Incidence rate and risk factors for suicide in patients with breast cancer in the USA: A surveillance, epidemiology, and end results analysis (SEER).

PURPOSE: To investigate suicide mortality and the related factors among female breast cancer patients in the United States. METHODS: The SEER database was used to identify 716,422 patients diagnosed with breast cancer between 2010 and 2018 to calculate a standardized mortality rate (SMR). An analysis of risk factors for suicide death was conducted using the univariate and multivariate Cox proportional risk model. An estimation of suicide probability was performed through a nomogram model. RESULTS: Compared with the expected suicide cases (n = 155) in the general population of the United States at the corresponding period (a suicide death rate of 5.71 per 100,000 person-years), the suicide rate among 716,422 breast cancer patients was followed during 2010-2018 and showed a relatively higher rate of 9.02 per 100,000 person-years. The SMR was 1.58 (95%CI: 1.39-1.79). White and other races were nine and seven times more likely to complete suicide than Black race, respectively (aHR = 9.013, 95%CI: 3.335-24.36, P < 0.001; aHR = 7.129, 95%CI: 2.317-21.931, P = 0.001); unmarried or single patients were at higher risk than married patients (aHR = 1.693, 95%CI: 1.206-2.377, P = 0.002). Patients receiving radiotherapy (aHR = 0.731, 95%CI: 0.545-0.980, P = 0.036) were less likely to complete suicide than those who did not. CONCLUSION: Female breast cancer patients in the United States have a higher suicide rate than the general public, and the risk factors consist of non-black ethnicity, being single or unmarried, and not being treated with radiotherapy. As a result of this study, clinicians may be able to identify female breast cancer patients who are at high risk of suicide, thus providing appropriate psychological support at the early stage.

A novel nomogram to predict glucocorticoid response in thyroid-associated ophthalmopathy: findings from a pilot study.

PURPOSE: Aimed to create a nomogram using clinical and eye-specific metrics to predict the efficacy of intravenous glucocorticoid (IVGC) therapy in patients with active and moderate-to-severe Thyroid-Associated Ophthalmopathy (TAO). METHODS: This study was conducted on 84 eyes from 42 moderate-to-severe TAO patients who received systemic IVGC therapy, and 42 eyes from 21 controls. Data were collected retrospectively from June 2020 to December 2021. The least absolute shrinkage and selection operator (LASSO) method was used to identify predictive factors for "unresponsiveness" to IVGC therapy. These factors were then analyzed using logistic regression to create a nomogram. The model's discriminative ability was robustly assessed using a Bootstrap resampling method with 1000 iterations for receiver operating characteristic (ROC) curve analysis. RESULTS: The LASSO analysis identified six factors with non-zero coefficients as significant, including Schirmer I test values, Meibomian gland (MG) diameter, MG length, disease duration, whole capillary vessel density (VD) in the radial peripapillary capillary (RPC), and whole macular VD for the superficial retinal capillary plexus (SRCP). The subsequent logistic regression model highlighted MG length, whole macular VD for SRCP, and disease duration as independent predictors of IVGC therapy response. The constructed nomogram demonstrated an area under the curve (AUC) of 0.82 (95% CI: 0.73-0.91), affirming the model's consistent and reliable ability to distinguish between responsive and non-responsive TAO patients. CONCLUSION: Our nomogram, combining MG length (<4.875 mm), SRCP VD (<50.25%), and disease duration (>5.5 months), reliably predicts lower IVGC therapy effectiveness in active, moderate-to-severe TAO patients.

Pyrenetetrasulfonate-grafted 2D ultrathin metal-organic layer as new electrochemiluminescence emitters for ultrasensitive microRNA-21 assay.

The exploration of novel electrochemiluminescence (ECL) luminophores with excellent ECL properties is a current research hotspot in the ECL field. Herein, a novel high-efficiency Ru-complex-free ECL emitter PyTS-Zr-BTB-MOL has been prepared by using porous ultrathin Zr-BTB metal-organic layer (MOL) as carrier to coordinatively graft the cheap and easily available polycyclic aromatic hydrocarbon (PAH) derivative luminophore PyTS whose ECL performance has never been investigated. Gratifyingly, the ECL intensity and efficiency of PyTS-Zr-BTB-MOL were markedly enhanced compared to both PyTS monomers and PyTS aggregates. The main reason was that the distance between pyrene rings was greatly expanded after the PyTS grafting on the Zr6 clusters of Zr-BTB-MOL, which overcame the aggregation-caused quenching (ACQ) effect of PyTS and thus enhanced the ECL emission. Meanwhile, the porous nanosheet structure of PyTS-Zr-BTB-MOL could distinctly increase the exposure of PyTS luminophores and shorten the diffusion paths of coreactants and electrons/ions, which effectively promoted the electrochemical excitation of more PyTS luminophores and thus achieved a further ECL enhancement. In light of the remarkable ECL property of PyTS-Zr-BTB-MOL, it was employed as an ECL indicator to build a novel high-sensitivity ECL biosensor for microRNA-21 determination, possessing a satisfactory response range (100 aM to 100 pM) and an ultralow detection limit (10.4 aM). Overall, this work demonstrated that using MOLs to coordinatively graft the PAH derivative luminophores to eliminate the ACQ effect and increase the utilization rate of the luminophores is a promising and efficient strategy to develop high-performance Ru-complex-free ECL materials for assembling ultrasensitive ECL biosensing platforms.

Case report: Successful combination therapy with isavuconazole and amphotericin B in treatment of disseminated Candida tropicalis infection.

Disseminated candidiasis is a severe complication in patients with hematological malignancies who have undergone chemotherapy or hematopoietic stem cell transplantation. It has a high mortality rate. When disseminated candidiasis caused by Candida tropicalis involves either the brain or heart, the prognosis is extremely poor. Traditional methods such as cultures are limited in diagnosing disseminated candidiasis. We describe a case report of a 55-year-old man with acute myeloid leukemia who developed candidemia caused by Candida tropicalis after chemotherapy, which disseminated extensively to the heart, brain, skin, liver, spleen and kidneys. In this instance, the patient was rapidly diagnosed with candida infection by metagenomic next generation sequencing, and successfully treated with combination therapy of isavuconazole and amphotericin B. The patient continued with treatment of leukemia while simultaneously receiving antifungal therapy, and both leukemia and disseminated candidiasis were effectively controlled. This case report provides real-world experience for treatment of patients with leukemia complicated by disseminated candidiasis.

CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status.

Chaperonin-containing TCP1 (CCT) is a multi-subunit complex, known to participate the correct folding of many proteins. Currently, the mechanism underlying CCT subunits in cancer progression is incompletely understood. Based on data analysis, the expression of CCT subunit 6 A (CCT6A) is found higher than the other subunits of CCT and correlated with an unfavorable prognosis in colon cancer. Here, we find CCT6A silencing suppresses colon cancer proliferation and survival phenotype in vitro and in vivo. CCT6A plays a role in cellular process, including the cell cycle, p53, and apoptosis signaling pathways. Further investigations have shown direct binding between CCT6A and both Wtp53 and Mutp53, and BIRC5 is found to act downstream of CCT6A. The highlight is that CCT6A inhibition significantly reduces BIRC5 expression independent of Wtp53 levels in Wtp53 cells. Conversely, in Mutp53 cells, downregulation of BIRC5 by CCT6A inhibition mainly depends on Mutp53 levels. Additionally, combined CCT6A inhibition and Wtp53 overexpression in Mutp53 cell lines effectively suppresses cell proliferation. It is concluded CCT6A is a potential oncogene that influences BIRC5 through distinct pathways in Wtp53 and Mutp53 cells.

A Mitochondria-Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR-II Fluorescence/Photoacoustic Imaging-Guided Phototherapy.

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near-infrared-II (NIR-II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria-targeting abilities, and a large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type-I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs-mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.

Research progress of nano delivery systems for intraocular pressure lowering drugs.

Glaucoma is a chronic ocular disease characterized by optic atrophy and visual field defect. The main risk factor for glaucoma onset and progression is elevated intraocular pressure, which is caused by increased aqueous humor outflow resistance. Currently, the primary method for glaucoma therapy is the use of intraocular pressure lowering drugs. However, these drugs, when administered through eye drops, have low bioavailability, require frequent administration, and often result in adverse effects. To overcome these challenges, the application of nanotechnology for drug delivery has emerged as a promising approach. Nanoparticles can physically adsorb, encapsulate, or chemically graft drugs, thereby improving their efficacy, retention time, and reducing adverse reactions. Moreover, nanotechnology has opened up new avenues for ocular administration. This article provides a comprehensive review of nano systems for intraocular pressure lowering drugs, encompassing cholinergic agonists, ß-adrenergic antagonists, α-adrenergic agonists, prostaglandin analogs, carbonic anhydrase inhibitors, Rho kinase inhibitors, and complex preparations. The aim is to offer novel insights for the development of nanotechnology in the field of intraocular pressure lowering drugs.

Liquid-liquid phase separation in diseases.

Liquid-liquid phase separation (LLPS), an emerging biophysical phenomenon, can sequester molecules to implement physiological and pathological functions. LLPS implements the assembly of numerous membraneless chambers, including stress granules and P-bodies, containing RNA and protein. RNA-RNA and RNA-protein interactions play a critical role in LLPS. Scaffolding proteins, through multivalent interactions and external factors, support protein-RNA interaction networks to form condensates involved in a variety of diseases, particularly neurodegenerative diseases and cancer. Modulating LLPS phenomenon in multiple pathogenic proteins for the treatment of neurodegenerative diseases and cancer could present a promising direction, though recent advances in this area are limited. Here, we summarize in detail the complexity of LLPS in constructing signaling pathways and highlight the role of LLPS in neurodegenerative diseases and cancers. We also explore RNA modifications on LLPS to alter diseases progression because these modifications can influence LLPS of certain proteins or the formation of stress granules, and discuss the possibility of proper manipulation of LLPS process to restore cellular homeostasis or develop therapeutic drugs for the eradication of diseases. This review attempts to discuss potential therapeutic opportunities by elaborating on the connection between LLPS, RNA modification, and their roles in diseases.

Mapping global prevalence of menopausal symptoms among middle-aged women: a systematic review and meta-analysis.

BACKGROUND: Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. METHODS: Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. RESULTS: A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51-68.29) and lowest of formication (20.5%, 95% CI 13.44-28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems. CONCLUSION: The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.

Base-resolution m5C profiling across the mammalian transcriptome by bisulfite-free enzyme-assisted chemical labeling approach.

5-methylcytosine (m5C) is a prevalent RNA modification crucial for gene expression regulation. However, accurate and sensitive m5C sites identification remains challenging due to severe RNA degradation and reduced sequence complexity during bisulfite sequencing (BS-seq). Here, we report m5C-TAC-seq, a bisulfite-free approach combining TET-assisted m5C-to-f5C oxidation with selective chemical labeling, therefore enabling direct base-resolution m5C detection through pre-enrichment and C-to-T transitions at m5C sites. With m5C-TAC-seq, we comprehensively profiled the m5C methylomes in human and mouse cells, identifying a substantially larger number of confident m5C sites. Through perturbing potential m5C methyltransferases, we deciphered the responsible enzymes for most m5C sites, including the characterization of NSUN5's involvement in mRNA m5C deposition. Additionally, we characterized m5C dynamics during mESC differentiation. Notably, the mild reaction conditions and preservation of nucleotide composition in m5C-TAC-seq allow m5C detection in chromatin-associated RNAs. The accurate and robust m5C-TAC-seq will advance research into m5C methylation functional investigation.

Elongatibacter sediminis gen. nov., sp. nov., isolated from intertidal sediment, and genomic comparison with all genera in the family Wenzhouxiangellaceae.

A novel slightly halophilic, aerobic, and Gram-stain-negative strain, designated as CH-27T, was isolated during a bacterial resource investigation of intertidal sediment collected from Xiaoshi Island in Weihai, PR China. Cells of strain CH-27T were rod-shaped with widths of 0.3-0.6 µm and lengths of 2.0-11.0 µm. Strain CH-27T grew optimally at 37 °C, pH 7.0 and with 2.0 % (w/v) NaCl. Catalase activity was weakly positive and oxidase activity was positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CH-27T was most related to Marinihelvus fidelis KCTC 92639T (93.6 %), followed by Wenzhouxiangella marina MCCC 1K00261T (92.0 %). Based on genome comparisons between strain CH-27T and M. fidelis KCTC 92639T, the average amino acid identity was 63.6 % and the percentage of conserved proteins was 48.3 %. The major cellular fatty acid of strain CH-27T (≥10 %) was iso-C15 : 0 and the sole respiratory quinone was quinone-8. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, and aminophospholipid. The DNA G+C content was 62.7 mol%. Based on comprehensive analysis of its phylogenetic, physiological, biochemical, and chemotaxonomic characteristics, strain CH-27T represents a novel species in a novel genus, for which the name Elongatibacter sediminis gen. nov., sp.nov. is proposed. The type strain is CH-27T (=MCCC 1H00480T=KCTC 8011T).

Energy Absorption and Failure Modes of Different Composite Open-Section Crush Elements under Axial Crushing Loading.

In order to study the energy absorption characteristics of the open-section thin-walled composite structures with different cross-sections, axial compression tests were carried out at loading speeds of 0.01 m/s, 0.1 m/s, and 1 m/s. Finite element models were built to predict the crushing response and energy absorption behaviors of these open-section structures. The effects of the cross-section's shape, cross-section aspect ratio, trigger mechanism, and loading speed on the energy absorption characteristics of the composite structures were analyzed. The results show that the average crushing loads of the hat-shaped and Ω-shaped open-section structures are 14.1% and 14.6% higher than those of C-shaped open-section structures, and the specific energy absorption (SEA) values are 14.3% and 14.8% higher than that of C-shaped open-section structures, respectively. For the C-shaped open-section structures, a 45° chamfer trigger is more effective in reducing the initial peak load, while a 15° steeple trigger is more appropriate for the hat-shaped open-section structures. The average crushing loads and SEA of C-shaped, hat-shaped, and Ω-shaped open-section structures are reduced when the loading speed is increased from 0.01 m/s to 1 m/s. The increase in loading speed leads to the splashing of debris and thus reduces the loading area and material utilization of open-section structures, leading to a decrease in energy absorption efficiency.

Impact of National Centralized Drug Procurement policy on chemical pharmaceutical enterprises' R&D investment: a difference-in-differences analysis in China.

Objective: This study aimed to evaluate the impact of the National Centralized Drug Procurement (NCDP) policy on chemical pharmaceutical enterprises' R&D investment and provide references for improving NCDP policy design and encouraging innovation in the pharmaceutical industry. Methods: Using the panel data of 102 Shanghai and Shenzhen A-share listed enterprises from 2016 to 2022 under the chemical pharmaceutical classification of Shenwan in Wind database as the research sample, this study developed difference-in-differences (DID) models on bid-winning and bid-non-winning enterprises, respectively, to evaluate the impact of NCDP policy on their R&D investment. In addition, this study tested the heterogeneity of bid-winning enterprises based on the bid success rate, the decline of drug price, and enterprise size. Results: The NCDP policy could encourage chemical pharmaceutical companies to increase R&D investment, but the low bid success rate and excessive drug price reduction would reduce their R&D enthusiasm, especially for small- and medium-sized enterprises. Discussion: It is suggested that the NCDP policy should be further improved: first, revise the bidding rule of the NCDP policy and increase the bid success rate so that more enterprises can win bids, and second, to solve the problem of excessive drug price reduction, evaluate the rationality of bid-winning prices, and introduce a two-way selection mechanism between medical institutions and supply enterprises. Integrate pharmacoeconomic evaluation into the NCDP rules to form a benign competition among enterprises. Third, attention should be paid to supporting policies for small- and medium-sized enterprises. By increasing procurement volume, shortening payment time limits, and increasing the proportion of advance payments, enterprises' cash flow shortages can be alleviated, thus achieving fairness and inclusiveness in the implementation of the NCDP policy.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and obstructive sleep apnea: a cross-sectional study from NHANES.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a widespread sleep disturbance linked to metabolic and cardiovascular conditions. The Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratios (NHHR) has been proposed as being a potential biomarker to gauge cardiovascular risk. However, its relationship with OSA remains unclear. METHODS: This survey investigated the link NHHR to OSA in American citizens aged 20 and older using information collected via the National Health and Nutrition Examination Survey (NHANES) during the years 2017 to 2020. Logistic regression models with multivariable adjustments were employed to assess this relationship. Nonlinear associations were explored using smooth curve fitting, with a two-part linear regression model identifying a threshold effect. Subgroup analyses were conducted to evaluate population-specific differences. RESULTS: The survey encompassed 6763 participants, with an average age of 50.75 ± 17.32. The average NHHR stood at 2.74, accompanied by a standard deviation of 1.34, while the average frequency of OSA was 49.93%. Upon adjusting for covariates, each unit increase in NHHR may be associated with a 9% rise in OSA incidence. (95% confidence intervals 1.04-1.14; P < 0.0001). Notably, a U-shaped curve depicted the NHHR-OSA relationship, with an inflection point at 4.12. Subgroup analyses revealed consistent associations, with educational attainment and diabetes status modifying the NHHR-OSA relationship. CONCLUSION: The study highlights NHHR as a potential tool for OSA prediction, presenting avenues for advanced risk evaluation, tailored interventions, personalized treatment approaches, and preventive healthcare.

The efficacy and safety of trastuzumab and albumin-bound paclitaxel with or without pyrotinib as neoadjuvant therapy for HER2-positive breast cancer: a prospective observational cohort study.

Background: In the past few years, the combination of trastuzumab and paclitaxel has become an important option for human epidermal growth factor receptor-2 (HER2)-positive breast cancer. Small molecule tyrosine kinase inhibitors (TKIs) can bring clinical benefit to HER2-positive breast cancer patients. However, the efficacy and safety of these two regimens have not been compared. This study explored the efficacy and safety of pyrotinib combined with trastuzumab and albumin-bound paclitaxel (nab-paclitaxel). Methods: Patients with newly diagnosed HER2-positive early or locally advanced breast cancer treated at The Tumor Hospital of Mudanjiang City from November 2020 to June 2022 were included. The control group received pertuzumab in combination with nab-paclitaxel, whereas the pyrotinib group received pyrotinib in combination with pertuzumab and nab-paclitaxel as treatment, in a 3-week cycle for 4 cycles. The primary endpoints of this study were total pathological complete response (tpCR) rate, breast pathological complete response (bpCR) rate, and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and the occurrence of adverse events (AEs). Results: A total of 72 patients were enrolled in the study and completed the study treatment. Baseline characteristics were well balanced between these two arms. In the control group, the tPCR rate was 23.68%, and the bpCR rate was 47.36%. In the pyrotinib group, the tPCR rate was 47.06%, and the bpCR rate was 64.71%. The tPCR rate in the pyrotinib group was significantly higher than that in the control group (P=0.049). The ORR in the pyrotinib group (67.65%) was significantly higher than that in the control group (42.11%, P=0.04 ). The median PFS (mPFS) for the control group was 9.24 months, with a mean PFS of 10.01±0.44 months [95% confidence interval (CI): 9.14-10.88 months]. In the pyrotinib group, mPFS was 9.74 months, with a mean PFS of 11.25±0.29 months (95% CI: 10.67-11.82 months). The PFS in the pyrotinib group was significantly longer than that in the control group (P=0.045). Safety results showed that the overall incidence of AEs in the control group was 68.42%, with a 3-grade adverse reaction rate of 21.05%. In the pyrotinib group, the overall incidence of AEs was 79.41%, with a 3-grade adverse reaction rate of 29.41%. The difference between the two groups was not statistically significant (P>0.05). Conclusions: Pyrotinib group in neoadjuvant treatment for HER2 positive breast cancer has obvious short-term efficacy advantages over control group. This treatment regimen can prolong PFS for 1 year, and the safety during medication is controllable. This study still has some limitations, with the relatively small sample size and relatively short follow-up period, and a further large-scale, multicenter, randomized controlled trial is necessary to verify the clinical value of this dual-target treatment regimen.

Topological differences of striato-thalamo-cortical circuit in functional brain network between premature ejaculation patients with and without depression.

INTRODUCTION: Premature ejaculation (PE), a common male sexual dysfunction, often accompanies by abnormal psychological factors, such as depression. Recent neuroimaging studies have revealed structural and functional brain abnormalities in PE patients. However, there is limited neurological evidence supporting the comorbidity of PE and depression. This study aimed to explore the topological changes of the functional brain networks of PE patients with depression. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 60 PE patients (30 with depression and 30 without depression) and 29 healthy controls (HCs). Functional brain networks were constructed for all participants based on rs-fMRI data. The nodal parameters including nodal centrality and efficiency were calculated by the method of graph theory analysis and then compared between groups. In addition, the results were corrected for multiple comparisons by family-wise error (FWE) (p < .05). RESULTS: PE patients with depression had increased degree centrality and global efficiency in the right pallidum, as well as increased degree centrality in the right thalamus when compared with HCs. PE patients without depression showed increased degree centrality in the right pallidum and thalamus, as well as increased global efficiency in the right precuneus, pallidum, and thalamus when compared with HCs. PE patients with depression demonstrated decreased degree centrality in the right pallidum and thalamus, as well as decreased global efficiency in the right precuneus, pallidum, and thalamus when compared to those without depression. All the brain regions above survived the FWE correction. CONCLUSION: The results suggested that increased and decreased functional connectivity, as well as the capability of global integration of information in the brain, might be related to the occurrence of PE and the comorbidity depression in PE patients, respectively. These findings provided new insights into the understanding of the pathological mechanisms underlying PE and those with depression.

Molecular Mechanism Study of Dietary Fiber Lignin Intervention in Ulcerative Colitis through GPR37.

Lignin is dietary fiber from plant cell walls with multiple biological antioxidant and anti-inflammatory activities. However, whether lignin protects from ulcerative colitis (UC) and underlying mechanisms is unclear. Herein, UC mouse modeling was established with dextran sulfate sodium (DSS) and treatment with lignin for 1 week. Results showed that lignin inhibited the disease activity index (DAI), histological damage, and cell death in UC mice. We also found that lignin reversed the alterations of ferroptotic features in DSS-induced mice and ferroptotic cells, as evidenced by increased expression of GPX4 and 4-HNE and decreased transferrin expression, ameliorating the phenomenon of iron overload, GSH depletion, and ROS and MDA production. Furthermore, the increased expression of NRF2 was observed in IECs under lignin treatment. Also, the upstream regulatory molecule ERK of NRF2 was activated. Further research revealed that lignin can bind GPR37. Meanwhile, lignin was able to alleviate colitis by improving the composition of the intestinal flora in DSS mice and its effect was similar to that of 5-ASA. Taken together, these findings suggest that lignin protects against ferroptosis in UC by combining GPR37 and activating the ERK-NRF2-GPX4 signaling axis, which provides new ideas for clinical intervention in the treatment of UC.

Meta-Analysis of Internet Gaming Disorder Prevalence: Assessing the Impacts of DSM-5 and ICD-11 Diagnostic Criteria.

With the inclusion of Internet gaming disorder (IGD) in both the DSM-5 and ICD-11, understanding the prevalence and diagnostic discrepancies is crucial for developing appropriate interventions. This study presents a meta-analysis of the prevalence of IGD based on two diagnostic criteria. We systematically searched the PubMed and Web of Science databases. A total of 22 studies were included in the final analysis. The analysis incorporated studies employing the DSM-5 and ICD-11 criteria and focused on the impact of various factors, including study location, sample characteristics, sample size, and quality score, on the reported prevalence rates using a random-effects model. The pooled prevalence of IGD is 6.7% (95% CI: 5.7-7.7%). The subgroup analysis indicated significant differences in the prevalence rates of IGD (DSM-5 criteria) and GD (ICD-11 criteria) (Q b = 38.46, p < 0.01). There were also significant differences in IGD prevalence rates between different scales (Q b = 54.23, p < 0.001). Our findings indicate that different diagnostic criteria and different assessment scales have a significant impact on the prevalence of IGD. This underscores the importance of adopting standardized methodologies to guide public health interventions. However, given the limited research based on ICD-11 diagnostic criteria, further investigation is necessary to determine the variations in prevalence rates of IGD under different diagnostic standards.

Effect of Inconel 718 Filler on the Microstructure and Mechanical Properties of Inconel 690 Joint by Ultrasonic Frequency Pulse Assisted TIG Welding.

Ultrasonic frequency pulse assisted TIG welding (UFP-TIG) experiments were conducted to join Inconel 690 alloy (IN690) by adding Inconel 718 alloy (IN718) as the filler. The effect of the filler on the microstructure, mechanical properties, and ductility dip cracking (DDC) susceptibility of IN690 joints were investigated. The results show that a variety of precipitates, including MC-type carbide and Laves phases, are formed in the weld zone (WZ), which are uniformly dispersed in the interdendritic region and grain boundaries (GBs). The increase in the thickness of the IN718 filler facilitates the precipitation and growth of Laves phases and MC carbides. However, the formation of Laves phases in the WZ exhibits a lower bonding force with the matrix and deteriorates the tensile strength of IN690 joints. Due to the moderate content of Laves phases in the WZ, the IN690 joint with 1.0 mm filler reaches the maximum tensile strength (627 MPa), which is about 96.5% of that of the base metal (BM). The joint with 1.0 mm filler also achieves the highest elongation (35.4%). In addition, the strain-to-fracture tests indicate that the total length of cracks in the joint with the IN718 filler decreases by 66.49% under a 3.8% strain. As a result, the addition of the IN718 filler significantly improves the mechanical properties and DDC resistance of IN690 joints.

Brain Short-Chain Fatty Acids Induce ACSS2 to Ameliorate Depressive-Like Behavior via PPARγ-TPH2 Axis.

Short-chain fatty acids (SCFAs) have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiota-gut-brain axis. However, the precise mechanism by which brain SCFAs extert multiple beneficial effects is not completely understood. Our previous research has demonstrated that the acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is a novel target of the rapid and long-lasting antidepressant responses. Here, we show that micromolar SCFAs significantly augment both total cellular and nuclear ACSS2 to trigger tryptophan hydroxylase 2 (TPH2) promoter histone acetylation and its transcription in SH-SY5Y cells. In chronic-restraint-stress-induced depression mice, neuronal ACSS2 knockdown by stereotaxic injection of adeno-associated virus in the hippocampus abolished SCFA-mediated improvements in depressive-like behaviors of mice, supporting that ACSS2 is required for SCFA-mediated antidepressant responses. Mechanistically, the peroxisome-proliferator-activated receptor gamma (PPARγ) is identified as a novel partner of ACSS2 to activate TPH2 transcription. Importantly, PPARγ is also responsible for SCFA-mediated antidepressant-like effects via ACSS2-TPH2 axis. To further support brain SCFAs as a therapeutic target for antidepressant effects, d-mannose, which is a naturally present hexose, can significantly reverse the dysbiosis of gut microbiota in the chronic-restraint-stress-exposure mice and augment brain SCFAs to protect against the depressive-like behaviors via ACSS2-PPARγ-TPH2 axis. In summary, brain SCFAs can activate ACSS2-PPARγ-TPH2 axis to play the antidepressive-like effects, and d-mannose is suggested to be an inducer of brain SCFAs in resisting depression.