Combined analysis of the effects of hypoxia and oxidative stress on DNA methylation and the transcriptome in HTR-8/SVneo trophoblast cells.

The alterations in DNA methylation and transcriptome in trophoblast cells under conditions of low oxygen and oxidative stress have major implications for pregnancy-related disorders. However, the exact mechanism is still not fully understood. In this study, we established models of hypoxia (H group) and oxidative stress (HR group) using HTR-8/SVneo trophoblast cells and performed combined analysis of genome-wide DNA methylation changes using reduced representation bisulphite sequencing and transcriptome expression changes using RNA sequencing. Our findings revealed that the H group exhibited a higher number of differentially methylated genes and differentially expressed genes than the HR group. In the H group, only 0.90% of all differentially expressed genes displayed simultaneous changes in DNA methylation and transcriptome expression. After the threshold was expanded, this number increased to 6.29% in the HR group. Notably, both the H group and HR group exhibited concurrent alterations in DNA methylation and transcriptome expression within Axon guidance and MAPK signalling pathway. Among the top 25 differentially methylated KEGG pathways in the promoter region, 11 pathways were commonly enriched in H group and HR group, accounting for 44.00%. Among the top 25 KEGG pathways in transcriptome with significant differences between the H group and HR group, 10 pathways were consistent, accounting for 40.00%. By integrating our previous data on DNA methylation from preeclamptic placental tissues, we identified that the ANKRD37 and PFKFB3 genes may contribute to the pathogenesis of preeclampsia through DNA methylation-mediated transcriptome expression under hypoxic conditions.

All-in-One Zinc-Doped Prussian Blue Nanozyme for Efficient Capture, Separation, and Detection of Copper Ion (Cu2+ ) in Complicated Matrixes.

Copper is a vital micronutrient for lives and an important ingredient for bactericides and fungicides. Given its indispensable biological and agricultural roles, there is an urgent need to develop simple, affordable, and reliable methods for detecting copper in complicated matrixes, particularly in underdeveloped regions where costly standardized instruments and sample dilution procedures hinder progress. The findings that zinc-doped Prussian blue nanoparticle (ZnPB NP) exhibits exceptional efficiency in capturing and isolating copper ions, and accelerates the generation of dissolved oxygen in a solution of H2 O2 with remarkable sensitivity and selectivity, the signal of which displays a positive correlation with the copper level due to the copper-enhanced catalase-like activity of ZnPB NP, are presented. Consequently, the ZnPB NP serves as an all-in-one sensor for copper ion. The credibility of the method for copper assays in human urine and farmland soil is shown by comparing it to the standard instrumentation, yielding a coefficient of correlation (R2 = 0.9890), but the cost is dramatically reduced. This ZnPB nanozyme represents a first-generation probe for copper ion in complicated matrixes, laying the groundwork for the future development of a practical copper sensor that can be applied in resource-constrained environments.

Circular RNA eukaryotic translation initiation factor 6 facilitates TPC-1 cell proliferation and invasion through the microRNA-138-5p/lipase H axis.

Both circular RNA eukaryotic translation initiation factor 6 (circEIF6) and microRNA (miR)-138-5p participate in thyroid cancer (TC) progression. Nevertheless, the relationship between them remains under-explored. Hence, this research ascertained the mechanism of circEIF6 in TC via miR-138-5p. After TC tissues and cells were harvested, circEIF6, miR-138-5p, and lipase H (LIPH) levels were assessed. The binding relationships among circEIF6, miR-138-5p, and LIPH were analyzed. The impacts of circEIF6, miR-138-5p, and LIPH on the invasive and proliferative abilities of TPC-1 cells were examined by Transwell and EdU assays. Tumor xenograft in nude mice was established for in vivo validation of the impact of circEIF6. CircEIF6 expression was high in TC cells and tissues. Additionally, miR-138-5p was poor and LIPH level was high in TC tissues. Mechanistically, circEIF6 competitively bound to miR-138-5p to elevate LIPH via a competitive endogenous RNA mechanism. Silencing of circEIF6 reduced TPC-1 cell proliferative and invasive properties, which was annulled by further inhibiting miR-138-5p or overexpressing LIPH. Likewise, circEIF6 silencing repressed the growth of transplanted tumors, augmented miR-138-5p expression, and diminished LIPH expression in nude mice. Conclusively, circEIF6 silencing reduced LIPH level by competitive binding to miR-138-5p, thus subduing the proliferation and invasion of TPC-1 cells.

Ubiquitin ligase MARCH8 promotes the malignant progression of hepatocellular carcinoma through PTEN ubiquitination and degradation.

Membrane-associated ring-CH-type finger 8 (MARCH8) belongs to the MARCH family of membrane-bound E3 ubiquitin ligases. The N-terminus of MARCH family members contains the C4HC3 RING-finger domain, which can bind to E2 ubiquitin-conjugating enzymes, ubiquitinate substrate proteins, and thereby promote protein degradation through the proteasome pathway. The aim of this study was to determine the role of MARCH8 in hepatocellular carcinoma (HCC). We first analyzed the clinical relevance of MARCH8 based on The Cancer Genome Atlas database. Immunohistochemical staining was used to detect MARCH8 expression in human HCC samples. Migration and invasion assays were conducted in vitro. Cell apoptosis and cell cycle distribution were analyzed by flow cytometry. The expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-related markers was evaluated in HCC cells through Western blot analysis. MARCH8 was highly expressed in human HCC tissues, and its high expression was inversely correlated with patients' survival. Disrupting MARCH8 expression significantly inhibited the proliferation, migration, and cell cycle progression of HCC cells, while also promoting their apoptosis. In contrast, the overexpression of MARCH8 significantly enhanced cell proliferation. Mechanistically, our results showed that MARCH8 interacted with PTEN and suppressed the protein stability of PTEN by enhancing its ubiquitination level via the proteasome. MARCH8 also activated AKT in HCC cells and tumors. In vivo, overexpression of MARCH8 could promote the growth of hepatic tumors through the AKT pathway. MARCH8 may promote the malignant progression of HCC by promoting the ubiquitination of PTEN, thereby relieving the inhibitory effect of PTEN on the malignant phenotype of HCC cells.

The Inflammatory Factors Associated with Disease Severity to Predict COVID-19 Progression.

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. Exploring the immune-inflammatory characteristics of COVID-19 patients is essential to reveal pathogenesis and predict progression. In this study, COVID-19 patients showed decreased CD3+, CD4+, and CD8+ T cells but increased neutrophils in circulation, exhibiting upregulated neutrophil-to-lymphocyte and neutrophil-to-CD8+ T cell ratio. IL-6, TNF-α, IL-1ß, IL-18, IL-12/IL-23p40, IL-10, Tim-3, IL-8, neutrophil extracellular trap-related proteinase 3, and S100A8/A9 were elevated, whereas IFN-γ and C-type lectin domain family 9 member A (clec9A) were decreased in COVID-19 patients compared with healthy controls. When compared with influenza patients, the expressions of TNF-α, IL-18, IL-12/IL-23p40, IL-8, S100A8/A9 and Tim-3 were significantly increased in critical COVID-19 patients, and carcinoembryonic Ag, IL-8, and S100A8/A9 could serve as clinically available hematologic indexes for identifying COVID-19 from influenza. Moreover, IL-6, IL-8, IL-1ß, TNF-α, proteinase 3, and S100A8/A9 were increased in bronchoalveolar lavage fluid of severe/critical patients compared with moderate patients, despite decreased CD4+ T cells, CD8+ T cells, B cells, and NK cells. Interestingly, bronchoalveolar IL-6, carcinoembryonic Ag, IL-8, S100A8/A9, and proteinase 3 were found to be predictive of COVID-19 severity and may serve as potential biomarkers for predicting COVID-19 progression and potential targets in therapeutic intervention of COVID-19.

LncRNA HCG18 Promotes Osteosarcoma Cells Proliferation, Migration, and Invasion in by Regulating miR-34a/RUNX2 Pathway.

Osteosarcoma (OS) is a type of tumor with high malignant behaviors. Increasing investigates have confirmed that long non-coding RNA HLA complex group 18 (lncRNA HCG18) acted as a tumor-promoting factor in multiple tumors. Nevertheless, the underlying mechanism of HCG18 on OS remains largely unclear. HCG18, miR-34a, and runt-related transcription factor 2 (RUNX2) expressions were detected by quantitative real-time PCR (RT-qPCR) or western blotting assays, respectively. The underlying tumorigenic phenotypes were detected by MTT, wound healing, transwell invasion, western blotting assays. Molecular interactions were verified by dual-luciferase report assay. HCG18 and RUNX2 were notably enhanced, whereas miR-34a was decreased in OS tumor tissues and cell lines. Functional experiments uncovered that HCG18 silencing significantly inhibited the capabilities of proliferation, migration, and invasion, while overexpression of HCG18 play the opposite roles. Furthermore, HCG18 directly bound to miR-34a, and miR-34a was confirm to be a negative regulator of RUNX2. Interestingly, the anti-tumor effects of HCG18 silencing were attenuated by miR-34a inhibitor and RUNX2 overexpression. Taken together, the present study suggested that HCG18 promoted the malignant biological behaviors of OS through regulating the miR-34a/RUNX2 pathway, implying HCG18 might serve as a new target for OS treatment.

Early Drain Removal is Safe in Patients With Low or Intermediate Risk of Pancreatic Fistula After Pancreaticoduodenectomy: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: This multicenter randomized controlled trial was designed to test the hypothesis that early drain removal (EDR) could decrease the incidence of grade 2 to 4 complications for patients undoing pancreaticoduodenectomy (PD) with low or intermediate risk of postoperative pancreatic fistula (POPF). BACKGROUND: The safety and effects of EDR on postoperative complications after PD are still controversial. METHODS: A multicenter randomized controlled trial at 6 tertiary referral hospitals was carried out (NCT03055676). Patients who met the inclusion criteria, including drain amylase level less than 5000 U/L on postoperative day (POD) 1 and POD 3, and drain output less than 300 mL per day within 3 days after surgery, were enrolled. Patients were then randomized to the EDR group or the routine drain removal (RDR) group. In the EDR group, all drainage tubes were removed on POD3. In the RDR group, drainage tubes were removed on POD 5 or beyond. Primary outcome was the incidence of Clavien-Dindo grade 2 to 4 complications. Secondary outcomes were comprehensive complication index, grade B/C POPF, total medical expenses and postoperative in-hospital stay etc, within 90 days after surgery. RESULTS: A total of 692 patients were screened, and 312 patients were eligible for randomization. Baseline characteristics were well balanced between the 2 groups and 96.8% of these 312 patients had low or intermediate risk of POPF, according to the 10-point fistula risk score. A total of 20.5% of the patients in the EDR group suffered at least 1 grade 2 to 4 complication, versus 26.3% in the RDR group (P = 0.229). Multi-variate analysis showed older age (>65 years old) and blood transfusion were independent risk factors for grade 2 to 4 complications. The rate of grade B/C POPF was low in either group (3.8% vs 6.4%, P = 0.305). The comprehensive complication index of the 2 groups was also comparable (20.9 vs 20.9, P = 0.253). Total medical expenses were not significantly different. Postoperative in-hospital stay was clinically similar (15 days vs 16 days, P = 0.010). CONCLUSIONS: Nearly half of the patients undergoing PD met the inclusion criteria, predicting low incidence of grade B/C POPF and major complications. EDR was safe in these patients but did not significantly decrease major complications.

LncRNA FGD5-AS1 enhances the proliferation and stemness of hepatocellular carcinoma cells through targeting miR-223 and regulating the expression of ECT2 and FAT1.

AIM: Hepatocellular carcinoma (HCC) is common and causes many deaths worldwide. The aim of this study is to explore the mechanism by which long non-coding RNA FGD5-AS1 regulates HCC cell proliferation and stemness. METHODS: Tumor and normal adjacent tissues were harvested from HCC patients. Real-time quantitative reverse transcription-PCR was applied to examine the expression of FGD5-AS1, miR-223, Epithelial cell transforming sequence 2 (ECT2) and FAT1. The protein levels of ECT2, FAT1, proliferating cell nuclear antigen (PCNA), OCT4, CD133 and CD90 were analyzed by western blot. The localization of FGD5-AS1 was examined by Fluorescence in situ hybridization. Cell proliferation was analyzed with CCK-8 and colony formation assays. Spheroid formation was used for analyzing cell stemness. Gene interaction was examined by RNA immunoprecipitation and luciferase activity assays. A subcutaneous xenograft mouse model was established to analyze HCC growth and stemness in vivo. Immunohistochemistry staining was used to analyze the expression PCNA and OCT4 in subcutaneous tumors. RESULTS: FGD5-AS1 was upregulated in HCC and its high expression indicated poor prognosis of patients. High expression of FGD5-AS1 enhanced HCC cell proliferation and stemness. Knockdown of FGD5-AS1 restrained tumor growth and stemness in mice. FGD5-AS1 directly sponged miR-223 and promoted the expression of ECT2 and FAT1 in HCC. Both knockdown of miR-223 and overexpression of ECT2 and FAT1 reversed FGD5-AS1 silencing-mediated suppression of HCC cell proliferation and stemness. CONCLUSION: FGD5-AS1 directly sponged miR-223 and promoted the expression of ECT2 and FAT1 in HCC, thus enhancing HCC cell proliferation and stemness. Our study identifies potential prognostic biomarkers and therapeutic targets for HCC.

Lewis acid-catalyzed [3 + 2] annulations of oxindole based spirocyclic donor-acceptor cyclopropanes with ynamides.

[3 + 2] annulations of oxindole based spirocyclic donor-acceptor cyclopropanes and ynamides catalyzed by copper triflate have been developed for the synthesis of biologically important spirocyclopenteneoxindoles. These reactions tolerated a wide scope of substrates and provided the desired products in good to high yields (up to 90%) with up to >40 : 1 diastereoselectivities under mild conditions.

Desymmetrization of 1-Symmetrical Donor-Acceptor (D-A) Cyclopropanes via Reactions with 1,3-Cyclodiones.

A new type of 1-unsymmetrical D-A cyclopropanes containing a cyclic enone motif was obtained by the desymmetrization of 1-symmetrical D-A cyclopropanes via first the Lewis acid-catalyzed O-nucleophilic ring-opening reaction with 1,3-cyclodiones followed by an organobase-promoted unexpected multistep intramolecular transformation.

Ring Opening of Donor-Acceptor Cyclopropanes with Acyclic 1,3-Diketones for the Synthesis of 1,6-Dicarbonyl Compounds.

1,6-Dicarbonyl compounds, representing the formal addition products of the α-position of acetophenone derivatives to donor-acceptor cyclopropanes, were synthesized in two steps via first ring opening of donor-acceptor cyclopropanes with acyclic 1,3-diketones followed by DBU catalyzed retro-Claisen-type C-C bond cleavage reactions. In the first step, acyclic 1,3-diketones selectively worked as C-nucleophiles to add to donor-acceptor cyclopropanes. In the second step, the alkyl ketone part of the ring-opening products resulting from unsymmetrical 1,3-diketones was selectively cleaved in the presence of DBU in methanol.

Ring-opening reactions of donor-acceptor cyclopropanes with cyclic ketals and thiol ketals.

1,3-Cyclohexandione derived cyclic ketals and thiol ketals were used as O- and S-nucleophiles, respectively, for the ring opening of donor-acceptor cyclopropanes catalyzed by Cu(OTf)2 and a series of functionalized alkylene glycol diethers and dithiol diethers were obtained in good to high yields under mild conditions.

Glucocorticoid exposure in early placentation induces preeclampsia in rats via interfering trophoblast development.

In pregnancy, placenta can be exposed to glucocorticoids (GCs) via several ways, which may disturb placentation and adversely affect pregnancy. Preeclampsia (PE) is thought to be attributed, in part, to impaired trophoblast development. The purpose of the present study was to confirm that GC exposure in early placentation could lead to PE in rats, with the mechanisms involving dysregulated trophoblast development. In the study, pregnant rats were administered with 2.5mg/kg Dex subcutaneously once per day from gestational day 7 to 13. Maternal systolic blood pressure and urinary albumin were increased, while both fetus and placenta were restricted after GC exposure relative to the control group. GC exposure also contributed to placental abnormalities and renal impairment. Moreover, placental oxidative damage was increased along with placental hypoxia-inducible factor 1-alpha (HIF1A) overexpression after GC treatment. Mechanically, GC induced PE in rat partially through inhibiting trophoblast proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), which involved phospho-extracellular signal regulated kinase (p-ERK) downregulation. Furthermore, GC receptor was required for the inhibition of GC on trophoblast proliferation, migration, invasion and EMT in vitro. These findings suggest that GC exposure in early placentation could contribute to PE in pregnant rats, with the mechanisms involving inhibition of trophoblast proliferation, migration, invasion and EMT by GC.

[Clinical application of precise liver surgery techniques for donor hepatectomy in living donor liver transplantation].

OBJECTIVE: To evaluate the effect of techniques of precise liver surgery for donor hepatectomy in living donor liver transplantation. METHODS: Eighty-nine donors aged from 19 to 57 years were performed by the same surgical team from June 2006 to December 2013 in Chinese People's Liberation Army General Hospital.Individualized surgical program were developed according to preoperative imaging examination and hepatic functional reserve examination. The evaluation included liver function, liver volume, vascular anatomy and bile duct anatomy. According to the results after the operation, preoperative evaluation accuracy, postoperative donor liver function and postoperative complications were analyzed. ANOVA analysis was used to compare the difference of graft volume by two-dimensional, three-dimensional calculation method and actual postoperative graft weight. Pearson correlation test and linear regression analysis were used to verify the correlation between the estimated graft volume each method and actual graft postoperative weight. RESULTS: All the 89 cases operation protocol as following, there were 5 cases with left lateral lobe graft, 10 cases with left lobe liver graft, 74 cases with right lobe graft. There were 59 cases with middle hepatic vein (MHV) harvested, and 30 cases without MHV. The mean graft volume by two-dimensional, three-dimensional calculation method and actual postoperative graft weight were (656.2±134.1) ml, (631.7±143.2) ml and (614.5±137.7) ml respectively. ANOVA analysis results showed that there were no statistically significant difference in the three methods (P>0.05). Compared to the actual postoperative graft weight, the average error rate of the two methods were 7.9% and 5.3% respectively. Pearson correlation test showed the graft volume calculated by two-dimensional and three-dimensional methods had a significantly positive correlation with actual graft weight (r=0.821, 0.890, P<0.01) and linear regression analyze showed the R2 were 0.674 and 0.792, respectively. The accuracy rate of preoperative evaluation about portal vein, hepatic vein, hepatic artery and bile duct were 100%, 100%, 97.8% and 95.5%, respectively. The preoperative plan and postoperative practical scheme coincidence rate was 95.5%. Overall donor complication rate was 7.4%. All donors were alive. Sixteen donors received right lobe hepatectomy with gallbladder preserved had a good liver function and gallbladder function. CONCLUSION: Through the precise preoperative evaluation, surgical planning, fine operation and excellent postoperative management, precise liver surgery technique can ensure the safety of donor in living donor liver transplantation.

Glucocorticoids sensitize rat placental inflammatory responses via inhibiting lipoxin A4 biosynthesis.

Inflammation dysregulation in placenta is implicated in the pathogenesis of numerous pregnancy complications. Glucocorticoids (GCs), universally considered anti-inflammatory, can also exert proinflammatory actions under some conditions, whereas whether and how GCs promote placental inflammation have not been intensively investigated. In this paper we report the opposing regulation of rat placental inflammation by synthetic GC dexamethasone (Dex). When Dex was subcutaneously injected 1 h after we administered an intraperitoneal lipopolysaccharide (LPS) challenge, neutrophil infiltration and proinflammatory Il1b, Il6, and Tnfa expression in rat placenta were significantly reduced. In contrast, Dex pretreatment for 24 h potentiated rat placental proinflammatory response to LPS and delayed inflammation resolution, which involved MAPKs and NF-kappaB activation. Mechanically, Dex pretreatment promoted 5-lipoxygenase (ALOX5) activation and increased leukotriene B4 production, whereas it inhibited the anti-inflammatory and proresolving lipid mediator lipoxin A4 (LXA4) biosynthesis in rat placenta via downregulating ALOX15 and ALOX15B expression. Moreover, LXA4 supplementation dampened Dex-potentiated placental inflammation and suppressed Dex-mediated ALOX5 activation in vivo and in vitro. Taken together, these findings suggest that GCs exposure could promote placental inflammation initiation and delay resolution via disrupting LXA4 biosynthesis.

[Liver transplantation for irresectable hilar cholangiocarcinoma].

OBJECTIVE: To evaluate the outcome of patients with irresectable hilar cholangiocarcinoma undergoing orthotopic liver transplantation (OLT) and to identify the prognostic factors that could influence survival. METHODS: The data of 18 patients who underwent OLT for irresectable hilar cholangiocarcinoma between June 2003 and October 2010 were analyzed retrospectively. There were 12 male and 6 female cases with median of 52 years(range from 34 to 65 years).Fifteen patients underwent modified piggyback liver transplantation, 2 patients underwent classical orthotopic liver transplantation and 1 patient underwent living donor liver transplantation. Data were evaluated regarding tumor size, pathologic stage, overall survival, recurrence rates and prognostic factors. RESULTS: OLT with lymphadenectomy was received by 18 patients with hilar cholangiocarcinoma. Median time until tumor recurrence was 20.5 months(range from 6.0 to 33.0 months). Seventeen patients died during follow-up.Of these, 14 patients died from recurrent or metastatic diseases, 2 patients died from multiple organ dysfunction syndrome during peri-operative period, and one patient died from other cause. The median survival time was 29.5 months(range from 3.0 to 84.0 months). The overall survival rate and recurrence-free survival rate at 1, 3, and 5 year were 16/18, 8/18, 1/18 and 13/18, 2/18, 1/18, respectively.Lymph node metastases had a statistically significant negative impact on overall survival. The 1, 3, and 5 year survival rates were 6/7, 1/7,0 and 10/11, 7/11, 1/11 (P < 0.05) in lymph node-positive and lymph node-negative patients. CONCLUSIONS: Acceptable survival rates can be achieved by OLT for irresectable hilar cholangiocarcinoma without lymph node metastases.Strict patient selection plus multimodal chemoradiation therapy prior to OLT are recommend for patients with lymph node metastases.

Effects of reverse osmosis membrane replacement of pure water system on clinical chemistry and immunoassay in clinical laboratory.

Introduction: Reverse osmosis (RO) membrane, key component of water-purifying equipment, is often stored in protection fluid containing substances such as glycerol, which may contaminate the water at replacement. This study aims to explore the effects of RO membrane replacement on clinical chemistry and immunoassay, particularly triglyceride (TG), providing reference for managing test interference caused by RO membrane replacement. Materials and methods: The RO membrane of water-purifying equipment A, which provided water to C16000 biochemistry analyzer (Abbott Laboratories, Abbott Park, USA) and E801 electrochemiluminescence analyzer (Roche, Basel, Switzerland), was replaced. Water resistivity was recorded, and quality control (QC) tests were performed on C16000 and E801. Moreover, TG was measured in 29 of selected serum samples on C16000 at 0.5h and 10.5h after RO membrane replacement and on reference biochemistry analyzer BS2000M (Mindray Biomedical Electronics Co., Shenzhen, China), which was connected to water-purifying equipment B without RO membrane replacement. Finally, blank, calibrator 1 and calibrator 2 of TG reagent were measured on C16000 before and at 0.5h, 2.5h and 10.5h after RO membrane replacement. All statistical analyses of data were done using GraphPad Prism (GraphPad Software Inc., San Diego, USA), and a value of P < 0.05 was considered statistically significant. Results: After RO membrane replacement, all QC results of clinical chemistry and immune tests passed except TG that showed positive bias of 536% and 371% at two levels, respectively. Moreover, TG results of the same serum samples were significantly higher at 0.5h than 10.5h after RO membrane replacement. Meanwhile, there was worse agreement and correlation of TG results between C16000 and BS2000M at 0.5h than 10.5h after replacement. Furthermore, the absorbance of TG blank, calibrator 1 and calibrator 2 was significantly higher at 0.5h and 2.5h after replacement than before replacement, and the absorbance gradually returned to normal value at 10.5h after replacement. Conclusions: Replacement of RO membrane could cause significant interference to TG test while have no effects on other laboratory tests performed in the study, which may be due to glycerol contamination. Our data provides important reference for management of test interference caused by RO membrane replacement. Clinical laboratory should observe the effects of RO membrane replacement on laboratory tests through both water quality monitoring and QC detection.

Association of air temperature exposure during pregnancy with risk of preeclampsia in Guangzhou, China.

Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12-1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10-1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy.

Toward Reliable Synthesis of Superconducting Infinite Layer Nickelate Thin Films by Topochemical Reduction.

Infinite layer (IL) nickelates provide a new route beyond copper oxides to address outstanding questions in the field of unconventional superconductivity. However, their synthesis poses considerable challenges, largely hindering experimental research on this new class of oxide superconductors. That synthesis is achieved in a two-step process that yields the most thermodynamically stable perovskite phase first, then the IL phase by topotactic reduction, the quality of the starting phase playing a crucial role. Here, a reliable synthesis of superconducting IL  nickelate films is reported after successive topochemical reductions of a parent perovskite phase with nearly optimal stoichiometry. Careful analysis of the transport properties of the incompletely reduced films reveals an improvement in the strange metal behavior of their normal state resistivity over subsequent topochemical reductions, offering insight into the reduction process.

Asymmetric ring-opening reactions of donor-acceptor cyclopropanes with 1,3-cyclodiones.

Asymmetric ring-opening reactions of donor-acceptor cyclopropanes with 1,3-cyclodiones have been established for the synthesis of enantioenriched γ-hydroxybutyric acid derivatives in the presence of Cu(ii)/trisoxazoline catalyst. These reactions offered the desired products in 70% to 93% yields with 79% to 99% enantiomeric excesses.