Diosmetin-7-O-ß-D-glucopyranoside from Pogostemonis Herba alleviated SARS-CoV-2-induced pneumonia by reshaping macrophage polarization and limiting viral replication.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.

Federated learning via multi-attention guided UNet for thyroid nodule segmentation of ultrasound images.

Accurate segmentation of thyroid nodules is essential for early screening and diagnosis, but it can be challenging due to the nodules' varying sizes and positions. To address this issue, we propose a multi-attention guided UNet (MAUNet) for thyroid nodule segmentation. We use a multi-scale cross attention (MSCA) module for initial image feature extraction. By integrating interactions between features at different scales, the impact of thyroid nodule shape and size on the segmentation results has been reduced. Additionally, we incorporate a dual attention (DA) module into the skip-connection step of the UNet network, which promotes information exchange and fusion between the encoder and decoder. To test the model's robustness and effectiveness, we conduct the extensive experiments on multi-center ultrasound images provided by 17 local hospitals. The model is trained using the federal learning mechanism to ensure privacy protection. The experimental results show that the Dice scores of the model on the data sets from the three centers are 0.908, 0.912 and 0.887, respectively. Compared to existing methods, our method demonstrates higher generalization ability on multi-center datasets and achieves better segmentation results.

Runx2 silencing sensitized human renal cell carcinoma cells to ABT-737 apoptosis.

The prognostic value of Runt-related transcription factor 2 (Runx2) and its involvement in cell growth and motility have been reported in patients diagnosed with renal cell carcinoma (RCC). Since Runx2 may have the potential to be a target for the purpose of antitumor intervention, there is an urgent need to gain insight into its oncogenic properties. Using human 786-O, Caki-1 and ACHN RCC cells as models, the silencing of cellular Runx2 expression brought about a reduction in cyclin D1 and ß-catenin expression, cell growth and migration without any significant cell death. Runx2-silenced cells turned into apoptosis vulnerable in the presence of ABT-737, a BH3 mimetic Bcl-2 inhibitor. Data from biochemical and molecular studies have revealed a positive correlation between Runx2 expression and Akt phosphorylation, Mcl-1 expression, and fibronectin expression. Results of genetic silencing studies have indicated the potential involvement of Mcl-1 and fibronectin in the decision of RCC cell ABT-737 resistance and sensitivity. The regulatory roles of the PI3K/Akt axis in the expression of Mcl-1 and fibronectin were suggested by means of the results taken from experiments involving pharmacological study of the PI3K/Akt. Since overexpression and prognostic roles of Runx2, activated Akt, Mcl-1, fibronectin, cyclin D1, and ß-catenin have been revealed in RCC, it is important to explore the precise mechanisms underlying Runx2 oncogenic effects. Although the linking details between Runx2 and PI3K/Akt have yet to be identified, our findings suggest that Mcl-1 and fibronectin are downstream effectors of Runx2 via a regulatory axis of the PI3K/Akt and their promotion of cell growth, migration, and ABT-737 resistance in RCC cells.

Diagnostic accuracy of exhaled nitric oxide for the non-invasive identification of patients with fibrotic metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Fibrotic metabolic dysfunction-associated steatohepatitis (MASH) is a condition at risk of progressing to advanced liver disease. We examined whether an innovative exhaled nitric oxide (eNO) breath test (BT) can accurately diagnose fibrotic MASH without requiring blood tests. METHODS: One hundred and forty-seven patients with MASH were recruited, and all tests were undertaken within 1 week of recruitment. With fibrotic MASH (NAS ≥ 4 and fibrosis stage ≥ 2) as the main outcome indicator, the diagnostic efficacy of eNO in identifying fibrotic MASH was compared to other validated models for advanced fibrosis requiring venesection, namely FAST, Agile 3+, and FIB-4 scores. RESULTS: The mean age was 40.36 ± 12.28 years, 73.5% were men. Mean body mass index was 28.83 ± 4.31 kg/m2. The proportion of fibrotic MASH was 29.25%. The area under the receiver operating curve for eNO in diagnosing fibrotic MASH was 0.737 [95% CI 0.650-0.823], which was comparable to FAST (0.751 [0.656-0.846]), Agile 3+ (0.764 [0.670-0.858]), and FIB-4 (0.721 [0.620-0.821]) (all DeLong test p > 0.05). A cut-off of eNO <8.5 ppb gave a sensitivity of 86.0% and a negative predictive value of 88.5% for ruling-out fibrotic MASH. A cut-off of eNO >13.5 ppb provided a specificity of 91.3% and a positive predictive value of 65.4% for ruling-in fibrotic MASH. Sensitivity analyses demonstrated that the diagnostic efficacy of eNO was similar across characteristics such as age. Moreover, adding vibration-controlled transient elastography-LSM (liver stiffness measurement) reduced the uncertainty interval from 46.9% to 39.5%. CONCLUSIONS: The eNO-BT is a promising simple test for non-invasively identifying fibrotic MASH, and its performance is further improved by adding LSM measurement.

Ultrasensitive SERS Detection of Five ß-Blockers Achieved Using Chemometrics with a Two-Dimensional Substrate Formed by Large-Sized Ag@SiO2 Nanoparticles.

We report on a surface-enhanced Raman scattering (SERS) platform for the detection of five beta-blockers (ß-blockers): atenolol, esmolol, labetalol, sotalol, and propranolol. Key to this platform was a two-dimensional substrate formed by self-assembling large Ag@SiO2 nanoparticles (Ag@SiO2 NPs) on a silicon wafer. The close arrangement of these large nanoparticles on the surface generated a strong and uniform electromagnetic field, which enhanced SERS signal intensity for the detection of small amounts of the target molecules. The intensities of characteristic peaks of the five ß-blocker drugs increased linearly with the increase of their concentrations in the range of 10-5 to 10-8 mol/L. The detection limits were 10-10 mol/L for propranolol, 10-9 mol/L for atenolol, labetalol, and sotalol, and 10-8 mol/L for esmolol. Determination of these five ß-blocker drugs added to human urine samples, using a portable Raman spectroscopy instrument, showed quantitative recovery (93-101%). Principal component analysis (PCA) and hierarchical cluster analysis (HCA) of SERS spectral data improved the differentiation among these five ß-blockers. This study highlights the potential of the developed SERS platform for rapid, on-site detection of illicit drugs and for antidoping screening.

Effects of the oxoaporphine alkaloid hernandonine on dengue virus. Evidence for its mechanisms of action.

BACKGROUND: Dengue, caused by the dengue virus (Orthoflavivirus dengue, encompassing DENV types 1-4), is a member of the Flaviviridae family. The symptoms of dengue range from subclinical or mild manifestations to potentially fatal complications. The management of severe dengue is exceptionally challenging due to the absence of effective antiviral medications. In this context, natural products, whether in the form of pure compounds or standardized plant extracts, have emerged as a promising source for the development of novel antiviral therapeutics. Hernandonine, an oxoaporphine alkaloid found in Hernandia nymphaeifolia (C. Presl) Kubitzki. serves both as a metabolite and an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase. PURPOSE: This study investigated the ability of hernandonine to inhibit DENV infection and explored its potential mechanisms. STUDY DESIGN: To assess the in vitro anti-DENV activity, cells or induced pluripotent stem cell (iPSC)-derived cerebral organoids were exposed to hernandonine before or after infection with DENV. Along with hernandonine, the endocytosis modulators, genistein, wortmannin, Methyl-ß-cyclodextrin (MßCD) and lovastatin, were used in the assays. METHODS: The DENV infectivity and virion production in cells or cerebral organoids treated with compounds were determined. Various methods, including cell and cerebral organoids imaging, protein and gene detection were conducted to explore their antiviral mechanisms. RESULTS: The results revealed notable antiviral properties of hernandonine, particularly in inhibiting DENV during the early stages of infection. Mechanistic analysis demonstrated that, akin to genistein, wortmannin, methyl-ß-cyclodextrin (MßCD), and lovastatin, hernandonine exerted an influence on cholesterol-rich lipid rafts. It also restrained the pseudopodial movement ability of cells, potentially through the downregulation of cytoskeleton and endocytosis regulatory genes or protein expression. Moreover, hernandonine's virucidal activity was demonstrated. Hernandonine's inhibition of DENV infection was further validated in a disease-relevant iPSC-derived cerebral organoids model, a novel DENV-2 infection system worthy of further application. CONCLUSION: This study evidenced the potential of hernandonine as a novel candidate in the fight against DENV infection.

Development of an agroinfiltration-based transient hairpin RNA expression system in pak choi leaves (Brassica rapa ssp. chinensis) for RNA interference against Liriomyza sativae.

The vegetable leafminer (Liriomyza sativae) is a devastating invasive pest of many vegetable crops and horticultural plants worldwide, causing serious economic loss. Conventional control strategy against this pest mainly relies on the synthetic chemical pesticides, but widespread use of insecticides easily causes insecticide resistance development and is harmful to beneficial organisms and environment. In this context, a more environmentally friendly pest management strategy based on RNA interference (RNAi) has emerged as a powerful tool to control of insect pests. Here we report a successful oral RNAi in L. sativae after feeding on pak choi (Brassica rapa ssp. chinensis) that transiently express hairpin RNAs targeting vital genes in this pest. First, potentially lethal genes are identified by searching an L. sativae transcriptome for orthologs of the widely used V-ATPase A and actin genes, then expression levels are assessed during different life stages and in different adult tissues. Interestingly, the highest expression levels for V-ATPase A are observed in the adult heads (males and females) and for actin in the abdomens of adult females. We also assessed expression patterns of the target hairpin RNAs in pak choi leaves and found that they reach peak levels 72 h post agroinfiltration. RNAi-mediated knockdown of each target was then assessed by letting adult L. sativae feed on agroinfiltrated pak choi leaves. Relative transcript levels of each target gene exhibit significant reductions over the feeding time, and adversely affect survival of adult L. sativae at 24 h post infestation in genetically unmodified pak choi plants. These results demonstrate that the agroinfiltration-mediated RNAi system has potential for advancing innovative environmentally safe pest management strategies for the control of leaf-mining species.

[NDVI Changes and Influencing Factors of Different Soil and Water Conservation Zones in Shandong Province].

Exploring the characteristics of vegetation change and its influencing factors is essential to construct an ecological environment. Based on the NDVI dataset from 2000 to 2020, this study analyzed the spatial temporal attributes of NDVI changes in Shandong Province using the Sen trend analysis and the gravity center migration model. Furthermore, the spatial heterogeneity of NDVI and its influencing factors within the whole study area and different soil and water conservation zones were investigated using a Geo-detector model, considering population, hydrological, topographic, soil types, and vegetation types. The results were as follows： ① The NDVI in Shandong Province from 2000 to 2020 showed a fluctuating upward trend with significant seasonal characteristics that varied from different zones. The annual NDVI change showed a trend of single-peak in the Ⅲ-4-2t, Ⅲ-4-1xt, and Ⅲ-5-2w but showed a trend of double-peak in the Ⅲ-5-3fn. ② Regarding the spatial distribution, the NDVI was higher in the west-north and west-south areas and lower in the north and coastal areas. During the 21 years, the primary type of NDVI change was "medium-high coverage → high coverage," especially in the northeastern part of the soil conservation area of the Ⅲ-4-2t, the western part of the Ⅲ-4-1xt, and the ecological maintenance area of the Ⅲ-5-2w. Overall, 61.47% of the area had a positive trend of NDVI change with the gravity center of high coverage mitigating to the northeast, and the ecological environment was improved. ③ Soil types and population density were the dominant factors affecting NDVI in Shandong Province, with q values of 0.174 and 0.130, respectively. The chief factor in the Ⅲ-5-3fn, Ⅲ-4-2t, and Ⅲ-4-1xt was population density, with q values higher than 0.22, and the dominant factors in the Ⅲ-5-2w were soil types and vegetation types, with q values of 0.326 and 0.227, respectively. The interaction of the two factors enhanced the influence of the single factor, and the relationship between the influencing factors showed two-factor enhancement and nonlinear enhancement. The q-value of population density ∩ relative humidity was the highest, with a value of 0.257 in the Ⅲ-5-3fn. The q-value of population density ∩ soil types was the highest in the Ⅲ-4-2t and Ⅲ-4-1xt, reaching 0.297 and 0.378, respectively. The q-value of soil types ∩ vegetation types was the highest, with a value of 0.444 in the Ⅲ-5-2w. The results are expected to provide valuable references for improving the ecological environment of Shandong Province and lay a scientific foundation to make different conservation strategies for the individual soil and water conservation zones.

Ultra-Fast Synthesis of Highly Dispersed Pt Nanoclusters Anchored on Sulfur-Doped Porous Carbon Carriers by Nanosecond Pulsed Laser for Hydrogen Evolution Reaction.

Nanosecond pulsed laser irradiation is employed for synthesis of highly active and stable Pt-based electrocatalysts by anchoring Pt nanoclusters on porous sulfur-doped carbon supports (L-Pt/SC). Strong metal-support interaction (SMSI) between Pt and S induces a local charge rearrangement and modulates the electronic structure of Pt surroundings, thus boosting the reaction kinetics and enhancing stability in long-term hydrogen evolution reaction (HER). The L-Pt/SC catalyst exhibits high activity toward HER, with an overpotential of 23 mV at current densities reaching 10 mA cm-2 and a Tafel slope of 24 mV dec-1. The unit mass activity of L-Pt/SC is calculated to be -10.8 A cm-2 mgPt -1 at an applied voltage of -0.3 V versus RHE. In situ Raman spectra reveals that L-Pt/SC catalyst exhibits fast hydrogen production efficiency and its electrocatalytic HER process is determined by the Tafel step. Density functional theory calculations suggest the strong bonding energy between SC and Pt induces the formation of smaller nanoclusters of L-Pt/SC during fast pulsed laser preparation, which increases the effective contact area during the HER process thereby increasing the activity per unit mass.

Carboxymethyl chitosan-based nanoparticles of acid response for the synergistic anti-tumor effect of PDT and chemotherapy.

The combination of multiple anti-tumor methods has shown significant application potential in overcoming the limitations of monotherapy. Photodynamic therapy (PDT) and chemotherapy combination is a promising strategy for reducing drug resistance and side effects. Here, inspired by the acidic environment of tumors, carboxymethyl chitosan-based pH-responsive nanovesicles were developed to co-deliver the chemotherapeutic drug doxorubicin (DOX) and photosensitizer 5-aminolevulinic acid (5-ALA). The in vitro drug release studies revealed that drugs could be responsively released when nanoparticles were triggered by the acidic environment. The controlled-release behavior improved drug retention and reduced the administration time. Our nanoparticles could significantly enhance the killing effect of drugs on tumor cells and increase intracellular levels of reactive oxygen species (ROS) compared to monotherapy, effectively achieving the effects of combined chemotherapy and PDT. The loaded DOX could kill tumor cells and the loaded 5-ALA could enhance the content of protoporphyrin IX (PpIX), resulting in excess ROS production to improve the effects of PDT. In summary, our nanoparticles could co-deliver the drugs and exert synergistical anti-tumor of PDT and chemotherapy by suppressing tumor cell proliferation and facilitating cell apoptosis.

Enhancing ocular protection against UVB: The role of irigenin in modulating oxidative stress and apoptotic pathways In Vivo.

Oxidative damage contributes to age-related macular degeneration. Irigenin possesses diverse pharmacologic properties, including antioxidative and antiapoptotic effects. Our in vivo experiments indicated that irigenin mitigates UVB-induced histopathologic changes and oxidative DNA damage. Histologic analyses and TUNEL staining revealed that this compound dose-dependently ameliorated UVB-induced retinal damage and apoptosis. Furthermore, irigenin substantially reduced the level of 8-hydroxyguanosine, a biomarker of UVB-induced oxidative DNA damage. We further explored the molecular mechanisms that mediate the protective effects of irigenin. Our findings suggested that UVB-induced generation of ROS disrupts the stability of the mitochondrial membrane, activating intrinsic apoptotic pathways; the underlying mechanisms include the release of cytochrome c, activation of caspase-9 and caspase-3, and subsequent degradation of PARP-1. Notably, irigenin reversed mitochondrial disruption and apoptosis. It also modulated the Bax and Bcl-2 expression but influenced the mitochondrial apoptotic pathways. Our study highlights the role of the Nrf2 pathway in mitigating the effects of oxidative stress. We found that UVB exposure downregulated, but irigenin treatment upregulated the expression of Nrf2 and antioxidant enzymes. Therefore, irigenin activates the Nrf2 pathway to address oxidative stress. In conclusion, irigenin exhibits protective effects against UVB-induced ocular damage, evidenced by the diminution of histological alterations. It mitigates oxidative DNA damage and apoptosis in the retinal tissues by modulating the intrinsic apoptotic pathways and the AIF mechanisms. Furthermore, irigenin effectively reduces lipid peroxidation, enhancing the activity of antioxidant enzymes by stimulating the Nrf2 pathway. This protective mechanism underscores the potential benefit of irigenin in combating UVB-mediated ocular damage.

A cross-sectional study of the association between blood cadmium and mortality among adults with myocardial infarction.

Cadmium (Cd) plays a key role in the occurrence of myocardial infarction (MI). We aimed to explore the association between blood Cd levels and all-cause mortality of MI on the basis of the National Health and Nutrition Examination Survey databases. This study included 800 adults with MI to obtain blood Cd concentrations and their follow-up information. The association between Cd concentrations and mortality was analyzed using Cox regression, restricted cubic spline (RCS) models, mediation analysis, receiver operating characteristic curve, and Kaplan-Meier curves. All the patients were divided into 4 groups according to the quartiles of blood Cd levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates indicated that Cd was the promoting factor of mortality, and patients with higher Cd had a higher death risk. The RCS model indicated an "inverted checkmark" shaped correlation between Cd levels and mortality, and a turning point of 1.06 µg/L was found. A significant positive correlation was observed on the left of the turning point. Grouped patients by turning point into 2 groups, Kaplan-Meier analysis showed that the low-concentration group had a lower death risk than the high-concentration group. Subgroup analysis revealed that the prognostic effect of Cd was more pronounced in patients with former smoking history, and receiver operating characteristic curve showed that blood Cd had a better-predicting function in patients with MI. Blood Cd levels were significantly related to all-cause mortality in patients with MI, especially in patients with Cd < 1.06 µg/L.

Gypenoside A-loaded mPEG-PLGA nanoparticles ameliorate high-glucose-induced retinal microvasculopathy by inhibiting ferroptosis.

Diabetic retinopathy (DR) is one of the chronic microvascular complications of type 2 diabetes mellitus (T2DM), which will cause retinal detachment and blindness without ideal therapies. Gypenoside A (GPA) are the main bioactive compound from Gynostemma pentaphyllum, and have various pharmacological effects. However, it suffered from poor bioavailability and potential cardiotoxicity in the clinical application. To overcome those limitations, in this study, nearly spherical nanoparticles (GPA-NP) with a mean particle size of 140.6 ± 22.4 nm were prepared by encapsulating GPA into mPEG-PLGA. This encapsulation efficiency was 84.4 ± 6.9 %, and the drug load was 4.02 %±0.35 %. The results showed that GPA-NP displayed more prolonged GPA release and higher bioavailability in vitro than GPA. GPA-NP obviously reduced the levels of oxidative stress markers and inflammatory cytokines in both retinal tissues of DR mice and high glucose-exposed HRMEC better than GPA alone. Mechanismly, GPA blocked the Nrf2-Keap1 interaction by binding with Kelch domain of Keap1 via alkyl and hydrogen bonds. Therefore, GPA-NP exerted more potent protectivity effects against high glucose-induced retinal microvascular endothelial ferroptosis in vitro and in vivo by activating Nrf2/HO-1/GPX4 pathway. It could be a promising therapeutic agent for preventing DR.

Convergent Multimodal Imaging Abnormalities in the Dorsal Precuneus in Subjective Cognitive Decline.

Background: A range of imaging modalities have reported Alzheimer's disease-related abnormalities in individuals experiencing subjective cognitive decline (SCD). However, there has been no consistent local abnormality identified across multiple neuroimaging modalities for SCD. Objective: We aimed to investigate the convergent local alterations in amyloid-ß (Aß) deposition, glucose metabolism, and resting-state functional MRI (RS-fMRI) metrics in SCD. Methods: Fifty SCD patients (66.4±5.7 years old, 19 men [38%]) and 15 normal controls (NC) (66.3±4.4 years old, 5 men [33.3%]) were scanned with both [18F]-florbetapir PET and [18F]-fluorodeoxyglucose PET, as well as simultaneous RS-fMRI from February 2018 to November 2018. Voxel-wise metrics were retrospectively analyzed, including Aß deposition, glucose metabolism, amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality(DC). Results: The SCD group showed increased Aß deposition and glucose metabolism (p < 0.05, corrected), as well as decreased ALFF, ReHo, and DC (p < 0.05, uncorrected) in the left dorsal precuneus (dPCu). Furthermore, the dPCu illustrated negative resting-state functional connectivity with the default mode network. Regarding global Aß deposition positivity, the Aß deposition in the left dPCu showed a gradient change, i.e., Aß positive SCD > Aß negative SCD > Aß negative NC. Additionally, both Aß positive SCD and Aß negative SCD showed increased glucose metabolism and decreased RS-fMRI metrics in the dPCu. Conclusions: The dorsal precuneus, an area implicated in early AD, shows convergent neuroimaging alterations in SCD, and might be more related to other cognitive functions (e.g., unfocused attention) than episodic memory.

Headspace-SERS assay for early mildewing tobacco leaves.

Mildewed tobacco leaves seriously impact on cigarette product quality and pose a health risk to person. However, early moldy tobacco leaves are hardly found by naked eyes in the workshop. In this work, we self-assemble AuAg nanoalloys on silicon wafers to construct Si/AuAg chips. The headspace-surface enhanced Raman scattering (SERS) protocol is developed to monitor volatile 1,2-dichloro-3-methoxybenzene (2,3-DCA) and 2,4,6-trichloroanisole (2,4,6-TCA) released from postharvest tobacco. Consequently, the visualization of the SERS peak at 1592 cm-1 assigned to ν(CC) after headspace collection for 10 min and the SERS intensity ratio of 1054 and 1035 cm-1 from 2,3-DCA and 2,4,6-TCA less than 0.5 could be used as indicators to predict early moldy tobacco. Additionally, with headspace collection time prolonging to 2 h, a SERS band at 682 cm-1 due to ν(CCl) of 2,4,6-TCA occurs, confirming the mildew of leaves. The headspace-SERS protocol paves a path for rapid and on-site inspection of the quality of tobacco leaves and cigarettes during storage with a portable Raman system.

Efficacy and Safety of Efdamrofusp Alfa versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized, Double-Masked, Active-Controlled, Noninferiority, Phase II Trial.

PURPOSE: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: Randomized, double-masked, multicenter, active-controlled, noninferiority phase II study. PARTICIPANTS: A total of 231 treatment-naive and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. METHODS: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa, or 2 mg aflibercept groups. Participants in all groups received 3 initial monthly loading doses, followed by treatment every 8 weeks, with assessment every 4 weeks up to week 52. MAIN OUTCOME MEASURES: The primary end point was the mean best-corrected visual acuity (BCVA) change from baseline to week 36. The prespecified noninferiority margin was set as -5 letters (80% confidence interval [CI]). RESULTS: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, and +12.0 letters, respectively; least squares mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. CONCLUSIONS: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Psychometric evaluation of the Chinese version of the Academic Resilience Scale-30 (C-ARS-30) in college students.

Background: Amidst the expansion of student enrollment in higher education, the well-being and retention rates of students have emerged as important concerns. Resilience, especially academic resilience, a multidimensional construct that can lead to academic success in adversity, is pivotal in enabling students to successfully cope with academic challenges. While the Academic Resilience Scale-30 (ARS-30) has been validated as an effective instrument in various languages, its applicability for Chinese students in higher education remains unexplored. Objective: This study aims to translate and validate the ARS-30 in Chinese, assessing its reliability and validity among Chinese college students in higher education. Methods: A convenience sample of 1,542 students participated in this study. The inventory included the demographic form, Chinese version of ARS-30 (C-ARS-30), 10-item Connor Davidson Resilience Scale (CD-RISC-10), and General Self-Efficacy Scale (GSES). The assessment of validity was conducted by analyzing content validity, construct validity, convergent and discriminant validity, as well as criterion-related validity. Construct validity was evaluated through Confirmatory Factor Analysis (CFA), Exploratory Factor Analysis (EFA) and Exploratory Structural Equation Modeling (ESEM). Reliability analysis was performed using Cronbach's alpha and test-retest reliability. Results: The C-ARS-30 demonstrated commendable content validity, with the CVI value of items ranging from 0.833 to 1.000, and a total scale CVI of 0.986. ESEM analysis revealed a solid four-factor structure, maintaining the scale's 30 items with excellent fit indices (χ2/df = 2.647, CFI = 0.937, TLI = 0.915, RMSEA = 0.057, SRMR = 0.027). The total score of C-ARS-30 exhibited positive correlations with the CD-RISC-10 (r = 0.542) and the GSES (r = 0.488). The scale demonstrated high internal consistency (Cronbach's α = 0.930) and test-retest reliability (0.794, p < 0.01). Conclusion: The C-ARS-30 is a reliable and valid instrument for assessing academic resilience among Chinese college students, offering a valuable tool for educational and psychological evaluations.

Systemic immune inflammation index is a valuable marker for predicting hemodialysis patients with depression: a cross-sectional study.

Objective: Maintenance hemodialysis (MHD) patients suffer from enormous physical, mental stress and poor quality of life, so an increasing number of patients are in a long-term state of depression. A prominent feature of MHD patients is chronic persistent inflammation, which is also an important mechanism for the onset of depression. Therefore, finding economically convenient inflammatory markers to predict and diagnose the onset of depression in MHD patients is of great value. As a novel inflammatory marker, systemic immune inflammation index (SII) can more comprehensively reflect the inflammation and immunity level of patients. This study aims to explore the relationship between SII and depressive symptoms in MHD patients. Methods: A cross-sectional study was conducted on 206 MHD patients from three dialysis centers. Based on the Hospital Anxiety and Depression Scale (HADS) scores, patients were divided into non-depression and depression groups. Inter group comparison and multivariate logistic regression analysis were performed to determine whether SII is an independent risk factor for depression in MHD patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SII on depression symptoms in MHD patients. Results: According to the HADS scale score, 38.83% of the included patients were in a state of depression. After adjusting for all confounding factors, MHD patients with SII>963.93 had a 4.709 times higher risk of depression than those with SII ≤ 478.32 (OR=4.709, 95% CI 1.821-12.178, P<0.01). ROC analysis showed that SII>685.11 was the best cutoff value for MHD depression patients, and the area under the curve (AUC) was 0.681. Conclusions: High SII is an independent risk factor for depressed MHD patients and an ideal inflammatory marker for predicting and identifying depression in MHD patients as assessed by the HADS scale.