[Prevalence of human papilloma virus infection and its risk factors in some rural areas of Jiangsu, China].

OBJECTIVE: To investigate human papilloma virus (HPV) infection in the male genital tract and its risk factors in some rural areas of Jiangsu Province. METHODS: This study included 398 men from six rural areas in Jiangsu Province, whose female partners, based on the results of cervical cytological examination, were divided into a normal (n = 104), a cervical intraepithelial neoplasia grade Ⅰ (CIN-Ⅰ, n = 100), a CIN-Ⅱ (n = 95), and a CIN-Ⅲ group (n = 99). We examined the male subjects for genital warts and other lesions, collected urethral swab samples for HPV detection, and obtained their sociodemographic data by questionnaire investigation. RESULTS: No megascopic lesions were observed in the genitals of the 398 participants. The total prevalence rate of HPV infection was 11.31% and that of high-risk HPV was 8.54%. Logistic regression analysis showed that daily cleaning of the genitals significantly decreased the risk of HPV infection (OR = 3.030, P = 0.003). CONCLUSIONS: There is a relatively high prevalence rate of recessive infection of genital HPV among the seemingly healthy males in the rural area of Jiangsu Province. Daily cleaning of the genitals may be a protective measure against HPV infection.

Depositional dynamics and vegetation succession in self-organizing processes of deltaic marshes.

Global deltaic marshes are currently facing a multitude of pressures, including insufficient sediment supply, rising sea levels, and habitat loss. Consequently, unraveling the internal regulatory mechanisms within deltaic marshes is of paramount importance. Here, we harness years of observational data and high-resolution numerical models to uncover depositional dynamics and vegetation succession in self-organizing processes of deltaic marshes. Our findings indicate that the colonization of salt marsh vegetation triggered a robust phase of growth in the initial stages of river deltas formation. However, as vertical accretion intensifies and inundation decreases, the delta is driven towards a state of critical slowing down due to insufficient sediment supply. We have captured a pivotal turning point in the evolution of deltaic marshes. In accordance with the critical submergence threshold we have established, when the inundation time of deltaic marshes exceeds 0.97 h/d, these salt marsh platforms sustain a higher annual growth rate. Conversely, when the inundation time of deltaic marshes falls below 0.97 h/d, the interannual accretion rate continues to decrease. Our research reveals that, in the absence of human disturbances, the deposition rate in deltaic marshes transitions from growth to decline. During this period, the delta undergoes an interesting succession of pioneer salt marshes (Suaeda salsa) and high-elevation salt marshes (Phragmites australis). Even without reductions in sediment input due to human activities, the vertical deposition rate within deltaic marshes will still shift from acceleration to deceleration under the influence of this internal negative feedback regulation. This adaptive capacity of marshes may foreshadow that when observing a slowdown in vertical accretion on deltaic marsh platforms, it cannot be solely attributed to reductions in sediment input caused by human activities.

Development and evaluation of a GPU-based coupled three-dimensional hydrodynamic and water quality model.

In this study, a graphics processing unit (GPU)-based three-dimensional coupled hydrodynamic and water quality numerical model (GPUOM-WQ) was developed for the first time, which introduces pollution sources of atmospheric deposition, aquaculture wastewater, and oil platform emission to describe marine pollution comprehensively. A test case with analytical solutions and a real case with measured data were used to validate the accuracy of GPUOM-WQ. Simulation results indicate that the maximum error between the numerical and analytical solutions is 0.9 %, and the average relative error between simulated and measured values of 5 water quality variables at 38 stations in spring, summer, fall and winter is 14.63 %. In the real case simulation, GPUOM-WQ accelerates the computation 62.48 times, which is 3.23 times faster than in 64-core central processing unit (CPU) parallel mode. This study makes it possible to accurately simulate the marine water quality variation and spatiotemporal distribution in a high-resolution and efficient way.

Genetic alterations in juvenile cervical clear cell adenocarcinoma unrelated to human papillomavirus.

Clear cell adenocarcinoma of the cervix (CCAC) is a special type of HPV-independent cervical cancer. It has a low incidence rate, can be difficult to diagnose early, has a poor prognosis. Its peak incidence is in adolescence, which poses a great threat to women's health. Therefore, it is very important to explore the pathogenesis of cervical clear cell adenocarcinoma to guide subsequent treatment and prevention. This study analyzed 3 juvenile patients with CCAC diagnosed at the First Affiliated Hospital of Zhengzhou University. Using next-generation sequencing methods, we analyzed the pathogenesis of the patients and their close relatives by analyzing the genetic alterations of patients. CMTM5 was identified as the only shared mutated gene. Using published literature and comparative analyses of related disease-causing genes, 6 of the 19 genes (ALKBH7, MYCBP, MZF1, RNF207, RRS1, and TUSC2) were screened as genes with mutations in patients and had higher mutation rates in reproductive cancers. Pathway analysis showed that downregulated genes in non-HPV cervical cancer were mainly related to the immune system response, suggesting that non-HPV cervical cancer differs from HPV-infected cervical cancer in that the immune response is weaker, which is consistent with the weak correlation with viral infection.

The immunoprotective role of interleukin-10 in abnormal pregnancy outcome induced by Toxoplasma gondii infection.

AIMS: To investigate the immunoprotective effect of IL-10 on pregnancy in Toxoplasma gondii-infected C57BL/6 mice. METHODS: Twenty-four pregnant mice were randomly divided into 3 equal groups, i.e. a control group (CG), an infected group (IG) and an infected group treated with IL-10 (IPTG). Each IPTG and IG mouse was infected with 400 T. gondii trophozoites on gestational day (GD) 8. Each IPTG mouse was injected with 1 µg recombinant mouse IL-10 via a tail vein on GD 10 and 12. The mice were sacrificed on day 7 postinfection. Qa-1 and NKG2A were analyzed in the placenta by flow cytometry and real-time PCR. IL-4, IL-10 and IFN-γ in the placenta supernatant were analyzed by ELISA. Statistical analysis was performed by one-way ANOVA. RESULTS: IPTG mice showed a better mental state, had larger fetuses and placentas with a better blood supply and a lower resorption ratio compared to IG mice. NKG2A and Qa-1 were significantly increased in IPTG mice compared to IG mice (p < 0.05). IL-4 and IL-10 in IPTG placenta supernatant were increased (p < 0.05), but IFN-γ was decreased (p < 0.05) compared to IG placenta supernatant. The ratios of IFN-γ/IL-4 and IFN-γ/IL-10 were decreased in IPTG mice compared to IG mice (p < 0.05, p < 0.05). CONCLUSION: IL-10 plays an immunoprotective role and improves the pregnancy outcome of T. gondii-infected mice.

An inverse planning simulated annealing algorithm with adaptive weight adjustment for LDR pancreatic brachytherapy.

PURPOSE: The inverse planning simulated annealing (IPSA) algorithm has shown good results in cancer surgical treatment planning. However, an adaptive approach has not well been proposed for different shapes and sizes of tumors. The purpose of this study was to propose an adaptive, efficient and safe algorithm to get high-quality treatment dose planning, which is presented for pancreatic cancer. METHODS: An algorithm employs an optimized IPSA and an adaptive process for adjusting the weight of organs at risk (OAR) and tumor. The algorithm, which was combined with ant colony optimization, was further optimized to reduce the number of needles. It could meet the clinical dose objectives within the tumors, reduce the dose distribution within the OAR and minimize the number of needles. Ten clinical cases were chosen randomly from patients, previously successfully treated in clinic to test our method. The algorithm was validated against clinical cases, using clinically relevant dose parameters. RESULTS: The results were compared with clinical results in ten cases, indicating that the dose distribution within the tumor meets the clinical dose objectives. The dose received by OAR had been greatly reduced, and the number of needles could be reduced by about 50%. It was a significant improvement over the clinical treatment planning. CONCLUSIONS: In this paper, we have devised an algorithm to optimize the treatment planning in brachytherapy. The method in this paper could meet the clinical dose objectives and reduce the difficulty of operation. The results were clinically acceptable. This algorithm is also applicable to other cancers such as lung cancer.

Higher Phytohormone Contents and Weaker Phytohormone Signal Transduction Were Observed in Cold-Tolerant Cucumber.

Cucumbers (Cucumis sativus L.) originated from the South Asian subcontinent, and most of them are fragile to cold stress. In this study, we evaluated the cold tolerance of 115 cucumber accessions and screened out 10 accessions showing high resistance to cold stress. We measured and compared plant hormone contents between cold-tolerant cucumber CT90R and cold-sensitive cucumber CT57S in cold treatment. Most of the detected plant hormones showed significantly higher content in CT90R. To elucidate the role of plant hormones, we compared the leaf- and root-transcriptomes of CT90R with those of CT57S in cold stress treatment. In leaves, there were 1209 differentially expressed genes (DEGs) between CT90R and CT57S, while there were 703 in roots. These DEGs were not evenly distributed across the chromosomes and there were significant enrichments at particular positions, including qLTT6.2, a known QTL controlling cucumber cold tolerance. The GO and KEGG enrichment analysis showed that there was a significant difference in the pathway of plant hormone transductions between CT90R and CT57S in leaves. In short, genes involved in plant hormone transductions showed lower transcription levels in CT90R. In roots, the most significantly different pathway was phenylpropanoid biosynthesis. CT90R seemed to actively accumulate more monolignols by upregulating cinnamyl-alcohol dehydrogenase (CAD) genes. These results above suggest a new perspective on the regulation mechanism of cold tolerance in cucumbers.

Identification and characterization of long non-coding RNA Carip in modulating spatial learning and memory.

CaMKII has long been known to be a key effector for synaptic plasticity. Recent studies have shown that a variety of modulators interact with the subunits of CaMKII to regulate the long-term potentiation (LTP) of hippocampal neurons. However, whether long non-coding RNAs modulate the activity of CaMKII and affect synaptic plasticity is still elusive. Here, we identify a previously uncharacterized long non-coding RNA Carip that functions as a scaffold, specifically interacts with CaMKIIß, and regulates the phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor subunits in the hippocampus. The absence of Carip causes dysfunction of synaptic transmission and attenuates LTP in hippocampal CA3-CA1 synapses, which further leads to impairment of spatial learning and memory. In summary, our findings demonstrate that Carip modulates long-term synaptic plasticity by changing AMPA receptor and NMDA receptor activities, thereby affecting spatial learning and memory in mice.

Discovery of Plasma Membrane-Associated RNAs through APEX-seq.

In addition to nucleic acids, a variety of other biomolecules have also been found on the plasma membrane. Although researchers have realized that RNA has the ability to bind to membrane vesicles in vitro, little is known about whether and how RNA connects to the plasma membrane of the cell. The combination of high-throughput sequencing and in situ labeling methods provides an innovative approach for large-scale identification of subcellular RNAs. Here, we applied the recently published method APEX-seq and identified 75 RNAs related to the plasma membrane, in which lncRNA PMAR72 (plasma membrane-associated RNA AL121772.1) has a considerable affinity with sphingomyelin (SM) and localizes within distinct membrane foci. Our findings will provide some new evidence to elaborate the relationship between RNA and the plasma membrane of mammalian cells.

Asymmetric copper-catalyzed propargylic amination with amine hydrochloride salts.

The highly enantioselective copper-catalyzed propargylic amination of propargylic esters with amine hydrochloride salts has been realized for the first time using copper salts with chiral N,N,P-ligands. This method features a broad substrate scope and wide functional group tolerance, generating propargylic amines in good to excellent yields with high enantioselectivities (up to 99% ee). The utility of the approach was demonstrated by late-stage functionalization of marketed pharmaceuticals.

Highly enantioselective copper-catalyzed propargylic amination to access N-tethered 1,6-enynes.

A highly enantioselective copper-catalyzed propargylic amination starting from benzylic allylic amines has been developed with a new chiral N,N,P ligand. A series of N-tethered 1,6-enynes were synthesized in good to excellent yields with excellent enantioselectivities. Utilization of transition metal-catalyzed cycloisomerization of 1,6-enynes provides several enantioselectively enriched chiral five-membered N-heterocycles efficiently.

IL-10 reduces levels of apoptosis in Toxoplasma gondii-infected trophoblasts.

BACKGROUND: To analyze the effects of IL-10 on the HLA-G expression and the apoptosis of trophoblasts infected with Toxoplasma gondii. METHODS: T. gondii-infected or uninfected human trophoblasts and immortalized human placental BeWo cells were cultured with or without human IL-10. Uninfected and infected cells without IL-10 cells served as controls. HLA-G expression was measured by real-time PCR and flow cytometry, respectively. Cells apoptosis were analyzed by flow cytometry. Apoptosis associated moleculars were measured by real-time PCR and Western bolt. RESULTS: HLA-G expression was increased in the infected trophoblasts and BeWo cells compared to uninfected cells. Treatment of infected cells with IL-10 decreased HLA-G expression compared to infected cells while no change in treatment of uninfected cells compared with uninfected cells. Levels of apoptosis and apoptosis associated caspase-3 and caspase-8 decreased and c-FLIP levels increased in treated infected cells with IL-10 compared to infected cells and no difference in IL-10 treated uninfected cells compared to uninfected cells. CONCLUSIONS: IL-10 regulates HLA-G expression in T. gondii-infected trophoblasts. IL-10 treatment of infected trophoblasts reduced levels of apoptosis. This may contribute to the improvement in pregnancy outcomes when women infected with T. gondii treated with IL-10.

The Treg/Th17 imbalance in Toxoplasma gondii-infected pregnant mice.

AIM: To evaluate whether impaired Treg/Th17 balance exists in the pregnant mice infected with Toxoplasma gondii. METHOD OF STUDY: Regulatory T (Treg) and T-helper type 17 (Th17) cells were measured in both placenta and spleens of the pregnant mice infected with and without T. gondii by flow cytometry. The mRNA and protein expression levels of transforming growth factor-ß (TGF-ß) and interleukin-17A (IL-17A) were analyzed using real-time PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of forkhead box P3 (Foxp3), retinoic acid-related orphan receptor γt (RORγt), and IL-6 were also analyzed using real-time PCR. The correlations of the ratio of Treg/Th17 to the mRNA or protein expression level of those factors were analyzed by Spearman's correlation analysis. Data were analyzed by unpaired t-test and paired t-test. RESULTS: The proportion of Tregs or Th17 cells in the placenta and spleens of the T. gondii-infected pregnant mice was significantly lower or higher than in those of non-infected mice, respectively. Upregulation of TGF-ß and downregulation of IL-17A were found in the placenta of T. gondii-infected pregnant mice. The ratio of Treg to Th17 was significantly lower in the infected mice than that in the non-infected mice (P<0.01).The ratio of Treg to Th17 positively or negatively correlated with the protein expression level of TGF-ß (r=0.6204, P<0.05) or IL-17A (r=-0.6296, P<0.05), respectively. The ratio also positively correlated with the mRNA expression level of Foxp3 (r=0.7985, P<0.01), but negatively correlated with the mRNA expression level of RORγt (r=-0.6153, P<0.05), and IL-6 (r=-0.7492, P<0.01). CONCLUSION: TheTreg/Th17 imbalance exists in the pregnant mice infected with T. gondii, which is associated with the expression of related cytokine and key transcription factors. This result suggests that the embryo loss caused by this parasite may be associated with a reduced ratio of Treg to Th17 cell number.

Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys.

An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses. It must generate CD8+ T lymphocytes that control HIV replication and CD4+ T lymphocytes that provide help for the generation and maintenance of both cellular and humoral immune responses against the virus. Creating immunogens that can elicit cellular immune responses against the genetically varied circulating isolates of HIV presents a key challenge for creating an HIV vaccine. Polyvalent mosaic immunogens derived by in silico recombination of natural strains of HIV are designed to induce cellular immune responses that recognize genetically diverse circulating virus isolates. Here we immunized rhesus monkeys by plasmid DNA prime and recombinant vaccinia virus boost with vaccine constructs expressing either consensus or polyvalent mosaic proteins. As compared to consensus immunogens, the mosaic immunogens elicited CD8+ T lymphocyte responses to more epitopes of each viral protein than did the consensus immunogens and to more variant sequences of CD8+ T lymphocyte epitopes. This increased breadth and depth of epitope recognition may contribute both to protection against infection by genetically diverse viruses and to the control of variant viruses that emerge as they mutate away from recognition by cytotoxic T lymphocytes.