Rational design of a near-infrared fluorescent probe for monitoring butyrylcholinesterase activity and its application in development of inhibitors.

Butyrylcholinesterase (BChE) is widely expressed in multiple tissues and has a vital role in several key human disorders, such as Alzheimer's disease and tumorigenesis. However, the role of BChE in human disorders has not been investigated. Thus, to quantitatively detect and visualize dynamical variations in BChE activity is essential for exploring the biological roles of BChE in the progression of a number of human disorders. Herein, based on the substrate characteristics of BChE, we customized and synthesized three near-infrared (NIR) fluorescent probe substrates with cyanine-skeleton, and finally selected a NIR fluorescence probe substrate named CYBA. The CYBA demonstrated a significant increase in fluorescence when interacting with BChE, but mainly avoided AChE. Upon the addition of BChE, CYBA could be specifically hydrolyzed to TBO, resulting in a significant NIR fluorescence signal enhancement at 710 nm. Systematic evaluation revealed that CYBA exhibited exceptional chemical stability in complex biosamples and possessed remarkable selectivity and sensitivity towards BChE. Moreover, CYBA was successfully applied for real-time imaging of endogenous BChE activity in two types of nerve-related living cells. Additionally, CYBA demonstrated exceptional stability in the detection of complex biological samples in plasma recovery studies (97.51%-104.01%). Furthermore, CYBA was used to construct a high-throughput screening (HTS) method for BChE inhibitors using human plasma as the enzyme source. We evaluated inhibitory effects of a series of natural products and four flavonoids were identified as potent inhibitors of BChE. Collectively, CYBA can serve as a practical tool to track the changes of BChE activity in complicated biological environments due to its excellent capabilities.

A bis(PCN) palladium pincer complex with a remarkably planar 2,5-diarylpyrazine core.

A bimetallic Pd complex of a bis(pincer) with a diarylpyrazine core has been prepared. The complex demonstrates near-perfect coplanarity of the aromatic core, is fluorescent under UV irradiation, and displays two quasi-reversible reduction events.

Total body water percentage and 3rd space water are novel risk factors for training-related lower extremity muscle injuries in young males.

PURPOSE: To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis. METHODS: A total of 282 healthy young male volunteers aged 18 - 20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conforms to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q1, Q3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. RESULTS: Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4 % (66 cases). These patients showed higher percentages of lean body mass (p = 0.001), total body water (TBW, p = 0.006), extracellular water (p = 0.020) and intracellular water (p = 0.010) as well as a larger ratio of basal metabolic rate/total weight (p = 0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat (p = 0.001) and body fat mass index (p = 0.002) was lower. Logistic regression analysis showed that TBW percentage > 65.35% (p = 0.050, OR = 3.114) and 3rd space water > 0.95% (p = 0.045, OR = 2.342) were independent risk factors for lower extremity muscle injuries. CONCLUSION: TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

A Novel Cargo Delivery System-AnCar-ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

Platycodin D inhibits the proliferation, invasion and migration of endometrial cancer cells by blocking the PI3K/Akt signaling pathway via ADRA2A upregulation.

Endometrial cancer (EC) is a complex disease that affects the reproductive health of females worldwide. Platycodin D (PD) is known to exert numerous anticancer effects, markedly inhibiting cell proliferation, inducing apoptosis and causing cell cycle arrest in several types of cancer. The present study aimed to explore the mechanisms underlying the effects of PD in EC cells. The viability and proliferation of human endometrial stromal cells (ESCs) and RL95-2 EC cells following treatment with PD were evaluated using Cell Counting Kit-8, MTT and colony formation assays. Wound healing and Transwell assays were also performed to assess the migration and invasion of EC cells following treatment with PD. The expression levels of α2A-adrenergic receptor (ADRA2A) were measured using reverse transcription-quantitative PCR and western blotting assays with and without PD treatment and following transfection with short hairpin (sh) RNAs targeting ADRA2A2. Moreover, western blot analysis was performed to measure the expression levels of Ki67, PCNA, MMP2 and MMP9 and the phosphorylation of proteins of the PI3K/Akt signaling pathway. The results demonstrated that treatment with PD markedly decreased the proliferation, invasion and migration of EC cells, and reduced activation of the PI3K/Akt signaling pathway in EC cells. Moreover, transfection with sh-ADRA2A attenuated the effects of PD. ADRA2A expression was downregulated in EC cells compared with ESCs, and ADRA2A expression was elevated in EC cells following treatment with PD. In conclusion, the present study indicates that PD blocked the PI3K/Akt signaling pathway via the upregulation of ADRA2A expression, thereby inhibiting the proliferation, invasion and migration of EC cells.

JDHY3 Inhibits Hypopharyngeal Carcinoma Cell Proliferation and Promotes Apoptosis by Inhibiting the PI3K/AKT Pathway.

BACKGROUND: Jieduhuayu No.3 (JDHY3) is a modified Chinese herbal formula beneficial for treating hypopharyngeal carcinoma (HC), but its pharmacological mechanism is unknown. OBJECTIVE: This study aimed to explore the mechanism of the herbal formula JDHY3 in inhibiting cell proliferation and promoting apoptosis in HC in vitro and in vivo. METHODS: In this study, HC cells were treated with cisplatin and different concentrations of JDHY3. The apoptosis rate was detected by flow cytometry. Western blotting was used to detect the proteins related to cell proliferation and apoptosis. Afterward, the xenograft mouse model was established and treated with cisplatin and JDHY3. Mouse tumour volume was measured, and the tumour tissues were assessed by HE staining and immunohistochemistry. RESULTS: JDHY3 significantly inhibited the proliferation of FaDu and Detroit-562 cells. In addition, JDHY3 significantly increased the apoptosis rate of HC cells and downregulated p-PI3K and p-Akt. In addition, JDHY3 upregulated the expression of the apoptosis-promoting proteins Bax, P53, and cleaved caspase-3. In addition, the expression of the antiapoptotic protein Bcl-2 was downregulated. Coincubation with SC79 attenuated the decrease in cell proliferation induced by JDHY3, further confirming that the proapoptotic effect of JDHY3 is associated with the inhibition of PI3K/Akt pathway activation. CONCLUSIONS: The results of in vivo experiments showed that JDHY3 could effectively inhibit the proliferation of HC cells, and HE staining showed that JDHY3 reduced the invasion of HC cells. Immunohistochemistry showed that the expression of P53 and cleaved caspase-3 was significantly increased in the tissues of the JDHY3-treated group.

Learning Skill Characteristics From Manipulations.

Percutaneous coronary intervention (PCI) has increasingly become the main treatment for coronary artery disease. The procedure requires high experienced skills and dexterous manipulations. However, there are few techniques to model PCI skill so far. In this study, a learning framework with local and ensemble learning is proposed to learn skill characteristics of different skill-level subjects from their PCI manipulations. Ten interventional cardiologists (four experts and six novices) were recruited to deliver a medical guidewire to two target arteries on a porcine model for in vivo studies. Simultaneously, translation and twist manipulations of thumb, forefinger, and wrist are acquired with electromagnetic (EM) and fiber-optic bend (FOB) sensors, respectively. These behavior data are then processed with wavelet packet decomposition (WPD) under 1-10 levels for feature extraction. The feature vectors are further fed into three candidate individual classifiers in the local learning layer. Furthermore, the local learning results from different manipulation behaviors are fused in the ensemble learning layer with three rule-based ensemble learning algorithms. In subject-dependent skill characteristics learning, the ensemble learning can achieve 100% accuracy, significantly outperforming the best local result (90%). Furthermore, ensemble learning can also maintain 73% accuracy in subject-independent schemes. These promising results demonstrate the great potential of the proposed method to facilitate skill learning in surgical robotics and skill assessment in clinical practice.

Expression and significance of CDX2, FXR, and TGR5 in esophageal cancer.

This study explored the expression and significance of three critical morphogenesis genes in normal esophagus, reflux esophagitis (RE), Barrett's esophagus (BE), esophageal adenocarcinoma (EA), and esophageal squamous cell carcinoma (ESCC). Esophageal tissue samples and tissue microarrays were used. CDX2, FXR, and TGR5 protein expression were measured by immunohistochemistry in normal esophageal, RE, BE, EA, and ESCC tissues. All 3 proteins had markedly changed expression during the progression of EA. The expressions of CDX2 and FXR were positively correlated in EA. In addition, TGR5 expression was positively correlated with CDX2 in RE and BE. The expressions of CDX2 and FXR were also positively correlated in ESCC. Although CDX2, FXR, and TGR5 were upregulated in ESCC, these factors might not be markers for the prognosis of ESCC. These results suggested that CDX2, FXR, and TGR5 might play different roles in EA and ESCC. They may represent novel therapeutic targets for patients with these cancers.

Predicting the distribution of plant associations under climate change: A case study on Larix gmelinii in China.

Association is the basic unit of plant community classification. Exploring the distribution of plant associations can help improve our understanding of biodiversity conservation. Different associations depend on different habitats and studying the association level is important for ecological restoration, regional ecological protection, regulating the ecological balance, and maintaining biodiversity. However, previous studies have only focused on suitable distribution areas for species and not on the distribution of plant associations. Larix gmelinii is a sensitive and abundant species that occurs along the southern margin of the Eurasian boreal forests, and its distribution is closely related to permafrost. In this study, 420 original plots of L. gmelinii forests were investigated. We used a Maxent model and the ArcGIS software to project the potential geographical distribution of L. gmelinii associations in the future (by 2050 and 2070) according to the climate scenarios RCP 2.6, RCP 4.5, and RCP 8.5. We used the multi-classification logistic regression analysis method to obtain the response of the suitable area change for the L. gmelinii alliance and associations to climate change under different climate scenarios. Results revealed that temperature is the most crucial factor affecting the distribution of L. gmelinii forests and most of its associations under different climate scenarios. Suitable areas for each association type are shrinking by varying degrees, especially due to habitat loss at high altitudes in special terrains. Different L. gmelinii associations should have different management measures based on the site conditions, composition structure, growth, development, and renewal succession trends. Subsequent research should consider data on biological factors to obtain more accurate prediction results.

[A Sero-epidemiological Study on Transfusion-Transmissible Infectious among Volunteer Blood Donors From 2016 to 2020 in Nanjing].

OBJECTIVE: To investigate the status of transfusion-transmissible infection (TTI) among voluntary blood donors in Nanjing in recent five years, in order to provide data support for the recruitment of blood donors and formulation and updating of blood screening strategies. METHODS: HIV/HBV/HCV/TP serological markers were detected by ELISA in 487 120 blood donors in Nanjing from 2016 to 2020. Confirmatory assay was applied in anti-HIV positive samples by Nanjing Municipal Center for Disease Control and Prevention. The prevalence of TTI was calculated and the trend of disease was analyzed under different demographic groups. RESULTS: The total positive rate of TTI in blood donors was 0.49% (2 411/487 120), in which the overall seroprevalence rate of HBsAg, anti-HCV, anti-HIV and anti-TP was 0.23%, 0.09%, 0.01% and 0.16%, respectively. The overall prevalence of HIV and TP remained relatively steady (P>0.05), whereas HBV and HCV decreased year by year (P<0.05). The prevalence of TTI was higher among people with lower education level, high age group and first-time blood donation. CONCLUSION: The prevalence of TTI among voluntary blood donors in Nanjing is at a low level from 2016 to 2020, but the risk still exists. The recruitment of regular donors and the improvement of blood screening technology can effectively reduce the risk of TTI.

One-Step Exfoliation Method for Plasmonic Activation of Large-Area 2D Crystals.

Advanced exfoliation techniques are crucial for exploring the intrinsic properties and applications of 2D materials. Though the recently discovered Au-enhanced exfoliation technique provides an effective strategy for the preparation of large-scale 2D crystals, the high cost of gold hinders this method from being widely adopted in industrial applications. In addition, direct Au contact could significantly quench photoluminescence (PL) emission in 2D semiconductors. It is therefore crucial to find alternative metals that can replace gold to achieve efficient exfoliation of 2D materials. Here, the authors present a one-step Ag-assisted method that can efficiently exfoliate many large-area 2D monolayers, where the yield ratio is comparable to Au-enhanced exfoliation method. Differing from Au film, however, the surface roughness of as-prepared Ag films on SiO2 /Si substrate is much higher, which facilitates the generation of surface plasmons resulting from the nanostructures formed on the rough Ag surface. More interestingly, the strong coupling between 2D semiconductor crystals (e.g., MoS2 , MoSe2 ) and Ag film leads to a unique PL enhancement that has not been observed in other mechanical exfoliation techniques, which can be mainly attributed to enhanced light-matter interaction as a result of extended propagation of surface plasmonic polariton (SPP). This work provides a lower-cost and universal Ag-assisted exfoliation method, while at the same time offering enhanced SPP-matter interactions.

Spatio-Temporal Causal Transformer for Multi-Grained Surgical Phase Recognition.

Automatic surgical phase recognition plays a key role in surgical workflow analysis and overall optimization in clinical work. In the complicated surgical procedures, similar inter-class appearance and drastic variability in phase duration make this still a challenging task. In this paper, a spatio-temporal transformer is proposed for online surgical phase recognition with different granularity. To extract rich spatial information, a spatial transformer is used to model global spatial dependencies of each time index. To overcome the variability in phase duration, a temporal transformer captures the multi-scale temporal context of different time indexes with a dual pyramid pattern. Our method is thoroughly validated on the public Cholec80 dataset with 7 coarse-grained phases and the CATARACTS2020 dataset with 19 fine-grained phases, outperforming state-of-the-art approaches with 91.4% and 84.2% accuracy, taking only 24.5M parameters.

Rapamycin Alleviates 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis through Autophagy Induction and NF-κB Pathway Inhibition in Mice.

Background: Recent genetic studies indicated that variants of autophagy genes were associated with the predisposition of Crohn's disease (CD). The autophagy deficiency may affect the innate and adaptive immunity, which is related to persistent and excessive inflammation of the bowel. However, it remains unclear how autophagy modulates the expression of immune response regulator NF-κB and proinflammatory cytokine TNF-α in CD. Aim: We aimed to investigate the role of rapamycin on the expression of NF-κB p65 and TNF-α in 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis and lipopolysaccharide (LPS)-induced HT-29 cells. Methods: TNBS-induced colitis mice were treated with saline or rapamycin, and the disease activity index (DAI) and histological scores of colonic mucosa were evaluated. The expressions of p65, ATG16L1 and LC3 were detected by western blot and immunohistochemistry staining. The monodansylcadaverine (MDC) staining and transmission electron microscopy were developed to study the autophagy in LPS-induced HT-29 cells. Expression of TNF-α from colon tissue and HT-29 cells were detected by ELISA. The expressions of p65, ATG16L1 and LC3 in active CD patients were also investigated. Results: Significantly more autophagosomes were observed in rapamycin-treated cells than in controls. Rapamycin remarkably upregulated the expression of ATG16L1 and LC3II, inhibited p65 nucleus translocation and secretion of TNF-α both in vivo and in vitro. The expression of both ATG16L1 and LC3II increased in mild to moderate CD specimens, while no significant difference was noted between severe CD and normal controls. The expression of p65 increased notably in severe CD compared to those in mild to moderate patients. Conclusions: In LPS-treated HT-29 cells and TNBS-induced colitis, p65 is overexpressed, which results in exaggerated secretion of TNF-α and induce or worsen the inflammation in the bowel. Rapamycin protects against colitis through induction of autophagy, thus inhibiting the activation of NF-κB pathway and secretion of TNF-α.

Efficacy and Safety of Conversion Therapy by Intraperitoneal and Intravenous Paclitaxel Plus Oral S-1 in Gastric Cancer Patients With Peritoneal Metastasis: A Prospective Phase II Study.

Background: Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) has shown promising results in gastric cancer (GC) with peritoneal metastasis. However, clinical practice experience of NIPS is still lacking in China. In this study, we investigate the efficacy and safety of NIPS in Chinese patients. Methods: Eligible patients received NIPS every 3 weeks. Gastrectomy was performed for patients who met the criteria of conversion surgery. The primary end point was 1-year overall survival (OS) rate. Secondary end points were the response rate, toxic effects, conversion surgery outcomes and median survival time (MST). Results: Sixty-seven patients were enrolled. The primary endpoint was achieved with 1-year OS rate reached 67.2% (95% CI, 56.8%-79.4%). Conversion surgery was performed in 42 patients (62.9%), and R0 resection was achieved in 23 patients (54.8%) with the MST of 31.3 months (95% CI, 24.3-38.3). And the MST was 19.3 months (95% CI, 16.4-22.2) for all patients. Toxicity and surgical complications were well-tolerated. Moreover, sex, R0 resection, pathological nodal stage and tumor regression grade (TRG) were independent prognostic factors for patients who underwent conversion surgery. Conclusion: The NIPS is effective and safe in treating GC patients with peritoneal metastasis. Male patients, patients who underwent R0 resection, patients with ypN0-1 or TRG 1 after conversion surgery are more likely to benefit from the NIPS. Clinical Trial Registration: http://www.chictr.org.cn/, identifier https://clinicaltrials.gov/ ().

Identifying transcranial magnetic stimulation induced EEG signatures of different neuronal elements in primary motor cortex.

OBJECTIVE: To investigate the neuronal elements involved in the activation of corticospinal neurons in the primary motor cortex (M1). METHODS: We studied 10 healthy subjects. Cortical evoked potentials with different components induced by monophasic transcranial magnetic stimulation (TMS) in anterior-posterior and posterior-anterior currents recorded with electroencephalography (EEG) were analyzed. RESULTS: EEG signatures with P25 and N45 components recorded at the C3 electrode with posterior-anterior current were larger than those with anterior-posterior current, while the signatures with P180 and N280 components recorded at the FC1 electrode with anterior-posterior current were larger than those with posterior-anterior current. The source localization analysis revealed that the cortical evoked potential with anterior-posterior current distributed both in the M1 and premotor cortex while that with posterior-anterior current only located in the M1. CONCLUSIONS: We conclude that the activation of corticospinal pyramidal neurons in the M1 is affected by various neuronal elements including the local intracortical circuits in the M1 and inputs from premotor cortex with different sensitivities to TMS in opposite current directions. SIGNIFICANCE: Our finding helped answer a longstanding question about how the corticospinal pathway from the M1 is functionally organized and activated.

Age-related strengthening of cerebello-cortical motor circuits.

Effective connectivity between the cerebellum and primary motor cortex (M1) is critical for motor learning and motor control. Despite evidence of cerebellar atrophy and declines in motor learning and motor control with advanced age, recent behavioral studies indicate that cerebellar-dependent motor learning processes are preserved or even enhanced in older adults. However, physiological evidence of heightened cerebellar excitability leading to strengthened cerebellar-M1 connectivity with advanced age is lacking. Here, we used transcranial magnetic stimulation to assess age-related effects on cerebellar inhibition, a measure of cerebellar-M1 connectivity, in 20 young and 19 older adults. We observed stronger cerebellar inhibition in older compared with young adults. The behavioral implications of strengthened cerebellar inhibition with advanced age found in this study remain to be determined.

Image-Based Differentiation of Benign and Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a dominant hereditary disease characterized by the mutation of the NF1 gene, affecting 1/3000 individuals worldwide. Most NF1 patients are predisposed to benign peripheral nerve sheath tumors (PNSTs), including cutaneous neurofibromas (CNFs) and plexiform neurofibromas (PNFs). However, 5%-10% of PNFs will ultimately develop into malignant peripheral nerve sheath tumors (MPNSTs), which have a poor prognosis. Early and reliable differentiation of benign and malignant tumors in NF1 patients is of great necessity. Pathological evaluation is the "gold standard" for a definite diagnosis, but the invasive nature of the biopsy procedure restricts it from applying as a screening tool during the decades-long follow-up of these patients. Non-invasive image-based diagnostic methods such as CT and MRI are often considered essential screening tools for multiple types of tumors. For NF1 patients' lifelong regular follow-ups, these radiological methods are currently used for tumor evaluation. However, no consensus was established on screening the malignant transformation of benign PNSTs. Moreover, novel technologies like radiogenomics and PET-MRI have not been well evaluated and fully adopted for NF1 patients. This review summarizes current studies of different imaging methods for differentiating benign and malignant tumors in NF1. Meanwhile, we discussed the prospects of the usage of new tools such as radiogenomics and PET-MRI to distinguish MPNST from benign PNSTs more precisely. Summarizing these findings will help clarify the directions of future studies in this area and ultimately contribute to the radiology images-based clinical screening of MPNST in NF1 patients and finally improve the overall survival rates of these patients.

Kernelized Deep Learning for Matrix Factorization Recommendation System Using Explicit and Implicit Information.

In the current matrix factorization recommendation approaches, the item and the user latent factor vectors are with the same dimension. Thus, the linear dot product is used as the interactive function between the user and the item to predict the ratings. However, the relationship between real users and items is not entirely linear and the existing recommendation model of matrix factorization faces the challenge of data sparsity. To this end, we propose a kernelized deep neural network recommendation model in this article. First, we encode the explicit user-item rating matrix in the form of column vectors and project them to higher dimensions to facilitate the simulation of nonlinear user-item interaction for enhancing the connection between users and items. Second, the algorithm of association rules is used to mine the implicit relation between users and items, rather than simple feature extraction of users or items, for improving the recommendation performance when the datasets are sparse. Third, through the autoencoder and kernelized network processing, the implicit data are connected with the explicit data by the multilayer perceptron network for iterative training instead of doing simple linear weighted summation. Finally, the predicted rating is output through the hidden layer. Extensive experiments were conducted on four public datasets in comparison with several existing well-known methods. The experimental results indicated that our proposed method has obtained improved performance in data sparsity and prediction accuracy.

Record Chemical-Shift Temperature Sensitivity in a Series of Trinuclear Cobalt Complexes.

Designing spins that exhibit long-lived coherence and strong temperature sensitivity is central to designing effective molecular thermometers and a fundamental challenge in the chemistry/quantum-information space. Herein, we provide a new pathway to both properties in the same molecule by designing a nuclear spin, which possesses a robust spin coherence, to mimic the strong temperature sensitivity of an electronic spin. This design strategy is demonstrated in the group of trinuclear Co(III) spin-crossover compounds [(CpCo(OP(OR)2)3)2Co](SbCl6) where Cp = cyclopentadienyl and R = Me (1), Et (2), i-Pr (3), and t-Bu (4). Nuclear magnetic resonance analyses of the 59Co nuclear spins reveal 59Co chemical-shift temperature sensitivity (Δδ/ΔT) values that span from 101(1) ppm/°C in 1 to 149(1) ppm/°C in 2 and 150(2) ppm/°C in 4, where the latter two are record temperature sensitivities for any nuclear spin. Additionally, complexes 2 and 4 have T2* values of 74 and 78 µs in solution at ambient temperatures surpassing those from electron-spin-based complexes, which typically display long coherence times only at extremely low temperatures. Our results suggest that spin-crossover phenomena can enable electron-spin-like temperature sensitivities in nuclear spins while retaining robust coherence times at room temperature.

Precise Metabolomics Reveals a Diversity of Aging-Associated Metabolic Features.

Mass spectrometry-based metabolomics has emerged as a powerful technique for biomedical research, although technical issues with its analytical precision and structural characterization remain. Herein, a robust non-targeted strategy for accurate quantitation and precise profiling of metabolomes is developed and applied to investigate plasma metabolic features associated with human aging. A comprehensive set of isotope-labeled standards (ISs) covering major metabolic pathways is incorporated to quantify polar metabolites. Matching rules to select ISs for calibration follow a primary criterion of minimal coefficients of variations (COVs). If minimal COVs between specific ISs for a particular metabolite fall within 5% window, a further selection of ISs is conducted based on structural similarities and proximity in retention time. The introduction and refined selection of appropriate ISs for quantitation reduces the COVs of 480 identified metabolites in quality control samples from 14.3% to 9.8% and facilitates identification of additional metabolite. Finally, the precise metabolomics approach reveals perturbations in a diverse array of metabolic pathways across aging that principally implicate steroid metabolism, amino acid metabolism, lipid metabolism, and purine metabolism, which allows the authors to draw correlates to the pathology of various age-related diseases. These findings provide clues for the prevention and treatment of these age-related diseases.