Monkeypox virus (MPV) is a smallpox-like virus belonging to the genus Orthopoxvirus of the family Poxviridae. Unlike smallpox with no animal reservoir identified and patients suffering from milder ...symptoms with less mortality, several animals were confirmed to serve as natural hosts of MPV. The reemergence of a recently reported monkeypox epidemic outbreak in nonendemic countries has raised concerns about a global outburst. Since the underlying mechanism of animal-to-human transmission remains largely unknown, comprehensive analyses to discover principal differences in gene signatures during disease progression have become ever more critical. In this study, two MPV-infected in vitro models, including human immortal epithelial cancer (HeLa) cells and rhesus monkey (Macaca mulatta) kidney epithelial (MK2) cells, were chosen as the two subjects to identify alterations in gene expression profiles, together with co-regulated genes and pathways that are affected during monkeypox disease progression. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and MetaCore analyses, we discovered that elevated expression of genes associated with interleukins (ILs), G protein-coupled receptors (GPCRs), heat shock proteins (HSPs), Toll-like receptors (TLRs), and metabolic-related pathways play major roles in disease progression of both monkeypox-infected monkey MK2 and human HeLa cell lines. Interestingly, our analytical results also revealed that a cluster of differentiation 40 (CD40), plasmin, and histamine served as major regulators in the monkeypox-infected monkey MK2 cell line model, while interferons (IFNs), macrophages, and neutrophil-related signaling pathways dominated the monkeypox-infected human HeLa cell line model. Among immune pathways of interest, apart from traditional monkeypox-regulated signaling pathways such as nuclear factor- (NF-κB), mitogen-activated protein kinases (MAPKs), and tumor necrosis factors (TNFs), we also identified highly significantly expressed genes in both monkey and human models that played pivotal roles during the progression of monkeypox infection, including CXCL1, TNFAIP3, BIRC3, IL6, CCL2, ZC3H12A, IL11, CSF2, LIF, PTX3, IER3, EGR1, ADORA2A, and DUOX1, together with several epigenetic regulators, such as histone cluster family gene members, HIST1H3D, HIST1H2BJ, etc. These findings might contribute to specific underlying mechanisms related to the pathophysiology and provide suggestions regarding modes of transmission, post-infectious sequelae, and vaccine development for monkeypox in the future.
Purpose
The cervicovaginal microbiota is essential for maintaining the health of the female reproductive tract. However, whether cervicovaginal microbiota status prior to frozen embryo transfer (FET) ...associates with pregnancy outcomes is largely unexplored.
Methods
Cervical mucus from 29 women who had undergone FET was collected. Microbial composition was analyzed using 16 S rRNA gene sequence to assess the correlation to the pregnancy outcomes.
Results
CST‐categorized Lactobacillus was the most dominant (41.71%) in the pregnant group, while CST‐IV‐based and BV‐related Gardnerella (34.96%) prevailed in the non‐pregnant group. The average abundance of Gardnerella compared non‐pregnant to pregnant women was the highest (34.96% vs. 4.22%, p = 0.0015) among other CST‐IV indicator bacteria. Multivariate analysis revealed that CST‐IV‐related bacteria have a significantly adverse effect on ongoing pregnancy outcomes (odds ratio, 0.083; 95% confidence index, 0.012–0.589, p = 0.013*).
Conclusions
The study found that the CST‐IV microbiota, with significantly increasing Gardnerella and the loss of Lactobacilli as the dominant bacteria, can potentially contribute to pregnancy failure. Therefore, dysbiotic microbiota may be a risk factor in women undergoing FET. Assessing the health of the cervicovaginal microbiota prior to FET would enable couples to make a more thoughtful decision on the timing and might improve pregnancy outcomes.
CSTIV typed cervical vaginal microbiota can potentially contribute to pregnancy failure, therefore, serving as a risk factor in women undergoing frozen thawed embryo transferFET). Assessing the health of the cervicoaginal microbiota before performing FET and giving appropriate treatment to avoid the CSTIV microbiota might improve pregnancy outcomes.
The purpose of this study was to compare the effects of nutritional supplement drinks (NSDs) and nutritional education (NE) on the nutritional status and physical performance of older nursing home ...residents who were at risk of malnutrition. This study was a clustered, randomized, parallel, multi-center clinical trial, with 107 participants more than 65 years old and at risk of malnutrition recruited from several nursing homes in this study. Participants were divided into two groups: an NE group (n = 50) and an NSD group (n = 57). The NE group was given NE by a dietitian, while the NSD group was provided with two packs of NSD except receiving NE (Mei Balance, Meiji Holdings, Tokyo, Japan) per day as a snack between meals and before bed. Anthropometric data, blood pressure, nutritional status, blood biochemical biomarkers, and physical performance were measured before and after 12-week interventions. After 12 weeks of NE combined with NSD intervention, body weight, body-mass index, the mini nutritional assessment-short form (MNA-SF) score, walking speed, and SF-36 questionnaire score were improved in older nursing home residents at risk of malnutrition.
With the rising need for accessible cervical cancer screening, self‐sampling methods offer a promising alternative to traditional physician‐led sampling. This study aims to evaluate the efficacy of ...the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high‐risk HPV (hrHPV) types between samples collected by physicians and those self‐collected by women using a self‐sampling kit for validation. Women aged 21–65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician‐sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self‐sampling kit closely matched the physician‐led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval 95% CI: 0.72–0.79; agreement: 87.7%, 95% CI: 85.8–89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72–0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user‐friendly alternative to traditional sampling methods. This suggests that self‐sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.
Phalaenopsis represents an important cash crop worldwide. Abundant flower colors observed in Phalaenopsis orchids range from red-purple, purple, purple-violet, violet, and violet-blue. However, ...violet-blue orchids are less bred than are those of other colors. Anthocyanin, vacuolar pH and metal ions are three major factors influencing flower color. This study aimed to identify the factors causing the violet-blue color in Phalaenopsis flowers and to analyze whether delphinidin accumulation and blue pigmentation formation can be achieved by transient overexpression of heterologous F3'5'H in Phalaenopsis.
Cyanidin-based anthocyanin was highly accumulated in Phalaenopsis flowers with red-purple, purple, purple-violet, and violet to violet-blue color, but no true-blue color and no delphinidin was detected. Concomitantly, the expression of PeF3'H (Phalaenopsis equestrsis) was high, but that of PhF3'5'H (Phalaenopsis hybrid) was low or absent in various-colored Phalaenopsis flowers. Transient overexpression of DgF3'5'H (Delphinium grandiflorum) and PeMYB2 in a white Phalaenopsis cultivar resulted a 53.6% delphinidin accumulation and a novel blue color formation. In contrast, transient overexpression of both PhF3'5'H and PeMYB2 did not lead to delphinidin accumulation. Sequence analysis showed that the substrate recognition site 6 (SRS6) of PhF3'5'H was consistently different from DgF3'5'Hs at positions 5, 8 and 10. Prediction of molecular docking of the substrates showed a contrary binding direction of aromatic rings (B-ring) with the SRS6 domain of DgF3'5'H and PhF3'5'H. In addition, the pH values of violet-blue and purple Phalaenopsis flowers ranged from 5.33 to 5.54 and 4.77 to 5.04, respectively. Furthermore, the molar ratio of metal ions (including Al
, Ca
and Fe
) to anthocyanin in violet-blue color Phalaenopsis was 190-, 49-, and 51-fold higher, respectively, than those in purple-color Phalaenopsis.
Cyanidin-based anthocyanin was detected in violet-blue color Phalaenopsis and was concomitant with a high pH value and high molar ratio of Al
, Ca
and Fe
to anthocyanin content. Enhanced expression of delphinidin is needed to produce true-blue Phalaenopsis.
Cell migration is a fundamental feature of cancer recurrence. Since recurrence is correlated with high mortality in lung cancer, it follows that reducing cell migration would decrease recurrence and ...increase survival rates. Semaphorin-6A (SEMA6A), a protein initially known as a regulator of axonal guidance, is down-regulated in lung cancer tissue, and low levels of SEMA6A are associated with cancer recurrence. Thus, we hypothesized that SEMA6A could suppress cancer cell migration. In this study, we found that the migration capability of H1299 lung cancer cells decreased with SEMA6A overexpression, while it increased with SEMA6A silencing. Moreover, silencing of the cellular homeostasis protein Heme-oxygenase-1 (HMOX1) and/or the transcription factor Nuclear Factor, Erythroid-2-Like-2 (NRF2) reversed the migration-suppressing effect of SEMA6A and the SEMA6A-driven alterations in expression of urokinase insulin-like-growth-factor-binding-protein-3, Matrix metalloproteinase (MMP)-1, and MMP9, the downstream effectors of HMOX1. Taken together, these results demonstrate that SEMA6A is a potential suppressor of cancer migration that functions through the NRF2/HMOX1 axis. Our results explain why low SEMA6A is linked to high recurrence in the clinical setting and suggest that SEMA6A could be useful as a biomarker or target in lung cancer therapy.
Effective therapeutic targets for triple‐negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with ...chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration‐approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR‐155 is upregulated in BC, but whether and how miR‐155 regulates DCA resistance is unclear. In this study, we demonstrated that miR‐155 was upregulated in CD24−CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR‐155 increased the number of CD24−CD44+ CSCs, DCA resistance and tumor clone formation in MDA‐231 and BT‐549 BC cells, and knockdown of miR‐155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR‐155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin‐5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR‐155 in promoting stemness and DCA resistance in BC cells. Our data show that miR‐155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR‐155/TSPAN5 signaling axis in the treatment of TNBC.
Optimization of the time-cost trade off (TCT) has received considerable attention for several decades. However, few studies have considered improving performance/productivity of existing crews. To ...shorten the gap to real-world applications, this study presents an improved TCT model that considers variable productivity using genetic algorithms (GAs). Through an illustrative case and a real world case, the results demonstrate that improving labor productivity of selected activities by allocating existing crews and management can yield an optimized solution. As such, a decision maker can implement a better optimized technique to reduce a project duration under budget while reducing the risk of liquidated damages. The main contribution of this study is to apply managerial improvement of labor productivity to TCT optimization, the project duration can be reduced owing to improved productivity of existing crews rather than inefficient overmanning, overlapping or costly substitution. In the end, three important managerial insights are presented and future research is recommended.
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•Organophosphate flame retardant exposure is common in chronic kidney disease.•Urinary organophosphate flame retardant level is associated with renal impairment.•Proteinuria could be ...impacted by organophosphate flame retardant exposure.•Organophosphate flame retardant exposure might be altered by age and diet.
Organophosphate flame retardants (OPFRs) are emerging and widespread environmental pollutants with potential health hazards, including nephrotoxicity. However, the exposure patterns and nephrotoxic potential of OPFRs are yet to be investigated in patients with chronic kidney disease (CKD). We conducted a cross-sectional study involving 166 patients with CKD stratified by estimated glomerular filtration rate (eGFR) and severity of proteinuria. The urinary concentrations of 10 OPFR compounds were measured to evaluate the exposure patterns. Clinical and urinary OPFR profiles were compared among subgroups to identify whether the OPFR compounds were independently correlated with eGFR and proteinuria. Additionally, lifestyle factors were compared among subgroups stratified by median concentrations of urinary OPFR compounds associated with renal disease severity. This study revealed universal exposure to OPFRs in the CKD population, with an overall urinary detection rate of 98.80 %. Furthermore, after adjusting for covariates, the urinary concentration of bis(2-chloroethyl) phosphate (BCEP) was identified as an independent predictor of lower eGFR (low vs high eGFR, odds ratio (OR) (95 % confidence interval (CI)), 1.761 (1.032–3.005) per log μg/g creatinine, p = 0.038), and the urinary concentration of bis(2-butoxyethyl) phosphate (BBOEP) was independently correlated with overt proteinuria in CKD patients (with vs without overt proteinuria, OR (95 % CI), 1.813 (1.065–3.086) per log μg/g creatinine, p = 0.028). Moreover, frequent seafood consumption was negatively correlated with urinary BCEP concentration (high vs low BCEP, OR (95 % CI), 0.455 (0.228–0.908), p = 0.025), and age was inversely associated with urinary BBOEP concentration (high vs low BBOEP, OR (95 % CI), 0.968 (0.937–0.999) per year, p = 0.048). In conclusion, our investigation highlights the extensive exposure to OPFRs and the independent association between renal disease severity and urinary BCEP/BBOEP concentrations in the CKD population, indicating the nephrotoxic potential of these pollutants.
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