Search

Abstract Background Precursor B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancers in children. Failure of induction chemotherapy is a major factor leading to relapse and death in children with B-ALL. Given the importance of altered metabolites in the carcinogenesis of pediatric B-ALL, studying the metabolic profile of children with B-ALL during induction chemotherapy and in different minimal residual disease (MRD) status may contribute to the management of pediatric B-ALL. Methods We collected paired peripheral blood plasma samples from children with B-ALL at pre- and post-induction chemotherapy and analyzed the metabolomic profiling of these samples by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Healthy children were included as controls. We selected metabolites that were depleted in pediatric B-ALL and analyzed the concentrations in pediatric B-ALL samples. In vitro, we study the effects of the selected metabolites on the viability of ALL cell lines and the sensitivity to conventional chemotherapeutic agents in ALL cell lines. Results Forty-four metabolites were identified with different levels between groups. KEGG pathway enrichment analyses revealed that dysregulated linoleic acid (LA) metabolism and arginine (Arg) biosynthesis were closely associated with pediatric B-ALL. We confirmed that LA and Arg were decreased in pediatric B-ALL samples. The treatment of LA and Arg inhibited the viability of NALM-6 and RS4;11 cells in a dose-dependent manner, respectively. Moreover, Arg increased the sensitivity of B-ALL cells to L-asparaginase and daunorubicin. Conclusion Arginine increases the sensitivity of B-ALL cells to the conventional chemotherapeutic drugs L-asparaginase and daunorubicin. This may represent a promising therapeutic approach.

Abstract Background Zhiguo ethnic groups, commonly known as “the directly-entering-socialism ethnic groups”, represent Chinese ethnic minorities who have undergone a unique social development trajectory by transforming directly from primitive societies to the socialist stage. In recent decades, significant lifestyle transformations have occurred among Zhiguo ethnic groups. Understanding their health lifestyles can play a strategic role in China’s pursuit of universal health coverage. This study aims to examine patterns of health-related lifestyle among Zhiguo ethnic groups and explore whether sociodemographic features and specific indicators related to health status are associated with particular classes. Methods A cross-sectional study was conducted in Yunnan Province, China, from July to December 2022. Stratified random sampling method was employed to recruit residents belonging to six Zhiguo ethnic groups aged between 15 and 64. Latent class analysis was performed to identify clusters of health-related behaviors within each ethnic group. Logistic regression was utilized to determine the predictors of health lifestyles. Results A total of 1,588 individuals from the Zhiguo ethnic groups participated in this study. Three latent classes representing prevalent health lifestyles among the Zhiguo ethnic groups were identified: “unhealthy lifestyle” (31.80%), “mixed lifestyle” (57.37%), and “healthy lifestyle” (10.83%). In the overall population, individuals belonging to the “healthy lifestyle” group exhibited a higher likelihood of being non-farmers (OR: 2.300, 95% CI: 1.347–3.927), women (OR: 21.459, 95% CI: 13.678–33.667), married individuals (OR: 1.897, 95% CI: 1.146–3.138), and those residing within a walking distance of less than 15 min from the nearest health facility (OR: 2.133, 95% CI: 1.415–3.215). Conversely, individuals in the age cohorts of 30–39 years (OR: 0.277, 95% CI: 0.137–0.558) and 40–49 years (OR: 0.471, 95% CI: 0.232–0.958) showed a decreased likelihood of adopting a healthy lifestyle. Conclusions A considerable proportion of the Zhiguo ethnic groups have not adopted healthy lifestyles. Targeted interventions aimed at improving health outcomes within these communities should prioritize addressing the clustering of unfavorable health behaviors, with particular emphasis on single male farmers aged 30–49, and expanding healthcare coverage for individuals residing more than 15 min away from accessible facilities.

Abstract Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration. Graphical Abstract

Abstract Skin wound infection has become a notable medical threat. Herein, the polysaccharide-based injectable hydrogels with multifunctionality were developed by a simple and fast gelation process not only to inactivate bacteria but also to accelerate bacteria-infected wound healing. Sodium nitroprusside (SNP) loaded PCN-224 nanoparticles were introduced into the polymer matrix formed by the dynamic and reversible coordinate bonds between Ag+ with carboxyl and amino or hydroxyl groups on carboxymethyl chitosan (CMCS), hydrogen bonds and electrostatic interactions in the polymer to fabricate SNP@PCN@Gel hydrogels. SNP@PCN@Gel displayed interconnected porous structure, excellent self-healing capacity, low cytotoxicity, good blood compatibility, and robust antibacterial activity. SNP@PCN@Gel could produce reactive oxygen species (ROS) and NO along with Fe2+, and showed long-term sustained release of Ag+, thereby effectively killing bacteria by synergistic photothermal (hyperthermia), photodynamic (ROS), chemodynamic (Fenton reaction), gas (NO) and ion (Ag+ and -NH3 + in CMCS) therapy. Remarkably, the hydrogels significantly promoted granulation tissue formation, reepithelization, collagen deposition and angiogenesis as well as wound contraction in bacteria-infected wound healing. Taken together, the strategy represented a general method to engineer the unprecedented photoactivatable “all-in-one” hydrogels with enhanced antibacterial activity and paved a new way for development of antibiotic alternatives and wound dressing. Graphical abstract

Abstract Nucleic acid tests are essential for the accurate diagnosis and control of infectious diseases. However, current assays are not easily scalable for a large population, due to the requirement of laboratory settings or special equipment. Here, we developed an integrated box for instant nucleic acid screening which fully integrates nucleic acid release, amplification, and results visualization for self-service standalone test. Importantly, the operation of the box runs on a novel gamepad-like interface, which allows deployment of the box in home settings and operation by users without any prior professional training. The performance of the box is empowered by an RNA extraction-free sample inactivation process and nested recombinase polymerase amplification chemistry and exhibits sensitivity comparable to reverse transcription-quantitative polymerase chain reaction with high specificity for severe acute respiratory syndrome coronavirus 2 RNA in a reaction time of 30 minutes directly from fresh swab sample to results. These innovations make the box a novel platform for a convenient, accurate, and deployable point-of-care testing scheme.

Abstract Background Recent studies have suggested that insulin resistance (IR) contributes to the development of cardiovascular diseases (CVD), and the estimated glucose disposal rate (eGDR) is considered to be a reliable surrogate marker of IR. However, most existing evidence stems from studies involving diabetic patients, potentially overstating the effects of eGDR on CVD. Therefore, the primary objective of this study is to examine the relationship of eGDR with incidence of CVD in non-diabetic participants. Method The current analysis included individuals from the China Health and Retirement Longitudinal Study (CHARLS) who were free of CVD and diabetes mellitus but had complete data on eGDR at baseline. The formula for calculating eGDR was as follows: eGDR (mg/kg/min) = 21.158 − (0.09 × WC) − (3.407 × hypertension) − (0.551 × HbA1c) [WC (cm), hypertension (yes = 1/no = 0), and HbA1c (%)]. The individuals were categorized into four subgroups according to the quartiles (Q) of eGDR. Crude incidence rate and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to investigate the association between eGDR and incident CVD, with the lowest quartile of eGDR (indicating the highest grade of insulin resistance) serving as the reference. Additionally, the multivariate adjusted restricted cubic spine (RCS) was employed to examine the dose–response relationship. Results We included 5512 participants in this study, with a mean age of 58.2 ± 8.8 years, and 54.1% were female. Over a median follow-up duration of 79.4 months, 1213 incident CVD cases, including 927 heart disease and 391 stroke, were recorded. The RCS curves demonstrated a significant and linear relationship between eGDR and all outcomes (all P for non-linearity > 0.05). After multivariate adjustment, the lower eGDR levels were founded to be significantly associated with a higher risk of CVD. Compared with participants with Q1 of eGDR, the HRs (95% CIs) for those with Q2 − 4 were 0.88 (0.76 − 1.02), 0.69 (0.58 − 0.82), and 0.66 (0.56 − 0.79). When assessed as a continuous variable, per 1.0-SD increase in eGDR was associated a 17% (HR: 0.83, 95% CI: 0.78 − 0.89) lower risk of CVD, with the subgroup analyses indicating that smoking status modified the association (P for interaction = 0.012). Moreover, the mediation analysis revealed that obesity partly mediated the association. Additionally, incorporating eGDR into the basic model considerably improve the predictive ability for CVD. Conclusion A lower level of eGDR was found to be associated with increased risk of incident CVD among non-diabetic participants. This suggests that eGDR may serve as a promising and preferable predictor and intervention target for CVD.

Abstract Background Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. Methods We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. Results The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. Conclusion Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

Introduction: The treatment of COVID-19 patients, especially high-risk patients, remains a large challenge. Glucocorticoids have been accepted as effective medicines for severe COVID-19. However, the glucocorticoid usage guidelines do not cover all the indications for high-risk patients. Objective: To identify more effective treatments for high-risk patients with COVID-19, this retrospective study analyzed routine epidemiological, clinical, and laboratory data from 33 high-risk patients with COVID-19 in Beijing Gobroad Boren Hospital, Beijing, China, most of whom responded well to treatment. Methods: Severe acute respiratory syndrome coronavirus-2 infection was confirmed via real-time reverse transcriptase polymerase chain reaction assays. Outcome measures such as duration of mechanical ventilation, intensive care unit length of stay, and 28-day mortality were analyzed. Patients were divided into two groups: mild to moderate COVID-19 ( n = 26) and severe COVID-19 ( n = 7). Chest computed tomography images were used to guide methylprednisolone administration or withdrawal. Results: Upon intensive care unit admission, 12.1% of patients were mechanically ventilated with an average partial pressure of oxygen/fraction of inspired oxygen(PaO 2 /FiO 2 ) ratio of 279 ± 146. No coinfections with other endemic viruses were observed. The duration of mechanical ventilation was 16 days (interquartile range: 8–28); the intensive care unit length of stay was 11 (interquartile range: 2–33) days; and the 28-day total mortality was 3.0%. Conclusion: Multivariate regression analysis revealed that low-dose, timely methylprednisolone administration was associated with a lower severe COVID-19 rate and mortality in high-risk patients. For high-risk patients, once there are ground-glass opacities (GGO) in the computed tomography image, continuous and low-dose methylprednisolone administration promotes inflammation remission and protects them from severe COVID-19 or mortality.

Music is an archaic form of emotional expression and arousal that can induce strong emotional experiences in listeners, which has important research and practical value in related fields such as emotion regulation. Among the various emotion recognition methods, the music-evoked emotion recognition method utilizing EEG signals provides real-time and direct brain response data, playing a crucial role in elucidating the neural mechanisms underlying music-induced emotions. Artificial intelligence technology has greatly facilitated the research on the recognition of music-evoked EEG emotions. AI algorithms have ushered in a new era for the extraction of characteristic frequency signals and the identification of novel feature signals. The robust computational capabilities of AI have provided fresh perspectives for the development of innovative quantitative models of emotions, tailored to various emotion recognition paradigms. The discourse surrounding AI algorithms in the context of emotional classification models is gaining momentum, with their applications in music therapy, neuroscience, and social activities increasingly coming under the spotlight. Through an in-depth analysis of the complete process of emotion recognition induced by music through electroencephalography (EEG) signals, we have systematically elucidated the influence of AI on pertinent research issues. This analysis offers a trove of innovative approaches that could pave the way for future research endeavors.

Promoting the efficiency of internal-combustion engine has great benefits, including low fuel-consumption rate and environmental friendliness. Flue gas waste heat thermoelectric generator (TEG) is such a promising solution owning to its solid-state energy conversion and structural simplicity. In this work, a novel heat collection enhancing strategy is first proposed to improve the uniformity of hot-end temperature distribution, which greatly augments the power generation performance under limited pressure drops. A flue gas waste heat TEG unit with 24 TE modules is able to generate an electric power of 103 W under the pressure drop of 375 Pa. The corresponding heat collection, TE, and overall efficiencies of the TEG unit are 36.53 %, 4.30 %, and 1.58 %, respectively. Several important parameters, including flue gas inlet temperature, cooling intensity, cooling mode, and TEG unit arrangement are explored in detail. A demonstration application of an 8-unit waste heat TEG is installed in an 800-ton inland waterway vessel on China's Grand Canal, and the waterway vessel is put into service for over three months. The generated electric power varies between 23.3 W and 463 W, and the average electric power is 177.6 W during the trip.

BackgroundPrevious research and safety advocacy groups have proposed various behaviors for older adults to actively engage in medication safety. However, little is known about how older adults perceive the importance and reasonableness of these behaviors in ambulatory settings. ObjectiveThis study aimed to assess older adults’ perceptions of the importance and reasonableness of 8 medication safety behaviors in ambulatory settings and compare their responses with those of younger adults. MethodsWe conducted a survey of 1222 adults in the United States using crowdsourcing to evaluate patient behaviors that may enhance medication safety in community settings. A total of 8 safety behaviors were identified based on the literature, such as bringing medications to office visits, confirming medications at home, managing medication refills, using patient portals, organizing medications, checking medications, getting help, and knowing medications. Respondents were asked about their perception of the importance and reasonableness of these behaviors on a 5-point Likert rating scale in the context of collaboration with primary care providers. We assessed the relative ranking of behaviors in terms of importance and reasonableness and examined the association between these dimensions across age groups using statistical tests. ResultsOf 1222 adult participants, 125 (10.2%) were aged 65 years or older. Most participants were White, college-educated, and had chronic conditions. Older adults rated all 8 behaviors significantly higher in both importance and reasonableness than did younger adults (P

Background: Alzheimer's disease is characterized by abnormal β-amyloid (Aβ) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to exert neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in the protective effect of myricetin. Methods: The effect of myricetin was assessed on Aβ42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. Behavioral tests were performed to assess the cognitive effects of myricetin (14 days, ip) in 3×Tg mice. The levels of beta-amyloid precursor protein (APP), synaptic and mitochondrial proteins, glycogen synthase kinase3β (GSK3β) and extracellular regulated kinase (ERK) 2 were assessed via Western blotting. Flow cytometry assays, immunofluorescence staining, and transmission electron microscopy were used to assess mitochondrial dysfunction and reactive oxidative stress. Results: We found that, compared with control treatment, myricetin treatment improved spatial cognition and learning and memory in 3×Tg mice. Myricetin ameliorated tau phosphorylation and the reduction in pre- and postsynaptic proteins in Aβ42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation, and rescued mitochondrial dysfunction via the associated GSK3β and ERK 2 signalling pathways. Conclusions: This study provides new insight into the neuroprotective mechanism of myricetin in vitro in cell culture and in vivo in a mouse model of Alzheimer’s disease.

In oligotrophic oceans, primary productivity is widely limited by nitrogen bioavailability. The broadly distributed and abundant nitrogen-fixing cyanobacterium Trichodesmium plays an important role in the oceanic nitrogen and carbon cycles by providing a “new” source of nitrogen to many non-diazotrophic microbes, thereby driving new primary production in the ocean. However, the underlying process and mechanism of nitrogen supply from Trichodesmium to other phytoplankton remain unclear. Here, our results demonstrated that the fixed nitrogen released by Trichodesmium could sustain the growth of a non-nitrogen-fixing cyanobacterium Synechococcus sp. PCC 7002, including a mutant strain (Mut-ureA) that cannot use urea. However, the growth rate of Mut-ureA was approximately 20% lower than that of the wild strain when Trichodesmium filtrate was used for nitrogen supply. This result was consistent with the composition of the Trichodesmium exudate, in which urea comprised more than 20% of the total fixed nitrogen that was released. It is evident from the experiments that a fraction of the Trichodesmium-derived nitrogen was not available to Mut-ureA. Our results suggested that Trichodesmium produces dissolved organic nitrogen, especially a certain amount of urea as a “new” nitrogen source, benefiting in particular populations of surrounding phytoplankton species.

Background: Although the changes of mitogen-activated protein kinase (MAPK) pathway in the central nervous system (CNS) induced by excessive fluoride has been confirmed by our previous findings, the underlying mechanism(s) of the action remains unclear. Here, we investigate the possibility that microRNAs (miRNAs) are involved in the aspect. Methods: As a model of chronic fluorosis, SD rats received different concentrations of fluoride in their drinking water for 3 or 6 months and SH-SY5Y cells were exposed to fluoride. Literature reviews and bioinformatics analyses were used to predict and real-time PCR to measure the expression of 12 miRNAs; an algorithm-based approach was applied to identify multiply potential target-genes and pathways; the dual-luciferase reporter system to detect the association of miR-132–3p with MAPK1; and fluorescence in situ hybridization to detect miR-132–3p localization. The miR-132–3p inhibitor or mimics or MAPK1 silencing RNA were transfected into cultured cells. Expression of protein components of the MAPK pathway was assessed by immunofluorescence or Western blotting. Results: In the rat hippocampus exposed with high fluoride, ten miRNAs were down-regulated and two up-regulated. Among these, miR-132–3p expression was down-regulated to the greatest extent and MAPK1 level (selected from the 220 genes predicted) was corelated with the alteration of miR-132–3p. Furthermore, miR-132–3p level was declined, whereas the protein levels MAPK pathway components were increased in the rat brains and SH-SY5Y cells exposed to high fluoride. MiR-132–3p up-regulated MAPK1 by binding directly to its 3′-untranslated region. Obviously, miR-132–3p mimics or MAPK1 silencing RNA attenuated the elevated expressions of the proteins components of the MAPK pathway induced by fluorosis in SH-SY5Y cells, whereas an inhibitor of miR-132–3p just played the opposite effect. Conclusion: MiR-132–3p appears to modulate the changes of MAPK signaling pathway in the CNS associated with chronic fluorosis.

Abstract Background Abdominal aortic calcification (AAC) is a crucial indicator of cardiovascular health. This study aims investigates the associations between dietary fatty acid intake and AAC. Methods In this study, a cross-sectional assessment was performed on a group of 2,897 individuals aged 40 and above, utilizing data from the NHANES. The focus was on examining dietary consumption of various fatty acids, including Saturated (SFA), Monounsaturated (MUFA), Polyunsaturated (PUFA), as well as Omega-3 and Omega-6. The evaluation of AAC was done by applying the Kauppila AAC score to results obtained from dual-energy X-ray absorptiometry scans. For statistical analysis, weighted multivariate linear and logistic regression were employed, with adjustments for variables like gender, age, ethnicity, and overall health condition. Results Participants with higher intake of SFA and PUFA showed a positive association with AAC score, while higher levels of dietary Omega-3 and Omega-6 fatty acids was connected with a negative correlation. Subgroup analyses indicated consistent associations across different sexes and age groups. The study found that an increase in SFA and PUFA intake correlated with an increase in AAC score, whereas Omega-3 and Omega-6 intake correlated with a decrease. Conclusion This study underscores the importance of dietary fatty acid composition in the prevalence of AAC and its potential implications for dietary guidelines and cardiovascular disease prevention strategies.

Abstract Lower back pain (LBP), which is a primary cause of disability, is largely attributed to intervertebral disc degeneration (IDD). Macrophages (MΦs) in degenerated intervertebral discs (IVDs) form a chronic inflammatory microenvironment, but how MΦs are recruited to degenerative segments and transform into a proinflammatory phenotype remains unclear. We evaluated chemokine expression in degenerated nucleus pulposus cells (NPCs) to clarify the role of NPCs in the establishment of an inflammatory microenvironment in IDD and explored the mechanisms. We found that the production of C-C motif chemokine ligand 2 (CCL2) and C-C motif chemokine ligand 7 (CCL7) was significantly increased in NPCs under inflammatory conditions, and blocking CCL2/7 and their receptor, C-C chemokine receptor type 2(CCR2), inhibited the inductive effects of NPCs on MΦ infiltration and proinflammatory polarization. Moreover, activation of the integrated stress response (ISR) was obvious in IDD, and ISR inhibition reduced the production of CCL2/7 in NPCs. Further investigation revealed that activating Transcription Factor 3 (ATF3) responded to ISR activation, and ChIP-qPCR verified the DNA-binding activity of ATF3 on CCL2/7 promoters. In addition, we found that Toll-like receptor 4 (TLR4) inhibition modulated ISR activation, and TLR4 regulated the accumulation of mitochondrial reactive oxygen species (mtROS) and double-stranded RNA (dsRNA). Downregulating the level of mtROS reduced the amount of dsRNA and ISR activation. Deactivating the ISR or blocking CCL2/7 release alleviated inflammation and the progression of IDD in vivo. Moreover, MΦ infiltration and IDD were inhibited in CCR2-knockout mice. In conclusion, this study highlights the critical role of TLR4/mtROS/dsRNA axis-mediated ISR activation in the production of CCL2/7 and the progression of IDD, which provides promising therapeutic strategies for discogenic LBP.

Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell responses, and 65.7% (23/35) had memory T-cell responses to VVT. Because of cross-immunity between the viruses, these findings can help guide mpox vaccination strategies in China.

Objective: A biological system's internal morphological structure or function can be changed as a result of the mechanical effect of focused ultrasound. Pulsed low-intensity focused ultrasound (LIFU) has mechanical effects that might induce follicle development with less damage to ovarian tissue. The potential development of LIFU as a non-invasive method for the treatment of female infertility is being considered, and this study sought to explore and confirm that LIFU can activate ovarian follicles. Results: We found a 50% increase in ovarian weight and in the number of mature follicles on the ultrasound-stimulated side with pulsed LIFU and intraperitoneal injection of 10 IU PMSG in 10-day-old rats. After ultrasound stimulation, the PCOS-like rats had a decrease in androgen levels, restoration of regular estrous cycle and increase in the number of mature follicles and corpora lutea, and the ratio of M1 and M2 type macrophages was altered in antral follicles of PCOS-like rats, consequently promoting further development and maturation of antral follicles. Conclusion: LIFU treatment could trigger actin changes in ovarian cells, which might disrupt the Hippo signal pathway to promote follicle formation, and the mechanical impact on the ovaries of PCOS-like rats improved antral follicle development.

Study area: Karst region in Guangxi Province, Southwest China. Study focus: Both soil properties and rainfall characteristics have a critical influence on splash erosion and aggregate stability. However, the impact of electrolytes on splash erosion has received less attention. In this study, soils from 4 typical land use types (cropland, orchard, artificial forest and secondary forest) in karst region were utilized as the research objects. NaCl, KCl, and MgCl2 solutions of different concentrations were used to determine the stability of the aggregates via fast wetting (FW) treatment of Le Bissonnais (LB) method and the characteristics of splash erosion via simulated rainfall experiments. New hydrological insights for the region: Results revealed that both the land use types and electrolyte significantly influenced the soil aggregate stability and splash characteristics. Specifically, the change in land use from cropland to orchard, artificial forest and secondary forest significantly increased the aggregate stability, thus decreasing soil erodibility. The aggregate stability decreased and the total splash rate increased as the electrolyte concentration increased. The total splash erosion rate of the 4 soils was positively correlated with the

ObjectiveTo examine the prognostic values of systemic immune-inflammation indices of hemodialysis (HD) vascular access failure and develop a prediction model for vascular access failure based on the most pertinent systemic immune-inflammation index.Study designA prospective cohort study.Setting & participantsPatients undergoing autogenous HD vascular access surgeries or arteriovenous graft as a permanent hemodialysis access in a tertiary center in southwest China from January 2020 to June 2022.PredictorsSystemic immune-inflammation indices, including NLR, dNLR, AAPR, SIRI, SII, PNI, PLR, and LIPI, and clinical variables.OutcomesThe outcome was defined as survival of the hemodialysis access, with both occluded and stenotic access being considered as instances of access failure.Analytical approachCox proportional hazard regression model.Results2690 patients were included in the study population, of whom 658 experienced access failure during the follow-up period. The median duration of survival for HD vascular access was 18 months. The increased systemic immune-inflammation indices, including dNLR, NLR, SII, PNI, SIRI, PLR, and LIPI, are predictive of HD access failure, with SII demonstrating the strongest prognostic value. A simple SII-based prediction model for HD access failure was developed, achieving C-indexes of 0.6314 (95% CI: 0.6249 – 0.6589) and 0.6441 (95% CI: 0.6212 – 0.6670) for predicting 6- and 12-month access survival, respectively.ConclusionsSystemic immune-inflammation indices are significantly and negatively associated with HD vascular access survival. A simple SII-based prediction model was developed and anticipates further improvement through larger study cohort and validation from diverse centers.

BackgroundPreventable harms from medications are significant threats to patient safety in community settings, especially among ambulatory older adults on multiple prescription medications. Patients may partner with primary care professionals by taking on active roles in decisions, learning the basics of medication self-management, and working with community resources. ObjectiveThis study aims to assess the impact of a set of patient partnership tools that redesign primary care encounters to encourage and empower patients to make more effective use of those encounters to improve medication safety. MethodsThe study is a nonrandomized, cross-sectional stepped wedge cluster-controlled trial with 1 private family medicine clinic and 2 public safety-net primary care clinics each composing their own cluster. There are 2 intervention sequences with 1 cluster per sequence and 1 control sequence with 1 cluster. Cross-sectional surveys will be taken immediately at the conclusion of visits to the clinics during 6 time periods of 6 weeks each, with a transition period of no data collection during intervention implementation. The number of visits to be surveyed will vary by period and cluster. We plan to recruit patients and professionals for surveys during 405 visits. In the experimental periods, visits will be conducted with two partnership tools and associated clinic process changes: (1) a 1-page visit preparation guide given to relevant patients by clinic staff before seeing the provider, with the intention to improve communication and shared decision-making, and (2) a library of short educational videos that clinic staff encourage patients to watch on medication safety. In the control periods, visits will be conducted with usual care. The primary outcome will be patients’ self-efficacy in medication use. The secondary outcomes are medication-related issues such as duplicate therapies identified by primary care providers and assessment of collaborative work during visits. ResultsThe study was funded in September 2019. Data collection started in April 2023 and ended in December 2023. Data was collected for 405 primary care encounters during that period. As of February 15, 2024, initial descriptive statistics were calculated. Full data analysis is expected to be completed and published in the summer of 2024. ConclusionsThis study will assess the impact of patient partnership tools and associated process changes in primary care on medication use self-efficacy and medication-related issues. The study is powered to identify types of patients who may benefit most from patient engagement tools in primary care visits. Trial RegistrationClinicalTrials.gov NCT05880368; https://clinicaltrials.gov/study/NCT05880368 International Registered Report Identifier (IRRID)DERR1-10.2196/57878

An increasing number of studies in pragmatics, second language acquisition, and related fields have opted to use sitcom conversations as a substitute for natural conversations in their analyses. However, few studies have critically examined the validity of this substitution. Taking this into consideration, the present study aims to examine the lexical similarities and differences between sitcom and natural conversations by utilizing the Friends Corpus and the Santa Barbara Corpus of Spoken American English as samples under a synthesized analytic framework of six lexical categories that have been frequently examined in previous research. The findings indicate that there are significant differences between sitcom and natural conversations at the lexical level, particularly in terms of word lengths, keywords, and the use of discourse markers, personal pronouns, vocatives, and religious words. While sitcom conversations tend to be more concise, interactive, evaluative, and involving, natural conversations provide more explanations for their speech acts and refer to their parties who are not present in the conversations. Additionally, sitcom conversations use more intensifiers and vocatives while using fewer tentative modals, expletives, and religious words. Based on these results, it can be concluded that sitcom conversations do not fully depict the conversations in sitcoms, and thus substituting natural conversations with those in sitcoms should be approached with caution in language teaching and research. This study provides insight into the differences in lexical patterns between two types of conversations, and highlights the importance of using natural conversations as a basis for language teaching and research.

This study aimed to design an evaluation scale of traditional Chinese medicine (TCM) confidence and then evaluate its validity and reliability.

Abstract Redundant nodes in a kernel incremental extreme learning machine (KI-ELM) increase ineffective iterations and reduce learning efficiency. To address this problem, this study established a novel improved hybrid intelligent deep kernel incremental extreme learning machine (HI-DKIELM), which is based on a hybrid intelligent algorithm and a KI-ELM. First, a hybrid intelligent algorithm was established based on the artificial transgender longicorn algorithm and multiple population gray wolf optimization methods to reduce the parameters of hidden layer neurons and then to determine the effective number of hidden layer neurons. The learning efficiency of the algorithm was improved through the reduction of network complexity. Then, to improve the classification accuracy and generalization performance of the algorithm, a deep network structure was introduced to the KI-ELM to gradually extract the original input data layer by layer and realize high-dimensional mapping of data. The experimental results show that the number of network nodes of HI-DKIELM algorithm is obviously reduced, which reduces the network complexity of ELM and greatly improves the learning efficiency of the algorithm. From the regression and classification experiments, its CCPP can be seen that the training error and test error of the HI-DKIELM algorithm proposed in this paper are 0.0417 and 0.0435, which are 0.0103 and 0.0078 lower than the suboptimal algorithm, respectively. On the Boston Housing database, the average and standard deviation of this algorithm are 98.21 and 0.0038, which are 6.2 and 0.0003 higher than the suboptimal algorithm, respectively.

Abstract Aims Coronary artery disease (CAD) is the most common cause of heart failure (HF). This study aimed to identify cytokine biomarkers for predicting HF in patients with CAD. Methods and results Twelve patients with CAD without HF (CAD‐non HF), 12 patients with CAD complicated with HF (CAD‐HF), and 12 healthy controls were enrolled for Human Cytokine Antibody Array, which were used as the training dataset. Then, differentially expressed cytokines among the different groups were identified, and crucial characteristic proteins related to CAD‐HF were screened using a combination of the least absolute shrinkage and selection operator, recursive feature elimination, and random forest methods. A support vector machine (SVM) diagnostic model was constructed based on crucial characteristic proteins, followed by receiver operating characteristic curve analysis. Finally, two validation datasets, GSE20681 and GSE59867, were downloaded to verify the diagnostic performance of the SVM model and expression of crucial proteins, as well as enzyme‐linked immunosorbent assay was also used to verify the levels of crucial proteins in blood samples. In total, 12 differentially expressed proteins were overlapped in the three comparison groups, and then four optimal characteristic proteins were identified, including VEGFR2, FLRG, IL‐23, and FGF‐21. After that, the area under the receiver operating characteristic curve of the constructed SVM classification model for the training dataset was 0.944. The accuracy of the SVM classification model was validated using the GSE20681 and GSE59867 datasets, with area under the receiver operating characteristic curve values of 0.773 and 0.745, respectively. The expression trends of the four crucial proteins in the training dataset were consistent with those in the validation dataset and those determined by enzyme‐linked immunosorbent assay. Conclusions The combination of VEGFR2, FLRG, IL‐23, and FGF‐21 can be used as a candidate biomarker for the prediction and prevention of HF in patients with CAD.

Elastomeric scaffolds, individually customized to mimic the structural and mechanical properties of natural tissues have been used for tissue regeneration. In this regard, polyester elastic scaffolds with tunable mechanical properties and exceptional biological properties have been reported to provide mechanical support and structural integrity for tissue repair. Herein, poly(4-methyl-ε-caprolactone) (PMCL) was first double-terminated by alkynylation (PMCL-DY) as a liquid precursor at room temperature. Subsequently, three-dimensional porous scaffolds with custom shapes were fabricated from PMCL-DY via thiol-yne photocrosslinking using a practical salt template method. By manipulating the Mn of the precursor, the modulus of compression of the scaffold was easily adjusted. As evidenced by the complete recovery from 90% compression, the rapid recovery rate of >500 mm min−1, the extremely low energy loss coefficient of

Abstract Exogenous stem cell therapy and endogenous repair has shown great potential in intervertebral disc regeneration. However, limited nutrients and accumulation of lactate largely impair the survival and regenerative capacity of implanted stem cells and endogenous nucleus pulposus cells (NPCs). Herein, an injectable hydrogel microsphere (LMGDNPs) have been developed by immersing lactate oxidase (LOX)‐manganese dioxide (MnO2) nanozyme (LM) into glucose‐enriched decellularized nucleus pulposus hydrogel microspheres (GDNPs) through a microfluidic system. LMGDNPs showed a delayed release profile of LOX and satisfactory enzymatic capacity in consuming lactate. Mesenchymal stem cells (MSCs) plated on LMGDNPs exhibited better cell viability than cells on GelMA and decellularized nucleus pulposus microspheres (DNP) and showed a obviously increased NPCs phenotype. LMGDNPs prevented MSCs and NPCs death and promoted extracellular matrix synthesis by exhausting lactate. It is determined that LMGDNPs promoted NPCs autophagy by activating transforming growth factor β2 overlapping transcript 1 (TGFB2‐OT1), relying on the nanozyme. MSCs‐loaded LMGDNPs largely preserved disc hydration and alleviated matrix degradation in vivo. Summarily, LMGDNPs promoted cell survival and matrix regeneration by providing a nutrient supply, exhausting lactate, and activating autophagy via TGFB2‐OT1 and its downstream pathway and may serve as an ideal delivery system for exogenous stem cell therapy and endogenous repair.

By the analytical method, this paper investigates the mode-coupling friction-induced instability and the resulting stick-slip self-excited vibration of the marine stern water-lubricated rubber bearing-shaft system. The 2-DOF simplified theoretical model is reasonably developed to characterize stern water-lubricated rubber bearing-shaft system. The complex eigenvalue analysis is conducted to analyze the instability behaviors of the model. Results show the normal force and nonlinear stiffness often deteriorate the stability of the model. Subsequently, two types of analytical expressions for stick-slip vibration amplitude of the model are by the Krylov-Bogoliubbov-Mitropolsky method, which match well with the results from numerical integration. Then, parameter discussion about the influences of friction coefficient, damping, normal force and nonlinear contact stiffness on self-excited vibration amplitudes are performed. The results indicate that the bearing-shaft system can keep the steady-state static equilibrium or the oscillations with small amplitude if the proper parameter values of the variables are chosen, which will benefits controlling the friction-induced vibration of the water-lubricated rubber bearing-shaft system. The novelty of this work is to give analytical expressions for stick-slip self-excited vibration amplitude of the simplified model.

BackgroundPituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory.MethodsWe systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform.ResultsOur study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs.ConclusionBased on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.

The gut microbiota undergoes substantial changes in COVID-19 patients; yet, the utility of these alterations as prognostic biomarkers at the time of hospital admission, and its correlation with immunological and hematological parameters, remains unclear. The objective of this study is to investigate the gut microbiota's dynamic change in critically ill patients with COVID-19 and evaluate its predictive capability for clinical outcomes alongside immunological and hematological parameters. In this study, anal swabs were consecutively collected from 192 COVID-19 patients (583 samples) upon hospital admission for metagenome sequencing. Simultaneously, blood samples were obtained to measure the concentrations of 27 cytokines and chemokines, along with hematological and biochemical indicators. Our findings indicate a significant correlation between the composition and dynamics of gut microbiota with disease severity and mortality in COVID-19 patients. Recovered patients exhibited a higher abundance of Veillonella and denser interactions among gut commensal bacteria compared to deceased patients. Furthermore, the abundance of gut commensal bacteria exhibited a negative correlation with the concentration of proinflammatory cytokines and organ damage markers. The gut microbiota upon admission showed moderate prognostic prediction ability with an AUC of 0.78, which was less effective compared to predictions based on immunological and hematological parameters (AUC 0.80 and 0.88, respectively). Noteworthy, the integration of these three datasets yielded a higher predictive accuracy (AUC 0.93). Our findings suggest the gut microbiota as an informative biomarker for COVID-19 prognosis, augmenting existing immune and hematological indicators.

Bulk grain categorized storage, is a modern grain storage technology with the aims to meet the requirements of optimal purchase, storage, and sales, guided by grain usage and quality control. The increase of high-quality grain supply represents the development direction of refined management in grain storage. The determination of the storage capacity of a single warehouse is directly related to the types, grain varieties, uses of grain, and quality control technology in the process of discharging the warehouse. Based on the analysis of the grain storage use, the problems existing in the sales and the acceptance capacity of customers, it is addressed that the size of the grain storage single warehouse for different grain varieties and different uses should be matched with the acceptance capacity of the sales destination. Under the existing technical conditions, the relevant opinions and suggestions were preliminary proposed on the appropriate single warehouse capacity scale, which could match the customer acceptance capacity, the grain storage quality control technology and the research on grain warehouse type.

Abstract Thermal homeostasis is vital for mammals and is controlled by brain neurocircuits. Yet, the neural pathways responsible for cold defense regulation are still unclear. Here, we found that a pathway from the lateral parabrachial nucleus (LPB) to the dorsomedial hypothalamus (DMH), which runs parallel to the canonical LPB to preoptic area (POA) pathway, is also crucial for cold defense. Together, these pathways make an equivalent and cumulative contribution, forming a parallel circuit. Specifically, activation of the LPB → DMH pathway induced strong cold-defense responses, including increases in thermogenesis of brown adipose tissue (BAT), muscle shivering, heart rate, and locomotion. Further, we identified somatostatin neurons in the LPB that target DMH to promote BAT thermogenesis. Therefore, we reveal a parallel circuit governing cold defense in mice, which enables resilience to hypothermia and provides a scalable and robust network in heat production, reshaping our understanding of neural circuit regulation of homeostatic behaviors.

To analyze the chemical components of the tender leaves of Cyclocarya paliurus, a rapid qualitative analysis of the chemical components of the percolation extracts of the tender leaves of Cyclocarya paliurus was carried out by ultrahigh-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). Mass spectrum data were collected in the positive and negative ion modes, and MassHunter qualitative analysis software was used, according to the retention time and mass spectrum information of each compound, combined with existing literature and mass spectrum databases, the compounds were analyzed for the fragmentation rule, 94 compounds were identified from Cyclocarya paliurus, including 29 flavonoids, 16 triterpenes, 25 organic acids, 24 other compounds. The analysis results showed that the percolation extract of Cyclocarya paliurus contained flavonoids, organic acids, triterpenoids, coumarins, amino acids, and other compounds, and malic acid, hesperidin, rosin, 6,7-dihydroxycoumarin, 6-methylcoumarin, 5,7-dimethoxycoumarin are found in Cyclocarya paliurus for the first time. This study can lay a foundation for further clarifying the material basis of Cyclocarya paliurus. It provides a theoretical basis for the development of relevant products of Cyclocarya paliurus.

Abstract A pediatric patient suffered from renal and hepatic abscesses (through hepatorenal space) and recovered by antibiotics and other therapies. By clinical analysis, the multi-organ abscesses might be caused by bloodstream-disseminated infection. In order to identify the pathogen, we collected kidney biopsy tissue, swabs, and plasma samples, and used metagenomics next-generation sequencing (mNGS) and some traditional methods. The results revealed that polymicrobial especially anaerobic bacteremia (Bacteroides fragilis, et al.) contributed to the abscess formation. What is more, systematic human adenovirus C (HAdV-C) infection was shown, and the virus was isolated. The titer of HAdV-2 neutralizing antibodies was 1/4 in the plasma after symptoms onset. Although the exact mechanism of HAdV-2 infection in multiple abscess formation has not been clarified, the case of multi-organ abscesses in the context of polymicrobial especially anaerobic bacteremia and HAdV infection in healthy children is infrequent.

Abstract Metabolomics, an emerging omics technology developed in the post‐gene age, is an important part of systems biology. It interprets the pathophysiological state of the subject by quantitatively describing the dynamic changes of metabolites through analytical methods, mainly mass spectrometry (MS) and nuclear magnetic resonance (NMR). Assisted reproductive technology (ART) is a method used to manipulate sperm, oocytes, and embryos to achieve conception. Recently, several studies have reported that metabolomics methods can be used to measure metabolites in ART samples; these metabolites can be used to evaluate the quality of gametes and embryos. This article reviews the progress of research on metabolomics and the application of this technology in the field of ART, thus providing a reference for research and development directions in the future.

The aerobic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) plays a pivotal role in the synthesis of renewable, biodegradable plastics and sustainable chemicals. Although supported gold nanoclusters (NCs) exhibit significant potential in this process, they often suffer from low selectivity. To address this challenge, a series of gold-M (M means Ni, Fe, Cu, and Pd) bimetallic NCs catalysts were designed and synthesized to facilitate the selective oxidation of HMF to FDCA. Our findings indicate that the introduction of doped metals, particularly Ni and Pd, not only improves the reaction rates for HMF tandem oxidation but also promotes high yields of FDCA. Various characterizations techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), in situ diffuse reflectance infrared Fourier transform spectroscopy of CO adsorption (CO-DRIFTS), and temperature-programmed desorption of oxygen (O2-TPD), were employed to scrutinize the structural and electronic properties of the prepared catalysts. Notably, an electronic effect was observed across the Au-based bimetallic catalysts, facilitating the activation of reactant molecules and enhancing the catalytic performance. This study provides valuable insights into the alloy effects, aiding in the development of highly efficient Au-based bimetallic catalysts for biomass conversions.

Abstract Diagnostic and therapeutic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, we present a flexible, biodegradable photonic device called iCarP with a micrometer scale air gap between a refractive polyester patch and the embedded removable tapered optical fiber. ICarP combines the advantages of light diffraction by the tapered optical fiber, dual refractions in the air gap, and reflection inside the patch to obtain a bulb-like illumination, guiding light towards target tissue. We show that iCarP achieves large area, high intensity, wide spectrum, continuous or pulsatile, deeply penetrating illumination without puncturing the target tissues and demonstrate that it supports phototherapies with different photosensitizers. We find that the photonic device is compatible with thoracoscopy-based minimally invasive implantation onto beating hearts. These initial results show that iCarP could be a safe, precise and widely applicable device suitable for internal organs and tissue illumination and associated diagnosis and therapy.

Abstract Background Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. Methods A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. Results Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06–92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p

Glued laminated bamboo (glubam) is a type of bamboo-based lamina, and manufactured by pressure lamination of phenol-formaldehyde saturated bamboo strips under elevated temperature. Estimating, controlling, and limiting the formaldehyde release from glubam are important issues in indoor air quality of building with glubam. This study investigates formaldehyde emission characteristics from two types of glubam under different conditions including temperature, relative humidity, edge treatment, and surface covering material. A series of formaldehyde concentration tests were performed using 1 m3 climate chamber. The results indicate that the peak values of the formaldehyde concentration of glubam specimens under all testing conditions are lower than 0.124 mg/m3, and thus can be classified as Class E1 according to EN 13986. An analysis model was provided to estimate formaldehyde release based on the test data and a first-order decay model. Initial formaldehyde emission rate E0 and decay rate constant k in the proposed model was utilized for comparison and analysis of the experimental parameters. This investigation reveals that the temperature and relative humidity have significant influence on the formaldehyde emission characteristics of glubam boards. Sealing cutting edges and covering surface layer of the samples can significantly reduce the releasing rate and amount of formaldehyde from glubam.

ABSTRACTThe adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not BA.4/5 and induced neutralization against prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to prototype strain and Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine dose only. The breakthrough infection individuals produced stronger adaptive immunity than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adaptive immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. Omicron sublineages, especially for those emerged after BA.4/5 strain, evade NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.

Liver cancer is a common malignant tumor, and its incidence is increasing yearly. Millions of people suffer from liver cancer annually, which has a serious impact on global public health security. Licochalcone A (Lico A), an important component of the traditional Chinese herb licorice, is a natural small molecule drug with multiple pharmacological activities. In this study, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma cell lines (HepG2 and Huh-7), and explored the inhibitory mechanism of Lico A on hepatocellular carcinoma. First, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma, and showed that Lico A significantly inhibited and killed HepG2 and Huh-7 cells in vivo and in vitro. Transcriptomic analysis showed that Lico A inhibited the expression of solute carrier family 7 member 11 (SLC7A11), which induced ferroptosis. We confirmed through in vivo and in vitro experiments that Lico A promoted ferroptosis in hepatocellular carcinoma cells by downregulating SLC7A11 expression, thereby inhibiting the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway and inducing activation of reactive oxygen species (ROS). In this study, we suggest that Lico A is a potential SLC7A11 inhibitor that induces ferroptotic death in hepatocellular carcinoma cells, thereby providing a theoretical basis for the development of natural small molecule drugs against hepatocellular carcinoma.

Objective To explore the different effects of rapid hypothermia on the electrophysiological characteristics of pyramidal neurons and interneurons in epileptic patients. Methods A total of 13 brain tissue samples were selected from patients with focal drug ⁃ resistant epilepsy who underwent epileptogenic lesion resection in Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University from June to December 2016. Using perfusion method, the brain tissue slice temperature was quickly reduced to 20 ℃ in a step manner, then rewarmed to 30 ℃, and maintained at 30 ℃ for 10 min (the target temperature was changed by 5 ℃ every 10 min). Patch clamping technique was used to record the resting membrane potential, synaptic activity and action potential of pyramidal neurons (n=18) and interneurons (n=6) in epileptic cerebral cortex. Results 1) Resting membrane potential: when the temperature dropped to 20 ℃, the resting membrane potential of the two kinds of neurons showed slight depolarization, but there was no statistical significance in the changes of resting membrane potential at different temperatures and the changes of resting membrane potential of the two kinds of neurons at the same temperature (P＞0.05, for all). 2) Synaptic activity: after cooling, the amplitude of excitatory postsynaptic current (EPSC) of interneuron was smaller (F=5.332, P=0.034). The normalized percentages of EPSC (F=8.811, P=0.000) and inhibitory postsynaptic current (IPSC; F=9.843, P=0.000) amplitude, EPSC event interval (F=7.065, P=0.001), EPSC (F=6.281, P=0.002) and IPSC (F=8.266, P=0.000) peak area were statistically significant. 3) Action potential: there were no significant differences in the effects of temperature change on the normalized percentages of the threshold, frequency, amplitude and half⁃width time of the action potential of the two kinds of neurons (P＞0.05, for all). However, the differences of normalized percentages of action potential frequency (F=4.801, P=0.008), amplitude (F=3.680, P=0.015) and half⁃width time (F=28.951, P=0.000) of neuronal action potentials at different temperatures were statistically significant. Conclusions When the temperature was reduced to 20 ℃, the electrophysiological activities of the two kinds of neurons were significantly inhibited. The inhibition of EPSC amplitude of synaptic activity in interneurons was stronger than that in pyramidal neurons. Inhibition of interneuron activity may be one of the reasons for hypothermia prevention and termination of epilepsy.

Studies of environmental chemistry and its related life science are essential to understand the exposure of environmental pollution to living species and the resulted health problems. During this process, mass spectrometry is an indispensably powerful tool thanks to its qualitative and quantitative abilities and remarkable mass resolution. In this review, the state-of-the art mass spectrometric methods were introduced, including inductively coupled plasma mass spectrometry (ICP-MS), electron capture negative ionization mass spectrometry (ECNI-MS), electrospray ionization mass spectrometry (ESI-MS), matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), high-resolution tandem mass spectrometry (HR-MS) and native mass spectrometry (nMS) as well as mass spectrometry imaging (MSI), which have been applied in environmental chemistry and the related life science research, with an emphasis on their role in the determination, characterization, discovery and biological impacts research of environmental pollutants in the environmental media, and the related metabolites during life process. Furthermore, the trend of MS methods from fundamental to applied perspectives was outlooked, in order to solve the emerging issues, such as the ambiguous interaction mechanisms of the environmental pollutants and/or their metabolites with biomolecules. It is very much expected that novel MS-based strategy like reactive proteomics approach together with the design of new molecular ruler will help to solve the “mystery” of the environmental pollutants and/or their biological metabolites impacted on a normal physiological process, deepening our understanding on the influence of environmental pollution on health.

The deep grooves often appeared in the commutator of aircraft photoelectric radar motors due to the brush's wear, which resulted in decreased of electrical performance and commutation accuracy, affecting combat performance. Here, we present that the blue laser cladding could be used to repair the faulty part of the pure copper motor commutator. The microstructure, microhardness, wear resistance, and electrical conductivity results show that the surface of the coating was smooth and there were no pores, cracks, and other defects in the bonding interface. There was an apparent transition zone between the matrix and the cladding layer, and a good metallurgical bonding with the matrix was formed. Compared with the matrix, the average microhardness and wear resistance of the cladding layer were increased by 2.22 times and 2.37 times, better than the copper substrate, while the electrical conductivity of the repaired layer was still about 97.7% of that of the pure copper substrate. Our study demonstrates the potential of applying the optimum technological parameters of laser cladding repair to provide the theoretical and experimental basis for mass repair.

The establishment and improvement of an innovation ecosystem have become important issues in building an innovative powerhouse. Built on the background of innovation ecosystem, from the perspective of cooperative interaction and dynamics, this study introduces value co-creation and dynamic capabilities, and analyzes how the proximity between enterprises and scientific research organizations and between enterprises affects enterprise innovation performance. The results demonstrate that, on the one hand, the proximity between enterprises and scientific research organizations and between enterprises can directly have an inverted U-shaped effect on enterprise innovation performance. On the other hand, it can indirectly have an inverted U-shaped effect on enterprise innovation performance through the partial mediating effect of value co-creation. Dynamic capabilities play a major role in regulating the relationship between proximity and enterprise innovation performance, as well as value co-creation and enterprise innovation performance. The research results expand the research in the field of innovation ecosystems, reveal the marginal effect of value co-creation on enterprise innovation performance, and help enterprises in the system to clarify how to improve innovation performance through proximity strategies and value co-creation activities with scientific institutions and other enterprises.

The use of gold nanoparticles (Au NPs) as catalysts has gained widespread attention in various reactions due to their high activity and selectivity under mild reaction conditions. However, one major challenge in utilizing these catalysts is their tendency to aggregate, leading to catalyst deactivation and hindering their amplification and industrial application. To overcome this issue, herein, we used a method by coating the surface of Au NPs with a thin layer of SiO2, which resulted in the formation of a superior catalyst denoted as Au@SiO2/ZA. Characterization studies revealed that the SiO2 layer is coated on the surface of Au NPs and effectively prevents the aggregation and growth of the gold particles during the reaction process, which makes the catalyst display excellent stability in furfural (FF) oxidative esterification to methyl furoate (MF). Moreover, the stabilization strategy is not limited to SiO2 alone. It can also be extended to other oxides such as ZrO2, CeO2, and TiO2. We believe this work will provide a good reference for the design and development of an efficient and stable gold catalyst for the oxidative esterification reaction.

Rare earths are a kind of mineral resource with important strategic value, playing an irreplaceable key role in modern high-tech development and other fields. However, how to realize the efficient and green mining of rare earth resources has been a key issue that the rare earth industry has been trying to break through, because the rare earth mining process is prone to pollute ecological environments such as soil and water. Ion adsorption rare earth ore, mainly distributed in the south of China, is one of the rare earths, for which rare earth researchers have developed a new process leaching system with magnesium salt. In this study, the soil environmental problems as well as the microbial community structure underneath this new process heap-leaching demonstration site are evaluated. The results of the study showed that under the new process, there was a significant accumulation of sulfate content in the soil of the heap-leaching site and an imbalance in the soil calcium-magnesium ratio, which may disrupt the soil structure and reduce soil fertility. Meanwhile, the microbial community structure before and after the leaching site showed large differences at different points and depths, but didn't cause ecological risks. This study helps us to understand the environmental problems and impacts that may be caused by the new process of magnesium salt, and also helps to promote the application of the new process of magnesium salt leaching of ion adsorption rare earth ore, which lays the foundation for the exploitation of rare earth resources.

Background Our aim was to understand actions by primary care teams to improve medication safety.Methods This was a qualitative study using one-on-one, semistructured interviews with the questions guided by concepts from collaborative care and systems engineering models, and with references to the care of older adults. We interviewed 21 primary care physicians and their team members at four primary care sites serving patients with mostly low socioeconomic status in Southwest US during 2019–2020. We used thematic analysis with a combination of inductive and deductive coding. First, codes capturing safety actions were incrementally developed and revised iteratively by a team of multidisciplinary analysts using the inductive approach. Themes that emerged from the coded safety actions taken by primary care professionals to improve medication safety were then mapped to key principles from the high reliability organisation framework using a deductive approach.Results Primary care teams described their actions in medication safety mainly in making standard-of-care medical decisions, patient-shared decision-making, educating patients and their caregivers, providing asynchronous care separate from office visits and providing clinical infrastructure. Most of the actions required customisation at the individual level, such as limiting the supply of certain medications prescribed and simplifying medication regimens in certain patients. Primary care teams enacted high reliability organisation principles by anticipating and mitigating risks and taking actions to build resilience in patient work systems. The primary care teams’ actions reflected their safety organising efforts as responses to many other agents in multiple settings that they could not control nor easily coordinate.Conclusions Primary care teams take many actions to shape medication safety outcomes in community settings, and these actions demonstrated that primary care teams are a reservoir of resilience for medication safety in the overall healthcare system. To improve medication safety, primary care work systems require different strategies than those often used in more self-contained systems such as hospital inpatient or surgical services.