Citrus nobilis) and from trees of pomelo, respectively, in other provinces of the Mekong River Delta, indicating a widespread occurrence of both Phytophthora species in this citrus-growing area. Koch’s postulates were fulfilled via pathogenicity tests on fruits of various Citrus species, including pomelo, grapefruit (Citrus x paradisi), sweet orange (Citrus x sinensis) and bergamot (Citrus x bergamia) as well as on the rootstock of 2-year-old trees of pomelo and sweet orange on ‘Carrizo’ citrange (C. sinensis ‘Washington Navel’ x Poncirus trifoliata). This is the first report of a Phytophthora species from Clade 2 other than P. citricola and P. citrophthora as causal agent of fruit brown rot of Citrus worldwide and the first report of P. insolita complex in Vietnam. Results indicate that likely Vietnam is still an unexplored reservoir of Phytophthora diversity. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical characteristics, diagnosis, treatment and prognosis of penicilliosis among the patients with acquired immunodeficiency syndrome (AIDS) in non-endemic areas of China, and then to discuss its incubation period and the diagnostic performance of serum galactomannan test for penicilliosis. Methods: Medical records and travel histories of penicilliosis patients in Zhongnan hospital from January 2006 to December 2013, and the interval from when the patients left the endemic area to the onset of the disease was analyzed. Serum galactomannan levels of penicilliosis patients and AIDS patients with fever were measured by the Platelia Aspergillus Enzyme Immunoassay Kit. Results: A total of 47 AIDS-associated penicilliosis were confirmed by fungal culture, which accounted for 4.8% of 981 AIDS-related admissions. The sensitivity and specificity of serum galactomannan test for penicilliosis were 95.8% (23/24) and 90.9% (30/33), respectively, (cutoff index = 1.0). Two independent predictors for early mortality (death within 12 weeks) of the patients (21.3%, 10/47) were a delayed diagnosis and no treatment with antifungal therapy. Among 14 patients who became ill after leaving endemic areas, ten patients presented with the onset symptoms within 12 months (from 11 days to 360 days). We found a patient living with asymptomatic P. marneffei fungemia who had not received any antifungal therapy until 18 months’ follow up. Conclusions: The co-infection of P. marneffei and HIV was not uncommon in the non-endemic areas of penicilliosis in China. There exists a latent form of infection for P. marneffei. The incubation period of penicilliosis may be quite different from one patient to another. In AIDS patients, the serum galactomannan test has utility for the diagnosis of penicilliosis. When patients with penicilliosis/AIDS were diagnosed early and treated with standardized antifungal therapy and combined antiretroviral therapy, their prognosis improved. [ABSTRACT FROM AUTHOR]

Recent studies suggest the potential involvement of CD8+ T cells in the pathogenesis of murine hypertension. We recently reported that immunization with apoB-100 related peptide, p210, modified CD8+ T cell function in angiotensin II (AngII)-infused apoE (-/-) mice. In this study, we hypothesized that p210 vaccine modulates blood pressure in AngII-infused apoE (-/-) mice. Male apoE (-/-) mice were immunized with p210 vaccine and compared to unimmunized controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII for 4 weeks. At 13 weeks of age, p210 immunized mice showed significantly lower blood pressure response to AngII compared to controls. CD8+ T cells from p210 immunized mice displayed a different phenotype compared to CD8+ T cells from unimmunized controls. Serum creatinine and urine albumin to creatinine ratio were significantly decreased in p210 immunized mice suggesting that p210 vaccine had renal protective effect. At euthanasia, inflammatory genes IL-6, TNF-α, and MCP-1 in renal tissue were down-regulated by p210 vaccine. Renal fibrosis and pro-fibrotic gene expression were also significantly reduced in p210 immunized mice. To assess the role of CD8+ T cells in these beneficial effects of p210 vaccine, CD8+ T cells were depleted by CD8 depleting antibody in p210 immunized mice. p210 immunized mice with CD8+ T cell depletion developed higher blood pressure compared to mice receiving isotype control. Depletion of CD8+ T cells also increased renal fibrotic gene expression compared to controls. We conclude that immunization with p210 vaccine attenuated AngII-induced hypertension and renal fibrosis. CD8+ T cells modulated by p210 vaccine could play an important role in the anti-hypertensive, anti-fibrotic and renal-protective effect of p210 vaccine. [ABSTRACT FROM AUTHOR]

Background: The lipid milleu exacerbates the inflammatory response in atherosclerosis but its effect on T cell mediated immune response has not been fully elucidated. We hypothesized that lipid lowering would modulate T cell mediated immune function. Methods and Results: T cells isolated from human PBMC or splenic T cells from apoE-/- mouse had higher proliferative response to T cell receptor (TCR) ligation in medium supplemented with 10% fetal bovine serum (FBS) compared to medium with 10% delipidated FBS. The differences in proliferation were associated with changes in lipid rafts, cellular cholesterol content, IL-10 secretion and subsequent activation of signaling molecule activated by TCR ligation. Immune biomarkers were also assessed in vivo using male apoE-/- mice fed atherogenic diet (AD) starting at 7 weeks of age. At 25 weeks of age, a sub-group was switched to normal diet (ND) whereas the rest remained on AD until euthanasia at 29 weeks of age. Dietary change resulted in a lower circulating level of cholesterol, reduced plaque size and inflammatory phenotype of plaques. These changes were associated with reduced intracellular IL-10 and IL-12 expression in CD4+ and CD8+ T cells. Conclusion: Our results show that lipid lowering reduces T cell proliferation and function, supporting the notion that lipid lowering modulates T cell function in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Background & Aim: The miR-221/222 cluster is upregulated in malignant plasma cells from multiple myeloma (MM) patients harboring the t(4;14) translocation. We previously reported that silencing of miR-221/222 by an antisense oligonucleotide induces anti-MM activity and upregulates canonical miR-221/222 targets. The in vivo anti-tumor activity occurred when miR-221/222 inhibitors were delivered directly into MM xenografts. The aim of the present study was to evaluate the anti-MM activity of a novel phosphorothioate modified backbone 13-mer locked nucleic acid (LNA)-Inhibitor-miR-221 (LNA-i-miR-221) specifically designed for systemic delivery. Methods: In vitro anti-MM activity of LNA-i-miR-221 was evaluated by cell proliferation and BrdU uptake assays. In vivo studies were performed with non-obese diabetic/severe combined immunodeficient (NOD.SCID) mice bearing t(4;14) MM xenografts, which were intraperitoneally or intravenously treated with naked LNA-i-miR-221. RNA extracts from retrieved tumors were analyzed for miR-221 levels and modulation of canonical targets expression. H&E staining and immunohistochemistry were performed on retrieved tumors and mouse vital organs. Results: In vitro, LNA-i-miR-221 exerted strong antagonistic activity against miR-221 and induced upregulation of the endogenous target p27Kip1. It had a marked anti-proliferative effect on t(4;14)-translocated MM cells but not on MM cells not carrying the translocation and not overexpressing miR-221. In vivo, systemic treatment with LNA-i-miR-221 triggered significant anti-tumor activity against t(4;14) MM xenografts; it also induced miR-221 downregulation, upregulated p27Kip1 and reduced Ki-67. No behavioral changes or organ-related toxicity were observed in mice as a consequence of treatments. Conclusions: LNA-i-miR-221 is a highly stable, effective agent against t(4;14) MM cells, and is suitable for systemic use. These data provide the rationale for the clinical development of LNA-i-miR-221 for the treatment of MM. [ABSTRACT FROM AUTHOR]

Background: Only a subset of radically resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of prognostic factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and innovative therapeutic targets, while high-throughput arrays are opening new opportunities to evaluate whether they can predict clinical outcome. The present study evaluated whether comprehensive miRNA expression profiling correlated with overall survival (OS) in resected PDAC patients. Methodology/Principal Findings: High-resolution miRNA profiles were obtained with the Toray's 3D-Gene™-miRNA-chip, detecting more than 1200 human miRNAs. RNA was successfully isolated from paraffin-embedded primary tumors of 19 out of 26 stage-pT3N1 homogeneously treated patients (adjuvant gemcitabine 1000 mg/m² /day, days-1/8/15, every 28days), carefully selected according to their outcome (OS,12 (N = 13) vs. OS.30 months (N = 6), i.e. short/long-OS). Highly stringent statistics included t-test, distance matrix with Spearman-ranked correlation, and iterative approaches. Unsupervised hierarchical analysis revealed that PDACs clustered according to their short/long-OS classification, while the feature selection algorithm RELIEF identified the top 4 discriminating miRNAs between the two groups. These miRNAs target more than 1500 transcripts, including 169 targeted by two or more. MiR-211 emerged as the best discriminating miRNA, with significantly higher expression in long- vs. short-OS patients. The expression of this miRNA was subsequently assessed by quantitative-PCR in an independent cohort of laser-microdissected PDACs from 60 resected patients treated with the same gemcitabine regimen. Patients with low miR-211 expression according to median value had a significantly shorter median OS (14.8, 95%CI = 13.1-16.5, vs. 25.7 months, 95%CI = 16.2-35.1, log-rank-P = 0.004). Multivariate analysis demonstrated that low miR-211 expression was an independent factor of poor prognosis (hazard ratio 2.3, P = 0.03) after adjusting for all the factors influencing outcome. Conclusions/Significance: Through comprehensive microarray analysis and PCR validation we identified miR-211 as a prognostic factor in resected PDAC. These results prompt further prospective studies and research on the biological role of miR-211 in PDAC. [ABSTRACT FROM AUTHOR]

Pancreatic islets from adult rats whose mothers were protein restricted during lactation undersecrete insulin. The current work analyzes whether this secretory dysfunction can be improved when the pancreatic islets are grafted into hyperglycemic diabetic rats. Two groups of rats were used: the adult offspring from dams that received a low protein diet (4%) during the initial 2/3 of lactation (LP) and, as a control, the adult offspring from dams that consumed a normal protein diet (23%) during the entire period of lactation (NP). Islets from NP- and LP-rats were transplanted into diabetic recipient rats, which were generated by streptozotocin treatment. The islets were transplanted via the portal vein under anesthesia. The fed blood glucose levels were monitored during the 4 days post-transplantation. Transplanted islets from LP-rats (T LP) decreased the fed glucose levels of diabetic rats 34% (21.37±0.24 mM, p<0.05); however, the levels still remained 2-fold higher than those of the sham-operated controls (6.88±0.39 mM, p<0.05). Grafts with NP-islets (T NP) produced the same effect as the LP-islets in diabetic rats. The high fasting blood glucose levels of diabetic rats were improved by the transplantations. Islet grafts from both rat groups recovered 50% of the retroperitoneal fat mass of the diabetic rats (0.55±0.08 g/100 g of body weight for T NP and 0.56±0.07 g/100 g of body weight for T LP, p<0.05). Because pancreatic islets from both the NP- and LP-rats were able to regulate fasting blood glucose concentrations in hyperglycemic rats, we propose that the altered function of pancreatic islets from LP-rats is not permanent. [ABSTRACT FROM AUTHOR]

Immunization of hypercholesterolemic mice with selected apoB-100 peptide antigens reduces atherosclerosis but the precise immune mediators of athero-protection remain unclear. In this study we show that immunization of apoE (-/-) mice with p210, a 20 amino acid apoB-100 related peptide, reduced aortic atherosclerosis compared with PBS or adjuvant/carrier controls. Immunization with p210 activated CD8+ T cells, reduced dendritic cells (DC) at the site of immunization and within the plaque with an associated reduction in plaque macrophage immunoreactivity. Adoptive transfer of CD8+ T cells from p210 immunized mice recapitulated the athero-protective effect of p210 immunization in naïve, non-immunized mice. CD8+ T cells from p210 immunized mice developed a preferentially higher cytolytic response against p210-loaded dendritic cells in vitro. Although p210 immunization profoundly modulated DCs and cellular immune responses, it did not alter the efficacy of subsequent T cell dependent or independent immune response to other irrelevant antigens. Our data define, for the first time, a role for CD8+ T cells in mediating the athero-protective effects of apoB-100 related peptide immunization in apoE (-/-) mice. [ABSTRACT FROM AUTHOR]

The output of state-of-the-art reverse-engineering methods for biological networks is often based on the fitting of a mathematical model to the data. Typically, different datasets do not give single consistent network predictions but rather an ensemble of inconsistent networks inferred under the same reverse-engineering method that are only consistent with the specific experimentally measured data. Here, we focus on an alternative approach for combining the information contained within such an ensemble of inconsistent gene networks called meta-analysis, to make more accurate predictions and to estimate the reliability of these predictions. We review two existing meta-analysis approaches; the Fisher transformation combined coefficient test (FTCCT) and Fisher's inverse combined probability test (FICPT); and compare their performance with five well-known methods, ARACNe, Context Likelihood or Relatedness network (CLR), Maximum Relevance Minimum Redundancy (MRNET), Relevance Network (RN) and Bayesian Network (BN). We conducted in-depth numerical ensemble simulations and demonstrated for biological expression data that the meta-analysis approaches consistently outperformed the best gene regulatory network inference (GRNI) methods in the literature. Furthermore, the meta-analysis approaches have a low computational complexity. We conclude that the meta-analysis approaches are a powerful tool for integrating different datasets to give more accurate and reliable predictions for biological networks. [ABSTRACT FROM AUTHOR]

BackgroundMobile health (mHealth) is a promising intervention mode for HIV prevention, but little is known about its feasibility and effects in promoting pre-exposure prophylaxis (PrEP) uptake among Chinese gay, bisexual and other men who have sex with men (GBMSM).MethodsWe evaluated an instant messaging application using a WeChat-based mini-app to promote PrEP uptake among GBMSM via a mixed-methods design that includes a 12-week, two-arm randomized controlled pilot trial and in-depth progress interviews in Guangzhou, China. Primary outcomes include the number of PrEP initiations, individual-level psychosocial variables related to PrEP initiation, and usability of the PrEP mini-app.ResultsBetween November 2020 and April 2021, 70 GBMSM were successfully enrolled and randomized into two arms at 2:1 ratio (46 to the intervention arm, 24 to the control arm). By the end of 12-week follow-up, 22 (31.4%) participants completed the initial consultation and lab tests for PrEP, and 13 (18.6%) filled their initial PrEP prescription. We observed modest but non-significant improvements in participants' intention to use PrEP, actual PrEP initiation, PrEP-related self-efficacy, stigma, and attitudes over 12 weeks when comparing the mini-app and the control arms. Qualitative interviews revealed the key barriers to PrEP uptake include anticipated stigma and discrimination in clinical settings, burden of PrEP care, and limited operating hours of the PrEP clinic. In-person clinic navigation support was highly valued.ConclusionsThis pilot trial of a mobile phone-based PrEP mini-app demonstrated feasibility and identified limitations in facilitating PrEP uptake among Chinese GBMSM. Future improvements may include diversifying the content presentation in engaging media formats, adding user engagement features, and providing off-line in-clinic navigation support during initial PrEP visit. More efforts are needed to understand optimal strategies to identify and implement alternative PrEP provision models especially in highly stigmatized settings with diverse needs.Trial registrationTrial registration: The study was prospectively registered on clinicaltrials.gov (NCT04426656) on 11 June, 2020.

Two distinct Phytophthora taxa were found to be associated with brown rot of pomelo (Citrus grandis), a new disease of this ancestral Citrus species, in the Vinh Long province, Mekong River Delta area, southern Vietnam. On the basis of morphological characters and using the ITS1-5.8S-ITS2 region of the rDNA and the cytochrome oxidase subunit 1 (COI) as barcode genes, one of the two taxa was provisionally named as Phytophthora sp. prodigiosa, being closely related to but distinct from P. insolita, a species in Phytophthora Clade 9, while the other one, was closely related to but distinct from the Clade 2 species P. meadii and was informally designated as Phytophthora sp. mekongensis. Isolates of P. sp. prodigiosa and P. sp. mekongensis were also obtained from necrotic fibrous roots of Volkamer lemon (C. volkameriana) rootstocks grafted with 'King' mandarin (Citrus nobilis) and from trees of pomelo, respectively, in other provinces of the Mekong River Delta, indicating a widespread occurrence of both Phytophthora species in this citrus-growing area. Koch's postulates were fulfilled via pathogenicity tests on fruits of various Citrus species, including pomelo, grapefruit (Citrus x paradisi), sweet orange (Citrus x sinensis) and bergamot (Citrus x bergamia) as well as on the rootstock of 2-year-old trees of pomelo and sweet orange on 'Carrizo' citrange (C. sinensis 'Washington Navel' x Poncirus trifoliata). This is the first report of a Phytophthora species from Clade 2 other than P. citricola and P. citrophthora as causal agent of fruit brown rot of Citrus worldwide and the first report of P. insolita complex in Vietnam. Results indicate that likely Vietnam is still an unexplored reservoir of Phytophthora diversity.

To investigate the clinical characteristics, diagnosis, treatment and prognosis of penicilliosis among the patients with acquired immunodeficiency syndrome (AIDS) in non-endemic areas of China, and then to discuss its incubation period and the diagnostic performance of serum galactomannan test for penicilliosis.Medical records and travel histories of penicilliosis patients in Zhongnan hospital from January 2006 to December 2013, and the interval from when the patients left the endemic area to the onset of the disease was analyzed. Serum galactomannan levels of penicilliosis patients and AIDS patients with fever were measured by the Platelia Aspergillus Enzyme Immunoassay Kit.A total of 47 AIDS-associated penicilliosis were confirmed by fungal culture, which accounted for 4.8% of 981 AIDS-related admissions. The sensitivity and specificity of serum galactomannan test for penicilliosis were 95.8% (23/24) and 90.9% (30/33), respectively, (cutoff index = 1.0). Two independent predictors for early mortality (death within 12 weeks) of the patients (21.3%, 10/47) were a delayed diagnosis and no treatment with antifungal therapy. Among 14 patients who became ill after leaving endemic areas, ten patients presented with the onset symptoms within 12 months (from 11 days to 360 days). We found a patient living with asymptomatic P. marneffei fungemia who had not received any antifungal therapy until 18 months' follow up.The co-infection of P. marneffei and HIV was not uncommon in the non-endemic areas of penicilliosis in China. There exists a latent form of infection for P. marneffei. The incubation period of penicilliosis may be quite different from one patient to another. In AIDS patients, the serum galactomannan test has utility for the diagnosis of penicilliosis. When patients with penicilliosis/AIDS were diagnosed early and treated with standardized antifungal therapy and combined antiretroviral therapy, their prognosis improved.

Recent studies suggest the potential involvement of CD8+ T cells in the pathogenesis of murine hypertension. We recently reported that immunization with apoB-100 related peptide, p210, modified CD8+ T cell function in angiotensin II (AngII)-infused apoE (-/-) mice. In this study, we hypothesized that p210 vaccine modulates blood pressure in AngII-infused apoE (-/-) mice. Male apoE (-/-) mice were immunized with p210 vaccine and compared to unimmunized controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII for 4 weeks. At 13 weeks of age, p210 immunized mice showed significantly lower blood pressure response to AngII compared to controls. CD8+ T cells from p210 immunized mice displayed a different phenotype compared to CD8+ T cells from unimmunized controls. Serum creatinine and urine albumin to creatinine ratio were significantly decreased in p210 immunized mice suggesting that p210 vaccine had renal protective effect. At euthanasia, inflammatory genes IL-6, TNF-α, and MCP-1 in renal tissue were down-regulated by p210 vaccine. Renal fibrosis and pro-fibrotic gene expression were also significantly reduced in p210 immunized mice. To assess the role of CD8+ T cells in these beneficial effects of p210 vaccine, CD8+ T cells were depleted by CD8 depleting antibody in p210 immunized mice. p210 immunized mice with CD8+ T cell depletion developed higher blood pressure compared to mice receiving isotype control. Depletion of CD8+ T cells also increased renal fibrotic gene expression compared to controls. We conclude that immunization with p210 vaccine attenuated AngII-induced hypertension and renal fibrosis. CD8+ T cells modulated by p210 vaccine could play an important role in the anti-hypertensive, anti-fibrotic and renal-protective effect of p210 vaccine.

BackgroundOnly a subset of radically resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of prognostic factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and innovative therapeutic targets, while high-throughput arrays are opening new opportunities to evaluate whether they can predict clinical outcome. The present study evaluated whether comprehensive miRNA expression profiling correlated with overall survival (OS) in resected PDAC patients.Methodology/principal findingsHigh-resolution miRNA profiles were obtained with the Toray's 3D-Gene™-miRNA-chip, detecting more than 1200 human miRNAs. RNA was successfully isolated from paraffin-embedded primary tumors of 19 out of 26 stage-pT3N1 homogeneously treated patients (adjuvant gemcitabine 1000 mg/m(2)/day, days-1/8/15, every 28 days), carefully selected according to their outcome (OS30 months (N = 6), i.e. short/long-OS). Highly stringent statistics included t-test, distance matrix with Spearman-ranked correlation, and iterative approaches. Unsupervised hierarchical analysis revealed that PDACs clustered according to their short/long-OS classification, while the feature selection algorithm RELIEF identified the top 4 discriminating miRNAs between the two groups. These miRNAs target more than 1500 transcripts, including 169 targeted by two or more. MiR-211 emerged as the best discriminating miRNA, with significantly higher expression in long- vs. short-OS patients. The expression of this miRNA was subsequently assessed by quantitative-PCR in an independent cohort of laser-microdissected PDACs from 60 resected patients treated with the same gemcitabine regimen. Patients with low miR-211 expression according to median value had a significantly shorter median OS (14.8, 95%CI = 13.1-16.5, vs. 25.7 months, 95%CI = 16.2-35.1, log-rank-P = 0.004). Multivariate analysis demonstrated that low miR-211 expression was an independent factor of poor prognosis (hazard ratio 2.3, P = 0.03) after adjusting for all the factors influencing outcome.Conclusions/significanceThrough comprehensive microarray analysis and PCR validation we identified miR-211 as a prognostic factor in resected PDAC. These results prompt further prospective studies and research on the biological role of miR-211 in PDAC.

Immunization of hypercholesterolemic mice with selected apoB-100 peptide antigens reduces atherosclerosis but the precise immune mediators of athero-protection remain unclear. In this study we show that immunization of apoE (-/-) mice with p210, a 20 amino acid apoB-100 related peptide, reduced aortic atherosclerosis compared with PBS or adjuvant/carrier controls. Immunization with p210 activated CD8(+) T cells, reduced dendritic cells (DC) at the site of immunization and within the plaque with an associated reduction in plaque macrophage immunoreactivity. Adoptive transfer of CD8(+) T cells from p210 immunized mice recapitulated the athero-protective effect of p210 immunization in naïve, non-immunized mice. CD8(+) T cells from p210 immunized mice developed a preferentially higher cytolytic response against p210-loaded dendritic cells in vitro. Although p210 immunization profoundly modulated DCs and cellular immune responses, it did not alter the efficacy of subsequent T cell dependent or independent immune response to other irrelevant antigens. Our data define, for the first time, a role for CD8(+) T cells in mediating the athero-protective effects of apoB-100 related peptide immunization in apoE (-/-) mice.