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Global warming has accelerated lake salinization, driving changes in microbial community structure and function. However, the dynamics of viral communities in response to salinity remain unclear. Here, we apply metagenomic sequencing to a lake on the Qinghai–Tibet Plateau, spanning a broad salinity gradient, to investigate viral community dynamics. Our findings reveal that salinity strongly influences viral composition and modulates viral lifestyles. Temperate viruses increase in relative abundance along the salinity gradient, whereas virulent viruses show a corresponding decline. These shifts are mirrored in the prokaryotic communities, with Alphaproteobacteria and their infecting temperate viruses, notably Casadabanvirus , becoming more prevalent in higher salinity zones. Viral genomes encode genes associated with osmotic stress adaptation, DNA recombination, and nutrient transport, which may facilitate host adaptation to saline stress. This study provides valuable insights into the interplay between viral and prokaryotic communities in response to lake salinization. Composition of viral communities, lifestyle of viruses, and virus–host interactions change dynamically in response to increasing lake salinity as the climate warms, according to metagenomic sequencing in a lake on the Qinghai–Tibet Plateau.

Autophagy is activated to maintain cellular energy homeostasis in response to nutrient starvation. However, au- tophagy is not persistently activated, which is poorly understood at a mechanistic level. Here, we report that turn- over of FoxO1 is involved in the dynamic autophagic process caused by glutamine starvation. X-box-binding protein- lu （XBP-lu） has a critical role in FoxO1 degradation by recruiting FoxO1 to the 20S proteasome. In addition, the phosphorylation of XBP-lu by extracellular regulated protein kinasesl/2 （ERK1/2） on Ser61 and Ser176 was found to be critical for the increased interaction between XBP-lu and FoxO1 upon glutamine starvation. Furthermore, knockdown of XBP-lu caused the sustained level of FoxO1 and the persistent activation of autophagy, leading to a significant decrease in cell viability. Finally, the inverse correlation between XBP-lu and FoxO1 expression agrees well with the expression profiles observed in many human cancer tissues. Thus, our findings link the dynamic process of autophagy to XBP-lu-induced FoxO1 degradation.

5-Hydroxymethylcytosine （5hmC） is an important mammalian DNA epigenetic modification that has been linked to gene regulation and cancer pathogenesis. Here we explored the diagnostic potential of 5hmC in circulating cell-free DNA （cfDNA） using a sensitive chemical labeling-based low-input shotgun sequencing approach. We sequenced cell- free 5hmC from 49 patients of seven different cancer types and found distinct features that could be used to predict cancer types and stages with high accuracy. Specifically, we discovered that lung cancer leads to a progressive global loss of 5hmC in cfDNA, whereas hepatocellular carcinoma and pancreatic cancer lead to disease-specific changes in the cell-free hydroxymethylome. Our proof-of-principle results suggest that cell-free 5hmC signatures may potentially be used not only to identify cancer types but also to track tumor stage in some cancers.

Spermatogonial stem cells （SSCs） can produce numerous male gametes after transplantation into recipient testes, presenting a valuable approach for gene therapy and continuous production of gene-modified animals. However, successful genetic manipulation of SSCs has been limited, partially due to complexity and low efficiency of currently available genetic editing techniques. Here, we show that efficient genetic modifications can be introduced into SSCs using the CRISPR-Cas9 system. We used the CRISPR-Cas9 system to mutate an EGFP transgene or the endogenous Crygc gene in SCCs. The mutated SSCs underwent spermatogenesis after transplantation into the seminiferous tubules of infertile mouse testes. Round spermatids were generated and, after injection into mature oocytes, supported the production of heterozygous offspring displaying the corresponding mutant phenotypes. Furthermore, a disease-causing mutation in Crygc （Crygc-/-） that pre-existed in SSCs could be readily repaired by CRISPR-Cas9-induced nonhomologous end joining （NHEJ） or homology-directed repair （HDR）, resulting in SSC lines carrying the corrected gene with no evidence of off-target modifications as shown by whole-genome sequencing. Fertilization using round spermatids generated from these lines gave rise to offspring with the corrected phenotype at an efficiency of 100%. Our results demonstrate efficient gene editing in mouse SSCs by the CRISPR-Cas9 system, and provide the proof of principle of curing a genetic disease via gene correction in SSCs.

Self-assembly has a unique presence when it comes to creating complicated, ordered supramolecular architectures from simple components under mild conditions. Here, we describe a self-assembly strategy for the generation of the first homogeneous supramolecular metal-organic framework (SMOF-1) in water at room temperature from a hexaarmed [Ru(bpy) 3 ] 2+ -based precursor and cucurbit[8]uril (CB[8]). The solution-phase periodicity of this cubic transition metal-cored supramolecular organic framework (MSOF) is confirmed by small-angle X-ray scattering and diffraction experiments, which, as supported by TEM imaging, is commensurate with the periodicity in the solid state. We further demonstrate that SMOF-1 adsorbs anionic Wells−Dawson-type polyoxometalates (WD-POMs) in a one-cage-one-guest manner to give WD-POM@SMOF-1 hybrid assemblies. Upon visible-light (500 nm) irradiation, such hybrids enable fast multi-electron injection from photosensitive [Ru(bpy) 3 ] 2+ units to redox-active WD-POM units, leading to efficient hydrogen production in aqueous media and in organic media. The demonstrated strategy opens the door for the development of new classes of liquid-phase and solid-phase ordered porous materials. Self-assembly is robust in creating advanced, homogeneous architectures under mild conditions. Here, the authors describe the generation of the first 3D metal-cored supramolecular organic framework using this strategy and illustrate its capacity in catalysing visible light-induced H 2 production.

Objective： The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase （MTHFR） C677T excision repair cross-complementation group 1 （ERCC1） genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer （NSCLC）. Methods： A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regi- mens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 Cl18T were genotyped using the TaqMan methods. Results： The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype （TT or CT） （41.2% versus 19.1%, P=0.01 ）. Median time to progression （TTP） of patients with MTHFR CC genotype was longer than that of patients with variant genotype （7.6 months versus 5.0 months, P=0.003）. No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions： Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

Self-assembly has emerged as a powerful approach to generating complex supramolecular architectures. Despite there being many crystalline frameworks reported in the solid state, the construction of highly soluble periodic supramolecular networks in a three-dimensional space is still a challenge. Here we demonstrate that the encapsulation motif, which involves the dimerization of two aromatic units within cucurbit[8]uril, can be used to direct the co-assembly of a tetratopic molecular block and cucurbit[8]uril into a periodic three-dimensional supramolecular organic framework in water. The periodicity of the supramolecular organic framework is supported by solution-phase small-angle X-ray-scattering and diffraction experiments. Upon evaporating the solvent, the periodicity of the framework is maintained in porous microcrystals. As a supramolecular ‘ion sponge’, the framework can absorb different kinds of anionic guests, including drugs, in both water and microcrystals, and drugs absorbed in microcrystals can be released to water with selectivity. The construction of soluble periodic supramolecular three-dimensional networks is challenging. Here, the authors use an encapsulated dimerization strategy to direct the assembly of a periodic three-dimensional supramolecular organic framework and evaluate its absorption properties.

The 56-day feeding trial was carried out to investigate the effects of dietary tryptophan (Trp) on growth performance, digestive and absorptive enzyme activities, intestinal antioxidant capacity, and appetite and GH–IGF axis-related genes expression of hybrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂). A total of 864 hybrid catfish (21.82 ± 0.14 g) were fed six different experimental diets containing graded levels of Trp at 2.6, 3.1, 3.7, 4.2, 4.7, and 5.6 g kg−1 diet. The results indicated that dietary Trp increased (P < 0.05) (1) final body weight, percent weight gain, specific growth rate, feed intake, feed efficiency, and protein efficiency ratio; (2) fish body protein, lipid and ash contents, protein, and ash production values; (3) stomach weight, stomach somatic index, liver weight, intestinal weight, length and somatic index, and relative gut length; and (4) activities of pepsin in the stomach; trypsin, chymotrypsin, lipase, and amylase in the pancreas and intestine; and γ-glutamyl transpeptidase, Na+, K+-ATPase, and alkaline phosphatase in the intestine. Dietary Trp decreased malondialdehyde content, increased antioxidant enzyme activities and glutathione content, but downregulated Keap1 mRNA expression, and upregulated the expression of NPY, ghrelin, GH, GHR, IGF1, IGF2, IGF1R, PIK3Ca, AKT1, TOR, 4EBP1, and S6K1 genes. These results indicated that Trp improved hybrid catfish growth performance, digestive and absorptive ability, antioxidant status, and appetite and GH–IGF axis-related gene expression. Based on the quadratic regression analysis of PWG, SGR, and FI, the dietary Trp requirement of hybrid catfish (21.82–39.64 g) was recommended between 3.96 and 4.08 g kg−1 diet (9.4–9.7 g kg−1 of dietary protein).

Although much progress has been made in artificial intelligence (AI), several challenges remain substantial obstacles to the development and translation of AI systems into clinical practice. Even large language models, which show excellent performance on various tasks, have progressed slowly in clinical practice tasks. Providing precise and explainable treatment plans with personalized details remains a big challenge for AI systems due to both the highly specialized medical knowledge required and patients' complicated conditions. This study aimed to develop an explainable and efficient decision support system named H-SYSTEM to assist neurosurgeons in diagnosing and treating patients with hypertensive intracerebral hemorrhage. The system was designed to address the limitations of existing AI systems by integrating a medical domain knowledge graph to enhance decision-making accuracy and explainability. The H-SYSTEM consists of 3 main modules: the key named entity recognition (NER) module, the semantic analysis and representation module, and the reasoning module. Furthermore, we constructed a medical domain knowledge graph for hypertensive intracerebral hemorrhage, named HKG, which served as an external knowledge brain of the H-SYSTEM to enhance its text recognition and automated decision-making capability. The HKG was exploited to guide the training of the semantic analysis and representation module and reasoning module, which makes the output of the H-SYSTEM more explainable., To assess the performance of the H-SYSTEM, we compared it with doctors and different large language models. The outputs based on HKG showed reliable performance as compared with neurosurgical doctors, with an overall accuracy of 94.87%. The bidirectional encoder representations from transformers, inflated dilated convolutional neural network, bidirectional long short-term memory, and conditional random fields (BERT-IDCNN-BiLSTM-CRF) model was used as the key NER module of the H-SYSTEM due to its fast convergence and efficient extraction of key named entities, achieved the highest performance among 7 key NER models (precision=92.03, recall=90.22, and F1-score=91.11), significantly outperforming the others. The H-SYSTEM achieved an overall accuracy of 91.74% in treatment plans, showing significant consistency with the gold standard (P<.05), with diagnostic measures achieving 88.18% accuracy, 97.03% area under the curve (AUC), and a κ of 0.874; surgical therapy achieving 98.53% accuracy, 98.53% AUC, and a κ of 0.971; and rescue therapies achieving 89.50% accuracy, 94.67% AUC, and a κ of 0.923 (all P<.05). Furthermore, the H-SYSTEM showed high reliability and efficiency when compared to doctors and ChatGPT, achieving statistically higher accuracy (95.26% vs 91.48%, P<.05). Additionally, the H-SYSTEM achieved a total accuracy of 92.22% (ranging from 91.14% to 95.35%) in treatment plans for 605 additional patients from 6 different medical centers. The H-SYSTEM showed significantly high efficiency and generalization capacity in processing electronic medical records, and it provided explainable and elaborate treatment plans. Therefore, it has the potential to provide neurosurgeons with rapid and reliable decision support, especially in emergency conditions. The knowledge graph-enhanced deep-learning model exhibited excellent performance in the clinical practice tasks.

[Objective]The model of regionalization management of specific equine disease-free zone were analysed and discussed. [Methods]International animal epidemics regionalization management experience and specific equine disease-free zone establishment were analysed and discussed based on the State and OIE principles. [Results]The regionalization management of specific equine disease-free zone with county administrative regions level of international recognition was established first in China,combined with the region＇s geographical barrier and animal health. [Conclusion]The aim is to to provide experience and reference for other areas to establish specific disease-free zone.