Pan-cancer transcriptome analysis reveals widespread regulation through alternative tandem transcription initiation.

Abnormal transcription initiation from alternative first exon has been reported to promote tumorigenesis. However, the prevalence and impact of gene expression regulation mediated by alternative tandem transcription initiation were mostly unknown in cancer. Here, we developed a robust computational method to analyze alternative tandem transcription start site (TSS) usage from standard RNA sequencing data. Applying this method to pan-cancer RNA sequencing datasets, we observed widespread dysregulation of tandem TSS usage in tumors, many of which were independent of changes in overall expression level or alternative first exon usage. We showed that the dynamics of tandem TSS usage was associated with epigenomic modulation. We found that significant 5' untranslated region shortening of gene TIMM13 contributed to increased protein production, and up-regulation of TIMM13 by CRISPR-mediated transcriptional activation promoted proliferation and migration of lung cancer cells. Our findings suggest that dysregulated tandem TSS usage represents an addtional layer of cancer-associated transcriptome alterations.

The landscape and clinical relevance of intronic polyadenylation in human cancers.

Intronic polyadenylation (IPA) is an RNA 3' end processing event which has been reported to play important roles in cancer development. However, the comprehensive landscape of IPA events across various cancer types is lacking. Here, we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas (TCGA) project. We totally identify 21,835 IPA events, almost half of which are ubiquitously expressed. We identify 2761 unique dynamically changed IPA events across cancer types. Furthermore, we observe 8855 non-redundant clinically relevant IPA events, which could potentially be used as prognostic indicators. Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response. Finally, we develop a user-friendly data portal, IPACancer Atlas (http://www.tingni-lab.com/Pancan_IPA/), to search and explore IPAs in cancer.

Mn2+/Mg2+ co-doped AlON ceramic with ultra-narrowband green emission combining high transparency toward a wide gamut backlight application.

Narrowband green-emission, combined with superior physicochemical stability and thermal performance, is regarded as a common pursuit in backlight display applications. However, mainstream phosphor-converted materials composed of resin or silicone resin easily encounter the dilemma of thermal decomposition and chemical corrosion for practical use. To overcome this problem, in this work, Mn2+/Mg2+ co-doped AlON ceramic is successfully realized with ultra-narrowband green-emission and high transparency. The luminescent property of AlON: Mn2+-Mg2+ ceramic exhibits narrowband green emission centered at 509 nm with a full width at half maximum of 36 nm, which is smaller than the corresponding powder counterpart (44 nm). Moreover, AlON: Mn2+-Mg2+ ceramic presents a wide color gamut (103.6%) and high color purity (74%). Concurrently, high transmittance of this ceramic, at 82%, unveils a potential innovation in the display technology field. This work may facilitate the development of narrowband green light-emitting converters based on AlON: Mn2+-Mg2+ transparent ceramics in large color gamut backlight display applications.

Fecal Microbiota Transplantation: A Prospective Treatment for Type 2 Diabetes Mellitus.

Purpose of Review: The aim of this review is to summarize the role of gastrointestinal microbiome (GM) in the development of type 2 diabetes mellitus (T2DM). Besides, we discuss the feasibility of applying FMT in the treatment of T2DM and propose a series of processes to refine the use of FMT in the treatment of T2DM. Recent Findings: T2DM is a metabolic disease which is connected with the GM. According to many researches, GM can produce a variety of metabolites such as bile acid, short chain fatty acids, lipopolysaccharides and trimethylamine oxide which play an important role in metabolism. FMT is a method to regulate GM and has been observed to be effective in the treatment of metabolic diseases such as T2DM in some mouse models and people. However, there is still a lack of direct evidence for the use of FMT in the treatment of T2DM, and the process of FMT is not standardized. Summary: Dysregulation of GM is closely related to the development of T2DM. Promoting the conversion of GM in T2DM patients to normal population through FMT can reduce insulin resistance and lower their blood glucose level, which is an optional treatment for T2DM patients in the future. At present, the feasibility and limitations of applying FMT to the treatment of T2DM need to be further studied.

A magnetically induced self-assembly of Ru@Fe3O4/rGO cathode for diclofenac degradation in electro-Fenton process.

In this study, a novel magnetic nanocomposite of Ru@Fe3O4/rGO was successfully synthesized by a simple hydro-thermal method. The Ru@Fe3O4/rGO particles were assembled and immobilized for innovative magnetically assembled electrode (MAE) without any binder, and the electrode was further applied in heterogeneous electro-Fenton (hetero-EF) process for the degradation of diclofenac (DCF). The results showed that rGO could remarkably enhance the conductivity and catalyze the two-electron oxygen reduction, which greatly improved the generation of H2O2. In addition, the mixture valence of Fe and Ru species might provide rich reaction sites and enhance electron transfer by synergy. Thus, the Ru@Fe3O4/rGO MAE exhibited a stable and high electrocatalytic activity in the hetero-EF process for DCF degradation over a wide pH range from 2 to 9 owing to the higher electroactive surface area (EASA) and lower charge/mass-transfer resistance. The DCF degradation efficiency could reach about 100% within 90 min under pH 5 and current 40 mA, and the Ru@Fe3O4/rGO MAE showed high stability and reusability after five cycles. Theoretically, 1O2 and •OH were the main reactive oxygen species (ROS) participating in DCF degradation in the Ru@Fe3O4/rGO MAE hetero-EF process. Furthermore, according to the LC-MS/MS intermediates, the possible DCF degradation pathway was deduced including dechlorination, hydroxylation and ring opening attacked by ROS. Eleven intermediates were detected during DCF degradation in the MAE hetero-EF process, and the ecological risk of DCF degradation in Ru@Fe3O4/rGO MAE hetero-EF process was significantly reduced. This study provides new insights into the magnetically assembled electrode of Ru@Fe3O4/rGO and displays a new practical application prospect of the materials for high-efficient removal and degradation of DCF from wastewater.

Proton Shuttle-Assisted Surface Reconstruction toward Nonpolar Facets-Terminated Zinc-Blende CdSe/CdS Core/Shell Quantum Dots.

Surface reconstruction can rearrange the surface atoms of a crystal without the need of growth processes and has the potential to synthesize crystals with novel morphologies and facets that cannot be obtained through regular synthesis. However, little is known about the molecular mechanisms of the surface reconstruction process. Here, utilizing surface reconstruction, we report the synthesis of nonpolar facets (110) facets)-terminated dodecahedral zinc-blende CdSe/CdS core/shell quantum dots. The morphology transformation is achieved by first fully exchanging the cadmium carboxylate ligand with oleylamine and then undergoing surface reconstruction. The surface reconstruction-induced morphology transformation is confirmed by transmission electron microscopy and absorption spectroscopy. Details of kinetic experiments and simulation results demonstrated that successful surface reconstruction must be assisted by a proton shuttle. Except for the first report on zinc-blende quantum dots terminated with (110) facets, the surface reconstruction aided by the proton shuttle offers valuable insights for devising methods to regulate the properties of nanocrystals.

Approximate estimation of cell-type resolution transcriptome in bulk tissue through matrix completion.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for uncovering cellular heterogeneity. However, the high costs associated with this technique have rendered it impractical for studying large patient cohorts. We introduce ENIGMA (Deconvolution based on Regularized Matrix Completion), a method that addresses this limitation through accurately deconvoluting bulk tissue RNA-seq data into a readout with cell-type resolution by leveraging information from scRNA-seq data. By employing a matrix completion strategy, ENIGMA minimizes the distance between the mixture transcriptome obtained with bulk sequencing and a weighted combination of cell-type-specific expression. This allows the quantification of cell-type proportions and reconstruction of cell-type-specific transcriptomes. To validate its performance, ENIGMA was tested on both simulated and real datasets, including disease-related tissues, demonstrating its ability in uncovering novel biological insights.

Probiotics therapy show significant improvement in obesity and neurobehavioral disorders symptoms.

Obesity is a complex metabolic disease, with cognitive impairment being an essential complication. Gut microbiota differs markedly between individuals with and without obesity. The microbial-gut-brain axis is an important pathway through which metabolic factors, such as obesity, affect the brain. Probiotics have been shown to alleviate symptoms associated with obesity and neurobehavioral disorders. In this review, we evaluated previously published studies on the effectiveness of probiotic interventions in reducing cognitive impairment, depression, and anxiety associated with obesity or a high-fat diet. Most of the probiotics studied have beneficial health effects on obesity-induced cognitive impairment and anxiety. They positively affect immune regulation, the hypothalamic-pituitary-adrenal axis, hippocampal function, intestinal mucosa protection, and glucolipid metabolism regulation. Probiotics can influence changes in the composition of the gut microbiota and the ratio between various flora. However, probiotics should be used with caution, particularly in healthy individuals. Future research should further explore the mechanisms underlying the gut-brain axis, obesity, and cognitive function while overcoming the significant variation in study design and high risk of bias in the current evidence.

Paeoniflorin, ferulic acid, and atractylenolide III improved LPS-induced neuroinflammation of BV2 microglia cells by enhancing autophagy.

Microglia hyperactivation is an important cause of neuroinflammation in Alzheimer's disease (AD). Paeoniflorin (PF), ferulic acid (FA), and atractylenolide III (ATL) are potent in anti-inflammation and neuroprotection. Multiple components can act on different targets simultaneously to exert synergistic therapeutic effects and exploring the synergistic potential between compounds is an important area of research. We investigated the effects of PF, FA, and ATL, alone or in combination, on LPS-induced neuroinflammation and autophagy in BV2 microglia cells. We found that PF, FA, and ATL, alone or in combination, significantly reduced the production of inflammatory factors such as IL-6, IL-1ß, and TNF-α, especially in the PF + FA + ATL group, which performed the best. In addition, the combination of PF, FA, and ATL significantly increased the expression of autophagy-related proteins p-AMPK, p-ULK1, Beclin1, LC3, and TFEB and decreased the expression of p62. Moreover, the restoration of autophagic flux by the combination of PF, FA, and ATL was abrogated by the addition of the autophagy inhibitor Wortmannin. In conclusion, PF, FA, and ATL have a synergistic effect in reducing LPS-induced inflammatory factor release from BV2 microglia cells, and its protective effect may be through activation of the AMPK/ULK1/TFEB autophagic signaling pathway.

Protective Effect of Ferulic Acid on Lipopolysaccharide-Induced BV2 Microglia Inflammation via AMPK/mTOR Signaling Pathway.

In neurodegenerative diseases, microglial activation and neuroinflammation are essential for the control and progression of neurodegenerative diseases. Mitigating microglium-induced inflammation is one strategy for hindering the progression of neurodegenerative diseases. Ferulic acid (FA) is an effective anti-inflammatory agent, but its potential role and regulation mechanism in neuroinflammatory reactions have not been fully studied. In this study, the neuroinflammation model was established by lipopolysaccharide (LPS), and the inhibitory effect of FA on neuroinflammation of BV2 microglia was studied. The results showed that FA significantly reduced the production and expression of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), leukocyte-6 (IL-6) and interleukin-1ß (IL-1ß). We further studied the mechanism of FA's regulation of LPS-induced BV2 neuroinflammation and found that FA can significantly reduce the expression of mTOR in BV2 microglia induced by LPS, and significantly increase the expression of AMPK, indicating that FA may have an anti-inflammatory effect by activating the AMPK/mTOR signaling pathway to regulate the release of inflammatory mediators (such as NLRP3, caspase-1 p20 and IL-1ß). We further added an autophagy inhibitor (3-MA) and an AMPK inhibitor (compound C, CC) for reverse verification. The results showed that FA's inhibitory effects on TNF-α, IL-6 and IL-1ß and its regulatory effect on AMPK/mTOR were destroyed by 3-MA and CC, which further indicated that FA's inhibitory effect on neuroinflammation is related to its activation of the AMPK/mTOR autophagy signaling pathway. In a word, our experimental results show that FA can inhibit LPS-induced neuroinflammation of BV2 microglia by activating the AMPK/mTOR signaling pathway, and FA may be a potential drug for treating neuroinflammatory diseases.

The landscape of cryptic antisense transcription in human cancers reveals an oncogenic noncoding RNA in lung cancer.

Cryptic transcription initiation has been previously linked to activation of oncogenic transcripts. However, the prevalence and impact of cryptic antisense transcription from the opposite strand of protein-coding genes were mostly unknown in cancer. Applying a robust computational pipeline to publicly available transcriptome and epigenome datasets, we identified hundreds of previously unannotated cryptic antisense polyadenylated transcripts (CAPTs) that were enriched in tumor samples. We showed that the activation of cryptic antisense transcription was associated with increased chromatin accessibility and active histone marks. Accordingly, we found that many of the antisense transcripts were inducible by treatment of epigenetic drugs. Moreover, CRISPR-mediated epigenetic editing assays revealed that transcription of a noncoding RNA LRRK1-CAPT promoted LUSC cell proliferation, suggesting its oncogenic role. Our findings largely expand our understanding of cancer-associated transcription events, which may facilitate the development of novel strategies for cancer diagnosis and treatment.

Quantitative assessment of selective degradation behavior of etoxazole in different classes of organisms by compound-specific isotope analysis.

In this paper, the stereoselective degradation and quantitative identification of chiral pesticide etoxazole in organisms with different classes of organisms (soil, chlorella algal fluid and mice) were carried out by compound-specific isotope analysis (CSIA). The degradation behavior and stable isotope fractionation effect of etoxazole in soil, chlorella and mice were investigated. The R-etoxazole degraded faster than S-etoxazole in different classes of organisms. The metabolites M1, M2 and M3 were detected in all three substrates. Biodegradation is the main factor for the change of stable isotope ratio of chiral pesticide etoxazole. Furthermore, the relationship between fractionation value of carbon isotope and residual concentration of etoxazole is established by Rayleigh equation, and the biodegradation rate of etoxazole could be calculated by using CSIA without measuring the concentration of etoxazole. Therefore, the use of CSIA can accurately assess the degradation behavior of pesticide pollution in the environment and provide a certain scientific evidence and technical support in the process of environmental remediation.

Inhibiting myostatin signaling partially mitigates structural and functional adaptations to hindlimb suspension in mice.

Novel treatments for muscle wasting are of significant value to patients with disease states that result in muscle weakness, injury recovery after immobilization and bed rest, and for astronauts participating in long-duration spaceflight. We utilized an anti-myostatin peptibody to evaluate how myostatin signaling contributes to muscle loss in hindlimb suspension. Male C57BL/6 mice were left non-suspended (NS) or were hindlimb suspended (HS) for 14 days and treated with a placebo vehicle (P) or anti-myostatin peptibody (D). Hindlimb suspension (HS-P) resulted in rapid and significantly decreased body mass (-5.6% by day 13) with hindlimb skeletal muscle mass losses between -11.2% and -22.5% and treatment with myostatin inhibitor (HS-D) partially attenuated these losses. Myostatin inhibition increased hindlimb strength with no effect on soleus tetanic strength. Soleus mass and fiber CSA were reduced with suspension and did not increase with myostatin inhibition. In contrast, the gastrocnemius showed histological evidence of wasting with suspension that was partially mitigated with myostatin inhibition. While expression of genes related to protein degradation (Atrogin-1 and Murf-1) in the tibialis anterior increased with suspension, these atrogenes were not significantly reduced by myostatin inhibition despite a modest activation of the Akt/mTOR pathway. Taken together, these findings suggest that myostatin is important in hindlimb suspension but also motivates the study of other factors that contribute to disuse muscle wasting. Myostatin inhibition benefitted skeletal muscle size and function, which suggests therapeutic potential for both spaceflight and terrestrial applications.

Network Meta-Analysis of Perioperative Analgesic Effects of Different Interventions on Postoperative Pain After Arthroscopic Shoulder Surgery Based on Randomized Controlled Trials.

Background: Shoulder arthroscopic surgery is a common surgical method used in orthopedics. However, severe postoperative pain can significantly limit the early joint movement of patients and adversely affect the impact of the surgery. At present, there is no consistent and effective analgesic scheme for the management of postoperative pain after arthroscopic surgery of the shoulder. Purpose: The aim of this study was to search for the most effective analgesic scheme to control pain in the perioperative period of arthroscopic surgery of the shoulder. Study Design: Network meta-analysis. Methods: We searched 5 different databases (i.e., Medline, PubMed, Embase, Web of Science, and the Cochrane Library) from January 2011 to January 2021 for English literature. Thereafter, we sifted out randomized controlled trials (RCTs), which compared different intervention schemes for pain management after shoulder arthroscopy and selected only 12 h, 24 h, or 48 h after the patient leaves the operating room as an optimal period for administration of analgesic intervention schemes. Only patients with shoulder disease who have undergone arthroscopic shoulder surgery were included in this study. The Cochrane "risk of bias" was used for the quality assessment. Moreover, some additional tests were performed to enhance the credibility of the results. Results: Twenty-nine RCTs involving 1,885 patients were included in this frequentist network meta-analysis (NMA). These articles mainly were divided into two distinct groups, namely, the nerve block group and the non-nerve block group. Regarding the nerve block group, at postoperative 12 h, the intervention suprascapular nerve block + interscalene nerve block (SSNB + INB) was ranked first, whereas INB + intra-articular injection (INB + IAI) was ranked first at 24 h and 48 h postoperation. In the non-nerve block group, external application (EA) was ranked first at postoperative 12 h, but oral administration (OA) exhibited a better analgesic effect at postoperative 24 h and postoperative 48 h. Conclusion: We conclude that the analgesic effect of SSNB+INB was the best at postoperative 12 h, and INB+IAI was the best at postoperative 24 h and 48 h in the nerve block group. For the non-nerve block group, the effect of EA was the best at postoperative 12 h, and the analgesic effect of OA at postoperative 24 h and 48 h was significantly better than any other interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021286777.

Evaluation of electrophysiological characteristics and ventricular synchrony: An intrapatient-controlled study during His-Purkinje conduction system pacing versus right ventricular pacing.

OBJECTIVES TO BACKGROUND: To compare electromechanical ventricular synchrony when pacing from different sites, including right ventricular apex pacing (RVAP), right ventricular septum pacing (RVSP), His bundle pacing (HBP), left bundle branch pacing (LBBP), and RVSP during unipolar pacing from the ring electrode of LBBP lead (RVSPring ) in each patient and evaluate the correlations between electrophysiological characteristics and ventricular synchrony. METHODS: Twenty patients with complete atrioventricular block indicated for dual-chamber pacemaker implantation were included in the study. Unipolar pacing at different sites, including RVAP, RVSP, HBP, LBBP, and RVSPring , was successively performed in each patient. The pacing characteristics and echocardiogram parameters were collected and compared among intrinsic rhythm and pacing at different sites. RESULTS: Similar to HBP (114.84 ± 18.67 ms), narrower paced QRSd was found in LBBP (116.15 ± 11.60 ms) as compared to RVSPring (135.11 ± 13.68 ms), RVSP (141.65 ± 14.26 ms), and RVAP (160.15 ± 19.35 ms) (p < .001). LBBP showed comparable pacing parameters to RVAP or RVSP and was significantly better than HBP, with maintained cardiac function. TS-12-SD was significantly improved in LBBP (41.80 ± 20.97 ms) than RVAP (69.70 ± 32.42 ms, p = .003) and RVSP (63.30.56 ± 32.53 ms, p = .018) but similar to HBP (51.50 ± 25.67 ms, p = .283) or RVSPring (57.80 ± 25.65 ms, p = .198). Among these pacing strategies, negative values of interventricular mechanical delay (IVMD) were only identified in LBBP (-19.25 ± 18.43 ms), significantly different from RVAP (35.00 ± 30.72 ms), RVSP (22.85 ± 22.05 ms), HBP (5.20 ± 18.64 ms), and RVSPring (16.00 ± 26.76 ms (all p < .05). Using Pearson's analysis, Sti-LVAT was positively correlated with QRS duration, IVMD, TS-12-SD, LVEDV, and LVESV, while a negative relationship could be observed for left ventricular ejection fraction. CONCLUSIONS: His-Purkinje conduction system pacing (HPCSP) achieved better electrical and mechanical synchrony than conventional RV pacing. For interventricular synchrony, only LBBP initiated earlier LV activation than RV, in accordance with the right bundle branch block (RBBB) pattern of paced QRS during LBBP. Sti-LVAT might be a good parameter correlating with LV systolic function and mechanical synchrony.

A Longitudinal Study on the Mental Health of College Students in Jinan During the Peak Stage of the COVID-19 Epidemic and the Society Reopening.

INTRODUCTION: COVID-19, a continuously emerging human-to-human infectious disease, has exerted a significant impact on the mental health of college students. However, little is known regarding the variations in the mental health issues experienced by college students during the peak versus reopening stages of the COVID-19 epidemic in China. METHODS: To assess these issues, an online longitudinal survey was conducted via a WeChat applet. Undergraduates (n = 300) were recruited from 26 universities throughout Jinan in February 2020 (T1 - the epidemic peak stage) and in January 2021 (T2 - the society reopening stage). Their mental status was determined using the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 item, and the Insomnia Severity Index. RESULTS: Of the original 300 college students recruited for this survey, 294 responses at T1 and 285 at T2 were analyzed. Compared with responses obtained at T1, college students at T2 showed a greater prevalence of depression (65.3 vs. 51.0%; p = 0.001) and anxiety (47.7 vs. 38.1%, p = 0.019), and experienced more severe depression (p < 0.001) and anxiety (p < 0.001). Both males (p = 0.03) and females (p < 0.01) showed higher levels of depression at T2 versus T1, while no differences were obtained with regard to anxiety and insomnia. At T1, Grade 4 students showed greater levels of depression (p = 0.005) and anxiety (p = 0.008) than that of Grade 1 students. While at T2, only greater levels of depression (p = 0.004) were present when compared with that of Grade 1 students. Additionally, Grade 4 college students demonstrated a greater prevalence of depression at T2 versus T1 (p = 0.03), but no statistically differences were present for anxiety and insomnia. No statistically significant differences were obtained among the 4 grades of college students for insomnia at either the T1 or T2. CONCLUSION: With progression of the COVID-19 epidemic, college students showed increasing levels of depression and anxiety, with Grade 4 college students being most seriously affected. It is imperative that intervention strategies be implemented to mitigate against these mental health issues resulting from the COVID-19 epidemic.

Effect of Molecular Weight and Degree of Substitution on the Physical-Chemical Properties of Methylcellulose-Starch Nanocrystal Nanocomposite Films.

This research studied the effect of molecular weight (Mw) and degree of substitution (DS) on the microstructure and physicochemical characteristics of methylcellulose (MC) films with or without SNC. The Mw and DS of three types of commercial MC (trade name of M20, A4C, and A4M, respectively) were in the range of 0.826 to 3.404 × 105 Da and 1.70 to 1.83, respectively. Mw significantly affected the viscosity of methylcellulose solutions as well as the microstructure and tensile strength of methylcellulose films, while DS had a pronounced effect on their oxygen permeability properties. The incorporation of 15% (w/w) SNC resulted in the efficient improvement of tensile strength, water, and oxygen barrier properties of films, particularly for the A4C nanocomposite films. The results from SEM and FTIR illustrated that relatively homogenous dispersion of SNC was distinguished in A4C-15% (w/w) SNC films. Furthermore, microstructures of MC-SNC nanocomposite films were strongly dependent on both Mw and DS of MC. This work offers a convenient and green method to fabricate MC-based nanocomposite films with desirable mechanical, light, oxygen, and water vapor barrier properties.

In vivo two-photon characterization of tumor-associated macrophages and microglia (TAM/M) and CX3CR1 during different steps of brain metastasis formation from lung cancer.

Brain metastases frequently occur in lung cancer and dramatically limit prognosis of affected patients. The influence of tumor-associated macrophages and microglia (TAM/M) and their receptor CX3CR1 on different steps of brain metastasis formation from lung cancer is poorly characterized. We established a syngeneic orthotopic cerebral metastasis model in mice by combining a chronic cranial window with repetitive intravital 2-photon laser scanning microscopy. This allowed in vivo tracking of fluorescence-expressing tumor cells and TAM/M on a single-cell level over weeks. Intracarotid injection of red tdTomato-fluorescent Lewis lung carcinoma cell was performed in transgenic mice either proficient or deficient for CX3CR1. After intracarotid cell injection, intravascular tumor cells extravasated into the brain parenchyma and formed micro- and mature macrometastases. We observed potential phagocytosis of extravasated tumor cells by TAM/M. However, during later steps of metastasis formation, these anti-tumor effects diminished and were paralleled by TAM/M accumulation and activation. Although CX3CR1 deficiency resulted in a lower number of extravasated tumor cells, progression of these extravasated cells into micro metastases was more efficient. Overall, this resulted in a comparable number of mature macrometastases in CX3CR1-deficient and -proficient mice. Our findings indicate that unspecific inhibition of CX3CR1 might not be a suitable therapeutic option to prevent dissemination of lung cancer cells to the brain. Given the close interaction between TAM/M and tumor cells during metastasis formation, other therapeutic approaches targeting TAM/M function may warrant further evaluation. The herein established orthotopic mouse model may be a useful tool to evaluate such concepts in vivo.

Mediating effects of social support between antenatal depression and fear of childbirth among nulliparous woman.

BACKGROUND: Although gestation and childbirth are progressive physical processes for most pregnant women, there are both physical and great psychosocial challenges throughout the process, which increase the sensitivity and vulnerability of women. Even for women with low-risk pregnancies, it is common to experience degrees of fear, especially for primipara women when faced with childbirth. During their first pregnancy, women may have no relevant health knowledge or experience with delivery and have difficulty identifying prenatal depression and other existing mental health factors; a fear of childbirth (FOC) may engender adverse outcomes for mothers and babies. Social support is a very important influential factor for prenatal depression. METHODS: This study adopted a descriptive cross-sectional design. The participant cohort involved 609 primipara women (≥18 years old) who had received routine prenatal care and visited a tertiary care hospital in Xi'an. The participants completed structured questionnaires, including the 10-item Edinburgh Postnatal Depression Scale (EPDS), 12-item Multidimensional Scale of Perceived Social Support (MSPSS), and 33-item Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ), alongside contribution of information regarding their demographic characteristics. Descriptive and correlation analyses were adopted to verify the correlations among these variables. Multiple regression models were examined by the SPSS PROCESS procedure with bootstrapping to confirm the significance of the mediation effect. RESULTS: The widespread prevalence of FOC in healthy pregnant women was 22.3% (WDEQ score ≥85). The mean scores of depression, social support, as well as FOC scores of participants were 9.50 (5.19), 70.91 (9.25), and 70.43 (20.88), respectively. Remarkable correlations were identified between pregnancy depressive symptoms, social support, and FOC. Results presented an indirect effect, indicating that the impacts of antenatal depression on FOC were mediated by social support. CONCLUSIONS: Perceived social support played a mediating role between antenatal depression and FOC among healthy primipara women. Techniques and suggestions for boosting social support may be expected to have a positive impact on the depressive symptoms of pregnant women with FOC.

Pleural Fluid GSDMD Is a Novel Biomarker for the Early Differential Diagnosis of Pleural Effusion.

OBJECTIVE: Gasdermin D (GSDMD), controlling pyroptosis in cells, has multiple physiological functions. The diagnostic role of GSDMD in pleural effusion (PE) remains unknown. METHODS: Sandwich ELISA kits that we developed were applied to measure the level of GSDMD for 335 patients with a definite cause of PE, including transudative PE, tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). The diagnostic accuracy of Light's criteria vs. the new marker GSDMD was performed. Clinical follow-up of 40 cases of PPE was conducted and divided into efficacy and non-efficacy groups according to the therapeutic outcome. Nucleated cells (NCs) in PE were isolated and further infected with bacteria to verify the cell source of GSDMD. RESULTS: The diagnostic accuracy of GSDMD for the diagnosis of PE were 96% (sensitivity) and 94% (specificity). The receiver operating characteristic (ROC) curve indicated that GSDMD can be an efficient biomarker for the differential diagnosis of transudative PE and other groups (all AUC > 0.973). Noteworthily, the highest AUC belonged to tuberculosis diagnosis of 0.990, and the cut-off value was 18.40 ng/mL. Moreover, the same cut-off value of PPE and MPE was 9.35 ng/mL. The combination of GSDMD, adenosine deaminase (ADA), and lactate dehydrogenase (LDH) will further improve the diagnostic efficiency especially between TPE and PPE (AUC = 0.968). The AUC of GSDMD change at day 4, which could predict the therapeutic effect at an early stage, was 0.945 (P < 0.0001). Interestingly, bacterial infection experiments further confirm that the pleural fluid GSDMD was expressed and secreted mainly by the NCs. CONCLUSION: GSDMD and its combination are candidates as a potentially novel biomarker not only to separate PEs early and effectively, but also monitor disease progression.