Bio-friendly long-term subcellular dynamic recording by self-supervised image enhancement microscopy.

Fluorescence microscopy has become an indispensable tool for revealing the dynamic regulation of cells and organelles. However, stochastic noise inherently restricts optical interrogation quality and exacerbates observation fidelity when balancing the joint demands of high frame rate, long-term recording and low phototoxicity. Here we propose DeepSeMi, a self-supervised-learning-based denoising framework capable of increasing signal-to-noise ratio by over 12 dB across various conditions. With the introduction of newly designed eccentric blind-spot convolution filters, DeepSeMi effectively denoises images with no loss of spatiotemporal resolution. In combination with confocal microscopy, DeepSeMi allows for recording organelle interactions in four colors at high frame rates across tens of thousands of frames, monitoring migrasomes and retractosomes over a half day, and imaging ultra-phototoxicity-sensitive Dictyostelium cells over thousands of frames. Through comprehensive validations across various samples and instruments, we prove DeepSeMi to be a versatile and biocompatible tool for breaking the shot-noise limit.

BMP signaling is required to form the anterior neural plate border in ascidian embryos.

Cranial neurogenic placodes have been considered vertebrate innovations. However, anterior neural plate border (ANB) cells of ascidian embryos share many properties with vertebrate neurogenic placodes; therefore, it is now believed that the last common ancestor of vertebrates and ascidians had embryonic structures similar to neurogenic placodes of vertebrate embryos. Because BMP signaling is important for specifying the placode region in vertebrate embryos, we examined whether BMP signaling is also involved in gene expression in the ANB region of ascidian embryos. Our data indicated that Admp, a divergent BMP family member, is mainly responsible for BMP signaling in the ANB region, and that two BMP-antagonists, Noggin and Chordin, restrict the domain, in which BMP signaling is activated, to the ANB region, and prevent it from expanding to the neural plate. BMP signaling is required for expression of Foxg and Six1/2 at the late gastrula stage, and also for expression of Zf220, which encodes a zinc finger transcription factor in late neurula embryos. Because Zf220 negatively regulates Foxg, when we downregulated Zf220 by inhibiting BMP signaling, Foxg was upregulated, resulting in one large palp instead of three palps (adhesive organs derived from ANB cells). Functions of BMP signaling in specification of the ANB region give further support to the hypothesis that ascidian ANB cells share an evolutionary origin with vertebrate cranial placodes.

Smoking-related cancer death among men and women in an ageing society (China 2020-2040): a population-based modelling study.

BACKGROUND: China is experiencing a postpeak smoking epidemic with accelerating population ageing. Understanding the impacts of these factors on the future cancer burden has widespread implications. METHODS: We developed predictive models to estimate smoking-related cancer deaths among men and women aged ≥35 years in China during 2020-2040. Data sources for model parameters included the United Nations World Population Prospects, China Death Surveillance Database, national adult tobacco surveys and the largest national survey of smoking and all causes of death to date. The main assumptions included stable sex-specific and age-specific cancer mortality rates and carcinogenic risks of smoking over time. RESULTS: In a base-case scenario of continuing trends in current smoking prevalence (men: 57.4%-50.5%; women: 2.6%-2.1% during 2002-2018), the smoking-related cancer mortality rate with population ageing during 2020-2040 would rise by 44.0% (from 337.2/100 000 to 485.6/100 000) among men and 52.8% (from 157.3/100 000 to 240.4/100 000) among women; over 20 years, there would be 8.6 million excess deaths (0.5 million more considering former smoking), and a total of 117.3 million smoking-attributable years of life lost (110.3 million (94.0%) in men; 54.1 million (46.1%) in working-age (35-64 years) adults). An inflection point may occur in 2030 if smoking prevalence were reduced to 20% (Healthy China 2030 goal), and 1.4 million deaths would be averted relative to the base-case scenario if the trend were maintained through 2040. CONCLUSIONS: Coordinated efforts are urgently needed to curtail a rising tide of cancer deaths in China, with intensified tobacco control being key.

A Manually Curated Gene Model Set for an Ascidian, Ciona robusta (Ciona intestinalis Type A).

Gene/transcript model sets predicted from decoded genome sequences are an important resource for a wide range of biological studies. Accuracy of gene models is therefore critical for deducing accurate conclusions. Computationally predicted models are sometimes inconsistent with experimental data from cDNA clones and RNA-sequencing. In an ascidian, Ciona robusta (Ciona intestinalis type A), a manually curated gene/transcript model set, which was constructed using an assembly in which 68% of decoded sequences were associated with chromosomes, had been used during the last decade. Recently a new genome assembly was published, in which over 95% of decoded sequences are associated with chromosomes. In the present study, we provide a high-quality version of the gene/transcript model set for the latest assembly. Because the Ciona genome has been used in a variety of studies such as developmental biological studies, evolutionary studies, and physiological studies, the current gene/transcript model set provides a fundamental biological resource.

Anxiety, depression and associated factors among caretakers of children with atopic dermatitis.

BACKGROUND: The prevalence of anxiety and depression symptoms among caretakers of children with atopic dermatitis (AD) and associated factors is unclear. The study was designed to explore anxiety and depression symptoms among caretakers of AD, and screen factors associated with anxiety and depression symptoms. METHODS: A total of 901 children with AD and their caretakers were continuously enrolled and interviewed at dermatology department of Capital Institute of Pediatrics, Beijing, China. Children's medication was administered by their caretakers. Caretakers' anxiety and depression symptoms were evaluated by Hamilton Depression Rating Scale-17 and Hamilton Depression Rating Scale, while medication compliance was evaluated and divided into poor (< 6 points), moderate (6-7 points), and good (> 7 points) by Morisky Medication Adherence Scale. Multilevel ordered logistic regression was used to screen factors associated with caretakers' anxiety and depression. RESULTS: Among caretakers, 41.5% had anxiety symptoms, 39.6% had depression symptoms, 51.4% have any of the two and 29.7% had both of the two. Factors associated with caretakers' anxiety symptoms included longer duration of the illness (OR, 0.99, 95% CI 0.98-0.99) and taking care of children with severe AD (OR, 2.55, 95% CI 1.43-4.55). Factors associated with caretakers' depression symptoms included higher educational level (OR, 0.56, 95% CI 0.39-0.80), taking care of children with moderate (OR, 2.01, 95% CI 1.15-3.50) and severe AD (OR, 3.99, 95% CI 2.10-7.59) and poor medication compliance (OR, 3.45, 95% CI 1.13-10.56). CONCLUSIONS: Prevalence of anxiety and depression symptoms among caretakers of AD were high. Attention should be paid to caretakers of AD at higher risk for those psychological problems.

The genetic program to specify ectodermal cells in ascidian embryos.

The ascidian belongs to the sister group of vertebrates and shares many features with them. The gene regulatory network (GRN) controlling gene expression in ascidian embryonic development leading to the tadpole larva has revealed evolutionarily conserved gene circuits between ascidians and vertebrates. These conserved mechanisms are indeed useful to infer the original developmental programs of the ancestral chordates. Simultaneously, these studies have revealed which gene circuits are missing in the ascidian GRN; these gene circuits may have been acquired in the vertebrate lineage. In particular, the GRN responsible for gene expression in ectodermal cells of ascidian embryos has revealed the genetic programs that regulate the regionalization of the brain, formation of palps derived from placode-like cells, and differentiation of sensory neurons derived from neural crest-like cells. We here discuss how these studies have given insights into the evolution of these traits.

Is exposure to tobacco associated with extrahepatic cholangiocarcinoma epidemics? A retrospective proportional mortality study in China.

BACKGROUND: Extrahepatic cholangiocarcinoma (ECC) has become one of the most rapidly increasing malignancies in China during recent decades. The relationship between tobacco exposure and ECC epidemics is unclear; this study aimed to explore this relationship. METHODS: We included 55,806 participants aged 30 years or older from the National Mortality and Smoking Survey of China. Smoking in participants and spouses was defined as 1 cigarette or more per day for up to 1 year. Spouses' smoking was taken as a measure of exposure to passive smoking. Smoking information in 1980 was ascertained and outcomes were defined as ECC mortality during 1986-1988. RESULTS: We found that either passive or active smoking increased the risk of death from ECC by 20% (risk ratio [RR], 1.20; 95% confidence interval [CI], 0.99-1.47), compared with no exposure to any tobacco. This risk was a notable 98% (RR, 1.98; 95% CI, 1.49-2.64) for individuals exposed to passive plus active smoking. These findings were highly consistent among men and women. Pathology-based analyses showed dose-response relationships of ECC with pack-years for all types of smoking exposure (Ps for trend < 0.05); the RR reached 2.75 (95% CI, 1.20-6.30) in individuals exposed to combined smoking with the highest exposure dose. The findings were similar for non-pathology-based analysis. CONCLUSIONS: This study indicates that tobacco exposure increases ECC risk. Given the dramatic increase of exposure to secondhand smoke and patients with ECC, an inadequate provision of smoke-free environments could be contributing to ECC epidemics and could further challenge public health and medical services, based on the current disease spectrum.

Aquaporin-1, a New Maternally Expressed Gene, Regulates Placental Development in the Mouse.

Imprinted genes play an important role in placental and embryonic development. Abnormalities in their regulation can result in placental and embryonic dysplasia, leading to congenital diseases. The imprinting state, expression, and function of aquaporin-1 (Aqp1) were explored in knockout mice by imprinting analysis, real-time PCR, and immunohistochemistry. In the present study, Aqp1 was identified as a new, imprinted, and placenta-specific maternally expressed gene in the mouse. Compared with wild-type Aqp1(+/+) mice, there was significant placental and embryonic overgrowth in Aqp1(-/+) (loss of maternal allele) and Aqp1(-/-) mice, but not in Aqp1(+/-) (loss of paternal allele) mice at Embryonic Day (E) 12.5-E18.5. In addition, the masses of Postnatal Day 0 (P0) embryos (Aqp1(-/-) and Aqp1(-/+)) were highest among the four types. In Aqp1(-/+) and Aqp1(-/-) mice, phenotypic analysis indicated that the number and branching of blood vessels, as well as the labyrinth area, increased significantly in placentae of E12.5-E18.5 mice. Moreover, there were abnormalities in the placental junctional zone and the labyrinthine zone at E15.5. Quantitative analysis showed that Aqp1 expression decreased significantly in the placentae of Aqp1(-/+) and Aqp1(-/-) mice at E15.5, and that the AQP1 protein expression signals were detected weakly in the decidual and spongioblast layers. Our results demonstrate that Aqp1 is maternally expressed in the placenta, and that its deficiency resulted in placental abnormalities in the mouse. Aqp1 may have a specific inhibitory role in mouse placental development. These results provide new insights for the treatment of diseases relating to placental and embryonic development.

Effects of active, passive, and combined smoking on cervical cancer mortality: a nationwide proportional mortality study in Chinese urban women.

PURPOSE: To determine whether smoking, in any form, is a risk factor in the development of cervical cancer (CC) among urban Chinese women. METHODS: We ascertained retrospectively the smoking habits of 1,865 women (aged 35+) who had died from CC (cases) and 48,781 who had died from causes unrelated to smoking (controls) in 24 cities using data from a large national survey of smoking and mortality in 1989-1991. We assessed the risk of smoking on CC mortality with and without considering passive smoke exposure from a spouse using a proportional mortality study design. RESULTS: Overall, there was a 51.0 % excess risk of death from CC among smokers. When the spouse's exposure was further considered, the RR (95 % CI) for exposed versus unexposed women was 1.28 (1.04-1.57) for passive smokers, 1.49 (1.02-2.20) for active smokers, and 1.69 (1.27-2.26) for women with both exposures (all p < 0.001). Significant dose-response associations were observed between smoking and CC for all categories of exposure. For example, individuals with both smoking exposure had the highest risk of CC mortality with moderate [RR = 1.67 (1.18-2.38)] and high [RR = 1.88 (1.04-3.41)] daily cigarette consumption, and they also had the highest risk with ≤15 years exposure [RR = 1.73 (1.19-2.52)] and >15 years exposure [RR = 1.95 (1.15-3.32)], compared with the active and passive groups (p for trend <0.001). CONCLUSIONS: Younger trend of CC death and the rapid increase in smoking among young women may have a profound impact on future incidence of CC. Our findings emphasize the need for preventive efforts among both women and men in China.

The roles of migrasome in development.

Migrasomes are newly identified vesicular structures that mainly come from the ends and crosspoints of retracting fibers in moving cells. Their creation is closely linked with cell movement and goes through three key steps: Nucleation, Maturation, and Expansion. They eventually get released in an event called migracytosis. Migrasomes have become an interesting focus in cell communication, especially during processes like development. They transport a mix of chemokines, growth factors, and morphogens. Their study can offer fresh perspectives on developmental gradients and improve our understanding of how development works. In the mini-review, we summarize our recent progress on the role of migrasomes in development, with a special focus on how migrasomes contribute to the spatial distribution of signalling molecules.

Enhanced risk of record-breaking regional temperatures during the 2023-24 El Niño.

In 2023, the development of El Niño is poised to drive a global upsurge in surface air temperatures (SAT), potentially resulting in unprecedented warming worldwide. Nevertheless, the regional patterns of SAT anomalies remain diverse, obscuring where historical warming records may be surpassed in the forthcoming year. Our study underscores the significant influence of El Niño and the persistence of climate signals on the inter-annual variability of regional SAT, both in amplitude and spatial distribution. The likelihood of global mean SAT exceeding historical records, calculated from July 2023 to June 2024, is estimated at 90%, contingent upon annual-mean sea surface temperature anomalies in the eastern equatorial Pacific exceeding 0.6 °C. Regions particularly susceptible to recording record-high SAT include coastal and adjacent areas in Asia such as the Bay of Bengal and the South China Sea, as well as Alaska, the Caribbean Sea, and the Amazon. This impending warmth heightens the risk of year-round marine heatwaves and escalates the threat of wildfires and other negative consequences in Alaska and the Amazon basin, necessitating strategic mitigation measures to minimize potential worst-case impacts.

Contributions of major smoking-related diseases to reduction in life expectancy associated with smoking in Chinese adults: a cross-sectional study.

BACKGROUND: Cigarette smoking is a prominent risk factor for a wide range of diseases. The current study aimed to evaluate the impact of smoking on deaths from major smoking-related diseases (neoplasms, vascular diseases and respiratory diseases) in Chinese adults by estimating the potential gains in life expectancy (LE) that would accrue from eliminating deaths from these diseases, and to determine the contribution of each disease to the reduction in LE associated with smoking. METHODS: Two cohorts of Chinese smokers and non-smokers were constructed from a retrospective national mortality survey that had been conducted in 1989-1991 and included one million all-cause deaths among adults during 1986-1988 in 103 geographical regions. For each cohort, potential gains in LE by eliminating deaths from each major smoking-related disease were estimated. The contributions of each disease to smoking-associated reduction in LE were assessed using the LE decomposition approach. RESULTS: Among the major smoking-related diseases, it was estimated that elimination of vascular diseases would provide the greatest potential gain in LE (years), regardless of smoking status. The gains for smokers versus non-smokers in populations of urban men, urban women, rural men and rural women aged 35 years were 3.5 vs. 4.3, 3.8 vs. 4.1, 2.4 vs. 3.0, and 2.6 vs. 2.9 years, respectively. Respiratory diseases contributed most to smoking-associated LE reductions in urban women, rural men and rural women of 43.6%, 46.4%, and 62.9%, respectively. In urban men, neoplasms contributed most to smoking-associated LE reduction, their contribution being estimated as 45.8%. CONCLUSIONS: Respiratory disease has the greatest influence on the LE reduction associated with smoking. Thus, smoking prevention could significantly reduce deaths from respiratory disease and improve LE.

The phosphatidylinositol (4,5)-bisphosphate-Rab35 axis regulates migrasome formation.

Migrasomes are recently discovered organelles, which are formed on the ends or branch points of retraction fibers at the trailing edge of migrating cells. Previously, we showed that recruitment of integrins to the site of migrasome formation is essential for migrasome biogenesis. In this study, we found that prior to migrasome formation, PIP5K1A, a PI4P kinase which converts PI4P into PI(4,5)P2, is recruited to migrasome formation sites. The recruitment of PIP5K1A results in generation of PI(4,5)P2 at the migrasome formation site. Once accumulated, PI(4,5)P2 recruits Rab35 to the migrasome formation site by interacting with the C-terminal polybasic cluster of Rab35. We further demonstrated that active Rab35 promotes migrasome formation by recruiting and concentrating integrin α5 at migrasome formation sites, which is likely mediated by the interaction between integrin α5 and Rab35. Our study identifies the upstream signaling events orchestrating migrasome biogenesis.

The formation of migrasomes is initiated by the assembly of sphingomyelin synthase 2 foci at the leading edge of migrating cells.

The migrasome is an organelle of migrating cells with diverse physiological functions. How migrasome formation is initiated is unknown. We found that sphingomyelin is enriched in migrasomes and identified sphingomyelin synthase 2 (SMS2) as an essential protein for migrasome biogenesis. SMS2 assembles into immobile foci that adhere on the basal membrane at the leading edge. When cells migrate away, the SMS2 foci 'move' out of cells and into retraction fibres, where they become migrasome formation sites and eventually grow into migrasomes. Mechanistically, SMS2 foci seed migrasomes by converting ceramide to sphingomyelin, which is essential for migrasome formation. Furthermore, CerS5, which is required for the synthesis of long-chain ceramide, and CERT, which transports ceramide from the endoplasmic reticulum to Golgi, are both required for migrasome formation. Our data reveal the essential role of ceramide and sphingomyelin in migrasome formation and suggest that SMS2 forms basal membrane-surface-connecting structures that pre-determine where migrasomes will grow.

Smoking-attributable deaths and potential years of life lost from a large, representative study in China.

OBJECTIVES: To provide a more accurate estimate of early smoking-attributable mortality and potential years of life lost using data from a representative study of 103 study areas in China. METHODS: Two datasets were employed as follows. Firstly, retrospective national mortality survey data, which included a population of 67 million in 103 study areas, and about 1 million adults who died in 1986-1988; secondly, nationally representative case-control comparative data was extracted from the survey data to measure the effect of smoking on age trends in smoking-attributable mortality. Potential years of life lost, and sex differences in life expectancy in smokers and non-smokers in the total population aged 35 and over were also estimated. RESULTS: Tobacco caused 11.2% (16.0% of men and 3.7% of women) of total deaths in 1987, and more than two-thirds of these excess deaths occurred between the ages of 50 and 74 years, but only less than 5% excess deaths occurred at ages under 50. Although life expectancies varied with region or sex differences, the years of life lost attributable to smoking was almost the same. Smokers at age 35 lost about 3 years of life expectancy in comparison with never smokers. The study also confirmed that more than 50% of the sex difference in life expectancy was accounted for by smoking. CONCLUSION: Fully understanding the consequences of smoking in relation to mortality can clarify its effects on the health and longevity of the entire population.

Case-spouse control design in practice: an experience in estimating smoking and chronic obstructive pulmonary disease deaths in Chinese adults.

BACKGROUND/PURPOSE: We assessed the effect of smoking on death from chronic obstructive pulmonary disease (COPD) in China by employing a large population-based, case-spouse control study design using data from a nationwide survey of mortality. METHODS: During 1989-1991, a nationwide retrospective survey of mortality was conducted in China. For approximately 1,000,000 adults dying from all causes during 1986-1988, their surviving spouses or other informants provided detailed information about their own as well as the deceased person's smoking history. For this study, 183,393 individuals who died of COPD at age > or = 40 years were taken as cases, while 272,984 sex-matched surviving spouses of subjects who died from any cause were taken as controls. RESULTS: COPD death rates for smokers were more than twice as high as those of non-smokers, with a dose-response risk pattern, despite the fact that COPD death rates varied widely by region and age. Tobacco accounted for 41.4% of COPD deaths in men, but only 13.5% of those in women, who had a lower rate of smoking. CONCLUSION: A case-spouse control study, as an alternative design, is valid and feasible in utilizing information from population-based, retrospective mortality survey data for an analytical epidemiological study of disease etiology.

Comparative study of control selection in a national population-based case-control study: Estimating risk of smoking on cancer deaths in Chinese men.

PURPOSE: To assess the validation of a novel control selection design by comparing the consistency between the new design and a routine design in a large case-control study that was incorporated into a nationwide mortality survey in China. METHODS: A nationwide mortality study was conducted during 1989-1991. Surviving spouses or other relatives of all adults who died during 1986-1988 provided detailed information about their own as well as the deceased person's smoking history. In this study, 130,079 males who died of various smoking-related cancers at age 35 or over were taken as cases, while 103,248 male surviving spouses (same age range with cases) of women who died during the same period and 49,331 males who died from causes other than those related to smoking were used as control group 1 and control group 2, respectively. Consistency in the results when comparing cases with each of the control groups was assessed. RESULTS: Consistency in the results was observed in the analyses using different control groups although cancer deaths varied with region and age. Equivalence could be ascertained using a 15% criterion in most cancer deaths which had high death rates in urban areas, but they were uncertain for most cancers in rural areas irrespective of whether the hypothesis testing showed significant differences or not. CONCLUSIONS: Sex-matched living spouse control design as an alternative control selection for a case-control study is valid and feasible, and the basic principles of the equivalence study are also supported by epidemiological survey data.

Foxg specifies sensory neurons in the anterior neural plate border of the ascidian embryo.

Foxg constitutes a regulatory loop with Fgf8 and plays an important role in the development of anterior placodes and the telencephalon in vertebrate embryos. Ascidians, which belong to Tunicata, the sister group of vertebrates, develop a primitive placode-like structure at the anterior boundary of the neural plate, but lack a clear counterpart of the telencephalon. In this animal, Foxg is expressed in larval palps, which are adhesive organs with sensory neurons. Here, we show that Foxg begins to be expressed in two separate rows of cells within the neural plate boundary region under the control of the MAPK pathway to pattern this region. However, Foxg is not expressed in the brain, and we find no evidence that knockdown of Foxg affects brain formation. Our data suggest that recruitment of Fgf to the downstream of Foxg might have been a critical evolutionary event for the telencephalon in the vertebrate lineage.

Passive smoking and stroke in men and women: a national population-based case-control study in China.

An association between passive smoking and stroke is unclear in China, particularly the association with hemorrhagic stroke. This study included 16205 deaths due to stroke aged ≥30 years and 16205 non-stroke controls randomly selected and frequency-matched to cases on gender and age. Smoking of spouses, defined as ≥1 cigarette per day for up to 1 year, was taken as a measure of exposure to passive smoking of subjects that was retrospectively ascertained by interviewing surviving spouses. After adjustment for variables, passive smoking increased the risk of death by 10% (odds ratio (OR), 1.10; 95% confidence interval (CI), 1.05-1.16) for all strokes, by 10% (OR, 1.10; 95% CI, 1.04-1.16) for hemorrhagic stroke, and by 12% (OR, 1.12; 95% CI, 1.03-1.23) for ischemic stroke, compared with non-exposure. This finding was highly consistent in men or women and in smokers or non-smokers, and was generally consistent among zones of China despite geographic diversity. The risk significantly increased with exposure-years and quantity of cigarettes smoked daily by spouses. This study indicated that passive smoking is associated with deaths from all-type strokes. It is highly advisable for the government to promote strong tobacco prevention and cessation programs and smoke-free environments.