Ketamine induced gut microbiota dysbiosis and barrier and hippocampal dysfunction in rats.

The microbiota-gut-brain axis (MGBA) plays a pivotal role in drug addiction. However, the pathophysiological mechanism of MGBA in ketamine addiction remains elusive. The present study investigated the ketamine-induced gut microbiota disorders, intestinal barrier dysfunction, and the alterations in brain function, using a conditioned place preference (CPP) model of ketamine addiction in rats. Compared with the control group, ketamine induced decreased amplitude of low-frequency fluctuation (ALFF) values in the hippocampus, and pyknotic nuclei and concentrated cytoplasm in hippocampal neurons, as well as alterations in gut microbiota composition, shortened ileum villi, and thinner colonic mucosa. We also found that the abundance of gut microbiota exhibited correlations with CPP score, hippocampal ALFF value, length of ileum villi, and thickness of colonic mucosa. Our findings provide evidence for abnormal alterations in the MGBA of ketamine-addicted rats, which improves our understating of the mechanism of ketamine addiction and the potential for developing new therapeutic strategies.

Novel Bulk Quantum Hall Effect in Nanostructured TaP Macroscopic Crystals.

Bulk quantum Hall effect (QHE), the natural extension of the two-dimensional (2D) QHE, is one of the representative phenomena of coherent electron transport. However, bulk QHE has rarely been reported in real materials with macroscopic sizes. Here, we report a novel bulk QHE in macroscopic millimeter-sized and nanostructured TaP crystals consisting of nanometer-scale lamellae. Specifically, the simultaneous quantum plateaus were observed in both transverse resistivity ρxy and vertical resistivity ρzz. The bulk QHE is attributable to synergetic action between Landau cyclotron movement under magnetic field B and periodically modulated potential due to the nanometer-scaled lamellae. This mechanism would form the fixed number of edge states along B-perpendicular and B-parallel directions respectively, equivalent to stacked 2D-QHE layers, leading to quantized ρxy and ρzz. Our work verifies that microstructure engineering could result in the coherent transport of electrons and generate new quantum phenomena in bulk materials.

Effects of Comorbid Depressive Symptoms and Diabetes Mellitus on Functional Dyspepsia in Older Patients.

Objective: Diabetes mellitus (DM) is a global epidemic; comorbid depressive symptoms are highly prevalent worldwide and commonly manifests as physical symptoms, including functional dyspepsia (FD), a gastrointestinal psychosomatic disorder. This study aimed to explore the effects of comorbid depressive symptoms and DM on FD in older patients. Methods: In total, 420 older patients with DM completed measures of depression, anxiety, and FD. Relevant demographic characteristics and medical information were self-reported and obtained from the hospital information system. Results: Among older patients with DM, 30.48% had depressive symptoms. Patients with depressive symptoms were more likely to have FD than those without (42.19% vs. 20.21%, P = .000). Dyspepsia symptoms were more frequent in patients with depression (P = .022). The greater the amount of dyspepsia symptoms, the higher the depression symptoms score (P = .000). Furthermore, dyspepsia symptoms were positively correlated with depressive symptoms (r values were 0.292, 0.311, 0.297, 0.369; all had P < .05). Both FD subtypes, postprandial distress, and epigastric pain syndromes affected depressive symptoms (P < .05). Smoking was significantly associated with FD (P < .05). Diabetes mellitus complications, such as diabetic neuropathy, different therapeutic methods, and anxiety symptoms, influenced FD overlap (x 2 values were 6.298, 16.314, and 30.744; P < .05). Anxiety (odds ratio = 1.832, 95% Confidence Intervals (CI) 1.185-2.834) was a risk factor for FD in comorbid depressive symptoms and diabetes (P < .05). Conclusion: Comorbid depressive symptoms and DM overlapped with physical symptoms, such as FD, in older patients with DM. Lifestyle, diabetic factors, and anxiety were the associated risk factors.

In-Situ Fabricated Transparent Flexible Nanowire Device with Wavelength-Regulated Dual-Function of Photodetector and Photonic Synapse.

Integrating the dual functionalities of a photodetector and photonic synapse into a single device is challenging due to their conflicting requirements for photocurrent decay rates. This study addresses this issue by seamlessly depositing transparent indium tin oxide (ITO) electrodes onto self-oriented copper hexadecafluoro-phthalocyanine (F16CuPc) nanowires growing horizontally along hot-stamped periodic nanogrooves on a transparent flexible polyimide plastic film. This in-situ-fabricated device achieves bending-stable dual functionalities through wavelength regulation while maintaining high transparency and flexibility. Upon exposure to 450-850 nm light, the device exhibits a rapid and sensitive photoresponse with excellent bending stability, making it ideal for optical sensing in both visible and near-infrared spectra. More importantly, the device exhibits a bending-stable excitation postsynaptic current when exposed to light spikes below 405 nm. This enables the successful emulation of various biological synaptic functionalities, including paired-pulse facilitation, spike-number-dependent plasticity, spike-duration-dependent plasticity, spike-rating-dependent plasticity, configurable plasticity between short-term plasticity and long-term plasticity, and memory learning capabilities. Utilizing this device in an artificial neural network achieves a recognition rate of 95% after 57 training epochs. Its ability to switch between photodetection and synaptic modes by adjusting the light wavelength marks a significant advancement in the field of multifunctional flexible electronics based on nanowire arrays.

Genetically predicted Caspase 8 levels mediates the causal association between CD4+ T cell and breast cancer.

Background: Breast cancer (BC) remains a significant contributor to female mortality globally, with inflammation and the immune system implicated in its pathogenesis. To elucidate potential causal relationships, we evaluated the relationship among 731 immune cell phenotypes and BC be at risk by using Mendelian randomization (MR), while also exploring inflammatory proteins as mediators in this association. Methods: We obtained immune cell genome-wide association study (GWAS) summary data and 91 inflammatory factors from the GWAS Catalog. BC GWAS data was obtained from the IEU Open GWAS project (ukb-b-16890 for discovery and GCST004988 for validation). We investigated the causal link between immune cells and BC risk by employing a two-sample MR method. Furthermore, we use a two-step MR to quantify the percentage of mediation of immune cell-BC causal effects mediated by inflammatory proteins. To make sure the causal findings were robust, a sensitivity analysis was done. Results: In both discovery and validation GWAS, a critical inverse correlation between CD4+ T cells and BC risk was found using MR analysis (Discovery: OR, 0.996; P = 0.030. Validation: OR, 0.843; P = 4.09E-07) with Caspase 8 levels mediating 18.9% of the reduced BC risk associated with immune cells(Mediation proportion=a×b/c, Discovery:0.151×-0.005/-0.004 = 18.9%; Validation:0.151×-0.214/-0.171 = 18.9%). Conclusion: Our study establishes a causal connection linking CD4+ T cells and BC, with Caspase 8 levels partially mediating this relationship. These findings enhance our genetic and molecular comprehension of BC, suggesting potential pathways for future BC immunotherapy drug development.

Yangzheng mixture reversed EMT against hepatocellular carcinoma metastasis via NF-κB/NLRP3/ß-catenin pathway.

Yangzheng mixture has been used as an adjuvant tumor therapy as a traditional Chinese medicine in clinical. However, less is known about the activity of Yangzheng mixture. In our study, we explored the anti-tumor activity of Yangzheng mixture for HCC in vitro and in vivo. The effects of Yangzheng mixture on HCC biological behaviors were assessed using colony formation assay, EdU staining, cell cycle assay, Annexin V/PI staining, and wound healing assay. Migration and invasion of HCC cells were further evaluated via transwell assays, while molecular mechanisms were investigated through western blotting and immunofluorescence staining. Additionally, the anticancer effect of Yangzheng mixture in vivo were examined using H22 xenograft and H22 metastatic hepatocellular carcinoma models. Our results revealed that Yangzheng mixture inhibited colony formation, EdU incorporation, cell migration, and invasion, while arresting cell cycle at the G2-M phase in Bel-7402 and SMMC-7721 cells. Mechanistic studies demonstrated that Yangzheng mixture showed a markedly inhibition on Bel-7402 and SMMC-7721 cells with higher NLRP3 expression. We further confirmed that Yangzheng mixture could activate NLRP3 inflammasome through NF-κB by western blotting and immunofluorescence staining. Additionally, Yangzheng mixture inhibited ß-catenin nucleus translocation and reversed EMT process. In vivo, the H22 xenograft model depicted that Yangzheng mixture significantly reduced tumor size and weight compared with control. Moreover, H22 lung metastasis model showed that Yangzheng mixture significantly inhibited liver cancer cell spreading to lungs in mice. Overall, our finding revealed that Yangzheng mixture inhibited HCC proliferation and migration in vitro and in vivo by reversing EMT via NF-κB/NLRP3/ß-catenin pathway. These results may serve new therapeutic evidences for Yangzheng mixture application in clinical.

Causal association between epilepsy and its DNA methylation profile and atrial fibrillation.

BACKGROUND: The "epileptic heart" concept is emerging, but the causal relationship between epilepsy and atrial fibrillation (AF) remains unclarified. OBJECTIVE: This study explores the genetic correlations and bidirectional causality between various epilepsy phenotypes and AF. METHODS: Genome-wide association study (GWAS) statistics for 10 epilepsy subtypes (29,944 cases, 52,538 controls) and AF (60,620 cases, 970,216 controls) were sourced from the International League Against Epilepsy (ILAE) and HGRI-EBI Catalog-GWAS, respectively. Linkage disequilibrium score regression (LDSC) and genome-wide Mendelian randomization (MR) evaluated genetic correlations and bidirectional causal relationships. Epilepsy-related DNA methylation data (N = ∼800) from Epigenome-Wide Association Study (EWAS) catalog were analyzed to identify causal CpG sites influencing risk of AF through epigenetic MR. RESULTS: LDSC revealed significant genetic correlations between 4 epilepsy subtypes and AF (correlation coefficient: rg from 0.116 to 0.241). Forward MR suggested a significant causal effect of focal epilepsy with hippocampal sclerosis (focal epilepsy [FE] with hippocampal sclerosis [HS]) on risk of AF (inverse variance weighting [IVW] and Mendelian randomized pleiotropy residual sum and outlier [MR-PRESSO]: odds ratio [OR] = 1.046, P ≤ .004), with results robust against heterogeneity, horizontal pleiotropy, and outliers. Epigenetic MR indicated that lower methylation at cg06222062 (OR = 0.994, P = 3.16E-04) mapped to PLA2G5 and cg08461451 mapped to SPPL2B gene (OR = 0.954, P = 1.19E-03), and higher cg10541930 in the C10orf143 promoter (OR = 1.043, P = 4.18E-22) increases risk of AF. Sensitivity analyses affirmed no pleiotropic bias. CONCLUSION: FE with HS significantly increases AF risk, highlighting the natural neural-cardiac connection and the need for cardiac monitoring in patients with epilepsy. Specific methylated CpG sites may serve as biomarkers and preventive targets for AF susceptibility.

Biomimetic Gd-Metal-Organic Framework Radiosensitizer for Near-Infrared Fluorescence Imaging-Guided Radiotherapy toward Nasopharyngeal Carcinoma.

Radiotherapy (RT) is recognized as a primary treatment modality for Nasopharyngeal carcinoma (NPC). However, enhancing RT's targeting accuracy and selectivity remains a significant challenge. In this study, we present an innovative radiosensitizer, Gd-metal-organic framework (MOF)-based nanocarrier coated with indocyanine green (ICG) and red blood cell membrane (RBCM), designed to bypass immune clearance and achieve prolonged circulation within the bloodstream. This design significantly enhances tumor localization and systemic circulation, as evidenced by in vivo analyses. The strategic accumulation of the Gd-MOF-ICG nanocarrier at the tumor site facilitates precise tumor localization and sensitization to RT, leveraging the RBCM camouflage to enhance the tumor uptake potential. Our comprehensive study introduces a potent approach for optimizing RT in NPC treatment through this advanced theranostic nanoplatform, which combines material science with biomedical engineering to augment the effectiveness of RT and underscores the significance of precision in cancer therapy. This strategy offers a promising avenue for clinical application and further research in targeted cancer treatments.

miR­25­3p serves as an oncogenic in colorectal cancer cells by regulating the ubiquitin ligase FBXW7 function.

Accumulating evidence indicates that the dysregulation of microRNAs (miRNAs or miRs), is associated with human malignancies and suggests a casual role of miRNAs in tumor initiation and progression. Even though it has been discovered that a number of miRNAs play significant parts in the development of colorectal cancer (CRC), it is crucial to comprehend the regulatory functions that other miRNAs play in CRC. Based on GSE183437 and GSE156719 microarray data that were obtained from Gene Expression Omnibus database, candidate miRNAs were researched. The oncogenic effects of miR­25­3p in different malignancies have led to its selection for additional investigation in the present study. The expression of miR­25­3p was verified by reverse transcription­quantitative PCR, and its correlation with clinicopathological characteristics in patients with CRC was then investigated. In vitro assays were conducted to investigate the influence of miR­25­3p on the proliferative and apoptotic behaviors of HCT116 and Caco­2 cells. The present data revealed that miR­25­3p exhibited one of the most significant upregulations in CRC tissues and cell lines. The expression levels of miR­25­3p were found to be intimately correlated with tumor size, distant metastasis, tumor­node­metastasis stage, and shorter overall survival rate. In terms of functionality, the downregulation of miR­25­3p led to the inhibition of cellular proliferation and the enhancement of apoptosis in both HCT116 and Caco­2 cell lines. The critical tumor suppressor F­box and WD repeat containing domain 7 (FBXW7) was identified as a direct molecular target for miR­25­3p, with an inverse relationship observed between the two in neoplastic tissues. Subsequent studies demonstrated that the tumor suppressive effects of miR­25­3p inhibitor were effectively negated by the silencing of FBXW7. Moreover, the ability of FBXW7 to inhibit the expression of several oncogenes was deemed essential for countering the anticancer effects mediated by miR­25­3p downregulation. These findings posit miR­25­3p as a promising therapeutic target and prognostic indicator for CRC.

Ginsenoside Re inhibits non-small cell lung cancer progression by suppressing macrophage M2 polarization induced by AMPKα1/STING positive feedback loop.

Tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC) promote tumor cell metastasis by interacting with cancer cells. Ginsenoside Re is capable of modulating the host immune system and exerts anticancer effects through multiple pathways. Both AMPK and STING are involved in the regulation of MΦ polarization, thereby affecting tumor progression. However, whether there is a regulatory relationship between them and its effect on MΦ polarization and tumor progression is unclear. The aim of this study was to provide mechanistic evidence that ginsenoside Re modulates MΦ phenotype through inhibition of the AMPKα1/STING positive feedback loop and thus exerts an antimetastatic effect in NSCLC immunotherapy. Cell culture models and conditioned media (CM) systems were constructed, and the treated MΦ were analyzed by database analysis, RT-PCR, Western blotting, flow cytometry, and immunofluorescence to determine the regulatory relationship between AMPK and STING and the effects of ginsenoside Re on MΦ polarization and tumor cells migration. The effects of ginsenoside Re (10, 20 mg/kg/day) on TAMs phenotype as well as tumor progression in mice were assessed by HE staining, immunohistochemical staining, and Western blotting. In this study, AMPKα1/STING positive feedback loop in NSCLC TAMs induced M2 type polarization, which in turn promoted NSCLC cell migration. In addition, ginsenoside Re was discovered to inhibit M2-like MΦ polarization, thereby inhibiting NSCLC cell migration. Mechanistically, Re was able to inhibit the formation of the AMPKα1/STING positive feedback loop, thereby inhibiting its induction of M2-like MΦ and consequently inhibiting the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Furthermore, in mouse models, Re was found to suppress LLC tumor growth and colonization by inhibiting M2-type polarization of TAMs. Our finding indicates that ginsenoside Re can effectively modulate MΦ polarization and thus play an important role in antimetastatic immunotherapy of NSCLC.

Additional EBUS-guided intralesional amphotericin B injection combined systemic intravenous therapy in pulmonary mucormycosis: a case report.

Mucormycosis is an invasive fungal infection that can result in severe lung infections, with pulmonary mucormycosis (PM) being one of the most prevalent manifestations. Prompt diagnosis is crucial for patient survival, as PM often exhibits rapid clinical progression and carries a high fatality rate. Broncho-alveolar lavage fluid or endobronchial biopsy (EBB) has been commonly employed for diagnosing PM, although there is limited mention of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the literature. In this report, we present a case of PM in a patient with diabetes. While EBB did not yield evidence of Rhizopus infection, a definitive diagnosis was obtained through EBUS-TBNA. The patient underwent combination therapy, including oral medication, nebulization, and EBUS-guided intrafocal amphotericin B injection, which resulted in significant improvement following the failure of initial therapy with amphotericin B injection cholesterol sulfate complex. Our case highlights the potential of EBUS-TBNA not only for mediastinal lymphadenopathy but also for obtaining extraluminal lesion specimens. Furthermore, for patients with an inadequate response to mono-therapy and no access to surgical therapy, the addition of EBUS-guided intralesional amphotericin B injection to systemic intravenous therapy may yield unexpected effects.

The impact of combined aerobic and resistance exercise on the prognosis of early Parkinson's disease patients.

BACKGROUND: Although literature suggests that exercise can improve symptoms in Parkinson's Disease (PD) patients, research on the effects of aerobic exercise and resistance training (AE&RT) in early-stage PD remains limited. Understanding the synergistic effects of these exercise modalities can provide valuable insights for optimizing exercise interventions for PD patients, particularly in the early stages of the disease, where interventions may have the greatest impact on long-term functional outcomes. OBJECTIVE: This study aimed to investigate the effects of a combined AE&RT program on motor function, postural stability, and cognitive processing speed in early stage PD patients. METHODS: A total of 236 participants with early-stage PD were assigned to either the Aerobic Exercise Group (AE group) (n= 112) or the AE&RT Group (n= 124) inthis controlled randomized trial. The study employed a one-year supervised exercise program, with the AE Group participating in aerobic activities and the AE&RT Group engaging in combined AE&RT. Outcome measures included symptom improvement, motor function, postural stability, cognitive processing speed, peak oxygen consumption, quality of life evaluation, and the incidence of adverse events. RESULTS: The AE&RT Group demonstrated greater improvements in tremor, muscle rigidity, gait instability, sleep problems, and hyposmia compared to the AE Group. Additionally, the combined exercise group exhibited better cognitive processing speed, as well as enhanced motor function and postural stability. Peak oxygen consumption was significantly higher in the AE&RT Group. However, the quality of life evaluation indicated a statistically higher quality of life in the AE Group. There was no significant difference in the incidence of adverse events between the two groups. CONCLUSION: The findings suggest that the integration of AE&RT in early-stage PD patients leads to more comprehensive improvements in motor symptoms, cognitive function, postural stability, and cardiovascular fitness compared to aerobic exercise alone. These results have important implications for developing tailored exercise interventions to enhance the physical and cognitive well-being of individuals with early-stage PD.

Deciphering and overcoming Anti-PD-1 resistance in Melanoma: A comprehensive review of Mechanisms, biomarker Developments, and therapeutic strategies.

Worldwide, tens of thousands of people die from melanoma each year, making it the most frequently fatal form of cutaneous cancer. Immunotherapeutic advancements, particularly with anti-PD-1 medications, have significantly enhanced treatment outcomes over recent decades. With the broad application of anti-PD-1 therapies, insights into the mechanisms of resistance have evolved. Despite the development of combination treatments and early predictive biomarkers, a comprehensive synthesis of these advancements is absent in the current literature. This review underscores the prevailing knowledge of anti-PD-1 resistance mechanisms and underscores the critical role of robust predictive biomarkers in stratifying patients for targeted combinations of anti-PD-1 and other conventional or innovative therapeutic approaches. Additionally, we offer insights that may shape future melanoma treatment strategies.

Betaine addition to the diet alleviates intestinal injury in growing rabbits during the summer heat through the AAT/mTOR pathway.

BACKGROUND: The aim of this experiment was to investigate the effect of different levels of betaine (Bet) inclusion in the diet on the intestinal health of growing rabbits under summer heat. A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61 ± 38.59 g were randomly divided into 5 treatment groups: control group (basal diet) and Bet groups (basal diet + 0.75, 1.0, 1.5 or 2.0 g/kg Bet). The average daily temperature in the rabbitry during the experiment was 30.48 °C and the relative humidity was 69.44%. RESULTS: Dietary addition of Bet had no significant effect on growth performance and health status of growing rabbits (P > 0.05), but it increased ileal secretory immunoglobulin A content compared to the control under summer heat (P < 0.05). Addition of 0.75 g/kg Bet up-regulated jejunal IL-4, down-regulated ileal TNF-α expression (P < 0.05). The addition of 1.0 g/kg Bet increased the villi height (VH) in the jejunum (P < 0.05). Serum glucose levels were reduced, and the expression of SLC6A20 was up-regulated in jejunum and ileum of rabbits fed with 1.5 g/kg Bet (P < 0.05). When added at 2.0 g/kg, Bet reduced serum HSP70 content, increased jejunal VH, and up-regulated duodenal SLC7A6, SLC38A2, mTOR and 4EBP-2 expression (P < 0.05). Correlation analysis revealed that intestinal mTOR expression was significantly and positively correlated with SLC7A6, SLC38A2, SLC36A1 and IL-4 expression (P < 0.05). CONCLUSIONS: Dietary addition of Bet can up-regulate the expression of anti-inflammatory factors through the AAT/mTOR pathway, improve the intestinal immune function, alleviate intestinal damage in growing rabbits caused by summer heat, and improve intestinal health.

Juice Vesicles Bioreactors Technology for Constructing Advanced Carbon-Based Energy Storage.

The construction of high-quality carbon-based energy materials through biotechnology has always been an eager goal of the scientific community. Herein, juice vesicles bioreactors (JVBs) bio-technology based on hesperidium (e.g., pomelo, waxberry, oranges) is first reported for preparation of carbon-based composites with controllable components, adjustable morphologies, and sizes. JVBs serve as miniature reaction vessels that enable sophisticated confined chemical reactions to take place, ultimately resulting in the formations of complex carbon composites. The newly developed approach is highly versatile and can be compatible with a wide range of materials including metals, alloys, and metal compounds. The growth and self-assembly mechanisms of carbon composites via JVBs are explained. For illustration, NiCo alloy nanoparticles are successfully in situ implanted into pomelo vesicles crosslinked carbon (PCC) by JVBs, and their applications as sulfur/carbon cathodes for lithium-sulfur batteries are explored. The well-designed PCC/NiCo-S electrode exhibits superior high-rate properties and enhanced long-term stability. Synergistic reinforcement mechanisms on transportation of ions/electrons of interface reactions and catalytic conversion of lithium polysulfides arising from metal alloy and carbon architecture are proposed with the aid of DFT calculations. The research provides a novel biosynthetic route to rational design and fabrication of carbon composites for advanced energy storage.

Piezosurgery versus conventional osteotomy: a randomized clinical trial on pain and anxiety in children with unerupted mandibular third molars.

OBJECTIVE: Dental anxiety for unerupted mandibular third molars extraction in children under local anesthesia is a tricky problem. The purpose of this study was to compare psychological and physiologic findings of extractions of unerupted mandibular third molars in children by piezosurgery and conventional osteotomy. MATERIALS AND METHODS: This prospective, single-center, double-blind study included children who required extraction of mandibular third molars under local anesthesia. All subjects were randomly divided into two groups: piezosurgery and conventional osteotomy (control). The primary outcome variables were dental anxiety assessed by the Modified Child Fear Survey Schedule Dental Subscale (CFSS-DS) and postoperative pain qualified by the visual analog scale (VAS). Secondary outcome variables included blood pressure, heart rate, saturation, and operation duration. The data were analyzed by t-test and chi-square test (P ≤ 0.05). RESULTS: All 40 study patients (37.5% males and 62.5% females with an average age of 14.43 ± 1.32 years) completed the entire trial. There were no statistically significant differences observed between the two groups in terms of gender allocation, age, side of extraction, and Winter's Classification (P > 0.05). The operation duration of the piezosurgery group was significantly longer than the conventional osteotomy group (P < 0.01). The VAS scores showed that pain levels of children in the piezosurgery group were significantly less than the conventional osteotomy group on the first and third days postoperatively (P < 0.05 and P < 0.01, respectively). The CFSS-DS score in the piezosurgery group significantly decreased compared to the conventional osteotomy group (P < 0.05). Compared with the conventional osteotomy group, a significant decrease in heart rate, and lower systolic and diastolic blood pressures were observed after extraction in the piezosurgery group (P < 0.05 and P < 0.01, respectively). CONCLUSION: Compared with conventional osteotomy, piezosurgery can effectively reduce postoperative pain and have some effect in relieving dental anxiety for the extraction of unerupted mandibular third molars in children. CLINICAL RELEVANCE: Piezosurgery may be a viable technique for the extraction of unerupted mandibular third molars in children under local anesthesia.

Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS).

Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).

PF-429242 exhibits anticancer activity in hepatocellular carcinoma cells via FOXO1-dependent autophagic cell death and IGFBP1-dependent anti-survival signaling.

Effective therapies for hepatocellular carcinoma (HCC) are urgently needed, as it is a type of cancer resistant to chemotherapy. Recent evidence showed that PF-429242, a membrane-bound transcription factor site-1 protease (MBTPS1) inhibitor, exhibited anticancer activities against glioblastomas, renal cell carcinoma, and pancreatic cancer. However, its anticancer activity against HCC has yet to be investigated. In this study, we found that PF-429242 induced autophagy-dependent cell death in HCC cells. RNA-sequencing analysis indicated that the primary effect of PF-429242 was inhibition of the sterol regulatory element-binding protein (SREBP) signaling pathway. However, overexpression of SREBP proteins did not efficiently rescue PF-429242-induced autophagy and cell death. Mechanistically, PF-429242 induced forkhead box protein O1 (FOXO1)-dependent autophagic cell death. Additionally, PF-429242 caused FOXO1-independent upregulation of insulin-like growth factor-binding protein 1 (IGFBP1), ultimately leading to autophagy-independent cell death. The in vivo anticancer activity of PF-429242 against HCC cells was demonstrated in a tumor xenograft mouse model. Therefore, PF-429242 is a potential anticancer agent to treat HCC by triggering FOXO1-dependent autophagic cell death and IGFBP1-mediated anti-survival signaling in parallel.

Experimental and Numerical Investigation of Shielding Gas Behaviors in Laser Welding of TC4 Alloy.

Gas protection is a crucial part of quality control in laser welding, especially for titanium alloy, which oxidizes easily at high temperatures. Substantial experiments concerning shielding gas characteristics in the welding process have been implemented. However, the common analysis conducted is simplistic and lacks a theoretical basis. This paper presented an investigation of the shielding gas behaviors based on numerical simulation and a titanium alloy laser welding experiment. The numerical model was established and validated by experiment. Subsequently, the temperature field and gas flow fields were calculated. By combining the two fields, the threshold temperature of gas protection was determined, and the influence of shielding gas parameters on the protection effect was examined. The results revealed that the protection of the high-temperature zone was primarily influenced by the nozzle height, nozzle inner diameter, and nozzle angle, while the plasma suppression effect was mainly correlated with the nozzle inner diameter and gas flow rate. These initial findings provide scientific guidance for the better quality production of laser beam welded components made of not only titanium alloy but also other metallic materials.

Spatiotemporal dynamics and influencing factors of carbon productivity in counties of Shandong Province, China.

In the context of the increasing global greenhouse effect, the Chinese government has proposed a "dual carbon" target. As a major carbon-emitting province in China, Shandong Province needs to improve its carbon productivity to coordinate carbon emission reductions and sustainable economic growth. This study analyzes the spatial and temporal evolution of carbon productivity at the county scale and the factors influencing it in Shandong Province from 2000 to 2017. The study uses the Dagum Gini coefficient, kernel density analysis, spatial autocorrelation model, and geographically and temporally weighted regression model. The results indicate that the carbon productivity in Shandong Province nearly doubled during the study period, revealing a spatial distribution characteristic of "high in the east and low in the west," together with a significant positive spatial autocorrelation. Intra-regional differences, the most important source of development differences among the three economic circles, rose to 32.11% during the study period, whereas inter-regional differences declined to 26.6%. Gross domestic product per capita and population density play a significant positive role in the development of carbon productivity. The balance of deposits in financial institutions at the end of the year has a weak positive effect, and the local average public finance expenditure and secondary industry structure on carbon productivity are negative in general. Shandong Province should identify specific regions with weak carbon productivity levels and understand the key factors to improve carbon productivity to promote the achievement of the "dual carbon" goal.