Effects of environmental temperature extremes exposure on sperm quality - evidence from a prospective cohort study in Anhui Province, China.

Extreme weather is becoming more frequent due to drastic changes in the climate. Despite this, the body of research focused on the association between temperature extreme events and sperm quality remains sparse. In this study, we elucidate the impact of exposure to environmental temperature extremes on sperm quality. Data for this investigation were derived from the Anhui Prospective Assisted Reproduction Cohort, encompassing the period from 2015 to 2020. Parameters such as sperm concentration, total sperm count, total motility, progressive motility, total motile sperm count, and progressive motile sperm count were quantified from semen samples. We assessed the exposure of participants to temperature extremes during the 0-90 days prior to sampling. This investigation encompassed 15,112 participants, yielding 28,267 semen samples. Our research findings indicate that exposure to low temperature extreme for three consecutive days (at the first percentile threshold) has a detrimental correlation with sperm count parameters and concentration. Similar trends were observed with the second percentile threshold, where significant adverse effects typically manifested after a four-day exposure sequence. Analysis of high temperature extreme showed that exposure at the 98th percentile had adverse effects on all six sperm quality parameters, and the sperm count parameter was particularly sensitive to high temperature, showing significant results immediately after three days of exposure. When considering even more temperature extreme (99th percentile), the negative consequences were more pronounced on the sperm count parameter. Additionally, progressive motility showed a stronger negative response. In summary, parameters associated with sperm count are particularly vulnerable to temperature extremes exposure. Exposure to high temperature extremes environments may also be associated with a decrease in sperm concentration and vitality. The findings of this study suggest that male population should pay attention to avoid exposure to temperature extreme environment, which has important significance for improving the quality of human fertility.

The impact of short-term exposure to meteorological factors on the risk of death from hypertension and its major complications: a time series analysis based on Hefei, China.

OBJECTIVES: This study aimed to reveal the short-term impact of meteorological factors on the mortality risk in hypertensive patients, providing a scientific foundation for formulating pertinent prevention and control policies. METHODS: In this research, meteorological factor data and daily death data of hypertensive patients in Hefei City from 2015 to 2018 were integrated. Time series analysis was performed using distributed lag nonlinear model (DLNM) and generalized additive model (GAM). Furthermore, we conducted stratified analysis based on gender and age. Relative risk (RR) combined with 95% confidence interval (95% CI) was used to represent the mortality risk of single day and cumulative day in hypertensive patients. RESULTS: Single-day lag results indicated that high daily mean temperature (T mean) (75th percentile, 24.9 °C) and low diurnal temperature range (DTR) (25th percentile, 4.20 °C) levels were identified as risk factors for death in hypertensive patients (maximum effective RR values were 1.144 and 1.122, respectively). Extremely high levels of relative humidity (RH) (95th percentile, 94.29%) reduced the risk of death (RR value was 0.893). The stratified results showed that the elderly and female populations are more susceptible to low DTR levels, whereas extremely high levels of RH have a more significant protective effect on both populations. CONCLUSION: Overall, we found that exposure to low DTR and high T mean environments increases the risk of death for hypertensive patients, while exposure to extremely high RH environments significantly reduces the risk of death for hypertensive patients. These findings contribute valuable insights for shaping targeted prevention and control strategies.

Independent and combined associations of polycyclic aromatic hydrocarbons exposure and sleep disorders among adults in the U.S. adult population.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are prevalent organic pollutants in the environment; however, limited research has been conducted to explore their potential effects on sleep disorders. This study aims to investigate the relationship between single and mixed PAHs exposures and sleep disorders. METHODS: This study analyzed National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2016, involving 7730 adult participants. To examine the relationship between PAHs exposure and sleep disorders, we employed survey-weighted multivariate logistic regression models and restricted cubic spline (RCS) models to evaluate single PAHs exposure. Additionally, we employed three mixed-exposure models to examine the relationship between combined PAHs exposure and sleep disorders. RESULTS: After adjusting for covariates, our analyses revealed positive associations between several urinary PAHs metabolites (1-hydroxynaphthalene (1-NAP), 2-NAP, 3-hydroxyfluorene (3-FLU), 2-FLU, and 1-hydroxypyrene (1-PYR)) and sleep disturbance. Consistency across various analytical methods underscores a discernible positive correlation between simultaneous exposure to PAHs and sleep disorders. This association is predominantly influenced by the presence of NAP and FLU. Remarkably, a positive relationship between combined PAHs exposure and sleep disorders emerged within the younger and middle-aged demographic but did not manifest within the elderly population. CONCLUSION: In conclusion, our study provides new epidemiological evidence suggesting that both single and mixed PAHs exposures may increase the risk of sleep disorders. Further prospective investigations are necessary to validate these findings.

Associations of perchlorate, nitrate, and thiocyanate exposure with arthritis and inflammation indicators in young and middle-aged adults, NHANES 2005-2016.

Background: Perchlorates, nitrates, and thiocyanates are prevalent environmental chemicals. Their potential association with arthritis remains unexplored. This study aimed to investigate the link between perchlorate, nitrate, and thiocyanate exposure and arthritis, as well as the potential role of inflammation in this context. Methods: Utilizing the National Health and Nutrition Examination Survey (NHANES) data spanning from 2005 to 2016, the study enrolled 6597 participants aged 20-59 (young and middle-aged), of which 1045 had arthritis. Employing multivariate logistic regression modeling, multiple linear regression models, restricted cubic spline analysis, Bayesian kernel machine regression (BKMR) modeling, and mediation analysis, we assessed these relationships. Results: There was a significant positive association between elevated urinary thiocyanate levels and arthritis risk [1.19 (1.11, 1.28)]. This association held true across subgroups of osteoarthritis (OA) [1.24 (1.10, 1.40)] and rheumatoid arthritis (RA) [1.33 (1.15, 1.55)]. Thiocyanate levels displayed a dose-dependent relationship with arthritis risk, showing a linear trend (nonlinear P > 0.05). Conversely, perchlorate and nitrate did not exhibit associations with arthritis risk. BKMR outcomes highlighted a positive correlation between a mixture of perchlorate, nitrate, and thiocyanate and arthritis risk, with thiocyanate being the predominant predictors. Moreover, BKMR and generalized linear model analyses unveiled no significant synergistic effect of urinary perchlorate, nitrate, and thiocyanate on arthritis risk. Furthermore, thiocyanate exposure has been linked to elevated levels of inflammatory indicators (white blood cell, neutrophils, lymphocytes, and systemic immune-inflammatory index (SII)). Conclusion: Heightened thiocyanate exposure may be linked to elevated arthritis risk, either single or in combined effects. Additionally, thiocyanate exposure is associated with heightened inflammation levels.

Interruption of KLF5 acetylation promotes PTEN-deficient prostate cancer progression by reprogramming cancer-associated fibroblasts.

Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Here, we report that PTEN deficiency induced Krüppel-like factor 5 (KLF5) acetylation and that interruption of KLF5 acetylation orchestrated intricate interactions between cancer cells and CAFs that enhance FGF receptor 1 (FGFR1) signaling and promote tumor growth. Deacetylated KLF5 promoted tumor cells to secrete TNF-α, which stimulated inflammatory CAFs to release FGF9. CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 and sensitized PTEN-deficient prostate cancer to the AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rationale for combined therapies using inhibitors of AKT and CX3CR1.

Role of ERRF, a novel ER-related nuclear factor, in the growth control of ER-positive human breast cancer cells.

Whereas estrogen-estrogen receptor α (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)-negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growth in vitro and tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER-mediated growth of breast cancer cells and could, thus, be a potential therapeutic target.

U-shaped association between plasma C-peptide and sarcopenia: A cross-sectional study of elderly Chinese patients with diabetes mellitus.

Limited research exists regarding the relationship between fasting plasma C-peptide levels and sarcopenia. As a result, our study aimed to examine this association in elderly Chinese diabetic patients. This cross-sectional study included 288 elderly patients with diabetes mellitus from the Fourth People's Hospital in Guiyang who were enrolled prospectively between March 2020 and February 2023. The independent variable of interest was fasting plasma C-peptide, while the dependent variable was sarcopenia. Data on several covariates, including demographic factors, lifestyle habits, co-morbidities, anthropometric indicators, and laboratory indicators, were also collected. Of the 288 participants, 27.43% (79/288) had sarcopenia. After adjusting for potential confounding variables, we found a U-shaped association between fasting plasma C-peptide levels and sarcopenia, with inflection points identified at approximately 774 pmol/L and 939 mmol/L. Within the range of 50-744 pmol/L, each 100 pmol/L increase in CysC was associated with a 37% decrease in the odds of sarcopenia (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.49 to 0.83; P < 0.001). Additionally, within the range of 939-1694 pmol/L, each 100 pmol/L increase in fasting plasma C-peptide was associated with a 76% increase in the odds of sarcopenia (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.11 to 2.81; P = 0.017). Our study revealed a U-shaped association between fasting plasma C-peptide levels and the likelihood of sarcopenia, with lower risk in the range of 774-939 pmol/L. These findings may assist in the development of more effective prevention and treatment strategies for sarcopenia in elderly diabetic patients.

Associations of exposure to heavy metal mixtures with kidney stone among U.S. adults: A cross-sectional study.

Assessing the effects of heavy metals (HMs) on kidney stone is often limited to analyzing individual metal exposures, with studies on the effects of exposure to mixtures of HMs being scarce. To comprehensively evaluate the relationship between exposure to mixed HMs and kidney stones, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2007-2016, which included 7809 adults. We used multiple statistical methods, including multiple logistic regression models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp) and bayesian kernel machine regression (BKMR), to assess the association between single HM and mixed exposure to HMs and kidney stones. Firstly, in single exposure analysis, urinary cadmium (Cd) and cobalt (Co) demonstrated a positive association with the risk of kidney stones. Secondly, various other approaches consistently revealed that mixed exposure to HMs exhibited a positive association with kidney stone risk, primarily driven by Cd, Co, and barium (Ba) in urine, with these associations being particularly notable among the elderly population. Finally, both BKMR and survey-weighted generalized linear models consistently demonstrated a significant synergistic effect between urinary Co and urinary uranium (Ur) in elevating the risk of kidney stones. Overall, this study provides new epidemiological evidence that mixed exposure to HMs is associated with an increased risk of kidney stones. Further prospectively designed studies are needed to confirm these findings.

Visual and Rapid Detection of Porcine Epidemic Diarrhea Virus (PEDV) Using Reverse Transcription Loop-Mediated Isothermal Amplification Method.

Porcine epidemic diarrhea virus (PEDV) can cause severe infectious porcine epidemic diarrhea (PED) and infect different ages of pigs, resulting in sickness and death among suckling pigs. For PEDV detection, finding an effective and rapid method is a priority. In this study, we established an effective reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for PEDV detection. Three sets of primers, specific for eight different sequences of the PEDV N gene, were designed in this study. The optimized RT-LAMP amplification program was as follows: 59 min at 61.9 °C and 3 min at 80 °C. The RT-LAMP results were confirmed with the addition of SYBR Green I fluorescence dye and with the detection of a ladder-like band by conventional gel electrophoresis analysis, which demonstrated a significant agreement between the two methods. The LOD of PEDV by RT-LAMP was 0.0001 ng/µL. Compared with RT-LAMP, the traditional RT-PCR method is 100-fold less sensitive. The RT-LAMP results had no cross-reaction with porcine parvovirus (PPV), porcine circovirus type 1 (PCV1), porcine pseudorabies virus (PRV), porcine circovirus type 2 (PCV2), rotavirus (RV), transmissible gastroenteritis virus (TGEV) and porcine reproductive and respiratory syndrome virus (PRRSV). Consequently, the newly developed RT-LAMP method could provide an accurate and reliable tool for PEDV diagnosis.

Research in porous structure of cellulose aerogel made from cellulose nanofibrils.

In this study, a simple strategy to fabricate the cellulose aerogel with homogeneous porous structure and good compression strength properties has been demonstrated. The cellulose aerogel was simply prepared by adding styrene acrylic emulsion (SAE) to the TEMPO-oxidized cellulose nanofibrils (CNF), followed by freeze-drying and oven-heating, in which covalent bond between CNF and SAE was confirmed by FT-IR. Meanwhile, the regulation process of porous structure of cellulose aerogels was investigated by varying the properties of CNF, and the addition of carboxymethyl cellulose (CMC) and SAE. The results demonstrated that the porous structure of cellulose aerogel was gradually improved with increasing carboxyl content of CNF. CMC could effectively increase in specific surface area of cellulose aerogel, achieving a more preferred porous structure due to the elimination of hornification. SAE could highly enhance the uniformity of structure with specific surface area up to 184 m2/g, porosity up to 99%, and successfully improve the strength properties, showing the fabricated cellulose aerogel as a potential cushion packaging material.

Role and mechanism of miR-144-5p in LPS-induced macrophages.

The aim of the present study was to explore the possible role of microRNA-144-5p (miR-144-5p) in rheumatoid arthritis (RA) and the associated mechanism. Following the induction of THP-1 cell differentiation into macrophages by phorbol ester (100 ng/ml) treatment, an in vitro inflammatory model of RA was established by treating the THP-1 macrophages with 1 µg/ml lipopolysaccharide (LPS). The level of miR-144-5p was subsequently measured using reverse transcription-quantitative PCR, which found that the expression of miR-144-5p was significantly reduced in LPS-treated THP-1 macrophages. Bioinformatics analysis and a dual-luciferase reporter assay were used to predict and confirm TLR2 as a direct target of miR-144-5p, respectively. Toll-like receptor 2 (TLR2) was then validated as a target gene of miR-144-5p. The effects of miR-144-5p upregulation and TLR2 silencing on LPS-treated THP-1 macrophages were then determined by transfection with miR-144-5p mimic and TLR2-siRNA, respectively. Cell viability was subsequently measured using a Cell Counting Kit-8 assay, whilst the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8 secreted by THP-1 macrophages was measured using ELISA. Western blotting was performed to measure p65 phosphorylation (p-p65) in the NK-κB signaling pathway. It was found that miR-144-5p overexpression reduced macrophage cell viability, reduced the expression of TNF-α, IL-6 and IL-8, and reduced the expression of TLR2 and p-p65 compared with the control group. Likewise, TLR2 silencing also reduced macrophage cell viability and reduced the expression of TNF-α, IL-6 and IL-8 in THP-1 macrophages. In conclusion, the data from the present study suggested that miR-144-5p overexpression reduced THP-1 macrophage cell viability and inhibited the expression of TNF-α, IL-6 and IL-8 in cells, possibly by inhibiting the expression of TLR2 and suppressing the activation of NK-κB signaling. Therefore, miR-144-5p may serve as a novel therapeutic target for the treatment of RA.

Establishment of a porcine parvovirus (PPV) LAMP visual rapid detection method.

Porcine parvovirus (PPV) is one of the major causes of reproductive pig disease. Due to its serious nature, wide spread and consequent great damage to the swine industry, an effective, rapid and convenient method for its detection is needed. A loop-mediated isothermal amplification (LAMP) assay was established to detect PPV infection. Two pairs of primers were specifically designed to recognize the six different sequences of open reading frame1 (ORF1) gene. The optimized LAMP program was as follows: 50 min at 59 °C followed by 3 min at 80 °C.The amplified products were analyzed both by visual inspection after staining with SYBR Green I dye and by conventional agarose gel electrophoresis. Both methods showed the same sensitivity. The limit of detection (LOD) for PPV by LAMP was 10 copies, which is 100-fold lower than conventional PCR. Our LAMP assay did not cross-react with other viruses. We used the established LAMP system to test 1100 field samples and detected 660 positives. The LAMP detection method for PPV represents a visual, sensitive and rapid assay which can detect the virus in the field, offering an attractive alternative for the PPV detection methods currently in use.

Klf5 acetylation regulates luminal differentiation of basal progenitors in prostate development and regeneration.

Prostate development depends on balanced cell proliferation and differentiation, and acetylated KLF5 is known to alter epithelial proliferation. It remains elusive whether post-translational modifications of transcription factors can differentially determine adult stem/progenitor cell fate. Here we report that, in human and mouse prostates, Klf5 is expressed in both basal and luminal cells, with basal cells preferentially expressing acetylated Klf5. Functionally, Klf5 is indispensable for maintaining basal progenitors, their luminal differentiation, and the proliferation of their basal and luminal progenies. Acetylated Klf5 is also essential for basal progenitors' maintenance and proper luminal differentiation, as deacetylation of Klf5 causes excess basal-to-luminal differentiation; attenuates androgen-mediated organoid organization; and retards postnatal prostate development. In basal progenitor-derived luminal cells, Klf5 deacetylation increases their proliferation and attenuates their survival and regeneration following castration and subsequent androgen restoration. Mechanistically, Klf5 deacetylation activates Notch signaling. Klf5 and its acetylation thus contribute to postnatal prostate development and regeneration by controlling basal progenitor cell fate.

TTK promotes mesenchymal signaling via multiple mechanisms in triple negative breast cancer.

Abnormal expression of TTK kinase has been associated with the initiation, progression, and therapeutic resistance of breast and other cancers, but its roles remain to be clarified. In this study, we examined the role of TTK in triple negative breast cancer (TNBC), and found that higher TTK expression correlated with mesenchymal and proliferative phenotypes in TNBC cells. Pharmacologic inhibition and genomic silencing of TTK not only reversed the epithelial-to-mesenchymal transition (EMT) in TNBC cells, but also increased the expression of KLF5, an effector of TGF-ß signaling and inhibitor of EMT. In addition, TTK inhibition decreased the expression of EMT-associated micro-RNA miR-21 but increased the expression of miR-200 family members and suppressed TGF-ß signaling. To test if upregulation of KLF5 plays a role in TTK-induced EMT, TTK and KLF5 were silenced simultaneously, which reversed the decreased EMT caused by loss of TTK. Consistently, the decrease in miR-21 expression and increase in miR-200 expression caused by TTK silencing were rescued by loss of KLF5. Altogether, this study highlights a novel role and signaling pathway for TTK in regulating EMT of TN breast cancer cells through TGF-ß and KLF5 signaling, highlighting targetable signaling pathways for TTK inhibitors in aggressive breast cancer.

[Study on challenge dose of pigeon paramyxovirus type 1 (Chuansha strain)].

In order to determine the challenge dose of pigeon paramyxovirus type 1 (PPMV-1) inactivated vaccine (S-1 strain). The virus titer of PPMV-1 E5 allantoic fluid (Chuansha strain) was determined using SPF chicken embryos in this research. After inoculating 30-day-old and 120-day-old pigeons with low-HI antibody against PPMV-1 (HI antibody < or =2) with different doses of PPMV-1 (Chuansha strain), the clinical symptoms and histopathological lesions of the challenged pigeons were examined. The results showed that the minimal lethal dose (MLD) of PPMV-1 (Chuansha strain) was 102.5 ELD50, so we determined that 10(5.5) ELD50, which was 1000 times the MLD, could be taken as the challenge dose in the vaccine efficacy test for PPMV-1 inactivated vaccine (S-1 strain).

Enhanced porcine circovirus Cap protein production by Pichia pastoris with a fuzzy logic DO control based methanol/sorbitol co-feeding induction strategy.

Porcine circovirus Cap protein production by P. pastoris with strong AOX promoter suffered with the problems with traditional pure methanol induction: (1) inefficient methanol metabolism; (2) extensive oxygen supply load; (3) difficulty in stable DO control; (4) low protein titer. In this study, based on the difference of DO change patterns in response to methanol and sorbitol additions, a novel fuzzy control system was proposed to automatically regulate the co-feeding rates of methanol and sorbitol for efficient Cap protein induction. With aid of the proposed control system when setting DO control level at 10%, overall fermentation performance was significantly improved: (1) DO could be stably controlled under mild aeration condition; (2) methanol consumption rate could be restricted at moderate level and the major enzymes involved with methanol metabolism were largely activated; (3) Cap protein concentration reached a highest level of 198mg/L, which was about 64% increase over the best one using the pure methanol induction strategies.

[Retrospective study on the treatment of ankylosing spondylitis with cervical spine fracture: 8 cases report].

OBJECTIVE: To discuss surgical procedures and curative effect of ankylosing spondylitis with cervical spine fracture. METHODS: From January 2003 to October 2011, 8 patients with ankylosing spondylitis with cervical spine fracture were respectively treated by surgical treatment (7 cases) and conservative treatment (1 case), 8 cases were male with an average of age 41 years old (ranged, 27 to 49). All patients were confirmed by CT and MRI,and 6 cases combined with spinal cord injury. One case was treated with skull-neck-thorax model, 7 cases were treated by surgery. The procedures included anterior approach (5 cases), posterior approach (1 case), and combined anteroposterior approach (1 case). Fracture fusion condition were evaluated according to CT at the final following up, improvement of spinal cord injury were assessed according to Frankel classification. RESULTS: Eight patients were followed up from 4 to 38 months with an average of 34 months. Seven cases obtained bone healing, 3 patients without spinal cord injury remained intact after operation, 5 patients with spinal cord injury improved at different degree after operation. Frankel classification of 7 patients were improved 1 degree, and 1 case delayed union for following up. CONCLUSION: Ankylosing spondylitis with cervical spine fracture is a special kind of trauma, which have a high rate of neurological deficits. Surgery should be performed as early as possible, and procedures were chosen depending on particular case.