Intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing elective on-pump cardiac surgery (INIPOD-MOPS): a prospective double-blinded randomized control study protocol.

BACKGROUND: Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients. METHOD: This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation. DISCUSSION: Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium. TRIAL REGISTRATION: ChiCTR ChiCTR2400081444. Registered on March 1, 2024.

Effects of ultrasound-guided serratus plane block combined with general anesthesia on postoperative early quality of recovery and analgesia in patients undergoing transapical transcatheter aortic valve implantation surgery: study protocol for a randomized controlled trial.

BACKGROUND: Compared to traditional thoracotomy, transapical transcatheter aortic valve implantation (TAVI) surgery offers reduced trauma and faster recovery, fostering the adoption of enhanced recovery after surgery (ERAS) protocols in cardiac surgery. Despite these advancements, postoperative pain management has received insufficient attention. The potential effects of multi-mode analgesia, including ultrasound-guided serratus anterior plane block (SAPB), on postoperative pain and early quality of recovery have not been widely studied, lacking comprehensive prospective evidence. Therefore, this study aims to investigate the impact of SAPB combined with general anesthesia on early recovery quality and analgesic efficacy in transapical TAVI patients. METHODS: This prospective, randomized controlled study will enroll 70 patients undergoing transapical TAVI, randomly allocated to either the SAPB group or the control group. The primary outcome, assessed using Quality of Recovery-40 (QOR-40) scale, focuses on the quality of recovery at 24 h and 48 h postoperatively. Secondary outcomes include the visual analog scale (VAS) pain scores at rest and during coughing at 6 h, 12 h, 24 h, and 48 h after surgery, frequency of patient-controlled analgesia (PCA) utilization at 24 h and 48 h, opioid consumption at 24 h and 48 h, time and frequency of rescue analgesia and severe pain at 24 h and 48 h, incidence of nausea and vomiting at 48 h after surgery, and dosage of antiemetic drugs. DISCUSSION: The purpose of our study is to evaluate the effects of ultrasound-guided SAPB combined with general anesthesia on postoperative early quality of recovery and analgesia in transapical TAVI patients. The results obtained may provide valuable insight for the implementation of multi-mode analgesia and enhanced ERAS in this specific patient population. TRIAL REGISTRATION: China Clinical Trial Register ChiCTR2300068584. Registered on 24 February 2023.

Inhibitory Effect and Mechanism upon Glucose-Insulin-Potassium Administration on Postpartum Mice with Uterine Cramping Pain.

This study aimed to explore the effect of glucose-insulin-potassium (GIK) on postpartum uterine cramping pain(UCP) in mice and the possible underlying mechanisms. Thirty full-term pregnancy C57BL/6 mice, within 6 h after spontaneous labor, the mice were randomly assigned into the following three groups: the control group (group C), the oxytocin group (group O), and the GIK plus oxytocin group (group G). Group G and group O were administered GIK and normal saline, respectively, and 10 min later, oxytocin was injected intraperitoneally; group C received normal saline twice. The pain scores of the mice were assessed after establishment of the postpartum UCP model. The differential expressions of energy metabolism and oxidized lipid metabolites in the uterus were analyzed. The behavioral scores in group G were significantly lower than those in group O (P < 0.05).When compared to group O, group G showed a significant increase in ATP levels (P = 0.046), and group G exhibited elevated levels of amino acids, including L-glutamine, L-aspartic acid, and ornithine. Additionally, phosphate compounds (2-phosphoglyceric acid and 3-phosphoglyceric acid) showed elevated levels. When compared to group O, group G exhibited a decrease in 19R-hydroxy PGF2α, an increase in 9,10-EpOME and 12,13-EpOME, and a decrease in trans-EKODE-E-Ib. Additionally, group G showed an elevation in 16,17-EpDPE and 8-HDoHE. This study confirms the analgesic effect of GIK during postpartum oxytocin infusion. Metabolomics and glycolysis product analysis suggest that GIK's alleviation of UCP is associated with its enhancement of glycolysis and the influence of phenylalanine synthesis, aspartate metabolism, and arginine synthesis pathways. Additionally, the effects of GIK appears to be linked to its influence on the linoleic acid metabolic pathway.

Characterizing the Dynamic Expression of C1q/TNF-α-Related Protein 6 (CTRP6) during Pregnancy in Humans and Mice with Gestational Diabetes Mellitus.

AIM: C1q/TNF-related protein 6 (CTRP6) is a novel adipokine involved in insulin resistance. Thus, we aim to investigate the expression profile of CTRP6 in the plasma, adipose tissue and placenta of GDM patients and mice. METHODS: Chinese Han pregnant women (GDM n = 9, control n = 10) with a scheduled caesarean section delivery were recruited. A number of high-fat diet (HFD) induced-pregnancy C57BL/6 mice were chosen as an animal model of GDM. Circulating levels of CTRP6 and adiponectin were examined by ELISA. CTRP6 expression in adipose tissue and placenta were detected by real-time qPCR and WB. RESULT: Plasma CTRP6 levels were decreased during the first and second trimesters in mice, as well as the second and third trimesters in patients, while they were increased at delivery in GDM patients and mice. Plasma CTRP6 levels were significantly correlated with WBC, systolic pressure, diastolic pressure and fasting blood glucose. Moreover, CTRP6 mRNA expression in the subcutaneous (sWAT) and omental white adipose tissue (oWAT), as well as in the placenta, was significantly higher in GDM human patients at cesarean delivery. Furthermore, the mRNA expression of Ctrp6 was increased in the sWAT and visceral WAT (vWAT), whilst decreased in the interscapular brown adipose tissue (iBAT), of GDM mice at cesarean delivery. CONCLUSION: Dynamically expressed CTRP6 may be served as a candidate target for treatment of GDM.

Engineering of Halide Methyltransferase BxHMT through Dynamic Cross-Correlation Network Analysis.

Halide methyltransferases (HMTs) provide an effective way to regenerate S-adenosyl methionine (SAM) from S-adenosyl homocysteine and reactive electrophiles, such as methyl iodide (MeI) and methyl toluene sulfonate (MeOTs). As compared with MeI, the cost-effective unnatural substrate MeOTs can be accessed directly from cheap and abundant alcohols, but shows only limited reactivity in SAM production. In this study, we developed a dynamic cross-correlation network analysis (DCCNA) strategy for quickly identifying hot spots influencing the catalytic efficiency of the enzyme, and applied it to the evolution of HMT from Paraburkholderia xenovorans. Finally, the optimal mutant, M4 (V55T/C125S/L127T/L129P), exhibited remarkable improvement, with a specific activity of 4.08 U/mg towards MeOTs, representing an 82-fold increase as compared to the wild-type (WT) enzyme. Notably, M4 also demonstrated a positive impact on the catalytic ability with other methyl donors. The structural mechanism behind the enhanced enzyme activity was uncovered by molecular dynamics simulations. Our work not only contributes a promising biocatalyst for the regeneration of SAM, but also offers a strategy for efficient enzyme engineering.

Sexual dimorphism in thermogenic regulators and metrnl expression in adipose tissue of offspring mice exposed to maternal and postnatal overnutrition.

Current study investigated the impact of maternal and postnatal overnutrition on phenotype of adipose, in relation to offspring thermogenesis and sex. Female C57BL/6 J mice were fed with CHOW or high fat diet (HFD) for 2 weeks before mating, throughout gestation and lactation. At weaning, pups were fed to 9 weeks old with CHOW or HFD, which resulted in four groups for each gender--male or female: CHOW-CHOW (CC), CHOW-HFD (CH), HFD-CHOW (HC), HFD-HFD (HH). Maternal and post-weaning HFD enhanced thermogenic factors such as Acox1, Dio2 and Cox8b in iBAT of male and female offspring, but increased SIRT1, PGC-1α and UCP1 only in female. However, Acox1, Dio2 and Cox8b mRNA expression and SIRT1, PGC-1α and UCP1 protein expression were only enhanced upon maternal and post-weaning HFD in sWAT and pWAT of female offspring. Increased metrnl expression in adipose were observed in sex- and depot-specific manner, while enhanced circulating metrnl level was only observed in male offspring undergoing maternal HFD. Palmitic acid changed metrnl expression during preadipocytes differentiation and siRNA-mediated knockdown of metrnl inhibited preadipocyte differentiation. Female offspring were more prone to resist adverse outcomes induced by maternal and post-weaning overnutrition, which probably related to metrnl expression and thermogenesis.

The relationship between postpartum negative life events and postpartum depression: a moderated mediation model of neuroticism and psychological flexibility.

BACKGROUND: Postpartum depression (PPD) is a major public health problem worldwide. Previous studies have shown that postpartum negative life events and neuroticism are both important risk factors for PPD. However, few studies have considered the role of protective factors in the influence of postpartum negative life events and neuroticism on PPD. Based on the diathesis-stress model and Acceptance and Commitment Therapy (ACT), a moderated mediating model was established to examine the mediating role of neuroticism between postpartum negative life events and PPD, as well as the moderating role of psychological flexibility in this mediating effect. METHODS: A sample of 776 parturients from three different Grade A hospitals in China were assessed using the Edinburgh Postpartum Depression Scale, the Postpartum Negative Life Events Scale, the Neuroticism Subscale of the Big Five Personality Scale, and the Acceptance and Action Questionnaire- II. RESULTS: PPD, postpartum negative life events, neuroticism, and experiential avoidance were significantly positively correlated with one another. Neuroticism partially mediated the relationship between postpartum negative life events and PPD. In this mediation model, the direct path and the second half of the mediation path were moderated by psychological flexibility. Specifically, the links between postpartum negative life events and PPD, as well as between neuroticism and PPD, were stronger when psychological flexibility was low, but weaker when psychological flexibility was high. CONCLUSIONS: The results show that psychological flexibility plays an important role in buffering the negative effects of postpartum negative life events and neuroticism on PPD. These findings provide implications for the prevention and intervention of PPD using an ACT approach.

N1-methylnicotinamide impairs gestational glucose tolerance in mice.

N1-methylnicotinamide (MNAM), a product of methylation of nicotinamide through nicotinamide N-methyltransferase, displays antidiabetic effects in male rodents. This study aimed to evaluate the ameliorative potential of MNAM on glucose metabolism in a gestational diabetes mellitus (GDM) model. C57BL/6N mice were fed with a high-fat diet (HFD) for 6 weeks before pregnancy and throughout gestation to establish the GDM model. Pregnant mice were treated with 0.3% or 1% MNAM during gestation. MNAM supplementation in CHOW diet and HFD both impaired glucose tolerance at gestational day 14.5 without changes in insulin tolerance. However, MNAM supplementation reduced hepatic lipid accumulation as well as mass and inflammation in visceral adipose tissue. MNAM treatment decreased GLUT4 mRNA and protein expression in skeletal muscle, where NAD+ salvage synthesis and antioxidant defenses were dampened. The NAD+/sirtuin system was enhanced in liver, which subsequently boosted hepatic gluconeogenesis. GLUT1 protein was diminished in placenta by MNAM. In addition, weight of placenta, fetus weight, and litter size were not affected by MNAM treatment. The decreased GLUT4 in skeletal muscle, boosted hepatic gluconeogenesis and dampened GLUT1 in placenta jointly contribute to the impairment of glucose tolerance tests by MNAM. Our data provide evidence for the careful usage of MNAM in treatment of GDM.

Translocation of TiO2 nanoparticles enhances phosphorus uptake by wetland plants: Evidence from Pistia stratiotes and Alisma plantago-aquatica.

Titanium dioxide nanoparticles (nTiO2) and phosphorus (P) are widely present in sewages. To verify the hypothesis and the associated mechanisms that root-to-shoot translocation of nTiO2 can enhance plant P uptake thus P removal during sewage treatment, two wetland plants (Pistia stratiotes and Alisma plantago-aquatica) with different lateral root structures were used to examine the effect of nTiO2 (89.7% anatase and 10.3% rutile) on plant growth and P uptake in a hydroponic system. Inductively coupled plasma-optical emission spectroscopy and transmission electron microscopy-energy dispersive spectroscopy showed that P. stratiotes with well-developed lateral roots translocated 1.4-16 fold higher nTiO2 than A. plantago-aquatica with poorly developed roots, indicating P. stratiotes is efficient in nTiO2 uptake. In addition, nTiO2 root-to-shoot translocation in P. stratiotes increased with increasing nTiO2 concentration, while the opposite occurred in A. plantago-aquatica. Corresponding to the stronger nTiO2 translocation in P. stratiotes, its P uptake efficiency (Imax) and P accumulation were greater than that in A. plantago-aquatica, with Imax being increased by 35.8% and -16.4% and shoot P concentrations being increased by 16.2-64.6% and 11.4%, respectively. The strong positive correlation between Ti and P concentrations in plant tissues (r = 0.72-0.89, P < 0.01) indicated that nTiO2 translocation enhanced P uptake. Moreover, nTiO2-enhanced P uptake promoted plant growth and photosynthetic pigment synthesis. Therefore, wetland plants with well-developed lateral roots like P. stratiotes have potential to be used in P removal from nTiO2-enriched sewages.

Anticoagulation decision-making before non-cardiac surgery in patients with mechanical heart valve: A retrospective study.

Objective: To clarify the timing of warfarin discontinuation at different ranges of INR. Improve anticoagulation management in non-cardiac surgical patients with MHV. Design: This is a single-center retrospective observational study. Setting: and participants This study used data from the Hospital Information System, and the Surgery and Anesthesia Information System of the Second Affiliated Hospital of Army Military Medical University. Participants included 121 adult patients with MHV who underwent non-cardiac surgery from 2012 to 2021. Results: Overall, 121 patients with MHV (15 aortic valve only, 56 mitral valve only, and 50 with multiple valves) underwent non-cardiac surgery. When the duration of warfarin discontinuation was ≤ 3 days, 3-5 days, and≥5 days, the INR was 1.45, 1.15, and 1.09, respectively. Bleeding between INR ≤1.2 and INR >1.2 groups was not statistically significant using Student's t-test (95% CI -0.57, 0.14 P = 0.24). Multivariate regression analysis revealed that Intraoperative bleeding volume correlated with preoperative albumin levels (OR = 0.68，95% CI 0.49, 0.89). Conclusions: When need preoperative INR is less than 1.5 in patients with MHV undergoing non-cardiac surgery, preoperative warfarin discontinuation for 3 days is sufficient. If INR less than 1.2, preoperative warfarin discontinuation for 3-5 days is appropriate. And in patients with MHV underwent abdominal surgery, intraoperative bleeding is not significant reduced by lower INR after preoperative warfarin discontinuation. Furthermore, the effect of albumin levels on coagulation function cannot be ignored in patients with MHV. Strengths and limitations: This study was derived from real-world clinical data. It's a retrospectively study to describe the INR changed according to the duration of warfarin discontinuation in patients with MHV and compared intraoperation of bleeding volume between INR>1.2 and INR ≤ 1.2after warfarin discontinuation. To clarify the timing of warfarin discontinuation at different ranges of INR. Improve anticoagulation management in non-cardiac surgical patients with MHV, while providing clinicians with a reference for preoperative warfarin adjustment. This study does have a few limitations. The number of cases is small because patients undergoing repeat noncardiac surgery after heart valve surgery are a special case population. And the patients were not followed up after non-cardiac surgery. The impact of changes in INR on postoperative complications could not be assessed in patients with MHV.

Equatorial waves as useful precursors to tropical cyclone occurrence and intensification.

Understanding and prediction of tropical cyclone (TC) activity on the medium range remains challenging. Here, we find that the pre-existing westward-moving equatorial waves can inform the risk of TC occurrence and intensification, based on a dataset obtained by synchronising objectively identified TCs and equatorial waves in a climate reanalysis. Globally, westward-moving equatorial waves can be precursors to 60-70% of pre-tropical cyclogenesis events, and to >80% of the events with the strongest vorticity, related to the favourable environmental conditions within the pouch of equatorial waves. We further find that when storms are in-phase with westward-moving equatorial waves, the intensification rate of TCs is augmented, whilst in other phases of the waves, storm intensity grows more slowly, or even decays. Coherent wave packets associated with TCs are identifiable up to two weeks ahead. Our findings show that westward-moving equatorial waves can be useful medium-range precursors to TC activity.

Analgesic outcomes of tramadol alone and in combination with Butorphanol or Flurbiprofen Axetil after cesarean section: a retrospective study with propensity score matching analysis.

BACKGROUND: The Society for Obstetric Anesthesia and Perinatology recommends a multimodal analgesia regimen for cesarean delivery analgesia. This study aimed to compare the analgesic effects of tramadol alone and combined with butorphanol or flurbiprofen axetil after a cesarean section. METHODS: We performed a retrospective analysis based on the electronic medical records of a teaching hospital in China from January 2018 to January 2020. We collected data on demographic characteristics, anesthesia, analgesia strategy, and pain intensity postoperatively during the first 48 hours. Inadequate postoperative analgesia during this period was defined as an NRS score ≥ 4. We also collected data regarding off-bed activity and intestinal function recovery. Participants were classified into three groups according to analgesia regimens. Groups T, TF, and TB received tramadol, a mixture of tramadol and flurbiprofen axetil, and a combination of tramadol and butorphanol, respectively. Analgesic outcomes were compared using propensity score matching analysis. RESULTS: Data from 2323 cases of caesarean section were included in the analysis, and 521 pairs were matched in each group according to their propensity score. Compared with group T, The inadequate analgesia on pain at rest and pain at movement was lower in group TF (RR: 0.42, 95% CI: 0.36-0.49, P = 0.001 and RR: 0.58, 95% CI: 0.48-0.69, P < 0.001, respectively),and the incidence of inadequate control of pain at movement was higher in group TB (RR: 1.38, 95% CI: 1.22-1.55, P < 0.001). Additionally, the percentage of off-bed activity at 2 days postoperatively was higher in group TB than in groups TF and T (78.7% vs. 68.5 and 78.7% vs. 64.9%, respectively, P < 0.001). The incidence of intestinal function recovery 2 days after cesarean delivery in group TB was higher than that in group TF (73.3% vs. 66.2%, P = 0.013). CONCLUSIONS: Combining tramadol and flurbiprofen axetil could enhance the analgesic effect and be safely used for analgesia after a cesarean section. However, combining tramadol and butorphanol may produce an antagonistic effect.

Tripartite Symbiotic Digestion of Lignocellulose in the Digestive System of a Fungus-Growing Termite.

Fungus-growing termites are efficient in degrading and digesting plant substrates, achieved through the engagement of symbiotic gut microbiota and lignocellulolytic Termitomyces fungi cultivated for protein-rich food. Insights into where specific plant biomass components are targeted during the decomposition process are sparse. In this study, we performed several analytical approaches on the fate of plant biomass components and did amplicon sequencing of the 16S rRNA gene to investigate the lignocellulose digestion in the symbiotic system of the fungus-growing termite Odontotermes formosanus (Shiraki) and to compare bacterial communities across the different stages in the degradation process. We observed a gradual reduction of lignocellulose components throughout the process. Our findings support that the digestive tract of young workers initiates the degradation of lignocellulose but leaves most of the lignin, hemicellulose, and cellulose, which enters the fresh fungus comb, where decomposition primarily occurs. We found a high diversity and quantity of monomeric sugars in older parts of the fungus comb, indicating that the decomposition of lignocellulose enriches the old comb with sugars that can be utilized by Termitomyces and termite workers. Amplicon sequencing of the 16S rRNA gene showed clear differences in community composition associated with the different stages of plant biomass decomposition which could work synergistically with Termitomyces to shape the digestion process. IMPORTANCE Fungus-farming termites have a mutualist association with fungi of the genus Termitomyces and gut microbiota to support the nearly complete decomposition of lignocellulose to gain access to nutrients. This elaborate strategy of plant biomass digestion makes them ecologically successful dominant decomposers in (sub)tropical Old World ecosystems. We employed acid detergent fiber analysis, high-performance anion-exchange chromatography (HPAEC), high-performance liquid chromatography (HPLC), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), pyrolysis gas chromatography-mass spectrometry (Py-GC-MS), and amplicon sequencing of the 16S rRNA gene to examine which lignocellulose components were digested and which bacteria were abundant throughout the decomposition process. Our findings suggest that although the first gut passage initiates lignocellulose digestion, the most prominent decomposition occurs within the fungus comb. Moreover, distinct bacterial communities were associated with different stages of decomposition, potentially contributing to the breakdown of particular plant components.

Glucose-insulin-potassium alleviates uterine cramping pain following cesarean delivery: A randomized, controlled trial.

Objectives: To explore the effect of glucose-insulin-potassium (GIK) therapy on uterine cramping pain (UCP) following cesarean delivery (CD). Design: Single-center, randomized controlled study. Setting: Second Affiliated Hospital of Army Medical University, Chongqing, China. Participants: A total of 140 women, aged 20-40 years, who underwent CD with a transverse incision were randomly assigned to the GIK (P) or control (C) groups in a 1:1 ratio. Interventions: GIK was intravenously administered to patients in Group P. Patients in Group C received normal saline (NS). After umbilical cord clamping, oxytocin was administered intravenously. The same GIK and NS regimens were administered on postoperative days 1 and 2, followed by oxytocin 10 min later. Primary and secondary outcome measures: Following oxytocin administration, UCP was assessed using the visual analog scale (VAS), and the maximum VAS score (primary outcome) was recorded. Results: Patients in Group P had significantly lower maximum VAS scores than those in Group C on postoperative days 1 (38.4 ± 21.1 vs. 52.3 ± 20.8, p < 0.001) and 2 (10 [0,30] vs. 30.5 [8.75,50], p < 0.001). Group P patients also had shorter pain duration on postoperative day 1 (39.6 ± 19.5 min vs. 50.6 ± 18.2 min, p = 0.001). Group P patients had a lower incidence of inadequate analgesia of UCP than Group C on days 1 (45.5% vs. 74.2%, p < 0.001) and 2 (10.6% vs. 47.0%, p < 0.001); the RRs for experiencing inadequate analgesia for UCP postpartum in Group P patients was 0.612 (95% CI: 0.454-0.826, p < 0.001) on day 1 and 0.226 (95% CI: 0.107-0.476, p < 0.001) on day 2. The absolute risk reduction (ARR) was 28.7%; thus number needed to treat (NNT) was 3 after rounding up. A subgroup analysis demonstrated that Group P patients undergoing repeat CD had lower maximum VAS scores for UCP on both postoperative days 1 and 2. Conclusion: Our findings suggest that GIK can relieve UCP and shorten its duration. Our results provide information to facilitate the development of novel approaches for managing UCP.Clinical Trial Registration: This study was approved by the Medical Ethics Committee of Second Affiliated Hospital of Army Medical University (2020-109-01, 19/11/2020) and registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR2100041607,01/01/2021).

Green synthesis of AgNP-ligand complexes and their toxicological effects on Nilaparvata lugens.

BACKGROUND: Despite developments in nanotechnology for use in the pharmaceutical field, there is still a need for implementation of this technology in agrochemistry. In this study, silver nanoparticles (AgNPs) were successfully prepared by a facile and an eco-friendly route using two different ligands, 2'-amino-1,1':4',1″-terphenyl-3,3″,5,5″-tetracarboxylic acid (H4L) and 1,3,6,8-tetrakis (p-benzoic acid)-pyrene (TBAPy), as reducing agents. The physiochemical properties of the as-obtained AgNPs were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The toxicity of H4L-AgNP and TBAPy-AgNP against the brown planthopper (BPH, Nilaparvata lugens) was also measured. RESULTS: SEM and TEM analyses demonstrated the formation of quasi-spherical AgNP structures in the presence of H4L and TBAPy. Insecticidal assays showed that TBAPy is less effective against N. lugens, with a median lethal concentration (LC50) of 810 mg/L, while the toxicity of H4L increased and their LC50 reached 786 mg/L 168 h posttreatment at a high concentration of 2000 mg/L. H4L-AgNPs were also highly toxic at a low concentration of 20 mg/L, with LC50 = ~ 3.9 mg/L 168 h posttreatment, while TBAPy-AgNPs exhibited less toxicity at the same concentration, with LC50 = ~ 4.6 mg/L. CONCLUSIONS: These results suggest that the synthesized AgNPs using the two ligands may be a safe and cheaper method compared with chemical insecticides for protection of rice plants from pests and has potential as an effective insecticide in the N. lugens pest management program.

Discovery of a Long-Acting Parathyroid Hormone 1-34 Analogue to Treat Hypoparathyroidism.

Hypoparathyroidism (HP) is a rare disease with clinical manifestations of hypocalcemia and hyperphosphatemia, resulting from deficient or absent parathyroid hormone (PTH) secretion. Conventional treatment for patients with HP involves extensive calcium and vitamin D supplementation. In 2015, PTH1-84 was approved by the United States Food and Drug Administration as an adjunct for HP patients who cannot be well-controlled on conventional treatment. However, PTH1-84 therapy requires a daily injection, leading to poor patient compliance. The purpose of this study was to develop a long-acting PTH1-34 analogue by increasing its affinity to albumin. Three PTH1-34 variants were generated by substituting two of the three lysine (Lys) residues with arginine, reserving a single Lys as the modification site in each sequence. A series of side chains, containing fatty acid, deoxycholic acid, or biotin groups, were synthesized to modify these PTH1-34 variants by using a solid-liquid phase synthesis approach. In vitro bioactivity and albumin affinity tests were used to screen these new PTH1-34 analogues. Finally, Lys27-AAPC was selected from 69 synthesized analogues as a candidate therapeutic compound because it retained potency and exhibited a high albumin-binding capacity. In pharmacodynamic experiments, Lys27-AAPC demonstrated enhanced and prolonged efficacy in serum calcium elevating relative to PTH1-84. Moreover, a lyophilized powder for injection containing Lys27-AAPC was developed for further testing and represented a potential long-acting HP treatment.

Continuous Blood purification on Influenza-Associated Neurological Disease in children: a retrospective cohort study.

BACKGROUND: Due to lack of proven therapies, we evaluated the effect of CBP on Influenza-Associated Neurological Disease in children. METHODS: A single-center, retrospective, cohort study was conducted in Luoyang, Henan province, China from January 2018 to January 2020. Children (<18 years) with influenza-associated neurological disease were enrolled in the study. Children with indications for CBP and parental consent received CBP (Continuous Blood purification), while others received maximal intensive care treatment because of the absence of parental consent. The outcomes of the CBP and non-CBP groups were compared. Categorical variables were presented as percentage and compared by Chi-square test. Continuous variables were expressed as median (interquartile ranges) and compared with non-parametric independent sample test. Statistical analyses were carried out by SPSS (version 26.0) and p < 0.05 (2 tailed) was considered to be statistically significant. RESULTS: 30 children with influenza-associated neurological disease were recruited to the study. 18 received CBP and the other 12 received maximal intensive care. There were no differences between CBP and non-CBP children in age, sex, body weight, type of influenza virus, neurological complications, Glasgow score, PIM-2 score and PCIS at admission (p > 0.05). The inflammatory factors (CRP, PCT and IL-6) of 30 cases were tested at admission and after 3 days of admission. In the CBP group, there was a significant decrease in IL-6 levels at 3 days of admission (p = 0.003) and a decrease in CRP and PCT levels, but no significant difference (p > 0.05). In the non-CBP group, there were no significant difference on levels of CRP, PCT and IL-6 at admission and 3-day of admission (p > 0.05). The 28-day mortality was significantly lower in the CBP group compared with the non-CBP group (11.11% vs. 50%, p = 0.034). CONCLUSIONS: CBP definitely reduces IL-6 levels significantly. We did find that the survival rate of patients in the CBP group was improved. But we don't know if there is a relationship between the reduction of IL-6 levels and the survival rate. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (ChiCTR2000031754).

Heart rate variability-derived features based on deep neural network for distinguishing different anaesthesia states.

BACKGROUND: Estimating the depth of anaesthesia (DoA) is critical in modern anaesthetic practice. Multiple DoA monitors based on electroencephalograms (EEGs) have been widely used for DoA monitoring; however, these monitors may be inaccurate under certain conditions. In this work, we hypothesize that heart rate variability (HRV)-derived features based on a deep neural network can distinguish different anaesthesia states, providing a secondary tool for DoA assessment. METHODS: A novel method of distinguishing different anaesthesia states was developed based on four HRV-derived features in the time and frequency domain combined with a deep neural network. Four features were extracted from an electrocardiogram, including the HRV high-frequency power, low-frequency power, high-to-low-frequency power ratio, and sample entropy. Next, these features were used as inputs for the deep neural network, which utilized the expert assessment of consciousness level as the reference output. Finally, the deep neural network was compared with the logistic regression, support vector machine, and decision tree models. The datasets of 23 anaesthesia patients were used to assess the proposed method. RESULTS: The accuracies of the four models, in distinguishing the anaesthesia states, were 86.2% (logistic regression), 87.5% (support vector machine), 87.2% (decision tree), and 90.1% (deep neural network). The accuracy of deep neural network was higher than those of the logistic regression (p < 0.05), support vector machine (p < 0.05), and decision tree (p < 0.05) approaches. Our method outperformed the logistic regression, support vector machine, and decision tree methods. CONCLUSIONS: The incorporation of four HRV-derived features in the time and frequency domain and a deep neural network could accurately distinguish between different anaesthesia states; however, this study is a pilot feasibility study. The proposed method-with other evaluation methods, such as EEG-is expected to assist anaesthesiologists in the accurate evaluation of the DoA.

Multipartite symbioses in fungus-growing termites (Blattodea: Termitidae, Macrotermitinae) for the degradation of lignocellulose.

Fungus-growing termites are among the most successful herbivorous animals and improve crop productivity and soil fertility. A range of symbiotic organisms can be found inside their nests. However, interactions of termites with these symbionts are poorly understood. This review provides detailed information on the role of multipartite symbioses (between termitophiles, termites, fungi, and bacteria) in fungus-growing termites for lignocellulose degradation. The specific functions of each component in the symbiotic system are also discussed. Based on previous studies, we argue that the enzymatic contribution from the host, fungus, and bacteria greatly facilitates the decomposition of complex polysaccharide plant materials. The host-termitophile interaction protects the termite nest from natural enemies and maintains the stability of the microenvironment inside the colony.

Termitomyces heimii Associated with Fungus-Growing Termite Produces Volatile Organic Compounds (VOCs) and Lignocellulose-Degrading Enzymes.

Termitomyces fungi associated with fungus-growing termites are the edible mushrooms and can produce useful chemicals, enzymes, and volatile organic compounds (VOCs) that have both fuel and biological potentials. To this purpose, we examined the Termitomyces mycelial growth performance on various substrates, clarified lignocellulose-degrading enzyme activity, and also identified the VOCs produced by Termitomyces. Our results indicated that the optimal nutrition and condition requirements for mycelial growth are D-sorbitol, D-(+)-glucose, and D-(-)-fructose as carbon sources; peptone as well as yeast extract and ammonium tartrate as nitrogen sources; and Mn2+, Na+, and Mg2+ as metal ions with pH range from 7.0 to 8.0. Besides, the orthogonal matrix method results revealed that the ideal composition for mycelial growth is 20 g/L D-(-)-fructose, 5 g/L yeast extract, 0.5 g/L Mg2+, and pH = 7. We also screened various substrates composition for the activity of lignocellulose-degrading enzymes, i.e., lignin peroxidase, manganese peroxidase, ß-glucosidase, a-L-arabinofuranosidase, and laccase. Furthermore, we identified 37 VOCs using GC-MS, and the most striking aspect was the presence of a big series of alcohols and acids, collectively constituted about 49% of the total VOCs. Ergosta-5, 8, 22-trien-3-ol, (3.beta.,22E) was the most plenteous compound constituted 30.369%. This study hopes to establish a better understanding for researchers regarding Termitomyces heimii cultivation on a large scale for the production of lignocellulosic enzymes and some fungal medicine.