Isoindoline-based fluorogenic probes bearing a self-immolative linker for the sensitive and selective detection of O-GlcNAcase activity.

O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.

Network mechanisms of ongoing brain activity's influence on conscious visual perception.

Sensory inputs enter a constantly active brain, whose state is always changing from one moment to the next. Currently, little is known about how ongoing, spontaneous brain activity participates in online task processing. We employed 7 Tesla fMRI and a threshold-level visual perception task to probe the effects of prestimulus ongoing brain activity on perceptual decision-making and conscious recognition. Prestimulus activity originating from distributed brain regions, including visual cortices and regions of the default-mode and cingulo-opercular networks, exerted a diverse set of effects on the sensitivity and criterion of conscious recognition, and categorization performance. We further elucidate the mechanisms underlying these behavioral effects, revealing how prestimulus activity modulates multiple aspects of stimulus processing in highly specific and network-dependent manners. These findings reveal heretofore unknown network mechanisms underlying ongoing brain activity's influence on conscious perception, and may hold implications for understanding the precise roles of spontaneous activity in other brain functions.

Gut-Derived Trimethylamine N-Oxide Promotes CCR2-Mediated Macrophage Infiltration in acute kidney injury.

BACKGROUND: Inflammation is crucial in the development of AKI and subsequent CKD following renal ischemia-reperfusion (IR) injury. Gut microbiota metabolites trigger inflammation and affect IR-induced renal damage. Yet, the driving factors and mechanisms are unclear. Trimethylamine N-oxide (TMAO), a gut-derived choline metabolite, is a strong pro-inflammatory factor that increases in patients with AKI and CKD. We hypothesized that TMAO can promote renal injury caused by IR. METHODS: Mice subjected to unilateral renal IR to induce AKI and CKD were fed a high-choline diet to observe the effects of TMAO on kidney inflammation, fibrosis, and macrophage dynamics. RESULTS: A choline-rich diet altered the gut microbiota and elevated TMAO levels, which exacerbated IR-induced AKI and subsequent CKD. Single-cell analysis identified a distinct subset of CCR2+ macrophages derived from monocytes as key responders to TMAO, intensifying immune cell interactions and worsening renal injury. TMAO promoted sustained CCR2 expression after IR, increasing macrophage infiltration. CCR2 deletion and antagonist RS-102895 improved TMAO-induced inflammation and fibrosis, alleviated renal injury induced by IR. CONCLUSIONS: Our study provides valuable insights into the link between TMAO and IR-incited renal inflammation and fibrosis, emphasizing the critical role of TMAO-mediated macrophage infiltration via CCR2 as a key therapeutic target in the acute and chronic phase after IR.

Risk stratification for infection during immunosuppressive therapy in patients with lupus nephritis: A nested case-control study.

BACKGROUND: The current prediction models for the risk of infection during immunosuppressive treatment for lupus nephritis (LN) lack a prediction time window and have poor pertinence. This study aimed to develop a risk stratification to predict infection during immunosuppressive therapy in patients with LN. METHODS: This retrospective nested case-control study collected patients with LN treated with immunosuppressive therapy between 2014 and 2022 in the Nephrology ward in Huashan Hospital affiliated to Fudan University and Huashan Hospital Baoshan Branch. Cases were defined as patients who experienced infection during the follow-up period; patients were eligible as controls if they did not have infection during the follow-up period. RESULTS: There were 53 patients with infection by CTCAE V5.0 grade ≥2. According to the 1:3 nested matching, the 53 patients with infection were matched with 159 controls. In the multivariable logistic regression model, the change rate of fibrinogen (OR = 0.97, 95% CI: 0.94-0.99, p = 0.008), leukopenia (OR = 8.68, 95% CI: 1.16-301.72, p = 0.039), and reduced albumin (OR = 6.25, 95% CI: 1.38-28.24, p = 0.017) were independently associated with infection. The AUC of the ROC curve in the validation set of the multivariable logistic regression model in the internal random sampling was 0.864. The scores range from -2 to 10. The infection risk stratification ranges from 2.8% at score -2 to 97.5% at score 10. CONCLUSION: A risk stratification was built to predict the risk of infection in patients with LN undergoing immunosuppressive therapy.

Association of frequent intradialytic hypotension with the clinical outcomes of patients on hemodialysis: a prospective cohort study.

Intradialytic hypotension (IDH) is a common complication of hemodialysis (HD), but there is no consensus on its definition. In 2015, Flythe proposed a definition of IDH (Definition 1 in this study): nadir systolic blood pressure (SBP) <90 mmHg during hemodialysis for patients with pre-dialysis SBP <159 mmHg, and nadir SBP <100 mmHg during hemodialysis for patients with pre-dialysis SBP ≥160 mmHg. This prospective observational cohort study investigated the association of frequent IDH based on Definition 1 with clinical outcomes and compared Definition 1 with a commonly used definition (nadir SBP <90 mmHg during hemodialysis, Definition 2). The incidence of IDH was observed over a 3-month exposure assessment period. Patients with IDH events ≥30% were classified as 'frequent IDH'; the others were 'infrequent IDH'. All-cause mortality, cardiovascular mortality, and all-cause hospitalization events were followed up for 36 months. This study enrolled 163 HD patients. The incidence of IDH was 11.1% according to Definition 1 and 10.5% according to Definition 2. The Kaplan-Meier curves showed that frequent IDH patients had higher risks of all-cause mortality (p = 0.009, Definition 1; p = 0.002, Definition 2) and cardiovascular mortality (p = 0.021, Definition 1). Multivariable Cox regression analysis indicated that frequent IDH was independently associated with a higher risk of all-cause mortality (Model 1: HR = 2.553, 95%CI 1.334-4.886, p = 0.005; Model 2: HR = 2.406, 95%CI 1.253-4.621, p = 0.008). In conclusion, HD patients classified as frequent IDH are at a greater risk of all-cause mortality. This highlights the significance of acknowledging and proactively managing frequent IDH within the HD patients.

Comparative chloroplast genome analyses provide insights into evolutionary history of Rhizophoraceae mangroves.

Background: The Rhizophoraceae family comprises crucial mangrove plants that inhabit intertidal environments. In China, eight Rhizophoraceae mangrove species exist. Although complete chloroplast (Cp) genomes of four Rhizophoraceae mangrove plants have been reported, the Cp genomes of the remaining four species remain unclear, impeding a comprehensive understanding of the evolutionary history of this family. Methods: Illumina high-throughput sequencing was employed to obtain the DNA sequences of Rhizophoraceae species. Cp genomes were assembled by NOVOPlasty and annotated using CpGAVAS software. Phylogenetic and divergence time analyses were conducted using MEGA and BEAST 2 software. Results: Four novel Cp genomes of Rhizophoraceae mangrove species (Bruguiera sexangula, Bruguiera gymnorrhiza, Bruguiera × rhynchopetala and Rhizophora apiculata) were successfully assembled. The four Cp genomes ranged in length from 163,310 to 164,560 bp, with gene numbers varying from 124 to 128. The average nucleotide diversity (Pi) value of the eight Rhizophoraceae Cp genomes was 0.00596. Phylogenetic trees constructed based on the complete Cp genomes supported the monophyletic origin of Rhizophoraceae. Divergence time estimation based on the Cp genomes of representative species from Malpighiales showed that the origin of Rhizophoraceae occurred at approximately 58.54-50.02 million years ago (Mya). The divergence time within the genus Rhizophora (∼4.51 Mya) was much earlier than the divergence time within the genus Bruguiera (∼1.41 Mya), suggesting recent speciation processes in these genera. Our data provides new insights into phylogenetic relationship and evolutionary history of Rhizophoraceae mangrove plants.

Comparison of effectiveness and safety of Da Vinci robot's "3 + 1" and "4 + 1" modes of treatment for colorectal cancer.

To compare the effectiveness of the Da Vinci Surgical Robot System (DSRS) "3 + 1" and "4 + 1" models for colorectal cancer (CRC). A total of 107 patients with CRC admitted to our hospital from February 2021 to May 2022 were selected for the retrospective analysis. Of these, 57 patients underwent the DSRS "4 + 1" model (control group), while the rest 50 underwent the DSRS "3 + 1" model (research group). The operation time, intraoperative bleeding, number of lymph nodes detected, time of first postoperative urinary catheter removal, time of first feeding, time of first venting and hospitalization were compared between the two groups. The changes of white blood cell (WBC) and C-reactive protein (CRP) levels before and after surgery were detected, and patients' adverse effects and treatment costs between surgery and hospital discharge were counted. The Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) were used to assess the psychological state of the patients. There was no difference in operative time, intraoperative bleeding, and number of lymph nodes detected between both groups (P > 0.05), while time to first postoperative urinary catheter removal, time to first feeding, time to first venting, length of stay (LOS), postoperative inflammatory factor levels, incidence of adverse events, and treatment costs were all lower in the research group than in the control group (P < 0.05). SAS and SDS scores decreased after treatment in both groups, but the decrease was more obvious in the research group (P < 0.05). Both DSRS "4 + 1" and "3 + 1" modes have better treatment effects for CRC. However, the "3 + 1" mode has higher safety and lower treatment cost, which can significantly improve the postoperative recovery process of patients and is more worthy to be promoted in clinical practice.

Exploring Restrictions to use of community greenways for physical activity through structural equation modeling.

Public health problems caused by rapid urbanization have attracted increasing amounts of attention. Existing studies show that improving the frequency and duration of physical activity among urban residents can effectively reduce their disease risk. A community greenway, as a green space for public activity directly serving community residents, is one of the best spatial place for bringing health benefits to people. Although the scale and scope of greenway construction have been increasing in recent years, the utilization rate of some greenways is not high for various reasons, restricting the extent to which people engage in healthy physical activities in greenway spaces. In this study, the greenway of Nancheng Community in Wenjiang District, Chengdu city, China was selected as the object of study, and structural equation modeling was conducted to explore the objective environmental factors and individual characteristics acting as barriers to use of the community greenway by the population for physical activity. The results show that user experience, the greenway landscape, and safety and accessibility are important factors that restrict people's willingness engage in physical activity in the community greenway environment. The results of this study provide a direction for further consideration of ways to enhance people's willingness to make use of greenways for physical activity, and further provide a theoretical basis for the healthy design and transformation of community greenway spaces.

New-Type Shearing Interference Detection System Based on Double-Grating Structure for Suppressing the Skylight Background.

To overcome the influence of the daytime skylight background on long-distance optical detection, a new type of shearing interference detection system was proposed to improve the detection performance of the traditional detection system for finding dark objects such as dim stars during the daytime. This article focuses on the basic principle and mathematical model as well as the simulation and experimental research of the new type of shearing interference detection system. The comparison of the detection performance between this new-type detection system and the traditional system is also carried out in this article. The experimental results show that the detection performance of the new type of shearing interference detection system is significantly better than that of the traditional system, and the image signal-to-noise ratio of this new-type system (about 13.2) is much higher than that of the best result of the traditional detection system (about 5.1).

An overview of 3D printed metal implants in orthopedic applications: Present and future perspectives.

With the ability to produce components with complex and precise structures, additive manufacturing or 3D printing techniques are now widely applied in both industry and consumer markets. The emergence of tissue engineering has facilitated the application of 3D printing in the field of biomedical implants. 3D printed implants with proper structural design can not only eliminate the stress shielding effect but also improve in vivo biocompatibility and functionality. By combining medical images derived from technologies such as X-ray scanning, CT, MRI, or ultrasonic scanning, 3D printing can be used to create patient-specific implants with almost the same anatomical structures as the injured tissues. Numerous clinical trials have already been conducted with customized implants. However, the limited availability of raw materials for printing and a lack of guidance from related regulations or laws may impede the development of 3D printing in medical implants. This review provides information on the current state of 3D printing techniques in orthopedic implant applications. The current challenges and future perspectives are also included.

Impact of frequent intradialytic hypotension on quality of life in patients undergoing hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is frequently accompanied by symptoms of nausea, dizziness, fatigue, muscle spasm, and arrhythmia, which can adversely impact the daily lives of patients who undergo hemodialysis and may lead to decreased quality of life (QoL). This study employed the KDQOL™-36 scale to evaluate the impact of frequent IDH, based on the definition determined by predialysis blood pressure (BP) and nadir systolic blood pressure (SBP) thresholds, on the QoL of patients. METHODS: This is a single center retrospective cohort study involving 160 hemodialysis patients. We enrolled adult patients with uremia who received routine hemodialysis (4 h/time, 3 times/week) from October 1, 2019, to September 30, 2021. Frequent IDH was defined as an absolute nadir SBP < 90 mmHg occurring in no less than 30% of hemodialysis sessions when predialysis SBP < 159 mmHg (or < 100 mmHg when predialysis BP ≥ 160 mmHg).The differences between patients with and without frequent IDH were compared using the independent t test, Kruskal‒Wallis test, or chi-square test. The primary visit was at month 36, and the remaining visits were exploratory outcomes. RESULTS: Compared to patients with infrequent IDH at baseline, those with frequent IDH had significantly lower scores on the symptoms and discomfort of kidney disease dimension at all follow-up points (P < 0.05). The symptoms and discomfort of kidney disease dimension were worse in patients with frequent IDH. Those with frequent IDH had a significantly poorer QoL regarding the dimensions of symptoms and discomfort of kidney disease and the impact of kidney disease on life. CONCLUSIONS: The findings of the study suggest an association between frequent IDH and QoL dimensions of symptoms and discomfort of kidney disease and the impact of kidney disease on life dimension under the definition of frequent IDH.

Spatiotemporal neural dynamics of object recognition under uncertainty in humans.

While there is a wealth of knowledge about core object recognition-our ability to recognize clear, high-contrast object images-how the brain accomplishes object recognition tasks under increased uncertainty remains poorly understood. We investigated the spatiotemporal neural dynamics underlying object recognition under increased uncertainty by combining MEG and 7 Tesla (7T) fMRI in humans during a threshold-level object recognition task. We observed an early, parallel rise of recognition-related signals across ventral visual and frontoparietal regions that preceded the emergence of category-related information. Recognition-related signals in ventral visual regions were best explained by a two-state representational format whereby brain activity bifurcated for recognized and unrecognized images. By contrast, recognition-related signals in frontoparietal regions exhibited a reduced representational space for recognized images, yet with sharper category information. These results provide a spatiotemporally resolved view of neural activity supporting object recognition under uncertainty, revealing a pattern distinct from that underlying core object recognition.