Analysis of alkaline phosphatase and γ-glutamyltransferase after radiofrequency ablation of primary liver cancer: A retrospective study.

BACKGROUND: Changes in alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) levels in patients with primary liver cancer (PLC) after radiofrequency ablation (RFA). Hepatocellular carcinoma is a malignant tumor with high incidence worldwide. As a common local treatment, RFA has attracted much attention for its efficacy and influence on liver function. AIM: To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA. METHODS: The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected. The chi-square test was used to compare the data between groups. The Kaplan-Meier method and Cox regression were used to analyze the associations between serum ALP and GGT levels and overall survival, progression-free survival (PFS) and clinical characteristics of patients before treatment. RESULTS: The 1-year survival rates of patients with normal (≤ 135 U/L) and abnormal (> 135 U/L) serum ALP before treatment were 91% and 79%, respectively; the 2-year survival rates were 90% and 68%, respectively; and the 5-year survival rates were 35% and 18%, respectively. The difference between the two groups was statistically significant (P = 0.01). Before treatment, the 1-year survival rates of patients with normal serum GGT levels (≤ 45 U/L) and abnormal serum GGT levels (> 45 U/L) were 95% and 87%, the 2-year survival rates were 85% and 71%, and the 5-year survival rates were 37% and 21%, respectively. The difference between the two groups was statistically significant (P < 0.001). Serum ALP [hazard ratio (HR) = 1.766, 95% confidence interval (95%CI): 1.068-2.921, P = 0.027] and GGT (HR = 2. 312, 95%CI: 1.367-3.912, P = 0.002) is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor. The 1-year PFS rates were 72% and 50%, the 2-year PFS rates were 52% and 21%, and the 5-year PFS rates were 14% and 3%, respectively. The difference between the two groups was statistically significant (P < 0001). The 1-year PFS rates were 81% and 56% in patients with normal and abnormal serum GGT levels before treatment, respectively; the 2-year PFS rates were 62% and 35%, respectively; and the 5-year PFS rates were 18% and 7%, respectively, with statistical significance between the two groups (P < 0.001). The serum ALP concentration (HR = 1. 653, 95%CI: 1.001-2.729, P = 0.049) and GGT (HR = 1.949, 95%CI: 1.296-2.930, P = 0.001) was closely associated with PFS after RFA in patients with PLC. The proportion of male patients with abnormal ALP levels is high, the Child-Pugh grade of liver function is poor, and the incidence of ascites is high. Among GGT-abnormal patients, the Child-Pugh grade of liver function was poor, the tumor stage was late, the proportion of patients with tumors ≥ 5 cm was high, and the incidence of hepatic encephalopathy was high. CONCLUSION: Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA, and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy.

[Construction of Saccharomyces cerevisiae cell factories for fermentation production of retinol].

Retinol is one of the main active forms of vitamin A, crucial for the organism's growth, development, and maintenance of eye and skin functions. It is widely used in cosmetics, pharmaceuticals, and feed additives. Although animals lack a complete pathway for synthesizing vitamin A internally, they can obtain vitamin A directly through diet or convert ß-carotene acquired from the diet. To boost the research on the biosynthesis of retinol, three different sources of alcohol dehydrogenase were firstly screened based on the ß-carotene synthesis platform CAR*1. It was determined that ybbO from Escherichia coli exhibited the highest catalytic activity,with a conversion rate of 95. 6%. To further enhance the reaction rate and yield of retinol, protein fusion technology was employed to merge two adjacent enzymes, blh and ybbO, within the retinol synthesis module. The evaluation was conducted using the high-yield engineered strain CAR*3 of ß-carotene. The optimal combination, blh-GGGS-ybbO, was obtained, with a 44. 9% increase in yield after fusion, reaching(111. 1± 3. 5) mg·L~(-1). Furthermore, through the introduction of human-derived retinol-binding protein(RBP4) and transthyretin(TTR), the process of hepatic cell secreting retinol was simulated in Saccharomyces cerevisiae, leading to an increased retinol yield of(158. 0±13. 1)mg·L~(-1). Finally, optimization strategies including overexpressing INO2 to enhance the reaction area for ß-carotene synthesis, enhancing hemoglobin VHb expression to improve oxygen supply, and strengthening PDR3m expression to facilitate retinol transport were implemented. A two-stage fermentation process resulted in the successful elevation of retinol production to(2 320. 0±26. 0)mg·L~(-1) in the fermentation tank of 5 L, which provided a significant foundation for the industrial development of retinol.

Neural responses to camouflage targets with different exposure signs based on EEG.

This study investigates the relationship between various target exposure signs and brain activation patterns by analyzing the EEG signals of 35 subjects observing four types of targets: well-camouflaged, with large color differences, with shadows, and of large size. Through ERP analysis and source localization, we have established that different exposure signs elicit distinct brain activation patterns. The ERP analysis revealed a strong correlation between the latency of the P300 component and the visibility of the exposure signs. Furthermore, our source localization findings indicate that exposure signs alter the current density distribution within the cortex, with shadows causing significantly higher activation in the frontal lobe compared to other conditions. The study also uncovered a pronounced right-brain laterality in subjects during target identification. By employing an LSTM neural network, we successfully differentiated EEG signals triggered by various exposure signs, achieving a classification accuracy of up to 96.4%. These results not only suggest that analyzing the P300 latency and cortical current distribution can differentiate the degree of visibility of target exposure signs, but also demonstrate the potential of using EEG characteristics to identify key exposure signs in camouflaged targets. This provides crucial insights for developing auxiliary camouflage strategies.

The role of cystathionine ß-synthase in cancer.

Cystathionine ß-synthase (CBS) occupies a key position as the initiating and rate-limiting enzyme in the sulfur transfer pathway and plays a vital role in health and disease. CBS is responsible for regulating the metabolism of cysteine, the precursor of glutathione (GSH), an important antioxidant in the body. Additionally, CBS is one of the three enzymes that produce hydrogen sulfide (H2S) in mammals through a variety of mechanisms. The dysregulation of CBS expression in cancer cells affects H2S production through direct or indirect pathways, thereby influencing cancer growth and metastasis by inducing angiogenesis, facilitating proliferation, migration, and invasion, modulating cellular energy metabolism, promoting cell cycle progression, and inhibiting apoptosis. It is noteworthy that CBS expression exhibits complex changes in different cancer models. In this paper, we focus on the CBS synthesis and metabolism, tissue distribution, potential mechanisms influencing tumor growth, and relevant signaling pathways. We also discuss the impact of pharmacological CBS inhibitors and silencing CBS in preclinical cancer models, supporting their potential as targeted cancer therapies.

Cilia-Inspired Magnetic Flexible Shear Force Sensors for Tactile and Fluid Monitoring.

Recently, there has been a burgeoning interest in flexible shear force sensors capable of precisely detecting both magnitude and direction. Despite considerable efforts, the challenge of achieving accurate direction recognition persists, primarily due to the inherent structural characteristics and sensing mechanisms. Here, we present a shear force sensor constructed by a magnetically induced assembled Ni/PDMS composite membrane, which is magnetized and integrated with a three-axis Hall sensor, facilitating its ability to simultaneously monitor both shear force magnitude (0.7-87 mN) and direction (0-360°). The cilia-inspired shear force magnetic sensor (CISFMS) exhibits admirable attributes, including exceptional flexibility, high sensitivity (0.76 mN-1), an exceedingly low detection limit (1° and 0.7 mN), and remarkable durability (over 10,000 bending cycles). Further, our results demonstrate the capacity of the CISFMS in detecting tactile properties, fluid velocity, and direction, offering substantial potential for future developments in wearable electronics.

Machine learning to guide the use of plasma technology for antibiotic degradation.

Antibiotics are misused and discharged into environmental water, posing a constant potential threat to the ecosystem. Utilising plasma's physical and chemical effects to remove antibiotics has emerged as a promising wastewater treatment technology. However, the complexity and high cost of reactor configurations represent significant limitations to the practical application of this technology. Furthermore, evaluating the degradation efficiency of antibiotics necessitates using costly and sophisticated testing instruments, coupled with time-consuming and labour-intensive experiments. The present study developed a generalised model using machine learning algorithms to predict the removal efficiency of antibiotics by a plasma system. Of the eight machine learning algorithms constructed, the ensemble model XGBoost exhibited the highest prediction accuracy, as indicated by a Pearson correlation coefficient of 0.943. This correlation indicates a strong relationship between the predicted removal rates and the experimental values. Moreover, the accuracy of the prediction was enhanced through the utilisation of a multi-model stacking approach. A further quantitative assessment of the key factors affecting the efficiency of the plasma process, and their synergistic effects, is provided by the interpretable analysis of the model's behaviour. It is anticipated that the results will facilitate the design of efficient plasma systems, reduce the need for extensive experimental screening, and improve practical applications in the removal of antibiotic contamination. This provides an informative view of the applications of plasma technology, opening the way for new environmental research questions.

Meta-analysis of probiotics efficacy in the treatment of minimum hepatic encephalopathy.

OBJECTIVE: This study aims to systematically evaluate the efficacy of probiotics in treating minimum hepatic encephalopathy (MHE). METHODS: A systematic search was conducted across three major databases: PubMed, China National Knowledge Infrastructure and Wanfang. The search period spanned from the inception of each database to 9 March 2023. The objective was to identify all randomised controlled trials (RCTs) examining the efficacy of probiotic preparations in treating MHE. The search terms included 'probiotics' along with other clinically relevant terms to comprehensively capture all pertinent studies. RESULTS: A total of 18 RCTs were included. The meta-analysis showed that probiotic treatment outperformed control groups in reducing blood ammonia levels (standard mean difference [MD] = -2.68, 95% confidence interval [CI]: -3.90 to -1.46, p < .0001), improving the remission rate of MHE (risk ratio [RR] = 2.79, 95% CI: 1.23-6.35, p = .01) and lowering alanine aminotransferase levels (MD = -11.10, 95% CI: -16.17 to -6.03, p < .0001). It also significantly reduced the Model for End-Stage Liver Disease scores (MD = -2.55, 95% CI: -3.56 to -1.54, p < .00001) and the incidence of MHE (RR = .18, 95% CI: .09-.34, p < .00001). CONCLUSION: Our study demonstrates that probiotics effectively improve blood ammonia levels, liver function and cognitive function in patients with MHE. They significantly enhance the remission rate of MHE and effectively reduce its incidence, providing solid new evidence for treating MHE with probiotics.

AXL inhibition prevents RPA2/CHK1-mediated homologous recombination to increase PARP inhibitor sensitivity in hepatocellular carcinoma.

Homologous recombination defects (HRD) render cells fail to repair DNA double-strand break (DSB), which causes synthetic lethality in these cells with punch by poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Here, we reveal a receptor tyrosine kinase, AXL, whose inhibition leads to HRD in hepatocellular carcinoma (HCC) cells. AXL is upregulated in HCC tumors, which is positively correlated with low survival rates. AXL knockdown or AXL inhibition by bemcentinib reduces HR efficiency in HCC cells, and AXL plays its role in HR repair through its kinase activity. Furthermore, we find that AXL interacts with RPA2, enhancing the recruitment of RPA2 to DNA damage sites. Mechanistically, AXL promotes the tyrosinization of RPA2 at tyrosine 9, promoting the phosphorylation of CHK1, thereby strengthens the HR repair ability in HCC cells to resist DNA damage. In conclusion, our results reveal that AXL is a promising therapeutic biomarker for HCC patients, and present that targeting AXL-RPA2-CHK1 pathway together with PARP inhibitor will be effective therapeutic strategy in HCC.

TaMYB-CC5 gene specifically expressed in root improve tolerance of phosphorus deficiency and drought stress in wheat.

Phosphate deficiency and drought are significant environmental constraints that impact both the productivity and quality of wheat. The interaction between phosphorus and water facilitates their mutual absorption processes in plants. Under conditions of both phosphorus deficiency and drought stress, we observed a significant upregulation in the expression of wheat MYB-CC transcription factors through the transcriptome analysis. 52 TaMYB-CC genes in wheat were identified and analyzed their evolutionary relationships, structures, and expression patterns. The TaMYB-CC5 gene exhibited specific expression in roots and demonstrated significant upregulation under phosphorus deficiency and drought stress compared to other TaMYB-CC genes. The overexpression of TaMYB-CC5A in Arabidopsis resulted in a significant increase of root length under stress conditions, thereby enhancing tolerance to phosphate starvation and drought stress. The wheat lines with silenced TaMYB-CC5 genes exhibited reduced root length under stress conditions and increased sensitivity to phosphate deficiency and drought stress. In addition, silencing the TaMYB-CC5 genes resulted in altered phosphorus content in leaves but did not lead to a reduction in phosphorus content in roots. Enrichment analysis the co-expression genes of TaMYB-CC5 transcription factors, we found the zinc-induced facilitator-like (ZIFL) genes were prominent associated with TaMYB-CC5 gene. The TaZIFL1, TaZIFL2, and TaZIFL5 genes were verified specifically expressed in roots and regulated by TaMYB-CC5 transcript factor. Our study reveals the pivotal role of the TaMYB-CC5 gene in regulating TaZIFL genes, which is crucial for maintaining normal root growth under phosphorus deficiency and drought stress, thereby enhanced resistance to these abiotic stresses in wheat.

ALDH2 deficiency augments atherosclerosis through the USP14-cGAS-dependent polarization of proinflammatory macrophages.

The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism commonly exists in the East Asian populations and is associated with high risks of cardiovascular disease (CVD). However, the cellular and molecular mechanisms that underlie the ALDH2 rs671 mutant-linked high CVD remain elusive. Here, we show that macrophages derived from human ALDH2 rs671 carriers and ALDH2 knockout mice exhibited an enhanced pro-inflammatory macrophage phenotype and an impaired anti-inflammatory macrophage phenotype. Transplanting bone marrow from ALDH2-/-ApoE-/- to ApoE-/- mice significantly increased atherosclerotic plaque growth and pro-inflammatory macrophage polarization in vivo. Mechanistically, ALDH2 inhibited activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in macrophages. Pharmacological inhibition of cGAS by RU.521 completely neutralized ALDH2-deficiency-induced macrophage polarization. In-depth mechanistic investigation showed that ALDH2 accelerated cGAS K48-linked polyubiquitination degradation at lysine 282 in macrophages by reducing the interaction between ubiquitin-specific protease 14 (USP14) and cGAS, mainly through its enzymatic role in mitigating 4-hydroxy-2-nonenal (4-HNE) accumulation. Consistently, USP14 knockdown in bone marrow cells alleviated proinflammatory responses in macrophages and protected against atherosclerosis. Our findings provide new mechanistic insights of ALDH2 deficiency-associated proinflammation and atherosclerosis and new therapeutic and preventive paradigms for treatment of atherosclerosis-associated CVD.

The lipidomics reporting checklist a framework for transparency of lipidomic experiments and repurposing resource data.

The rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, comparability, and repeatability. Here, we describe the structure and rationale of the established Lipidomics Minimal Reporting Checklist to increase transparency in lipidomics research.

Vitamin D and selenium for type 2 diabetes mellitus with Hashimoto's thyroiditis: Dosage and duration insights.

This letter discusses the publication by Feng et al. Iodine, selenium, and vitamin D are closely associated with thyroid hormone production in humans; however, the efficacy of selenium and vitamin D supplementation for type 2 diabetes mellitus (T2DM) patients with Hashimoto's thyroiditis (HT) remains controversial. In the retrospective study we discuss herein, the authors highlighted significant improvements in thyroid function, thyroid antibodies, blood glucose, and blood lipid in T2DM patients with HT following addition of vitamin D and selenium to their antidiabetic regimens, underscoring the value of these supplements. Our team is currently engaged in research exploring the relationship between micronutrients and HT, and we have obtained invaluable insights from the aforementioned study. Based on this research and current literature, we recommend a regimen of 4000 IU/day of vitamin D and 100-200 µg/day of selenium for over three months to six months for patients with HT, particularly for those with concurrent T2DM.

[Spatiotemporal Distribution Characteristics of Ground-level-ozone and Its Relationship with Meteorological Conditions in a Representative City in the Bohai Rim from 2017 to 2022].

In recent years, ground-level-ozone（O3） pollution in urban areas in the Bohai Rim has attracted wide attention. Based on the analysis of the spatiotemporal distribution characteristics of O3 concentration in Dongying, a representative city in the Bohai Rim from 2017 to 2022, the effects of meteorological factors and sea-land breeze circulation on O3 concentration were evaluated. The results showed that： ① From 2017 to 2022, the annual assessment value of O3 concentration in Dongying showed a fluctuating upward trend, and the pollution days with O3 as the primary pollutant increased. O3 pollution mainly occurred in spring, summer, and autumn, with the most severe O3 pollution episodes typically occurring in May and June, and the duration of O3 pollution season tended to be longer. The monthly variation in the daily maximum 8-h average ozone （MDA8 O3） presented a bimodal distribution, with significant increases in the 5th and 25th percentiles, and the spatial distribution was "high in the north and south, low in the middle." In addition, the nocturnal O3 concentration in recent years in Dongying also showed a significant increase trend. ② Meteorological factors greatly influenced O3 concentration in Dongying. When the temperature was greater than 30℃, the relative humidity was less than 50%, and the wind direction was south-southwest or east-northeast, a high O3 value was more likely to occur. Meteorological factors contributed 30% of the MDA8 O3 variation in Dongying during the study period. In the case of moderate and severe O3 pollution, the contribution of meteorological factors to the change in MDA8 O3 could be as high as 40%. ③ To some extent, sea-land breeze contributed to the occurrence of MDA8 O3 exceeding the secondary standard limit value of the National Ambient Air Quality Standard. In the afternoon, the hourly concentration of O3 during the sea-land breeze days was approximately 20 µg·m-3 higher than that during the non-sea-land breeze days. On the days of moderate and severe O3 pollution, the O3 concentration during the sea-land breeze days from 10：00 to 16：00 was higher than that during non-sea-land breeze days, and the O3 concentration was also at a high level from 20：00 to 23：00 on sea-land breeze days. In the O3 pollution season, the sea-land breeze could significantly affect the O3 level in coastal cities, which could bring significant challenges for O3 pollution prevention and control in this region. In the future, cities in the Bohai Rim need to further strengthen regional joint prevention and control of O3 pollution and increase emission reduction efforts of nitrogen oxides and volatile organic compounds. This strategy could effectively lower pollutant concentrations within the land breeze air mass, consequently reducing the impact of the sea breeze air mass on air quality in cities in the Bohai Rim.

Promoting CO2 Electroreduction to Hydrocarbon Products via Sulfur-Enhanced Proton Feeding in Atomically Precise Thiolate-Protected Cu Clusters.

Thiolate-protected Cu clusters with well-defined structures and stable low-coordinated Cu+ species exhibit remarkable potential for the CO2RR and are ideal model catalysts for establishing structure-electrocatalytic property relationships at the atomic level. However, extant Cu clusters employed in the CO2RR predominantly yield 2e- products. Herein, two model Cu4(MMI)4 and Cu8(MMI)4(tBuS)4 clusters (MMI = 2-mercapto-1-methylimidazole) are prepared to investigate the synergistic effect of Cu+ and adjacent S sites on the CO2RR. Cu4(MMI)4 can reduce CO2 to deep-reduced products with a 91.0% Faradaic efficiency (including 53.7% for CH4) while maintaining remarkable stability. Conversely, Cu8(MMI)4(tBuS)4 shows a remarkable preference for C2+ products, achieving a maximum FE of 58.5% with a C2+ current density of 152.1 mA∙cm-2. In situ XAS and ex situ XPS spectra reveal the preservation of Cu+ species in Cu clusters during CO2RR, extensively enhancing the adsorption capacity of *CO intermediates. Moreover, kinetic analysis and theoretical calculations confirm that S sites facilitate H2O dissociation into *H species, which directly participate in the protonation process on adjacent Cu sites for the protonation of *CO to *CHO. This study highlights the important role of Cu-S dual sites in Cu clusters and provides mechanistic insights into the CO2RR pathway at the atomic level.

Discovery of Novel Imidazo[1,2-a]pyridine-Based HDAC6 Inhibitors as an Anticarcinogen with a Cardioprotective Effect.

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.

Role of gasotransmitters in necroptosis.

Gasotransmitters are endogenous gaseous signaling molecules that can freely pass through cell membranes and transmit signals between cells, playing multiple roles in cell signal transduction. Due to extensive and ongoing research in this field, we have successfully identified many gasotransmitters so far, among which nitric oxide, carbon monoxide, and hydrogen sulfide are best studied. Gasotransmitters are implicated in various diseases related to necroptosis, such as cardiovascular diseases, inflammation, ischemia-reperfusion, infectious diseases, and neurological diseases. However, the mechanisms of their effects on necroptosis are not fully understood. This review focuses on endogenous gasotransmitter synthesis and metabolism and discusses their roles in necroptosis, aiming to offer new insights for the therapeutic approaches to necroptosis-associated diseases.

An all-in-one microfluidic SlipChip for power-free and rapid biosensing of pathogenic bacteria.

Point-of-care testing of pathogens is becoming more and more important for the prevention and control of food poisoning. Herein, a power-free colorimetric biosensor was presented for rapid detection of Salmonella using a microfluidic SlipChip for fluidic control and Au@PtPd nanocatalysts for signal amplification. All the procedures, including solution mixing, immune reaction, magnetic separation, residual washing, mimicking catalysis and colorimetric detection, were integrated on this SlipChip. First, the mixture of the bacterial sample, immune magnetic nanobeads (IMBs) and immune Au@PtPd nanocatalysts (INCs), washing buffer and H2O2-TMB chromogenic substrate were preloaded into the sample, washing and catalysis chambers, respectively. After the top layer of this SlipChip was slid to connect the sample chamber with the separation chamber, the mixture was moved back and forth through the asymmetrical split-and-recombine micromixer by using a disposable syringe to form the IMB-Salmonella-INC sandwich conjugates. Then, the conjugates were captured in the separation chamber using a magnetic field, and the top layer was slid to connect the washing chamber with the separation chamber for washing away excessive INCs. Finally, the top layer was slid to connect the catalysis chamber with the separation chamber, and the colorless substrate was catalyzed by the INCs with peroxidase-mimic activity to generate color change, followed by using a smartphone app to collect and analyze the image to determine the bacterial concentration. This all-in-one microfluidic biosensor enabled simple detection of Salmonella as low as 101.2 CFU mL-1 within 30 min and was featured with low cost, straightforward operation, and compact design.

Individual suicide risk factors with resting-state brain functional connectivity patterns in bipolar disorder patients based on latent Dirichlet allocation model.

BACKGROUND: The widespread problem of suicide and its severe burden in bipolar disorder (BD) necessitate the development of objective risk markers, aiming to enhance individual suicide risk prediction in BD. METHODS: This study recruited 123 BD patients (61 patients with prior suicide attempted history (PSAs), 62 without (NSAs)) and 68 healthy controls (HEs). The Latent Dirichlet Allocation (LDA) model was used to decompose the resting state functional connectivity (RSFC) into multiple hyper/hypo-RSFC patterns. Thereafter, according to the quantitative results of individual heterogeneity over latent factor dimensions, the correlations were analyzed to test prediction ability. RESULTS: Model constructed without introducing suicide-related labels yielded three latent factors with dissociable hyper/hypo-RSFC patterns. In the subsequent analysis, significant differences in the factor distributions of PSAs and NSAs showed biases on the default-mode network (DMN) hyper-RSFC factor (factor 3) and the salience network (SN) and central executive network (CEN) hyper-RSFC factor (factor 1), indicating predictive value. Correlation analysis of the individuals' expressions with their Nurses' Global Assessment of Suicide Risk (NGASR) revealed factor 3 positively correlated (r = 0.4180, p < 0.0001) and factor 1 negatively correlated (r = - 0.2492, p = 0.0055) with suicide risk. Therefore, it could be speculated that patterns more associated with suicide reflected hyper-connectivity in DMN and hypo-connectivity in SN, CEN. CONCLUSIONS: This study provided individual suicide-associated risk factors that could reflect the abnormal RSFC patterns, and explored the suicide related brain mechanisms, which is expected to provide supports for clinical decision-making and timely screening and intervention for individuals at high risks of suicide.

GDNF's Role in Mitigating Intestinal Reactive Gliosis and Inflammation to Improve Constipation and Depressive Behavior in Rats with Parkinson's disease.

Constipation is a common symptom in patients with Parkinson's disease (PD) and is often associated with depression. Enteric glial cells (EGCs) are crucial for regulating intestinal inflammation and colon motility, and their activation can lead to the death of intestinal neurons. Glial cell line-derived neurotrophic factor (GDNF) has been recognized for its neuroprotective properties in various neurological disorders, including PD. This study explores the potential of GDNF in alleviating intestinal reactive gliosis and inflammation, thereby improving constipation and depressive behavior in a rat model of PD. A PD model was established via unilateral stereotaxic injection of 6-hydroxydopamine (6-OHDA). Five weeks post-injury, AAV5-GDNF (2 ~ 5 × 10^11) was intraperitoneally injected into experimental and control rats. Fecal moisture percentage (FMP) and colonic propulsion rate (CPPR) were used to evaluate colon motility. Colon-related inflammation and colonic epithelial morphology were assessed, and depressive behavior was analyzed one week before sampling. PD rats exhibited reduced colonic motility and GDNF expression, along with increased EGC reactivity and elevated levels of pro-inflammatory cytokines IL-1, IL-6, and TNF-α. Additionally, there was an up-regulation of CX43 and a decrease in PGP 9.5 expression. The intraperitoneal injection of AAV-GDNF significantly protected colonic neurons by inhibiting EGC activation and down-regulating CX43. This treatment also led to a notable reduction in depressive-like symptoms in PD rats with constipation. GDNF effectively reduces markers of reactive gliosis and inflammation, and promotes the survival of colonic neurons, and improves colonic motility in PD rats by regulating CX43 activity. Furthermore, GDNF treatment alleviates depressive behavior, suggesting that GDNF or its agonists could be promising therapeutic agents for managing gastrointestinal and neuropsychiatric symptoms associated with PD.