Characterization of the key odorants in goji wines in three levels of sweetness by applications of sensomics approach.

The correlations and differences of the key odorants were systematically conducted among three sweetness of goji wines by the sensomics approach. After aroma (extract) dilution analysis, 67, 67, and 66 odorants were screened in sweet goji wine, semi-dry goji wine, and dry goji wine, in which, 63 odorants were identified in all goji wines. Determination of 53 odorants revealed a total of 30 odorants with the concentrations surpassing their olfactory thresholds. Overall, the odor activity values (OAVs) of ketones decreased, while esters, alcohols, phenols, and aldehydes increased with the decrease in sweetness in goji wine samples. Nevertheless, (E)-ß-damascenone, trans- and cis-whisky lactones, and 3-methyl-2,4-nonanedione, evoked cooked apple-like, coconut-like, and hay-like odor impressions in goji wines and showed the highest OAVs. A reliable evaluation of the aroma contributions was executed as aroma recombinations and suggested a successful evaluation of key odorants in goji wines.

Octopus[5]arene from Pagoda[5]arene by Macrocycle-to-Macrocycle Conversion.

Macrocycle-to-macrocycle conversion is an effective strategy to construct new macrocyclic arenes with specific structures. Herein, a new class of chiral macrocyclic arene, namely, octopus[5]arenes (Oc5s), cannot be synthesized by the direct approach from the corresponding chiral monomers but can be successfully achieved by a macrocycle-to-macrocycle conversion strategy utilizing racemic pagoda[5]arenes as the starting materials. It was found that enantiomeric Oc5s showed fixed conformations and stable chiral structures and exhibited significant chiral recognition toward chiral diamines.

Effective process quality control management for constipation prevention in hospitalized patients with acute coronary syndrome: An observational study.

Objective: To evaluate the effectiveness of monitoring and managing process quality control indicators in the prevention of constipation among hospitalized patients with acute coronary syndrome (ACS). Methods: A total of 512 hospitalized patients diagnosed with ACS between January and June 2022 were screened for inclusion in the study. Ultimately, 456 eligible participants were enrolled and divided into two groups based on the chronological order of admission: the control group and the observation group. Upon admission, both groups of patients received routine constipation prevention measures in the department. However, the observation group was subjected to targeted process quality control management, which included monitoring and managing five indicators related to constipation prevention: correctness of bowel movement recording; usage rate of laxatives; execution rate of physical interventions; implementation rate of constipation prevention education; completion rate of dietary structure and habit assessments. Data were analyzed using SPSS, with t tests and χ 2 tests for group comparisons. Results: In comparison to the control group, the observation group demonstrated significant advantages in terms of constipation incidence, completion rates of the five process quality control indicators, occurrence rates of adverse cardiac events during defecation, and PHQ-9 scores before discharge. These disparities demonstrated statistical significance with a p value < 0.05. Conclusion: Target-oriented process quality control management is shown to be effective in reducing constipation incidence and adverse cardiac events during constipation episodes, as well as alleviating depressive symptoms among ACS patients, thus providing a safe and effective approach to constipation prevention.

Genome-wide identification and expression analysis of the U-box E3 ubiquitin ligase gene family related to bacterial wilt resistance in tobacco (Nicotiana tabacum L.) and eggplant (Solanum melongena L.).

The E3 enzyme in the UPS pathway is a crucial factor for inhibiting substrate specificity. In Solanaceae, the U-box E3 ubiquitin ligase has a complex relationship with plant growth and development, and plays a pivotal role in responding to various biotic and abiotic stresses. The analysis of the U-box gene family in Solanaceae and its expression profile under different stresses holds significant implications. A total of 116 tobacco NtU-boxs and 56 eggplant SmU-boxs were identified based on their respective genome sequences. Phylogenetic analysis of U-box genes in tobacco, eggplant, tomato, Arabidopsis, pepper, and potato revealed five distinct subgroups (I-V). Gene structure and protein motifs analysis found a high degree of conservation in both exon/intron organization and protein motifs among tobacco and eggplant U-box genes especially the members within the same subfamily. A total of 15 pairs of segmental duplication and 1 gene pair of tandem duplication were identified in tobacco based on the analysis of gene duplication events, while 10 pairs of segmental duplication in eggplant. It is speculated that segmental duplication events are the primary driver for the expansion of the U-box gene family in both tobacco and eggplant. The promoters of NtU-box and SmU-box genes contained cis-regulatory elements associated with cellular development, phytohormones, environment stress, and photoresponsive elements. Transcriptomic data analysis shows that the expression levels of the tobacco and eggplant U-box genes in different tissues and various abiotic stress conditions. Using cultivar Hongda of tobacco and cultivar Yanzhi of eggplant as materials, qRT-PCR analysis has revealed that 15 selected NtU-box genes and 8 SmU-box may play important roles in response to pathogen Ras invasion both in tobacco and eggplant.

Mesenchymal stem cells-derived exosomes alleviate liver fibrosis by targeting Hedgehog/SMO signaling.

BACKGROUND & AIMS: Despite increasing knowledge regarding the cellular and molecular mechanisms of liver fibrogenesis, there is currently no approved drug for the treatment of liver fibrosis. Mesenchymal stem cells (MSCs) are multipotent progenitor cells representing an attractive therapeutic tool for tissue damage and inflammation. This study was designed to determine the protective effect and underlying mechanism of human umbilical cord-derived MSCs (UC-MSCs) on thioacetamide-induced liver fibrosis. METHODS: Liver fibrosis was induced in mice by intraperitoneal injection of thioacetamide (TAA). Some mice were then given injection of UC-MSCs or UC-MSCs-derived exosomes (UC-MSCs-Exo) via the tail vein. Liver tissues were collected for histologic analysis. RESULTS: We found that administration of UC-MSCs significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels, and attenuated hepatic inflammation and fibrosis. Moreover, the therapeutic effect of UC-MSCs-derived exosomes was similar to that of UC-MSCs. Intriguingly, UC-MSCs-Exo treatment downregulated the expression of smoothened (SMO), a fundamental component of Hedgehog signaling which plays a critical role in fibrogenesis, and subsequently inhibited the activation of hepatic stellate cells, a central driver of fibrosis in experimental and human liver injury. Furthermore, the anti-inflammatory and anti-fibrotic effects of UCMSCs- Exo was reversed by the SMO agonist SAG treatment in mice. CONCLUSION: Our findings suggest that UC-MSCs-Exo exert therapeutic effects on liver fibrosis, at least in part, through inhibiting the Hedgehog/SMO signaling pathway.

Circ-PITX1 promotes non-small-cell lung cancer progression through regulating ETS1 expression via miR-615-5p.

BACKGROUND: Circular RNAs (circRNAs), produced by reverse splicing, act as important players in human cancers. We aimed to assess the biological functions of circRNA pituitary homeobox 1 (circ-PITX1) in non-small-cell lung cancer (NSCLC). METHODS: qRT-PCR was employed to determine RNA expression. Biological behaviors of NSCLC cells were assessed by CCK-8, colony formation, EdU assay, flow cytometry, wound healing, and transwell assays. Glutamine catabolism was examined via the measurement of glutamine consumption, α-ketoglutarate levels, as well as ATP levels. Protein levels were detected by western blot assays. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to reveal the mechanism responsible for circ-PITX1 regulating NSCLC cell malignancy. The murine xenograft model was established to investigate circ-PITX1's effect on tumor formation. RESULTS: Circ-PITX1 was overexpressed in NSCLC tissue samples and cells. Its low expression repressed NSCLC cell proliferation and motility. Moreover, our data revealed its downregulation inhibited glutamine catabolism and tumor formation and promoted cell apoptosis. In addition, circ-PITX1 bound to miR-615-5p, and its inhibitory effect on tumor cellular behaviors could be reversed after decreasing miR-615-5p expression. The miRNA targeted E26 transformation specific-1 (ETS1), whose upregulation abolished miR-615-5p overexpression-induced effects in NSCLC cells. Furthermore, circ-PITX1 positively modulated ETS1 production through interaction with miR-615-5p. CONCLUSION: Circ-PITX1 facilitated NSCLC progression via modulating miR-615-5p/ETS1 pathway.

Gut antibiotic resistome during pregnancy associates with the risk of gestational diabetes mellitus: New evidence from a prospective nested case-control study.

Antibiotic resistome has emerged as a global threat to public health. However, gestational antibiotic resistome and potential link with adverse pregnancy outcomes remains poorly understood. Our study reports for the first time an association between gut antibiotic resistome during early pregnancy and the risk of gestational diabetes mellitus (GDM) based on a prospective nested case-control cohort including 120 cases and 120 matched controls. A total of 214 antibiotic resistance gene (ARG) subtypes belonging to 17 ARG types were identified in > 10 % fecal samples collected during each trimester. The data revealed dynamic profiles of gut antibiotic resistome through pregnancy, and significant positive associations between selected features (i.e., ARG abundances and a GDM-ARG score which is a new feature characterizing the association between ARGs and GDM) of gut antibiotic resistome during early pregnancy and GDM risk as well as selected endogenous metabolites. The findings demonstrate ubiquitous presence of ARGs in pregnant women and suggest it could constitute an important risk factor for the development of GDM.

Perceived Taste and Olfactory Dysfunctions and Subsequent Stroke Risk.

Background: Taste and olfactory dysfunction are commonly associated with neurodegenerative diseases and cardiovascular risk factors, but their specific associations with stroke risk remain uncertain. Objectives: The purpose of this paper was to explore whether perceived taste and olfactory dysfunctions were associated with stroke risk. Methods: Included were 85,656 participants (mean age 51.0 ± 15.3 years) of the Kailuan study. Perceived olfactory and taste dysfunctions were assessed via a questionnaire at baseline (in 2014-2016). Incident stroke cases were confirmed by review of medical records. Cox proportional hazards models were used to investigate associations of perceived olfactory and taste dysfunctions with stroke risk, and mediation analysis was used to estimate the mediating effect of chronic disease statuses. Results: We documented 2,198 incident stroke cases during a mean of 5.6 years of follow-up. Perceived taste dysfunction was associated with a doubled risk of developing total stroke (adjusted HR: 2.03; 95% CI: 1.36-3.04; P < 0.001) even with adjustment of lifestyle factors, biomarkers (ie, blood lipids, blood glucose, blood pressure, and uric acid), and other potential confounders. However, perceived olfactory dysfunction (adjusted HR: 1.22; 95% CI: 0.79-1.90; P = 0.34) was not significantly associated with a high risk of total stroke. Similar results of both perceived taste and olfactory dysfunctions were observed for ischemic stroke. Presence of chronic diseases, including hypertension, diabetes, chronic kidney disease, and overweight/obesity, mediated 4% to 5% of the association of perceived taste dysfunction with both total stroke and ischemic stroke. Conclusions: In this large cohort study, perceived taste dysfunction was associated with a high risk of developing stroke.

Metabolic syndrome and cardiovascular disease among adult cancer patients: results from NHANES 2007-2018.

BACKGROUND: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease (CVD), and CVD is a major challenge for cancer patients. This study aimed to investigate the prevalence and association of MetS and CVD among adult cancer patients. METHODS: This cross-sectional study included cancer patients aged > 18 years from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. The prevalence of MetS and CVD was calculated using weighted analysis. Multivariable logistic regression was used to assess the association between MetS and CVD. RESULTS: The study included 2658 adult cancer patients, of whom 1260 exhibited MetS and 636 had CVD. The weighted prevalence of MetS and CVD in cancer patients was 45.44%, and 19.23%, respectively. Multivariable logistic regression showed a 79% increased risk in higher CVD prevalence in cancer patients with MetS, with the OR (95% CI) of 1.79 (1.31, 2.44). Notably, obesity, elevated blood pressure (BP), high glucose, and low high density lipoprotein cholesterol (HDL-C) in the MetS components were significantly associated with higher CVD prevalence after adjusting for covariates. Moreover, the risk of CVD prevalence in cancer patients increased with more MetS components. Notably, MetS was more strongly linked to CVD in patients aged < 65 and women. CONCLUSIONS: Among adult cancer patients, over two-fifths (45.44%) were estimated to have MetS, while about one-fifth (19.23%) were considered to have CVD. Notably, obesity, elevated BP, high glucose, low HDL-C, and higher number of MetS components were found to be significantly associated with higher CVD prevalence among cancer adults. Cancer patients under 65 and women with MetS may be at increased risk of CVD.

Knowledge and practices of neonatal intensive care unit nurses concerning hypothermia in preterm infants: A descriptive cross-sectional study.

AIM: To investigate the knowledge level and clinical practice of neonatal intensive care unit nurses on the whole process of hypothermia prevention in preterm infants. DESIGN: A polycentric descriptive cross-sectional study was conducted in 23 hospitals in Shandong province involving 254 neonatal intensive care unit nurses. METHODS: An evidence-based knowledge and clinical practice questionnaire on hypothermia prevention in preterm infants and a general information questionnaire were used to collect data. SPSS and EXCEL 24.0 database were used for data statistics and analysis. RESULTS: Nearly one-third of nurses were unclear about the definition of mild hypothermia and heat preservation measures during labour management and resuscitation. Knowledge about the correct rate of amniotic fluid evaporation was low. The higher the hospital level and nurses' education level, professional title, work experience, and position, the higher the knowledge level. The clinical practice of nurses differed in terms of body temperature assessment tools, measurement sites, and measurement frequency for premature infants. CONCLUSIONS: Nurses in neonatal intensive care units need to apply evidence-based knowledge and carry out practice interventions to ensure preterm infants' safe transition from the delivery room to the neonatal intensive care unit. IMPACT: There have been few studies evaluating neonatal nurses' knowledge and practices with regards to the preventing hypothermia of premature infants from delivery room to neonatal intensive care unit. The study identifies the deficiencies and problems in temperature management that can be attributed to the knowledge level of nurses. The findings will help improve the current curriculum, teaching strategies, and the nurses' knowledge levels, preventing premature hypothermia in infants. REPORTING METHOD: This study adhered to the STROBE statement for observational studies and obtained approval (KYLL-2023LW045) from the ethics committee of The Second Hospital of Shandong University. The other 22 third- and second-level hospitals, as our alliance members, recognized our chairperson status within the alliance and were willing to join our academic activities. Mutual responsibility for ethical filing between alliance units. PUBLIC CONTRIBUTION: 254 nurses were recruited from 23 tertiary and secondary public hospitals in Shandong province. No public or patient involvement. Members of the research group used the Questionnaire Star platform to prepare the electronic questionnaire, including obtaining informed consent, taking precautions for questionnaire completion, and using the aforementioned measurement tools. The project research team contacted the head nurses of 23 neonatal intensive care units in Shandong Province. After obtaining consent from the head nurses, they were asked to send the requirements and link of the electronic questionnaire to their WeChat management group. The nurses go through each question and make a choice which has two options of 'agree' or 'disagree.' Based on their answers, nurses were evaluated as having 'mastered' or 'not mastered' each item. Each 'mastered' item (correct answer) was given a score of 4; an item 'not mastered' (incorrect answer) was given a score of 0. The total score ranged from 0 to 100.

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel in Relapsed or Refractory Large B-cell Lymphoma.

BACKGROUND: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. OBJECTIVE: ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. STUDY DESIGN: Patients with R/R LBCL were enrolled in Cohort 3 and received conditioning chemotherapy on Days -5 through -3 followed by a single infusion of axi-cel (2 × 106 cells/kg) on Day 0. Prophylactic tocilizumab (8 mg/kg) was administered 48 hours after axi-cel infusion. Primary endpoints were incidence and severity of CRS and NEs. Key secondary endpoints included the incidence of adverse events, objective response rate (ORR), duration of response, progression-free survival, overall survival (OS), and biomarker analyses (eg, circulating CAR T cells, cytokines, chemokines). RESULTS: Forty-two patients were enrolled in Cohort 3, 38 of whom received axi-cel. In the 24-month analysis, any-grade CRS and NEs occurred in 92% and 87% of patients, and Grade ≥3 CRS and NEs occurred in 3% and 42% of patients, respectively. One Grade 5 NE (cerebral edema) occurred. With 24-month minimum follow-up, the ORR was 63%, and 39.5% of patients had ongoing response. With 48-month follow-up, median OS was 34.8 months (95% CI, 5.4-not estimable). CAR T-cell expansion in ZUMA-1 Cohort 3 was comparable with pivotal Cohorts 1 and 2. Consistent with tocilizumab-mediated inhibition of IL-6R, serum IL-6 levels were increased relative to Cohorts 1 and 2. Grade ≥3 NEs were associated with elevated IL-6 levels, proinflammatory cytokines, and myeloid cells in the cerebrospinal fluid. CONCLUSIONS: Based on these findings, prophylactic tocilizumab is not recommended to prevent CAR T-cell-related adverse events, and beneficial effects of prophylactic levetiracetam remain uncertain in patients with R/R LBCL.

Oral microbiome diversity and diet quality in relation to mortality.

AIM: To examine the independent and joint associations of oral microbiome diversity and diet quality with risks of all-cause and cause-specific mortality. MATERIALS AND METHODS: We included 7,055 eligible adults from the U.S. National Health and Nutrition Examination Survey (NHANES). Oral microbiome diversity was measured with α-diversity, including the Simpson Index, observed amplicon sequence variants (ASVs), Faith's phylogenetic diversity, and Shannon-Weiner index. Dietary quality was assessed using the Healthy Eating Index-2015 (HEI-2015). Cox proportional hazard models were used to assess the corresponding associations. RESULTS: During a mean follow-up of 9.0 years, we documented 382 all-cause deaths. We observed independent associations of oral microbiome diversity indices and dietary quality with all-cause mortality (hazard ratio [HR] = 0.63; 95% confidence interval [CI]: 0.49-0.82 for observed ASVs; HR = 0.68, 95% CI: 0.52-0.89 for HEI-2015). Jointly, participants with the highest tertiles of both oral microbiome diversity (in Simpson index) and HEI-2015 had the lowest hazard of mortality (HR = 0.37, 95% CI: 0.23-0.60). In addition, higher oral microbiome diversity was associated with lower risks of deaths from cardiometabolic disease and cancer. CONCLUSIONS: Higher oral microbiome α-diversity and diet quality were independently associated with lower risk of mortality.

Fahr's syndrome as the initial imaging characteristics of MELAS syndrome with a possible seizure activity and cardiac arrest: a case report.

This study reported a case of MELAS syndrome presenting as the initial imaging characteristics of Fahr's syndrome with "near" sudden unexpected death in epilepsy (SUDEP) and lateralized periodic discharges (LPD). The patient, a young boy, experienced loss of consciousness 2 days prior, which was followed by two limb and facial convulsions. He was later found in cardiac arrest during hospitalization, but regained consciousness gradually after receiving cardiopulmonary resuscitation and tracheal intubation. The patient exhibited short stature, intellectual disability, poor sports abilities, and academic performance since childhood, but had no family history. Emergency head computed tomography (CT) revealed high density calcification in bilateral caudate nucleus, lentiform nucleus, thalamus, and dentate nucleus with evidence of an acute process. The patient was transferred to the neurology department where he continued to recover consciousness, though he experienced dysarthria, left limb hemiplegia, and hemiparesthesia. Changes in head magnetic resonance imaging (MRI) findings were noted at admission, 1 month later, and 6 months later. LPD were observed in his video electroencephalogram. The CT urography indicated a narrow left ureteropelvic junction with left hydronephrosis, which was suggestive of ureteropelvic junction obstruction. Ultimately, a diagnosis of near-SUDEP was suspected in this patient, indicating a rare case of MELAS syndrome with near-SUDEP and LPD. The gene tests results revealed the presence of the mitochondrial DNA A3243G mutation, leading to the final diagnosis of MELAS syndrome. This case expands the clinical disease spectrum of the MELAS syndrome.

Systemic Inflammation-Based Staging System for Hepatocellular Carcinoma After Drug-Eluting Beads Transarterial Chemoembolization: A Multicenter Study.

RATIONALE AND OBJECTIVES: The optimal prognostic assessment for patients with hepatocellular carcinoma (HCC) after drug-eluting bead transarterial chemoembolization (DEB-TACE) remains unclear. This study aimed to propose a novel staging system in comparison with the current staging systems for HCC following DEB-TACE. MATERIALS AND METHODS: From four centers, patients with HCC undergoing DEB-TACE as the initial therapy were retrospectively included and classified into training and validation sets. Multivariable regression was used to determine the independent prognostic factors in the training set. A novel staging system incorporating the independent factors was proposed and externally validated in terms of discrimination and calibration compared to other staging systems in both sets. RESULTS: The training and validation sets included 335 and 99 patients, respectively. Multivariable regression revealed independent factors including alpha-fetoprotein level, aspartate aminotransferase to lymphocyte count ratio index, maximum tumor diameter, Child-Pugh class, and portal vein invasion. The novel prognostic staging system, named PADCA, was proposed and outperformed other staging systems with the highest C-index, area under the curve, Wald test value, clinical benefit, and the lowest Akaike information criterion in the training and validation sets. CONCLUSION: The PADCA staging system has a superior prognostic predictive ability compared to the current staging systems. PADCA can assist clinicians in screening out the patients most likely to derive benefit from DEB-TACE and guiding the formulation of therapy and follow-up strategy.

The phytoplankton community affects the energy metabolism and immunomodulation strategy of oyster during breeding seasons.

The mass mortality of Pacific oyster Crassostrea gigas has become a severe ecological and economic concern to Chinese aquaculture, which is proposed to be linked to the phytoplankton community in the farming waters. In the present study, both field and laboratory experiments were conducted to identify the phytoplankton taxa associated with oyster mortality and explore the molecular mechanism by which they affect the physiological health of oysters. The field experiment showed that more serious mortality of oysters was observed in the North Yellow Sea from July to September in 2018 (average survival rate of 75.11 %) than in 2019 (average survival rate of 85.78 %), with the proportion of Bacillariophyta (diatoms) in the phytoplankton community in 2018 lower than that in 2019. In comparison to 2019, reduced dry weight, lower glycogen and triglyceride contents in hepatopancreas, lower 17ß-estradiol and testosterone concentrations in gonad, as well as a generally weaker immune response against Vibrio splendidus stimulation were detected in the oysters sampled in 2018. The treatment of oysters with either starvation (starvation group) or Nitzschia closterium f. minutissima feeding (N. closterium group) was conducted to verify the field findings, with individuals reared in natural seawater as control. After 40 days of N. closterium feeding, dry weight, glycogen and triglyceride contents in hepatopancreas significantly increased, as well as the biosynthesis of sex hormones and gonadal maturation were promoted compared to the control and starvation groups. Moreover, a much stronger immune response against V. splendidus stimulation was observed in the oysters of N. closterium group, with the fold-changes of norepinephrine content in serum, SOD activity in hepatopancreas, and the mRNA expression level of IL17-5 and HSP70 in haemocytes higher than those in the control and starvation groups. Collectively, these results suggested that lack of diatoms in the farming waters suppressed the energy storage and gonadal maturation of adult oysters, and also resulted in a compromised immune response against bacterial infection, which may be a leading cause of the mass mortality of oysters living in diatom-deficient waters during breeding seasons.

Hyaluronic acid-coated porphyrin nanoplatform with oxygen sustained supplying and glutathione depletion for enhancing photodynamic/ion/chemo synergistic cancer treatment.

Hypoxia and high concentration of glutathione (GSH) in tumor seriously hinder the role of reactive oxygen species (ROS) and oxygen-dependence strategy in tumor treatment. In this work, a self-generating oxygen and self-consuming GSH hyaluronic acid (HA)-coated porphyrin nanoplatform (TAPPP@CaO2/Pt(IV)/HA) is established for enhancing photodynamic/ion/chemo targeting synergistic therapy of tumor. During the efforts of ROS production by nanosystems, a GSH consuming strategy is implemented for augmenting ROS-induced oxidative damage for synergetic cancer therapy. CaO2 in the nanosystems is decomposed into O2 and H2O2 in an acidic environment, which alleviates hypoxia and enhances the photodynamic therapy (PDT) effect. Calcium overload causes mitochondria dysfunction and induces apoptosis. Pt (IV) reacts with GSH to produce Pt (II) for chemotherapy and reduce the concentration of GSH, protecting ROS from scavenging for augmenting ROS-induced oxidative damage. In vitro and in vivo results demonstrated the self-generating oxygen and self-consuming GSH strategy can enhance ROS-dependent PDT coupled with ion/chemo synergistic therapy. The proposed strategy not only solves the long-term problem that hypoxia limits therapeutic effect of PDT, but also ameliorates the highly reducing environment of tumors. Thus the preparation of TAPPP@CaO2/Pt(IV)/HA provided a novel strategy for the effective combined therapy of cancers.

17ß-estradiol promotes the progression of temporomandibular joint osteoarthritis by regulating the FTO/IGF2BP1/m6A-NLRC5 axis.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17ß-estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms. METHODS: Primary fibroblast-like synoviocytes (FLSs) isolated from rats were treated with TNF-α to establish cell model, and phenotypes were evaluated using cell counting kit-8, EdU, Tanswell, enzyme-linked immunosorbent assay, and quantitative real-time PCR (qPCR). The underlying mechanism of E2, FTO-mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA-like rat model was established by intra-articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro-CT and H&E staining. RESULTS: The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF-α-treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown. CONCLUSION: E2 promoted the progression of TMJOA.

Effect of Home-Based Cardiac Telerehabilitation in Patients After Percutaneous Coronary Intervention: A Randomized Controlled Trial.

Low adherence to hospital-based cardiac rehabilitation has been observed in patients after percutaneous coronary intervention. The effectiveness of home-based cardiac telerehabilitation in this setting is unclear. This study aimed to investigate the impact of home-based cardiac telerehabilitation on exercise endurance, disease burden status, cardiac function, and quality of life in patients after percutaneous coronary intervention. A total of 106 patients after percutaneous coronary intervention were randomly assigned to either the intervention group (receiving routine rehabilitation care and home-based cardiac telerehabilitation) or the control group (receiving routine care only), with 53 patients in each group. The 6-minute walking test, anerobic threshold, physical component summary score, mental component summary score, Vo2max, and left ventricular ejection fraction were measured in both groups before and 3 months after the intervention. Additionally, the Short-Form 12 scale and Family Burden Interview Schedule were used to assess quality of life and disease burden status. The intervention group demonstrated significant improvements in 6-minute walking test, anerobic threshold, Vo2max, physical component summary score, mental component summary score, Short-Form 12 scale, and Family Burden Interview Schedule scale scores compared with the control group (P<0.05). Results suggest that home-based cardiac telerehabilitation may improve exercise endurance and quality of life and reduce disease burden status in patients after percutaneous coronary intervention.

Characterization of microbial community assembly in parasitic plant systems and the influence of microorganisms on metabolite accumulation in parasitic plants: case study of Cistanche salsa and Kalidium foliatum.

Introduction: Cistanche salsa (C.A.Mey.) G. Beck is a perennial holoparasitic herb recognized for its medicinal properties, particularly in kidney-tonifying and laxative treatments. Despite its therapeutic potential, little is known about the endophyte communities inhabiting C. salsa and its host plants, and how these microorganisms may impact the production and accumulation of metabolites in C. salsa. Methods: We conducted a dual analysis focusing on metabolomics of wild C. salsa and microbiome characterization of both C. salsa and its host plant, Kalidium foliatum (Pall.) Moq. The metabolomics analysis revealed variations in metabolite composition across different parts of C. salsa. Additionally, the microbiome analysis involved studying endophytic bacteria and fungi, comparing their community structures between parasitic C. salsa and its host plant. Results: Significant variations in metabolite composition were observed through metabolomic profiling, which identified 93 secondary metabolites and 398 primary metabolites across various parts of C. salsa. Emphasis was placed on differences in metabolite composition within the flowers. Microbiome analysis revealed differential community compositions of endophytic bacteria between the parasitic and host plants, whereas differences in endophytic fungi were less pronounced. Certain endophytes, such as Bacteroidota, Proteobacteria, Ascomycota, and Basidiomycota, were associated with the production of specific secondary metabolites in C. salsa, including the plant-specific compound salsaside. Discussion: Our findings highlight the intricate relationship between C. salsa and its endophytic microbiota, suggesting a potential role of these microorganisms in modulating the biosynthesis of bioactive compounds. The differential preferences of endophytic bacteria and fungi across various microenvironments within the parasitic plant system underscore the complexity of these interactions. Further elucidation of these dynamics could enhance our understanding of C. salsa's medicinal properties and its ecological adaptations as a holoparasitic herb.