Safety, efficacy and immunogenicity of aerosolized Ad5-nCoV COVID-19 vaccine in a non-inferiority randomized controlled trial.

This phase 3, observer-blinded, non-inferiority randomized trial (ClinicalTrials.gov: NCT05517642), conducted from September 2022 to May 2023 at three Malaysian sites, involved 540 adults previously vaccinated with three COVID-19 doses. Participants were randomized 1:1 to receive either one dose of inhaled Recombinant COVID-19 Vaccine (Ad5-nCoV-IH) or intramuscular tozinameran (BNT-IM). The study assessed safety, vaccine efficacy (VE) and immunogenicity against SARS-CoV-2 variants. The primary outcome was the non-inferiority of anti-spike protein receptor-binding domain (S-RBD IgG) antibodies, with a 97.5% confidence interval lower limit for the geometric mean concentration (GMC) ratio >0.67. Ad5-nCoV-IH showed lower immunogenicity than BNT-IM, with a GMC ratio of 0.22 and a seroconversion rate difference of -71.91%. Adverse drug reactions (ADRs) were less frequent with Ad5-nCoV-IH (39.26%) compared to BNT-IM (64.68%). No serious vaccine-related adverse events were reported. Both vaccines had comparable efficacy against COVID-19 variants. This study was funded by Tianjin Biomedical Science and Technology Major Project.

Yam Carbon Dots Promote Bone Defect Repair by Modulating Histone Demethylase 4B.

Introduction: Chronic apical periodontitis is a typical inflammatory disease of the oral cavity, the pathology is characterized by an inflammatory reaction with bone defects in the periapical area. Chinese medicine is our traditional medicine, Carbon Dots (CDs) are a new type of nanomaterials. The purpose of this study was to prepare Yam Carbon Dots (YAM-CDs) to investigate the mechanism of action of YAM-CDs on bone differentiation in vivo and in vitro. Methods: We characterized YAM-CDs using transmission electron microscopy (TEM), Fourier Transform Infrared Spectrometer (FTIR), X-Ray Diffraction (XRD) and photoluminescence (PL). CCK-8 assay, Real-time qPCR, and Western Blot were conducted using bone marrow mesenchymal stem cells (BMSCs) to verify that YAM-CDs promote osteoblast differentiation. In addition, we investigated the role of YAM-CDs in promoting bone formation in an inflammatory setting in an in vivo mouse model of cranial defects. Results: The results of TEM and PL showed that the YAM-CDs mostly consisted of the components C1s, O1s, and N1s. Additionally the average sizes of YAM-CDs were 2-6 nm. The quantum yield was 4.44%, with good fluorescence stability and biosafety. Real-time qPCR and Western blot analysis showed that YAM-CDs promoted osteoblast differentiation under an inflammatory environment by regulating expression of histone demethylase 4B (KDM4B). In vivo, results showed that YAM-CDs effectively repaired cranial bone defects in a mouse model and reduced the expression of inflammatory factors under the action of lipopolysaccharides (LPS). Conclusion: YAM-CDs promoted the proliferation and differentiation of osteoblasts by regulating the expression of KDM4B to repair cranial bone defects in mice under an LPS-induced inflammatory milieu, which will provide a new idea for the treatment of clinical periapical inflammation and other bone defect diseases.

How policy advocacy promotes regulated antibiotic use: Evidence from meat duck farmers of China.

Antibiotic residues resulting from the misuse of veterinary antibiotics pose a serious threat to global food safety and the ecological environment. Regulating the use of antibiotics is currently a major concern; however, existing literature on this issue remains insufficient. Therefore, to advance research in this area, this study utilizes data from 988 questionnaires collected across 9 provinces in China and employs the 3SLS systematic estimation method. It constructs an analytical framework to explore the mechanisms through which policy advocacy (PA) influences regulating antibiotics use (RAU) among meat duck farmers. Specifically, the study examines two pathways: " PA - public opinion pressure perception (POPP) - RAU" and " PA - moral responsibility (MR) - RAU." Additionally, it explores the potential mechanisms through which PA impacts RAU among farmers. The results show that PA (Coef = 0.070, SE = 0.014) can promote RAU by increasing the level of POPP (Coef = 0.173, SE = 0.091). PA (Coef = 0.351, SE = 0.028) can also promote RAU by enhancing MR (Coef = 0.239, SE = 0.035). Meanwhile, this study introduces Internet use (IU) and reputational incentives (RI) as moderating variables to analyze their role in moderating the impact of PA on RAU. It was demonstrated that IU (Coef = 0.088, SE = 0.016) significantly enhances farmers' awareness of the value of RAU and amplifies the impact of PA on MR. However, IU (Coef = -0.017, SE = 0.008) was found to inhibit the effect of PA on POPP. RI fully satisfies farmers' need for " honor " and enhances the effectiveness of PA in promoting both POPP (Coef = 0.009, SE = 0.002) and MR (Coef = 0.058, SE = 0.004). Finally, the study proposes that the government expand PA channels, innovate methods, and combine online outreach with demonstrations to improve farmers' awareness of antibiotic use and address their reputational needs.

Immunometabolic changes and potential biomarkers in CFS peripheral immune cells revealed by single-cell RNA sequencing.

The pathogenesis of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains unclear, though increasing evidence suggests inflammatory processes play key roles. In this study, single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) was used to decipher the immunometabolic profile in 4 ME/CFS patients and 4 heathy controls. We analyzed changes in the composition of major PBMC subpopulations and observed an increased frequency of total T cells and a significant reduction in NKs, monocytes, cDCs and pDCs. Further investigation revealed even more complex changes in the proportions of cell subpopulations within each subpopulation. Gene expression patterns revealed upregulated transcription factors related to immune regulation, as well as genes associated with viral infections and neurodegenerative diseases.CD4+ and CD8+ T cells in ME/CFS patients show different differentiation states and altered trajectories, indicating a possible suppression of differentiation. Memory B cells in ME/CFS patients are found early in the pseudotime, indicating a unique subtype specific to ME/CFS, with increased differentiation to plasma cells suggesting B cell overactivity. NK cells in ME/CFS patients exhibit reduced cytotoxicity and impaired responses, with reduced expression of perforin and CD107a upon stimulation. Pseudotime analysis showed abnormal development of adaptive immune cells and an enhanced cell-cell communication network converging on monocytes in particular. Our analysis also identified the estrogen-related receptor alpha (ESRRA)-APP-CD74 signaling pathway as a potential biomarker for ME/CFS in peripheral blood. In addition, data from the GSE214284 database confirmed higher ESRRA expression in the monocyte cell types of male ME/CFS patients. These results suggest a link between immune and neurological symptoms. The results support a disease model of immune dysfunction ranging from autoimmunity to immunodeficiency and point to amyloidotic neurodegenerative signaling pathways in the pathogenesis of ME/CFS. While the study provides important insights, limitations include the modest sample size and the evaluation of peripheral blood only. These findings highlight potential targets for diagnostic biomarkers and therapeutic interventions. Further research is needed to validate these biomarkers and explore their clinical applications in managing ME/CFS.

An adhesive, highly stretchable and low-hysteresis alginate-based conductive hydrogel strain sensing system for motion capture.

A strain sensor stands as an indispensable tool for capturing intricate motions in various applications, ranging from human motion monitoring to electronic skin and soft robotics. However, existing strain sensors still face difficulties in simultaneously achieving superior sensing performance sufficing for practical applications like high stretchability and low hysteresis, as well as seamless device fabrication like desirable interfacial adhesion and system-level integration. Herein, we develop a highly stretchable and low-hysteresis strain sensor with adhesive poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)/polyacrylamide (PAAm)-sodium alginate (SA) composite hydrogel, allowing the successful construction of a wireless motion capture sensing system that can provide precise data collection within a large deformation range. The resultant composite hydrogel displays favorable interfacial adhesion and robust mechanical stability, and the fabricated strain sensor demonstrates a wide working strain range (up to 500%) with high sensitivity (gauge factor = 11) and ultra-low hysteresis (1.52%), outperforming previous PEDOT-based hydrogel strain sensors. Enabled by the intriguing material properties and high sensing performance, we further demonstrate the fabrication and integration of a wireless motion capture sensing system for diverse applications like human motion monitoring, gesture recognition, and interactive communication.

The women's cardiovascular disease risk perception after hypertensive disorders of pregnancy: A qualitative meta-synthesis.

BACKGROUND: Hypertensive disorders of pregnancy is associated with increased risk of cardiovascular disease later in life, but studies suggest that women with previous hypertensive disorders of pregnancy are not aware of this. Little is known about how these women perceive the condition and the associated long-term risks. OBJECTIVES: This study aims to examine and synthesize qualitative evidence on the perceptions and awareness of women with hypertensive disorders of pregnancy following perceived cardiovascular disease risk. METHODS: Computer searches of Pub Med, Embase, Web of Science, Cochrane Library, CINAHL, CNKI, Wanfang database, Vip and SinoMed for all qualitative studies that met the inclusion criteria. The time frame for the search was from the establishment of the database to April 2024. Literature quality was assessed using the Australian Joanna Briggs Institute Centre for Evidence-Based Health Care Qualitative Research quality assessment criteria, and results were summarised and integrated using a pooled integration approach. RESULTS: Eleven studies that fulfilled the inclusion criteria and quality assessment were included in the meta synthesis. Three themes were identified during the analysis: (1)Factors affecting perceived cardiovascular risk in women with hypertensive disorders of pregnancy; (2)Women with hypertensive disorders of pregnancy use different strategies to cope with cardiovascular risk; (3)Needs and expectations for coping with cardiovascular disease risk. CONCLUSIONS: Both women with hypertensive disorders of pregnancy and healthcare providers lack knowledge of the link between hypertensive disorders of pregnancy and cardiovascular risk. Healthcare professionals should establish a multidimensional support model, pay timely attention to postpartum women's psycho-emotional and risk awareness, and give individualised health education to promote health behaviour change. At the same time, professionals should be given standardised training and personalised follow-up services to reduce the incidence of cardiovascular disease in the future.

Maintenance hemodialysis patients participate in a virtual reality rehabilitation training experience: a qualitative study.

Maintenance hemodialysis patients' psychology and physiology will have negative effects. Adherence to exercise can effectively enhance the physical function of maintenance hemodialysis patients and reduce the negative psychological emotions. In recent years, virtual reality technology has been gradually applied to the hemodialysis group, providing a new way for the rehabilitation training and healthy life of maintenance hemodialysis patients. OBJECTIVES: To understand the real experience of maintenance hemodialysis patients participating in virtual reality rehabilitation training, and to make reference for the future clinical development of a more perfect virtual reality rehabilitation training program. METCHODS: Phenomenological research method was used to conduct semi-structured interviews with 10 maintenance hemodialysis patients, and the interview data were compiled and analyzed using Colaizzi's seven-step analysis. RESULTS: Four themes were distilled: (1) Maintenance hemodialysis patients' overall perceptual experience of the virtual reality rehabilitation system; (2) Physical and psychological improvement of maintenance hemodialysis patients with virtual reality rehabilitation system; (3) Individualized needs of maintenance hemodialysis patients during virtual reality rehabilitation training; (4) Future improvements and recommendations for the virtual reality rehabilitation system. CONCLUSION: The results of the study suggest that virtual reality improves patients' motivation to recover and shows positive results and potential benefits in improving physical functioning and negative emotions in maintenance hemodialysis patients.

Regular and continuous rehabilitation training is a very effective non-pharmacological treatment to improve the physical functioning and mental health of maintenance hemodialysis patients.Virtual reality technology can stimulate the underlying motivation of maintenance hemodialysis patients to undergo rehabilitation, thus, they are guided to adopt a healthy lifestyle.Virtual reality technology can be an effective aid in the rehabilitation of maintenance hemodialysis patients, thus reducing the workload of rehabilitation clinicians.

Self-compassion and work engagement among Chinese nurses: exploring mediating effects of depression, anxiety, and stress.

Objective: Work engagement significantly influences both the quality of nursing care and nurses' job performance. In this study, we aimed to explore the mediating effects of negative emotions on the relationship between self-compassion and work engagement among Chinese nurses. Method: A cross-sectional study was performed on nurses in a tertiary A hospital located in Henan province from September, 2023 to December, 2023. Custom-designed digital surveys were disseminated to gather pertinent data. Structural Equation Modelling (SEM) were utilised to analyse the data and determine relationships among self-compassion, negative emotions and work engagement. Results: A total of 1,201 nurses were included. According to the statistical model, self-compassion (ß = 0.116, CI: -0.036 to -0.008, p < 0.001) and negative emotions (ß = -0.372, CI: -0.053 to -0.033, p < 0.001) were correlated with work engagement. Furthermore, our analysis revealed that negative emotions partially mediated the relationship between self-compassion and work engagement (ß = 0.174, CI: -0.066 to -0.020, p < 0.01). Conclusion: These findings indicate that incorporating self-compassion and negative emotion regulation in interventions targeting work engagement may enhance the overall level of work engagement among nurses, thereby improving job satisfaction and the quality of patient care.

Pharmacokinetics, Pharmacodynamics, and Safety of Intravenous Efgartigimod and Subcutaneous Efgartigimod PH20 in Healthy Chinese Participants.

BACKGROUND: Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and China for the treatment of gMG. OBJECTIVE: We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants. METHODS: In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 3:1 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters. RESULTS: After the fourth IV infusion, a mean maximum observed concentration (Cmax) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC0-168h) was 5300 µg × h/mL. After the fourth SC injection, a mean Cmax of 42.1 µg/mL was achieved with a median Tmax of 47.74 h; the mean AUC0-168h was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study. CONCLUSIONS: The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. Both formulations effectively reduced total IgG levels by a similar percentage. CLINICAL TRIAL REGISTRATION: CTR20211952 and CTR20211805.

Anti-inflammatory effects of Tao Hong Si Wu Tang in mice with lung cancer and chronic obstructive pulmonary disease.

BACKGROUND: Lung cancer (LC) combined with chronic obstructive pulmonary disease (COPD) is a common combination of comorbidities. Anti-inflammation and modulation of oxidative/antioxidative imbalance may prevent COPD-induced LC, and are also crucial to the treatment of LC combined with COPD. Modern studies have shown that Tao Hong Si Wu Tang (THSW) has vasodilatory, anti-inflammatory, anti-fatigue, anti-shock, immunoregulatory, lipid-reducing, micronutrient-supplementing, and anti-allergy effects. AIM: To observe the effects of THSW on COPD and LC in mice. METHODS: A total of 100 specific pathogen-free C57/BL6 mice were randomly divided into five groups: Blank control group (group A), model control group (group B), THSW group (group C), IL-6 group (group D), and THSW + IL-6 group (group E), with 20 mice in each group. A COPD mouse model was established using fumigation plus lipopolysaccharide intra-airway drip, and an LC model was replicated by in situ inoculation using the Lewis cell method. RESULTS: The blank control group exhibited a clear alveolar structure. The model control and IL-6 groups had thickened alveolar walls, with smaller alveolar lumens, interstitial edema, and several inflammatory infiltrating cells. Histopathological changes in the lungs of the THSW and THSW + IL-6 groups were less than those of the model control group. The serum IL-1ß, IL-6, and TNF-α levels and IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R expression levels in lung tissues of mice in the rest of the groups were significantly higher than those of the blank control group (P < 0.01). Compared with the model control group, the IL-6 group demonstrated significantly higher levels for the abovementioned proteins in the serum and lung tissues (P < 0.01), and the THSW group had significantly higher serum IL-1ß, IL-6, and TNF-α levels and IL-7R expression levels in lung tissues (P < 0.01) but significantly decreased IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R levels (P < 0.01). CONCLUSION: THSW reduces the serum IL-1ß, IL-6, and TNF-α levels in the mouse model with anti-inflammatory effects. Its anti-inflammatory mechanism lies in inhibiting the overactivation of the JAK/STAT1/3 signaling pathway.

Arginine as a regulator of antioxidant and gel formation in yak Myofibrillar proteins: Efficacy and mechanistic insights.

Arginine (Arg), a safe basic amino acid, modulates interprotein interactions and impacts the processing characteristics of myofibrillar proteins (MP) in meat products, as numerous studies have demonstrated. This study aimed to explore the effects of varying concentrations of Arg (0.025, 0.050, 0.100, 0.200 %) on the physicochemical properties and gel behavior of yak MP. Utilizing yak MP as the substrate, we assessed and analyzed the physicochemical attributes and gel performance of the MP-Arg composite system. The findings revealed that Arg facilitates MP unfolding and internal group exposure, effectively mitigating oxidative tertiary structure alterations. Arg exerts potent antioxidant activity on MP, augmenting their water-holding capacity, which ameliorates gel properties. In this experiment, 0.05 % Arg maximally inhibited oxidative damage to MP, with protection being concentration-dependent. Collectively, these findings suggest that Arg effectively inhibits the oxidative degradation of MP structure and promotes the formation of enhanced gel characteristics.

Hydrogen-Bonded Complexes of HPN• and HNP• Radicals with Carbon Monoxide.

Phosphorus mononitride (PN) is a carrier of phosphorus in the interstellar medium. As the simplest derivatives of PN, the radical species HPN• and HNP• have remained elusive. Herein, we report the generation, characterization, and photochemistry of HPN• and HNP• in N2-matrix at 3 K. Specifically, HPN• was formed as a weakly bonded complex with CO in the matrix by 254 nm photolysis of the novel phosphinyl radical HPNCO•. The •NPH-CO complex is extremely unstable, as it undergoes spontaneous isomerization to the lower-energy isomer •PNH-CO through fast quantum mechanical tunneling (QMT) with a half-life of 6.1 min at 3 K. Upon further irradiation at 254 nm, the reverse conversion of •PNH-CO to •NPH-CO along with dehydrogenation to yield PN was observed. The characterization •NPH-CO and •PNH-CO with matrix-isolation IR spectroscopy is supported by D, 15N, and 13C isotope labeling and quantum chemical calculations at the XYGJ-OS/AVTZ level of theory, and the mechanism by hydrogen atom tunneling is consistent with multidimensional instanton theory calculations.

Review of Atrioventricular Node Ablation Combined with Permanent His-Purkinje Conduction System Pacing in Patients with Atrial Fibrillation with Heart Failure.

With the advancement of pacing technologies, His-Purkinje conduction system pacing (HPCSP) has been increasingly recognized as superior to conventional right ventricular pacing (RVP) and biventricular pacing (BVP). This method is characterized by a series of strategies that either strengthen the native cardiac conduction system or fully preserve physical atrioventricular activation, ensuring optimal clinical outcomes. Treatment with HPCSP is divided into two pacing categories, His bundle pacing (HBP) and left bundle branch pacing (LBBP), and when combined with atrioventricular node ablation (AVNA), can significantly improve left ventricular (LV) function. It effectively prevents tachycardia and regulates ventricular rates, demonstrating its efficacy and safety across different QRS wave complex durations. Therefore, HPCSP combined with AVNA can alleviate symptoms and improve the quality of life in patients with persistent atrial fibrillation (AF) who are unresponsive to multiple radiofrequency ablation, particularly those with concomitant heart failure (HF) who are at risk of further deterioration. As a result, this "pace and ablate" strategy could become a first-line treatment for refractory AF. As a pacing modality, HBP faces challenges in achieving precise localization and tends to increase the pacing threshold. Thus, LBBP has emerged as a novel approach within HPCSP, offering lower thresholds, higher sensing amplitudes, and improved success rates, potentially making it a preferable alternative to HBP. Future large-scale, prospective, and randomized controlled studies are needed to evaluate patient selection and implantation technology, aiming to clarify the differential clinical outcomes between pacing modalities.

Comprehensive analysis identifies YKT6 as a potential prognostic and diagnostic biomarker in lung adenocarcinoma.

BACKGROUND: Lung cancer is the most common cause of cancer-related death worldwide. The most prevalent histological subtype of lung cancer is lung adenocarcinoma (LUAD), with incidence rising each year. Treating LUAD remains a significant issue due to a lack of early diagnosis and poor therapy outcomes. YKT6 is a member of the SNARE protein family, whose clinical value and biological function in LUAD has yet to be established. METHODS: TCGA, HPA and UALCAN were used to analyze YKT6 mRNA and protein levels, the correlation between YKT6 expression and clinicopathological features and prognosis. YKT6 mRNA and protein expression were verified by qRT-PCR, immunohistochemistry (IHC) and tissue microarrays (TMA). Additionally, lung cancer cell lines were chosen for YKT6 silencing to explore the effects on cell proliferation and migration. The cBioPortal was used to select YKT6-related genes. Protein-protein interaction (PPI) network was created based on STRING database and hub genes were screened, with their expression levels and prognosis values in LUAD analyzed accordingly. YKT6-related genes were enriched by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses. RESULTS: In LUAD, YKT6 was distinctly highly expressed with relation to clinical features of staging, smoking, lymph node metastasis, and TP53 mutation. Elevated YKT6 expression was linked to adverse prognosis, serving as an independent unfavorable prognostic factor. Moreover, YKT6 presented high diagnostic value in LUAD patients (AUC = 0.856). Experimental validation indicated that freshly collected LUAD tissues showed significantly high mRNA expression of YKT6. IHC and TMA verified increased YKT6 protein level in LUAD. Knockdown of YKT6 inhibited cell proliferation and promoted apoptosis, with mitigated capability of migration and invasion. The top ten hub genes screened by PPI network were highly expressed in LUAD, and significantly associated with poor prognosis. GO and KEGG analyses showed that YKT6-related genes were mainly involved in cell cycle. CONCLUSION: Elevated YKT6 expression is related to poor prognosis of LUAD patients. YKT6 can serve as a novel biomarker for LUAD diagnosis and prognosis. Cell proliferation, migration and invasion was impaired with increased apoptosis upon YKT6 silencing in lung cancer cells. In summary, this study comprehensively uncovered that YKT6 could be identified as a potential prognostic and diagnostic biomarker in LUAD.

Effectiveness of digital health interventions in improving mental health of older adults with mild cognitive impairment: A systematic review and meta-analysis protocol.

Background: Mental health issues are highly prevalent in older adults with mild cognitive impairment (MCI). Digital Health Interventions (DHIs) for individuals with MCI have proven effective in improving cognitive function, but their impact on mental health has received less attention. Objective: Reporting a protocol for a systematic review and meta-analysis to evaluate the effectiveness of DHIs for older adults with MCI, focusing on mental health outcomes both overall and within homogeneous subgroups. Methods: A systematic review and meta-analysis of randomized controlled trials will be conducted, with searches performed in the Cochrane Library, PubMed, Embase, Web of Science, CINAHL, CNKI, and WanFang date from inception to March 2024. Mental health outcomes are the primary outcome. Risk of bias will be assessed with the Cochrane Collaboration tool, and evidence quality will be evaluated with Grading of Recommendations Assessment, Development, and Evaluation. If sufficient studies are available, subgroup analysis will assess variations based on population and intervention characteristics, including types and modalities of DHIs, intervention settings, session frequency, and duration, focusing on specific mental health outcomes and both short- and long-term effects. Additionally, sensitivity analysis and meta-regression analysis will identify sources of other potential heterogeneity. Conclusion: The protocol will guide a systematic review and meta-analysis to determine the effectiveness of DHIs in improving mental health of older adults with MCI. This effort will enhance understanding and optimization of DHIs, vital for reducing mental health disparities and improving psychotherapy access for older adults with MCI. PROSPERO registration number: CRD42024522342.

Host RNA N6-methyladenosine and incoming DNA N6-methyldeoxyadenosine modifications cooperatively elevate the condensation potential of DNA to activate immune surveillance.

Self-nonself discrimination is fundamental to life, thereby even microbes can apply DNA modifications to recognize nonself-DNA. However, mammalian cytosolic DNA sensors indiscriminately bind DNA, necessitating specific mechanism(s) for self-nonself discrimination. Here, we show that mammalian RNA N6-methyladenosine (m6A) and incoming DNA N6-methyldeoxyadenosine (6mdA) cooperatively elevate the condensation potential of DNA to activate immunosurveillance. RNA m6A modification was found to enhance the activation of cyclic GMP-AMP synthase (cGAS) via increasing DNA phase separation. And 6mdA further increased the phase separation potential of DNA. Consistently, host RNA m6A and incoming DNA 6mdA modifications cooperatively elevated the incoming DNA condensation and cGAS activation. Moreover, we developed a prodrug, QKY-613. QKY-613 promoted a discriminative incorporation of 6mdA into viral DNAs to elevate host immune surveillance, and decreased mortality in virus-infected aged mice. Our results link nucleic acid modification diversity with immune surveillance via phase separation, which might be targeted for therapeutic intervention.

ITS and 16S rRNA Gene Revealed Multitudinous Microbial Contaminations of Residential Air Conditioning Filters in Megacity Shanghai, China.

Air conditioning is a crucial participant in indoor air circulation and harmful microorganism transmission. To elucidate microbial contamination in air conditioning systems, bacteria, fungi, and pollens in residential air conditioning (AC) filters in Shanghai were revealed. The concentrations of fungal ITS (1,972,037 ± 5,025,505 copies/cm2) in most filter samples were considerably higher than the 16S rRNA gene (21,587 ± 21,461 copies/cm2). The multitudinous bacteria determined a higher richness, whereas the trend was not in line with fungi, owing to Aspergillus flourishing, with an average of 43.75%. Numerous bacteria that may often be prevalent in human skin, mucous membranes, and intestines, such as Enhydrobacter, Micrococcus, Staphylococcus, Streptococcus, and Haemophilus, were also discovered in AC filters. The pollens were affiliated with Streptophyta at phylum, and Humulus was the most abundant genus (mean value 67.84%), raising the possibility of allergic responses. This study provides a better understanding of the microbial characteristics of AC filters, enables more rational approaches for microbe contaminant control, and ultimately improves human health in megacities.

The transcription factor MYC2 positively regulates terpene trilactone biosynthesis through activating GbGGPPS expression in Ginkgo biloba.

Terpene trilactones (TTLs) have important medicinal value, but their low content in Ginkgo biloba leaves makes their exploitation extremely costly, thereby limiting the development of TTL-related industries. It was found that exogenous methyl jasmonate (MeJA) treatment increased the accumulation of TTLs, but the molecular mechanism is still unclear. Here, we identified two bHLH transcription factors in G. biloba, with the protein subcellular localizations in the nucleus. Expression of GbMYC2s was strongly induced by MeJA treatment, and the interactions between GbJAZs and GbMYC2s were demonstrated by yeast two-hybrid and bimolecular fluorescence complementation experiments. Overexpression of GbMYC2_4 and GbMYC2_5 enhanced Arabidopsis root sensitivity and significantly increased TTL content. In addition, GbGGPPS was found to be a common target of GbMYC2_4 and GbMYC2_5 by yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase reporter assays and DAP-seq, and they achieved regulation of GbGGPPS by binding to the G-box. Further findings revealed that GbMYC2_4 and GbMYC2_5 bind the G-box not universally but selectively. Our study revealed that jasmonic acid signaling mediates TTL biosynthesis through the GbJAZ-GbMYC2-GbGGPPS module, which enriches the terpenoid biosynthesis regulatory networks and provides a research basis and target genes for enhancing TTL content through genetic engineering.

Internship and postgraduate entrance examination: A qualitative study on the psychological experience of undergraduate nursing students under dual pressure in China.

Background: With the development of nursing positions and nursing disciplines in China's tertiary hospitals, the number of people applying for the master's degree in nursing is also increasing year by year. Postgraduate examinations are held during internship, so nursing students face the dual pressure of testing and internship, which brings varying degrees of negative experiences and emotional fluctuations. Objective: To explore the psychological experiences and influencing factors of undergraduate nursing students under the dual pressures of clinical nursing internships and postgraduate examination preparations. Design: Descriptive qualitative study. Method: Purposeful sampling was used to recruit 18 participants from eight tertiary hospitals in China between October and December 2023. Semi-structured in-depth interviews were conducted, with interview recordings transcribed verbatim. Thematic analysis was then applied to the data. Results: Four themes were identified: negative experiences under dual pressures, coping mechanisms for negative experiences, motivational effects under dual pressures, and evaluations of significant individuals. Nursing students improved their overall abilities through internships and exam preparations, gaining a clear understanding of themselves and certain hospital roles. However, at this stage, students also experienced adverse psychological experiences for various reasons. Thus, they employed several methods to alleviate their psychological stress, aiming for a better state to face internships and exam preparations. Conclusion: Schools and hospitals should pay more attention to the needs of nursing students under dual pressures, monitoring their emotional states, and providing psychological support to enhance their stress-coping abilities. It is important to ensure the overall well-being of students while strengthening the motivational effects of internships and learning experiences.

Optimization of Charge Extraction and Interconnecting Layers for Highly Efficient Perovskite/Organic Tandem Solar Cells with High Fill Factor.

Perovskite/organic tandem solar cells (POTSCs) have garnered significant attention due to their potential for achieving high photovoltaic (PV) performance. However, the reported power conversion efficiencies (PCEs) and fill factors (FFs) are still subpar due to the challenges associated with charge extraction in the organic bulk-heterojunction (BHJ) and significant energy losses in the interconnecting layers (ICLs). Here, a quaternary organic BHJ blend is developed to enhance the charge extraction in the organic subcell, contributing to an increased FF of ≥78% under 1 sun illumination and even more under lower illumination intensities. Meanwhile, energy losses in the ICLs are reduced via the incorporation of a self-assembly monolayer (SAM), (4-(3,6-Dimethyl-9H-carbazol-9-yl)butyl)phosphonic acid (Me-4PACz), in organic BHJ to form a MoOx/SAM interface and the thorough control of the MoOx thickness to suppress parasitic absorption. The resultant POTSCs achieve a remarkable PCE of 25.56% (certified: 24.65%), with a record FF of 83.62%, which is among the highest PCEs of POTSCs and the highest FF of all types of perovskite-based tandem solar cells (TSCs) till now. This work proves the optimization of charge extraction and ICLs are effective strategies to promote the performance of POTSCs to surpass other solution-processed perovskite-based TSCs in the near future.