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关键词： A 1 km nationwide NDVI dataset for China (1982-2015)   downscaling   High-Performance Super-Resolution (HPSR) method   Normalized Difference Vegetation Index (NDVI)   vegetation monitoring  

摘要： The Normalized Difference Vegetation Index (NDVI) serves as a crucial indicator for assessing extended vegetation trends. Existing 1 km MODIS NDVI products start from 2000, leaving a gap in high-resolution observations for 1982-2000 and limiting systematic studies of vegetation change across China. To fill this spatio-temporal void, we built a 1 km nationwide NDVI time series dataset covering 1982-2015 by downscaling the 5 km AVHRR NDVI with a High-Performance Super-Resolution (HPSR) method. The proposed network architecture is composed of three key submodules that work sequentially and synergistically i) A multi-scale feature extraction network first extracts texture information across different receptive fields through parallel convolutions at varying scales, achieving multi-scale fusion via feature splicing. (ii) The resulting fused features are then passed to an attention refinement network that utilizes the Convolutional Block Attention Module (CBAM incorporating channel and spatial attention mechanisms, to adaptively weight the fusedu features, thereby emphasizing significant vegetation regions while reducing irrelevant noise. (iii) Finally, the refined features are fed into a super-resolution network that utilizes up-sampling modules and residual blocks to reconstruct the feature maps to a high resolution. The model spatially downscales AVHRR NDVI data from an approximately 5 km resolution to 1 km, utilizing high-quality 1 km MODIS NDVI as a reference dataset, and integrating DEM terrain factors and the China Land Cover Database (CLCD) as ancillary data. The experimental findings indicate that the HPSR framework effectively mitigates the numerical centralization common in standard convolutional models through an integrated attention mechanism, achieving a significant reduction in MAE (0.050) and RMSE (0.061) while maintaining a PSNR above 27 dB. By ensuring a holistic enhancement of NDVI sequences from high spatial fidelity to long-term physical and logical c

关键词： Tryptophan   diabetes mellitus   GLP-1  

摘要： L-Tryptophan, an essential amino acid, precursor of serotonin, melatonin and niacin, has been implicated in glucose metabolism and gut hormone regulation. However, its role in diabetes remains obscure. This pilot study evaluated the effects of L-Tryptophan (Trp) supplementation on glycemic control, intestinal glucose absorption, biochemical markers and tissue histology in streptozotocin (STZ)-induced diabetic rats. Adult Wistar rats (n = 24) were divided into four groups: normal control, diabetic control, diabetic + Trp (50 mg/kg and Trp control. Diabetes was induced by STZ (50 mg/kg). Trp was administered orally for 10 days. Blood glucose, serum biochemical parameters, intestinal glucose absorption, and Na+/K+-ATPase activity were assessed. Qualitative histological analysis of pancreatic and hepatic tissues was performed. Trp treatment in diabetic rats significantly reduced blood glucose and intestinal glucose absorption compared to diabetic controls. Pancreatic and intestinal Na+/K+-ATPase(NKA) remained statistically insignificant (p > 0.669 and 0.369). Improvements were observed in serum protein and cholesterol levels, pancreatic and hepatic histology as well as pancreatic GLP-1. L-Tryptophan demonstrated improved glycemia, metabolic benefits and tissue integrity in diabetic rats. These findings are preliminary and are interpreted within the limitations of a short duration. Further Mechanistic studies may elucidate Tryptophan-mediated mechanisms to evaluate its relevance in hyperglycemia.

关键词： Enzymatic inhibitor   microscale thermophoresis   non-competitive inhibition   paraxonase-2   triazolo[4,3-a]quinoline  

摘要： A plethora of studies have demonstrated the pathophysiological roles played by paraxonase 2 (PON2) in oxidative stress control, inhibition of apoptosis, infections, and the progression of various types of malignancies. The continuous interest in PON2 has not gone hand in hand with the development of its inhibitors. Indeed, only one inhibitor for PON2, namely TQ416, is known, although neither its preparation nor a systematic structure-activity relationship analysis has been so far reported. Herein, we outline the first study aimed at the definition of structure-activity relationships of TQ416 by the preparation of a small library of its analogues. Successfully, we identified some [1,2,4]triazolo[4,3-a]quinoline derivatives more potent than TQ416 as PON2 inhibitors, and among them one endowed with an IC50 value in the nanomolar range. We tested the parent TQ416 and its most effective congener 2 in cells showing their effectiveness and complex behaviour.

关键词： Hypertensive disorders of pregnancy   fetal growth restriction   insulin-like growth factor binding protein-1   chordin-like 1   gestational hypertension  

摘要： Objective: To investigate the association between mid-pregnancy serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) and chordin-like 1 (CHRDL1) and the occurrence of fetal growth restriction (FGR) in late pregnancy among women with gestational hypertension (GH). Methods: This prospective nested case-control study was conducted within an established cohort of pregnant women with GH from January 2021 to January 2025. A total of 731 singleton pregnant women with GH at 20-24 gestational weeks were enrolled and followed up by dedicated nurses (those lost to follow-up were contacted at least three times) until late pregnancy (>= 28 weeks with 711 completing the entire follow-up. Based on prenatal ultrasound diagnosis, 106 cases of FGR were identified. These cases were individually matched in a 1:2 ratio (matching factors: maternal age, pre-pregnancy body mass index (BMI and parity) with 212 controls selected from women without FGR, resulting in a final nested case-control sample of 318 participants. Fasting serum samples were collected at 20-24 weeks of gestation, and IGFBP-1 and CHRDL1 levels were measured by enzyme-linked immunosorbent assay (ELISA). FGR occurrence was assessed based on estimated fetal weight (EFW) monitored by B-ultrasound. Spearman's correlation analysis evaluated associations between mid-pregnancy serum concentrations of IGFBP-1 and CHRDL1 with EFW. Conditional logistic regression identified determinants of FGR development in late pregnancy within the GH cohort. The discriminative performance of mid-pregnancy serum IGFBP-1 and CHRDL1 for late-pregnancy FGR prediction was assessed using receiver operating characteristic (ROC) curve analysis. Results: Among 731 pregnant women with GH, 20 (2.74%) were lost to follow-up, and 711 completed the entire follow-up;of these, 106 (14.91%) developed FGR. Following 1:2 matching with 212 controls, 318 participants were included in the nested analysis. Serum levels of IGFBP-1 and CHRDL1 were sign

关键词： Dietary fiber   cancer   immunotherapy   NSCLC   gut microbiome   SCFA   butyrate  

摘要： The gut microbiome is increasingly recognized as a key modulator of cancer immunotherapy efficacy. Given that diet is one of the most important determinants of the gut microbiome composition and function, nutritional strategies have emerged as promising tools to modulate anti-tumor immune responses. Here, we demonstrate that dietary supplementation with inulin reduces tumor growth and enhances alpha PD-1 efficacy in mice. These effects were associated with increased frequencies of intra-tumoral CD8(+) and CD4(+) T cells, particularly CCR9(+)CXCR3(+) subsets, and enrichment of beneficial taxa such as Akkermansia and Lachnospiraceae, alongside elevated short-chain fatty acids (SCFA) levels. Among the SCFA, butyrate alone recapitulated the anti-tumor effect of inulin and had an additive effect when combined with alpha PD-1 therapy in a CD8(+) T cell-dependent manner. Butyrate exerted its anti-tumor effects by transcriptional changes in CD8(+) T cells involving activation of proliferation, trafficking, and metabolic pathways. In a cohort of 117 non-small cell lung cancer (NSCLC) patients amenable to immunotherapy, the median dietary fiber intake was lower than previously published studies but correlated with enrichment of Faecalibacterium praunitzii and metabolic pathways related to sucrose degradation and tryptophan biosynthesis. Collectively, our findings highlight the therapeutic potential of targeting diet-microbiome-immune system interactions to improve cancer immunotherapy outcomes.

关键词： Sars-CoV-2   deep mutational scanning   spike   receptor-binding domain   antibody  

摘要： SARS-CoV-2 continuously accumulates mutations in the spike receptor-binding domain (RBD affecting both viral infectivity and antibody evasion. Systematic characterization of RBD mutations is therefore essential for understanding viral adaptation under immune pressure and predicting evolutionary trajectories. In this study, we employed a two-step, non-replicating pseudovirus deep mutational scanning (DMS) platform to measure the effects of all single amino acid substitutions in the RBD of Omicron variant JN.1 and its descendant lineage XEC within a full-length spike background. To identify representative antibodies for escape profiling, we first evaluated six RBD-targeting monoclonal antibodies against JN.1 and XEC pseudoviruses. Only BD55-1205 and 719-14 sIgA retained substantial neutralizing activity and were selected for subsequent escape mapping. The results showed that most single RBD amino acid mutations did not significantly enhance pseudovirus cellular invasion. Among mutations that are functionally retaining and confer marked escape from either antibody, most high escape substitutions cluster within the receptor-binding motif (RBM) and receptor-binding ridge. Furthermore, BD55-1205 and 719-14 sIgA each exhibited distinct, antibody-specific escape sites, demonstrating that different epitope preferences exert unique selective pressures within the same viral lineage. Overall, this pseudovirus-based DMS analysis elucidates the molecular mechanisms of immune escape and fitness for the JN.1 and XEC lineages. Our findings provide critical insights for forecasting SARS-CoV-2 evolution under population immunity and offer guidance for assessing emerging variants, selecting vaccine strains, and optimizing therapeutic antibodies.

关键词： hypervirulent Klebsiella pneumoniae   carbapenem resistance   italic>rmpDnic site   rmpADC cascade   poly T-track  

摘要： K39 Klebsiella pneumoniae, a previously unrecognized hypervirulent serotype, was isolated from a septicemic neonate. It was assessed for the acquisition of hypervirulence determinants and virulence potential. Transmissibility of plasmids, functional expression of virulence determinants, capsule visualization (TEM comparative genome analysis and virulence potential (in vitro, in vivo assays) were studied. Carbapenem-resistant ST985-K39 K. pneumoniae (Sil80 harbored rmpA, rmpA2, iucA, iroB, peg-344 in IncFIB(K)/IncHI1B(pNDM-MAR) hypervirulent plasmid;blaNDM-1 in IncFIB(pQIL)/IncFII(K) plasmid and other antimicrobial resistance determinants in IncFII plasmid. Comparative genomic analysis of global K39 isolates revealed, for the first time, the acquisition of a hypervirulent plasmid in the K39 study isolate. IncFIB(pQil)/IncFII(K) carrying blaNDM-1 showed successful conjugation independently. However, hypervirulent plasmid [IncFIB(K)/IncHI1B(pNDM-MAR could not successfully transmit alone, but was co-transmitted along with IncFII plasmid, because of nic site similarity. The strain was serum-resistant and produced a strong biofilm. Despite possessing hypervirulence determinants, Sil80 showed a negative string test, a thin capsule, and attenuated virulence in adult mice. Deletion of 10 amino acids in RmpD and mutation in rmpADC promoter having 10T track (P10T) were observed. Expression of rmpA, rmpD, and rmpC in Sil80 was also downregulated. Mutations in the rmpADC promoter and truncated RmpD of Sil80 caused attenuated virulence in adult mice;nonetheless, the isolate was capable of causing sepsis in an immunocompromised neonate. The transfer of the non self-conjugative virulence plasmid was facilitated by the helper plasmid with a similar nic site. This phenomenon could facilitate the spread of such plasmids to hitherto unknown serotypes.

关键词： Bandgap engineering   charge carrier   defect-mediated catalysis   energy materials   LSMO nanoperovskites   photocatalytic kinetics   photon scattering   solar cell coatings  

摘要： Renewable energy requires photovoltaic (PV) technologies, which can overcome the drawbacks of previously researched silicon cells in efficiency, heaviness, and price. Perovskite nanomaterials are promising options, but questions about their stability and practical use remain unresolved. This research investigated La(1-x)Sr(x)MnO3 (LSMO) nanoperovskites as performance-enhancing coatings on PV cells. The samples of LSMO with different concentrations of Sr (x = 0.5, 0.7) have been synthesised by co-precipitation and identified using XRD, FTIR, UV-Vis, photoluminescence, BET surface analysis and antimicrobial tests. The composition-dependent reduction in the grain size, surface area and modulation of the band gaps (5.69-5.94 eV) were found to enhance photon absorption and charge transport. LSMO coatings incorporated greatly increased the output power and efficiency, with x = 0.7 composition improving the efficiency by almost 40% over that of the uncoated cells. Critical knowledge gap between the design of perovskite materials and actual PV operation, demonstrating that LSMO is a potentially successful source of solar technology.

关键词： Bergamottin   acute kidney injury   ferroptosis   BACE-1   GPX4  

摘要： Bergamottin is a natural furanocoumarin compound that possesses antioxidative and anticancer properties. However, the effect of bergamottin (BGM) on acute kidney injury (AKI) is unknown. Human renal tubular HK-2 cells and mice that received cisplatin were pretreated with BGM, after which their cytotoxicity and renal function were evaluated. BGM pretreatment alleviated cisplatin-induced cytotoxicity in vitro. Moreover, synergistic protection against cisplatin-induced cytotoxicity was observed when BGM and apoptosis, autophagy, or necrosis inhibitors were used together. There was no synergistic effect between BGM and the ferroptosis inhibitor. Furthermore, BGM significantly inhibited ferroptosis induction-induced damage to HK-2 cells. BGM pretreatment alleviated renal dysfunction and pathological damage by reducing renal proinflammatory cytokines and inhibiting inflammatory cell infiltration, lipid peroxidation and ferroptosis. Based on predictions by SwissTarget and molecular docking, BGM strongly interacts with residues of beta-secretase 1 (BACE-1) via hydrogen and hydrophobic interactions. Moreover, BACE-1 expression was significantly upregulated in the kidneys of AKI mice and HK-2 cells treated with cisplatin but markedly reduced following BGM intervention. Interestingly, siRNA-mediated silencing of BACE-1 in vitro substantially abolished the protective effect of BGM on HK-2 cells that received cisplatin. BGM effectively alleviated AKI by targeting BACE-1 to reduce ferroptosis, suggesting that BGM could be developed as a potential agent for managing and pretreating AKI.

关键词： SIRT1   single-nucleotide polymorphism   rs3758391   rs10823108   genotyping  

摘要： Polymorphisms in antioxidant proteins, such as sirtuin 1 (SIRT1 may contribute to susceptibility to type 2 diabetes (T2D) and diabetic nephropathy (DN). SIRT1 rs3758391 and rs10823108 are associated with T2D and DN in other ethnicities;however, their role in susceptibility to T2D and DN in Saudi patients is unclear. Therefore, we investigated this association and examined the relationship between SIRT1 variants and serum SIRT1 protein levels. This case-control study included 126 patients with T2D (49 with DN and 77 controls). The associations between single-nucleotide polymorphisms and T2D with or without DN and SIRT1 expression were explored using logistic regression analysis. SIRT1 rs3758391 presence in controls and patients with T2D without DN of the T/C type and T/C genotype differed significantly. The presence of rs3758391 between patients with T2D with and without the T/C type and T/C genotype differed significantly. However, no association was observed with rs10823108. There was no association between rs3758391 and serum SIRT1 protein levels. SIRT1 rs3758391 was associated with T2D and DN in this Saudi cohort;however, rs10823108 showed no association. Serum SIRT1 was elevated in T2D irrespective of DN but was not correlated with rs3758391. These preliminary findings require further confirmation in future studies.