Jun-activated SOCS1 enhances ubiquitination and degradation of CCAAT/enhancer-binding protein ß to ameliorate cerebral ischaemia/reperfusion injury.

This study investigates the molecular mechanisms behind ischaemia/reperfusion (I/R) injury in the brain, focusing on neuronal apoptosis. It scrutinizes the role of the Jun proto-oncogene in apoptosis, involvement of SOCS1 in neural precursor cell accumulation in ischaemic regions, and the upregulation of C-EBPß in the hippocampus following I/R. Key to the study is understanding how Jun controls C-EBPß degradation via SOCS1, potentially offering new clinical treatment avenues for I/R. Techniques such as mRNA sequencing, KEGG enrichment analysis and protein-protein interaction (PPI) in mouse models have indicated involvement of Jun (AP-1) in I/R-induced cerebral damage. The study employs middle cerebral artery occlusion in different mouse models and oxygen-glucose deprivation/reoxygenation in cortical neurons to examine the impacts of Jun and SOCS1 manipulation on cerebral I/R injury and neuronal damage. The findings reveal that I/R reduces Jun expression in the brain, but its restoration lessens cerebral I/R injury and neuron death. Jun activates SOCS1 transcriptionally, leading to C-EBPß degradation, thereby diminishing cerebral I/R injury through the SOCS1/C-EBPß pathway. These insights provide a deeper understanding of post-I/R cerebral injury mechanisms and suggest new therapeutic targets for cerebral I/R injury. KEY POINTS: Jun and SOCS1 are poorly expressed, and C-EBPß is highly expressed in ischaemia/reperfusion mouse brain tissues. Jun transcriptionally activates SOCS1. SOCS1 promotes the ubiquitination-dependent C-EBPß protein degradation. Jun blunts oxygen-glucose deprivation/reoxygenation-induced neuron apoptosis and alleviates neuronal injury. This study provides a theoretical basis for the management of post-I/R brain injury.

The role of DNA damage in neural stem cells ageing.

Neural stem cells (NSCs) are pluripotent stem cells with the potential to differentiate into a variety of nerve cells. NSCs are susceptible to both intracellular and extracellular insults, thus causing DNA damage. Extracellular insults include ultraviolet, ionizing radiation, base analogs, modifiers, alkyl agents and others, while intracellular factors include Reactive oxygen species (ROS) radicals produced by mitochondria, mismatches that occur during DNA replication, deamination of bases, loss of bases, and more. When encountered with DNA damage, cells typically employ three coping strategies: DNA repair, damage tolerance, and apoptosis. NSCs, like many other stem cells, have the ability to divide, differentiate, and repair DNA damage to prevent mutations from being passed down to the next generation. However, when DNA damage accumulates over time, it will lead to a series of alterations in the metabolism of cells, which will cause cellular ageing. The ageing and exhaustion of neural stem cell will have serious effects on the body, such as neurodegenerative diseases. The purpose of this review is to examine the processes by which DNA damage leads to NSCs ageing and the mechanisms of DNA repair in NSCs.

Dual-Mechanism Design Strategy for High-Efficiency and Long-Lived Organic Afterglow Materials.

Organic room-temperature phosphorescence (RTP) and afterglow materials hold great potential for various applications, but there remain inherent trade-offs between the afterglow efficiency and the lifetime. Here, we propose a dual-mechanism design strategy, leveraging the RTP or thermally activated delayed fluorescence (TADF) mechanism for a high afterglow efficiency and the organic long-persistent luminescence (OLPL) mechanism for a prolonged afterglow duration. The intramolecular charge transfer (ICT)-type difluoroboron ß-diketonate molecules with a large S1 dipole moment are doped as the luminescent component into the organic matrix with a large dipole moment, and a series of TADF-type afterglow materials can be achieved with an afterglow efficiency of up to 88.7% and an afterglow lifetime of 200 ms. To prolong the afterglow duration, an electron donor is introduced as the third component to generate traps and facilitate charge separation. The obtained materials exhibit a dual afterglow mechanism, first exhibiting a TADF/RTP afterglow with an afterglow efficiency of up to 50.9%, followed by an hours-long OLPL afterglow emission with an afterglow efficiency of up to 13.1%. Further investigations reveal that an appropriate heavy-atom effect can facilitate the intersystem crossing process, which can promote the charge separation process and thus improve the OLPL afterglow performance. Additionally, rare-earth upconversion materials are introduced into OLPL materials to enable their near-infrared excitation properties, showcasing their potential applications in bioimaging.

Achieving Visible-Light-Excitable Blue TADF-Type Afterglow via Delicate Control of Excited States in Difluoroboron ß-Diketonate Systems.

Blue afterglow constitutes of one of the primary afterglow colors and can convert into other afterglow colors through energy transfer. The reported studies show the fabrication of blue afterglow emitters, but most of them are formed by room-temperature phosphorescence mechanism and require UVB lights as excitation source (these high-energy lights may damage organic systems). Here we report visible-light-excitable blue thermally activated delayed fluorescence type (TADF-type) afterglow materials via delicate control of excited states in difluoroboron ß-diketonate (BF2bdk) systems. Tiny change of the substituents in BF2bdk system has been found to pose significant influence on excited state energy levels and consequently narrow the singlet-triplet splitting energy of the system. As a result, both forward and reverse intersystem crossing have been accelerated, leading to the emergence of BF2bdk's TADF-type organic afterglow in rigid crystalline matrices. The resultant TADF-type afterglow materials exhibit emission lifetimes of several hundred milliseconds, photoluminescence quantum yield (PLQY) of 24.7 % and display temperature responsive property.

Polymer-Based Room-Temperature Phosphorescence Materials Exhibiting Emission Lifetimes up to 4.6 s under Ambient Conditions.

The long-emission-lifetime nature of room-temperature phosphorescence (RTP) materials lays the foundation of their applications in diverse areas. Despite the advantage of mechanical property, processability and solvent dispersity, the emission lifetimes of polymer-based room-temperature phosphorescence materials remain not particularly long because of the labile nature of organic triplet excited states under ambient conditions. Specifically, ambient phosphorescence lifetime (τP) longer than 2 s and even 4 s have rarely been reported in polymer systems. Here, luminescent compounds with small phosphorescence rate on the order of approximately 10-1 s-1 are designed, ethylene-vinyl alcohol copolymer (EVOH) as polymer matrix and antioxidant 1010 to protect organic triplets are employed, and ultralong phosphorescence lifetime up to 4.6 s under ambient conditions by short-term and low-power excitation are achieved. The resultant materials exhibit high afterglow brightness, long afterglow duration, excellent processability into large area thin films, high transparency and thermal stability, which display promising anticounterfeiting and data encryption functions.

Engineering high-brightness and long-lived organic room-temperature phosphorescence via systematic molecular design.

We report a systematic molecular design in BF2bdk-based afterglow emitters with photoluminescence quantum yields up to 46.3% and lifetimes around 1 s. Suitable excited-state types, diverse excited state species, relatively small singlet-triplet energy gaps and strong dipole-dipole interactions are critical in determining the afterglow properties.

A new generation of effective core potentials: Selected lanthanides and heavy elements.

We construct correlation-consistent effective core potentials (ccECPs) for a selected set of heavy atoms and f elements that are currently of significant interest in materials and chemical applications, including Y, Zr, Nb, Rh, Ta, Re, Pt, Gd, and Tb. As is customary, ccECPs consist of spin-orbit (SO) averaged relativistic effective potential (AREP) and effective SO terms. For the AREP part, our constructions are carried out within a relativistic coupled-cluster framework while also taking into account objective function one-particle characteristics for improved convergence in optimizations. The transferability is adjusted using binding curves of hydride and oxide molecules. We address the difficulties encountered with f elements, such as the presence of large cores and multiple near-degeneracies of excited levels. For these elements, we construct ccECPs with core-valence partitioning that includes 4f subshell in the valence space. The developed ccECPs achieve an excellent balance between accuracy, size of the valence space, and transferability and are also suitable to be used in plane wave codes with reasonable energy cutoffs.

Narrowband Organic/Inorganic Hybrid Afterglow Materials.

Narrowband afterglow materials display interesting functions in high-quality anti-counterfeiting and multiplexed bioimaging. However, there is still a limited exploration of these afterglow materials, especially for those with a full width at half maxima (FWHM) around 30 nm. Here, we report the fabrication of narrowband organic/inorganic hybrid afterglow materials via energy transfer technology. Coronene (Cor) with a long phosphorescence feature and broad phosphorescence band is selected as the donor for energy transfer, and inorganic quantum dots (QDs) of CdSe/ZnS with a narrowband emission are used as acceptors. Upon doping into the organic matrix, the resultant three-component materials exhibit a narrowband afterglow with an afterglow lifetime of approximately 3.4 s and an FWHM of 31 nm. The afterglow wavelength of the afterglow materials can be controlled by the QDs. This work based on organic/inorganic hybrids provides a facile approach for developing multicolor and narrowband afterglow materials, as well as opens a new way for expanding the features of organic afterglow for multifunctional applications. It is expected to rely on narrowband afterglow emitters to solve the "spectrum congestion" problem of high-density information storage in optical anti-counterfeiting and information encryption.

Experimental Study on Combined Microwave-Magnetic Separation-Flotation Coal Desulfurization.

In order to reduce the content of sulfur and ash in coal, improve the desulfurization and deashing rates, a combined experiment method of microwave magnetic separation-flotation was proposed for raw coal. The desulfurization and deashing rates of three experiment methods, namely, single magnetic separation, microwave magnetic separation, and microwave magnetic separation-flotation, were compared. Taking the microwave magnetic separation-flotation experiment method as the main line, the effects of the microwave irradiation time, microwave power, grinding time, magnetic field intensity, plate seam width, foaming agent dosage, collector dosage, and inhibitor dosage on desulfurization and deashing were discussed, and the mechanism of microwave irradiation on magnetic separation and flotation was revealed. The results show that under the conditions of a microwave irradiation time of 60 s, a microwave power of 80% of the rated power (800 W), a grinding time of 8 min, a plate seam width (the plate seam width of a magnetic separator sorting box) of 1 mm, a magnetic field intensity of 2.32 T, a foaming agent dosage of 90 g/t, a collector dosage of 2125 g/t, and an inhibitor dosage of 1500 g/t, the desulfurization and deashing effect is the best. The desulphurization rate is 76.51%, the sulfur removal rate of pyrite is 96.50%, and the deashing rate is 61.91%. Microwaves have the characteristic of selective heating, and the thermal conductivity of organic matter in coal is greater than that of mineral. Microwave irradiation can improve the reactivity of pyrite in coal, pyrolyze pyrite into high-magnetic pyrite, improve the magnetic properties, and improve the magnetic separation effect. Therefore, microwave irradiation plays a role in promoting magnetic separation. Through microwave irradiation, the positive and negative charges in coal molecules constantly vibrate and create friction under the action of an electric field force, and the thermal action generated by this vibration and friction process affects the structural changes in oxygen-containing functional groups in coal. With the increase in the irradiation time and power, the hydrophilic functional groups of -OH and -COOH decrease and the hydrophilicity decreases. Microwave heating evaporates the water in the pores of coal samples and weakens surface hydration. At the same time, microwave irradiation destroys the structure of coal and impurity minerals, produces cracks at the junction, increases the surface area of coal to a certain extent, enhances the hydrophobicity, and then improves the effect of flotation desulfurization and deashing. Therefore, after the microwave irradiation of raw coal, the magnetic separation effect is enhanced, and the flotation desulfurization effect is also enhanced.

[Genetic analysis of a child with Hereditary hemorrhagic telangiectasia type I in conjunct with Splenic sinus shore cell hemangioma].

OBJECTIVE: To explore the genetic basis and pathogenesis for a child with type I Hereditary hemorrhagic telangiectasia (HHTⅠ) and Splenic sinus shore cell hemangioma (LCA). METHODS: A child with HHT complicated with LCA diagnosed at the First Affiliated Hospital of Dali University in April 2022 was selected as the study subject. Clinical data of the child and her relatives were collected, and pathogenic variants were screened by whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient, a 16-year-old female, had recurrent epitaxis since childhood, which sometimes necessitated hemostasis treatment. She also had splenectomy due to splenic rupture and was diagnosed with LCA. Her father and grandmother also had a history of recurrent epitaxis. Her father had deceased due to cerebral vascular rupture. The child was found to harbor a c.360+1G>A variant in the ENG gene. The same variant was not found in her asymptomatic mother and brother. CONCLUSION: The c.360+1G>A variant of the ENG gene probably underlay the pathogenesis in this child.

Polarization-mismatching transmissive metasurface for independent amplitude and phase control of circular polarization.

This work presents a strategy for independent control of the amplitude and phase of transmissive circular-polarization (CP) waves. The designed meta-atom consists of an elliptical-polarization receiver and a CP transmitter. By changing the axial ratio (AR) and polarization of the receiver, amplitude modulation can be realized based on polarization mismatching theory, with negligible cumbrous components. While by rotating the element, a full phase coverage enabled by the geometric phase is achieved. Subsequently, a CP transmitarray antenna (TA) with high gain and low side-lobe level (SLL) is implemented to experimentally validate our strategy, and the tested results match well with the simulated ones. During the operating band from 9.6 to 10.4 GHz, the proposed TA obtains an average SLL of -24.5 dB, a lowest SLL of -27.7 dB at 9.9 GHz, and a maximum gain of 19 dBi at 10.3 GHz, with the measured AR lower than 1 dB, which mainly benefits from high polarization purity (HPP) of the proposed elements. The proposed strategy for full amplitude-phase manipulation of CP waves together with HPP paves a way for complicated field manipulations and indicates a promising candidate in antenna applications, such as anti-jamming systems and wireless communications.

Sirt1 Protects Subventricular Zone-Derived Neural Stem Cells from DNA Double-Strand Breaks and Contributes to Olfactory Function Maintenance in Aging Mice.

DNA damage is assumed to accumulate in stem cells over time and their ability to withstand this damage and maintain tissue homeostasis is the key determinant of aging. Nonetheless, relatively few studies have investigated whether DNA damage does indeed accumulate in stem cells and whether this contributes to stem cell aging and functional decline. Here, we found that, compared with young mice, DNA double-strand breaks (DSBs) are reduced in the subventricular zone (SVZ)-derived neural stem cells (NSCs) of aged mice, which was achieved partly through the adaptive upregulation of Sirt1 expression and non-homologous end joining (NHEJ)-mediated DNA repair. Sirt1 deficiency abolished this effect, leading to stem cell exhaustion, olfactory memory decline, and accelerated aging. The reduced DSBs and the upregulation of Sirt1 expression in SVZ-derived NSCs with age may represent a compensatory mechanism that evolved to protect stem cells from excessive DNA damage, as well as mitigate memory loss and other stresses during aging.

Manipulation of Organic Afterglow in Fluoranthene-Containing Dopant-Matrix Systems: From Conventional Room-Temperature Phosphorescence to Efficient Red TADF-Type Organic Afterglow.

It remains challenging to fabricate highly-efficient and long-lived organic afterglow materials, especially in the case of red afterglow systems. Here we develop advanced charge transfer (CT) technology to boost afterglow efficiency and lifetimes in fluoranthene-containing dopant-matrix systems. First, organic CT molecules possess singlet-triplet splitting energy (ΔEST ) of around 0.5 eV, much smaller than localized excitation systems. Second, upon doping into suitable organic matrices, dipole-dipole interactions between 1 CT states and organic matrices reduce 1 CT levels with less effect on 3 CT levels, and thus further narrow ΔEST and enhance intersystem crossing. Third, the rigid planar structure of fluoranthene groups and the rigid microenvironment provided by organic matrices can suppress phosphorescence quenching. Forth, the multiple donor design enables spectral red-shifts to red region and switches on TADF mechanism to improve afterglow efficiency to 13.1 % and maintain afterglow lifetime of 0.1 s. Such high-performance afterglow materials have been rarely explored in reported studies.

Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease involving cartilage. Exosomes derived from Mesenchymal stem cells (MSCs) therapy improves articular cartilage repair, but subcutaneous fat (SC) stromal cells derived exosomes (MSCsSC-Exos), especially engineering MSCsSC-Exos for drug delivery have been rarely reported in OA therapy. This objective of this study was to clarify the underlying mechanism of MSCsSC-Exos on cartilage repair and therapy of engineering MSCsSC-Exos for drug delivery in OA. MSCsSC-Exos could ameliorate the pathological severity degree of cartilage via miR-199a-3p, a novel molecular highly enriched in MSCsSC-Exos, which could mediate the mTOR-autophagy pathway in OA rat model. Intra-articular injection of antagomiR-199a-3p dramatically attenuated the protective effect of MSCsSC-Exos-mediated on articular cartilage in vivo. Furthermore, to achieve the superior therapeutic effects of MSCsSC-Exos on injured cartilage, engineering exosomes derived from MSCsSC as the chondrocyte-targeting miR-199a-3p delivery vehicles were investigated in vitro and in vivo. The chondrocyte-binding peptide (CAP) binding MSCsSC-Exos could particularly deliver miR-199a-3p into the chondrocytes in vitro and into deep articular tissues in vivo, then exert the excellent protective effect on injured cartilage in DMM-induced OA mice. As it is feasible to obtain human subcutaneous fat from healthy donors by liposuction operation in clinic, meanwhile engineering MSCsSC-Exos to realize targeted delivery of miR-199a-3p into chondrocytes exerted excellent therapeutic effects in OA animal model in vivo. Through combining MSCsSC-Exos therapy and miRNA therapy via an engineering approach, we develop an efficient MSCsSC-Exos-based strategy for OA therapy and promote the application of targeted-MSCsSC-Exos for drug delivery in the future.

Malignant cerebral edema after cranioplasty: a case report and literature review.

BACKGROUND: Cranioplasty is a common surgery in the neurosurgery for patients with skull defects following decompression craniectomy. Concomitant rare complications are increasingly reported, such as malignant cerebral edema after cranioplasty. CASE REPORT: A 45-year-old man underwent decompression craniectomy due to traumatic brain injury. At 3 months after the decompression craniectomy, the patient developed refractory subdural hydrogen and received ipsilateral refractory subdural effusion capsule resection, but no significant relief was seen. Therefore, the cranioplasty was decided to treat subdural hydrogen and restore the normal appearance of the skull. After the successful cranioplasty surgery and the expected anesthesia recovery period, the pupils of the patients were continued to be dilated and fixed, without light reflection and spontaneous breathing. The Computed Tomography of the patient 1 hour after surgery showed malignant cerebral edema. CONCLUSIONS: Malignant cerebral edema is a rare and lethal complication after cranioplasty. Negative pressure drainage and deregulation of cerebral blood flow at the end of cranioplasty may partially explain the malignant cerebral after cranioplasty. In addition, patients with epileptic seizures, no spontaneous breathing, dilated pupils without reflection, and hypotension within a short period after cranioplasty may show the occurrence of malignant cerebral.

Near-Space Wide-Area and High-Resolution Imaging System Design and Implementation.

The near-space atmosphere is thin, and the atmospheric refraction and scattering on optical observation is very small, making it very suitable for wide-area and high-resolution surveillance using high-altitude balloon platforms. This paper adopts a 9344 × 7000 CMOS sensor to obtain high-resolution images, generating large-field-of-view imaging through the swing scanning of the photoelectric sphere and image stitching. In addition, a zoom lens is designed to achieve flexible applications for different scenarios, such as large-field-of-view and high-resolution imaging. The optical design results show that the camera system has good imaging quality within the focal length range of 320 mm-106.7 mm, and the relative distortion values at different focal lengths are less than 2%. The flight results indicate that the system can achieve seamless image stitching at a resolution of 0.2 m@20 km and the imaging field of view angle exceeds 33°. This system will perform other near-space flight experiments to verify its ultra-wide (field of view exceeding 100°) high-resolution imaging application.

[Genetic analysis of a Chinese pedigree with chronic kidney disease due to variant of PAX2 gene].

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with chronic kidney disease (CKD). METHODS: A Chinese pedigree comprised of 10 individuals from four generation who had visited the First Affiliated Hospital of Dali University from August 15, 2018 to July 5, 2021 was selected as the study subject. Clinical data of the proband were collected, and a pedigree survey was conducted. The proband was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband, a 41-year-old female, has been diagnosed with chronic nephritis for more than 4 years. Routine urinary examination showed proteinuria and blood creatinine of 1 130 µmol/L. Renal biopsy has revealed hyperplastic glomerulonephritis, moderate tubulointerstitial disease and renal arteriosclerosis. Her elder sister, younger brother, younger sister and mother were all diagnosed with CKD stage 5. Except for her elder sister, all of them had deceased, whilst no abnormality was found in the remainders. Genetic testing revealed that the proband and four family members had harbored a c.467G>A missense variant of the PAX2 gene. The variant has been associated with focal segmental glomerulosclerosis and classified as likely pathogenic (PS1+PP3+PP4) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION: The c.167G＞A variant of the PAX2 gene probably underlay the CKD in this Chinese pedigree.

Surface Chemistry and Catalytic Reactivity of Borocarbonitride in Oxidative Dehydrogenation of Propane.

Borocarbonitride (BCN) materials are newly developed oxidative dehydrogenation catalysts that can efficiently convert alkanes to alkenes. However, BCN materials tend to form bulky B2 O3 due to over-oxidation at the high reaction temperature, resulting in significant deactivation. Here, we report a series of super stable BCN nanosheets for the oxidative dehydrogenation of propane (ODHP) reaction. The catalytic performance of the BCN nanosheets can be easily regulated by changing the guanine dosage. The control experiment and structural characterization indicate that the introduction of a suitable amount of carbon could prevent the formation of excessive B2 O3 from BCN materials and maintain the 2D skeleton at a high temperature of 520 °C. The best-performing catalyst BCN exhibits 81.9 % selectivity towards olefins with a stable propane conversion of 35.8 %, and the propene productivity reaches 16.2 mmol h-1 g-1 , which is much better than hexagonal BN (h-BN) catalysts. Density functional theory calculation results show that the presence of dispersed rather than aggregated carbon atoms can significantly affect the electronic microenvironment of h-BN, thereby boosting the catalytic activity of BCN.

Hybrid metasurface-based broadband high gain stealth antenna.

In this paper, a novel hybrid metasurface (HMS) is proposed for reducing antenna RCS and maintaining the gain of the antenna. The HMS consists of a polarization-selective absorbing surface (PSAS) and an asymmetric transmission metasurface (ATMS). PSAS can absorb the in-band and out-of-band x-polarized waves, while completely transmitting y-polarized waves. The out-of-band y-polarized waves transmitting the PSAS is reflected by the ATMS with 90° polarization rotation when the ATMS is located under the PSAS, and the reflected wave is absorbed by the PSAS. The in-band y-polarized wave passing through the PSAS can completely pass through the ATMS and the antenna array. Thus the RCS reduction of the antenna can be achieved. Based on antenna reciprocity principle, the in-band y-polarized wave radiated by the metasurface lens antenna can completely pass through the HMS. The measurement results show that the antenna RCS is significantly reduced for x-polarized and y-polarized incident waves in 8∼18 GHz. The 3 dB gain relative bandwidth of stealth antenna is 40% (8∼12 GHz). The realized gain of the antenna at the center frequency reaches 26.3 dB. It is noteworthy that the stealth antenna balances both radiation performance and scattering performance, which makes it have the merits of high gain and excellent stealth performance simultaneously.

Designing an ultra-thin and wideband low-frequency absorber based on lumped resistance.

Traditional absorbers are mostly limited by their large size and high profile, which renders them unfavorable for practical devices. To solve this problem, we design and test an ultra-thin metamaterial absorber (UTMA). The top layer of the metamaterial absorber is designed as a patterned combination of split ring and metal strips, so that its resonant frequency point is in the target low frequency. Meanwhile, ohmic loss is enhanced by loading lumped resistance in the gap of the meta-surface to improve the absorb efficiency (> 90%) and to expand the working bandwidth (1.24-3.14 GHz). Moreover, the total thickness of the absorber is 9 mm (0.037λwith respect to the lowest operating frequency). The working mechanism of UTMA is analyzed based on the equivalent media theory, surface current and electric field energy distribution. The experimental results are in good agreement with the simulation, which verifies the feasibility of the design. In this work, the metamaterial absorber is designed to meet the target requirements from three performance indexes: low frequency, ultra-thin, and wideband, leading to the prospect of broad applications in the military and civil fields.