Engineering an optimized hypercompact CRISPR/Cas12j-8 system for efficient genome editing in plants.

The Cas12j-8 nuclease, derived from the type V CRISPR system, is approximately half the size of Cas9 and recognizes a 5'-TTN-3' protospacer adjacent motif sequence, thus potentially having broad application in genome editing for crop improvement. However, its editing efficiency remains low in plants. In this study, we rationally engineered both the crRNA and the Cas12j-8 nuclease.

Prevalence of chronic kidney disease and anemia in Hirakud Command Area, Odisha, India: unveiling the role of environmental toxicants.

Background: The present community-based study assessed the prevalence of chronic kidney disease (CKD)/chronic kidney disease of unknown origin (CKDu) as well as anemia in some intense agricultural zones under Hirakud Command Area and evaluated their association with pesticides and heavy metal exposure.

Methods: Random cluster sampling method was used to assess the prevalence of CKD and anemia. Hematological analysis was carried out using autoanalyzer.

Exploring the antioxidant, anticancer properties and phenolic composition of Anchusa strigosa.

This study utilised A. strigose, a herbaceous plant widely used in folk medicine and commonly distributed in the Middle East. The antioxidant activity in the extracts of this plant has been underscored.

The basal level of salicylic acid represses the PRT6 N-degron pathway to modulate root growth and stress response in rice.

Maintaining a stable basal level of salicylic acid (SA) is crucial for plant growth, development, and stress response, though basal levels of SA vary significantly among plant species. However, the molecular mechanisms by which basal SA regulates plant growth and stress response remain to be elucidated. In this study, we performed a genetic screen to identify suppressors of the root growth defect in Osaim1, a rice mutant deficient in basal SA biosynthesis.

AXL: shapers of tumor progression and immunosuppressive microenvironments.

As research progresses, our understanding of the tumor microenvironment (TME) has undergone profound changes. The TME evolves with the developmental stages of cancer and the implementation of therapeutic interventions, transitioning from an immune-promoting to an immunosuppressive microenvironment. Consequently, we focus intently on the significant role of the TME in tumor proliferation, metastasis, and the development of drug resistance.

Ferroptosis-related genes participate in the microglia-induced neuroinflammation of spinal cord injury via NF-κB signaling: evidence from integrated single-cell and spatial transcriptomic analysis.

Background: Ferroptosis and immune responses are critical pathological events in spinal cord injury (SCI), whereas relative molecular and cellular mechanisms remain unclear.

Methods: Micro-array datasets (GSE45006, GSE69334), RNA sequencing (RNA-seq) dataset (GSE151371), spatial transcriptome datasets (GSE214349, GSE184369), and single cell RNA sequencing (scRNA-seq) datasets (GSE162610, GSE226286) were available from the Gene Expression Omnibus (GEO) database. Through weighted gene co-expression network analysis and differential expression analysis in GSE45006, we identified differentially expressed time- and immune-related genes (DETIRGs) associated with chronic SCI and differentially expressed ferroptosis- and immune-related genes (DEFIRGs), which were validated in GSE151371.

Factors associated with malaria in pregnancy among women attending ANC clinics in selected districts of the Ashanti Region, Ghana.

Background: Malaria is a disease deeply rooted in poverty. Malaria in pregnant women leads to severe complications, including low birth weight and neonatal mortality, which can adversely affect both mother and child. This study aimed to identify the factors associated with malaria in pregnancy among women attending antenatal care (ANC) clinics in three districts of the Ashanti Region, Ghana.

Targeting KRAS: from metabolic regulation to cancer treatment.

The Kirsten rat sarcoma viral oncogene homolog (KRAS) protein plays a key pathogenic role in oncogenesis, cancer progression, and metastasis. Numerous studies have explored the role of metabolic alterations in KRAS-driven cancers, providing a scientific rationale for targeting metabolism in cancer treatment. The development of KRAS-specific inhibitors has also garnered considerable attention, partly due to the challenge of acquired treatment resistance.

Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot study.

Background: Effective treatment of late antibody-mediated rejection (late AMR) is still an unmet medical need. Clearing donor-specific antibody (DSA) and preventing its rebound is the ideal goal of treatment.

Methods: We have summarized the clinical data from seven patients with late or chronic active AMR after renal transplantation who received daratumumab (Dara)-based treatment first (Phase 1) and then tocilizumab (TCZ) therapy (Phase 2).

A PDMS/chitosan/MPMs composite film based on multi-field coupling enhancement for African swine fever virus P72 protein detection.

African swine fever (ASF) is an acute hemorrhagic disease in pigs caused by the African swine fever virus (ASFV), which has a high mortality rate and brought great damage to global pig farming industry. At present, there is no effective treatment or vaccine to combat ASFV infection, so early detection of ASFV has become particularly important. Therefore, the PDMS/chitosan/MPMs composite film was proposed to detect ASFV P72.

Improving 3D deep learning segmentation with biophysically motivated cell synthesis.

Biomedical research increasingly relies on three-dimensional (3D) cell culture models and artificial-intelligence-based analysis can potentially facilitate a detailed and accurate feature extraction on a single-cell level. However, this requires for a precise segmentation of 3D cell datasets, which in turn demands high-quality ground truth for training. Manual annotation, the gold standard for ground truth data, is too time-consuming and thus not feasible for the generation of large 3D training datasets.

The integration of optimizing train timetables with EMU route plans.

Generally, to address the resource management issues in high-speed railway operations, particularly in the context of large-scale networked high-speed train transportation organizations, a phased optimization approach is introduced. This approach divides the problem into two stages: the high-speed train timetabling and the planning of Electric Multiple Unit (EMU) route. The lack of direct integration between these stages has hindered the flexible and efficient utilization of line capacity and EMU resources based on large-scale network, limiting the potential for mutual compensation and coordination among different types of resources across different regions.

The mediating role of inflammatory biomarkers in the association between serum copper and sarcopenia.

This study aims to investigate the association between serum copper (Cu), selenium (Se), zinc (Zn), Se/Cu and Zn/Cu ratios and the risk of sarcopenia. In this study, which involved 2766 adults aged ≥ 20 years enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016, multivariable logistic regression, restricted cubic spline (RCS) models and mediation analyses were used. After full adjustment, multivariable logistic regression revealed that higher serum copper levels were correlated with an increased risk of sarcopenia.

Associations between biomarkers of inflammation and depressive symptoms-potential differences between diabetes types and symptom clusters of depression.

Inflammation is a probable biological pathway underlying the relationship between diabetes and depression, but data on differences between diabetes types and symptom clusters of depression are scarce. Therefore, this cross-sectional study aimed to compare associations of a multimarker panel of biomarkers of inflammation with depressive symptoms and its symptom clusters between people with type 1 diabetes (T1D) and type 2 diabetes (T2D). This cross-sectional study combined data from five studies including 1260 participants (n = 706 T1D, n = 454 T2D).

Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria.

Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infections (UTIs). Invasion into bladder epithelial cells (BECs) on the bladder luminal surface via type 1 fimbria is the first critical step in UPEC infection. Although type 1 fimbria expression increases during UPEC invasion of BECs, the underlying regulatory mechanisms remain poorly understood.

Diverse real-life outcomes after intensive risk-adapted therapy for 1034 AML patients from the CETLAM Group.

Given the heterogeneity of acute myeloid leukemia patients, it is necessary to identify patients considered fit for intensive therapy but who will perform poorly, and in whom alternative approaches deserve investigation. We analyzed 1034 fit adults ≤70 years intensively treated between 2012 and 2022 in the CETLAM group. Young adults ( ≤ 60 years) presented higher remission rates and improved survival than older adults above that age (CR 79% vs.

Sequential addition of cations increases photoluminescence quantum yield of metal nanoclusters near unity.

Photoluminescence is one of the most intriguing properties of metal nanoclusters derived from their molecular-like electronic structure, however, achieving high photoluminescence quantum yield (PLQY) of metal core-dictated fluorescence remains a formidable challenge. Here, we report efficient suppression of the total structural vibrations and rotations, and management of the pathways and rates of the electron transfer dynamics to boost a near-unity absolute PLQY, by decorating progressive addition of cations. Specifically, with the sequential addition of Zn, Ag, and Tb into the 3-mercaptopropionic acids capped Au nanoclusters (NCs), the low-frequency vibration of the metal core progressively decreases from 144.

A membrane-targeted photoswitch restores physiological ON/OFF responses to light in the degenerate retina.

The lack of effective therapies for visual restoration in Retinitis pigmentosa and macular degeneration has led to the development of new strategies, such as optogenetics and retinal prostheses. However, visual restoration is poor due to the massive light-evoked activation of retinal neurons, regardless of the segregation of visual information in ON and OFF channels, which is essential for contrast sensitivity and spatial resolution. Here, we show that Ziapin2, a membrane photoswitch that modulates neuronal capacitance and excitability in a light-dependent manner, is capable of reinstating, in mouse and rat genetic models of photoreceptor degeneration, brisk and sluggish ON, OFF, and ON-OFF responses in retinal ganglion cells evoked by full-field stimuli, with reactivation of their excitatory and inhibitory conductances.

Tailoring industrial enzymes for thermostability and activity evolution by the machine learning-based iCASE strategy.

The pursuit of obtaining enzymes with high activity and stability remains a grail in enzyme evolution due to the stability-activity trade-off. Here, we develop an isothermal compressibility-assisted dynamic squeezing index perturbation engineering (iCASE) strategy to construct hierarchical modular networks for enzymes of varying complexity. Molecular mechanism analysis elucidates that the peak of adaptive evolution is reached through a structural response mechanism among variants.

From 2D kaolinite to 3D amorphous cement.

Kaolinite is a single 2D layer of kaolin or metakaolin (MK), common clays that can be characterized as layered 3D materials. We show that because of its chemical composition, kaolinite can be converted into an amorphous 3D material by chemical means. This dimensional transformation is possible due to the large surface to volume ratio and chemical reactivity of kaolinite.

Optimized molecule detection in localization microscopy with selected false positive probability.

Single-molecule localization microscopy (SMLM) allows imaging beyond the diffraction limit. Detection of molecules is a crucial initial step in SMLM. False positive detections, which are not quantitatively controlled in current methods, are a source of artifacts that affect the entire SMLM analysis pipeline.

Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice.

Reactive oxygen species exacerbate nonalcoholic steatohepatitis (NASH) by oxidizing macromolecules; yet how they promote NASH remains poorly understood. Here, we show that peroxidase activity of global hepatic peroxiredoxin (PRDX) is significantly decreased in NASH, and palmitic acid (PA) binds to PRDX1 and inhibits its peroxidase activity. Using three genetic models, we demonstrate that hepatic PRDX1 protects against NASH in male mice.

Limosilactobacillus reuteri fermented brown rice alleviates anxiety improves cognition and modulates gut microbiota in stressed mice.

Chronic stress disrupts gut microbiota homeostasis, contributing to anxiety and depression. This study explored the effects of Limosilactobacillus reuteri fermented brown rice (FBR) on anxiety using an ICR mouse chronic mild stress (CMS) model. Anxiety was assessed through body weight, corticosterone levels, neurotransmitter profiles, and behavioral tests.