Brain Stimulation of Dorsolateral Prefrontal Cortices Influences Impulsivity in Delay Discounting Choices.

Intertemporal decision-making is pivotal for human interests and health. Recently, studies instructed participants to make intertemporal choices for both themselves and others, but the specific mechanisms are still debated. To address the issue, in the current study, the cost-unneeded conditions (i.e., "Self Immediately - Self Delay" and "Other Immediately - Other Delay" conditions) and the cost-needed conditions (i.e., "Self Immediately - Other Delay" and "Self delay - Other immediately" conditions) were set with the identity of OTHER being a stranger. We manipulated the magnitude of reward (Experiment 1) and disrupted the activation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation (rTMS; Experiment 2). We found that both the behavioral and rTMS manipulations increased smaller but sooner choice probability via reducing self-control function. The reduced self-control function elicited by rTMS affected both self- and other-related intertemporal choices via increasing the choice preference for SS options, which may help people deeply understand the relationship between self- and other-related intertemporal choices in processing mechanism, especially when the "OTHER" condition is set as a stranger.

Prognostic significance of collagen signatures in pancreatic ductal adenocarcinoma obtained from second-harmonic generation imaging.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest types of cancer, and it will be meaningful to search for new biomarkers with prognostic value to help clinicians tailor therapeutic strategies. METHODS: Here we tried to use an advanced optical imaging technique, multiphoton microscopy (MPM) combining second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging, for the label-free detection of PDAC tissues from a cohort of 149 patients. An automated image processing method was used to extract collagen features from SHG images and the Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the prognostic value of collagen signatures. RESULTS: SHG images clearly show the different characteristics of collagen fibers in tumor microenvironment. We gained eight collagen morphological features, and a Feature-score was derived for each patient by the combination of these features using ridge regression. Statistical analyses reveal that Feature-score is an independent factor, and can predict the overall survival of PDAC patients as well as provide well risk stratification. CONCLUSIONS: SHG imaging technique can potentially be a tool for the accurate diagnosis of PDAC, and this optical biomarker (Feature-score) may help clinicians make more approximate treatment decisions.

Papiliotrema flavescens, a plant growth-promoting fungus, alters root system architecture and induces systemic resistance through its volatile organic compounds in Arabidopsis.

The current trend in agricultural development is the establishment of sustainable agricultural systems. This involves utilizing and implementing eco-friendly biofertilizers and biocontrol agents as alternatives to conventional fertilizers and pesticides. A plant growth-promoting fungal strain, that could alter root system architecture and promote the growth of Arabidopsis seedlings in a non-contact manner by releasing volatile organic compounds (VOCs) was isolated in this study. 26S rDNA sequencing revealed that the strain was a yeast-like fungus, Papiliotrema flavescens. Analysis of plant growth-promoting traits revealed that the fungus could produce indole-3-acetic acid and ammonia and fix nitrogen. Transcriptome analysis in combination with inhibitor experiments revealed that P. flavescens VOCs triggered metabolic alterations, promoted auxin accumulation and distribution in the roots, and coordinated ethylene signaling, thus inhibiting primary root elongation and inducing lateral root formation in Arabidopsis. Additionally, transcriptome analysis and fungal infection experiments confirmed that pretreatment with P. flavescens stimulated the defense response of Arabidopsis to boost its resistance to the pathogenic fungus Botrytis cinerea. Solid-phase microextraction, which was followed by gas chromatography-mass spectrometry analysis, identified three VOCs (acetoin, naphthalene and indole) with significant plant growth-promoting attributes. Their roles were confirmed using further pharmacological experiments and upregulated expression of auxin- and ethylene-related genes. Our study serves as an essential reference for utilizing P. flavescens as a potential biological fertilizer and biocontrol agent.

Investigation the mechanism of iron overload-induced colonic inflammation following ferric citrate exposure.

Iron overload occurs due to excessive iron intake compared to the body's demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

SIRT1 activation ameliorates rhesus monkey liver fibrosis by inhibiting the TGF-ß/smad signaling pathway.

TGF-ß/Smad signaling pathway plays an important role in the pathogenesis and progression of liver fibrosis. Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+) dependent enzyme and responsible for deacetylating the proteins. Increasing numbers of reports have shown that the molecular mechanism of SIRT1 as an effective therapeutic target for liver fibrosis but the transformation is not very clear. In the present study, liver fibrotic tissues were screened by staining with Masson, hematoxylin-eosin staining (H&E) and Immunohistochemistry (IHC) for histopathological observation from the liver biopsy of seventy-seven rhesus monkey, which fixed with 4% paraformaldehyde (PFA) after treatment with high-fat diet (HFD) for two years. And the liver function was further determined by serum biochemical tests. The mRNA levels and protein expression of rat hepatic stellate (HSC-T6) cells were determined after treatment with Resveratrol (RSV) and Nicotinamide (NAM), respectively. The results showed that with the increasing of hepatic fibrosis in rhesus monkeys, the liver function impaired, and the transforming growth factor-ß1 (TGF-ß1), p-Smad3 (p-Smad3) and alpha-smooth muscle actin (α-SMA) was up-regulated, while SIRT1 and Smad7 were down-regulated. Moreover, when stimulated the HSC-T6 with RSV to activate SIRT1 for 6, 12, and 24 h, the results showed that RSV promoted the expression of smad7, while the expression of TGF-ß1, p-Smad3 and α-SMA were inhibited. In contrast, when the cells stimulated with NAM to inhibit SIRT1 for 6, 12, and 24 h, the Smad7 expression was decreased, while TGF-ß1, p-Smad3, and α-SMA expressions were increased. These results indicate that SIRT1 acts as an important protective factor for liver fibrosis, which may be attributed to inhibiting the signaling pathway of TGF-ß/Smad in hepatic fibrosis of the rhesus monkey.

MTS-LOF: Medical Time-Series Representation Learning via Occlusion-Invariant Features.

Medical time series data are indispensable in healthcare, providing critical insights for disease diagnosis, treatment planning, and patient management. The exponential growth in data complexity, driven by advanced sensor technologies, has presented challenges related to data labeling. Self-supervised learning (SSL) has emerged as a transformative approach to address these challenges, eliminating the need for extensive human annotation. In this study, we introduce a novel framework for Medical Time Series Representation Learning, known as MTS-LOF. MTS-LOF leverages the strengths of Joint-Embedding SSL and Masked Autoencoder (MAE) methods, offering a unique approach to representation learning for medical time series data. By combining these techniques, MTS-LOF enhances the potential of healthcare applications by providing more sophisticated, context-rich representations. Additionally, MTS-LOF employs a multi-masking strategy to facilitate occlusion-invariant feature learning. This approach allows the model to create multiple views of the data by masking portions of it. By minimizing the discrepancy between the representations of these masked patches and the fully visible patches, MTS-LOF learns to capture rich contextual information within medical time series datasets. The results of experiments conducted on diverse medical time series datasets demonstrate the superiority of MTS-LOF over other methods. These findings hold promise for significantly enhancing healthcare applications by improving representation learning. Furthermore, our work delves into the integration of Joint-Embedding SSL and MAE techniques, shedding light on the intricate interplay between temporal and structural dependencies in healthcare data. This understanding is crucial, as it allows us to grasp the complexities of healthcare data analysis.

Non-cytopathic bovine viral diarrhea virus (BVDV) inhibits innate immune responses via induction of mitophagy.

Bovine viral diarrhea virus (BVDV) belongs to the genus Pestivirus within the family Flaviviridae. Mitophagy plays important roles in virus-host interactions. Here, we provide evidence that non-cytopathic (NCP) BVDV shifts the balance of mitochondrial dynamics toward fission and induces mitophagy to inhibit innate immune responses. Mechanistically, NCP BVDV triggers the translocation of dynamin-related protein (Drp1) to mitochondria and stimulates its phosphorylation at Ser616, leading to mitochondrial fission. In parallel, NCP BVDV-induced complete mitophagy via Parkin-dependent pathway contributes to eliminating damaged mitochondria to inhibit MAVS- and mtDNA-cGAS-mediated innate immunity responses, mtROS-mediated inflammatory responses and apoptosis initiation. Importantly, we demonstrate that the LIR motif of ERNS is essential for mitophagy induction. In conclusion, this study is the first to show that NCP BVDV-induced mitophagy plays a central role in promoting cell survival and inhibiting innate immune responses in vitro.

Knowledge distillation under ideal joint classifier assumption.

Knowledge distillation constitutes a potent methodology for condensing substantial neural networks into more compact and efficient counterparts. Within this context, softmax regression representation learning serves as a widely embraced approach, leveraging a pre-established teacher network to guide the learning process of a diminutive student network. Notably, despite the extensive inquiry into the efficacy of softmax regression representation learning, the intricate underpinnings governing the knowledge transfer mechanism remain inadequately elucidated. This study introduces the 'Ideal Joint Classifier Knowledge Distillation' (IJCKD) framework, an overarching paradigm that not only furnishes a lucid and exhaustive comprehension of prevailing knowledge distillation techniques but also establishes a theoretical underpinning for prospective investigations. Employing mathematical methodologies derived from domain adaptation theory, this investigation conducts a comprehensive examination of the error boundary of the student network contingent upon the teacher network. Consequently, our framework facilitates efficient knowledge transference between teacher and student networks, thereby accommodating a diverse spectrum of applications.

Hydrous ruthenium oxide triggers template-free and spontaneous growth of metal nanostructures.

Intrinsically conductive ruthenium oxide is an excellent material for energy storage and conversion. Herein, we present hydrous RuO2 (H-RuO2) as a potent reducing agent to achieve spontaneous growth of multiple noble metals at room temperature. Self-assembled gold and platinum, comprising small-sized nanoparticles, are generated on the surface of H-RuO2 without the need for additional templates. Structural analysis reveals that the disordered structure and the presence of oxygen vacancies trigger interfacial redox reactions between H-RuO2 and oxidative metal salts. The resulting integrated nanostructures, consisting of a metal oxide and different metals (H-RuO2@metal), are subsequently used to treat inflammatory bowel diseases. In addition to biomedical applications, our developed synthetic strategy, using reactive oxides to spontaneously generate multicomponent nanostructures, also holds great significance for other catalysis-based applications.

Wearable Sensors for Breath Monitoring Based on Water-Based Hexagonal Boron Nitride Inks Made with Supramolecular Functionalization.

Wearable humidity sensors are attracting strong attention as they allow for real-time and continuous monitoring of important physiological information by enabling activity tracking as well as air quality assessment. Amongst 2Dimensional (2D) materials, graphene oxide (GO) is very attractive for humidity sensing due to its tuneable surface chemistry, high surface area, processability in water, and easy integration onto flexible substrates. However, strong hysteresis, low sensitivity, and cross-sensitivity issues limit the use of GO in practical applications, where continuous monitoring is preferred. Herein, a wearable and wireless impedance-based humidity sensor made with pyrene-functionalized hexagonal boron nitride (h-BN) nanosheets is demonstrated. The device shows enhanced sensitivity towards relative humidity (RH) (>1010 Ohms/%RH in the range from 5% to 100% RH), fast response (0.1 ms), no appreciable hysteresis, and no cross-sensitivity with temperature in the range of 25-60 °C. The h-BN-based sensor is able to monitor the whole breathing cycle process of exhaling and inhaling, hence enabling to record in real-time the subtlest changes of respiratory signals associated with different daily activities as well as various symptoms of flu, without requiring any direct contact with the individual.

Mitochondria-mediated ferroptosis contributes to the inflammatory responses of bovine viral diarrhea virus (BVDV) in vitro.

Bovine viral diarrhea virus (BVDV) belongs to the family Flaviviridae and includes two biotypes in cell culture: cytopathic (CP) or non-cytopathic (NCP) effects. Ferroptosis is a non-apoptotic form of programmed cell death that contributes to inflammatory diseases. However, whether BVDV induces ferroptosis and the role of ferroptosis in viral infection remain unclear. Here, we provide evidence that both CP and NCP BVDV can induce ferroptosis in Madin-Darby bovine kidney cells at similar rate. Mechanistically, biotypes of BVDV infection downregulate cytoplasmic and mitochondrial GPX4 via Nrf2-GPX4 pathway, thereby resulting in lethal lipid peroxidation and promoting ferroptosis. In parallel, BVDV can degrade ferritin heavy chain and mitochondrial ferritin via NCOA4-mediated ferritinophagy to promote the accumulation of Fe2+ and initiate ferroptosis. Importantly, CP BVDV-induced ferroptosis is tightly associated with serious damage of mitochondria and hyperactivation of inflammatory responses. In contrast, mild or unapparent damage of mitochondria and slight inflammatory responses were detected in NCP BVDV-infected cells. More importantly, different mitophagy pathways in response to mitochondria damage by both biotypes of BVDV are involved in inflammatory responses. Overall, this study is the first to show that mitochondria may play key roles in mediating ferroptosis and inflammatory responses induced by biotypes of BVDV in vitro.IMPORTANCEBovine viral diarrhea virus (BVDV) threatens a wide range of domestic and wild cattle population worldwide. BVDV causes great economic loss in cattle industry through its immunosuppression and persistent infection. Despite extensive research, the mechanism underlying the pathogenesis of BVDV remains elusive. Our data provide the first direct evidence that mitochondria-mediated ferroptosis and mitophagy are involved in inflammatory responses in both biotypes of BVDV-infected cells. Importantly, we demonstrate that the different degrees of injury of mitochondria and inflammatory responses may attribute to different mitophagy pathways induced by biotypes of BVDV. Overall, our findings uncover the interaction between BVDV infection and mitochondria-mediated ferroptosis, which shed novel light on the physiological impacts of ferroptosis on the pathogenesis of BVDV infection, and provide a promising therapeutic strategy to treat this important infectious disease with a worldwide distribution.

Association between diabetes mellitus and postoperative urinary retention after cerebral angiography.

AIMS: The aim of this study is to examine the association between diabetes mellitus and postoperative urinary retention on cerebral angiography (including intravascular interventional therapy). METHODS: We collected data on the demographic characteristics and comorbidities, imaging and routine laboratory data, surgical information, and medications of patients who underwent cerebral angiography. Multivariate logistic regression was used to explore the correlation between diabetes and the incidence of postoperative urinary retention. RESULTS: A total of 932 patients were included, with a mean age of 59.7 years (74.1% men). Postoperative urinary retention occurred in 40.8% of the diabetes mellitus group and 30.3% of the group without diabetes. Compared with the group without diabetes, those with diabetes were more likely to experience postoperative urinary retention. Patients with higher glycosylated hemoglobin A1c levels had a higher risk of developing postoperative urinary retention. CONCLUSIONS: Diabetes was independently linked to postoperative urinary retention following cerebral angiography and patients with glycosylated hemoglobin A1c levels > 6% were more likely to experience postoperative urinary retention. Therefore, clinically regulating blood glucose levels may help to reduce the likelihood of postoperative urinary retention after cerebral angiography.

The association between depressive symptoms with fear of falling and cognitive decline in older adults in the Korean community: An analysis of the Korean Longitudinal Study of Aging (KLoSA), 2006-2020.

OBJECTIVES: This study aimed to investigate the effects of fear of falling (FOF) on cognitive decline in older adults in the Korean community, depending on the presence of accompanying depressive symptoms. METHODS: A total of 6263 individuals were included in the final analysis. Based on their baseline evaluation results for depressive symptoms and FOF, the subjects were divided into four groups: "normal control" (NC, n = 3783), "depression only" (Dep-only, n = 291), "fear of falling only" (FOF-only, n = 1755), and "depression with fear of falling" (Dep-FOF, n = 434). Cognitive decline was defined as a loss of more than three points in the K-MMSE score in participants with at least two years of follow-up. We examined the association between FOF accompanied by depressive symptoms and cognitive decline using a multivariate Cox proportional hazard model. RESULTS: Cognitive decline occurred in 76.3%, 68.5%, 63.9%, and 56.4% of the Dep-FOF, FOF-only, Dep-only, and NC groups, respectively. Our findings suggest that individuals with FOF do not always have cognitive decline (HR = 1.03, 95% CI = 0.95-1.12, P = 0.43) compared to individuals without FOF. Furthermore, depressive symptoms with FOF are associated with a higher risk of cognitive decline (HR = 1.23, 95% CI = 1.08-1.41, P = 0.002) in community-dwelling older adults in Korea. CONCLUSION: Healthcare providers should be attentive to community-dwelling older adults who experience both depressive symptoms and FOF because our findings suggest that this unique combination increases the risk of cognitive decline.

A nomogram predicts early neurological deterioration after mechanical thrombectomy in patients with ischemic stroke.

Introduction: Early neurological deterioration (END) is common in acute ischemic stroke and is directly associated with poor outcome after stroke. Our aim is to develop and validate a nomogram to predict the risk of END after mechanical thrombectomy (MT) in acute ischemic stroke patients with anterior circulation large-vessel occlusion. Methods: We conducted a real-world, multi-center study in patients with stroke treated with mechanical thrombectomy. END was defined as a worsening by 2 or more NIHSS points within 72-hour after stroke onset compared to admission. Multivariable logistic regression was used to determine the independent predictors of END, and the discrimination of the scale was assessed using the C-index. Calibration curves were constructed to evaluate the calibration of the nomogram, and decision curves were used to describe the benefits of using the nomogram. Results: A total of 1007 patients were included in our study. Multivariate logistic regression analysis found age, admission systolic blood pressure, initial NIHSS scores, history of hyperlipemia, and location of occlusion were independent predictors of END. We developed a nomogram that included these 6 factors, and it revealed a prognostic accuracy with a C-index of 0.678 in the derivation group and 0.650 in the validation group. The calibration curves showed that the nomogram provided a good fit to the data, and the decision curves demonstrated a large net benefit. Discussion: Our study established and validated a nomogram to stratify the risk of END before mechanical embolectomy and identify high-risk patients, who should be more cautious when making clinical decisions.

Detection of nasopharyngeal cancer cells using the laser tweezer Raman spectroscopy technology.

Nasopharyngeal cancer (NPC), which arises from the nasopharyngeal epithelial lining, is one of the common malignant otorhinolaryngological tumors in China. Due to its insidious anatomical location and highly invasive and metastatic features, it is challenging to detect NPC at early stages. In this work, a rapid laser tweezer Raman spectroscopic (LTRS) system was built and used to trap and characterize single NPC cells. Using LTRS, high-quality Raman signals of the normal nasopharyngeal cell line (NP69) and NPC cells could be successfully obtained. By analysing the Raman peaks, some unique changes were found in components, such as DNA, amide I and amide III, in NPC cells compared with normal cells. In addition, we also used a multivariate statistical algorithm to establish a diagnostic model for identifying NPC cells with an accuracy of 90.0%. These results demonstrate that LTRS in combination with the multivariate statistical analysis is a convenient and high-efficiency cell identification technology, providing a novel and rapid methodology for NPC detection at the single cell level.

Reducing Cellular Autolysis of Bacillus subtilis to Improve Keratinase Production.

Bacillus subtilis has been shown to be an excellent expression host for keratinases due to its powerful secretion system. However, cellular autolysis limits its production capacity. Here, we selected seven genes with significantly upregulated transcript levels from 15 genes associated with cellular autolysis as knockout targets by qRT-PCR and constructed a total of 127 strains to reduce cellular autolysis. Among them, the biomass of B. subtilis BSΔXLPC-ker deficient in xpf, lytC, pcfA, and cwlC increased by 57%. This was confirmed by cell staining, green fluorescent protein imaging, and extracellular nucleic acid leakage assay. Keratinase activity was increased by 1.46-fold in the 5 L fermenter. In addition, the activities of nattokinase and subtilisin E were also increased by 1.50-fold and 1.43-fold, respectively, in the modified chassis cells, which further confirms the generalizability of the strategy. Thus, reducing cellular autolysis to increase the ability of B. subtilis to produce subtilisins is promising.

Interphase Boundaries and Their Impact on Carrier Dynamics in Lead Halide Perovskites.

Interphase boundaries (IBs) are widely present in lead halide perovskites (LHPs) owing to their relatively low phase transition barriers. However, their atomic structures and electronic properties have rarely been investigated. In this study, various IB structures were constructed computationally, and their influences on the charge carrier transport properties of LHPs were studied by calculating the effective interphase boundary energy and analyzing the electronic structure. The results show that the presence of IBs plays a significant role in carrier transport and that they may be tuned to prolong carrier lifetimes. This study provides insights for improving the performance of LHPs by engineering IBs, primarily by their compositional phases and ratios.

E3 ligase ATL5 positively regulates seed longevity by mediating the degradation of ABT1 in Arabidopsis.

Ubiquitination is a fundamental mechanism regulating the stability of target proteins in eukaryotes; however, the regulatory mechanism in seed longevity remains unknown. Here, we report that an uncharacterized E3 ligase, ARABIDOPSIS TÓXICOS EN LEVADURA 5 (ATL5), positively regulates seed longevity by mediating the degradation of ACTIVATOR OF BASAL TRANSCRIPTION 1 (ABT1) in Arabidopsis. Seeds in which ATL5 was disrupted showed faster accelerated aging than the wild-type, while expressing ATL5 in atl5-2 basically restored the defective phenotype. ATL5 was highly expressed in the embryos of seeds, and its expression could be induced by accelerated aging. A yeast two-hybrid screen identified ABT1 as an ATL5 interacting protein, which was further confirmed by bimolecular fluorescence complementary assay and co-immunoprecipitation analysis. In vitro and in vivo assays showed that ATL5 functions as an E3 ligase and mediates the polyubiquitination and degradation of ABT1. Disruption of ATL5 diminished the degradation of translated ABT1, and the degradation could be induced by seed ageing and occurred in a proteasome-dependent manner. Furthermore, disruption of ABT1 enhanced seed longevity. Taken together, our study reveals that ATL5 promotes the polyubiquitination and degradation of the ABT1 protein posttranslationally and positively regulates seed longevity in Arabidopsis.

Diagnostic accuracy of the upper limb neurodynamic test with median bias (ULNT1) for cervical radiculopathy: a systematic review and meta-analysis.

BACKGROUND: The upper limb neurodynamic test for median nerve (ULNT1) is commonly applied for assessment of cervical radiculopathy (CR). However, the diagnostic accuracy of ULNT1 in diagnosing CR remains unclear. OBJECTIVE: This study aimed to examine the diagnostic accuracy of the ULNT1 for the CR. DATA SOURCES: Four databases were searched for relevant studies published up to April 30, 2023. STUDY SELECTION: Cross-sectional or cohort studies that assessed the diagnostic accuracy of ULNT1 for CR were included. DATA SYNTHESIS: The methodological quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist. A bivariate random-effects regression model was used for the data synthesis. The overall quality of evidence was evaluated using the GRADE approach. RESULTS: A total of 592 references were identified, and five studies with 465 patients met the inclusion criteria. The overall quality of the body of evidence was very low across studies. Heterogeneity of studies was high. The pooled sensitivity and specificity of the ULNT1 were 0.69 (95% CI 0.50-0.83) and 0.54 (95% CI 0.36-0.71), respectively. The summary receiver operating characteristic curve area was 0.65 (95% CI 0.61-0.69). CONCLUSION: There is low certainty of evidence that the ULNT1 has only fair accuracy in diagnosing CR. The ULNT1 was recommended as an add-on test after the existing diagnostic pathway to enhance diagnostic accuracy further. High-quality studies which follow the Standards for Reporting of Diagnostic Accuracy and the QUADAS-2; a revised tool for the quality assessment of diagnostic accuracy, are needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO: CRD42021255686 CONTRIBUTION OF THE PAPER.

Dunaliella Ds-26-16 acts as a global regulator to enhance salt tolerance by coordinating multiple responses in Arabidopsis seedlings.

MAIN CONCLUSION: Based on phenotypic, physiological and proteomic analysis, the possible mechanism by which Ds-26-16 regulates salt tolerance in Arabidopsis seedlings was revealed. Functional and mechanistic characterization of salt tolerance genes isolated from natural resources is crucial for their application. In this study, we report the possible mechanism by which Ds-26-16, a gene from Dunaliella, and its point mutation gene EP-5, enhance salt tolerance in Arabidopsis seedlings. Both Ds-26-16 and EP-5 transgenic lines displayed higher seed germination rates, cotyledon-greening rates, soluble sugar contents, decreased relative conductivity and ROS accumulation when germinating under 150 mM NaCl conditions. Comparative proteomic analysis revealed that there were 470 or 391 differentially expressed proteins (DEPs) in Ds-26-16 or EP-5, respectively, compared with the control (3301) under salt stress. The GO and KEGG enrichment analyses showed the DEPs in Ds-26-16 vs. 3301 and EP-5 vs. 3301 were similar and mainly enriched in photosynthesis, regulation of gene expression, carbohydrate metabolism, redox homeostasis, hormonal signal and defense, and regulation of seed germination. Thirty-seven proteins were found to be stably expressed under salt stress due to the expression of Ds-26-16, and eleven of them contain the CCACGT motif which could be bound by the transcription factor in ABA signaling to repress gene transcription. Taken together, we propose that Ds-26-16, as a global regulator, improves salt-tolerance by coordinating stress-induced signal transduction and modulating multiple responses in Arabidopsis seedlings. These results provide valuable information for utilizing natural resources in crop improvement for breeding salt-tolerant crops.