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Long non-coding RNA LINC00908 is a functional biomarker in regulating tumour progression. Its dysregulation in gastric cancer implies its potential functional role. Few studies have noted the functional role of LINC00908 in gastric cancer. The potential of LINC00908 to serve as a biomarker in gastric cancer was evaluated. A total of 113 paired gastric cancer tissues and normal tissues were collected from patients with gastric cancer. LINC00908 levels were evaluated by polymerase chain reaction, and its significance in disease progression and patients' prognosis was assessed. In vitro, the function of LINC00908 in tumour-related cellular processes was evaluated with CCK8 and Transwell assay. Significant downregulation of LINC00908 was observed in gastric cancer and was negatively associated with disease development and overall survival of patients. LINC00908 showed significant inhibitory effects on the proliferation, migration, and invasion of gastric cancer cells. Additionally, miR-627-3p was sponged by LINC00908 and therefore mediated the function of LINC00908 in gastric cancer cells. LINC00908 functioned as a prognostic biomarker and tumour suppressor of gastric cancer, providing a therapeutic target for gastric cancer.
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Biomarcadores de Tumor , Proliferación Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , ARN Largo no Codificante/genética , Femenino , Masculino , Pronóstico , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Proliferación Celular/genética , Movimiento Celular/genética , Línea Celular Tumoral , Anciano , MicroARNs/genética , MicroARNs/metabolismo , Invasividad Neoplásica/genéticaRESUMEN
We report a facile interfacial assembly strategy for the preparation of flexible polyphenol-based films for antibacterial and antiultraviolet applications. The free-standing films can be instantaneously formed via spraying tannic acid (TA) at the surface of carboxymethyl chitosan (CMCS) solutions. Compared with the traditional casting-evaporation procedure on solid substrates, the liquid interfacial assembly method for the construction of free-standing films is rapid and facile, which prevents the interface separation procedure from the substrates. The thickness and mechanical properties of the films are well controlled by changing the incubation time. The low-field nuclear magnetic resonance was used to analyze the water distributions inside the films and to distinguish the cross-linked structure of CMCS-TA films with different thicknesses, revealing the dynamics of the film formation process. Importantly, the films exhibit outstanding antibacterial and antiultraviolet properties, which are promising in the applications of wound dressings. This study provides a new avenue for the assembly of flexible free-standing films with multifunctionality via a facile and low-cost fabrication process.
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The energy consumption of up to 90 % of the total power input in the anodic oxygen evolution reaction (OER) slows down the implementation of electrochemical CO2 reduction reaction (CO2RR) to generate valuable chemicals. Herein, we present an alternative strategy that utilizes methanol oxidation reaction (MOR) to replace OER. The iron single atom anchored on nitrogen-doped carbon support (Fe-N-C) use as the cathode catalyst (CO2RR), low-loading platinum supported on the composites of tungsten phosphide and multiwalled carbon nanotube (Pt-WP/MWCNT) use as the anode catalyst (MOR). Our results show that the Fe-N-C exhibits a Faradaic selectivity as high as 94.93 % towards CO2RR to CO, and Pt-WP/MWCNT exhibits a peak mass activity of 544.24 mA mg-1Pt, which is 5.58 times greater than that of PtC (97.50 mA mg-1Pt). The well-established MOR||CO2RR reduces the electricity consumption up to 52.4 % compared to conventional OER||CO2RR. Moreover, a CO2 emission analysis shows that this strategy not only saves energy but also achieves carbon neutrality without changing the existing power grid structure. Our findings have crucial implications for advancing CO2 utilization and lay the foundation for developing more efficient and sustainable technologies to address the rising atmospheric CO2 levels.
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Amino oligosaccharides (AOs) possess various biological activities and are valuable in the pharmaceutical, food industries, and agriculture. However, the industrial manufacturing of AOs has not been realized yet, despite reports on physical, chemical, and biological approaches. In this study, the de novo production of chitin oligosaccharides (CHOS), a type of structurally defined AOs, was achieved in Escherichia coli through combinatorial pathway engineering. The most suitable glycosyltransferase for CHOS production was found to be NodCL from Mesorhizobium Loti. Then, by knocking out the nagB gene to block the flow of N-acetyl-d-glucosamine (NAG) to the glycolytic pathway in E. coli and adjusting the copy number of NodCL-coding gene, the CHOS yield was increased by 6.56 times. Subsequently, by introducing of UDP-N-acetylglucosamine (UDP-GlcNAc) salvage pathway for and optimizing fermentation conditions, the yield of CHOS reached 207.1 and 468.6 mg/L in shake-flask cultivation and a 5-L fed-batch bioreactor, respectively. Meanwhile, the concentration of UDP-GlcNAc was 91.0 mg/L, the highest level reported in E. coli so far. This study demonstrated, for the first time, the production of CHOS with distinct structures in plasmid-free E. coli, laying the groundwork for the biosynthesis of CHOS and providing a starting point for further engineering and commercial production.
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Carbon source is crucial for the cell growth and metabolism in microorganisms, and its utilization significantly affects the synthesis efficiency of target products in microbial cell factories. Compared with a single carbon source, co-utilizing carbon sources provide an alternative approach to optimize the utilization of different carbon sources for efficient biosynthesis of many chemicals with higher titer/yield/productivity. However, the efficiency of bioproduction is significantly limited by the sequential utilization of a preferred carbon source and secondary carbon sources, attributed to carbon catabolite repression (CCR). This review aimed to introduce the mechanisms of CCR and further focus on the summary of the strategies for co-utilization of carbon sources, including alleviation of CCR, engineering of the transport and metabolism of secondary carbon sources, compulsive co-utilization in single culture, co-utilization of carbon sources via co-culture, and evolutionary approaches. The findings of representative studies with a significant improvement in the bioproduction of chemicals via the co-utilization of carbon sources were discussed in this review. It suggested that by combining rational metabolic engineering and irrational evolutionary approaches, co-utilizing carbon sources can significantly contribute to the bioproduction of chemicals.
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Carbono , Ingeniería Metabólica , Carbono/metabolismo , Represión Catabólica , Bacterias/metabolismoRESUMEN
Synergetic management of waste activated sludge, heavy metals (HMs) and CO2 for their valorization and cyclic utilization is rarely reported. Herein, we employed sludge-derived extracellular polymeric substances (EPS) and HMs in wastewater to fabricate a gas diffusion electrode (GDE) for electrochemical CO2 reduction. This approach atomically dispersed Ni at each nanofiber of the GDE. Abundant N element in the EPS proved to play a key role in the formation of Nx-Ni (mixture of N3-Ni and N4-Ni) sites for highly efficient CO2 to CO conversion. The atomical Ni3+ shows high catalytic activity. Direct gaseous CO2 reduction in a membrane electrode assembly generated a current density up to 50 mA·cm-2 with CO:H2 ratio of â¼100 and â¼75% FECO under 2.69 cell voltage. This strategy takes advantage of all waste streams generated on site and consolidates traditionally separated treatment processes to save costs, produces value-added products and generates carbon benefits during wastewater treatment.
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Chitin is the second largest renewable biomass resource in nature, it can be enzymatically degraded into high-value chitin oligosaccharides (CHOSs) by chitinases. In this study, a chitinase (ChiC8-1) was purified and biochemically characterized, its structure was analyzed by molecular modeling. ChiC8-1 had a molecular mass of approximately 96 kDa, exhibited its optimal activity at pH 6.0 and 50 °C. The Km and Vmax values of ChiC8-1 towards colloidal chitin were 10.17 mgmL-1 and 13.32 U/mg, respectively. Notably, ChiC8-1 showed high chitin-binding capacity, which may be related to the two chitin binding domains in the N-terminal. Based on the unique properties of ChiC8-1, a modified affinity chromatography method, which combines protein purification with chitin hydrolysis process, was developed to purify ChiC8-1 while hydrolyzing chitin. In this way, 9.36 ± 0.18 g CHOSs powder was directly obtained by hydrolyzing 10 g colloidal chitin with crude enzyme solution. The CHOSs were composed of 14.77-2.83 % GlcNAc and 85.23-97.17 % (GlcNAc)2 at different enzyme-substrate ratio. This process simplifies the tedious purification and separation steps, and may enable its potential application in the field of green production of chitin oligosaccharides.
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Quitina , Quitinasas , Quitina/química , Quitinasas/química , Oligosacáridos , Especificidad por SustratoRESUMEN
A segmented primary mirror (PM) is an efficient solution to the problems of a monolithic PM manufacture, testing, transportation, and launch. However, the problem of the radius of curvature (ROC) matching among PM segments will arise, which if not solved will seriously degrade the final imaging quality of the system. Accurately detecting ROC mismatch among PM segments from the wavefront map is of crucial importance for efficiently correcting this kind of manufacturing error, while currently there are few related studies. Based on the inherent relation between the PM segment's ROC error and corresponding sub-aperture defocus aberration, this paper proposes that the ROC mismatch can be accurately estimated from the sub-aperture defocus aberration. Secondary mirror (SM) lateral misalignments will influence the accuracy of estimating ROC mismatch. A strategy is also proposed to reduce the influence of SM lateral misalignments. Detailed simulations are performed to demonstrate the effectiveness of the proposed method for detecting ROC mismatch among PM segments. This paper paves a road for detecting ROC mismatch using image-based wavefront sensing methods.
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PURPOSE: Pichia pastoris is well known for its ability to produce short and low-immunogenic humanized glycosyl chains onto recombinant glycoproteins, it was thus speculated to be applicable to synthesize oligosaccharides. In this study, generally recognized as safe (GRAS) microorganism Pichia pastoris GS115 was tested for its potential to be used as a new synthetic chassis to produce the most abundant human milk oligosaccharide 2'-fucosyllactose (2'-FL). METHODS: To enable the de novo synthesis of 2'-FL, lactose transporter lac12, two enzymes of gmd, gmer, and fucosyltransferases futC were integrated into the genome of P. pastoris, under the control of constitutive PGAP promoter. RESULTS: The resulting recombinant yeasts yielded up to 0.276 g/L through culture optimization in a 5 L bioreactor. CONCLUSION: To our knowledge, this is the first report of 2'-FL production in engineered Pichia pastoris. This work is a good starting point to produce 2'-FL using Pichia pastoris as a viable chassis.
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Saccharomycetales , Trisacáridos , Humanos , Trisacáridos/genética , Oligosacáridos , Pichia/genéticaRESUMEN
Improving the urban thermal environment and improving the quality of human settlements are important prerequisites for creating ecologically livable cities. The current research on the relationship between urban expansion and the thermal environment is mostly based on remote sensing data, and the application of multi-source data is weak. Here, we selected the Xi'an metropolitan core area, measured the urban expansion and temporal and spatial evolution of the thermal environment based on Landsat remote sensing images in 2010 and 2020, and used multi-source data, such as interest points and the Baidu thermal index, to study the response mechanism of the urban thermal environment through geoscience statistical analysis methods. The results showed that:â the construction land in the study area had expanded by 200.84 km2, and the area and intensity showed that "the center and the periphery are weaker, and the difference between the two" characteristics, and the expansion mode was mainly edge type and infill type. â¡ Between 2010 and 2020, the overall thermal environment in the study area deteriorated, and the area of the heat island area increased by 282.65 km2. The spread of the heat island area was in the same direction as the urban expansion, and the distribution pattern evolved from "southeast-northwest" to "northeast-southwest;" however, the average temperature in the central area of the city decreased 1.09â. ⢠Urban expansion was strongly positively correlated with the deterioration of the urban thermal environment. The expansion of urban space had a contribution rate of 60.40% to the deterioration of the thermal environment, and various socio-economic factors had a weaker effect, with an overall contribution rate of 39.60%. The vegetation water body had an obvious cooling effect; under the influence of multiple factors, the surface temperature increased by 0.241 units. In the process of urban expansion, changes in surface parameters and two-dimensional urban morphology were still the main factors for thermal environment changes, whereas three-dimensional morphology had a small effect on the warming of social and economic activities, and the contribution of water bodies and vegetation to cooling was prominent.
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Monitoreo del Ambiente , Calor , Ciudades , Monitoreo del Ambiente/métodos , Humanos , Temperatura , AguaRESUMEN
This paper discusses compensation strategies for the aberration fields caused by the error in the radius of curvature (ROC) of the primary mirror (PM) in pupil-offset off-axis three-mirror anastigmatic (TMA) astronomical telescopes. Based on the nodal aberration theory framework, the specific astigmatic and coma aberrations of the off-axis three-mirror system in the presence of the ROC error of the PM are derived. It is demonstrated that some field-dependent aberration components can be induced by ROC error in the off-axis TMA telescopes, apart from the dominating field-constant aberration terms. To reduce the influence of the ROC error on the aberration fields, we propose two aberration compensation strategies: adjusting the position of the PM and introducing axial misalignment of the secondary mirror (SM). Through theoretical analysis and simulations, we conclude that the compensation strategy of changing the axial position of the PM can make the aberration distribution close to the nominal state; the compensation strategy of axially adjusting the SM can make the aberration distribution meet the observation requirements, which is more suitable for space applications. We also discuss compensating the effect of the ROC error using lateral misalignments.
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Space-based optical astronomical telescopes are susceptible to mirror misalignments due to space disturbance in mechanics and temperature. Therefore, it is of great importance to actively align the telescope in orbit to continuously maintain imaging quality. Traditional active alignment methods usually need additional delicate wavefront sensors and complicated operations (such as instrument calibration and pointing adjustment). This paper proposes a novel active alignment approach by matching the geometrical features of several stellar images at arbitrary multiple field positions. Based on nodal aberration theory and Fourier optics, the relationship between stellar image intensity distribution and misalignments of the system can be modeled for an arbitrary field position. On this basis, an objective function is established by matching the geometrical features of the collected multi-field stellar images and modeled multi-field stellar images, and misalignments can then be solved through nonlinear optimization. Detailed simulations and a real experiment are performed to demonstrate the effectiveness and practicality of the proposed approach. This approach eliminates the need for delicate wavefront sensors and pointing adjustment, which greatly facilitates the maintainance of imaging quality.
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Segmented primary mirror provides many crucial important advantages for the construction of extra-large space telescopes. The imaging quality of this class of telescope is susceptible to phasing error between primary mirror segments. Deep learning has been widely applied in the field of optical imaging and wavefront sensing, including phasing segmented mirrors. Compared to other image-based phasing techniques, such as phase retrieval and phase diversity, deep learning has the advantage of high efficiency and free of stagnation problem. However, at present deep learning methods are mainly applied to coarse phasing and used to estimate piston error between segments. In this paper, deep Bi-GRU neural work is introduced to fine phasing of segmented mirrors, which not only has a much simpler structure than CNN or LSTM network, but also can effectively solve the gradient vanishing problem in training due to long term dependencies. By incorporating phasing errors (piston and tip-tilt errors), some low-order aberrations as well as other practical considerations, Bi-GRU neural work can effectively be used for fine phasing of segmented mirrors. Simulations and real experiments are used to demonstrate the accuracy and effectiveness of the proposed methods.
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Aminooligosaccharides possess various biological activities and can exploit wide applications in food, pharmaceutical and cosmetic industries. Commercial aminooligosaccharides are often prepared by the hydrolysis of chitin and chitosan. In this study, a novel GH family 20 ß-N-acetylhexosaminidases gene named AoNagase was cloned from Aspergillus oryzae and expressed in Pichia pastoris. The purified AoNagase had maximal activity at pH 5.5 and 65°C. It exhibited good pH stability in the range of pH 6.0-7.5 and at temperatures below 50°C. AoNagase was capable of hydrolyzing not only colloidal chitosan (508.26 U/mg) but also chitin (29.78 U/mg). The kinetic parameters (K m and V max ) of AoNagase were 1.51 mM, 1106.02 U/mg for chitosan and 0.41 mM, 40.31 U/mg for colloidal chitin. To our knowledge, AoNagase is the first GH family 20 ß-N-acetylhexosaminidase capable of hydrolyzing both chitosan and chitin. AoNagase is an endo-type ß-N-acetylhexosaminidases and can potentially be used for the manufacturing of aminooligosaccharides.
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ETHNOPHARMACOLOGICAL RELEVANCE: The Scutellariae Radix (SR) and Coptidis Rhizoma (CR) herb couple is widely used in traditional Chinese medicine prescriptions for the treatment of diabetes mellitus due to its interaction and synergistic effect compared to either herb alone, but the underlying mechanism of interaction between these herbs is unclear. This study aimed to investigate the effects of CR on the metabolism and absorption of SR. MATERIALS AND METHODS: After rats were treated with normal saline (NS group) or the CR extract (CR-treated group) for seven consecutive days, the intestinal flora was extracted from rat faeces for a co-incubation with the SR extract to investigate the metabolism of SR flavonoids, and a non-everted gut sac was prepared in vitro to evaluate the intestinal absorption of the SR extract. The components of the SR extract, the metabolites of the SR extract that was co-incubated with intestinal flora, and the dialysate acquired from non-everted gut sacs were identified and determined by an HPLC-MS/MS method. The absorption rate constant (Ka) and the apparent permeability (Papp) of each compound were calculated, and the effects of CR on the metabolism and absorption of flavonoids in SR were evaluated, by comparison the Ka and Papp between two groups using Student's t-test. RESULTS: Twenty-nine flavonoids were detected and identified in the SR extract, including 16 glycosides and 13 aglycones. In the co-incubation with the intestinal flora, differences in metabolite classes were not observed between the NS group and CR-treated group; however, the metabolic rates of 17 flavonoids in the CR-treated group were significantly higher than the NS group. The Papp of 11 compounds (4 glycosides and 7 aglycones) across the gut sac were greater than 2 × 10-5 cm/s in both groups, while the Papp values of 7 compounds including wogonoside (WG) and other aglycones were significantly decreased in the CR-treated group. CONCLUSION: Based on these results, CR decreased the metabolism and absorption of SR flavonoids, and exerted much greater inhibitory effects on aglycones than glycosides, which may be one of the potential mechanisms underlying the therapeutic effects of the combination of SR and CR on diabetes mellitus.
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Medicamentos Herbarios Chinos/farmacología , Absorción Intestinal/efectos de los fármacos , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacocinética , Animales , Cromatografía Líquida de Alta Presión/métodos , Coptis chinensis , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Heces/química , Flavonoides/antagonistas & inhibidores , Flavonoides/metabolismo , Flavonoides/farmacocinética , Contenido Digestivo/química , Microbioma Gastrointestinal/efectos de los fármacos , Glicósidos/antagonistas & inhibidores , Glicósidos/metabolismo , Glicósidos/farmacocinética , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Ratas Sprague-Dawley , Scutellaria baicalensis , Espectrometría de Masas en Tándem/métodosRESUMEN
Fat separation is a limiting factor for the shelf life of UHT milk. It may be promoted by the proteolysis of fat surface-adsorbed proteins (FSAP) by proteases that remain active after UHT treatment. The aim of this research was to explore the relationship between the proteolysis of FSAP and fat destabilization. In this study, we developed a full-fat UHT milk-based model system and added either the major bacterial protease AprX from Pseudomonas fluorescens or the major native milk protease plasmin at high levels to induce fast destabilization of the milk fat globules. We monitored changes in physical properties and FSAP composition, and structural changes in fat globules, over 24 h. Our results showed that AprX-induced sedimentation as a result of the flocculation of fat globules, and plasmin induced cream to float as a result of the coalescence of fat globules. This study confirmed that AprX and plasmin can both lead to fat destabilization in full-fat UHT milk, and it provides insights in the underlying mechanisms.
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Proteínas Bacterianas/metabolismo , Fibrinolisina/análisis , Glucolípidos/química , Glicoproteínas/química , Leche/enzimología , Péptido Hidrolasas/metabolismo , Pseudomonas fluorescens/enzimología , Serina Endopeptidasas/metabolismo , Animales , Proteínas Bacterianas/genética , Gotas Lipídicas , Leche/química , Proteolisis , Pseudomonas fluorescens/fisiología , Serina Endopeptidasas/genéticaRESUMEN
This paper proposes an image-based wavefront sensing approach using deep learning, which is applicable to both point source and any extended scenes at the same time, while the training process is performed without any simulated or real extended scenes. Rather than directly recovering phase information from image plane intensities, we first extract a special feature in the frequency domain that is independent of the original objects but only determined by phase aberrations (a pair of phase diversity images is needed in this process). Then the deep long short-term memory (LSTM) network (a variant of recurrent neural network) is introduced to establish the accurate non-linear mapping between the extracted feature image and phase aberrations. Simulations and an experiment are performed to demonstrate the effectiveness and accuracy of the proposed approach. Some other discussions are further presented for demonstrating the superior non-linear fitting capacity of deep LSTM compared to Resnet 18 (a variant of convolutional neural network) specifically for the problem encountered in this paper. The effect of the incoherency of light on the accuracy of the recovered wavefront phase is also quantitatively discussed. This work will contribute to the application of deep learning to image-based wavefront sensing and high-resolution image reconstruction.
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Protecting active species from aggregation and corrosion may be feasible to obtain stable catalytic activities for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Herein, bamboo-shaped N-doped carbon nanotubes (hollow BS-NCNTs as shells) are self-generated to in situ wrap the Co/CoOx schottky junctions (cores) to obtain the Co/CoOx@BS-NCNTs as bifunctional ORR/OER catalysts by using the Co-chelated melamine precursor. For ORR, Co/CoOx@BS-NCNTs (700⯰C) exhibits more positive peak (0.822â¯V vs. RHE) and half-wave (0.842â¯V vs. RHE) potential than those of commercial Pt/C (10â¯wt%). Superior ORR activity is mainly attributed to the enriched coordination-unsaturated Co2+ (tetrahedral CoTd2+) in the CoOx wrapped in the tubular structure of BS-NCNTs featuring high electrical conductivity and active N species. Moreover, the π-π bonds of CNTs are activated by N substitution, which provides a stunning electron capture and transmission capability for enhancing ORR activity. For OER, Co/CoOx@BS-NCNTs (700⯰C) obtains a smaller potential (1.590â¯V vs. RHE) than that of RuO2/C at 10â¯mAâ¯cm-2. The outstanding OER activity and durability of Co/CoOx@BS-NCNTs (700⯰C) originates from strong interactions between C-skeleton and Co species, and efficient Co3+/Co4+ (Co4+OOH as active sites) transition protected by the externally-grown CNTs. Furthermore, abundant oxygen vacancies on CoOx surface can facilitate the adsorption of OH-/or OER-related intermediates to improve OER activity. Therefore, this study provides a promising strategy to develop NCNTs-wrapped Co species with high catalytic activity and stability for energy conversion.
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The high frequency of multiple HIV-1 recombinant events among the B, C and CRF01_AE were constantly occurring in Yunnan China. Here, we characterized a novel HIV-1 circulating recombinant form (CRF) consisting of CRF01_AE and subtype B (CRF101_01B) from three epidemiologically unlinked individuals. Phylogenetic analysis based on near full length genome (NFLG) sequences revealed that CRF101_01B formed a distinct monophyletic cluster supported by a high bootstrap value of 100%, distantly related to all known HIV-1 CRFs. CRF101_01B had a CRF01_AE backbone with two B segments inserted, respectively, in the gag and pol region. Further, subregion tree analysis showed that CRF01_AE backbone and subtype B segment inserted originated from a Thailand lineage. In addition, our study found that CRF101_01B originated around the year 1996-1998. This findings described a novel HIV-1 CRF, and highlighted the importance of continual monitoring of genetic diversity and complexity of HIV-1 strains in Yunnan, China.
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Genoma Viral , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/genética , Virus Reordenados/genética , Recombinación Genética , China , Variación Genética , Genotipo , VIH-1/clasificación , Humanos , Epidemiología Molecular , FilogeniaRESUMEN
The negative effects of proteases produced by psychrotrophic bacteria on dairy products, especially ultra-high-temperature (UHT) milk, are drawing increasing attention worldwide. These proteases are especially problematic, because it is difficult to control psychrotrophic bacteria during cold storage and to inactivate their heat-resistant proteases during dairy processing. The predominant psychrotrophic species with spoilage potential in raw milk, Pseudomonas, can produce a thermostable extracellular protease, AprX. A comprehensive understanding of AprX on the aspects of its biological properties, regulation, proteolytic potential, and its impact on UHT milk can contribute to finding effective approaches to minimize, detect, and inactivate AprX. AprX also deserves attention as a representative of all extracellular metalloproteases produced by psychrotrophic bacteria in milk. The progress of current research on AprX is summarized in this review, including a view on the gap in current understanding of this enzyme. Reducing the production and activity of AprX has considerable potential for alleviating the problems that arise from the instability of UHT milk during shelf-life.