Comprehensive Proteomic Analysis Reveals Distinct Features and a Diagnostic Biomarker Panel for Early Pregnancy Loss in Histological Subtypes.

Early pregnancy loss (EPL) is a common event in human reproduction and is classified into histological subtypes such as hydropic abortion (HA) and hydatidiform moles, including complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs). However, accurate diagnosis and improved patient management remain challenging due to high rates of misdiagnosis and diverse prognostic risks. Therefore, diagnostic biomarkers for EPL are urgently needed. Our study aimed to identify biomarkers for EPL through comprehensive proteomic analysis. Ten CHMs, six PHMs, ten HAs, and 10 normal control products of conception were used to obtain a proteomic portrait. Parallel reaction monitoring-targeted proteomic and regression analyses were used to verify and select the diagnostic signatures. Finally, 14 proteins were selected and a panel of diagnostic classifiers (DLK1, SPTB/COL21A1, and SAR1A) was built to represent the CHM, PHM, and normal control groups (area under the receiver operating characteristic curve = 0.900, 0.804/0.885, and 0.991, respectively). This high diagnostic power was further validated in another independent cohort (n = 148) by immunohistochemistry (n = 120) and Western blot analyses (n = 28). The protein SPTB was selected for further biological behavior experiments in vitro. Our data suggest that SPTB maintains trophoblast cell proliferation, angiogenesis, cell motility, and the cytoskeleton network. This study provides a comprehensive proteomic portrait and identifies potential diagnostic biomarkers. These findings enhance our understanding of EPL pathogenesis and offer novel targets for diagnosis and therapeutic interventions.

Interfacial Stereoelectronic Effect Induced by Anchoring Orientation.

Heterogeneous interfaces in most devices play a key role in the material performance. Exploring the atomic structure and electronic properties of metal-molecule interfaces is critical for various potential applications, such as surface sensing, molecular recognition, and molecular electronic devices. This study unveils a ubiquitous interfacial stereoelectronic effect in conjugated molecular junctions by combining first-principles simulation and scanning tunneling microscopy break junction technology. Single-molecule junctions with same-side interfacial anchoring (cis configuration) exhibit higher conductance than those with opposite-side interfacial anchoring (trans configuration). The cis and trans configurations can undergo reversible conversions, resulting in a conductance switching. The stability of these configurations can be adjusted by an electric field, achieving precise regulation of conductance states. Our findings provide important insights for designing high-quality materials and enhancing the device performance.

In Situ Detection of Interfacial Ions at the Single-Bond Level.

Detecting the ionic state at the solid-liquid interface is essential to reveal the various chemical and physical processes that occur at the interface. In this study, the adsorption states of the highly electronegative ions F- and OH- at the solid-liquid interface are detected by using the scanning tunneling microscopy break junction technique. With the active hydrogen atom of the amino group as a probe, the formed ionic hydrogen bonds are successfully detected, thereby enabling in situ monitoring of the ionic state at the solid-liquid interface. Through noise power spectral density analysis and theoretical simulations, we reveal the mechanism by which ionic hydrogen bonds at the interface affect the charge transport properties. In addition, we discover that the ionic state at the solid-liquid interface can be effectively manipulated by electric fields. Under high electric fields, the concentration of the anion near the electrode is higher, and the proportion of hydrogen bonds formed is greater than that under low electric fields. This study of the interfacial ionic state at the single-bond level provides guidance for the design of high-performance materials for energy conversion and environmental purification.

Curcuminoid PBPD induces cuproptosis and endoplasmic reticulum stress in cervical cancer via the Notch1/RBP-J/NRF2/FDX1 pathway.

Curcumin has been shown to have antitumor properties, but its low potency and bioavailability has limited its clinical application. We designed a novel curcuminoid, [1-propyl-3,5-bis(2-bromobenzylidene)-4-piperidinone] (PBPD), which has higher antitumor strength and improves bioavailability. Cell counting kit-8 was used to detect cell activity. Transwell assay was used to detect cell invasion and migration ability. Western blot and quantitative polymerase chain reaction were used to detect protein levels and their messenger RNA expression. Immunofluorescence was used to detect the protein location. PBPD significantly inhibited the proliferation of cervical cancer cells, with an IC50 value of 4.16 µM for Hela cells and 3.78 µM for SiHa cells, leading to the induction of cuproptosis. Transcriptome sequencing analysis revealed that PBPD significantly inhibited the Notch1/Recombination Signal Binding Protein for Immunoglobulin kappa J Region (RBP-J) and nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathways while upregulating ferredoxin 1 (FDX1) expression. Knockdown of Notch1 or RBP-J significantly inhibited NRF2 expression and upregulated FDX1 expression, leading to the inhibition of nicotinamide adenine dinucleotide phosphate activity and the induction of oxidative stress, which in turn activated endoplasmic reticulum stress and induced cell death. The overexpression of Notch1 or RBP-J resulted in the enrichment of RBP-J within the NRF2 promoter region, thereby stimulating NRF2 transcription. NRF2 knockdown resulted in increase in FDX1 expression, leading to cuproptosis. In addition, PBPD inhibited the acidification of tumor niche and reduced cell metabolism to inhibit cervical cancer cell invasion and migration. In conclusion, PBPD significantly inhibits the proliferation, invasion, and migration of cervical cancer cells and may be a novel potential drug candidate for treatment of cervical cancer.

First-line treatment of driver gene-negative metastatic lung adenocarcinoma with malignant pleural effusion: Should chemotherapy be combined with an immune checkpoint inhibitor or bevacizumab?

Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (K‒M) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.

Targeting osteopontin alleviates endometriosis and inflammation by inhibiting the RhoA/ROS axis and achieves non-invasive in vitro detection via menstrual blood.

STUDY QUESTION: How does osteopontin (OPN) in endometriosis ectopic stromal cells (EESCs) participate in the pathogenesis of endometriosis and achieve non-invasive detection in vitro? SUMMARY ANSWER: Targeted OPN regulates endometriosis's necroptosis and inflammatory state by inhibiting the RhoA/reactive oxygen species (ROS) axis, thereby alleviating endometriosis and enabling non-invasive detection of menstrual blood in vitro. WHAT IS KNOWN ALREADY: Endometriosis is a chronic inflammatory disease. Recent studies have shown that OPN plays an important role in disease progression by regulating cell death and inflammation. STUDY DESIGN, SIZE, DURATION: The study included 20 patients diagnosed with endometriosis (confirmed by laparoscopy and histology) and 10 controls without endometriosis. Endometriotic stromal cells were isolated from endometrial samples, while menstrual blood endometrial cells (MESCs) were isolated from menstrual blood. These cells were then cultured in vitro and utilized in subsequent experiments. PARTICIPANTS/MATERIALS, SETTING, METHODS: OPN expression in EESCs was assessed using inflammatory factor sequencing, immunohistochemical staining (IHC), quantitative real-time PCR (qRT-PCR) analysis, and Western blotting (WB). The biological behavior of OPN and its effects on inflammatory factors were examined using EdU, wound-healing, Transwell, and ELISA assays. Necroptosis in EESCs and its impact on inflammatory factors were detected through qRT-PCR, WB, and Calcein-AM/PI fluorescence assays. The examination of mitochondrial stress in EESCs involved the use of the Mitochondrial Membrane Potential (ΔΨm) Assay, ROS detection, and Calcein-AM Loading/cobalt chloride Quenching. qRT-PCR, WB, and other experiments were conducted to verify the regulation of necroptosis and inflammatory factor levels in EESCs by OPN through the RhoA/ROS axis. Knockdown of OPN and its inhibitory effect on endometriosis lesion size were confirmed using AAV9 virus, IHC, qRT-PCR, WB, and other experiments. Additionally, OPN expression in MESCs was detected using transcriptome sequencing, RT-PCR, WB, and other experiments. MAIN RESULTS AND THE ROLE OF CHANCE: In vitro assays demonstrated a significant upregulation of OPN in EESCs, and the knockdown of OPN effectively inhibited necroptosis and the release of inflammatory factors. OPN inhibited necroptosis and inflammatory factor release by mediating RhoA-dependent ROS production and blocking mixed lineage kinase domain-like protein phosphorylation at the cell membrane. In vivo, targeting of OPN can inhibit the growth of endometriosis lesions. Clinically, OPN was also significantly upregulated in the menstrual blood of patients with endometriosis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Due to limitations in obtaining surgical specimens, our study primarily involved collecting endometriosis tissues from women during the proliferative and secretory phases of the menstrual cycle. We observed a significant overexpression of OPN in the samples used for our investigation. However, the expression of OPN in endometriosis tissues during the intermenstrual phase remains unknown. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the pivotal role of the OPN/RhoA/ROS axis in the regulation of necroptosis and the release of inflammatory factors. OPN knockdown exerts a therapeutic effect in vivo, and the high expression detection of OPN in menstrual blood in vitro. In summary, targeting OPN provides possibilities for the treatment and detection of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (82071626), the Zhejiang Province Public Welfare Technology Application Research Project (LGF21H040010), and the Clinical Research project of the Second Affiliated Hospital of Wenzhou Medical University (1010293). The authors have no conflicts of interest.

Structure-activity relationship and mechanistic study of organotins as inhibitors of human, pig, and rat gonadal 3ß-hydroxysteroid dehydrogenases.

Organotins have been widely used in various industrial applications. This study investigated the structure-activity relationship as inhibitors of human, pig, and rat gonadal 3ß-hydroxysteroid dehydrogenases (3ß-HSD). Human KGN cell, pig, and rat testis microsomes were utilized to assess the inhibitory effects of 18 organotins on the conversion of pregnenolone to progesterone. Among them, diphenyltin, triethyltin, and triphenyltin exhibited significant inhibitory activity against human 3ß-HSD2 with IC50 values of 114.79, 106.98, and 5.40 µM, respectively. For pig 3ß-HSD, dipropyltin, diphenyltin, triethyltin, tributyltin, and triphenyltin demonstrated inhibitory effects with IC50 values of 172.00, 100.19, 87.00, 5.75, and 1.65 µM, respectively. Similarly, for rat 3ß-HSD1, dipropyltin, diphenyltin, triethyltin, tributyltin, and triphenyltin displayed inhibitory activity with IC50 values of 81.35, 43.56, 55.55, 4.09, and 0.035 µM, respectively. They were mixed inhibitors of pig and rat 3ß-HSD, while triphenyltin was identified as a competitive inhibitor of human 3ß-HSD2. The mechanism underlying the inhibition of organotins on 3ß-HSD was explored, revealing that they may disrupt the enzyme activity by binding to cysteine residues in the catalytic sites. This proposition was supported by the observation that the addition of dithiothreitol reversed the inhibition caused by all organotins except for triethyltin, which was partially reversed. In conclusion, this study provides valuable insights into the structure-activity relationship of organotins as inhibitors of human, pig, and rat gonadal 3ß-HSD. The mechanistic investigation suggests that these compounds likely exert their inhibitory effects through binding to cysteine residues in the catalytic sites.

Characterization of ovarian progenitor cells for their potential to generate steroidogenic theca cells in vitro.

In brief: Progenitor cells with ovulation-related tissue repair activity were identified with defined markers (LGR5, EPCR, LY6A, and PDGFRA), but their potentials to form steroidogenic cells were not known. This study shows that the cells can generate progenies with different steroidogenic activities. Abstract: Adult mammalian ovaries contain stem/progenitor cells necessary for folliculogenesis and ovulation-related tissue rupture repair. Theca cells are recruited and developed from progenitors during the folliculogenesis. Theca cell progenitors were not well defined. The aim of current study is to compare the potentials of four ovarian progenitors with defined markers (LY6A, EPCR, LGR5, and PDGFRA) to form steroidogenic theca cells in vitro. The location of the progenitors with defined makers was determined by immunohistochemistry and immunofluorescence staining of ovarian sections of adult mice. Different progenitor populations were purified by magnetic-activated cell sorting (MACS) and/or fluorescence-activated cell sorting (FACS) techniques from ovarian cell preparation and were tested for their abilities to generate steroidogenic theca cells in vitro. The cells were differentiated with a medium containing LH, ITS, and DHH agonist for 12 days. The results showed that EPCR+ and LGR5+ cells primarily distributed along the ovarian surface epithelium (OSE), while LY6A+ cells distributed in both the OSE and parenchyma. However, PDGFRA+ cells were exclusively located in interstitial compartment. When the progenitors were purified by these markers and differentiated in vitro, LY6A+ and PDGFRA+ cells formed steroidogenic cells expressing both CYP11A1 and CYP17A1 and primarily producing androgens, showing characteristics of theca-like cells, while LGR5+ cells generated steroidogenic cells devoid of CYP17A1 expression and androgen production, showing a characteristic of progesterone-producing cells (granulosa- or lutea-like cells). In conclusion, progenitors from both OSE and parenchyma of adult mice are capable of generating steroidogenic cells with different steroidogenic capacities, showing a possible lineage preference.

Exosomal miR-1a-3p derived from glucocorticoid-stimulated M1 macrophages promotes the adipogenic differentiation of BMSCs in glucocorticoid-associated osteonecrosis of the femoral head by targeting Cebpz.

BACKGROUND: By interacting with bone marrow mesenchymal stem cells (BMSCs) and regulating their function through exosomes, bone macrophages play crucial roles in various bone-related diseases. Research has highlighted a notable increase in the number of M1 macrophages in glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). Nevertheless, the intricate crosstalk between M1 macrophages and BMSCs in the glucocorticoid-stimulated environment has not been fully elucidated, and the underlying regulatory mechanisms involved in the occurrence of GA-ONFH remain unclear. METHODS: We employed in vivo mouse models and clinical samples from GA-ONFH patients to investigate the interactions between M1 macrophages and BMSCs. Immunofluorescence staining was used to assess the colocalization of M1 macrophages and BMSCs. Flow cytometry and transcriptomic analysis were performed to evaluate the impact of exosomes derived from normal (n-M1) and glucocorticoid-stimulated M1 macrophages (GC-M1) on BMSC differentiation. Additionally, miR-1a-3p expression was altered in vitro and in vivo to assess its role in regulating adipogenic differentiation. RESULTS: In vivo, the colocalization of M1 macrophages and BMSCs was observed, and an increase in M1 macrophage numbers and a decrease in bone repair capabilities were further confirmed in both GA-ONFH patients and mouse models. Both n-M1 and GC-M1 were identified as contributors to the inhibition of osteogenic differentiation in BMSCs to a certain extent via exosome secretion. More importantly, exosomes derived from GC-M1 macrophages exhibited a heightened capacity to regulate the adipogenic differentiation of BMSCs, which was mediated by miR-1a-3p. In vivo and in vitro, miR-1a-3p promoted the adipogenic differentiation of BMSCs by targeting Cebpz and played an important role in the onset and progression of GA-ONFH. CONCLUSION: We demonstrated that exosomes derived from GC-M1 macrophages disrupt the balance between osteogenic and adipogenic differentiation in BMSCs, contributing to the pathogenesis of GA-ONFH. Inhibiting miR-1a-3p expression, both in vitro and in vivo, significantly mitigates the preferential adipogenic differentiation of BMSCs, thus slowing the progression of GA-ONFH. These findings provide new insights into the regulatory mechanisms underlying GA-ONFH and highlight potential therapeutic targets for intervention.

Exploring a Linear Combination Feature for Predicting the Conductance of Parallel Molecular Circuits.

An accurate rule for predicting conductance is the cornerstone of developing molecular circuits and provides a promising solution for miniaturizing electric circuits. The successful prediction of series molecular circuits has proven the possibility of establishing a rule for molecular circuits under quantum mechanics. However, the quantitatively accurate prediction has not been validated by experiments for parallel molecular circuits. Here we used 1,3-dihydrobenzothiophene (DBT) to build the parallel molecular circuits. The theoretical simulation and single-molecule conductance measurements demonstrated that the conductance of the molecule containing one DBT is the unprecedented linear combination of the conductance of the two individual channels with respective contribution weights of 0.37 and 0.63. With these weights, the conductance of the molecule containing two DBTs is predicted as 1.81 nS, matching perfectly with the measured conductance (1.82 nS). This feature offers a potential rule for quantitatively predicting the conductance of parallel molecular circuits.

Study on the space field reconstruction method of the radial basis function of electromagnetic radiation under optimal parameters.

Electromagnetic radiation (EM) pollution has a certain impact on human life and health, and the reconstruction of the EM space field in this paper is of great practical significance for EM analysis and research. The radial basis function (RBF) sufficiently considers the influence of each sampling point and is more suitable for reconstructing the EM space field than other spatial interpolation methods. Currently, when RBF is used to reconstruct the EM space field, the optimal determination of the basis function and shape parameter (SP) is rarely considered. This ultimately leads to low reconstruction accuracy of the EM space field. Therefore, in this paper, the particle swarm optimization (PSO) is used to calculate the optimal SP of the RBF. On this basis, reliable EM space field reconstruction is performed, which helps people understand the EM distribution characteristics in actual situations from a visual perspective. The EM sampling data of a region on the Yunnan Normal University campus are used as the data source, and the RBF under the optimal parameters is used for EM reconstruction. The accuracy of its interpolation results is evaluated and compared and analyzed with inverse distance weighting (IDW) after distance index optimization. The results show that the RBF under optimal parameters reconstructs the EM space field with high accuracy and good effect, which can truly reflect the actual distribution of EM.

Electromagnetic radiation (EM) pollution has a great impact on the surrounding environment. Therefore, EM space field reconstruction can help us analyze the characteristics of the electromagnetic environment in a visual way. Radial Basis Function (RBF) is a method more suitable for EM space field reconstruction than other methods because it fully considers the influence of each sampling point. However, when currently using RBF to reconstruct the EM space field, few researchers consider how to choose the most appropriate basis function and shape parameter (SP). This results in low reconstruction accuracy. Therefore, this study uses particle swarm optimization (PSO) to find the optimal SP parameters for reliable EM space field reconstruction. The study used the EM sampling data of an area within the campus of Yunnan Normal University as the study material, and a parameter-optimized RBF method was adopted for the reconstruction of the EM space field. The reconstruction results were then evaluated for accuracy and compared and analyzed with the IDW method optimized with a distance index. Research results show that using RBF with optimal parameters to reconstruct the EM space field has high accuracy and can effectively reflect the actual EM distribution, thereby helping people better understand the characteristics of the electromagnetic environment.

Real-world clinical analysis in 190 advanced NSCLC patients with uncommon EGFR mutations: A multi-center study.

Differently from epidermal growth factor receptor (EGFR) 19Del and L858R mutations, the panoramic description of uncommon EGFR mutations is far from mature. Our understanding of its population characteristics, treatment response, and drug resistance mechanisms needs urgent expansion and deepening. Our study enrolled 437 patients with non-small-cell lung cancer from four clinical centers and who had uncommon EGFR mutations. The clinical characteristics of all patients and the treatment outcomes of 190 advanced patients who received pharmacotherapy were analyzed. Moreover, the acquired resistance mechanisms were explored based on 53 tissue or liquid re-biopsy data in 45 patients. Patients with EGFR 20ins had a shorter survival time compared with patients with non-20ins mutations. In total, 149 cases had received EGFR-tyrosine kinase inhibitors (TKI); afatinib was significantly superior to other EGFR-TKIs both in ORR and mPFS in all uncommon mutations and especially in the L861Q group. The most common acquired drug resistance mechanism was MET amplification, followed by EGFR T790M, which was significantly different from common EGFR mutations.

PREDISPOSING CHARACTERISTICS OF OPTICAL COHERENCE TOMOGRAPHY FOR PATIENTS WITH PERSISTENT SUBRETINAL FLUID AFTER SUCCESSFUL REPAIR OF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To investigate the predisposing clinical parameters and characteristics of fundus imaging of patients with persistent subretinal fluid (PSF) after successful repair of rhegmatogenous retinal detachment. METHODS: A retrospective study recruiting 57 patients was conducted. All patients underwent pars plana vitrectomy with silicone oil tamponade. Patients were divided into two groups: patients presenting PSF by the time of silicone oil removal as PSF group and patients presenting no PSF by the time of silicone oil removal as control group. All patients were followed up for 3 months or longer after primary surgery. Ophthalmic examinations, including fundus photography and optical coherence tomography, were performed. RESULTS: There were significant differences between the two groups in average age, durations of preoperative symptoms, and type of retinal breaks ( P < 0.05). These clinical parameters showed statistical correlations with PSF ( P < 0.05). The proportions of patients presenting distinctive boundaries of the detached retina on fundus photograph and patients showing a hyperreflective line underlying the detached retina on optical coherence tomography in the PSF group were both significantly higher than the control group ( P < 0.05). The macular detachment heights on optical coherence tomography in the PSF group were significantly lower than the control group ( P < 0.05). These imaging characteristics also showed strong correlations with PSF ( P < 0.05). CONCLUSION: This study suggests that patients with PSF have younger age, longer symptom duration, and higher incidence of retinal holes. The distinctive detachment boundary on fundus photograph, lower macular detachment height, and hyperreflective line underlying the detached retina on optical coherence tomography may be the predisposing characteristics of PSF.

Transport Modulation Through Electronegativity Gating in Multiple Nitrogenous Circuits.

Investigating the correlations of electron transport between multiple channels shows vital promises for the design of molecule-scale circuits with logic operations. To control the electron transport through multiple channels, the modulation of electronegativity shows an effective frontier orbit control method with high universality to explore the interactions between transport channels. Here, two series of compounds with a single nitrogenous conductive channel (Sg) and dual-channels (Db) are designed to explore the influence of electronegativity on electron tunneling transport. Single-molecule conductance measured via the scanning tunneling microscope break junction technique (STM-BJ) reveals that the conductance of Db series is significantly suppressed as the electronegativity of nitrogen becomes negative, while the suppression on Sg is less obvious. Theoretical calculations confirm that the effect of electronegativity extends to a dispersive range of molecular frameworks owing to the delocalized orbital distribution from the dual-channel structure, resulting in a more significant conductance suppression effect than that on the single-channel. This study provides the experimental and theoretical potentials of electronegativity gating for molecular circuits.

Tracking Confined Reaction Based on Host-Guest Interaction Using Single-Molecule Conductance Measurement.

The host-guest interaction acts as an essential part of supramolecular chemistry, which can be applied in confined reaction. However, it is challenging to obtain the dynamic process during confined reactions below micromolar concentrations. In this work, a new method is provided to characterize the dimerization process of the guest 1,2-bis(4-pyridinyl) ethylene in host cucurbit[8]curil using scanning tunneling microscope-break junction (STM-BJ) technique. The guest reaction kinetics is quantitatively by nuclear magnetic resonance (NMR) and in situ single-molecule junctions. It is found that in the single-molecule conductance measurements, the electrical signals of the reactants with a concentration as low as 5 × 10-6  m are clearly detected, and the reaction kinetics at micromolar concentrations are further obtained. However, in NMR measurements, the characteristic peak signal of the reactants is undetectable when the concentration of the reactants is lower than 0.5 × 10-3  m and it cannot be quantified. In addition, the strong electric field from the nanogap accelerates the reaction. This work reveals that single-molecule STM-BJ techniques are more sensitive for tracking confined reactions than that by NMR techniques and can be used to study effect of extremely strong electric field on kinetics.

Capturing the Rotation of One Molecular Crank by Single-Molecule Conductance.

Unveiling the internal dynamics of rotation in molecular machine at single-molecule scale is still a challenge. In this work, three crank-shaped molecules are elaborately designed with the conformational flipping between syn and anti fulfilled by two naphthyl groups rotating freely along 1,3-butadiynyl axis. By investigating the single-molecule conductance using scanning tunnelling microscope break junction (STM-BJ) technique and theoretical simulation, the internal rotation of these crank-shaped molecules is well identified through low and high conductance corresponding to syn- and anti-conformations. As demonstrated by theoretically computational study, the orbital energy changes with the conformational flipping and influences the intraorbital quantum interference, thus eventually modulating the single-molecule conductance. This work demonstrates single-molecule conductance measurement to be a rational approach for characterizing the internal rotation of molecular machines.

Fano Resonance in Single-Molecule Junctions.

The Fano resonance in single-molecule junctions could be created by interaction with discrete and continuous molecular orbitals and enables effective electron transport modulation between constructive and destructive interference within a small energy range. However, direct observation of Fano resonance remains unexplored because of the disappearance of discrete orbitals by molecule-electrode coupling. We demonstrated the room-temperature observation of Fano resonance from electrochemical gated single-molecule conductance and current-voltage measurements of a para-carbazole anion junction. Theoretical calculations reveal that the negative charge on the nitrogen atom induces a localized HOMO on the molecular center, creating Fano resonance by interfering with the delocalized LUMO on the molecular backbone. Our findings demonstrate that the Fano resonance in electron transport through single-molecule junctions opens pathways for designs of interference-based electronic devices.

DCLK1 might be a therapeutic target of osthole against cervical cancer.

Discovering compounds with anti-cervical cancer effect and clarifying their targets will help promoting the precise treatment of cervical cancer. The present study intended to clarify the effect of osthole on cervical cancer cells, and to explore the possibility of DCLK1 as its target. Annexin V-PE staining and flow cytometry methods were used to determine cell apoptosis. Meanwhile, apoptosis related biomarkers were probed by immunoblotting. The MTT assay was employed to study the effect of osthole in combined with or without LRRK2-IN-1 (a DCLK1 inhibitor) on cell proliferation. Then, combination index was determined. To examine the interaction of osthole with DCLK1, molecular docking was carried out. Based on the biological database from cBioPortal, the association between DCLK1 and clinical manifestations of cervical cancer were evaluated. The results showed that osthole can significantly induce apoptosis of HeLa and Me-180. When combined with LRRK2-IN-1, the effect of osthole on cell proliferation was antagonized, suggesting that it might competitive binding to DCLK1. Furthermore, molecular docking showed that osthole interacts with Val468 residues of DCLK1 to form hydrogen bonds. The analysis of database showed that DCLK1 frequently mutant and deleted in cervical cancer, and is related to cell survival, tumor progression and recurrence. However, no obvious correlations were found between DCLK1 and lymphatic metastasis/differentiation. In conclusion, osthole significantly inhibits the survival of cervical cancer cells. It's probably target DCLK1 mechanistically via interacting with Val468. DCLK1 could be a potential therapeutic target for cervical cancer.

Association of polymorphisms in MALAT1 with the risk of endometriosis in Southern Chinese women.

Endometriosis is a common estrogen-dependent inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, which causes infertility and pelvic pain. Polymorphisms in MALAT1 have been demonstrated to play crucial roles in many diseases. However, the roles of MALAT1 polymorphisms in the etiology of endometriosis have not been well documented. We genotyped three MALAT1 polymorphisms in 555 endometriosis patients and 535 female control participants using quantitative polymerase chain reaction with TaqMan probes. To estimate the associations between MALAT1 polymorphisms and endometriosis risk, an unconditional logistic regression model was conducted to calculate an odds ratio (OR) and the 95% confidence interval (CI), adjusting for age, abortion history, number of deliveries, Body Mass Index (BMI), and The International Federation of Gynecology and Obstetrics (FIGO) stage. We found that the MALAT1 rs591291 C > T polymorphism significantly enhanced endometriosis risk (heterogeneous: adjusted OR = 1.36, 95% CI = 1.00-1.85, P = 0.050; homogenous: adjusted OR = 1.55, 95% CI = 1.03-2.33, P = 0.037; dominant: adjusted OR = 1.41, 95% CI = 1.05-1.88, P = 0.021). In stratification analyses, these associations were more predominant in the patients younger than 35 years old, with a relatively high number of deliveries and with a BMI between 25 and 29.9. Compared with wild-type CCG haplotype carriers, individuals with TCC haplotypes had a higher risk of developing endometriosis. The MALAT1 rs591291 C > T polymorphism was associated with a significant increase in endometriosis risk.

Safety considerations during return to work in the context of stable COVID-19 epidemic control: an analysis of health screening results of all returned staff from a hospital.

In March 2020, China had periodically controlled the coronavirus disease-19 (COVID-19) epidemic. We reported the results of health screening for COVID-19 among returned staff of a hospital and conducted a summary analysis to provide valuable experience for curbing the COVID-19 epidemic and rebound. In total, 4729 returned staff from Zhongnan Hospital of Wuhan University, Wuhan, China were examined for COVID-19, and the basic information, radiology and laboratory test results were obtained and systematically analysed. Among the 4729 employees, medical staff (62.93%) and rear-service personnel (30.73%) were the majority. The results of the first physical examination showed that 4557 (96.36%) were normal, 172 (3.64%) had abnormal radiological or laboratory test results. After reexamination and evaluation, four were at high risk (asymptomatic infections) and were scheduled to transfer to a designated hospital, and three were at low risk (infectivity could not be determined) and were scheduled for home isolation observation. Close contacts were tracked and managed by the Center for Disease Control and Prevention (CDC) in China. Asymptomatic infections are a major risk factor for returning to work. Extensive health screening combined with multiple detection methods helps to identify asymptomatic infections early, which is an important guarantee in the process of returning to work.