Cornuside alleviates psoriasis-like skin lesions in mice by relieving inflammatory effects.

Psoriasis is a chronic inflammatory skin disease substantially affecting the quality of life, with no complete cure owing to its complex pathogenesis. Cornuside, a major bioactive compound present in Cornus officinalis Sieb. et Zucc., which is a well-known traditional Chinese medicine with a variety of biological and pharmacological activities, such as anti-apoptotic, antioxidant, and anti-inflammatory properties. However, its effects on psoriasis remain unclear. Our preliminary analysis of network pharmacology showed that cornuside may be involved in psoriasis by regulating the inflammatory response and IL-17 signaling pathway. Thus, we investigated the protective role and mechanism of cornuside in the pathogenesis of psoriasis in an imiquimod (IMQ)-induced psoriasis mouse model. In-vivo experiments demonstrated that cornuside-treated mice had reduced skin erythema, scales, thickness, and inflammatory infiltration. The Psoriasis Area Severity Index score was significantly lower than that of the IMQ group. Flow cytometry analysis indicated that cornuside effectively inhibited Th1- and Th17-cell infiltration and promoted aggregation of Th2 cells in skin tissues. Cornuside also inhibited the infiltration of macrophages to the skin. Furthermore, in-vitro experiments indicated that cornuside also decreased the polarization of M1 macrophages and reduced the levels of associated cytokines. Western blotting demonstrated that cornuside suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular receptor kinase (ERK) in bone marrow-derived macrophages. Our findings indicate that cornuside has a protective effect against IMQ-induced psoriasis by inhibiting M1 macrophage polarization through the ERK and JNK signaling pathways and modulating the infiltration of immune cells as well as the expression of inflammatory factors.

Hypoxia inhibits ferritinophagy-mediated ferroptosis in esophageal squamous cell carcinoma via the USP2-NCOA4 axis.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive system. Hypoxia is a crucial player in tumor ferroptosis resistance. However, the molecular mechanism of hypoxia-mediated ferroptosis resistance in ESCC remains unclear. Here, USP2 expression was decreased in ESCC cell lines subjected to hypoxia treatment and was lowly expressed in clinical ESCC specimens. Ubiquitin-specific protease 2 (USP2) depletion facilitated cell growth, which was blocked in USP2-overexpressing cells. Moreover, USP2 silencing enhanced the iron ion concentration and lipid peroxidation accumulation as well as suppressed ferroptosis, while upregulating USP2 promoted ferroptotic cell death in ESCC cells. Furthermore, knockout of USP2 in ESCC models discloses the essential role of USP2 in promoting ESCC tumorigenesis and inhibiting ferroptosis. In contrast, overexpression of USP2 contributes to antitumor effect and ferroptosis events in vivo. Specifically, USP2 stably bound to and suppressed the degradation of nuclear receptor coactivator 4 (NCOA4) by eliminating the Lys48-linked chain, which in turn triggered ferritinophagy and ferroptosis in ESCC cells. Our findings suggest that USP2 plays a crucial role in iron metabolism and ferroptosis and that the USP2/NCOA4 axis is a promising therapeutic target for the management of ESCC.

Metallofullerenol alleviates alcoholic liver damage via ROS clearance under static magnetic and electric fields.

Alcoholic liver disease (ALD) is a common chronic redox disease caused by increased alcohol consumption. Abstinence is a major challenge for people with alcohol dependence, and approved drugs have limited efficacy. Therefore, this study aimed to explore a new treatment strategy for ALD using ferroferric oxide endohedral fullerenol (Fe3O4@C60(OH)n) in combination with static magnetic and electric fields (sBE). The primary hepatocytes of 8-9-week-old female BALB/c mice were used to evaluate the efficacy of the proposed combination treatment. A mouse chronic binge ethanol feeding model was established to determine the alleviatory effect of Fe3O4@C60(OH)n on liver injury under sBE exposure. Furthermore, the ability of Fe3O4@C60(OH)n to eliminate •OH was evaluated. Alcohol-induced hepatocyte and mitochondrial damage were reversed in vitro. Additionally, the combination therapy reduced liver damage, alleviated oxidative stress by improving antioxidant levels, and effectively inhibited liver lipid accumulation in animal experiments. Here, we used a combination of magnetic derivatives of fullerenol and sBE to further improve the ROS clearance rate, thereby alleviating ALD. The developed combination treatment may effectively improve alcohol-induced liver damage and maintain redox balance without apparent toxicity, thereby enhancing therapy aimed at ALD and other redox diseases.

Identification of shared molecular mechanisms and diagnostic biomarkers between heart failure and idiopathic pulmonary fibrosis.

Background: Heart failure (HF) and idiopathic pulmonary fibrosis (IPF) are global public health concerns. The relationship between HF and IPF is widely acknowledged. However, the interaction mechanisms between these two diseases remain unclear, and early diagnosis is particularly difficult. Through the integration of bioinformatics and machine learning, our work aims to investigate common gene features, putative molecular causes, and prospective diagnostic indicators of IPF and HF. Methods: The Gene Expression Omnibus (GEO) database provided the RNA-seq datasets for HF and IPF. Utilizing a weighted gene co-expression network analysis (WGCNA), possible genes linked to HF and IPF were found. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were then employed to analyze the genes that were shared by HF and IPF. Using the cytoHubba and iRegulon algorithms, a competitive endogenous RNA (ceRNA) network was built based on seven basic diagnostic indicators. Additionally, hub genes were identified using machine learning approaches. External datasets were used to validate the findings. Lastly, the association between the number of immune cells in tissues and the discovered genes was estimated using the CIBERSORT method. Results: In total, 63 shared genes were identified between HF- and IPF-related modules using WGCNA. Extracellular matrix (ECM)/structure organization, ECM-receptor interactions, focal, and protein digestion and absorption, were shown to be the most enrichment categories in GO and KEGG enrichment analysis of common genes. Furthermore, a total of seven fundamental genes, including COL1A1, COL3A1, THBS2, CCND1, ASPN, FAP, and S100A12, were recognized as pivotal genes implicated in the shared pathophysiological pathways of HF and IPF, and TCF12 may be the most important regulatory transcription factor. Two characteristic molecules, CCND1 and NAP1L3, were selected as potential diagnostic markers for HF and IPF, respectively, using a support vector machine-recursive feature elimination (SVM-RFE) model. Furthermore, the development of diseases and diagnostic markers may be associated with immune cells at varying degrees. Conclusions: This study demonstrated that ECM/structure organisation, ECM-receptor interaction, focal adhesion, and protein digestion and absorption, are common pathogeneses of IPF and HF. Additionally, CCND1 and NAP1L3 were identified as potential diagnostic biomarkers for both HF and IPF. The results of our study contribute to the comprehension of the co-pathogenesis of HF and IPF at the genetic level and offer potential biological indicators for the early detection of both conditions.

Nanoplatform based on carbon nanoparticles loaded with doxorubicin enhances apoptosis by generating reactive oxygen species for effective cancer therapy.

At present, due to its wide application and relatively low cost, chemotherapy remains a clinically important cancer treatment option; however, a number of chemotherapeutic drugs have important limitations, such as lack of specificity, high toxicity and side effects, and multi-drug resistance. The emergence of nanocarriers has removed numerous clinical application limitations of certain antitumor chemotherapy drugs and has been widely used in the treatment of tumors with nanodrugs. The present study used carbon nanoparticles (CNPs) as a nanocarrier for doxorubicin (DOX) to form the novel nanomedicine delivery system (CNPs@DOX)was demonstrated by UV-vis and fluorescence spectrophotometry, ζ potential and TEM characterization experiments. The results confirmed the successful preparation of CNPs@DOX nanoparticles with a particle size of 96±17 nm, a wide range of absorption and a negatively charged surface. Furthermore, CNPs@DOX produced more reactive oxygen species and induced apoptosis, and thus exhibited higher cytotoxicity than DOX, which is a small molecule anticancer drug without a nanocarrier delivery system.. The present study provides a strategy for the treatment of tumors with nanomedicine.

Preperitoneal pelvic balloon tamponade-an effective intervention to control pelvic injury hemorrhage in a swine model.

Objective: This study aimed to estimate the effects of the volume of preperitoneal balloon (PPB) on arterial and venous hemorrhage in a swine pelvic fracture model. Methods: Twenty-four swine were randomized into 0-mL, 500-mL, 800-mL, and 1000-mL intra-hematoma PPB groups. They were subjected to open-book pelvic fracture and reproducible injuries in the external iliac artery and vein. The pelvic binder and IH-PPBs with different volumes of fluid were applied to control the active hemorrhage after arterial and venous injuries. The survival time and rate during 60-min observation and digital subtraction angiography (DSA) images were the primary endpoints in this study. Secondary endpoints included survival rate within 70 min, peritoneal pressure, hemodynamics, blood loss, infusion fluid, blood pH, and lactate concentration. Results: Our results indicated that the 800-mL and 1000-mL groups had a higher survival rate (0%, 50%, 100% and 100% for 0, 500, 800, and 1000-mL groups respectively; p < 0.0001) and longer survival time (13.83 ± 2.64, 24.50 ± 6.29, 55.00 ± 6.33, and 60.00 ± 0.00 min for 0, 500, 800, and 1,000 groups respectively; p < 0.0005) than the 0-mL or 500-mL groups during the 60 min observation. Contrastingly, survival rate and time were comparable between 800-mL and 1000-mL groups during the 60-min observation. The IH-PPB volume was associated with an increase in the pressure of the balloon and the preperitoneal pressure but had no effect on the bladder pressure. Lastly, the 1000-mL group had a higher mean arterial pressure and systemic vascular resistance than the 800-mL group. Conclusion: IH-PPB volume-dependently controls vascular bleeding after pelvic fracture in the swine model. IH-PPB with a volume of 800 mL and 1000 mL efficiently managed pelvic fracture-associated arterial and venous hemorrhage and enhanced survival time and rate in the swine model without evidences of visceral injury.

A chronic stress-induced microbiome perturbation, highly enriched in Ruminococcaceae_UCG-014, promotes colorectal cancer growth and metastasis.

Purpose: Mounting evidence indicates that psychological stress adversely affects cancer progression including tumor growth and metastasis. The aim of this study was to investigate the role of chronic stress-induced microbiome perturbation in colorectal cancer (CRC) progression. Methods: Chronic restraint stress (CRS) was used to establish the chronic stress mouse model, behavioral tests were used for the CRS model evaluation. Subcutaneous xenograft model and lung metastasis model were established to investigate the growth and metastasis of CRC promoted by CRS exposure. 16S rRNA gene sequencing and liquid chromatograph-mass spectrometer (LC-MS) were applied to observe the effects of CRS exposure on the alteration of the gut microbiome and microbial metabolites. Bioinformatics analysis and correlation analyses were applied to analyse the changes in the frequency of body mass, tumor volume, inflammatory factors, neuroendocrine hormones and metabolites of the gut microbiota. Results: In this study, we identifed that CRS exposure model was appropriately constructed by achieving expected increases in disease activity index and enhanced depressive-like behaviors. CRS exposure can promote growth and metastasis of CRC. Besides, the data indicated that CRS exposure not only increased the neuro- and immune-inflammation, but also weakened the gut mucosal immunological function. The 16s rRNA gene sequencing data showed that CRS exposure increased the abundance of g_Ruminococcaceae_UCG_014. Furthermore, the LC-MS data indicated that with only 2 exceptions of carpaine and DG (15:0/20:4(5Z,8Z,11Z,14Z)/0:0), the majority of these 24 metabolites were less abundant in CRS-exposed mice. Bioinformatics analysis and correlation analyses indicated that only Ruminoscoccaceae-UCG-014 was significantly associated with inflammation (IL-6), neurotransmission (5-HT), and microbial metabolism (PS). Conclusion: CRS exposure altered diversity, composition and metabolites of the gut microbiome, with Ruminococcaceae_UCG-014 perturbation consistently correlated to inflammatory responses, suggesting a particular role of this bacterial genus in CRC growth and metastasis.

Emerging concern on air pollution and health: Trade-off between air pollution exposure and physical activity.

Air pollution is a major contributor to the global disease burden, especially affecting respiratory and cardiovascular health. However, physical activity is associated with improved lung function, a slower decline in lung function, and lower mortality. The public is more likely to be exposed to air pollution during outdoor physical activity. However, studies on how long-term and short-term exposure to air pollution interacts with physical activity yield inconsistent results, and the thresholds for air pollution and physical activity remain unclear. Thus, more studies are needed to provide sufficient evidence to guide the public to safely engage in outdoor physical activity when exposed to air pollution.

circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA.

Circular RNAs (circRNAs) play crucial biological functions in various tumors, including bladder cancer (BCa). However, the roles and underlying molecular mechanisms of circRNAs in the malignant proliferation of BCa are yet unknown. CircKDM1A was observed to be downregulated in BCa tissues and cells. Knockdown of circKDM1A promoted the proliferation of BCa cells and bladder xenograft growth, while the overexpression of circKDM1A exerts the opposite effect. The dual-luciferase reporter assay revealed that circKDM1A was directly bound to miR-889-3p, acting as its molecular sponge to downregulate CPEB3. In turn, the CPEB3 was bound to the CPE signal in p53 mRNA 3'UTR to stabilize its expression. Thus, circKDM1A-mediated CPEB3 downregulation inhibits the stability of p53 mRNA and promotes BCa malignant progression. In conclusion, circKDM1A functions as a tumor suppressor in the malignant proliferation of BCa via the miR-889-3p/CPEB3/p53 axis. CircKDM1A may be a potential prognostic biomarker and therapeutic target of BCa.

Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia.

Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.

Dry Reforming of Methane over Pyrochlore-Type La2Ce2O7-Supported Ni Catalyst: Effect of Particle Size of Support.

The properties of supports (such as oxygen vacancies, oxygen species properties, etc.) significantly impact the anti-carbon ability due to their promotional effect on the activation of CO2 in dry reforming of methane (DRM). Herein, pyrochlore-type La2Ce2O7 compounds prepared using co-precipitation (CP), glycine nitrate combustion (GNC) and sol-gel (S-G) methods, which have highly thermal stability and unique oxygen mobility, are applied as supports to prepare Ni-based catalysts for DRM. The effect of the calcining temperature (500, 600 and 700 °C) on La2Ce2O7(CP) has also been investigated. Based on multi-technique characterizations, it is found that the synthesis method and calcination temperature can influence the particle size of the La2Ce2O7 support. Changes in particle size strongly modulate the pore volume, specific surface area and numbers of surface oxygen vacancies of the La2Ce2O7 support. As a result, the distribution of supported Ni components is affected due to the different metal-support interaction, thereby altering the activity of the catalysts for cracking CH4. Moreover, the supports' abilities to adsorb and activate CO2 are also adjusted accordingly, accelerating the removal of the carbon deposited on the catalysts. Finally, La2Ce2O7(CP 600) with an appropriate particle size exhibits the best catalytic activity and stability in DRM.

Nasal oxidative stress mediating the effects of colder temperature exposure on pediatric asthma symptoms.

BACKGROUND: Colder temperature exposure is a known trigger for pediatric asthma exacerbation. The induction of oxidative stress is a known pathophysiologic pathway for asthma exacerbation. However, the role of oxidative stress in linking colder temperature exposure and worsened pediatric asthma symptoms is poorly understood. METHODS: In a panel study involving 43 children with asthma, aged 5-13 years old, each child was visited 4 times with a 2-week interval. At each visit, nasal fluid, urine, and saliva samples were obtained and measured for biomarkers of oxidative stress in the nasal cavity (nasal malondialdehyde [MDA]), the circulatory system (urinary MDA), and the oral cavity (salivary MDA). Childhood Asthma-Control Test (CACT) was used to assess asthma symptoms. RESULTS: When ambient daily-average temperature ranged from 7 to 18 °C, a 2 °C decrement in personal temperature exposures were significantly associated with higher nasal MDA and urinary MDA concentrations by 47-77% and 6-14%, respectively. We estimated that, of the decrease in child-reported CACT scores (indicating worsened asthma symptoms and asthma control) associated with colder temperature exposure, 14-57% were mediated by nasal MDA. CONCLUSION: These results suggest a plausible pathway that colder temperature exposure worsens pediatric asthma symptoms partly via inducing nasal oxidative stress. IMPACT: The role of oxidative stress in linking colder temperature exposure and worsened asthma symptoms is still poorly understood. Lower temperature exposure in a colder season was associated with higher nasal and systemic oxidative stress in children with asthma. Nasal MDA, a biomarker of nasal oxidative stress, mediated the associations between colder temperature exposures and pediatric asthma symptoms. The results firstly suggest a plausible pathway that colder temperature exposure worsens pediatric asthma symptoms partly via inducing oxidative stress in the nasal cavity.

Bi-directional association between outdoor or social activities and cognitive function: do the PM2.5 exposure catalyze the detrimental inactivity-poor cognition cycle?

BACKGROUND: Previous research has shown that lack of leisure activities, either outdoor or social activities, impedes cognitive function. However, the interrelationship between poor cognition and deficient activities is understudied. In addition, whether exposure to air pollution, such as PM2.5, can accelerate the detrimental 'inactivity-poor cognition' cycle, is worthy of investigation. METHODS: We used data from the 2008, 2011, 2014, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We assessed the frequency of outdoor or social activities at each wave. The cognitive function was examined using a China-Modified Mini-mental State Examination. We estimated the residential exposure to fine particular matter (PM2.5) via a satellite-based model. We applied cross-lagged panel (CLP) model to examine the bi-directional relationship between outdoor or social activities and cognitive function. We then examined the effect of PM2.5 exposure with sequent cognitive function and activities using generalized estimation equation (GEE) model. FINDINGS: Overall, we observed significant bi-directional associations between outdoor or social activities and cognitive function. Participants with better cognitive function in the last wave were more likely to engage in outdoor or social activities in the following wave (outdoor activities: ß = 0.37, 95% CI [0.27,0.48], P < 0.01; social activities: ß = 0.05, 95% CI [0.02,0.09] P < 0.01). Meanwhile, higher engagement in outdoor or social activities in the last wave was associated with more favorable cognitive function in the following wave (outdoor activities: ß = 0.06, 95% CI [0.03,0.09], P < 0.01; social activities: ß = 0.10, 95% CI [0.03,0.18], P < 0.01). Notably, an increase in PM2.5 exposure during the preceding year was significantly associated with a declining cognitive function (ß = -0.05, 95% CI [-0.08,-0.03], P < 0.01), outdoor activities (ß = -0.02, 95% CI [-0.04, -0.01], P < 0.01) and social activities (ß = -0.02, 95% CI [-0.02, -0.01], P < 0.01) in the current year; the lagged effects of the PM2.5 exposure in the past year of the last wave on activities and cognitive function of the following wave were also observed. INTERPRETATION: Our findings not only indicate the bi-directional links between the frequency of outdoor or social activities and cognitive function, but also report that PM2.5 exposure plays a role in catalyzing the detrimental inactivity-poor cognition cycle. Future research should investigate whether the policy-driven interventions, such as clean air policies, can break the unfavorable activity-cognition cycle, and thereby promoting health from the dual gains in leisure activities and cognition.

Development of a Highly Efficient CRISPR/Cas9-Mediated Herpesvirus of Turkey-Based Vaccine against Novel Variant Infectious Bursal Disease Virus.

Infectious bursal disease (IBD), caused by IBD virus (IBDV), is an extremely contagious immunosuppressive disease that causes major losses for the poultry industry worldwide. Recently, the novel variant IBDV (G2d) has been highly prevalent in Korea, but the current vaccines against this very virulent IBDV have limited efficacy against this novel variant. To develop a vaccine against this variant IBDV, a recombinant virus designated rHVT-VP2 was constructed by inserting the IBDV (G2d) VP2 gene into herpesvirus of turkeys (HVT) using CRISPR/Cas9 gene-editing technology. The PCR and sequencing results obtained showed that the recombinant virus rHVT-VP2 was successfully constructed. Vaccination with rHVT-VP2 generated IBDV-specific antibodies in specific pathogen-free chickens starting from 2 weeks post-immunization. Seven days after the challenge, the autopsy results showed that the bursa atrophy rates of the rHVT-VP2, HVT, vaccine A, and positive control groups were 0%, 100%, 60%, and 100%, respectively, and the BBIX values were 1.07 ± 0.22, 0.27 ± 0.05, 0.64 ± 0.33, and 0.32 ± 0.06, respectively. These results indicate that rHVT-VP2 can provide 100% protection against a challenge with the IBDV (G2d), whereas vaccine A only provides partial protection. In conclusion, vaccination with the recombinant virus rHVT-VP2 can provide chickens with effective protection against variant IBDV (G2d).

Evaluation of post-dilatation on longitudinal stent deformation and postprocedural stent malapposition in the left main artery by optical coherence tomography (OCT): an in vitro study.

BACKGROUND: The diameter of the ostial and proximal left main coronary artery can be greater than 5.0 mm. However, the diameters of the mostly available coronary drug-eluting stents (DESs) are ≤ 4.0 mm. Whether high-pressure dilatation can increase the diameter of stents from 4.0 to 5.0 mm and whether post-dilatation leads to longitudinal stent deformation (LSD) of 4.0-mm-diameter stents have rarely been studied. Therefore, this study aims to evaluate LSD and stent malapposition of six types of commercially available 4.0-mm-diameter stents in China in a 5.0-mm-diameter artificial blood vessel model by optical coherence tomography (OCT) in vitro. METHODS: The left main coronary artery was simulated by a truncated cone-shaped silicone tube. The internal diameters were 4.0 mm at one end of the silicone tube and 5.0 mm at the other end. Six different types of coronary stents widely used in China were selected for this study. Each stent was respectively implanted into the simulated blood vessel and dilated to a diameter of 4.2 mm according to the stent-balloon pressure compliance table. The stents were subjected to post-dilatation with a 5.0 × 15-mm noncompliant balloon. The LSD ratio of the longitudinal axis of each stent and stent malapposition were measured through OCT, and any fractures of the stents were determined. RESULTS: None of the six types of stents fractured following post-dilatation. The longitudinal axes of the BuMA and Excrossal stents were slightly shortened, while the other stents were elongated after high-pressure post-dilatation. All stents expanded to a diameter of 5.0 mm without incomplete stent apposition, except for the Nano Plus stent, which remained malapposed after high-pressure post-dilatation. CONCLUSION: All 4.0-mm-diameter stents can be expanded to a diameter of 5.0 mm by noncompliant balloon post-dilatation without stent strut fracture. Most stents were found to be well apposed after high-pressure post-dilatation. However, LSD was observed after post-balloon dilatation. Stent malapposition might be positively correlated with the percentage change in stent length.

Humanistic Health Management and Cancer: Associations of Psychology, Nutrition, and Exercise with Cancer Progression and Pathogenesis.

The incidence rate of cancer is increasing year by year due to the aging of the population, unhealthy living, and eating habits. At present, surgery and medication are still the main treatments for cancer, without paying attention to the impact of individual differences in health management on cancer. However, increasing evidence suggests that individual psychological status, dietary habits, and exercise frequency are closely related to the risk and prognosis of cancer. The reminder to humanity is that the medical concept of the unified treatment plan is insufficient in cancer treatment, and a personalized treatment plan may become a breakthrough point. On this basis, the concept of "Humanistic Health Management" (HHM) is proposed. This concept is a healthcare plan that focuses on self-health management, providing an accurate and comprehensive evaluation of individual lifestyle habits, psychology, and health status, and developing personalized and targeted comprehensive cancer prevention and treatment plans. This review will provide a detailed explanation of the relationship between psychological status, dietary, and exercise habits, and the regulatory mechanisms of cancer. Intended to emphasize the importance of HHM concept in cancer prevention and better prognostic efficacy, providing new ideas for the new generation of cancer treatment.

Susceptibility of hypertensive individuals to acute blood pressure increases in response to personal-level environmental temperature decrease.

BACKGROUND: Environmental temperature is negatively associated with blood pressure (BP), and hypertension may exacerbate this association. The aim of this study is to investigate whether hypertensive individuals are more susceptible to acute BP increases following temperature decrease than non-hypertensive individuals. METHODS: The study panel consisted of 126 hypertensive and 125 non-hypertensive (n = 251) elderly participants who completed 940 clinical visits during the winter of 2016 and summer of 2017 in Beijing, China. Personal-level environmental temperature (PET) was continuously monitored for each participant with a portable sensor platform. We associated systolic BP (SBP) and diastolic BP (DBP) with the average PET over 24 h before clinical visits using linear mixed-effects models and explored hourly lag patterns for the associations using distributed lag models. RESULTS: We found that per 1 °C decrease in PET, hypertensive individuals showed an average (95 % confidence interval) increase of 0.96 (0.72, 1.19) and 0.28 (0.13, 0.42) mmHg for SBP and DBP, respectively; and non-hypertensive participants showed significantly smaller increases of 0.28 (0.03, 0.53) mmHg SBP and 0.14 (-0.01, 0.30) mmHg DBP. A lag pattern analysis showed that for hypertensive individuals, the increases in SBP and DBP were greatest following lag 1 h PET decrease and gradually attenuated up to lag 10 h exposure. No significant BP change was observed in non-hypertensive individuals associated with lag 1-24 h PET exposure. The enhanced increase in PET-associated BP in hypertensive participants (i.e., susceptibility) was more significant in winter than in summer. CONCLUSIONS: We found that a decrease in environmental temperature was associated with acute BP increases and these associations diminished over time, disappearing after approximately 10 hours. This implies that any intervention measures to prevent BP increases due to temperature drop should be implemented as soon as possible. Such timely interventions are particularly needed for hypertensive individuals especially during the cold season due to their increased susceptibility.

Protection of Chickens against H9N2 Avian Influenza Isolates with a Live Vector Vaccine Expressing Influenza Hemagglutinin Gene Derived from Y280 Avian Influenza Virus.

Since the outbreak of the H9N2/Y439 avian influenza virus in 1996, the Korean poultry industry has incurred severe economic losses. A novel possibly zoonotic H9N2 virus from the Y280-like lineage (H9N2/Y280) has been prevalent in Korea since June 2020, posing a threat to the poultry sector. Rapid mutation of influenza viruses urges the development of effective vaccines against newly generated strains. Thus, we engineered a recombinant virus rHVT/Y280 to combat H9N2/Y280. We integrated the hemagglutinin (HA) gene of the H9N2/Y280 strain into the US2 region of the herpesvirus of turkeys (HVT) Fc126 vaccine strain, utilizing CRISPR/Cas9 gene-editing technology. The successful construction of rHVT/Y280 was confirmed by polymerase chain reaction and sequencing, followed by efficacy evaluation. Four-day-old specific pathogen-free chickens received the rHVT/Y280 vaccine and were challenged with the H9N2/Y280 strain A21-MRA-003 at 3 weeks post-vaccination. In 5 days, there were no gross lesions among the vaccinated chickens. The rHVT/Y280 vaccine induced strong humoral immunity and markedly reduced virus shedding, achieving 100% inhibition of virus recovery in the cecal tonsil and significantly lowering tissue viral load. Thus, HVT vector vaccines expressing HA can be used for protecting poultry against H9N2/Y280. The induction of humoral immunity by live vaccines is vital in such cases. In summary, the recombinant virus rHVT/Y280 is a promising vaccine candidate for the protection of chickens against the H9N2/Y280.

Suppression of A-to-I RNA-editing enzyme ADAR1 sensitizes hepatocellular carcinoma cells to oxidative stress through regulating Keap1/Nrf2 pathway.

BACKGROUND: A-to-I RNA editing is an abundant post-transcriptional modification event in hepatocellular carcinoma (HCC). Evidence suggests that adenosine deaminases acting on RNA 1 (ADAR1) correlates to oxidative stress that is a crucial factor of HCC pathogenesis. The present study investigated the effect of ADAR1 on survival and oxidative stress of HCC, and underlying mechanisms. METHODS: ADAR1 expression was measured in fifty HCC and normal tissues via real-time quantitative PCR, and immunohistochemistry. For stable knockdown or overexpression of ADAR1, adeno-associated virus vectors carrying sh-ADAR1 or ADAR1 overexpression were transfected into HepG2 and SMMC-7721 cells. Transfected cells were exposed to oxidative stress agonist tBHP or sorafenib Bay 43-9006. Cell proliferation, apoptosis, and oxidative stress were measured, and tumor xenograft experiment was implemented. RESULTS: ADAR1 was up-regulated in HCC and correlated to unfavorable clinical outcomes. ADAR1 deficiency attenuated proliferation of HCC cells and tumor growth and enhanced apoptosis. Moreover, its loss facilitated intracellular ROS accumulation, and elevated Keap1 and lowered Nrf2 expression. Intracellular GSH content and SOD activity were decreased and MDA content was increased in the absence of ADAR1. The opposite results were observed when ADAR1 was overexpressed. The effects of tBHP and Bay 43-9006 on survival, apoptosis, intracellular ROS accumulation, and Keap1/Nrf2 pathway were further exacerbated by simultaneous inhibition of ADAR1. CONCLUSIONS: The current study unveils that ADAR1 is required for survival and oxidative stress of HCC cells, and targeting ADAR1 may sensitize HCC cells to oxidative stress via modulating Keap1/Nrf2 pathway.

Indoor Air Sources of Outdoor Air Pollution: Health Consequences, Policy, and Recommendations: An Official American Thoracic Society Workshop Report.

Indoor sources of air pollution worsen indoor and outdoor air quality. Thus, identifying and reducing indoor pollutant sources would decrease both indoor and outdoor air pollution, benefit public health, and help address the climate crisis. As outdoor sources come under regulatory control, unregulated indoor sources become a rising percentage of the problem. This American Thoracic Society workshop was convened in 2022 to evaluate this increasing proportion of indoor contributions to outdoor air quality. The workshop was conducted by physicians and scientists, including atmospheric and aerosol scientists, environmental engineers, toxicologists, epidemiologists, regulatory policy experts, and pediatric and adult pulmonologists. Presentations and discussion sessions were centered on 1) the generation and migration of pollutants from indoors to outdoors, 2) the sources and circumstances representing the greatest threat, and 3) effective remedies to reduce the health burden of indoor sources of air pollution. The scope of the workshop was residential and commercial sources of indoor air pollution in the United States. Topics included wood burning, natural gas, cooking, evaporative volatile organic compounds, source apportionment, and regulatory policy. The workshop concluded that indoor sources of air pollution are significant contributors to outdoor air quality and that source control and filtration are the most effective measures to reduce indoor contributions to outdoor air. Interventions should prioritize environmental justice: Households of lower socioeconomic status have higher concentrations of indoor air pollutants from both indoor and outdoor sources. We identify research priorities, potential health benefits, and mitigation actions to consider (e.g., switching from natural gas to electric stoves and transitioning to scent-free consumer products). The workshop committee emphasizes the benefits of combustion-free homes and businesses and recommends economic, legislative, and education strategies aimed at achieving this goal.