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This study aimed to clarify the role of Orosomucoid 1 (ORM1) in the development and therapy resistance in hepatocellular carcinoma (HCC). The mRNA expression level of ORM1 was analyzed via integrative analysis of Gene Express Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The protein expression level of ORM1 in our cohort was determined using immunohistochemistry. Correlation analysis was used to investigate the relationship between ORM1 expression and clinical parameters. The Cell Counting Kit-8 assay was used to clarify the role of ORM1 in HCC malignant behaviors, including cell growth and sorafenib sensitivity, in vitro. The results indicated that ORM1 was significantly downregulated in the hepatic cancer cells compared to that in the non-cancerous cells. However, it was upregulated in microvascular invasion samples, especially in the cancer embolus compared to that in the surrounding tumor cells. Though Kaplan-Meier analysis did not show an association of ORM1 expression with the overall survival rates of HCC patients, univariate analysis indicated that ORM1 expression was highly correlated with tumor grade and stage. An in vitro assay also revealed that downregulation of ORM1 led to the suppression of tumor growth and enhancement of sorafenib sensitivity without epithelial-to-mesenchymal transition (EMT) alteration, which was consistent with our bioinformatic analysis. Hence, ORM1 played a key role in HCC tumorigenesis and may serve as a potential target for the development of therapeutics against HCC in the future.

Glutathione S-transferases (GSTs), a multifunctional protein family, are involved in insecticide resistance. However, a systematic analysis of GSTs in Anopheles sinensis, an important vector for malaria transmission, is lacking. In this study, we investigated the diversity and characteristics of GST genes, and analyzed their expression patterns and functions associated with insecticide resistance in this species.We identified 32 putative cytosolic and three putative microsomal GST genes in the An. sinensis genome. Transcriptome analysis showed that GSTs were highly expressed in larvae, and mainly expressed in the antennae, midgut and Malpighian tubules of adults. In addition, we found that GSTd2 and GSTe2 were significantly upregulated in four An. sinensis pyrethroid-resistant field populations. Furthermore, silencing of GSTd2 and GSTe2 significantly increased the susceptibility of An. sinensis to deltamethrin, and recombinant GSTd2 and GSTe2 exhibited high enzymatic activity in the metabolism of 1-chloro-2,4-dinitrobenzene and dichlorodiphenyltrichloroethane (DDT).These results showed that GSTs are involved in the development of insecticide resistance in An. sinensis through transcriptional overexpression and enzymatic metabolization, facilitating our understanding of insecticide resistance in insects. © 2022 Society of Chemical Industry.

BackgroundAntiretroviral therapy (ART) initiation before pregnancy was reported to have an increased risk of adverse pregnancy outcomes (APOs) than ART initiation during pregnancy. However, the risks of APOs associated with different ART regimens initiated before or during pregnancy remain unknown.MethodsPregnant women living with HIV (PWLHIV) from Hubei Province, China, were retrospectively enrolled between January 1, 2004, and December 31, 2021. The trends of ART initiation time and application of different ART regimens were evaluated over time, separately. Using no ART exposure before and during pregnancy as control, the risks of APOs associated with protease inhibitor (PI) based regimens and non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens initiated before pregnancy were analyzed; and the risks of APOs associated with PI-based regimens, NNRTIs based regimens and zidovudine (AZT) monotherapy initiated during pregnancy were analyzed. APOs, including low birthweight (LBW), stillbirth, preterm birth (PTB) and early miscarriage, were reviewed.ResultsAmong 781 PWLHIV including 1,010 pregnancies, 522 pregnancies (51.7%) were exposed to ART before or during pregnancy. Of them, the proportion of ART initiation before pregnancy per year increased from around 20% in the early period to more than 60% after 2019. Efavirenz (EFV)-nucleoside reverse transcriptase inhibitors (NRTIs) (32.2%), LPV/r-NRTIs (31.2%), and nevirapine (NVP)-NRTIs (27.4%) were the most commonly used regimens, and the proportion of LPV/r-NRTIs used per year has increased to around 50.0% in recent years. LPV/r-NRTIs was associated with higher risks of LBW whether initiated before pregnancy [adjusted OR (aOR) = 2.59, 95%CI 1.04–6.45, p = 0.041] or during pregnancy (aOR = 2.19, 95%CI 1.03–4.67, p = 0.041), compared with no exposure to ART before and during pregnancy. However, no matter initiated before or during pregnancy, LPV/r-NRTIs had no significantly increased risks of stillbirth, PTB and early miscarriage, and EFV /NVP-NRTIs and AZT monotherapy had no significantly increased risks of LBW, stillbirth, PTB and early miscarriage when compared with no exposure to ART before and during pregnancy.ConclusionOur data suggests that LPV/r-NRTIs has been widely used among PWLHIV in recent years. However, the potential risk of LBW should be continuously monitored among PWLHIV whether LPV/r-NRTIs is initiated before or during pregnancy.

After the emergence of COVID-19 in 2019, it has now become a pandemic. COVID-19 has brought painful disasters to people all over the world. It not only threatens lives and health but also induces economic crises. At present, promising methods to eradicate COVID-19 mainly include drugs and vaccines. Enzyme inhibitors have always been a reliable strategy for the treatment of related diseases. Scientists worldwide have worked together to study COVID-19, obtained the structure of key SARS-CoV-2 associated enzymes, and reported the research of inhibitors of these enzymes. This article summarizes COVID-19-related enzyme inhibitors' recent development, mainly including 3CLpro, PLpro, TMPRSS2, and RdRp inhibitors, hoping to provide valuable weapons in the ensuing battle against COVID-19.

Objective We aimed to analyze the angioarchitecture characters and changes after combined bypass surgery (CBS) in pediatric moyamoya disease (MMD). Methods We retrospectively analyzed our database of consecutive patients with moyamoya angiopathy who received treatment. Only pediatric MMD cases aged between 3 and 19 years with pre- and post-operative imaging examinations including digital subtraction angiography and magnetic resonance imaging were enrolled in this study. The main trunk vessels' stenosis and the collaterals from the superficial-meningeal system and deep parenchymal system were evaluated before and after CBS. Results During short-term follow-up period after the unilateral CBS, the stenosis of main trunk vessels both in operative (5.7 ± 2.1 vs. 6.8 ± 1.8; p Conclusions The successful CBS could decrease the collaterals from the PCA-MCA leptomeningeal system and the subependymal compensations in deep parenchyma significantly, while the main trunk stenosis would aggravate rapidly both in operative and non-operative hemisphere in short-term follow-up after unilateral CBS. Therefore, strict and regular follow-ups for the changes of vascular architecture and prompt surgical intervention for the contralateral side might be of benefit to pediatric MMD.

Reindeer (Rangifer tarandus tarandus) are exposed to the pathogenic parasitic nematode Elaphostrongylus rangiferi during grazing. The severity of disease is dose-dependent. Prophylactic anthelmintic treatment is needed to improve animal health and reindeer herding sustainability. Herds are traditionally only gathered once during the summer, requiring a drug with a persistent effect. In this study we investigated the suitability of long-acting eprinomectin, given as a single subcutaneous injection at 1 mg/kg bodyweight in adult reindeer and calves. Plasma and faeces concentrations were determined using ultra-high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS). Plasma concentrations remained above the presumed effect level of 2 ng/mL for 80 days, demonstrating the drug's potential. Pharmacokinetic parameters were compared to other species using allometric scaling. Calves and adults had slightly different profiles. No viable faecal nematode eggs were detected during treatment. Eprinomectin was measurable in the reindeer faeces up to 100 days, which is of environmental concern.

A metallaphotoredox-catalyzed strategy for the selective and divergent aminocarbonylation of alkynes with amines and 1 atm of CO is reported. This synergistic protocol not only enables the Markovnikov-selective hydroaminocarbonylation of alkynes to afford α,β-unsaturated amides, but also facilitates a sequential four-component hydroaminocarbonylation/radical alkylation in the presence of tertiary and secondary alkyl boronate esters, which allows for straightforward conversion of alkynes into corresponding amides. Preliminary mechanistic studies disclose that a photoinduced oxidative insertion of aniline and CO into nickel followed by a migratory insertion of (carbamoyl)nickel species could be involved.

Background New ischemic cerebral lesions (NICL) are commonly occur after carotid artery stenting (CAS) with an incidence rate ranging from 18-58% and are detected by diffusion-weighted imaging-magnetic resonance imaging (DWI-MRI). Numerous studies have reported that NICL could increase the risk of future cerebrovascular events and cognitive impairment. This systematic review and meta-analysis aimed to identify risk factors for NICL after CAS. Methods Relevant literature reporting risk factors for NICL after CAS were searched. Randomized controlled trials, case-control studies, or cohort studies were included in accordance with the pre-specified eligibility criteria. The risk of bias was assessed using the Cochrane Collaboration criteria and the quality of evidence was assessed with the corresponding scale. Data were analyzed using the RevMan V. 5.3 analysis software. Results The final analyses included a total of 21 studies and 1907 participants, including 764 NICL-positives and 1143 NICL-negatives. Determinants for NICL-positivity were age (mean deviation (MD): 2.60; 95% confidence interval (CI): [1.53-3.68]), symptomatic carotid lesions (odds ratio (OR): 1.77; 95% CI: [1.39-2.25]) and smoking (OR: 0.74; 95% CI: [0.58-0.94]). For symptomatic patients, risk factors for NICL-positive included diabetes mellitus (OR: 1.76; 95% CI: [1.09-2.82]), but smoking (OR: 0.54; 95% CI: [0.31-0.93]) was a protective factor. Risk factors for centers with high NICL incidence were age (MD: 2.05; 95% CI: [0.93-3.17]) and symptomatic carotid lesions (OR: 1.77; 95% CI: [1.29-2.45]). Conclusions Older age and symptomatic carotid lesions are associated with an increased risk of post-CAS NICL whereas smoking is associated with a decreased risk. Risk factors for NICL in symptomatic patients is diabetes mellitus, while those for patients at centers with high incidence are age and symptomatic carotid lesions. Systematic review registration: CRD42019121129

The heptafluoroisopropyl group (CF(CF3 )2 ) is prevalent in pharmaceuticals and agrichemicals. However, heptafluoroisopropoxylated (OCF(CF3 )2 ) compounds remain largely underexplored, presumably due to the lack of efficient access to these compounds. Herein, we disclose the practical and efficient heptafluoroisopropoxylation reactions through the invention of a series of redox-active N-OCF(CF3 )2 reagents. These reagents were readily prepared from the oxidative heptafluoroisopropylation of hydroxylamines with AgCF(CF3 )2 . The substitutions on the nitrogen atom significantly affected the properties and reactivities of N-OCF(CF3 )2 reagents. Accordingly, two types of N-OCF(CF3 )2 reagents including N-OCF(CF3 )2 phthalimide A and N-OCF(CF3 )2 benzotriazolium salt O' were used as OCF(CF3 )2 anion and radical precursors, respectively. This protocol enables the direct heptafluoroisopropoxylation of a range of substrates, delivering the corresponding products in moderate to excellent yields.

A photochemically induced selective and divergent cyanation reaction of alkynes, enabled by phosphorus radicals, is described. With the use of simple triarylphosphine as a co-catalyst, three cyanation reactions, including di-hydrocyanation, anti-Markovnikov hydrocyanation, and domino hydrocyanation/reduction, can be divergently achieved, furnishing a wide array of alkyl dinitriles, alkenyl nitriles, and alkyl nitriles under mild conditions. Terminal and internal alkynes are applicable with high efficiency and excellent selectivity. Synthetic applications for biologically active agents and preliminary experimental and computational mechanistic studies are reported.

Pentafluorosulfanyl chloride (SF5 Cl) is the most prevalent reagent for the incorporation of SF5 group into organic compounds. However, the preparation of SF5 Cl often relies on hazardous reagents and specialized apparatus. Herein, we described a safe and practical synthesis of a bench-stable and easy-to-handle solution of SF5 Cl in n-hexane under gas-reagent-free conditions. The synthetic application of SF5 Cl was demonstrated through the unprecedented reaction with diazo compounds. The chemoselective hydro- and chloropentafluorosulfanylations of α-diazo carbonyl compounds were developed in the presence of K3 PO4 or copper catalyst, respectively. These reactions provide a direct and efficient access to various α-pentafluorosulfanyl carbonyl compounds of high value for potential applications.

Uveal melanoma is the most common primary intraocular tumour in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. (−)-4-O-(4-...

The most dominant arbuscular mycorrhizal (AM) symbiont can be established on roots of most terrestrial plants by beneficial AM fungi. A type of polycationic and aliphatic compounds, polyamines (PAs), are involved in plant physiological activities including stress responses. Interestingly, small amounts of PAs such as putrescine (Put) and spermidine (Spd) were found in AM fungal spores, and they are considered to be a component involved in mycorrhizal development, including mycorrhizal colonization, appressoria formation, spore germination and mycelial growth. Thus, PAs are regulatory factors in plant-AM symbiosis. Inoculation of AM fungi also affects the metabolism of endogenous PAs in host plants, including PAs synthesis and catabolism, thus, regulating various physiological events of the host. As a result, there seems to be a dialogue between PAs and AM fungi. Existing knowledge makes us understand that endogenous or exogenous PAs are an important regulator factor in the growth of AM fungi, as well as a key substance to colonize roots, which further enhances mycorrhizal benefits in plant growth responses and root architecture. The presence of AM symbiosis in roots alters the dynamic balance of endogenous PAs, triggering osmotic adjustment and antioxidant defense systems, maintaining charge balance and acting as a stress signalling molecule, which affects various physiological activities, such as plant growth, nutrient acquisition, stress tolerance and improvement of root architecture. This review mainly elucidated (i) what is the role of fungal endogenous PAs in fungal growth and colonization of roots in host plants? (ii) how AM fungi and PAs interact with each other to alter the growth of fungi and plants and subsequent activities, providing the reference for the future combined use of AM fungi and PAs in agricultural production, although there are still many unknown events in the dialogue.

The transplantation of human mesenchymal stem cells (hMSCs), such as bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs), has shown beneficial effects in protecting transplanted tissues and cells against graft

We report herein the three-component radical addition reaction of SF

BackgroundHemorrhagic fever with renal syndrome (HFRS) is a serious public health problem in China. The geographic distribution has went throughout China, among which Zhejiang Province is an important epidemic area. Since 1963, more than 110,000 cases have been reported.MethodsWe collected the meteorological factors and socioeconomic indicators of Zhejiang Province, and constructed the HFRS ecological niche model of Zhejiang Province based on the algorithm of maximum entropy.ResultsModel AUC from 2009 to 2018, is 0.806–0.901. The high incidence of epidemics in Zhejiang Province is mainly concentrated in the eastern, western and central regions of Zhejiang Province. The contribution of digital elevation model ranged from 2009 to 2018 from 4.22 to 26.0%. The contribution of average temperature ranges from 6.26 to 19.65%, Gross Domestic Product contribution from 7.53 to 21.25%, and average land surface temperature contribution with the highest being 16.73% in 2011. In addition, the average contribution of DMSP/OLS, 20-8 precipitation and 8-20 precipitation were all in the range of 9%. All-day precipitation increases with the increase of rainfall, and the effect curve peaks at 1,250 mm, then decreases rapidly, and a small peak appears again at 1,500 mm. Average temperature response curve shows an inverted v-shape, where the incidence peaks at 17.8°C. The response curve of HFRS for GDP and DMSP/OLS shows a positive correlation.ConclusionThe incidence of HFRS in Zhejiang Province peaked in areas where the average temperature was 17.8°C, which reminds that in the areas where temperature is suitable, personal protection should be taken when going out as to avoid contact with rodents. The impact of GDP and DMSP/OLS on HFRS is positively correlated. Most cities have good medical conditions, but we should consider whether there are under-diagnosed cases in economically underdeveloped areas.

A silver-mediated oxidative difluoromethylation of styrenes and vinyl trifluoroborates with TMSCF2 H is reported for the first time. This method enables direct and facile access to CF2 H-alkenes from abundant alkenes with excellent functional-group compatibility. Moreover, this Ag/TMSCF2 H protocol could further enable a series of radical difluoromethylation reactions of a wide array of substrates, offering a generic and complementary platform for the construction of diversified C-CF2 H bonds.

The increasing pharmaceutical importance of trifluoromethylarenes has stimulated the development of more efficient trifluoromethylation reactions. Tremendous efforts have focused on copper- and palladium-mediated/catalyzed trifluoromethylation of aryl halides. In contrast, no general method exists for the conversion of widely available inert electrophiles, such as phenol derivatives, into the corresponding trifluoromethylated arenes. Reported herein is a practical nickel-mediated trifluoromethylation of phenol derivatives with readily available trimethyl(trifluoromethyl)silane (TMSCF3 ). The strategy relies on PMe3 -promoted oxidative addition and transmetalation, and CCl3 CN-induced reductive elimination. The broad utility of this transformation has been demonstrated through the direct incorporation of trifluoromethyl into aromatic and heteroaromatic systems, including biorelevant compounds.

OBJECTIVE: To provide clinical management guidelines for novel coronavirus (COVID-19) in pregnancy. METHODS: On February 5, 2020, a multidisciplinary teleconference comprising Chinese physicians and researchers was held and medical management strategies of COVID-19 infection in pregnancy were discussed. RESULTS: Ten key recommendations were provided for the management of COVID-19 infections in pregnancy. CONCLUSION: Currently, there is no clear evidence regarding optimal delivery timing, the safety of vaginal delivery, or whether cesarean delivery prevents vertical transmission at the time of delivery; therefore, route of delivery and delivery timing should be individualized based on obstetrical indications and maternal-fetal status.

As an aggressive musculoskeletal malignancy, osteosarcoma (OSa) is popular among young adults and teenagers worldwide. S100 calcium-binding protein A10 (S100A10) functioned as a novel tumor-promoting protein in several human cancers. However, its role in OSa remains obscure. In this study, gene and protein levels were respectively determined by RT-qPCR or Western blotting. OSa cell proliferation, apoptosis, and metastasis were evaluated via CCK-8, colony formation, flow cytometry, and Transwell assays. To assess the glycolysis level, glucose consumption and lactate production were detected. It was found S100A10 was highly expressed in OSa tissues and cell lines. Besides, S100A10 facilitated proliferation and metastasis, and inhibited apoptosis in OSa cells. In addition, S100A10 regulated OSa cell proliferation, metastasis and apoptosis via mediating the glycolysis process. Furthermore, S100A10-mediated AKT/mTOR signaling accelerated glycolysis, thereby promoting malignant behaviors in OSa cells. Taken together, our findings indicated that S100A10 might promote malignant phenotypes of OSa cells by accelerating glycolysis and activating the AKT/mTOR signaling, providing a promising target for OSa treatment.

Background K1 capsular polysaccharide (CPS)-associated Klebsiella pneumoniae is the primary cause of pyogenic liver abscesses (PLA) in Asia. Patients with PLA often have serious complications, ultimately leading to a mortality of ~ 5%. This K1 CPS has been reported as a promising target for development of glycoconjugate vaccines against K. pneumoniae infection. The pyruvylation and O-acetylation modifications on the K1 CPS are essential to the immune response induced by the CPS. To date, however, obtaining the fragments of K1 CPS that contain the pyruvylation and O-acetylation for generating glycoconjugate vaccines still remains a challenge. Methods We analyzed the digested CPS products with NMR spectroscopy and mass spectrometry to reveal a bacteriophage-derived polysaccharide depolymerase specific to K1 CPS. The biochemical and biophysical properties of the enzyme were characterized and its crystal structures containing bound CPS products were determined. We also performed site-directed mutagenesis, enzyme kinetic analysis, phage absorption and infectivity studies, and treatment of the K. pneumoniae-infected mice with the wild-type and mutant enzymes. Results We found a bacteriophage-derived polysaccharide lyase that depolymerizes the K1 CPS into fragments of 1–3 repeating trisaccharide units with the retention of the pyruvylation and O-acetylation, and thus the important antigenic determinants of intact K1 CPS. We also determined the 1.46-Å-resolution, product-bound crystal structure of the enzyme, revealing two distinct carbohydrate-binding sites in a trimeric β-helix architecture, which provide the first direct evidence for a second, non-catalytic, carbohydrate-binding site in bacteriophage-derived polysaccharide depolymerases. We demonstrate the tight interaction between the pyruvate moiety of K1 CPS and the enzyme in this second carbohydrate-binding site to be crucial to CPS depolymerization of the enzyme as well as phage absorption and infectivity. We also demonstrate that the enzyme is capable of protecting mice from K1 K. pneumoniae infection, even against a high challenge dose. Conclusions Our results provide insights into how the enzyme recognizes and depolymerizes the K1 CPS, and demonstrate the potential use of the protein not only as a therapeutic agent against K. pneumoniae, but also as a tool to prepare structurally-defined oligosaccharides for the generation of glycoconjugate vaccines against infections caused by this organism.

BackgroundAlthough the angioarchitecture of perimedullary arteriovenous fistulas (PMAVFs) is straightforward, their size and blood flow are highly heterogeneous. This study aimed to evaluate the differences in clinical features and outcomes of PMAVFs based on lesion size and blood flow.Methods114 consecutive patients with PMAVFs from two institutes were retrospectively reviewed. The lesions were classified as either micro-PMAVFs (shunt point diameter ResultsThe patients with micro-PMAVFs were older at the first presentation (33.50 vs 13.50 years, pConclusionsThe clinical risks, treatment strategies and obliteration rates of PMAVFs differ based on their size and blood flow.

Background: Prior prelabor cesarean delivery (CD) was associated with an increase in the risk of placenta previa (PP) in a second delivery, whether it may impact postpartum hemorrhage (PPH) independent of abnormal placentation. This study aimed to assess the risk of PPH stratified by abnormal placentation following a first CD before the onset of labor (prelabor) or intrapartum CD.Methods: This multicenter, historical cohort study involved singleton, pregnant women at 28 weeks of gestation or greater with a CD history between January 2017 and December 2017 in 11 public tertiary hospitals within 7 provinces of China. PPH was analyzed in the subsequent pregnancy between women with prior prelabor CD and women with intrapartum CD. Furthermore, PPH was analyzed in pregnant women stratified by complications with PP alone [without placenta accreta spectrum (PAS) disorders], complications with PP and PAS, complications with PAS alone (without PP), and normal placentation. We performed multivariate logistic regression to calculate adjusted odds ratios (aOR) and 95% CI controlling for predefined covariates.Results: Out of 10,833 pregnant women, 1,197 (11%) women had a history of intrapartum CD and 9,636 (89%) women had a history of prelabor CD. Prior prelabor CD increased the risk of PP (aOR 1.91, 95% CI 1.40–2.60), PAS (aOR 1.68, 95% CI 1.11–2.24), and PPH (aOR 1.33, 95% CI 1.02–1.75) in a subsequent pregnancy. After stratification by complications with PP alone, PP and PAS, PAS alone, and normal placentation, prior prelabor CD only increased the risk of PPH (aOR 3.34, 95% CI 1.35–8.23) in a subsequent pregnancy complicated with PP and PAS.Conclusion: Compared to intrapartum CD, prior prelabor CD increased the risk of PPH in a subsequent pregnancy only when complicated by PP and PAS.

OBJECTIVE: The purpose of this review is to clarify the potential roles of forkhead box transcription factor M1 (FoxM1) in the occurrence and progression of breast cancer, as well as the predictive value of FoxM1 as a prognostic biomarker and potential therapeutic target for breast cancer. BACKGROUND: Breast cancer, well-known as a molecularly heterogeneous cancer, is still one of the most frequently diagnosed malignant tumors among females worldwide. Tumor recurrence and metastasis are the central causes of high mortality in breast cancer patients. Many factors contribute to the occurrence and progression of breast cancer, including FoxM1. FoxM1, widely regarded as a classic proliferation-related transcription factor, plays pivotal roles in the occurrence, proliferation, invasion, migration, drug resistance, and epithelial-mesenchymal transition (EMT) processes of multiple human tumors including breast cancer. METHODS: The PubMed database was searched for articles published in English from February 2008 to May 2021 using related keywords such as “forkhead box transcription factor M1”, “human breast cancer”, “FoxM1”, and “human tumor”. About 90 research papers and reports written in English were identified, most of which were published after 2015. These papers mainly concentrated on the functions of FoxM1 in the occurrence, development, drug resistance, and treatment of human breast cancer. CONCLUSIONS: Considering that the abnormal expression of FoxM1 plays a significant role in the proliferation, invasion, metastasis, and chemotherapy drug resistance of breast cancer, and its overexpression is closely correlated with the unfavorable clinicopathological characteristics of breast tumor patients, it is considerably important to comprehend the regulatory mechanism of FoxM1 in breast cancer. This will provide strong evidence for FoxM1 as a potential biomarker for the targeted treatment and prognostic evaluation of breast cancer patients.

Highlights • Zhejiang was the third worst-affected province of COVID-19 in China • This study monitored transmissibility of COVID-19, accounting transmission from imported cases • An interruption of local transmission was observed in early/mid-February 2020 • Early response followed by large-scale measures was effective for the interruption, Owing to the frequent travel connections between Wuhan and Zhejiang, Zhejiang was the third worst-affected province in China with 1,205 cases confirmed before 26 February 2020. The transmissibility of the 2019 novel coronavirus disease was monitored in Zhejiang, accounting for the transmissions from imported cases. Even though Zhejiang was one of the worst-affected provinces, an interruption of disease transmission (i.e. instantaneous reproduction numbers

Background: The abnormal expression Dopamine D1 receptor (DRD1) gives rise to the dysfunction of dopaminergic neurotransmitter and may be associated with the occurrence of schizophrenia. Mi...

For the surgical treatment of coronary artery disease, renal artery stenosis and other peripheral vascular diseases, there is significant demand for small diameter (inner diameter6 mm) vascular grafts. However, autologous grafts are not always available when the substitute vascular grafts are severely diseased. In our previous work, hybrid small-diameter vascular grafts were successfully fabricated by combining electrospun polycaprolactone (PCL) and decellularized rat aorta (DRA). However, histological assessments of these grafts revealed the development of intimal hyperplasia, indicating potential negative impacts on the long-term patency of these grafts. To address this challenge, PCL nanofibers blended with rapamycin (RM) were electrospun outside the decellularized vascular graft to fabricate a RM-loaded hybrid tissue-engineered vascular graft (RM-HTEV), endowing the graft with a drug delivery function to prevent intimal hyperplasia. RM-HTEV possessed superior mechanical properties compared to DRA and exhibited a sustained drug release profile. To evaluate the applicability of RM-HTEV in vivo, abdominal aorta transplantation was performed on rats. Doppler sonography showed that the grafts were functional for up to 8 weeks in vivo. Moreover, histological analysis of explanted grafts 12 weeks postimplantation demonstrated that RM-HTEV significantly decreased neo-intimal hyperplasia compared with HTEV, without impairing reendothelialization and M2 macrophage polarization. Overall, RM-HTEV represents a promising strategy for developing small-diameter vascular grafts with great clinical translational potential. STATEMENT OF SIGNIFICANCE: In this study, a new type of rapamycin-loaded hybrid tissue-engineered vascular graft (RM-HTEV) was fabricated using electrospinning technology. The unique hybrid bi-layer structure endowed the RM-HTEV with multi-functionality: the exterior rapamycin-loaded electrospun PCL nanofibrous layer enhanced the mechanical properties of the graft and possessed drug releasing property; the interior decellularized aorta layer with porous structure could facilitate cell proliferation and migration. In in vivo implantation experiment, RM-HTEV exhibited satisfying long-term patency rate and significantly inhibited intimal hyperplasia without impairing re-endothelialization and M2 macrophage polarization. This strategy is expected to be a promising strategy for developing bioactive small-diameter vascular grafts with great clinical translational potential.

The dopamine transporter is coded by the SLC6A3 gene and plays an important role in regulation of the neurotransmitter dopamine. To detect the association between the SLC6A3 gene and the risk of schizophrenia, 31 case-control articles were included in this meta-analysis. There were 23 studies with 40 bp VNTR (3246 cases and 3639 controls), 4 studies with rs40184 (2020 cases and 1674 controls), rs6347 (1317 cases and 1917 controls), rs403636 (2045 cases and 1704 controls), and rs2975226 (849 cases and 904 controls); and 3 studies with rs12516948 (1920 cases and 1569 controls), rs27072 (984 cases and 1015 controls), rs6869645 (1142 cases and 1082 controls), rs37022 (1168 cases and 1091 controls), rs464049 (1169cases and 1096 controls), rs2652511 (707 cases and 714 controls), and rs3756450 (1176 cases and 1096 controls). Pooled, subgroup, and sensitivity analyses were performed, and the results were visualized by forest and funnel plots. In the dominant genetic model, the genotype AA+AT of rs2975226 in the Indian population (Pz = 0, odds ratio [OR] = 3.245, 95% confidence interval [CI] = 1.806–5.831), TT of rs464049 (Pz = 0.002, OR = 1.389, 95% CI = 1.129–1.708), and TT of rs3756450 (Pz = 0.014, OR = 1.251, 95% CI = 1.047–1.495) might be risk factors for schizophrenia. Additionally, no other single nucleotide polymorphisms were observed. These results indicate that more functional studies are warranted.

Aim Acetaminophen (APAP) overdose is the most frequent cause of drug-induced liver damage. Magnolia officinalis is a traditional hepatoprotective Chinese medicine and Honokiol (HO) is the major active constituent. The present study was to investigate the effect of HO on APAP-induced hepatotoxicity and related mechanisms. Main methods Four groups of mice were subjected to treatment as vehicle, APAP, APAP + HO and APAP + HO + NRF2 inhibitor. The morphological and biochemical assessments were used to evaluate the hepatoprotective effects. The extent of APAP-protein adducts was determined through evaluate the hepatic content 3‑(cystein‑S‑yl)acetaminophen (APAP-Cys), the hydrolysis products of APAP-protein adducts. The activities of CYP2E1, CYP1A2 and CYP3A4 were evaluated by cocktail incubation, and the protein expression levels of NRF2, GCLC, GCLM, GS and GST were evaluated by western blot analysis. Key findings Morphological and biochemical assessments clearly demonstrated that HO could alleviate APAP-induced liver damage. The hepatoprotective effect of HO was positively associated with the reduction of APAP-protein adducts. Further investigation suggested that HO induced inhibition of CYP 2E1 and CYP2A1 as well as upregulation of GSH co-contributed to the reduction of APAP-protein adducts. Furthermore, HO induced activations of NRF2 and its target enzymes, such as GCLC, GCLM and GST, gave rise to the upregulation of GSH. Significance Our results suggested that HO could alleviate APAP-induced liver damage through reducing the generation of APAP-protein adducts, which might be mediated by inhibiting the activity of CYP 2E1 and CYP2A1 as well as enhancing the generation of GSH via NRF2 pathway.

BACKGROUND The aim of this study was to investigate the role of deubiquitinase [ovarian tumor domain-containing protein 5 (OTUD5)] in regulating Akt ubiquitination and its effect on the radiosensitivity of cervical cancer. MATERIAL AND METHODS Cervical cancer C33A cells were cultured, and then 2 groups of cells (overexpressed cells and silenced cells) were established by overexpressing and silencing OTUD5 gene. Next, quantitative polymerase chain reaction (qPCR) was employed to detect the expression level of OTUD5 in cells in each group. Co-immunoprecipitation and Western blot (WB) analysis were applied to measure the expression level of phosphorylated protein kinase B (Akt) and the level of ubiquitination. The sensitivity of cells to radiotherapy in each group was detected via clone-forming efficiency assay. After that, Statistical Product and Service Solutions (SPSS) 17.0 software was employed for analyses. The t test, one-way analysis of variance (ANOVA), and p test were used. P

Tubiechong (Eupolyphaga sinensis) is an important material used in traditional Chinese medicine (TCM). However, the immunoregulation effects of E. sinensis Lyophilized Powder (ESL) are uncl...

Background:. Although osteopontin (OPN) is expressed in the liver and pigment gallstones of patients with hepatolithiasis, its role in pigment gallstone formation remains unclear. This study aimed to explore the function of OPN in pigment gallstone formation. Methods:. Rats were fed a chow diet (CD) or lithogenic diet (LD) for 10 consecutive weeks; blocking tests were then performed using an OPN antibody (OPN-Ab). Incidence of gallstones and levels of several bile components, OPN, tumor necrosis factor alpha (TNF-α), and cholesterol 7 alpha-hydroxylase (CYP7A1) were analyzed. To determine TNF-α expression in hepatic macrophages and both CYP7A1 and bile acid (BA) expression in liver cells, recombinant rat OPN and recombinant rat TNF-α were used to treat rat hepatic macrophages and rat liver cells, respectively. Chi-square or Fisher exact tests were used to analyze qualitative data, Student t-test or one-way analysis of variance were used to analyze qualitative data. Results:. Incidence of gallstones was higher in LD-fed rats than in CD-fed rats (80% vs. 10%, P

G-protein-coupled receptors (GPCRs) have been reported to participate in the occurrence and development of a variety of human cancers. CALCR is one of the hundreds of GPCRs, but its expression level and functional importance have never been investigated in non-small-cell lung cancer (NSCLC). In the present study, the protein expression level of CALCR was detected by immunohistochemical staining and western blot analysis. The Celigo cell counting assay was used to assess cell proliferation. Both the wound-healing assay and the transwell assay were performed to evaluate cell migration. Flow cytometric analysis was utilized to detect cell apoptosis and cell cycle. A mouse xenograft model was constructed to conduct the in vivo experiments. The results indicated that the CALCR expression was abundantly up-regulated in NSCLC and positively related to tumor infiltrate. Besides, CALCR knockdown could significantly suppress cell proliferation, migration, enhance apoptosis and arrest cell cycle. The in vivo study verified the inhibitory effects of CALCR knockdown on NSCLC tumorigenesis. The abovementioned results provided a reference for the treatment of NSCLC, that was, CALCR knockdown might be a considerable therapeutic strategy.

Medical advances have enabled zygomatic complex (ZMC) fractures to be treated by various approaches. This study aims to analyze the demographics and treatment outcomes of unilateral ZMC fractures, treated nonsurgically or surgically.This 5-year nonrandomized prospective study had included 65 cases of unilateral ZMC fractures from October 2014 until December 2019. Patients were treated and divided into nonsurgical and surgically treated group. Treatment outcomes in terms of step deformities, malar depression, diplopia, infraorbital hypoaesthesia, and mouth opening were evaluated up to six months post-trauma/intervention.Road traffic accident (96.9%) was the main cause, with predominant male involvement (80%) and median age of 28 years. Significant improvements (P0.05) were observed for step deformities and malar depression among the surgically treated group at postoperative day 1 and week 1. Throughout the six months review, infraorbital hypoesthesia and diplopia showed no significant differences between both groups, (P0.05). Besides, all patients showed significant mouth opening improvement (P 0.05) over six months period.The authors found that infraorbital hypoaesthesia and limited of mouth opening should not be the absolute indications for surgical treatment of ZMC fractures. Nonsurgical treatment that included early jaw exercise and symptomatic treatment had potential value for satisfactory functional gain.

Background Anoectochilus roxburghii and Anoectochilus formosanus, belong to the Anoectochilus genus, have been used for Chinese herbal drugs as well as health food. Phenylalanine ammonia-lyase (PAL), the key enzyme in primary metabolism and phenylpropanoid metabolism, produces secondary metabolites (flavonoids) in plants, which are beneficial for the biosynthesis of phenylpropanoid metabolites. Methods The PAL genes were cloned from A. formosanus and A. roxburghii according to our previous transcriptomic analysis. The PALs were introduced into pCAMBIA2300-35S-PAL-eGFP to generate 35S-PAL-eGFP. The constructs were further used for subcellular localization and transgenic Arabidopsis. The expression of AfPAL and ArPAL under precursor substance (L-Phe), NaCl, UV, and red-light were analyzed by real-time quantitative PCR (RT-qPCR). Results AfPAL and ArPAL , encoding 2,148 base pairs, were cloned from A. formosanus and A. roxburghii. The subcellular localization showed that the ArPAL and AfPAL were both localized in the nucleus with GPF. Quantitative RT-PCR analysis indicated that the ArPAL and AfPAL genes function in the phenylalanine pathway as well as response to induced conditions. Overexpression of the AfPAL and ArPAL could increase flavonoids and anthocyanin content in the transgenic Arabidopsis. Discussion The results suggest that AfPAL and ArPAL play a crucial role in the flavonoid biosynthesis in Anoectochilus. Also, our study provides new insights into the enrichment of secondary metabolites of traditional Chinese medicines A. formosanus and A. roxburghii, which can improve their medicinal active ingredients and be used for drug discovery in plants.

BACKGROUND The rate of delivery by cesarean section is rising in China, where vaginal birth after cesarean (VBAC) is in its early stages. There are no validated screening tools to predict VBAC success in China. The objective of this study was to identify the variables predicting the likelihood of successful VBAC to create a predictive model. MATERIAL AND METHODS This multicenter, retrospective study included 1013 women at ≥28 gestational weeks with a vertex singleton gestation and 1 prior low-transverse cesarean from January 2017 to December 2017 in 11 public tertiary hospitals within 7 provinces of China. Two multivariable logistic regression models were developed: (1) at a first-trimester visit and (2) at the pre-labor admission to hospital. The models were evaluated with the area under the receiver operating characteristic curve (AUC) and internally validated using k-fold cross-validation. The pre-labor model was calibrated and a graphic nomogram and clinical impact curve were created. RESULTS A total of 87.3% (884/1013) of women had successful VBAC, and 12.7% (129/1013) underwent unplanned cesarean delivery after a failed trial of labor. The AUC of the first-trimester model was 0.661 (95% confidence interval [CI]: 0.61-0.712), which increased to 0.758 (95% CI: 0.715-0.801) in the pre-labor model. The pre-labor model showed good internal validity, with AUC 0.743 (95% CI: 0.694-0.785), and was well calibrated. CONCLUSIONS VBAC provides women the chance to experience a vaginal delivery. Using a pre-labor model to predict successful VBAC is feasible and may help choose mode of birth and contribute to a reduction in cesarean delivery rate.

BackgroundTo investigate the clinical efficacy and safety of bone cement combined with radiofrequency ablation (RFA) in the treatment of spinal metastases.MethodsThe medical records of patients with spinal metastatic tumor admitted to our hospital from January 2016 to December 2018 were retrospectively analyzed. Based on different surgical methods, the patients were divided into groups A (treated with RFA combined with bone cement) and B (treated with bone cement only). Group A included 35 patients with 47 segments of diseased vertebral bodies. Group B consisted of 52 patients with 78 vertebral segments. Pain, quality of life score, vertebra height, bone cement leakage, postoperative tumor recurrence, and complications were assessed 3 days and 1 and 6 months after surgery.ResultsAll the patients had smooth operation without paraplegia, spinal cord injury, and perioperative death. Visual analogue scales (VAS) and Oswestry Disability Index (ODI) scores of the two groups significantly improved 3 days and 1 month after surgery compared with those before surgery (P P > 0.05). Six months after surgery, the VAS and ODI scores of patients in group A were lower than those in group B, with statistically significant differences (P P P > 0.05). Postoperative bone cement permeability in group A was 6.4%, and postoperative tumor recurrence rate was 11.4%. The permeability of bone cement in group B was 20.5%, and the tumor recurrence rate was 30.8%. The bone cement permeability and tumor recurrence rate in group A were lower than those in group B, with statistically significant differences (P ConclusionsBone cement combined with RFA for the treatment of spinal metastases can achieve good efficacy, desirable analgesic effect, low incidence of complications, small surgical trauma, and high safety. The proposed method has the value of clinical popularization and application.

Background Monitoring the reproduction number (Rt) of the disease could help determine whether there is sustained transmission in a population, but areas with similar epidemic trends could have different transmission dynamics given the risk from imported cases varied across regions. In this study, we examined the Rt of coronavirus disease 2019 (COVID-19) by taking different dynamics of imported cases into account and compared the transmissibility of COVID-19 at different intervention periods in Hangzhou and Shenzhen. Methods We obtained the daily aggregated counts of laboratory-confirmed imported and local cases of COVID-19 infections in Hangzhou and Shenzhen from January 1 to March 13, 2020. Daily Rt and piecewise Rt before and after Wuhan lockdown were estimated, accounting for imported cases. Results Since the epidemic of COVID-19 in Shenzhen was dominated by imported cases, Rt was around 0.1 to 0.7 before the Wuhan lockdown. After the lockdown of Wuhan and the initialization of measures in response to the outbreak, local transmission was well-controlled as indicated by a low estimated value of piecewise Rt, 0.15 (95% CI [0.09–0.21]). On the contrary, Rt obtained for Hangzhou ranged from 1.2 to 4.9 with a piecewise Rt of 2.55 (95% CI [2.13–2.97]) before the lockdown of Wuhan due to the surge in local cases. Because of the Wuhan lockdown and other outbreak response measures, Rt dropped below unity in mid-February. Conclusions Even though Shenzhen had more cases than Hangzhou, local transmission did not sustain probably due to limited transmission from imported cases owing to the reduction in local susceptibles as residents left the city during Chunyun. The lockdown measures and local outbreak responses helped reduce the local transmissibility.

Objectives Human infection with avian influenza virus A(H7N9) remains a big threat and has a great potential to cause a pandemic in the foreseeable future. Antiviral treatment using the neuraminidase inhibitors has been recommended to treat H7N9 patients as early as possible, while evidence-based research on its effectiveness for the specific H7N9 infection was lacking. Methods We reviewed data from all laboratory-confirmed avian influenza A H7N9 cases in Zhejiang province between 2013 and 2017 and fit time-dependent survival models to evaluate the effectiveness of neuraminidase inhibitors treatment as an intervention to reduce death risk. Results The result of our final model indicated that there is no significant association (Odds Ratio = 1.29, 95% Confidence Interval [0.78–2.15]) between time to neuraminidase inhibitors treatment and survivorship after controlling for both age and white cell count. Sensitivity analyses with multiple imputation for missing data concurred with the primary complete case analysis. Conclusions . We did not find an association between neuraminidase inhibitors treatment and survival benefit in H7N9 patients across various adjusted models and sensitivity analyses of missing data imputations.

Objectives To evaluate whether the non-pharmaceutical interventions (NPIs) introduced to curb the spread of coronavirus disease 2019 (COVID-19) also interrupted the transmission of influenza. Study Design This is a descriptive epidemiological study. Methods Data on changes in the number of reported influenza cases, number of influenza-like illness (ILI) visits, ILI percentage and influenza virus positivity were compared between the in the first 18 weeks of 2020 and the same period in 2019. Results The changes in weekly average number of influenza cases were statistically significant between 2020 and 2019 (-4319 vs -525 per week; p < 0.05). The slopes of regression lines for the number of ILI visits were also statistically significant between 2020 and 2019 (-911 vs -98 per week; p < 0.05). Conclusions This study found that the prevalence of influenza was substantially decreased when NPIs were implemented for the containment of COVID-19., Highlights • The prevalence of influenza was substantially decreased when non-pharmaceutical interventions were implemented for the containment of COVID-19. • Changes in weekly average number of influenza cases were statistically significant between 2020 and 2019 (-4319 vs -525 per week; p < 0.05). • Changes in number of ILI visits were also statistically significant between 2020 and 2019 (-911 vs -98 per week; p < 0.05).

Background Venous air embolism (VAE) during craniotomy operation with semi-sitting position is closely related to intracranial venous pressure. The objective of current study was to explore the relationship between intracranial venous pressure and VAE during operation with semi-sitting position. Methods Between April 2018 and January 2019, 25 patients with vestibular schwannoma and 1 patient with posterior fossa meningioma received operation under semi-sitting position. Catheterization at jugular bulb was conducted by puncture of jugular vein with central venous catheter under guidance of ultrasound. The central venous catheter was then connected to a pressure sensor to continuously monitor the jugular bulb pressure (JBP). Both JBP and VAE were continuously monitored during operation to explore the relationship between JBP and intraoperative VAE under semi-sitting position. Results Under supine position, JBP significantly increased when the head was rotated 45° to the right compared with that recorded at neutral head position. Among all 26 patients, VAE occurred in 4 (15.4%) cases during operation including 2 minor VAE and 2 moderate VAE. Among 3 patients with negative JBP relative to atmosphere pressure, 2 occurred VAE during operation; while only 2 patients occurred VAE among other 23 cases whose JBP was positive relative to atmosphere pressure (P = 0.009). Conclusion The pressure of intracranial sinus could be continuously monitored by catheterization at jugular bulb. JBP monitoring could be used for prediction of intraoperative VAE. The rate of intraoperative VAE was significantly increased when JBP was negative relative to atmosphere pressure.

The development of placenta into the various trophoblast subtypes helps to determine the success of a pregnancy outcome...

Glucuronoxylomannan (AAPS) from the edible wood ear mushroom Auricularia auricula-judae has been demonstrated to exhibit immunostimulatory properties through its binding to TLR4. However, the mechanisms of immune modulation by AAPS in mammalian cells remains unclear. In the present study, we demonstrated that AAPS induced immunostimulatory effects were regulated by reactive oxygen species, mitogen-activated protein kinases, protein kinase C-α and NF-κB. AAPS remarkably increased the phagocytosis and bactericidal activity of macrophages. In lipopolysaccharide-activated macrophages, AAPS induced endotoxin tolerance like effect characterized by the downregulation of nitric oxide, interleukin-6 and TNF-α via the downregulation of NF-κB activation. Our findings provide firm scientific evidences for the immunoenhancing properties of wood ear mushroom, and the potential of AAPS to be strong candidates for the development of new carbohydrate-based nutraceutical supplements in the management of immunity related disorders in the future.