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As natural nanoparticle, the bacterial outer membrane vesicles (OMV) hold great potential in protein vaccines because of its self-adjuvant properties and good biocompatibility. However, the inherent immunotoxicity seriously hampers the application of OMV as protein antigens delivery carrier. Here, an attenuated OMV was constructed by elimination of the flagella protein from its surface and removal of the phosphate group of LPS at position one via gene-editing strategy. The gene-edited outer membrane vesicles (EMV) effectively reduced the levels of pro-inflammatory factors TNF-α and IL-6 in mouse blood by at least 10-fold and 15-fold respectively, compared to wild type OMV (WT-OMV). Importantly, protein antigens are conveniently displayed on EMV by employing a plug-and-display procedure, whereby the exterior of biotinylated EMV can be readily decorated with a synthetic protein comprised of target antigen fused to a biotin-binding protein. EMV greatly increased the uptake of antigen by dendritic cells (DCs) and promoted their maturation. EMV-antigen complex induces a robust antigen-specific antibody responses and cellular immune responses. We propose that EMV have great potential as protein antigens delivery vehicle for preventing different infectious diseases., Competing Interests: Declaration of competing interest All the authors declare they are no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Tumor-stroma percentage (TSP) is a prognostic risk factor in numerous solid tumors. Despite this, the prognostic significance of TSP in gastric cancer (GC) remains underexplored. Through the development of a personalized predictive model and a semi-automatic identification system, our study aimed to fully unlock the predictive potential of TSP in GC., Methods: We screened GC patients from Shanghai General Hospital (SGH) between 2012 and 2019 to develop and validate a nomogram. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic factors influencing the prognosis for GC patients. The nomogram was further validated externally by using a cohort from Bengbu Medical College (BMC). All patients underwent radical gastrectomy, with those diagnosed with locally advanced GC receiving adjuvant chemotherapy. The primary outcome measured was overall survival (OS). The semi-automatic identification of the TSP was achieved through a computer-aided detection (CAD) system, denoted as TSP-cad, while TSP identified by pathologists was labeled as TSP-visual., Results: A total of 813 GC patients from SGH and 59 from BMC were enrolled in our study. TSP-visual was identified as an adverse prognostic factor for OS in GC and was found to be associated with pathological Tumor Node Metastasis staging system (pTNM) stage, T stage, N stage, perineural invasion (PNI), lymphovascular invasion (LVI), TSP-visual, tumor size, and other factors. Multivariate Cox regression using the training cohort revealed that TSP-visual (hazard ratio [HR], 2.042; 95% confidential interval [CI], 1.485-2.806; P  <   0.001), N stage (HR, 2.136; 95% CI, 1.343-3.397; P  =   0.010), PNI (HR , 1.791; 95% CI, 1.270-2.526; P  =   0.001), and LVI (HR, 1.482; 95% CI, 1.021-2.152; P  =   0.039) were independent predictors. These factors were incorporated into a novel nomogram, which exhibited strong predictive accuracy for 5-year OS in the training, internal validation, and external validation cohorts (area under the curve = 0.744, 0.759, and 0.854, respectively). The decision curve analysis of the nomogram and concordance indexes across the three cohorts outperformed the traditional pTNM ( P  <   0.05). Additionally, TSP-cad assessment using a rapid multi-dynamic algorithm demonstrated good agreement with TSP-visual., Conclusions: The novel nomogram based on TSP could effectively identify individuals at risk of a poor prognosis among patients with GC. TSP-cad is anticipated to enhance the evaluation process of TSP., Competing Interests: The authors declare that there is no conflict of interests in this study., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Engineered bacteria-mediated antitumor approaches have been proposed as promising immunotherapies for cancer. However, the off-target bacterial toxicity narrows the therapeutic window. Living microbes will benefit from their controllable immunogenicity within tumors for safer antitumor applications. In this study, a genetically encoded microbial activation strategy is reported that uses tunable and dynamic expression of surface extracellular polysaccharides to improve bacterial biocompatibility while retaining therapeutic efficacy. Based on screening of genes associated with Salmonella survival in macrophages, a novel attenuated Salmonella chassis strain AIS (htrA gene-deficient) highly enriched in tumors after administration and rapidly cleared from normal organs are reported. Subsequently, an engineered bacterial strain, AISI-H, is constructed based on the AIS strain and an optimized quorum-sensing regulatory system. The AISI-H strain can achieve recovery of dynamic tumor-specific bacterial virulence through a novel HTRA-RCSA axis-based and quorum-sensing synthetic gene circuit-mediated increase in extracellular polysaccharide content. These strains act "off" in normal organs to avoid unwanted immune activation and "on" in tumors for precise tumor suppression in mice. The AISI-H strain shows significant tumor inhibition and potent activation of anticancer immunity in a melanoma mouse model. The AISI-H strain exhibits excellent biocompatibility. This bacterial regulation strategy expands the applications of microbe-based antitumor therapeutics., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Lung metastases are the leading cause of death among cancer patients. The challenges of inefficient drug delivery, compounded by a robust immunosuppressive microenvironment, make effective treatment difficult. Here, an innovative dual-engineered macrophage-microbe encapsulation (Du-EMME) therapy is developed that integrates modified macrophages and engineered antitumor bacteria. These engineered macrophages, termed R-GEM cells, are designed to express RGD peptides on extracellular membranes, enhancing their tumor cell binding and intratumor enrichment. R-GEM cells are cocultured with attenuated Salmonella typhimurium VNP20009, producing macrophage-microbe encapsulation (R-GEM/VNP cells). The intracellular bacteria maintain bioactivity for more than 24 h, and the bacteria released from R-GEM/VNP cells within the tumor continue to exert bacteria-mediated antitumor effects. This is further supported by macrophage-based chemotaxis and camouflage, which enhance the intratumoral enrichment and biocompatibility of the bacteria. Additionally, R-GEM cells loaded with IFNγ-secreting strains (VNP-IFNγ) form R-GEM/VNP-IFNγ cells. Treatment with these cells effectively halts lung metastatic tumor progression in three mouse models (breast cancer, melanoma, and colorectal cancer). R-GEM/VNP-IFNγ cells vigorously activate the tumor microenvironment, suppressing tumor-promoting M2-type macrophages, MDSCs, and Tregs, and enhancing tumor-antagonizing M1-type macrophages, mature DCs, and Teffs. Du-EMME therapy offers a promising strategy for targeted and enhanced antitumor immunity in treating cancer metastases., (© 2024 Wiley‐VCH GmbH.)

Aims: To explore the inter-predictive role and causal relationship between family functioning, self-perceived burden and loneliness in people with type 2 diabetes., Methods: In this study, patients with type 2 diabetes admitted to two tertiary care hospitals in China were selected for an 8-month follow-up, and the patients' scores on the Family Functioning, Self-perceived Burden, and Loneliness scales were measured repeatedly at three time periods: during hospitalisation (T1), 1 month after discharge (T2), and 3 months after discharge (T3)., Results: The results showed that family function at the T1 time point had a negative predictive effect on self-perceived burden at the T2 time point, β = - 0.43, P = 0.005. Loneliness at the T1 time point had a positive predictive effect on self-perceived burden at the T2 time point, β = 0.08, P = 0.021. Unlike the pathway at time point T1, family functioning at time point T2 negatively predicted loneliness at time point T3, β = - 0.32, P = 0.013. Loneliness at time point T2 positively predicted family functioning at time point T3, β = 0.025, P = 0.013. Loneliness at time point T2 negatively predicted self-perceived burden at time point T3 (P = 0.011)., Conclusions: The results of the cross-lagged analysis show that there is a mutually predictive and moderating relationship between family functioning and loneliness in patients with type 2 diabetes. Loneliness can predict the level of self-perceived burden at the next time point., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

The limited anthropogenic activities on the Tibetan Plateau make this an ideal natural laboratory to elucidate how climate change impacts lake changes. Previous studies have mainly focused on decadal lake changes, yet their rapid evolutions at short temporal intervals and the associated atmospheric origins remain elusive. Here, we produce a new lake area change dataset at monthly sampling over 2015-2020 from 16,801 satellite images. Our estimates achieve an accuracy of <30 m, as evidenced by in-situ GPS field survey validations of representative lake shorelines. We found contrasting patterns in recent rapid area changes: deaccelerating in the north and accelerating in the south. Such contrasting pattern was unprecedented in the last two decades and is likely caused by recent precipitation anomalies, indicating that lakes in TP may experience a tipping point. Lakes are found to store only a small portion (<5 %) of net precipitation in summer, increased to ∼11 % for years with heavy precipitation, which helps understand the water mass budget for lakes over there. Our study highlights the importance of investigating short-term lake area changes as a climate proxy to study their rapid responses to intra- and inter-annual climate variability., Competing Interests: Declaration of competing interest The contact author has declared that no conflict of interest exits in the submission of this manuscript, and the manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2023. Published by Elsevier B.V.)

Aims: To examined the relationship between fear of hypoglycemia and certain variables in people with type 2 diabetes mellitus (T2DM) based on the Capability, Opportunity, Motivation, and Behavior model, combined with the context unique to people with diabetes to provide a basis for developing targeted nursing interventions., Methods: In this cross-sectional study, 212 people with T2DM were recruited from February 2021 to July 2021. Data were collected using the Hypoglycaemia Fear Survey, Gold score, Patient Assessment of Chronic Illness Care (PACIC) scale and Diabetic Self-Management Attitudes Scale. Multiple linear regression analysis was performed to determine the predictors of fear of hypoglycemia using SPSS 26.0., Results: The mean fear of hypoglycemia score was 74.88 ± 18.28 (range: 37.00-132.00). In people with T2DM, the frequency of blood glucose monitoring, the frequency of hypoglycemia in the past half-year, degree of understanding of hypoglycemia, impaired awareness of hypoglycemia, PACIC, and self-management attitude of diabetes were the influencing factors of fear of hypoglycemia (adjusted R 2  = 0.560, F [21,190]  = 13.800, P < 0.001). These variables explained 56.0% of the variance in the fear of hypoglycemia., Conclusions: The level of fear of hypoglycemia in people with T2DM was relatively high. In addition to paying attention to the disease characteristics of people with T2DM, medical staff should also pay attention to patients' own perception and handling ability of disease and hypoglycemia, attitude toward self-management behavior and external environment support, all of which have a positive effect on improving the fear of hypoglycemia in people with T2DM, optimizing the self-management level and improving quality of life., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

The majority of sprawling-posture quadrupedal vertebrates, such as geckos and lizards, adopt a cyclical lateral swing pattern of their trunk that is coordinated with limb movements to provide extraordinary flexibility and mobility. Inspired by the gecko's locomotory gait and posture, a gecko-like robot with a flexible spine driven by shape memory alloy (SMA) springs was proposed in this work. The static parameters of the SMA spring were experimentally measured, and the flexible spine driven by SMA springs can be deflected bidirectionally. A kinematic model of the spine mechanism was established, and the mathematical relationship between the thermodynamic behavior of the SMA springs and spinal deflection was systematically analyzed. When a gecko trots with a lateral swing pattern of its trunk, the body and the spine show a standing wave shape and a single-peak C-type curve, respectively. The lateral spine deflection and trotting gait were combined in a collaborative model of a flexible spine and limbs to describe in detail the specific relationships between leg joint variables and spine deflection angle. Planar motion tests of a prototype robot were also conducted by using four high-speed cameras to record the trajectory of each point of the body, which verified the proposed model. From the acquired results, it was demonstrated that, compared with a rigid body, a robot with a flexible spine has a longer stride length, higher speed, and a greatly reduced turning radius.

Background: Infertility has been confirmed as a significant medical and social problem. Heavy metal exposure refers to a risk factor for infertility, which is capable of damaging the reproductive system of males and females. However, heavy metal exposure and female infertility have rarely been investigated. The aim of this study was to analyze the association between heavy metal exposure and female infertility., Methods: A cross-sectional study using data from three cycles of the National Health and Nutrition Examination Survey (NHANES, 2013-2018) was performed. Female infertility was evaluated by positive responses to question rhq074 in the questionnaire. Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) levels in blood or urine were examined by inductively coupled plasma mass spectrometry. The correlation between heavy metal and female infertility was analyzed through weighted logistic regression., Results: A total of 838 American women aged 20-44 years were covered in the study. Among all participants, 112 (13.37%) women were subjected to infertility. Urinary Cd and urinary As levels were significantly higher in infertile women than in control women ( P < 0.05, P < 0.05). Urinary As showed a positive correlation with the prevalence of female infertility, and the risk of infertility rose with the increase of urinary As levels ( P for trend = 0.045). Urinary Cd was associated with female infertility in some weighted logistic regression (Crude, Q2: OR = 3.99, 95% CI 1.82, 8.74, Q3: OR = 2.90, 95% CI 1.42, 5.92. Model 1, Q2: OR = 3.68, 95% CI 1.64, 8.27, Q3: OR = 2.33, 95% CI 1.13, 4.48. Model 2, Q2: OR = 4.11, 95% CI 1.63, 10.07, Q3: OR = 2.44, 95% CI 1.07, 5.53. Model 3, Q2: OR = 3.77, 95% CI 1.52, 9.35). Moreover, blood Pb (OR = 1.52, 95% CI 1.07, 2.16), urinary Pb (OR = 1.68, 95% CI 1.11, 2.55), and urinary As (OR = 1.02, 95% CI 1.00, 1.03) were positively correlated with the risk of infertility in women aged 35-44 years. The blood Pb (OR = 1.67, 95% CI 1.16, 2.40, 2.49) and urinary Pb (OR = 1.54, 95% CI 1.00, 2.38) in women with BMI ≥25 were positively correlated with the risk of infertility., Conclusions: Urinary As was significantly associated with female infertility, and the risk of infertility increased with higher urinary As levels. To some extent, urinary Cd was correlated with infertility. Blood/urine Pb was related to infertility in advanced age and overweight/obese women. The results of this study need to be further validated in future prospective studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Lin, Qiu, You and Xu.)

Traditional mobile robots are mainly divided into wheeled robots and legged robots. They have good performance at fast-moving speeds and crossing obstacles, and weak terrain adaptability and moving speeds, respectively. Combining the advantages of these two types mentioned, a multi-functional wheel-legged hexapod robot with strong climbing capacity was designed in this paper. Each wheel-leg of the robot is driven directly by a single motor and can move smoothly and quickly in a diagonal tripod gait. Based on the obstacle-crossing way of the wheel-leg and combined with the characteristics of insects moving stably in nature, the middle part of the robot body is wider than head and tail. Tripod gait was selected to control the robot locomotion. A series of simulations and experiments were conducted to validate its excellent adaptability to various environmental conditions. The robot can traverse rugged, broken, and obstacle-ridden ground and cross rugged surfaces full of obstacles without any terrain sensing or actively controlled adaptation. It can negotiate obstacles of approximately its own height, which is much higher than its centre of gravity range.

Purpose: To explore the regulatory effect of let-7a-5p/TGFBR1/Smad3 on the proliferation activity of cervical cancer cells., Methods: The difference in let-7a-5p expression between normal people and patients with cervical cancer was detected by miREIA assay. The differences of let-7a-5p expression between cervical cancer cell line C33a and adjacent normal epithelial cell line HUCEC were determined by qRT-PCR., Results: miREIA result showed that let-7a-5p concentrations were 178.5 ± 24.3 μg/L in healthy individuals and 106.1 ± 14.8 μg/L in cervical cancer patients (P = 0.0002). qRT-PCR showed that let-7a-5p in cervical cancer tissue (0.57 ± 0.03) was lower than that in adjacent normal tissue (0.84 ± 0.04, P = 0.0107). Compared with normal cervical epithelial cells (HUCEC), the expression of let-7a-5p was lower in cervical cancer cells (C33a, Hela, P = 0.0001). The results of CCK-8 and EDU detection showed that activation of let-7a-5p inhibited the proliferation of C33a (P = 0.00130, P << 0.0001) and Hela (P = 0.00254, P = 0.0066) cells. According to the analysis using Starbase V2.0 online database, let-7a-5p could target TGFβR1 in cervical cancer cell lines, and the let-7a-5p mimic reduces the mRNA expression level of TGFβR1 in cervical cancer cell C33a (P = 0.0067). Western blot results showed that TGFBR1 expression significantly decreased in cervical cancer cells after let-7a-5p mimic treatment (P = 0.0048) and significantly increased after let-7a-5p mimic inhibitor treatment (P = 0.0003)., Conclusions: let-7a-5p represents the independent novel anti-oncogenes in cervical cancer, which can regulate TGF-β1/TGFBR1/pSmad3 cell pathway and interfere with the proliferation of cervical cancer cells. Therefore, let-7a-5p can serve as a novel potential therapeutic target for the treatment of cervical cancer., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Students frequently generate mnemonic cues to help them remember difficult or abstract information (Tullis & Maddox, Metacognition and Learning , 2020, 15, 129). Self-generated mnemonics have the potential to be particularly effective means of remembering target information because they can transform abstract information into meaningful units, connect information to existing schema, and create distinct retrieval routes to the targets. Across five experiments, we compared the effectiveness of self-generated mnemonics to mnemonics generated by others for remembering chemistry information. Generating one's own mnemonics consistently boosted recall for both the chemistry content and the mnemonic itself. However, experimentally boosting recall of mnemonics through retrieval practice did not affect recall of associated chemistry content. These results indicate that improved recall of chemistry content is not caused by better recall of the mnemonic itself; rather, generating a mnemonic involves deep and effortful processing of chemistry content that boosts recall more than reading someone else's mnemonic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pseudoachondroplasia (PSACH) is known as an autosomal dominant disorder associated with mutations in the gene of cartilage oligomeric matrix protein (COMP). The pathomolecular mechanisms of PSACH as a result of C-terminal globular region (CTD) mutations remain unclear. A heterozygous mutation (E559 K) in a Chinese family diagnosed with PSACH was reported in this study. To understand the pathogenesis of this mutation, we studied chondrogenic differentiation of patient menstrual blood-derived stem cells (MenSCs), and the impact of the mutation on structural changes of COMP was investigated using all-atom molecular dynamics simulation. The results suggested that the interactions with calcium and other molecules in the mutant structure were affected resulting in misfolding of the protein, which leads to ER stress and finally affects the survival of chondrocytes. The findings may promote the understanding of the pathomolecular mechanisms of PSACH, and possibly the development of drugs to treat the disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

As an electron transport component, cytochrome b 5 is an essential component of the Class II cytochrome P450 monooxygenation system and widely present in animals, plants, and fungi. However, the roles of Cyt-b 5 domain proteins in pathogenic oomycetes remain unknown. Peronophythora litchii is an oomycete pathogen that causes litchi downy blight, the most destructive disease of litchi. In this study, we identified a gene, designated PlCB5L1 , that encodes a Cyt-b 5 domain protein in P . litchii , and characterized its function. PlCB5L1 is highly expressed in the zoospores, cysts, germinated cysts, and during early stages of infection. PlCB5L1 knockout mutants showed reduced growth rate and β-sitosterol utilization. Importantly, we also found that PlCB5L1 is required for the full pathogenicity of P . litchii . Compared with the wild-type strain, the PlCB5L1 mutants exhibited significantly higher tolerance to SDS and sorbitol, but impaired tolerance to cell wall stress, osmotic stress, and oxidative stress. Further, the expression of genes involved in oxidative stress tolerance, including peroxidase, cytochrome P450, and laccase genes, were down-regulated in PlCB5L1 mutants under oxidative stress. This is the first report that a Cyt-b 5 domain protein contributes to the development, stress response, and pathogenicity in plant pathogenic oomycetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Li, Zhou, Situ, Lin, Qiu, Yuan, Xi, Jiang and Kong.)

Background: Extranodal extension (ENE) and log odds of positive lymph nodes (LODDS) are associated with the aggressiveness of both colon and rectal cancers. The current study evaluated the clinicopathological significance and the prognostic impact of ENE and LODDS in the colon and rectal patients independently., Methods: The clinical and histological records of 389 colorectal cancer (CRC) patients who underwent curative surgery were reviewed., Results: For the ENE system, 244 patients were in the ENE1 group and 145 in the ENE2 system. Compared with the ENE1 system, the patients included in the ENE2 system were prone to nerve invasion (P < 0.001) and vessel invasion (P < 0.001) with higher TNM (P = 0.009), higher T category (P = 0.003), higher N category (P < 0.001), advanced differentiation (P = 0.013), more number of positive lymph nodes (NPLN) (P < 0.001), more lymph node ratio (LNR) (P < 0.001), and a higher value of LODDS (P < 0.001). ENE was more frequent in patients with left and rectal than right cancer. For the LODDS system, 280 patients were in the LODDS1 group, and 109 in the LODDS2 group. Compared to the LODDS1 group, the patients included in the LODDS2 group were more prone to nerve invasion (P = 0.0351) and vessel invasion (P < 0.001) with a higher rate of N2 stage, less NDLN (P < 0.001), more NPLN (P < 0.001), more LNR (P < 0.001), and a higher value of ENE (P < 0.001). Based on the results in the univariable analysis, the N, NPLN, LNR, LODDS, and ENE were separately incorporated into five different Cox regression models combined with the same confounders. The multivariable Cox regression analysis demonstrated that all the five staging systems were independent prognostic factors for overall survival., Conclusion: The current study confirmed that the LODDS stage is an independent influence on the prognosis of both CRC and CC patients. ENE is an independent influencing factor on the prognosis of both CRC and CC patients, and the prognostic impact of extracapsular lymph node was observed in both CRC and CC. The frequency of ENE increases from the proximal (right) to the distal (left) colon as well as the rectum. Therefore, combining ENE and LODDS into the current TNM system to compensate for the inadequacy of pN staging needs further investigation., (Copyright © 2021. Published by Elsevier Inc.)

Background: Exposure to ambient air pollution has been reported to be inversely correlated with human reproductive health. However, the results of previous studies exploring the association between air pollution and in vitro fertilization (IVF) outcomes are conflicting, and further research is needed to clarify this association., Objectives: This study aimed to investigate the associations between exposure to air pollutants and IVF outcomes., Methods: We conducted a multicenter retrospective cohort study involving 20,835 patients from four cities in Northern China, contributing to 11,787 fresh embryo transfer cycles, 9050 freeze-all cycles, and 17,676 frozen-thawed embryo transfer (FET) cycles during 2014-2018. We calculated the daily average concentrations of six criteria air pollutants (PM 2.5 , PM 10 , O 3 , NO 2 , CO, and SO 2 ) during different exposure windows in IVF treatment timeline using data from the air monitoring station nearest to the residential site as approximate individual exposure. Generalized estimation equation models were used to assess the association between air pollution exposure and IVF outcomes., Results: Exposure to O 3 , NO 2 , and CO during most exposure windows in fresh embryo transfer cycles were correlated with lower possibilities of biochemical pregnancy, clinical pregnancy, and live birth. An inverse association of exposure to O 3 and SO 2 with pregnancy outcomes was observed in FET cycles. In addition, we found a significant association of exposure to air pollutants with a higher risk of ectopic pregnancy and lower oocyte yield., Conclusions: Our study provided large-scale human evidence of the association between air pollution and adverse human reproductive outcomes in the population opting for IVF. Thus, exposure to air pollutants in the population opting for IVF should be limited to improve treatment outcomes., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Toxic and essential trace elements are associated with human fertility. However, limited studies have been conducted on the relationship between trace elements and in vitro fertilization (IVF) outcomes in the Chinese population. In this exploratory study, 103 couples who underwent IVF/intracytoplasmic sperm injection (ICSI) treatment in our reproductive center were recruited. Serum and follicular fluid (FF) samples and seminal plasma samples were collected from the female and male partners, respectively, on the day of oocyte retrieval. Concentrations of chromium (Cr), nickel (Ni), arsenic (As), selenium (Se), cadmium (Cd), and lead (Pb) in the specimens were measured by inductively coupled plasma-mass spectrometry. Generalized linear models were used to evaluate the associations of toxic and essential trace element levels with the intermediate parameters and outcomes of IVF at both the sex-specific and couple levels. The Cr level in the serum of the female partners was inversely associated with the count of mature oocytes retrieved (p for trend = 0.033). In terms of embryo development, As concentrations in female serum and FF were inversely associated with the probabilities to obtain good-quality cleavage embryos (p for trend < 0.01). There were significant correlations between follicular Se concentrations and seminal As concentrations and higher quality cleavage embryos (p for trend < 0.01). Moreover, a positive correlation was observed between the female serum Se concentrations and blastocyst formation (p for trend = 0.031). In contrast, a higher follicular Se level was negatively correlated with embryo development at the blastocyst stage (p for trend < 0.01). Regarding the clinical outcomes, a positive association of Se levels in seminal plasma and a negative association of follicular Cd levels was observed with the probabilities of pregnancy (p for trend = 0.006 and 0.035, respectively) and live birth (p for trend = 0.014 and 0.027, respectively). The results indicate that exposure to toxic elements (Cr, As and Cd) is associated with intermediate parameters and outcomes of IVF. Furthermore, male Se exposure may be related to better pregnancy outcomes., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder with heterogeneous manifestations and complex etiology. As a leading cause of anovulatory infertility, the molecular diversity of the follicular microenvironment has not been fully elucidated. The aim of the present study was to investigate the follicular fluid proteomic profiles of overweight/obese and normal-weight women with PCOS, to identify novel molecular mechanisms underlying PCOS and to determine the effect of obesity on the follicular fluid protein profiles. Methods: Follicular fluid samples were collected from 3 different groups: overweight/obese PCOS patients ( n = 29), normal-weight PCOS patients ( n = 29), and normo-ovulatory controls ( n = 29). We used a quantitative approach with tandem mass tag labeling and liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins. Differential abundance of four selected proteins was confirmed by ELISA. Gene Set Enrichment Analysis was also conducted to further explore our findings. Furthermore, we compared the clinical, hormonal, and biochemical characteristics of overweight/obese and normal-weight patients with PCOS to determine the effects of obesity. Results: A total of 1,153 proteins were identified, of which 41 and 19 proteins were differentially expressed in the overweight/obese PCOS group vs. the control group, and in the normal-weight PCOS group vs. the control group, respectively. Bioinformatics analyses showed that the inflammatory, immunological, and metabolic-related biological processes were co-enriched in both subgroups of PCOS. Apolipoprotein A-II, complement C5, fetuin-B, and stromal cell-derived factor 1 were found to be involved in various processes and were validated using the ELISA analysis. From clinical features and proteomic data, obesity was found to worsen follicular development disturbances in PCOS. Conclusion: In this proteomic study, a panel of proteins were found differentially expressed in the follicular fluid of PCOS. Inflammatory, immunological, and metabolic abnormalities were identified inside the intra-follicular environment, which could be aggravated by obesity. The identified proteins were correlated with follicular growth and may be considered as candidate biomarkers as well as therapeutic targets of PCOS., (Copyright © 2019 Zhang, Xu, Li, Zhou, Kong, Qiu, Yuan and Tan.)

To assess the associations between air pollution and the pregnancy rate of IVF, we performed a retrospective cohort study on 1455 women who underwent the first fresh IVF cycle at a fertility center from January 2014 to April 2018 and lived in Shenyang during treatment. Binary logistic regression models were used to evaluate the effect of an interquartile range increase in each pollutant on the intrauterine pregnancy rate. Both average chronic and daily acute exposure to air pollution were considered. Increased O 3 (adjusted OR = 0.87, 95% CI: 0.81, 0.98) during the period from gonadotropins starting to oocyte retrieval was associated with decreased probability of intrauterine pregnancy, especially the day before oocyte retrieval (adjusted OR = 0.86, 95% CI: 0.78, 0.95). Our results suggest that exposure to O 3 before oocyte retrieval has an adverse effect on intrauterine pregnancy. Future studies should be performed in order to confirm our findings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Infertility has become a global health issue with the number of couples seeking in vitro fertilization (IVF) worldwide continuing to rise. Some couples remain childless after several IVF cycles. Women undergoing IVF face greater risks and financial burden. A prediction model to predict the live birth chance prior to the first IVF treatment is needed in clinical practice for patients counselling and shaping expectations., Methods: Clinical data of 7188 women who underwent their first IVF treatment at the Reproductive Medical Center of Shengjing Hospital of China Medical University during 2014-2018 were retrospectively collected. Machine-learning based models were developed on 70% of the dataset using pre-treatment variables, and prediction performances were evaluated on the remaining 30% using receiver operating characteristic (ROC) analysis and calibration plot. Nested cross-validation was used to make an unbiased estimate of the generalization performance of the machine learning algorithms., Results: The XGBoost model achieved an area under the ROC curve of 0.73 on the validation dataset and showed the best calibration compared with other machine learning algorithms. Nested cross-validation resulted in an average accuracy score of 0.70 ± 0.003 for the XGBoost model., Conclusions: A prediction model based on XGBoost was developed using age, AMH, BMI, duration of infertility, previous live birth, previous miscarriage, previous abortion and type of infertility as predictors. This study might be a promising step to provide personalized estimates of the cumulative live birth chance of the first complete IVF cycle before treatment.

Clinical named entity recognition (CNER) is a fundamental and crucial task for clinical and translation research. In recent years, deep learning methods have achieved significant success in CNER tasks. However, these methods depend greatly on recurrent neural networks (RNNs), which maintain a vector of hidden activations that are propagated through time, thus causing too much time to train models. In this paper, we propose a residual dilated convolutional neural network with the conditional random field (RD-CNN-CRF) for the Chinese CNER, which makes the model asynchronous in computation and thus speeding up the training period dramatically. To be more specific, Chinese characters and dictionary features are first projected into dense vector representations, then they are fed into the residual dilated convolutional neural network to capture contextual features. Finally, a conditional random field is employed to capture dependencies between neighboring tags and obtain the optimal tag sequence for the entire sequence. Computational results on the CCKS-2017 Task 2 benchmark dataset show that our proposed RD-CNN-CRF method competes favorably with state-of-the-art RNN-based methods both in terms of computational performance and training time.