Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke.

JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Weakly supervised low-dose computed tomography denoising based on generative adversarial networks.

Background: Low-dose computed tomography (LDCT) is a diagnostic imaging technique designed to minimize radiation exposure to the patient. However, this reduction in radiation may compromise computed tomography (CT) image quality, adversely impacting clinical diagnoses. Various advanced LDCT methods have emerged to mitigate this challenge, relying on well-matched LDCT and normal-dose CT (NDCT) image pairs for training. Nevertheless, these methods often face difficulties in distinguishing image details from nonuniformly distributed noise, limiting their denoising efficacy. Additionally, acquiring suitably paired datasets in the medical domain poses challenges, further constraining their applicability. Hence, the objective of this study was to develop an innovative denoising framework for LDCT images employing unpaired data. Methods: In this paper, we propose a LDCT denoising network (DNCNN) that alleviates the need for aligning LDCT and NDCT images. Our approach employs generative adversarial networks (GANs) to learn and model the noise present in LDCT images, establishing a mapping from the pseudo-LDCT to the actual NDCT domain without the need for paired CT images. Results: Within the domain of weakly supervised methods, our proposed model exhibited superior objective metrics on the simulated dataset when compared to CycleGAN and selective kernel-based cycle-consistent GAN (SKFCycleGAN): the peak signal-to-noise ratio (PSNR) was 43.9441, the structural similarity index measure (SSIM) was 0.9660, and the visual information fidelity (VIF) was 0.7707. In the clinical dataset, we conducted a visual effect analysis by observing various tissues through different observation windows. Our proposed method achieved a no-reference structural sharpness (NRSS) value of 0.6171, which was closest to that of the NDCT images (NRSS =0.6049), demonstrating its superiority over other denoising techniques in preserving details, maintaining structural integrity, and enhancing edge contrast. Conclusions: Through extensive experiments on both simulated and clinical datasets, we demonstrated the superior efficacy of our proposed method in terms of denoising quality and quantity. Our method exhibits superiority over both supervised techniques, including block-matching and 3D filtering (BM3D), residual encoder-decoder convolutional neural network (RED-CNN), and Wasserstein generative adversarial network-VGG (WGAN-VGG), and over weakly supervised approaches, including CycleGAN and SKFCycleGAN.

GMAEEG: A Self-Supervised Graph Masked Autoencoder for EEG Representation Learning.

Annotated electroencephalogram (EEG) data is the prerequisite for artificial intelligence-driven EEG autoanalysis. However, the scarcity of annotated data due to its high-cost and the resulted insufficient training limits the development of EEG autoanalysis. Generative self-supervised learning, represented by masked autoencoder, offers potential but struggles with non-Euclidean structures. To alleviate these challenges, this work proposes a self-supervised graph masked autoencoder for EEG representation learning, named GMAEEG. Concretely, a pretrained model is enriched with temporal and spatial representations through a masked signal reconstruction pretext task. A learnable dynamic adjacency matrix, initialized with prior knowledge, adapts to brain characteristics. Downstream tasks are achieved by finetuning pretrained parameters, with the adjacency matrix transferred based on task functional similarity. Experimental results demonstrate that with emotion recognition as the pretext task, GMAEEG reaches superior performance on various downstream tasks, including emotion, major depressive disorder, Parkinson's disease, and pain recognition. This study is the first to tailor the masked autoencoder specifically for EEG representation learning considering its non-Euclidean characteristics. Further, graph connection analysis based on GMAEEG may provide insights for future clinical studies.

Clinical stratification of 1318 Primary Sjögren's Syndrome patients.

OBJECTIVE: Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by diverse clinical manifestations yet lacking effective therapeutic strategies currently. This study aims to gain a thorough understanding of the clinical landscape of pSS and further delineate its clinical subtypes, thereby enabling the efficient management for pSS. METHODS: We conducted a cross-sectional observational study of 1318 pSS patients. The pSS patients were categorized and compared based on gender, anti-SSA antibodies, and labial salivary gland biopsies (LGSB). Unsupervised clustering analysis was employed to identify pSS subtypes using systemic involvement among patients. Furthermore, we assessed clinical and biological variances among these subtypes. RESULTS: Through group comparisons, we observed more pronounced extraglandular manifestations among male patients, SSA-negative group, and those with positive LGSB results. Based on systemic involvement, pSS patients were categorized into four groups. C1 exhibited minimal systemic involvement, lacking hematologic or serologic manifestations, with the lowest ESSDAI scores. C2 presented with serologic changes in all patients, partial joint involvement, and no hematologic systemic manifestations. C3 lacked joint involvement but all members displayed hematologic systemic involvement, with higher rates of renal, cutaneous, and systemic manifestations. C4 encompassed patients with joint and hematologic involvement, displaying the highest ESSDAI scores. The positivity rates of antibodies, immunological parameters, and inflammatory markers exhibited significant differences among the groups. Furthermore, notable variances were observed in the expression of peripheral blood transcriptomic modules among these groups. CONCLUSION: In this cohort study, we summarized the clinical characteristics of Chinese patients with pSS and identified four distinct subgroups of pSS based on systemic involvement, revealing clinical and molecular disparities that unveil distinct pathobiological endotypes. Our findings hold significant implications for clinical management.

Hydrogen-rich water alleviates asthma airway inflammation by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation.

Hydrogen-rich water (HRW) is a beverage containing a high concentration of hydrogen that has been researched for its antioxidant, anti-apoptotic, and anti-inflammatory properties in asthma. This study investigates the potential therapeutic impact of HRW on the gut-lung axis. Using 16S rRNA and serum metabolomics, we examined changes in gut microbiota and serum metabolites in asthmatic mice after HRW intervention, followed by validation experiments. The findings revealed that HRW influenced gut microbiota by increasing Ligilactobacillus and Bifidobacterium abundance and enhancing the presence of indole-3-acetic acid (IAA), a microbially derived serum metabolite. Both in vivo and in vitro experiments showed that HRW's protective effects against airway inflammation in asthmatic mice may be linked to the gut microbiota, with IAA potentially playing a role in reducing asthmatic airway inflammation through the aryl hydrocarbon receptors (AhR) signaling pathway. In summary, HRW can modify gut microbiota, increase Bifidobacterium abundance, elevate microbial-derived IAA levels, and activate AhR, which could potentially alleviate inflammation in asthma.

A subset of dopamine receptor-expressing neurons in the nucleus accumbens controls feeding and energy homeostasis.

Orchestrating complex behaviors, such as approaching and consuming food, is critical for survival. In addition to hypothalamus neuronal circuits, the nucleus accumbens (NAc) also controls appetite and satiety. However, specific neuronal subtypes of the NAc that are involved and how the humoral and neuronal signals coordinate to regulate feeding remain incompletely understood. Here we decipher the spatial diversity of neuron subtypes of the NAc shell (NAcSh) and define a dopamine receptor D1-expressing and Serpinb2-expressing subtype controlling food consumption in male mice. Chemogenetics and optogenetics-mediated regulation of Serpinb2+ neurons bidirectionally regulate food seeking and consumption specifically. Circuitry stimulation reveals that the NAcShSerpinb2→LHLepR projection controls refeeding and can overcome leptin-mediated feeding suppression. Furthermore, NAcSh Serpinb2+ neuron ablation reduces food intake and upregulates energy expenditure, resulting in reduced bodyweight gain. Our study reveals a neural circuit consisting of a molecularly distinct neuronal subtype that bidirectionally regulates energy homeostasis, providing a potential therapeutic target for eating disorders.

Novel insight into astrocyte-mediated gliotransmission modulates the synaptic plasticity in major depressive disorder.

Major depressive disorder (MDD) is a form of glial cell-based synaptic dysfunction disease in which glial cells interact closely with neuronal synapses and perform synaptic information processing. Glial cells, particularly astrocytes, are active components of the brain and are responsible for synaptic activity through the release gliotransmitters. A reduced density of astrocytes and astrocyte dysfunction have both been identified the brains of patients with MDD. Furthermore, gliotransmission, i.e., active information transfer mediated by gliotransmitters between astrocytes and neurons, is thought to be involved in the pathogenesis of MDD. However, the mechanism by which astrocyte-mediated gliotransmission contributes to depression remains unknown. This review therefore summarizes the alterations in astrocytes in MDD, including astrocyte marker, connexin 43 (Cx43) expression, Cx43 gap junctions, and Cx43 hemichannels, and describes the regulatory mechanisms of astrocytes involved in synaptic plasticity. Additionally, we investigate the mechanisms acting of the glutamatergic, gamma-aminobutyric acidergic, and purinergic systems that modulate synaptic function and the antidepressant mechanisms of the related receptor antagonists. Further, we summarize the roles of glutamate, gamma-aminobutyric acid, d-serine, and adenosine triphosphate in depression, providing a basis for the identification of diagnostic and therapeutic targets for MDD.

Feasibility of a novel unassisted single-channel transcolonic endoscopic appendectomy for the treatment of appendiceal lesions (with video).

BACKGROUND: Transcolonic endoscopic appendectomy (TEA) is rapidly evolving and has been reported as a minimally invasive alternative to appendectomy. We aimed to characterize the feasibility and safety of a novel unassisted single-channel TEA. METHOD: We retrospectively investigated 23 patients with appendicitis or appendiceal lesions who underwent TEA from February 2016 to December 2022. We collected clinicopathological characteristics, procedure­related parameters, and follow­up data and analyzed the impact of previous abdominal surgery and traction technique. RESULTS: The mean age was 56.0 years. Of the 23 patients with appendiceal lesions, fourteen patients underwent TEA and nine underwent traction-assisted TEA (T-TEA). Eight patients (34.8%) had previous abdominal surgery. The En bloc resection rate was 95.7%. The mean procedure duration was 91.1 ± 45.5 min, and the mean wound closure time was 29.4 ± 18.6 min. The wounds after endoscopic appendectomy were closed with clips (21.7%) or a combination of clip closure and endoloop reinforcement (78.3%), and the median number of clips was 7 (range, 3-15). Three patients (13.0%) experienced major adverse events, including two delayed perforations (laparoscopic surgery) and one infection (salvage endoscopic suture). During a median follow-up of 23 months, no residual or recurrent lesions were observed, and no recurrence of abdominal pain occurred. There were no significant differences between TEA and T-TEA groups and between patients with and without abdominal surgery groups in each factor. CONCLUSION: Unassisted single-channel TEA for patients with appendiceal lesions has favorable short- and long-term outcomes. TEA can safely and effectively treat appendiceal disease in appropriately selected cases.

Impact of childhood socioeconomic status on depression among postdoctoral researchers in universities: The chain mediating role of current subjective socioeconomic status and perceived stress. / ç«¥å¹´ç¤¾ä¼šç»æµŽåœ°ä½å¯¹é«˜æ ¡åšå£«åŽæŠ‘éƒçš„å½±å“ï¼šå½“ä¸‹ä¸»è§‚ç¤¾ä¼šç»æµŽåœ°ä½å’ŒåŽ‹åŠ›æ„ŸçŸ¥çš„é“¾å¼ä¸­ä»‹ä½œç”¨.

OBJECTIVES: Postdoctoral researchers in Chinese universities commonly face a high risk of mental health issues, such as depression, yet the underlying causes and mechanisms remain unclear. This study aims to explore the influence of childhood socioeconomic status (SES) on depression among postdoctoral researchers and the mediating roles of current subjective SES and perceived stress in this process. METHODS: An online survey was conducted among postdoctoral researchers at a university. The survey included a general information questionnaire, the Childhood Socioeconomic Status Scale, the Subjective Socioeconomic Status Scale, the Perceived Stress Scale, and the Patient Health Questionnaire. A total of 505 valid responses were collected. Pearson correlation analysis was used to analyze the data, and the PROCESS macro was employed for chain mediation analysis. RESULTS: Childhood SES was significantly positively correlated with current subjective SES (P<0.05) and significantly negatively correlated with postdoctoral tenure, perceived stress, and depression (all P<0.05). Current subjective SES was significantly negatively correlated with perceived stress and depression (both P<0.05), while perceived stress was significantly positively correlated with depression (P<0.05). The chain mediation effect of childhood SES → current subjective SES → perceived stress → depression was significant (P<0.05). CONCLUSIONS: Childhood socioeconomic status can influence depression among postdoctoral researchers through the mediating roles of current subjective socioeconomic status and perceived stress. These findings provide a target for the prevention and intervention of depression in postdoctoral populations and offer a reference for the development of mental health promotion strategies for young university faculty.

Candidate Antigens and the Development of Helicobacter pylori Vaccines.

BACKGROUND: Infection with Helicobacter pylori (Hp) mostly occurs during childhood, and persistent infection may lead to severe gastric diseases and even gastric cancer. Currently, the primary method for eradicating Hp is through antibiotic treatment. However, the increasing multidrug resistance in Hp strains has diminished the effectiveness of antibiotic treatments. Vaccination could potentially serve as an effective intervention to resolve this issue. AIMS: Through extensive research and analysis of the vital protein characteristics involved in Hp infection, we aim to provide references for subsequent vaccine antigen selection. Additionally, we summarize the current research and development of Hp vaccines in order to provide assistance for future research. MATERIALS AND METHODS: Utilizing the databases PubMed and the Web of Science, a comprehensive search was conducted to compile articles pertaining to Hp antigens and vaccines. The salient aspects of these articles were then summarized to provide a detailed overview of the current research landscape in this field. RESULTS: Several potential antigens have been identified and introduced through a thorough understanding of the infection process and pathogenic mechanisms of Hp. The conserved and widely distributed candidate antigens in Hp, such as UreB, HpaA, GGT, and NAP, are discussed. Proteins such as CagA and VacA, which have significant virulence effects but relatively poor conservatism, require further evaluation. Emerging antigens like HtrA and dupA have significant research value. In addition, vaccines based on these candidate antigens have been compiled and summarized. CONCLUSIONS: Vaccines are a promising method for preventing and treating Hp. While some Hp vaccines have achieved promising results, mature products are not yet available on the market. Great efforts have been directed toward developing various types of vaccines, underscoring the need for developers to select appropriate antigens and vaccine formulations to improve success rates.

HNRNPA2B1 induces cell proliferation and acts as biomarker in breast cancer.

BACKGROUND: Numerous studies have shown that m6A plays an important regulatory role in the development of tumors. HNRNPA2B1, one of the m6A RNA methylation reading proteins, has been proven to be elevated in human cancers. OBJECTIVE: In this study, we aimed to identify the role of HNRNPA2B1 in breast cancer. MATERIALS AND METHODS: HNRNPA2B1 expression was investigated via RT-qPCR and TCGA database in breast cancer. Then, the function of HNRNPA2B1 on cancer cell was measured by CCK8 assays, colony formation and scratch assays. In addition, HNRNPA2B1 expression in BRCA was explored via the Wilcoxon signed-rank test, KruskalWallis test and logistic regression. The association with HNRNPA2B1 expression and survival were considered by KaplanMeier and Cox regression analyses. The biological function of HNRNPA2B1 was analyzed via gene set enrichment analysis (GSEA) and the cluster Profiler R software package. RESULTS: We found that HNRNPA2B1 was highly expressed and induced cell proliferation and migration in breast cancer. Moreover, we observed HNRNPA2B1 induced tumor growth in vivo. In addition, we also found HNRNPA2B1 expression was associated with characteristics and prognosis in breast cancer patients. CONCLUSION: Our findings suggested that HNRNPA2B1 promoted tumor growth and could function as a new potential molecular marker in breast cancer.

Evaluating cognitive performance: Traditional methods vs. ChatGPT.

Background: NLP models like ChatGPT promise to revolutionize text-based content delivery, particularly in medicine. Yet, doubts remain about ChatGPT's ability to reliably support evaluations of cognitive performance, warranting further investigation into its accuracy and comprehensiveness in this area. Method: A cohort of 60 cognitively normal individuals and 30 stroke survivors underwent a comprehensive evaluation, covering memory, numerical processing, verbal fluency, and abstract thinking. Healthcare professionals and NLP models GPT-3.5 and GPT-4 conducted evaluations following established standards. Scores were compared, and efforts were made to refine scoring protocols and interaction methods to enhance ChatGPT's potential in these evaluations. Result: Within the cohort of healthy participants, the utilization of GPT-3.5 revealed significant disparities in memory evaluation compared to both physician-led assessments and those conducted utilizing GPT-4 (P < 0.001). Furthermore, within the domain of memory evaluation, GPT-3.5 exhibited discrepancies in 8 out of 21 specific measures when compared to assessments conducted by physicians (P < 0.05). Additionally, GPT-3.5 demonstrated statistically significant deviations from physician assessments in speech evaluation (P = 0.009). Among participants with a history of stroke, GPT-3.5 exhibited differences solely in verbal assessment compared to physician-led evaluations (P = 0.002). Notably, through the implementation of optimized scoring methodologies and refinement of interaction protocols, partial mitigation of these disparities was achieved. Conclusion: ChatGPT can produce evaluation outcomes comparable to traditional methods. Despite differences from physician evaluations, refinement of scoring algorithms and interaction protocols has improved alignment. ChatGPT performs well even in populations with specific conditions like stroke, suggesting its versatility. GPT-4 yields results closer to physician ratings, indicating potential for further enhancement. These findings highlight ChatGPT's importance as a supplementary tool, offering new avenues for information gathering in medical fields and guiding its ongoing development and application.

Causal effects of gut microbiota on diabetic neuropathy: a two-sample Mendelian randomization study.

Objective: Previous observational studies have suggested an association between gut microbiota and diabetic neuropathy (DN). However, confounding factors and reverse causality make the causal relationship between gut microbiota and DN uncertain. We aimed to investigate the interactive causal relationships between the abundance of gut microbiota and DN. Methods: We conducted a Mendelian randomization (MR) analysis to examine the causal relationship between gut microbiota and DN. Genomic data on gut microbiota at the genus level were obtained from the MiBioGen Consortium, including 18,340 individuals of European descent. Data on diabetic polyneuropathy (DPN) were obtained from the FinnGen Consortium, which included 1,048 cases and 374,434 controls, while data on diabetic autonomic neuropathy (DAN) were also obtained from the FinnGen Consortium, including 111 cases and 374,434 controls. Causal effects were primarily estimated using inverse variance weighted (IVW) analysis, supplemented with four validation methods, and additional sensitivity analyses to assess the pleiotropy, heterogeneity, and robustness of instrumental variables. Results: The IVW analysis indicated that Prevotella 9 had a protective effect on DPN (OR = 0.715, 95% CI: 0.521-0.982, P = 0.038), and Bacteroides also showed a protective effect (OR = 0.602, 95% CI: 0.364-0.996, P = 0.048). On the other hand, Ruminococcus 2 had a promoting effect on DPN (OR = 1.449, 95% CI: 1.008-2.083, P = 0.045). Blautia (OR = 0.161, 95% CI: 0.035-0.733, P = 0.018), Clostridium innocuum group (OR = 3.033, 95% CI: 1.379-6.672, P = 0.006), and Howardella (OR = 2.595, 95% CI: 1.074-6.269, P = 0.034) were causally associated with DAN in the IVW analysis, with no evidence of heterogeneity or pleiotropy. Sensitivity analyses showed no significant pleiotropy or heterogeneity. Conclusion: Our study identified a causal relationship between gut microbiota and the increased or decreased risk of diabetic neuropathy. These findings underscore the importance of adopting a comprehensive approach that combines gut microbiota modulation with other therapeutic interventions in the management of diabetic neuropathy.

Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications.

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.

Electrophysiological Mechanism of Catestatin Antiarrhythmia: Enhancement of Ito, IK, and IK1 and Inhibition of ICa-L in Rat Ventricular Myocytes.

BACKGROUND: Cardiovascular disease remains one of the leading causes of death globally. Myocardial ischemia and infarction, in particular, frequently cause disturbances in cardiac electrical activity that can trigger ventricular arrhythmias. We aimed to investigate whether catestatin, an endogenous catecholamine-inhibiting peptide, ameliorates myocardial ischemia-induced ventricular arrhythmias in rats and the underlying ionic mechanisms. METHODS AND RESULTS: Adult male Sprague-Dawley rats were randomly divided into control and catestatin groups. Ventricular arrhythmias were induced by ligation of the left anterior descending coronary artery and electrical stimulation. Action potential, transient outward potassium current, delayed rectifier potassium current, inward rectifying potassium current, and L-type calcium current (ICa-L) of rat ventricular myocytes were recorded using a patch-clamp technique. Catestatin notably reduced ventricular arrhythmia caused by myocardial ischemia/reperfusion and electrical stimulation of rats. In ventricular myocytes, catestatin markedly shortened the action potential duration of ventricular myocytes, which was counteracted by potassium channel antagonists TEACl and 4-AP, and ICa-L current channel agonist Bay K8644. In addition, catestatin significantly increased transient outward potassium current, delayed rectifier potassium current, and inward rectifying potassium current density in a concentration-dependent manner. Catestatin accelerated the activation and decelerated the inactivation of the transient outward potassium current channel. Furthermore, catestatin decreased ICa-L current density in a concentration-dependent manner. Catestatin also accelerated the inactivation of the ICa-L channel and slowed down the recovery of ICa-L from inactivation. CONCLUSIONS: Catestatin enhances the activity of transient outward potassium current, delayed rectifier potassium current, and inward rectifying potassium current, while suppressing the ICa-L in ventricular myocytes, leading to shortened action potential duration and ultimately reducing the ventricular arrhythmia in rats.

[Determination of individual components in finished motor gasoline by dual-channel three-column gas chromatography].

A method based on a dual-channel gas chromatograph equipped with three columns and three detectors was established for the determination of individual components in finished motor gasoline. The gasoline samples were separately introduced into the two injection ports of the chromatograph using two autosamplers. The components of the sample introduced into the first injection port (channel 1) were separated on a nonpolar PONA column (50 m×0.20 mm×0.5 µm) for gasoline analysis and detected by an flame ionization detector (FID). The components of the sample introduced into the second injection port (channel 2) were separated on another PONA column. Oxygenates (e.g., ethers and alcohols), other unconventional and prohibited additives that would co-elute with the hydrocarbons (e.g., methylal, dimethyl carbonate, sec-butyl acetate, and anilines), and some difficult-to-separate hydrocarbon pairs (e.g., 2,3,3-trimethylpentane and toluene) eluted from the PONA column and entered a DM-624 column (30 m×0.25 mm×1.4 µm) to achieve further separation according to the switch timetable using the Deans switch procedure and detected by an FID. The peak of 3-methylpentane, a common component in gasoline samples, also entered the DM-624 column by the Deans switch procedure for calculation purposes. The peak areas of target components on the PONA column in channel 1 were calculated using the peak areas on the DM-624 column as well as those of 3-methylpentane on both the DM-624 and PONA columns in channel 1 with a calibration factor between the two channels. The peak areas of co-eluted components were obtained by subtracting the calculated peak areas of the target components from those of the co-eluted peaks. The mass percentages of the individual components were calculated according to the normalization method using all peak areas on the PONA column in channel 1 with relative response factors. The mass percentages of the oxygenates, anilines, and individual hydrocarbons were determined, and the group-type distribution was calculated according to the carbon number. Separation and quantitation interferences between the additives and hydrocarbons were eliminated using this procedure. Twenty oxygenates and unconventional additives, each with a mass percentage of approximately 3%, were added to a real motor gasoline-92 sample and analyzed using the proposed method. The recoveries of the target components were between 90.1% and 118.2% with relative standard deviations (RSDs) between 0.2% and 5.1% (n=6). The analysis of a real ethanol-gasoline sample showed that the RSDs of contents of most components was less than 3% (n=6). Because the heart-cut of peaks using Deans switch technique requires the precise repeatability of retention times, the retention-time repeatability of components on the PONA column in channel 2 was investigated over an extended period of time after thousands of runs of real-sample analysis. The retention times of the same component in several randomly selected motor gasoline-92 samples varied from 0.01 to 0.03 min, indicating that the proper timetable for the Deans switch remained stable for two years. The precise repeatability of retention times was achieved owing to the high precision of the electric pneumatic control of the chromatograph and the stability of the column used. Real finished motor gasoline samples with different octane numbers (gasoline-92, gasoline-95, and ethanol gasoline-95) were analyzed using the developed method, and the results acquired were consistent with those of standard methods (GB/T 30519-2016, NB/SH/T 0663-2014, and SH/T 0693-2000). If some unconventional additives (such as methylal) were added to gasoline samples, the contents of these unconventional additives could also be detected, which means one run of the proposed method could provide results corresponding to three or four runs of different standard methods. The acquisition of information on the individual components of finished motor gasoline will assist in research on precise gasoline blending.

Identification of a Novel ECM Remodeling Macrophage Subset in AKI to CKD Transition by Integrative Spatial and Single-Cell Analysis.

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneity and dynamic characterization of macrophages are still poorly understood. Here, we used integrated single-cell RNA sequencing and spatial transcriptomic to characterize the spatiotemporal heterogeneity of macrophages in murine AKI-to-CKD model of unilateral ischemia-reperfusion injury. A marked increase in macrophage infiltration at day 1 was followed by a second peak at day 14 post AKI. Spatiotemporal profiling revealed that injured tubules and macrophages co-localized early after AKI, whereas in late chronic stages had spatial proximity to fibroblasts. Further pseudotime analysis revealed two distinct lineages of macrophages in this transition: renal resident macrophages differentiated into the pro-repair subsets, whereas infiltrating monocyte-derived macrophages contributed to chronic inflammation and fibrosis. A novel macrophage subset, extracellular matrix remodeling-associated macrophages (EAMs) originating from monocytes, linked to renal fibrogenesis and communicated with fibroblasts via insulin-like growth factors (IGF) signalling. In sum, our study identified the spatiotemporal dynamics of macrophage heterogeneity with a unique subset of EAMs in AKI-to-CKD transition, which could be a potential therapeutic target for preventing CKD development.

Effect of Tai Chi exercise on bone health and fall prevention in postmenopausal women: a meta-analysis.

BACKGROUND: The bone status of postmenopausal women is worsening. In fact, postmenopausal period is the high incidence stage of osteoporosis and falls. Notably, a recent study has pointed out that exercise can improve bone health in postmenopausal women. However, the effect of Tai Chi exercise on postmenopausal women is controversial. Therefore, a meta-analysis was designed to analyze the effect of Tai Chi exercise on bone health and fall prevention in postmenopausal women. METHODS: The researches on Tai Chi improving the bone health of postmenopausal women before August 31, 2023 were collected from Chinese and English databases, such as PubMed, Embase, and Web of Science, etc. The risk of bias of the included studies was assessed using the Cochrane risk-of-bias tool for randomized trials. Besides, R software 4.3.1 was employed to analyze the effect sizes in the meta-analysis to summarize the impact of Tai Chi on vertebral bone mineral density, serum calcium, clinical balance scores, the number of falls, total falls, and health status scores in postmenopausal women. RESULTS: There were 12 studies eventually included in this meta-analysis. A total of 1,272 postmenopausal women were involved, including 628 in the experimental group (intervention with Tai Chi exercise) and 644 in the control group (without any intervention). Briefly, postmenopausal women practicing Tai Chi presented a significant increase in vertebral bone density [standardized mean difference (SMD) = 0.37, 95% confidence interval (CI) (0.04-0.71), P = 0.03] and health status score [SMD = 0.25, 95% CI (0.01-0.49), P = 0.04]. In contrast, there were no significant differences for postmenopausal women between the two groups in terms of serum calcium [SMD = -0.01, 95% CI (-0.39, 0.36), P = 0.77], clinical balance [SMD = 0.17, 95% CI (-0.01, 0.46), P = 0.23], number of falls [SMD = -0.61, 95% CI (-1.24, 0.02), P = 0.06] and total falls [odds ratio = 0.35, 95% CI (0.11-1.12), P = 0.07]. CONCLUSION: Tai Chi exercise can improve the bone mineral density of postmenopausal women, thereby maintaining bone health. Hence, Tai Chi exercise is necessary to prevent osteoporosis.