Activation of NLRP3 inflammasome in a rat model of cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is increasingly being recognized as a leading contributor to cognitive impairment in the elderly. However, there is a lack of effective preventative or therapeutic options for CSVD. In this exploratory study, we investigated the interplay between neuroinflammation and CSVD pathogenesis as well as the cognitive performance, focusing on NLRP3 signaling as a new therapeutic target. Spontaneously hypertensive stroke-prone (SHRSP) rats served as a CSVD model. We found that SHRSP rats showed decline in learning and memory abilities using morris water maze test. Activated NLRP3 signaling and an increased expression of the downstream pro-inflammatory factors, including IL (interleukin)-6 and tumor necrosis factor α were determined. We also observed a remarkable increase in the production of pyroptosis executive protein gasdermin D, and elevated astrocytic and microglial activation. In addition, we identify several neuropathological hallmarks of CSVD, including blood-brain barrier breakdown, white matter damage, and endothelial dysfunction. These results were in correlation with the activation of NLRP3 inflammasome. Thus, our findings reveal that the NLRP3-mediated inflammatory pathway could play a central role in the pathogenesis of CSVD, presenting a novel target for potential CSVD treatment.

Precise Layer-by-Layer Assembly of Dual Quantum Dots Artificial Photosystems Enabling Solar Water Oxidation.

Quantum dots (QDs) colloidal nanocrystals are attracting enduring interest by scientific communities for solar energy conversion due to generic physicochemical merits including substantial light absorption coefficient, quantum confinement effect, enriched catalytically active sites, and tunable electronic structure. However, photo-induced charge carriers of QDs suffer from ultra-short charge lifespan and poor stability, rendering controllable vectorial charge modulation and customizing robust and stable QDs artificial photosystems challenging. Herein, tailor-made oppositely charged transition metal chalcogenides quantum dots (TMCs QDs) and MXene quantum dots (MQDs) are judiciously harnessed as the building blocks for electrostatic layer-by-layer assembly buildup on the metal oxides (MOs) framework. In these exquisitely designed LbL assembles MOs/(TMCs QDs/MQDs)n heterostructured photoanodes, TMCs QDs layer acts as light-harvesting antennas, and MQDs layer serves as electron-capturing mediator to relay cascade electrons from TMCs QDs to the MOs substrate, thereby yielding the spatially ordered tandem charge transport chain and contributing to the significantly boosted charge separation over TMCs QDs and solar water oxidation efficiency of MOs/(TMCs QDs/MQDs)n photoanodes. The relationship between interface configuration and charge transfer characteristics is unambiguously unlocked, by which photoelectrochemical mechanism is elucidated. This work would provide inspiring ideas for precisely mediating interfacial charge transfer pathways over QDs toward solar energy conversion.

[Spatial-temporal Variation and Spatial Differentiation Geographic Detection of PM2.5 Concentration in the Shandong Province Based on Spatial Scale Effect].

PM2.5 remote sensing data was applied in this study, and Theil-Sen Median trend analysis and the Mann-Kendall significance test were utilized to analyze the temporal and spatial variation in PM2.5 in the Shandong Province from 2000 to 2021. The influencing power of the influencing factors on the spatial differentiation of PM2.5 concentration in the Shandong Province was detected at the provincial-city-county levels based on Geo-detector data. The results showed that:① on the temporal scale, the mean ρ(PM2.5)in the Shandong Province ranged from 38.15 to 88.63 µg·m-3 from 2000 to 2021, which was slightly higher than the secondary limit of inhalable particulate matter (35 µg·m-3) in the Ambient Air Quality Standards. On the interannual scale, 2013 was the peak year for the variation in ρ(PM2.5) with a value of 83.36 µg·m-3, according to which the trend of PM2.5 concentrations in the Shandong Province was divided into two phases:a continuous increase and a rapid decrease. On the seasonal scale, PM2.5 concentration presented the distribution characteristics of "low in summer and high in winter and moderate in spring and autumn" and the U-shaped change rule of first decreasing and then increasing. ② On the spatial scale, the PM2.5 concentration in the Shandong Province presented a spatial distribution pattern of "high in the west and low in the east." The areas with high PM2.5 concentration were distributed in the western area of the Shandong Province, whereas the areas with low PM2.5 concentration were distributed in the eastern peninsula region. The spatial variation in the changing trend of PM2.5 concentration showed significant spatial heterogeneity, and the extremely significant decrease was mainly distributed in the eastern peninsula region. ③ The results of factor detection showed that climate factor was an important factor affecting the spatial differentiation of PM2.5 concentration in the Shandong Province. Mean temperature had the highest influence on the spatial differentiation of PM2.5 concentration in the Shandong Province, with a q value of 0.512. Provincial-city-county multi-scale detection results showed that the influencing factors affecting the spatial differentiation of PM2.5 concentration and their influencing power differed at different spatial scales. At the provincial scale, mean temperature, sunshine duration, and slope were the main factors affecting the spatial differentiation of PM2.5 concentration. At the city level, precipitation, elevation, and relative humidity were the main factors affecting the spatial differentiation of PM2.5. At the county level, precipitation, mean temperature, and sunshine duration were the main factors affecting the spatial variation in PM2.5 concentration.

Association of cytokines levels, psychopathology and cognition among CR-TRS patients with metabolic syndrome.

Clozapine-resistant treatment-refractory schizophrenia (CR-TRS) patients face significant clinical challenges. While links between metabolic syndrome (MetS) and inflammatory cytokines in schizophrenia have been established, the relationship between MetS and cytokine levels in CR-TRS patients remains unexplored. This study aimed to investigate the relationship between cytokines levels, clinical symptoms and cognitive impairments in CR-TRS patients, both with and without MetS. The study included 69 CR-TRS patients (31with MetS and 38 without MetS) and 84 healthy controls. The levels of IL-2, IL-6, TNF-α and routine biochemical parameters were measured. Psychopathological symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. We found that CR-TRS patients with MetS displayed lower cognitive function scores compared to those without MetS, even when accounting for potential confounders. TNF-α levels were significantly higher in CRTRS patients with MetS compared to those without MetS, demonstrating substantial pathophysiological potential for CR-TRS patients with MetS via receiver operating characteristic curve (ROC). In CR-TRS patients without MetS, IL-2 independently contributed to the total score and general psychopathology subscore of PANSS. Additionally, IL-6 exhibited an independent contribution to the positive subscore of PANSS. In terms of cognition function, IL-6 independently contributed to the delayed memory of RBANS in CR-TRS patients without MetS. TNF-α could potentially serve as a predictive marker for distinguishing between CR-TRS patients with/without MetS, while IL-2 and IL-6 could independently contribute to psychopathological symptoms or cognitive function in CRTRS patients without MetS. Our study provided insights into the potential interplay between cytokines, clinical symptoms and cognitive impairments in CR-TRS patients with/without MetS.

Extending the reach of multi-core fiber via Voronoi constellations with concatenated multilevel coding.

This Letter proposes a novel, to the best of our knowledge, coded modulation scheme for randomly coupled multi-core fiber (RC-MCF) via multidimensional (MD) constellation with concatenated two-level multilevel coding (MLC). In the proposed system, the 16-dimensional (16D) Voronoi constellation (VC), naturally fitting with the 16 degrees of freedom of a four-core fiber (two quadratures, two polarizations, and four cores), is generated by a latticed-based shaping method to provide higher shaping gains. Moreover, combining it with the concatenated two-level MLC can further achieve better performance-complexity trade-off. It is demonstrated by simulation results of long-haul multi-channel RC-MCF transmission that the proposed coded modulation scheme for four-core fiber transmission offers 77% reduction in the number of decoding operations and up to 21% (585 km) reach increase over the conventional bit-interleaved coded modulation scheme for quadrature amplitude modulation.

Ni-Catalyzed Csp2 and Csp3 Coupling for Divergent Bisboronic Ester Synthesis.

Bisboronic esters are critical compounds in various research fields, including drug discovery, chemical biology, and material sciences. Currently, the bisboronic esters with reactive functional groups are difficult to synthesize; this is partially due to the lack of a robust method to produce these products with diverse structures and various functional groups at specific locations. To overcome this issue, this study introduced a Ni-catalysis approach to produce bisboronic esters efficiently via cross-coupling and homocoupling using readily available halogenated boronic esters as the starting material under mild reaction conditions. This newly developed strategy enables Csp2-Csp2, Csp3-Csp3, and Csp2-Csp3 couplings, demonstrating a broad substrate scope and excellent compatibility with various functional groups.

Factors associated with pain intensity and analgesic use during inpatient rehabilitation for hip fracture.

PURPOSE: Effective pain management is vital for hip fracture recovery, yet the factors influencing pain reporting and pain medication use during inpatient rehabilitation for hip fractures are not well understood. This observational study aimed to (a) determine how cognitive abilities, expressive and receptive language abilities, and age are related to average daily pain intensity and analgesic use and (b) how average daily pain intensity and analgesic use are related to length of stay and functional outcomes in rehabilitation. DESIGN: Data were retrospectively obtained from 163 patients recovering from unilateral trochanteric fractures of the femur. RESULTS: During the first week of rehabilitation, patients received a daily average of 1,147.8 ± 978 mg of acetaminophen and a morphine milligram equivalent of 15.3 ± 18.2. Multivariable regression revealed independent relationships between more intact general cognitive abilities (B = -0.40, 95% CI [-0.70, -0.11]), and older age (B = -0.41, 95% CI [-0.70, -0.11]) with lower average daily pain intensity. Higher average daily pain intensity (B = 0.97, 95% CI [0.75, 1.20]) was independently related to greater opioid use. The length of stay was shorter among patients administered higher daily doses of acetaminophen (B = 0.03, 95% CI [-0.05, -0.01]). Average daily pain intensity and analgesic use were not related to functional outcomes in multivariable models. CONCLUSIONS: These findings inform the considerations for assessing and treating pain during inpatient rehabilitation. Supplemental strategies for assessing pain in older patients and alternative pain mitigation strategies for patients with impaired cognitive abilities should be considered. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Histopathological staging and differential diagnosis of marginal zone lymphoma of gastric mucosa-associated lymphoid tissue.

The purpose of this study was to explore the histopathological staging and differential diagnosis of marginal zone lymphoma in gastric mucosa-associated lymphoid tissue (MALT lymphoma). We performed detailed histomorphology and immunohistochemistry investigations as well as genetic testing on endoscopic biopsy and endoscopic mucosal resection specimens from 18 patients with gastric MALT lymphoma. We found that gastric MALT lymphoma typically begins as a small, isolated area outside the lymphoid follicular mantle zone or proliferates in a multifocal, patchy manner, gradually spreads to the interfollicular zone, forming diffuse proliferation, invades the gastric mucosal glands, and infiltrates or proliferates into the center of peripheral reactive lymphoid follicles. Abnormally proliferating lymphocytes invade the surrounding lymphoid follicles, resulting in damage, atrophy, and disappearance of their normal follicles as well as of the gastric mucosa glands, forming diffuse proliferation. Redifferentiation and proliferation lead to the transformation of lymphocytes; that is, MALT transitions into highly invasive lymphoma. Based on our findings in this study, we propose the following five stages in the process of development and progression of gastric MALT lymphoma: the stage of cell proliferation outside the lymphoid follicular mantle zone; the stage of heterogeneous proliferative lymphoepithelial lesion; the stage of reactive lymphoid follicular implantation; the stage of lymphoid follicular clonal proliferation; and the stage of MALT transforming into highly invasive lymphoma. We examined the differential diagnosis of histopathological features at each stage. The clinicopathological staging of gastric MALT lymphoma can help clinicians provide accurate treatment and track malignant cell transformation, thus playing a significant role in controlling its development and progression.

Phenolic acids from Chicory roots ameliorate dextran sulfate sodium-induced colitis in mice by targeting TRP signaling pathways and the gut microbiota.

BACKGROUND: Inflammatory bowel disease (IBD) is a type of immune-mediated condition associated with intestinal homeostasis. Our preliminary studies disclosed that Cichorium intybus L., a traditional medicinal plant, also known as Chicory in Western countries, contained substantial phenolic acids displaying significant anti-inflammatory activities. We recognized the potential of harnessing Chicory for the treatment of IBD, prompting a need for in-depth investigation into the underlying mechanisms. METHODS: On the third day, mice were given 100, 200 mg/kg of total phenolic acids (PA) from Chicory and 200 mg/kg of sulfasalazine (SASP) via gavage, while dextran sodium sulfate (DSS) concentration was 2.5 % for one week. The study measured and evaluated various health markers including body weight, disease activity index (DAI), colon length, spleen index, histological score, serum concentrations of myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD), lipid oxidation (MDA), and inflammatory factors. We evaluated the TRP family and the NLRP3 inflammatory signaling pathways by Western blot, while 16S rDNA sequencing was used to track the effects of PA on gut microbes. RESULTS: It was shown that PA ameliorated the weight loss trend, attenuated inflammatory damage, regulated oxidative stress levels, and repaired the intestinal barrier in DSS mice. Analyses of Western blots demonstrated that PA suppressed what was expressed of transient receptor potential family TRPV4, TRPA1, and the expression of NLRP3 inflammatory signaling pathway, NLRP3 and GSDMD. In addition, PA exerted therapeutic effects on IBD by regulating gut microbiota richness and diversity. Meanwhile, the result of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis showed that gut microbiota was mainly related to Membrane Transport, Replication and Repair, Carbohydrate Metabolism and Amino Acid Metabolism. CONCLUSION: PA derived from Chicory may have therapeutic effects on IBD by regulating the TRPV4/NLRP3 signaling pathway and gut microbiome. This study provides new insights into the effects of phenolic acids from Chicory on TRP ion channels and gut microbiota, revealing previously unexplored modes of action.

Social isolation and cognitive function in patients with schizophrenia: A two years follow-up study.

Cognitive impairment is a core characteristic of schizophrenia. Social isolation has been linked to impaired cognitive function among the general population. In this longitudinal study, we examined the association between social isolation and cognitive function among inpatients with schizophrenia. Two waves of data (2019 and 2021) were collected from chronic psychiatric wards. A total of 166 inpatients completed all measurements at baseline and follow-up. Social isolation was measured by incorporating the frequency of social contact and participation, while cognitive functions were assessed by the Taiwan version of the Montreal Cognitive Assessment (MoCA-T). We used multiple linear regression to evaluate the link between baseline social isolation and cognitive function. For the total sample, social isolation was significantly related to poor language abilities (ß = -0.17, p = 0.013) and delayed recall (ß = -0.15, p = 0.023). Sex-stratified analysis showed that social isolation was significantly related to poor global cognitive function (ß = -0.14, p = 0.021) and domain-specific cognitive functions including language abilities (ß = -0.26, p = 0.003) and delayed recall (ß = -0.19, p = 0.045) in male inpatients. No significant association was found between social isolation and global cognitive function or any cognitive domain (all ps > 0.05) for females. All associations were independent of loneliness and other covariates. These findings suggested that social isolation could predict poor subsequent cognitive function in inpatients with schizophrenia, especially in males. Interventions aimed at enhancing social connections could potentially improve cognitive function in this population.

N-linked α2,6-sialylation of integrin ß1 by the sialyltransferase ST6Gal1 promotes cell proliferation and stemness in gestational trophoblastic disease.

INTRODUCTION: Gestational trophoblastic disease (GTD) encompasses a spectrum of rare pre-malignant and malignant entities originating from trophoblastic tissue, including partial hydatidiform mole, complete hydatidiform mole and choriocarcinoma. ß-galactoside α2,6 sialyltransferase 1 (ST6Gal1), the primary sialyltransferase responsible for the addition of α2,6 sialic acids, is strongly associated with the occurrence and development of several tumor types. However, the role of ST6Gal1/α2,6 -sialylation of trophoblast cells in GTD is still not well understood. METHODS: The expression of ST6Gal1 was investigated in GTD and human immortalized trophoblastic HTR-8/SVneo cells and human gestational choriocarcinoma JAR cells. We evaluated the effect of ST6Gal1 on proliferation and stemness of trophoblastic cells. We also examined the effect of internal miR-199a-5p on ST6Gal1 expression. The role of ST6Gal1 in regulating α2,6-sialylated integrin ß1 and its significance in the activation of integrin ß1/focal adhesion kinase (FAK) signaling pathway were also explored. RESULTS: ST6Gal1 was observed to be highly expressed in GTD. Overexpression of ST6Gal1 promoted the proliferation and stemness of HTR-8/SVneo cells, whereas knockdown of ST6Gal1 suppressed the viability and stemness of JAR cells. MiR-199a-5p targeted and inhibited the expression of ST6Gal1 in trophoblastic cells. In addition, we revealed integrin ß1 was highly α2,6-sialylated in JAR cells. Inhibition of ST6Gal1 reduced α2,6-sialylation on integrin ß1 and suppressed the integrin ß1/FAK pathway in JAR cells, thereby affecting its biological functions. DISCUSSION: This study demonstrated that ST6Gal1 plays important roles in promoting proliferation and stemness through the integrin ß1 signaling pathway in GTD. Therefore, ST6Gal1 may have a potential role in the occurrence and development of GTD.

Prospective association of comorbid hypertension and depressive symptoms with C-reactive protein in older adults.

BACKGROUND: Hypertension and depressive symptoms often occur together in the older population, and each has been separately linked to elevated C-reactive protein (CRP). This study investigated the prospective association between comorbid hypertension and depressive symptoms and high-sensitivity CRP (hs-CRP) in a Chinese older population. METHODS: This study used data from 4978 participants aged 50 and above, who took part in two waves (2011 and 2015) of the China Health and Retirement Longitudinal Study (CHARLS). Hypertension, depressive symptoms and hs-CRP were measured. Logistic regressions adjusted for confounding variables were used to examine the association between the baseline comorbidity of hypertension and depressive symptoms and the change in hs-CRP levels. RESULTS: Hypertension and depressive symptoms did not show independent associations with an elevated level of hs-CRP. Participants with comorbid hypertension and depressive symptoms were more likely to develop a higher level of hs-CRP at follow-up (OR = 1.39, 95 % CI: 1.12-1.74) even after adjusting for covariates. Sex- and age-stratified analyses indicated that the association between the comorbidity and higher levels of hs-CRP were prone to be observed in women (OR = 1.55, 95 % CI: 1.16-2.08) and older adults (OR = 1.74, 95 % CI: 1.20-2.52). CONCLUSIONS: Comorbid hypertension and depressive symptoms is related to a higher risk of elevated hs-CRP levels. This association appears to be more pronounced among women and older adults compared to their counterparts. LIMITATION: Depression was self-reported by participants, which might be considered less unreliable than clinical diagnoses.

Numerical study on the axial collapse of thin-walled columns.

In order to investigate the damage characteristics of structural components under axial compression, thin-walled columns are chosen as a more straightforward construct due to the complex structural properties of composite materials, diverse fiber laying angles, and varied geometries associated with thin-walled columns. Despite the limitations imposed by labor-intensive testing procedures, high costs, and the poor repeatability inherent in experimental research methods, there remains an insufficient exploration of axial compressive damage in columns composed of aluminum and fiber-reinforced polymers. This article utilizes the finite element technique to quantitatively analyze the crushing processes of four materials: aluminum, carbon fiber-reinforced aluminum, carbon fiber-reinforced polymer, and glass fiber-reinforced polymer. It examines the effects of varying fibers and matrix materials on their mechanical attributes. The study also evaluates the impact of different cross-sectional designs on the mechanical behavior of the columns.

Dynamic nonlinear CO2 emission effects of urbanization routes in the eight most populous countries.

A dynamic STIRPAT model used in the current study is based on panel data from the eight most populous countries from 1975 to 2020, revealing the nonlinear effects of urbanization routes (percentage of total urbanization, percentage of small cities and percentage of large cities) on carbon dioxide (CO2) emissions. Using "Dynamic Display Unrelated Regression (DSUR)" and "Fully Modified Ordinary Least Squares (FMOLS)" regressions, the outcomes reflect that percentage of total urbanization and percentage of small cities have an incremental influence on carbon dioxide emissions. However, square percentage of small cities and square percentage of total urbanization have significant adverse effects on carbon dioxide (CO2) emissions. The positive relationship between the percentage of small cities, percentage of total urbanization and CO2 emissions and the negative relationship between the square percentage of small cities, square percentage of total urbanization and CO2 emissions legitimize the inverted U-shaped EKC hypothesis. The impact of the percentage of large cities on carbon dioxide emissions is significantly negative, while the impact of the square percentage of large cities on carbon dioxide emissions is significantly positive, validating a U-shaped EKC hypothesis. The incremental effect of percentage of small cities and percentage of total urbanization on long-term environmental degradation can provide support for ecological modernization theory. Energy intensity, Gross Domestic Product (GDP), industrial growth and transport infrastructure stimulate long-term CO2 emissions. Country-level findings from the AMG estimator support a U-shaped link between the percentage of small cities and CO2 emissions for each country in the entire panel except the United States. In addition, the Dumitrescu and Hulin causality tests yield a two-way causality between emission of carbon dioxide and squared percentage of total urbanization, between the percentage of the large cities and emission of carbon dioxide, and between energy intensity and emission of carbon dioxide. This study proposes renewable energy options and green city-friendly technologies to improve the environmental quality of urban areas.

The Degradation of Aqueous Oxytetracycline by an O3/CaO2 System in the Presence of HCO3-: Performance, Mechanism, Degradation Pathways, and Toxicity Evaluation.

This research constructed a novel O3/CaO2/HCO3- system to degrade antibiotic oxytetracycline (OTC) in water. The results indicated that CaO2 and HCO3- addition could promote OTC degradation in an O3 system. There is an optimal dosage of CaO2 (0.05 g/L) and HCO3- (2.25 mmol/L) that promotes OTC degradation. After 30 min of treatment, approximately 91.5% of the OTC molecules were eliminated in the O3/CaO2/HCO3- system. A higher O3 concentration, alkaline condition, and lower OTC concentration were conducive to OTC decomposition. Active substances including ·OH, 1O2, ·O2-, and ·HCO3- play certain roles in OTC degradation. The production of ·OH followed the order: O3/CaO2/HCO3- > O3/CaO2 > O3. Compared to the sole O3 system, TOC and COD were easier to remove in the O3/CaO2/HCO3- system. Based on DFT and LC-MS, active species dominant in the degradation pathways of OTC were proposed. Then, an evaluation of the toxic changes in intermediates during OTC degradation was carried out. The feasibility of O3/CaO2/HCO3- for the treatment of other substances, such as bisphenol A, tetracycline, and actual wastewater, was investigated. Finally, the energy efficiency of the O3/CaO2/HCO3- system was calculated and compared with other mainstream processes of OTC degradation. The O3/CaO2/HCO3- system may be considered as an efficient and economical approach for antibiotic destruction.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

Mechanism of Acupuncture in Treating Obesity: Advances and Prospects.

Obesity is a common metabolic syndrome that causes a significant burden on individuals and society. Conventional therapies include lifestyle interventions, bariatric surgery, and pharmacological therapies, which are not effective and have a high risk of adverse events. Acupuncture is an effective alternative for obesity, it modulates the hypothalamus, sympathetic activity and parasympathetic activity, obesity-related hormones (leptin, ghrelin, insulin, and CCK), the brain-gut axis, inflammatory status, adipose tissue browning, muscle blood flow, hypoxia, and reactive oxygen species (ROS) to influence metabolism, eating behavior, motivation, cognition, and the reward system. However, hypothalamic regulation by acupuncture should be further demonstrated in human studies using novel techniques, such as functional MRI (fMRI), positron emission tomography (PET), electroencephalogram (EEG), and magnetoencephalography (MEG). Moreover, a longer follow-up phase of clinical trials is required to detect the long-term effects of acupuncture. Also, future studies should investigate the optimal acupuncture therapeutic option for obesity. This review aims to consolidate the recent improvements in the mechanism of acupuncture for obesity as well as discuss the future research prospects and potential of acupuncture for obesity.

Utility of Circulating Tumor DNA Assessment in Characterizing Recurrence Sites after Optimal Resection for Metastatic Colorectal Cancer.

INTRODUCTION: Plasma ctDNA is a promising biomarker for metastatic colorectal cancer (mCRC); however, its role in characterizing recurrence sites after mCRC resection remains poorly understood. This single-institution study investigated the timing of ctDNA detection and its levels in the context of recurrence at different sites following mCRC resection. METHODS: Patients who underwent optimal resection of CRC metastases involving the peritoneum, distant lymph nodes, or liver, with serial postoperative tumor-informed ctDNA assessments (Signatera) were included. Recurrence sites, as defined by surveillance imaging or laparoscopy, were categorized as peritoneal-only and other distant sites (liver, lung, lymph nodes, or body wall). RESULTS: Among the 31 included patients, ctDNA was detected in all 26 (83.4%) patients with postoperative recurrence and was persistently undetectable in five patients who did not experience recurrence. At three months post-surgery, ctDNA was detected in 2/8 (25.0%) patients with peritoneal-only recurrence and 17/18 (94.4%) patients with distant recurrence (p < 0.001). Beyond three months, ctDNA was detected in the remaining six patients with peritoneal-only disease and one patient with distant disease. ctDNA detection preceded the clinical diagnosis of recurrence by a median of nine weeks in both groups. At recurrence, peritoneal-only recurrent cases exhibited lower ctDNA levels (median 0.4 MTM/ml, IQR 0.1-0.8) compared to distant recurrence (median 5.5 MTM/ml, IQR 0.8-33.3, p = 0.004). CONCLUSION: Peritoneal-only recurrence was associated with delayed ctDNA detection and low levels of ctDNA after optimal resection for mCRC. ctDNA testing may effectively characterize recurrence sites and may help guide subsequent treatments specific to the disease sites involved.

ADORA2B, transcriptionally suppressing by MYC, promotes ferroptosis of chondrocytes via inhibition of the PI3K/Akt pathway in mice with osteoarthritis.

Recent studies have shown that chondrocyte ferroptosis contributes importantly to the pathogenesis of osteoarthritis (OA). However, it is largely unknown how it is regulated. In this study, the data sets GSE167852 and GSE190184 were downloaded from the Gene Expression Omnibus (GEO) database, and 161 differentially expressed genes (DEGs) related to ferroptosis were screened by bioinformatics analysis. Subsequently, ADORA2B was screened as a candidate gene from DEGs, which was significantly upregulated in palmitic acid (PA) treated chondrocytes. CCK-8, EdU, Western blotting, and ferroptosis-related kits assays demonstrated that knockdown of ADORA2B constrained ferroptosis and promoted viability of chondrocytes. Overexpression of ADORA2B promoted ferroptosis, while the PI3K/Akt pathway inhibitor LY294002 reversed the promotion of ADORA2B on ferroptosis. Dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assays indicated MYC was a transcription suppressor of ADORA2B, and overexpression of MYC promoted the viability, and inhibited the ferroptosis of chondrocytes, while ADORA2B overexpression abated the promotion of MYC on chondrocyte viability and the inhibition on ferroptosis. In vivo experiments showed that MYC overexpression alleviated cartilage tissue damage in OA mice, which was able to reversed by ADORA2B overexpression. In summary, ADORA2B, transcriptionally suppressing by MYC, promotes ferroptosis of chondrocytes via inhibition of the PI3K/Akt pathway. Thus, ADORA2B can be used as a potential treatment target for ferroptosis-related diseases.