Graph-Based Pangenome of Actinidia chinensis Reveals Structural Variations Mediating Fruit Degreening.

Fruit ripening is associated with the degreening process (loss of chlorophyll) that occurs in most fruit species. Kiwifruit is one of the special species whose fruits may maintain green flesh by accumulating a large amount of chlorophyll even after ripening. However, little is known about the genetic variations related to the fruit degreening process. Here, a graph-based kiwifruit pangenome by analyzing 14 chromosome-scale haplotype-resolved genome assemblies from seven representative cultivars or lines in Actinidia chinensis is built. A total of 49,770 non-redundant gene families are identified, with core genes constituting 46.6%, and dispensable genes constituting 53.4%. A total of 84,591 non-redundant structural variations (SVs) are identified. The pangenome graph integrating both reference genome sequences and variant information facilitates the identification of SVs related to fruit color. The SV in the promoter of the AcBCM gene determines its high expression in the late developmental stage of fruits, which causes chlorophyll accumulation in the green-flesh fruits by post-translationally regulating AcSGR2, a key enzyme of chlorophyll catabolism. Taken together, a high-quality pangenome is constructed, unraveled numerous genetic variations, and identified a novel SV mediating fruit coloration and fruit quality, providing valuable information for further investigating genome evolution and domestication, QTL genes function, and genomics-assisted breeding.

Impact of Indacaterol/Glycopyrrolate on Pulmonary Function and St. George's Respiratory Questionnaire Score in Individuals with Stable Chronic Obstructive Pulmonary Disease.

Objective: This study aims to investigate the impact of indacaterol/glycopyrrolate on pulmonary function and St. George's Respiratory Questionnaire (SGRQ) scores in patients with stable chronic obstructive pulmonary disease (COPD). Methods: A prospective randomized controlled trial (RCT) was conducted. A total of 100 stable COPD patients admitted to our hospital between September 2020 and October 2022 were selected as study participants. They divided into a conventional group (n=50) and a combined compound preparation (CCP) group (n=50) using a random number table. The conventional group received oral carbocisteine tablets, while the combined compound preparation group received indacaterol/glycopyrrolate inhalation powder spray in addition to the conventional treatment. Clinical efficacy, pulmonary function indices, serum inflammatory factors, psychological resilience, and quality of life were compared between the two groups. Results: The CCP group exhibited a significantly higher total effective rate (92.00%) compared to the conventional group (76.00%) (P < .05). Post-treatment, both groups showed increased values in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and FEV1% with a more substantial improvement in the CCP group (P < .05). Additionally, the CCP group demonstrated decreased post-treatment levels of serum inflammatory factors (TNF-α, IL-6, CRP, and PCT), elevated scores on the Connor Davidson Resilience Scale (CD-RISC), and reduced SGRQ scores compared to the conventional group (P < .05). Conclusions: In treatment of stable COPD patients, the combination of indacaterol/glycopyrrolate with carbocisteine tablets enhances pulmonary function, alleviates airway inflammatory reactions, improves clinical efficacy, enhances psychological resilience, and elevates the quality of life compared to carbocisteine tablets alone. These findings underscore the potential therapeutic benefits of the combined compound preparation in managing stable COPD.

Effect of propofol and ciprofol on the euphoric reaction in patients with painless gastroscopy: A prospective randomized controlled trial.

Objective: To explore the effects of propofol and ciprofol on patient euphoric reactions during sedation in patients undergoing gastroscopy and to investigate potential factors that may influence euphoric reactions in patients. Methods: A total of 217 patients were randomly divided into two groups: the propofol group (P group, n = 109) and the ciprofol group (C group, n = 108). The patients in the P group were given 2 mg/kg propofol, and those in the C group were given 0.5 mg/kg ciprofol. The patients were assessed using the Addiction Research Center Inventory-Chinese Version (ARCI-CV) to measure euphoric reactions at three time points: preexamination, 30 min after awakening, and 1 week after examination. Anxiety, depression, and sleep status were evaluated using appropriate scales at admission and 1 week after the examination. The dream rate, sedative effects, vital sign dynamics, and adverse reactions were documented during the sedation process. Results: After 30 min of awakening, the P group and C group showed no statistically significant differences in the mean morphine-benzedrine group (MBG) score (8.84 vs. 9.09, P > 0.05), dream rate (42.2 % vs. 40.7 %, P > 0.05), or MBG score one week after the examination (7.04 vs. 7.05, P > 0.05). The regression analysis revealed that sex, dream status, Alcohol Use Disorders Identification Test (AUDIT) score, and examination time had notable impacts on the MBG-30 min score. No statistically significant differences were observed in sedative effects, anxiety, depression, or sleep status between the two groups (P > 0.05). The incidence of injection pain and severe hypotension was significantly lower in the C group (P < 0.05), and hemodynamics and SpO2 were more stable during sedation (P < 0.05). Conclusion: There was no significant difference between propofol and ciprofol in terms of euphoria experienced by patients after sedation in patients undergoing gastroscopy. Ciprofol has demonstrated addictive potential similar to that of propofol, warranting careful attention to its addictive potential during clinical application.

Effectiveness of mobile health applications on clinical outcomes and health behaviors in patients with coronary heart disease: A systematic review and meta-analysis.

Objective: Mobile health applications (apps) have gained significant popularity and widespread utilization among patients with coronary heart disease (CHD). The objective of this study is to evaluate the effects of mHealth apps on clinical outcomes and health behaviors in patients with CHD. Methods: Databases were searched from inception until December 2023, including Cochrane Library, PubMed, EMBASE, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Service System (SinoMed), Wanfang Data, China Science and Technology Journal Database (VIP), for randomized controlled trials (RCTs) regarding the effectiveness of mHealth apps in patients with CHD. Two researchers conducted a comprehensive review of the literature, extracting relevant data and evaluating each study's methodological quality separately. The meta-analysis was performed utilizing Review Manager v5.4 software. Results: A total of 34 RCTs were included, with 5,319 participants. The findings demonstrated that using mHealth apps could decrease the incidence of major adverse cardiac events (RR = 0.68, P = 0.03), readmission rate (RR = 0.56, P < 0.001), total cholesterol (WMD = -0.19, P = 0.03), total triglycerides (WMD = -0.24, P < 0.001), waist circumference (WMD = -1.92, P = 0.01), Self-Rating Anxiety Scale score (WMD = -6.70, P < 0.001), and Self-Rating Depression Scale score (WMD = -7.87, P < 0.001). They can also increase the LVEF (WMD = 6.50, P < 0.001), VO2 max (WMD = 1.89, P < 0.001), 6-min walk distance (6MWD) (WMD = 19.43, P = 0.004), Morisky Medication Adherence Scale-8 score (WMD = 0.96, P = 0.004), and medication adherence rate (RR = 1.24, P = 0.03). Nevertheless, there is no proof that mHealth apps can lower low-density lipoprote in cholesterol, blood pressure, BMI, or other indicator (P > 0.05). Conclusion: Mobile health apps have the potential to lower the incidence of major adverse cardiac events (MACEs), readmission rates, and blood lipids in patients with CHD. They can also help enhance cardiac function, promote medication adherence, and alleviate symptoms of anxiety and depression. To further corroborate these results, larger-scale, multi-center RCTs with longer follow-up periods are needed.

The hidden threat: Unraveling the impact of microplastics on reproductive health.

Microplastics, with intricate physical and chemical characteristics, infiltrate the food chain and extensively impact ecosystems. Despite acknowledging the link between environmental pollution and declining fertility, the specific mechanisms affecting reproductive health remain to be elucidated. This review emphasizes the global correlation between microplastics and subfertility, focusing on entry pathways and impacts on ecosystems. Research suggests that microplastics disrupt the neuroendocrine system, influencing sex hormone synthesis through the hypothalamic-pituitary-gonadal (HPG) axis. In the reproductive system, microplastics interfere with the blood-testis barrier, impairing spermatogenesis in males, and causing placental dysfunction, ovarian atrophy, endometrial hyperplasia, and fibrosis in females. Moreover, microplastics potentially affect offspring's lipid metabolism and reproductive functions. However, complex microplastic compositions and detection method limitations impede research progress. Mitigation strategies for reproductive effects, combined with addressing microplastic pollution through sustainable practices, are imperative. This review underscores the urgency of global initiatives and collaborative research to safeguard reproductive health amid escalating microplastic contamination.

Sesquilignans: Current research and potential prospective.

Lignans are widely distributed in nature, primarily found in the xylem and resins of plants, with the constituent units C6-C3, and their dimers are the most common in plants. In recent years, the trimeric sesquilignans have also received increasing attention from scholars. More than 200 derivatives have been isolated and identified from nearly 50 families, most of which are different types (monoepoxy lignans, bisepoxy lignans, benzofuran lignans) connected with simple phenylpropanoids through ether bonds, C-C bonds, and oxygen-containing rings to constitute sesquilignans. Some of them also possess pharmacological properties, including antioxidants, hepatoprotectives, antitumors, anti-inflammatory properties, and other properties. In addition, the chemical structure of sesquilignans is closely related to the pharmacological activity, and chemical modification of methoxylation enhances the pharmacological activity. In contrast, phenolic hydroxyl and hydroxyl glycosides reduce the pharmacological activity. Therefore, the present review aims to summarize the chemical diversity, bioactivities, and constitutive relationships to provide a theoretical basis for the more profound development and utilization of sesquilignans.

Multifunctional Antimonene-Silver Nanocomposites for Ultra-Multi-Mode and Multi-Analyte Sensing, Parallel and Batch Logic Computing, Long-Text Information Protection.

To simulate life's emergent functions, mining the multiple sensing capabilities of nanosystems, and digitizing networks of transduction signals and molecular interactions, is an ongoing endeavor. Here, multifunctional antimonene-silver nanocomposites (AM-Ag NCs) are synthesized facilely and fused for molecular sensing and digitization applications (including ultra-multi-mode and multi-analyte sensing, parallel and batch logic computing, long-text information protection). By mixing surfactant, AM, Ag+ and Sodium borohydride (NaBH4) at room temperature for 5 min, the resulting NCs are comprised of Ag nanoparticles scattered within AM nanosheets and protected by the surfactant. Interestingly, AM-Ag NCs exhibit ultra-multi-mode sensing ability for multiplex metal ions (Hg2+, Fe3+, or Al3+), which significantly improved selectivity (≈2 times) and sensitivity (≈400 times) when analyzing the combined channels. Moreover, multiple sensing capabilities of AM-Ag NCs enable diverse batch and parallel molecular logic computations (including advanced cascaded logic circuits). Ultra-multi-mode selective patterns of AM-Ag NCs to 18 kinds of metal ions can be converted into a series of binary strings by setting the thresholds, and realized high-density, long-text information protection for the first time. This study provides new ideas and paradigms for the preparation and multi-purpose application of 2D nanocomposites, but also offers new directions for the fusion of molecular sensing and informatization.

Polarization-engineered photon statistics and its tomography via optomagnonic interaction.

Cavity optomagnonics has received considerable research interest in recent years, due to the coherent magnetic Brillioun light scattering in the ferromagnetic material. Here, we theoretically propose and numerically verify a feasible scheme for the full polarization tomography on photon statistics in an optomagnonic whispering-gallery-mode microresonator system in the weak-coupling regime. By performing the polarization pre- and post-selections to manipulate the polarization states of the input and output photons, we find that the rich sub- and super-Poissonian photon statistics can be selectively generated, thanks to quantum interferences. In the parameter space of phase delay, the evolution from photon bunching to antibunching indicates the change from phase to amplitude squeezing. Our obtained result has potential applications in tunable quantum polarized light sources based on the cavity optomagnonic platform in micro-nano scale. It also offers a deeper understanding for full quantum cavity optomagnonics.

E-M349E and NS2A/2B-P1(T) are compensatory mutations of rDTMUV-NS2AB-P1P1'(AA), which regain virus proliferation by enhancing the virus package and restoring NS2A/2B cleavage.

Duck Tembusu virus (DTMUV) belongs to the Flaviviridae family and mainly infects ducks. The genome of DTMUV is translated into a polyprotein, which is further cleaved into several protein by viral NS2B3 protease and host proteases. Crucially, the cleavage of the NS2A/2B precursor during this process is essential for the formation of replication complexes and viral packaging. Previous research has demonstrated that alanine mutations in NS2A/2B (P1P1' (AA)) result in an attenuated strain (rDTMUV-NS2A/2B-P1P1' (AA)) by disrupting NS2A/2B cleavage. In this study, we investigate the effects of the P1P1' (AA) mutation on the viral life cycle and explore compensatory mutations in rDTMUV-NS2A/2B-P1P1' (AA). Infected ducklings exhibit similar body weight gain and viral tissue loads to DTMUV-WT. Compensatory mutations E-M349E and P1(T) emerge, restoring proliferation levels to those of rDTMUV-WT. Specifically, E-M349E enhances viral packaging, while P1(T) reinstates NS2A/2B proteolysis in vitro. Thus, our findings reveal novel compensatory sites capable of restoring the attenuated DTMUV during polyprotein cleavage and packaging.

Determining cut-off values and predictors for the Snaith-Hamilton Pleasure Scale: comparison between clinical and school settings.

BACKGROUND: Few previous studies have established Snaith-Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups. AIMS: To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan. METHOD: This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses. RESULTS: The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values. CONCLUSIONS: Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.

Machine learning and weighted gene co-expression network analysis identify a three-gene signature to diagnose rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a systemic immune-related disease characterized by synovial inflammation and destruction of joint cartilage. The pathogenesis of RA remains unclear, and diagnostic markers with high sensitivity and specificity are needed urgently. This study aims to identify potential biomarkers in the synovium for diagnosing RA and to investigate their association with immune infiltration. Methods: We downloaded four datasets containing 51 RA and 36 healthy synovium samples from the Gene Expression Omnibus database. Differentially expressed genes were identified using R. Then, various enrichment analyses were conducted. Subsequently, weighted gene co-expression network analysis (WGCNA), random forest (RF), support vector machine-recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO) were used to identify the hub genes for RA diagnosis. Receiver operating characteristic curves and nomogram models were used to validate the specificity and sensitivity of hub genes. Additionally, we analyzed the infiltration levels of 28 immune cells in the expression profile and their relationship with the hub genes using single-sample gene set enrichment analysis. Results: Three hub genes, namely, ribonucleotide reductase regulatory subunit M2 (RRM2), DLG-associated protein 5 (DLGAP5), and kinesin family member 11 (KIF11), were identified through WGCNA, LASSO, SVM-RFE, and RF algorithms. These hub genes correlated strongly with T cells, natural killer cells, and macrophage cells as indicated by immune cell infiltration analysis. Conclusion: RRM2, DLGAP5, and KIF11 could serve as potential diagnostic indicators and treatment targets for RA. The infiltration of immune cells offers additional insights into the underlying mechanisms involved in the progression of RA.

Obesity paradox of cardiovascular mortality in older adults in the United States: A cohort study using 1997-2018 National Health Interview Survey data linked with the National Death Index.

BACKGROUND: Large-scale, population-based investigations primarily investigating the association between body mass index (BMI) and cardiovascular disease (CVD) mortality among older and younger adults in the United States (U.S.) are lacking. OBJECTIVE: To evaluate the relationship between BMI and CVD mortality in older (≥65 years) and younger (<65 years) adults and to identify the nadir for CVD mortality. DESIGN: This cohort study used serial cross-sectional data from the 1997 to 2018 National Health Interview Survey (NHIS) linked with the National Death Index. NHIS is an annual nationally representative household interview survey of the civilian noninstitutionalized U.S. SETTING: Residential units of the civilian noninstitutionalized population in the U.S. PARTICIPANTS: The target population for the NHIS is the civilian noninstitutionalized U.S. population at the time of the interview. We included all adults who had BMI data collected at 18 years and older and with mortality data being available. To minimize the risk of reverse causality, we excluded adults whose survival time was ≤2 years of follow-up after their initial BMI was recorded and those with prevalent cancer and/or CVD at baseline. METHODS: We used the BMI record obtained in the year of the NHIS survey. Total CVD mortality used the NHIS data linked to the latest National Death Index data from the survey inception to December 31, 2019. We performed multivariable Cox proportional hazards regression models to estimate adjusted hazard ratios (aHRs) and 95 % confidence intervals (CIs). RESULTS: The study included 425,394 adults; the mean (SD) age was 44 (16.7) years. During a median follow-up period of 11 years, 12,089 CVD-related deaths occurred. In older adults, having overweight was associated with a lower risk of CVD mortality (aHR 0.92 [95 % CI, 0.87-0.97]); having class I obesity (1.04 [0.97-1.12]) and class II obesity (1.12 [1.00-1.26]) was not significantly associated with an increased CVD mortality; and having class III obesity was associated with an increased risk of CVD mortality (1.63 [1.35-1.98]), in comparison with adults who had a normal BMI. Yet, in younger adults, having overweight, class I, II, and III obesity was associated with a progressively higher risk of CVD mortality. The nadir for CVD mortality is 28.2 kg/m2 in older adults and 23.6 kg/m2 in younger adults. CONCLUSION: This U.S. population-based cohort study highlights the significance of considering age as a crucial factor when providing recommendations and delivering self-care educational initiatives for weight loss to reduce CVD mortality.

The global clinical studies of long COVID.

Long COVID are those who still have symptoms, signs, and conditions after the initial phase of infection of SARS-CoV-2. The incidence of long COVID varies among regions - 31% in North America, 44% in Europe, and 51% in Asia, which is challenging the healthcare system, but there is limited guideline for its treatment. With more and more nation-wide projects funded by the government such as RECOVER initiative in US and NIHR funding in UK, an increasing number of ongoing clinical trials are investigating the efficacy of diverse therapies on reversing long COVID. After searching the WHO International Clinical Trial Registry Platform, 587 clinical studies are identified as long COVID studies. Among these, 312 studies (53.2%) are testing potential therapies. Most of the long COVID trials were conducted in the United States (58 trials [18.6%]), followed by India (55 trials [17.6%]), and Spain (20 trials [6.4%]). Interventions in these clinical trials include physical exercise, rehabilitation therapy, behavioral therapy, and pharmacological therapies including herbs, paxlovid, and fluvoxamine. These trials are aiming to deal with these long COVID symptoms and signs including fatigue, decreased pulmonary function, reduce cognitive function, and others. To date, only 11 of these 312 studies have published their results that were not confirmative unfortunately. Future studies should be designed to address sleep disorders which were seldomly included in registered clinical studies. Moreover, interventions aimed at treating the underlying pathophysiology of long COVID are also necessary but currently lacking.

Non-equilibrium compression achieving high sensitivity and linearity for iontronic pressure sensors.

Flexible pressure sensors with high sensitivity and linearity are highly desirable for robot sensing and human physiological signal detection. However, the current strategies for stabilizing axial microstructures (e.g., micro-pyramids) are mainly susceptible to structural stiffening during compression, thereby limiting the realization of high sensitivity and linearity. Here, we report a bending-induced non-equilibrium compression process that effectively enhances the compressibility of microstructures, thereby crucially improving the efficiency of interfacial area growth of electric double layer (EDL). Based on this principle, we fabricate an iontronic flexible pressure sensor with vertical graphene (VG) array electrodes. Ultra-high sensitivity (185.09 kPa-1) and linearity (R2 = 0.9999) are realized over a wide pressure range (0.49 Pa-66.67 kPa). It also exhibits remarkable mechanical stability during compression and bending. The sensor is successfully employed in a robotic gripping task to recognize the targets of different materials and shapes based on a multilayer perception (MLP) neural network. It opens the door to realizing haptic sensing capabilities for robotic hands and prosthetic limbs.

Increasing structure diversity of farnesylated chalcones by a fungal aromatic prenyltransferase.

Farnesylated chalcones were favored by researchers due to their different biological activities. However, only five naturally occurring farnesylated chalcones were described in the literature until now. Here, the farnesylation of six chalcones by the Aspergillus terreus aromatic prenyltransferase AtaPT was reported. Fourteen monofarnesylated chalcones (1F1-1F5, 2F1-2F3, 3F1, 3F2, 4F1, 4F2, 5F1, 6F1, and 6F2) and a difarnesylated product (2F3) were obtained, enriching the diversity of natural farnesylated chalcones significantly. Ten of them are C-farnesylated products, which complement O-farnesylated chalcones by chemical synthesis. Fourteen products have not been reported prior to this study. Nine of the produced compounds (1F2-1F5, 2F1-2F3, 5F1, and 6F1) exhibited inhibitory effect on α-glucosidase with IC50 values ranging from 24.08 ± 1.44 to 190.0 ± 0.28 µM. Among them, compounds 2F3 with IC50 value at 24.08 ± 1.44 µM and 1F4 with IC50 value at 30.09 ± 0.59 µM showed about 20 times stronger than the positive control acarbose with an IC50 at 536.87 ± 24.25 µM in α-glucosidase inhibitory assays.

Columbianadin ameliorates experimental acute reflux esophagitis in rats via suppression of NF-κB pathway.

PURPOSE: Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents into the esophagus. Columbianadin is a coumarin derivative that exhibits anti-inflammatory and antioxidant effects. In this study, we tried to scrutinize the protective effect of Columbianadin against acute reflux esophagitis in rats. METHODS: RAW 264.7 cells were utilized to assess cell viability and measure the production of inflammatory parameters. The rats received anesthesia, and reflux esophagitis was induced via ligation of pylorus and fore stomach and corpus junction. Rats received the oral administration of Columbianadin (25, 50 and 100 mg/kg) and omeprazole (20 mg/kg). The gastric secretion volume, acidity, and pH were measured. Additionally, the levels of oxidative stress parameters, cytokines, and inflammatory markers were determined. At the end of the study, mRNA expression was assessed. RESULTS: Columbianadin remarkably suppressed the cell viability and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin (PGE2). Columbianadin treatment remarkably suppressed the secretion of gastric volume, total acidity and enhanced the pH level in the stomach. Columbianadin remarkably altered the level of hydrogen peroxidase, free iron, calcium, and plasma scavenging activity, sulfhydryl group; oxidative stress parameters like malonaldehyde, glutathione, superoxide dismutase, catalase, glutathione peroxidase; inflammatory cytokines viz., TNF-α, IL-6, IL-1ß, IL-10, IL-17, and monocyte chemoattractant protein-1; inflammatory parameters including PGE2, iNOS, COX-2, and nuclear kappa B factor (NF-κB). Columbianadin remarkably (P < 0.001) suppressed the mRNA expression TNF-α, IL-6, IL-1ß and plasminogen activator inhibitor-1. CONCLUSIONS: Columbianadin demonstrated a protective effect against acute reflux esophagitis via NF-κB pathway.

Associations between postoperative cognitive dysfunction, serum interleukin-6 and postoperative delirium among patients after coronary artery bypass grafting: A mediation analysis.

BACKGROUND: POCD is a common complication among patients who underwent coronary artery bypass graft (CABG), it is linked to loss of independence and reduced quality of life. AIMS AND OBJECTIVES: To examine the association between postoperative cognitive dysfunction (POCD), postoperative delirium (POD) and interleukin-6 (IL-6). DESIGN: A prospective cohort study. METHODS: Patients who underwent elective isolated CABG were enrolled. POCD was assessed by a set of cognitive function tools. Delirium was assessed using the CAM-ICU. The logistic regression analyses were used to identify the predictive value of POD or IL-6 on POCD. The path analysis was used to analyse the relationship among POD, IL-6 and POCD. RESULTS: A total of 212 patients were enrolled, with 25.0% of patients developing POD and 32.5% developing POCD. The multiple logistic regression analysis revealed that patients with POD had a four-fold increased hazard of POCD (OR = 3.655), and patients with IL-6 ≥ 830.50 pg/mL at the 6th hours after surgery had a 5-fold increased risk of experiencing POCD (OR = 5.042). However, the mediation effect of POD between IL-6 and POCD was not statistically significant (ß = 0.059, p = .392). CONCLUSIONS: POD and IL-6 at the 6th hour after surgery (≥830.50 pg/mL) are two potent predictors for POCD, while POD did not play a mediation effect between IL-6 and POCD. RELEVANCE TO CLINICAL PRACTICE: Early identification of risk factors (e.g., delirium assessment and testing for serum IL-6 levels) by clinical nurses for POCD may contribute to the clinical practice for the targeted prevention nursing strategies.

Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.

The multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus.

Hepatic IRE1α-XBP1 signaling promotes GDF15-mediated anorexia and body weight loss in chemotherapy.

Platinum-based chemotherapy drugs can lead to the development of anorexia, a detrimental effect on the overall health of cancer patients. However, managing chemotherapy-induced anorexia and subsequent weight loss remains challenging due to limited effective therapeutic strategies. Growth differentiation factor 15 (GDF15) has recently gained significant attention in the context of chemotherapy-induced anorexia. Here, we report that hepatic GDF15 plays a crucial role in regulating body weight in response to chemo drugs cisplatin and doxorubicin. Cisplatin and doxorubicin treatments induce hepatic Gdf15 expression and elevate circulating GDF15 levels, leading to hunger suppression and subsequent weight loss. Mechanistically, selective activation by chemotherapy of hepatic IRE1α-XBP1 pathway of the unfolded protein response (UPR) upregulates Gdf15 expression. Genetic and pharmacological inactivation of IRE1α is sufficient to ameliorate chemotherapy-induced anorexia and body weight loss. These results identify hepatic IRE1α as a molecular driver of GDF15-mediated anorexia and suggest that blocking IRE1α RNase activity offers a therapeutic strategy to alleviate the adverse anorexia effects in chemotherapy.