Associations of toxic metals and their mixture with hyperuricemia in Chinese rural older adults.

Previous studies have related single toxic metals (TMs) to hyperuricemia (HUA) among the general population, however, the association of the TM mixture with HUA, especially in older adults, remains poorly understood. We aimed to examine the relationships between individual TMs and their mixture and HUA in Chinese rural older adults. This study consisted of 2075 rural older adults aged 60 years or over. Blood concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), gallium (Ga), mercury (Hg), lead (Pb), thallium (Tl), and uranium (U) were detected using inductively coupled plasma mass spectrometry. The associations of single TMs with HUA were assessed using logistic regression and restricted cubic spline (RCS) models, and the association of TM mixture with HUA was explored using the elastic net with environmental risk score (ENET-ERS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted logistic regression model showed that Cs (OR = 1.65, 95% CI 1.37-1.99) and Pb (OR = 1.46, 95% CI 1.28-1.67) were positively related to HUA, and RCS model exhibited a positive linear association of Cs and Pb with HUA. ENET-ERS and QGC models quantified a positive correlation between the TM mixture and the odds of HUA, with estimated ORs of 1.15 (95% CI 1.11-1.19) and 1.84 (95% CI 1.37-2.47), respectively, and Cs and Pb had the most weight. BKMR model demonstrated a significant linear association between the TM mixture and increased odds of HUA, with the posterior inclusion probabilities (PIPs) of both Cs and Pb being 1.00. Moreover, we observed a positive interaction between Cs and Pb on HUA. The TM mixture is associated with increased odds of HUA in rural older adults, which may mainly be driven by Cs and Pb. Subsequent studies are warranted to confirm these findings and clarify the mechanisms linking multiple TMs with HUA.

Oral frailty: a concept analysis.

BACKGROUND: Oral frailty has become a worldwide problem among older adults. Although researchers have conducted various studies on oral frailty, its definition remains controversial. PURPOSE: To clarify the concept of oral frailty. METHODS: Online databases PubMed, Web of Science, CINAHL, Cochrane Library, ProQuest, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang database were searched from inception to September 20, 2023. The reference lists of relevant studies were searched manually. Eligible articles, theses, and books were analyzed using Walker & Avant's concept analysis model. RESULTS: The attributes of oral frailty were abnormal oral structure and/or decline in multi-faceted oral function and coexisting decline in physical, cognitive and social functions. Its antecedents were aging, social frailty, and severe periodontitis, whereas its consequences were decline in physical health and mental health, social withdrawal, lower quality of life and systemic frailty. CONCLUSION: Oral frailty could result in worse conditions among older adults physically, psychologically and socially. Tools based on the concept analysis need to be developed to comprehensively assess oral frailty.

APOE ε4 allele modifies the associations of toxic metals and their mixture with cognitive impairment among older adults.

BACKGROUND: The evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people. METHODS: A total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment. RESULTS: Pb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (Ptrend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR=1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively. CONCLUSIONS: APOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention.

Fibrous MXene Synapse-Based Biomimetic Tactile Nervous System for Multimodal Perception and Memory.

Biomimetic tactile nervous system (BTNS) inspired by organisms has motivated extensive attention in wearable fields due to its biological similarity, low power consumption, and perception-memory integration. Though many works about planar-shape BTNS are developed, few researches could be found in the field of fibrous BTNS (FBTNS) which is superior in terms of strong flexibility, weavability, and high-density integration. Herein, a FBTNS with multimodal sensibility and memory is proposed, by fusing the fibrous poly lactic acid (PLA)/Ag/MXene/Pt artificial synapse and MXene/EMIMBF4 ionic conductive elastomer. The proposed FBTNS can successfully perceive external stimuli and generate synaptic responses. It also exhibits a short response time (23 ms) and low set power consumption (17 nW). Additionally, the proposed device demonstrates outstanding synaptic plasticity under both mechanical and electrical stimuli, which can simulate the memory function. Simultaneously, the fibrous devices are embedded into textiles to construct tactile arrays, by which biomimetic tactile perception and temporary memory functions are successfully implemented. This work demonstrates the as-prepared FBTNS can generate biomimetic synaptic signals to serve as artificial feeling signals, it is thought that it could offer a fabric electronic unit integrating with perception and memory for Human-Computer interaction, and has great potential to build lightweight and comfortable Brain-Computer interfaces.

Reduced eye gaze fixation during emotion recognition among patients with temporal lobe epilepsy.

OBJECTIVES: To investigate the facial scan patterns during emotion recognition (ER) through the dynamic facial expression task and the awareness of social interference test (TASIT) using eye tracking (ET) technology, and to find some ET indicators that can accurately depict the ER process, which is a beneficial supplement to existing ER assessment tools. METHOD: Ninety-six patients with TLE and 88 healthy controls (HCs) were recruited. All participants watched the dynamic facial expression task and TASIT including a synchronized eye movement recording and recognized the emotion (anger, disgust, happiness, or sadness). The accuracy of ER was recorded. The first fixation time, first fixation duration, dwell time, and fixation count were selected and analyzed. RESULTS: TLE patients exhibited ER impairment especially for disgust (Z = - 3.391; p = 0.001) and sadness (Z = - 3.145; p = 0.002). TLE patients fixated less on the face, as evidenced by the reduced fixation count (Z = - 2.549; p = 0.011) of the face and a significant decrease in the fixation count rate (Z = - 1.993; p = 0.046). During the dynamic facial expression task, TLE patients focused less on the eyes, as evidenced by the decreased first fixation duration (Z = - 4.322; p = 0.000), dwell time (Z = - 4.083; p = 0.000), and fixation count (Z = - 3.699; p = 0.000) of the eyes. CONCLUSION: TLE patients had ER impairment, especially regarding negative emotions, which may be attributable to their reduced fixation on the eyes during ER, and the increased fixation on the mouth could be a compensatory effect to improve ER performance. Eye-tracking technology could provide the process indicators of ER, and is a valuable supplement to traditional ER assessment tasks.

Short-term effects of ambient PM1, PM2.5, and PM10 on internal metal/metalloid profiles in older adults: A distributed lag analysis in China.

There is limited evidence linking exposure to ambient particulate matter (PM) with internal doses of metals and metalloids (metal(loid)s). This study aimed to evaluate the effects of short-term exposure to ambient PM on urine metal(loid)s among Chinese older adults. Biological monitoring data of 15 urine metal(loid)s collected in 3, 970 community-dwelling older adults in Fuyang city, Anhui Province, China, from July to September 2018, were utilized. PMs with an aerodynamic diameter ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) up to eight days before urine collection were estimated by space-time extremely randomized trees (STET) model. Residential greenness was reflected by Normalized Difference Vegetation Index (NDVI). We used generalized additive model (GAM) combined with distributed lag linear/non-linear models (DLMs/DLNMs) to estimate the associations between short-term PM exposure and urine metal(loid)s. The results suggested that the cumulative exposures to PM1, PM2.5, or PM10 over two days (lag0-1 days) before urine collection were associated with elevated urine metal(loid)s in DLMs, while exhibited linear or "inverted U-shaped" relationships with seven urine metal(loid)s in DLNMs, including Gallium (Ga), Arsenic (As), Aluminum (Al), Magnesium (Mg), Calcium (Ca), Uranium (U), and Barium (Ba). Aforementioned results indicated robust rather than spurious associations between PMs and these seven metal(loid)s. After standardizations for three PMs, PM1 was the greatest contributor to U, PM2.5 made the greatest contributions to Ga, As, Al, and Ba, and PM10 contributed the most to Mg and Ca. Furthermore, the effects of three PMs on urine Ga, As, Al, Mg, Ca, and Ba were reduced when exposed to higher levels of NDVI. Overall, short-term exposures to ambient PMs contribute to elevated urinary metal(loid) levels in older adults, and three PMs exhibit various contributions to different urine metal(loid)s. Moreover, residential greenness may attenuate the effects of PMs on urine metal(loid)s.

Event-related potentials reveal visual episodic memory deficits in patients with temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) patients usually suffer from impaired episodic memory (EM), but its underlying electrophysiologic mechanism and impacted cognitive performance are unclear. We aim to investigate the association between episodic memory reserve and physiological measures of memory workload in TLE patients using Event-related potentials (ERP). METHODS: A change detection task with image stimuli assesses visual episodic memory. During the memory encoding and decoding phases, the ERP signals were analyzed from twenty-nine TLE patients (twelve with left TLE patients, seventeen with TLE), and thirty healthy controls. Given that EM is a complex process involving many fundamental cognitive processes, the amplitudes and latencies of EM-related ERP (FN400, late positive potential (LPC), and late posterior negativity (LPN)), and the ERP reflecting the fundamental processes (P100, N100, P200, and P300) were calculated. Then we used a three-by-two factorial design on the ERP metrics for interaction and main effects. The correlation analysis among Wechsler Memory Scales-Chinese Revision (WMS-RC) results, behavioral data, and the ERPs was carried out. RESULTS: The TLE patients performed worse in WMS-RC and the memory task. The increased P200 and decreased P300 amplitudes were observed in the TLE patients, and LPN was abnormal in only LTLE patients. For EM-related components, differences were observed in both the LTLE and RTLE patients: the lack of the FN400 effect, the lack of the reversed LPC effect, and the reduced FN400. No significant inter-group difference was detected for the latencies of all the ERPs. Additionally, there were significant correlations among WMS-RC scores, behaviors, and some ERP amplitudes. CONCLUSIONS: The impaired EM is linked to the increased P200 and decreased P300 amplitudes. LPN seems to be sensitive to left temporal lobe dysfunction. More importantly, the abnormal old or new effects of the FN400 and LPC, and the reduced FN400 amplitude might be associated with the visual EM deficit in the TLE patients. These findings may assist in the deep understanding of the EM disorder and the evaluation of the side effects of antiepileptic drugs.

Automatic Seizure Detection and Prediction Based on Brain Connectivity Features and a CNNs Meet Transformers Classifier.

(1) Background: Epilepsy is a neurological disorder that causes repeated seizures. Since electroencephalogram (EEG) patterns differ in different states (inter-ictal, pre-ictal, and ictal), a seizure can be detected and predicted by extracting various features. However, the brain connectivity network, a two-dimensional feature, is rarely studied. We aim to investigate its effectiveness for seizure detection and prediction. (2) Methods: Two time-window lengths, five frequency bands, and five connectivity measures were used to extract image-like features, which were fed into a support vector machine for the subject-specific model (SSM) and a convolutional neural networks meet transformers (CMT) classifier for the subject-independent model (SIM) and cross-subject model (CSM). Finally, feature selection and efficiency analyses were conducted. (3) Results: The classification results on the CHB-MIT dataset showed that a long window indicated better performance. The best detection accuracies of SSM, SIM, and CSM were 100.00, 99.98, and 99.27%, respectively. The highest prediction accuracies were 99.72, 99.38, and 86.17%, respectively. In addition, Pearson Correlation Coefficient and Phase Lock Value connectivity in the ß and γ bands showed good performance and high efficiency. (4) Conclusions: The proposed brain connectivity features showed good reliability and practical value for automatic seizure detection and prediction, which expects to develop portable real-time monitoring equipment.

Effects of nitric acid rain stress on soil nitrogen fractions and fungal communities in a northern subtropical forest, China.

Acid rain has severely negatively impacted terrestrial ecosystems and biogeochemical cycles. However, the potential impacts of nitric acid rain (NAR) on soil nitrogen (N) fractions and fungal community diversity in northern subtropical forest soils remain largely unevaluated. In this study, treatments of NAR at pH = 4.5 (AR4.5), pH = 3.5 (AR3.5), and pH = 2.5 (AR2.5) were randomly sprayed in a typical Quercus acutissima Carruth. stand in northern subtropical China. The soil N fractions and soil fungal communities were analyzed after a 12-month experimental period. The results revealed that compared to the control, the soil total N (TN), microbial biomass N (MBN), hydrolysable ammonium N (HAN), amino-sugar N (ASN) and amino-acid N (AAN) contents decreased significantly by 19.61-13.07 %, 20.10-9.04 %, 60.41-28.87 %, 74.10-62.25 %, and 65.69-45.64 % under stronger acidity inputs (i.e., AR2.5 and AR3.5), respectively. Besides, the AR2.5 and AR3.5 treatments increased the α-diversity indices of soil fungal communities and altered the soil fungal community structure. Moreover, the NAR treatments represented an increase in the relative abundance of Ascomycota and Mortierellomycota and a decrease in that of Basidiomycota. Mortierella, Penicillium, and Tomentella can be used as indicator genera for changes in soil fungal community structures under NAR stress. Furthermore, AAN was the main environmental factor affecting soil fungal community at the phylum and genus levels. Cumulatively, findings from this research provide valuable insight into NAR's effects on N cycling and microbial communities in forest soils.

Knowledge-Based Recurrent Neural Network for TCM Cerebral Palsy Diagnosis.

Cerebral palsy is one of the most prevalent neurological disorders and the most frequent cause of disability. Identifying the syndrome by patients' symptoms is the key to traditional Chinese medicine (TCM) cerebral palsy treatment. Artificial intelligence (AI) is advancing quickly in several sectors, including TCM. AI will considerably enhance the dependability and precision of diagnoses, expanding effective treatment methods' usage. Thus, for cerebral palsy, it is necessary to build a decision-making model to aid in the syndrome diagnosis process. While the recurrent neural network (RNN) model has the potential to capture the correlation between symptoms and syndromes from electronic medical records (EMRs), it lacks TCM knowledge. To make the model benefit from both TCM knowledge and EMRs, unlike the ordinary training routine, we begin by constructing a knowledge-based RNN (KBRNN) based on the cerebral palsy knowledge graph for domain knowledge. More specifically, we design an evolution algorithm for extracting knowledge in the cerebral palsy knowledge graph. Then, we embed the knowledge into tensors and inject them into the RNN. In addition, the KBRNN can benefit from the labeled EMRs. We use EMRs to fine-tune the KBRNN, which improves prediction accuracy. Our study shows that knowledge injection can effectively improve the model effect. The KBRNN can achieve 79.31% diagnostic accuracy with only knowledge injection. Moreover, the KBRNN can be further trained by the EMRs. The results show that the accuracy of fully trained KBRNN is 83.12%.

Electrolyte-Gated Graphene Field Effect Transistor-Based Ca2+ Detection Aided by Machine Learning.

Flexible electrolyte-gated graphene field effect transistors (Eg-GFETs) are widely developed as sensors because of fast response, versatility and low-cost. However, their sensitivities and responding ranges are often altered by different gate voltages. These bias-voltage-induced uncertainties are an obstacle in the development of Eg-GFETs. To shield from this risk, a machine-learning-algorithm-based LgGFETs' data analyzing method is studied in this work by using Ca2+ detection as a proof-of-concept. For the as-prepared Eg-GFET-Ca2+ sensors, their transfer and output features are first measured. Then, eight regression models are trained with the use of different machine learning algorithms, including linear regression, support vector machine, decision tree and random forest, etc. Then, the optimized model is obtained with the random-forest-method-treated transfer curves. Finally, the proposed method is applied to determine Ca2+ concentration in a calibration-free way, and it is found that the relation between the estimated and real Ca2+ concentrations is close-to y = x. Accordingly, we think the proposed method may not only provide an accurate result but also simplify the traditional calibration step in using Eg-GFET sensors.

The immunomodulatory activity and mechanism of docosahexenoic acid (DHA) on immunosuppressive mice models.

In this study, the immunomodulatory activity of docosahexaenoic acid (DHA) on the immunosuppressive BALB/c mice model and its molecular mechanism are elucidated. It was found that the weight indexes of the spleen and thymus were significantly increased by DHA (44.0 mg kg-1 and 88.0 mg kg-1) treatment in the prevention or cure groups. The result of macrophages showed that DHA (44.0 mg kg-1 and 88.0 mg kg-1) could promote the proliferation and phagocytosis activity of macrophages in the prevention or cure groups. In addition, DHA could activate macrophages by the G-protein coupled cell membrane receptor GPR120- Mitogen-Activated Protein Kinases (MAPKs)-nuclear factor κB (NF-κB) p65 pathway in vivo. The result of the spleen showed that DHA (44.0 mg kg-1 and 88.0 mg kg-1) could promote the proliferation of spleen cells and the natural killer (NK) cells activity in vivo. In the prevention or cure groups, the quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that DHA (44.0 mg kg-1 and 88.0 mg kg-1) could enhance the production of cytokines IL-1ß, IL-2, TNF-α and IFN-γ in the spleen of immunosuppressive mice. The HE (hematoxylin and eosin) stained histopathological images showed that DHA could repair the damage induced by CTX in the spleen cells of the prevention or cure groups. These results suggested that DHA has a remarkable immunomodulatory activity on the immunosuppressive mice model in the prevention or cure groups.

Sinus of Valsalva aneurysms with concomitant aortic insufficiency: how should the aortic valve be managed?

OBJECTIVES: Sinus of Valsalva aneurysms (SVAs) are rare and are often complicated by aortic insufficiency (AI). Treating AI is important for achieving good long-term results in patients with SVA. Here, we have summarized our experience with the surgical management of patients with SVA with concomitant AI. METHODS: Patients who were diagnosed with SVA and underwent surgical treatment between January 2008 and May 2016 were included. Clinical characteristics, including age, gender, SVA anatomy and concurrent anomalies, were analysed. The surgical strategies, intraoperative results and early and late outcomes were evaluated. RESULTS: A total of 178 patients (age 37.4 ± 13.1 years, 114 men) were identified. Eighty-seven (48.9%) patients had at least 2+ AI preoperatively. Patients with AI had a significant higher incidence of right coronary SVA with concomitant ventricular septal defects (80.5% vs 54.9%, P < 0.001). Concurrent aortic valve surgery was performed in 70 patients with 63 valve replacements and 7 valve repairs. The other 17 patients underwent SVA repair only. The mean follow-up time was 44.4 ± 33.8 months. During the follow-up, no patients who underwent valve replacement experienced perivalvular leakage, whereas 7 patients who underwent aortic valve repair had trivial-to-mild AI and 3 of the 17 patients who underwent SVA repair only presented with moderate AI. CONCLUSIONS: Various surgical techniques can be utilized to manage concomitant AI without compromising short-term outcomes. Valve replacement yields good long-term results. According to our experience, valve repair, especially valve-sparing procedures performed by experienced surgeons, could be an acceptable option when managing concomitant AI in young patients.

Surgical management of aortic coarctation in adolescents and adults.

Objectives: Coarctation of the aorta (CoA) in adolescents and adults is often complicated by other cardiac or aortic problems and may carry additional surgical difficulties. Limited studies have reported the surgical outcomes of CoA repair in this particular patient population. We reviewed our contemporary experience of open surgical management of CoA in adolescents and adults. Methods: From 2008 to 2016, a total of 60 adolescents and adults (mean age, 32 years) underwent CoA repair at our centre. Of this cohort, 43 patients only underwent CoA repair (isolated group), while the remaining 17 underwent other concomitant cardiac procedures (concomitant group). Ascending-to-descending aortic bypass was the preferred repair technique in the concomitant group. Aortic valve replacement and a Bentall/David procedure were the two most frequently combined procedures. Results: There were no in-hospital deaths in the isolated group compared with three in the concomitant group (0% vs 17.6%, P = 0.029). The median intensive care unit stay (1 vs 2 days, P <0.01) and postoperative hospital stay (6 vs 9 days, P <0.01) were significantly longer in the concomitant group. Postoperative respiratory failure occurred more frequently in the concomitant group (0% vs 17.6%, P = 0.029). The isolated group had better overall survival during follow-up ( P = 0.037). The 5-year overall survival rate was 98% in the isolated group and 82% in the concomitant group. Conclusions: Surgical management of coarctation in adolescents and adults can achieve similar satisfactory outcomes as their neonatal counterparts, but the complexity of the concomitant procedures is a risk factor for this particular patient population.

Highly Sensitive and Selective Ethanol Sensor Fabricated with In-Doped 3DOM ZnO.

ZnO is an important n-type semiconductor sensing material. Currently, much attention has been attracted to finding an effective method to prepare ZnO nanomaterials with high sensing sensitivity and excellent selectivity. A three-dimensionally ordered macroporous (3DOM) ZnO nanostructure with a large surface area is beneficial to gas and electron transfer, which can enhance the gas sensitivity of ZnO. Indium (In) doping is an effective way to improve the sensing properties of ZnO. In this paper, In-doped 3DOM ZnO with enhanced sensitivity and selectivity has been synthesized by using a colloidal crystal templating method. The 3DOM ZnO with 5 at. % of In-doping exhibits the highest sensitivity (∼88) to 100 ppm ethanol at 250 °C, which is approximately 3 times higher than that of pure 3DOM ZnO. The huge improvement to the sensitivity to ethanol was attributed to the increase in the surface area and the electron carrier concentration. The doping by In introduces more electrons into the matrix, which is helpful for increasing the amount of adsorbed oxygen, leading to high sensitivity. The In-doped 3DOM ZnO is a promising material for a new type of ethanol sensor.

Strong metal-support interaction in novel core-shell Au-CeO2 nanostructures induced by different pretreatment atmospheres and its influence on CO oxidation.

Yolk-shell Au/CeO2 (Y-Au/CeO2) and encapsulated Au/CeO2 (E-Au/CeO2) nanocatalysts were prepared by using silica templates. A strong metal-support interaction (SMSI) in the Au/CeO2 nanostructures induced by different pretreatment atmospheres and its influence on CO oxidation were studied. E-Au/CeO2 pretreated in O2 had the best performance, followed by Y-Au/CeO2 pretreated in O2, Y-Au/CeO2 pretreated in H2, and E-Au/CeO2 pretreated in H2. The reasons for the different activities were discussed. There were two kinds of strong metal-support interactions (SMSI) between Au and CeO2 termed as R-SMSI (pretreated in reductive atmosphere) and O-SMSI (pretreated in oxidation atmosphere). Because of the smaller size of the Au and the larger contact area, both the R-SMSI and O-SMSI of E-Au/CeO2 were larger than those of Y-Au/CeO2. The O-SMSI was accompanied by the formation of cationic Au species that were beneficial to the enhancing of activity. As expected, the activity of E-Au/CeO2 pretreated in O2 with a Au size less than 5 nm was higher than that of Y-Au/CeO2 pretreated in O2 with 25 nm Au. However, it is surprisingly found that the activity of Y-Au/CeO2 pretreated in H2 with 25 nm Au was higher than that of E-Au/CeO2 pretreated in H2 with a Au size less than 5 nm. R-SMSI resulted in the formation of a AuCe alloy that had a negative effect on the activity. Compared with E-Au/CeO2 pretreated in H2, Y-Au/CeO2 pretreated in H2 exhibited a smaller relative content of the AuCe alloy, leading to a better activity of Y-Au/CeO2 pretreated in H2.