Citrulline depletion by ASS1 is required for proinflammatory macrophage activation and immune responses.

Citrulline can be converted into argininosuccinate by argininosuccinate synthetase (ASS1) in the urea cycle and the citrulline-nitric oxide cycle. However, the regulation and biological function of citrulline metabolism remain obscure in the immune system. Unexpectedly, we found that macrophage citrulline declines rapidly after interferon gamma (IFN-γ) and/or lipopolysaccharide (LPS) stimulation, which is required for efficient proinflammatory signaling activation. Mechanistically, IFN-γ and/or LPS stimulation promotes signal transducers and activators of transcription 1 (STAT1)-mediated ASS1 transcription and Janus kinase2 (JAK2)-mediated phosphorylation of ASS1 at tyrosine 87, thereby leading to citrulline depletion. Reciprocally, increased citrulline directly binds to JAK2 and inhibits JAK2-STAT1 signaling. Blockage of ASS1-mediated citrulline depletion suppresses the host defense against bacterial infection in vivo. We therefore define a central role for ASS1 in controlling inflammatory macrophage activation and antibacterial defense through depletion of cellular citrulline and, further, identify citrulline as an innate immune-signaling metabolite that engages a metabolic checkpoint for proinflammatory responses.

Dbf4 recruitment by forkhead transcription factors defines an upstream rate-limiting step in determining origin firing timing.

Initiation of eukaryotic chromosome replication follows a spatiotemporal program. The current model suggests that replication origins compete for a limited pool of initiation factors. However, it remains to be answered how these limiting factors are preferentially recruited to early origins. Here, we report that Dbf4 is enriched at early origins through its interaction with forkhead transcription factors Fkh1 and Fkh2. This interaction is mediated by the Dbf4 C terminus and was successfully reconstituted in vitro. An interaction-defective mutant, dbf4ΔC, phenocopies fkh alleles in terms of origin firing. Remarkably, genome-wide replication profiles reveal that the direct fusion of the DNA-binding domain (DBD) of Fkh1 to Dbf4 restores the Fkh-dependent origin firing but interferes specifically with the pericentromeric origin activation. Furthermore, Dbf4 interacts directly with Sld3 and promotes the recruitment of downstream limiting factors. These data suggest that Fkh1 targets Dbf4 to a subset of noncentromeric origins to promote early replication in a manner that is reminiscent of the recruitment of Dbf4 to pericentromeric origins by Ctf19.

Red blood cell distribution width is associated with sarcopenia risk in early-stage non-small cell lung cancer.

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.

Cytomegalovirus colitis as intestinal obstruction in an immunocompetent adolescent: a case report and literature review.

BACKGROUND: Cytomegalovirus infection manifests varying clinical characteristics and severity in diverse populations with different immune statuses. The signs and symptoms of gastrointestinal involvement are nonspecific. Here, we present a case of cytomegalovirus colitis in an immunocompetent adolescent, which manifested as intestinal pseud-obstruction. CASE PRESENTATION: A 15-year-old man who had contracted novel coronavirus infection one month earlier was admitted to our hospital with fever, abdominal pain, and hematochezia. His abdomen was distended, and laboratory evaluation revealed a decrease in the blood count, an increase in inflammatory indicators and hepatic impairment. Imaging shows bowel wall thickening and dilatation of the colon. A diagnosis of intestinal infection combined with acute intestinal pseud-obstruction was made. Diarrhea persisted despite conservative treatment with empirical antibiotics. A colonoscopy was performed. Pathology confirmed cytomegalovirus infection. Ganciclovir therapy was initiated, and subsequent review showed a good recovery. CONCLUSIONS: The case was diagnosed as cytomegalovirus colitis. We reviewed the reports of 9 cases of bowel obstruction, including our own, and found that the majority of the adult patients were elderly with underlying disease. Clinical and endoscopic manifestations are typically nonspecific, and imaging shows typical signs of intestinal obstruction. The final diagnosis was confirmed by pathology. Most of them have a good prognosis. We suggest that cytomegalovirus colitis can also lead to intestinal obstruction and that viral reactivation in immunocompetent individuals may be associated with inflammatory conditions and viral coinfection, particularly with the novel coronavirus.

Associations of school physical activity environment with comorbid obesity and myopia in children and adolescents: Findings from a Chinese national follow-up study.

BACKGROUND: Overweight and obesity (OWOB) and myopia have become two of the most important issues affecting the health of children and adolescents worldwide. Despite the recognition that the school physical activity (PA) environment is a critical factor for preventing and controlling overweight, obesity (OWOB), and myopia in children and adolescents, research on OWOB and myopia as a comorbidity remains unexplored, with evidence for effective strategies still being inconclusive. Hence, this study aimed to assess the prevalence and progression of comorbid OWOB/myopia and each condition alone, and to explore the association with school PA environment. METHODS: A total of 9814 children and adolescents aged 6-18 years were included from the Chinese National Survey on Students' Constitution and Health follow-up survey conducted from November 2019 to November 2020 in China. Anthropometric measurements, unaided distance vision acuity and non-cycloplegic refraction data were collected to assess OWOB and myopia, while eight indicators from questionnaires for children and adolescents aged 9-18 years were investigated to assess school PA environment. We calculated the one-year incidence and progression rates of comorbid OWOB/myopia, OWOB alone, and myopia alone. Mixed effect logistic regression was evaluated the association between school PA environment and incidence and progression of comorbid OWOB/myopia, OWOB, and myopia. RESULTS: The prevalence of comorbid OWOB/myopia increased from 11.1% in 2019 to 17.9% in 2020, and the incidence of comorbid OWOB/myopia was 10.9%. Children and adolescents experiencing an unfavorable school PA environment had a higher risk of the incidence of comorbid OWOB/myopia compared to a favorable school environment (OR = 1.85, 95% CI: 1.42-2.42). Similar findings were seen in the incidence of obesity (OR = 1.86, 95% CI: 1.26-2.75). Children and adolescents in an unfavorable school PA environment had a higher risk of myopia progression (OR = 1.29, 95% CI: 1.01-1.65). CONCLUSIONS: Obesity and myopia and their comorbidity have been serious among children and adolescents in China. A favorable school PA environment might mitigate the risk of comorbid OWOB/myopia, OWOB, and myopia progression.

Changes in disease burden and global inequalities in bladder, kidney and prostate cancers from 1990 to 2019: a comparative analysis based on the global burden of disease study 2019.

BACKGROUND: Bladder, kidney and prostate cancers make significant contributors to cancer burdens. Exploring their cross-country inequalities may inform equitable strategies to meet the 17 sustainable development goals before 2030. METHODS: We analyzed age-standardized disability-adjusted life-years (ASDALY) rates for the three cancers based on Global Burden of Diseases Study 2019. We quantified the inequalities using slope index of inequality (SII, absolute measure) and concentration index (relative measure) associated with national sociodemographic index. RESULTS: Varied ASDALY rates were observed in the three cancers across 204 regions. The SII decreased from 35.15 (95% confidence interval, CI: 29.34 to 39.17) in 1990 to 15.81 (95% CI: 7.99 to 21.79) in 2019 for bladder cancers, from 78.94 (95% CI: 75.97 to 81.31) in 1990 to 59.79 (95% CI: 55.32 to 63.83) in 2019 for kidney cancer, and from 192.27 (95% CI: 137.00 to 241.05) in 1990 to - 103.99 (95% CI: - 183.82 to 51.75) in 2019 for prostate cancer. Moreover, the concentration index changed from 12.44 (95% CI, 11.86 to 12.74) in 1990 to 15.72 (95% CI, 15.14 to 16.01) in 2019 for bladder cancer, from 33.88 (95% CI: 33.35 to 34.17) in 1990 to 31.13 (95% CI: 30.36 to 31.43) in 2019 for kidney cancer, and from 14.61 (95% CI: 13.89 to 14.84) in 1990 to 5.89 (95% CI: 5.16 to 6.26) in 2019 for prostate cancer. Notably, the males presented higher inequality than females in both bladder and kidney cancer from 1990 to 2019. CONCLUSIONS: Different patterns of inequality were observed in the three cancers, necessitating tailored national cancer control strategies to mitigate disparities. Priority interventions for bladder and kidney cancer should target higher socioeconomic regions, whereas interventions for prostate cancer should prioritize the lowest socioeconomic regions. Additionally, addressing higher inequality in males requires more intensive interventions among males from higher socioeconomic regions.

[Status and pathways of factors influencing physical activity time among elementary and junior high school students in Beijing].

OBJECTIVE: To describe the current distribution of daily physical activity time among elementary and junior high school students in Beijing, and to analyze the influencing factors and pathways at the individual, family, school and community levels. METHODS: Data were drawn upon from a cross-sectional investigation in Beijing in 2023, and a total of 3 157 elementary and junior high school students were included in the final analysis. Questionnaire was used to collect data on basic characteristics, overall and in-school physical activity time per day, the number of sports mastered, perceived physical activity benefits and barriers scales, perceived family, school, and community physical activity supportive environment scales. Log-binomial regression model was used to analyze the associations between physical activity time and influencing factors, and structural equation modeling was used for the path analysis of the influencing factors. RESULTS: The reported rates of ≥2 hours of overall physical activity per day and ≥1 hour of physical activity in school per day among elementary and junior high school students in Beijing in 2023 were 33.1% and 64.8%, respectively. The associations between the number of sports mastered by students and the reported rate of ≥2 hours of overall physical activity per day showed a typical dose-response relationship (P-trend<0.001). The perceived physical activity benefits-to-barriers ratio (PR=1.24, 95%CI: 1.20-1.28), scores of perceived family, school, and community physical acti-vity supportive environment scales were all positively associated with the reported rate of ≥2 hours of overall physical activity per day (PR=1.51, 95%CI: 1.38-1.66; PR=1.50, 95%CI: 1.37-1.64; PR=1.21, 95%CI: 1.16-1.27). The structural equation modeling showed that the number of sports mastered by the students (ß=0.11, P<0.001), perceived physical activity benefits-to-barriers ratios (ß=0.15, P<0.001), and scores of supportive environment scales consisting of family, school, and community (ß=0.13, P<0.001) were associated with the reported rates of ≥2 hours of overall physical activity per day directly. In addition, the scores of supportive environment scales could indirectly influence the reported rates of ≥2 hours of overall physical activity per day by influencing the number of sports mastered by the students (ß=0.21, P<0.001) and the perceived physical activity benefits-to-barriers ratio (ß=0.56, P<0.001), while the number of sports mastered by the students could indirectly influence the reported rates of ≥2 hours of overall physical activity per day by influencing the perceived physical activity benefits-to-barriers ratios (ß=0.05, P=0.003). The influencing factors and pathways of the reported rates of ≥1 hour of physical activity in school per day were similar with those of the reported rates of ≥2 hours of overall physical activity per day described above. CONCLUSION: The daily physical activity time among elementary and junior high school students in Beijing in 2023 fell short of meeting the national requirement. There was a need to build a supportive environment consisting of family, school, and community for physical activity, to promote the students ' sports skills, to establish the idea of independent physical activity, and to ensure that primary and secondary school students were given one hour of physical activity time every day, both inside and outside the school.

[Clinicians' Practice and Opinions on Sedation Therapy in End-Stage Patients].

Objective To investigate clinicians' practice and opinions on sedation therapy in end-stage patients at Peking Union Medical College Hospital. Methods From August,2022 to April,2023,an online questionnaire survey was conducted among clinicians involved in end-stage patient management. Results A total of 205 questionnaires were distributed,with an effective response rate of 56.1%.Among the clinicians,55.7% of them had experience of applying sedation therapy in end-stage patients;85.2% of clinicians believed that sedation could relieve the suffering of terminal patients from physical refractory symptoms;75.7% of clinicians considered that sedation therapy could be used to relieve agony from psycho-existential distress.Most clinicians had concerns about sedation therapy due to the lack of legal support(86.1%)and the lack of understanding of patients or families(59.1%).The majority (90.4%) of clinicians were willing to receive training on palliative sedation. Conclusions A majority of clinicians agree that sedation therapy could relieve the physical distress and psycho-existential distress in end-stage patients.However,most clinicians have concerns about the application of sedation therapy due to the lack of legal support.It is necessary to enhance the training on palliative sedation.

One-Pot Cyclization to Large Peptidomimetic Macrocycles by In Situ-Generated ß-Turn-Enforced Folding.

Macrocycles have been targets of extensive synthetic efforts for decades because of their potent molecular recognition and self-assembly capabilities. Yet, efficient syntheses of macrocyclic molecules via irreversible covalent bonds remain challenging. Here, we report an efficient approach to large peptidomimetic macrocycles by using the in situ-generated ß-turn structural motifs afforded in the amidothiourea moieties from the early steps of the reaction of 2 molecules of bilateral amino acid-based acylhydrazine with 2 molecules of diisothiocyanate. Four chiral and achiral peptidomimetic large macrocycles were successfully synthesized in high yields of 45-63% in a feasible one-pot reaction under sub-molar concentration conditions and were purified by simple filtration. X-ray crystallographic characterization of three macrocycles reveals an important feature that their four ß-turn structures, each maintained by four 10-membered intramolecular hydrogen bonds, alternatively network the four aromatic arms. This affords an interesting conformation switching mode upon anion binding. Binding of SO42- to 1L or 1D that contains 4 alanine residues (with the lowest steric hinderance among the macrocycles) leads to an inside-out structural change of the host macrocycle, as confirmed by the X-ray crystal structure of 1L-SO42- and 1D-SO42- complexes, accompanied by an inversion of the CD signals. On the basis of the strong sulfate affinity of the macrocycles, we succeeded in the removal of sulfate anions from water via a macrocycle-mediated liquid-liquid extraction method. Our synthetic protocol can be easily extended to other macrocycles of varying arms and/or chiral amino acid residues; thus, a variety of structurally and functionally diverse macrocycles are expected to be readily made.

Superior Selective CO2 Adsorption and Separation over N2 and CH4 of Porous Carbon Nitride Nanosheets: Insights from GCMC and DFT Simulations.

Development of high-performance materials for the capture and separation of CO2 from the gas mixture is significant to alleviate carbon emission and mitigate the greenhouse effect. In this work, a novel structure of C9N7 slit was developed to explore its CO2 adsorption capacity and selectivity using Grand Canonical Monte Carlo (GCMC) and Density Functional Theory (DFT) calculations. Among varying slit widths, C9N7 with the slit width of 0.7 nm exhibited remarkable CO2 uptake with superior CO2/N2 and CO2/CH4 selectivity. At 1 bar and 298 K, a maximum CO2 adsorption capacity can be obtained as high as 7.06 mmol/g, and the selectivity of CO2/N2 and CO2/CH4 was 41.43 and 18.67, respectively. In the presence of H2O, the CO2 uptake of C9N7 slit decreased slightly as the water content increased, showing better water tolerance. Furthermore, the underlying mechanism of highly selective CO2 adsorption and separation on the C9N7 surface was revealed. The closer the adsorption distance, the stronger the interaction energy between the gas molecule and the C9N7 surface. The strong interaction between the C9N7 nanosheet and the CO2 molecule contributes to its impressive CO2 uptake and selectivity performance, suggesting that the C9N7 slit could be a promising candidate for CO2 capture and separation.

Integrating Physiologically Based Pharmacokinetic Modeling-Based Forward Dosimetry and in Vitro Bioassays to Improve the Risk Assessment of Organophosphate Esters on Human Health.

The ability to accurately assess the health risks of contaminants is limited by the shortcomings of toxicological standards. Using organophosphate esters (OPEs) as an example, this study attempted to integrate physiologically based pharmacokinetic (PBPK)-based forward dosimetry and in vitro bioassays to assess the likelihood of contaminants inducing biological effects in humans. The total exposure level of OPEs for Chinese residents was 19.5 ± 8.71 ng/kg/day with inhalation being the main exposure pathway. Then, human PBPK models were developed for individual OPEs to predict their steady-state concentrations in human tissues, and the predicted median levels in blood were close to the measurements. The reference doses (RfDs) of OPEs based on in vitro bioassays were comparable to in vivo animal-derived RfDs, demonstrating the reliability of in vitro bioassays. Therefore, the likelihood of OPEs inducing bioactivities in humans (RQin-vitro) was calculated using in vitro toxicity data and OPE levels in human tissues. The RQin-vitros of tris(2-chloroisopropyl) phosphate, tris(1,3-dichloropropyl) phosphate, and triphenyl phosphate (7.68 × 10-5-3.18 × 10-3) were comparable to the risks assessed using traditional RfDs (5.22 × 10-5-1.94 × 10-3), indicating the credibility of the method proposed in this study. This study establishes a new framework to improve the health risk assessment of contaminants without sufficient toxicity data and minimize the need for animal experimentation.

Associations between combinations of 24-h movement behaviors and physical fitness among Chinese adolescents: Sex and age disparities.

OBJECTIVE: To analyze the relationship between 24-h movement behaviors and adolescents' physical fitness, with sex difference and age disparity explored specifically. METHODS: A total of 135 852 Chinese adolescents aged 13-22 years were included in this cross-sectional study. Self-reported 24-h movement behavioral times, including moderate to vigorous physical activity (MVPA), recreational screen, and sleep, were identified as meeting guidelines based on Canadian recommendations. Physical fitness indicator (PFI) was calculated through sex- and age-specific z scores of body mass index, forced vital capacity, 50 m dash, sit-and-reach, standing long jump, body muscle strength, and endurance running, and then classified as: low level (<20th), middle level (20th-80th), and high level (>80th). Mixed effect logistic regression was applied to analyze the association, and interaction terms were constructed to prove the sex and age disparities. RESULTS: Only 12.4% of adolescents aged 13-22 years met all three recommendations. The number of meeting guidelines exhibited a typical dose-response relationship with high level PFI (OR = 1.22 [95% CI: 1.19-1.25]), and in detail, meeting MVPA + recreational screen (OR = 2.29 [95% CI: 2.09-2.51]) or MVPA-only (OR = 2.16 [95% CI: 1.93-2.41]) guidelines were better associated with high-level PFI. Besides, meeting MVPA-only guideline was proved with stronger association with high-level PFI for boys (p-interaction = 0.005). The dose-response relationship in boys of the number of guidelines met with PFI was stronger in 19- to 22-year-olds (p-interaction <0.001) and 16- to 18-year-olds (p-interaction = 0.001) than that in 13- to 15-year-olds. CONCLUSION: The prevalence of meeting 24-h movement behaviors guidelines among Chinese adolescents aged 13-22 years was relatively low. It was associated with adolescents' physical fitness, with meeting MVPA + recreational screen or MVPA-only guidelines bringing greater benefits, and sex difference and age disparity existing.

A cluster randomized trial of a comprehensive intervention nesting family and clinic into school centered implementation to reduce myopia and obesity among children and adolescents in Beijing, China: study protocol.

BACKGROUND: Myopia and obesity in children and adolescents have become serious public health problems that endanger public health, especially in China. Unhealthy lifestyle behaviors are environmental drivers of both myopia and obesity. This protocol describes a study to evaluate the effectiveness of "22510SS", that is 2 h of daytime outdoor activities ('2'); Limit screen time to no more than 2 h per day ('2'); Consume at least 5 servings of fruits and vegetables daily ('5'); Attain 1 h of physical activity daily ('1'); Consume 0 sugar-sweetened beverages ('0'); Reasonable sleep duration ('S'); Regular supervision ('S'). A school-based, multifaceted intervention strategy for myopia and obesity prevention, and to assess and explore the implementation of "22510SS" with regards to acceptability, feasibility, adoption, usage and maintenance. METHODS AND ANALYSIS: This study aims to develop a comprehensive intervention strategy "22510SS" based on the socio-ecological model, and A two-arm cluster randomized trial with a parallel-group of a 1:1 allocation ratio in 36 primary and secondary schools to test its evidence-based intervention programs on the effects and implementation of myopia and obesity epidemics in children and adolescents in grades 4 and 7. The primary outcomes will include differences in visual acuity, body mass index, outdoor activity indicators, screen time, fruit and vegetable intake, high-quality protein intake, sugar-sweetened beverage intake, sleep duration, and level of monitoring among children and adolescents. Secondary outcomes will assess the acceptability, feasibility, uptake, use, and maintenance of the intervention. Effects on the primary and secondary outcomes will be analyzed using linear and logistic regression analyses, as well as difference-in-difference analysis, taking into account cluster effects and possible confounding factors. Process assessments will also be conducted through quantitative and qualitative analyses, including acceptability, feasibility, gender, adoption, implementation, and sustainability. DISCUSSION: This study will evaluate the effectiveness of "22510SS" and examine its implementation in the school-based network nesting family and clinic. Following this intervention study, the integrated intervention program focused on myopia and obesity among children and adolescents have great potential to be implemented in China to promote and support healthy lifestyle behavior change and reduce the risk of myopia and obesity in children and adolescents. TRIAL REGISTRATION: NCT05275959. Registered 23 Mach 2022.

Secular trend and urban-rural disparity for age at spermarche among Chinese Han boys from 1995 to 2019.

AIM: To examine the secular trend and the urban-rural disparity of spermarche among Chinese Han boys from 1995 to 2019. METHODS: A total of 392 775 boys of Han ethnicity aged 11-18 years were extracted from the 1995, 2000, 2005, 2010, 2014 and 2019 Chinese National Surveys on Students' Constitution and Health. The median age at spermarche was estimated using the status quo data and probit analysis. The chi-square, ANOVA and LSD tests were used to compare the differences between the year-subgroups. U-test was used to compare the difference between urban and rural areas at each year. RESULTS: The median age at spermarche in Chinese Han boys decreased from 14.6 years in 1995 to 13.9 years in 2019 (p < 0.001). The rural boys showed a faster decreasing pace with a 1-year advance of age at spermarche while the urban boys had only a 0.5-year decrement, and there was still a statistically significant difference between urban-rural areas in 2019 (p < 0.001). Similar to urban-rural disparity, the age gap at spermarche between areas with different urbanisation rates became smaller over time. CONCLUSIONS: In general, spermarche in Chinese Han boys showed a decreasing trend, but the pace was slowing down. The urban-rural disparity in puberty development still existed but was gradually narrowing.

Automatic Life Detection Based on Efficient Features of Ground-Penetrating Rescue Radar Signals.

Good feature engineering is a prerequisite for accurate classification, especially in challenging scenarios such as detecting the breathing of living persons trapped under building rubble using bioradar. Unlike monitoring patients' breathing through the air, the measuring conditions of a rescue bioradar are very complex. The ultimate goal of search and rescue is to determine the presence of a living person, which requires extracting representative features that can distinguish measurements with the presence of a person and without. To address this challenge, we conducted a bioradar test scenario under laboratory conditions and decomposed the radar signal into different range intervals to derive multiple virtual scenes from the real one. We then extracted physical and statistical quantitative features that represent a measurement, aiming to find those features that are robust to the complexity of rescue-radar measuring conditions, including different rubble sites, breathing rates, signal strengths, and short-duration disturbances. To this end, we utilized two methods, Analysis of Variance (ANOVA), and Minimum Redundancy Maximum Relevance (MRMR), to analyze the significance of the extracted features. We then trained the classification model using a linear kernel support vector machine (SVM). As the main result of this work, we identified an optimal feature set of four features based on the feature ranking and the improvement in the classification accuracy of the SVM model. These four features are related to four different physical quantities and independent from different rubble sites.

Frequency Comb-Based Ground-Penetrating Bioradar: System Implementation and Signal Processing.

Radars can be used as sensors to detect the breathing of victims trapped under layers of building materials in catastrophes like earthquakes or gas explosions. In this contribution, we present the implementation of a novel frequency comb continuous wave (FCCW) bioradar module using a commercial software-defined radio (SDR). The FCCW radar transmits multiple equally spaced frequency components simultaneously. The data acquisition of the received combs is frequency domain-based. Hence, it does not require synchronization between the transmit and receive channels, as time domain-based broadband radars, such as ultra wideband (UWB) pulse radar and frequency-modulated CW (FMCW) radar, do. Since a frequency comb has an instantaneous wide bandwidth, the effective scan rate is much higher than that of a step frequency CW (SFCW) radar. This FCCW radar is particularly suitable for small motion detection. Using inverse fast Fourier transform (IFFT), we can decompose the received frequency comb into different ranges and remove ghost signals and interference of further range intervals. The frequency comb we use in this report has a bandwidth of only 60 MHz, resulting in a range resolution of up to 2.5 m, much larger than respiration-induced chest wall motions. However, we demonstrate that in the centimeter range, motions can be detected and evaluated by processing the received comb signals. We want to integrate the bioradar into an unmanned aircraft system for fast and safe search and rescue operations. As a trade-off between ground penetrability and the size and weight of the antenna and the radar module, we use 1.3 GHz as the center frequency. Field measurements show that the proposed FCCW bioradar can detect an alive person through different nonmetallic building materials.

Clinicopathologic features and abnormal signaling pathways in plasmablastic lymphoma: a multicenter study in China.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare but aggressive B-cell lymphoma subtype with poor prognosis. Knowledge about the etiology, clinicopathologic and molecular features, and outcomes of PBL is limited. This study aimed to examine the clinicopathologic characteristics, therapeutic approaches, and clinical outcomes of PBL patients in a Chinese population. METHODS: A total of 102 PBL patients were recruited from three cancer centers. The pathologic features and clinical outcomes of 56 patients with available treatment details and follow-up data were reviewed and analyzed. RNA sequencing was performed in 6 PBL and 11 diffuse large B-cell lymphoma (DLBCL) patients. RESULTS: Most patients in our cohort were male (n = 36, 64.3%), and 35 patients presented with Ann Arbor stage I/II disease at diagnosis. All these patients showed negative findings for human immunodeficiency virus, and the vast majority of patients in our cohort were immunocompetent. Lymph nodes (n = 13, 23.2%) and gastrointestinal tract (n = 10, 17.9%) were the most commonly involved site at presentation. Post-treatment complete remission (CR) was the only prognostic factor affecting overall survival (OS) and progression-free survival (PFS) in the multivariate analysis. RNA-seq demonstrated that B-cell receptor (BCR), T-cell receptor (TCR), P53, calcium signaling, and Wnt signaling pathways were significantly downregulated in PBLs compared with GCB (or non-GCB) DLBCLs. CONCLUSIONS: In this multicenter study in the Chinese population, PBL mainly occurred in immunocompetent individuals and most patients present with early-stage disease at diagnosis. Post-treatment CR was an important prognostic factor affecting OS and PFS. RNA-seq showed that the B-cell receptor (BCR), P53, calcium signaling, cell adhesion molecules, and Wnt signaling pathways significantly differed between PBL and GCB (or non-GCB) DLBCL, which provided theoretical basis for its pathogenesis and future treatment.

[Practice of Palliative Care Consultation Proposed by the Emergency Department in Peking Union Medical College Hospital].

Objective To summarize the palliative care consultations proposed by the Emergency Department of Peking Union Medical College Hospital. Methods A retrospective study was conducted on 22 palliative care consultations in the Emergency Department of Peking Union Medical College Hospital from January 2017 to June 2020. Results A total of 18 patients (6 males and 12 females) received palliative care consultations in the Emergency Department,with the average age of (65±8) years (36-88 years).Specifically,10 and 6 patients received once and twice consultations,respectively,and 2 patients did not complete the consultation.Of the patients receiving palliative care consultations,15 had malignant tumors and 3 had non-neoplastic diseases.The reasons for palliative care consultations included communication (61.1%,11/18) and pain relief (61.1%,11/18).In terms of the place of death,8 patients died in the hospital and 6 patients in other medical institutions. Conclusion There is a clear demand for palliative care consultation in the Emergency Department of Peking Union Medical College Hospital,and the consultation can bring help to both emergency doctors and patients.

The acetyltransferase Eco1 elicits cohesin dimerization during S phase.

Cohesin is a DNA-associated protein complex that forms a tripartite ring controlling sister chromatid cohesion, chromosome segregation and organization, DNA replication, and gene expression. Sister chromatid cohesion is established by the protein acetyltransferase Eco1, which acetylates two conserved lysine residues on the cohesin subunit Smc3 and thereby ensures correct chromatid separation in yeast (Saccharomyces cerevisiae) and other eukaryotes. However, the consequence of Eco1-catalyzed cohesin acetylation is unknown, and the exact nature of the cohesive state of chromatids remains controversial. Here, we show that self-interactions of the cohesin subunits Scc1/Rad21 and Scc3 occur in a DNA replication-coupled manner in both yeast and human cells. Using cross-linking MS-based and in vivo disulfide cross-linking analyses of purified cohesin, we show that a subpopulation of cohesin may exist as dimers. Importantly, upon temperature-sensitive and auxin-induced degron-mediated Eco1 depletion, the cohesin-cohesin interactions became significantly compromised, whereas deleting either the deacetylase Hos1 or the Eco1 antagonist Wpl1/Rad61 increased cohesin dimer levels by ∼20%. These results indicate that cohesin dimerizes in the S phase and monomerizes in mitosis, processes that are controlled by Eco1, Wpl1, and Hos1 in the sister chromatid cohesion-dissolution cycle. These findings suggest that cohesin dimerization is controlled by the cohesion cycle and support the notion that a double-ring cohesin model operates in sister chromatid cohesion.

Centrifugal-Force-Induced Flow Bifurcations in Turbulent Thermal Convection.

An important and unresolved issue in rotating thermal turbulence is when the flow starts to feel the centrifugal effect. This onset problem is studied here by a novel experiment in which the centrifugal force can be varied over a wide range at fixed Rossby numbers by offsetting the apparatus from the rotation axis. Our experiment clearly shows that the centrifugal force starts to separate the hot and cold fluids at the onset Froude number 0.04. Additionally, this flow bifurcation leads to an unexpected heat transport enhancement and the existence of an optimal state. Based on the dynamical balance and characteristics of local flow structures, both the onset and optimal states are quantitatively explained.