bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case Study of Enhancing Reservoir Performance Through Protecting the Matrix
Authors: Cottingham Byron , Ph.D. Charles Landis, , Jordan Josh , Hall Chad
Published: February 2024

The North American oil and gas industry continues to focus on smaller pore space and there is a continued need to protect and enhance the pore space and fracture networks in our reservoirs. To achieve this, our team has developed and tested a new category of bio-based embedment control fluid additives, that has shown to directly improve reservoir performance after flowback by slowing the reduction of fracture conductivity in hydraulically fractured rock.

Unconventional reservoirs are mineralogically complex. There is an array of minerals that are sensitive to invading waters including 2:1 layer silicates; "clays", oxides, substituted carbonates and freshly fractured silicates like quartz and feldspars. In North America, the clay fraction of the major plays is largely barren of discrete smectite, thus common clay control additives or the use of produced water brines for this purpose is poorly justified, and in fact promotes sloughing of the finest fractions from the fracture face (Landis et. al, 2018). In addition to fracture face softening, fines generation is a pronounced risk factor in reservoir damage mechanism especially with the use of common clay control additives.

To address this problem in our industry, the team functionalized bio-based polymers to maximize polydentate encapsulation of fluid sensitive minerals on the fracture face. This interaction is exploited to reduce reservoir damage in the crucial early stages of the stimulation process.

Molecular design, regain permeability testing and, finally, controlled field applications of the embedment control additive are shown in this paper to provide new realized value in the first year of production and beyond. The new bio-based additive differs from other higher molecular weight polymers used in the stimulation process. Smaller linear molecules functionalized with inhibitive substituents that do not exchange with the cations or anions in the mineral structures. When compared the larger polymers used for friction reduction, the targeted approach for the most interactive sites along the fracture face are addressed preferentially.

A more direct indicator of embedment control is obtained with regain permeability analyses. Assessment of the new bio-based product was conducted on Wolfcamp landing zone facies, and the Eagle Ford formation targets. All tests were run at representative confining pressures and temperatures, and against KCl baselines. A case study was performed in the field and highlighted the product's capability with both a reduction in turbidity during flowback by 350%, and production enhancement of the wells performance indicating the potential of increased performance with proper reservoir protection. In summary, this paper highlights the need for reservoir protection, a novel approach to minimize formation damage, and both laboratory and field testing of the process to prove the performance enhancement of minimizing formation damage.
Breaking Barriers: Revolutionary Acid Stimulation and Diversion Methods Unleash Offshore Brownfield's Oil Production Potential - Case Study from Gulf of Suez
Authors: Hakim Emad Abdel , Hegazy Amr , Ramadan Ahmed , Saleh Khaled
Published: February 2024

Dealing with the intricacies of carbonate formations presents significant challenges in enhancing oil production, particularly in offshore brownfields plagued by water breakthroughs in commingled completions. While mechanical diversion using straddle packers is a commonly employed method to achieve effective zonal coverage and selective matrix acidizing treatment, it is noteworthy that these mechanical isolation techniques tend to be more expensive compared to chemical diverters.

This paper outlines a comprehensive approach to improving production in such demanding scenarios. The strategy encompasses various factors, including addressing the root causes of water breakthroughs, formulating suitable acid chemicals, choosing effective chemical diversion methods, and optimizing the execution of the overall process. To illustrate the application of this approach, three candidates from the Gulf of Suez Basin, a complex and heterogeneous region in the Eastern Desert of Egypt with carbonate reservoirs, are examined as case studies.

A viscous pill underwent testing in the laboratory before transitioning to field applications. This pill was designed to temporarily isolate fractures or fissure networks, diverting the primary treatment away from water and/or thief zones before the acid treatment. The results of this innovative chemical diversion technique demonstrate a remarkable four-fold increase in well productivity, coupled with a reduction in water cuts.

This paper introduces the workflow and laboratory test results of a purpose-built acid and diversion technique explicitly tailored for fractured and watered-out carbonate reservoirs. Furthermore, it shares valuable insights and practical guidelines gleaned from the lessons learned while applying these methods, providing valuable guidance for future cases with similar challenges.
An Integrated Study with an Effective Strategy Leads to a Great Discovery in a Challenging Fractured Jurassic Reservoir in West Kuwait
Authors: BinSafar Ahmad , AL-Ibrahim Abdullah , Ayyavoo Mani Maran , Al-Otaibi Fahad , Ibrahim Anwar , Al-Khlaifi Omar
Published: February 2024

To overcome the challenges in drilling, completion and testing for one of the highly fractured reservoir in West Kuwait oil field by intercepting the natural fractures and eliminating the causes of formation damage. An integrated multi-disciplinary study was carried out, to understand the underlying drivers of success and causes of failure in Najmah/Sargelu (NJ/SG) reservoirs in west Kuwait area and propose solutions to improve the chance of success. High reservoir pressure, high API oil and the limited success in some areas suggest that this reservoir has significant potential, despite the poor matrix permeability. The key to well success is to intercept the natural fractures and connect them to the production system without damaging them. Various potential damage mechanisms have been encountered, including mud invasion, cement plugging, formation solids plugging and formation collapse. The previous wells were drilled vertically with heavy oil based mud (OBM) and completed with cemented liner against the zone of interest. The study has identified robust well types that are designed to intercept the maximum number of natural fractures with high angle and open hole section with un-cemented 5" slotted liner. In addition, the plan was to drill the wells with high angle (80°) in the Lower Najmah Limestone and Upper Sargelu Limestone Formations but due to some drilling difficulties the plan was changed to 50° only. Therefore, number of wells in west Kuwait were planned to be drilled and completed as per the above strategy.

The first well drilled and completed as per the new strategy did not reach the expectations after inconclusive test, and it needs to be revisited for better evaluation. The second well was drilled in a very challenging environment with high angle trajectory to encounter the natural fractures in the targeted zone. The un-cemented perforated liner was run and installed as planned, which eliminated the usual damage by cementation. During the well activation using Coiled Tubing and without any stimulation treatment, the targeted reservoir became active and the well showed commercial production of oil and gas with high well head pressure, which was announced as a great discovery in west Kuwait. This discovery is considered as a significant mark in Kuwait and opens a new window for exploring and developing of NJ/SG reservoir in other areas.

New drilling, completion and testing strategy was applied in the challenging Jurassic reservoir, which lead to a great discovery in the state of Kuwait. Detailed drilling, completion, testing strategy and production performance with the lessons learned will be discussed in this paper.
Breaker Placement in Sand Control Lower Completions – New Challenges and Potential Solutions
Authors: Byrne M. , Djayapertapa L. , Watson K
Published: February 2024

Production and injection wells for oil and gas and carbon storage reservoirs often require sand control across the reservoir section to enable fluids to flow and to prevent larger formation solids from moving. In many of these wells, chemical breaker treatments are pumped prior to production or injection to help to reduce any drilling or completion induced formation or completion damage. Delivering these breakers to the target such as residual drilling mud cake can be challenging and rules of thumb have often been used to guide this process. More rigorous methods to optimise breaker placement and design are now available.

CFD (Computational Fluid Dynamics) enables fluid flow in complex geometries to be modelled and predicted. Breaker placement during the well completion process involves the complex geometry of the well, the lower completion and the reservoir and fluid flow or displacement. The full geometry of vertical or horizontal wells, with induced fractures, multiple wellbores, perforations or mini-bores should and can be captured using CFD. Breaker pumping whether bull-headed, through a wash pipe, coiled tubing or more sophisticated rotating and jetting needs to be simulated in order to determine its efficiency.

Numerous simulations for different well types, completions and breaker deployment methods have revealed that even with the best intentions and rules of thumb, it can be challenging to place breaker to the target and for breaker concentrations required for efficient dissolution of residual damage to be maintained. In particular gravel packed completions present challenges. Fluids will always take the path of least resistance and in gravel packed completions this is often back up the well between the wash pipe and the screens missing the intended target. The additional resistance of the gravel in the annulus tends to prevent efficient breaker penetration to mud cake or perforations beyond. If the breaker does penetrate, then coverage of the damaged zone can be patchy and early losses can result. Simulations have also identified potential mitigations such as alternative deployment rates, displacement fluids prior to breakers and duration of breaker placement. The benefits of targeted breaker placement during pump and pull or jetting operations has also been evaluated.

Challenges in placing breaker effectively in sand controlled wells are addressed using complex numerical modelling. Replicating well geometry and all fluid flow paths are essential in order to optimise breaker placement and reduce residual formation and completion damage. The methods and examples shared will enable more effective clean-up of oil, gas, water, hydrogen and CO2 wells.
Acid Stimulation Case Study in Deepwater GoM
Authors: Farinas M. , Akajagbor C. , Vreeling C.
Published: February 2024

This paper describes a case study of an acid stimulation performed in the Shenzi field, deep water Gulf of Mexico; the candidate well was an oil producer with a cased hole frac pack completion. Despite having low skin values from the initial completion, the well started to build skin gradually through time which prompted an assessment of formation damage, a list a of possible mechanisms was created and ranked according to their likelihood of occurrence, fines migration due to sand failure near wellbore was deemed to be the leading cause; this mechanism consists of fines entering the perforating tunnel and annular pack thus creating an internal filter cake and reducing proppant permeability, especially in the perforations where linear flow through proppant pack occurs and pressure drop is the highest. Based on this assessment, a HF/HCl acid stimulation was formulated to dissolve silica/clay particles with pre and post flush fluids selected to prevent corrosion in the well and facilities for flow back purposes. The acid job was conveyed via coiled tubing and the results showed a complete reduction of skin to original levels. The stimulation was successful in removing skin and a reduction in skin build post stimulation was achieved by applying a stage drawdown management to prevent excessive sand failure. This paper provides additional experience in deep water acid stimulation in wells with frac pack completions affected by fines migration/sand failure.
Development and Field Testing of a New Diverter Sub Model for Gravel Pack Operations
Authors: Govinathan Kesavan , Tibbles Raymond , Wassouf Philip , Jain Samyak , Samuel Elvy , Nopsiri Noppanan , Selamat Kasim
Published: February 2024

A significant recent advancement in sand control technology is the use of diverter subs in conjunction with shunt tube gravel packing, further increasing the application window of this popular technique. This follows several reported cases where excessive amounts of slurry were lost to the formation after exceeding the fracture pressure and, despite the use of shunts, the screen annulus was not completely packed. Diverter subs minimize this risk by allowing fluid to bypass portions of the wash-pipe, which helps to reduce bottom hole pressure and maintain it below the fracture pressure.

However, this effect is heavily dependent on the number and placement of diverter subs, so effective modelling becomes critical as improper design may still fracture the formation and result in an incomplete pack. The introduction of diverter subs results in fluid being distributed in multiple directions at various points along the wellbore, making the flow path progressively harder to model as the number of subs increases. Consequently, no models existed that could accurately design or evaluate shunted gravel pack treatments with diverter subs.

This paper discusses the development and validation of the industry’s first simulator which incorporates diverter subs with a commercially available gravel pack model to accurately design their optimal number and placement. This was validated with a case history using both shunts and diverter subs, confirming the model can accurately design and evaluate these complex treatments. The paper further extends this work to demonstrate how the model can be used to optimize future designs, expanding the application window of these treatments into tight pore-frac margin wells by reducing the risk of incomplete packing.
Assessment of Sand Control Methods for Cased Dual-Annulus Gas Wells: Scaled Laboratory Experiments
Authors: Miri R. , Salimi M. , Stewart S. , Bermudez J.M. , Mazo C. , Nouri A.
Published: February 2024

Sand production poses a significant challenge in high flow rate offshore gas wells, as the elevated flow velocities can lead to well completion erosion, perforations blockage and subsequent sand influx. This paper presents a comprehensive analysis to assess and rank multiple sand control solutions for mitigating sand production, plugging and erosion in a cased dual-annulus gas well.

A sand retention testing (SRT) setup accommodating a purpose-built component mimicking the dual-annulus wellbore completion was employed to quantify sanding and plugging performance. A novel erosion testing setup was used to assess the erosion risk of different sand control screens. Wire-wrapped screen (WWS), slotted liner (SL), and punched screen (PS) were assessed in conjunction with a novel multi-layer open cell matrix polymer (OCMP) filter. Actual wellbore conditions were replicated to ensure a representative evaluation. The testing used flow rates per single perforation shot and matched sand mineralogy, particle size distribution, gas viscosity, and perforation shot size.

The laboratory tests demonstrated that the OCMP filter exhibited superior performance in sanding, plugging and erosion compared to the other three screens tested. Sand retention performance of WWS was poor, with 0.27 lbm/ft2 being produced compared to 0.015 lbm/ft2 and 0.07 lbm/ft2 for slotted liner and punched shroud, respectively, and the OCMP produced zero sand throughout the test. The WWS also exhibited a high susceptibility to erosion, and the PS displayed a high tendency for erosion and plugging. The OCMP filter was also examined for long-term exposure to formation fluids and short-term exposure to aqueous and solvent-based chemical treatments that are potentially employed in the wells, with no adverse effects observed.

This paper reports, for the first time, a comprehensive study replicating a cased dual-annulus in offshore gas field conditions comparing multiple remedial sand control solutions, including OCMP, offering the industry objective data to aid sand control selection.
Return Permeability and Critical Velocity Testing: Formation Damage in CO2 Storage Projects
Authors: de Itriago Yani Araujo , Palencia Clara , Singletary Phillip
Published: February 2024

CO2 Geological Sequestration (GS) is by far the most tangible and practical solution when compared with the other options, such as wind and solar, in the race to reach net zero global goals. GS includes depleted oil and gas reservoirs, in different minerologies, being sandstones, carbonates and dolomite the most common ones. One key parameter for subsurface CO2 storage is well injectivity. Change in well injectivity is a well-known problem in CO2 injection wells, either in enhanced oil recovery or sequestration projects (Grigg and Svec 2003). The well injectivity might change due to precipitation of sulfate and carbonate scales, which are the reaction products between CO2/ rock/brine. This change depends on petrophysical properties, such as pore throat and pore body sizes, minerology, which impacts wettability. It is an interesting problem that the industry needs to take more into consideration to be able to store CO2 in the levels needed to achieve the global temperature goals. The risk for solid precipitation and for water blockage is present. The primary objective of this paper is to quantify the reduction on permeability and changes in pore throat distribution, due to CO2 interaction with the rock.

A core flood study was conducted using core plugs with a range of minerologies including sandstone, carbonate, and dolomite. Cores were saturated with 35K NaCl brine and effluent samples were collected, and the concentrations of calcium, potassium, magnesium, aluminum, sulfate, iron, and silicon ions were measured by Inductively Coupled Plasma (ICP) and Ion Chromatography (IC).

CO2 was injected under supercritical conditions at a pressure of 3000 psi, and at 250°F at 8 different injection flow rate for 7 days. After the test, return permeability, pore throat distribution, NMR, and precipitated material collected after the tests will be analyzed using XRD and XRF. The air and water permeability (Kair and Kw) will be measured before and after the test to evaluate the changes in per permeability.
A Workflow for Circulation Rate Optimization to Exploit Enhanced Geothermal System Productivity
Authors: Ashena Rahman , Ghalambor Ali , Bataee Mahmood , Thiruvelcham Vinesh
Published: February 2024

To ascertain sustainability of geothermal productions in an Enhanced Geothermal System (EGS), several important design parameters must be optimized. One of the important design parameters is the circulation rate to maximize thermal productivity. Optimization of this parameter is of great practical interest, but it is not adequately discussed in the available literature and thus further research is required with clear criteria set as shown in the outcome of this paper.

This research work follows an innovative simulation model construction and benchmarking with a case of a reservoir with extremely high geothermal gradient. Then optimizing the circulation rate using an innovative algorithm. The model uses two main criteria of the net generated power and an updated coefficient of performance (COP) as defined in this current work. The maximum possible net power was selected while the COP being kept high enough with some stability, to guarantee the optimum heat energy that can be exploited from the reservoir with maximum productivity over the project lifespan.

In the investigated case study, using the recommended workflow, an optimum circulation rate of 0.0736 m3/s (40 M-bbl/day) was found with the net heat energy of 50,617 trillion-Joule, the net produced heat power of 64.2 Mw and the updated COP of 55, following 25 years of production. An updated COP is defined in this research work outcome.

This is a pioneer engineering design work aimed to present an innovative workflow on how to maximize heat productivity via circulation rate maximization.
Application of Nanofluids for Altering Wettability in Heavy Oil: A Field Test
Authors: Cárdenas J. C. , Jaimes M. , Dorado R. , Galvis H. , Conde O. R. , Prada A.
Published: February 2024

The production of heavy crudes presents a considerable challenge due to several factors. These include complex geology, active aquifers, wells influenced by water injection patterns, reservoirs with mixed wettability tendencies favoring oil (high affinity between heavy crude and the rock minerals in the reservoir), and the intrinsic nature of heavy crude, characterized by its high viscosity. Moreover, artificial lift systems often exhibit low efficiency under high bottomhole pressures, and formation damage can occur during drilling, completion, and production stages. Consequently, an unfavorable mobility ratio of the crude can result in early water breakthrough in the wells.

Nanotechnology, in the form of aqueous and organic-based nanodispersions, is proposed as a technological solution to enhance the productivity of heavy crudes and mitigate the aforementioned challenges. This study introduces an experimental methodology for assessing nanofluids, which includes tests for colloidal stability, basic formation fluid characterization, fluid-fluid evaluation, and fluid-rock assessment. During the implementation phase, nanofluids are injected near the wellbore using the matrix stimulation technique, allowing them to be adsorbed onto the rock. This process influences relative permeability curves, modifies wettability, increases the oil recovery factor, and optimizes oil production while simultaneously reducing water production.

Finally, the study presents production results following the implementation of nanofluids in a heavy crude well operated by Ecopetrol. The outcomes reveal a significant increase in production, with rates rising from 10 BOPD to 467 BOPD, accompanied by a 37% reduction in %BS&W (based on preliminary post-stimulation tests). The stimulation process included an initial acid stimulation phase, followed by the flowback of the acid returns and subsequent injection of nanofluids.
Nano Relative Permeability Modifier (NanoRPM): A Promising Solution for Water Control in Colombian Oilfields
Authors: Cardenas J. C. , Ariza E. , Torres R. , Patiño J. C , Jaimes M. G , Prada A. , Conde O. R. , Galvis H.
Published: February 2024

The objectives of the proposed paper are to investigate the effectiveness of NanoRPM, a nanotechnology-based solution, in controlling water production in Colombian hydrocarbon reservoirs. The scope of the paper includes evaluating the adsorption capacity and durability of NanoRPM compared to conventional RPM, as well as assessing its performance under static and dynamic conditions. Additionally, the field pilot results will be analyzed to confirm the viability and long-term effectiveness of NanoRPM for water control in reservoirs. The study evaluated the efficacy of NanoRPM, a nanotechnology-based solution, in reducing water production in Colombian hydrocarbon reservoirs. Experimental tests, including fluid-fluid and rock-fluid interaction tests under various conditions, were conducted. Specific factors of the Eastern Llanos Basin were considered. The adsorption capacity and durability of NanoRPM were compared to conventional RPM. The findings were aligned with field pilot results to validate NanoRPM's effectiveness in mitigating water production and ensuring long-term performance. The study found that NanoRPM showed exceptional performance in controlling water production in Colombian hydrocarbon reservoirs. It exhibited six times greater adsorption capacity than conventional RPM under static and dynamic conditions. These results were consistent with the field pilot data, which demonstrated a significant 15% reduction in water production over an eighteen-month period. The high surface area-to-volume ratio of NanoRPM was identified as a key factor contributing to its improved adsorption on rock surfaces. Additionally, NanoRPM exhibited superior durability in the porous medium compared to conventional RPM, indicating its long-term effectiveness in water control. Consequently, the study concluded that NanoRPM is a technically viable and durable solution for addressing water control challenges in hydrocarbon reservoirs. The findings offer valuable insights into the application of nanotechnology in reservoir engineering and water management strategies, presenting a promising approach to reducing water-related costs in mature Colombian fields. This paper presents novel information by exploring the use of NanoRPM, a nanotechnology-based solution, for water control in Colombian hydrocarbon reservoirs. The study provides new insights into the effectiveness of NanoRPM compared to conventional RPM, showcasing its exceptional adsorption capacity and durability. The findings contribute to the existing body of literature by offering a promising technological advancement in mitigating water production and reducing associated costs in the petroleum industry.
Study on the Law of Reservoir Damage Caused by Deformable Gel Particles During Profile Control and the Methods of Reducing Damage
Authors: Zhao Wenjing , Wang Jing , Qi Zhongyang , Zhang Xu , Liu Huiqing , Wang Wuchao
Published: February 2024

This study focuses on the damage caused by deformable gel particles (DGP) during profile controlling in the high water cut stage. The law of filter cake damage and invasive damage caused by DGP were studied. The effect of common methods to reduce different types of damage was evaluated, and a method to reduce damage was put forward. The change of DGP filter cake under the action of subsequent water was qualitatively studied by the NMR experiment. The experimental method was used to characterize the effect of filter cake damage and invasive damage on the follow-up water. The effects of sodium hypochlorite (NaClO) on the particle size of DGP and the damage reduction rules of different types of damage were revealed. In this paper, a method of meticulous control of particle size was proposed. And the best range of particle size distribution was obtained combined with the calculation model of the plugging effect. The DGP filter cake goes through three processes under the influence of injected water: compression, water entering the filter cake, and water breaking through the filter cake. The filter cake will cause the start-up pressure gradient of 0.13Mpa/m to the subsequent injection water when the ratio of particle diameter to pore throat was 10.56. The breakage of DGP will cause invasive damage. NaClO can reduce the particle size of DGP by more than 50%. And it can reduce filter cake damage by 5.10% but only reduces invasive damage by 0.21%. NaClO can effectively reduce the damage of conventional reservoirs only under low speed and large amounts of injection, but it will corrode the reservoir and injection equipment. According to the particle size reconstruction model, the particle size distribution and the pore throat size distribution were brought into the plugging effect calculation mode. And the coincidence between the calculated and experimental results was 98.55%. Compared with no meticulous particle size control, the damage degree of the remaining oil enrichment area decreased by 45.29% after meticulous particle size control. The invasive damage empirical model and the filter cake damage starting pressure gradient obtained in this paper can guide the field in evaluating the damage degree. They can also be applied to numerical simulations. The damage reduction method proposed in this paper can reduce the damage from the source without corroding the injection equipment and has the advantages of easy operation and low cost.
Oil Detachment Mechanism in Natural Surfactant Flooding from Silica Surface: Molecular Dynamics Simulation
Authors: Yang Shuo , Liu Pengcheng , Deng Song , Wang Yanwei
Published: February 2024

International regulations have compelled Europe and the United States to phase out certain traditional surfactants to mitigate the use of toxic and nonbiodegradable chemicals. Sodium cocoyl propionate (SCA), as a natural surfactant with high performance, has been proved to have the potential to replace traditional surfactants in previous studies. However, its performance has not fully met practical application requirements. Therefore, in this paper, molecular dynamics (MD) simulation was used to study the detachment behavior and mechanism of SCA, lauryl dimethylamine oxide (OA-12), emulsifier OP-10, and SOO (combination of SCA, OA-12, and OP-10) on crude oil (dodecane, C12) at different temperatures (80–120°C) and salinities (20 000–200 000 mg/L). The complex interaction mechanism between surfactant molecules and C12 molecules was revealed by analyzing the simulated snapshot, radial distribution function (RDF), mean square displacement (MSD), and interaction energy. The simulated snapshot captures the conformational evolution of surfactant molecules at different time points, emphasizing the spatiotemporal and spatial changes of their dynamic behavior. A comparison of two desorption modes reveals that dispersive adsorption displacement and concentrated adsorption displacement are two possible desorption mechanisms. RDF analysis shows that the probability of SOO molecules near C12 remains high even at high-salinity and -temperature conditions. MSD analysis showed that the diffusion capacity of SOO was the highest at 100°C, reaching 1.52867×10 –5 cm2/ps. The calculation of interaction energy results reveals that SOO has a strong adsorption capacity for C12, which is mainly due to the effect of van der Waals (vdW) force. This is because the C12 molecules are inert, and their molecular movement is mainly determined by the polar groups of the surfactant. The main contribution of this study is to provide a natural surfactant with superior performance as a viable alternative, offering experimental settings for further improvement in SCA performance. This research provides theoretical guidance for on-site applications of SCA and SOO to enhance oil recovery.
Additional feedforward mechanism of Parkin activation via binding of phospho-UBL and RING0 in trans
Authors: Lenka Dipti , Dahe Shakti , Antico Odetta , Sahoo Pritiranjan , Prescott Alan R. , Muqit Miratul M. K. , Kumar Atul
Published: February 2024

Loss of function Parkin mutations lead to early-onset of Parkinson’s disease. Parkin is an auto-inhibited ubiquitin E3 ligase activated by phosphorylation of its ubiquitin-like (Ubl) domain and ubiquitin by PINK1. Herein, we show a competitive binding mode of the phospho-Ubl and RING2 domains on the RING0 domain, which regulates Parkin activity. We show that phosphorylated Parkin can directly complex with unmodified Parkin, leading to the activation of autoinhibited Parkin in trans. Furthermore, we show that the activator element (ACT) of Parkin is required to maintain the enzyme’s kinetics, and the removal of ACT slows the enzyme catalysis. We also demonstrate that ACT can activate Parkin in trans but less efficiently than when present in the cis molecule. Furthermore, crystal structure reveals a new donor ubiquitin binding pocket that plays a crucial role in function. This study provides new molecular insights into Parkin activation, which may aid the development of Parkin activators as a therapeutic strategy against Parkinson’s.
Formin-like 1 β phosphorylation at S1086 is necessary for secretory polarized traffic of exosomes at the immune synapse
Authors: Izquierdo Manuel , Ruiz-Navarro Javier , Fernández-Hermira Sara , Sanz-Fernández Irene , Barbeito Pablo , Garcia-Gonzalo Francesc , Calvo Víctor
Published: February 2024

T-cell receptor stimulation by antigen bound to the major histocompatibility complex (MHC) on an antigen-presenting cell (APC) induces protein kinase C (PKC) activation and the formation of the immune synapse (IS), followed by depletion of filamentous actin (F-actin) at the central region of the IS (cIS) and the polarization of multivesicular bodies (MVB) and the microtubule-organizing center (MTOC) to the IS. These events lead to polarized exosome secretion at the IS. These exosomes are involved in several crucial immune responses such as autocrine activation-induced cell death (AICD) of T lymphocytes and citotoxicity. We analysed here how formin-like 1 β (FMNL1β), an actin cytoskeleton-regulatory protein, regulates MTOC/MVB polarization and exosome secretion at the IS in a phosphorylation-dependent manner. IS formation was associated with transient recruitment of FMNL1β to the IS, which was independent of protein kinase C δ (PKCδ). Simultaneous RNA interference of all FMNL1 isoforms prevented MTOC/MVB polarization and exosome secretion, which were restored by FMNL1β expression. However, expression of the non-phosphorylatable mutant FMNL1βS1086A did not restore either MTOC/MVB polarization nor exosome secretion to control levels, supporting the crucial role of S1086 phosphorylation in MTOC/MVB polarization and secretion. In contrast, the phosphomimetic mutant, FMNL1βS1086D, restored MTOC/MVB polarization and exosome secretion. Conversely, FMNL1βS1086D mutant did not recover the deficient MTOC/MVB polarization occurring in a PKCδ-interfered clone, indicating that S1086 phosphorylation alone is not sufficient for MTOC/MVB polarization and exosome secretion. FMNL1 interference inhibited the depletion of F-actin at the cIS, which is necessary for MTOC/MVB polarization. FMNL1βWT and FMNL1βS1086D, but not FMNL1βS1086A expression, restored F-actin depletion at cIS. Thus, actin cytoskeleton reorganization at the IS underlay the effects of all these FMNL1β variants on polarized secretory traffic. Taken together, these results point out a crucial role of S1086 phosphorylation in FMNL1β activation, leading to cortical actin reorganization and subsequent control of MTOC/MVB polarization and exosome secretion.
PIM2 Kinase Regulates TIGIT Expression and Function in NK Cells from Multiple Myeloma Patients
Authors: Fu Rong , Liu Zhaoyun , Wang Hao , Li Yiman , Li Nianbin , Peng Fengping , Jiang Fengjuan , Yan Siyang , Meng Nanhao , Liu Hui , Ding Kai
Published: February 2024

PIM2 kinase influences plasma cell generation and bone loss in multiple myeloma (MM), which is highly associated with tumor progression and is a potential therapeutic target. Although PIM2 kinase is essential for natural killer (NK) cell homeostasis and development, its role in NK cells function remains unclear.Here,the expression of PIM2 kinase was reanalyzed in NK cells from MM patients and healthy donors using single-cell RNA sequencing (RNA-seq). The effect of PIM2 kinase on NK cell immune checkpoints and function were analyzed in NK cell and MM cell co-culture system. Mechanistically, The regulation of PIM2 kinase on TIGIT expression on NK cell was explored through NCBI, UCSC, JASPAR, GEPIA databases and ETS-1 knockdown in NK-92 cells.For further clinical application,PIM2 kinase inhibitors were screened in 160 natural flavonoids through kinase functional assays (ADP-Glo).Our findings reveal that PIM2 kinase was highly expressed in NK cells from MM patients and PIM2 kinase inhibitor increased NK cell function and downregulated TIGIT expression. Mechanistically, the PIM2 kinase inhibitor down-regulated TIGIT expression by reducing transcription factor ETS-1, which binds directly to the TIGIT promoter. For pre-clinical translational application, we screened two natural flavonoids kaempferol and quercetin dihydrate, which show higher efficacy in inhibiting PIM2 kinase. Subsequent co-culture system results demonstrated that kaempferol and quercetin dihydrate can decrease TIGIT expression and improved the anti-myeloma function in NK cells.All the above results confirm PIM2 kinase regulates TIGIT expression and function in NK cells from MM patients.PIM2 kinase inhibitor play a vital role in MM therapy.
The Pulsatile Brain, Pulse Pressure, Cognition, and Antihypertensive Treatments in Older Adults: A Functional NIRS Study
Authors: Mohammadi Hanieh , Besnier Florent , Vincent Thomas , Fraser Sarah , Nigam Anil , Lesage Frédéric , Bherer Louis
Published: February 2024

Age-related arterial stiffness increases pulsatility that reaches the cerebral microcirculation, compromises cerebrovascular health and lead to cognitive decline. The presence of cardiovascular risk factors (CVRFs) such as high blood pressure can exacerbate this effect. Despite extensive research on the impact of antihypertensive treatments on reducing arterial stiffness, little is known about the impact of antihypertensive treatments on pulsatility in cerebral microcirculation. This study investigated the impact of antihypertensive treatments on cerebral pulsatility and cognition in older adults with CVRFs. Participants were 42 older adults with diverse CVRFs in two groups of untreated (\(n=\) 21, mean 67.2 \(\pm\) 5.9 years old, 57.1\(\text{\%}\) female) and treated with antihypertensive medications (\(n=\) 21, mean 67.2 \(\pm\) 5.5 years old, 61.1\(\text{\%}\) female). Cognitive scores of processing speed and executive functions were evaluated behaviorally using the four subsets of the Stroop test. A near-infrared spectroscopy (NIRS) device recorded hemodynamics data from the frontal and motor cortex subregions. The data were then used to extract an optical index of cerebral pulsatility. Results indicated that after controlling for CVRFs, the antihypertensive treatment is associated with lower cerebral pulsatility (untreated 33.99 \(\pm\) 6.68 vs. treated 28.88 \(\pm\) 5.39 beats/min, \(p\) \(=\) 0.009). In both groups cerebral pulsatility was associated with pulse pressure (\(p\) \(<\)0.05). Also, treated group had significantly higher cognitive scores in executive functions compared with the untreated group (\(p\) \(<\)0.05). These results suggest that beyond its known effect on blood pressure, antihypertensive treatments might also favor cerebrovascular health by reducing pulsatility in the cerebral microcirculation.
Clinically applicable optimized periprosthetic joint infection diagnosis via AI-based pathology
Authors: Ni Ming , Tao Ye , Hu Hanwen , Li Jie , Luo Yazhi , Wang Shuhao , Zheng Qingyuan , Zhang Tianwei , Zhang Guoqiang
Published: February 2024

Periprosthetic joint infection (PJI) is a severe complication following joint replacement surgery, often requiring complex multi-stage joint revisions or fusion, and imposing significant burdens on individuals and society as a whole. Accurate diagnosis is crucial for effective treatment. This study aimed to enhance the pathological diagnostic accuracy of PJI by standardizing an intelligent pathological diagnostic process, improving its applicability and practicality in clinical settings, and providing guidance for intelligent diagnosis of infectious diseases. We developed supervised learning models, weakly supervised learning models, and unsupervised learning PJI intelligent classification models and conducted image-level, patient-level testing, and visual verification for the first two models. The weakly supervised learning model performed nearly as well as the supervised learning model in image-level tests, achieving comparable levels of accuracy, recall rates, and ROC curves. However, in patient-level testing, the weakly supervised learning model outperformed its supervised learning counterpart. By adjusting the area threshold for the recognition regions, we significantly improved the sensitivity of PJI pathological diagnosis without compromising specificity (AUC curve area of 0.9460 for the supervised model and 0.9078 for the weakly supervised model). Based on our criteria, the existing diagnostic standard for five high-power fields in a single slide was reduced to only 3. The visualization results also revealed structural changes and loosening in the surrounding tissues, apart from localized neutrophil aggregation. Moreover, the distribution patterns of neutrophil morphology might provide clues for the diagnosis and treatment of PJI. Using an intelligent quantification and statistical approach, we successfully elevated the sensitivity of PJI pathological diagnosis to 88.42% and specificity to 92.31%. Moreover, we established unsupervised rapid auxiliary annotation models, supervised classification models, and unsupervised approximate segmentation models, thereby achieving an intelligent PJI diagnosis. Our study lays the foundation for further intelligent optimization of pathological diagnosis of other infectious diseases.
MRI subtypes in Parkinson’s disease:
Unraveling differences across diverse populations and clustering approaches
Authors: Inguanzo Anna , Mohanty Rosaleena , Poulakis Konstantinos , Ferreira Daniel , Segura Bàrbara , Albrecht Franziska , Muehlboeck J-Sebastian , Granberg Tobias , Sjostrom Henrik , Svenningsson Per , Franzen Erika , Junque Carme , Westman Eric
Published: February 2024

Parkinson’s disease (PD) is clinically heterogeneous, which suggests the existence of subtypes; however, there has been no consensus regarding their characteristics. This study included 633 PD individuals across distinct cohorts: unmedicated de novo PD, medicated PD, mild-moderate PD and a cohort based on diagnostic work-up in clinical practice. Additionally, 233 controls were included. Clustering based on cortical and subcortical grey matter measures was conducted with and without adjusting for global atrophy in the entire sample and validated within each cohort. Subtypes were characterized using baseline and longitudinal demographic and clinical data. Unadjusted results identified three clusters showing a gradient of neurodegeneration and symptom severity across both the entire sample and individual cohorts. When adjusting for global atrophy eight clusters were identified, lacking consistency across cohorts in validation. This study identified atrophy-based subtypes in PD, emphasizing the significant impact of global atrophy on subtype number, patterns, and interpretation in cross-sectional analyses.
Triazoles nanoencapsulation in polylactic acid to reduce phytotoxicity in roots
Authors: Beltrán Jahsive Sujey Quintero , Viveros Gabriela Sánchez , Contreras Roberto Gregorio Chiquito , Saito Greta Hanako Rosas , Castro Randy Ortíz , Landa Israel Bonilla , Romero José Luis Olivares , Méndez Felipe Barrera
Published: February 2024

The use of effective fungicides, such as propiconazole, a high-efficacy and broad-spectrum systemic fungicide, has been a common commercial strategy to combat fungal diseases. However, their indiscriminate and uncontrolled use provokes phytotoxicity in plant roots. Therefore, the objective of this study is to reduce the root phytotoxicity of triazole fungicides through their nanoencapsulation in biodegradable polylactic acid polymer matrices. Using the emulsion and solvent evaporation encapsulation method, the obtained nanoparticles had a hydrodynamic diameter of approximately 200 to 400 nm, an encapsulation efficiency of around 40%, a smooth surface, and a zeta potential close to -40 mV, having great colloidal stability. Experiments with Arabidopsis thaliana demonstrated that the nanoencapsulation of a fungicide derived from propiconazole reduced its phytotoxicity, increasing the length of the roots over 70% more than when the molecule was applied directly, losing only about 15% of its antifungal activity, as shown by the test performed on Fusarium solani. This suggests that nanoencapsulation with biodegradable polymer matrices acts as a protective mechanism for plant roots, which may have practical applications in crop protection and the promotion of sustainable agriculture. However, further research is needed to evaluate its efficacy under field conditions and its long-term environmental impact.
Use of passive samplers as sewage surveillance tool to monitor a hepatitis A outbreak at a school in Amsterdam, the Netherlands, Oct 2022 – March 2023
Authors: de Jong Maarten , Loeff Maarten F. Schim van der , Schilperoort Rémy , Vennema Harry , Weijden Charlie van der , Langeveld Jeroen , Welkers Matthijs , Prins Maria , Husman Ana Maria Roda , Fanoy Ewout , Medema Gertjan
Published: February 2024

Background
Enteric hepatitis A virus (HAV) infections during childhood are often asymptomatic but may cause severe illness in adults. To improve public health surveillance we assessed the applicability of sewage monitoring during an HAV outbreak at a primary school.
Methods
Between October 19 and December 27, 2022, five symptomatic HAV cases were notified to the Public Health Service Amsterdam; all attended the same primary school. Passive samplers, small absorbent tools, were deployed in sewage near the school from November 14, 2022, to March 22, 2023. The absorbents were subjected to RNA extraction, HAV PCR testing, and, if positive, sequencing. PCR and sequencing were also performed on plasma and feces samples of HAV cases.
Results
In 22 out of 88 (25%) of sewage samples, HAV RNA was detected. All HAV-RNA-positive sewage samples until 8 February 2023 were subgenotype IB, matching the strain detected in all cases. Another strain of HAV (subgenotype IA) was detected in sewage from 15 February 2023 onwards, without associated cases.
Conclusions
Passive sampler-based sewage monitoring is an effective method to rapidly detect HAV shedding linked to diagnosed cases. It detects unnoticed viral infections and allows monitoring of outbreaks. This suggests that passive sampler-based monitoring is a promising tool supporting the public health response during HAV and other outbreaks.
Sucrose-preferring gut microbes prevent host obesity by producing exopolysaccharides
Authors: Kimura Ikuo , Shimizu Hidenori , Miyamoto Junki , Hisa Keiko , Ohue-Kitano Ryuji , Takada Hiromi , Yamano Mayu , Nishida Akari , Sasahara Daiki , Masujima Yuki , Watanabe Keita , Nishikawa Syota , Takahashi Sakura , Ikeda Takako , Nakajima Yuya , Yoshida Naofumi , Matsuzaki Chiaki , Kageyama Takuya , Hayashi Ibuki , Matsuki Akari , Akashi Ryo , Kitahama Seiichi , Ueyama Masako , Murakami Takumi , Inuki Shinsuke , Irie Junichiro , Satoh-Asahara Noriko , Toju Hirokazu , Mori Hiroshi , Nakaoka Shinji , Yamashita Tomoya , Toyoda Atsushi , Yamamoto Kenji , Ohno Hiroaki , Katayama Takane , Itoh Hiroshi
Published: February 2024

Commensal bacteria affect host health by producing various metabolites from dietary carbohydrates via bacterial glycometabolism; however, the underlying mechanism of action remains unclear. Here, we identified Streptococcus salivarius as a unique anti-obesity commensal bacterium. We found that S. salivarius may prevent host obesity caused by excess sucrose intake via the exopolysaccharide (EPS)-short-chain fatty acid (SCFA)-carbohydrate metabolic axis. Healthy human donor-derived S. salivarius produced high EPS levels from sucrose but not from other sugars. S. salivarius abundance was significantly decreased in human donors with obesity, and the EPS-SCFA bacterial carbohydrate metabolic process was attenuated. Our findings reveal an important mechanism by which host–commensal interactions in glycometabolism affect energy regulation, suggesting an approach for preventing lifestyle-related diseases via prebiotics and probiotics by targeting bacteria and EPS metabolites.