Dynamics of a Reaction-Diffusion System with Quiescence

In this paper,the dynamical behavior of a reaction-diffusion system with quiescence in a closed environment is investigated.The global existence of the solution is obtained by the upper and lower solution method,and the dissipative structure of the system is derived by constructing Lyapunov functions.

Stem cell quiescence and its clinical relevance

Quiescent state has been observed in stem cells(SCs),including in adult SCs and in cancer SCs(CSCs).Quiescent status of SCs contributes to SC self-renewal and conduces to averting SC death from harsh external stimuli.In this review,we provide an overview of intrinsic mechanisms and extrinsic factors that regulate adult SC quiescence.The intrinsic mechanisms discussed here include the cell cycle,mitogenic signaling,Notch signaling,epigenetic modification,and metabolism and transcriptional regulation,while the extrinsic factors summarized here include microenvironment cells,extracellular factors,and immune response and inflammation in microenvironment.Quiescent state of CSCs has been known to contribute immensely to therapeutic resistance in multiple cancers.The characteristics and the regulation mechanisms of quiescent CSCs are discussed in detail.Importantly,we also outline the recent advances and controversies in therapeutic strategies targeting CSC quiescence.

Seismicity gap and seismic quiescence before 1999 Jiji(Chi-Chi) M_W7.6 earthquake

The September 21, 1999, Jiji （Chi-Chi） Mw7.6 earthquake is the strongest event occurred since 1900 in Taiwan of China. It is located in the middle segment of the western seismic zone of Taiwan. Based on several versions of China earthquake catalogue this study found that a seismic gap of M≥5 earthquakes appeared, in and around the epicenter region, 24 years before and lasted up to the mainshock occurrence. This study also noticed that there existed a lager seismically quiet region of M≥4 earthquakes, which lasted for about 2.5 years before the mainshock occurrence, The spatial variation pattern of regional seismicity before the mainshock seems to match with its coseismic source rupture process. The mentioned seismicity gap and seismic quiescence might be an indication of the preparation process of the Jiji strong earthquake.

Sperm quiescence in cauda epididymis: a mini-review

The concentration of sodium chloride is of prime importance in the initiation and reversal of sperm quiescence inthe cauda epididymis. Other factors such as inorganic and organic constituents of the luminal fluid are of secondary im-portance and might assist in inducing sperm quiescence. (Asian J Androl 2001; 3; 181 — 183 )

Rehmannia glutinosa exhibits anti-aging effect through maintaining the quiescence and decreasing the senescence of hematopoietic stem cells

Background: The time-related decline in regenerative capacity and organ homeostasis is a major feature of aging. Rehmannia glutinosa and Astragalus membranaceus have been used as traditional Chinese herbal medicines for enhanced immunity and prolonged life. However, the mechanism by which this herbal medicine slows aging is unknown. In this study, we investigated the mechanism of the herbal anti-aging effect.Methods: Mice were fed diets supplemented with R. glutinosa or A. membranaceus for 10 months; the control group was fed a standard diet. The phenotypes were evaluated using a grading score system and survival analysis. The percentages of the senescence phenotypes of hematopoietic stem cells(HSCs) were determined by fluorescence-activated cell sorting analysis. The function and the mechanism of HSCs were analyzed by clonogenic assay and the real-time polymerase chain reaction.Results: The anti-aging effect of R. glutinosa is due to the enhanced function of HSCs. Mice fed with R. glutinosa displayed characteristics of a slowed aging process,including decreased senescence and increased rate of survival. Flow cytometry analysis showed decreased numbers of Lin–Sca1^+c-kit–(LSK) cells, long-term HSCs(LT-HSCs) and short-term HSCs(ST-HSCs) in the R. glutinosa group. In vitro, clonogenic assays showed increased self-renewal ability of LT-HSCs from the R. glutinosa group as well as maintaining LSK quiescence through upregulated p18 expression. The R. glutinosa group also showed decreased reactive oxygen species levels and the percentage of β-gal^+ cells through downregulation of the cellular senescence-associated protein p53 and p16.Conclusion: Rehmannia glutinosa exerts anti-aging effects by maintaining the quiescence and decreasing the senescence of HSCs.

The middle-long term prediction of the February 3,1996 Lijiang earthquake(M_S=7) by the "criterion of activity in quiescence

Earthquake activities in history are characterized by active and quiet periods. In the quiet period, the place where earthquake M_≥6 occurred means more elastic energy store and speedy energy accumulation there. When an active period of big earthquake activity appeared in wide region, in the place where earthquake (M_≥6) occurred in the past quiet period, the big earthquake with magnitude of 7 or more often occur there. We call the above-mentioned judgement for predicting big earthquake the 'criterion of activity in quiescence'. The criterion is relatively effective for predicting location of big earthquake. In general, error of predicting epicenter is no more than 100 km. According to the criterion, we made successfully a middle-term prediction on the 1996 Lijiang earthquake in Yunnan Province, the error of predicted location is about 50 km. Besides, the 1994 Taiwan strait earthquake (M_s=7.3), the 1995 Yunnan-Myanmar boundary earthquake (M_s=7.2) and the Mani earthquake (M_s=7.9) in north Tibet are accordant with the retrospective predictions by the 'criterion of activity in quiescence'. The windows of 'activity in quiescence' identified statistically by us are 1940-1945, 1958-1961 and 1979-1986. Using the 'criterion of activity in quiescence' to predict big earthquake in the mainland of China,the earthquake defined by 'activity in quiescence' has magnitude of 6 or more; For the Himalayas seismic belt, the Pacific seismic belt and the north-west boundary seismic belt of Xinjiang, the earthquake defined by 'activity in quiescence' has magnitude of 7, which is corresponding to earthquake with magnitude of much more than 7 in future. For the regions where there are not tectonically and historically a possibility of occurring big earthquake (M_s=7), the criterion of activity in quiescence is not effective.

Seismicity patterns before the 2021 Fin (Iran) doublet earthquakes using the region-time-length and time-to-failure methods

Knowledge regarding earthquake hazards and seismicity is crucial for crisis management, and the occurrence of foreshocks, seismic activity patterns, and spatiotemporal variations in seismic activity have been studied. Furthermore, the estimation of the region-time-length (RTL) parameter has been proposed to detect seismic quiescence before the occurrence of a large earthquake. In addition, the time-to-failure method has been used to estimate the time occurrence of large earthquakes. Hence, in this study, to gain deeper insight into seismic activity in the southern Zagros region, we utilized the RTL algorithm to identify the quiescence and activation phases leading to the Fin doublet earthquakes. Temporal variations in the RTL parameter showed two significant anomalies. One corresponded to the occurrence time of the first earthquake (2017-12-12);the other anomaly was associated with the occurrence time of the second event (2021-11-14). Based on a negative value of the RTL parameter observed in the vicinity of the Fin epicenters (2021), seismic quiescence (a decrease in seismicity compared to the preceding background rate) was identified. The spatial distribution of the RTL prognostic parameters confirms the appearance of seismic quiescence surrounding the epicenter of the Fin doublet earthquakes (2021). The time-to-failure method was designed using precursory events that describe the acceleration of the seismic energy release before the mainshock. Using the time-to-failure method for the earthquake catalog, it was possible to estimate both the magnitude and time of failure of the Fin doublet. Hence, the time-tofailure technique can be a useful supplementary method to the RTL algorithm for determining the characteristics of impending earthquakes.

Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism

Extracellular membrane proteins are crucial for mediating cell attachment,recognition,and signal transduction in the testicular microenvironment,particularly germline stem cells.Cadherin 18(CDH18),a type Ⅱ classical cadherin,is primarily expressed in the nervous and reproductive systems.Here,we investigated the expression of CDH18in neonatal porcine prospermatogonia(ProSGs)and murine spermatogonial stem cells(SSCs).Disruption of CDH18 expression did not adversely affect cell morphology,proliferation,self-renewal,or differentiation in cultured porcine ProSGs,but enhanced cell adhesion and prolonged cell maintenance.Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion.To further elucidate the function of CDH18 in germ cells,Cdh18 knockout mice were generated,which exhibited normal testicular morphology,histology,andspermatogenesis.Transcriptomic analysis showed increased expression of genes associated with adhesion,consistent with the observations in porcine ProSGs.The interaction of CDH18withβ-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency.Collectively,these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs.Understanding this regulatory mechanism provides significant insights into the testicular niche.

Earthquake hazard potential in the Eastern Anatolian Region of Turkey： seismotectonic b and Dc-values and precursory quiescence Z-value

The Eastern Anatolian Region of Turkey is one of the most seismically and tectonically active regions due to the frequent occurrence of earthquakes. Thus, the main goal of this study is to analyze the regional and temporal characteristics of seismicity in the Eastern Anatolia in terms of the seismotectonic b-value, fractal dimension Dcvalue, precursory seismic quiescence Z-value, and their interrelationships. This study also seeks to obtain a reliable empirical relation between b and De-values and to evaluate the temporal changes of these parameters as they relate to the earthquake potential of the region. A more up-to-date relation of De = 2.55 -0.39＊b is found with a very strong negative correlation coefficient （r=- 0.95） by using the orthogonal regression method. The b-values less than 1.0 and the De-values greater than 2.2 are observed in the Northeast Anatolian Fault Zone, Askale, Erzurum, Igdlr and Caldlran Faults, Dogubeyazlt Fault Zone, around the Genc Fault, the western part of the Bitlis-Zagros Thrust Zone, Pulumir and Karakogan Faults, and the SancakUzunpmar Fault Zone. In addition, the regions having small b-values and large Z-values are calculated around the Geng, Piulumur and Karakogan Faults as well as the Saneak-Uzunpmar Fault Zone. Remarkably, the combinations of these seismotectonic parameters could reveal the earthquake hazard potential in the Eastern Anatolian Region of Turkey, thus creating an increased interest in these anomaly regions.

New function of an old molecule——VCAM1 guides neural stem cells from proliferation to quiescence

Subject Code:C12With the support by the National Natural Science Foundation of China,the group led by Prof.Shen Qin(沈沁)from the Center for Stem Cell Biology and Regenerative Medicine,School of Medicine,and the IDG/McGovern Institute for Brain Research at Tsinghua University,reported a newly discovered

Mechanism of Dormancy in the Buds and Cambium of Eucommia ulmoides

This paper describes changes in the structure of buds and vascular cambium as well as in protein content of one-year-old dormant branches of Eucommia ulmoides Oliv. in water-culture conditions. Results confirm the existence of 2 quiescences (Q1, Q2) and 1 rest (R) phases in this tree during the dormancy period. In the R time, the E. ulmoides cambium was unable to reactivate even though the tree was subjected to exogenous IAA, suitable temperature or required luminosity. Furthermore, pistillate trees entered the dormant phase earlier than staminate ones. The protein content in the bark during Q1 increased significantly ( P < 0.01), but drastically decreased in the R period, before rising up again at the onset of Q2 ( P < 0.01). Even though the change pattern of protein content was similar, its occurrence is much earlier in staminate than in pistillate plants. SDS-PAGE revealed a 'special' protein band of 11.8 kD in the transitional Q1-R-Q2 stages. This 'special' protein bands would be related to the cambial dormancy and to the regulation of the Q1-R-Q2 transition.

Molecular mechanism of extrinsic factors affecting antiaging of stem cells

Scientific evidence suggests that stem cells possess the anti-aging ability to self-renew and maintain differentiation potentials, and quiescent state. The objective of this review is to discuss the microenvironment where stem cells reside in vivo, the secreted factors to which stem cells are exposed, thehypoxic environment, and intracellular factors including genome stability, mitochondria integrity, epigenetic regulators, calorie restrictions, nutrients, and vitamin D. Secreted tumor growth factor-β and fibroblast growth factor-2 are reported to play a role in stem cell quiescence. Extracellular matrices may interact with caveolin-1, the lipid raft on cell membrane to regulate quiescence. N-cadherin, the adhesive protein on niche cells provides support for stem cells. The hypoxic micro-environment turns on hypoxia-inducible factor-1 to prevent mesenchymal stem cells aging through p16 and p21 down-regulation. Mitochondria express glucosephosphate isomerase to undergo glycolysis and prevent cellular aging. Epigenetic regulators such as p300, protein inhibitors of activated Stats and H19 help maintain stem cell quiescence. In addition, calorie restriction may lead to secretion of paracrines cyclic ADP-ribose by intestinal niche cells, which help maintain intestinal stem cells. In conclusion, it is crucial to understand the anti-aging phenomena of stem cells at the molecular level so that the key to solving the aging mystery may be unlocked.

Retinal regeneration requires dynamic Notch signaling

Retinal damage in the adult zebrafish induces Müller glia reprogramming to produce neuronal progenitor cells that proliferate and differentiate into retinal neurons.Notch signaling,which is a fundamental mechanism known to drive cell-cell communication,is required to maintain Müller glia in a quiescent state in the undamaged retina,and repression of Notch signaling is necessary for Müller glia to reenter the cell cycle.The dynamic regulation of Notch signaling following retinal damage also directs proliferation and neurogenesis of the Müller glia-derived progenitor cells in a robust regeneration response.In contrast,mammalian Müller glia respond to retinal damage by entering a prolonged gliotic state that leads to additional neuronal death and permanent vision loss.Understanding the dynamic regulation of Notch signaling in the zebrafish retina may aid efforts to stimulate Müller glia reprogramming for regeneration of the diseased human retina.Recent findings identified DeltaB and Notch3 as the ligand-receptor pair that serves as the principal regulators of zebrafish Müller glia quiescence.In addition,multi-omics datasets and functional studies indicate that additional Notch receptors,ligands,and target genes regulate cell proliferation and neurogenesis during the regeneration time course.Still,our understanding of Notch signaling during retinal regeneration is limited.To fully appreciate the complex regulation of Notch signaling that is required for successful retinal regeneration,investigation of additional aspects of the pathway,such as post-translational modification of the receptors,ligand endocytosis,and interactions with other fundamental pathways is needed.Here we review various modes of Notch signaling regulation in the context of the vertebrate retina to put recent research in perspective and to identify open areas of inquiry.

Characteristics of seismic activity before the M_S8.0 Wenchuan earthquake

The characteristics of spatio-temporal seismicity evolution before the Wenchuan earthquake are studied. The results mainly involve in the trend abnormal features and its relation to the Wenchuan earthquake. The western Chinese mainland and its adjacent area has been in the seismically active period since 2001, while the seismic activity shows the obvious quiescence of M≥7.0, M≥6.0 and M≥5.0 earthquakes in Chinese mainland. A quiescence area with M≥7.0 has been formed in the middle of the North-South seismic zone since 1988, and the Wenchuan earthquake occurred just within this area. There are a background seismicity gap of M≥5.0 earthquakes and a seismogenic gap of ML〉4.0 earthquakes in the area of Longrnenshan fault zone and its vicinity prior to the Wenchuan earthquake. The seismic activity obviously strengthened and a doughnut-shape pattern of M≥4.6 earthquakes is formed in the middle and southern part of the North-South seismic zone after the 2003 Dayao, Yunnan, earthquake. Sichnan and its vicinity in the middle of the doughnut-shape pattern show abnormal quiescence. At the same time, the seismicity of earthquake swarms is significant and shows heterogeneity in the temporal and spatial process. A swarm gap appears in the M4.6 seismically quiet area, and the Wenchuan earthquake occurred just on the margin of the gap. In addition, in the short term before the Wenchuan earthquake, the quiescence of earthquake with ML≥4.0 appears in Qinghai-Tibet block and a seismic belt of ML〉3.0 earthquakes, with NW striking and oblique with Longmenshan fault zone, is formed.

New insights into the epigenetic control of satellite cells

Epigenetics finely tunes gene expression at a functionallevel without modifying the DNA sequence, thereby contributing to the complexity of genomic regulation. Satellite cells(SCs) are adult muscle stem cells that are important for skeletal post-natal muscle growth, homeostasis and repair. The understanding of the epigenome of SCs at different stages and of the multiple layers of the post-transcriptional regulation of gene expression is constantly expanding. Dynamic interactions between different epigenetic mechanisms regulate the appropriate timing of muscle-specific gene expression and influence the lineage fate of SCs. In this review, we report and discuss the recent literature about the epigenetic control of SCs during the myogenic process from activation to proliferation and from their commitment to a muscle cell fate to their differentiation and fusion to myotubes. We describe how the coordinated activities of the histone methyltransferase families Polycomb group(Pc G), which represses the expression of developmentally regulated genes, and Trithorax group, which antagonizes the repressive activity of the Pc G, regulate myogenesis by restricting gene expression in a time-dependent manner during each step of the process. We discuss how histone acetylation and deacetylation occurs in specific loci throughout SC differentiation to enable the time-dependent transcription of specific genes. Moreover, we describe the multiple roles of micro RNA, an additional epigenetic mechanism, in regulating gene expression in SCs, by repressing or enhancing gene transcription or translation during each step of myogenesis. The importance of these epigenetic pathways in modulating SC activation and differentiation renders them as promising targets for disease interventions. Understanding the most recent findings regarding the epigenetic mechanisms that regulate SC behavior is useful from the perspective of pharmacological manipulation for improving muscle regeneration and for promoting muscle homeostasis under pathological conditions.

Linking stemness with colorectal cancer initiation, progression, and therapy

The discovery of cancer stem cells caused a paradigm shift in the concepts of origin and development of colorectal cancer. Several unresolved questions remain in this field though. Are colorectal cancer stem cells the cause or an effect of the disease? How do cancer stem cells assist in colorectal tumor dissemination to distant organs? What are the molecular or environmental factors affecting the roles of these cells in colorectal cancer? Through this review, we investigate the key findings until now and attempt to elucidate the origins, physical properties, microenvironmental niches, as well as the molecular signaling network that support the existence, self-renewal, plasticity, quiescence, and the overall maintenance of cancer stem cells in colorectal cancer. Increasing data show that the cancer stem cells play a crucial role not only in the establishment of the primary colorectal tumor but also in the distant spread of the disease. Hence, we will also look at the mechanisms adopted by cancer stem cells to influence the development of metastasis and evade therapeutic targeting and its role in the overall disease prognosis. Finally, we will illustrate the importance of understanding the biology of these cells to develop improved clinical strategies to tackle colorectal cancer.

Insect Diapause： A Review

Diapause is defined as a period of suspended development in insects and other invertebrates during unfavorable environmental conditions. Diapause is commonly confused with term ＂quiescence＂ as both are dormant development stages. Here this paper aimed to review the research work done on different aspects of diapause. Attempt was made to explain definitions of diapause, incidence, stages and termination of diapause, genetic control, factors affecting diapauses, including temperature, photoperiod, moisture and food, etc..

New insights into tumor dormancy:Targeting DNA repair pathways

Over the past few decades, major strides have advanced the techniques for early detection and treatment of cancer. However, metastatic tumor growth still accounts for the majority of cancer-related deaths worldwide. In fact, breast cancers are notorious for relapsing years or decades after the initial clinical treatment, and this relapse can vary according to the type of breast cancer. In estrogen receptor-positive breast cancers, late tumor relapses frequently occur whereas relapses in estrogen receptor-negative cancers or triple negative tumors arise early resulting in a higher mortality risk. One of the main causes of metastasis is tumor dormancy in which cancer cells remain concealed, asymptomatic, and untraceable over a prolonged period of time. Under certain conditions, dormant cells can re-enter into the cell cycle and resume proliferation leading to recurrence. However, the molecular and cellular regulators underlying this transition remain poorly understood. To date, three mechanisms have been identified to trigger tumor dormancy including cellular, angiogenic, and immunologic dormancies. In addition, recent studies have suggested that DNA repair mechanisms may contribute to the survival of dormant cancer cells. In this article, we summarize the recent experimental and clinical evidence governing cancer dormancy. In addition, we will discuss the role of DNA repair mechanisms in promoting the survival of dormant cells. This information provides mechanistic insight to explain why recurrence occurs, and strategies that may enhance therapeutic approaches to prevent disease recurrence.

Protecting future antimalarials from the trap of resistance:Lessons from artemisinin-based combination therapy (ACT) failures

Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine.However,triple mutants have now emerged,suggesting that drug rotations may not be adequate to keep resistance at bay.There is,therefore,an urgent need for alternative treatment strategies to tackle resistance and prevent its spread.A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement.This review highlights the role of the key players in artemisinin resistance,the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.