Millennial changes and cooling trends in land surface warm-season temperatures during the Holocene.

The scarcity of proxies and calibration models for quantitatively reconstructing millennial timescale seasonal temperature tremendously constraints our understanding of the Holocene thermal variation and its driven mechanisms. Here, we established two global warm-season temperature models by applying deep learning neural network analysis to the branched tetraether membrane lipids originating from surface soil and lacustrine sediment bacteria. We utilized these optimal models in global well-dated lacustrine, peatland, and loess profiles covering the Holocene. All reconstructions of warm-season temperatures, consistent with climate model simulations, indicate cooling trends since the early Holocene, primarily induced by decreased solar radiation in the Northern Hemisphere due to the precession peak at the early. We further demonstrated that the membrane lipids can effectively enhance the future millennial seasonal temperature research, including winter temperatures, without being restricted by geographical location and sedimentary carrier.

Polygonum Cuspidatum Alcohol Extract Exerts Analgesic Effects via the MAPK/ERK Signaling Pathway.

Objective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism. Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses. Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues. Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer.

The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MicroRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, this study aimed to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, and human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that inhibiting miR-122-5p expression led to the activation of p53. This inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration, and promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than the corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for developing targeted drugs.

The impact of sleep on in vitro fertilization embryo transfer outcomes: a prospective study.

OBJECTIVE: To prospectively examine the association between sleep quality before embryo transfer with pregnancy outcomes in a population with infertility. DESIGN: Prospective observational cohort study. SETTING: Center for Reproductive Medicine, Shandong University. PATIENT(S): From 7,847 women who enrolled from July 2019 to July 2020, 3,183 were eligible. INTERVENTION(S): Information about sleep, including sleep quality, sleep duration, and sleep chronology, were collected before embryo transfer using an integrated questionnaire. Sleep quality is quantified by the Pittsburgh Sleep Quality Index (PSQI) with a cut-point of 5 (PSQI >5 identifying poor sleep vs. PSQI ≤5 identifying good sleep). Average weekly sleep duration was calculated and divided into 5 groups (≤7, 7-8, 8-9, 9-10, and >10 h/d). In defining sleep chronotype, women with a sleep midpoint earlier than 2:30 AM were defined as morningness type, whereas those with a sleep midpoint later than 3:30 AM were defined as eveningness type, and the remainder were defined as an intermediate type. MAIN OUTCOME MEASURE(S): Rate of clinical pregnancy and live birth. RESULT(S): Compared with those reporting poor sleep quality, those reporting good sleep quality showed higher clinical pregnancy (69.3% vs. 65.1%) and live birth rates (50.5% vs. 45.7%). After adjusting for confounding factors, women who self-reported good sleep had a higher probability of acquiring clinical pregnancy (RR, 1.07; 95% confidence interval, 1.01-1.13) and of live birth (RR, 1.12; 95% confidence interval, 1.02-1.23). Women with the morningness chronotype had the lowest rates of clinical pregnancy and live birth and had the highest rate of miscarriage. Sleep duration was found to have no significant association with any outcomes. In the stratified analyses, the positive associations of good sleep quality with clinical pregnancy and live birth existed only among women younger than 35 years old or who had undergone fresh embryo transfer. CONCLUSION(S): Good sleep quality was positively associated with outcomes in in vitro fertilization embryo transfer (IVF-ET), particularly with clinical pregnancy and live birth. Poor sleep quality may be a risk factor for adverse IVF-ET outcomes for women <35 years old. Treating sleep disorders and providing sleep behavior guidance to patients receiving IVF-ET may improve pregnancy outcomes.

Decoupled Asian monsoon intensity and precipitation during glacial-interglacial transitions on the Chinese Loess Plateau.

The discrepancies among the variations in global ice volume, cave stalagmite δ18O and rainfall reconstructed by cosmogenic 10Be tremendously restrain our understanding of the evolution of the East Asian summer monsoon (EASM). Here, we present a 430-ka EASM mean annual precipitation record on the Chinese Loess Plateau obtained using branched glycerol dialkyl glycerol tetraethers based on a deep learning neural network; this rainfall record corresponds well with cave-derived δ18O data from southern China but differs from precipitation reconstructed by 10Be. Both branched tetraether membrane lipids and cave δ18O may be affected by soil moisture and atmospheric temperature when glacial and interglacial conditions alternated and were thus decoupled from atmospheric precipitation; instead, they represent variations in the intensity of the EASM. Furthermore, we demonstrate that the brGDGT-DLNN method can significantly extend the temporal scale record of the EASM and is not restricted by geographic location compared with stalagmite records.

[Active ingredients and in vitro anti-inflammatory effects of Polygoni Cuspidati Rhizoma et Radix decoction pieces by integrated processing and traditional processing: a comparative analysis].

The present study explored the differences in active ingredients and in vitro anti-inflammatory effects of the decoction pieces by integrated processing(IPDP) and traditional processing(TPDP) of Polygoni Cuspidati Rhizoma et Radix(PCRER).The content of polydatin, resveratrol, emodin-8-O-ß-D-glucoside, emodin, and physcion in IPDP and TPDP was determined by high-performance liquid chromatography(HPLC).The inflammation model was induced by lipopolysaccharide(LPS) in RAW264.7 cells.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in 60% ethanol extracts of IPDP and TPDP of different concentrations(5 and 10 µg·mL~(-1)) were determined by PCR.The results showed that the content of polydatin and emodin-8-O-ß-D-glucoside in IPDP was significantly higher than that in TPDP, while the content of resveratrol, emodin, and physcion was higher in TPDP.The anti-inflammatory results showed that ethanol extracts of IPDP of different concentrations(5 and 10 µg·mL~(-1)) significantly inhibited the increase in the mRNA levels of IL-1ß and TNF-α induced by LPS, whereas TPDP only had a significant inhibitory effect on IL-1ß.This study preliminarily showed that the total content of five active ingredients in IPDP was higher than that in TPDP, and IPDP was superior to TPDP in anti-inflammatory activity in vitro, which provided an experimental basis for the production and application of IPDP.

Thada Is Dispensable for Female Fertility in Mice.

Genome-wide association studies (GWAS) have identified THADA as one of the susceptibility genes for polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs) in the THADA gene showed significant over-transmission in PCOS and strong correlations with testosterone level. However, there was insufficient evidence to verify the effect of THADA in vivo on female reproductive system. In this study, we investigated the impacts of Thada ablation on ovarian function and reproductive outcomes with knockout (KO) mice. The results showed that the Thada deletion was insufficient to affect ovarian folliculogenesis, steroidogenesis, and female fertility. Additionally, we stressed the mice with high-fat-high-sugar diet (HFHS). In this case, the KO mice still merely had a negligible impact on ovarian function. These findings indicated that Thada deficiency was dispensable for female fertility in mice, which enriched our knowledge about in vivo functions of PCOS susceptibility genes.

Enhancing single-cell hyaluronic acid biosynthesis by microbial morphology engineering.

Microbial morphology engineering is a novel approach for cell factory to improve the titer of target product in bio-manufacture. Hyaluronic acid (HA), a valuable glycosaminoglycan polymerized by HA synthase (HAS), a membrane protein, is particularly selected as the model product to improve its single-cell HA-producing capacity via morphology engineering. DivIVA and FtsZ, the cell-elongation and cell division related protein, respectively, were both down/up dual regulated in C. glutamicum via weak promoter substitution or plasmid overexpression. Different from the natural short-rod shape, varied morphologies of engineered cells, i.e. small-ellipsoid-like (DivIVA-reduced), bulb-like (DivIVA-enhanced), long-rod (FtsZ-reduced) and dumbbell-like (FtsZ-enhanced), were observed. Applying these morphology-changed cells as hosts for HA production, the reduced expression of both DivIVA and FtsZ seriously inhibited normal cell growth; meanwhile, overexpression of DivIVA didn't show morphology changes, but overexpression of FtsZ surprisingly change the cell-shape into long and thick rod with remarkably enlarged single-cell surface area (more than 5.2-fold-increase). And finally, the single-cell HA-producing capacity of the FtsZ-overexpressed C. glutamicum was immensely improved by 13.5-folds. Flow cytometry analyses verified that the single-cell HAS amount on membrane was enhanced by 2.1 folds. This work is pretty valuable for high titer synthesis of diverse metabolic products with microbial cell factory.

Long non-coding RNA XIST promotes malignant behavior of epithelial ovarian cancer.

PURPOSE: This study aims to investigate the functional role of long non-coding RNA XIST in epithelial ovarian cancer (EOC). METHODS: Detection of XIST expression levels in EOC tissues and cell lines was done using qRT-PCR. The relationship between XIST expression and clinicopathological features of EOC patients was compared and analyzed. The cumulative survival rates were calculated using Kaplan-Meier. A Cox hazard model was used to identify risk factors for survival. Lastly, the effects of XIST on EOC cell were assessed in vitro. RESULTS: XIST was up-regulated in EOC tissues and cell lines. The expression of XIST was closely related to the tumor grade, distant metastasis, and FIGO stage in the EOC patients. The Cox regression analysis showed that high XIST expression was an independent predictor of prognosis in patients with EOC. In in vitro experiments, reducing XIST expression significantly suppressed cell proliferation, migration and invasion in EOC cells. CONCLUSION: XIST highly expressed in the EOC and plays a role in tumor promotion, which may be a potential target for the treatment of EOC.