Adaptive evolution of the enigmatic Takakia now facing climate change in Tibet.

The most extreme environments are the most vulnerable to transformation under a rapidly changing climate. These ecosystems harbor some of the most specialized species, which will likely suffer the highest extinction rates. We document the steepest temperature increase (2010-2021) on record at altitudes of above 4,000 m, triggering a decline of the relictual and highly adapted moss Takakia lepidozioides. Its de-novo-sequenced genome with 27,467 protein-coding genes includes distinct adaptations to abiotic stresses and comprises the largest number of fast-evolving genes under positive selection. The uplift of the study site in the last 65 million years has resulted in life-threatening UV-B radiation and drastically reduced temperatures, and we detected several of the molecular adaptations of Takakia to these environmental changes. Surprisingly, specific morphological features likely occurred earlier than 165 mya in much warmer environments. Following nearly 400 million years of evolution and resilience, this species is now facing extinction.

Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer - possible implications for immunotherapy.

BACKGROUND: The immune response has important clinical value in colorectal cancer (CRC) in both prognosis and response to immunotherapy. This study aims to explore tumour immune cell infiltration in relation to clinically well-established molecular markers of CRC. METHODS: Multiplex immunohistochemistry and multispectral imaging was used to evaluate tumour infiltration of cytotoxic T cells (CD8+), Th1 cells (T-bet+), T regulatory cells (FoxP3+), B cells (CD20+), and macrophages (CD68+) in a cohort of 257 CRC patients. RESULTS: We found the expected association between higher immune-cell infiltration and microsatellite instability. Also, whereas BRAF-mutated tumours displayed increased immune-cell infiltration compared to BRAF wild-type tumours, the opposite was seen for KRAS-mutated tumours, differences that were most prominent for cytotoxic T cells and Th1 cells. The opposing relationships of BRAF and KRAS mutations with tumour infiltration of cytotoxic T cells was validated in an independent cohort of 608 CRC patients. A positive prognostic importance of cytotoxic T cells was found in wild-type as well as KRAS and BRAF-mutated CRCs in both cohorts. CONCLUSION: A combined evaluation of MSI status, KRAS and BRAF mutational status, and immune infiltration (cytotoxic T cells) may provide important insights to prognosis and response to immunotherapy in CRC.

The Regulatory Effect of the Paraventricular Nucleus on Hypertension.

Hypertension is among the most harmful factors of cardiovascular and cerebrovascular diseases and poses an urgent problem for the development of human society. In addition to previous studies on its pathogenesis focusing on the peripheral sympathetic nervous system, investigating the central causes of high blood pressure involving the neuroendocrine and neuroinflammatory mechanisms of the hypothalamic paraventricular nucleus (PVN) is paramount. This nucleus is considered to regulate the output of neurohormones and sympathetic nerve activity. In this article, we focussed on the neuroendocrine mechanism, primarily exploring the specific contributions and interactions of various neurons and neuroendocrine hormones, including GABAergic and glutamatergic neurons, nitric oxide, arginine vasopressin, oxytocin, and the renin-angiotensin system. Additionally, the neuroinflammatory mechanism in the PVN was discussed, encompassing microglia, reactive oxygen species, inflammatory factors, and pathways, as well as immune connections between the brain and extracerebral organs. Notably, the two central mechanisms involved in the PVN not only exist independently but also communicate with each other, jointly maintaining the hypertensive state of the body. Furthermore, we introduce well-known molecules and signal transduction pathways within the PVN that can play a regulatory role in the two mechanisms to provide a basis and inspire ideas for further research.

Perceptions, barriers, and challenges of oral care among nursing assistants in the intensive care unit: a qualitative study.

BACKGROUND: Although oral hygiene is closely related to various diseases, it is sub-optimal in the Intensive Care Unit (ICU). Oral care in the ICU is challenged by nursing workloads, low staffing, and higher acuity patients, there are few policies and written guidelines for oral care. Nurses often delegate oral care to nursing assistants (NAs) whose role is overlooked. This study is to explore the perspectives, obstacles, and challenges of NAs in the oral care of the ICU. METHODS: A qualitative study and semi-structured interviews were conducted with NAs in three ICU units, and Colaizzi's phenomenological method was used to analyze the records. RESULTS: Initially, 13 NAs met the inclusion criteria, and two did not participate in this study as they refused to be recorded. Finally, 11 ICU NAs were interviewed, with three receiving face-to-face interviews and eight receiving telephone interviews. Using Colaizzi's phenomenological method, two themes and eight subthemes emerged from the data, we examined the self-perception, barriers and challenges of NAs regarding oral care and identified the subthemes: (1) The target audience, frequency, and importance; (2) Role; (3) Evaluation; (4) Patient-related factors; (5) Oral care tools; (6) Psychology of NAs; (7) Lack of education and training; (8) Lack of team support. CONCLUSION: Nursing assistants whose roles are overlooked by the nursing team are important members of the ICU team. Though oral care is closely related to disease prevention, it is rarely considered an essential task. Major barriers to implementing oral care in the ICU environment and patients include the psychological quality of participants, non-standard education and training, and inadequate team support. The expectation is that medical personnel will prioritize oral hygiene and recognize the significance of NAs in nursing work. Furthermore, future ICU oral care should investigate suitable tools and mouthwashes, simplified and standardized processes, standardized training, and multidisciplinary team collaboration.

Effect of integrated intervention to prevent child drowning in rural areas of Guangdong, China: a cluster randomized controlled trial.

BACKGROUND: Drowning is the leading cause of death for children under the age of 15 years in Guangdong Province, China. This serious public health issue also exists in low- and middle-income countries (LMICs), which have few value-integrated intervention programs. The current study presents an integrated intervention project that aims to explore an effective pattern of prevention for child drowning in rural areas and feasibility to perform in other LMICs. METHODS: We conducted a cluster randomized controlled trial by comparing the incidence of non-fatal drowning among children in two groups in rural areas of southern China. We recruited the participants in two phases and reached a total of 10 687 students from 23 schools at two towns in Guangdong Province, China. At the first and second phases, 8966 and 1721 students were recruited, respectively. RESULTS: The final evaluation questionnaires were collected after 18 months of integrated intervention, where we obtained 9791 data from Grades 3-9. The incidence of non-fatal drowning between the intervention and control groups after intervention did not differ significantly from the baseline according to the total number of students, male students, female students and Grades 6-9 [0.81; 95% confidence interval (CI): [0.66, 1.00]; p = 0.05, 1.17; 95% CI: [0.90, 1.51]; p = 0.25, 1.40; 95% CI: [0.97, 2.02]; p = 0.07 and 0.97; 95% CI: [0.70, 1.34]; p = 0.86], except for Grades 3-5 (1.36; 95% CI: [1.02, 1.82]; p = 0.037). The study observed a significantly positive benefit of awareness and risk behaviours of non-fatal drowning between the intervention and control groups (0.27, 95% CI: [0.21, 0.33]; p = 0.00, -0.16; 95% CI: [-0.24, -0.08]; p = 0.00). CONCLUSIONS: The integrated intervention exerted a significant impact on the prevention and management of child non-fatal drowning, especially in rural areas.

Parvimonas micra is associated with tumour immune profiles in molecular subtypes of colorectal cancer.

The importance of the tumour microbiome in different aspects of colorectal cancer (CRC) has been increasingly recognised, but many questions remain. The aim of this study was to explore the effect of specific CRC associated microbes on the tumour immune response, which has a considerable prognostic value in CRC. We applied specific qPCR to detect Parvimonas micra and Fusobacterium nucleatum in tumour tissues from an immunologically well-characterised cohort of 69 CRC patients. This cohort included detailed analyses of immune profiles based on flow cytometry and transcriptomics in tumour tissue and blood, along with comprehensive analyses of molecular subtypes. P. micra and F. nucleatum were detected in 24% and 64% of tumour tissues, respectively. We found a significant association of P. micra with high-grade tumours and tumours of CMS1 subtype. F. nucleatum was significantly associated with right-sided tumours, microsatellite instability, and CMS1 tumours. The immunological analyses revealed significant associations of P. micra with activated CD69+ T lymphocytes and increased antigen-presenting HLA-DR+ B lymphocytes. P. micra was also positively associated with M1 and M2 macrophage traits. The impact of P. micra tumour colonisation on the immune response was further assessed using transcriptomics in validation of our findings. No associations were found between F. nucleatum and immune profiles in this study. Our findings support novel associations between P. micra and the immune response in CRC. A better understanding of these interactions might help to identify important predictive and prognostic tools as well as new targets for therapy.

Source apportionment of PM2.5 and visibility in Jinan, China.

Atmospheric extinction is impacted by the chemical composition of particles. To better understand the chemical composition of PM2.5 (particles with diameters of less than 2.5 µm) and its relationship with extinction, one-month sampling campaigns were carried out in four different seasons from 2013 to 2014 in Jinan, China. The seasonal average concentrations of PM2.5 were 120.9 (autumn), 156.6 (winter), 102.5 (spring), and 111.8 µg/m3 (summer). The reconstructed PM2.5 chemical composition showed that sulfate, nitrate, chlorine salt, organic matter (OM), mineral dust, elemental carbon (EC) and others accounted for 25%, 14%, 2%, 24%, 22%, 3% and 10%, respectively. The relationship between the chemical composition of PM2.5 and visibility was reconstructed by the IMPROVE method, and ammonium sulfate, ammonium nitrate, OM and EC dominated the visibility. Seven main sources were resolved for PM2.5, including secondary particles, coal combustion, biomass burning, industry, motor vehicle exhaust, soil dust and cooking, which accounted for 37%, 21%, 13%, 13%, 12%, 3% and 1%, respectively. The contributions of different sources to visibility were similar to those to PM2.5. With increasing severity of air pollution, the contributions of secondary particles and coal combustion increased, while the contribution of motor vehicle exhaust decreased. The results showed that coal combustion and biomass burning were still the main sources of air pollution in Jinan.

Seasonal variation and sources of derivatized phenols in atmospheric fine particulate matter in North China Plain.

Qualitative and quantitative analyses of derivatized phenols in Beijing and in Xinglong were performed from 2016 to 2017 using gas chromatography-mass spectrometry. The results showed substantially more severe pollution in Beijing. Of the 14 compounds detected, the total average concentration was 100 ng/m3 in Beijing, compared with 11.6 ng/m3 in Xinglong. More specifically, concentration of nitro-aromatic compounds (NACs) (81.9 ng/m3 in Beijing and 8.49 ng/m3 in Xinglong) was the highest, followed by aromatic acids (14.6 ng/m3 in Beijing and 2.42 ng/m3 in Xinglong) and aromatic aldehydes (3.62 ng/m3 in Beijing and 0.681 ng/m3 in Xinglong). In terms of seasonal variation, the highest concentrations were found for 4-nitrocatechol in winter in Beijing (79.1 ± 63.9 ng/m3) and 4-nitrophenol in winter in Xinglong (9.72 ± 8.94 ng/m3). The analysis also revealed diurnal variations across different seasons. Most compounds presented higher concentrations at night in winter because of the decreased boundary layer height and increased heating intensity. While some presented higher levels during the day, which attributed to the photo-oxidation process for summer and more biomass burning activities for autumn. Higher concentrations appeared in winter and autumn than in spring and summer, which resulted from more coal combustions and adverse meteorological conditions. The significant correlations among NACs indicated similar sources of pollution. Higher correlations presented within each subgroup than those between the subgroups. Good correlations between levoglucosan and nitrophenols, nitrocatechols, nitrosalicylic acids, with correlation coefficients (r) of 0.66, 0.69 and 0.69, respectively, indicating an important role of biomass burning among primary sources.

Secondary organic aerosols in Jinan, an urban site in North China: Significant anthropogenic contributions to heavy pollution.

Secondary organic aerosols (SOAs) are an important component of particulates, but whether biogenic SOAs (BSOAs) or anthropogenic SOAs (ASOAs) are the dominant contributors to haze pollution remains poorly characterized. In this study, particulate samples were collected from September 2014 to August 2015 at an urban site in Jinan, which is the capital of Shandong Province and a typical city in the North China Plain. The PM2.5 samples were analyzed for BSOA (isoprene (SOAI) and monoterpenes (SOAM)) and ASOA (aromatic (SOAA)) tracers. The concentrations of the SOAA tracer (1.1 ±â€¯1.0 ng/m3) were lowest, and those of SOAI tracers (41.8 ±â€¯86.2 ng/m3) were highest, with the concentrations of SOAM tracers (19.4 ±â€¯9.9 ng/m3) being intermediate. The SOAI tracers were more abundant in the summer and less abundant in the winter. Both SOAI and SOAM increased with increasing ozone level but decreased with increasing NOx level. Correlation analysis revealed a good correlation between 2,3-dihydroxy-4-oxopentanoic acid and levoglucosan levels in three seasons. These results suggested that biomass burning activities occurring in the NCP can enhance the emissions of aromatics and should be controlled, especially in the autumn and winter. SOA tracers were classified according to pollution degree, and the results showed that as pollution increases, the contributions of SOAA increase. These results indicate that reducing anthropogenic emissions is necessary to prevent SOA pollution, especially during heavy pollution episodes.

WT1 enhances proliferation and impedes apoptosis in KRAS mutant NSCLC via targeting cMyc.

BACKGROUND: A novel link between oncogenic KRAS signalling and WT1 was recently identified. We sought to investigate the role of WT1 and KRAS in proliferation and apoptosis. METHODS: KRAS mutations and WT1 (cMyc) expression were detected using Sanger sequencing and real-time PCR in 77 patients with non-small cell lung cancer (NSCLC). Overexpression and knockdown of WT1 were generated with plasmid and siRNA via transient transfection technology in H1299 and H1568 cells. MTT assay for detection of cell proliferation, and TUNEL assay and proteomic profiler assay for apoptosis evaluation were carried out. Dual luciferase reporter assay and ChIP-PCR were performed to validate the effect of WT1 on the cMyc promoter. RESULTS: KRAS mutations showed a negative impact on overall survival (OS). High expressions of WT1 and cMyc were associated with poor OS in KRAS mutant subgroup. The potential mechanisms that WT1 promotes proliferation and impedes apoptosis through affecting multiple apoptosis-related regulators in KRAS mutant NSCLC cells were identified. WT1 could activate cMyc promoter directly in KRAS mutant cells. CONCLUSION: The results suggest that WT1 and c-MYC expression is important for survival in KRAS mutant tumors as opposed to KRAS wild-type tumors. For treatment of KRAS mutant NSCLC, targeting WT1 and cMyc may provide alternative therapeutic strategies.

Wilms' tumor gene 1 regulates p63 and promotes cell proliferation in squamous cell carcinoma of the head and neck.

BACKGROUND: Wilms' tumor gene 1 (WT1) can act as a suppressor or activator of tumourigenesis in different types of human malignancies. The role of WT1 in squamous cell carcinoma of the head and neck (SCCHN) is not clear. Overexpression of WT1 has been reported in SCCHN, suggesting a possible oncogenic role for WT1. In the present study we aimed at investigating the function of WT1 and its previously identified protein partners p63 and p53 in the SCCHN cell line FaDu. METHODS: Silencing RNA (siRNA) technology was applied to knockdown of WT1, p63 and p53 in FaDu cells. Cell proliferation was detected using MTT assay. Chromatin immunoprecipitation (ChIP)/PCR analysis was performed to confirm the effect of WT1 on the p63 promoter. Protein co-immunoprecipitation (co-IP) was used to find protein interaction between WT1 and p53/p63. Microarray analysis was used to identify changes of gene expression in response to knockdown of either WT1 or p63. WT1 RNA level was detected using real-time quantitative PCR (RT-qPCR) in patients with SCCHN. RESULTS: We found that WT1 and p63 promoted cell proliferation, while mutant p53 (R248L) possessed the ability to suppress cell proliferation. We reported a novel positive correlation between WT1 and p63 expression. Subsequently, p63 was identified as a WT1 target gene. Furthermore, expression of 18 genes involved in cell proliferation, cell cycle regulation and DNA replication was significantly altered by downregulation of WT1 and p63 expression. Several known WT1 and p63 target genes were affected by WT1 knockdown. Protein interaction was demonstrated between WT1 and p53 but not between WT1 and p63. Additionally, high WT1 mRNA levels were detected in SCCHN patient samples. CONCLUSIONS: Our findings suggest that WT1 and p63 act as oncogenes in SCCHN, affecting multiple genes involved in cancer cell growth.

A Novel Swarm-Exploring Neurodynamic Network for Obtaining Global Optimal Solutions to Nonconvex Nonlinear Programming Problems.

A swarm-exploring neurodynamic network (SENN) based on a two-timescale model is proposed in this study for solving nonconvex nonlinear programming problems. First, by using a convergent-differential neural network (CDNN) as a local quadratic programming (QP) solver and combining it with a two-timescale model design method, a two-timescale convergent-differential (TTCD) model is exploited, and its stability is analyzed and described in detail. Second, swarm exploration neurodynamics are incorporated into the TTCD model to obtain an SENN with global search capabilities. Finally, the feasibility of the proposed SENN is demonstrated via simulation, and the superiority of the SENN is exhibited through a comparison with existing collaborative neurodynamics methods. The advantage of the SENN is that it only needs a single recurrent neural network (RNN) interact, while the compared collaborative neurodynamic approach (CNA) involves multiple RNN runs.

Pollution Characteristics and Source Apportionment of Black Carbon Aerosols during Spring in Beijing.

Black carbon (BC) aerosols are important for absorbing aerosols, affecting global climate change and regional air quality, and potentially harming human health. From March to May 2023, we investigated black carbon aerosol levels and air pollution in Beijing. Employing methods such as linear regression, Potential Source Contribution Function (PSCF) and Concentration-Weighted Trajectory (CWT), we analyzed the characteristics and sources of black carbon aerosols in the region. Results indicate that the light absorption coefficients of BC and BrC decrease with increasing wavelength, with BrC accounting for less than 40% at 370 nm. Daily variations in BC and PM2.5 concentrations exhibit similar trends, peaking in March, and BC displays a distinct bimodal hourly concentration structure during this period. Aethalometer model results suggest that liquid fuel combustion contributes significantly to black carbon (1.08 ± 0.71 µg·m-3), surpassing the contribution from solid fuel combustion (0.31 ± 0.2 µg·m-3). Furthermore, the significant positive correlation between BC and CO suggests that BC emissions in Beijing predominantly result from liquid fuel combustion. Potential source area analysis indicates that air masses of spring in Beijing mainly originate from the northwest (40.93%), while potential source areas for BC are predominantly distributed in the Beijing-Tianjin-Hebei region, as well as parts of the Shandong, Shanxi and Henan provinces. Moreover, this study reveals that dust processes during spring in Beijing have a limited impact on black carbon concentrations. This study's findings support controlling pollution in Beijing and improving regional air quality.

Paroxysmal sympathetic hyperexcitability after brain injury: A clinical analysis of case series.

BACKGROUND: Paroxysmal sympathetic hyperexcitability (PSH) is a group of complex syndromes with various etiologies. Previous studies were limited to the description of traumatic brain injury (TBI), and the description of PSH after other types of brain injury was rare. We explored the clinical features, treatment, and prognosis of PSH after various types of brain injuries. METHODS: Patients admitted to the neurosurgery intensive care unit with PSH after brain injury from July 2019 to December 2022 were included. Demographic data, clinical manifestations, drug therapy, and disease prognosis were retrospectively collected and analyzed. RESULTS: Fifteen male and 9 female patients with PSH after brain injury were selected. TBI was most likely to cause PSH (66.7%), followed by spontaneous intracerebral hemorrhage (25%). Glasgow coma scale scores of 19 patients (79.2%) were lower than 8 and 14 patients (58.3%) underwent tracheotomy. Electroencephalogram monitoring was performed in 12 individuals, none of which showed epileptic waves. Clinical symptom scale showed mild symptoms in 17 cases (70.8%). Almost all patients were administered a combination of drugs. After follow-up, most patients had a poor prognosis and 2 (8.3%) died after discharge. CONCLUSION: The etiology of PSH is complex. TBI may be the most common cause of PSH. Non-TBI may also be an important cause of PSH. Therefore, early identification, prevention and diagnosis are helpful for determining the prognosis and outcome of the disease.

Cretaceous crown male ant reveals the rise of modern lineages.

Most described Mesozoic ants belong to stem groups that existed only during the Cretaceous period. Previously, the earliest known crown ants were dated to the Turonian (Late Cretaceous, ca. 94-90 million years ago (Ma)) deposits found in the USA, Kazakhstan, and Botswana. However, the recent discovery of an alate male ant in Kachin amber from the earliest Cenomanian (ca. 99 Ma), representing a new genus and species, Antiquiformica alata, revises the narrative on ant diversification. Antiquiformica can be distinctly differentiated from all known male stem ants by its geniculate antennae with elongated scape, extending far beyond the occipital margin of the head and half the length of the funiculus, as well as its partly reduced forewing venation. Furthermore, the combination of a one-segmented waist with a well-developed node, elongated scape extending beyond the occipital margin, and reduced forewing venation, particularly the completely reduced m-cu and rs-m crossveins and absence of rm and mcu closed cells, firmly places the fossil within the extant subfamily Formicinae. Fourier transform infrared spectroscopy (FTIR) confirmed that the amber containing Antiquiformica alata originated from the Kachin mines in Myanmar. This discovery significantly revises our understanding of the early evolution of Formicinae. The presence of Antiquiformica in Cenomanian amber indicates that the subfamily Formicinae emerged at least by the start of the Late Cretaceous, with crown ants likely originating earlier during the earliest Cretaceous or possibly the Late Jurassic, although paleontological evidence is lacking to support the latter hypothesis.

Seasonal variation and source apportionment of organic and inorganic compounds in PM2.5 and PM10 particulates in Beijing, China.

The distribution and source of the solvent-extractable organic and inorganic components in PM2.5 (aerodynamics equivalent diameter below 2.5 microns), and PM10 (aerodynamics equivalent diameter below 10 microns) fractions of airborne particles were studied weekly from September 2006 to August 2007 in Beijing. The extracted organic and inorganic compounds identified in both particle size ranges consisted of n-alkanes, PAHs (polycyclic aromatic hydrocarbons), fatty acids and water soluble ions. The potential emission sources of these organic compounds were reconciled by combining the values of n-alkane carbon preference index (CPI), %waxC(n), selected diagnostic ratios of PAHs and principal component analysis in both size ranges. The mean cumulative concentrations of n-alkanes reached 1128.65 ng/m3 in Beijing, 74% of which (i.e., 831.7 ng/m3) was in the PM2.5 fraction, PAHs reached 136.45 ng/m3 (113.44 ng/m3 or 83% in PM2.5), and fatty acids reached 436.99 ng/m3 (324.41 ng/m3 or 74% in PM2.5), which resulted in overall enrichment in the fine particles. The average concentrations of SO4(2-), NO3(-), and NH4(+) were 21.3 +/- 15.2, 6.1 +/- 1.8, 12.5 +/- 6.1 microg/m3 in PM2.5, and 25.8 +/- 15.5, 8.9 +/- 2.6, 16.9 +/- 9.5 microg/m3 in PM10, respectively. These three secondary ions primarily existed as ammonium sulfate ((NH4)2SO4), ammonium bisulfate (NH4HSO4) and ammonium nitrate (NH4NO3). The characteristic ratios of PAHs revealed that the primary sources of PAHs were coal combustion, followed by gasoline combustion. The ratios of stearic/palmitic acid indicated the major contribution of vehicle emissions to fatty acids in airborne particles. The major alkane sources were biogenic sources and fossil fuel combustion. The major sources of PAHs were vehicular emission and coal combustion.

Study on the Fingerprint and Atmospheric Activity of Volatile Organic Compounds from Typical Industrial Emissions.

China is prone to severe surface ozone pollution in summer, so it is very important to understand the source of volatile organic compounds (VOCs) to control ozone formation. In this work, the emission characteristics of 91 VOC components from the plastic products industry, packaging and printing industries, printing ink industry, furniture manufacturing and vehicle manufacturing industries were studied. The results show that there are significant differences between these sources, and for the plastic products industry, alkanes (48%) are the most abundant VOCs. The main emission species in the packaging and printing industry are OVOCs (36%) and alkanes (34%). The proportion of OVOCs in the printing ink (73%) and furniture manufacturing industries (49%) is dominated by VOC emissions; aromatic hydrocarbons (33%), alkanes (33%), and OVOCs (17%) are the main emission species in the vehicle manufacturing industry. At the same time, the ozone generation potential (OFP) and secondary organic aerosol formation potential (SOA) of anthropogenic VOC emissions were evaluated, and the top 10 contributors to OFP and SOA were identified. Toluene, o-xylene, and m-xylene had a significant tendency to form OFP or SOA. Then, a health risk assessment of VOC components was carried out. These data can supplement the existing VOC emission characteristics of anthropogenic emissions, thus enriching the research progress of VOC emission sources.

Dynamic regulation of drug biodistribution by turning tumors into decoys for biomimetic nanoplatform to enhance the chemotherapeutic efficacy of breast cancer with bone metastasis.

Breast cancer with bone metastasis accounts for serious cancer-associated pain which significantly reduces the quality of life of affected patients and promotes cancer progression. However, effective treatment using nanomedicine remains a formidable challenge owing to poor drug delivery efficiency to multiple cancer lesions and inappropriate management of cancer-associated pain. In this study, using engineered macrophage membrane (EMM) and drugs loaded nanoparticle, we constructed a biomimetic nanoplatform (EMM@DJHAD) for the concurrent therapy of bone metastatic breast cancer and associated pain. Tumor tropism inherited from EMM provided the targeting ability for both primary and metastatic lesions. Subsequently, the synergistic combination of decitabine and JTC801 boosted the lytic and inflammatory responses accompanied by a tumoricidal effect, which transformed the tumor into an ideal decoy for EMM, resulting in prolonged troop migration toward tumors. EMM@DJHAD exerted significant effects on tumor suppression and a pronounced analgesic effect by inhibiting µ-opioid receptors in bone metastasis mouse models. Moreover, the nanoplatform significantly reduced the severe toxicity induced by chemotherapy agents. Overall, this biomimetic nanoplatform with good biocompatibility may be used for the effective treatment of breast cancer with bone metastasis.

State Observer Design of Coupled Genetic Regulatory Networks With Reaction-Diffusion Terms via Time-Space Sampled-Data Communications.

In this paper, state observation of coupled reaction-diffusion genetic regulatory networks (GRNs) with time-varying delays is investigated under Dirichlet boundary conditions. First, the above GRNs are constructed to model gene regulatory properties, where the feedback regulation function of the GRNs is assumed to exhibit the Hill form and a novel method to deal with it is introduced. Then a time-space sampled-data state observer is designed for the mentioned networks and new criteria are established by utilizing the Lyapunov stability theory and the inequality techniques of Halanay et al. Finally, the validity of the theoretical results is proved by numerical examples.

Space-Dividing-Based Cluster Synchronization of Reaction-Diffusion Genetic Regulatory Networks via Intermittent Control.

In this paper, we focus on the cluster synchronization of reaction-diffusion genetic regulatory networks (RDGRNs) with time-varying delays, where the state of the system is not only time-dependent but also spatially-dependent due to the presence of the reaction-diffusion terms. First, we construct an intermittent space-dividing controller that effectively combines the two control strategies, making it more cost-effective. Furthermore, based on the activation function division approach, we propose a regulation function division method that can improve the delay upper bound of RDGRNs; meanwhile, the cluster synchronization criteria of RDGRNs under the proposed controller are derived based on the Lyapunov theory and Halanay's et al. inequality techniques. Finally, the criteria's effectiveness is demonstrated by numerical examples of the system in one- and two-dimensional space.