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Objective: Peripheral nerve injury (PNI) is characterized by high incidence and sequela rate. Recently, there was increasing evidence that has shown ferroptosis may impede functional recovery. Our objective is to explore the novel mechanism that regulates ferroptosis after PNI., Methods: LC-MS/MS proteomics was used to explore the possible differential signals, while PCR array was performed to investigate the differential factors. Besides, we also tried to activate or inhibit the key factors and then observe the level of ferroptosis. Regeneration of myelin sheath was finally examined in vivo via transmission electron microscopy., Results: Proteomics analysis suggested coagulation signal was activated after sciatic nerve crush injury, in which high expression of F2 (encoding thrombin) and F2r (encoding PAR1) were observed. Both thrombin and PAR1-targeted activator TRAP6 can induce ferroptosis in RSC96 cells, which can be rescued by Vorapaxar (PAR1 targeted inhibitor) in vitro. Further PCR array revealed that activation of PAR1 induced ferroptosis in RSC96 cells by increasing expression of YAP and ACSL4. Immunofluorescence of sciatic nerve confirmed that the expression of YAP and ACSL4 were simultaneously reduced after PAR1 inhibition, which may contribute to myelin regeneration after injury in SD rats., Conclusion: Inhibition of PAR1 can relieve ferroptosis after sciatic nerve crush injury in SD rats through Hippo-YAP/ACSL4 pathway, thereby regulating myelin regeneration after injury. In summary, PAR1/Hippo-YAP/ACSL4 pathway may be a promising therapeutic target for promoting functional recovery post-sciatic crush injury., (Copyright © 2024. Published by Elsevier Inc.)

Efficiently adsorbing Pd(II) from acidic radioactive waste liquid is crucial for ensuring the safety of the radioactive waste vitrification process and significantly alleviating the scarcity of precious metals. However, the stability and selectivity of most current adsorbents are limited, hindering their practical application under acidic conditions. To address these limitations, a covalent organic framework (DHTP-TPB COF) was prepared with a high nitrogen content, leveraging the high affinity of its soft ligand N with palladium to achieve high selectivity. This work demonstrated that DHTP-TPB COF exhibits rapid adsorption kinetics, with equilibrium achieved within 10 min. The framework also boasts a high adsorption capacity of 142.8 mg/g and impressive reusability in 1.0 M nitric acid. Moreover, the DHTP-TPB COF displays excellent selectivity for Pd(II), even in the presence of 13 interfering ions. By combining FT-IR, XPS spectroscopy, and DFT theoretical calculations, the dense N sites in the framework have a strong affinity for Pd(II), resulting in exceptional adsorption performance that was confirmed. The findings of this study highlight the potential of COFs with robust linkers and customized functional groups to effectively and selectively capture Pd(II) under harsh environmental conditions of high-level liquid waste.

Objective: To reveal the potential underlying mechanism of the Shenqi Tiaoshen formula (, SQTS) in the treatment of chronic obstructive pulmonary disease (COPD) by utilizing network pharmacology, molecular docking, and experimental verification., Methods: Multiple open-source databases and research related to Traditional Chinese Medicine or compounds were employed to screen active ingredients and corresponding potential targets of the SQTS. The protein-protein interaction network screened hub genes, the relevant molecular mechanism and gene regulation were initially identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, and molecular docking was used to confirm further the interaction of the main components bound to the core targets. In vivo experiments on the COPD combined Qi-deficiency syndrome rat model were performed to verify the intervention effects and predicted potential molecular mechanisms of the SQTS., Results: This study selected 156 active compounds and 326 candidate targets for treating COPD. Quercetin, Nobiletin, Kaempferol, Luteolin, Ginsenoside Rh2 and Formononetin were probably the main active compounds of SQTS in COPD treatment as they affected the most COPD-related targets, and interleukin-1 (IL-6), signal transducing activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor A (VEGFA), protein kinase B (AKT1), hypoxia-inducible factor-1α (HIF-1α), and forkhead box O3 (FoxO3) were identified as the hub genes associated with its therapeutic effect. KEGG analysis was mainly enriched in the signaling pathways closely related to inflammation, immunity and oxidative stress, such as HIF-1, tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)-AKT, FoxO, apoptosis, IL-17, and toll-like receptor. Molecular docking confirmed that the main active components shared a good affinity with the hub genes. In vivo experiments, the SQTS was found to improve the body weight, exhaustive swimming time, tail-hanging immobility time and struggle times, airway inflammation, lung functions, and inflammatory factors in the rat model of COPD. The up-regulation of p-PI3K, p-AKT, HIF-1α, FoxO3α, toll like receptor 4, VEGFA, Caspase 3, TNF-α, and IL-17 in COPD rats were down-regulated by SQTS, consistent with the network pharmacology results., Conclusions: This study provides evidence that the SQTS plays a critical role in anti-inflammation via suppressing immune inflammation and oxidative stress related pathways, indicating that the SQTS is a candidate herbal drug for further investigation in treating COPD.

As a widely used pesticide, abamectin could be a threat to nontarget organisms. In this study, the toxic mechanism of abamectin on osmoregulation in Procambarus clarkii was explored for the first time. The results of this study showed that with increasing abamectin concentration, the membrane structures of gill filaments were damaged, with changes in ATPase activities, transporter contents, biogenic amine contents, and gene expression levels. The results of this study indicated that at 0.2 mg/L abamectin, ion diffusion could maintain osmoregulation. At 0.4 mg/L abamectin, passive transport was inhibited due to damage to the membrane structures of gill filaments, and active transport needed to be enhanced for osmoregulation. At 0.6 mg/L abamectin, the membrane structures of gill filaments were seriously damaged, and the expression level of osmoregulation-related genes decreased, but the organisms were still mobilizing various transporters, ATPases, and biogenic amines to address abamectin stress. This study provided a theoretical basis for further study of the effects of contaminations in aquatic environment on the health of crustaceans., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study is to delineate the distinctive high-resolution computed tomography features of pulmonary cryptococcosis in non-HIV-infected patients. This retrospective analysis encompasses high-resolution computed tomography scans from 58 patients with histologically confirmed pulmonary cryptococcosis, focusing on the diagnostic challenges and the factors that lead to misdiagnosis. Analysis of computed tomography scans from these patients indicated that nodular or mass-like presentations were evident in 32 cases (55.2%), consolidation presentations in 7 cases (12.1%), and mixed presentations in 19 cases (32.8%). Lesions were predominantly located in the lower lobes of the lungs (40 cases, 69.0%) and in peripheral zones (55 cases, 94.8%). Notable radiographic signs included the presence of the burr sign in 55 cases (94.8%), lobulation sign in 53 cases (91.4%), halo sign in 53 cases (91.4%), and air bronchogram in 46 cases (79.0%). Moreover, 24 cases (41.4%) exhibited necrosis or cavitation, mediastinal lymphadenopathy was noted in 6 cases (10.3%), and pleural effusion was present in 5 cases (8.6%). Lesions were devoid of calcification. Pulmonary cryptococcosis ought to be contemplated in the differential diagnosis when computed tomography imaging exhibits patterns including, but not limited to, lower lobe and peripheral distribution, a broad base abutting the pleura, clustered growth with a propensity for fusion, air bronchogram within lesions, and peripheral halo sign., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Bioluminescent indicators are power tools for studying dynamic biological processes. In this study, we present the generation of novel bioluminescent indicators by modifying the luciferin molecule with an analyte-binding moiety. Specifically, we have successfully developed the first bioluminescent indicator for potassium ions (K + ), which are critical electrolytes in biological systems. Our approach involved the design and synthesis of a K + -binding luciferin named potassiorin. Additionally, we engineered a luciferase enzyme called BRIPO (bioluminescent red indicator for potassium) to work synergistically with potassiorin, resulting in optimized K + -dependent bioluminescence responses. Through extensive validation in cell lines, primary neurons, and live mice, we demonstrated the efficacy of this new tool for detecting K + . Our research demonstrates an innovative concept of incorporating sensory moieties into luciferins to modulate luciferase activity. This approach has great potential for developing a wide range of bioluminescent indicators, advancing bioluminescence imaging (BLI), and enabling the study of various analytes in biological systems.

BACKGROUND. MRI-based prognostic evaluation in patients with dilated cardiomyopathy (DCM) has historically used markers of late gadolinium enhancement (LGE) and feature tracking (FT)-derived left ventricular global longitudinal strain (LVGLS). Early data indicate that FT-derived left atrial strain (LAS) parameters, including reservoir, conduit, and booster, may also have prognostic roles in such patients. OBJECTIVE. The purpose of our study was to evaluate the prognostic utility of LAS parameters, derived from MRI FT, in patients with ischemic or nonischemic DCM, including in comparison with the traditional parameters of LGE and LVGLS. METHODS. This retrospective study included 811 patients with ischemic or nonischemic DCM (median age, 60 years; 640 men, 171 women) who underwent cardiac MRI at any of five centers. FT-derived LAS parameters and LVGLS were measured using two- and four-chamber cine images. LGE percentage was quantified. Patients were assessed for a composite outcome of all-cause mortality or heart failure hospitalization. Multivariable Cox regression analyses including demographic characteristics, cardiovascular risk factors, medications used, and a wide range of cardiac MRI parameters were performed. Kaplan-Meier analyses with log-rank tests were also performed. RESULTS. A total of 419 patients experienced the composite outcome. Patients who did, versus those who did not, experience the composite outcome had larger LVGLS (-6.7% vs -8.3%, respectively; p < .001) as well as a smaller LAS reservoir (13.3% vs 19.3%, p < .001), LAS conduit (4.7% vs 8.0%, p < .001), and LAS booster (8.1% vs 10.3%, p < .001) but no significant difference in LGE (10.1% vs 11.3%, p = .51). In multivariable Cox regression analyses, significant independent predictors of the composite outcome included LAS reservoir (HR = 0.96, p < .001) and LAS conduit (HR = 0.91, p < .001). LAS booster and LGE were not significant independent predictors in the models. LVGLS was a significant independent predictor only in a model that initially included LAS booster but not the other LAS parameters. In Kaplan-Meier analysis, all three LAS parameters were significantly associated with the composite outcome ( p < .001). CONCLUSION. In this multicenter study, LAS reservoir and LAS conduit were significant independent prognostic markers in patients with ischemic or nonischemic DCM, showing greater prognostic utility than the currently applied markers of LVGLS and LGE. CLINICAL IMPACT. FT-derived LAS analysis provides incremental prognostic information in patients with DCM.

An enterprise innovation strategy is the driving force for the healthy and sustainable development of enterprises, and high-quality, efficient innovation is important for improving enterprises' market value and promoting their high-quality development. Customer relationships are an important factor affecting enterprise product technology and enterprise innovation; however, few studies have evaluated the impact of customer change on innovation efficiency. Therefore, from the perspective of social capital, we use China's listed manufacturing companies' data from 2013 to 2020 to systematically examine how customer changes affect enterprise innovation performance, and test the impact of social networks on the relationship between customer change and enterprise innovation efficiency. The empirical research shows that customer change reduces enterprises' innovation efficiency, and that social network relationships have an intermediary effect on the relationship between customer change and innovation efficiency; that is, the social network relationships reduce the negative impact of customer change on enterprise innovation efficiency. Further analysis shows that this mediating effect is not obvious for enterprises experiencing large customer changes but is prominent for nonstate-owned or nontechnology-intensive enterprises. Our study enriches and expands the research on how customer relationships influence enterprise innovation efficiency, clarifies different mechanisms due to various "networks", and provides new empirical evidence to enable enterprises to improve their competitiveness., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introducing 3-aminotyrosine (aY), a noncanonical amino acid (ncAA), into green fluorescent protein (GFP)-like chromophores shows promise for achieving red-shifted fluorescence. However, inconsistent results, including undesired green fluorescent species, hinder the effectiveness of this approach. In this study, we optimized expression conditions for an aY-derived cpGFP (aY-cpGFP). Key factors like rich culture media and oxygen restriction pre- and post-induction enabled high-yield, high-purity production of the red-shifted protein. We also engineered two variants of aY-cpGFP with enhanced brightness by mutating a few amino acid residues surrounding the chromophore. We further investigated the sensitivity of the aY-derived protein to metal ions, reactive oxygen species (ROS), and reactive nitrogen species (RNS). Incorporating aY into cpGFP had minimal impact on metal ion reactivity but increased the response to RNS. Expanding on these findings, we examined aY-cpGFP expression in mammalian cells and found that reductants in the culture media significantly increased the red-emitting product. Our study indicates that optimizing expression conditions to promote a reduced cellular state proved effective in producing the desired red-emitting product in both E. coli and mammalian cells, while targeted mutagenesis-based protein engineering can further enhance brightness and increase method robustness.

In this study, three phenylpyridine diamide ligands, namely, 2,2'-((pyridine-2,6-diylbis(3,1-phenylene))bis(oxy))bis( N , N -diethylacetamide) (PPEA, L1), 2,2'-((pyridine-2,6-diylbis(3,1-phenylene))bis(oxy))bis( N -ethyl- N -phenylacetamide) (PEPA, L2), and 2,2'-(((4-phenylpyridine-2,6-diyl)bis(3,1-phenylene))bis(oxy))bis( N , N -dioctylacetamide) (PPOA, L3), were synthesized and explored for the solvent extraction of Pu(iv) in a HNO 3 medium using 1-(trifluoromethyl)-3-nitrobenzene as the diluent. The effects of HNO 3 concentration, extractant concentration, and temperature on the Pu(iv) extraction efficiency were studied. All three extractants displayed high selectivity for Pu(iv) over other metals such as U(vi), Np(v), Am(iii), and various fission elements. At 3 M HNO 3 , the distribution ratio for Pu(iv) reached 27.18, in contrast to 1.11, 0.3, and 0.03 for U(vi), Np(v), Am(iii), respectively. Slope analysis and UV titration revealed the formation of 1 : 1 Pu(NO 3 ) 4 /ligand complexes during extraction. The extraction reactions had negative Gibbs free energies, indicating the spontaneous nature of Pu(iv) extraction at room temperature. Furthermore, the extractants demonstrated good stripping ability and reusability, and their radiolytic stability was reasonable up to an absorbed dose of 100 kGy, underscoring their potential for practical applications. Overall, this study broadens our understanding of actinide-diamide ligand coordination and actinide chemistry during coordination, paving the way for the design and synthesis of new extractants., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Our previous research has shown that prenatal methcathinone exposure affects the neurodevelopment and neurobehavior of adolescent offspring, but the study on whether these findings continue into adulthood is limited., Objective: This study aims to explore the effects of prenatal methcathinone exposure on anxiety-like behavior, learning and memory abilities, as well as serum 5-hydroxytryptamine and dopamine concentrations in adult offspring., Methods: Pregnant rats were injected daily with methcathinone between the 7th and 20th days of gestation. The neurobehavioral performance of both male and female adult offspring rats was evaluated by neurobehavioral tests, including open-field tests, Morris water maze (MWM) tests, and novel object recognition (NOR) tests. The levels of 5-hydroxytryptamine and dopamine concentration in rat serum were detected by ELISA., Results: Significant differences were found in the length of center distance and time of center duration in the open-field test, as well as the times of crossing the platform in the MWM test, between the prenatal methcathinone exposure group and the control group. Results of the NOR test showed that adult offspring rats exposed to methcathinone need more time to discriminate the novel object. No gender differences were detected in the neurobehavioral tests. The serum concentrations of 5-hydroxytryptamine and dopamine in rats exposed to methcathinone prenatally were lower than that in the control group, and the serum dopamine concentration was independent of gender in each group., Conclusion: Prenatal methcathinone exposure affects the neurological behavior in adult offspring, and 5-hydroxytryptamine and dopamine might be involved in the process., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Purpose: The use of oncolytic viruses as a gene therapy vector is an area of active biomedical research, particularly in the context of cancer treatment. However, the actual therapeutic success of this approach to tumor elimination remains limited. As such, the present study was developed with the goal of simultaneously enhancing the antitumor efficacy of oncolytic viruses and the local immune response by combining the Ad-GD55 oncolytic adenovirus and an antibody specific for the TIM-3 immune checkpoint molecule (α-TIM-3)., Approach and Key Results: The results of Virus and cell-mediated cytotoxicity assay, qPCR, and Western immunoblotting showed that Ad-GD55-α-Tim-3 oncolytic adenovirus is capable of inducing α-TIM-3 expression within hepatoma cells upon infection, and Ad-GD55-α-TIM-3 exhibited inhibitory efficacy superior to that of Ad-GD55 when used to treat these tumor cells together with the induction of enhanced intracellular immunity. In vivo experiments revealed that Ad-GD55-α-TIM-3 administration was sufficient to inhibit tumor growth and engage in a more robust local immune response within the simulated tumor immune microenvironment., Conclusion and Implications: These results highlighted the promising therapeutic effects of Ad-GD55-α-TIM-3 oncolytic adenovirus against HCC in vitro and in vivo. As such, this Ad-GD55-α-TIM-3 oncolytic adenovirus may represent a viable approach to the treatment of hepatocellular carcinoma., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study aims to investigate the safety of Shu-Xue-Ning injection (SXNI) in real-world clinical applications. Methods: A prospective, multi-center, large-sample intensive monitoring method was used to monitor the use of SXNI in several medical institutions across China while collecting patients' dosing and adverse event information. Patients who suspected as adverse reactions made comparisons with patients who did not report adverse reactions to calculate the correlation between relevant risk factors and suspected adverse reactions. Statistical analysis software SAS 9.1 was used for data analysis. Results: A total of 48 hospitals participated in this intensive monitoring study of SXNI, and 30,122 patients were monitored from July 2015 to December 2018. A total of 1,908 adverse events were reported during the use of SXNI, with an adverse event rate of 6.33% and a 95% confidence interval (CI) of 6.06%-6.61%. Association assessment showed that 54 cases presented with SXNI-related adverse reactions with an incidence of 0.18% and a 95% CI of 0.13%-0.23%, thereby indicating that the incidence of SXNI-related adverse reactions was occasional. SXNI-related adverse reactions involved 9 systems-organs with 20 clinical manifestations, and the most common adverse reactions were rash, pruritus, and other damages of skin and its appendages. No serious adverse reactions were observed; 27.78% of the adverse reactions occurred within 30 min of drug administration and more than half of them occurred within 2 h of drug administration; 96.3% of the adverse reactions were cured or improved. Causal analysis showed that women, long dispensing time, and slow dripping speed rate were considered as risk factors. Conclusion: The incidence of SXNI-related adverse reactions in real-world clinical applications is occasional and in a reasonable range with a good prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xinyao, Yifan, Keyi, Wentai, Chunyang, Hui, Chunxiang, Yunhua and Wenke.)

Background: In children with CKD, Protein Energy Wasting (PEW) is common, which affects the outcome of children and is an important cause of poor prognosis. We are aiming to explore the pathogenesis of muscle wasting in CKD-PEW children., Methods: Blood samples of 32 children diagnosed with chronic kidney disease (CKD) and protein energy wasting (PEW) in our hospital from January 2016 to June 2021 were collected. RNA sequencing and bioinformatics analysis were performed., Results: Based on GO (Gene Ontology) functional enrichment analysis, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis and differential gene expression analysis, a total of 25 CKD-PEW related genes were obtained including CRP, IL6, TNF, IL1B, CXCL8, IL12B, IL12A, IL18, IL1A, IL4, IL10, TGFB2, TGFB1, TGFB3, ADIPOQ, NAMPT, RETN, RETNLB, LEP, CD163, ICAM1, VCAM1, SELE, NF-κB1, NF-κB2. The most significantly differentially expressed gene was NF-κB2 (adjusted P = 2.81 × 10 -16 ), and its expression was up-regulated by 3.92 times (corresponding log2FoldChange value was 1.979). Followed by RETN (adjusted P = 1.63 × 10 -7 ), and its expression was up-regulated by 8.306 times (corresponding log2FoldChange value was 2.882). SELE gene were secondly significant (adjusted P = 5.81 × 10 -7 ), and its expression was down-regulated by 22.05 times (corresponding log2FoldChange value was -4.696)., Conclusions: A variety of inflammatory factors are involved in the pathogenesis of CKD-PEW in children, and chronic inflammation may lead to the development of muscle atrophy in CKD-PEW. It is suggested for the first time that NF-κB is a key gene in the pathogenesis of muscle wasting in CKD-PEW children, and its increased expression may play an important role in the pathogenesis of muscle wasting in children with CKD-PEW., (© 2023. The Author(s).)

Cardiac hypertrophy is initially an adaptive response to physiological and pathological stimuli. Although pathological myocardial hypertrophy is the main cause of morbidity and mortality, our understanding of its mechanism is still weak. NFAT3 (nuclear factor of activated T-cell-3) is a member of the nuclear factor of the activated T cells (NFAT) family. NFAT3 plays a critical role in regulating the expression of cardiac hypertrophy genes by inducing their transcription. Recently, accumulating evidence has indicated that NFAT3 is a potent regulator of the progression of cardiac hypertrophy. This review, for the first time, summarizes the current studies on NFAT3 in cardiac hypertrophy, including the pathophysiological processes and the underlying pathological mechanism, focusing on the nuclear translocation and transcriptional function of NFAT3. This review will provide deep insight into the pathogenesis of cardiac hypertrophy and a theoretical basis for identifying new therapeutic targets in the NFAT3 network., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Previous studies have reported lipoprotein(a) was related to increased risk of ischemic stroke. However, the role of fibrinogen in their associations was not fully elucidated., Aim: We aimed to investigate the mediating role of fibrinogen in the association between lipoprotein(a) and risk of ischemic stroke., Methods: A total of 516 patients with ischemic stroke were matched 1:1 to patients without ischemic stroke for age and gender. Serum lipoprotein(a) and plasma fibrinogen levels were collected on the basis of the results of biochemical tests. Multivariate conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for lipoprotein(a) levels and ischemic stroke risk. Mediation analysis were further conducted to evaluate the potential mediating role of fibrinogen in the association between lipoprotein(a) and ischemic stroke risk., Results: The lipoprotein(a) level of subjects with ischemic stroke was significantly higher than that of subjects without ischemic stroke (P < 0.001). Each SD increment of lipoprotein(a) was associated with 27% higher odds (OR 1.27, 95%CI: 1.11, 1.45) increment in ORs of ischemic stroke. Furthermore, mediation analyses indicated that fibrinogen mediated 10.15% of the associations between lipoprotein(a) and ischemic stroke., Conclusions: Higher level of lipoprotein(a) was independently associated with increased risk of ischemic stroke and fibrinogen partially mediated the associations of lipoprotein(a) and ischemic stroke risk., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

There is great interest in developing boronolectins that are synthetic lectin mimics containing a boronic acid functional group for reversible recognition of diol-containing molecules, such as glycans and ribonucleotides. However, it remains a significant challenge to gain specificity. Here, we present a genetically encoded boronolectin which is a hybrid protein consisting of a noncanonical amino acid (ncAA) p -boronophenylalanine ( p BoF), natural-lectin-derived peptide sequences, and a circularly permuted red fluorescent protein (cpRFP). The genetic encodability permitted a straightforward protein engineering process to derive a red fluorescent biosensor that can specifically bind uridine diphosphate N -acetylglucosamine (UDP-GlcNAc), an important nucleotide sugar involved in metabolic sensing and cell signaling. We further characterized the resultant b oronic a cid- and p eptide- a ssisted U DP- G lcN Ac sensor (bapaUGAc) both in vitro and in live mammalian cells. Because UDP-GlcNAc in the endoplasmic reticulum (ER) and Golgi apparatus plays essential roles in glycosylating biomolecules in the secretory pathway, we genetically expressed bapaUGAc in the ER and Golgi and validated the sensor for its responses to metabolic disruption and pharmacological inhibition. In addition, we combined bapaUGAc with UGAcS, a recently reported green fluorescent UDP-GlcNAc sensor based on an alternative sensing mechanism, to monitor UDP-GlcNAc level changes in the ER and cytosol simultaneously. We expect our work to facilitate the future development of specific boronolectins for carbohydrates. In addition, this newly developed genetically encoded bapaUGAc sensor will be a valuable tool for studying UDP-GlcNAc and glycobiology.

High temperature and high humidity (HTHH) conditions increase plant susceptibility to a variety of diseases, including bacterial wilt in solanaceous plants. Some solanaceous plant cultivars have evolved mechanisms to activate HTHH-specific immunity to cope with bacterial wilt disease. However, the underlying mechanisms remain poorly understood. Here we find that CaKAN3 and CaHSF8 upregulate and physically interact with each other in nuclei under HTHH conditions without inoculation or early after inoculation with R. solanacearum in pepper. Consequently, CaKAN3 and CaHSF8 synergistically confer immunity against R. solanacearum via activating a subset of NLRs which initiates immune signaling upon perception of unidentified pathogen effectors. Intriguingly, when HTHH conditions are prolonged without pathogen attack or the temperature goes higher, CaHSF8 no longer interacts with CaKAN3. Instead, it directly upregulates a subset of HSP genes thus activating thermotolerance. Our findings highlight mechanisms controlling context-specific activation of high-temperature-specific pepper immunity and thermotolerance mediated by differential CaKAN3-CaHSF8 associations., (© 2023. The Author(s).)

Boronic acid-containing fluorescent molecules have been widely used to sense hydrogen peroxide and peroxynitrite, which are important reactive oxygen and nitrogen species in biological systems. However, it has been challenging to gain specificity. Our previous studies developed genetically encoded, green fluorescent peroxynitrite biosensors by genetically incorporating a boronic acid-containing noncanonical amino acid (ncAA), p -boronophenylalanine ( p BoF), into the chromophore of circularly permuted green fluorescent proteins (cpGFPs). In this work, we introduced p BoF to amino acid residues spatially close to the chromophore of an enhanced circularly permuted red fluorescent protein (ecpApple). Our effort has resulted in two responsive ecpApple mutants: one bestows reactivity toward both peroxynitrite and hydrogen peroxide, while the other, namely, pnRFP, is a selective red fluorescent peroxynitrite biosensor. We characterized pnRFP in vitro and in live mammalian cells. We further studied the structure and sensing mechanism of pnRFP using X-ray crystallography, 11 B-NMR, and computational methods. The boron atom in pnRFP adopts an sp 2 -hybridization geometry in a hydrophobic pocket, and the reaction of pnRFP with peroxynitrite generates a product with a twisted chromophore, corroborating the observed "turn-off" fluorescence response. Thus, this study extends the color palette of genetically encoded peroxynitrite biosensors, provides insight into the response mechanism of the new biosensor, and demonstrates the versatility of using protein scaffolds to modulate chemoreactivity.

The incorporation of noncanonical amino acids (ncAAs) into fluorescent proteins is promising for red-shifting their fluorescence and benefiting tissue imaging with deep penetration and low phototoxicity. However, ncAA-based red fluorescent proteins (RFPs) have been rare. The 3-aminotyrosine modified superfolder green fluorescent protein (aY-sfGFP) represents a recent advance, yet the molecular mechanism for its red-shifted fluorescence remains elusive while its dim fluorescence hinders applications. Herein, we implement femtosecond stimulated Raman spectroscopy to obtain structural fingerprints in the electronic ground state and reveal that aY-sfGFP possesses a GFP-like instead of RFP-like chromophore. Red color of aY-sfGFP intrinsically arises from a unique "double-donor" chromophore structure that raises ground-state energy and enhances charge transfer, notably differing from the conventional conjugation mechanism. We further developed two aY-sfGFP mutants (E222H and T203H) with significantly improved (∼12-fold higher) brightness by rationally restraining the chromophore's nonradiative decay through electronic and steric effects, aided by solvatochromic and fluorogenic studies of the model chromophore in solution. This study thus provides functional mechanisms and generalizable insights into ncAA-RFPs with an efficient route for engineering redder and brighter fluorescent proteins.

Quantitative identification of water utilization characteristics of xerophytic shrubs is an important prerequisite for the selection and optimization of a regional artificial sand-fixing vegetation system. In this study, a hydrogen (δD) stable isotope technique was used to study the changes in water use characteristics of four typical xerophytic shrubs, Caragana korshinskii , Salix psammophila , Artemisia ordosica , and Sabina vulgaris in the Hobq Desert under light (4.8 mm after 1 and 5 days) and heavy (22.4 mm after 1 and 8 days) rainfall events. Under light rainfall, C. korshinskii and S. psammophila primarily used the 80-140 cm layer of soil water (37-70%) and groundwater (13-29%), and the water use characteristics did not change significantly after the light rainfall event. However, the utilization ratio of A. ordosica to soil water in the 0-40 cm layer increased from less than 10% on the first day after rain to more than 97% on the fifth day after rain, whereas the utilization ratio of S. vulgaris to soil water in the 0-40 cm layer also increased from 43% to nearly 60%. Under heavy rainfall, C. korshinskii and S. psammophila still used the 60-140 cm layer (56-99%) and groundwater (~15%), while the main water utilization depth of A. ordosica and S. vulgaris expanded to 0-100 cm. Based on the above results, C. korshinskii and S. psammophila primarily use the soil moisture of the 80-140 cm layer and groundwater, while A. ordosica and S. vulgaris use the soil moisture of the 0-100 cm layer. Therefore, the co-existence of A. ordosica and S. vulgaris will increase the competition between artificial sand-fixing plants, while the combination of the two plants with C. korshinskii and S. psammophila will avoid competition between artificial sand-fixing plants to some extent. This study provides important guidance for regional vegetation construction and sustainable management of an artificial vegetation system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yongsheng, Zilong, Xiangqian, Qiang, Hui and Li.)

Reliable disease management can guarantee healthy plant production and relies on the knowledge of pathogen prevalence. Modeling the dynamic changes in spore concentration is available for realizing this purpose. We present a novel model based on a time-series modeling machine learning method, i.e., a long short-term memory (LSTM) network, to analyze oomycete Plasmopara viticola sporangia concentration dynamics using data from a 4-year field experiment trial in North China. Principal component analysis (PCA)-based high-quality input screening and simulation result calibration were performed to ensure model performance, obtaining a high determination coefficient (0.99), a low root mean square error (0.87), and a low mean bias error (0.55), high sensitivity (91.5%), and high specificity (96.5%). The impact of the variability of relative factors on daily P. viticola sporangia concentrations was analyzed, confirming that a low daily mean air temperature restricts pathogen development even during a long period of high humidity in the field., (© 2023. The Author(s) under exclusive licence to International Society of Biometeorology.)

Synaptic zinc ion (Zn 2+ ) has emerged as a key neuromodulator in the brain. However, the lack of research tools for directly tracking synaptic Zn 2+ in the brain of awake animals hinders our rigorous understanding of the physiological and pathological roles of synaptic Zn 2+ . In this study, we developed a genetically encoded far-red fluorescent indicator for monitoring synaptic Zn 2+ dynamics in the nervous system. Our engineered far-red fluorescent indicator for synaptic Zn 2+ (FRISZ) displayed a substantial Zn 2+ -specific turn-on response and low-micromolar affinity. We genetically anchored FRISZ to the mammalian extracellular membrane via a transmembrane (TM) ⍺ helix and characterized the resultant FRISZ-TM construct at the mammalian cell surface. We used FRISZ-TM to image synaptic Zn 2+ in the auditory cortex in acute brain slices and awake mice in response to electric and sound stimuli, respectively. Thus, this study establishes a technology for studying the roles of synaptic Zn 2+ in the nervous system.

A promising direction in the research on Alzheimer's Disease (AD) is the identification of biomarkers that better inform the disease progression of AD. However, the performance of amyloid-based biomarkers in predicting cognitive performance has been shown to be suboptimal. We hypothesise that neuronal loss could better inform cognitive impairment. We have utilised the 5xFAD transgenic mouse model that displays AD pathology at an early phase, already fully manifested after 6 months. We have evaluated the relationships between cognitive impairment, amyloid deposition, and neuronal loss in the hippocampus in both male and female mice. We observed the onset of disease characterized by the emergence of cognitive impairment in 6-month-old 5xFAD mice coinciding with the emergence of neuronal loss in the subiculum, but not amyloid pathology. We also showed that female mice exhibited significantly increased amyloid deposition in the hippocampus and entorhinal cortex, highlighting sex-related differences in the amyloid pathology of this model. Therefore, parameters based on neuronal loss might more accurately reflect disease onset and progression compared to amyloid-based biomarkers in AD patients. Moreover, sex-related differences should be considered in studies involving 5xFAD mouse models.

Lactate has emerged as a central metabolic fuel and an important signaling molecule. In this issue of Cell Metabolism, Li et al. develop a high-quality lactate sensor, allowing them to monitor lactate levels in cells, subcellular organelles, live mice, and human body fluids., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Heterologous expression systems have been used as a powerful experimental strategy to study the function of many proteins, particularly ion transporters. For this experiment, it is fundamental to prepare an expression vector encoding a protein of interest. However, we encountered problems in vector preparation of the voltage sensor domain (VSD) of murine sperm-specific Na + /H + exchanger (sNHE) due to its severe toxicity to bacteria. We overcame the problems by insertion of an amber stop codon or a synthetic intron into the coding sequence of the VSD in the expression vectors. Both methods allowed us to express the protein of interest in HEK293 cells (combined with a stop codon suppression system for amber codon). The VSD of mouse sNHE generates voltage-dependent outward ionic currents, which is a probable cause of toxicity to bacteria. We propose these two strategies as practical solutions to study the function of any protein toxic to bacteria., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The purpose of this paper is to study how the Delta variant spread in a China city, and to what extent the non-pharmaceutical prevention measures of local government be effective by reviewing the contact network of COVID-19 cases in Xi'an, China., Methods: We organize the case reports of the Shaanxi Health Commission into a database by text coding and convert them into a network matrix. Then we construct a dynamic contact network for the corresponding analysis and calculate network indicators. we analyze the cases' dynamic contact network structure and intervals between diagnosis time and isolation time by using data visualization, network analysis method, and Ordinary Least Square (OLS) regression., Results: The contact network for this outbreak in Xi'an is very sparse, with a density of less than 0.0001. The contact network is a scale-free network. The average degree centrality is 0.741 and the average PageRank score is 0.0005. The network generated from a single source of infection contains 1371 components. We construct three variables of intervals and analyze the trend of intervals during the outbreak. The mean interval (interval 1) between case diagnosis time and isolation time is - 3.9 days. The mean of the interval (interval 2) between the infector's diagnosis time and the infectee's diagnosis time is 4.2 days. The mean of the interval (interval 3) between infector isolation time and infectee isolation time is 2.9 days. Among the three intervals, only interval 1 has a significant positive correlation with degree centrality., Conclusions: By integrating COVID-19 case reports of a Chinese city, we construct a contact network to analyze the dispersion of the outbreak. The network is a scale-free network with multiple hidden pathways that are not detected. The intervals of patients in this outbreak decreased compared to the beginning of the outbreak in 2020. City lockdown has a significant effect on the intervals that can affect patients' network centrality. Our study highlights the value of case report text. By linking different reports, we can quickly analyze the spread of the epidemic in an urban area., (© 2022. The Author(s).)

This study explores the relationship between the proportion of basic research investment in R&D expenditure and regional economic growth efficiency and its influence path. A panel of data from 31 China's provincial was analysed by the fixed-effects model over 2009 to 2019. Empirical results highlight that: (1) the increase in the proportion of basic research investment has a significant promoting effect on regional economic growth efficiency, but it presents an "inverted U-shaped" impact path. Meanwhile, the threshold effect model test results reveal that basic research investment plays a more significant role in promotion when the per capita income level exceeds a certain threshold. (2) The test results of the mediating effect model indicate that the improvement of the level of human capital is the intermediate channel through which the investment in basic research affects regional economic growth efficiency, while the mediating effect of the increase of knowledge storage on the process of the investment in basic research affecting regional economic growth efficiency is not supported by data. Potential policy measures are discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study aimed to investigate the influence of orthokeratology (OK) on myopia control and ocular surface and meibomian gland function in myopic adolescents., Methods: A prospective study was conducted over a 12-month period. The subjects were classified into two groups, namely, the OK lens group and the frame glasses control group. Axial length, corneal curvature, ocular surface, and meibomian gland parameters were measured at baseline, 1, 3, 6, and 12 months after wearing OK lenses., Results: The axial length growth rate in the OK group was significantly slower than in the control group ( P < 0.01). The naked eye vision and the ocular surface disease index (OSDI) scores recorded 1, 3, 6, and 12 months after wearing OK lenses were significantly higher than the scores recorded before wearing OK lenses. There was no significant difference in other ocular parameters at each follow-up time point compared with pre-wearing ( P > 0.05). After using the OK lens for 6 months, the OSDI score and corneal fluorescein staining (CFS) score increased significantly ( P < 0.001), but there were no significant differences in other parameters among the groups. No infectious keratitis occurred during the study., Conclusion: These results provide evidence that the use of OK lenses can control the axial growth and progress rate of myopia compared with frame glasses. During the 12-month follow-up, although wearing OK lenses may have aggravated dry eye symptoms, each patient's ocular surface and meibomian gland function did not change significantly, indicating that the use of OK lenses is a relatively safe modality for the control of myopia in adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hui, Xiao-feng, Song-guo, Jing-jing, Xuan and Yong.)

Purpose: To determine the macular and peripapillary area choroid microstructure parameters of hyperopic anisometropic amblyopia eyes and compare to fellow and age-matched control eyes. To assess the correlation between the axial length (AL), choroidal thickness (CT) and choroid microstructure parameters., Methods: This cross-sectional comparative, non-interventional study involved 52 hyperopic anisometropic amblyopia children and 48 age-matched heathy controls. 52 eyes with hyperopic anisometropic amblyopia and 48 age-matched control eyes were studied. The peripapillary and subfoveal CT were determined. The total choroidal area (TCA), luminal area (LA), and stromal area (SA) of the subfoveal and peripapillary choroid were measured. In addition, the correlation between the AL, CT and choroid microstructure parameters were calculated., Results: The peripapillary and subfoveal CT of the amblyopic eyes was significantly thicker than the fellow and control eyes (all P  < 0.05). The subfoveal and peripapillary choroidal SA, LA and TCA of the amblyopic eyes were significantly increased than that of the fellow and control eyes (all P  < 0.05). The choroidal vascularity index (CVI) values of the amblyopic eye were significantly different among the three groups ( P  < 0.05). There was a statistically significant negative correlation between AL and subfoveal CT (SFCT), LA and TCA levels ( P  < 0.001, P  = 0.039, P  = 0.027, respectively). Spherical equivalent (SE) was positive correlated with SFCT, LA and TCA levels ( P  = 0.456, 0.229 and 0.240, respectively; all P  < 0.05). There was a statistically significant positive correlation between SFCT, SE, LA, SA, TCA and CVI levels (all P  < 0.05)., Conclusion: The subfoveal and peripapillary CT of amblyopic children abnormally increased and correlated with shorter AL and higher SE. The choroidal structure of the amblyopic eyes was different from the fellow and control eyes, the hyperopic anisometropic amblyopic eyes had significantly thicker sub-foveal choroid, higher LA, SA, and TCA. AL and CT affect choroidal structure and vascular density. Choroidal blood flow may be increased in amblyopic eyes. The larger LA, SA, TCA, and lower CVI were characteristic of the amblyopic eye., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Hui, Xiaofeng, Hua, Yihan and Yong.)

Aim: The aim of this study is to investigate the compassion satisfaction and compassion fatigue among Chinese frontline nurses during the COVID-19 pandemic in Wuhan, China and to explore the related factors., Background: Frontline nurses undertake a huge nursing workload with a risk of infection, causing great pressure on them and making them face a risk of compassion fatigue during the pandemic., Methods: A cross-sectional online survey was conducted from 9 March to 15 March 2020. A total of 1582 nurses caring for critical patients with COVID-19 participated. Compassion satisfaction and compassion fatigue (comprising burnout and secondary traumatic stress) were assessed with the Professional Quality of Life Scale, and resilience was measured with the Chinese 10-item Connor-Davidson Resilience Scale., Results: Moderate levels of compassion satisfaction (36.99 ± 6.71), burnout (24.14 ± 5.33) and secondary traumatic stress (24.53 ± 5.24) were experienced by frontline nurses. Resilience and perceived work pressure were the main predictors., Conclusions: Frontline nurses demonstrated a moderate level of compassion satisfaction and compassion fatigue., Implications for Nursing Management: The compassion fatigue of frontline nurses should be considered. Strategies aiming to reduce stress and enhance resilience, such as training about psychological adjustment, developing professional skills and creating a supportive workplace environment, are several options. The trial is not registered. This study is a cross-sectional study, and according to China's clinical trial registration standards, such studies are not required to be registered. So the trial is not registered. However, oral consent was obtained from the ethics committee of the hospital before this study was conducted., (© 2022 John Wiley & Sons Ltd.)

Purpose: To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the adapted Prostate Cancer Working Group Criteria 3 (aPCWG3), the adapted Positron Emission Tomography Response Criteria in Solid Tumors (aPERCIST), the PSMA PET Progression (PPP), and the Response Evaluation Criteria In PSMA-Imaging (RECIP) 1.0 for response evaluation using prostate-specific membrane antigen (PSMA)-PET/CT in men with metastatic castration-resistant prostate cancer (mCRPC) treated with 177 Lu-PSMA radioligand therapy., Methods: A total of 124 patients were included in this multicenter retrospective study. All patients received 177 Lu-PSMA and underwent PSMA-PET/CT scans at baseline (bPET) and at 12 weeks (iPET). Imaging responses according to RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 were interpreted by consensus among three blinded readers. Changes in total tumor burden were obtained using the semi-automatic qPSMA software. The response according to each criterion was classified to progressive disease (PD) vs no-PD. Primary outcome measure was the prognostic value (by Cox regression analysis) for overall survival (OS). Secondary outcome measure was the inter-reader reliability (by Cohen's κ coefficient)., Results: A total of 43 (35%) of patients had non-measurable disease according to RECIST 1.1. Sixteen (13%), 66 (52%), 72 (58%), 69 (56%), and 39 (32%) of 124 patients had PD according to RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP, respectively. PD vs no-PD had significantly higher risk of death according to aPCWG3 (HR = 2.37; 95%CI, 1.62-3.48; p < 0.001), aPERCIST (HR = 2.48; 95%CI, 1.68-3.66; p < 0.001), PPP (HR = 2.72; 95%CI, 1.85-4.01; p < 0.001), RECIP 1.0 (HR = 4.33; 95%CI, 2.80-6.70; p < 0.001), but not according to RECIST 1.1 (HR = 1.29; 95%CI, 0.73-2.27; p = 0.38). The κ index of RECIST 1.1, aPCWG3, aPERCIST 1.0, PPP, and RECIP 1.0 for identifying PD vs no-PD were 0.50 (95%CI, 0.32-0.76), 0.72 (95%CI, 0.63-0.82), 0.68 (95%CI, 0.63-0.73), 0.73 (95%CI, 0.63-0.83), and 0.83 (95%CI, 0.77-0.88), respectively., Conclusion: PSMA-PET-specific criteria for early response evaluation in men with mCRPC treated with 177 Lu-PSMA achieved higher prognostic values and inter-reader reliabilities in comparison to conventional CT assessment or to criteria adapted to PSMA-PET from other imaging modalities. RECIP 1.0 identified the fewest patients with PD and achieved the highest risk of death for PD vs. no-PD, suggesting that other classification methods tend to overcall progression. Prospective validation of our findings on an independent patient cohort is warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent years, the practice of dentistry and periodontology has become complicated by several risk factors, including the treatment of an increasing number of patients with substance use disorder. This review presents an update in the current literature of the impact of illegal drug use on periodontal conditions and their possible effect as risk factors or indicators. The main illegal drugs that may have an impact on periodontal health and conditions are described, including their effect, medical manifestations, risks, and the overall effect on oral health and on the periodontium. Where available, data from epidemiologic studies are analyzed and summarized. The clinical management of periodontal patients using illegal drugs is reported in a comprehensive approach inclusive of the detection of illicit drug users, screening, interviewing and counseling, the referral to treatment, and the dental and periodontal management. With regard to the impact of illegal substance use on periodontal conditions, there is moderate evidence that regular long-term use of cannabis is a risk factor for periodontal disease, manifesting as a loss of periodontal attachment, deep pockets, recessions, and gingival enlargements. Limited evidence also shows that the use of cocaine can cause a series of gingival conditions that mostly presents as chemical induced-traumatic lesions (application of cocaine on the gingiva) or necrotizing ulcerative lesions. There is a scarcity of data regarding the impact of other drug use on periodontal health. There is evidence to suggest that regular long-term use of cannabis is a risk factor for periodontal disease and that the use of cocaine can cause a series of periodontal conditions. The dental treatment of subjects that use illegal substances is becoming more common in the daily clinical practice of periodontists and other dental clinicians. When the clinicians encounter such patients, it is essential to manage their addiction properly taking into consideration the impact of it on comprehensive dental treatment. Further studies and clinical observations are required to obtain sound and definitive information., (© 2022 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.)

The NanoLuc luciferase (NLuc) and its furimazine (FRZ) substrate have revolutionized bioluminescence (BL) assays and imaging. However, the use of the NLuc-FRZ luciferase-luciferin pair for mammalian tissue imaging is hindered by the low tissue penetration of the emitting blue photons. Here, we present the development of an NLuc mutant, QLuc, which catalyzes the oxidation of a synthetic QTZ luciferin for bright and red-shifted emission peaking at ∼585 nm. Compared to other small single-domain NLuc mutants, this amber-light-emitting luciferase exhibited improved performance for imaging deep-tissue targets in live mice. Leveraging this novel bioluminescent reporter, we further pursued in vivo immunobioluminescence imaging (immunoBLI), which used a fusion protein of a single-chain variable antibody fragment (scFv) and QLuc for molecular imaging of tumor-associated antigens in a xenograft mouse model. As one of the most red-shifted NLuc variants, we expect QLuc to find broad applications in noninvasive mammalian imaging. Moreover, the immunoBLI method complements immunofluorescence imaging and immuno-positron emission tomography (immunoPET), serving as a convenient and nonradioactive molecular imaging tool for animal models in basic and preclinical research.

Background: Joubert Syndrome (JS) is a rare genetic developmental disorder. We are aiming for increasing awareness of this disease especially kidney involvement in children with JS., Methods: Clinical and genetic data of 17 cases of JS in Beijing children's hospital in the past 21 years were collected retrospectively., Results: Twelve males and 5 females, aged from 12d to 15y8m. The most common involvement was neurological system involvement. The second most common involvement was renal involvement: end stage kidney disease in 6 cases (35%), hematuria in 5 cases (29%), proteinuria in 5 cases (29%), renal diffuse lesions in 4 cases (24%), renal cystic lesions in 2 cases (12%), and echogenic enhancement of parenchyma in 2 cases (12%). 10 cases did genetic tests. 3 cases with renal deficiency all had RPGRIP1L gene mutation., Conclusions: The most common involvement of JS is neurological involvement, and the second is renal involvement. Pediatricians should improve awareness of JS and conduct systemic evaluation of children. More attention should be paid to renal involvement which may be onset hidden but fatal. Early recognition and diagnosis are the goals to delay the start to dialysis and improve quality of patients' life. The RPGRIP1L gene mutation maybe the most common gene mutation in JS and may have correlations with renal involvement., (© 2022. The Author(s).)

Although fluorescent indicators have been broadly utilized for monitoring bioactivities, fluorescence imaging, when applied to mammals, is limited to superficial targets or requires invasive surgical procedures. Thus, there is emerging interest in developing bioluminescent indicators for noninvasive mammalian imaging. Bioluminescence imaging (BLI) of neuronal activity is highly desired but hindered by insufficient photons needed to digitalize fast brain activities. In this work, we develop a luciferase prosubstrate deliverable at an increased dose and activated in vivo by nonspecific esterase. We further engineer a bright, bioluminescent indicator with robust responsiveness to calcium ions (Ca 2+ ) and appreciable emission above 600 nm. Integration of these advantageous components enables the imaging of the activity of neuronal ensembles in awake mice minimally invasively with excellent signal-to-background and subsecond temporal resolution. This study thus establishes a paradigm for studying brain function in health and disease., (© 2022. The Author(s).)

The current study aimed to explore the correlation between Mir-34A-3p, Mir-31, PLEK2 and the occurrence, development and prognosis of colorectal cancer. For this paper, 120 patients with colorectal cancer were selected as the study group, and their adjacent normal tissues were selected as the control group. The quantitative real-time PCR (QRT-PCR) method was used to detect miR-34a-3p and miR-31 in tissues, and the immunohistochemistry EnVision two-step method was used to detect PLEK2 positive expression. The expressions of miR -34a-3p, miR -31, and PLEK2 in colon cancer tissues and normal cancer tissues were compared, and the correlation between miR -34a-3p, miR -31, and PLEK2 and clinic-pathological characteristics of colorectal cancer patients were analyzed. The results showed that expression of miR -34a-3p, miR -31 and positive expression rate of PLEK2 in colorectal cancer tissues were higher than those in normal adjacent tissues (P<0.05). The expression of miR -34a-3p was related to tumor size, degree of tissue differentiation, lymph node metastasis and TNM stage (P < 0.05). The 3-year survival rate of miR -34a-3p with low expression was lower than miR -34a-3p with high expression, which was a protective factor affecting the poor prognosis of colorectal cancer (P < 0.05). The expression of miR -31 was related to tumor size and TNM stage. The 3-year survival rate of the group with high expression of miR -31 was lower than the group with low expression of miR -31, which was a risk factor affecting the poor prognosis of colorectal cancer (P < 0.05). PLEK2 positive expression was associated with lymph node metastasis, and the 3-year survival rate of the PLEK2 positive group was lower than the PLEK2 low expression group, which was a risk factor for poor prognosis of colorectal cancer (P < 0.05). In general, miR -34a-3p, miR -31, and PLEK2 are closely associated with the occurrence and development of colorectal cancer, and they are all influential factors affecting the prognosis of patients with colorectal cancer, which can provide a basis for the evaluation and treatment of patients, and are worthy of widespread clinical application.

Aims: To investigate the efficacy and safety of minimally invasive bronchoscopic interventions for patients with tracheobronchial mucoepidermoid carcinoma (MEC)., Methods: Patients with tracheobronchial MEC were included in this retrospective study, and the clinical features, histologic grading, treatments, and cumulative survival rates were calculated. Patients were categorized into child (n = 16) and adult (n = 19) group according to their ages. Histologic grading, treatments, and survival status were compared between the two groups., Results: In pathology, high-grade MEC counts for 6.77% and 42.10% in the child and adult group, respectively. As tumor growth pattern was concerned, 93.33% and 21.05% tumors in the child and adult group present intratracheal type. Multiple bronchoscopic interventions were conducted, including rigid bronchoscopy, argon plasma coagulation (APC), dioxide carbon cryotherapy, and electric loop. Tumors could be removed by multiple bronchoscopic interventions. Bronchoscopy-associated complications were rare, including an oral mucosa injury and a glottis edema. In the child group, one patient underwent left upper lung lobectomy. In the adult group, lobectomy and/or chemotherapy and/or radiotherapy were conducted in seven patients. The 5-year survival rate was 100% and 68.90% in the child and the adult group, respectively., Conclusions: Almost all children have low-grade and intratracheal MEC; 2/5 adults have invasive high-grade MEC. Multiple bronchoscopic interventions are effective in erasing low-grade intratracheal MEC without severe complications. For high-grade invasive MEC, aggressive and comprehensive therapy should be considered.

Oxidative stress is important for the etiology and pathogenesis of Alzheimer's disease (AD). Research tools that can conveniently evaluate oxidative stress in AD models are expected to catalyze and accelerate research on AD. This study explored the use of genetically encoded fluorescent indicators (GEFIs) to detect mitochondrial oxidative stress in organotypic brain slices and AD mouse models. To enable ratiometric normalization and avoid tissue autofluorescence, we genetically fused a green fluorescent hydrogen peroxide (H 2 O 2 ) indicator, HyPer7, with each of two selected, bright red fluorescent proteins (RFPs), mScarlet-I and tdTomato. The resultant indicators, namely, HyPerGR S and HyPerGR T , were tagged with mitochondrial targeting sequences and examined for localization and function in cultured HeLa cells and primary mouse neurons. We further utilized HyPerGR T , which is a genetic fusion of HyPer7 with tdTomato, to monitor mitochondrial H 2 O 2 in response to the human β-amyloid 1-42 isoform (Aβ 42 ) in cultured brain slices and an AD mouse model. Owing to the high sensitivity and low autofluorescence interference resulting from HyPerGR T , we successfully detected Aβ 42 -mediated mitochondrial H 2 O 2 in these AD models. The results suggest that HyPerGR T is a valuable tool for studying mitochondrial oxidative stress in tissues and animals.

Thioredoxin (Trx) is one of the major thiol-dependent antioxidants in living systems. The study of Trx functions in redox biology was impeded by the lack of practical tools to track Trx redox dynamics in live cells. Our previous work developed TrxRFP1, the first genetically encoded fluorescent indicator for Trx redox. In this work, we report an improved fluorescent indicator, TrxRFP2, for tracking the redox of Trx1, which is primarily cytosolic and nuclear. Furthermore, because mitochondria specifically express Trx2, we have created a new genetically encoded fluorescent indicator, MtrxRFP2, for the redox of mitochondrial Trx. We characterized MtrxRFP2 as a purified protein and used subcellularly localized MtrxRFP2 to image mitochondrial redox changes in live cells.

Allostery enables proteins to interconvert different biochemical signals and form complex metabolic and signaling networks. We hypothesize that circular permutation of proteins increases the probability of functional coupling of new N- and C- termini with the protein's active center through increased local structural disorder. To test this we construct a synthetically allosteric version of circular permutated NanoLuc luciferase that can be activated through ligand-induced intramolecular non-covalent cyclisation. This switch module is tolerant of the structure of binding domains and their ligands, and can be used to create biosensors of proteins and small molecules. The developed biosensors covers a range of emission wavelengths and displays sensitivity as low as 50pM and dynamic range as high as 16-fold and could quantify their cognate ligand in human fluids. We apply hydrogen exchange kinetic mass spectroscopy to analyze time resolved structural changes in the developed biosensors and observe ligand-mediated folding of newly created termini., (© 2022. The Author(s).)

Long, noncoding RNAs reportedly play vital roles in tuberculosis (TB). For example, upregulation of LINC00870 has been observed in tuberculosis, though its role and underlying mechanism remains unclear. In this study, we investigated the expression and effect of LINC00870 in Mycobacterium tuberculosis (MTB) infection by comparing MTB-infected peripheral blood mononuclear cells (PBMCs) with controls. The results showed LINC00870 was significantly increased in MTB infected PBMCs. Additionally, LINC00870 overexpression inhibited Th1-secreted cytokines while promoted Th2-secreted cytokine in MTB-infected PBMCs. Furthermore, LINC00870 promoted p-STAT5 and p-JAK2 protein expression, thus activating JAK/STAT signaling in MTB-infected PBMCs. Sputum and plasma samples were obtained from TB, latent tuberculosis infection (LTBI) patients and healthy controls. The qRT-PCR results showed higher levels of LINC00870 in the sputum and plasma from TB and LTBI patients compared to healthy controls. In addition, LINC00870 were decreased in both TB and LTBI patients after three month of therapy, respectively. The results showed a correlation between LINC00870 inhibition and Th1/Th2, as well as JAK/STAT signaling pathway in PBMCs from active TB patients. In conclusion, higher levels of LINC00870 in tuberculosis might be associated with Th1/Th2-related immune responses by activating JAK/STAT signaling. LINC00870 thus may be a novel biomarker for diagnosing and treating tuberculosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To study the effect of a seven-step rehabilitation training program on cardiac function and quality of life in acute myocardial infarction (AMI) patients after percutaneous coronary intervention (PCI)., Methods: In this study one hundred AMI patients undergoing emergency PCI at The First Hospital of Fangshan District between June 2019 and June 2020 were included. Patients were retrospectively divided into two equal groups based on the type of physiotherapy regiment. The training group included patients who underwent seven-step rehabilitation training while the control group had patients who received routine nursing. Left ventricular ejection fraction (LVEF), self-care capability, hospitalization duration, quality of life, and adverse cardiac event incidence were compared., Results: The number of patients with LVEF values ≥ 50% was significantly higher in the training group after one week of training. Training group patients also showed decreased hospitalization duration and larger improvement in self-care capacity scores. At three months after training, training group patients had overall superior quality of life and lower incidence rates of arrhythmia and angina pectoris., Conclusion: The seven-step rehabilitation training program has a significant effect on improving AMI patient quality of life and cardiac function post-PCI, and is worthy of continued study and promotion., (Copyright: © Pakistan Journal of Medical Sciences.)

Purpose: To evaluate the performance of combined PET and multiparametric MRI (mpMRI) radiomics for the group-wise prediction of postsurgical Gleason scores (psGSs) in primary prostate cancer (PCa) patients., Methods: Patients with PCa, who underwent [ 68  Ga]Ga-PSMA-11 PET/MRI followed by radical prostatectomy, were included in this retrospective analysis (n = 101). Patients were grouped by psGS in three categories: ISUP grades 1-3, ISUP grade 4, and ISUP grade 5. mpMRI images included T1-weighted, T2-weighted, and apparent diffusion coefficient (ADC) map. Whole-prostate segmentations were performed on each modality, and image biomarker standardization initiative (IBSI)-compliant radiomic features were extracted. Nine support vector machine (SVM) models were trained: four single-modality radiomic models (PET, T1w, T2w, ADC); three PET + MRI double-modality models (PET + T1w, PET + T2w, PET + ADC), and two baseline models (one with patient data, one image-based) for comparison. A sixfold stratified cross-validation was performed, and balanced accuracies (bAcc) of the predictions of the best-performing models were reported and compared through Student's t-tests. The predictions of the best-performing model were compared against biopsy GS (bGS)., Results: All radiomic models outperformed the baseline models. The best-performing (mean ± stdv [%]) single-modality model was the ADC model (76 ± 6%), although not significantly better (p > 0.05) than other single-modality models (T1w: 72 ± 3%, T2w: 73 ± 2%; PET: 75 ± 5%). The overall best-performing model combined PET + ADC radiomics (82 ± 5%). It significantly outperformed most other double-modality (PET + T1w: 74 ± 5%, p = 0.026; PET + T2w: 71 ± 4%, p = 0.003) and single-modality models (PET: p = 0.042; T1w: p = 0.002; T2w: p = 0.003), except the ADC-only model (p = 0.138). In this initial cohort, the PET + ADC model outperformed bGS overall (82.5% vs 72.4%) in the prediction of psGS., Conclusion: All single- and double-modality models outperformed the baseline models, showing their potential in the prediction of GS, even with an unbalanced cohort. The best-performing model included PET + ADC radiomics, suggesting a complementary value of PSMA-PET and ADC radiomics., (© 2021. The Author(s).)