Dihydroorotase MoPyr4 is required for development, pathogenicity, and autophagy in rice blast fungus.

Dihydroorotase (DHOase) is the third enzyme in the six enzymatic reaction steps of the endogenous pyrimidine nucleotide de novo biosynthesis pathway, which is a metabolic pathway conserved in both bacteria and eukaryotes. However, research on the biological function of DHOase in plant pathogenic fungi is very limited. In this study, we identified and named MoPyr4, a homologous protein of Saccharomyces cerevisiae DHOase Ura4, in the rice blast fungus Magnaporthe oryzae and investigated its ability to regulate fungal growth, pathogenicity, and autophagy. Deletion of MoPYR4 led to defects in growth, conidiation, appressorium formation, the transfer and degradation of glycogen and lipid droplets, appressorium turgor accumulation, and invasive hypha expansion in M. oryzae, which eventually resulted in weakened fungal pathogenicity. Long-term replenishment of exogenous uridine-5'-phosphate (UMP) can effectively restore the phenotype and virulence of the ΔMopyr4 mutant. Further study revealed that MoPyr4 also participated in the regulation of the Pmk1-MAPK signaling pathway, co-localized with peroxisomes for the oxidative stress response, and was involved in the regulation of the Osm1-MAPK signaling pathway in response to hyperosmotic stress. In addition, MoPyr4 interacted with MoAtg5, the core protein involved in autophagy, and positively regulated autophagic degradation. Taken together, our results suggested that MoPyr4 for UMP biosynthesis was crucial for the development and pathogenicity of M. oryzae. We also revealed that MoPyr4 played an essential role in the external stress response and pathogenic mechanism through participation in the Pmk1-MAPK signaling pathway, peroxisome-related oxidative stress response mechanism, the Osm1-MAPK signaling pathway and the autophagy pathway.

Csn5 inhibits autophagy by regulating the ubiquitination of Atg6 and Tor to mediate the pathogenicity of Magnaporthe oryzae.

Csn5 is subunit 5 of the COP9 signalosome (CSN), but the mechanism by which it strictly controls the pathogenicity of pathogenic fungi through autophagy remains unclear. Here, we found that Csn5 deficiency attenuated pathogenicity and enhanced autophagy in Magnaporthe oryzae. MoCSN5 knockout led to overubiquitination and overdegradation of MoTor (the core protein of the TORC1 complex [target of rapamycin]) thereby promoted autophagy. In addition, we identified MoCsn5 as a new interactor of MoAtg6. Atg6 was found to be ubiquitinated through linkage with lysine 48 (K48) in cells, which is necessary for infection-associated autophagy in pathogenic fungi. K48-ubiquitination of Atg6 enhanced its degradation and thereby inhibited autophagic activity. Our experimental results indicated that MoCsn5 promoted K48-ubiquitination of MoAtg6, which reduced the MoAtg6 protein content and thus inhibited autophagy. Aberrant ubiquitination and autophagy in ΔMocsn5 led to pleiotropic defects in the growth, development, stress resistance, and pathogenicity of M. oryzae. In summary, our study revealed a novel mechanism by which Csn5 regulates autophagy and pathogenicity in rice blast fungus through ubiquitination.

Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer.

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.

Availability of family care resources, bathing assistance and toileting assistance among older adults with functional limitations: an evidence-based study from China.

BACKGROUND: An aging population has contributed to an increasing prevalence of functional limitations among older adults. Family support plays a crucial role in toileting and bathing assistance. Yet, the relationship between availability of family care resources and such actual assistance remains insufficiently explored. Our study aims to describe availability of family care resources and identify the association between availability of family care resources and toileting assistance or bathing assistance. METHODS: This study employed a cross-sectional analysis of data from the 2018 National Survey of the China Health and Retirement Longitudinal Study (CHARLS). The availability of family care resources was assessed using measurements of spouse availability, adult child availability, and living arrangement. Bathing assistance and toileting assistance were measured based on self-reported receipt of such assistance. Descriptive statistics were used to depict the overall and subgroup situation of availability of family care resources. Multivariable logistic models were employed to investigate the relationship between availability of family care resources and the receipt of toileting assistance or bathing assistance. RESULTS: Among the sample of older adults with functional limitations, 69% had a spouse, 63% had at least one adult child, and 80% resided with family members. Among those with bathing disability, 13% reported lacking bathing assistance, and among those with toileting disability, 54% reported lacking toileting assistance. Participants with 1-2 adult children had lower odds of receiving toileting assistance (OR: 0.28, 95% CI: 0.09, 0.91, p= 0.034) compared to those with three or more adult children. Spouse availability and living arrangement did not exhibit statistically significant associations with toileting assistance. Participants without a spouse had lower odds of receiving bathing assistance (OR: 0.27, 95% CI: 0.09-0.78, p= 0.016) in comparison to those with a spouse; however, adult child availability and living arrangement did not display statistically significant associations with bathing assistance. CONCLUSION: The present findings suggest a gap in family commitment when it comes to assisting older adults with functional limitations in bathing/toileting. To address this, policymakers are encouraged to prioritize the implementation of proactive mechanisms for identifying family caregivers, alongside incentives to enhance their engagement in practical caregiving activities. Furthermore, it is crucial to emphasize the prioritization of affordable and easily accessible formal toileting/bathing assistance options for older adults who lack sufficient family care resources.

Electrochemical Synthesis of C(sp3)-Rich Amines by Aminative Carbofunctionalization of Carbonyl Compounds.

Alkylamines form the backbone of countless nitrogen-containing small molecules possessing desirable biological properties. Despite advances in amine synthesis through transition metal catalysis and photoredox chemistry, multicomponent reactions that leverage inexpensive materials to transform abundant chemical feedstocks into three-dimensional α-substituted alkylamines bearing complex substitution patterns remain scarce. Here, we report the design of a catalyst-free electroreductive manifold that merges amines, carbonyl compounds and carbon-based radical acceptors under ambient conditions without rigorous exclusion of air and moisture. Key to this aminative carbofunctionalization process is the chemoselective generation of nucleophilic α-amino radical intermediates that readily couple with electrophilic partners, providing straightforward access to architecturally intricate alkylamines and drug-like scaffolds which are inaccessible by conventional means.

NPI-GNN: Predicting ncRNA-protein interactions with deep graph neural networks.

Noncoding RNAs (ncRNAs) play crucial roles in many biological processes. Experimental methods for identifying ncRNA-protein interactions (NPIs) are always costly and time-consuming. Many computational approaches have been developed as alternative ways. In this work, we collected five benchmarking datasets for predicting NPIs. Based on these datasets, we evaluated and compared the prediction performances of existing machine-learning based methods. Graph neural network (GNN) is a recently developed deep learning algorithm for link predictions on complex networks, which has never been applied in predicting NPIs. We constructed a GNN-based method, which is called Noncoding RNA-Protein Interaction prediction using Graph Neural Networks (NPI-GNN), to predict NPIs. The NPI-GNN method achieved comparable performance with state-of-the-art methods in a 5-fold cross-validation. In addition, it is capable of predicting novel interactions based on network information and sequence information. We also found that insufficient sequence information does not affect the NPI-GNN prediction performance much, which makes NPI-GNN more robust than other methods. As far as we can tell, NPI-GNN is the first end-to-end GNN predictor for predicting NPIs. All benchmarking datasets in this work and all source codes of the NPI-GNN method have been deposited with documents in a GitHub repo (https://github.com/AshuiRUA/NPI-GNN).

Dynamic Cerebral Autoregulation After Carotid Endarterectomy.

OBJECTIVE: Studies have shown that dynamic cerebral autoregulation (dCA) is impaired in patients with severe internal carotid artery (ICA) stenosis and that carotid endarterectomy (CEA) may improve dCA in these patients. However, the time course of dCA changes in patients after CEA remains unclear. Therefore, this study aimed to investigate the effects of CEA on the dCA in patients with carotid artery stenosis at different time points. METHODS: This prospective study enrolled 44 patients (19 symptomatic stenosis patients and 25 asymptomatic stenosis patients) who underwent CEA and 44 age- and sex-matched controls. In the CEA group, the patients underwent dCA measurements at baseline, within 3 days, and 1 month after CEA. Transfer function parameters, phase difference (PD), and gain were used to quantify dCA. Changes in dCA before and after CEA were analyzed in detail. RESULTS: The bilateral PD of the patients before CEA was significantly lower than that of the control group. This damage did not improve within 3 days after surgery. One month after surgery, the PD on the affected side of the patients significantly improved compared with before surgery and reached the level of the control group. The PD of affected side across time points in symptomatic and asymptomatic stenosis patients is consistent with that in all patients. CONCLUSIONS: The dCA level did not improve immediately after CEA but significantly improved 1 month after surgery. This suggests that the occurrence of stroke should be considered in the acute period after CEA surgery, and its preventive effect on stroke may be effective after 1 month. CLINICAL IMPACT: We found the dCA level did not improve immediately after CEA but significantly improved 1 month after surgury. This suggests that the occuttencce of stroke and surgical complications (such as cerebral hyperperfusion syndrome) associated with impaired dCA in the acute phase after CEA surgery should be of particular concern.

Impact on etiology diagnosis by high-resolution vessel wall imaging in young adults with ischemic stroke or transient ischemic attack.

PURPOSE: The etiological features of stroke in young adults are different from those in older adults. We aimed to investigate the impact of high-resolution vessel wall imaging (HRVWI) on etiologic diagnosis in young adults with ischemic stroke or transient ischemic attack (TIA). METHODS: A total of 253 young adults (aged 18-45 years) who consecutively underwent HRVWI for clarifying stroke etiology were retrospectively recruited. Two experienced neurologists classified stroke etiology for each patient using Trial of Org 10,172 in Acute Stroke Treatment categories with and without the inclusion of HRVWI diagnosis. Multivariate logistic regression was performed to determine which etiologic category would be significantly impacted after including HRVWI. RESULTS: The etiologic classification was altered in 39.1% (99/253) of patients after including HRVWI in the conventional investigations. The proportion of patients classified as having stroke of undetermined etiology (SUE) and the proportion of patients classified as having small-artery occlusion (SAO) both significantly decreased (36.4 to 13.8% and 9.1 to 2.0%), whereas the proportion of patients classified as having large artery atherosclerosis (LAA) significantly increased (28.5 to 58.1%) (all P < 0.001). The inclusion of HRVWI had a significant diagnostic impact on young adults who were primarily classified as SAO (odds ratio [OR] 14.4, 95% confidence interval [CI] [2.9, 71.8], P < 0.001) or SUE (OR 8.3, 95% CI [2.2, 31.5], P < 0.01). CONCLUSIONS: HRVWI had a substantial impact on etiologic classification in young adults with ischemic stroke or TIA, particularly for those primarily classified as having SAO or SUE. This impact of HRVWI will be beneficial for therapeutic decision-making.

MoCbp7, a Novel Calcineurin B Subunit-Binding Protein, Is Involved in the Calcium Signaling Pathway and Regulates Fungal Development, Virulence, and ER Homeostasis in Magnaporthe oryzae.

Calcineurin, a key regulator of the calcium signaling pathway, is involved in calcium signal transduction and calcium ion homeostasis. Magnaporthe oryzae is a devastating filamentous phytopathogenic fungus in rice, yet little is known about the function of the calcium signaling system. Here, we identified a novel calcineurin regulatory-subunit-binding protein, MoCbp7, which is highly conserved in filamentous fungi and was found to localize in the cytoplasm. Phenotypic analysis of the MoCBP7 gene deletion mutant (ΔMocbp7) showed that MoCbp7 influenced the growth, conidiation, appressorium formation, invasive growth, and virulence of M. oryzae. Some calcium-signaling-related genes, such as YVC1, VCX1, and RCN1, are expressed in a calcineurin/MoCbp7-dependent manner. Furthermore, MoCbp7 synergizes with calcineurin to regulate endoplasmic reticulum homeostasis. Our research indicated that M. oryzae may have evolved a new calcium signaling regulatory network to adapt to its environment compared to the fungal model organism Saccharomyces cerevisiae.

Core-Shell Reactor Partitioning Enzyme and Prodrug by ZIF-8 for NADPH-Sensitive In Situ Prodrug Activation.

Enzyme-prodrug therapies have shown unique advantages in efficiency, selectivity, and specificity of in vivo prodrug activation. However, precise spatiotemporal control of both the enzyme and its substrate at the target site, preservation of enzyme activity, and in situ substrate depletion due to low prodrug delivery efficiency continue to be great challenges. Here, we propose a novel core-shell reactor partitioning enzyme and prodrug by ZIF-8, which integrates an enzyme with its substrate and increases the drug loading capacity (DLC) using a prodrug as the building ligand to form a Zn-prodrug shell. Cytochrome P450 (CYP450) is immobilized in ZIF-8, and the antitumor drug dacarbazine (DTIC) is coordinated and deposited in its outer layer with a high DLC of 43.6±0.8 %. With this configuration, a much higher prodrug conversion efficiency of CYP450 (36.5±1.5 %) and lower IC50 value (26.3±2.6 µg/mL) are measured for B16-F10 cells with a higher NADPH concentration than those of L02 cells and HUVECs. With the tumor targeting ability of hyaluronic acid, this core-shell enzyme reactor shows a high tumor suppression rate of 96.6±1.9 % and provides a simple and versatile strategy for enabling in vivo biocatalysis to be more efficient, selective, and safer.

Reducing circuit complexity in optical quantum computation using 3D architectures.

Integrated photonic architectures based on optical waveguides are one of the leading candidates for the future realisation of large-scale quantum computation. One of the central challenges in realising this goal is simultaneously minimising loss whilst maximising interferometric visibility within waveguide circuits. One approach is to reduce circuit complexity and depth. A major constraint in most planar waveguide systems is that beamsplitter transformations between distant optical modes require numerous intermediate SWAP operations to couple them into nearest neighbour proximity, each of which introduces loss and scattering. Here, we propose a 3D architecture which can significantly mitigate this problem by geometrically bypassing trivial intermediate operations. We demonstrate the viability of this concept by considering a worst-case 2D scenario, where we interfere the two most distant optical modes in a planar structure. Using femtosecond laser direct-writing technology we experimentally construct a 2D architecture to implement Hong-Ou-Mandel interference between its most distant modes, and a 3D one with corresponding physical dimensions, demonstrating significant improvement in both fidelity and efficiency in the latter case. In addition to improving fidelity and efficiency of individual non-adjacent beamsplitter operations, this approach provides an avenue for reducing the optical depth of circuits comprising complex arrays of beamsplitter operations.

Pulmonary function changes after sublobar resection in patients with peripheral non-subpleural nodules.

BACKGROUND: In the treatment of peripheral early-staged lung cancer and benign lesions, segmentectomy and wedge resection are both reliable treatment methods. It is debatable that how much pulmonary function will be lost after different sublobar resection in the treatment of early-staged deep-located peripheral NSCLC (non-small cell lung cancer). The purpose of this study was to explore postoperative pulmonary function changes of sublobar resection in enrolled patients with non-subpleural peripheral nodules. METHODS: We collected clinical data of patients undergoing VATS (video-assisted thoracoscopic surgery) segmentectomy or wedge resection for single nodule. These nodules were confirmed as peripheral non-subpleural nodules by preoperative 3D imaging. Patients were divided into two groups according to the operation procedure. Demographic characteristics, pulmonary function, postoperative outcomes, and others were collected. All data was gathered at the First Affiliated Hospital of Soochow University. Outcomes after wedge resection were compared with those after segmentectomy resection. RESULTS: A total of 88 patients were included in this study, including 46 patients with VATS wedge resection and 42 patients with VATS segmentectomy. No difference was detected when comparing FEV1 (forced expiratory volume in 1 s) loss between these two groups (17.6 ± 2.1%, wedge resection vs. 19.4 ± 5.4%, segmentectomy, P = 0.176). FVC (forced vital capacity) loss (8.7 ± 2.3%, wedge resection vs. 17.1 ± 2.2%, segmentectomy, P < 0.001) and MVV (maximum ventilatory volume) loss (11.5 ± 3.1%, wedge resection vs. 20.6 ± 7.8%, segmentectomy, P < 0.001) in segmentectomy group was significantly higher than those in wedge resection group. Discrepancies were investigated when comparing duration of surgery (70 ± 22 min, wedge resection vs. 111 ± 52 min, segmentectomy, P = 0.0002), postoperative drainage (85 ± 45 mL, wedge resection vs. 287 ± 672 mL, segmentectomy, P = 0.0123), and treatment hospitalization expenses [35148 ± 889CNY, wedge resection vs. 52,502 (38,276-57,772) CNY, segmentectomy, P < 0.0002]. No significant difference was found between air leak time (1.7 ± 0.7 days, wedge resection vs. 2.5 ± 1.7 days, segmentectomy, P = 0.062) and hospitalization time (2.7 ± 0.7 days, wedge resection vs. 3.5 ± 1.7 days, segmentectomy, P = 0.051). CONCLUSIONS: For patients with peripheral non-subpleural nodules, we observed that patients who underwent wedge resection had less lung function loss than those who underwent segmentectomy when their lung function was reviewed at the 6th month after surgery. Patients undergoing wedge resection had partial advantages over patients with segmental resection in terms of hospitalization cost, operation time and postoperative drainage, etc. Wedge resection, as a treatment for peripheral non-subpleural pulmonary nodules, seemed to have more advantages in preserving patients' pulmonary function.

[Analysis of Nursery Services for Children under 3 in Sichuan Province Based on the Theory of Supply and Demand Adaptability].

Objective: To analyze the supply and demand adaptation of nursery care services for children under 3 in Sichuan Province and to provide strategic suggestions for optimizing nursery care services in Sichuan Province. Methods: Data on the supply and demand of nursery school services in all 21 cities (prefectures) of Sichuan Province were collected with questionnaires for nursery care institutions and family needs questionnaires. Applying the theory of supply and demand adaptability, we analyzed the adaptability of nursery care services in Sichuan Province in four dimensions, including relevance, adaptability, accessibility and quality. Results: A total of 6883 valid institutional questionnaires and 41081 valid family questionnaires were collected. The analysis of the adaptability of supply and demand showed that there was insufficient adaptability in all four dimensions of relevance, adaptability, accessibility, and quality of nursery care services for children under 3 in Sichuan Province, which was characterized by the coexistence of insufficient supply and underutilization of services, the mismatch between the structure of services provided and the needs of families with children under 3, low economic accessibility for the general population, and low quality of services. Conclusion: There is insufficient adaptability in the supply and demand of nursery care services for children under 3 in Sichuan Province. Demand-oriented supply-side reforms should be implemented to promote the construction of a system of government-subsidized affordable nursery care services, reinforced support for the care of infants and toddlers for families, standardized management of infant and toddler care institutions, and the implementation of various supportive policies so as to comprehensively meet the diversified needs of infant and toddler care and promote their healthy growth.

[Effect of Family Function on Suicide-Related Behaviors of Junior Middle School Students: The Mediating Effect of Depression].

Objective: To examine the prevalence of suicide-related behaviors among junior middle school students, and to explore the mediating role of depression in the relationship between suicide-related behaviors and family function. Methods: A total of 2572 junior middle school students from three middle schools in Chengdu were interviewed face-to-face by using suicide-related items from Youth Risk Behavior Surveillance System (YRBSS), Chinese Family Assessment Instrument (C-FAI), and Center for Epidemiologic Studies Depression Scale for Children (CES-DC). The mediating role of depression was analyzed with structural equation model. Results: The prevalence of suicide-related behaviors was 26.01% among the respondents. The prevalence of suicide ideation, suicide plan and suicide attempt were 24.38%, 13.49% and 10.77%, respectively. Depression played a partial mediating role in how family function impacted on suicide-related behaviors, presenting a direct effect value of 0.170 (95% CI: 0.117-0.218, P<0.001) and an indirect effect value of 0.205 (95% CI: 0.176-0.234, P<0.001), with the mediating effect accounting for 54.67% of the total effect. Conclusion: Poor family function may increase the risk of suicide-related behaviors, and this effect is produced mostly through the impact on children's mental health. Improving family function will not only improve children's psychological status, but also reduce suicide-related behaviors.

Characterization of the Sperm Proteome and Reproductive Outcomes with in Vitro, Fertilization after a Reduction in Male Ejaculatory Abstinence Period.

Semen samples from men after a short ejaculatory abstinence show improved sperm quality and result in increased pregnancy rates, but the underlying mechanisms remain unclear. Herein, we report that ejaculates from short (1-3 h) compared with long (3-7 days) periods of abstinence showed increases in motile sperm count, sperm vitality, normal sperm morphology, acrosome reaction capacity, total antioxidant capacity, sperm mitochondrial membrane potential, high DNA stainability, and a decrease in the sperm DNA fragmentation index (p, < 0.05). Sperm proteomic analysis showed 322 differentially expressed proteins (minimal fold change of ±1.5 or greater and p, < 0.05), with 224 upregulated and 98 downregulated. These differentially expressed proteins are profoundly involved in specific cellular processes, such as motility and capacitation, oxidative stress, and metabolism. Interestingly, protein trimethyllysine modification was increased, and butyryllysine, propionyllysine, and malonyllysine modifications were decreased in ejaculates from a short versus, long abstinence (p, < 0.05). Finally, the rates of implantation, clinical pregnancy, and live births from in vitro, fertilization treatments were significantly increased in semen samples after a short abstinence. Our study provides preliminary mechanistic insights into improved sperm quality and pregnancy outcomes associated with spermatozoa retrieved after a short ejaculatory abstinence.

The role and possible mechanism of long noncoding RNA PVT1 in modulating 3T3-L1 preadipocyte proliferation and differentiation.

Obesity is considered as a high-risk susceptibility state for most metabolic disorders and is directly related to preadipocyte differentiation or adipogenesis. Long noncoding RNAs (lncRNAs) are the key factors which have regulatory functions on various critical physiological and biological processes. PVT1 was identified as an oncogenic lncRNA which could promote angiogenesis in gastric cancer. However, the functions and molecular pathways related to PVT1 in adipogenesis had not been clarified yet. In the current study, the purpose was to identify the effects of lncRNA PVT1 on adipogenesis and the relevant molecular processes. Quantitative real-time polymerase chain reaction (RT-qPCR) was used to quantify PVT1 expression. The mechanism for PVT1 to participate in 3T3-L1 adipogenesis was identified by lentivirus-mediated gain- and loss-of-function tests. The potential association of PVT1 with cell viability was checked by CCK-8 assay and EdU staining. The gene expression for cytokines was determined by quantitative PCR (qPCR) and western blotting. PVT1 expression level was strongly upregulated after 3T3-L1 preadipocytes differentiated. In mice, PVT1 was abundantly expressed in adipose tissue, and the obese mice had higher PVT1 expression in adipose tissue than that of nonobese mice. Predominantly, PVT1 was found inside the nuclei. Overexpressed PVT1 could promote 3T3-L1 adipocyte differentiation as proved, which was the cause for the ability to accelerate lipid accumulation, by upregulating the expression of peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein α, and adipocyte protein 2, while knockdown of PVT1 caused opposite effects. The RNA immunoprecipitation demonstrated the binding relationship between PVT1 and STAT3 suggesting the potential role of STAT3 in 3T3-L1 preadipocyte differentiation. Furthermore, PVT1 could promote fatty acid synthesis but inhibit fatty acid oxidation. PVT1 was positively associated with 3T3-L1 preadipocyte differentiation, which highlighted the potential of PVT1 as a therapeutic target for obesity treatment.

Experimental composable security decoy-state quantum key distribution using time-phase encoding.

Quantum key distribution (QKD) promises provably secure communications. In order to improve the secret key rate, combining a biased basis choice with the decoy-state method is proposed. Concomitantly, there is a basis-independent detection efficiency condition, which usually cannot be satisfied in a practical system, such as the time-phase encoding. Fortunately, this flaw has been recently removed theoretically and experimentally in the four-intensity decoy-state BB84 QKD protocol using the fact that the expected yields of single-photon states prepared in two bases stay the same for a given measurement basis. However, the security proofs do not fully consider the finite-key effects for general attacks. In this work, we provide the rigorous finite-key security bounds in the universally composable framework for the four-intensity decoy-state BB84 QKD protocol. We build a time-phase encoding system with 200 MHz clock to implement this protocol, in which the real-time secret key rate is more than 60 kbps over 50 km single-mode fiber.

Selective serotonin reuptake inhibitor use during early pregnancy and congenital malformations: a systematic review and meta-analysis of cohort studies of more than 9 million births.

BACKGROUND: In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication. METHODS: The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs). RESULTS: Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32). CONCLUSIONS: The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.

Autophagy is activated in the ovarian tissue of polycystic ovary syndrome.

The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased. In addition, the ratio of LC3-II/LC3-I was markedly elevated in human PCOS ovarian tissue compared with normal ovarian tissue. Real-time PCR arrays indicated that 7 and 34 autophagy-related genes were down- and up-regulated in human PCOS , Signal-Net, and regression analysis suggested that there are a wide range of interactions among these 41 genes, and a potential network based on EGFR, ERBB2, FOXO1, MAPK1, NFKB1, IGF1,TP53 and MAPK9 may be responsible for autophagy activation in PCOS. Systematic functional analysis of 41 differential autophagy-related genes indicated that these genes are highly involved in specific cellular processes such as response to stress and stimulus, and are linked to four significant pathways, including the insulin, ERBB, mTOR signaling pathways and protein processing in the endoplasmic reticulum. This study provides evidence for a potential role of autophagy disorders in PCOS in which autophagy may be an important molecular event in the pathogenesis of PCOS.

Assessment of the development of assisted reproductive technology in Liaoning province of China, from 2012 to 2016.

BACKGROUND: The development of assisted reproduction techniques (ART) has resulted in rapid advances in the treatment of infertility. However, a systematic assessment of ART and its processes and outcomes in China has never been carried out. The goal of this study was to assess the features of ART status from 2012 to 2016 in clinics and in vitro fertilization (IVF) laboratories in Liaoning, the largest IVF province in the northeast of China. METHODS: Data from Jan 1, 2012 to Dec 31, 2016 was retrieved from the assisted reproductive certificate registry of Liaoning province. We extracted data from: i) fresh and thawed cycles; ii) donor sperm and donor egg cycles; iii) intrauterine insemination with husband semen and donor semen (AIH and AID). RESULTS: We showed that: (i) there has been a significant increase in the number of IVF fresh and thawed cycles, and the proportion of cases of primary infertility and secondary infertility has decreased and increased, respectively; (ii) standard long GnRH agonist was the major ovarian stimulation protocol. During the observation period, increasing trends in the use of GnRH antagonists, mild stimulation, and natural cycles were observed; (iii) significant differences in the number of cycles, number of retrieved oocytes, fertilization rates, implantation rates, and sex ratio were noticed between conventional IVF and intracytoplasmic sperm injection; (iv) significant differences in age at treatment for infertility, number of cycles, and ectopic pregnancy rates were noticed between donor sperm cycles and donor egg cycles; (v) significant differences in number of thawed cycles, number of thawed embryos, embryo recovery rates, implantation rates, and clinical pregnancy rates were noticed between day 3 and day 5 embryos; (vi) significant differences in age at treatment for infertility, number of cycles, clinical pregnancy rates, ectopic pregnancy rates, and live birth ratio were noticed between AIH and AID. CONCLUSIONS: ART in Liaoning province has undergone substantial development from 2012 to 2016 in clinics and IVF laboratories. This presentation of detailed ART data will provide researchers, policy makers, and potential ART users a rich source of information about IVF characteristics in the northeast of China.