Preliminary Studies Research Articles

Ameliorative potential of synbiotic combination of Lactobacillus sp. and polyphenols against Benzo[a]pyrene-induced toxicity in Caco-2 cell line

Exposure to benzo[a]pyrene (B[a]P), a major global food safety concern, is often associated with increasing incidence of colorectal cancers. This in-vitro study was focused on the identification of potential B[a]P-adsorbing Lactobacillus strains and evaluation of the ameliorative effect of synbiotic combination of selected Lactobacillus sp. and polyphenols (quercetin or resveratrol) against B[a]P-induced intestinal toxicity in Caco-2 cells. Preliminary studies lead to the selection of Lactiplantibacillus plantarum MTCC 25433 strain that showed 86% of B[a]P adsorption in 2 h as compared to L. rhamnosus GG that showed 74% of B[a]P adsorption. B[a]P adsorption by MTCC 25433 was reduced to 9%, 16% and 20% upon pre-treatment with SDS, NaIO4 and mutanolysin, attributing the involvement of cell wall proteins and polysaccharides in the adsorption. Additionally, peptidoglycan of both strains adsorbed >50% of B[a]P. In-vitro assays revealed that the selected LAB mitigated the B[a]P-induced epithelial cell damage. Among the polyphenols, quercetin, resveratrol and curcumin, varied in their potency to mitigate B[a]P-induced oxidative stress, with curcumin being least effective. Combinations of selected Lactobacillus sp. and polyphenols were more potent in averting B[a]P-induced toxicity via increase in GSH (17–30 %), SOD (50–88 %), catalase (19–45 %), and reduction in IL-8 secretion (14–28 %) and barrier dysfunction. Principal component analysis affirmed the superior potency of combination of L. plantarum MTCC 25433 and quercetin in averting B[a]P-induced toxicity. Overall, this study highlighted a novel promising strategy of synbiotic combination of Lactobacillus sp. and polyphenols (quercetin or resveratrol) in alleviating the B[a]P-induced toxicity in intestinal epithelial cells.

Bioactivity and efficacy of a hyperimmune bovine colostrum product- Travelan, against shigellosis in a non-Human primate model (Macaca mulatta)

Infectious diarrhea is a World Health Organization public health priority area due to the lack of effective vaccines and an accelerating global antimicrobial resistance crisis. New strategies are urgently needed such as immunoprophylactic for prevention of diarrheal diseases. Hyperimmune bovine colostrum (HBC) is an established and effective prophylactic for infectious diarrhea. The commercial HBC product, Travelan® (Immuron Ltd, Australia) targets multiple strains of enterotoxigenic Escherichia coli (ETEC) is highly effective in preventing diarrhea in human clinical studies. Although Travelan® targets ETEC, preliminary studies suggested cross-reactivity with other Gram-negative enteric pathogens including Shigella and Salmonella species. For this study we selected an invasive diarrheal/dysentery-causing enteric pathogen, Shigella, to evaluate the effectiveness of Travelan®, both in vitro and in vivo. Here we demonstrate broad cross-reactivity of Travelan® with all four Shigella spp. (S. flexneri, S. sonnei, S. dysenteriae and S. boydii) and important virulence factor Shigella antigens. Naïve juvenile rhesus macaques (NJRM) were randomized, 8 dosed with Travelan® and 4 with a placebo intragastrically twice daily over 6 days. All NJRM were challenged with S. flexneri 2a strain 2457T on the 4th day of treatment and monitored for diarrheal symptoms. All placebo-treated NJRM displayed acute dysentery symptoms within 24–36 hours of challenge. Two Travelan®-treated NJRM displayed dysentery symptoms and six animals remained healthy and symptom-free post challenge; resulting in 75% efficacy of prevention of shigellosis (p = 0.014). These results strongly indicate that Travelan® is functionally cross-reactive and an effective prophylactic for shigellosis. This has positive implications for the prophylactic use of Travelan® for protection against both ETEC and Shigella spp. diarrheal infections. Future refinement and expansion of pathogens recognized by HBC including Travelan® could revolutionize current management of gastrointestinal infections and outbreaks in travelers’ including military, peacekeepers, humanitarian workers and in populations living in endemic regions of the world.

Preliminary Studies on Site Fidelity, Residence Index, and Population Size of Irrawaddy Dolphins in West Penang, Malaysia

The Irrawaddy dolphin is found in the coastal and estuarine areas of West Penang, Malaysia. Studies were conducted to estimate the site fidelity, residence index, and population size of Irrawaddy dolphins in West Penang. Photo-identification studies were conducted using boat surveys from 2019 to 2021. Thirty-nine marked Irrawaddy dolphins were identified, with thirty-six newly identified individuals and three individuals observed in 2013. Resightings of four individuals indicated that they were found north of Sungai Burung and Sungai Pinang in West Penang. The majority of individuals had low sighting rates, ranging from 2.6 to 7.7%, with three individuals having medium sighting rates, the highest being 15.4%. The residence index was 0.01 for all 36 individuals, and the highest value of 0.36 was recorded for one individual. Using open population models and closed models, the population size was determined to be 64 or and 52, respectively. The results suggest that although there is a population present, it is probably open, as the residence index is low. The population size appeared to be stable from 2013 to 2021. This information will inform conservation managers of the best way forward for the conservation of Irrawaddy dolphins in Penang.

Regioselective Thiol-yne Reaction of Thiol with ((Methyl-d3)sulfonyl)ethyne: Synthesis of (2-((Methyl-d3)sulfonyl)vinyl)sulfides.

Herein, we have developed a new method for the synthesis of ((methyl-d3)sulfonyl)ethyne, which is cost-effective and environmentally friendly and can be synthesized at the gram level. As an ideal thiol-yne reagent, it can be reacted with various types of thiols to afford (Z)- and (E)-type vinyl sulfides under different conditions with high selectivity. In addition, it can complete the conformational transition from Z- to E-type products under suitable conditions, and can also carry out further derivatization smoothly. The deuterium content of all products was greater than 99%. The preliminary mechanistic studies support the visible light-mediated radical course, and herein provide a novel and efficient synthetic strategy for the direct introduction of deuterated methyl groups, enriching the methods for the construction of C-S bond-containing compounds.

Cobalt‐Catalyzed Annulation of o‐Phenylenediamines and Internal Alkynes: Efficient Synthesis of Quinoxaline Derivatives

AbstractA cobalt‐catalyzed annulation of o‐phenylenediamines and internal alkynes for the synthesis of quinoxalines is developed. This method provides a variety of quinoxalines in good to high yields under a simple and mild reaction conditions with molecular O2 as a terminal oxidant. Preliminary mechanistic studies show that a novel reaction mechanism is involved in the current reaction, which is different from the previous reported dicarbonyl compound mechanism via the oxidation of the alkyne.

Preparation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein via Sulfur [18F]Fluoride Exchange Reaction.

Early detection and treatment of cancers can significantly increase patient prognosis and enhance the quality of life of affected patients. The emerging significance of the tumor microenvironment (TME) as a new frontier for cancer diagnosis and therapy may be exploited by radiolabeled tracers for diagnostic imaging techniques such as positron emission tomography (PET). Cancer-associated fibroblasts (CAFs) within the TME are identified by biomarkers such as fibroblast activation protein alpha (FAPα), which are expressed on their surfaces. Targeting FAPα using small-molecule 18F-labeled inhibitors (FAPIs) has recently garnered significant attention for non-invasive tumor visualization using PET. Herein, two potent aryl-fluorosulfate-based FAPIs, 12 and 13, were synthetically prepared, and their inhibition potency was determined using a fluorimetric FAP assay to be IC50 9.63 and 4.17 nM, respectively. Radiofluorination was performed via the sulfur [18F]fluoride exchange ([18F]SuFEx) reaction to furnish [18F]12 and [18F]13 in high activity yields (AY) of 39-56% and molar activities (Am) between 20-55 GBq/µmol. In vitro experiments focused on the stability of the radiolabeled FAPIs after incubation with human serum, liver microsomes and liver cytosol. Preliminary PET studies of the radioligands were performed in healthy mice to investigate the in vivo biodistribution and 18F defluorination rate. Fast pharmacokinetics for the FAP-targeting tracers were retained and considerable bone uptake, caused by either 18F defluorination or radioligand accumulation, was observed. In summary, our findings demonstrate the efficiency of [18F]SuFEx as a radiolabeling method as well as its advantages and limitations with respect to PET tracer development.

Sodium Carbonate-Promoted Formation of 5-Amino-1,2,4-thiadiazoles and 5-Amino-1,2,4-selenadiazoles with Elemental Sulfur and Selenium.

Sodium carbonate-promoted facile synthesis of 5-amino-1,2,4-thiadiazoles and 5-amino-1,2,4-selenadiazoles with elemental sulfur and selenium, respectively, was developed. This method was carried out with O2 in the air as the green oxidant, and it has several advantages, including low cost, low toxicity, and stable sulfur and selenium sources, good to excellent yields with water as the sole byproduct, simple operation, and a broad substrate scope. Preliminary mechanistic studies indicate that the formation of the 1,2,4-thiadiazole ring and the 1,2,4-selenadiazole ring undergoes different processes.

The rhizobacterial strain, Pseudomonas putida AKMP7, causes conditional pathogenesis in Arabidopsis thaliana via negative regulation of salicylic acid signaling, under water stress

We have previously reported a phenomenon of “conditional pathogenesis”, in which, a drought-tolerant rhizobacterium, Pseudomonas putida AKMP7, promotes plant growth under well-watered conditions, while, deteriorating plant health under water-stressed conditions, in Arabidopsis thaliana seedlings. To understand the molecular mechanisms behind this phenomenon, we studied the modulation of salicylic acid (SA) biosynthesis as well as SA-responsive gene expression, involved in systemic acquired resistance (SAR), in A. thaliana, by AKMP7, under well-watered and water-stressed conditions. We found that, the plant SA levels were upregulated by AKMP7, both under, well-watered as well as water-stressed conditions. However, the SA signaling gene, Non-expressor of Pathogenesis Related gene 1 (NPR1) and Pathogenesis Related gene 1 (PR1) were upregulated under well-watered conditions and suppressed under water-stress, in AKMP7 inoculated seedlings. To understand the reason for this, we studied the expression of NPR4, a negative regulator of NPR1, and, NPR3, a negative regulator of PR1. We observed that, AKMP7 suppresses NPR1 and, consequently, PR1 genes, by upregulating NPR4 under water stress. To understand the potential role of NPR4 in conditional-pathogenesis, we performed physiological studies with NPR4 knockout mutants of A. thaliana and found that the NPR4 mutants did not exhibit any signs of the characteristic growth retardation caused by AKMP7 inoculation, under water stress. Preliminary studies with the model pathogen, Pseudomonas syringae, indicate that AKMP7 may lead to enhanced disease suppression under well-watered conditions, but not under water-stress. Taken together, our data suggest that, AKMP7 causes conditional pathogenesis by an overall compromise in plant immune response under water-stress.

Sialyl LewisX glycomimetics bearing an extended anionic chain targeting E- and P- selectin binding sites

Neutrophil binding to vascular P- and E-selectin is the rate-limiting step in the recruitment of immune cells to sites of inflammation. Many diseases, including sickle cell anemia, post-myocardial infarction reperfusion injury, and acute respiratory distress syndrome are characterized by dysregulated inflammation. We have recently reported sialyl Lewisx analogues as potent antagonists of P- and E-selectin and demonstrated their in vivo immunosuppressive activity. A key component of these molecules is a tartrate diester that serves as an acyclic tether to orient the fucoside and the galactoside moiety in the required gauche conformation for optimal binding. The next stage of our study involved attaching an extended carbon chain onto one of the esters. This chain could be utilized to tether other pharmacophores, lipids, and contrast agents in the context of enhancing pharmacological applications through the sialyl Lewisx / receptor-mediated mechanism. Herein, we report our preliminary studies to generate a small library of tartrate based sialyl Lewisx analogues bearing extended carbon chains. Anionic charged chemical entities are attached to take advantage of proximal charged amino acids in the carbohydrate recognition domain of the selectin receptors. Starting with a common azido intermediate, synthesized using copper-catalyzed Huisgen 1,3-dipolar cycloadditions, these molecules demonstrate E- and P-selectin binding properties.

In Ischemic Heart Disease, Reduced Sensitivity to Pressure at the Sternum Accompanies Lower Mortality after Five Years: Evidence from a Randomized Controlled Trial.

Background: Autonomic nervous system dysfunction (ANSD) is associated with negative prognosis of ischemic heart disease (IHD). Elevated periosteal pressure sensitivity (PPS) at the sternum relates to ANSD and sympathetic hyperactivity. Two previous observational case-control studies of the effect of reduction of PPS suggested lower all-cause mortality from IHD and stroke. We now used a specific daily, adjunct, non-pharmacological program of reduction of elevated PPS to test the hypothetical association between the intervention and reduced all-cause mortality in patients with stable IHD in a randomized controlled trial (RCT). Methods: We completed active (n = 106) and passive interventions (n = 107) and compared the five-year mortalities. We also compared the five-year individual all-cause mortality of each participant to approximately 35.000 members of the general population of Denmark. Pooling the mortality data from the active group of the RCT with the two preliminary studies, we registered the mortality following active intervention of 1.168 person-years, compared to 40 million person-years of the pooled general population. Results: We recorded fewer deaths of the active RCT intervention group than of the corresponding control group from the general population (p = 0.01), as well as of the passive RCT intervention group (p = 0.035). The meta-analysis of the three studies together demonstrated reduced 4.2-year all-cause mortality of 60% (p = 0.007). Conclusions: The test of the hypothetical effect of an intervention aimed at the attenuation of ANSD accompanied by a lowered PPS revealed reduced all-cause mortality in patients with stable IHD.

Synthesis, Characterization, and Single-Crystal X-ray Structures of Refractory Metal Compounds as Precursors for the Single-Source Chemical Vapor Deposition of Metal Nitrides.

The chemical vapor deposition of refractory metal nitrides requires volatile precursors and has previously been achieved by using metal complexes containing a variety of imide ligands. Recently, the 1,4-di-tert-butyl-1,3-diazabutadiene (DAD) adduct of bis(tert-butylimide)dichloridemolybdenum(VI) was shown to be an excellent precursor for the single-source CVD of Mo2N thin films. Leveraging the success of this work, we prepared chromium and tungsten compounds with the same framework. Additionally, the framework has been modified slightly to allow the isolation of mono(tert-butylimide)trichloride complexes of vanadium, niobium, tantalum, and molybdenum(V) to extend the search for new vapor-phase precursors. These compounds were all fully characterized using the standard methods of multinuclear magnetic resonance spectroscopy, combustion analysis, and single-crystal X-ray diffraction. Their thermal properties were determined by using thermogravimetric analysis and differential scanning colorimetry to assess their utility as vapor-phase precursors. Finally, preliminary deposition studies were carried out to investigate their potential as single-source CVD precursors.

Design, synthesis and evaluation of novel UDCA-aminopyrimidine hybrids as ATX inhibitors for the treatment of hepatic and pulmonary fibrosis

To discover novel anti-fibrotic agents, a series of UDCA-aminopyrimidine hybrids were designed and synthesized as potent ATX inhibitors by molecular hybridization strategy. The ATX inhibitory activities of all synthesized compounds were evaluated using the LPC choline release assay. The preliminary structure-activity relationship was concluded. Among them, 12a and 12h exhibited the strongest ATX inhibitory activities with IC50 values of 7.62 ± 0.62 and 7.51 ± 0.72 nM respectively, which were 9-fold more effective than the positive control drug GLPG-1690. Molecular docking studies revealed that 12a and 12h occupied the hydrophobic pocket and tunnel of the ATX binding site. The cytotoxicity assay of 12a and 12h revealed that they had no obvious toxicity at concentrations up to 80 μM, therefore their anti-hepatic fibrosis and anti-pulmonary fibrosis activities were further investigated. The results suggested that 12a and 12h significantly decreased the gene and protein expression of α-SMA, COL1A1 and FN in both TGF-β1-induced HSC-LX2 and CCC-HPF-1 cells. In addition, 12a and 12h significantly inhibited cells migration in both TGF-β1-induced HSC-LX2 and CCC-HPF-1 cells. Preliminary mechanistic studies indicated that 12a and 12h exerted anti-hepatic fibrosis and anti-pulmonary fibrosis effects by inhibiting the TGF-β/Smad signaling pathway. Overall, our findings suggested that 12a and 12h might be two promising anti-fibrotic agents, or might serve as two new lead compounds for the further development of anti-fibrotic agents.

Enhancement of dieckol extraction yield from Ecklonia cava through optimization of major variables in generally recognized as safe solvent-based process

Ecklonia cava (EC), an edible brown macroalga abundant in intertidal areas of East Asia (Korea, Japan, and China), contains high-value bioactive compounds such as dieckol, which has antifungal, anti-inflammatory, antitumor, and antihyperlipidemic activities. However, no studies have been reported on the utilization of EC as a biorefinery feedstock, and the design of a more economical and high-yield process is required for the utilization of dieckol for the human healthcare industry. In this study, we designed a bioprocess for the high-yield recovery of dieckol from EC in a generally recognized as safe (GRAS) solvent to facilitate its application in the food and healthcare industries. Preliminary studies identified ethanol as an efficient solvent with the highest dieckol extraction yield (2.9 mg/g biomass). In order to maximize the recovery of dieckol from EC, the major extraction variables (solvent concentration, reaction temperature, and reaction time) were optimized based on statistical methods. Based on the predictive model, the numerical optimization determined that the solution with the highest dieckol content per weight of extract (62.6 vol% ethanol concentration, 54.2°C temperature, 13.2 min) was the optimal extraction condition. Under the determined conditions, the dieckol yield from EC achieved 6.4 mg dieckol/g EC (95.5% agreement with the predicted value). The designed process offers several advantages, including improving the utilization feasibility of EC, utilizing GRAS solvents with potential human applications, short extraction time (13.2 min), maximized process yield, and the highest dieckol recovery compared to previous reports.

First enantioselective total synthesis of human MAO inhibitor (+)-Colveol A

We present the first enantioselective total synthesis of the human MAO inhibitor (+)-colveol A and preliminary studies toward the synthesis of (+)-colveol B. Three strategies, centered on Sharpless asymmetric dihydroxylation, were explored to construct the vicinal syn-dihydroxyl system. The initial attempt involving direct asymmetric dihydroxylation of a chalcone derivative was unsuccessful. Alternatively, successful synthetic routes for (+)-colveol A involved Sharpless dihydroxylation of a cinnamyl ester, a Grignard addition of a resorcinol moiety, Wittig reaction and BBr3-mediated global deprotection of MOM ethers as key steps. The synthesis of (+)-colveol A was accomplished in 30 % yield over 7 steps.

Catalytic Asymmetric α-Alkylation of Ketones with Unactivated Alkyl Halides.

A catalytic, enantioselective method for direct α-alkylation of ketones with unactivated alkyl halides is realized by employing an α-enolizable ketone in a nickel-catalyzed C(sp3)-C(sp3) cross-coupling reaction. The key to the success is attributed to a unique bimetallic ligand. A variety of acyclic ketones and unactivated alkyl iodides can serve as suitable substrates under mild conditions to generate chiral ketones with α-quaternary carbon stereocenters in high yields with good enantioselectivities. A range of transformations based on the ketone moiety are also demonstrated to show the potential application of this method. Preliminary mechanistic studies support a dinickel-catalyzed cross-coupling mechanism.

Treatment of rheumatoid arthritis with dissymmetric fluorine and pyridyl-substituted 3,5-bis(aryl)-4-piperidone derivatives by inhibition of NF-κB and MAPK activation

Inhibition of inflammation-related NF-κB and MAPK activation could treat rheumatoid arthritis (RA). Previously, some fluorine-substituted 3,5-bis(aryl)-4-piperidone derivatives (BAPs) exhibited promising anti-inflammatory activity. Herein, interesting structural optimization was carried out and generated thirty-eight dissymmetric fluorine and pyridyl-substituted BAPs (4a-s and 5a-s). They were confirmed by NMR and HRMS. A preliminary structure–activity relationship was summarized and discovered 3,5-CF3 and 3-pyridyl-substituted 4k exhibited less toxicity and higher anti-inflammatory activity. Preliminary mechanistic studies revealed that 4k inhibited Lipopolysaccharide-induced nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) activation by suppressing LPS-induced phosphorylation levels of NF-κB/p65, NF-κB/IκBα, c-Jun N-terminal kinase (JNK), extracellular regulated protein kinases (ERK), and NF-κB/p38 in RAW264.7 cells. In vivo, 4k inhibited the development of inflammation and synovial proliferation in rat joint tissues, significantly decreasing paw swelling and arthritis index in adjuvant-induced arthritis rats. More importantly, 4k did not affect body weight and splenic index values. Overall, 4k showed optimistic anti-RA effects, which may be developed as a potential multifunctional agent for the clinical treatment of RA.

Construction of Bridged Benzazepines via Photo‐Induced Dearomatization

AbstractBridged benzazepine scaffolds, possessing unique structural and physicochemical activities, are widespread in various natural products and drugs. The construction of these skeletons often requires elaborate synthetic effort with low efficiency. Herein, we develop a simple and divergent approach for constructing various bridged benzazepines by a photocatalytic intermolecular dearomatization of naphthalene derivatives with readily available α‐amino acids. The bridged motif is created via a cascade sequence involving photocatalytic 1,4‐hydroaminoalkylation, alkene isomerization and cyclization. Interestingly, the diastereoselectivity can be regulated through different reaction modes in the cyclization step. Moreover, aminohydroxylation and its further bromination have also been demonstrated to access highly functionalized bridged benzazepines. Preliminary mechanistic studies have been performed to get insights into the mechanism. This method provides a divergent synthetic approach for construction of highly functionalized bridged benzazepines, which have been otherwise difficult to access.

Construction of Bridged Benzazepines via Photo-Induced Dearomatization.

Bridged benzazepine scaffolds, possessing unique structural and physicochemical activities, are widespread in various natural products and drugs. The construction of these skeletons often requires elaborate synthetic effort with low efficiency. Herein, we develop a simple and divergent approach for constructing various bridged benzazepines by a photocatalytic intermolecular dearomatization of naphthalene derivatives with readily available α-amino acids. The bridged motif is created via a cascade sequence involving photocatalytic 1,4-hydroaminoalkylation, alkene isomerization and cyclization. Interestingly, the diastereoselectivity can be regulated through different reaction modes in the cyclization step. Moreover, aminohydroxylation and its further bromination have also been demonstrated to access highly functionalized bridged benzazepines. Preliminary mechanistic studies have been performed to get insights into the mechanism. This method provides a divergent synthetic approach for construction of highly functionalized bridged benzazepines, which have been otherwise difficult to access.

Huanglian Jiedu Wan intervened with “Shi-Re Shanghuo” syndrome through regulating immune balance mediated by biomarker succinate

With increasing stress in daily life and work, subhealth conditions induced by “Shi-Re Shanghuo” syndrome was gradually universal. “Huanglian Jiedu Wan” (HLJDW) was the first new syndrome Chinese medicine approved for the treatment of “Shi-Re Shanghuo” with promising clinical efficacy. Preliminary small-sample clinical studies have identified some notable biomarkers (succinate, 4-hydroxynonenal, etc.). However, the correlation and underlying mechanism between these biomarkers of HLJDW intervention on “Shi-Re Shanghuo” syndrome remained ambiguous. Therefore, this study was designed as a randomized, double-blind, multicenter, placebo-controlled Phase II clinical trial, employing integrated analysis techniques such as non-targeted and targeted metabolomics, salivary microbiota, proteomics, parallel peaction monitoring, molecular docking and surface plasmon resonance (SPR). The results of the correlation analysis indicated that HLJDW could mediate the balance between inflammation and immunity through succinate produced via host and microbial source to intervene “Shi-Re Shanghuo” syndrome. Further through the HIF1α/MMP9 pathway, succinate regulated downstream arachidonic acid metabolism, particularly the lipid peroxidation product 4-hydroxynonenal. Finally, an animal model of recurrent oral ulcers induced by “Shi-Re Shang Huo” was established and HLJDW was used for intervention, key essential indicators (succinate, glutamine, 4-hydroxynonenal, arachidonic acid metabolism) essential in the potential pathway HIF1α/MMP9 discovered in clinical practice were validated. The results were found to be consistent with our clinical findings. Taken together, succinate was observed as an important signal that triggered immune responses, which might serve as a key regulatory metabolic switch or marker of “Shi-Re Shanghuo” syndrome treated with HLJDW.

Pelaksanaan Quality Control Pesawat Sinar X di Pelayanan Radiodiagnostik

Background: Quality Control can be used as a monitoring of the reliability of X-Ray Unit during the validity period of the Conformity Test Certificate. During the use of X-ray Unit, there is the potential for damage to components during the validity period of the certificate of passing the Compliance Test. If the X-Ray Unit Reliability Test is only carried out during the Compliance Test, then if there is a decrease in the quality and safety of the X-ray Unit it cannot be immediately known. This has the potential to endanger patients, radiation workers and the public. In Banyumas Regency, there are 80 Radiation Source Utilization Permits spread across 34 radiodiagnostic installation. Preliminary studies show that not all radiodiagnostic installation carry out routine X-ray machine reliability tests according to the Keputusan Menteri Kesehatan Republik Indonesia Nomor 1250/Menkes/SK/XII/2009 Tentang Pedoman Kendali Mutu (Quality Control) Peralatan Radiodiagnostik.
 Method: This research type is qualitative with survey of 20 radiodiagnostic installation using a questionnaire instrument. Quality control conducted periodically includes kVp accuracy test, linearity and reproducibility mA, exposure time accuracy test, tube leak test, collimator beam suitability test, collimator shutter efficiency test, collimator light strength test, HVL measurement, implementation of reject analysis program and availability and qualifications of quality control officers and availability of quality control equipment. Then the data will be grouped based on research objectives and presented descriptively.
 Result: From the results of data collection, 1 hospital did not have a quality control officer and 4 hospitals had a quality control officer with an educational background of Diploma IV in Radiology Engineering without any Radiology Equipment Quality Control training. Meanwhile, 15 hospitals have quality control officers with an educational background in the Medical Physics Undergraduate Program and have attended training in Quality Control of Radiology Equipment. Of the 20 hospital radiology installations, there were 7 hospitals that did not carry out the Reject Analysis Program. This was done with the assumption that Digital Radiography had been used in both the CR and DR modalities. A number of 13 hospitals continued to carry out the Reject Analysis Program even though they had used Digital Radiography. Of the 20 hospital radiology installations, there are 6 hospitals that independently carry out X-ray unit testing within the framework of a quality control program. However, only 1 hospital conducts regular testing. Testing is also limited to the accuracy of the collimator field and the strong light of the collimator. Fourteen hospitals did not carry out a quality control program independently but only carried out an X-ray unit calibration test once a year which was carried out by BPFK and an X-ray unit distributor company.
 Conclusion: The implementation of quality control of x-ray machines on a regular basis has not been carried out by all radiodiagnostic services, even though they already have quality control officers. One of the reasons is the availability of quality control equipment needed for testing and supervision of radiodiagnostic service management. The role of management of radiodiagnostic services is needed to overcome these problems.
 
 Keyword : Quality Control Programe, Compliance Test, X-Ray Unit