Low-dose IL-2 treatment confers anti-inflammatory effect against subarachnoid hemorrhage in mice.

Objective: Subarachnoid hemorrhage (SAH) was a stroke with high occurrence and mortality. At the early stage, SAH patients have severe cerebral injury which is contributed by inflammation. In this study, we aimed to explore the anti-inflammation effect of low-dose IL-2 in SAH mice. Methods: The 12-week-old C57BL/6J male mice were conducted with SAH surgery (Internal carotid artery puncture method). Different dose of IL-2 was injected intraperitoneally for 1 h, 1 day, and 2 days after SAH. Single-cell suspension and flow cytometry were used for the test of regulatory T (Treg) cells. Immunofluorescence staining was used to investigate the phenotypic polarization of microglia and inflammation response around neurons. Enzyme-Linked Immuno-sorbent Assay (ELISA) was applied to detect the level of pro-inflammatory factors. Results: Low-dose IL-2 could enrich the Treg cells and drive the microglia polarizing to M2. The level of pro-inflammatory factors, IL-1α, IL-6, and TNF-α decreased in the low-dose IL-2 group. The inflammation response around neurons was attenuated. Low-dose IL-2 could increase the number of Treg cells, which could exert a neuroprotective effect against inflammation after SAH. Conclusion: Low-dose IL-2 had the potential to be an effective clinical method to inhibit inflammation after SAH.

A Wood-Derived Periosteum for Spatiotemporal Drug Release: Boosting Bone Repair through Anisotropic Structure and Multiple Functions.

Existing artificial periostea face many challenges, including difficult-to-replicate anisotropy in mechanics and structure, poor tissue adhesion, and neglected synergistic angiogenesis and osteogenesis. Here, inspired by natural wood (NW), a wood-derived elastic artificial periosteum is developed to mimic the structure and functions of natural periosteum, which combines an elastic wood (EW) skeleton, a polydopamine (PDA) binder layer, and layer-by-layer (LBL) biofunctional layers. Specifically, EW derived from NW is utilized as the anisotropic skeleton of artificial periosteum to guide cell directional behaviors, moreover, it also shows a similar elastic modulus and flexibility to natural periosteum. To further enhance its synergistic angiogenesis and osteogenesis, surface LBL biofunctional layers are designed to serve as spatiotemporal release platforms to achieve sequential and long-term release of pamidronate disodium (PDS) and deferoxamine (DFO), which are pre-encapsulated in chitosan (CS) and hyaluronic acid (HA) solutions, respectively. Furthermore, the combined effect of PDA coating and LBL biofunctional layers enables the periosteum to tightly adhere to damaged bone tissue. More importantly, this novel artificial periosteum can boost angiogenesis and bone formation in vitro and in vivo. This study opens up a new path for biomimetic design of artificial periosteum, and provides a feasible clinical strategy for bone repair.

Number of Pregnancies and Risk of Atherosclerotic Cardiovascular Disease in Postmenopausal Women: A Cross-Sectional Study of NHANES from 1999 to 2018.

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the most common cause of death in women. Pregnancy is an exposure unique to women leading to significant changes in maternal cardiovascular function. However, studies of the relationship between the number of pregnancies and ASCVD are rare. We aimed to clarify the association between the number of pregnancies and ASCVD. Methods: In this cross-sectional study, we used publicly available data from the National Health and Nutrition Examination Survey from 1999 to 2018. The number of pregnancies was divided into 0 (reference), 1, 2-3, 4-5, or ≥6, to create more stable estimates. A multiple logistic regression approach was used to examine the correlation between pregnancy and ASCVD in women aged 45 years or older who reported no menstruation in the past 12 months due to menopause, as well as in those aged 55 years or older, encompassing various age groups. We also separately estimated the association between the exposure of pregnancy and individual components of ASCVD. Results: In this study, age-adjusted data showed that women with six or more pregnancies had a doubled risk (odds ratio [OR]: 2.07) of ASCVD. The risk remained elevated at 1.69 times in women with four to five pregnancies and further increased to 1.90 times in women with six or more pregnancies, after adjusting for social factors. Similar patterns were observed when considering reproductive health and cardiovascular risk factors. Across the full population, every model that accounted for these variables consistently indicated that with an increasing number of pregnancies, we observed higher ORs for ASCVD risk (all p values <0.05). Conclusions: A higher number of pregnancies was associated with a higher risk of ASCVD after menopause, especially among women aged 45-64 years. Moreover, this association is particularly significant in the risk of stroke, cardiovascular heart disease, and heart attack.

[Effect of Erchen Decoction on liver mitochondrial function by inhibiting mTORC1/SREBP1/CAV1 pathway in mice with high-fat diet].

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

Chitin whisker/chitosan liquid crystal hydrogel assisted scaffolds with bone-like ECM microenvironment for bone regeneration.

Natural bone exhibits a complex anisotropic and micro-nano hierarchical structure, more importantly, bone extracellular matrix (ECM) presents liquid crystal (LC) phase and viscoelastic characteristics, providing a unique microenvironment for guiding cell behavior and regulating osteogenesis. However, in bone tissue engineering scaffolds, the construction of bone-like ECM microenvironment with exquisite microstructure is still a great challenge. Here, we developed a novel polysaccharide LC hydrogel supported 3D printed poly(l-lactide) (PLLA) scaffold with bone-like ECM microenvironment and micro-nano aligned structure. First, we prepared a chitin whisker/chitosan polysaccharide LC precursor, and then infuse it into the pores of 3D printed PLLA scaffold, which was previously surface modified with a polydopamine layer. Next, the LC precursor was chemical cross-linked by genipin to form a hydrogel network with bone-like ECM viscoelasticity and LC phase in the scaffold. Subsequently, we performed directional freeze-casting on the composite scaffold to create oriented channels in the LC hydrogel. Finally, we soaked the composite scaffold in phytic acid to further physical cross-link the LC hydrogel through electrostatic interactions and impart antibacterial effects to the scaffold. The resultant biomimetic scaffold displays osteogenic activity, vascularization ability and antibacterial effect, and is expected to be a promising candidate for bone repair.

Succinylated chitosan derivative restore HUVEC cells function damaged by TNF-α and high glucose in vitro and enhanced wound healing.

The inflammation of chronic wounds plays a key hindering role in the wound healing process. Slowing down the inflammatory response is significant for the repair of chronic wounds. Studies have revealed that succinate can inactivate gastrin D (GSDMD) and prevent cell pyroptosis. Chitosan has anti-inflammatory properties and is commonly used as wound healing material. Therefore, we used succinic anhydride to modify chitosan and found that N-succinylated chitosan (NSC) was more effective in inhibiting inflammation. The results showed that the stimulation of TNF-α and high glucose induces overexpression of capase-1 and TNF-α in human umbilical vein endothelial cells (HUVEC), and down-expression of CD31. However, the expression of capase-1 and TNF-α decreased, while the expression of CD31, VEGF and IL-10 was up-regulated significantly in dysfunctional HUVEC cells after treated by NSC. Moreover, NSC can speed wound healing, histological examination results showed that wounds treated with NSC exhibited faster epithelial tissue regeneration and thicker collagen deposition. Overall, this study results suggested that NSC has the function of restoring the physiological functions of dysfunctional HUVEC cells induced by high glucose and TNF-α, and can accelerate wound healing, indicating that NSC has good potential to be applied in inflammatory chronic wounds such as diabetic foot.

ß-Ga2O3nanotube arrays for high-performance self-powered ultraviolet photoelectrochemical photodetectors.

Self-powered ultraviolet (UV) photodetectors (PDs) are critical for future energy-efficient optoelectronic systems due to their low energy consumption and high sensitivity. In this paper, the vertically alignedß-Ga2O3nanotube arrays (NTs) have been prepared on GaN/sapphire substrate by the thermal oxidation process combined with the dry etching technology, and applied in the UV photoelectrochemical photodetectors (PEC-PDs) for the first time. Based on the large specific surface area ofß-Ga2O3NTs on GaN/sapphire substrates and the solid/liquid heterojunction, the PEC-PDs exhibit excellent self-powered characteristics under 255 nm (UVA) and 365 nm (UVC) light illumination. Under 255 nm (365 nm) light illumination, the maximum responsivity of 49.9 mA W-1(32.04 mA W-1) and a high detectivity of 1.58 × 1011Jones (1.01 × 1011Jones) were achieved for theß-Ga2O3NTs photodetectors at 0 V bias. In addition, the device shows a fast rise/decay time of 8/4 ms (4/2 ms), which is superior to the level of the previously reported self-powered UV PEC-PDs. This high-performance PEC-PD has potential applications in next-generation low-energy UV detection systems.

Key Determinants of Immune-Mediated Adverse Reactions to Oncology Drugs.

To overcome the epidemiological severity of cancer, developing effective treatments is urgently required. In response, immune checkpoint inhibitors (ICIs) have been revealed as a promising resolution for treatment-resistant cancers across the world. Yet, they have both advantages and disadvantages, bringing therapeutic benefits while simultaneously inducing toxicity, and in particular, immune-mediated adverse drug reactions (imADRs), to the human body. These imADRs can be pathogenic and sometimes lethal, hampering health prediction and monitoring following the provision of ICI treatment. Therefore, it is necessary to collectively identify the determinant factors that contribute to these imADRs induced by ICIs. This article evaluated treatment-, tumor-, and patient-related determinants, and indicated a research gap for future investigations on the pathogenic mechanism of imADRs and translational conversion of determinants into clinical biomarkers to aid pharmacovigilance and cancer therapies.

3D Printing Drug-Free Scaffold with Triple-Effect Combination Induced by Copper-Doped Layered Double Hydroxides for the Treatment of Bone Defects.

Tissue-engineered poly(l-lactide) (PLLA) scaffolds have been widely used to treat bone defects; however, poor biological activities have always been key challenges for its further application. To address this issue, introducing bioactive drugs or factors is the most commonly used method, but there are often many problems such as high cost, uncontrollable and monotonous drug activity, and poor bioavailability. Here, a drug-free 3D printing PLLA scaffold with a triple-effect combination induced by surface-modified copper-doped layered double hydroxides (Cu-LDHs) is proposed. In the early stage of scaffold implantation, Cu-LDHs exert a photothermal therapy (PTT) effect to generate high temperature to effectively prevent bacterial infection. In the later stage, Cu-LDHs can further have a mild hyperthermia (MHT) effect to stimulate angiogenesis and osteogenic differentiation, demonstrating excellent vascularization and osteogenic activity. More importantly, with the degradation of Cu-LDHs, the released Cu2+ and Mg2+ provide an ion microenvironment effect and further synergize with the MHT effect to stimulate angiogenesis and osteogenic differentiation, thus more effectively promoting the healing of bone tissue. This triple-effect combined scaffold exhibits outstanding antibacterial, osteogenic, and angiogenic activities, as well as the advantages of low cost, convenient procedure, and long-term efficacy, and is expected to provide a promising strategy for clinical repair of bone defects.

Flexible Hybrid Wearable Sensors for Pressure and Thermal Sensing Based on a Double-Network Hydrogel.

Flexible sensors have attracted great attention due to their wide applications in various fields such as motion monitoring and medical health. It is reasonable to develop a sensor with good flexibility, sensitivity, and biocompatibility for wearable device applications. In this study, a double-network hydrogel was obtained by blending poly(vinyl alcohol) (PVA) with poly(ethylene glycol) diacrylate (PEGDA), which combines the flexibility of the PVA network and the fast photocuring ability of PEGDA. Subsequently, polydopamine-coated carbon nanotubes were used as conductive fillers of the PVA-PEG hydrogel matrix to prepare a flexible sensor that exhibits an effective mechanical response and significant stability in mechanics and conductivity. More importantly, the resistance of the sensor is very sensitive to pressure and thermal changes due to the optimized conductive network in the hydrogel. A motion monitoring test showed that the flexible sensor not only responds quickly to the motion of different joints but also keeps the output signal stable after many cycles. In addition, the excellent cell affinity of the hybrid hydrogel also encourages its application in health monitoring and motion sensors.

DFT-Based Study of the Structure, Stability, and Spectral and Optical Properties of Gas-Phase NbMgn (n = 2-12) Clusters.

Gas-phase NbMgn (n = 2-12) clusters were fully searched by CALYPSO software, and then the low-energy isomers were further optimized and calculated under DFT. It is shown that the three lowest energy isomers of NbMgn (n = 3-12) at each size are grown from two seed structures, i.e., tetrahedral and pentahedral structures, and the transition size occurs at the NbMg8 cluster. Interestingly, the relative stability calculations of the NbMg8 cluster ground-state isomer stand out under the examination of several parameters' calculations. The charge-transfer properties of the clusters of the ground-state isomers of various sizes had been comprehensively investigated. In order to be able to provide data guidance for future experimental probing of these ground-state clusters, this work also predicted infrared and Raman spectra at the same level of theoretical calculations. The results show that the multipeak nature of the IR and Raman spectra predicts that it is difficult to distinguish them directly. Finally, the optical properties of these clusters were investigated by calculating the static linear, second-order nonlinear, and third-order nonlinear coefficients. Importantly and interestingly, the NbMg8 cluster was shown to have superior nonlinear optical characteristics to all other clusters; thus, it is a powerful candidate for a potentially ultrasensitive nonlinear optical response device for some special purpose.

Anisodamine hydrobromide in the treatment of critically ill patients with septic shock: a multicenter randomized controlled trial.

BACKGROUND: Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock. METHODS: This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis. RESULTS: Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups. CONCLUSION: Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results.

Regulation of recombinant humanized collagen on HAP growth and its molecule simulation.

Hydroxyapatite (HAP) in natural bone is formed under the regulation of natural collagen I. Here, we report how recombinant humanized collagen I (rhCol I) regulates the growth of HAP nanocrystals in a long belt shape 100-150 nm in width and 200-300 nm in length. MD simulation results showed that the interactions between rhCol I and the (001), (100), and (211) planes of HAP mainly contributed to the electrostatic force and van der Waals forces via COO⋯Ca, -NH⋯Ca, CH⋯OPO3, and NH⋯OPO3 bonds, respectively. On the (001) plane, the interaction between -COO- and Ca was stronger than on the (100) and (211) planes, resulting in a large electrostatic force, which inhibited the growth of the (001) plane. The lowest energy of adsorption to the (211) plane resulted in the preferential growth of the (211) plane due to the weakest interaction with rhCol I. The detailed correlation between HAP and rhCol I could explain HAP growth under regulation by rhCol I. This study provides a reference for the bio-application of recombinant collagen.

Highly anisotropic and elastic cellulosic scaffold guiding cell orientation and osteogenic differentiation via topological and mechanical cues.

Inspired by the similarity of anisotropic channels in wood to the canals of bone, the elastic wood-derived (EW) scaffolds with anisotropic channels were prepared via simple delignification treatment of natural wood (NW). We hypothesize that the degree of delignification will lead to differences in mechanical properties of scaffolds, which in turn directly affect the behaviors and fate of stem cells. The delignification process did not destroy the anisotropic channel structure of the scaffolds, but endowed the scaffolds with good elasticity and rapid stress relaxation. Interestingly, the micron-scale anisotropic channels of the scaffolds can highly promote the polarization of cells along the direction of channels. We also found that the alkaline phosphatase of EW scaffold can reach to about 13.1 U/gprot, which was about double that of NW scaffold. Moreover, the longer the delignification time, the better the osteogenic activity of the EW scaffolds. We further hypothesize that the osteogenic activity of scaffolds is related to the stress relaxation properties. The immunofluorescence staining showed that when the stress relaxation time of scaffold was shortened to about 10 s, the nuclear ratio of YAP of scaffold increased to 0.22, which well supports our hypothesis.

Modulating of Bouligand Structure and Chirality Constructed Bionically Based on the Self-Assembly of Chitin Whiskers.

Chitin can self-assemble into a liquid crystal phase with supramolecular chirality and Bouligand structure, which is widely found in the exoskeletons of arthropods. However, bionically replicating this structure via the self-assembly of chitin whiskers (CHWs) is still a challenge. Here, the effects of several internal and external parameters on the self-assembly of CHWs were revealed based on liquid crystal phase, chirality, Bouligand structure, and rheological properties. The formation of chiral liquid crystal phase and Bouligand structure largely depends on the concentration of CHWs and, meanwhile, is affected by the aspect ratio and zeta potential of CHWs and the self-assembly time. Impressively, introducing electrolytes and changing pH significantly affect the thickness of the electrical double layer, thereby also affecting the self-assembly of CHWs. This study offers a comprehensive understanding of CHWs' self-assembly process, which is beneficial for the bionic design of new nature-inspired functional materials with chiral characteristic and Bouligand structure.

Preparation of chitin/MXene/poly(L-arginine) composite aerogel spheres for specific adsorption of bilirubin.

Currently, hemoperfusion is clinically the most rapid and effective treatment for removing toxins from the blood. The core of hemoperfusion is the sorbent inside the hemoperfusion device. Due to the complex composition of the blood, adsorbents tend to adsorb substances such as proteins in the blood (non-specific adsorption) while adsorbing toxins. Hyperbilirubinemia is caused by excessive levels of bilirubin in the human blood, causing irreversible damage to the patient's brain and nervous system, and even leading to death. High adsorption and high biocompatibility adsorbents with specific bilirubin adsorption are urgently needed to treat hyperbilirubinemia. Herein, poly(L-arginine) (PLA) which can specifically adsorb bilirubin, was introduced into chitin/MXene (Ch/MX) composite aerogel spheres. Ch/MX/PLA prepared by supercritical CO2 technology had higher mechanical properties than Ch/MX and can withstand 50,000 times its own weight. The in vitro simulated hemoperfusion test showed that the adsorption capacity of Ch/MX/PLA was as high as 596.31 mg/g, which was 15.38 % higher than that of Ch/MX. Binary and ternary competitive adsorption tests showed that Ch/MX/PLA also had good adsorption capacity in the presence of a variety of interfering molecules. In addition, hemolysis rate testing and CCK-8 testing confirmed that Ch/MX/PLA had better biocompatibility and hemocompatibility. Ch/MX/PLA can meet the required properties of clinical hemoperfusion sorbents and has the ability to produce mass production. It has good application potential in the clinical treatment of hyperbilirubinemia.

Tandem-Parallel Electrochemical Cells to Produce Hydrogen Peroxide at Reduced Energy Consumption.

Large-scale industrialization of oxygen electroreduction requires producing hydrogen peroxide (H2O2) at large yield rates (current density >1 A cm-2, Faradic efficiency >95%). Under such vigorous reaction conditions, however, serious electric energy consumption (EEC) has been caused. According to the formula (EEC=Y×1000×R×F2172×FE2), a linear relationship can be identified between H2O2 yield rates (Y) and EEC, and therefore, achieving high yield rates (Y) while reducing EEC is very challenging in common electrochemical systems. In this work, we have designed a tandem-parallel oxygen electroreduction system composed of two oxygen electroreduction units. The tandem unit can effectively improve the Faradaic efficiency (FE) while the parallel section reduces total internal resistance (R). Consequently, the overall system can achieve a high H2O2 yield rate (592 mg h-1) with the lowest EEC (2.41 kWh kg-1) ever reported to the best of our knowledge. Further, the tandem-parallel system has shown promising stability by working for more than 10 cycles or 24 h. Besides oxygen electroreduction, other applications have been also demonstrated for the tandem-parallel system that can generate H2O2 for in situ degradation of rhodamine B pollutant.

Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange.

Modular SCF (SKP1-CUL1-Fbox) ubiquitin E3 ligases orchestrate multiple cellular pathways in eukaryotes. Their variable SKP1-Fbox substrate receptor (SR) modules enable regulated substrate recruitment and subsequent proteasomal degradation. CAND proteins are essential for the efficient and timely exchange of SRs. To gain structural understanding of the underlying molecular mechanism, we reconstituted a human CAND1-driven exchange reaction of substrate-bound SCF alongside its co-E3 ligase DCNL1 and visualized it by cryo-EM. We describe high-resolution structural intermediates, including a ternary CAND1-SCF complex, as well as conformational and compositional intermediates representing SR- or CAND1-dissociation. We describe in molecular detail how CAND1-induced conformational changes in CUL1/RBX1 provide an optimized DCNL1-binding site and reveal an unexpected dual role for DCNL1 in CAND1-SCF dynamics. Moreover, a partially dissociated CAND1-SCF conformation accommodates cullin neddylation, leading to CAND1 displacement. Our structural findings, together with functional biochemical assays, help formulate a detailed model for CAND-SCF regulation.

Association between the insulin resistance marker TyG index and subsequent adverse long-term cardiovascular events in young and middle-aged US adults based on obesity status.

BACKGROUND: A lthough the triglyceride-glucose (TyG) index has been shown to closely correlate with cardiometabolic outcomes and predict cardiovascular events in many groups, it remains unclear whether obese status in young and middle-aged adults is associated with long-term unfavorable cardiovascular events. This warrants further investigation. METHODS: This retrospective cohort study analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999-2018, with follow-up for mortality status until December 31, 2019. To categorize participants based on the TyG level, the optimal critical value was determined through restricted cubic spline function analysis, dividing them into high and low TyG groups. The study assessed the relationship between TyG and cardiovascular events and all-cause mortality in young and middle-aged adults stratified by obesity status. Kaplan‒Meier and Cox proportional risk models were used to analyze the data. RESULTS: During a follow-up period of 123 months, a high TyG index increased the risk of cardiovascular events by 63% (P = 0.040) and the risk of all-cause mortality by 32% (P = 0.010) in individuals after adjusting for all covariates. High TyG was shown to be linked to cardiovascular events in obese people (Model 3: HR = 2.42, 95% CI = 1.13-5.12, P = 0.020); however, there was no significant difference in TyG groups for nonobese adults in Model 3 (P = 0.08). CONCLUSIONS: TyG was independently associated with harmful long-term cardiovascular events in young and middle-aged US populations, with a stronger association observed in those who were obese.

Advanced lung cancer inflammation index is associated with long-term cardiovascular death in hypertensive patients: national health and nutrition examination study, 1999-2018.

Background: Hypertension is one of the main causes of cardiovascular death. Inflammation was considered influential factors of cardiovascular (CVD) death in patients with hypertension. Advanced lung cancer inflammation index (ALI) is an index to assess inflammation, few studies have investigated the relationship between advanced lung cancer inflammation index and cardiovascular death in hypertensive patients. Objective: The aim of this study was to investigate the association between advanced lung cancer inflammation index and long-term cardiovascular death in hypertensive patients. Method: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 with mortality follow-up through 31 December 2019 were analyzed. Advanced lung cancer inflammation index was calculated as BMI (kg/㎡) × serum albumin level (g/dL)/neutrophil to lymphocyte ratio (NLR). A total of 20,517 participants were evaluated. Patients were divided into three groups based on tertiles of advanced lung cancer inflammation index as follows: T1 (n = 6,839), T2 (n = 6,839), and T3 (n = 6,839) groups. The relationship between advanced lung cancer inflammation index and long-term cardiovascular death was assessed by survival curves and Cox regression analysis based on the NHANES recommended weights. Results: The median advanced lung cancer inflammation index value in this study was 61.9 [44.4, 84.6]. After full adjustment, the T2 group (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50-0.69; p < 0.001) and T3 group (HR: 0.48, 95% CI: 0.39-0.58; p < 0.001) were found to have a significantly lower risk of cardiovascular death compared to the T1 group. Conclusion: High levels of advanced lung cancer inflammation index were associated with reduced risk of cardiovascular death in hypertensive patients.