Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

Preweaning period is a critical window for rumen microbial regulation of average daily gain in Holstein heifer calves

Background Rumen bacterial groups can affect growth performance,such as average daily gain(ADG),feed intake,and efficiency.The study aimed to investigate the inter-relationship of rumen bacterial composition,rumen fermentation indicators,serum indicators,and growth performance of Holstein heifer calves with different ADG.Twelve calves were chosen from a trail with 60 calves and divided into higher ADG(HADG,high pre-and post-weaning ADG,n=6)and lower ADG(LADG,low pre-and post-weaning ADG,n=6)groups to investigate differences in bacterial composition and functions and host phenotype.Results During the preweaning period,the relative abundances of propionate producers,including g_norank_f_Butyricicoccaceae,g_Pyramidobacter,and g_norank_f_norank_o_Clostridia_vadin BB60_group,were higher in HADG calves(LDA>2,P<0.05).Enrichment of these bacteria resulted in increased levels of propionate,a gluconeogenic precursor,in preweaning HADG calves(adjusted P<0.05),which consequently raised serum glucose concentrations(adjusted P<0.05).In contrast,the relative abundances of rumen bacteria in post-weaning HADG calves did not exert this effect.Moreover,no significant differences were observed in rumen fermentation parameters and serum indices between the two groups.Conclusions The findings of this study revealed that the preweaning period is the window of opportunity for rumen bacteria to regulate the ADG of calves.

Thermal and photoperiodic requirements of the seedling stage of three tropical forest species

Air temperature and photoperiod play an important role in the seedling development for tropical forest species.Both variables are sensitive to climate,and so evaluating thermal and photoperiodic effects on seedling development is fundamental,especially for climate change studies.Methods to quantify thermal time and the energy required for plants to reach a development stage include air temperature and cardinal temperatures.The photoperiod will also affect physiological reactions of a plant and thus its development.Here we evaluated the six thermal time methods widely used to compute thermal requirement,and identified the influence of the photoperiod from the 2015 and2016 growing seasons and 12 sowing dates in Itajubá,Minas Gerais state,Brazil,on seedling development of three native tropical forest species Psidium guajava L.(Myrtaceae),Citharexylum myrianthum Cham.(Verbenaceae),and Bixa orellana L.(Bixaceae).The method used to quantify thermal time influenced the analytical results of seedling development;the one that considered three cardinal temperatures and compared them with the mean air temperature(Method5)performed better in computing thermal requirements.The influence of photoperiod on seedling development was inconclusive for the three species,but all three developed better in mild temperatures(between 13.3℃and 26.9℃)with a photoperiod shorter than 13 h.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

ON THE STABILITY OF PERIODIC SOLUTIONS OF PIECEWISE SMOOTH PERIODIC DIFFERENTIAL EQUATIONS

In this paper,we address the stability of periodic solutions of piecewise smooth periodic differential equations.By studying the Poincarémap,we give a sufficient condition to judge the stability of a periodic solution.We also present examples of some applications.

Tim4 deficiency reduces CD301b+macrophage and aggravates periodontitis bone loss

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b^(+)macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b^(+)macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b^(+)macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b^(+)macrophages was significantly upregulated compared to CD301b^(-) macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b^(+)macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b^(+)macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b^(+)macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b^(+)macrophages phenotype.In a word,Tim4 might regulate CD301b^(+)macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

Tuning Second Chern Number in a Four-Dimensional Topological Insulator by High-Frequency Time-Periodic Driving

Floquet engineering has attracted considerable attention as a promising approach for tuning topological phase transitions.We investigate the effects of high-frequency time-periodic driving in a four-dimensional(4D)topological insulator,focusing on topological phase transitions at the off-resonant quasienergy gap.The 4D topological insulator hosts gapless three-dimensional boundary states,characterized by the second Chern number C_(2).We demonstrate that the second Chern number of 4D topological insulators can be modulated by tuning the amplitude of time-periodic driving.This includes transitions from a topological phase with C_(2)=±3 to another topological phase with C_(2)=±1,or to a topological phase with an even second Chern number C_(2)=±2,which is absent in the 4D static system.Finally,the approximation theory in the high-frequency limit further confirms the numerical conclusions.

Solitons and Their Biperiodic Pulsation in Ultrafast Fiber Lasers Based on CB/GO

The carbon black(CB)is introduced to manufacture CB/graphene oxide(GO)composite material to mitigate limitations of GO as a saturable absorber with the excellent performance in ultrafast fiber lasers.At a central wavelength of 1555.5 nm,the stable mode-locked pulse with width of 656 fs,repetition rate of 20.16 MHz,and high signal-to-noise ratio of 82.07 dB is experimentally obtained.Additionally,experimental observations for pulsation phenomena of vector biperiodic solitons combining period-1 and period-17,period-2 and period-32,period-3 and period-36 are verified via simulations.

Ecological network analysis reveals complex responses of tree species life stage interactions to stand variables

Tree interactions are essential for the structure,dynamics,and function of forest ecosystems,but variations in the architecture of life-stage interaction networks(LSINs)across forests is unclear.Here,we constructed 16 LSINs in the mountainous forests of northwest Hebei,China based on crown overlap from four mixed forests with two dominant tree species.Our results show that LSINs decrease the complexity of stand densities and basal areas due to the interaction cluster differentiation.In addition,we found that mature trees and saplings play different roles,the first acting as“hub”life stages with high connectivity and the second,as“bridges”controlling information flow with high centrality.Across the forests,life stages with higher importance showed better parameter stability within LSINs.These results reveal that the structure of tree interactions among life stages is highly related to stand variables.Our efforts contribute to the understanding of LSIN complexity and provide a basis for further research on tree interactions in complex forest communities.

Feedback linearization and equivalent-disturbance compensation control strategy for piezoelectric stage

Piezoelectric stages use piezoelectric actuators and flexure hinges as driving and amplifying mechanisms,respectively.These systems have high positioning accuracy and high-frequency responses,and they are widely used in various precision/ultra-precision positioning fields.However,the main challenge with these devices is the inherent hysteresis nonlinearity of piezoelectric actuators,which seriously affects the tracking accuracy of a piezoelectric stage.Inspired by this challenge,in this work,we developed a Hammerstein model to describe the hysteresis nonlinearity of a piezoelectric stage.In particular,in our proposed scheme,a feedback-linearization algorithm is used to eliminate the static hysteresis nonlinearity.In addition,a composite controller based on equivalent-disturbance compensation was designed to counteract model uncertainties and external disturbances.An analysis of the stability of a closed-loop system based on this feedback-linearization algorithm and composite controller was performed,and this was followed by extensive comparative experiments using a piezoelectric stage developed in the laboratory.The experimental results confirmed that the feedback-linearization algorithm and the composite controller offer improved linearization and trajectory-tracking performance.

Cranial ultrasound in perioperative period of acute severe traumatic brain injury

Objective To observe the value of cranial ultrasound for perioperative patients with acute severe traumatic brain injury(sTBI).Methods Data of 55 sTBI patients who underwent craniotomy were retrospectively analyzed.The patients were divided into observation group(n=15)and control group(n=40)according to received perioperative cranial ultrasound or not.The general data and surgical data were compared between groups,and ultrasonic data of observation group were analyzed.Results The proportions of good prognosis 1 and 6 months after operation in observation group were both higher than those in control group,while the incidence of cerebral infarction in observation group was lower than that in control group(all P<0.05).No significant difference of general data nor other surgical data was found between groups(all P>0.05).Acute encephalocele occurred in 1 case in observation group during operation,and cranial ultrasound accurately showed the contralateral secondary epidural hematoma.Increased intracranial pressure in different degrees were found in all 15 cases(15/15,100%)in observation group after operation with transcranial color coded Doppler(TCCD)or transcranial Doppler(TCD),while cerebral vascular spasm was observed in 5 cases(5/15,33.33%),among them 4 cases(4/5,80.00%)were diagnosed cerebral infarction based on CT examination.Conclusion Cranial ultrasound could be used to evaluate changes of sTBI in perioperative period and guide adjusting treatment strategy in time,being valuable for reducing risk of postoperative cerebral infarction and improving prognosis.

A Brief Introduction to the English Periodical of Contemporary Social Sciences

The English periodical of Contemporary Social Sciences is an English periodical founded by Sichuan Academy of Social Sciences and is published every two months.It was approved by the National Radio and Television Administration of the People’s Republic of China(formerly the State Administration of Press,Publication,Radio,Film and Television of the People’s Republic of China)in March 2016.

An Elite-Class Teaching-Learning-Based Optimization for Reentrant Hybrid Flow Shop Scheduling with Bottleneck Stage

Bottleneck stage and reentrance often exist in real-life manufacturing processes;however,the previous research rarely addresses these two processing conditions in a scheduling problem.In this study,a reentrant hybrid flow shop scheduling problem(RHFSP)with a bottleneck stage is considered,and an elite-class teaching-learning-based optimization(ETLBO)algorithm is proposed to minimize maximum completion time.To produce high-quality solutions,teachers are divided into formal ones and substitute ones,and multiple classes are formed.The teacher phase is composed of teacher competition and teacher teaching.The learner phase is replaced with a reinforcement search of the elite class.Adaptive adjustment on teachers and classes is established based on class quality,which is determined by the number of elite solutions in class.Numerous experimental results demonstrate the effectiveness of new strategies,and ETLBO has a significant advantage in solving the considered RHFSP.

Dry eye rate and its relationship with disease stage in patients with primary hypertension:a cross-sectional study in Vietnam

AIM:To determine the dry eye(DE)rate and its relationship with disease stage in patients with primary hypertension.METHODS:A cross-sectional study included 432 patients with primary hypertension(with an equal number of patients in each group:144 in stage Ⅰ,Ⅱ,and Ⅲ hypertension)and 144 healthy subjects as a control group.The Ocular Surface Disease Index(OSDI)and Schirmer Ⅰ test without anesthetics were conducted on all 576 subjects.Subjects with OSDI scores<13 and Schirmer Ⅰ values equal to or under 10 mm were diagnosed with DE.RESULTS:The ratio of DE in hypertension patients was higher than in the control group(41.7%versus 18.8%;P<0.001).The proportion of patients with DE increased gradually according to the hypertension stage:27.1% in stage Ⅰ,40.3% in stage Ⅱ,and 57.6% in stage Ⅲ,P<0.001.Age,duration of hypertension,plasma urea,creatinine,and high-sensitivity C-reactive protein(CRP-hs)levels in hypertension patients with DE were higher than those without DE,P<0.001.Advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma creatinine,and CRP-hs levels were independent factors associated with DE in primary hypertension patients,P<0.001.CONCLUSION:DE is a common disorder associated with advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma CRP-hs,and creatinine levels in patients with primary hypertension.

CmMYB3-like negatively regulates anthocyanin biosynthesis and flower color formation during the post-flowering stage in Chrysanthemum morifolium

Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulation decreases during the post-flowering stage still unclear,which greatly restricts design of molecular breeding in chrysanthemum.Here,a chrysanthemum SG7 R2R3 MYB transcription factor(TF),CmMYB3-like,was identified to have a function in regulating anthocyanin biosynthesis during the post-flowering stage.Quantitative real time PCR(qRT-PCR)assays showed that the expression of CmMYB3-like was gradually downregulated when anthocyanin content increased during the flowering stage and was significantly upregulated during the post-flowering stage.Genetic transformation of chrysanthemum and dual-luciferase assays in N.benthamiana leaves showed that CmMYB3-like suppressed anthocyanin accumulation by inhibiting the transcription of CmCHS and CmANS directly and that of CmF3H indirectly.However,overexpression or suppression of CmMYB3-like did not affect the biosynthesis of flavones or flavonols.Genetic transformation of chrysanthemum revealed that the overexpression of CmMYB3-like inhibited anthocyanin accumulation,but its suppression prevented the decrease in anthocyanin accumulation during the post-flowering stage.Our results revealed a crucial role of CmMYB3-like in regulating the color of petals during the post-flowering stage and provided a target gene for molecular design breeding to improve the postharvest quality of chrysanthemum.

Single-cell profiling of the pig cecum at various developmental stages

The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.

Novel method for identifying the stages of discharge underwater based on impedance change characteristic

It is difficult to determine the discharge stages in a fixed time of repetitive discharge underwater due to the arc formation process being susceptible to external environmental influences. This paper proposes a novel underwater discharge stage identification method based on the Strong Tracking Filter(STF) and impedance change characteristics. The time-varying equivalent circuit model of the discharge underwater is established based on the plasma theory analysis of the impedance change characteristics and mechanism of the discharge process. The STF is used to reduce the randomness of the impedance of repeated discharges underwater, and then the universal identification resistance data is obtained. Based on the resistance variation characteristics of the discriminating resistance of the pre-breakdown, main, and oscillatory discharge stages, the threshold values for determining the discharge stage are obtained. These include the threshold values for the resistance variation rate(K) and the moment(t).Experimental and error analysis results demonstrate the efficacy of this innovative method in discharge stage determination, with a maximum mean square deviation of Scrless than 1.761.

Periodic signal extraction of GNSS height time series based on adaptive singular spectrum analysis

Singular spectrum analysis is widely used in geodetic time series analysis.However,when extracting time-varying periodic signals from a large number of Global Navigation Satellite System(GNSS)time series,the selection of appropriate embedding window size and principal components makes this method cumbersome and inefficient.To improve the efficiency and accuracy of singular spectrum analysis,this paper proposes an adaptive singular spectrum analysis method by combining spectrum analysis with a new trace matrix.The running time and correlation analysis indicate that the proposed method can adaptively set the embedding window size to extract the time-varying periodic signals from GNSS time series,and the extraction efficiency of a single time series is six times that of singular spectrum analysis.The method is also accurate and more suitable for time-varying periodic signal analysis of global GNSS sites.

Optimal design for rubber concrete layered periodic foundations based on the analytical approximations of band gaps and mapping relations

The seismic performance of rubber concrete-layered periodic foundations are significantly influenced by their design,in which the band gaps play a paramount role.Aiming at providing better designs for these foundations,this study first proposes and validates the analytical formulas to approximate the bounds of the first few band gaps.In addition,the mapping relations linking the frequencies of different band gaps are presented.Furthermore,an optimal design method for these foundations is developed,which is validated through an engineering example.It is demonstrated that ensuring the superstructure’s resonance zones are completely covered by the corresponding periodic foundation’s band gaps can achieve satisfactory vibration attenuation effects,which is a good strategy for the design of rubber concrete layered periodic foundations.