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The peptide/histidine transporter PHT1 (SLC15A4) is expressed in the lysosomal membranes of immune cells where it plays an important role in metabolic and inflammatory signaling. PHT1 is an H+-coupled/histidine symporter that can transport a wide range of oligopeptides, including a variety of bacterial-derived peptides. Moreover, it enables the scaffolding of various metabolic signaling molecules and interacts with key regulatory elements of the immune response. Not surprisingly, PHT1 has been implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Unfortunately, the pharmacological development of PHT1 modulators has been hampered by the lack of suitable transport assays. To address this shortcoming, a novel transport assay based on solid-supported membrane-based electrophysiology (SSME) is presented. Key findings of the present SSME studies include the first recordings of electrophysiological properties, a pH dependence analysis, an assessment of PHT1 substrate selectivity, as well as the transport kinetics of the identified substrates. In contrast to previous work, PHT1 is studied in its native lysosomal environment. Moreover, observed substrate selectivity is validated by molecular docking. Overall, this new SSME-based assay is expected to contribute to unlocking the pharmacological potential of PHT1 and to deepen the understanding of its functional properties.

Snails are the first intermediate host in the life cycle of trematodes. Previous research found that Trichopodus microlepis fish, cultured in earthen ponds in Tan Nhut Commune, Binh Chanh District, Ho Chi Minh City, Vietnam had a high infection rate with metacercariae of Centrocestus formosanus and Procevorum sp. It is necessary to investigate whether habitats supplying water to the ponds may contribute to the transmission by carrying intermediate hosts and/or cercariae into these ponds or not. A study of cercariae and snail composition in rice fields and canal supplying water directly to these Trichopodus microlepis ponds was carried out with six samplings in the years 2022 and 2023. A total of 1,151 snails were collected, and nine snail species belonging to 8 genera and 6 families were identified. Three snail species in both rice fields and canal were infected with trematode (cercariae stage) including Bithynia siamensis, Lymnaea viridis and Indoplanorbis exustus. The overall prevalence in the dry season (25.9%) was significantly higher than in the wet season (10.6%) (P<0.05). Three cercariae morphotypes were recovered from snails: xiphidio (in all three snails), echinostome (in Lymnaea viridis and Indoplanorbis exustus), and pleurolophocercous in Bithynia siamensis. This finding shows that Bithynia siamensis is one of the infected sources for Trichopodus microlepis fish cultured in ponds, as pleurolophocercous is also the cercariae in the family of Heterophyidae (including Centrocestus formosanus and Procevorum sp.). Further research should be done to clarify the transmission of fish-borne zoonotic diseases to cultured Trichopodus microlepis in other habitats including the actual fishponds, and sources of trematodes in order to produce Trichopodus microlepis free of metacercariae, contributing to clean aquaculture development and safe food for local people in the area. [ABSTRACT FROM AUTHOR]

NHA2, also known as SLC9B2, is an orphan intracellular Na+/H+ exchanger (NHE) that has been associated with arterial hypertension and diabetes mellitus in humans. The objective of this NCCR TransCure project was to define the physiological and molecular function of NHA2, to develop a high resolution kinetic transport assay for NHA2 and to identify specific and potent compounds targeting NHA2. In this review, we summarize the results of this highly interdisciplinary and interfaculty effort, led by the groups of Proffs. Jean-Louis Reymond, Christoph von Ballmoos and Daniel Fuster.

This study investigates the load transfer mechanism that includes the effect of helix bending deflection on end-bearing capacity, distribution of ground pressure under the helix and soil deformation around the screw pile. The helix to shaft diameter ratio of 2.5 and 2.8 with a strong helix and a weak helix were used. The model ground was prepared with fine sand at 80% of relative density. To investigate the load transfer mechanism, the experimental tests were modelled in a 3D finite element code. A good agreement between the experimental and numerical approaches was found. The numerical analyses showed that large influence zone exists under screw pile with strong helix, which resulted in higher mobilized soil shear strength that contributed to higher end-bearing capacity. In the case of strong helix, uniform pattern of pressure distribution was observed under the central shaft and the helix. Similar pattern of pressure distribution under the central shaft was observed in weak helix case but the pattern of pressure distribution under the helix changed from uniform to triangular to trapezoidal at various stages during the load test. The normalized end-bearing capacity decreased linearly with the increase in normalized helix bending deflection in both approaches, i.e. experimental and numerical.

The SLC9 gene family encodes Na+/H+ exchangers (NHEs), a group of membrane transport proteins critically involved in the regulation of cytoplasmic and organellar pH, cell volume, as well as systemic acid-base and volume homeostasis. NHEs of the SLC9A subfamily (NHE 1–9) are well-known for their roles in human physiology and disease. Much less is known about the two members of the SLC9B subfamily, NHA1 and NHA2, which share higher similarity to prokaryotic NHEs than the SLC9A paralogs. NHA2 (also known as SLC9B2) is ubiquitously expressed and has recently been shown to participate in renal blood pressure and electrolyte regulation, insulin secretion and systemic glucose homeostasis. In addition, NHA2 has been proposed to contribute to the pathogenesis of polycystic kidney disease, the most common inherited kidney disease in humans. NHA1 (also known as SLC9B1) is mainly expressed in testis and is important for sperm motility and thus male fertility, but has not been associated with human disease thus far. In this review, we present a summary of the structure, function and regulation of expression of the SLC9B subfamily members, focusing primarily on the better-studied SLC9B paralog, NHA2. Furthermore, we will review the potential of the SLC9B subfamily as drug targets.

Abstract Background Sustainability of methadone maintenance treatment (MMT) program involves regularly assessing its impact on health and social outcomes of drug users in different settings, particularly in disadvantaged areas. In this study, we evaluated the change in quality of life (QoL), and identified associated factors amongst drug users over the course of 12-month MMT in Vietnamese mountainous provinces. Methods We conducted a longitudinal study among patients from 6 MMT clinics in three mountainous provinces of Vietnam. At baseline, we screened 300 participants and after a 12-month treatment, 244 participants remained to involve in the study. World Health Organization Quality of Life short form instrument (WHOQOL-BREF) was used to measure the QoL of patients. The magnitude of the changes was extrapolated. Results There were significant changes in all four dimensions of quality of life measured by WHOQoL-BREF between baseline and 12 months with the effect size ranged from 0.21 to 0.24. Increased age, being workers compared to unemployment and having health problems or comorbidities were positively related to reduced scores of QoL. Conclusions To conclude, we observed a significant increase in the QoL level regarding physical, psychological, social relationships and environmental aspects among people who used drug after 12 months of MMT. Findings from this study emphasize the role of continuously receiving MMT treatment among people using drugs to enhance their QoL.

Objective: The purpose of this study was to identify factors associated with twin pregnancy following day 3 double embryo transfer (DET). Methods: This retrospective cohort study incorporated data from 16,972 day 3 DET cycles. The participants were women aged between 18 and 45 years who underwent in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) at My Duc Assisted Reproduction Technique Unit (IVFMD), My Duc Hospital, located in Ho Chi Minh City, Vietnam. Results: Of the 16,972 day 3 DET cycles investigated, 8,812 (51.9%) resulted in pregnancy. Of these, 6,108 cycles led to clinical pregnancy, with 1,543 (25.3% of clinical pregnancies) being twin pregnancies. Factors associated with twin pregnancy included age under 35 years (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.32 to 1.71; p<0.001) and cycles involving the transfer of at least one grade I embryo. Relative to the transfer of two grade III embryos, the risk of twin pregnancy was significantly elevated following the transfer of two grade I embryos (OR, 1.40; 95% CI, 1.16 to 1.69; p<0.001) or a combination of one grade I and one grade II embryo (OR, 1.27; 95% CI, 1.05 to 1.55; p=0.001). Conclusion: By analyzing a large number of IVF/ICSI cycles, we identified several predictors of twin pregnancy. These findings can assist medical professionals in tailoring treatment strategies for couples with infertility. [ABSTRACT FROM AUTHOR]