A nanofluidic spiking synapse.

Currently, the nanofluidic synapse can only perform basic neuromorphic pulse patterns. One immediate problem that needs to be addressed to further its capability of brain-like computing is the realization of a nanofluidic spiking device. Here, we report the use of a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate membrane to achieve bionic ionic current-induced spiking. In addition to the simulation of various electrical pulse patterns, our synapse could produce transmembrane ionic current-induced spiking, which is highly analogous to biological action potentials with similar phases and excitability. Moreover, the spiking properties could be modulated by ions and neurochemicals. We expect that this work could contribute to biomimetic spiking computing in solution.

Associations between adverse childhood experiences and pain in middle-aged and older adults: findings from the China Health and Retirement Longitudinal Study.

OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations. METHODS: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTS: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain. CONCLUSIONS: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics.

Verapamil inhibits respiratory syncytial virus infection by regulating Ca2+ influx.

AIMS: The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. MATERIALS AND METHODS: RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. KEY FINDINGS: Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication. SIGNIFICANCE: Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.

Chemoproteomic strategy identifies PfUCHL3 as the target of halofuginone.

The human malaria parasite Plasmodium falciparum (P. falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti-P. falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P. falciparum. Our results reveal that ubiquitin carboxyl-terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6' region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P. falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti-malarial agents in the future.

Scalp acupuncture targets for neurological disorders：evidence from neuroimaging studies (part 1). / åŸºäºŽç¥žç»å½±åƒå­¦çš„å¸¸è§ç¥žç»ç³»ç»Ÿç–¾ç— å¤´é’ˆåˆºæ¿€é¶ç‚¹ç ”ç©¶ï¼ˆä¸Šï¼‰.

OBJECTIVES: Scalp acupuncture is a unique acupuncture method developed based on brain functional and pathophysiological knowledge. In past decades, there has been significant development in the understanding of the brain pathology of many neurological disorders through cutting-edge brain imaging techniques. Yet, these findings have not been incorporated into scalp acupuncture. In the present paper, we aimed to initiate an attempt to develop/identify scalp acupuncture targets based on neuroimaging findings. METHODS: Based on the meta-analysis of neuroimaging studies in the Neurosynth database platform (http：//neurosynth.org/), the brain clusters related to neurological disorders were automatically identified according to the search terms "Parkinson's disease"(PD), "chronic pain"(CP), "aphasia"(APH), "dyslexia"(DYS), "mild cognitive impairment", "Alzheimer's disease" and "dementia". Subsequently, the discovered brain region clusters projected onto the brain surface and scalp surface were listed, and the peak points of the clusters projected to the scalp surface were proposed as the potential stimulation targets for the corresponding diseases. Further, by combining the traditional scalp acupoints (including the scalp acupuncture lines) with 10-20 EEG system sites, we made localization suggestions for scalp stimulation targets and made acupuncture operation suggestions by combining with the shape of the brain region clusters. The literature search was conducted on July 30, 2022. RESULTS: The localization and manipulation suggestions of neuroimage-based scalp acupuncture targets were introduced in two parts. This part (part 1) includes PD, CP, APH, and DYS. Here are 3 target examples of each of these 4 diseases simply introduced due to word limitation. 1) PD. Based on the 175 articles retrieved from Neurosynth, we identified 7 potential scalp acupuncture targets for PD, the locations of the acupuncture stimulation and the recommended acupuncture needle operation (RANO) as well as the corresponding brain regions (CBRs) respectively are as below. PD1：about 0.5 cun (1 cun≈33.3 mm) superior-posterior to the left Xuanlu (GB5)；puncturing subcutaneously and forward-upward；the left premotor area, subfrontal cortex of the island, inferior frontal gyrus and middle frontal gyrus. PD2：about 1 cun lateral-inferior to the left Chengling (GB18)；puncturing subcutaneously and backward-upward；the inferior parietal lobule and postcentral gyrus. PD3：about 0.5 cun lateral-anterior to the left GB18；puncturing subcutaneously and inward-backward；left anterior central gyrus and posterior central gyrus. 2) CP. Based on the retrieved 92 articles, we identified 8 potential scalp acupuncture targets, the location of the acupuncture stimulation and the RANO, and CBRs respectively are as below. CP1：about 1 cun anterior-inferior to the left Xuanli (GB8)；puncturing subcutaneously and backward-inwards；the left inferior frontal gyrus orbitalis and pars triangularis. CP2：about 0.5 cun posterior-superior to the left GB5；puncturing subcutaneously and forward-upward；the left anterior central gyrus and premotor area. CP3：about 0.5 cun posterior-superior to the left GB8；puncturing subcutaneously and forward；left inferior central area/central sulci operculum (second somatosensory area). 3) APH. Based on the retrieved 82 papers, we identified 7 potential scalp acupuncture targets for APH, their locations, RANO, and CBRs respectively are as below. APH1：close to the left GB5；puncturing subcutaneously and forward-downward；left subfrontal gyrus operculi/triangularis. APH2：about 0.5 cun posterior to the left Hanyan (GB4)；puncturing subcutaneously and backward-upward；the left anterior central gyrus and posterior central gyrus. APH3：about 0.5 cun anterior-inferior to the left Qubin (GB7)；puncturing subcutaneously and backward-downward；left medial/superior temporal gyrus. 4) DYS. Based on the retrieved 76 researches, we identified 8 potential scalp acupuncture targets for DYS, their locations, RANO and CBRs respectively are as below. DYS1：about 1 cun anterior-inferior to the left GB5；puncturing subcutaneously and forward-upward；the pars triangularis of the left inferior frontal gyrus. DYS2：about 0.5 cun posterior-superior to the left GB5；puncturing subcutaneously and forward-downward；the left subfrontal gyrus operculum, pars triangularis and anterior central gyrus. DYS3：the midpoint between the left GB5 and GB18；puncturing subcutaneously and forward；the left anterior central gyrus and posterior central gyrus. CONCLUSIONS: We identified scalp acupuncture targets for several common neurological disorders based on neuroimaging evidence for clinical application and research. The proposed targets may also be used for treating these disorders using brain stimulation methods.

Cerebral 18F-FDG PET/CT Metabolism as Diagnostic Signature for Central Nervous System Toxicity After Immune Checkpoint Blockade Cancer Treatment.

Our aim was to investigate probable biomarkers specific to immune-related central nervous system toxicity (CNST) in cancer patients treated with immune checkpoint inhibitors (ICI) by analysis of 18F-FDG PET/CT images. Methods: Cancer patients receiving ICI treatment were enrolled in a multicenter observational study that analyzed regional metabolic changes before and during CNST onset from January 2020 to February 2022. In 1:1 propensity score-matched pairs, the regional SUVmean of each bilateral brain lobe of CNST patients (CNST+) was compared with that of patients who had central nervous system infections (CNSIs) and patients without CNST or CNSI (CNST-). In a validation cohort, patients were recruited from February 2022 to July 2023 and followed up for 24 wk after the start of ICI. Early changes in regional SUVmean at 5-6 wk after therapy initiation were evaluated for ability to predict later CNST onset. Results: Of 6,395 ICI-treated patients, 2,387 underwent prognostic 18F-FDG PET/CT and 125 of the scanned patients had CNST (median time from ICI treatment to onset, 9 wk; quartile range, 2-23 wk). Regional 18F-FDG PET/CT SUVmean changes were higher in CNST+ than in CNST- patients (117 patient pairs) but were lower than in CNSI patients (50 pairs). Differentiating analysis reached an area under the curve (AUC) of 0.83 (95% CI, 0.78-0.88) for CNST+ versus CNST- and of 0.80 (95% CI, 0.72-0.89) for CNST+ versus CNSI. Changes in SUVmean were also higher before CNST onset than for CNST- (60 pairs; AUC, 0.74; 95% CI, 0.66-0.83). In a validation cohort of 2,878 patients, preonset changes in SUVmean reached an AUC of 0.86 (95% CI, 0.79-0.94) in predicting later CNST incidence. Conclusion: Brain regional hypermetabolism could be detected during and before CNST clinical onset. CNST may be a distinct pathologic entity versus brain infections defined by 18F-FDG PET/CT brain scans. Regional SUV differences may be translated into early diagnostic tools based on moderate differentiating accuracy in our study.

Electropositive Citric Acid-Polyethyleneimine Carbon Dots Carrying the PINK1 Gene Regulate ATP-Related Metabolic Dysfunction in APP/PS1-N2a Cells.

(1) Background: Alzheimer's disease (AD) is characterized by ß-amyloid (Aß) peptide accumulation and mitochondrial dysfunction during the early stage of disease. PINK1 regulates the balance between mitochondrial homeostasis and bioenergy supply and demand via the PINK1/Parkin pathway, Na+/Ca2+ exchange, and other pathways. (2) Methods: In this study, we synthesized positively charged carbon dots (CA-PEI CDs) using citric acid (CA) and polyethyleneimine (PEI) and used them as vectors to express PINK1 genes in the APP/PS1-N2a cell line to determine mitochondrial function, electron transport chain (ETC) activity, and ATP-related metabolomics. (3) Results: Our findings showed that the CA-PEI CDs exhibit the characteristics of photoluminescence, low toxicity, and concentrated DNA. They are ideal biological carriers for gene delivery. PINK1 overexpression significantly increased the mitochondrial membrane potential in APP/PS1-N2a cells and reduced reactive-oxygen-species generation and Aß1-40 and Aß1-42 levels. An increase in the activity of NADH ubiquinone oxidoreductase (complex I, CI) and cytochrome C oxidase (complex IV, CIV) induces the oxidative phosphorylation of mitochondria, increasing ATP generation. (4) Conclusions: These findings indicate that the PINK gene can alleviate AD by increasing bioenergetic metabolism, reducing Aß1-40 and Aß1-42, and increasing ATP production.

[Intraoperative slide rail CT assistance in percutaneous sacroiliac joint screws for the treatment of pelvic posterior ring injury].

OBJECTIVE: To compare the clinical efficacy of intraoperative slide rail CT combined with C-arm X-ray assistance and just C-arm for percutaneous screw in the treatment of pelvic posterior ring injury. METHODS: A retrospective analysis was performed on the patient data of 76 patients with posterior pelvic ring injury admitted to the Department of Orthopedic Trauma from December 2018 to February 2022. Among them, 39 patients in the CT group were treated with C-arm combined with slide rail CT-assisted inline fixation including 23 males and 16 females with an average age of (44.98±7.33) years old;and the other 37 patients in the C-arm group were treated with intraline fixation treatment under only C-arm fluoroscopy including 24 males and 13 females with an average age of (44.37±10.82) years old. Among them, 42 patients with anterior ring fractures were treated with percutaneous inferior iliac spines with internal fixation (INFIX) or suprapubic support screws to fix the anterior pelvic ring. Postoperative follow-up time, operation time, complications of the two groups were compared. Results of Matta reduction criteria, Majed efficacy evaluation, the CT grading and the rate of secondary surgical revision were compared. RESULTS: The nailing time of (32.63±7.33) min in CT group was shorter than that of (52.95±10.64) min in C-arm group (t=-9.739, P<0.05). The follow-up time between CT group (11.97±1.86) months and C-arm group (12.03±1.71) months were not statistically significant(P>0.05). The postoperative complication rates between two groups were not statistically significant (χ2=0.159, P>0.05). Results of Matta reduction criteria (Z=2.79, P<0.05), Majeed efficacy evaluation(Z=2.79, P<0.05), CT grading (Z=2.83, P<0.05) in CT group were better than those in C-arm group(P<0.05); the secondary surgical revision rate in the CT group was significantly lower than that in the C-arm group (χ2=5.641, P<0.05). CONCLUSION: Compared with traditional C-arm fluoroscopy, intraoperative slide rail CT combined with C-arm assisted percutaneous sacroiliac joint screw placement surgery has the characteristics of short operation time, high accuracy and safety, and significant decrease in postoperative secondary revision rate, and is one of the effective methods for re-establishing the stability of the posterior ring of pelvic fracture.

Characterization of Escherichia coli Strains for Novel Production of Plasmodium ovale Lactate Dehydrogenase.

Malaria is one of the most prevalent diseases worldwide with high incidence and mortality. Among the five species that can infect humans, Plasmodium ovale morphologically resembles Plasmodium vivax, resulting in misidentification and confusion in diagnosis, and is responsible for malarial disease relapse due to the formation of hypnozoites. P. ovale receives relatively less attention compared to other major parasites, such as P. falciparum and P. vivax, primarily due to its lower pathogenicity, mortality rates, and prevalence rates. To efficiently produce lactate dehydrogenase (LDH), a major target for diagnosing malaria, this study used three Escherichia coli strains, BL21(DE3), BL21(DE3)pLysS, and Rosetta(DE3), commonly used for recombinant protein production. These strains were characterized to select the optimal strain for P. ovale LDH (PoLDH) production. Gene cloning for recombinant PoLDH production and transformation of the three strains for protein expression were performed. The optimal PoLDH overexpression and washing buffer conditions in nickel-based affinity chromatography were established to ensure high-purity PoLDH. The yields of PoLDH expressed by the three strains were as follows: BL21(DE3), 7.6 mg/L; BL21(DE3)pLysS, 7.4 mg/L; and Rosetta(DE3), 9.5 mg/L. These findings are expected to be highly useful for PoLDH-specific diagnosis and development of antimalarial therapeutics.

Salivary metabolites are promising noninvasive biomarkers of drug-induced liver injury.

BACKGROUND: Drug-induced liver injury (DILI) is one of the most common adverse events of medication use, and its incidence is increasing. However, early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests. AIM: To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools. METHODS: Saliva samples from 31 DILI patients and 35 healthy controls (HCs) were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry. Subsequent analyses, including partial least squares-discriminant analysis modeling, t tests and weighted metabolite coexpression network analysis (WMCNA), were conducted to identify key differentially expressed metabolites (DEMs) and metabolite sets. Furthermore, we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction. The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves. RESULTS: We found 247 differentially expressed salivary metabolites between the DILI group and the HC group. Using WMCNA, we identified a set of 8 DEMs closely related to liver injury for further prediction testing. Interestingly, the distinct separation of DILI patients and HCs was achieved with five metabolites, namely, 12-hydroxydodecanoic acid, 3-hydroxydecanoic acid, tetradecanedioic acid, hypoxanthine, and inosine (area under the curve: 0.733-1). CONCLUSION: Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients. Our study may provide a potentially feasible and noninvasive diagnostic method for DILI, but further validation is needed.

Extracellular volume fraction derived from dual-energy CT: a potential predictor for acute pancreatitis after pancreatoduodenectomy.

OBJECTIVES: To investigate the value of extracellular volume (ECV) fraction and fat fraction (FF) derived from dual- energy CT (DECT) for predicting postpancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD). METHODS: This retrospective study included patients who underwent DECT and PD between April 2022 and September 2022. PPAP was determined according to the International Study Group for Pancreatic Surgery (ISGPS) definition. Iodine concentration (IC) and FF of the pancreatic parenchyma were measured on preoperative DECT. The ECV fraction was calculated from iodine map images of the equilibrium phase. The independent predictors for PPAP were assessed by univariate and multivariable logistic regression analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Sixty-nine patients were retrospectively enrolled (median age, 60 years; interquartile range, 55-70 years; 47 men). Of these, nine patients (13.0%) developed PPAP. These patients had lower portal venous phase IC, equilibrium phase IC, FF, and ECV fraction, and higher pancreatic parenchymal-to-portal venous phase IC ratio and pancreatic parenchymal-to-equilibrium phase IC ratio, compared with patients without PPAP. After multivariable analysis, ECV fraction was independently associated with PPAP (odd ratio [OR], 0.87; 95% confidence interval [CI]: 0.79, 0.96; p < 0.001), with an area under the curve (AUC) of 0.839 (sensitivity 100.0%, specificity 58.3%). CONCLUSIONS: A lower ECV fraction is independently associated with the occurrence of PPAP after PD. ECV fraction may serve as a potential predictor for PPAP after PD. CLINICAL RELEVANCE STATEMENT: DECT-derived ECV fraction of pancreatic parenchyma is a promising biomarker for surgeons to preoperatively identify patients with higher risk for postpancreatectomy acute pancreatitis after PD and offer selective perioperative management. KEY POINTS: PPAP is a complication of pancreatic surgery, early identification of higher-risk patients allows for risk mitigation. Lower DECT-derived ECV fraction was independently associated with the occurrence of PPAP after PD. DECT aids in preoperative PAPP risk stratification, allowing for appropriate treatment to minimize complications.

Osthole exhibits the remedial potential for polycystic ovary syndrome mice through Nrf2-Foxo1-GSH-NF-κB pathway.

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro-inflammatory cytokine interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF-κB) subunit p65 by DHEA and weakened the transcriptional activity of NF-κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF-κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2-Foxo1-GSH-NF-κB pathway.

The neuroimmune pathway of high-altitude adaptation: influence of erythrocytes on attention networks through inflammation and the autonomic nervous system.

Introduction: Many studies have shown that the functional adaptation of immigrants to high-altitude is closely related to oxygen transport, inflammatory response and autonomic nervous system. However, it remains unclear how human attention changes in response to hypoxia-induced neurophysiological activity during high-altitude exposure. Methods: In the present study, we analyzed the relationship between hypoxic-induced neurophysiological responses and attention networks in 116 immigrants (3,680 m) using an attention network test to simultaneously record electroencephalogram and electrocardiogram in combination with specific routine blood markers. Results: Our analysis revealed that red blood cells exert an indirect influence on the three attention networks, mediated through inflammatory processes and heart rate variability. Discussion: The present study provides experimental evidence for the role of a neuroimmune pathway in determining human attention performance at high- altitude. Our findings have implications for understanding the complex interactions between physiological and neurocognitive processes in immigrants adapting to hypoxic environments.

Inhalation of 2, 4-di-tert-butylphenol-Loaded micelles suppresses respiratory syncytial virus infection in mice.

Human respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants, young children, and elderly people. However, there are no effective treatments or vaccines available in most countries. In this study, we explored the anti-RSV potential of 2, 4-Di-tert-butylphenol (2, 4-DTBP), a compound derived from Houttuynia cordata Thunb. To overcome the poor solubility of 2, 4-DTBP, we encapsulated it in polymeric micelles and delivered it by inhalation. We found that 2, 4-DTBP-loaded micelles inhibited RSV infection in vitro and improved survival, lung pathology, and viral clearance in RSV-infected mice. Our results suggested that 2, 4-DTBP-loaded micelle is a promising novel therapeutic agent for RSV infection.

Apolipoprotein A-IV polymorphisms Q360H and T347S attenuate its endogenous inhibition of thrombosis.

Platelets are small anucleate cells that play a key role in thrombosis and hemostasis. Our group previously identified apolipoprotein A-IV (apoA-IV) as an endogenous inhibitor of thrombosis by competitive blockade of the αIIbß3 integrin on platelets. ApoA-IV inhibition of platelets was dependent on the N-terminal D5/D13 residues, and enhanced with absence of the C-terminus, suggesting it sterically hinders its N-terminal platelet binding site. The C-terminus is also the site of common apoA-IV polymorphisms apoA-IV-1a (T347S) and apoA-IV-2 (Q360H). Interestingly, both are linked with an increased risk of cardiovascular disease, however, the underlying mechanism remains unclear. Here, we generated recombinant apoA-IV and found that the Q360H or T347S polymorphisms dampened its inhibition of platelet aggregation in human platelet-rich plasma and gel-filtered platelets, reduced its inhibition of platelet spreading, and its inhibition of P-selectin on activated platelets. Using an ex vivo thrombosis assay, we found that Q360H and T347S attenuated its inhibition of thrombosis at both high (1800s-1) and low (300s-1) shear rates. We then demonstrate a conserved monomer-dimer distribution among apoA-IV WT, Q360H, and T347S and use protein structure modelling software to show Q360H and T347S enhance C-terminal steric hindrance over the N-terminal platelet-binding site. These data provide critical insight into increased cardiovascular risk for individuals with Q360H or T347S polymorphisms.

J-MISFET Hybrid Dual-Gate Switching Device for Multifunctional Optoelectronic Logic Gate Applications.

High-performance and low operating voltage are becoming increasingly significant device parameters to meet the needs of future integrated circuit (IC) processors and ensure their energy-efficient use in upcoming mobile devices. In this study, we suggest a hybrid dual-gate switching device consisting of the vertically stacked junction and metal-insulator-semiconductor (MIS) gate structure, named J-MISFET. It shows excellent device performances of low operating voltage (<0.5 V), drain current ON/OFF ratio (∼4.7 × 105), negligible hysteresis window (<0.5 mV), and near-ideal subthreshold slope (SS) (60 mV/dec), making it suitable for low-power switching operation. Furthermore, we investigated the switchable NAND/NOR logic gate operations and the photoresponse characteristics of the J-MISFET under the small supply voltage (0.5 V). To advance the applications further, we successfully demonstrated an integrated optoelectronic security logic system comprising 2-electric inputs (for encrypted data) and 1-photonic input signal (for password key) as a hardware security device for data protection. Thus, we believe that our J-MISFET, with its heterogeneous hybrid gate structures, will illuminate the path toward future device configurations for next-generation low-power electronics and multifunctional security logic systems in a data-driven society.

Effects of fluorescent protein tdTomato on mouse retina.

Fluorescent proteins (FPs) have been widely used to investigate cellular and molecular interactions and trace biological events in many applications. Some of the FPs have been demonstrated to cause undesirable cellular damage by light-induced ROS production in vivo or in vitro. However, it remains unknown if one of the most popular FPs, tdTomato, has similar effects in neuronal cells. In this study, we discovered that tdTomato expression led to unexpected retinal dysfunction and ultrastructural defects in the transgenic mouse retina. The retinal dysfunction mainly manifested in the reduced photopic electroretinogram (ERG) responses and decreased contrast sensitivity in visual acuity, caused by mitochondrial damages characterized with cellular redistribution, morphological modifications and molecular profiling alterations. Taken together, our findings for the first time demonstrated the retinal dysfunction and ultrastructural defects in the retinas of tdTomato-transgenic mice, calling for a more careful design and interpretation of experiments involved in FPs.

Lower Melatonin Indicates Poor Short-term Prognosis in Patients with Acute Ischemic Stroke.

AIMS: We evaluated endogenous melatonin levels in the acute phase of cerebral infarction and explored the impact of possible changes in melatonin levels on the prognosis of patients. METHODS: This study recruited acute ischemic stroke (AIS) patients from the Department of the Second Affiliated Hospital of Soochow University between December 2019 and June 2021, along with healthy control subjects. Salivary melatonin samples were collected from each participant between 7 pm and 10 pm, and fasting plasma was collected the following morning to measure the levels of inflammatory markers. The prognosis was assessed through follow-up three months after discharge. The relationship between melatonin levels and plasma inflammatory markers was assessed, followed by an analysis of the effect of melatonin levels on patient prognosis. RESULTS: The study enrolled a total of 160 participants, including 120 AIS patients aged 50 years or older (61.7% male) and 40 age-matched controls (55.0% male). The AIS group exhibited lower salivary melatonin levels at 19 (P = 0.002), 20 (P < 0.001), 21 (P < 0.001), and 22 (P < 0.001) o'clock, and the average melatonin level was also lower (P < 0.001). Logistic regression analysis models indicated an association between low melatonin levels and poor prognosis. Salivary melatonin levels demonstrated good predictive ability for the prognosis of AIS patients. CONCLUSION: Melatonin levels were lower in AIS patients compared to controls. In addition, lower melatonin levels were associated with a poorer prognosis among AIS patients.

Immediate Effect of Electro-acupuncture on Endometrial Blood Flow in Patients with Recurrent Implantation Failure: A Randomized Controlled Trial.

OBJECTIVE: To investigate the immediate effects of electro-acupuncture (EA) on endometrial blood flow among recurrent implantation failure (RIF) patients. METHODS: Eighty RIF patients, enrolled from March 2022 to December 2022, were randomly allocated into either the EA group (40 cases) or the waiting-list (WL) group (40 cases) by using a random number table. The EA group underwent acupuncture at points of Shenting (GV 24), Baihui (GV 4), Benshen (GB 13), bilateral Zigong (EX-CA 1), Huangshu (KI 16), Sanyinjiao (SP 6) and Xuehai (SP10), and electric acupuncture apparatus was connected to EX-CA 1, KI 16, SP 6, and SP 10 with disperse-dense waves at 4/20 Hz frequencies for 30 min after transvaginal ultrasound, while the WL group received no intervention. The primary outcome measured was the endometrial volume blood flow. The secondary outcomes included the bilateral uterine artery index, endometrial volume, endometrial blood flow type, vascular distribution index (VIMV) for endometrial and ovary, clinical pregnancy rate, and embryo implantation rate. RESULTS: In the EA group, there was a notable decrease in the bilateral pulsatility index and a significant improvement in the endometrial blood flow type post-EA (P<0.05). Both the endometrial blood flow type and VIMV for the endometrium and right ovary were markedly higher in the EA group compared to the WL group post-treatment (P<0.05). Conversely, no significant disparities were observed in vascular index, flow index, vascular blood flow index, uterine arterial blood flow indices, endometrial volume, clinical pregnancy rate and embryo implantation rate between the two groups after treatment (P>0.05). Besides, no adverse events related to EA were observed. CONCLUSIONS: EA can promptly ameliorate VIMV for the endometrial and right ovary, and endometrial blood flow type. Future randomized controlled trials are warranted to investigate the long-term effects of EA on blood flow of RIF patients and its implications for pregnancy outcomes. (Trial registration No. ChiCTR2200057377).

Ultrasound-Guided Radiofrequency Ablation for Chronic Osteoarthritis Knee Pain in the Elderly: A Randomized Controlled Trial.

BACKGROUND: Osteoarthritis of the knee (KOA) is the main cause of disability in elderly people. Patients with KOA may often not achieve adequate pain control even after receiving all treatment modalities. OBJECTIVES: The objective of this study was to examine the efficacy of ultrasound-guided radiofrequency ablation (RFA) as a treatment for moderate and severe KOA. STUDY DESIGN: A prospective randomized controlled study. SETTING: The study was performed in the National Pain Management and Research Center of China-Japan Friendship Hospital. METHODS: Eligible participants were over 50 years old and had suffered from chronic knee joint pain for more than 6 months, scoring at least 4 on a numeric rating scale (NRS) and grade III-IV according to the Kellgren-Lawrence classification system. The target nerve selection principle was as follows: the superomedial genicular nerve (SMGN) branch and inferior medial genicular nerve (IMGN) branch of the saphenous nerve for medial knee pain, the superolateral genicular nerve (SLGN) branch of the femoral nerve for lateral pain, and the SMGN, IMGN, and SLGN branches for total knee pain. The main outcomes were the NRS pain score (including the most severe pain), the average pain, and the proportion of patients who had reached pain reduction of more than 2 points. The secondary outcome was the Western Ontario McMaster University Osteoarthritis Index (WOMAC) score. RFA at 70ºC was performed for 120 seconds per patient in the RFA group, and knee nerve blocks were performed in the control group. RESULTS: A total of 120 patients who met the inclusion criteria were selected in this study. The treatment groups showed significant differences in their mean NRS scores and worst pain during the first, third, and sixth months after treatment. There were significant differences in the mean WOMAC pain, physical function, and total scores between the treatment groups and over time. Between the treatment groups and over time, the mean WOMAC stiffness scores were not different. At each time point after treatment, the proportion of patients who needed analgesic drugs was significantly lower in the RFA group than in the control group. Univariate analysis showed that gender, age, pain course, and body mass index were not significantly correlated with the positive rate (NRS >= 2 score reduction). After we adjusted for multiple factors, the perceived beneficial effect of therapy was less when gonarthritis was more severe (P < 0.01). LIMITATION: This study's limitation is that it was performed in only one unit of the National Pain Management and Research Center. CONCLUSIONS: Ultrasound-guided RFA applied to knee nerves can significantly reduce KOA pain, improve knee joint function, improve patient satisfaction, and provide a feasible, safe, and effective minimally invasive procedure for moderate to severe KOA in elderly patients.