ABSTRACT
OBJECTIVE: To describe a novel technique, posterior thoracic antidisplacement and fusion (PTAF), for a special type of ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL), and to evaluate its safety and efficacy. METHODS: From July to December 2020, 5 consecutive patients with beak-type T-OPLL located at the thoracic vertebral body level underwent PTAF surgery. Their demographic data, radiological parameters, perioperative complications, and surgery-related findings were recorded and analyzed. The surgical outcomes were assessed using a modified Japanese Orthopedic Association scale, and the recovery rate was calculated using the Hirabayashi's method. RESULTS: All patients were followed up for at least two years. The mean thickness of OPLL was 9.4 ± 1.0 mm, and the OPLL spinal canal occupying ratio was 67.7% ± 8.5%. Postoperatively, the mean antidisplacement distance of OPLL was 8.1 ± 1.8 mm, and the average shortened distance of the spinal column was 6.0 ± 1.13 mm. The mean operation time and blood loss were 158.2 ± 26.3 minutes and 460 ± 89.4 mL, respectively. Perioperative complications were cerebrospinal fluid leakage and instrument failure, 2 cases each. The mean modified Japanese Orthopedic Association score was increased from 3.6 ± 2.9 before surgery to 9.4 ± 3.0 at the last follow-up, and the average recovery rate was 84.2 ± 30.5%. CONCLUSIONS: The preliminary clinical outcomes indicate that PTAF is a safe and effective method for the treatment of beak-type T-OPLL, which has its apex located at the vertebral body level and has a high spinal canal occupation ratio.
ABSTRACT
It has long been an aspirational goal to create artificial channel structures that replicate the feat achieved by ion channel proteins. Biological ion channels occasionally demonstrate multiple conductance states (known as subconductance), remaining a challenging property to achieve in artificial channel molecules. We report a funnel-shaped single-molecule channel constructed by an electron-deficient macrocycle and two electron-deficient aromatic imide arms. Planar lipid bilayer measurements reveal distinct current recordings, including a closed state, two conducting states, and spontaneous transitions between the three states, resembling the events seen in biological ion channels. The transitions result from conformational changes induced by chloride transport in the channel molecule. Both opening states show a non-linear and rectifying I-V relationship, indicating voltage-dependent transport due to the asymmetrical channel structure. This work could enhance our understanding of ion permeation and channel opening mechanism.
ABSTRACT
Presented herein is the exploration of a novel non-covalent anion-carbonyl (X-···CâO) interaction using aromatic imides as receptors and halides as lone pair donors. Combined theoretical calculations and experimental methods including 13C NMR, IR, and crystallographic analyses were performed to provide the physical origin and experimental evidence of anion-carbonyl interactions. The EDA analysis (energy decomposition analysis) based on DFT calculation indicates that electrostatic terms are the dominant contributions for the binding energy while electron delocalization also significantly contributes alongside the electrostatic attraction. Orbital interaction (n â π*) involving the delocalization of halide lone pairs on the carbonyl antibonding orbitals was visualized with NBO (Natural Bond Orbital) analysis. 13C NMR and IR spectra demonstrated upfield chemical shifts and red-shift frequency of hosts upon the addition of halides, reflecting the effect of orbital overlap between the halide lone pairs and π* of carbonyl (n â π* contribution). The anion-carbonyl interactions were directly revealed by X-ray structural analysis of anion and benzene triimide complexes.
ABSTRACT
BACKGROUND: With rapid urbanization, massive migration, and non-family-based eldercare involvement, Chinese concepts of eldercare responsibility and filial piety are shifting. We performed age-period-cohort (APC) analyses to assess the transition of old-age pension coverage, eldercare responsibility, and filial piety concepts and its urban-rural differences among Chinese adults using data from the China General Social Survey (2006-2017). METHODS: Old-age pension coverage (yes/no) and primary eldercare responsibility (government/offspring/self/sharing) were investigated in 2010, 2012, 2013, 2015, and 2017. Filial piety was evaluated using customized questionnaires in 2006 and 2017. The APC effects were estimated using mixed effects and generalized additive models. RESULTS: Among 66,182 eligible participants (mean age: 48.8 years, females: 51.7%) in the six waves, APC analyses indicated that old-age pension coverage increased with aging and over time. Across cohort groups, it grew as the cohort was younger in urban residents but decreased in rural residents. The concept of offspring-based (> 50%) and government/self/offspring-shared eldercare (> 30%) predominated. APC analyses revealed that the offspring-based concept declined with aging (OR = 0.81, 95% CI: 0.79-0.84), whereas the government-based (OR = 1.37, 95% CI: 1.33-1.41) and self-based (OR = 1.55, 95% CI: 1.47-1.63) concepts increased with aging. People born around the 1940s have a comparatively higher possibility to perceive that the primary eldercare responsibility should be undertaken by the government and elder parents. In contrast, people born in the younger cohort were more likely to perceive that adult children are responsible for their parents' primary eldercare. Filial piety score slightly increased with aging (ß = 0.18, SD: 0.05) but decreased as the birth cohort was younger. In addition, rural participants were more likely to perceive offspring-based eldercare and maintain filial piety, and the related urban-rural difference was intensified by aging. CONCLUSIONS: The traditional concept that eldercare solely relies on offspring has changed to relying on multiple entities, including the government and self-reliance. Diluted filial piety in people born in the young cohort requires reinforcement. Moreover, future healthy aging policies need to focus more on urban-rural disparities to promote equity in social well-being.
Subject(s)
Rural Population , Urban Population , Humans , China , Female , Male , Middle Aged , Rural Population/statistics & numerical data , Aged , Urban Population/statistics & numerical data , Adult , Cohort Studies , Intergenerational Relations , Pensions/statistics & numerical data , Surveys and Questionnaires , Social ResponsibilityABSTRACT
π-stacking interaction, as a fundamental type of intermolecular interaction, plays a crucial role in generating new functional molecules, altering the optoelectronic properties of materials, and maintaining protein structural stability. However, regulating intermolecular π-π interactions at the single-molecule level without altering the molecular conformation as well as the chemical properties remains a significant challenge. To this end, via conductance measurement with thousands of single molecular junctions employing a series of aromatic molecules, we demonstrate that the π-π coupling between neighboring aromatic molecules with rigid structures in a circuit can be greatly enhanced by increasing the bias voltage. We further reveal that this universal regulating effect of bias voltage without molecular conformational variation originates from the increases of the molecular dipole upon an applied electric field. These findings not only supply a non-destructive method to regulate the intermolecular interactions offering an approach to modulate the electron transport through a single molecular junction, but also deepen the understanding of the mechanism of π-π interactions.
ABSTRACT
OBJECTIVE: The aim of this study was to investigate the combined effect of handgrip strength (HGS) and obesity phenotype on the risk of stroke in Chinese middle-aged and elderly people. METHODS: The data was used from the China Health and Retirement Longitudinal Study (CHARLS). Middle-aged and older adults who participated in surveys between 2011 and 2018 were included in the study. They were divided into 4 different types of obesity phenotypes based on obesity and metabolic status: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically abnormal non-overweight/obesity (MANO), and metabolically abnormal overweight/obesity (MAO). The HGS level was divided into low and high groups according to the median values. Cox proportional risk regression model was used to analyze the joint effect of HGS and obesity phenotype on the risk of stroke among participants. RESULTS: A total of 7904 participants aged 58.89±9.08 years were included in this study. After adjusting for potential confounders, high HGS&MHO (HR=1.86, 95 % CI=1.12-3.09), high HGS&MANO (HR=2.01, 95 %CI=1.42-2.86), high HGS&MAO (HR=2.01, 95 % CI=1.37-2.93), low HGS&MHNO (HR=1.57, 95 % CI=1.00-2.46), low HGS&MHO (HR=2.09, 95 % CI=1.29-3.38), low HGS&MANO (HR=2.02, 95 % CI=1.35-3.03), and low HGS&MAO (HR=2.48, 95 % CI=1.72-3.58) group had significantly higher risks of stroke than the high HGS&MHNO group. CONCLUSION: The coexistence of metabolically unhealthy and low HGS can synergistically increase the risk of stroke in Chinese middle-aged and elderly people.
Subject(s)
Hand Strength , Obesity , Phenotype , Stroke , Humans , Male , Female , Middle Aged , Hand Strength/physiology , Obesity/epidemiology , Obesity/complications , China/epidemiology , Stroke/epidemiology , Aged , Risk Factors , Longitudinal Studies , Cohort Studies , East Asian PeopleABSTRACT
Background: Lung adenocarcinoma (LUAD) has a complex tumor heterogeneity. Our research attempts to clearness LUAD subtypes and build a reliable prognostic signature according to the activity changes of the hallmark and immunologic gene sets. Methods: According to The Cancer Genome Atlas (TCGA) - LUAD dataset, changes in marker and immune gene activity were analyzed, followed by identification of prognosis-related differential gene sets (DGSs) and their related LUAD subtypes. Survival analysis, correlation with clinical characteristics, and immune microenvironment assessment for subtypes were performed. Moreover, the differentially expressed genes (DEGs) between different subtypes were identified, followed by the construction of a prognostic risk score (RS) model and nomogram model. The tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) of different risk groups were compared. Results: Two LUAD subtypes were determined according to the activity changes of the hallmark and immunologic gene sets. Cluster 2 had worse prognosis, more advanced tumor and clinical stages than cluster 1. Moreover, a prognostic RS signature was established using two LUAD subtype-related DEGs, which could stratify patients at different risk levels. Nomogram model incorporated RS and clinical stage exerted good prognostic performance in LUAD patients. A shorter survival time and higher TMB were observed in the high-risk patients. Conclusions: Our findings revealed that our constructed prognostic signature could exactly predict the survival status of LUAD cases, which was helpful in predicting the prognosis and guiding personalized therapeutic strategies for LUAD.
ABSTRACT
Heteroatom substitution and anchoring groups have an important impact on the thermoelectric properties of single-molecule junctions. Herein, thermoelectric properties of several anthracene derivative based single-molecule junctions are studied by means of first-principles calculations. In particular, we pay great attention to the edge substitution effects and find that edge substitution with nitrogen can induce a transmission peak near the Fermi energy, leading to large transmission coefficients and electrical conductance at the Fermi energy. Additionally, the steep shape of the transmission function gives rise to a high Seebeck coefficient. Therefore, an enhanced power factor can be expected. The robustness of this edge substitution effect has been examined by altering the electrode distance and introducing heteroatoms at different positions. The enhancement of the power factor due to edge substitution makes the studied single-molecule junction a promising candidate for efficient thermoelectric devices.
ABSTRACT
Incorporation of privileged catalytic scaffolds into a macrocyclic skeleton represents an attractive strategy to furnish supramolecular catalysis systems with enzyme-mimetic cavity and multi-site cooperation. Herein we reported the synthesis, structure, binding properties and catalytic application of a series of chiral bis-phosphate macrocycles toward the challenging asymmetric electrophilic fluorination. With a large, integrated chiral cavity and two cooperative phosphate sites, these macrocycles exhibited good inclusion toward 1,4-diazabicyclo[2.2.2]octane (DABCO) dicationic ammoniums through complementary ion-pair and C-Hâ â â O interactions, as confirmed by crystallographic and solution binding studies. In fluorocyclization of tryptamines with Selectfluor reagent which has a similar DABCO-based dicationic structure, only 2â mol% macrocycle catalyst afforded the desired pyrroloindoline products in moderate yields and up to 91 % ee. For comparison, the acyclic mono-phosphate analogue gave obviously lower reactivity and enantioselectivity (<20 % ee), suggesting a remarkable macrocyclic effect. The high catalytic efficiency and superior stereocontrol were ascribed to the tight ion-pair binding and cavity-directed noncovalent interaction cooperation.
ABSTRACT
Benzoylaconitine is a natural product in the treatment of cardiovascular disease. However, its pharmacological effect, direct target protein, and molecular mechanisms for the treatment of heart failure are unclear. In this study, benzoylaconitine inhibited Ang II-induced cell hypertrophy and fibrosis in rat primary cardiomyocytes and rat fibroblasts, while attenuating cardiac function and cardiac remodeling in TAC mice. Using the limited proteolysis-mass spectrometry (LiP-MS) method, the angiotensin-converting enzyme 2 (ACE2) was confirmed as a direct binding target of benzoylaconitine for the treatment of heart failure. In ACE2-knockdown cells and ACE2-/- mice, benzoylaconitine failed to ameliorate cardiomyocyte hypertrophy, fibrosis, and heart failure. Online RNA-sequence analysis indicated p38/ERK-mediated mitochondrial reactive oxygen species (ROS) and nuclear factor kappa B (NF-κB) activation are the possible downstream molecular mechanisms for the effect of BAC-ACE2 interaction. Further studies in ACE2-knockdown cells and ACE2-/- mice suggested that benzoylaconitine targeted ACE2 to suppress p38/ERK-mediated mitochondrial ROS and NF-κB pathway activation. Our findings suggest that benzoylaconitine is a promising ACE2 agonist in regulating mitochondrial ROS release and inflammation activation to improve cardiac function in the treatment of heart failure.
Subject(s)
Aconitine/analogs & derivatives , Heart Failure , NF-kappa B , Rats , Mice , Animals , NF-kappa B/genetics , NF-kappa B/metabolism , Angiotensin-Converting Enzyme 2/genetics , Reactive Oxygen Species/metabolism , Peptidyl-Dipeptidase A/metabolism , Angiotensin II/metabolism , Heart Failure/drug therapy , Heart Failure/genetics , Myocytes, Cardiac/metabolism , Fibrosis , HypertrophyABSTRACT
ClC is the main family of natural chloride channel proteins that transport Cl- across the cell membrane with high selectivity. The chloride transport and selectivity are determined by the hourglass-shaped pore and the filter located in the central and narrow region of the pore. Artificial unimolecular channel that mimics both the shape and function of the ClC selective pore is attractive, because it could provide simple molecular model to probe the intriguing mechanism and structure-function relevance of ClC. Here we elaborated upon the concept of molecular hourglass plus anion-π interactions for this purpose. The concept was validated by experimental results of molecular hourglasses using shape-persistent 1,3-alternate tetraoxacalix[2]arene[2]triazine as the central macrocyclic skeleton to control the conductance and selectivity, and anion-π interactions as the driving force to facilitate the chloride dehydration and movement along the channel.
ABSTRACT
Herein a series of chiral BTI radical anions bearing different chiral substituents were efficiently prepared by chemical reduction. X-ray crystallography revealed finely-tuned packing and helix assemblies of the radicals by the size of chiral substituents in crystalline state. In accordance with the crystalline-state packing, the powder ESR spectra indicate that 4 a- â CoCp2 + and 4 c- â CoCp2 + π-dimers exhibit thermally excited triplet states arising from strong spin-spin interactions, while discrete 4 b- â CoCp2 + shows a broad doublet-state signal reflecting weak spin-spin interactions. The interplay between the unpaired electron spin and chiral substituents was studied by UV-Vis-NIR spectra, electronic circular dichroism (ECD) and TD DFT calculations. Different NIR absorptions of the radicals attributing to isolated SOMOâLUMO+1 (~889â nm) transitions were recorded. The emergence of Cotton effects (CEs) at the NIR region for 4 c- â CoCp2 + radical enantiomers suggest the interplay between chirality and unpaired electron spin. The origin of the different circularly polarized light absorptions regarding SOMO derived transitions (around 880â nm) was attributed to chiral substitutes regulated electric and magnetic transition dipole moments of the unpaired electron participated transition.
ABSTRACT
Mounting evidence supports the beneficial role of breastfeeding in lowering obesity risk, but the enduring impact of breastfeeding on longitudinal changes in body mass index (BMI) (i.e., BMI trajectories) remains unclear. This systematic review summarized evidence on how breastfeeding influenced the longitudinal trajectories of BMI later in life. Literature searches were conducted in Medline, Embase, Web of Science, and ScienceDirect to identify studies that assessed how breastfeeding (versus other feeding types or duration) was associated with longitudinal trajectories of BMI or BMI z-score. Three randomized controlled trials (RCTs) and 24 longitudinal cohort studies were included. Two-thirds (18/27) of studies were rated as acceptable or high quality. Most cohort studies (9/11) showed that children who continued to breastfeed at 3 to 12 mo of age had a lower BMI trajectory or lower odds of following a high BMI trajectory than those who were formula-fed or mixed-fed. The BMI differences between breastfeeding and other feeding groups were evident from age 7 mo and remained up to 8 y, and the magnitude of between-group BMI differences increased with age. For breastfeeding duration, 12 out of 15 cohort studies found that longer breastfeeding duration was associated with lower BMI trajectories up to age 18 y. Moreover, beneficial associations were observed for both exclusive and any breastfeeding with BMI trajectory. In contrast, mixed findings were reported from 3 RCTs that compared BMI trajectories from birth to ages 12 to 24 mo between breastfeeding promotion versus control or breastfeeding versus formula-feeding groups. The current review provides further longitudinal evidence from cohort studies that breastfeeding versus formula/mixed feeding or longer breastfeeding duration was associated with lower BMI trajectories. Such associations initiated in early childhood became more apparent with age and were sustained into early adulthood. The existing evidence substantiates the importance of breastfeeding promotion and continuation to support obesity prevention.
Subject(s)
Breast Feeding , Obesity , Child , Child, Preschool , Female , Humans , Infant , Adolescent , Body Mass Index , Obesity/prevention & control , Cohort Studies , Longitudinal Studies , Weight LossSubject(s)
Adenoma , Neuroendoscopy , Pituitary Neoplasms , Humans , Adenoma/surgery , Pituitary Neoplasms/surgery , Cerebrospinal Fluid Leak/etiology , Cerebrospinal Fluid Leak/surgery , Endoscopy/adverse effects , Risk Factors , Retrospective Studies , Treatment Outcome , Postoperative Complications/etiology , Neuroendoscopy/adverse effectsABSTRACT
Photothermal therapy (PTT) using near-infrared (NIR) conjugated polymers as photosensitizers has exhibited enormous potential for tumor treatment. However, most NIR conjugated polymers have poor therapeutic efficacy due to their faint absorbance in the NIR region and low photothermal conversion efficiency (PCE). Herein, a valuable strategy for designing NIR polymeric photosensitizer PEKBs with an enhanced PCE accompanied by strong NIR absorbance is proposed by means of inserting TPA-AQ as a thermally activated delayed fluorescence unit into a polymeric backbone. In these PEKBs, PEKB-244 with the appropriate molar content of the TPA-AQ unit displays the strongest NIR absorbance and the highest PCE of 64.5%. Theoretical calculation results demonstrate that the TPA-AQ unit in the polymeric backbone can modulate the intramolecular charge transfer effects and the excited energy decay routes for generating higher heat. The prepared nanoparticles (PEKB-244 NPs) exhibit remarkable photothermal conversion capacities and great biocompatibility in aqueous solutions. Moreover, PEKB-244 NPs also show outstanding photothermal stability, displaying negligible changes in the absorbance within 808 nm irradiation of 1 h (800 mW cm-2). Both in vitro and in vivo experimental results further indicate that PEKB-244 NPs can substantially kill cancer cells under NIR laser irradiation. We anticipate that this novel molecular design strategy can be employed to develop excellent NIR photosensitizers for cancer photothermal therapy.
Subject(s)
Nanoparticles , Photothermal Therapy , Photosensitizing Agents , Polymers/pharmacology , Fluorescence , PhototherapyABSTRACT
An arm modification strategy, by replacing relatively rigid, electron-deficient side arms with flexible ether chain arms and linking them onto a tetraoxacalix[2]arene[2]triazine skeleton, was utilized to design an artificial molecular hourglass. The planar bilayer experiments confirmed the unimolecular channel mechanism and suggested reversed ion selectivity from the previously reported anion selectivity to weak cation selectivity.
ABSTRACT
OBJECTIVES: To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths. METHODS: The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected. RESULTS: In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied. CONCLUSIONS: Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.
Subject(s)
Poisoning , Suicide , Humans , Retrospective Studies , Piperidines , AutopsyABSTRACT
BACKGROUND: There was a high prevalence of overweight/obesity among patients with severe mental disorders (SMD). However, studies on the lifestyle-based interventions in patients with SMD are limited. OBJECTIVE: To examine the effects of an educational lifestyle intervention on body weight and psychological health among Chinese community-dwelling overweight/obese patients with SMD. METHODS: Community-dwelling overweight/obese patients with SMD was recruited from Shenzhen, China in October 2020. They were randomly allocated into intervention group (IG) and control group (CG). Participants in IG received a 12-month educational lifestyle intervention, while the CG was exposed to routine care. A generalized estimating equation model was used to assess the effect of the intervention over time. RESULTS: A total of 176 subjects (88 in IG and 88 in CG) aged 42.2 ± 10.9 years were included in this study. After adjusting for potential confounders, body weight (p = 0.001), body mass index (BMI, p = 0.001), and waist circumference (p = 0.027) in IG significantly decreased compared with CG after 12 months. Besides, IG had significantly higher life satisfaction than CG after intervention (p = 0.026), whereas significant reductions in depressive symptoms were observed in IG from 26.1 % at baseline to 13.6 % after the intervention (p = 0.027), and the between-group differences were marginally significant (p = 0.086). CONCLUSION: An educational lifestyle intervention can effectively reduce body weight parameters and improve psychological health in overweight/obese patients with SMD.
ABSTRACT
Evidence on the association between dietary nutrient-wide intake and cardiovascular disease (CVD) is inconclusive. Therefore, we systematically assessed the association between dietary intake of 29 nutrients and CVD risk using a nutrient-wide association study. Data were obtained from 7878 Chinese adults participating in the China Health and Nutrition Survey (CHNS) wave 2004-2015. We estimated the association of 29 nutrients with CVD risk. Significant findings were replicated in the National Health and Nutrition Examination Survey (NHANES). Four nutrients (selenium, vitamin A, carotenoids, and total protein) were significantly associated with CVD risk in the CHNS. The hazard ratio (HR) and 95% confidence interval (CI) for nutrient intake in the third tertile compared to the first tertile were 0.68 (0.51-0.90), 0.70 (0.54-0.91), 0.64 (0.50-0.83), and 0.54 (0.38-0.77), respectively. In the NHANES replication, selenium maintained a similar direction and strength of association, while the other nutrients were not replicated successfully. Our results provide support for a negative association between selenium intake and CVD risk, while the association of vitamin A, carotenoids and protein with CVD warrants further studies to confirm.
Subject(s)
Cardiovascular Diseases , Selenium , Humans , Nutrition Surveys , Cardiovascular Diseases/epidemiology , Vitamin A , Nutrients , Carotenoids , China/epidemiologyABSTRACT
Schizophrenia (SCZ), a serious mental disorder, is one of the leading causes of disease burden worldwide. Exosomes, as a natural nanocarrier, are able to cross the blood-brain barrier (BBB) and play a key bridging role in central nervous system (CNS) communication, participating in important physiological processes such as neural regeneration, prominent plasticity, axonal support, and neuroinflammation. In recent years, exosomes have received widespread attention in the field of neurodegenerative diseases and mental disorders, especially Alzheimer's disease. However, there are few reviews on exosomes and SCZ. Therefore, we conducted a literature search in PubMed and Web of Science using the following search terms: "schizophrenia", "mental disorder", "central system", "exosome", "extracellular vesicles" to identify publications from January 2010 to December 2022. Our review summarized exosomes secreted by different cell types in the CNS and the double-edged role of exosomes in the development of SCZ, and discussed their future potential as biomarkers and therapeutic targets. In conclusion, this article provides an up-to-date overview of the current research on the involvement of exosomes in SCZ, while also highlighting the challenges that are currently faced in this field.