Association between pulse pressure and carotid plaques in old adults with uncontrolled hypertension: results from a community-based screening in Hangzhou, China.

BACKGROUND: There is a broad pulse pressure (PP) and a high prevalence of carotid plaques in old adults. Previous studies have indicated that PP is strongly associated with carotid plaque formation. This study aimed to explore this association in old adults with uncontrolled hypertension. METHODS: 1371 hypertensive patients aged ≥ 60 years with uncontrolled hypertension were enrolled in a community-based screening in Hangzhou, China. Carotid plaques were assessed using ultrasonography. Logistic regression models were used to estimate the association between PP and carotid plaques by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Carotid plaques were detected in 639 (46.6%) of subjects. Multiple plaques were found in 408 (63.8%) and soft plaques in 218 (34.1%). Elevated PP was associated with a high prevalence of carotid plaques. After adjusting for traditional risk factors, compared to patients within the lowest tertile of PP, those within the highest tertiles had an increased risk of carotid plaques (OR 2.061, CI 1.547-2.745). For each 1-SD increase, the risk increased by 40.1% (OR 1.401, CI 1.237-1.587). There was a nonlinear association between PP and carotid plaques (P nonlinearity = 0.039). The risk increased rapidly after the predicted PP level reached around 60 mmHg. The associations were stronger among participants with multiple and soft plaques. CONCLUSIONS: Our findings suggested that PP was independently associated with carotid plaques in old adults with uncontrolled hypertension who have an increased risk of atherosclerosis.

cGAS/STING cross-talks with cell cycle and potentiates cancer immunotherapy.

The correct duplication and transfer of genetic material to daughter cells is the major event of cell division. Dysfunction of DNA replication or chromosome segregation presents challenges in cancer initiation and development as well as opportunities for cancer treatment. Cyclic GMP-AMP synthase (cGAS) of the innate immune system detects cytoplasmic DNA and mediates downstream immune responses through the molecule stimulator of interferon genes (STING). However, how cytosolic DNA sensor cGAS participates in guaranteeing accurate cell division and preventing tumorigenesis is still unclear. Recent evidence indicates malfunction of cGAS/STING pathway in cancer progression. Cell cycle-targeted therapy synergizes with immunotherapy via cGAS/STING activation, leading to promising therapeutic benefit. Here, we review the interactions between cell cycle regulation and cGAS/STING signaling, thus enabling us to understand the role of cGAS/STING in cancer initiation, development, and treatment.

Nkx2-5 defines a subpopulation of pacemaker cells and is essential for the physiological function of the sinoatrial node in mice.

The sinoatrial node (SAN), the primary cardiac pacemaker, consists of a head domain and a junction/tail domain that exhibit different functional properties. However, the underlying molecular mechanism defining these two pacemaker domains remains elusive. Nkx2-5 is a key transcription factor essential for the formation of the working myocardium, but it was generally thought to be detrimental to SAN development. However, Nkx2-5 is expressed in the developing SAN junction, suggesting a role for Nkx2-5 in SAN junction development and function. In this study, we present unambiguous evidence that SAN junction cells exhibit unique action potential configurations intermediate to those manifested by the SAN head and the surrounding atrial cells, suggesting a specific role for the junction cells in impulse generation and in SAN-atrial exit conduction. Single-cell RNA-seq analyses support this concept. Although Nkx2-5 inactivation in the SAN junction did not cause a malformed SAN at birth, the mutant mice manifested sinus node dysfunction. Thus, Nkx2-5 defines a population of pacemaker cells in the transitional zone. Despite Nkx2-5 being dispensable for SAN morphogenesis during embryogenesis, its deletion hampers atrial activation by the pacemaker.

Oxygen Vacancy-Governed Opposite Catalytic Performance for C3H6 and C3H8 Combustion: The Effect of the Pt Electronic Structure and Chemisorbed Oxygen Species.

Revealing the role of engineered surface oxygen vacancies in the catalytic degradation of volatile organic compounds (VOCs) is of importance for the development of highly efficient catalysts. However, because of various structures of VOC molecules, the role of surface oxygen vacancies in different catalytic reactions remains ambiguous. Herein, a defective Pt/TiO2-x catalyst is proposed to uncover the different catalytic mechanisms of C3H6 and C3H8 combustion via experiments and theoretical calculations. The electron transfer, originated from the oxygen vacancy, facilitates the formation of reduced Pt0 species and simultaneously interfacial chemisorbed O2, thus promoting the C3H6 combustion via efficient C═C cleavage. The reduced Pt nanoparticles facilitate the robust chemisorption of bridging dimer O22- (Pt-O-O-Ti) species. This chemisorbed oxygen inhibits the C3H8 combustion by depressing C3H8 adsorption. This work offers insights for the rational design of highly efficient catalysts for activating the C═C bond in alkene or C-H bond in alkane.

Association between socio-ecological factors and leisure time physical activity (LTPA) among older adults in Sichuan, China: a structural equation modeling analysis.

BACKGROUND: Few studies examined socio-ecological factors and leisure time physical activities (LTPA) and rarely focused on self-regulation and social capital, which might play a significant role in impacting people's physical activity behavior. This study aimed to examine the direct and indirect effects of individual level (perceived benefits, perceived barriers, and self-efficacy), interpersonal level (self-regulation), social level (social capital), and environmental level factors (perceived physical environment) on LTPA among older adults. METHODS: A cross-sectional study was conducted in 737 older adults from Sichuan, China. Structural equation modeling (SEM) analysis was used to examine the associations of individual, interpersonal, social, and environmental level factors with LTPA. RESULTS: The mean age of all participants was 71.22 (range, 60-97), and 56.1% of them were women. The SEM results showed that individual level variables (ß = 0.32, ρ < 0.001), self-regulation (ß = 0.18, ρ < 0.001) and social capital (ß = 0.14, ρ < 0.001) could all directly affect LTPA while there was no significant association of perceived physical environment with LTPA. Self-regulation served as a bridge linking social capital and LTPA. Individual level variables contributed the largest total effect (0.32) on LTPA. Self-regulation and social capital had the same total effect (0.18) on LTPA. CONCLUSIONS: Factors on three levels were all significantly associated with LTPA. Interventions that incorporate individual, interpersonal, social factors may be considered to promote LTPA in older adults. Self-regulation should receive more attention in future interventions.

Dual Activation of Molecular Oxygen and Surface Lattice Oxygen in Single Atom Cu1 /TiO2 Catalyst for CO Oxidation.

The in-depth mechanism on the simultaneous activation of O2 and surface lattice O2- on one active metallic site has not been elucidated yet. Herein, we report a strategy for the construction of abundant oxygen activation sites by rational design of Cu1 /TiO2 single atom catalysts (SACs). The charge transfer between isolated Cu and TiO2 support generates abundant CuI and 2-coordinated Olat sites in Cu1 -O-Ti hybridization structure, which facilitates the chemisorption and activation of O2 molecules. Simultaneously, the Cu1 -O-Ti induced TiO2 lattice distortion activate the adjacent surface lattice O2- , achieving the dual activation of O2 and surface lattice O2- . The Cu1 -O-Ti active site switches the CO oxidation mechanism from Eley-Rideal (80 °C) to Mars-van Krevelen route (200 °C) with the increase of reaction temperature. The dual activation of O2 and surface lattice O2- can by modulating the electron properties of SACs can boost the heterogeneous catalytic oxidation activity.

The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice.

Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre -mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre ;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis.

Shox2 regulates osteogenic differentiation and pattern formation during hard palate development in mice.

During mammalian palatogenesis, cranial neural crest-derived mesenchymal cells undergo osteogenic differentiation and form the hard palate, which is divided into palatine process of the maxilla and the palatine. However, it remains unknown whether these bony structures originate from the same cell lineage and how the hard palate is patterned at the molecular level. Using mice, here we report that deficiency in Shox2 (short stature homeobox 2), a transcriptional regulator whose expression is restricted to the anterior palatal mesenchyme, leads to a defective palatine process of the maxilla but does not affect the palatine. Shox2 overexpression in palatal mesenchyme resulted in a hyperplastic palatine process of the maxilla and a hypoplastic palatine. RNA sequencing and assay for transposase-accessible chromatin-sequencing analyses revealed that Shox2 controls the expression of pattern specification and skeletogenic genes associated with accessible chromatin in the anterior palate. This highlighted a lineage-autonomous function of Shox2 in patterning and osteogenesis of the hard palate. H3K27ac ChIP-Seq and transient transgenic enhancer assays revealed that Shox2 binds distal-acting cis-regulatory elements in an anterior palate-specific manner. Our results suggest that the palatine process of the maxilla and palatine arise from different cell lineages and differ in ossification mechanisms. Shox2 evidently controls osteogenesis of a cell lineage and contributes to the palatine process of the maxilla by interacting with distal cis-regulatory elements to regulate skeletogenic gene expression and to pattern the hard palate. Genome-wide Shox2 occupancy in the developing palate may provide a marker for identifying active anterior palate-specific gene enhancers.

Engineering the Nucleophilic Active Oxygen Species in CuTiOx for Efficient Low-Temperature Propene Combustion.

Industrialization has resulted in the rapid increase of volatile organic compound (VOC) emissions, which have caused serious issues to human health and the environment. In this study, an extensive Cu incorporating TiO2 induced nucleophilic oxygen structure was constructed in the CuTiOx catalyst, which exhibited superior low-temperature catalytic activity for C3H6 combustion. Thorough structural, surface characterization and density functional theory (DFT) calculations revealed that the Cu-O-Ti hybridization induced nucleophilic oxygen initiates C3H6 combustion by abstracting the C-H bond. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) results indicated that incorporated copper species acted as the major adsorbent site for the propene molecule. In combination of the DRIFTS and DFT results, the promotion effect of the nucleophilic O on the C-H bond abstraction and CO2 formation pathway was proposed. The surface doping induced nucleophilic oxygen as strong Brønsted basic sites for low-temperature propene combustion exemplified an efficient strategy for rational design of next-generation environmental catalysts.

Facile incorporation of DNA-templated quantum dots for sensitive electrochemical detection of the oral cancer biomarker interleukin-8.

Recent studies reveal a great value of interleukin-8 (IL-8), a pro-inflammatory cytokine, as a potent biomarker for early diagnosis of oral cancer. Herein, a new electrochemical method is proposed to detect IL-8 by facilely incorporating DNA-templated quantum dots (QDs). In principle, target IL-8 is first treated with the reducing agent tris(2-carboxyethyl)phosphine (TCEP) to yield active thiols and then captured by antibody-functionalized magnetic beads (MBs). Thereafter, via the Michael addition reaction between the active thiol and maleimide group, a maleimide-modified DNA probe is linked to the surface of MBs, which can initiate a process of rolling circle amplification. In this way, long-range DNA strands are generated on the MB surface, subsequently recruiting DNA-templated CdTe/CdS QDs (DNA-QDs) to act as electrochemical reporters. By tracing the responses of DNA-QDs, the method allows IL-8 detection in a linear range from 5 to 5000 fg/mL with a detection limit of 3.36 fg/mL. The selectivity, reproducibility, and applicability in complex serum samples are also demonstrated to be favorable, indicating that the method may have a great potential in the future. More importantly, the use of TCEP treatment in the method not only provides a facile way to incorporate DNA-QDs, avoiding the complicated and time-consuming preparation process of antibody-DNA conjugates or functional nanomaterials; but also makes the method capable of being extended to detect other protein biomarkers in view of widespread presence of disulfides, which may hold a broad potential to facilitate efficient biosensing designs.

Exogenous FGF8 signaling in osteocytes leads to mandibular hypoplasia in mice.

OBJECTIVE: Fibroblast growth factor 8 (FGF8) signaling is essential in regulating craniofacial osteogenesis. This study aims to explore the effect of altered FGF8 signaling in maxillomandibular development during embryogenesis. MATERIALS AND METHODS: Dmp1Cre ;R26RmTmG mice were generated to trace Dmp1+ cell lineage, and Dmp1Cre ;R26RFgf8 mice were generated to explore the effects of augmented FGF8 signaling in Dmp1+ cells on osteogenesis with a focus on maxillomandibular development during embryogenesis, as assessed by whole mount skeletal staining, histology, and immunostaining. Additionally, cell proliferation rate and the expression of osteogenic genes were examined. RESULTS: Osteocytes of maxillomandibular bones were found Dmp1-positive prenatally, and Fgf8 over-expression in Dmp1+ cells led to mandibular hypoplasia. While Dmp1Cre allele functions in the osteocytes of the developing mandibular bone at as early as E13.5, and enhanced cell proliferation rate is observed in the bone forming region of the mandible in Dmp1Cre ;R26RFgf8 mice at E14.5, histological examination showed that osteogenesis was initially impacted at E15.5, along with an inhibition of osteogenic differentiation markers. CONCLUSIONS: Augmented FGF8 signaling in Dmp1+ cells lead to osteogenic deficiency in the mandibular bones, resulting in mandibular hypoplasia.

A unique stylopod patterning mechanism by Shox2-controlled osteogenesis.

Vertebrate appendage patterning is programmed by Hox-TALE factor-bound regulatory elements. However, it remains unclear which cell lineages are commissioned by Hox-TALE factors to generate regional specific patterns and whether other Hox-TALE co-factors exist. In this study, we investigated the transcriptional mechanisms controlled by the Shox2 transcriptional regulator in limb patterning. Harnessing an osteogenic lineage-specific Shox2 inactivation approach we show that despite widespread Shox2 expression in multiple cell lineages, lack of the stylopod observed upon Shox2 deficiency is a specific result of Shox2 loss of function in the osteogenic lineage. ChIP-Seq revealed robust interaction of Shox2 with cis-regulatory enhancers clustering around skeletogenic genes that are also bound by Hox-TALE factors, supporting a lineage autonomous function of Shox2 in osteogenic lineage fate determination and skeleton patterning. Pbx ChIP-Seq further allowed the genome-wide identification of cis-regulatory modules exhibiting co-occupancy of Pbx, Meis and Shox2 transcriptional regulators. Integrative analysis of ChIP-Seq and RNA-Seq data and transgenic enhancer assays indicate that Shox2 patterns the stylopod as a repressor via interaction with enhancers active in the proximal limb mesenchyme and antagonizes the repressive function of TALE factors in osteogenesis.

Novel role of zonula occludens-1: A tight junction protein closely associated with the odontoblast differentiation of human dental pulp cells.

Zonula occludens-1 (ZO-1), a tight junction protein, contributes to the maintenance of the polarity of odontoblasts and junctional complex formation in odontoblast layer during tooth development. However, expression and possible role of ZO-1 in human dental pulp cells (hDPCs) during repair process remains unknown. Here, we investigated the expression of ZO-1 in hDPCs and the relationship with odontoblast differentiation. We found the processes of two adjacent cells were fused and formed junction-like structure using scanning electron microscopy. Fluorescence immunoassay and Western blot confirmed ZO-1 expression in hDPCs. Especially, ZO-1 was high expressed at the cell-cell junction sites. More interestingly, ZO-1 accumulated at the leading edge of lamellipodia in migrating cells when a scratch assay was performed. Furthermore, ZO-1 gradual increased during odontoblast differentiation and ZO-1 silencing greatly inhibited the differentiation. ZO-1 binds directly to actin filaments and RhoA/ROCK signaling mainly regulates cell cytoskeleton, thus RhoA/ROCK might play a role in regulating ZO-1. Lysophosphatidic acid (LPA) and Y-27632 were used to activate and inhibit RhoA/ROCK signaling, respectively, with or without mineralizing medium. In normal cultured hDPCs, RhoA activation increased ZO-1 expression and especially in intercellular contacts, whereas ROCK inhibition attenuated the effects induced by LPA. However, expression of ZO-1 was upregulated by Y-27632 but not significantly affected by LPA after odontoblast differentiation. Hence, ZO-1 highly expresses in cell-cell junctions and is related to odontoblast differentiation, which may contribute to dental pulp repair or even the formation of an odontoblast layer. RhoA/ROCK signaling is involved in the regulation of ZO-1.

Positive therapy of andrographolide in vocal fold leukoplakia.

PURPOSE: Vocal fold leukoplakia is a premalignant precursor of squamous cell carcinoma. Although many efforts have been contributed to therapy of this disease, none exhibits a satisfactory result. The aims of this study were to investigate the effectiveness and feasibility of andrographolide therapy in vocal fold leukoplakia and to explore the preliminary mechanism underlying. MATERIALS AND METHODS: Forty-one eligible patients were enrolled in the study. The patients were treated for 10-minute exposures of 5 ml (25mg/ml) andrographolide injection aerosols twice a day, and 2 weeks was considered as one treatment course. Electronic laryngoscope was used to observe the condition of vocal fold leukoplakia during the treatment. Every patient received one or two treatment courses, and the follow-up was carried out for 12 months. Toxic reactions of treatments were evaluated on the basis of the standards of the United States MD Anderson Cancer Center. Moreover, laryngeal carcinoma cell line Hep2 was applied to explore the mechanism of effect of andrographolide. Anti-proliferative effect on Hep2, cell nuclear morphology, express of mitogen-activated protein kinases (MAPK) and pro-apoptotic protein were detected after andrographolide treatment. RESULTS: We found that andrographolide exhibited significant curative effects on treatments, which were accompanied by thinning of the lesion of leukoplakia, reduction in the whitish surface area, and return of pink or red epithelium. A complete response up to 85% was observed, and no toxic side effect events occurred during the study. No patient with a complete response had a recurrence in the follow-up. Moreover, cellular experiments in Hep2 indicated that andrographolide activated MAPK pathway and caspase cascade, and finally induced apoptosis in laryngeal carcinoma cell. CONCLUSIONS: The advantages of andrographolide are connected with minimally invasive and localized character of the treatment and no damage of collagenous tissue structures, which are more convenient and less painful for patients. These results suggest that andrographolide treatment is a viable strategy for curing vocal fold leukoplakia.

Heterogeneity of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells in mice.

OBJECTIVES: This study aimed to explore the heterogeneity and gene ontology of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells (CNCs) in mice. METHODS: The embryos of Wnt1-Cre;R26RmTmG and Pax2-Cre;R26RmTmG at embryonic day (E)8.0-E9.25 were collected for histological observation. We performed immunostaining to compare green fluorescent protein (GFP)-positive CNCs in Pax2-Cre;R26RAi9 and Wnt1-Cre;R26RAi9 mice at E15.5. Single-cell RNA sequencing (scRNA-seq) was used to analyze the first branchial arch GFP-positive CNCs from Wnt1-Cre;R26RmTmG and Pax2-cre;R26RmTmGmice at E10.5. Real time fluorescence quantitative polymerase chain reaction (q-PCR) was performed to validate the differential genes. RESULTS: Wnt1-Cre-marked and Pax2-Cre-marked CNCs migrated from the neural plateto first and second branchial arches and to the first branchial arch, respectively, at E8.0. Although Wnt1-Cre-marked and Pax2-Cre-marked CNCs were found mostly in cranial-facial tissues, the former had higher expression in palate and tongue. The results of scRNA-seq showed that Pax2-Cre-marked CNCs specifically contributed to osteoblast differentiation and ossification, while Wnt1-Cre-marked CNCs participated in limb development, cell migration, and ossification. The q-PCR data also confirmed the results of gene ontology analysis. CONCLUSIONS: Pax2-Cre mice are perfect experimental animal models for research on first branchial arch CNCs and derivatives in osteoblast differentiation and ossification.

Increased incidence risks of cardiovascular disease among cancer patients: Evidence from a population-based cohort study in China.

BACKGROUND: Cardiovascular disease (CVD) is becoming a major concern among cancer patients, leading to the development of a new field named cardio-oncology. However, previous studies were mainly based on the western population and focused on CVD mortality. Evidence from the Chinese population is limited. Furthermore, few studies investigated the incidence risks of CVD among cancer patients. METHODS: 85,787 eligible cancer patients were included from Hangzhou city, China. Age-standardized standard incidence ratio (SIR) was used to reflect the incidence risks of CVD among cancer patients as compared with the standard population, which was defined as all residents in Hangzhou city during the same period. RESULTS: After three years of follow-up, cancer patients showed elevated incidence risks of CVD (SIR = 1.41, 95%CI: 1.35-1.47) as compared with the standard population. The elevated risks of CVD were highest in the first year after cancer diagnosis (SIR = 1.68, 95%CI: 1.58-1.78), then followed by the second (SIR = 1.21, 95%CI: 1.11-1.31) and the third (SIR = 1.18, 95%CI: 1.07-1.29) year. These results were consistent in males and females. Furthermore, different risks of CVD were observed among different cancer sites. Patients with pancreatic cancer showed the highest risks of CVD, then followed by liver cancer, lung cancer, kidney cancer, gastric cancer, bladder cancer, prostate cancer, and colorectal cancer. CONCLUSIONS: Cancer patients have increased incidence risks of CVD, especially in the first year after cancer diagnosis. The increased risks of CVD vary by different cancer sites. Our findings highlight the importance of paying close attention to the CVD risks among cancer patients.

Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer.

Background: Ovarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains a significant challenge in achieving optimal tumor control. However, the exploration of intratumoral heterogeneity of malignant epithelial cells and the ovarian cancer tumor microenvironment is still limited, hindering our comprehensive understanding of the disease. Materials and methods: Utilizing single-cell RNA sequencing (scRNA-seq), we comprehensively investigated the cellular composition across six ovarian cancer patients with omental metastasis. Our focus centered on analysis of the malignant epithelial cells. Employing CytoTRACE and slingshot pseudotime analyses, we identified critical subpopulations and explored associated transcription factors (TFs) influencing ovarian cancer progression. Furthermore, by integrating clinical factors from a large cohort of bulk RNA sequencing data, we have established a novel prognostic model to investigate the impact of the tumor immune microenvironment on ovarian cancer patients. Furthermore, we have investigated the condition of immunological exhaustion. Results: Our study identified a distinct and highly proliferative subgroup of malignant epithelial cells, known as C2 TOP2A+ TCs. This subgroup primarily consisted of patients who hadn't received neoadjuvant chemotherapy. Ovarian cancer patients with elevated TOP2A expression exhibited heightened sensitivity to neoadjuvant chemotherapy (NACT). Moreover, the transcription factor MYBL2 in this subgroup played a critical role in ovarian cancer development. Additionally, we developed an independent prognostic indicator, the TOP2A TCs Risk Score (TTRS), which revealed a correlation between the High TTRS Group and unfavorable outcomes. Furthermore, immune infiltration and drug sensitivity analyses demonstrated increased responsiveness to Paclitaxel, Cisplatin, and Gemcitabine in the Low TTRS Group. Conclusion: This research deepens our understanding of malignant epithelial cells in ovarian cancer and enhances our knowledge of the ovarian cancer immune microenvironment and immune exhaustion. We have revealed the heightened susceptibility of the C2 TOP2A+ TCs subgroup to neoadjuvant chemotherapy and emphasized the role of MYBL2 within the C2 subgroup in promoting the occurrence and progression of ovarian cancer. These insights provide valuable guidance for the management of ovarian cancer treatment.

Recent Advances on Antimicrobial Peptides from Milk: Molecular Properties, Mechanisms, and Applications.

Traditional antibiotics are facing a tremendous challenge due to increased antimicrobial resistance; hence, there is an urgent need to find novel antibiotic alternatives. Milk protein-derived antimicrobial peptides (AMPs) are currently attracting substantial attention considering that they showcase an extensive spectrum of antimicrobial activities, with slower development of antimicrobial resistance and safety of raw materials. This review summarizes the molecular properties, and activity mechanisms and highlights the applications and limitations of AMPs derived from milk proteins comprehensively. Also the analytical technologies, especially bioinformatics methodologies, applied in the process of screening, identification, and mechanism illustration of AMPs were underlined. This review will give some ideas for further research and broadening of the applications of milk protein-derived AMPs in the food field.

Association between sleep duration, suicidal ideation, suicidal attempt and suicidal behavior among Chinese adolescents.

BACKGROUND: A relatively small number of studies have researched the relationship between sleep duration and suicidal ideation, attempts, and behavior. This research aims to investigate the link between sleep duration and suicide in Chinese adolescents, and to examine the role of depression as a mediating factor. METHOD: Data were collected from 3315 students using a multi-stage random cluster sampling method and self-administered questionnaires. The study applied logistic regression to investigate the relationship between sleep duration and various forms of suicidal behavior, and mediation analysis to understand how depression might influence this relationship. RESULTS: The average sleep duration among the adolescents was 7.25 h (±0.20), with 59.67 % reporting insufficient sleep. The logistic regression analysis showed that longer sleep duration is linked with lower risks of suicidal ideation (OR: 0.753, 95%CI: 0.696 to 0.814), suicidal attempts (OR: 0.830, 95%CI: 0.748 to 0.922), and suicidal behavior (OR: 0.841, 95%CI: 0.713 to 0.992). Analysis using restricted cubic spline plots indicated the connection between sleep duration and these suicidal factors was not linear. The study found that depression plays a partial mediating role between sleep duration and suicidal ideation, with an effect of 52.29 %. LIMITATIONS: The cross-sectional study design could not prove causation. CONCLUSIONS: There is a clear non-linear association between sleep duration and suicidal tendencies in adolescents, with depression acting as a mediator. This suggests that future research could focus on sleep and mood management as ways to address suicide risk in this age group.

Air pollution and cancer daily mortality in Hangzhou, China: an ecological research.

BACKGROUND: Long-term exposure to air pollution has been linked to cancer incidence. However, the evidence is limited regarding the effect of short-term exposure to air pollution on cancer mortality. OBJECTIVES: This study aimed to investigate associations between short-term exposure to air pollutants (sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <10 mm (PM10) and PM2.5) and cancer daily mortality. METHODS: This study used air quality, meteorological and daily cancer death data from 2014 to 2019 in Hangzhou, China. Generalised additive models (GAM) with quasi-Poisson regression were used to analyse the associations between air pollutants and cancer mortality with adjustment for confounding factors including time trends, day of week, temperature and humidity. Then, we conducted stratified analyses by sex, age, season and education. In addition, stratified analyses of age, season and education were performed within each sex to determine whether sex difference was modified by such factors. RESULTS: After adjusting for potential confounders, the GAM results indicated a statistically significant relationship between increased cancer mortality and elevated air pollution concentrations, but only in the female population. For every 10 µg/m3 rise in pollutant concentration, the increased risk of cancer death in females was 6.82% (95% CI 3.63% to 10.10%) for SO2 on lag 03, and 2.02% (95% CI 1.12% to 2.93%) for NO2 on lag 01 and 0.89% (95% CI 0.46% to 1.33%) for PM10 on lag 03 and 1.29% (95% CI 0.64% to 1.95%) for PM2.5 on lag 03. However, no statistically significant association was found among males. Moreover, the differences in effect sizes between males and females were more pronounced during the cold season, among the elderly and among subjects with low levels of education. CONCLUSIONS: Increased cancer mortality was only observed in females with rising concentrations of air pollutants. Further research is required to confirm this sex difference. Advocate for the reduction of air pollutant emissions to protect vulnerable groups.