Diagnostic significance of serum levels of serum amyloid A, procalcitonin, and high-mobility group box 1 in identifying necrotising enterocolitis in newborns.

BACKGROUND: Necrotising enterocolitis (NEC) is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates. Serum amyloid A (SAA), procalcitonin (PCT), and high-mobility group box 1 (HMGB1) have emerged as potential biomarkers for NEC due to their roles in inflammatory response, tissue damage, and immune regulation. AIM: To evaluate the diagnostic value of SAA, PCT, and HMGB1 in the context of NEC in newborns. METHODS: The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital. Clinical, radiological, and laboratory findings, including serum SAA, PCT, and HMGB1 Levels, were collected, and specific detection methods were used. The diagnostic value of the biomarkers was evaluated through statistical analysis, which was performed using chi-square test, t-test, correlation analysis, and receiver operating characteristic (ROC) analysis. RESULTS: The study demonstrated significantly elevated levels of serum SAA, PCT, and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls. The correlation analysis indicated strong positive correlations among serum SAA, PCT, and HMGB1 Levels and the presence of NEC. ROC analysis revealed promising sensitivity and specificity for serum SAA, PCT, and HMGB1 Levels as potential diagnostic markers. The combined model of the three biomarkers demonstrating an extremely high area under the curve (0.908). CONCLUSION: The diagnostic value of serum SAA, PCT, and HMGB1 Levels in NEC was highlighted. These biomarkers potentially improve the early detection, risk stratification, and clinical management of critical conditions. The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.

Cross-sectional study of hepatitis B virus infection in female breast cancer patients in China for the first time diagnosed.

BACKGROUND: The correlation between breast cancer and hepatitis B virus (HBV) remains inconclusive. This study aims to explore the serological status of HBV infection and past infection in different age groups of female breast cancer patients, patients with benign breast diseases, and individuals undergoing routine physical examinations. METHODS: Serum data on HBV serological markers were collected and analyzed from 6072 female breast cancer patients first diagnosed from September 2012 to July 2020 at the First Affiliated Hospital of Chongqing Medical University, along with 4019 women with benign breast diseases and 54,740 healthy females undergoing routine physical examinations in the same period. The data were stratified by age for comparison between groups. RESULTS: The prevalence of HBV infection and past infection in the breast cancer group (7.9%, 55.1%) was higher than that in the benign breast disease group (6.5%, 39.1%) and the healthy females group(5.0%, 17.6%);the rate of only HBV surface antibody positivity (HBsAb ( +)) in the breast cancer group (10.3%) was lower than that in the benign breast disease group (26.9%) and the healthy females group (49.2%), with significant differences between the three groups (p < 0.05). Stratified by age, the prevalence of HBV infection in the breast cancer group (8%, 8.9%) and benign breast disease group (7.75%, 8.1%)was higher than that in the healthy females group (4.5%, 6.3%) in the 30-39 and 40-49 age group, respectively. The past infection rate of HBV in the breast cancer group (24.8%, 45.0%) was higher than that in the benign breast disease group (16.1%, 35.4%) in the ≤ 29 and 30-39 age group, respectively.. The past infection rate of HBV in the breast cancer group was higher than that in the healthy females group in all age groups, while the rate of only HBsAb ( +) in the breast cancer group was lower than that in the benign breast disease group and the routine physical examination group in all age groups. CONCLUSIONS: Breast cancer women and women with benign breast diseases have higher rates of hepatitis B virus infection and previous infections, with more significant differences among middle-aged women. Breast cancer women and women with benign breast diseases have lower rates of only HBsAb ( +) for HBV.

Site-Selective Deuteration of α-Amino Esters with 2-Hydroxynicotinaldehyde as a Catalyst.

An efficient method has been developed for the synthesis of α-deuterated α-amino esters via hydrogen isotope exchange of α-amino esters in D2O with 2-hydroxynicotinaldehyde as a catalyst under mild conditions. This methodology exhibits a wide range of substrate scopes, remarkable functional group tolerance, and affording the desired products in good yields with excellent deuterium incorporation. Notably, the ortho-hydroxyl group and the pyridine ring of the catalyst play a crucial role in the catalytic activity, which not only stabilizes the carbon-anion intermediates but also enhances the acidity of the amino esters' α-C-H bond.

Performance improvement of reflective phosphor film via adjusting the thickness realizing bright and efficient laser lighting.

Phosphor-in-glass-film (PiG-F) has been extensively investigated, showing great potential for use in laser lighting technique. Thickness is apparently a key parameter for PiG-F, affecting the heat dissipation, absorption, and reabsorption, thus determining the luminous efficacy and luminescence saturation threshold (LST). Conventional studies suggest that thinner films often have lower thermal load than that of the thicker ones. Unexpectedly, we found that the Lu3Al5O12:Ce (LuAG:Ce)-based PiG-F with a moderate thickness (78 µm) yielded the optimal LST of 31.9 W (14.2 W·mm-2, rather than 28.0 W (12.3 W·mm-2) for the thinnest one (56 µm). This unexpected result was further verified by thermal simulations. With the high saturation threshold together with a high luminous efficacy (∼296 lm·W-1), an ultrahigh luminous flux of 7178 lm with a luminous exitance of 2930 lm·mm-2 was thus attained. We believe the new, to the best of our knowledge, findings in this study will substantially impact the design principles of phosphors for laser lighting.

Metagenomic Next-Generation Sequencing as an Effective Diagnostic Tool for Talaromycosis in HIV-Negative Patients.

The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis.

Amino-Functionalized NDI-Based MOFs as Unusual "Turn On" and "Turn Off" Fluorescent Sensors for Phenolic Pollutants with Double Solvent Channel Response and Iodine Adsorbents.

Regulating mixed ligands to change the functional properties of metal-organic frameworks (MOFs) has been an important topic; especially, the structural changes have significant implications for the transformation of sensing response in different solvent channels. Herein, two [Cd (DPNDI) (NH2-BDC)0.5(NO3)]·2.25DMF (1) and [Cd(DPNDI)(NH2-AIPA)]·0.5DMF (2) (DPNDI = N,N-di(4-pyridyl)-1,4,5,8-naphthalenetetracarboxydiimide, NH2-BDC = 2-amino terephthalic acid, NH2-AIPA = 5-aminoisophthalic acid) were synthesized by the solvothermal method. Structural analysis shows that complex 1 has a two-dimensional planar network structure and complex 2 exhibits a three-dimensional network structure, endowing its potential as an efficient fluorescence sensor for phenolic compound detection under different solvent environments. Both complexes showed high fluorescence quenching sensitivity to phenolics in a water medium. Conversely, complex 1 showed a fluorescence enhancement response to phenolic pollutants in an ethanol system with significantly low detection limits and recyclability. The detection limits were 0.58 µM for TNP, 1.3 µM for DNP, and 2.43 µM for PCP. In addition, the uncoordinated amino groups in the complexes promote them to exhibit excellent iodine adsorption performance. Especially, complex 2 can serve as an adsorbent for iodine in cyclohexane solution with better adsorption efficiency than that of complex 1, and its adsorption capacity can reach 505 mg/g. The mixed ligands regulation strategy of NDI-based MOFs will open up an effective avenue for the conversion of fluorescence signals in dual-solvent channels and play simultaneously important roles in multiple applications.

NMR-Guided Isolation of Anti-inflammatory Carabranolides from the Fruits of Carpesium abrotanoides L.

Carabranolides present characteristic NMR resonances for the cyclopropane moiety, which distinctly differ from those of other compounds and were used for an NMR-guided isolation in this study. As a result, 11 undescribed carabranolides (1-11), along with five known ones (12-16), were isolated from the fruits of Carpesium abrotanoides L. Compounds 1-11 are new esters of carabrol at C-4 with different carboxylic acids. Their structures were elucidated by HRESIMS and NMR spectroscopic data analysis. The biological evaluation showed that compounds 2-4, 15, and 16 exhibited significant inhibitory activity against LPS-induced NO release with an IC50 value of 5.6-9.1 µM and dose-dependently decreased iNOS protein expression in RAW264.7 cells.

Development of Novel N-Acylhydrazone Derivatives with High Anti-obesity Activity and Improved Safety by Exploring the Pharmaceutical Properties of Aldehyde Group.

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.

Full-length GSDME mediates pyroptosis independent from cleavage.

Gasdermin (GSDM) family proteins, known as the executors of pyroptosis, undergo protease-mediated cleavage before inducing pyroptosis. We here discovered a form of pyroptosis mediated by full-length (FL) GSDME without proteolytic cleavage. Intense ultraviolet-C irradiation-triggered DNA damage activates nuclear PARP1, leading to extensive formation of poly(ADP-ribose) (PAR) polymers. These PAR polymers are released to the cytoplasm, where they activate PARP5 to facilitate GSDME PARylation, resulting in a conformational change in GSDME that relieves autoinhibition. Moreover, ultraviolet-C irradiation promotes cytochrome c-catalysed cardiolipin peroxidation to elevate lipid reactive oxygen species, which is then sensed by PARylated GSDME, leading to oxidative oligomerization and plasma membrane targeting of FL-GSDME for perforation, eventually inducing pyroptosis. Reagents that concurrently stimulate PARylation and oxidation of FL-GSDME, synergistically promoting pyroptotic cell death. Overall, the present findings elucidate an unreported mechanism underlying the cleavage-independent function of GSDME in executing cell death, further enriching the paradigms and understanding of FL-GSDME-mediated pyroptosis.

Prediction of antimicrobial resistance in Klebsiella pneumoniae using genomic and metagenomic next-generation sequencing data.

OBJECTIVES: Klebsiella pneumoniae is a significant pathogen with increasing resistance and high mortality rates. Conventional antibiotic susceptibility testing methods are time-consuming. Next-generation sequencing has shown promise for predicting antimicrobial resistance (AMR). This study aims to develop prediction models using whole-genome sequencing data and assess their feasibility with metagenomic next-generation sequencing data from clinical samples. METHODS: On the basis of 4170 K. pneumoniae genomes, the main genetic characteristics associated with AMR were identified using a LASSO regression model. Consequently, the prediction model was established, validated and optimized using clinical isolate read simulation sequences. To evaluate the efficacy of the model, clinical specimens were collected. RESULTS: Four predictive models for amikacin, ciprofloxacin, levofloxacin and piperacillin/tazobactam, initially had positive predictive values (PPVs) of 90%, 85%, 84% and 94%, respectively, when they were originally constructed. When applied to clinical specimens, their PPVs increased to 96%, 96%, 95% and 100%, respectively. Meanwhile, there were negative predictive values (NPVs) of 100% for ciprofloxacin and levofloxacin, and 'not applicable' (NA) for amikacin and piperacillin/tazobactam. Our method achieved antibacterial phenotype classification accuracy rates of 96.08% for amikacin, 96.15% for ciprofloxacin, 95.31% for levofloxacin and 100% for piperacillin/tazobactam. The sequence-based prediction antibiotic susceptibility testing (AST) reported results in an average time of 19.5 h, compared with the 67.9 h needed for culture-based AST, resulting in a significant reduction of 48.4 h. CONCLUSIONS: These preliminary results demonstrated that the performance of prediction model for a clinically significant antimicrobial-species pair was comparable to that of phenotypic methods, thereby encouraging the expansion of sequence-based susceptibility prediction and its clinical validation and application.

Structurally diverse diterpenoids from the leaves of Croton mangelong and their anti-diabetic activity.

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg.

The dichloromethane fraction from Calotropis gigantea (L.) dryand. Stem bark extract prevents liver cancer in SDT rats with insulin-independent diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: Calotropis gigantea (L.) Dryand. (C. gigantea) is a traditional medicinal plant, recognized for its effectiveness in managing diabetes, along with its notable antioxidant, anti-inflammatory, and anticancer properties. Type II diabetes mellitus (T2DM) is characterized by chronic metabolic disorders associated with an elevated risk of hepatocellular carcinoma (HCC) due to hyperglycemia and impaired insulin response. The scientific validation of C. gigantea's ethnopharmacological efficacy offers advantages in alleviating cancer progression in T2DM complications, enriching existing knowledge and potentially aiding future clinical cancer treatments. AIM: This study aimed to investigate the preventive potential of the dichloromethane fraction of C. gigantea stem bark extract (CGDCM) against diethylnitrosamine (DEN)-induced HCC in T2DM rats, aiming to reduce cancer incidence associated with diabetes while validating C. gigantea's ethnopharmacological efficacy. MATERIALS AND METHODS: Spontaneously Diabetic Torii (SDT) rats were administered DEN to induce HCC (SDT-DEN-VEH), followed by treatment with CGDCM. Metformin was used as a positive control (SDT-DEN-MET). All the treatments were administered for 10 weeks after the initial DEN injection. Diabetes-related parameters, including serum levels of glucose, insulin, and glycosylated hemoglobin (HbA1c), as well as liver function enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase), were quantified. Serum inflammation biomarkers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated. Liver tissue samples were analyzed for inflammation protein expression (IL-6, TNF-α, transforming growth factor-ß1 (TGF-ß1), and α-smooth muscle actin (α-SMA)). Histopathological evaluation was performed to assess hepatic necrosis, inflammation, and fibrosis. Liver cell proliferation was determined using immunohistochemistry for Ki-67 expression. RESULTS: Rats with SDT-DEN-induced HCC treated with CGDCM exhibited reduced serum glucose levels, elevated insulin levels, and decreased HbA1c levels. CGDCM treatment also reduced elevated hepatic IL-6, TNF-α, TGF-ß1, and α-SMA levels in SDT-DEN-VEH rats. Additionally, CGDCM treatment prevented hepatocyte damage, fibrosis, and cell proliferation. No adverse effects on normal organs were observed with CGDCM treatment, suggesting its safety for the treatment of HCC complications associated with diabetes. Additionally, the absence of adverse effects in SD rats treated with CGDCM at 2.5 mg/kg further supports the notion of its safe usage. CONCLUSIONS: These findings suggest that C. gigantea stem bark extract exerts preventive effects against the development of HCC complications in patients with T2DM, expanding the potential benefits of its ethnopharmacological advantages.

Gradient Lithium Ion Regulation Current Collectors for High-Performance and Dendrite-Free Li Metal Batteries.

Lithium metal anode has attracted wide attention due to its ultrahigh theoretical specific capacity, lowest reduction potential, and low density. However, uncontrollable dendritic growth and volume change caused by uneven Li+ deposition still seriously hinder the large-scale commercial application of lithium metal batteries, even causing serious battery explosions and other safety problems. Hence, gold nanoparticles with a gradient distribution anchored on 3D carbon fiber paper (CP) current collectors followed by the encapsulation of polydopamine (PDA) (CP/Au/PDA) are constructed for stable and dendrite-free Li metal anodes for the first time. Significantly, lithiophilic Au nanoparticles showing a gradient distribution in the carbon fiber paper could guide the transfer of Li+ from the outside to the inside of the CP/Au/PDA electrode as well as lower the nucleation overpotential of Li, thereby obtaining the uniform Li deposition. Meanwhile, the PDA layer could in situ be converted to Li-PDA which could serve as an efficient Li+ conductor to further facilitate uniform Li+ transport among the whole CP/Au/PDA electrode. Besides, 3D carbon fiber paper could effectively accommodate the volume change during the plating/stripping process of Li metal. As a result, CP/Au/PDA electrodes deliver a low nucleation overpotential (∼9 mV) and a high Coulombic efficiency (mean value of ∼98.8%) at a current density of 1 mA cm-2 with the capacity of 1 mA h cm-2. Furthermore, Li@CP/Au/PDA electrodes also can demonstrate an ultralow voltage hysteresis (∼20 mV) and a long cycle life (1000 h) in symmetric cells. Finally, with LiFePO4 (LFP) as the cathode, the Li@CP/Au/PDA-LFP full cell delivers a high discharge capacity of 136 mA h g-1 even after 350 cycles at 1C, exhibiting a per cycle loss as low as 0.01%. This gradient lithium ion regulation current collector is of great significance for the development of lithium metal anodes.

Follow-up study of gallbladder stones in 44 children.

BACKGROUND: Cholesterol stones affect a certain subpopulation of children. Concerns have been raised on the impact of gallbladder surgery on the growth of children and adolescents. AIM: To study the population characteristics, clinical features, treatment, and prognosis of gallstones in children. METHODS: The clinical data of 44 children with gallstones admitted to The First Affiliated Hospital of Naval Medical University from August 2009 to August 2021 were collected, the children were followed up by telephone to monitor their prognoses. The follow-up ended in August 2023. The shortest follow-up time was 2 years and 6 months, whereas the longest was 13 years and 11 months. The population characteristics, general clinical characteristics, and treatments were retrospectively analyzed. The children were divided according to whether they underwent surgical gallbladder removal into an operation group (n = 28) and a non-operation group (n = 16), The effects of surgical gallbladder resection on the growth and development of children were analyzed. RESULTS: The male-female ratio in the population was 6:5 and 84.09% of the children had onset in adolescence. Furthermore, 29.55% of the children were overweight or obese. The study identified 26 cases with metabolic abnormalities, 9 with hemolytic anemia, and 4 with choledochal cyst. Of the population, 68.18% had recurrent symptomatic cholecystolithiasis. Surgical treatment accounted for 63.64%, with laparoscopic cholecystectomy accounting for 71.43% of surgical treatment. No significant differences were observed in symptoms and complications between the surgery and non-surgery groups. Furthermore, no significant differences were found between the two groups in the attainment of genetic height target and the rightward shift of height curve during follow-up. CONCLUSION: The sex characteristics of gallstones in children were not observed. Most gallstones occurred in adolescents and rarely in young children. A considerable proportion of children have inborn causes, which are often concurrent with metabolic abnormalities and hemolytic anemia. Most children had recurrent symptomatic gallstones. Surgical treatment, especially laparoscopic cholecystectomy, is still the main treatment for gallstones in children. Surgical treatment did not affect the growth and development of children who underwent gallstone removal.

Lithium carbonate-induced giant goiter and subclinical hyperthyroidism in a patient with schizophrenia: A case report and review of literature.

BACKGROUND: Lithium carbonate is used to manage various mood disorders, but it can cause thyroid abnormalities, including goiter, hypothyroidism, and hyperthyroidism. In rare cases, it can lead to giant goiter and subclinical hyperthyroidism, which may require surgical intervention in severe cases. CASE SUMMARY: This case represents a rare development of giant goiter and subclinical hyperthyroidism in a schizophrenia patient who was subjected to prolonged lithium carbonate treatment. The enlarged thyroid gland caused pressure on the airway and recurrent laryngeal nerve, which led to respiratory distress, hoarseness, and dysphagia. The immediate danger of suffocation required urgent surgical intervention. In this report, we describe the case of a 41-year-old Chinese woman. This sheds light on the etiology and challenges associated with managing a giant goiter. The patient underwent a subtotal thyroidectomy to relieve airway compression and facilitate airway expansion. Prior to the procedure, the patient was given iodine to prepare. Concurrently, changes were made to the psychiatric medication regimen. Following surgery, the patient's respiratory function and vocal cord functionality improved significantly, and her mental state remained stable. CONCLUSION: It is essential to monitor thyroid function, test thyroid antibody levels, and perform thyroid ultrasounds consistently in all patients undergoing long-term lithium carbonate treatment. This vigilance helps prevent severe and potentially life-threatening thyroid enlargement.

[Plankton Community Stability and Drive Factor Identification Guizhou Plateau Reservoir].

In order to understand the stability of the zooplankton and phytoplankton communities in the Guizhou plateau reservoir environment, the process of reservoir water quality change affecting the stability of plankton was studied. The changes in the plankton community and water quality in three different nutrient reservoirs （Huaxi Reservoir, Goupitan Reservoir, and Hailong Reservoir） were studied from October 2020 to August 2021. The stability of the zooplankton and phytoplankton communities was studied using time-lag analysis （TLA）. Variance decomposition analysis （VPA） was used to explore the response of the two communities to environmental changes. The driving factors of plankton community changes in reservoirs were also revealed. The results showed that Huaxi Reservoir and Goupitan Reservoir were mesotrophic reservoirs, and Hailong Reservoir was a eutrophic reservoir. The average comprehensive nutrition indices of the three reservoirs were 44.07, 44.68, and 50.25. A total of 51 species of zooplankton rotifers, 39 species of rotifers, three species of copepods, and nine species of cladocera were identified. Among them, the abundance of rotifers was the highest, accounting for 85.96%. A total of seven phyla and 73 species of phytoplankton were identified, including 16 species in the phylum Cyanophyta, 32 species in the phylum Chlorophyta, 16 species in the phylum Diatoma, three species in the phylum Chlorophyta, four species in the phylum Euglenophyta, and one species each in the phyla Cryptophyta and Chrysophyta. Among them, the abundance of cyanobacteria and diatoms was the highest, accounting for 66.2% and 27.35%, respectively. The median absolute deviation （MAD） of the Bray-Curtis distance of zooplankton and phytoplankton community in the three reservoirs were 0.67 and 0.65 in Huaxi Reservoir, 0.80 and 0.69 in Goupitan Reservoir, and 0.85 and 0.47 in Hailong Reservoir, respectively. The larger the value, the greater the variation in the community. The absolute value of the slope of zooplankton was greater than that of phytoplankton in the TLA results, and the absolute values of the slopes were 0.018 and 0.004, respectively. The larger the absolute value of the slope, the faster the community variability. The zooplankton community in the three reservoirs was less stable than the phytoplankton community and more sensitive to environmental changes, and the degree of variation was greater. The higher the degree of eutrophication of the reservoir, the more obvious this phenomenon. VPA showed that the changes in plankton communities in Huaxi Reservoir and Hailong Reservoir were mainly influenced by water temperature and eutrophication factors. The changes in planktonic community in Goupitan Reservoir were mainly influenced by water temperature and chemical factors. The driving factors of Huaxi Reservoir were water temperature, TP, permanganate index, and SD. The driving factors of Goupitan Reservoir were water temperature, NO3-- N, and pH. The driving factors of Hailong Reservoir were water temperature and TP. Nutrients and water temperature were the main factors affecting the stability of plankton communities in reservoirs.

SIRT3/AMPK signaling pathway regulates lipid metabolism and improves vulnerability to atrial fibrillation in Dahl salt sensitive rats.

BACKGROUND: Hypertension may result in atrial fibrillation (AF) and lipid metabolism disorders. The Sirtuins3 (SIRT3) / AMP-activated protein kinase (AMPK) signaling pathway has the capacity to regulate lipid metabolism disorders and the onset of AF. We hypothesize that the SIRT3/AMPK signaling pathway suppresses lipid metabolism disorders, thereby mitigating salt-sensitive hypertension (SSHT)-induced susceptibility to AF. METHODS: The study involved 7-week-old male Dahl salt-sensitive that were fed either high-salt diet (8% NaCl; DSH group) or normal diet (0.3% NaCl; DSN group). Then DSH group were administered either oral metformin (MET, an AMPK agonist) or intraperitoneal injection of Honokiol (HK, a SIRT3 agonist). This experimental model allowed for the measurement of SBP, the expression levels of lipid metabolism-related biomarker, pathological examination of atrial fibrosis and lipid accumulation, as well as AF inducibility and AF duration. RESULTS: DSH decrease SIRT3, phosphorylation-AMPK and VLCAD expression, increased FASN and FABP4 expression and concentrations of FFA and TG, atrial fibrosis and lipid accumulation in atrial tissue, enhanced level of SBP, promoted AF induction rate and prolonged AF duration, which are blocked by MET and HK. Our results also showed that the degree of atrial fibrosis was negatively correlated with VLCAD expression, but positively correlated with the expression of FASN and FABP4. CONCLUSIONS: We have confirmed that high-salt diet can result in hypertension, associated atrial tissue lipid metabolism dysfunction. This condition is linked to the inhibition of the SIRT3/AMPK signaling pathway, which plays a significant role in the progression of susceptibility to AF in SSHT rats.

Interfacing Neuron-Motor Pathways with Stretchable and Biocompatible Electrode Arrays.

ConspectusIn the field of neuroscience, understanding the complex interactions within the intricate neuron-motor system depends crucially on the use of high-density, physiological multiple electrode arrays (MEAs). In the neuron-motor system, the transmission of biological signals primarily occurs through electrical and chemical signaling. Taking neurons for instance, when a neuron receives external stimuli, it generates an electrical signal known as the action potential. This action potential propagates along the neuron's axon and is transmitted to other neurons via synapses. At the synapse, chemical signals (neurotransmitters) are released, allowing the electrical signal to traverse the synaptic gap and influence the next neuron. MEAs can provide unparalleled insights into neural signal patterns when interfacing with the nerve systems through their excellent spatiotemporal resolution. However, the inherent differences in mechanical and chemical properties between these artificial devices and biological tissues can lead to serious complications after chronic implantation, such as body rejection, infection, tissue damage, or device malfunction. A promising strategy to enhance MEAs' biocompatibility involves minimizing their thickness, which aligns their bending stiffness with that of surrounding tissues, thereby minimizing damage over time. However, this solution has its limits; the resulting ultrathin devices, typically based on plastic films, lack the necessary stretchability, restricting their use to organs that neither stretch nor grow.For practical deployments, devices must exhibit certain levels of stretchability (ranging from 20 to 70%), tailored to the specific requirements of the target organs. In this Account, we outline recent advancements in developing stretchable MEAs that balance stretchability with sufficient electrical conductivity for effective use in physiological research, acting as sensors and stimulators. By concentrating on the neuron-motor pathways, we summarize how the stretchable MEAs meet various application needs and examine their effectiveness. We distinguish between on-skin and implantable uses, given their vastly different requirements. Within each application scope, we highlight cutting-edge technologies, evaluating their strengths and shortcomings. Recognizing that most current devices rely on elastic films with a Young's modulus value between ∼0.5 and 5 MPa, we delve into the potential for softer MEAs, particularly those using multifunctional hydrogels for an optimizing tissue-device interface and address the challenges in adapting such hydrogel-based MEAs for chronic implants. Additionally, transitioning soft MEAs from lab to fab involves connecting them to a rigid adapter and external machinery, highlighting a critical challenge at the soft-rigid interface due to strain concentration, especially in chronic studies subject to unforeseen mechanical strains. We discuss innovative solutions to this integration challenge, being optimistic that the development of durable, biocompatible, stretchable MEAs will significantly advance neuroscience and related fields.

Association between the C-Reactive Protein-Albumin-Lymphocyte (CALLY) Index and Adverse Clinical Outcomes in CAD Patients after PCI: Findings of a Real-World Study.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 10 4 ). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 ( ≤ 0.69, n = 950), Q2 (0.69-2.44, n = 950), Q3 (2.44-9.52, n = 950), and Q4 ( > 9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan-Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147-0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150-0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422-0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401-0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).

H/D Exchange of Aromatic Sulfones via Base Promotion and Silver Catalysis.

Aromatic sulfones are the prevailing scaffolds in pharmaceutical and material sciences. However, compared to their widespread application, the selective deuterium labeling of these structures is restricted due to their electron-deficient properties. This study presents two comprehensive strategies for the deuteration of aromatic sulfones. The base-promoted deuteration uses DMSO-d6 as the deuterium source, resulting in a rapid H/D exchange within 2 h. Meanwhile, a silver-catalyzed protocol offers a much milder option by using economical D2O to furnish the labeled sulfones.