Accurate prediction of pure uric acid urinary stones in clinical context via a combination of radiomics and machine learning.

PURPOSE: Oral chemolysis is an effective and non-invasive treatment for uric acid urinary stones. This study aimed to classify urinary stones into either pure uric acid (pUA) or other composition (Others) using non-contrast-enhanced computed tomography scans (NCCTs). METHODS: Instances managed at our institution from 2019 to 2021 were screened. They were labeled as either pUA or Others based upon composition analyses, and randomly split into training or testing data set. Several instances contained multiple NCCTs which were all collected. In each of NCCTs, individual urinary stone was treated as individual sample. From manually drawn volumes of interest, we extracted original and wavelet radiomics features for each sample. The most important features were then selected via the Least Absolute Shrinkage and Selection Operator for building the final model on a Support Vector Machine. Performance on the testing set was evaluated via accuracy, sensitivity, specificity, and area under the precision-recall curve (AUPRC). RESULTS: There were 302 instances, of which 118 had pUA urinary stones, generating 576 samples in total. From 851 original and wavelet radiomics features extracted for each sample, 10 most important features were ultimately selected. On the testing data set, accuracy, sensitivity, specificity, and AUPRC were 93.9%, 97.9%, 92.2%, and 0.958, respectively, for per-sample prediction, and 90.8%, 100%, 87.5%, and 0.902, respectively, for per-instance prediction. CONCLUSION: The machine learning algorithm trained with radiomics features from NCCTs can accurately predict pUA urinary stones. Our work suggests a potential assisting tool for stone disease treatment selection.

Novel single nucleotide polymorphisms of insulin-like growth factor-binding protein 7 (IGFBP7) gene significantly associated with growth traits in striped catfish (Pangasianodon hypophthalmus Sauvage, 1878).

Breeding program to improve economically important growth traits in striped catfish (Pangasianodon hypophthalmus) requires effective molecular markers. This study was conducted to identify single nucleotide polymorphisms (SNPs) of Insulin-like Growth Factor-Binding Protein 7 (IGFBP7) gene which plays multiple roles in regulating growth, energy metabolism and development. The association between SNPs in IGFBP7 gene and growth traits in striped catfish was analyzed in order to uncover the SNPs that have potential to be valuable markers for improving growth traits. Firstly, fragments of IGFBP7 gene from ten fast-growing fish and ten slow-growing fish were sequenced in order to discover SNPs. After filtering the detected SNPs, an intronic SNP (2060A > G) and two non-synonymous SNPs (344 T > C and 4559C > A) causing Leu78Pro and Leu189Met in protein, respectively, were subjected to further validated by individual genotyping in 70 fast-growing fish and 70 slow-growing fish using single base extension method. Our results showed that two SNPs (2060A > G and 4559 C > A (p. Leu189Met)) were significantly associated with the growth in P. hypophthalmus (p < 0.001), thus being candidate SNP markers for the growth traits of this fish. Moreover, linkage disequilibrium and association analysis with growth traits of haplotypes generated from the 3 filtered SNPs (344 T > C, 2060 A > G and 4559 C > A) were examined. These revealed that the non-coding SNP locus (2060A > G) had higher genetic diversity at which the G allele was predominant over the A allele in the fast-growing fish. Furthermore, the results of qPCR showed that expression of IGFBP7 gene with genotype GG (at locus 2060) in fast-growing group was significantly higher than that with genotype AA in slow-growing group (p < 0.05). Our study provides insights into the genetic variants of IGFBP7 gene and useful data source for development molecular marker for growth traits in breeding of the striped catfish.

Spotlighting of microbial electrodeionization cells for sustainable wastewater treatment: Application of machine learning.

Microbial electrodeionization cells (MECs) have been investigated for various potential applications, including the elimination of persistent pollutants, chemical synthesis, the recovery of resources, and the development of biosensors. Nevertheless, MEC technology is still developing, and practical large-scale applications face significant obstacles. This review aims to investigate MEC implementations in sustainable wastewater treatment. Ideas and concepts of MEC technology, the setup of the electrodeionization component, the membranes of MECs, the working mechanism of MECs, and the various microorganisms used in MECs are discussed. Additionally, difficulties and prospective outcomes were discussed. The goal of this review is to support scientists and engineers in fully grasping the most recent developments in MEC technologies and applications.

Application of logistic regression, support vector machine and random forest on the effects of titanium dioxide nanoparticles using macroalgae in treatment of certain risk factors associated with kidney injuries.

The use of titanium dioxide (TiO2) nanoparticles in many biological and technical domains is on the rise. There hasn't been much research on the toxicity of titanium dioxide nanoparticles in biological systems, despite their ubiquitous usage. In the current investigation, samples were exposed to various dosages of TiO2 nanoparticles for 4 days, 1 month, and 2 months following treatment. ICP-AES was used to dose TiO2 into the tissues, and the results showed that the kidney had a significant TiO2 buildup. On the other hand, apoptosis of renal tubular cells is one of the most frequent cellular processes contributing to kidney disease (KD). Nevertheless, the impact of macroalgal seaweed extract on KD remains undetermined. In this work, machine learning (ML) approaches have been applied to develop prediction algorithms for acute kidney injury (AKI) by use of titanium dioxide and macroalgae in hospitalized patients. Fifty patients with (AKI) and 50 patients (non-AKI group) have been admitted and considered. Regarding demographic data, and laboratory test data as input parameters, support vector machine (SVM), and random forest (RF) are utilized to build models of AKI prediction and compared to the predictive performance of logistic regression (LR). Due to its strong antioxidant and anti-inflammatory powers, the current research ruled out the potential of using G. oblongata red macro algae as a source for a variety of products for medicinal uses. Despite a high and fast processing of algorithms, logistic regression showed lower overfitting in comparison to SVM, and Random Forest. The dataset is subjected to algorithms, and the categorization of potential risk variables yields the best results. AKI samples showed significant organ defects than non-AKI ones. Multivariate LR indicated that lymphocyte, and myoglobin (MB) ≥ 1000 ng/ml were independent risk parameters for AKI samples. Also, GCS score (95% CI 1.4-8.3 P = 0.014) were the risk parameters for 60-day mortality in samples with AKI. Also, 90-day mortality in AKI patients was significantly high (P < 0.0001). In compared to the control group, there were no appreciable changes in the kidney/body weight ratio or body weight increases. Total thiol levels in kidney homogenate significantly decreased, and histopathological analysis confirmed these biochemical alterations. According to the results, oral TiO2 NP treatment may cause kidney damage in experimental samples.

Nanocatalysts as fast and powerful medical intervention: Bridging cochlear implant therapies and advanced modelling using Hidden Markov Models (HMMs) for effective treatment of inner ear infections.

As human population growth and waste from technologically advanced industries threaten to destabilise our delicate ecological equilibrium, the global spotlight intensifies on environmental contamination and climate-related changes. These challenges extend beyond our external environment and have significant effects on our internal ecosystems. The inner ear, which is responsible for balance and auditory perception, is a prime example. When these sensory mechanisms are impaired, disorders such as deafness can develop. Traditional treatment methods, including systemic antibiotics, are frequently ineffective due to inadequate inner ear penetration. Conventional techniques for administering substances to the inner ear fail to obtain adequate concentrations as well. In this context, cochlear implants laden with nanocatalysts emerge as a promising strategy for the targeted treatment of inner ear infections. Coated with biocompatible nanoparticles containing specific nanocatalysts, these implants can degrade or neutralise contaminants linked to inner ear infections. This method enables the controlled release of nanocatalysts directly at the infection site, thereby maximising therapeutic efficacy and minimising adverse effects. In vivo and in vitro studies have demonstrated that these implants are effective at eliminating infections, reducing inflammation, and fostering tissue regeneration in the ear. This study investigates the application of hidden Markov models (HMMs) to nanocatalyst-loaded cochlear implants. The HMM is trained on surgical phases in order to accurately identify the various phases associated with implant utilisation. This facilitates the precision placement of surgical instruments within the ear, with a location accuracy between 91% and 95% and a standard deviation between 1% and 5% for both sites. In conclusion, nanocatalysts serve as potent medicinal instruments, bridging cochlear implant therapies and advanced modelling utilising hidden Markov models for the effective treatment of inner ear infections. Cochlear implants loaded with nanocatalysts offer a promising method to combat inner ear infections and enhance patient outcomes by addressing the limitations of conventional treatments.

An update on the US adult thalassaemia population: a report from the CDC thalassaemia treatment centres.

Thalassaemia is caused by genetic globin defects leading to anaemia, transfusion-dependence and comorbidities. Reduced survival and systemic organ disease affect transfusion-dependent thalassaemia major and thalassaemia intermedia. Recent improvements in clinical management have reduced thalassaemia mortality. The therapeutic landscape of thalassaemia may soon include gene therapies as functional cures. An analysis of the adult US thalassaemia population has not been performed since the Thalassemia Clinical Research Network cohort study from 2000 to 2006. The Centers for Disease Control and Prevention supported US thalassaemia treatment centres (TTCs) to compile longitudinal information on individuals with thalassaemia. This dataset provided an opportunity to evaluate iron balance, chelation, comorbidities and demographics of adults with thalassaemia receiving care at TTCs. Two adult cohorts were compared: those over 40 years old (n = 75) and younger adults ages 18-39 (n = 201). The older adult cohort was characterized by higher numbers of iron-related comorbidities and transfusion-related complications. By contrast, younger adults had excess hepatic and cardiac iron and were receiving combination chelation therapy. The ethnic composition of the younger cohort was predominantly of Asian origin, reflecting the demographics of immigration. These findings demonstrate that comprehensive care and periodic surveys are needed to ensure optimal health and access to emerging therapies.

Prevalence of comorbid conditions among older males with haemophilia receiving care in haemophilia treatment centers in the United States.

INTRODUCTION: Increased survival among men with haemophilia has brought with it an increased risk of age-related comorbidities that may be challenging to treat in the presence of a bleeding disorder. AIM: Estimate the prevalence of several age-related comorbidities among older males with haemophilia receiving care in the U.S. haemophilia treatment center (HTC) network compared to that among the general population. METHODS: People with bleeding disorders who receive care in network HTCs can volunteer to participate in a surveillance registry that collects detailed clinical information including the presence of comorbid conditions at annual visits. We used registry data collected on males with haemophilia age 45 years and older to calculate lifetime prevalence of obesity, diabetes, hypertension, cardiovascular disease, renal disease, cancer, anxiety and depression. Comparable data on the U.S. general male population was obtained from the National Health Interview Survey. RESULTS: During the surveillance period, 1592 middle-aged (45-64 years) and 645 older (≥65 years) patients with haemophilia had comorbidity data collected during 6435 HTC visits. Most haemophilia patients in both age groups had a higher prevalence of anxiety, depression and diabetes, but a lower prevalence of hypertension, coronary heart disease, stroke and myocardial infarction compared to the general U.S. male population. In addition, middle-aged patients had lower rates of leukemia, whereas older patients had higher rates of obesity than the general population. CONCLUSION: These findings highlight the mental stress associated with this chronic condition and support continued public health obesity prevention efforts in the haemophilia community.

An Efficient Method of Observing Diatom Frustules via Digital Holographic Microscopy.

Herein, we propose a convenient method to enable pretreatment of target objects using digital holographic microscopy (DHM). As a test sample, we used diatom frustules (Nitzschia sp.) as the target objects. In the generally used sample preparation method, the frustule suspension is added dropwise onto a glass substrate or into a glass chamber. While our work confirms good observation of purified frustules using the typical sample preparation method, we also demonstrate a new procedure to observe unseparated structures of frustules prepared by baking them on a mica surface. The baked frustules on the mica surface were transferred to a glass chamber with 1% sodium dodecyl sulfate solution. In this manner, the unseparated structures of the diatom frustules were clearly observed. Furthermore, metal-coated frustules prepared by sputtering onto them on a mica surface were also clearly observed using the same procedure. Our method can be applied for the observation of any target object that is pretreated on a solid surface. We expect our proposed method to be a basis for establishing DHM techniques for microscopic observations of biomaterials.

Occurrence rates of haemophilia among males in the United States based on surveillance conducted in specialized haemophilia treatment centres.

INTRODUCTION: Estimates of the size and characteristics of the US haemophilia population are needed for healthcare planning and resource needs assessment. A network of comprehensive haemophilia treatment centres (HTCs) located throughout the United States receives federal support for diagnosis and management of haemophilia and other rare bleeding disorders. AIM: Estimate the incidence and prevalence of haemophilia among US males using the HTC network. METHODS: During the period 2012-2018, de-identified surveillance data were collected on all males who visited an HTC that included year of birth, gender, race, Hispanic ethnicity, residence zip code, haemophilia type and severity. Data from all patients were used to calculate period prevalence by haemophilia type, severity and state of residence. Data from a subset of patients born 1995-2014 were used to estimate incidence rates over the 20-year period. RESULTS: During the period, 21 748 males with haemophilia visited the HTCs resulting in an age-adjusted prevalence of 15.7 cases per 100 000 males (12 for haemophilia A and 3.7 for haemophilia B). Prevalence was higher among whites (15.1) than blacks (12.4) or Hispanics of either race (12.4). State-specific prevalence varied from 1.6 to 23.3 cases per 100 000. Based on 9587 males born during the index period, the average haemophilia incidence was 1 case per 4334 live male births. CONCLUSION: Based on these data, we estimate that there are between 29 761 and 32 985 males with haemophilia living in the United States today, the majority of whom receive comprehensive care in specialized clinical centres.

A novel circular ssDNA virus of the phylum Cressdnaviricota discovered in metagenomic data from otter clams (Lutraria rhynchaena).

In this study, we present an analysis of metagenome sequences obtained from a filtrate of a siphon tissue homogenate of otter clams (Lutraria rhynchaena) with swollen-siphon disease. The viral signal was mined from the metagenomic data, and a novel circular ssDNA virus was identified. Genomic features and phylogenetic analysis showed that the virus belongs to the phylum Cressdnaviricota, which consists of viruses with circular, single-stranded DNA (ssDNA) genomes. Members of this phylum have been identified in various species and in environmental samples. The newly found virus is distantly related to the currently known members of the phylum Cressdnaviricota.

T7 exo-mediated FRET-breaking combined with DSN-RNAse-TdT for the detection of microRNA with ultrahigh signal-amplification.

A DSN-RNAse-TdT-T7 exo probing system allows the detection of miRNA 21 with very high sensitivity (LOD = 2.57 fM) and selectivity-the result of (i) avoiding the false-positive signal from miRNA reacting with TdT polymerase and (ii) signal amplification occurring through a FRET-breaking mechanism involving T7 exo.

A draft genome of the striped catfish, Pangasianodon hypophthalmus, for comparative analysis of genes relevant to development and a resource for aquaculture improvement.

BACKGROUND: The striped catfish, Pangasianodon hypophthalmus, is a freshwater and benthopelagic fish common in the Mekong River delta. Catfish constitute a valuable source of dietary protein. Therefore, they are cultured worldwide, and P. hypophthalmus is a food staple in the Mekong area. However, genetic information about the culture stock, is unavailable for breeding improvement, although genetics of the channel catfish, Ictalurus punctatus, has been reported. To acquire genome sequence data as a useful resource for marker-assisted breeding, we decoded a draft genome of P. hypophthalmus and performed comparative analyses. RESULTS: Using the Illumina platform, we obtained both nuclear and mitochondrial DNA sequences. Molecular phylogeny using the mitochondrial genome confirmed that P. hypophthalmus is a member of the family Pangasiidae and is nested within a clade including the families Cranoglanididae and Ictaluridae. The nuclear genome was estimated at approximately 700 Mb, assembled into 568 scaffolds with an N50 of 14.29 Mbp, and was estimated to contain ~ 28,600 protein-coding genes, comparable to those of channel catfish and zebrafish. Interestingly, zebrafish produce gadusol, but genes for biosynthesis of this sunscreen compound have been lost from catfish genomes. The differences in gene contents between these two catfishes were found in genes for vitamin D-binding protein and cytosolic phospholipase A2, which have lost only in channel catfish. The Hox cluster in catfish genomes comprised seven paralogous groups, similar to that of zebrafish, and comparative analysis clarified catfish lineage-specific losses of A5a, B10a, and A11a. Genes for insulin-like growth factor (IGF) signaling were conserved between the two catfish genomes. In addition to identification of MHC class I and sex determination-related gene loci, the hypothetical chromosomes by comparison with the channel catfish demonstrated the usefulness of the striped catfish genome as a marker resource. CONCLUSIONS: We developed genomic resources for the striped catfish. Possible conservation of genes for development and marker candidates were confirmed by comparing the assembled genome to that of a model fish, Danio rerio, and to channel catfish. Since the catfish genomic constituent resembles that of zebrafish, it is likely that zebrafish data for gene functions is applicable to striped catfish as well.

Direct incorporation and extension of a fluorescent nucleotide through rolling circle DNA amplification for the detection of microRNA 24-3P.

We designed and synthesized several fluorescent nucleotides from thiophene, anthracene and pyrene, which have different sizes, and screened their incorporation and extension capability during the rolling circle amplification of DNA. The thiophene-based fluorescent nucleotide (dUthioTP) could highly incorporate and extended into the rolling circle DNA product, while other fluorescent nucleotides (dUanthTP, and dUpyrTP) could not. This dUthioTP fluorescent nucleotide could be used for the detection of miRNA 24-3P, which is related PRRSV. This direct labeling system during rolling circle DNA amplification exhibited an increased fluorescence signal showing gel formation for the detection of miRNA 24-3P. This direct labeling system is a very simple and cost-efficient method for the detection miRNA 24-3P and also exhibited highly sensitive and selective detection properties.

Large-Stokes-shift-based folded DNA probing systems targeting DNA and miRNA 21 with signal amplification.

Large-Stokes-shift based simple folded DNA probing system (LSFP) had a simple folded DNA structure and exhibited a large Stokes-shifted (194 nm) fluorescence signal upon excitation at a single wavelength (386 nm). This Stokes shift was achieved through a simple combination of donor and acceptor fluorophores and employing multi-FRET systematically. This unique large Stokes-shifted fluorescence signal was used to detect target DNA with large increases in the fluorescence signal (9.7-14.2 fold). This LSFP exhibited enough selectivity, distinguishing a perfectly matched sequence from the probe itself and mismatched sequences. Surprisingly, when DSN was used for signal amplification with miR21P probing system whose target is miRNA 21, it showed high sensitivity (13.7 aM) and selectivity (one base mismatch discrimination). This system has several advantages over other molecular beacons (MBs): (i) it is easy to design and synthesize the probing system that does not require the construction of a finely designed stem and loop, as in most MBs (this can prevent the degradation of miR21P itself by DSN enzyme without special backbone modification); (ii) it can control unique fluorescence, such as large Stokes-shifted fluorescence through a simple combination of donor and acceptor fluorophores; and (iii) through signal amplification using DSN, it can efficiently detect extremely small amounts of target miRNA with high sensitivity (13.7 aM).

Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.

Background: Most insights into the cascade of immune events after acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models. Methods: In this study, we investigated host gene expression profiles in nasopharyngeal (NP) swabs and whole blood samples during natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in 83 hospitalized patients <2 years old with lower respiratory tract infections. Results: Respiratory syncytial virus infection induced strong and persistent innate immune responses including interferon signaling and pathways related to chemokine/cytokine signaling in both compartments. Interferon-α/ß, NOTCH1 signaling pathways and potential biomarkers HIST1H4E, IL7R, ISG15 in NP samples, or BCL6, HIST2H2AC, CCNA1 in blood are leading pathways and hub genes that were associated with both RSV load and severity. The observed RSV-induced gene expression patterns did not differ significantly in NP swab and blood specimens. In contrast, hRV infection did not as strongly induce expression of innate immunity pathways, and significant differences were observed between NP swab and blood specimens. Conclusions: We conclude that RSV induced strong and persistent innate immune responses and that RSV severity may be related to development of T follicular helper cells and antiviral inflammatory sequelae derived from high activation of BCL6.

Selective area epitaxy of AlGaN nanowire arrays across nearly the entire compositional range for deep ultraviolet photonics.

Semiconductor light sources operating in the ultraviolet (UV)-C band (100-280 nm) are in demand for a broad range of applications but suffer from extremely low efficiency. AlGaN nanowire photonic crystals promise to break the efficiency bottleneck of deep UV photonics. We report, for the first time, site-controlled epitaxy of AlGaN nanowire arrays with Al incorporation controllably varied across nearly the entire compositional range. It is also observed that an Al-rich AlGaN shell structure is spontaneously formed, significantly suppressing nonradiative surface recombination. An internal quantum efficiency up to 45% was measured at room-temperature. We have further demonstrated large area AlGaN nanowire LEDs operating in the UV-C band on sapphire substrate, which exhibit excellent optical and electrical performance, including a small turn-on voltage of ~4.4 V and an output power of ~0.93 W/cm2 at a current density of 252 A/cm2. The controlled synthesis of AlGaN subwavelength nanostructures with well-defined size, spacing, and spatial arrangement and tunable emission opens up new opportunities for developing high efficiency LEDs and lasers and promises to break the efficiency bottleneck of deep UV photonics.

AuNP-CTG based probing system targeting CAG repeat DNA and RNA sequences.

We have developed a AuNP-CTG based probing system that is applicable to the detection of many units of CAG repeat sequences which was synthesized by a rolling circle amplification (RCA) system with changes in fluorescence. We also demonstrate that our AuNP-CTG based probing system could transfect without using transfection reagent and detect target CAG repeat sequences in HeLa cells with dramatic changes in fluorescence. This AuNP-CTG based probing system could also be used, in conjunction with the CAG repeat RCA system, to detect target DNA. This system was so sensitive to the target DNA that it could detect even picomolar amounts with amplification of the fluorescence signal. Furthermore, we have used our gold-based CAG probing system for the detection of RNA CAG repeat sequences.

Diverse size approach to incorporate and extend highly fluorescent unnatural nucleotides into DNA.

We have prepared a series of size-diverse unnatural nucleotides containing fluorescent (dApyrTP, dUpyrTP, dUantTP, dUthiTP) and quencher (dUazoTP) units, as well as nucleotides presenting small functional groups (dAethTP, dAoctTP, dUethTP, dUiodTP), all based on deoxyadenosine and deoxyuridine, and examined their suitability for use in enzymatic incorporation and extension into DNA. We observed a size-dependence of the incorporation and extension capability (following the order dUiodTP=dUethTP=dUthiTP>dUazoTP>dUpyrTP>dUantTP) during primer extension. This result was supported by circular dichroism (CD) spectra, which revealed a trend in the different B-form DNA structures depending on the size of the unit at the 5-position of the deoxyuridine (dUiodTP>dUethTP>dUthiTP>dUpyrTP), obtained from the PCR products. Interestingly, dUthiTP could be incorporated and extended into long DNA strands during primer extension and even PCR amplification, with CD spectroscopy confirming a stable secondary B-form duplex DNA structure. We observed full-length extension products even when combining dUthiTP with a template containing 24 continuous dA units during the primer extension. Thus, we believe that dUthiTP is a promising fluorescent nucleotide for a diverse range of biological applications requiring multiple incorporation and extension directly without disruption of B-form DNA structures.

Prevention and recognition of abusive head trauma: training for healthcare professionals in Vietnam.

AIM: This study presents results from an intervention designed to improve identification and response to abusive head trauma in a tertiary paediatric hospital in Vietnam. METHODS: One hundred and sixteen healthcare professionals (paediatric medical and nursing staff) completed a clinical training programme and participated in its evaluation. A pre-post-test and follow-up design was used to evaluate the outcomes. Questionnaires were used to collect data prior to training, at six weeks and at six months. Generalised linear modelling was used to examine changes in diagnostic skills and knowledge of the consequences of shaken baby syndrome (SBS) (a form of abusive head trauma), its prevention and treatment. RESULTS: At baseline, awareness and knowledge reflected no former abusive head trauma training. Following the intervention, participants had an increased awareness of shaken baby syndrome and the potential consequences of shaking infants and had acquired techniques to inform parents how to manage the crying infant. CONCLUSION: The intervention was effective in raising awareness of shaken baby syndrome and its consequences amongst the participating healthcare professionals in Vietnam. Training can improve detection and prevention of abusive head trauma, and the intervention has the potential to be adapted for similar settings internationally.

Structural basis for the substrate selectivity of a HAD phosphatase from Thermococcus onnurineus NA1.

Proteins in the haloalkaloic acid dehalogenase (HAD) superfamily, which is one of the largest enzyme families, is generally composed of a catalytic core domain and a cap domain. Although proteins in this family show broad substrate specificities, the mechanisms of their substrate recognition are not well understood. In this study, we identified a new substrate binding motif of HAD proteins from structural and functional analyses, and propose that this motif might be crucial for interacting with hydrophobic rings of substrates. The crystal structure of TON_0338, one of the 17 putative HAD proteins identified in a hyperthermophilic archaeon, Thermococcus onnurineus NA1, was determined as an apo-form at 2.0 Å resolution. In addition, we determined the crystal structure TON_0338 in complex with Mg(2+) or N-cyclohexyl-2-aminoethanesulfonic acid (CHES) at 1.7 Å resolution. Examination of the apo-form and CHES-bound structures revealed that CHES is sandwiched between Trp58 and Trp61, suggesting that this Trp sandwich might function as a substrate recognition motif. In the phosphatase assay, TON_0338 was shown to have high activity for flavin mononucleotide (FMN), and the docking analysis suggested that the flavin of FMN may interact with Trp58 and Trp61 in a way similar to that observed in the crystal structure. Moreover, the replacement of these tryptophan residues significantly reduced the phosphatase activity for FMN. Our results suggest that WxxW may function as a substrate binding motif in HAD proteins, and expand the diversity of their substrate recognition mode.