Early prediction of response to palliative chemotherapy in patients with stage-IV gastric and esophageal cancer.

BACKGROUND: The goal of therapy for many patients with advanced stage malignancies, including those with metastatic gastric and esophageal cancers, is to extend overall survival while also maintaining quality of life. After weighing the risks and benefits of treatment with palliative chemotherapy (PC) with non-curative intent, many patients decide to pursue treatment. It is known that a subset of patients who are treated with PC experience significant side effects without clinically significant survival benefits from PC. METHODS: We use data from 150 patients with stage-IV gastric and esophageal cancers to train machine learning models that predict whether a patient with stage-IV gastric or esophageal cancers would benefit from PC, in terms of increased survival duration, at very early stages of the treatment. RESULTS: Our findings show that machine learning can predict with high accuracy whether a patient will benefit from PC at the time of diagnosis. More accurate predictions can be obtained after only two cycles of PC (i.e., about 4 weeks after diagnosis). The results from this study are promising with regard to potential improvements in quality of life for patients near the end of life and a potential overall survival benefit by optimizing systemic therapy earlier in the treatment course of patients.

A Peptide Derived from IKK-Interacting Protein Attenuates NF-κB Activation and Inflammation.

The IκB kinase (IKK) complex plays a vital role in regulating the NF-κB activation. Aberrant NF-κB activation is involved in various inflammatory diseases. Thus, targeting IKK activation is an ideal therapeutic strategy to cure and prevent inflammatory diseases related to NF-κB activation. In a previous study, we demonstrated that IKK-interacting protein (IKIP) inhibits the phosphorylation of IKKα/ß and the activation of NF-κB through disruption of the formation of IKK complex. In this study, we identified a 15-aa peptide derived from mouse IKIP (46-60 aa of IKIP), which specifically suppressed IKK activation and NF-κB targeted gene expression via disrupting the association of IKKß and NEMO. Importantly, administration of the peptide reduced LPS-induced acute inflammation and attenuated Zymosan-induced acute arthritis in mice. These findings suggest that this IKIP peptide may be a promising therapeutic reagent in the prevention and treatment of inflammatory diseases.

SERS-fluorescence dual-mode nanoprobe for the detection and imaging of Bax mRNA during apoptosis.

A dual-mode nanoprobe was constructed to detect Bax messenger RNA (mRNA), consisting of gold nanotriangles (AuNTs), a Cy5-modified recognition sequence, and a thiol-modified DNA sequence. Bax mRNA is one of the key pro-apoptotic factors in the apoptosis pathway. Raman enhancement and fluorescence quenching of the signal group Cy5 were performed using AuNTs as substrates. The thiol-modified nucleic acid chain is partially complementary to the Cy5-modified nucleic acid chain to form a double strand and is linked to the AuNTs by the Au-S bond. When Bax mRNA is present, the Cy5-modified strand specifically binds to it to form a more stable duplex, making Cy5 far away from AuNTs, and SERS signal is weakened while fluorescence signal is enhanced. The nanoprobe can be used for the quantitative detection of Bax mRNA in vitro. Combined with the high sensitivity of SERS and the visualization of fluorescence, this method has good specificity and can be used for in situ imaging and dynamic monitoring of Bax mRNA during deoxynivalenol (DON) toxin-induced apoptosis of HepG2 cells. DON plays a pathogenic role mainly by inducing cell apoptosis. The results confirmed that the proposed dual-mode nanoprobe has good versatility in various human cell lines.

SAR exploration of the non-imidazole histamine H3 receptor ligand ZEL-H16 reveals potent inverse agonism.

Histamine H3 receptor (H3 R) agonists without an imidazole moiety remain very scarce. Of these, ZEL-H16 (1) has been reported previously as a high-affinity non-imidazole H3 R (partial) agonist. Our structure-activity relationship analysis using derivatives of 1 identified both basic moieties as key interaction motifs and the distance of these from the central core as a determinant for H3 R affinity. However, in spite of the reported H3 R (partial) agonism, in our hands, 1 acts as an inverse agonist for Gαi signaling in a CRE-luciferase reporter gene assay and using an H3 R conformational sensor. Inverse agonism was also observed for all of the synthesized derivatives of 1. Docking studies and molecular dynamics simulations suggest ionic interactions/hydrogen bonds to H3 R residues D1143.32 and E2065.46 as essential interaction points.

Interactions on Proteins Arising from the Self-Assembly of a Polyelectrolyte Brush.

Surfaces grafted with polyelectrolyte chains for excellent performance in protein antifouling are highly desired in many applications, such as biomedical implants and devices. In general, the adsorbing/resisting behaviors of proteins can be mainly attributed to the electrostatic interactions that are associated with the charge properties of proteins and polyelectrolytes. By coarse-grained molecular dynamics simulations, we examined the self-assembled structures of polyanion and polyzwitterion brushes as well as the interactions on negatively and positively charged proteins. We found that in addition to charges, the structural polarization induced by self-assembly with a certain charge distribution shows significant influences on protein behavior. The large-scale dipole-dipole interactions between brushes and proteins can dominate the behavior of proteins on the brushes under certain circumstances. To ensure simulation accuracy, we compared two models and found a polar Martini model that explicitly treats electrostatic interactions as long-ranged ones, giving a more reasonable structural description compared with the normal Martini model that truncates electrostatic interactions.

A finite element model of the shoulder: application to the changes of biomechanical environment induced by postoperative malrotation of humeral shaft fracture.

OBJECTIVES: The humerus fracture is one of the most commonly occurring fractures. In this research, we attempted to evaluate and compare the extent of malrotation and biomechanical environment after surgical treatment of humeral shaft fractures. METHODS: A finite element (FE) model of the shoulder was built based on Computed Tomography (CT) data of a patient with a humeral shaft fracture. The muscle group around the shoulder joint was simulated by spring elements. The changes of shoulder stresses under rotation were analyzed. The biomechanics of the normal shoulder and postoperative malrotation of the humeral shaft was analyzed and compared. RESULTS: During rotations, the maximum stress was centered in the posterosuperior part of the glenoid for the normal shoulder. The von Mises shear stresses were 4.40 MPa and 4.89 MPa at 40° of internal and external rotations, respectively. For internal rotation deformity, the shear contact forces were 7-9 times higher for the shoulder internally rotated 40° than for the normal one. For external rotation deformity, the shear contact forces were about 3-5 times higher for the shoulder with 40° external rotation than the normal one. CONCLUSION: Postoperative malrotation of humeral shaft fracture induced the changes of the biomechanical environment of the shoulders. The peak degree of malrotation was correlated with increased stresses of shoulders, which could be paid attention to in humeral shaft fracture treatment. We hoped to provide information about the biomechanical environment of humeral malrotation.

A NanoBRET-Based H3R Conformational Biosensor to Study Real-Time H3 Receptor Pharmacology in Cell Membranes and Living Cells.

Conformational biosensors to monitor the activation state of G protein-coupled receptors are a useful addition to the molecular pharmacology assay toolbox to characterize ligand efficacy at the level of receptor proteins instead of downstream signaling. We recently reported the initial characterization of a NanoBRET-based conformational histamine H3 receptor (H3R) biosensor that allowed the detection of both (partial) agonism and inverse agonism on living cells in a microplate reader assay format upon stimulation with H3R ligands. In the current study, we have further characterized this H3R biosensor on intact cells by monitoring the effect of consecutive ligand injections in time and evaluating its compatibility with photopharmacological ligands that contain a light-sensitive azobenzene moiety for photo-switching. In addition, we have validated the H3R biosensor in membrane preparations and found that observed potency values better correlated with binding affinity values that were measured in radioligand competition binding assays on membranes. Hence, the H3R conformational biosensor in membranes might be a ready-to-use, high-throughput alternative for radioligand binding assays that in addition can also detect ligand efficacies with comparable values as the intact cell assay.

BRET-Based Biosensors to Measure Agonist Efficacies in Histamine H1 Receptor-Mediated G Protein Activation, Signaling and Interactions with GRKs and ß-Arrestins.

The histamine H1 receptor (H1R) is a G protein-coupled receptor (GPCR) and plays a key role in allergic reactions upon activation by histamine which is locally released from mast cells and basophils. Consequently, H1R is a well-established therapeutic target for antihistamines that relieve allergy symptoms. H1R signals via heterotrimeric Gq proteins and is phosphorylated by GPCR kinase (GRK) subtypes 2, 5, and 6, consequently facilitating the subsequent recruitment of ß-arrestin1 and/or 2. Stimulation of a GPCR with structurally different agonists can result in preferential engagement of one or more of these intracellular signaling molecules. To evaluate this so-called biased agonism for H1R, bioluminescence resonance energy transfer (BRET)-based biosensors were applied to measure H1R signaling through heterotrimeric Gq proteins, second messengers (inositol 1,4,5-triphosphate and Ca2+), and receptor-protein interactions (GRKs and ß-arrestins) in response to histamine, 2-phenylhistamines, and histaprodifens in a similar cellular background. Although differences in efficacy were observed for these agonists between some functional readouts as compared to reference agonist histamine, subsequent data analysis using an operational model of agonism revealed only signaling bias of the agonist Br-phHA-HA in recruiting ß-arrestin2 to H1R over Gq biosensor activation.

Pulmonary arteries of Williams syndrome patients exhibit altered serotonin metabolism genes and degenerated medial layer architecture.

BACKGROUND: Williams-Beuren syndrome (WS) is characterized by cardiovascular abnormalities associated with a multigene deletion on 7q11.23, in particular elastin (ELN). Peripheral pulmonary artery stenosis (PPAS) frequently affects pediatric patients with WS. Molecular investigation of WS pulmonary arterial (PA) tissue is limited by tissue scarcity. METHODS: We compared transcriptomes, tissue architecture, and localized changes in protein expression in PA tissue from patients with WS (n = 8) and donors (n = 5). RESULTS: Over 100 genes were differentially expressed at the ≥4-fold level, including genes related to the serotonin signaling pathway: >60-fold downregulation of serotonin transporter SLC6A4 and >3-fold upregulation of serotonin receptor HTR2A. Histologic examination revealed abnormal elastin distribution and smooth muscle cell morphology in WS PA, with markedly shorter, disorganized elastin fibers, and expanded proteoglycan-rich extracellular matrix between muscle layers. CONCLUSIONS: There were significant abnormalities in the PA expression of genes regulating serotonin signaling, metabolism, and receptors in WS. Those changes were associated with distinct changes in the arterial structure and may play a role in the stenosis-promoting effects of elevated shear stress at PA bifurcations in WS. IMPACT: Serotonin pathway signaling is significantly altered in the pulmonary arteries of patients with Williams syndrome and severe peripheral arterial stenosis. The present study compares the histological and biochemical characteristics of pulmonary arteries from patients with Williams syndrome to those of controls, something that has not, to our knowledge, been done previously. It demonstrates marked abnormalities in the pulmonary arteries of patients with Williams syndrome, especially significant pathologic alterations in the signaling of the serotonin pathway. The findings of this study provide direction for the development of potential therapies to treat pulmonary artery stenosis in patients with Williams syndrome.

Fabrication of gold/silver nanodimer SERS probes for the simultaneous detection of Salmonella typhimurium and Staphylococcus aureus.

Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) are the two most important foodborne pathogens which can easily cause disease infections. Here, the aptamer-facilitated gold/silver nanodimer SERS probes were built for the simultaneous detection of the two bacteria with the help of magnetic separation enrichment. First, two nanodimer SERS signal probes and two magnetic capture probes each connected with the specific aptamer were fabricated. The distance between gold and silver nanoparticles in the dimer can amplify the Raman signal (Cy3 and Rox) at the junction but modified in the aptamer sequence. Then, after the addition of S. typhimurium and S. aureus, the sandwich-like composite structures "SERS signal probes-target-magnetic capture probes" formed because of the high affinity between aptamer sequences and their target bacteria. Under the optimal experimental conditions, the linear correlations between Raman intensity and the logarithm of the concentration of bacteria were y = 876.95x-67.84 (R2 = 0.9865) for S. typhimurium and y = 1280.43x-1752.6 (R2 = 0.9883) for S. aureus. The SERS detection showed the nanodimer probe had high selectivity. Besides, the recovery experiment in milk sample indicated good accuracy compared with the traditional plate counting method.

Analysis of Missense Variants in the Human Histamine Receptor Family Reveals Increased Constitutive Activity of E4106.30×30K Variant in the Histamine H1 Receptor.

The Exome Aggregation Consortium has collected the protein-encoding DNA sequences of almost 61,000 unrelated humans. Analysis of this dataset for G protein-coupled receptor (GPCR) proteins (available at GPCRdb) revealed a total of 463 naturally occurring genetic missense variations in the histamine receptor family. In this research, we have analyzed the distribution of these missense variations in the four histamine receptor subtypes concerning structural segments and sites important for GPCR function. Four missense variants R1273.52×52H, R13934.57×57H, R4096.29×29H, and E4106.30×30K, were selected for the histamine H1 receptor (H1R) that were hypothesized to affect receptor activity by interfering with the interaction pattern of the highly conserved D(E)RY motif, the so-called ionic lock. The E4106.30×30K missense variant displays higher constitutive activity in G protein signaling as compared to wild-type H1R, whereas the opposite was observed for R1273.52×52H, R13934.57×57H, and R4096.29×29H. The E4106.30×30K missense variant displays a higher affinity for the endogenous agonist histamine than wild-type H1R, whereas antagonist affinity was not affected. These data support the hypothesis that the E4106.30×30K mutation shifts the equilibrium towards active conformations. The study of these selected missense variants gives additional insight into the structural basis of H1R activation and, moreover, highlights that missense variants can result in pharmacologically different behavior as compared to wild-type receptors and should consequently be considered in the drug discovery process.

Agmatine Protects Against the Progression of Sepsis Through the Imidazoline I2 Receptor-Ribosomal S6 Kinase 2-Nuclear Factor-κB Signaling Pathway.

OBJECTIVES: The knowledge that agmatine is found in the human body has existed for several years; however, its role in sepsis has not yet been studied. In the present study, we investigate the role of agmatine in the progression and treatment of sepsis. DESIGN: Clinical/laboratory investigations. SETTING: Medical centers/University-based research laboratory. SUBJECTS: Elective ICU patients with severe sepsis and healthy volunteers; C57BL/6 mice weighing 18-22 g. INTERVENTIONS: Serum agmatine level and its associations with inflammatory markers were assessed in patients with sepsis. Agmatine was administered intraperitoneally to mice before a lipopolysaccharide challenge. Human peripheral blood mononuclear cells and murine macrophages were pretreated with agmatine followed by lipopolysaccharide stimulation. MEASUREMENTS AND MAIN RESULTS: Serum agmatine levels were significantly decreased in patients with sepsis and lipopolysaccharide-induced mice, and correlated with Acute Physiology and Chronic Health Evaluation II score, procalcitonin, tumor necrosis factor-α, and interleukin-6 levels. In a therapeutic experiment, exogenous agmatine attenuated the cytokine production of peripheral blood mononuclear cells from patients with sepsis and healthy controls. Agmatine also exerted a significant beneficial effect in the inflammatory response and organ damage and reduced the death rate in lipopolysaccharide-induced mice. Imidazoline I2 receptor agonist 2-benzofuran-2-yl blocked the pharmacological action of agmatine; whereas, other imidazoline receptor ligands did not. Furthermore, agmatine significantly impaired the inflammatory response by inactivating nuclear factor-κB, but not protein 38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and inducible nitric oxide synthase signaling in macrophages. Activation of imidazoline I2 receptor or knockdown of ribosomal S6 kinase 2 counteracted the effects of agmatine on phosphorylation and degradation of inhibitor of nuclear factor-κBα. CONCLUSIONS: Endogenous agmatine metabolism correlated with the progression of sepsis. Supplemental exogenous agmatine could ameliorate the lipopolysaccharide-induced systemic inflammatory responses and multiple organ injuries through the imidazoline I2 receptor-ribosomal S6 kinase 2-nuclear factor-κB pathway. Agmatine could be used as both a clinical biomarker and a promising pharmaconutrient in patients with severe sepsis.

Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis.

The hydroxylase cytochrome P450 1A1 (CYP1A1) is regulated by the inflammation-limiting aryl hydrocarbon receptor (AhR), but CYP1A1 immune functions remain unclear. We observed CYP1A1 overexpression in peritoneal macrophages (PMs) isolated from mice following LPS or heat-killed Escherichia. coli (E. coli) challenge. CYP1A1 overexpression augmented TNF-α and IL-6 production in RAW264.7 cells (RAW) by enhancing JNK/AP-1 signalling. CYP1A1 overexpression also promoted 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) production in activated RAW, while a 12(S)-HETE antibody attenuated and 12(S)-HETE alone induced inflammatory responses. Macrophages harbouring hydroxylase-deficient CYP1A1 demonstrated reduced 12(S)-HETE generation and LPS-induced TNF-α/IL-6 secretion. CYP1A1 overexpression also impaired phagocytosis of bacteria via decreasing the expression of scavenger receptor A (SR-A) in PMs. Mice injected with CYP1A1-overexpressing PMs were more susceptible to CLP- or E. coli-induced mortality and bacteria invading, while Rhapontigenin, a selective CYP1A1 inhibitor, improved survival and bacteria clearance of mice in sepsis. CYP1A1 and 12(S)-HETE were also elevated in monocytes and plasma of septic patients and positively correlated with SOFA scores. Macrophage CYP1A1 disruption could be a promising strategy for treating sepsis. Video abstract.

Correction to: Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis.

An amendment to this paper has been published and can be accessed via the original article.

Surface-Enhanced Raman Scattering-Fluorescence Dual-Mode Nanosensors for Quantitative Detection of Cytochrome c in Living Cells.

During apoptosis process, the release of cytochrome c (Cyt c) is considered to be a key factor in the intrinsic pathway and is often defined as no regression point. Quantitative detection of intracellular Cyt c remains a challenge. Herein, we have developed surface-enhanced Raman scattering (SERS)-fluorescence dual-mode nanosensors for the quantitative assay of Cyt c in living cells. Dual signal detection was achieved by constructing gold nanotriangles (AuNTs) nanosensors capable of specifically recognizing Cyt c. The nanosensors were prepared by modifying the aptamer of Cyt c on AuNTs and connecting the complementary strands modified with Cy5. The AuNTs provided both enhanced SERS signals and fluorescence quenching effects. Once cells were induced by external stimulus (such as toxins) to release Cyt c, Cyt c would specifically bind to its aptamer, and the complementary strands modified with Cy5 would detach which would result in weakened SERS signal and recovery of fluorescence signal. The experimental results showed that the nanosensors not only had excellent selectivity and sensitivity but also realized real-time monitoring of Cyt c translocation event from mitochondria to cytoplasm. The SERS and fluorescence intensity showed good linear relationship with Cyt c concentration ranging from 0.044 to 9.95 µM and achieved a minimum limit of detection (LOD) of 0.02 µM in living cells. The accuracy of intracellular Cyt c quantitative results was more than 90% compared with the ELISA results.

Chiroptical Activity of Type II Core/Shell Cu2S/CdSe Nanocrystals.

Ligand-induced chirality in core/shell nanocrystals (NCs) has attracted extensive attention because of many valuable potential applications. However, the cause of chirality especially in semiconductor nanomaterials is still under debate despite the creation of chiral type I core/shell structures. Herein, we synthesized a kind of new Cu2S/CdSe core/shell nanostructure to study the underlying reason. Four samples of Cu2S/CdSe were synthesized utilizing successive ion layer adsorption and reaction to vary the thickness of the CdSe shell upon a Cu2S core with 5 nm diameter. The chirality of type II Cu2S/CdSe NCs is imparted by l-/d-cysteine and penicillamine, which could be modulated with an increasing thickness of the CdSe shell. To the best of our knowledge, this is the first report of chiral type II core/shell semiconductor NCs. The hybridization theory can explain the variation trend of g factors with every increase in shell thickness from four monolayers (4 ML) to 7 ML. The results indicate that the chiroptical activity of semiconductor NCs is mainly due to hybridization between the holes in the valence band of NCs and the highest occupied molecular orbitals of the chiral ligands. In addition, Cu2S/CdSe NCs show a better chiroptical intensity in comparison with the type I structure according to previous work. The first design of chiral type II Cu2S/CdSe core/shell NCs and a detailed investigation of chiral variation trend help to give a better understanding of the chiral interaction between ligands and core/shell semiconductor nanostructures.

EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation.

Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox). These mice developed early cartilage degeneration at 6 mo of age. By 2 mo of age, although their gross cartilage morphology appears normal, CKO mice had a drastically reduced number of superficial chondrocytes and decreased lubricant secretion at the surface. Using superficial chondrocyte and cartilage explant cultures, we demonstrated that EGFR signaling is critical for maintaining the number and properties of superficial chondrocytes, promoting chondrogenic proteoglycan 4 (Prg4) expression, and stimulating the lubrication function of the cartilage surface. In addition, EGFR deficiency greatly disorganized collagen fibrils in articular cartilage and strikingly reduced cartilage surface modulus. After surgical induction of OA at 3 mo of age, CKO mice quickly developed the most severe OA phenotype, including a complete loss of cartilage, extremely high surface modulus, subchondral bone plate thickening, and elevated joint pain. Taken together, our studies establish EGFR signaling as an important regulator of the superficial layer during articular cartilage development and OA initiation.

Measurement and Analysis of Near-Ground Propagation Models under Different Terrains for Wireless Sensor Networks.

The propagation model is an essential component in the design and deployment of a wireless sensor network (WSN). Although much attention has been given to near-ground propagation models, few studies place the transceiver directly on the ground with the height of antennas at the level of a few centimeters, which is a more realistic deployment scenario for WSNs. We measured the Received Signal Strength Indication (RSSI) of these truly near-ground WSNs at 470 MHz under four different terrains, namely flat concrete road, flat grass and two derived scenarios, and obtained the corresponding path loss models. By comprehensive analysis of the influence of different antenna heights and terrain factors, we showed the limit of existing theoretical models and proposed a propagation model selection strategy to more accurately reflect the true characteristics of the near-ground wireless channels for WSNs. In addition, we implemented these models on Cooja simulator and showed that simplistic theoretical models would induce great inaccuracy of network connectivity estimation.

The program of antiviral agents inhibits virus infection.

Virus infections are the root cause of epidemics in the world. Vaccines and antiviral agents have been the two important methods to control viral diseases; in recent times, RNA-mediated therapeutics and prevention have received much attention. In this review, we provide an overview of the current information regarding the use of vaccines, antiviral agents, and RNA-mediated methods in controlling or preventing viral infections. We stress specifically on the potential of existing RNA-mediated methods in clinical applications.

Purification, characterization, and gene cloning of a new cold-adapted ß-galactosidase from Erwinia sp. E602 isolated in northeast China.

ß-Galactosidases are widely used in industry for elimination of lactose from milk products. A new ß-galactosidase was obtained from bacterial strain Erwinia sp. E602, newly isolated in northeast China. The enzyme was purified with the methods of ammonium sulfate fractionation, ion exchange, and gel filtration chromatography for further study of the enzymatic characteristics. The purified enzyme had a molecular weight of near 110 kDa. The optimum reaction temperature and pH of this enzyme was determined to be 40°C and 7.0, respectively, indicating that this enzyme was a mesophilic neutral ß-galactosidase. Furthermore, the enzyme retained near 10% of the activity at 0°C, which also suggested its cold-adapted property. Kinetics of the ß-galactosidase was studied, and the Km (Michaelis constant) and Vmax (maximum enzymatic reaction rate) of this enzyme were 0.21 mmol/L and 263.16 µmol/mg per minute, respectively. The effects of metal ions on the enzymatic activity and the lactose hydrolysis efficiency in milk, as well as its trans-glycosylation activity, were studied in this work. The ß-galactosidase coding gene was cloned to be a 3-kb length fragment, which shared at most 81% of identity with the published sequences in NCBI Blast database (https://blast.ncbi.nlm.nih.gov). Results in this work suggested it is a new ß-galactosidase and it has potential to be used in dairy and food processing.