Deviceization of high-performance and flexible Ag2Se films for electronic skin and servo rotation angle control.

Ag2Se shows significant potential for near-room-temperature thermoelectric applications, but its performance and device design are still evolving. In this work, we design a novel flexible Ag2Se thin-film-based thermoelectric device with optimized electrode materials and structure, achieving a high output power density of over 65 W m-2 and a normalized power density up to 3.68 µW cm-2 K-2 at a temperature difference of 42 K. By fine-tuning vapor selenization time, we strengthen the (013) orientation and carrier mobility of Ag2Se films, reducing excessive Ag interstitials and achieving a power factor of over 29 µW cm-1 K-2 at 393 K. A protective layer boosts flexibility of the thin film, retaining 90% performance after 1000 bends at 60°. Coupled with p-type Sb2Te3 thin films and rational simulations, the device shows rapid human motion response and precise servo motor control, highlighting the potential of high-performance Ag2Se thin films in advanced applications.

Melatonin Ameliorates Abnormal Sleep-Wake Behavior via Facilitating Lipid Metabolism in a Zebrafish Model of Parkinson's Disease.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.

Surface-Enhanced Raman Scatting microfluidic chip based on the identification competition strategy were used for rapid and simultaneous detection of liver cancer related proteins.

Biomarker testing plays a crucial role in the early detection of liver cancer. Herein, we developed a dual-signal amplification approach utilizing magnetic aggregation and a recognition competition strategy for the simultaneous detection of alpha-fetoprotein (AFP) and manganese superoxide dismutase (MnSOD) in serum. 4-MBA@AuNPs@H1 and DTNB@AuNPs@H2 were synthesized by functionalizing Raman signaling molecules and aptamer complementary chains onto the surface of gold nanoparticles (AuNPs). The detection complex Raman signal molecule@AuNPs@H-Fe3O4@cDNA was assembled by conjugating 4-MBA@AuNPs@H1 and DTNB@AuNPs@H2 with two nucleic acid aptamers (cDNA1 and cDNA2) modified with Fe3O4 through partial base complementary pairing. The target protein exhibited specific binding with the aptamer, leading to the competitive displacement of 4-MBA@AuNPs@H1 and DTNB@AuNPs@H2 from the Fe3O4 array surface, consequently resulting in a reduction of the Surface-Enhanced Raman Spectroscopy (SERS) signal. Through this approach, the limit of detection (LOD) for AFP and MnSOD in serum was achieved at remarkably low levels of 5.89 pg/mL and 6.23 pg/mL, respectively, with a reaction incubation period of only 5 min. Finally, the platform was utilized for the quantification of AFP and MnSOD in the serum of a nude mouse hepatocellular carcinoma model. The results obtained through SERS were consistent with those from enzyme-linked immunosorbent assay (ELISA), validating its accuracy. This methodology presents a novel approach for the swift and concurrent detection of proteins, holding significant clinical promise for the early diagnosis of hepatocellular carcinoma.

Association of ambient air pollutant mixtures with IVF/ICSI-ET clinical pregnancy rates during critical exposure periods.

STUDY QUESTION: Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles? SUMMARY ANSWER: The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO2) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy. WHAT IS KNOWN ALREADY: Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods. STUDY DESIGN SIZE DURATION: This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (<8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study. PARTICIPANTS/MATERIALS SETTING METHODS: Daily average levels of six air pollutants (fine particulate matter (PM2.5), inhalable particulate matter (PM10), SO2, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3)) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations. MAIN RESULTS AND THE ROLE OF CHANCE: The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM2.5 during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70-0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69-0.98), and SO2 in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86-0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were observed with dual air pollution models. In the multi-pollution analysis, QG-C indicated a 12% reduction in clinical pregnancy rates per IQR increment of mixed pollutants during specific exposure Period 3 (aOR = 0.89, 95% CI: 0.79-0.99). Among these pollutants, SO2 (33.40%) and NO2 (33.40%) contributed the most to the negative effects. The results from BKMR and QG-C were consistent. Stratified analysis revealed increased susceptibility to ambient air pollution among individuals who underwent transfer of two embryos, those with BMI ≥ 24 kg/m2 and those under 35 years old. LIMITATIONS REASONS FOR CAUTION: Caution was advised in interpreting the results due to the retrospective nature of the study, which was prone to selection bias from non-random sampling. Smoking and alcohol, known confounding factors in IVF/ICSI-ET, were not accounted for. Only successful cycles that reached the hCG test were included, excluding a few patients who did not reach the ET stage. While IDW was used to estimate pollutant concentrations at residential addresses, data on participants' work locations and activity patterns were not collected, potentially affecting the accuracy of exposure prediction. WIDER IMPLICATIONS OF THE FINDINGS: Exposure to a mixture of pollutants, spanning from ET to the serum hCG test (Period 3), appeared to be correlated with a diminished probability of achieving clinical pregnancy. This association suggested a potential impact of mixed pollutants on the interaction between embryos and the endometrium, as well as embryo implantation during this critical stage, potentially contributing to clinical pregnancy failure. This underscored the importance of providing women undergoing ART with comprehensive information to comprehend the potential environmental influences and motivating them to adopt suitable protective measures when feasible, thereby mitigating potential adverse effects of contaminants on reproductive health. STUDY FUNDING/COMPETING INTERESTS: This work received support from the National Key Research and Development Program of China (No. 2023YFC2705900), the National Natural Science Foundation of China (Nos. 82171664, 81971391, 82171668), the Natural Science Foundation of Chongqing Municipality of China (Nos. CSTB2022NSCQ-LZX0062, CSTB2023TIAD-KPX0052) and the Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (No. 2021KFKT013). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

The association of early pregnancy dyslipidemia with preterm birth in twin pregnancies: a retrospective cohort study.

BACKGROUND: Maternal lipid metabolism has been implicated in elevating the risk of adverse pregnancy outcomes, which is a particularly significant concern in twin pregnancies. However, the precise relationship between early pregnancy dyslipidemia and the risk of preterm birth (PTB) in twin pregnancies remains unclear. METHODS: This retrospective cohort study included women with twin pregnancies between January 2018 and December 2023. Early pregnancy blood lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), were examined. Dyslipidemia was diagnosed based on the diagnostic criteria outlined in the 2016 guidelines for the prevention and treatment of dyslipidemia in Chinese adults. PTB was defined as birth occurring before 37 weeks of pregnancy. Logistic regression models were used to evaluate the association of early pregnancy dyslipidemia with PTB in twin pregnancies. RESULTS: A total of 613 women with twin pregnancies were included, and 141 women were complicated with dyslipidemia. The incidence of PTB < 37 weeks was significantly higher in the dyslipidemia group compared to the group without dyslipidemia (64.5% vs. 50.4%, P = 0.003). After adjusting for confounding factors, dyslipidemia was positively associated with PTB < 37 weeks (adjusted odds ratio: 1.71; 95% confidence interval: 1.13-2.58). However, these associations varied depending on the chorionicity and mode of conception of the twins. The positive associations between early pregnancy dyslipidemia and PTB < 37 weeks remained significant only in spontaneously conceived (SC) or dichorionic diamniotic (DCDA) twin pregnancies. No statistically significant associations were observed between dyslipidemia and the other secondary outcomes. CONCLUSION: Early pregnancy dyslipidemia was positively associated with PTB < 37 weeks in twin pregnancies, and this association remained significant in SC or DCDA twin pregnancies. Comprehensive lipid profile assessment in the first trimester may be beneficial for patients' monitoring and implementing interventions to mitigate adverse pregnancy outcomes.

The Effect of Lidocaine-Prilocaine Cream Combined with or Without Remimazolam on VAS and APAIS Anxiety Score in Patient Undergoing Spinal Anesthesia.

Purpose: This study aimed to investigate patients' expectative pain of spinal anesthesia puncture and anxiety pre-anesthesia, and to examine the effect of lidocaine-prilocaine cream and remimazolam prior to spinal anesthesia puncture on pain relief and anxiety release. Methods: Patients undergoing spinal anesthesia were divided into control, lidocaine-prilocaine cream, and lidocaine-prilocaine cream with remimazolam groups. A questionnaire consisting of The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and patient's concerns and Visual Analog Scale (VAS) was used to evaluate patient's anxiety and pain. The primary outcomes were differences in VAS and anxiety scores. Patient's spinal anesthesia-related concerns, advent events and hemodynamic index were also recorded. Results: The expected spinal anesthesia puncture pain was 5.34±0.27 and anxiety scores before spinal anesthesia was 10.88 ± 0.64. A statistically significant positive correlation of 31.3% was detected between VAS and APAIS scores (r = 0.313; P=0.003). The VAS score at the time of puncture decreased by 29.7% (3.78±0.40, P=0.001) in lidocaine-prilocaine cream group and 29.2% (3.75±0.39, P=0.001) in lidocaine-prilocaine cream with remimazolam group compared with the expected VAS score. Lidocaine-prilocaine cream combined with or without remimazolam reduced the percentage of moderate pain (21.4% and 31.3% vs 50.0%, P=0.0001) and increased mild pain (60.7% vs 59.4% vs 22.7%, P=0.03). Anxiety score in lidocaine-prilocaine cream group was reduced by 2.84 (8.04±0.76 vs 10.88 ± 0.46, P=0.05) when compared with pre-anesthesia. Concerns about postoperative pain (P=0.03) and fear of the needle or intervention (P=0.000) both decreased post-anesthesia among groups. Conclusion: Approximately half of the patients scheduled for spinal anesthesia experienced a moderate level of preoperative anxiety. The patient's pain expectation from the spinal anesthesia puncture was moderate, which was higher than the actual pain. Lidocaine-prilocaine cream with or without remimazolam sedative before spinal anesthesia puncture reduced the patient's pain and anxiety scores after surgery.

Fast flow field prediction of pollutant leakage diffusion based on deep learning.

Predicting pollutant leakage and diffusion processes is crucial for ensuring people's safety. While the deep learning method offers high simulation efficiency and superior generalization, there is currently a lack of research on predicting pollutant leakage and diffusion flow field using deep learning. Therefore, it is necessary to conduct further studies in this area. This paper introduces a two-level network method to model the flow characteristics of pollutant diffusion. The proposed method in this study demonstrates a significant enhancement in flow field prediction accuracy compared to traditional deep learning methods. Moreover, it improves computational efficiency by over 800 times compared to traditional computational fluid dynamics (CFD) methods. Unlike conventional CFD methods that require grid expansion to calculate all operation conditions, the deep learning method is not confined by grid limitations. While deep learning methods may not entirely replace CFD methods, they can serve as a valuable supplementary tool, expanding the versatility of CFD methods. The findings of this research establish a robust foundation for incorporating deep learning methods in addressing pollutant leakage and diffusion challenges.

Accumulation of ß-aminoisobutyric acid mediates hyperalgesia in ovariectomized mice through Mas-related G protein-coupled receptor D signaling.

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. ß-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women.

Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization.

BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

Study on the optimal time limit of frozen embryo transfer and the effect of a long-term frozen embryo on pregnancy outcome.

In this retrospective study conducted at Sichuan Jinxin Xinan Women and Children's Hospital spanning January 2015 to December 2021, our objective was to investigate the impact of embryo cryopreservation duration on outcomes in frozen embryo transfer. Participants, totaling 47,006 cycles, were classified into 3 groups based on cryopreservation duration: ≤1 year (Group 1), 1 to 6 years (Group 2), and ≥6 years (Group 3). Employing various statistical analyses, including 1-way ANOVA, Kruskal-Wallis test, chi-square test, and a generalized estimating equation model, we rigorously adjusted for confounding factors. Primary outcomes encompassed clinical pregnancy rate and Live Birth Rate (LBR), while secondary outcomes included biochemical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late miscarriage rates, preterm birth rate, neonatal birth weight, weeks at birth, and newborn sex. Patient distribution across cryopreservation duration groups was as follows: Group 1 (40,461 cycles), Group 2 (6337 cycles), and Group 3 (208 cycles). Postcontrolling for confounding factors, Group 1 exhibited a decreased likelihood of achieving biochemical pregnancy rate, clinical pregnancy rate, and LBR (OR < 1, aOR < 1, P < .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (OR > 1, aOR > 1), notably significant after 6 years of freezing time [aOR = 4.141, 95% confidence intervals (1.013-16.921), P = .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (OR > 1, aOR > 1). No statistically significant differences were observed in birth weight or sex between groups. However, male infant birth rates were consistently higher than those of female infants across all groups. In conclusion, favorable pregnancy outcomes align with embryo cryopreservation durations within 1 year, while freezing for more than 1 year may diminish clinical pregnancy and LBRs, concurrently elevating the risk of ectopic pregnancy and preterm birth.

Disrupted topological properties of structural brain networks present a glutamatergic neuropathophysiology in people with narcolepsy.

STUDY OBJECTIVES: Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy. METHODS: Diffusion tensor imaging was conducted for people with narcolepsy (n = 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. RESULTS: A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA). CONCLUSIONS: People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only closely related to narcolepsy symptoms but also glutamatergic signatures.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis.

BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.

The association of post-embryo transfer SARS-CoV-2 infection with early pregnancy outcomes in in vitro fertilization: a prospective cohort study.

BACKGROUND: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies. OBJECTIVE: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. STUDY DESIGN: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m2, undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes. RESULTS: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71). CONCLUSION: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m2. This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer.

Young obese patients may benefit from GnRH-a long protocol contributing to higher implantation rate and live birth rate of fresh IVF-ET cycles.

Introduction: Obesity has detrimental influences on women reproductive health. There is little experience in optimizing controlled ovarian hyperstimulation (COH) protocols to treat Chinese obese patients who are undergoing in vitro fertilization and embryo transfer (IVF-ET) therapy. Methods: The clinical outcome differences were retrospectively analyzed among obese patients who received gonadotrophin-releasing hormone agonist (GnRH-a), GnRH antagonist (GnRH-ant), micro dose GnRH-a (mGnRH-a) and GnRH-a long protocol in IVF-ET cycle at Chengdu Jinjiang Hospital for Women's and Children's Health from January 2014 to December 2019. Results: The transplantation rate of the GnRH-a long protocol group (59.1%) was higher than that of the GnRH-ant (25.9%) and mGnRH-a (36.7%) groups. The total live birth rate of the GnRH-a long protocol group (46.2%) was higher than that of the GnRH-a group (25.9%) and GnRH-ant group (40.3%). The total number of frozen embryos in the GnRH-ant group was higher than in the other groups (P < 0.05). After adjusting for confounding factors, the logistic regression analysis showed that the GnRH-a long protocol group had higher probabilities of biochemical pregnancy, clinical pregnancy, and live birth than the GnRH-a protocol group. The Gn dose in the mGnRH-a group was higher than the other three groups. Whether single or twin, there were similar neonatal outcomes among the four groups including premature birth rate, Apgar score, newborn weight, and length. Conclusion: For young obese patients undergoing IVF-ET, the GnRH-a long protocol for COH gives better pregnancy outcomes.

Chinese medicine Jiangzhuo mixture regulates glucose and lipid metabolism in obese rats through TLR4/IκBα/NF-κB signaling pathway. / 降浊合剂通过调节TLR4/IκBα/NF-κBä¿¡å·é€šè·¯å½±å“è‚¥èƒ–å¤§é¼ ç³–è„‚ä»£è°¢.

OBJECTIVES: To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats. METHODS: Thirty healthy male SD rats were randomly divided into normal control group, model control group, and Jiangzhuo mixture treatment group, with 10 rats in each group. The rats in the normal control group were fed with normal diet, the obesity model was induced by feeding high-fat diet in the model control group and the Jiangzhuo mixture treatment group, the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage. After 8 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in the three groups. Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP1) in white and brown adipose tissues of the rats in each group; Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats, and Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) and inhibitor of NF-κB alpha (IκBα) in the white adipose tissue; immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues. RESULTS: Compared with the normal control group, the white fat weight (P<0.01), white fat coefficient (P<0.05) and Lee's coefficient (P<0.01) were significantly increased in the model control group; the contents of GLU, TC, TG and LDL-C were all increased, and the content of TG was significantly increased (P<0.05) in the model control group. The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased (P<0.05) in the model control group. Compared with the model control group, the white fat weight and white fat coefficient and Lee's coefficient were significantly reduced in the Jiangzhuo mixture treatment group (all P<0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (P<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all P<0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all P<0.05). CONCLUSIONS: Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.

Effects of doxofylline as an adjuvant on severe exacerbation and long-term prognosis for COPD with different clinical subtypes.

OBJECTIVE: This study aimed to investigate the effectiveness of doxofylline as an adjuvant in reducing severe exacerbation for different clinical subtypes of chronic obstructive pulmonary disease (COPD). METHODS: The clinical trial was an open-label non-randomized clinical trial that enrolled patients with COPD. The patients were divided into two groups (doxofylline group[DG] and non-doxofylline group[NDG]) according to whether the adjuvant was used. Based on the proportion of inflammatory cells present, the patients were divided into neutrophilic, eosinophilic, and mixed granulocytic subtypes. The rates of severe acute exacerbation, use of glucocorticoids, and clinical symptoms were followed up in the first month, the third month, and the sixth month after discharge. RESULTS: A total of 155 participants were included in the study. The average age of the participants was 71.2 ± 10.1 years, 52.3% of the patients were male, and 29.7% of the participants had extremely severe cases of COPD. In the third month after discharge the numbers of patients exhibiting severe exacerbation among the neutrophilic subtype were 5 (6.6%) in the DG versus 17 (22.4%) in the NDG (incidence rate ratio[IRR] = 0.4 [95% CI: 0.2-0.9] P = 0.024). In the sixth month after discharge, the numbers were 3 (3.9%) versus 13 (17.1%; IRR = 0.3 [95%; CI: 0.1-0.9], P = 0.045), and those for the eosinophilic subtype were 0 (0.0%) versus 4 (14.8%), P = 0.02. In the eosinophilic subtype, the results for forced expiratory volume in the first second and maximal mid-expiratory flow were significantly higher in the DG. The mean neutrophil and eosinophil levels were significantly lower than in the NDG among the neutrophilic subtype, and the neutrophil percentage was lower than in the NDG among the eosinophilic subtype. At the six-month follow-up, the dose adjustment rates of the neutrophilic and eosinophilic subtypes showed a significant difference (P< 0.05). CONCLUSIONS: As an adjuvant drug, doxofylline has a good therapeutic effect on patients with the neutrophilic and eosinophilic clinical subtypes of COPD. It can reduce the incidence of severe exacerbation, the use of glucocorticoids, and inflammatory reactions in the long term (when used for a minimum of 3 months).

PWLU: Learning Specialized Activation Functions With the Piecewise Linear Unit.

The choice of activation functions is crucial to deep neural networks. ReLU is a popular hand-designed activation function. Swish, the automatically searched activation function, outperforms ReLU on many challenging datasets. However, the search method has two main drawbacks. First, the tree-based search space is highly discrete and restricted, which is difficult to search. Second, the sample-based search method is inefficient in finding specialized activation functions for each dataset or neural architecture. To overcome these drawbacks, we propose a new activation function called Piecewise Linear Unit (PWLU), incorporating a carefully designed formulation and learning method. PWLU can learn specialized activation functions for different models, layers, or channels. Besides, we propose a non-uniform version of PWLU, which maintains sufficient flexibility but requires fewer intervals and parameters. Additionally, we generalize PWLU to three-dimensional space to define a piecewise linear surface named 2D-PWLU, which can be treated as a non-linear binary operator. Experimental results show that PWLU achieves SOTA performance on various tasks and models, and 2D-PWLU is better than element-wise addition when aggregating features from different branches. The proposed PWLU and its variation are easy to implement and efficient for inference, which can be widely applied in real-world applications.

IL-23/IL-17 immune axis mediates the imiquimod-induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF-κB pathway in macrophages and keratinocytes.

The interleukin-23 (IL-23)/IL-17 immune axis has been linked to the pathology of psoriasis, but how this axis contributes to skin inflammation in this disease remains unclear. We measured inflammatory cytokines associated with the IL-23/IL-17 immune axis in the serum of patients with psoriasis using enzyme-linked immunosorbent assays. Psoriasis was induced in male C57BL/6J mice using imiquimod (IMQ) cream, and animals received intraperitoneal injections of recombinant mouse anti-IL-23A or anti-IL-17A antibodies for 7 days. The potential effects of the IL-23/IL-17 immune axis on skin inflammation were assessed based on pathology scoring, hematoxylin-eosin staining of skin samples, and quantitation of inflammatory cytokines. Western blotting was used to evaluate levels of the following factors in skin: ACT1, TRAF6, TAK1, NF-κB, and pNF-κB. The serum of psoriasis patients showed elevated levels of several cytokines involved in the IL-23/IL-17 immune axis: IL-2, IL-4, IL-8, IL-12, IL-17, IL-22, IL-23, and interferon-γ. Levels of IL-23p19 and IL-17 were increased in serum and skin of IMQ-treated mice, while ACT1, TRAF6, TAK1, NF-κB, and pNF-κB were upregulated in the skin. A large proportion of NF-κB p65 localized in nucleus of involucrin+ cells in the epidermis and in F4/80+ cells of the dermis of psoriatic lesional skin. Treating these animals with anti-IL-23 or anti-IL-17 antibodies improved pathological score and immune imbalance, mitigated skin inflammation and downregulated ACT1, TRAF6, TAK1, NF-κB, and pNF-κB in skin. Our results suggest that skin inflammation mediated by the IL-23/IL-17 immune axis in psoriasis involves activation of the ACT1/TRAF6/TAK1/NF-κB pathway in keratinocytes and macrophage.

Effect of serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte ratio on pregnancy and neonatal outcomes in women undergoing ICSI cycle.

BACKGROUND: The serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte (P/MII) ratio might be a more predictable indicator of pregnancy and neonatal outcomes as compare to P/estradiol (E2) or P alone. Hence, we conducted a larger population study to compare the pregnancy and neonatal outcomes in the low and high P/MII ratio. METHODS: A retrospective, single-center, larger population cohort study between January 2015 and August 2021. Calculate the threshold effect of P/MII ratio on clinical pregnancy rate according to the construct smooth curve fitting. Divide data into two groups by threshold for comparison. RESULTS: 3566 fresh ICSI-ET cycles were included, in which 929 singleton delivery and 676 twin deliveries. Compare to P/MII ≤ 0.367 group, it indicated that the P/MII > 0.367 group had a lower clinical pregnancy rate and live birth rate, furthermore, a significantly higher rate of LBW and SGA were observed in the singleton and twin deliveries. No deleterious impact of high P/MII ratio on embryo quality and undesirable pregnancy outcomes was shown. CONCLUSIONS: When P/MII is higher than 0.367, may have adverse impacts on pregnancy and neonatal outcomes for ICSI cycle.