Engaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to ...salivary microbiota, which, combined with an individual's positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect.
Based on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4
T lymphocyte counts ≥ 500, 200-499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM.
The core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts.
As HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.
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•Commercial dried ginger in China can be aggregated into two groups.•A total of 35 compounds were identified as contributing to differentiation, with sulfonated conjugates being the ...key chemical differentiator.•Sulfur-containing treatment was proved to be the main reason of the formation of sulfonated conjugates.•The anti-inflammatory efficacy of dried ginger was significantly decreased due to containing sulfated conjugates.•A targeted quantification approach was developed to assess whether dried ginger was treated with sulfur and to evaluate its quality.
Dried ginger, a well-known medicine and food homologous production, has been widely circulated in China with high health benefits and economic value. Currently, there is still a lack of quality assessment on whether dried ginger in China exhibits chemically and biologically distinct properties, which creates a barrier to its quality control in commercial circulation. In this study, the chemical characteristics of 34 batches of common dried ginger samples in China were first explored using non-targeted chemometrics based on the UPLC-Q/TOF-MS analysis, leading to the identification of 35 chemicals that contributed to clustering into two categories, with sulfonated conjugates being the key chemically distinct components. By comparing the samples before and after sulfur-containing treatment and the further synthesis of a key differentiating component of 6-gingesulfonic acid, it was then demonstrated that sulfur-containing treatment was the primary cause of the formation of sulfonated conjugates, as opposed to regional or environmental factors. Furthermore, the anti-inflammatory efficacy of dried ginger with high presence of sulfonated conjugates was significantly decreased. Consequently, for the first time, UPLC-QqQ-MS/MS was used to develop a targeted quantification method for 10 characteristic chemicals in dried ginger, allowing researchers to quickly determine whether dried ginger has been processed with sulfur and quantitatively evaluate the quality of dried ginger. These results provided an insight into the quality of commercial dried ginger in China and a suggested method for its quality supervision as well.
Cancer-associated fibroblasts (CAFs), an important type of stromal cells in the tumor microenvironment (TME), are responsible for creating physical barriers to drug delivery and penetration in tumor ...tissues. Thus, effectively downregulating CAFs to destroy the physical barrier may allow enhanced penetration and accumulation of therapeutic drugs, thereby improving therapeutic outcomes. Herein, a matrix metalloproteinase (MMP)-triggered dual-targeting hybrid micelle-in-liposome system (RPM@NLQ) was constructed to sequentially deliver quercetin (Que) and paclitaxel (PTX) for fibrotic TME remodeling and chemotherapy potentiation. Specifically, antifibrotic Que and small-sized RGD-modified micelles containing PTX (RPM) were co-encapsulated into MMP-sensitive liposomes, and the liposomes were further adorned with the NGR peptide (NL) as the targeting moiety. The resulting RPM@NLQ first specifically accumulated at the tumor site under the guidance of the NGR peptide after intravenous administration and then released Que and RPM in response to the extensive expression of MMP in the TME. Subsequently, Que was retained in the stroma to remarkably downregulate fibrosis and decrease the stromal barrier by downregulating Wnt16 expression in CAFs, which further resulted in a significant increase of RPM for deeper tumor. Thus, RPM could precisely target and kill breast cancer cells locally. Consequently, prolonged blood circulation, selective cascade targeting of tumor tissue and tumor cells, enhanced penetration, and excellent antitumor efficacy have been demonstrated in vitro and in vivo. In conclusion, as-designed sequential delivery systems for fibrotic TME remodeling and chemotherapy potentiation may provide a promising adjuvant therapeutic strategy for breast and other CAF-rich tumors.
Lily is a popular flower around the world not only because of its elegant appearance, but also due to its appealing scent. Little is known about the regulation of the volatile compound biosynthesis ...in lily flower scent. Here, we conducted an approach combining two-dimensional analysis and weighted gene co-expression network analysis (WGCNA) to explore candidate genes regulating flower scent production. In the approach, changes of flower volatile emissions and corresponding gene expression profiles at four flower developmental stages and four circadian times were both captured by GC-MS and RNA-seq methods. By overlapping differentially-expressed genes (DEGs) that responded to flower scent changes in flower development and circadian rhythm, 3,426 DEGs were initially identified to be candidates for flower scent production, of which 1,270 were predicted as transcriptional factors (TFs). The DEGs were further correlated to individual flower volatiles by WGCNA. Finally, 37, 41 and 90 genes were identified as candidate TFs likely regulating terpenoids, phenylpropanoids and fatty acid derivatives productions, respectively. Moreover, by WGCNA several genes related to auxin, gibberellins and ABC transporter were revealed to be responsible for flower scent production. Thus, this strategy provides an important foundation for future studies on the molecular mechanisms involved in floral scent production.
Cyanobacteria are supposed to be promising photosynthetic microbial platforms that recycle carbon dioxide driven into biomass and bioproducts by solar energy. Glycogen synthesis serves as an ...essential natural carbon sink mechanism, storing a large portion of energy and organic carbon source of photosynthesis. Engineering glycogen metabolism to harness and rewire carbon flow is an important strategy to optimize efficacy of cyanobacteria platforms. ADP-glucose pyrophosphorylase (GlgC) catalyzes the rate-limiting step for glycogen synthesis. However, knockout of
fails to promote cell growth or photosynthetic production in cyanobacteria, on the contrary,
deficiency impairs cellular fitness and robustness. In this work, we adopted a theophylline-responsive riboswitch to engineer and control
expression in
PCC7942 and achieved flexible regulation of intracellular GlgC abundance and glycogen storage. With this approach, glycogen synthesis and glycogen contents in PCC7942 cells could be regulated in a range from about 40 to 300% of wild type levels. In addition, the results supported a positive role of glycogen metabolism in cyanobacteria cellular robustness. When glycogen storage was reduced, cellular physiology and growth under standard conditions was not impaired, while cellular tolerance toward environmental stresses was weakened. While when glycogen synthesis was enhanced, cells of PCC7942 displayed optimized cellular robustness. Our findings emphasize the significance of glycogen metabolism for cyanobacterial physiology and the importance of flexible approaches for engineering and understanding cellular physiology and metabolism.
Background: Cough is one of the most common complications following intravenous administration of sufentanil during anesthesia induction. The study aimed to investigate the protective effect of ...alfentanil, afentanyl derivative with short onset time and short duration, in reducing sufentanil-induced cough. Patients and methods: Eighty patients that scheduled for thyroid surgery under general anesthesia were randomly divided into the alfentanil group and normal saline group, with 40 cases per group. Patients in the alfentanil group received intravenous administration of 2 microg/kg alfentanil prior to sufentanil injection during general anesthesia induction, while the same dose of normal saline was administered in the normal saline group. The outcomes measures included the incidence and severity of cough and common side effects of opioids following the administration of sufentanil during the induction of general anesthesia, intraoperative hemodynamics parameters and major adverse events during anesthesia recovery period. Results: The incidence of cough within one minute after the injection of sufentanil during anesthesia induction was 40% in the normal saline group, and the pretreatment of alfentanil significantly reduced the incidence of sufentanil-induced cough to 5% (p < 0.05). Correspondingly, the patients in the alfentanil group had decreased severity of sufentanil-induced cough compared with the normal saline group (p < 0.05). No significant differences in the incidences of common side effects of opioids (dizziness, nausea and vomiting, chest tightness and respiratory depression) within one minute after sufentanil injection were found (p > 0.05). Furthermore, there were no significant differences between the two groups in intraoperative hemodynamic parameters, extubation time, or the incidences of emergence agitation, respiratory depression, delayed recovery from anesthesia and postoperative nausea and vomiting during Postanesthesia Care Unit stay (p > 0.05). Conclusion: Pretreatment with low-dose alfentanil (2 ng/kg) effectively and safely reduced both the incidence and severity of sufentanil-induced cough during anesthesia induction. Clinical Trial Registration Number: Chinese Clinical Trial Registry (identifier: ChiCTR2300069286). Keywords: alfentanil, sufentanil, cough, anesthesia induction
Salivary virome is important for oral ecosystem, but there are few reports on people living with HIV. We performed metagenomic sequencing to compare composition and functional genes of salivary ...virobiota between one HIV-negative and four HIV-positive groups in which participants were all men who have sex with men (MSM) with different immunosuppression statuses (five samples per group) to find the evidence that salivary virobiota plays a role in the pathogenesis of oral disease. Acute-stage subjects achieved a positive result of HIV RNA, but HIV antibody negative or indeterminate, whereas individuals with mild, moderate, and severe immunosuppression exhibited CD4
T-lymphocyte counts of at least 500, 200-499, and less than 200 cells/μL or opportunistic infection, respectively. The results showed the composition of salivary virus genera in subjects with mild immunosuppression was the most similar to that in healthy people, followed by that in the acute stage; under severe immunosuppression, virus genera were suppressed and more similar to that under moderate immunosuppression. Furthermore, abnormally high abundance of
was particularly obvious in MSM with HIV infection. Analysis of KEGG Pathway revealed that
cell cycle, which affects cell duplication, became shorter in HIV-positive subjects. It is worth noting that in acute-stage participants, protein digestion and absorption related to the anti-HIV-1 activity of secretory leukocyte protease inhibitor was increased. Moreover, in the severely immunosuppressed subjects, glutathione metabolism, which is associated with the activation of lymphocytes, was enhanced. Nevertheless, the ecological dysbiosis in HIV-positive salivary virobiota possibly depended on the changes in blood viral load, and salivary dysfunction of MSM infected with HIV may be related to CD4 counts. Ribonucleoside diphosphate reductase subunit M1 in purine metabolism was negatively correlated, though weakly, to CD4 counts, which may be related to the promotion of HIV-1 DNA synthesis in peripheral blood lymphocytes. 7-Cyano-7-deazaguanine synthase in folate biosynthesis was weakly positively correlated with HIV viral load, suggesting that this compound was produced excessively to correct oral dysfunction for maintaining normal cell development. Despite the limited number of samples, the present study provided insight into the potential role of salivary virome in the oral function of HIV infected MSM.
The rare-earth telluride compound EuTe4 exhibits a charge density wave (CDW) and an unconventional thermal hysteresis transition. Herein, we report a comprehensive study of the CDW states in EuTe4 by ...using low-temperature scanning tunneling microscopy. Two types of charge orders are observed at 4 K, including a newly discovered spindle-shaped pattern and a typical stripe-like pattern. As an exotic charge order, the spindle-shaped CDW is off-axis and barely visible at 77 K, indicating that it is a hidden order developed at low temperature. Based on our first-principles calculations, we reveal the origins of the observed electronic instabilities. The spindle-shaped charge order stems from a subsequent transition based on the stripe-like CDW phase. Our work demonstrates that the competition and cooperation between multiple charge orders can generate exotic quantum phases.
Given a new feature request during software evolution, developers are used to employing existing third-party libraries and APIs for implementation. However, it is usually non-trivial to find suitable ...APIs and to decide where to use these APIs in the original software. In this paper, we develop an approach for recommending API methods and usage locations through mining various software repositories. First, we analyze software repositories and use the feature location technique to localize feature-related files as API usage locations. Then, we utilize the feature-related files and API libraries to identify potential API methods for the implementation of the incoming feature request. We evaluate our approach on 5000 feature requests selected from five Java projects, and the results demonstrate that our approach can achieve 29.7% and 9.6% improvement in terms of Hit@5 and Hit@10 in recommending API methods, compared with the existing approach. For API usage localization, our approach can get MAP, MRR, Hit@1, HIt@5, and Hit@10 values with 0.293, 0.434, 0.303, 0.602, and 0.685, respectively.
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