Normal Function Research Articles

Risk factors and outcomes associated with systolic dysfunction following traumatic brain injury.

Systolic dysfunction has been observed following isolated moderate-severe traumatic brain injury (Ims-TBI). However, early risk factors for the development of systolic dysfunction after Ims-TBI and their impact on the prognosis of patients with Ims-TBI have not been thoroughly investigated. A prospective observational study among patients aged 16 to 65 years without cardiac comorbidities who sustained Ims-TBI (Glasgow Coma Scale [GCS] score ≤12) was conducted. Systolic dysfunction was defined as left ventricular ejection fraction <50% or apparent regional wall motion abnormality assessed by transthoracic echocardiography within 24 hours after admission. The primary endpoint was the incidence of systolic dysfunction after Ims-TBI. The secondary endpoint was survival on discharge. Clinical data and outcomes were assessed within 24 hours after admission or during hospitalization. About 23 of 123 patients (18.7%) developed systolic dysfunction after Ims-TBI. Higher admission heart rate (odds ratios [ORs]: 1.05, 95% confidence interval [CI]: 1.02-1.08; P = .002), lower admission GCS score (OR: 0.77, 95% CI: 0.61-0.96; P = .022), and higher admission serum high-sensitivity cardiac troponin T (Hs-cTnT) (OR: 1.14, 95% CI: 1.06-1.22; P < .001) were independently associated with systolic dysfunction among patients with Ims-TBI. A combination of heart rate, GCS score, and serum Hs-cTnT level on admission improved the predictive performance for systolic dysfunction (area under curve = 0.85). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality of patients with systolic dysfunction was higher than that of patients with normal systolic function (P < .05). Lower GCS (OR: 0.66, 95% CI: 0.45-0.82; P = .001), lower admission oxygen saturation (OR: 0.82, 95% CI: 0.69-0.98; P = .025), and the development of systolic dysfunction (OR: 4.85, 95% CI: 1.36-17.22; P = .015) were independent risk factors for in-hospital mortality in patients with Ims-TBI. Heart rate, GCS, and serum Hs-cTnT level on admission were independent early risk factors for systolic dysfunction in patients with Ims-TBI. The combination of these 3 parameters can better predict the occurrence of systolic dysfunction.

Retinoic acid-dependent loss of synaptic output from bipolar cells impairs visual information processing in inherited retinal degeneration.

In retinitis pigmentosa (RP), rod and cone photoreceptors degenerate, depriving downstream neurons of light-sensitive input, leading to vision impairment or blindness. Although downstream neurons survive, some undergo morphological and physiological remodeling. Bipolar cells (BCs) link photoreceptors, which sense light, to retinal ganglion cells (RGCs), which send information to the brain. While photoreceptor loss disrupts input synapses to BCs, whether BC output synapses remodel has remained unknown. Here we report that synaptic output from BCs plummets in RP mouse models of both sexes owing to loss of voltage-gated Ca2+ channels. Remodeling reduces the reliability of synaptic output to repeated optogenetic stimuli, causing RGC firing to fail at high stimulus frequencies. Fortunately, functional remodeling of BCs can be reversed by inhibiting the retinoic acid receptor (RAR). RAR inhibitors targeted to BCs present a new therapeutic opportunity for mitigating detrimental effects of remodeling on signals initiated either by surviving photoreceptors or by vision-restoring tools.Significance Statement Photoreceptor degenerative disorders such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) lead to vision impairment or blindness. Vision mediated by surviving photoreceptors or artificial vision restoration technologies, rely on bipolar cells retaining normal function despite photoreceptor death. We find that in two animal models of RP, synaptic transmission from both rod and cone bipolar cells is severely impaired owing to diminished voltage-gated calcium current, preventing postsynaptic amacrine cells and retinal ganglion cells from properly receiving and encoding visual information. We find that an inhibitor of the retinoic acid receptor restores both the calcium current and synaptic release from bipolar cells. These discoveries about bipolar cells reveal a new functional deficit in blindness and a potential therapeutically important solution.

Just passing through: Deploying aquaporins in microbial cell factories.

As microbial membranes are naturally impermeable to even the smallest biomolecules, transporter proteins are physiologically essential for normal cell functioning. This makes transporters a key target area for engineering enhanced cell factories. As part of the wider cellular transportome, aquaporins (AQPs) are responsible for transporting small polar solutes, encompassing many compounds which are of great interest for industrial biotechnology, including cell feedstocks, numerous commercially relevant polyols and even weak organic acids. In this review, examples of cell factory engineering by targeting AQPs are presented. These AQP modifications aid in redirecting carbon fluxes and boosting bioconversions either by enhanced feedstock uptake, improved intermediate retention, increasing product export into the media or superior cell viability against stressors with applications in both bacterial and yeast production platforms. Additionally, the future potential for AQP deployment and targeting is discussed, showcasing hurdles and considerations of this strategy as well as recent advances and future directions in the field. By leveraging the natural diversity of AQPs and breakthroughs in channel protein engineering, these transporters are poised to be promising tools capable of enhancing a wide variety of biotechnological processes.

Implications of altered pyramidal cell morphology on clinical symptoms of neurodevelopmental disorders.

The prevalence of pyramidal cells (PCs) in the mammalian cerebral cortex underscore their value as they play a crucial role in various brain functions, ranging from cognition, sensory processing, to motor output. PC morphology significantly influences brain connectivity and plays a critical role in maintaining normal brain function. Pathological alterations to PC morphology are thought to contribute to the aetiology of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia. This review explores the relationship between abnormalities in PC morphology in key cortical areas and the clinical manifestations in schizophrenia and ASD. We focus largely on human postmortem studies and provide evidence that dendritic segment length, complexity and spine density are differentially affected in these disorders. These morphological alterations can lead to disruptions in cortical connectivity, potentially contributing to the cognitive and behavioural deficits observed in these disorders. Furthermore, we highlight the importance of investigating the functional and structural characteristics of PCs in these disorders to illuminate the underlying pathogenesis and stimulate further research in this area.

Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis with Mildly Decreased and Normal Lung Function: A Real-Life Observational Study.

Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis with Mildly Decreased and Normal Lung Function: A Real-Life Observational Study.

Fezolinetant- A novel NK3R antagonist for treating postmenopausal vasomotor symptoms

Madam, It has been estimated that up to 80% of postmenopausal women experience vasomotor symptoms (VMS) such as hot flushes, night sweats, mood swings and difficulty in concentrating1. These symptoms markedly affect different aspects of daily life for women, including, sleep, mental well-being, sex, interpersonal communication and overall quality of life (QOL). Furthermore, they cause a significant burden on healthcare and workplace productivity. Hormone therapy (HT), involving combined estrogen and progesterone or estrogen alone, is the standard management for VMS associated with menopause. However, safety and tolerability issues have discouraged the use of HT, due to the associated risk of breast cancer, stroke and venous thromboembolism2. Alternative treatments, including selective serotonin reuptake inhibitors (SSRIs), clonidine, gabapentin, and herbal remedies, have demonstrated limited effectiveness with undesirable side effects like sedation and nausea3. This situation warrants a safe and effective non-hormonal therapy for managing menopause-associated VMS. Neurokinin-3 receptor (NK3R) antagonists offer a unique therapeutic approach with minimal adverse effects (AEs). This class of drugs functions by inhibiting the stimulation of KNDy neurons, thereby restoring the normal function of the thermoregulatory centre, which is altered by reduced estrogen levels and subsequent unopposed action of the neuropeptide neurokinin B on NK3 receptors located on KNDy neurons in the hypothalamus4, 5. In 2023 the United States Food and Drug Administration, has,approved the first ever NK3R antagonist, Fezolinetant, (Veozah) for VMS in postmenopausal women. The approval was granted following two phase 3, double-blind placebo controlled trials: SKYLIGHT 1 and 2. The efficacy of the drug was tested for 12 weeks including women aged between 40 and 65 with confirmed menopause and at least 7 episodes of hot flushes a day. Vasomotor symptoms , like hot flushes and night sweats, were effectively improved in the control group with beneficial effects on sleep. The most common AE was a headache. Other infrequent and non-serious AEs included abdominal pain, nausea, fatigue and oropharyngeal pain4, 5 NK3R antagonists are an innovative class of drugs that are an effective therapeutic option for postmenopausal symptoms with better efficacy and safety. Availability of the oral form of these drugs makes it an easier option for postmenopausal women, improving overall QOL. ---Continue

Time-dependent analysis of erectile dysfunction in kidney transplant recipients: insights from four distinct time periods

Background and intentionErectile dysfunction (ED) is an underappreciated clinical condition in men. This study aims to compare the dynamic changes in the distribution of ED among male kidney transplant recipients (mKTRs) in four epochs: end-stage renal disease period (ESRDp), early post-transplant period (EPTP), pre-COVID-19, and post-COVID-19.MethodsGeneral information was gathered through interviews, follow-ups, and medical records. The International Index of Erectile Function Questionnaire-5 was used to assess erectile function. The Mann–Whitney U test and chi-square test were used to analyze differences in ED strength. Univariate and logistic regression analyses were conducted to identify risk factors for ED.ResultsThe database contains 230 mKTRs. In the ESRDp, 17.0% had normal erectile function, 53.5% had mild ED, 18.3% had moderate ED, and 11.3% had severe ED. In the EPTP, the distribution was 38.2% normal, 42.6% mild, 10.8% moderate, and 8.2% severe. In the pre-COVID-19 period, it was 34.3%, 47.3%, 10.4%, and 7.8%, and in the post-COVID-19 period, it was 23.0%, 45.6%, 21.3%, and 10.0%. Overall, erectile function improved after kidney transplant (KT). However, post-COVID-19, the proportion of erectile function significantly decreased compared to EPTP and pre-COVID-19 periods. Risk factors for post-pandemic ED included degree, Generalized Anxiexy Disorder-7, kidney donor type, postoperative time, hypertension and hemoglobin concentration.ConclusionKT improves erectile function in mKTRs within 5 years, but post-SARS-CoV-2 viral infection, ED worsens due to altered risk factors. These findings inform future research for comprehensive ED prevention and management strategies in this population.

In vivo movement interrelationships among the medial meniscus, joint capsule, and semimembranosus during tibial rotation

The meniscal position within the knee is critical to maintain normal knee function. The joint capsule might dynamically coordinate the medial meniscus (MM) by transmitting a semimembranosus action. However, their interrelationships in vivo are unclear. We aimed to determine relationships among the MM, joint capsule, and semimembranosus during passive tibial external-internal and isometric tibial internal rotation at the medial and posteromedial knees of 10 healthy individuals in vivo using ultrasound. We analyzed images of the MM and joint capsule locations at the medial and posteromedial knee and the velocity waveform similarity of each structure during rotational tasks. Both isometric internal rotation with semimembranosus action and passive tibial external rotation displaced the MM inward at the medial knee. The MM and joint capsule during these MM displacements coordinately moved with more than moderate cross-correlation coefficients (passive external and isometric internal rotations, ≥ 0.54 and ≥ 0.90, respectively). The movements of the MM and joint capsule to the semimembranosus during isometric internal rotation also coordinated with moderate cross-correlation coefficients (≥ 0.62). Therefore, the joint capsule might dynamically coordinate the MM by transmitting semimembranosus action. Whether increased tibial internal rotation or semimembranosus shortening causes MM extrusion awaits further investigation.

Neural Histogram‐Based Glint Rendering of Surfaces With Spatially Varying Roughness

AbstractThe complex, glinty appearance of detailed normal‐mapped surfaces at different scales requires expensive per‐pixel Normal Distribution Function computations. Moreover, large light sources further compound this integration and increase the noise in the Monte Carlo renderer. Specialized rendering techniques that explicitly express the underlying normal distribution have been developed to improve performance for glinty surfaces controlled by a fixed material roughness. We present a new method that supports spatially varying roughness based on a neural histogram that computes per‐pixel NDFs with arbitrary positions and sizes. Our representation is both memory and compute efficient. Additionally, we fully integrate direct illumination for all light directions in constant time. Our approach decouples roughness and normal distribution, allowing the live editing of the spatially varying roughness of complex normal‐mapped objects. We demonstrate that our approach improves on previous work by achieving smaller footprints while offering GPU‐friendly computation and compact representation.

The effect of aluminum- and silicon-containing enterosorbent on the thymic cellular composition in mice kept under two-week all-night lighting

Background. Continuous lighting contributes to the development of desynchronosis, which is stressful for the body. As a result, the normal functioning of the immune system is disrupted, which in turn can shift the physiological balance towards pathology and endotoxemia. It is relevant to develop innovative drugs based on a sorbent matrix, which can be modified with biologically active molecules that extendedly leave the sorbent surface. At the same time, the sorbent retains the properties of a detoxifier, fixing toxic agents on the surface and removing them from the body, which helps restore the internal environment and normalizes the overall reactivity of the body in extreme conditions.The aim. To study the effect of aluminum- and silicon-containing enterosorbent (based on aluminum oxide and polydimethylsiloxane) on the cellular composition of the thymus and the distribution of thymocytes in the organ according to the cell cycling state in C57Bl/6 mice kept under the all-night lighting.Materials and methods. Animals received sorbent (0.665 g per 1 kg of body weight in 200 μl of distilled water) through an intragastric tube once a day for 14 days against the background of continuous lighting. Intact mice and placebo animals composed control group. We used flow cytometry to assess the percentage of CD3hi and CD3low lymphocytes of the thymus, the CD3low/CD3hi ratio, viability and distribution of cells across according to the cell cycling state.Results. Continuous lighting inhibited the differentiation and maturation of young CD3low lymphocytes into mature forms of CD3hi, reduced the proliferation of thymic epithelial cells, and activated apoptosis of lymphocytes and epithelial cells in the organ. The introduction of the sorbent restored the content and viability of young CD3low lymphocytes and contributed to the preservation of the viability and proliferation of thymic epithelial cells.Conclusion. Using an enterosorbent based on aluminum oxide and polydimethylsiloxane under conditions of continuous lighting helps maintain the functional activity of the thymus, preventing its involution, and is advisable against the background of circadian disruption.

The effects of high doses of selenium supplementation on mRNA and protein levels of cMLCK levels and total antioxidant capacity in rat heart tissue

BackgroundHigh doses of selenium are associated with heart disease prevalence in high-risk areas. Cardiac myosin light chain kinase (cMLCK) is an essential enzyme for normal function of heart tissue. Therefore, we studied the effect of high doses of selenium on the expression of cMLCK gene and its protein in normal heart tissue in rats. Materials and MethodsTwenty male rats were randomly divided into four groups: control, Se 0.3mg/kg, Se 1.5mg/kg, and Se 3mg/kg. Sodium-selenite was administered orally into drinking water for 20 weeks. Se levels of heart tissue were measured by atomic absorption. Serum creatine phosphokinase (CPK) and total serum antioxidant-capacity were measured. Moreover, the concentration of MLCK protein and the gene expression level of cMLCK in normal heart tissue were analyzed. ResultsExcess Se in dietary can significantly increase CPK. Se concentration of heart tissue in the Se 3mg/kg-group was significantly higher than the control. cMLCK mRNA levels were decreased by 0.3mg/kg and 3mg/kg sodium selenite intake. There was no significant difference between three-groups for total antioxidant-capacity and MLCK protein. ConclusionHigh concentrations of selenium can probably effect on normal function of the heart tissue by changing the expression levels of cMLCK.

A modified handling stability control strategy for steer-by-wire vehicles based on variable steering ratio and active front steering control

Steer-by-wire (SBW) systems with steering actuator motors rotating the front wheels allow more flexibility for handling stability control; however, determining the desired steering angle and accurately tracking the desired steering angle are still key challenges. Therefore, a modified handling stability control strategy for handling stability is proposed in this paper. Firstly, based on the normal function, a unified variable steering ratio (UniVSR) model that varies with vehicle speed and steering wheel angle is developed. Then, the UniVSR model parameters are optimized by particle swarm optimization (PSO) algorithm in speed segments to improve the steering sensitivity at low speeds and the stability at medium and high speeds. Next, the active front steering (AFS) controller that considers the intervention timing and intervention threshold is proposed to improve the stability of the SBW vehicle under the driving conditions of low-adhesion road, split-μ road, and lateral wind interference. Lastly, the linear active disturbance rejection control (LADRC) based angle tracking control algorithm is presented to guarantee the desired angle tracking accuracy of the steering actuator motor under both internal parameter and external torque perturbations. The simulations validate the effectiveness of the proposed UniVSR model and AFS controller in improving handling stability.

Analysis of the Dimensional and Shape Accuracy and Repeatability of Models Produced in the Process of Additive Extrusion of Thermoplastic Polymers Using Fused Filament Fabrication Technology

To achieve high precision and repeatability of prototyped models, work is carried out to improve existing solutions and thus expand the areas of application of 3D printers. Ways to increase the efficiency of 3D printing are being sought. The subject of the work concerns the analysis of dimensional and shape accuracy and repeatability of samples produced by a technology based on layered extrusion of thermoplastic polymers using FFF—fused filament fabrication technology. The key parameter for assessing the quality of parts is the property most expected by 3D printer users regarding the accuracy of dimensions of manufactured prototypes. As part of the research, conclusions were drawn regarding the precision of the samples as original patterns. The dimensional accuracy in the x, y, and z axes of the 3D printer was determined in terms of the design of the 3D printer’s actuator system. Three-dimensional maps of deviations of the pattern surface were used in relation to the nominal 3D CAD model to test the accuracy. The analytical results obtained during the research work, together with the graphs of the normal distribution probability function, indicate a high repeatability for each of the axes, and the highest repeatability was for the z-axis. The dimensions in the remaining axes were within the assumed tolerance of 0.1 mm, except for the two extreme dimensions, which were caused by a different method of heat dissipation, proving the influence of the arrangement of samples on the working platform.

Iodine-123-Iomazenil Single-Photon Emission Computed Tomography Revealed Recovery of Neuronal Viability in Association With Improvement of Cognitive Dysfunction After Revascularization in Moyamoya Disease.

Recent studies indicate that 123I-iomazenil (123I-IMZ) single-photon emission computed tomography (SPECT) can demonstrate neuronal viability. Although cognitive dysfunction has been recognized as an important issue in adult patients with moyamoya disease (MMD), no standard neuroradiological methods to define such conditions have been established. We examined the relationship between cognitive function and 123I-IMZ SPECT before and after revascularization in patients with MMD. The study participants were 16 adult patients with MMD whose cerebrovascular reactivities were decreased only on the surgical sides of combined revascularization. Cognitive function was examined using the Mini-Mental State Examination (MMSE; cutoff: 27) and the Frontal Assessment Battery (FAB; cutoff: 16) before and at 3 to 6 months after surgery. 123I-iodoamphetamine (123I-IMP) SPECT with acetazolamide challenge and 123I-IMZ SPECT were performed concurrently while evaluating cognitive function. The radioreactivities of 123I-IMZ SPECT in regions with decreased cerebrovascular reactivities on 123I-IMP SPECT were investigated using affected-to-contralateral side asymmetry ratio (IMZ-ACR). Twelve patients showed normal cognitive function (MMSE: 29.8 ± 0.4, FAB: 18 ± 0) before surgery. No evident laterality of 123I-IMZ uptake was seen (IMZ-ACR: 0.98 ± 0.04). Neither cognitive function nor 123I-IMZ SPECT worsened after surgery (MMSE: 29.8 ± 0.3, FAB: 18 ± 0, IMZ-ACR: 1.00 ± 0.04). By contrast, 4 patients presented cognitive dysfunction (MMSE: 24.3 ± 3.9, FAB: 14.8 ± 2.7) before revascularization. Preoperative imaging of these patients showed decreased 123I-IMZ uptake, and their IMZ-ACRs (0.83 ± 0.08) were significantly lower than those of the normal group. After revascularization, cognitive functions and 123I-IMZ uptake tended to ameliorate (MMSE: 27.5 ± 1.7, FAB: 16.3 ± 2.2, IMZ-ACR: 0.94 ± 0.09). Preoperative cognitive function was associated with 123I-IMZ uptake in adult patients with MMD. After revascularization, cognitive function could be recovered in the viable areas of the brain, which is consistent with 123I-IMZ SPECT findings.

Baseline lung allograft dysfunction after bilateral deceased-donor lung transplantation: A single-center experience in Japan

BackgroundBaseline lung allograft dysfunction (BLAD) refers to a condition in which a lung transplant recipient does not achieve normal pulmonary function (i.e., forced expiratory volume in 1 s or forced vital capacity of <80% of predicted values). Although BLAD is reportedly associated with a poor prognosis, the condition has not been examined in Japanese patients. MethodsIn this study, we retrospectively examined 38 Japanese adults who underwent bilateral lung transplantation from 2015 to 2022 in a single center. ResultsTwenty-one (55%) patients met the criteria for BLAD. No significant differences were found in recipient or donor factors between the BLAD and non-BLAD groups, but the donor–recipient ratio of the predicted vital capacity was lower in the BLAD group (p = 0.009). The intensive care unit length of stay, ventilator duration, and blood loss during transplant surgery were significantly higher in the BLAD group (p < 0.05). No significant difference was found in survival. The median observation period was significantly shorter in the BLAD than non-BLAD group (744 vs.1192 days, respectively; p = 0.031). The time to reach the normal threshold of pulmonary function after lung transplantation varied among the patients, ranging from 6 months to 4 years. ConclusionsThe characteristics of these Japanese patients with BLAD were similar to those of other patients in previous reports. The effects of the observation period and donor–recipient age discrepancy on BLAD require further exploration.

IDO1 promotes CSFV replication by mediating tryptophan metabolism to inhibit NF-κB signaling.

Tryptophan metabolism plays a crucial role in facilitating various cellular processes essential for maintaining normal cellular function. Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the conversion of tryptophan (Trp) into kynurenine (Kyn), thereby initiating the degradation of Trp. The resulting Kyn metabolites have been implicated in the modulation of immune responses. Currently, the role of IDO1-mediated tryptophan metabolism in the process of viral infection remains relatively unknown. In this study, we discovered that classical swine fever virus (CSFV) infection of PK-15 cells can induce the expression of IDO1, thereby promoting tryptophan metabolism. IDO1 can negatively regulate the NF-κB signaling by mediating tryptophan metabolism, thereby facilitating CSFV replication. We found that silencing the IDO1 gene enhances the expression of IFN-α, IFN-β, and IL-6 by activating the NF-κB signaling pathway. Furthermore, our observations indicate that both silencing the IDO1 gene and administering exogenous tryptophan can inhibit CSFV replication by counteracting the cellular autophagy induced by Rapamycin. This study reveals a novel mechanism of IDO1-mediated tryptophan metabolism in CSFV infection, providing new insights and a theoretical basis for the treatment and control of CSFV.IMPORTANCEIt is well known that due to the widespread use of vaccines, the prevalence of classical swine fever (CSF) is shifting towards atypical and invisible infections. CSF can disrupt host metabolism, leading to persistent immune suppression in the host and causing significant harm when co-infected with other diseases. Changes in the host's metabolic profiles, such as increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, can also influence virus replication. Mammals utilize various pathways to modulate immune responses through amino acid utilization, including increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, thereby limiting viral replication. Therefore, this study proposes that targeting the modulation of tryptophan metabolism may represent an effective approach to control the progression of CSF.

Relapsing Polychondritis Masquerading as Auricular Pseudolymphoma: Case Report and Literature Review

Relapsing Polychondritis (RP) is a rare autoimmune disease associated with recurring inflammatory episodes predominantly affecting cartilage and other tissues throughout the body, including proteoglycan-rich structures. It is characterized by gradual deformation of tissue that leads to impairment of normal function. Areas involved include, but are not limited to, the respiratory tract, eyes, nose, joints, and vascular system. The inflammation targets cartilage, most commonly causing auricular and nasal chondritis but can involve cartilage throughout the body. Diagnosis of RP is often hindered by the vast variety of symptoms associated with this systemic disease and subtle symptomatology. In this paper, we demonstrate a case of relapsing polychondritis masquerading as pseudolymphoma and review recent literature relating to pathogenesis, diagnosis and treatment.

Hydroxyl-functionalized cationic porous organic polymers for efficient enrichment and detection of phenolic endocrine disrupting chemicals in water and snapper

Endocrine-disrupting chemicals (EDCs) can disrupt the normal functioning of the endocrine system in organisms, leading to various health issues. Therefore, monitoring EDCs in the environment and food is of significant importance. In this study, a hydroxyl-functionalized ionic porous organic polymer (OH-IPOP) has been synthesized for the first time using 2-benzimidazolemethanol as a monomer. The OH-IPOP exhibited excellent adsorption performance towards phenolic EDCs. An efficient method for determination of phenolic EDCs (p-tert-butylphenol, bisphenol B, bisphenol A and bisphenol F) in environmental water and snapper samples was successfully established by with OH-IPOP as solid-phase extraction sorbent and determination with high-performance liquid chromatography-ultraviolet detection. The method showed good linearity (r2 > 0.998), low detection limits (0.008–0.020 ng mL−1 for lake water, 1.00–3.00 ng/g for snapper), high recovery rates (82.3–106 %), and good precision (relative standard deviation < 6.6 %), making it a highly efficient adsorbent for the enrichment of EDCs in complex sample matrices.

Advances in Ubiquitination and Proteostasis in Retinal Degeneration.

Retinal degeneration (RD) is a group of chronic blinding diseases characterised by progressive retinal cell death. As the disease progresses, vision deteriorates due to retinal cell death and impaired retinal integrity, eventually leading to complete loss of vision. Therefore, the function and environmental homeostasis of the retina have an important impact on the pathogenesis and treatment of RD. Ubiquitination, as a complex post-translational modification process, plays an essential role in maintaining retinal homeostasis and normal function. It covalently combines ubiquitin with protein through a series of enzyme-mediated reactions, and participates in cell processes such as gene transcription, cell cycle process, DNA repair, apoptosis and immune response. At the same time, it plays a central role in protein degradation. There are two major protein degradation systems in eukaryotic cells: the ubiquitin-proteasome system and the autophagy-lysosomal system. The protein degradation pathway maintains retinal protein homeostasis by reducing abnormal protein accumulation in the retina through two modes of degradation. Either dysregulation of ubiquitination or disruption of protein homeostasis may lead to the development of RD. This article aims to comprehensively review recent research progress on ubiquitin-related genes, proteins and protein homeostasis in the pathogenesis of RD, and to summarize the potential targeted therapy strategies for it. The review is expected to provide valuable guidance for further development and application of ubiquitination in RD.

Caspase-1 inhibitor CZL80 protects against acute seizures via amplifying the inhibitory neural transmission

Current anti-seizure medications (ASDs) primarily target ion channels or neurotransmissions; however, their practicability is limited by unwanted side-effects and pharmacoresistance. Cumulative evidence has proposed pro-inflammatory caspase-1 as a potential target for developing ASDs. In this study, we showed that the small-molecular caspase-1 inhibitor CZL80 can prevent seizures in various models including the maximal electroshock (MES), the pentylenetetrazol (PTZ), and the amygdaloid kindled models. Specifically, we discovered that CZL80 prevented death, reduced the duration of generalized seizures, and increased the threshold of generalized seizures in a dose-dependent manner in the MES model. In the PTZ model, CZL80 decreased the seizure stages, prolonged the latency to stage 4 seizures, and decreased the death rate. And in amygdaloid kindled rats, CZL80 inhibited the seizure stages, shortened the durations of both generalized seizures and after-discharges. And the anti-seizure efficacy of CZL80 was diminished in caspase-1 knockout mice. In vitro electrophysiology recordings revealed that CZL80 was able to decreased the excitability of glutamatergic pyramidal neurons, as denoted by reducing the spontaneous neuronal firings and increasing the rheobase injected currents to elicit action potentials. Furthermore, CZL80 was able to increase the amplitudes of inhibitory post-synaptic currents (IPSC), while the excitatory post-synaptic currents (EPSC) were not influenced. Lastly, daily administration of CZL80 for 3 weeks did not influence the normal locomotor functions in mice. In sum, our results highlighted CZL80 as a potential anti-seizure therapy with therapeutic significance.