JANUS, a spliceosome-associated protein, promotes miRNA biogenesis in Arabidopsis.

MicroRNAs (miRNAs) are important regulators of genes expression. Their levels are precisely controlled through modulating the activity of the microprocesser complex (MC). Here, we report that JANUS, a homology of the conserved U2 snRNP assembly factor in yeast and human, is required for miRNA accumulation. JANUS associates with MC components Dicer-like 1 (DCL1) and SERRATE (SE) and directly binds the stem-loop of pri-miRNAs. In a hypomorphic janus mutant, the activity of DCL1, the numbers of MC, and the interaction of primary miRNA transcript (pri-miRNAs) with MC are reduced. These data suggest that JANUS promotes the assembly and activity of MC through its interaction with MC and/or pri-miRNAs. In addition, JANUS modulates the transcription of some pri-miRNAs as it binds the promoter of pri-miRNAs and facilitates Pol II occupancy of at their promoters. Moreover, global splicing defects are detected in janus. Taken together, our study reveals a novel role of a conserved splicing factor in miRNA biogenesis.

Transcription factor OsMYB30 increases trehalose content to inhibit α-amylase and seed germination at low temperature.

Low-temperature germination (LTG) is an important agronomic trait for direct-seeding cultivation of rice (Oryza sativa). Both OsMYB30 and OsTPP1 regulate the cold stress response in rice, but the function of OsMYB30 and OsTPP1 in regulating LTG and the underlying molecular mechanism remains unknown. Employing transcriptomics and functional studies revealed a sugar signaling pathway that regulates seed germination in response to low temperature (LT). Expression of OsMYB30 and OsTPP1 was induced by LT during seed germination, and overexpressing either OsMYB30 or OsTPP1 delayed seed germination and increased sensitivity to LT during seed germination. Transcriptomics and qPCR revealed that expression of OsTPP1 was upregulated in OsMYB30-overexpressing lines but downregulated in OsMYB30-knockout lines. In vitro and in vivo experiments revealed that OsMYB30 bound to the promoter of OsTPP1 and regulated the abundance of OsTPP1 transcripts. Overaccumulation of trehalose (Tre) was found in both OsMYB30- and OsTPP1-overexpressing lines, resulting in inhibition of α-amylase 1a (OsAMY1a) gene during seed germination. Both LT and exogenous Tre treatments suppressed the expression of OsAMY1a, and the osamy1a mutant was not sensitive to exogenous Tre during seed germination. Overall, we concluded that OsMYB30 expression was induced by LT to activate the expression of OsTPP1 and increase Tre content, which thus inhibited α-amylase activity and seed germination. This study identified a phytohormone-independent pathway that integrates environmental cues with internal factors to control seed germination.

Fujian cytoplasmic male sterility and the fertility restorer gene OsRf19 provide a promising breeding system for hybrid rice.

Cytoplasmic male sterility (CMS) determined by mitochondrial genes and restorer of fertility (Rf) controlled by nuclear-encoded genes provide the breeding systems of many hybrid crops for the utilization of heterosis. Although several CMS/Rf systems have been widely exploited in rice, hybrid breeding using these systems has encountered difficulties due to either fertility instability or complications of two-locus inheritance or both. In this work, we characterized a type of CMS, Fujian Abortive cytoplasmic male sterility (CMS-FA), with stable sporophytic male sterility and a nuclear restorer gene that completely restores hybrid fertility. CMS is caused by the chimeric open reading frame FA182 that specifically occurs in the mitochondrial genome of CMS-FA rice. The restorer gene OsRf19 encodes a pentatricopeptide repeat (PPR) protein targeted to mitochondria, where it mediates the cleavage of FA182 transcripts, thus restoring male fertility. Comparative sequence analysis revealed that OsRf19 originated through a recent duplication in wild rice relatives, sharing a common ancestor with OsRf1a/OsRf5, a fertility restorer gene for Boro II and Hong-Lian CMS. We developed six restorer lines by introgressing OsRf19 into parental lines of elite CMS-WA hybrids; hybrids produced from these lines showed equivalent or better agronomic performance relative to their counterparts based on the CMS-WA system. These results demonstrate that CMS-FA/OsRf19 provides a highly promising system for future hybrid rice breeding.

Myometrium infection decreases TREK1 through NHE1 and increases contraction in pregnant mice.

Intrauterine infection during pregnancy can enhance uterine contractions. A two-pore K+ channel TREK1 is crucial for maintaining uterine quiescence and reducing contractility, with its properties regulated by pH changes in cell microenvironment. Meanwhile, the sodium hydrogen exchanger 1 (NHE1) plays a pivotal role in modulating cellular pH homeostasis, and its activation increases smooth muscle tension. By establishing an infected mouse model of Escherichia coli (E. coli) and lipopolysaccharide (LPS), we used Western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence to detect changes of TREK1 and NHE1 expression in the myometrium, and isometric recording measured the uterus contraction. The NHE1 inhibitor cariporide was used to explore the effect of NHE1 on TREK1. Finally, cell contraction assay and siRNA transfection were performed to clarify the relationship between NHE1 and TREK1 in vitro. We found that the uterine contraction was notably enhanced in infected mice with E. coli and LPS administration. Meanwhile, TREK1 expression was reduced, whereas NHE1 expression was upregulated in infected mice. Cariporide alleviated the increased uterine contraction and promoted myometrium TREK1 expression in LPS-injected mice. Furthermore, suppression of NHE1 with siRNA transfection inhibited the contractility of uterine smooth muscle cells and activated the TREK1. Altogether, our findings indicate that infection increases the uterine contraction by downregulating myometrium TREK1 in mice, and the inhibition of TREK1 is attributed to the activation of NHE1.NEW & NOTEWORTHY Present work found that infection during pregnancy will increase myometrium contraction. Infection downregulated NHE1 and followed TREK1 expression and activation decrease in myometrium, resulting in increased myometrium contraction.

Effectiveness of a single low-dose computed tomography screening for lung cancer: A population-based perspective cohort study in China.

The purpose of this perspective cohort study was to evaluate the effectiveness of low-dose computed tomography (LDCT) screening for lung cancer in China. This study was conducted under the China Urban Cancer Screening Program (CanSPUC). The analysis was based on participants aged 40 to 74 years from 2012 to 2019. A total of 255 569 eligible participants were recruited in the study. Among the 58 136 participants at high risk of lung cancer, 20 346 (35.00%) had a single LDCT scan (defined as the screened group) and 37 790 (65.00%) not (defined as the non-screened group). Overall, 1162 participants were diagnosed with lung cancer at median follow-up time of 5.25 years. The screened group had the highest cumulative incidence of lung cancer and the non-screened group had the highest cumulative lung cancer mortality and all-cause cumulative mortality. We performed inverse probability weighting (IPW) to account for potential imbalances, and Cox proportional hazards model to estimate the weighted association between mortality and LDCT scans. After IPW adjusted with baseline characteristics, the lung cancer incidence density was significantly increased (37.0% increase) (HR1.37 [95%CI 1.12-1.69]), lung cancer mortality was decreased (31.0% decrease) (HR0.69 [95%CI 0.49-0.97]), and the all-cause mortality was significantly decreased (23.0% lower) (HR0.77 [95% CI 0.68-0.87]) in the screened group. In summary, a single LDCT for lung cancer screening will reduce the mortality of lung cancer and all-cause mortality in China.

Relative efficacy of antibody-drug conjugates and other anti-HER2 treatments on survival in HER2-positive advanced breast cancer: a systematic review and meta-analysis.

BACKGROUND: Novel antibody-drug conjugates (ADCs) drugs present a promising anti-cancer treatment, although survival benefits for HER2-positive advanced breast cancer (BC) remain controversial. The aim of this meta-analysis was to evaluate the comparative effect of ADCs and other anti-HER2 therapy on progression-free survival (PFS) and overall survival (OS) for treatment of HER2-positive locally advanced or metastatic BC. METHODS: Relevant randomized controlled trials (RCTs) were retrieved from five databases. The risk of bias was assessed with the Cochrane Collaboration's tool for RCTs by RevMan5.4 software. The hazard ratio (HR) and 95% confidence intervals (CIs) were extracted to evaluate the benefit of ADCs on PFS and OS in HER2-positive advanced BC by meta-analysis. RESULTS: Meta-analysis of six RCTs with 3870 patients revealed that ADCs significantly improved PFS (HR: 0.63, 95% CI: 0.49-0.80, P = 0.0002) and OS (HR: 0.79, 95% CI: 0.72-0.86, P < 0.0001) of patients with HER2-positive locally advanced or metastatic BC. Subgroup analysis showed that PFS and OS were obviously prolonged for patients who previously received HER2-targeted therapy. Sensitivity analysis and publication bias suggested that the results were stable and reliable. CONCLUSION: Statistically significant benefits for PFS and OS were observed with ADCs in HER2-positive locally advanced or metastatic BC, especially for those who received prior anti-HER2 treatment.

Measuring Equity in Readmission as a Distinct Assessment of Hospital Performance.

Importance: Equity is an essential domain of health care quality. The Centers for Medicare & Medicaid Services (CMS) developed 2 Disparity Methods that together assess equity in clinical outcomes. Objectives: To define a measure of equitable readmissions; identify hospitals with equitable readmissions by insurance (dual eligible vs non-dual eligible) or patient race (Black vs White); and compare hospitals with and without equitable readmissions by hospital characteristics and performance on accountability measures (quality, cost, and value). Design, Setting, and Participants: Cross-sectional study of US hospitals eligible for the CMS Hospital-Wide Readmission measure using Medicare data from July 2018 through June 2019. Main Outcomes and Measures: We created a definition of equitable readmissions using CMS Disparity Methods, which evaluate hospitals on 2 methods: outcomes for populations at risk for disparities (across-hospital method); and disparities in care within hospitals' patient populations (within-a-single-hospital method). Exposures: Hospital patient demographics; hospital characteristics; and 3 measures of hospital performance-quality, cost, and value (quality relative to cost). Results: Of 4638 hospitals, 74% served a sufficient number of dual-eligible patients, and 42% served a sufficient number of Black patients to apply CMS Disparity Methods by insurance and race. Of eligible hospitals, 17% had equitable readmission rates by insurance and 30% by race. Hospitals with equitable readmissions by insurance or race cared for a lower percentage of Black patients (insurance, 1.9% [IQR, 0.2%-8.8%] vs 3.3% [IQR, 0.7%-10.8%], P < .01; race, 7.6% [IQR, 3.2%-16.6%] vs 9.3% [IQR, 4.0%-19.0%], P = .01), and differed from nonequitable hospitals in multiple domains (teaching status, geography, size; P < .01). In examining equity by insurance, hospitals with low costs were more likely to have equitable readmissions (odds ratio, 1.57 [95% CI, 1.38-1.77), and there was no relationship between quality and value, and equity. In examining equity by race, hospitals with high overall quality were more likely to have equitable readmissions (odds ratio, 1.14 [95% CI, 1.03-1.26]), and there was no relationship between cost and value, and equity. Conclusion and Relevance: A minority of hospitals achieved equitable readmissions. Notably, hospitals with equitable readmissions were characteristically different from those without. For example, hospitals with equitable readmissions served fewer Black patients, reinforcing the role of structural racism in hospital-level inequities. Implementation of an equitable readmission measure must consider unequal distribution of at-risk patients among hospitals.

Women's mental health during late pregnancy: A survey conducted in Shandong Province, China.

BACKGROUND: The study aimed to investigate the general mental health status and its associated factors in women during late pregnancy. The objective was to provide a scientific basis for developing psychological interventions tailored to this specific population. METHODS: The research was conducted from May 2021 to July 2022, involving the recruitment of 200 women attending maternal and child health clinics for their late-pregnancy checkups. Data collection was carried out using a comprehensive approach, involving several validated tools. The participants completed a general demographic and sociological questionnaire along with four standardized psychological assessment scales: the 12-item General Health Questionnaire (GHQ-12), the Athens Insomnia Scale (AIS-8), the Generalized Anxiety Disorder 7 (GAD-7), and the 9-question Patient Health Questionnaire (PHQ-9). A total of 200 valid questionnaires were collected for analysis. RESULTS: The study revealed that the overall prevalence of positive detection of general mental health problems in women during late pregnancy was 11%. Significant differences were observed in the positive detection rate of general mental health status based on various factors such as the quality of relationships with husbands, pregnancy intentions, insomnia, anxiety, and depression (p<0.01). Furthermore, participants with general mental health problems displayed notably higher scores on the AIS-8, PHQ-9, and GAD-7 scales compared to those without such problems (p<0.01). Regression analysis indicated that pregnancy intention and PHQ-9 scores were influential factors affecting the general mental health of women during late pregnancy (p<0.05). CONCLUSION: The study highlights high rates of general mental health problems during late pregnancy, with unplanned pregnancy and elevated depression scores as key risk factors. Regular mental health screening and targeted interventions are essential to support women during this critical period and enhance the well-being of both mothers and babies.

Synergistic interaction between ABA and IAA due to moderate soil drying promotes grain filling of inferior spikelets in rice.

Poor grain filling of inferior spikelets is becoming a severe problem in some super rice varieties with large panicles. Moderate soil drying (MD) after pollination has been proven to be a practical strategy to promote grain filling. However, the molecular mechanisms underlying this phenomenon remain largely unexplored. Here, transcriptomic analysis of the most active grain filling stage revealed that both starch metabolism and phytohormone signaling were significantly promoted by MD treatment, accompanied by increased enzyme activities of starch synthesis and elevated abscisic acid (ABA) and indole-3-acetic acid (IAA) content in the inferior spikelet. Moreover, the IAA biosynthesis genes OsYUC11 and OsTAR2 were upregulated, while OsIAA29 and OsIAA24, which encode two repressors of auxin signaling, were downregulated by MD, implying a regulation of both IAA biosynthesis and auxin signal transduction in the inferior spikelet by MD. A notable improvement in grain filling of the inferior spikelet was found in the aba8ox2 mutant, which is mutated in an ABA catabolism gene. In contrast, overexpression of OsABA8ox2 significantly reduced grain filling. Interestingly, not only the IAA content, but also the expression of IAA biosynthesis and auxin-responsive genes displayed a similar trend to that in the inferior spikelet under MD. In addition, several OsTPP genes were downregulated in the inferior spikelets of both MD/ABA-treated wild-type plants and the aba8ox2 mutant, resulting in lower trehalose content and higher levels of -6-phosphate (T6P), thereby increasing the expression of OsTAR2, a target of T6P. Taken together, our results suggest that the synergistic interaction of ABA-mediated accumulation of IAA promotes grain filling of inferior spikelets under MD.

Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.

BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months. CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. CLINICAL TRIALS REGISTRATION: NCT04610515.

Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study.

BACKGROUND: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). METHODS: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. RESULTS: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. CONCLUSIONS: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515.

Prolonged stretching of rat uteri causes hypoxia and inhibits contractility via potassium channel TREK1.

In brief: During pregnancy, uterine kept quiescence along with uterine overdistention before labor. Prolonged stretching induced uterus myometrial hypoxia, increased TREK1 expression, and relaxed the myometrium, which may contribute to uterine quiescence and atony during pregnancy. Abstract: The mechanisms underlying pre-labor uterine quiescence and uterine atony during overdistention are unclear. TREK1 (a two-pore domain potassium channel) and hypoxia-inducible factor-1α (HIF-1α) are activated by mechanical stretch, and their expression is upregulated by decreased uterine contractility. HIF-1α is a nuclear factor which regulates numerous target proteins, but whether it regulates TREK1 during the uterine stretch to cause uterine quiescence and/or atony is unclear. We investigated uterine contractility at different gestational stages in rats, as well as in non-pregnant uteri, which were induced by prolonged stretching and hypoxia. We also assessed the effects of incubating the uteri with or without echinomycin or l-methionine. Moreover, we analyzed HIF-1α and TREK1 expression levels in each group, as well as at various gestational stages of pregnant human uteri. We found that contractility was significantly decreased in pregnant uteri when compared with non-pregnant uteri, and this decrease was associated with increases in HIF-1α and TREK1 expression levels. HIF-1α and TREK1 expression levels in human uteri increased with the gestational length. Decreased uterine contractility and increased HIF-1α and TREK1 expression levels were also observed in non-pregnant rat uteri under 8 g of stretching tension or hypoxia. Inhibition of hypoxia with echinomycin restored normal uterine contractility, while HIF-1α and TREK1 protein expression remained reduced. TREK1 inhibition with l-methionine also restored uterine contractility under tension or hypoxia. In conclusion, we demonstrated that prolonged stretching induces myometrial hypoxia, increases TREK1 expression, and relaxes the myometrium, which may contribute to uterine quiescence and atony.

Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID-19 Testing Status Among Adults - United States, December 2020-March 2023.

To further the understanding of post-COVID conditions, and provide a more nuanced description of symptom progression, resolution, emergence, and reemergence after SARS-CoV-2 infection or COVID-like illness, analysts examined data from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a prospective multicenter cohort study. This report includes analysis of data on self-reported symptoms collected from 1,296 adults with COVID-like illness who were tested for SARS-CoV-2 using a Food and Drug Administration-approved polymerase chain reaction or antigen test at the time of enrollment and reported symptoms at 3-month intervals for 12 months. Prevalence of any symptom decreased substantially between baseline and the 3-month follow-up, from 98.4% to 48.2% for persons who received a positive SARS-CoV-2 test results (COVID test-positive participants) and from 88.2% to 36.6% for persons who received negative SARS-CoV-2 test results (COVID test-negative participants). Persistent symptoms decreased through 12 months; no difference between the groups was observed at 12 months (prevalence among COVID test-positive and COVID test-negative participants = 18.3% and 16.1%, respectively; p>0.05). Both groups reported symptoms that emerged or reemerged at 6, 9, and 12 months. Thus, these symptoms are not unique to COVID-19 or to post-COVID conditions. Awareness that symptoms might persist for up to 12 months, and that many symptoms might emerge or reemerge in the year after COVID-like illness, can assist health care providers in understanding the clinical signs and symptoms associated with post-COVID-like conditions.

Yield and cost of government-organized colorectal cancer screening in young high-risk population in Northeast China.

Guidelines for colorectal cancer (CRC) screening recommend screening at age 40 for high-risk population in China. However, the yield and cost of CRC screening in younger population are lacking. This analysis aimed to evaluate the yield and cost of CRC screening in high-risk 40- to 54-year-olds. Individuals aged 40-54 years who were determined to have a high risk of CRC were recruited from December 2012 to December 2019. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the detection rate of colorectal lesions among the three age groups and further calculated number of colonoscopies needed to screen (NNS) to detect one advanced lesion and cost of each group. The detection rates of advanced colorectal neoplasm in men aged 45-49 years (OR = 2.00, 95% CI: 0.93-4.30) and 50-54 years (OR = 2.19, 95% CI: 1.04-4.62) were higher than that aged 40-44 years. The detection rates of colorectal adenoma in women aged 50-54 years was higher than that aged 40-44 years (OR = 1.64, 95% CI: 1.23-2.19). Among the male screening population, NNS and cost to detect one advanced lesion in participants aged 45-49 years were similar to that aged 50-54 years, saving approximately half endoscopic resources and financial expenses compared with screening that aged 40-44 years. From the perspective of screening results and costs, it might be beneficial to delay the starting age of screening by gender. This study may provide reference for optimizing CRC screening strategies.

A population-based cross-sectional study on the situation of cervical cancer screening in Liaoning, China.

BACKGROUND: Cervical cancer (CC) screening is currently recognized as an effective intervention for CC. Previous studies found that the proportion of screening was low in China, especially in Liaoning. Therefore, we performed a population-based cross-sectional survey to investigate the situation of cervical cancer screening and analyze their related factors for providing a decision-making basis for sustainable and effective development of cervical cancer screening. METHODS: This population-based cross-sectional study involved aged 30 to 69 years in nine counties/districts in Liaoning from 2018 to 2019. Data were collected using the quantitative data collection methods, and analyzed in SPSS version 22.0. RESULTS: Overall, only 22.37% of 5334 respondents reported having ever been screened for cervical cancer in past 3 years, and 38.41% of respondents reported having the willingness for cervical cancer screening in next 3 years. In the rate of CC screening, multilevel analysis indicated that age, marital status, education level, type of occupation, medical insurance, family income, place of residence and regional economic level had a significant impact on proportion of screening. In the rate of CC screening willingness, multilevel analysis indicated that age, family income, health status, place of residence, regional economic level and CC screening still had a significant impact, but marital status, education level and medical insurance type had no significant impact. There was no significant difference in marital status, education level and medical insurance type after the factors of CC screening were added in the model. CONCLUSION: Our study found both proportion of screening and willingness were at a low level, and age, economic and regional factors were the main factors for implementation of CC screening in China. In the future, targeted policies should be formulated according to the characteristics of different groups of people, and reduce the gap in the current health service capacity between different regions.

Grain size characterization of Ti-6Al-4V titanium alloy based on laser ultrasonic random forest regression.

In this paper, a random forest regression (RFR) rain size characterization method based on a laser ultrasound technique is investigated to predict the grain size of titanium alloy (Ti-6Al-4V). The longitudinal wave velocity of the ultrasound signal and the attenuation coefficient at different frequencies are used as the input and the grain size is used as the output. An RFR algorithm was used to develop a grain size prediction model. Meanwhile, the grain size calculation model based on conventional scattering attenuation was established by calibrating the n value in the classical scattering theory using the attenuation coefficients at different frequencies of ultrasonic signals. The results show that the RFR algorithm is feasible for the grain size characterization of titanium alloys.

The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice.

The diversity of the human microbiome heralds the difference of the impact that gut microbial metabolites exert on allogenic graft-versus-host (GVH) disease (GVHD), even though short-chain fatty acids and indole were demonstrated to reduce its severity. In this study, we dissected the role of choline-metabolized trimethylamine N-oxide (TMAO) in the GVHD process. Either TMAO or a high-choline diet enhanced the allogenic GVH reaction, whereas the analog of choline, 3,3-dimethyl-1-butanol reversed TMAO-induced GVHD severity. Interestingly, TMAO-induced alloreactive T-cell proliferation and differentiation into T-helper (Th) subtypes was seen in GVHD mice but not in in vitro cultures. We thus investigated the role of macrophage polarization, which was absent from the in vitro culture system. F4/80+CD11b+CD16/32+ M1 macrophage and signature genes, IL-1ß, IL-6, TNF-α, CXCL9, and CXCL10, were increased in TMAO-induced GVHD tissues and in TMAO-cultured bone marrow-derived macrophages (BMDMs). Inhibition of the NLRP3 inflammasome reversed TMAO-stimulated M1 features, indicating that NLRP3 is the key proteolytic activator involved in the macrophage's response to TMAO stimulation. Consistently, mitochondrial reactive oxygen species and enhanced NF-κB nuclear relocalization were investigated in TMAO-stimulated BMDMs. In vivo depletion of NLRP3 in GVHD recipients not only blocked M1 polarization but also reversed GVHD severity in the presence of TMAO treatment. In conclusion, our data revealed that TMAO-induced GVHD progression resulted from Th1 and Th17 differentiation, which is mediated by the polarized M1 macrophage requiring NLRP3 inflammasome activation. It provides the link among the host choline diet, microbial metabolites, and GVH reaction, shedding light on alleviating GVHD by controlling choline intake.

Modulating the Molecular Geometry and Solution Self-Assembly of Amphiphilic Polypeptoid Block Copolymers by Side Chain Branching Pattern.

Solution self-assembly of coil-crystalline diblock copolypeptoids has attracted increasing attention due to its capability to form hierarchical nanostructures with tailorable morphologies and functionalities. While the N-substituent (or side chain) structures are known to affect the crystallization of polypeptoids, their roles in dictating the hierarchical solution self-assembly of diblock copolypeptoids are not fully understood. Herein, we designed and synthesized two types of diblock copolypeptoids, i.e., poly(N-methylglycine)-b-poly(N-octylglycine) (PNMG-b-PNOG) and poly(N-methylglycine)-b-poly(N-2-ethyl-1-hexylglycine) (PNMG-b-PNEHG), to investigate the influence of N-substituent structure on the crystalline packing and hierarchical self-assembly of diblock copolypeptoids in methanol. With a linear aliphatic N-substituent, the PNOG blocks pack into a highly ordered crystalline structure with a board-like molecular geometry, resulting in the self-assembly of PNMG-b-PNOG molecules into a hierarchical microflower morphology composed of radially arranged nanoribbon subunits. By contrast, the PNEHG blocks bearing bulky branched aliphatic N-substituents are rod-like and prefer to stack into a columnar hexagonal liquid crystalline mesophase, which drives PNMG-b-PNEHG molecules to self-assemble into symmetrical hexagonal nanosheets in solution. A combination of time-dependent small/wide-angle X-ray scattering and microscopic imaging analysis further revealed the self-assembly mechanisms for the formation of these microflowers and hexagonal nanosheets. These results highlight the significant impact of the N-substituent architecture (i.e., linear versus branched) on the supramolecular self-assembly of diblock copolypeptoids in solution, which can serve as an effective strategy to tune the geometry and hierarchical structure of polypeptoid-based nanomaterials.

Genome-wide discovery of natural variation in pre-mRNA splicing and prioritising causal alternative splicing to salt stress response in rice.

Pre-mRNA splicing is an essential step for the regulation of gene expression. In order to specifically capture splicing variants in plants for genome-wide association studies (GWAS), we developed a software tool to quantify and visualise Variations of Splicing in Population (VaSP). VaSP can quantify splicing variants from short-read RNA-seq datasets and discover genotype-specific splicing (GSS) events, which can be used to prioritise causal pre-mRNA splicing events in GWAS. We applied our method to an RNA-seq dataset with 328 samples from 82 genotypes from a rice diversity panel exposed to optimal and saline growing conditions. In total, 764 significant GSS events were identified in salt stress conditions. GSS events were used as markers for a GWAS with the shoot Na+ accumulation, which identified six GSS events in five genes significantly associated with the shoot Na+ content. Two of these genes, OsNUC1 and OsRAD23 emerged as top candidate genes with splice variants that exhibited significant divergence between the variants for shoot growth under salt stress conditions. VaSP is a versatile tool for alternative splicing analysis in plants and a powerful tool for prioritising candidate causal pre-mRNA splicing and corresponding genomic variations in GWAS.

Serrate-Associated Protein 1, a splicing-related protein, promotes miRNA biogenesis in Arabidopsis.

MicroRNAs (miRNAs) are essential regulators of gene expression in metazoans and plants. In plants, most miRNAs are generated from primary miRNA transcripts (pri-miRNAs), which are processed by the Dicer-like 1 (DCL1) complex along with accessory proteins. Serrate-Associated Protein 1 (SEAP1), a conserved splicing-related protein, has been studied in human and yeast. However, the functions of SEAP1 in plants remain elusive. Lack of SEAP1 results in embryo lethality and knockdown of SEAP1 by an artificial miRNA (amiRSEAP1 ) causes pleiotropic developmental defects and reduction in miRNA accumulation. SEAP1 associates with the DCL1 complex, and may promote the interaction of the DCL1 complexes with pri-miRNAs. SEAP1 also enhances pri-miRNA accumulation, but does not affect pri-miRNA transcription, suggesting it may indirectly or directly stabilize pri-miRNAs. In addition, SEAP1 affects the splicing of some pri-miRNAs and intron retention of messenger RNAs at global levels. Our findings uncover both conserved and novel functions of SEAP1 in plants. Besides the role as a splicing factor, SEPA1 may promote miRNA biogenesis by positively modulating pri-miRNA splicing, processing and/or stability.