Cattle hair as a bioindicator for short- and medium-chain chlorinated paraffin monitoring on cattle farms.

Short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) are hazardous industrial chemicals that tend to bioaccumulate in animal-derived foodstuffs through the food supply chain. However, the lack of reliable noninvasive bioindicators hinders the monitoring of farm animal exposure to CPs. In this study, 169 cattle hair samples were collected from beef cattle farms in six Chinese provinces, with further beef, feed, and soil samples being collected in Hebei province. Geographical differences in CP concentrations were observed in the hair samples, and CP concentrations in samples collected from Hebei province decreased in the following order: hair > feed > beef > soil. C10-11Cl6-7 and C14Cl7-8 were the predominant SCCPs and MCCPs, respectively, in all the hair, beef, feed, and soil samples. CP concentrations in hair samples significantly correlated with those in beef, feed, and soil samples, indicating that hair can be used as a bioindicator of cattle exposure to CPs. The possible health risks associated with exposure to CPs through beef consumption, especially for children and high-volume beef consumers, should be further investigated.

Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Objective: Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. Methods: To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Results: Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Conclusion: Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

AZIN2 is associated with apoptosis of germ cells in undescended testis.

Undescended testis (UDT), known as cryptorchidism (CRY), is a common congenital disorder in which one or both testicles do not descend normally into the scrotum. A unilateral UDT model was established by inducing UDT in mice through surgery. The results showed that the testis in the UDT model group was abnormal; the lumen of the seminiferous tubule was atrophic; apoptosis, necrosis and shedding were observed in many of the germ cells; the level of sex hormones was abnormal; and mature sperm was reduced. Subsequently, transcriptome sequencing was conducted on the testicular tissue of UDT model mice. Through analysis and verification of differential genes, AZIN2 was identified as playing a key role in the decline in male fertility caused by cryptorchidism. AZIN2 expression and spermine content was down-regulated in the testis of the UDT group. We then used a combination of hypoxanthine and xanthine to create a GC-1 cell damage model. In this model, AZIN2 expression and spermine content was down-regulated. When si-Azin2 transfected GC-1 cells, cell viability and proliferation were decreased. However, in the GC-1 cell damage model transfected with Azin2 over-expressed plasmid, AZIN2 expression and spermine content was up-regulated, reversing the cell damage caused by hypoxanthine and xanthine, and restoring the proliferation ability of GC-1 cells. These results indicate that in UDT, down-regulated AZIN2 expression is a factor in testicular damage. This discussion of the connection between AZIN2 and germ cells has important clinical significance as it provides an important reference for the diagnosis and treatment of cryptorchidism.

Cross-ancestry genome-wide association studies of brain imaging phenotypes.

Genome-wide association studies of brain imaging phenotypes are mainly performed in European populations, but other populations are severely under-represented. Here, we conducted Chinese-alone and cross-ancestry genome-wide association studies of 3,414 brain imaging phenotypes in 7,058 Chinese Han and 33,224 white British participants. We identified 38 new associations in Chinese-alone analyses and 486 additional new associations in cross-ancestry meta-analyses at P < 1.46 × 10-11 for discovery and P < 0.05 for replication. We pooled significant autosomal associations identified by single- or cross-ancestry analyses into 6,443 independent associations, which showed uneven distribution in the genome and the phenotype subgroups. We further divided them into 44 associations with different effect sizes and 3,557 associations with similar effect sizes between ancestries. Loci of these associations were shared with 15 brain-related non-imaging traits including cognition and neuropsychiatric disorders. Our results provide a valuable catalog of genetic associations for brain imaging phenotypes in more diverse populations.

A novel entity of HIPK2::YAP1 pulmonary fibromatosis.

BACKGROUND: Pulmonary fibromatosis (PF) is a specific variant of fibromatosis, which is rarely reported occurring in the lung. PF with HIPK2-YAP1 fusion was a novel entity. CASE PRESENTATION: In this report, a 66-year-old male with PF had been smoking over 40 years. Multiple cords and small nodules in both lungs had been detected in a health examination two years earlier at our hospital. But approximately twofold enlarged in the lingual segment of the upper lobe in the left lung were disclosed in this year. Immunohistochemical analysis demonstrated that the vimentin and ß-Catenin were positive in the largest nodule. After underwent a DNA/RNA panel next-generation sequencing (NGS), missense mutations and HIPK2-YAP1 fusion were found in this sample. Ultimately, the case diagnosis as PF with HIPK2-YAP1 fusion after multidisciplinary treatment. Currently, the patient is doing well and recurrence-free at 14 months post-surgery. CONCLUSIONS: It's difficult for patients with complex morphology to make accurate diagnosis solely based on morphology and immunohistochemistry. But molecular detection is an effective method for further determining pathological subtypes.

Functional Connectivity-Based Searchlight Multivariate Pattern Analysis for Discriminating Schizophrenia Patients and Predicting Clinical Variables.

BACKGROUND: Schizophrenia, a multifaceted psychiatric disorder characterized by functional dysconnectivity, poses significant challenges in clinical practice. This study explores the potential of functional connectivity (FC)-based searchlight multivariate pattern analysis (CBS-MVPA) to discriminate between schizophrenia patients and healthy controls while also predicting clinical variables. STUDY DESIGN: We enrolled 112 schizophrenia patients and 119 demographically matched healthy controls. Resting-state functional magnetic resonance imaging data were collected, and whole-brain FC subnetworks were constructed. Additionally, clinical assessments and cognitive evaluations yielded a dataset comprising 36 clinical variables. Finally, CBS-MVPA was utilized to identify subnetworks capable of effectively distinguishing between the patient and control groups and predicting clinical scores. STUDY RESULTS: The CBS-MVPA approach identified 63 brain subnetworks exhibiting significantly high classification accuracies, ranging from 62.2% to 75.6%, in distinguishing individuals with schizophrenia from healthy controls. Among them, 5 specific subnetworks centered on the dorsolateral superior frontal gyrus, orbital part of inferior frontal gyrus, superior occipital gyrus, hippocampus, and parahippocampal gyrus showed predictive capabilities for clinical variables within the schizophrenia cohort. CONCLUSION: This study highlights the potential of CBS-MVPA as a valuable tool for localizing the information related to schizophrenia in terms of brain network abnormalities and capturing the relationship between these abnormalities and clinical variables, and thus, deepens our understanding of the neurological mechanisms of schizophrenia.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia: A Prospective, Randomized, Open, Parallel Controlled and Multicenter Clinical Study.

OBJECTIVE: This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. METHODS: A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. RESULTS: After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). CONCLUSION: The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

Prognostic performance of MRI LI-RADS version 2018 features and clinical-pathological factors in alpha-fetoprotein-negative hepatocellular carcinoma.

PURPOSE: To evaluate the role of the magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS) version 2018 features and clinical-pathological factors for predicting the prognosis of alpha-fetoprotein (AFP)-negative (≤ 20 ng/ml) hepatocellular carcinoma (HCC) patients, and to compare with other traditional staging systems. METHODS: We retrospectively enrolled 169 patients with AFP-negative HCC who received preoperative MRI and hepatectomy between January 2015 and August 2020 (derivation dataset:validation dataset = 118:51). A prognostic model was constructed using the risk factors identified via Cox regression analysis. Predictive performance and discrimination capability were evaluated and compared with those of two traditional staging systems. RESULTS: Six risk factors, namely the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin-bilirubin grade, were associated with recurrence-free survival. The prognostic model constructed using these factors achieved C-index of 0.705 and 0.674 in the derivation and validation datasets, respectively. Furthermore, the model performed better in predicting patient prognosis than traditional staging systems. The model effectively stratified patients with AFP-negative HCC into high- and low-risk groups with significantly different outcomes (p < 0.05). CONCLUSION: A prognostic model integrating the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin-bilirubin grade may serve as a valuable tool for refining risk stratification in patients with AFP-negative HCC.

Efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer.

BACKGROUND: Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world, and the choice of its treatment is very important for the survival rate and prognosis of patients. Traditional open surgery is the main treatment for ovarian cancer, but it has the disadvantages of big trauma and slow recovery. With the continuous development of minimally invasive technology, minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery. However, the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial. AIM: To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer. METHODS: The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively. According to the different surgical treatment methods, patients were divided into study group and control group (45 cases in each group). The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer, while the control group received traditional open surgery for ovarian cancer. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), clinical efficacy and safety of the two groups were compared. RESULTS: The intraoperative blood loss, length of hospital stay, postoperative gas evacuation time, and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group (P < 0.05). The incidence of postoperative complications in the study group was significantly lower than in the control group (P < 0.05). The two groups had no significant differences in the preoperative adrenocorticotropic hormone (ACTH), androstenedione (AD), cortisol (Cor), cluster of differentiation 3 positive (CD3+), and cluster of differentiation 4 positive (CD4+) indexes (P > 0.05). In contrast, postoperatively, the study group's ACTH, AD, and Cor indexes were lower, and the CD3+ and CD4+ indexes were higher than those in the control group (P < 0.05). CONCLUSION: Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety, improve the short-term prognosis and quality of life of patients, and is worth popularizing.

TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

Objective Evaluation of Pulse Width Using an Array Pulse Diagram.

BACKGROUND: Pulse width, which can reflect qi, blood excess, and deficiency, has been used for diagnosing diseases and determining the prognosis in traditional Chinese medicine (TCM). This study aimed to devise an objective method to measure the pulse width based on an array pulse diagram for objective diagnosis. METHODS: The channel 6, the region wherein the pulse wave signal is the strongest, is located in the middle of the pulse sensor array and at the guan position of cunkou during data collection. Therefore, the main wave (h1) time of the pulse wave was collected from the channel 6 through calculation. The left h1 time was collected from the remaining 11 channels. The amplitudes at these time points were extracted as the h1 amplitudes for each channel. However, the pulse width could not be calculated accurately at 12 points. Consequently, a bioharmonic spline interpolation algorithm was used to interpolate the h1 amplitude data obtained from the horizontal and vertical points, yielding 651 (31 × 21) h1 amplitude data. The 651 data points were converted into a heat map to intuitively calculate the pulse width. The pulse width was calculated by multiplying the number of grids on the vertical axis with the unit length of the grid. The pulse width was determined by TCM doctors to verify the pulse width measurement accuracy. Meanwhile, a color Doppler ultrasound examination of the volunteers' radial arteries was performed and the intravascular meridian widths of the radial artery compared with the calculated pulse widths to determine the reliability. RESULTS: The pulse width determined using the maximal h1 amplitude method was comparable with the radial artery intravascular meridian widths measured using color Doppler ultrasound. The h1 amplitude was higher in the high blood pressure group and the pulse width was greater. CONCLUSIONS: The pulse width determined using the maximal h1 amplitude was objective and accurate. Comparison between the pulse widths of the normal and high blood pressure groups verified the reliability of the method.

5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination.

INTRODUCTION: Excessive immune activation induces tissue damage during infection. Compared to external strategies to reconstruct immune homeostasis, host balancing ways remain largely unclear. OBJECTIVES: Here we found a neuroimmune way that prevents infection-induced tissue damage. METHODS: By FACS and histopathology analysis of brain Streptococcus pneumonia meningitis infection model and behavioral testing. Western blot, co-immunoprecipitation, and ubiquitination analyze the Fluoxetine initiate 5-HT7R-STUB1-CCR5 K48-linked ubiquitination degradation. RESULTS: Fluoxetine, a selective serotonin reuptake inhibitor, or the agonist of serotonin receptor 5-HT7R, protects mice from meningitis by inhibiting CCR5-mediated excessive immune response and tissue damage. Mechanistically, the Fluoxetine-5-HT7R axis induces proteasome-dependent degradation of CCR5 via mTOR signaling, and then recruits STUB1, an E3 ubiquitin ligase, to initiate K48-linked polyubiquitination of CCR5 at K138 and K322, promotes its proteasomal degradation. STUB1 deficiency blocks 5-HT7R-mediated CCR5 degradation. CONCLUSION: Our results reveal a neuroimmune pathway that balances anti-infection immunity via happiness neurotransmitter receptor and suggest the 5-HT7R-CCR5 axis as a potential target to promote neuroimmune resilience.

Identification and characterization of the receptors of a microneme adhesive repeat domain of Eimeria maxima microneme protein 3 in chicken intestine epithelial cells.

Eimeria maxima microneme protein 3 (EmMIC3) is pivotal in the initial recognition and attachment of E. maxima sporozoites to host cells. EmMIC3 comprises 5 tandem Type I microneme adhesive repeat (MAR) domains, among which MAR2 of EmMIC3 (EmMAR2) has been identified as the primary determinant of EmMIC3-mediated tissue tropism. Nonetheless, the mechanisms through which EmMAR2 guides the parasite to its invasion site through interactions with host receptors remained largely uncharted. In this study, we employed yeast two-hybrid (YTH) screening assays and shotgun LC-MS/MS analysis to identify EmMAR2 receptors in chicken intestine epithelial cells. ATPase H+ transporting V1 subunit G1 (ATP6V1G1), receptor accessory protein 5 (REEP5), transmembrane p24 trafficking protein (TMED2), and delta 4-desaturase sphingolipid 1 (DEGS1) were characterized as the 4 receptors of EmMAR2 by both assays. By blocking the interaction of EmMAR2 with each receptor using specific antibodies, we observed varying levels of inhibition on the invasion of E. maxima sporozoites, and the combined usage of all 4 antibodies resulted in the most pronounced inhibitory effect. Additionally, the spatio-temporal expression profiles of ATP6V1G1, REEP5, TMED2, and DEGS1 were assessed. The tissue-specific expression patterns of EmMAR2 receptors throughout E. maxima infection suggested that ATP6V1G1 and DEGS1 might play a role in early-stage invasion, whereas TMED2 could be involved in middle and late-stage invasion and REEP5 and DEGS1 may participate primarily in late-stage invasion. Consequently, E. maxima may employ a multitude of ligand-receptor interactions to drive invasion during different stages of infection. This study marks the first report of EmMAR2 receptors at the interface between E. maxima and the host, providing insights into the invasion mechanisms of E. maxima and the pathogenesis of coccidiosis.

Systematic investigation of cerebellar functional alterations and their association with surgical outcomes in patients with degenerative cervical myelopathy: a resting-state fMRI study.

OBJECTIVE: The aim of this study was to systematically investigate the changes in cerebellar neural activity and cerebellar-cortical functional connectivity (FC) in patients with degenerative cervical myelopathy (DCM) using resting-state functional magnetic resonance imaging (fMRI). METHODS: In this study, we collected clinical data and resting-state fMRI data from 54 DCM patients and 50 healthy controls (HCs). We analyzed voxel-wise regional fMRI metrics, including amplitude of low frequency fluctuation (ALFF), fractional ALFF, regional homogeneity, functional connectivity density, and voxel-mirrored homotopic connectivity. In analysis 1, we examined the differences in regional fMRI metrics within the cerebellum between the DCM patient group and the healthy control group, as well as their correlation with preoperative neurological status and prognosis. In analysis 2, we investigated cerebellar-cortical functional connectivity differences between the two groups and their correlation with preoperative neurological status and prognosis. Lastly, in analysis 3, we explored the internetwork connectivity between the 'cerebellar-SMN' (sensorimotor network) system, examined the between-group differences, and investigated its correlation with preoperative neurological status and prognosis. RESULTS: (1) Relative to HCs, DCM patients exhibited functional alterations in wide-spread cerebellar regions; (2) DCM patients exhibited altered cerebellar-cortical FC which was associated with the preoperative neurological status and prognosis; (3) DCM patients exhibited altered internetwork connectivity between 'cerebellar-SMN' system which was associated with duration of symptom. CONCLUSION: Wide-spread cerebellar functional alterations occur in DCM pathogenesis and the deficits in cerebellar-SMN functional connectivity may be beneficial in future studies for predicting surgical outcomes in patients with DCM.

Characteristic changes and environmental indicators of magnetic spherules in the South Yellow Sea mud area for about 7.5 ka.

Magnetic spherules originate from anthropogenic and natural sources and can be differentiated based on morphology and composition. Using magnetic measurement, diameter measurement, scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS) analysis of a 10 m sediment core in the mud area of the South Yellow Sea, we found that magnetic spherules occur at all observed depths of the core. The magnetic spherule concentrations vary from 10 spherules/0.5 g to 62 spherules/0.5 g. Here, concentrations generally less than 10 spherules/0.5 g are considered as the background value in the core. The peak value of magnetic spherules appeared at the 0.02, 0.3, 2 and 8 m, and their concentrations are 62, 52, 36, 48 spherules/0.5 g, respectively. According to the deposition age, concentration, diameter, morphology and chemical characteristics of the spherules, it is found that the spherules at 0.02 m are produced by industrial coal burning. A volcanic eruption event was the main responsible for the accumulation of spherules at 0.3 and 8 m, while the spherules located at 2 m are related to a wildfire event. Magnetic spherules are common in continental shelf regions and can well document the human activities and natural environment events.

Individualized Texture Similarity Network in Schizophrenia.

BACKGROUND: Structural covariance network disruption has been considered an important pathophysiological indicator for schizophrenia. Here, we introduced a novel individualized structural covariance network measure, referred to as a texture similarity network (TSN), and hypothesized that the TSN could reliably reveal unique intersubject heterogeneity and complex dysconnectivity patterns in schizophrenia. METHODS: The TSN was constructed by measuring the covariance of 180 three-dimensional voxelwise gray-level co-occurrence matrix feature maps between brain areas in each participant. We first tested the validity and reproducibility of the TSN in characterizing the intersubject variability in 2 longitudinal test-retest healthy cohorts. The TSN was further applied to elucidate intersubject variability and dysconnectivity patterns in 10 schizophrenia case-control datasets (609 schizophrenia cases vs. 579 controls) as well as in a first-episode depression dataset (69 patients with depression vs. 69 control participants). RESULTS: The test-retest analysis demonstrated higher TSN intersubject than intrasubject variability. Moreover, the TSN reliably revealed higher intersubject variability in both chronic and first-episode schizophrenia, but not in depression. The TSN also reproducibly detected coexistent increased and decreased TSN strength in widespread brain areas, increased global small-worldness, and the coexistence of both structural hyposynchronization in the central networks and hypersynchronization in peripheral networks in patients with schizophrenia but not in patients with depression. Finally, aberrant intersubject variability and covariance strength patterns revealed by the TSN showed a missing or weak correlation with other individualized structural covariance network measures, functional connectivity, and regional volume changes. CONCLUSIONS: These findings support the reliability of a TSN in revealing unique structural heterogeneity and complex dysconnectivity in patients with schizophrenia.

Immunoregulatory function of SP-A.

Surfactant protein A (SP-A), a natural immune molecule, plays an important role in lung health. SP-A recognizes and binds microbial surface glycogroups through the C-type carbohydrate recognition domain, and then binds corresponding cell surface receptors (such as C1qRp, CRT-CD91 complex, CD14, SP-R210, Toll-like receptor, SIRP-α, CR3, etc.) through collagen-like region, and subsequently mediates biological effects. SP-A regulates lung innate immunity by promoting surfactant absorption by alveolar type II epithelial cells and phagocytosis of pathogenic microorganisms by alveolar macrophages. SP-A also regulates lung adaptive immunity by inhibiting DC maturation, and T cell proliferation and differentiation. This article reviews latest relationships between SP-A and adaptive and intrinsic immunity.

Luminescent Porous Organic Crystals for Adsorptive Separation of Toluene and Methylcyclohexane.

A butterfly-shaped phenothiazine derivative, PTTCN, was synthesized to obtain pure organic porous crystals for the highly efficient absorptive separation of toluene (Tol) and methylcyclohexane (Mcy). Due to the presence of three polar cyano groups and nonplanar conformation, these molecules self-assembled into a hydrogen-bonded organic framework (X-HOF-5) with distinct cavities capable of accommodating Tol molecules through multiple hydrogen-bonding interactions. Upon solvent removal via heating, the activated X-HOF-5 retained its cavity structure albeit with altered stacking arrangements, accompanied by a remarkable fluorescent color change from cyan to green. X-HOF-5a can undergo a phase transformation into X-HOF-5 upon reabsorption of Tol, while exhibiting no accommodation of Mcy due to the weak intermolecular interaction between PTTCN and Mcy. This suggests that the activated HOF material prefers Tol over Mcy. Moreover, X-HOF-5a may selectively accommodate Tol in a Tol/Mcy equimolar mixture, and the purity of Tol can reach 97% after release from the framework. Additionally, it is noteworthy that the HOF material exhibits recyclability without any discernible loss in performance.

Hypidone hydrochloride (YL-0919) protects mice from meningitis via Sigma1R-STAT1-NLRP3-GSDMD pathway.

BACKGROUND: A growing number of studies have found that antidepressants have anti-inflammatory effects while protecting nerves. Hypidone hydrochloride (YL-0919) is a novel highly selective 5-HT reuptake blocker. Our previous studies have demonstrated that YL-0919 exerts notable antidepressant- and anxiolytic-like as well as procognitive effects. However, whether YL-0919 can be used to treat inflammatory and infectious diseases remain unknown. In this study, we aimed to verify the anti-inflammatory effect of YL-0919 on bacterial meningitis and further explore the potential molecular mechanisms. METHODS: We performed the experiments on pneumococcal meningitis mice in vivo and S. pneumoniae infected macrophages/microglia in vitro, with or without YL-0919 treatment. Cognitive function was evaluated by open-field task, Morris water maze test, and novel object recognition test. Histopathological staining and immunofluorescence staining were used to detect the pathological damage of meningitis and NLRP3 inflammasome activation in microglia/macrophages. The expression of the STAT1/NLRP3/GSDMD signal pathway was measured by western blots. Proinflammatory cytokines associated with pyroptosis were detected by ELISA. RESULTS: YL-0919 protected mice from fatal pneumococcal meningitis, characterized by attenuated cytokine storms, decreased bacterial loads, improved neuroethology, and reduced mortality. NLRP3 plays a key role in the regulation of inflammation. When the underlying mechanisms were investigated, we found that YL-0919 inhibited the activation of NLRP3 via STAT1, and thus inhibited macrophages/microglia pyroptosis, resulting in downregulation of proinflammatory cytokines. In addition, Sigma1R was identified as a pivotal receptor that can be engaged by YL-0919 to inhibit NLRP3 activation and pyroptosis pathway in microglia/macrophages. CONCLUSIONS: These results provide new insights into the mechanisms of inflammation regulation mediated by the antidepressant YL-0919. Moreover, targeting the STAT1/NLRP3 pyroptosis pathway is a promising strategy for the treatment of infectious diseases like bacterial meningitis.

Factors influencing willingness to participate in ophthalmic clinical trials and strategies for effective recruitment.

AIM: To explore the factors influencing individuals' willingness to participate in ophthalmic clinical trials. METHODS: A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center, Sun Yat-sen University, in Guangzhou, China. The survey gathered data on respondents' willingness, demographic and socioeconomic profiles, as well as their reasons and concerns regarding engagement in clinical trials. RESULTS: Of the 1078 residents surveyed (mean age 31.2±13.1y; 65.8% females) in Guangzhou, 749 (69.5%) expressed a willingness to participate in future ophthalmic clinical trials. Specific characteristics associated with greater willingness included a younger age, lower annual income, higher education, prior participation experience, previous ophthalmic treatment, and a better understanding of clinical trials. With the exception of age, these characteristics were significantly linked to a higher willingness. The primary barrier to participation, expressed by 64.8% of those willing and 54.4% of those unwilling, was "Uncertain efficacy". In terms of motivations, the willing group ranked "Better therapeutic benefits" (35.0%), "Professional monitoring" (34.3%), and "Trust in healthcare professionals" (33.1%) as their top three reasons, whereas the unwilling participants indicated "Full comprehension of the protocol" (46.2%) as the key facilitator. CONCLUSION: This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors. Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies. Importantly, the need for and trust in healthcare professionals stand out as powerful motivations, underscoring the importance of enhancing physician-patient relationships, adopting patient-centered communication approaches, and addressing individualized needs to improve accrual rates.