Asiatic acid alleviates vascular remodeling in BAPN-induced aortic dissection through inhibiting NF-κB p65/CX3CL1 signaling.

Inflammation assumes a pivotal role in the aortic remodeling of aortic dissection (AD). Asiatic acid (AA), a triterpene compound, is recognized for its strong anti-inflammatory properties. Yet, its effects on ß-aminopropionitrile (BAPN)-triggered AD have not been clearly established. The objective is to determine whether AA attenuates adverse aortic remodeling in BAPN-induced AD and clarify potential molecular mechanisms. In vitro studies, RAW264.7 cells pretreated with AA were challenged with lipopolysaccharide (LPS), and then the vascular smooth muscle cells (VSMCs)-macrophage coculture system was established to explore intercellular interactions. To induce AD, male C57BL/6J mice at three weeks of age were administered BAPN at a dosage of 1 g/kg/d for four weeks. To decipher the mechanism underlying the effects of AA, RNA sequencing analysis was conducted, with subsequent validation of these pathways through cellular experiments. AA exhibited significant suppression of M1 macrophage polarization. In the cell coculture system, AA facilitated the transformation of VSMCs into a contractile phenotype. In the mouse model of AD, AA strikingly prevented the BAPN-induced increases in inflammation cell infiltration and extracellular matrix degradation. Mechanistically, RNA sequencing analysis revealed a substantial upregulation of CX3CL1 expression in BAPN group but downregulation in AA-treated group. Additionally, it was observed that the upregulation of CX3CL1 negated the beneficial impact of AA on the polarization of macrophages and the phenotypic transformation of VSMCs. Crucially, our findings revealed that AA is capable of downregulating CX3CL1 expression, accomplishing this by obstructing the nuclear translocation of NF-κB p65. The findings indicate that AA holds promise as a prospective treatment for adverse aortic remodeling by suppressing the activity of NF-κB p65/CX3CL1 signaling pathway.

Rapid Photoacoustic Exhaust Gas Analyzer for Simultaneous Measurement of Nitrogen Dioxide and Sulfur Dioxide.

A rapid photoacoustic (PA) exhaust gas analyzer is presented for simultaneous measurements of nitrogen dioxide (NO2) and sulfur dioxide (SO2). A laser diode (LD) emitting at 450 nm and a light-emitting diode (LED) with a peak wavelength of 275 nm operated simultaneously, producing PA signals of NO2 and SO2, respectively. The LD and LED were modulated at different frequencies of 2568 and 2570 Hz, and their emission light beams were transmitted through two resonant tubes in a differential PA cell (DPAC), respectively. A self-made dual-channel digital lock-in amplifier was used to realize the simultaneous detection of dual-frequency PA signals. Cross interference between the PA signals at the two different frequencies was reduced to 0.02% by using a lock-in amplifier. In order to achieve a rapid dynamic measurement, gas sampling was accelerated by an air pump. The use of mufflers and the differential PA detection technique significantly reduced the gas sampling noise. When the gas flow rate was 1000 sccm, the response time of the PA dual-gas analyzer was 8 and 17 s for NO2 and SO2, respectively. The minimum detection limits of NO2 and SO2 were 1.7 and 26.1 ppb when the averaging time of the system was 10 s, respectively. Due to the wide spectral bandwidth of the LED, NO2 produced an interference to the detection of SO2. The interference was reduced by the precise detection of NO2. Since the radiations of the LD and LED passed through two different PA tubes, the impact of NO2 photochemical dissociation caused by UV LED luminescence on NO2 gas detection was negligible. The sharing of the PA cell, the gas lines, and the signal processing modules significantly reduced the size and cost of the PA dual-gas analyzer.

Role of protein arginine methyltransferase 1 in obesity-related metabolic disorders: Research progress and implications.

Obesity has become a major global problem that significantly confers an increased risk of developing life-threatening complications, including type 2 diabetes mellitus, fatty liver disease and cardiovascular diseases. Protein arginine methyltransferases (PRMTs) are enzymes that catalyse the methylation of target proteins. They are ubiquitous in eukaryotes and regulate transcription, splicing, cell metabolism and RNA biology. As a key, epigenetically modified enzyme, protein arginine methyltransferase 1 (PRMT1) is involved in obesity-related metabolic processes, such as lipid metabolism, the insulin signalling pathway, energy balance and inflammation, and plays an important role in the pathology of obesity-related metabolic disorders. This review summarizes recent research on the role of PRMT1 in obesity-related metabolic disorders. The primary objective was to comprehensively elucidate the functional role and regulatory mechanisms of PRMT1. Moreover, this study attempts to review the pathogenesis of PRMT1-mediated obesity-related metabolic disorders, thereby offering pivotal information for further studies and clinical treatment.

A novel bispecific antibody drug conjugate targeting HER2 and HER3 with potent therapeutic efficacy against breast cancer.

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.

T cell-redirecting antibody for treatment of solid tumors via targeting mesothelin.

T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC50: 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence of non-membrane-anchored MSLN (soluble MSLN). Moreover, the anti-tumor activity of MSLN490 was enhanced when combined with either Atezolizumab or TAA × CD28 BsAbs. Notably, a synergistic effect was observed between MSLN490 and paclitaxel, as paclitaxel disrupted the immunosuppressive microenvironment within solid tumors, enhancing immune cells infiltration and improved anti-tumor efficacy. Overall, MSLN490 exhibits robust anti-tumor activity, resilience to soluble MSLN interference, and enhanced anti-tumor effects when combined with other therapies, offering a promising future for the treatment of a variety of solid tumors. This study provides a strong foundation for further exploration of MSLN490's clinical potential.

Variations of plasma oxidative stress levels in male patients with chronic schizophrenia. Correlations with psychopathology and matrix metalloproteinase-9: a case-control study.

BACKGROUND: Accumulating evidence has indicated that oxidative stress (OS) and matrix metalloproteinase-9 (MMP-9) may contribute to the mechanism of schizophrenia. In the present study, we aimed to evaluate the associations of OS parameters and MMP-9 levels with psychopathological symptoms in male chronic schizophrenia patients. METHODS: This study was an observational, cross-sectional, retrospective case-control study. Plasma hydrogen peroxide (H2O2), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), serum matrix metalloproteinase-9 (MMP-9), and tissue inhibitors of metalloproteinases-1 (TIMP-1) levels were assayed in 80 male patients with chronic schizophrenia and 80 matched healthy controls. Schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Multivariate regression was used to analyze relationships between OS parameters and MMP-9, and clinical symptoms. RESULTS: Our results demonstrated that levels of antioxidant enzymes, SOD, GSH-Px, H2O2, and MDA were significantly decreased, whereas CAT and MMP-9 levels were increased in patients with schizophrenia, when compared with healthy controls (all P < 0.05). In schizophrenia patients, correlation analyses showed that H2O2 levels were significantly and positively correlated with PANSS positive scores, CAT and MDA levels were significant negatively correlated with PANSS negative scores and PANSS total scores, and MDA levels were significantly positively correlated with MMP-9 levels (all P < 0.05). However, we did not find that MMP-9 played an interaction role between OS parameters and PANSS total scores and subscales scores (all P > 0.05). CONCLUSIONS: Our results showed that alterations of plasma OS parameters in male patients with chronic schizophrenia were associated with psychopathology and MMP-9, suggesting that OS and neuroinflammation may play important role in the mechanism of schizophrenia.

Non-linear relationship between TSH and psychotic symptoms on first episode and drug naïve major depressive disorder patients: a large sample sized cross-sectional study in China.

INTRODUCTION: Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical outcomes. TSH may involve in the development of PD. This study aims to explore relationship between TSH and PD. METHODS: A total of 1718 outpatients diagnosed as FEDN MDD were recruited in this study. The relationship between PD and TSH was evaluated using multivariable binary logistic regression analysis. To assess the presence of non-linear associations, a two-piecewise linear regression model was employed. Furthermore, interaction and stratified analyses were conducted with respect to sex, education, marital status, comorbid anxiety, and suicide attempt. RESULTS: Multivariable logistic regression analysis revealed that TSH was positively associated with the risk of PD after adjusting for confounders (OR = 1.26, 95% CI: 1.11 to 1.43; p < 0.05). Smoothing plots showed a nonlinear relationship between TSH and PD, with the inflection point of TSH being 4.94 mIU/L. On the right of the inflection point, for each unit increase in serum TSH level on the right side of the inflection point, the probability of PD increased substantially by 47% (OR = 1.47, 95% CI: 1.25 to 1.73, p < 0.001), while no significant association was observed on the left side of the inflection point (OR = 0.87, 95% CI: 0.67 to 1.14, p = 0.32). CONCLUSION: Our investigation showed a nonlinear TSH-PD relationship in FEDN MDD patients, thus contributing to effective intervention strategies for psychotic symptoms in depression patients.

U-shaped association between fasting blood glucose and suicide attempts in Chinese patients with first-episode drug-naïve major depressive disorder.

BACKGROUND: Evidence regarding the relationship between fasting blood glucose (FBG) and suicide attempts (SA) in patients with major depressive disorder (MDD) was limited. Therefore, the objective of this research was to investigate whether FBG was independently related to SA in Chinese patients with first-episode drug-naïve (FEDN) MDD after adjusting for other covariates. METHODS: The present study was a cross-sectional study. A total of 1718 participants (average age: 34.9 ± 12.4 years, 65.8% females) with FEDN MDD were involved in a hospital in China from September 2016 to December 2018. Multiple logistic regression analysis and smooth curve fitting were used to estimate the association between FBG and the risk of SA. The threshold effect was examined by the two-piecewise linear regression model. Interaction and stratified analyses were conducted according to sex, education, marital status, comorbid anxiety, and psychotic symptoms. RESULTS: The prevalence of SA in patients with FEDN MDD was 20.1%. The result of fully adjusted binary logistic regression showed FBG was positively associated with the risk of SA (odds ratio (OR) = 1.62, 95% CI: 1.13-2.32). Smoothing plots also revealed a nonlinear relationship between FBG and SA, with the inflection point of FBG being 5.34 mmol/l. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 0.53 (0.32-0.88, P = 0.014) and 1.48 (1.04-2.10, P = 0.030), respectively. CONCLUSIONS: A U-shaped relationship between FBG and SA in FEDN MDD patients was found, with the lowest risk of SA at a FBG of 5.34 mmol/l, indicating that both the lower and higher FBG levels may lead to an increased risk of SA.

Genome-Wide Association Study Reveals Polygenic Architecture for Limber Pine Quantitative Disease Resistance to White Pine Blister Rust.

Development of durable resistance effective against a broad range of pathotypes is crucial for restoration of pathogen-damaged ecosystems. This study dissected the complex genetic architecture for limber pine quantitative disease resistance (QDR) to Cronartium ribicola using a genome-wide association study. Eighteen-month-old seedlings were inoculated for resistance screening under controlled conditions. Disease development was quantitatively assessed for QDR-related traits over 4 years postinoculation. To reveal the genomic architecture contributing to QDR-related traits, a set of genes related to disease resistance with genome-wide distribution was selected for targeted sequencing for genotyping of single-nucleotide polymorphisms (SNPs). The genome-wide association study revealed a set of SNPs significantly associated with quantitative traits for limber pine QDR to white pine blister rust, including number of needle spots and stem cankers, as well as survival 4 years postinoculation. The peaks of marker-trait associations displayed a polygenic pattern, with genomic regions as potential resistant quantitative trait loci, distributed over 10 of the 12 linkage groups (LGs) of Pinus. None of them was linked to the Cr4-controlled major gene resistance previously mapped on LG08. Both normal canker and bole infection were mapped on LG05, and the associated SNPs explained their phenotypic variance up to 52%, tagging a major resistant quantitative trait locus. Candidate genes containing phenotypically associated SNPs encoded putative nucleotide-binding site leucine-rich repeat proteins, leucine-rich repeat-receptor-like kinase, cytochrome P450 superfamily protein, heat shock cognate protein 70, glutamate receptor, RNA-binding family protein, and unknown protein. The confirmation of resistant quantitative trait loci broadens the genetic pool of limber pine resistance germplasm for resistance breeding.

Prognostic factors for invasive mucinous adenocarcinoma of the lung: systematic review and meta-analysis.

BACKGROUND: Invasive mucinous adenocarcinoma of the lung (IMA) is a unique and rare subtype of lung adenocarcinoma with poorly defined prognostic factors and highly controversial studies. Hence, this study aimed to comprehensively identify and summarize the prognostic factors associated with IMA. METHODS: A comprehensive search of relevant literature was conducted in the PubMed, Embase, Cochrane, and Web of Science databases from their inception until June 2023. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (CI) of overall survival (OS) and/or disease-free survival (DFS) were obtained to evaluate potential prognostic factors. RESULTS: A total of 1062 patients from 11 studies were included. In univariate analysis, we found that gender, age, TNM stage, smoking history, lymph node metastasis, pleural metastasis, spread through air spaces (STAS), tumor size, pathological grade, computed tomography (CT) findings of consolidative-type morphology, pneumonia type, and well-defined heterogeneous ground-glass opacity (GGO) were risk factors for IMA, and spiculated margin sign was a protective factor. In multivariate analysis, smoking history, lymph node metastasis, pathological grade, STAS, tumor size, and pneumonia type sign were found to be risk factors. There was not enough evidence that epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) mutations, CT signs of lobulated margin, and air bronchogram were related to the prognosis for IMA. CONCLUSION: In this study, we comprehensively analyzed prognostic factors for invasive mucinous adenocarcinoma of the lung in univariate and multivariate analyses of OS and/or DFS. Finally, 12 risk factors and 1 protective factor were identified. These findings may help guide the clinical management of patients with invasive mucinous adenocarcinoma of the lung.

Couples' preconception urinary essential trace elements concentration and spontaneous abortion risk: A nested case-control study in a community population.

BACKGROUND: Previous studies have indicated a correlation between maternal imbalances in essential trace elements during pregnancy and the occurrence of spontaneous abortion (SA). Nonetheless, the impact of these elements from both partners and during the preconception period remains unexplored. OBJECTIVE: This study sought to evaluate the relationship between preconception essential trace elements and spontaneous abortion (SA) based on husband-wife dyads. METHODS: This study selected 390 couples with spontaneous abortion (SA) and 390 matched couples with live births from a preconception cohort of 33,687 couples. Urine samples collected prior to pregnancy were analyzed for ten essential trace elements (Se, Cr, Mo, Cu, Zn, Fe, Mn, V, Co, and Ni) using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Multivariate conditional logistic regression analysis identified that elevated concentrations of Zn (OR = 0.73) and Ni (OR = 0.69) in couples were associated with a reduced risk of SA, whereas elevated levels of Cr (OR = 1.30) and Mn (OR = 1.39) were linked to an increased risk. Restricted cubic spline models suggested a U-shaped association between couples' Cu and Co concentrations and SA. Bayesian Kernel Machine Regression further supported a U-shaped relationship between the mixture of ten elements and SA, showing significant protection at the 50th and 55th percentiles compared to the 10th percentile. Additionally, the effects of Cr, Zn, Mn, and Ni on SA varied when the concentrations of the other nine elements were held constant at their 25th, 50th, and 75th percentiles. Stratified analysis revealed that maternal Cu (OR = 0.43) and Fe (OR = 0.63) reduced the risk of SA when paternal Cu and Fe were in the lower quartile. Conversely, maternal Cu (OR = 2.03) and Fe (OR = 1.77) increased the risk of SA when paternal concentrations were in the higher quartile. Similar patterns were observed for Cr, Mn, Co, and Zn. CONCLUSION: Elevated urinary concentrations of Zn and Ni in couples were associated with a reduced risk of SA, while higher levels of Cr and Mn were linked to an increased risk. Cu, Co, and a mixture of ten essential trace elements exhibited a U-shaped relationship with SA. The impact of certain essential trace elements (Cu, Fe, Cr, Mn, Co, and Zn) on SA in one partner was influenced by their concentrations in the other partner.

Bio-inspired Two-dimensional Nanofluidic Ionic Transistor for Neuromorphic Signal Processing.

Voltage-gated ion channels prevalent in neurons play important roles in generating action potential and information transmission by responding to transmembrane potential. Fabricating bio-inspired ionic transistors with ions as charge carriers will be crucial for realizing neuro-inspired devices and brain-liking computing. Here, we reported a two-dimensional nanofluidic ionic transistor based on a MXene membrane with sub-1 nm interlayer channels. By applying a gating voltage on the MXene nanofluidic, a transmembrane potential will be generated to active the ionic transistor, which is similar to the transmembrane potential of neuron cells and can be effectively regulated by changing membrane parameters, e.g., thickness, composition, and interlayer spacing. For the symmetric MXene nanofluidic, a high on/off ratio of ~2000 can be achieved by forming an ionic depletion or accumulation zone, contingent on the sign of the gating potential. An asymmetric PET/MXene-composited nanofluidic transitioned the ionic transistor from ambipolar to unipolar, resulting in a more sensitive gate voltage characteristic with a low subthreshold swing of 560 mV/decade. Furthermore, ionic logic gate circuits, including the "NOT", "NAND", and "NOR" gate, were implemented for neuromorphic signal processing successfully, which provides a promising pathway towards highly parallel, low energy consumption, and ion-based brain-like computing.

Long-Term Outcomes of Endovascular Treatment for Type B Aortic Dissection with Simple Renal Cysts: A Multicenter Retrospective Study.

Background: Few studies have investigated the characteristics and long-term outcomes of type B aortic dissection (BAD) patients with simple renal cysts (SRC) after thoracic endovascular aortic repair (TEVAR). Methods: A multi-center retrospective cohort study was performed, including 718 BAD patients undergoing TEVAR from 2003 to 2016. The prevalence of SRC was 34.5% (n = 248). After propensity score matching, 214 matched pairs were selected for further analysis. Primary outcomes were long-term aortic-related adverse events (ARAEs). The effects of SRC in each subgroup of interest and their interactions were analyzed. Results: BAD patients with SRC were older and had a greater prevalence of comorbidities, including hypertension, coronary artery disease and chronic occlusive pulmonary disease. In addition, the SRC group presented a greater proportion of pleural effusion and aortic calcification. Compared with the non-SRC group, a significantly higher maximal diameter of ascending aorta was observed in the SRC group. Apart from the timing of the operation, no differences were found in the medication regime or intra-operative parameters. In the matched population, patients with SRC were at a higher risk of ARAEs in the long term. The multivariable Cox model indicated that SRC was an independent predictor of long-term ARAEs (hazard ratio: 1.84, 95% confidence interval: 1.13-3.00). The interaction between SRC and hypertension on rupture after TEVAR was statistically significant (p = 0.023). Conclusions: Compared with the non-SRC group, BAD patients with SRC experienced a higher risk of long-term ARAEs after TEVAR. Among the SRC subgroup, hypertensive patients had the highest risk of rupture after TEVAR.

Progresses of T-cell-engaging bispecific antibodies in treatment of solid tumors.

T-cell-engaging bispecific antibody (TCB) therapies have emerged as a promising immunotherapeutic approach, effectively redirecting effector T cells to selectively eliminate tumor cells. The therapeutic potential of TCBs has been well recognized, particularly with the approval of multiple TCBs in recent years for the treatment of hematologic malignancies as well as some solid tumors. However, TCBs encounter multiple challenges in treating solid tumors, such as on-target off-tumor toxicity, cytokine release syndrome (CRS), and T cell dysfunction within the immunosuppressive tumor microenvironment, all of which may impact their therapeutic efficacy. In this review, we summarize clinical data on TCBs for solid tumor treatment, highlight the challenges faced, and discuss potential solutions based on emerging strategies from current clinical and preclinical research. These solutions include TCB structural optimization, target selection, and combination strategies. This comprehensive analysis aims to guide the development of TCBs from design to clinical application, addressing the evolving landscape of cancer immunotherapy.

Selenium Counteracts Tight Junction Disruption and Attenuates the NF-κB-Mediated Inflammatory Response in Staphylococcus aureus-Infected Mouse Mammary Glands.

Tight junctions (TJs) are the key determinant of barrier function in the mammary gland, with their disruption being associated with the pathogenesis and progression of mastitis, especially in the case of Staphylococcus aureus (S. aureus) infection. This study investigated whether selenium (Se) could attenuate S. aureus-induced mastitis by inhibiting inflammation and protecting mammary gland TJs in mice. The expression profiles of S. aureus-infected gland tissues derived from the gene expression omnibus dataset were analyzed. We found cytokine production, cell junctions, the nuclear transcription factor-κB (NF-κB) signalling pathway, and inflammatory responses associated with the differentially expressed genes, as revealed by Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses. Se reduced the mRNA expression and production of inflammatory cytokines, including tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and decreased phosphorylation levels of the NF-κB complex. Moreover, Se alleviated structural damage and microvillus injury in mammary glands. Immunohistochemical staining revealed that Se increased the expression of Claudin-3; Western blot analysis revealed increased protein levels of Occludin and Tricellulin in the group supplemented with dietary Se. In summary, Se counteracted TJ disruption and attenuated NF-κB-mediated inflammatory responses in S. aureus-infected mouse mammary glands.

Ecosystem-based management approaches for watershed conservation and geosustainability.

When contributors' goals and legislative and political structures vary, as they often do in the case of worldwide fish populations, it becomes more challenging to implement ethical fishing tactics. Canada, the United States, and Mexico all fish from Pacific regions anchovies in the California Modern. Climate-driven numbers and geographic dynamics may pollute the waters of collaborative aquaculture and lead to overloading. This research expands upon prior works using a game theoretic model of Tran's boundary sardine fisheries in different climatic conditions to account for ecological links. More significant economic advantages accrue from cooperation fishing tactics that consider the mackerel's role as feed for other species in the natural system, as opposed to plans that merely take note of the worth of mackerel harvests to a particular fishing nation. The maximum environmental benefit is obtained at a fishery rate for sardines barely less than the sardine Fishery Management Safe Yield. Ecological-based control of fisheries can increase sustainability and profits, but only if investors and policy makers consider the ecology in business-applicable models. Understanding and adapting to the fast alterations in habitat distributions due to climate change and designing ways to achieve viable and lucrative fishery amidst altering environments will necessitate an increased emphasis on ecosystem-based governance.

Prevalence and related factors of first-time suicide attempts in the past 14 days in Chinese adult patients with first-episode drug-naïve major depressive disorder.

Background: This study aimed to identify socio-demographic, physiologic, and psychologic related factors of the first-time suicide attempt (FSA) in the past 14 days in Chinese adult patients with first-episode drug-naïve (FEDN) major depressive disorder (MDD). Methods: A total of 1718 adult patients with FEDN MDD were enrolled in this cross-sectional survey. Depression, anxiety symptoms, and suicide attempts were assessed. Additionally, biological samples were collected and measured, while Logistic regression analysis was employed to explore the risk factors for FSA in the past 14 days among FEDN MDD patients. Results: Among suicide attempters, 12.11% (208 out of 1718) reported experiencing FSA in the past 14 days. Logistic regression analysis showed that the risk factors for FSA included more severe anxiety symptoms (OR=1.37, 95%CI: 1.28-1.48, p<0.001), higher levels of total cholesterol (TC) (OR=1.42, 95%CI: 1.13-1.77, p=0.003), and elevated thyroid-stimulating hormone (TSH) (OR=1.13, 95%CI: 1.03-1.25, p=0.01). The regression model exhibited good discriminatory power for FSA with an area under the curve (AUC) of 0.82. Conclusion: FEDN MDD patients with more severe anxiety and higher levels of TSH and TC are more likely to develop FSA in the past 14 days. These factors are risk factors for short-term (in the past 14 days) FSA and may serve as indicators for early intervention.

The regulatory role of m6A methylation modification in metabolic syndrome pathogenesis and progression.

Metabolic syndromes are characterized by various complications caused by disrupted glucose and lipid metabolism, which are major factors affecting the health of a population. However, existing diagnostic and treatment strategies have limitations, such as the lack of early diagnostic and therapeutic approaches, variability in patient responses to treatment, and cost-effectiveness. Therefore, developing alternative solutions for metabolic syndromes is crucial. N6-methyladenosine (m6A) is one of the most abundant modifications that determine the fate of RNA. m6A modifications are closely associated with metabolic syndrome development and present novel prospects for clinical applications. Aberrant m6A modifications have been detected during inflammatory infiltration, apoptosis, autophagy, iron sagging, necrosis, and scorching during metabolic syndrome pathogenesis and progression. However, few reviews have systematically described the correlation between m6A modifications and these factors concerning metabolic syndrome pathogenesis and progression. This study summarizes the m6A methylation regulators and their roles in metabolic syndrome development, highlighting the potential of m6A modification as a biomarker in metabolic disorders.

Process-Based Modeling of Phenology and Radial Growth in Pinus tabuliformis in Response to Climate Factors over a Cold and Semi-Arid Region.

(1) Background: Climate change significantly impacts the phenology and dynamics of radial tree growth in alpine dryland forests. However, there remains a scarcity of reliable information on the physiological processes of tree growth and cambial phenology in response to long-term climate change in cold and semi-arid regions. (2) Methods: We employed the process-based Vaganov-Shashkin (VS) model to simulate the phenology and growth patterns of Chinese pine (Pinus tabuliformis) in the eastern Qilian Mountains, northeastern Tibetan Plateau. The model was informed by observed temperature and precipitation data to elucidate the relationships between climate factors and tree growth. (3) Results: The simulated tree-ring index closely aligned with the observed tree-ring chronology, validating the VS model's effectiveness in capturing the climatic influences on radial growth and cambial phenology of P. tabuliformis. The model outputs revealed that the average growing season spanned from mid-April to mid-October and experienced an extension post-1978 due to ongoing warming trends. However, it is important to note that an increase in the duration of the growing season did not necessarily result in a higher level of radial growth. (4) Conclusions: While the duration of the growing season was primarily determined by temperature, the growth rate was predominantly influenced by water conditions during the growing season, making it the most significant factor contributing to ring formation. Our study provides valuable insights into the potential mechanisms underlying tree growth responses to climate change in cold and semi-arid regions.

Exceptional Lithography Sensitivity Boosted by Hexafluoroisopropanols in Photoresists.

Advanced lithography requires highly sensitive photoresists to improve the lithographic efficiency, and it is critical, yet challenging, to develop high-sensitivity photoresists and imaging strategies. Here, we report a novel strategy for ultra-high sensitivity using hexafluoroisopropanol (HFIP)-containing fluoropolymer photoresists. The incorporation of HFIP, with its strong electrophilic property and the electron-withdrawing effect of the fluorine atoms, significantly increases the acidity of the photoresist after exposure, enabling imaging without conventional photoacid generators (PAGs). The HFIP-containing photoresist has been evaluated by electron beam lithography to achieve a trench of ~40 nm at an extremely low dose of 3 µC/cm2, which shows a sensitivity enhancement of ~10 times compared to the commercial system involving PAGs, revealing its high sensitivity and high-resolution features. Our results demonstrate a new type of PAGs and a novel approach to higher-performance imaging beyond conventional photoresist performance tuning.