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Abstract We conducted a retrospective study to investigate risk factors for tuberculosis care-seeking delay and diagnostic delays among pediatric pulmonary tuberculosis cases in Zhejiang Province from 2013 to 2022. Among 1274 cases, 49.61% experienced tuberculosis care-seeking delays (> 14 days from symptom onset to first hospital visit) and 14.91% faced diagnostic delays (> 14 days from initial consultation to diagnosis). The proportion of care-seeking delays ranged from 37.42 to 64.89%, while diagnostic delay fluctuated from 6.11 to 21.02%. Urban residence (OR = 0.78, 95% CI 0.62–0.98, P = 0.030), first visiting a municipal-level hospital (OR = 0.57, 95% CI 0.45–0.72, P

ObjectiveTo analyze transmission characteristics of a coronavirus disease 2019 (COVID-19) outbreak caused by Omicron variant BA.5.2 in Yiwu city of Zhejiang province, China. MethodsMedical records and the information on epidemiological investigation, laboratory tests were collected for all local COVID-19 cases diagnosed during August 2 – 21, 2022 – a period of an COVID-19 outbreak in Yiwu city. The transmission characteristics of the outbreak was analyzed using indicators including family secondary attack rate, transmission generations (TG), serial interval (SI), the time interval from symptom onset to positive nucleic acid test, as well as time-varying reproduction number (Rt). ResultsThe indicator case of the outbreak was confirmed with the history of living in high-risk area of other provinces and close contact with COVID-19 infected persons 7 days before the onset of disease symptoms. Genome sequencing of the virus isolated from the indicator case's secondary cases indicated that the viral strain of the outbreak was severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant BA.5.2. Totally 713 cases (343 males and 370 females) from 13 subdistricts (except for Chi'an township) of Yiwu city were confirmed during the outbreak lasting for 20 days. The median age of the cases (percentile 25 [P25], percentile 75[P75]) was 33 (20, 74) years. A total of 138 household clusters (involving 74.2% of all infections) were identified in the outbreak. For the 101 household clusters with clear transmission chain, the secondary attack rate was 62.2% (95% confidence interval: 56.5% – 67.5%); 39.6% of the household clusters affected all family members of the households involved; the median TG (P25, P75) was 1.7 (1.0, 2.8) days for the primary cases and 197 secondary cases and the TG was equal or less than 2 days for 50.8% of the cases being involved. For 65 household clusters, the median SI (P25, P75) was 2.0 （1.0，3.0）days for the primary cases and 99 secondary cases with clinic symptoms and the SI was equal or less than 2 days for 44.4% of the cases being involved. Of the 364 cases (51.1% of the cases undergoing epidemiological surveys) with self-reported symptoms, 64.3%, 23.4%, and 20.1% reported fever, cough, and sore/dry throat, respectively. For the 364 symptomatic cases, the median time interval (P25, P75) from symptom onset to positive nucleic acid test was 0（0，1）day and the time interval was one day for 67.7% of the cases and two days for 22.6% of the cases. No significant differences were observed in gender, age, site and daily time point of specimen sampling for nucleic acid test, and cycle threshold (Ct) value between the cases with and without lag time (day) of positive nucleic acid test from symptom onset. The maximum Rt was 6.18 in early period of the COVID-19 outbreak and the Rt decreased to less than one week after the implementation of containment measures. ConclusionThe COVID-19 outbreak caused by Omicron variant BA.5.2 was characterized by high family secondary attack rate, short transmission generation and serial interval, and a high proportion of cases with lag time of positive nucleic acid test from symptom onset.

IntroductionThe COVID-19 pandemic continues to ravage the world, and mutations of the SARS-CoV-2 continues. The new strain has become more transmissible. The role of aerosol transmission in the pandemic deserves great attention.MethodsIn this observational study, we collected data from market customers and stallholders who had been exposed to the virus in the Qingkou night market on July 31 and were subsequently infected. We analyzed the possible infection zones of secondary cases and aerosol suspension time in ambient air. We described and analyzed the characteristics of the secondary cases and the transmission routes for customers.ResultsThe point source outbreak of COVID-19 in Qingkou night market contained a cluster of 131 secondary cases. In a less-enclosed place like the Qingkou night market, aerosols with BA.5.2 strain released by patients could suspend in ambient air up to 1 h 39 min and still be contagious.ConclusionAerosols with viruses can spread over a relatively long distance and stay in ambient air for a long time in a less enclosed space, but shorter than that under experimental conditions. Therefore, the aerosol suspension time must be considered when identifying and tracing close contact in outbreak investigations.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

Metabolic reprogramming is a core hallmark of cancer and is key for tumorigenesis and tumor progression. Investigation of metabolic perturbation by anti-cancer compounds would allow a thorough understanding of the underlying mechanisms of these agents and identification of new anti-cancer targets. Here, we demonstrated that the administration of oleanolic acid (OA) rapidly altered cancer metabolism, particularly suppressing the purine salvage pathway (PSP). PSP restoration significantly opposed OA-induced DNA replication and cell proliferation arrest, underscoring the importance of this pathway for the anti-cancer activity of OA. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and 5′-nucleotidase (5′-NT), two metabolic enzymes essential for PSP activity, were promptly degraded by OA via the lysosome pathway. Mechanistically, OA selectively targeted superoxide dismutase 1 (SOD1) and yielded reactive oxygen species (ROS) to activate the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/macroautophagy pathway, thus eliciting lysosomal degradation of HGPRT and 5′-NT. Furthermore, we found that the PSP was overactivated in human lung and breast cancers, with a negative correlation with patient survival. The results of this study elucidated a new anti-cancer mechanism of OA by restraining the PSP via the SOD1/ROS/AMPK/mTORC1/macroautophagy/lysosomal pathway. We also identified the PSP as a new target for cancer treatment and highlighted OA as a potential therapeutic agent for cancers with high PSP activity.

To improve the accuracy of personnel positioning in underground coal mines, in this paper, we propose a convolutional neural network (CNN) three-dimensional (3D) visible light positioning (VLP) system based on the Inception-v2 module and efficient channel attention mechanism. The system consists of two LEDs and four photodetectors (PDs), with the four PDs on the miner’s helmet. Considering the height fluctuation of PD and the impact of wall reflection on the received light power, we adopt the Inception module to perform a multi-scale extraction of the features of the received light power, thus solving the limitation of the single-scale convolution kernel on the positioning accuracy. In order to focus on the information that is more critical to positioning among the numerous input features, giving different features of the optical power data corresponding weights, we use an efficient channel attention mechanism to make the positioning model more accurate. The simulation results show that the average positioning error of the system was 1.63 cm in the space of 6 m × 3 m × 3.6 m when both the line-of-sight (LOS) and non-line-of-sight (NLOS) links were considered, with 90% of the localization errors within 4.55 cm. During the experimental stage, the average positioning error was 11.12 cm, with 90% of the positioning errors within 28.75 cm. These show that the system could achieve centimeter-level positioning accuracy and meet the requirements for underground personnel positioning in coal mines.

Abstract Background Hypotension following spinal anesthesia (SA) during cesarean delivery (CD) occurs commonly and is related with maternal and fetal complications. Norepinephrine infusion is increasingly used for prevention of post-SA hypotension; however, its effects as compared to the traditional phenylephrine infusion remain unclear. This study aimed to compare the effects of phenylephrine and norepinephrine administered as continuous infusion during elective CD on maternal hemodynamic parameters and maternal and fetal outcomes. Methods This prospective, single-center, randomized, controlled study included 238 consecutive term parturients who underwent CD from February 2019 to October 2019. They were randomized to receive continuous infusion of 0.25 μg/kg/min phenylephrine, 0.05 μg/kg/min norepinephrine, or placebo. Hemodynamic monitoring was performed at 10 time points using LiDCOrapid. We analyzed umbilical vein (UV), umbilical artery (UA), and peripheral vein (PV) blood gas indexes and recorded intraoperative complications. Results In phenylephrine group, the systolic blood pressure (SBP) remain during the whole operation. Compared to the control group, phenylephrine, but not norepinephrine, significantly increased the systemic vascular resistance (SVR) to counteract the SA-induced vasodilatation, 3 min following norepinephrine/phenylephrine/LR administration (T4): 957.4 ± 590.3 vs 590.1 ± 273.7 (P

The aim of this study was to evaluate the effect of Hermetia illucens larvae meal (HI) on the growth performance and intestinal barrier function of weaned pigs. To achieve this, 72 weaned pigs [28-day-old, 8.44 ± 0.04 kg body weight (BW)] were randomly assigned to three dietary treatments: basal diet (negative control, NC), zinc oxide-supplemented diet (positive control, PC), and HI-supplemented diet [100% replacement of fishmeal (FM), HI], for 28 days in the presence of enterotoxigenic Escherichia coli (ETEC). The results showed that HI and PC increased (p < 0.05) the average daily gain (ADG) and average daily feed intake (ADFI) of weaned pigs from day 1 to 14, and decreased diarrhea incidence from day 1 to 28. Additionally, HI increased (p < 0.05) claudin-1, occludin, mucin-1 (MUC-1), and MUC-2 expression, goblet cell number, and secretory immunoglobulin A (sIgA) concentration in the intestine of weaned pigs. Compared with NC, HI downregulated (p < 0.05) interleukin-1β (IL-1β) and IL-8 expression, and upregulated IL-10, transforming growth factor-β (TGF-β), antimicrobial peptide [porcine β defensin 1 (pBD1), pBD2, protegrin 1-5 (PG1-5)] expression in the jejunum or ileum. Moreover, HI decreased (p < 0.05) toll-like receptor 2 (TLR2), phosphorylated nuclear factor-κB (p-NF-κB), and phosphorylated mitogen-activated protein kinase (p-MAPK) expression, and increased sirtuin 1 (SIRT1) expression in the ileum. Additionally, HI increased histone deacetylase 3 (HDAC3) expression and acetylation of histone 3 lysine 27 (acH3k27) in the ileum. Furthermore, HI positively influenced the intestinal microbiota composition and diversity of weaned pigs and increased (p < 0.05) butyrate and valerate concentrations. Overall, dietary HI improved growth performance and intestinal barrier function, as well as regulated histone acetylation and TLR2-NF-κB/MAPK signaling pathways in weaned pigs.

Abstract Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC‐related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top‐ranked prognostic proteins X‐prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well‐known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi‐omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC.

Abstract Background The prevalence of CGG repeat expansion mutation in FMR1 gene varies among different populations. In this study, we investigated the prevalence of this mutation in women of reproductive age from northern China. Methods A total of 11,891 pre-conceptional or pregnant women, including 5037 pregnant women and 7357 women with the history of spontaneous abortion or induced abortion due to delayed growth of the embryos, were recruited. The number of CGG repeats in FMR1 was measured by the TRP-PCR method. We also offered genetic counseling and prenatal diagnosis to the women carrying pre-mutation or full mutation alleles. Results The prevalence of pre-mutation in reproductive women in northern China was 1/410, higher than that in southern China and Korea but lower than that in western countries. We also found that the prevalence of pre-mutation was relatively high (1/320) in women with abortion history. Conclusion Screening for CGG repeat expansion mutation in FMR1 should be recommended to the women with the history of spontaneous abortion or induced abortion due to delayed growth of the embryos.

Wood formation is a complicated process under the control of a large set of transcription factors. NAC transcription factors are considered “master switches” in this process. However, few NAC members have been cloned and characterized in Eucalyptus, which is one of the most economically important woody plants. Here, we reported an NAC transcription factor from Eucalyptus grandis, EgNAC141, which has no Arabidopsis orthologs associated with xylogenesis-related processes. EgNAC141 was predominantly expressed in lignin-rich tissues, such as the stem and xylem. Overexpression of EgNAC141 in Arabidopsis resulted in stronger lignification, larger xylem, and higher lignin content. The expression of lignin biosynthetic genes in transgenic plants was significantly higher compared with wild-type plants. The transient expression of EgNAC141 activated the expression of Arabidopsis lignin biosynthetic genes in a dual-luciferase assay. Overall, these results showed that EgNAC141 is a positive regulator of lignin biosynthesis and may help us understand the regulatory mechanism of wood formation.

Abstract Background Henoch-Schönlein purpura nephritis (HSPN) is the most common pediatric secondary glomerular disease. This study aimed to investigate the significance of glomerular fibrinogen (Fib) deposition in children with HSPN. Methods Eighty-two patients with HSPN were enrolled retrospectively at the Children’s Hospital of Soochow University from January 2015 to March 2017. Patients were divided into groups according to the presence or absence and intensity of glomerular Fib deposits, and clinical and pathological features were compared among the groups. Results Glomerular Fib deposition was observed in 64 children (78.05%), including 1 Fib± case (1.22%), 23 Fib+ cases (28.05%), 37 Fib++ cases (45.12%), and 3 Fib+++ cases (3.66%). Significantly different levels of high-sensitivity C-reactive protein (hs-CRP), D-dimer (DD), proportions of CD19 + CD23+ cells and urine microalbumin:creatinine ratios (UMA/Cr) were noted among the different Fib deposition groups (no, mild and severe). Pairwise comparison in multiple groups revealed significantly increased hs-CRP, proportion of CD19 + CD23+ cells and UMA/Cr in the severe deposition group compared with the mild and no deposition groups, and remarkably increased DD levels were noted in the severe and mild deposition groups compared with the no deposition group. The degree of glomerular Fib deposition was positively correlated with the degree of glomerular IgA deposition, and the incidence of glomerular IgG deposition in the severe deposition group was increased compared with the no deposition group. Conclusion HSPN children with glomerular Fib deposition, especially those with severe Fib deposition, exhibit more severely disordered immunologic function, inflammatory reactions and hypercoagulability; glomerular damage in these patients may also be more severe.

Abstract We report a shockwave method for altering the properties of the superconductor material Bi2Sr2CaCu2O8+δ (Bi2212). We find that the superconducting transition temperature (T c) increases from 84 K for the pristine sample to 94 K for the sample treated at a temperature and pressure of ~1200 K and ~31 GPa, respectively. X-ray diffraction and transmission electron microscopy characterizations indicate that this T c enhancement arises from a phase transition from pristine Bi2212 to a mixture of superconducting Bi2212 and semiconducting Bi2Sr2CuO6+δ (Bi2201) during the shockwave treatment. The shockwave-treated sample exhibits n-type semiconductor properties (with an on-off ratio ~5), in contrast to the pure metallic pristine sample. Our study offers an alternative route for modifying the superconducting properties via a shockwave treatment. Furthermore, this method may provide a new approach for studying other temperature- and pressure-sensitive materials.

Layered lithium-rich manganese oxide (LLO) cathode materials have attracted much attention for the development of high-performance lithium-ion batteries. However, they have suffered seriously from disadvantages, such as large irreversible capacity loss during the first cycle, discharge capacity decaying, and poor rate performance. Here, a novel method was developed to coat the surface of 0.4Li2MnO3∙0.6LiNi1/3Co1/3Mn1/3O2 cathode material with reduced graphene-oxide (rGO) in order to address these drawbacks, where a surfactant was used to facilitate the well-wrapping of rGO. As a result, the modified LLO (LLO@rGO) cathode exhibits superior electrochemical performance including cycling stability and rate capability compared to the pristine LLO cathode. In particular, the LLO@rGO with a 0.5% rGO content can deliver a high discharge capacity of 166.3 mAh g−1 at a 5C rate. The novel strategy developed here can provide a vital approach to inhibit the undesired side reactions and structural deterioration of Li-rich cathode materials, and should be greatly useful for other cathode materials to improve their electrochemical performance.

According to the requirements of the mobile robot complete coverage path planning for some special missions, this paper introduces a bounded strategy based on the integration of the Lorenz dynamic system and the robot kinematics equation. Chaotic variables of the Lorenz system are confined in a limited range, while when they are used to produce the robot's coordinate position, the trajectory range is determined by the starting point, iterative times, and iterative step. The proposed bounded strategy can constrain all the robot positions in the workplace by a mirror mapping method that can reflect the overflow waypoints returning to it. Moreover, the statistical characteristics of the Lorenz chaotic variables and the robot trajectory are discussed in order to choose the best mapping variable. The simulation results show that the bounded strategy that uses the chosen variable can achieve a higher coverage rate contrary to other similar works.

This paper presents a chaotic motion path planner based on a Logistic Map (SCLCP) for an autonomous mobile robot to cover an unknown terrain randomly, namely entirely, unpredictably and evenly. The path planner has been improved by arcsine and arccosine transformation. A motion path planner based only on the Logistic Chaotic Map (LCP) can show chaotic behaviour, which possesses the chaotic characteristics of topological transitivity and unpredictability, but lacks better evenness. Therefore, the arcsine and arccosine transformations are used to enhance the randomness of LCP. The randomness of the followed path planner, LCP, the improved path planner SCLCP and the commonly used Random Path Planner (RP) are discussed and compared under different sets of initial conditions and different iteration rounds. Simulation results confirm that a better evenness index of SCLCP can be obtained with regard to previous works.

NAC1 encoded by NACC1 is a member of the BTB/POZ family of proteins and participates in several pathobiological processes. However, its function during tissue development has not been elucidated. In this study, we compared homozygous null mutant Nacc1(-/-) and wild type Nacc1(+/+) mice to determine the consequences of diminished NAC1 expression. The most remarkable change in Nacc1(-/-) mice was a vertebral patterning defect in which most knockout animals exhibited a morphological transformation of the sixth lumbar vertebra (L6) into a sacral identity; thus, the total number of pre-sacral vertebrae was decreased by one (to 25) in Nacc1(-/-) mice. Heterozygous Nacc1(+/-) mice had an increased tendency to adopt an intermediate phenotype in which L6 underwent partial sacralization. Nacc1(-/-) mice also exhibited non-closure of the dorsal aspects of thoracic vertebrae T10-T12. Chondrocytes from Nacc1(+/+) mice expressed abundant NAC1 while Nacc1(-/-) chondrocytes had undetectable levels. Loss of NAC1 in Nacc1(-/-) mice was associated with significantly reduced chondrocyte migratory potential as well as decreased expression of matrilin-3 and matrilin-4, two cartilage-associated extracellular matrix proteins with roles in the development and homeostasis of cartilage and bone. These data suggest that NAC1 participates in the motility and differentiation of developing chondrocytes and cartilaginous tissues, and its expression is necessary to maintain normal axial patterning of murine skeleton.

We give an abstraction of verifiable multi-secret sharing schemes that is accessible to a fully mechanized analysis. This abstraction is formalized within the applied pi-calculus by using an equational theory which characterizes the cryptographic semantics of secret share. We also present an encoding from the equational theory into a convergent rewriting system, which is suitable for the automated protocol verifier ProVerif. Based on that, we verify the threshold certificate protocol in ProVerif.