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We report a 36-year-old male patient died of V. vulnificus-induced septicaemia and multiple organ failure syndrome after oyster consumption at a restaurant. We isolated and identified V. vulnificus vv16015 from the patient's blood sample and antibiotic susceptibility tests indicated sensitivity to all 21 antibiotics. Oyster samples were subsequently collected from the restaurant's supplier and three strains of V. vulnificus were isolated. Whole genome sequencing and analysis revealed vv16015 to be distantly related to these strains and confirmed that V. vulnificus contamination was present in the seafood of the restaurant and supplier. Using a Galleria mellonella larvae infection model, the virulence of vv16015 was determined to be higher than that of comparison strains isolated from a surviving patient (vv15018) and an oyster (vv220015). The human and environment distribution of V. vulnificus in Shenzhen is sporadic and heterogeneous, and vv16015 is highly virulent compared to other strains. [ABSTRACT FROM AUTHOR]

Patchouli alcohol, a significant bioactive component of the herbal plant Pogostemon cablin, has considerable medicinal and commercial potential. Several genes and transcription factors involved in the biosynthesis pathway of patchouli alcohol have been identified. However, so far, regulatory factors directly interacting with patchouli synthase (PTS) have not been reported. This study was conducted to analyze the interaction between PcENO3 and PcPTS to explore the molecular regulation effect of PcENO3 on patchouli alcohol biosynthesis. PcENO3, a homologous protein of Arabidopsis ENO3 belonging to the enolase family, was identified and characterized. Subcellular localization experiments in Arabidopsis protoplast cells indicated that the PcENO3 protein was localized in both the cytoplasm and nucleus. The physical interaction between PcENO3 and PcPTS was confirmed through yeast two‐hybrid (Y2H), GST pull‐down, and bimolecular fluorescence complementation assays. Furthermore, the Y2H assay demonstrated that PcENO3 could also interact with JAZ proteins in the JA pathway. Enzymatic assays showed that the interaction with PcENO3 increased the catalytic activity of patchoulol synthase. Additionally, suppression of PcENO3 expression with VIGS (virus‐induced gene silencing) decreased patchouli alcohol content compared to the control. These findings suggest that PcENO3 interacts with patchoulol synthase and modulates patchoulol biosynthesis by enhancing the enzymatic activity of PcPTS. [ABSTRACT FROM AUTHOR]

Background: Postprandial distress syndrome (PDS) is the most common subtype of functional dyspepsia. Acupuncture is commonly used to treat PDS, but its effect is uncertain because of the poor quality of prior studies.Objective: To assess the efficacy of acupuncture versus sham acupuncture in patients with PDS.Design: Multicenter, 2-group, randomized clinical trial. (ISRCTN registry number: ISRCTN12511434).Setting: 5 tertiary hospitals in China.Participants: Chinese patients aged 18 to 65 years meeting Rome IV criteria for PDS.Intervention: 12 sessions of acupuncture or sham acupuncture over 4 weeks.Measurements: The 2 primary outcomes were the response rate based on overall treatment effect and the elimination rate of all 3 cardinal symptoms: postprandial fullness, upper abdominal bloating, and early satiation after 4 weeks of treatment. Participants were followed until week 16.Results: Among the 278 randomly assigned participants, 228 (82%) completed outcome measurements at week 16. The estimated response rate from generalized linear mixed models at week 4 was 83.0% in the acupuncture group versus 51.6% in the sham acupuncture group (difference, 31.4 percentage points [95% CI, 20.3 to 42.5 percentage points]; P < 0.001). The estimated elimination rate of all 3 cardinal symptoms was 27.8% in the acupuncture group versus 17.3% in the sham acupuncture group (difference, 10.5 percentage points [CI, 0.08 to 20.9 percentage points]; P = 0.034). The efficacy of acupuncture was maintained during the 12-week posttreatment follow-up. There were no serious adverse events.Limitation: Lack of objective outcomes and daily measurement, high dropout rate, and inability to blind acupuncturists.Conclusion: Among patients with PDS, acupuncture resulted in increased response rate and elimination rate of all 3 cardinal symptoms compared with sham acupuncture, with sustained efficacy over 12 weeks in patients who received thrice-weekly acupuncture for 4 weeks.Primary Funding Source: Beijing Municipal Science and Technology Commission. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the utility of plasma microRNAs (miRNAs) as biomarkers in cervical cancer (CC). METHODS: Some studies were conducted about the specific expression of plasma miRNAs in the diagnosis of CC. Plasma samples of 97 CC patients and 87 normal controls (NCs) were used to identify dysregulation of miRNAs in the training, testing, and external validation phases. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were used to evaluate the sensitivity and specificity of identified individual miRNAs and miRNA panels for the diagnosis of CC. Expression levels of specific miRNAs were also examined in plasma exosomes and tissue samples of CC patients. RESULTS: Four plasma miRNAs (miR-146a-5p, miR-151a-3p, miR-2110 and miR-21-5p) which showed up-regulation were identified and validated in CC patients. A panel of the four miRNAs were constructed as potential diagnostic markers for CC. The AUCs of the panel of these four-miRNAs for the training, testing, and external validation phases were 0.911, 0.774, and 0.786, respectively. miR-146a-5p and miR-21-5p levels were all up-regulated in CC tissue specimens, whereas miR-146a-5p, miR-151a-3p, and miR-2110 levels were up-regulated in plasma exosomes. CONCLUSION: The signature of the four-miRNAs identified in peripheral plasma is a promising novel biomarker for the diagnosis of CC. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems, especially type II (Cas9) systems, have been widely used in gene/genome targeting. Modifications of Cas9 enable these systems to become platforms for precise DNA manipulations. However, the utilization of CRISPR-Cas systems in RNA targeting remains preliminary. The discovery of type VI CRISPR-Cas systems (Cas13) shed light on RNA-guided RNA targeting. Cas13d, the smallest Cas13 protein, with a length of only ~930 amino acids, is a promising platform for RNA targeting compatible with viral delivery systems. Much effort has also been made to develop Cas9, Cas13a and Cas13b applications for RNA-guided RNA targeting. The discovery of new RNA-targeting CRISPR-Cas systems as well as the development of RNA-targeting platforms with Cas9 and Cas13 will promote RNA-targeting technology substantially. Here, we review new advances in RNA-targeting CRISPR-Cas systems as well as advances in applications of these systems in RNA targeting, tracking and editing. We also compare these Cas protein-based technologies with traditional technologies for RNA targeting, tracking and editing. Finally, we discuss remaining questions and prospects for the future. • RNA targeting and editing are becoming increasingly important • CRISPR-Cas systems are advancing for RNA targeting, tracking and editing • The type VI CRISPR-Cas systems are useful for RNA-guided RNA targeting • Use of Cas9 and Cas13 will advance RNA-targeting technologies [ABSTRACT FROM AUTHOR]

Mitochondrial succinate dehydrogenase (SDH), also known as electron transport chain (ETC) Complex II, is the only enzyme complex engaged in both oxidative phosphorylation and the tricarboxylic acid (TCA) cycle. SDH has received increasing attention due to its crucial role in regulating mitochondrial metabolism and human health. Despite having the fewest subunits among the four ETC complexes, functional SDH is formed via a sequential and well-coordinated assembly of subunits. Along with the discovery of subunit-specific assembly factors, the dynamic involvement of the SDH assembly process in a broad range of diseases has been revealed. Recently, we reported that perturbation of SDH assembly in different tissues leads to interesting and distinct pathophysiological changes in mice, indicating a need to understand the intricate SDH assembly process in human health and diseases. Thus, in this review, we summarize recent findings on SDH pathogenesis with respect to disease and a focus on SDH assembly. [Display omitted] • Succinate dehydrogenase (SDH) connects oxidative phosphorylation and TCA cycle. • Four major assembly factors that facilitate the assembly and maturation of the SDH complex. • SDHA is the most commonly identified pathogenic variant in SDH deficiency. • Mutations related to SDH deficiency induce the loss of tumor suppressor function. • SDHAF4 was the most sensitive assembly factor under pathophysiological stress. [ABSTRACT FROM AUTHOR]

• Transmissibility of three variants was Omicron BA.2>Omicron BA.1 > Delta. • Omicron BA.2 variant has less pathogenicity than Omicron BA.1 and Delta variant. • Transmissibility in cycle threshold value should be discussed in further research. The Omicron BA.2 variant is probably the main epidemic strain worldwide at present. Comparing the epidemiological characteristics, transmissibility, and influencing factors of SARS-CoV-2, the results obtained in this paper will help to provide theoretical support for disease control. This study was a historical information analysis, using the R programming language and SPSS 24.0 for statistical analysis. The Geoda and Arc GIS were used for spatial autocorrelation analysis. Local spatial autocorrelations of the incidence rate were observed in Delta and Omicron BA.1 outbreaks, whereas Omicron BA.2 outbreaks showed a random distribution in incidence rate. The time-dependent reproduction number of Delta, Omicron BA.1, and Omicron BA.2 were 3.21, 4.29, and 2.96, respectively, and correspondingly, the mean serial interval were 4.29 days (95% confidence interval [CI]: 0.37-8.21), 3.84 days (95% CI: 0-8.37), and 2.77 days (95% CI: 0-5.83). The asymptomatic infection rate of cases in Delta, Omicron BA.1, and Omicron BA.2 outbreaks were 21.71%, 6.25%, and 4.35%, respectively. The Omicron BA.2 variant had the greatest serial interval, transmissibility, and transmission speed, followed by BA.1, and then Delta. Compared with Delta and Omicron BA.1 variants, the Omicron BA.2 variant may be less pathogenic and more difficult to control than Omicron BA.1 and Delta. [ABSTRACT FROM AUTHOR]

Masses for 664 single-lined hot subdwarf stars identified in LAMOST were calculated by comparing synthetic fluxes from spectral energy distribution with observed fluxes from a Virtual Observatory service. Three groups of hot subdwarf stars were selected from the whole sample according to their parallax precision to study the mass distributions. We found that He-poor sdB/sdOB stars present a wide mass distribution from 0.1 to 1.0 M ⊙ with a sharp mass peak at around 0.46 M ⊙, which is consistent with canonical binary model prediction. He-rich sdB/sdOB/sdO stars present a much flatter mass distribution than He-poor sdB/sdOB stars and with a mass peak at around 0.42 M ⊙. By comparing the observed mass distributions to the predictions of different formation scenarios, we concluded that the binary merger channel, including two helium white dwarfs (He-WDs) and He-WD + main-sequence mergers, cannot be the only main formation channel for He-rich hot subdwarfs, and other formation channels, such as the surviving companions from Type Ia supernovae, could also make impacts on producing this special population, especially for He-rich hot subdwarfs with masses less than 0.44 M ⊙. He-poor sdO stars also present a flatter mass distribution with an inconspicuous peak mass at 0.18 M ⊙. The similar mass– Δ RV max distribution between He-poor sdB/sdOB and sdO stars supports the scenario that He-poor sdO stars could be the subsequent evolution stage of He-poor sdB/sdOB stars. [ABSTRACT FROM AUTHOR]

X-linked ocular albinism (OA1) is an X-linked inherited disease characterized by hypopigmentation of the fundus and nystagmus. Our study performed mutation analysis of the G protein-coupled receptor 143 gene (GPR143) and assessed the clinical characteristics of OA1 in three Chinese families. Three novel mutations, c.333_360+14del42insCTT, c.276G>A (p.W92X), and c.793C>T (p.R265X), were identified in GPR143 by PCR followed by Sanger sequencing in these families. All affected individuals presented with nystagmus, photophobia, poor visual acuity, foveal hypoplasia and varying degrees of hypopigmentation of the fundus. The fundus of female carriers showed pigmented streaks alternating with hypopigmented streaks. These results allowed us to expand the spectrum of mutations in GPR143 and phenotypes associated with ocular albinism. [ABSTRACT FROM AUTHOR]

Abstract Whether plasma miRNAs could be used as novel non-invasive biomarkers in diagnosing papillary thyroid carcinoma (PTC) remains unknown. In this study, we designed a four-phase study to identify differentially expressed plasma miRNAs in Chinese PTC patients. Exiqon panel was initially utilized to conduct plasma miRNA profile (3 PTC pools VS. 1 healthy control (HC) pool; each 10 samples were pooled as 1 sample). The dysregulated miRNAs were then analyzed in the training (30 PTC VS. 30 HCs), testing (57 PTC VS. 54 HCs) and external validation phases (33 PTC VS. 30HCs). The identified miRNAs were further affirmed in benign nodules (2 nodular goiter (NG) pool VS. 1 HC pool). We also verified the expression of identified miRNAs in 17 matched malignant and normal tissue samples, NG plasma samples (29 PTC VS. 29 NG) and plasma exosomes (25 PTC VS. 25 HCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of the identified miRNAs. As a result, the screening phase demonstrated 30 dysregulated plasma miRNAs in PTC patients compared with HCs. After multiphase experiment processes, miR-346, miR-10a-5p and miR-34a-5p were found significantly elevated in PTC plasma samples relative to HCs. The areas under the ROC curve (AUC) of the three-miRNA panel for the training, testing and validation phases were 0.926, 0.811 and 0.816, separately. The panel could also differentiate PTC from NG with the AUC of 0.877. MiR-346 and miR-34a-5p but not miR-10a-5p were up-regulated in PTC tissues. And the three miRNAs showed consistently up-regulation in PTC plasma exosomes. In conclusion, our study established a three-miRNA panel in plasma with considerable clinical value in discriminating PTC from HC or NG. Highlights • Plasma miR-346, miR-10a-5p and miR-34a-5p were elevated in PTC patients relative to HCs. • The three-miRNA panel could differentiate PTC patients from NG patients or HCs. • MiR-346 and miR-34a-5p but not miR-10a-5p were elevated in tumor tissues to normal tissues. • All the three miRNAs were up-regulated in exosomes from PTC plasma samples compared to HCs. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the common malignant tumors in the head and neck, characterized by high malignancy, rapid growth and metastasis, high invasive ability, and high mortality. In recent years, surgery combined with chemotherapy or radiotherapy remains the preferred clinical treatment for OSCC, despite considerable advances in diagnostic and therapeutic techniques. Hence, new targeted therapy is urgently needed. Histone modification affects the function of massive cells through histone acetyltransferase and histone deacetylase. Accompanied by the progress of some diseases, especially tumors, these proteins often show abnormal functions, and by reversing these abnormalities with drugs or gene therapy, the cancer phenotype can even be restored to normal. As a result, they are potential drug targets. This article reviewed the role of the histone dynamic process of acetylation modifications and their associated active modifying enzymes in the pathogenesis and progress of OSCC. Moreover, we explored the value of histone acetylation modification as a potential therapeutic target and the new progress of related drugs in clinical treatment. [ABSTRACT FROM AUTHOR]

Raw observation processing method with prior knowledge of ionospheric delay could strengthen the ambiguity resolution (AR), but it does not make full use of the relatively longer wavelength of wide-lane (WL) observation. Furthermore, the accuracy of calculated atmospheric delays from the regional augmentation information has quite different in quality, while the atmospheric constraint used in the current methods is usually set to an empirical value. A proper constraint, which matches the accuracy of calculated atmospheric delays, can most effectively compensate the residual systematic biases caused by large inter-station distances. Therefore, the standard deviation of the residual atmospheric parameters should be fine-tuned. This paper presents an atmosphere-constrained AR method for undifferenced network RTK (URTK) rover, whose ambiguities are sequentially fixed according to their wavelengths. Furthermore, this research systematically analyzes the residual atmospheric error and finds that it mainly varies along the positional relationship between the rover and the chosen reference stations. More importantly, its ionospheric part of certain location will also be cyclically influenced every day. Therefore, the standard deviation of residual ionospheric error can be modeled by a daily repeated cosine or other functions with the help of data one day before, and applied by rovers as pseudo-observation. With the data collected at 29 stations from a continuously operating reference station network in Guangdong Province (GDCORS) in China, the efficiency of the proposed approach is confirmed by improving the success and error rates of AR for 10-20 % compared to that of the WL-L1-IF one, as well as making much better positioning accuracy. [ABSTRACT FROM AUTHOR]

Background: To promote influenza vaccination coverage, a Chinese megacity, Shenzhen provides free influenza vaccination to its residents aged 60 years and above through community health centres (CHCs) since October 2016. A community health centre-based experiment was conducted by asking primary care physicians (PCPs) working in the intervention health centres to proactively recommend influenza vaccination to their patients aged 60 and above during their patients' visits. Methods: This study used an experimental design and a survey design. The experimental design evaluated the effect of PCP recommendation on influenza vaccination. A total of 24 CHCs were randomly selected as the intervention (involving 3814 participants) and control (3072 participants) group evenly. The intervention study period was during the 2017–2018 flu season. The 2016–2017 flu season was considered as the baseline comparison. The survey design examined changes in knowledge, attitude, and practice of influenza vaccination among older participants before and after the free influenza vaccination implementation. We randomly invited 1200 participants aged 60 and above during their visits to CHCs in October 2016 and followed them up until October 2017; among them, 958 participants completed the follow-up survey using the same questionnaire. Results: In the 2017–2018 flu season, 1,100 more patients got vaccinated in the intervention group under PCP recommendation compared with the 2016–2017 flu season. Among the 958 older adults in the post-implementation period, 77.5% had heard about the influenza vaccine, which was 24.7% higher than in the pre-implementation period; 84.8% of participants were aware where to take influenza vaccines, with the most improvement of 37.2% among all knowledge related questions; 62.5% of them agreed that patients with chronic diseases should have influenza vaccine, which was 19.1% higher than those being surveyed before the implementation period. About 83.6% of participants agreed older adults should have influenza vaccine, but there were still 58.4% who considered themselves too healthy to get vaccinated. Conclusion: PCP recommendation improved influenza vaccine uptake and knowledge, attitude, and practice levels regarding influenza vaccination among older adults. More health policies and health education should be made to raise vaccination willingness and improve vaccination coverage among older adults. [ABSTRACT FROM AUTHOR]

Auxin plays a critical role in organogenesis in plants. The classical auxin signaling pathway holds that auxin initiates downstream signal transduction by degrading Aux/IAA transcription repressors that interact with ARF transcription factors. In this study, 23 MoIAA genes were identified in the drumstick tree genome. All MoIAA genes were located within five subfamilies based on phylogenetic evolution analysis; the gene characteristics and promoter cis-elements were also analyzed. The protein interaction network between the MoIAAs with MoARFs was complex. The MoIAA gene family responded positively to NAA treatment, exhibiting different patterns and degrees, notably for MoIAA1, MoIAA7 and MoIAA13. The three genes expressed and functioned in the nucleus; only the intact encoding protein of MoIAA13 exhibited transcriptional activation activity. The shoot regeneration capacity in the 35S::MoIAA13-OE transgenic line was considerably lower than in the wild type. These results establish a foundation for further research on MoIAA gene function and provide useful information for improved tissue culture efficiency and molecular breeding of M. oleifera. [ABSTRACT FROM AUTHOR]

Methane emission from the ruminants is not only a significant amount of greenhouse gases contributing to climate change but also a reduction in feed efficacy. Mitigation of ruminal CH 4 emission is a great challenge for cleaner livestock production. It is difficult to reduce CH 4 production without any adverse effects on feed digestion. The present investigation was conducted to explore the sustainable mitigation of ruminal CH 4 production with positive effects on feed digestibility using Neolamarckia cadamba leaves extract (NE). Stylo was added and ensiled with or without 1% and 2% NE, and the silage was engaged in vitro ruminal fermentation. Metagenomics was used to analyze the microbial communities and functional genes. The results indicated that the addition of 1% and 2% NE decreased (P < 0.001) CH 4 production significantly and increased (P < 0.001) dry matter digestibility at the same time. The concentrations of volatile fatty acids were not altered by NE. Some genes related to glycoside hydrolases, glycosyl transferases, carbohydrate-binding modules were upregulated by 2%NE. The addition of NE showed little influence on the ruminal microbial community, but reduced (P < 0.05) the relative abundance of Methanobrevibacter , especially the Methanobrevibacter curvatus , which was positively correlated (correlation = 0.561, P = 0.011) with the ruminal CH 4 production. In CH 4 metabolism, genes related to the serine pathway were highly detected. The addition of NE inhibited (P < 0.05) CH 4 metabolism by downregulating the great majority of involved genes. In conclusion, the present study provides new insights into the pathway of CH 4 metabolism and useful information for understanding and controlling ruminal CH 4 production in livestock production. The addition of NE might be a sustainable option to reduce CH 4 while enhancing animal feed utilization efficiency. It could be used as a pronounced cleaner way for the ecosystem as well as livestock. [Display omitted] • Neolamarckia cadamba leaves extract (NE) increased digestibility of stylo silage. • Genes related to carbohydrate-active enzymes were upregulated by NE. • NE reduced CH 4 production by decreasing the abundance of Methanobrevibacter curvatus. • NE inhibited CH 4 metabolism by downregulating the great majority of involved genes. [ABSTRACT FROM AUTHOR]

Simple Summary: The swimming ability of fish plays a guiding role in the construction of fish passing facilities. However, it is not enough to know the swimming ability of fish. We need to know the behavior and energy consumption of fish in the process of movement, so as to determine the activity area and migration suitable for fish. Therefore, a video tracking program was used to record and analyze the motion of five test fish in a Brett-type flume during each velocity step. The results obtained the kinematic and dynamic parameters of fish. Secondly, we found that steady fish swimming is not entirely steady in flowing water, with swimming speed varying by 2.2% to 8.4% and increasing with flow velocity. Further, because energy expenditure increases with the cube of swimming speed, a slight excess in fish passage flow velocity could result in a disproportionately large decrease in the rate of passage success. Therefore, we recommend guarding against an excessive flow velocity in the main velocity zone and ensuring that resting pools along the passageway are adequate. Our characterization of the kinematics and dynamics of fish swimming provides important new information to consider when indices of swimming ability from controlled tank testing are applied to fish passage design. The swimming kinematics (how fish move) and dynamics (how forces effect movement) of Schizopygopsis malacanthus were investigated during the determination of U c r i t by stepped velocity testing. A video tracking program was used to record and analyze the motion of five test fish in a Brett-type flume during each velocity step. The findings fell into three groups: (1) Even when flow was uniform, fish did not swim steadily, with speeds fluctuating by 2.2% to 8.4% during steady swimming. The proportion of unsteady swimming time increased with water velocity, and defining steady and unsteady swimming statistically, in terms of the definition of standard deviation of instantaneous displacements, may have higher accuracy. (2) In steady swimming, the forward velocity and acceleration of fish were correlated with body length (p < 0.05), but in unsteady swimming the correlations were not significant. The maximum swimming speed (1.504 m/s) and acceleration (16.54 m/s2) occurred during unsteady swimming, but these measurements may not be definitive because of tank space constraints on fish movement and the passive behavior of the test fish with respect to acceleration. (3) Burst-coast swimming in still water, investigated by previous scholars as an energy conserving behavior, is not the same as the gait transition from steady to unsteady swimming in flowing water. In this study, the axial force of fish swimming in the unsteady mode was significantly higher (×1.2~1.6) than in the steady mode, as was the energy consumed (×1.27~3.33). Thus, gait transition increases, rather than decreases, energy consumption. Our characterization of the kinematics and dynamics of fish swimming provides important new information to consider when indices of swimming ability from controlled tank testing are applied to fish passage design. [ABSTRACT FROM AUTHOR]

Background: Intraductal papillary mucinous neoplasms (IPMNs) are characterized by their abundant mucin production and malignant potential. IPMNs of the pancreas are mainly managed according to their radiographic indications, but this approach lacks accuracy with regard to IPMN grading. Therefore, serological biomarkers such as CA19-9 and CA125 (MUC16) should be employed to assist in predicting the invasiveness of IPMNs. Methods: We investigated the preoperative serum levels of CA19-9, CA125 and CEA in 381 surgical patients with a definite pathological diagnosis of IPMN from July 2010 to December 2019 at the Shanghai Cancer Center. We calculated the Youden indices of each point on the receiver operating characteristic (ROC) curves to identify the most appropriate cut-off values of CA19-9, CA125 and CEA for recognizing malignant IPMNs. Serological biomarker differences were correlated with clinicopathological features of IPMNs, and diagnostic indices of different scenarios were calculated to find the optimum strategy. Results: The malignant group had higher serum levels of CA19-9, CA125 and CEA. According to the ROC curves, the cut-off values of CA19-9, CA125 and CEA were readjusted to 38.3 U/ml, 13.4 U/ml and 5.3 μg/L. CA19-9 elevation was significantly associated with vascular invasion and perineural infiltration. CA125 showed good efficacy in predicting invasive IPMN in the CA19-9-negative subgroup. Conclusions: Serological biomarkers are useful and sensitive indicators for recognizing invasive IPMNs. CA19-9 is the most important diagnostic index among all routinely measured serum biomarkers for differentiating malignant from benign IPMNs. CA19-9 should be combined with CA125 to enable more accurate predictions of IPMN malignancy. [ABSTRACT FROM AUTHOR]

Background. The purpose of this study is to understand the oral mucosal immune status of cancer patients and to make clear whether antibacterial proteins such as salivary secretory immunoglobulin (SIgA) and lysozyme in saliva were influenced by patients’ health status and certain medical treatment therapy. Materials and Methods. This study included 221 patients with malignant tumor receiving antineoplastic treatment and 171 age- and gender-matched healthy controls. Results. The results showed that patients suffering malignant tumor had lower level of SIgA and higher level of lysozyme than healthy subjects (P<0.05). The SIgA level was significantly different among different cancer tumors, while the lysozyme level showed significant difference only between patients with digestive tract malignant tumor and hematopoietic system tumor. Pretreatment before transplantation for hematopoietic system tumor patients significantly affected the lysozyme level other than SIgA. SIgA level was affected by many factors such as age, therapy factors, and oral hygiene. Conclusion. Malignant tumor and the antineoplaston may weaken the patients’ oral mucosal immunity, influence levels of some salivary proteins, and decrease the level of SIgA, resulting in aggregation of oral bacteria and failure of clearing them from the oral cavity. [ABSTRACT FROM AUTHOR]

Objectives: Oral colonization of Candida could lead to later development of oropharyngeal candidiasis or candidemia among the immunocompromised patients. This study aims to describe the occurrence and risk factors of oral Candida colonization in patients with malignancies. Materials and methods: From October 2012 to March 2013, 78 patients with pulmonary cancer (group I), 101 patients with gastrointestinal tract tumor (group II), 79 patients with hematopoietic system malignant tumor (group III), and 101 healthy controls were consecutively recruited in a hospital in Beijing, China. The oral rinse samples were taken and Candida species were identified; the enzymes activities were tested. Results: In total, 110 and 27 Candida strains were isolated from 91 patients and 26 controls, respectively. The oral colonization rate with Candida albicans in group III (12.7 %) was significant lower than that in group I (30.8 %), group II (33.7 %), and control group (25.7 %). The oral colonization rates with non- albicans Candida species in group I, group II, and group III were 15.4, 10.9, and 12.7 %, respectively, while only one non- albicans Candida strain was identified in control group. The non- albicans Candida species exhibited a lower virulence than C. albicans. Age was an independent risk factor for Candida colonization in patients with pulmonary cancer and digestive tract malignant tumor, 'Teeth brush <1 time/day' was an independent risk factor for Candida colonization in patients with hematopoietic system tumor. Conclusions: The differences of risk factors for oral Candida colonization in patients with different cancers require different strategies for the prevention and control of Candida infection. Clinical relevance: Old aged patients with pulmonary cancer and digestive tract malignant tumor are high-risk population for Candida colonization. Increasing frequency of teeth brush might be helpful for preventing Candida colonization. [ABSTRACT FROM AUTHOR]

Lysine acetyltransferase 7 (KAT7), a histone acetyltransferase, has recently been identified as an oncoprotein and has been implicated in the development of various malignancies. However, its specific role in head and neck squamous carcinoma (HNSCC) has not been fully elucidated. Our study revealed that high expression of KAT7 in HNSCC patients is associated with poor survival prognosis and silencing KAT7 inhibits the Warburg effect, leading to reduced proliferation, invasion, and metastatic potential of HNSCC. Further investigation uncovered a link between the high expression of KAT7 in HNSCC and tumor-specific glycolytic metabolism. Notably, KAT7 positively regulates Lactate dehydrogenase A (LDHA), a key enzyme in metabolism, to promote lactate production and create a conducive environment for tumor proliferation and metastasis. Additionally, KAT7 enhances LDHA activity and upregulates LDHA protein expression by acetylating the lysine 118 site of LDHA. Treatment with WM3835, a KAT7 inhibitor, effectively suppressed the growth of subcutaneously implanted HNSCC cells in mice. In conclusion, our findings suggest that KAT7 exerts pro-cancer effects in HNSCC by acetylating LDHA and may serve as a potential therapeutic target. Inhibiting KAT7 or LDHA expression holds promise as a therapeutic strategy to suppress the growth and progression of HNSCC. • Research on post-translational modifications rather than transcriptional regulation in head and neck squamous cell carcinoma. • New discovery of KAT7 capable of acetylating LDHA K118 site. • The regulatory mechanism of KAT7 in tumor metabolism of head and neck squamous cell carcinoma. • The inhibitor of KAT7 had a certain inhibitory effect on tumor growth in mice in vivo. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) displays a typical mucin expression pattern which is characterized by MUC1 positive, MUC2 negative, and MUC5AC positive. More and more evidences show that mucins are involved in the development of pancreatic diseases. However, the relationship between mucin expression and prognosis of PDAC patients has been controversial in the past decades; therefore, we aim to figure out the association of mucin expression with survival in PDAC patients who underwent radical resection.Methods: We performed immunohistochemistry (IHC) to detect the expression of MUC1, MUC2, and MUC5AC in resected PDAC specimens from Shanghai Cancer Center, Fudan University (FUSCC, n = 427) and obtained the corresponding clinical statistical data for retrospective study. Kaplan-Meier methods and Mantel-Cox tests were used to compare the survival curves, and the Cox regression model was employed for multivariate analyses to determine the independent risk factors. Survival analysis was also performed in the Queensland Centre for Medical Genomics (QCMG, n = 70) PDAC cohort to verify the conclusion.Results: Both the FUSCC cohort and the QCMG cohort demonstrated that MUC1 absence was significantly correlated with worse overall survival (OS). The presence of MUC2 showed marginal significance in predicting shorter OS of PDAC patients, while MUC5AC had no prognostic value. In the FUSCC cohort, MUC1 absence was associated with increased proportion of stage III PDAC (p = 0.011), and MUC1 absence and MUC2 presence were associated with tumour perineural aggression (p = 0.011 and p = 0.030, respectively). Multivariable adjusted hazard ratios (HRs) for mortality of MUC1 and MUC2 were 0.492 (95% CI: 0.274-0.883, p = 0.017) and 1.596 (95% CI: 1.061-2.401, p = 0.025), respectively.Conclusions: MUC1 absence or MUC2 presence is independently associated with poor OS among patients with resectable PDAC. MUC5AC absence tended to be associated with short-term death. [ABSTRACT FROM AUTHOR]

The global BeiDou Navigation Satellite System (BDS-3) has been formally operated together with the regional system (BDS-2) for more than one year. However, the different frequency numbers between BDS-2 and BDS-3 makes their integration a troublesome problem, especially when all available frequencies are taken into account. To make a comprehensive analysis of multi-frequency precise positioning models in BDS-2 and BDS-3, the popular real-time kinematic positioning is taken as an example for data processing. Since in general the reliable, successful and rapid ambiguity resolution is the key of an appropriate multi-frequency positioning model, the framework of multi-frequency ambiguity resolution (AR) is summarized first. The usual loose combined model for the joint BDS-2 and BDS-3 system is described. To make full use of the common frequencies B1I and B3I in BDS-2 and BDS-3, an improved combined model is proposed where both the loose combined mode and tightly combined mode are applied. The performance of ambiguity resolution (AR) and positioning precision are obtained from four short baselines with different lengths in the above two models and with different elevation masks. The comparison results show that: (1) Both the combined model and improved combined model can achieve nearly 100% AR success rate and correctly-fixed rate, as well as consistent centimeter level's fixed solution; (2) The improved combined model can obtain higher AR fixed rate and shorter time to first fix (TTFF) compared with the usual combined model, and the improvements can be up to 15% for the fixed rate and 37% for TTFF; (3) To achieve the largest AR fixed rate while keep reliable AR and precise positioning, a relative large elevation mask such as 30° is highly recommended for a joint BDS-2 and BDS-3 system with sufficient observed satellites. [ABSTRACT FROM AUTHOR]

Multidrug‐resistant Pseudomonas aeruginosa (MDR‐P. aeruginosa) cannot be extirpated with any of the antipseudomonal antibiotics available in clinic because P. aeruginosa exhibit natural resistance to antibiotics and form a stable biofilm. Biofilm formed by P. aeruginosa is a leading cause of bacterial keratitis which may cause corneal perforation and even blindness. Antibacterial photodynamic therapy (aPDT) is a promising bactericidal method in combatting drug‐resistant bacteria. Unfortunately, the use of broad‐spectrum aPDT that kills bacteria indiscriminately may lead to microbiota imbalance and cause serious side effects in normal cells. Herein, PαGal50‐b‐PGRB20, which can effectively disperse biofilms and selectively kill MDR‐P. aeruginosa inside biofilms by binding to Lec A in the extracellular polymeric substances and on the P. aeruginosa membrane with low phototoxicity caused by broad‐spectrum aPDT, is designed and synthesized. PαGal50‐b‐PGRB20 has bactericidal activities by damaging DNA, RNA, protein, and membrane. In vivo study of the MDR‐P. aeruginosa biofilm infected keratitis model demonstrates the potential of PαGal50‐b‐PGRB20 for a better corneal recovery. This work provides a dedicated antibacterial material for preferentially killing MDR‐P. aeruginosa over normal cells and other bacteria. [ABSTRACT FROM AUTHOR]

BACKGROUND Type 1 diabetes is an autoimmune disease that results in the specific destruction of insulin‐producing beta cells in the pancreas. The aim of this study was to investigate the mechanism of exopolysaccharide from Leuconostoc pseudomesenteroides XG5 (XG5 EPS) against type 1 diabetes. RESULTS: Long‐term drench of XG5 EPS delayed the onset of autoimmune diabetes and had fewer islets with high‐grade infiltration (an insulitis score of 3 or 4) than untreated NOD mice. Oral administration of 50 mg kg−1 d−1 XG5 EPS increased the insulin and glucagon‐like peptide‐1 (GLP‐1) levels of serum, stimulated GLP‐1 secretion and upregulated gcg mRNA expression of colon in NOD mice. Moreover, oral administration of 50 mg kg−1 d−1 XG5 EPS significantly increased total short‐chain fatty acids levels in the colon contents, especially those of acetic acid and butyric acid. In NCI‐H716 cells, 500 and 1000 μmol L−1 sodium butyrate promoted the secretion of GLP‐1 and upregulated the mRNA expression of gcg and PC3, while XG5 EPS and sodium acetate did not stimulate the GLP‐1 secretion. Therefore, long‐term drench of XG5 EPS delayed the onset of autoimmune diabetes, which may be directly correlated with the increase of butyrate in the colon of NOD mice. CONCLUSION: Long‐term drench of 50 mg kg−1 d−1 XG5 EPS promoted the expression and secretion of GLP‐1 by increasing the production of butyric acid, thereby delaying T1D onset in NOD mice. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Alternate day fasting (ADF), the most popular form of caloric restriction, has shown to improve metabolic health in preclinical subjects, while intrinsic network underpinning the process remains unclear. Here, it is found that liver undergoes dramatic metabolic reprogramming during ADF, accompanied surprisingly with unique complex II dysfunction attributing to suspended complex II assembly via suppressing SDHAF4, a recently identified assembly factor. Despite moderate mitochondrial complex II dysfunction, hepatic Sdhaf4 knockout mice present intriguingly improved glucose tolerance and systemic insulin sensitivity, consistent with mice after ADF intervention. Mechanistically, it is found that hepatocytes activate arginine‐nitric oxide (NO) biosynthesis axle in response to complex II and citric acid cycle dysfunction, the release of NO from liver can target muscle and adipocytes in addition to its autocrine action for enhanced insulin sensitivity. These results highlight the pivotal role of liver in ADF‐associated systemic benefits, and suggest that targeting hepatic complex II assembly can be an intriguing strategy against metabolic disorders. [ABSTRACT FROM AUTHOR]

Purposes: North Carolina macular dystrophy (NCMD) is a rare autosomal dominant inherited disorder characterized by macular impairment with a variety of phenotypic manifestations. The aims of this study were to assess the clinical features of a Chinese family with NCMD and to identify the underlying genetic cause of the disease. Methods: Three patients from a Chinese family were included in this study. Detailed ophthalmological examinations were performed, including best corrected visual acuity (BCVA), slit lamp, dilated indirect ophthalmoscopy, fundus photography, optical coherence tomography (OCT), fundus autofluorescence, full-field electroretinography (ERG), and electrooculography (EOG). Genomic DNA was extracted from peripheral blood samples. Whole-genome sequencing and long-read genome sequencing were applied to detect the pathogenic variants. Sanger sequencing was performed to confirm the breakpoints. Results: All three patients had macular involvement ranging from patchy yellowish-white lesions to big-area thinning, which are typical for NCMD. The BCVA ranged from 20/50 to 20/20. OCT revealed varying degrees of macular structure disorganization. The ERG responses were normal, and the Arden ration of the EOG was reduced. A novel 134.6 kb (g.99932464-100067110dup) tandem duplication on chromosome 6 (NC_000006.11) encompassing the entire CCNC and PRDM13 genes and a DNase 1 hypersensitivity site in the MCDR1 locus was identified. Conclusion: A novel large tandem duplication in MCDR1 locus was confirmed in a Chinese family with NCMD with a variety of macular phenotypes. [ABSTRACT FROM AUTHOR]

Abstract: A Mediterranean diet rich in olive oil has profound influence on health outcomes including metabolic syndrome. However, the active compound and detailed mechanisms still remain unclear. Hydroxytyrosol (HT), a major polyphenolic compound in virgin olive oil, has received increased attention for its antioxidative activity and regulation of mitochondrial function. Here, we investigated whether HT is the active compound in olive oil exerting a protective effect against metabolic syndrome. In this study, we show that HT could prevent high-fat-diet (HFD)-induced obesity, hyperglycemia, hyperlipidemia, and insulin resistance in C57BL/6J mice after 17 weeks supplementation. Within liver and skeletal muscle tissues, HT could decrease HFD-induced lipid deposits through inhibition of the SREBP-1c/FAS pathway, ameliorate HFD-induced oxidative stress by enhancing antioxidant enzyme activities, normalize expression of mitochondrial complex subunits and mitochondrial fission marker Drp1, and eventually inhibit apoptosis activation. Moreover, in muscle tissue, the levels of mitochondrial carbonyl protein were decreased and mitochondrial complex activities were significantly improved by HT supplementation. In db/db mice, HT significantly decreased fasting glucose, similar to metformin. Notably, HT decreased serum lipid, at which metformin failed. Also, HT was more effective at decreasing the oxidation levels of lipids and proteins in both liver and muscle tissue. Similar to the results in the HFD model, HT decreased muscle mitochondrial carbonyl protein levels and improved mitochondrial complex activities in db/db mice. Our study links the olive oil component HT to diabetes and metabolic disease through changes that are not limited to decreases in oxidative stress, suggesting a potential pharmaceutical or clinical use of HT in metabolic syndrome treatment. [Copyright &y& Elsevier]

Characterization of tumor-responsive T cell receptors (TCRs) is a critical step in personalized TCR-T cell therapy, and remains challenging for pancreatic ductal adenocarcinoma (PDAC). Here we report a proof-of-concept study to identify and validate antitumor TCRs in two representative PDAC patients using ultradeep single-cell TCR/RNA sequencing and autologous organoids, and reveal the phenotypic dynamics of TCR repertoire in different T cell expansions from the same patient. We first performed comparative sequencing on freshly harvested peripheral blood mononuclear cells (PBMCs) and uncultured tumor infiltrating lymphocytes (TILs), followed by reactivity tests of TIL-enriched TCRs with autologous organoids, in which two tumor-responsive TCRs were successfully characterized and the corresponding TILs were mostly tissue-resident memory-like T cells, and partially expressed both naïve and exhausted T cell markers. For the PDAC patient without high-quality TILs, PBMCs were cultured with neoantigen peptide (KRASG12D), organoids, or anti-CD3 antibody in presence, and experienced extensive clonal expansions within ten days. All derived PBMCs were sequenced in parallel (>82,000 cells), and TCRs enriched in both peptide- and organoid-experienced, but not anti-CD3-treated CD8 T cells, were assessed for their reactivity to antigen-presenting cells (APCs) and organoids, in which three neoantigen-reactive TCRs were identified as tumor-responsive, and the corresponding T cells were characterized by mixed transcriptional signatures including but not limited to typical exhausted T cell markers. Together, our study revealed that the combination of ultradeep single-cell sequencing and organoid techniques enabled rapid characterization of tumor-responsive TCRs for developing practical personalized TCR-T therapy in an antigen/human leukocyte antigen (HLA)-agnostic manner. • Characterization of antitumor TCRs for PDAC via scRNA/TCR-seq and organoid evaluation in an antigen/HLA manner. • Boolean analysis of overlapping TCR repertoire of multiple enriched T cell populations from the same patient. • Tumor-responsive T cells in PDAC microenvironment are mostly tissue-resident memory-like. • Tumor-responsive T cells in peptide/organoid-experienced PBMCs display a variety of molecular signatures. [ABSTRACT FROM AUTHOR]

The plant embryogenic callus (EC) is an irregular embryogenic cell mass with strong regenerative ability that can be used for propagation and genetic transformation. However, difficulties with EC induction have hindered the breeding of drumstick, a tree with diverse potential commercial uses. In this study, three drumstick EC cDNA libraries were sequenced using an Illumina NovaSeq 6000 system. A total of 7191 differentially expressed genes (DEGs) for embryogenic callus development were identified, of which 2325 were mapped to the KEGG database, with the categories of plant hormone signal transduction and Plant-pathogen interaction being well-represented. The results obtained suggest that auxin and cytokinin metabolism and several embryogenesis-labeled genes are involved in embryogenic callus induction. Additionally, 589 transcription factors from 20 different families were differentially expressed during EC formation. The differential expression of 16 unigenes related to auxin signaling pathways was validated experimentally by quantitative real time PCR (qRT-PCR) using samples representing three sequential developmental stages of drumstick EC, supporting their apparent involvement in drumstick EC formation. Our study provides valuable information about the molecular mechanism of EC formation and has revealed new genes involved in this process. [ABSTRACT FROM AUTHOR]

BACKGROUND: Circulating miRNAs are promising biomarkers for detection of various cancers. As a "developmental" disorder, cancer showed great similarities with embryos. OBJECTIVE: A comprehensive analysis of circulating miRNAs in umbilical cord blood (UCB) and pan-cancers was conducted to identify circulating miRNAs with potential for cancer detection. METHODS: A total of 3831 cancer samples (2050 serum samples from 15 types of cancers and 1781 plasma samples from 13 types of cancers) and 248 UCB samples (120 serum and 128 plasma samples) with corresponding NCs from Chinese populations were analyzed via consistent experiment workflow with Exiqon panel followed by multiple-stage validation with qRT-PCR. RESULTS: Thirty-four serum and 32 plasma miRNAs were dysregulated in at least one type of cancer. Eighteen serum and 16 plasma miRNAs were related with embryos. Among them, 9 serum and 8 plasma miRNAs with consistent expression patterns between pan-cancers and UCB were identified as circulating oncofetal miRNAs. Retrospective analysis confirmed the diagnostic ability of circulating oncofetal miRNAs for specific cancers. And the oncofetal miRNAs were mainly up-regulated in tissues of pan-cancers. CONCLUSIONS: Our study might serve as bases for the potential application of the non-invasive biomarkers in the future clinical. [ABSTRACT FROM AUTHOR]

In the current study, thermal-denatured whey protein-milk fat emulsion gel microparticles (WPI-EGs) were used as stabilizers and fat replacers in low-fat yogurt. The effects of emulsion gel microparticles were studied on the texture, rheology, microstructure, and sensory evaluation of low-fat yogurt. The results showed that yogurt with WPI-EGs had a better (p < 0.05) water-holding capacity. The hardness of low-fat yogurt (1.50% (wt/wt) fat) added with WPI-EGs (1.5% LF-EY) increased (p < 0.05) significantly compared than skim yogurt and whole fat yogurt. Results from scanning electron microscopy showed that with the addition of WPI-EGs, yogurt has a more compact network structure and smaller pores. This study shows that WPI-EGs can be used as an effective fat replacer and stabilizer in yogurt. WPI-EGs have broad application prospects in dairy products, such as low-fat ice cream and processed cheese. • WPI-EGs have an effective effect in low-fat yogurt. • WPI-EGs could improve WHC and texture properties in low-fat yogurt. • WPI-EGs could be used as potential stabilizer and fat replacer in low-fat yogurt. [ABSTRACT FROM AUTHOR]

Mitochondrial epigenetics is rising as intriguing notion for its potential involvement in aging and diseases, while the details remain largely unexplored. Here it is shown that among the 13 mitochondrial DNA (mtDNA) encoded genes, NADH‐dehydrogenase 6 (ND6) transcript is primarily decreased in obese and type 2 diabetes populations, which negatively correlates with its distinctive hypermethylation. Hepatic mtDNA sequencing in mice unveils that ND6 presents the highest methylation level, which dramatically increases under diabetic condition due to enhanced mitochondrial translocation of DNA methyltransferase 1 (DNMT1) promoted by free fatty acid through adenosine 5'‐monophosphate (AMP)‐activated protein kinase (AMPK) activation. Hepatic knockdown of ND6 or overexpression of Dnmt1 similarly impairs mitochondrial function and induces systemic insulin resistance both in vivo and in vitro. Genetic or chemical targeting hepatic DNMT1 shows significant benefits against insulin resistance associated metabolic disorders. These findings highlight the pivotal role of ND6 epigenetic network in regulating mitochondrial function and onset of insulin resistance, shedding light on potential preventive and therapeutic strategies of insulin resistance and related metabolic disorders from a perspective of mitochondrial epigenetics. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA). Methods: In this multicenter, randomized, sham‐controlled trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent‐to‐treat population, which included all randomized participants who had ≥1 post‐baseline measurement. Results: Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between‐group differences were 13.0% (97.5% confidence interval [97.5% CI] 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI −1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26. Conclusion: Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow‐up. [ABSTRACT FROM AUTHOR]

The floral transition is a critical developmental switch in plants, and has profound effects on the flower production and yield. Magnolia × soulangeana 'Changchun' is known as a woody ornamental plant, which can bloom in spring and summer, respectively. In this study, anatomical observation, physiological measurement, transcriptome, and small RNA sequencing were performed to investigate potential endogenous regulatory mechanisms underlying floral transition in 'Changchun'. Transition of the shoot apical meristem from vegetative to reproductive growth occurred between late April and early May. During this specific developmental process, a total of 161,645 unigenes were identified, of which 73,257 were significantly differentially expressed, while a number of these two categories of miRNAs were 299 and 148, respectively. Further analysis of differentially expressed genes (DEGs) revealed that gibberellin signaling could regulate floral transition in 'Changchun' in a DELLA-dependent manner. In addition, prediction and analysis of miRNA targeted genes suggested that another potential molecular regulatory module was mediated by the miR172 family and other several novel miRNAs (Ms-novel_miR139, Ms-novel_miR229, and Ms-novel_miR232), with the participation of up- or down-regulating genes, including MsSVP, MsAP2, MsTOE3, MsAP1, MsGATA6, MsE2FA, and MsMDS6. Through the integrated analysis of mRNA and miRNA, our research results will facilitate the understanding of the potential molecular mechanism underlying floral transition in 'Changchun', and also provide basic experimental data for the plant germplasm resources innovation in Magnolia. [ABSTRACT FROM AUTHOR]

This 16-week randomised controlled trial (8-week treatment followed by 8-week follow-up) evaluated the symptomatic improvement in patients with knee osteoarthritis on 3 sessions per week of acupuncture (TSWA) compared to 1 session per week of acupuncture (OSWA). Sixty participants were randomised to either the TSWA or the OSWA group in a 1:1 ratio. The primary outcome was response rate, defined as the percentage of participants achieving ≥2 points decrease on the numerical rating scale (NRS) and ≥6 points decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Additional outcomes included response rates at weeks 4 and 16, NRS, WOMAC, Patient Global Assessment, 12-item Short Form Health Survey (SF-12), and treatment credibility and expectancy. No significant difference was seen in response rate between TSWA and OSWA groups at week 8 (64.7% vs 50.0%; difference, 14.7 percentage points [95% CI, -10.1 to 39.4 percentage points], P = 0.435). At weeks 4 and 16, the TSWA group had higher response rates than the OSWA group (week-4: difference, 44.7 percentage points [95% CI, 23.2-66.1 percentage points], P = 0.001; week-16: difference, 46.0 percentage points [95% CI, 24.4-67.6 percentage points], P < 0.001). Participants in the TSWA group experienced significantly greater improvements in NRS, WOMAC function, and Patient Global Assessment than those in the OSWA group. There were no significant between-group differences in WOMAC stiffness and SF-12. In summary, TSWA immediately improved knee pain and dysfunction compared with OSWA. In addition, the benefit of TSWA persists throughout follow-up. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 Delta variant outbreak on airplane: vaccinated air passengers are more protected than unvaccinated Keywords: SARS-CoV-2; Delta variant; inflight transmission; vaccine EN SARS-CoV-2 Delta variant inflight transmission vaccine 1 3 3 01/05/22 20211201 NES 211201 An emerging variant of SARS-CoV-2, Delta (Pango lineage B.1.617.2) was labelled as one of the variants of concern on June 2021 due to the increased transmissibility.1 Other unaffected countries face an increased risk of importation of the Delta-related cases. SARS-CoV-2, Delta variant, inflight transmission, vaccine. [Extracted from the article]

Background: Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures.Methods: From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk.Findings: Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20-22). Cases were isolated on average 4·6 days (95% CI 4·1-5·0) after developing symptoms; contact tracing reduced this by 1·9 days (95% CI 1·1-2·7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6·27 [95% CI 1·49-26·33] for household contacts and 7·06 [1·43-34·91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11·2% (95% CI 9·1-13·8), and children were as likely to be infected as adults (infection rate 7·4% in children <10 years vs population average of 6·6%). The observed reproductive number (R) was 0·4 (95% CI 0·3-0·5), with a mean serial interval of 6·3 days (95% CI 5·2-7·6).Interpretation: Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control.Funding: Emergency Response Program of Harbin Institute of Technology, Emergency Response Program of Peng Cheng Laboratory, US Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

The loose combination (LC) and the tight combination (TC) are two different models in the combined processing of four global navigation satellite systems (GNSSs). The former is easy to implement but may be unusable with few satellites, while the latter should cope with the inter-system bias (ISB) and is applicable for few tracked satellites. Furthermore, in both models, the inter-frequency bias (IFB) in the GLObal NAvigation Satellite System (GLONASS) system should also be removed. In this study, we aimed to investigate the performance difference of ambiguity resolution and position estimation between these two models simultaneously using the single-frequency data of all four systems (GPS + GLONASS + Galileo + BeiDou Navigation Satellite System (BDS)) in three different environments, i.e., in an open area, with surrounding high buildings, and under a block of high buildings. For this purpose, we first provide the definition of ISB and IFB from the perspective of the hardware delays, and then propose practical algorithms to estimate the IFB rate and ISB. Thereafter, a comprehensive performance comparison was made between the TC and LC models. Experiments were conducted to simulate the above three observation environments: the typical situation and situations suffering from signal obstruction with high elevation angles and limited azimuths, respectively. The results show that in a typical situation, the TC and LC models achieve a similar performance. However, when the satellite signals are severely obstructed and few satellites are tracked, the float solution and ambiguity fixing rates in the LC model are dramatically decreased, while in the TC model, there are only minor declines and the difference in the ambiguity fixing rates can be as large as 30%. The correctly fixed ambiguity rates in the TC model also had an improvement of around 10%. Once the ambiguity was fixed, both models achieved a similar positioning accuracy. [ABSTRACT FROM AUTHOR]

Background: The evidence for different frequencies of acupuncture treatment in postprandial distress syndrome (PDS) is insufficient. This study determined whether 3 sessions per week of acupuncture treatment are superior to 1 session per week for symptomatic outcomes in PDS. Methods: This 16‐week randomized clinical pilot trial was conducted in an outpatient setting in China. Patients with PDS were randomly assigned to receive 3 sessions per week of acupuncture (group H) or 1 session per week of acupuncture (group L) for 4 weeks. The primary outcome was the complete elimination of core symptoms at week 4. Secondary outcomes included overall treatment efficacy, dyspepsia symptoms, quality of life, anxiety, and depression. Key Results: Sixty patients were randomized of whom 53 (88.3%) completed this trial. The complete elimination rate of core symptoms was 26.7% (95% CI 12.3%‐45.9%) in group H and 10.0% (95% CI 2.1%‐26.5%) in group L at week 4 (P =.095). There was a significant difference between H and group L at weeks 8, 12, and 16 (P =.038,.02, and.02). All secondary outcomes were better in group H at all time points. No serious adverse events occurred in either groups. Conclusions: This trial showed that acupuncture, at 3 sessions per week, tended to improve symptoms and the quality of life among patients with PDS as compared to once a week. Acupuncture treatment for 4 weeks was feasible and safe. A larger sample, multicenter, randomized controlled trial of acupuncture for PDS appears to be justified in the future. [ABSTRACT FROM AUTHOR]

Background: This study aimed to overexpress or silence connexin 43 (Cx43) and A‐kinase anchoring protein 95 (AKAP95) in human A549 cells to explore their effects on cyclins and on G1/S conversion when the interrelationship of Cx43, AKAP95, and cyclin E1/E2 changes. Methods: The study mainly used Western blot analysis and Co‐immuno precipitation to detect the target protein in Cx43/AKAP95 over expressed human A549 cells, and the relationship of proteins Cx43, AKAP95 and Cyclin E during G1‐S phase was explored with qualitative and quantitative analysis. Results: The overexpression of Cx43 inhibited the expression of cyclin D1 and E1 by accelerating their degradation and reduced the Cdk2 activity that blocked the DNA transcription activity. However, the overexpression of AKAP95 increased the expression of cyclin D1 and E1 and inhibited their degradation, and enhanced the Cdk2 activity that promoted the DNA transcription activity. Cx43 and AKAP95 competitively bound to cyclin E1/E2, and the competitive binding affected the Cdk2 activity, Rb phosphorylation, DNA transcription activity, and G1/S conversion. Conclusions: This study showed that the expression of ERK1/2, PKA, and PKB increased when BEAS‐2B cells were treated with PDGF‐BB, suggesting that ERK1/2, PKA, and PKB might be involved in the binding of AKAP95 with cyclin E, or the separation of AKAP95 from Cx43 from cyclin E1/E2. The specific mechanism underlying this process still needs further exploration. [ABSTRACT FROM AUTHOR]

Understanding the habitat preferences of a fish species is crucial for protecting fish resources because it can guide development of appropriate conservation measures. Field surveys suggest that water flow velocity and substrate are the main influences on fish microhabitat selection. Controlled experiments are better suited to assessing fish microhabitat preferences than field surveys but experimental data are not yet sufficient for cyprinids. We conducted experiments with Schizothorax wangchiachii in an experimental system comprised of four parallel channels, with a different substrate type in each channel. Fish preference for each substrate was tested at four levels of water flow. Results show that flow velocity influences channel preference more than substrate type. Test fish entered channels more frequently as flow velocity increased from 0.01 m/s to 0.37 m/s. Surface stability and interstitial space were the major factors influencing preference for substrate type. The horizontal velocity gradient perpendicular to flow direction, resulting in shear stress, was hypothesized to be a third explanatory variable for channel preference, but it did not significantly influence channel preference. Test fish spent most of the day in a shaded (shelter) area and were far less active during the day than at night. This study provides information on S. wangchiachii preferences for water flow and substrate, circadian rhythm and daylight sheltering, information that will help guide efforts to conserve wild populations of S. wangchiachii. [ABSTRACT FROM AUTHOR]

To describe the clinical and genetic characteristics of the cohort enrolled in the East Asian studies of occult macular dystrophy (OMD). International, multicenter, retrospective cohort studies. A total of 36 participants from 21 families with a clinical diagnosis of OMD and harboring pathogenic RP1L1 variants (i.e., Miyake disease) were enrolled from 3 centers in Japan, China, and South Korea. A detailed history was obtained, and comprehensive ophthalmological examinations including spectral-domain OCT were performed. All detected sequence variants in the RP1L1 gene were reviewed, and in silico analysis was performed, including allele frequency analyses and pathogenicity predictions. Onset of disease, visual acuity (VA) converted to the logarithm of the minimum angle of resolution (logMAR), OCT findings, and effect of detected variants. Eleven families from Japan, 6 from South Korea, and 4 from China were recruited. There were 12 female and 24 male participants. The median age of onset was 25.5 years (range, 2–73), and the median age at the latest examination was 46.0 years (range, 11–86). The median VA (logMAR) was 0.65 (range, –0.08–1.22) in the right eye and 0.65 (–0.08–1.10) in the left eye. A significant correlation between onset of disease and VA was revealed. The Classical morphologic phenotype showing both blurred ellipsoid zone and absence of interdigitation zone of the photoreceptors was demonstrated in 30 patients (83.3%), and subtle photoreceptor architectural changes were demonstrated in 6 patients (16.6%). Eight pathogenic RP1L1 variants were identified, including 6 reported variants and 1 novel variant: p.R45W, p.T1194M/p.T1196I (complex), p.S1199C, p.G1200A, p.G1200D, p.V1201G, and p.S1198F, respectively. Two variants were recurrent: p.R45W (11 families, 52.4%) and p.S1199C (5 families, 23.8%). The pathogenic missense variants in 10 families (47.6%) were located within the previously reported unique motif, including 6 amino acids (1196–1201). There is a large spectrum of clinical findings in Miyake disease, including various onset of disease and VA, whereas the characteristic photoreceptor microstructures were shared in most cases. Two hot spots including amino acid numbers 45 and 1196–1201 in the RP1L1 gene were confirmed in the East Asian population. [ABSTRACT FROM AUTHOR]

α-L-Fucosidase (AFU) is a promising therapeutic target for the treatment of inflammation, cancer, cystic fibrosis, and fucosidosis. Some of the existing analytical methods for the assessment of AFU activity are lacking in sensitivity and selectivity, since most of them are based on spectrofluorimetric methods. More recently, mass spectrometry (MS) has evolved as a key technology for enzyme assays and inhibitor screening as it enables accurate monitoring of the conversion of substrate to product in enzymatic reactions. In this study, UHPLC-MS has been utilized to develop a simple, sensitive, and accurate assay for enzyme kinetics and inhibition studies of AFU3, a member of the AFU family. A reported method for analyzing saccharide involving a porous graphitic carbon column, combined with reduction by NaBH4/CH3OH, was used to improve sensitivity. The conversion of saccharide into alditol could reach nearly 100% in the NaBH4 reduction reaction. In addition, the bioanalytical quantitative screening method was validated according to US-FDA guidance, including selectivity, linearity, precision, accuracy, stability, and matrix effect. The developed method displayed a good accuracy, high sensitivity (LOD = 0.05 mg L−1), and good reproducibility (RSD < 15%). The assay accurately measured an IC50 value of 0.40 μM for the known AFU inhibitor, deoxyfuconojirimycin, which was consistent with results reported in the literature. Further validation of the assay was achieved through the determination of a high Z′-factor value of 0.89. The assay was applied to screen a marine-derived chemical library against AFU3, which revealed two marine-oriented pyrimidine alkaloids as potential AFU3 inhibitors. Graphical abstract [ABSTRACT FROM AUTHOR]

Highlights • A multi-target AMEs inhibitor screening assay was developed with UHPLC-QTOF MS. • Screening of the AAC(6'), APH(2") and AAC(6')-APH(2") inhibitors simultaneously. • The assay was developed for the treatment of multidrug-resistant bacteria. • Kinetic parameters determined were in agreement with those reported in literatures. • Two pyrimidinyl indole derivatives had potential to treat antibiotic resistance. Abstract Resistance to aminoglycoside antibiotics occurs primarily as a result of aminoglycoside-modification enzymes (AMEs) that modify the antibiotics. In this work, a novel strategy to combat the effects of antibiotic resistance was developed by screening multiple AMEs inhibitors with ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF MS). The method screened inhibitors of three AMEs (AAC(6')-APH(2"), AAC(6') and APH(2")) simultaneously through measuring the acetyltransferase activity and phosphotransferase activity of AAC(6')-APH(2") enzyme in a single assay. Screening inhibitors of multiple targets could greatly improve the screening efficiency at early-stages of drug discovery. In this study, enzyme reaction conditions including cosubstrate, enzyme concentration and cosubstrate concentration were optimized. The inhibition constants (K i) for two known inhibitors, paromomycin and quercetin, were determined to be 1.23 and 20.27 μM, respectively. The assay was further validated through the determination of a high Z' factor value of 0.73. The developed assay was applied to screen a chemical library against bifunctional AAC(6')-APH(2") enzyme. Using this assay, two pyrimidinyl indole derivatives were found to be potent, and effective AAC(6')-APH(2") inhibitors. The assay of exploring the selective inhibitory effect on two AAC(6')-APH(2") active sites was further performed. Two pyrimidinyl indole derivatives were found to exhibit striking inhibitory activities on AAC(6'). [ABSTRACT FROM AUTHOR]

Abstract Many epidemiological studies suggested a correlation between obesity and asthma. However, little is known about the molecular details explaining this correlation. Here, we show that asthma decreased body weight of asthmatic male mice fed with high fat diet via increasing energy expenditure and insulin sensitivity. The increase of energy expenditure was mainly due to upregulation of pAMPK and Sirt1. The activation of AMPK/Sirt1/PGC1α signaling promoted the expression of the thermogenic genes like ucp1, PRDM16, cidea, Elovl3, PPARα, which occurred in brown adipocyte tissue and subcutaneous white adipose tissue. Besides, by activating IL33/ILC2/AAMac pathway in subcutaneous white adipose tissue, asthma promoted subcutaneous white adipose tissue into beige fat. In addition, insulin sensitivity was improved in the asthmatic male mice by decreasing the expression of G6Pase in the liver, which was recapitulated in HepG2. In human, we found that Body Mass Index (BMI) and waist circumference were significantly lower in males suffering asthma compared with the control in the National Health and Nutrition Examination Survey (NHANES) cohort. These data together suggest asthma in males decreases obesity by improving the metabolism function of brown and subcutaneous adipose tissue, and decreasing insulin resistant in the liver. Highlights • Allergic asthma inhibits obesity, promotes white adipocytes browning in male mice. • Asthma-activated AMPK/PGC1a signaling promotes thermogenic gene expression in brown adipose tissue. • In asthmatic mice, the activation of AMPK / PGC1a and IL33/ILC2 promotes SAT into beige fat. • Asthma negatively associated with obesity in men. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA.Methods/design: This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8 weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ≥2 points on the numerical rating scale and ≥6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation.Discussion: This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals.Trial Registration: ClinicalTrials.gov, NCT03274713 . Registered on 20 November 2017. [ABSTRACT FROM AUTHOR]

Abstract: Rapid technological advances enabling the construction of designer gene networks, biosynthetic pathways, and even entire genomes are moving the fields of genetics and genomics from descriptive to synthetic applications. Following the synthesis of small viral genomes, advances in DNA assembly and rewriting have enabled the hierarchical synthesis of bacterial genomes, such as Mycoplasma genitalium, as well as recoding of the Escherichia coli genome by reducing the number of codons from 64 to 57. The field has advanced to the point of synthesizing an entire eukaryotic genome. The Synthetic Yeast Genome Project (Sc2.0) is underway and aims to rewrite all 16 Saccharomyces cerevisiae chromosomes by 2018; to date, 6.5 chromosomes have been designed and synthesized. Using bottom‐up assembly and applying genome‐wide alterations will improve our understanding of genome structure and function. This approach will not only provide a platform for systematic studies of eukaryotic chromosomes but will also generate diverse “streamlined” strains that are potentially suitable for medical and industrial applications. Herein, we review the current state of synthetic genome research and discuss potential applications of this emerging technology. [ABSTRACT FROM AUTHOR]

Abstract: Rasante technische Fortschritte, die die Konstruktion von genetischen Netzwerken, Biosynthesepfaden und sogar ganzer Genome ermöglichen, konvertieren derzeit die Genetik und Genomik von rein deskriptiven zu synthetischen Wissenschaften. Anknüpfend an die Synthese kleiner viraler Genome haben Fortschritte bei der Assemblierung und Neusynthese von DNA die hierarchische Synthese bakterieller Genome, z. B. von Mycoplasma genitalium, sowie die Umkodierung des Genoms von Escherichia coli durch Reduzierung der Zahl an Codons von 64 auf 57 ermöglicht. Das Gebiet ist an dem Punkt angekommen, dass wir ein gesamtes eukaryotisches Genom synthetisieren können. Das “Synthetic Yeast Genome Project” (Sc2.0) folgt den Plan, bis 2018 alle 16 Saccharomyces cerevisiae‐Chromosomen neu zu synthetisieren; bisher wurden 6.5 Chromosomen konzipiert und synthetisiert. Bottom‐up‐Assemblierung und die Anwendung genomweiter Modifikationen werden unser Verständnis der Genomstruktur und ‐funktion verbessern. Dieser Ansatz wird nicht nur eine Plattform für die systemische Erforschung eukaryotischer Chromosomen bieten, sondern auch “verschlankte” Stämme hervorbringen, die für medizinische und industrielle Anwendungen potenziell geeignet sind. In diesem Kurzaufsatz fassen wir den aktuellen Stand der Forschung im Bereich synthetischer Genome zusammen und diskutieren mögliche Anwendungen dieser neuen Technologie. [ABSTRACT FROM AUTHOR]