Research on the Development of Methods for Detection of Substandard and Falsified Medicines by Clarifying Their Pharmaceutical Characteristics Using Modern Technology.

The existence of substandard and falsified medicines threatens people's health and causes economic losses as well as a loss of trust in medicines. As the distribution of pharmaceuticals becomes more globalized and the spread of substandard and falsified medicines continues worldwide, pharmaceutical security measures must be strengthened. To eradicate substandard and falsified medicines, our group is conducting fact-finding investigations of medicines distributed in lower middle-income countries (LMICs) and on the Internet. From the perspective of pharmaceutics, such as physical assessment of medicines, we are working to clarify the actual situation and develop methods to detect substandard and falsified medicines. We have collected substandard and falsified medicines distributed in LMICs and on the Internet and performed pharmacopoeial tests, mainly using HPLC, which is a basic analytic method. In addition to quality evaluation, we have evaluated the applicability of various analytic methods, including observation of pharmaceuticals using an electron microscope, Raman scattering analysis, near-IR spectroscopic analysis, chemical imaging, and X-ray computed tomography (CT) to detect substandard and falsified medicines, and we have clarified their limitations. We also developed a small-scale quality screening method using statistical techniques. We are engaged in the development of methods to monitor the distribution of illegal medicines and evolve research in forensic and policy science. These efforts will contribute to the eradication of substandard and falsified medicines. Herein, I describe our experience in the development of detection methods and elucidation of the pharmaceutical status of substandard and falsified medicines using novel technologies.

A longer-chain acylated derivative of Dictyostelium differentiation-inducing factor-1 enhances the antimalarial activity against Plasmodium parasites.

The spread of malarial parasites resistant to first-line treatments such as artemisinin combination therapies is a global health concern. Differentiation-inducing factor 1 (DIF-1) is a chlorinated alkylphenone (1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) hexan-1-one) originally found in the cellular slime mould Dictyostelium discoideum. We previously showed that some derivatives of DIF-1, particularly DIF-1(+2) (1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) octan-1-one), exert potent antimalarial activities. In this study, we synthesised DIF-1(+3) (1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) nonan-1-one). We then evaluated the effects of DIF-1(+3) in vitro on Plasmodium falciparum and in vivo over 7 days (50-100 mg/kg/day) in a mouse model of Plasmodium berghei. DIF-1(+3) exhibited a half-maximal inhibitory concentration of approximately 20-30 % of DIF-1(+2) in three laboratory strains with a selectivity index > 263, including in strains resistant to chloroquine and artemisinin. Parasite growth and multiplication were almost completely suppressed by treatment with 100 mg/kg DIF-1(+3). The survival time of infected mice was significantly increased (P = 0.006) with no apparent adverse effects. In summary, addition of an acyl group to DIF-1(+2) to prepare DIF-1(+3) substantially enhanced antimalarial activity, even in drug-resistant malaria, indicating the potential of applying DIF-1(+3) for malaria treatment.

Detection of drug-resistant malaria in resource-limited settings: efficient and high-throughput surveillance of artemisinin and partner drug resistance.

OBJECTIVES: Artemisinin-resistant Plasmodium falciparum malaria is currently spreading globally, including in Africa. Artemisinin resistance also leads to resistance to partner drugs used in artemisinin-based combination therapies. Sequencing of kelch13, which is associated with artemisinin resistance, culture-based partner drug susceptibility tests, and ELISA-based growth measurement are conventionally used to monitor resistance; however, their application is challenging in resource-limited settings. METHODS: An experimental package for field studies with minimum human/material requirements was developed. RESULTS: First, qPCR-based SNP assay was applied in artemisinin resistance screening, which can detect mutations within 1 h and facilitate sample selection for subsequent processes. It had 100% sensitivity and specificity compared with DNA sequencing in the detection of the two common artemisinin resistance mutations in Uganda, C469Y and A675V. Moreover, in the partner drug susceptibility test, the cultured samples were dry-preserved on a 96-well filter paper plate and shipped to the central laboratory. Parasite growth was measured by ELISA using redissolved samples. It well reproduced the results of direct ELISA, reducing significant workload in the field (Pearson correlation coefficient: 0.984; 95% CI: 0.975-0.990). CONCLUSIONS: Large-scale and sustainable monitoring is required urgently to track rapidly spreading drug-resistant malaria. In malaria-endemic areas, where research resources are often limited, simplicity and feasibility of the procedure is especially important. Our approach combines a qPCR-based rapid test, which is also applicable to point-of-care diagnosis of artemisinin resistance and centralized analysis of ex vivo culture. The approach could improve efficiency of field experiments and accelerate global drug resistance surveillance.

Human ocular thelaziasis with genetic analysis in Niigata Prefecture, Japan: A case report on an emerging zoonosis.

Purpose: We report the clinical findings and molecular identification of ocular Thelazia callipaeda from Niigata Prefecture in the Hokuriku area of Japan during winter. Observations: A 77-year-old male visited an ophthalmology clinic in Niigata Prefecture in January 2022 after a 2-week-duration of a conjunctival injection in the left eye and foreign body sensation. Slit-lamp microscopy revealed 11 active nematodes in the left conjunctival sac. Morphological characteristics included longer female body length than male, buccal cavity lacking teeth and lips, and serrated striations along the body surface. The specimens were determined to be T. callipaeda. Genetic analysis of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene revealed an h9 haplotype. Conclusions and Importance: T. callipaeda infection, especially the h9 haplotype, commonly occurs in western Japan owing to its higher incidence in warmer climates, suggesting the origin of the case. Here, we report a human case of Thelaziasis diagnosed in a cold region of Japan (the Hokuriku area) during winter. This human case of T. callipaeda infection from a cold, previously unassociated region, raises concerns about the potential geographical widening of its distribution, and further investigation may be warranted to prevent its spread.

Multi-anode enhanced the bioelectricity generation in air-cathode microbial fuel cells towards energy self-sustaining wastewater treatment.

Microbial fuel cells (MFCs) hold considerable promise for harnessing the substantial energy resources present in wastewater. However, their practical application in wastewater treatment is limited by inadequate removal of organic matter and inefficient power recovery. Previous studies have investigated aeration as a method to enhance the removal of organic matter, but this method is energy-intensive. To address this issue, this study proposed using MFC-recovered bioelectricity for aeration, thereby mitigating the associated expenses. An air-cathode MFC with multi-anode was constructed and optimized to maximize electricity supply for aeration. Carbon-felt anodes were chosen as the most effective anode configuration, due to the high abundance of electroactive bacteria and genes observed in the biofilm generated on their surface. By incorporating six carbon felt anodes, the MFC achieved a 1.7 and 1.1 fold enhancement in the maximum power and current density, respectively. The optimized MFC unit achieved a stable current density of 0.32 A/m2 and achieved COD removal of 60% in the long-term operation of 140 days in a 50 L reactor. In a reactor scaled up to 1600 L, 72 MFCs successfully powered a mini air pump work for 10 s after an 81-s charging period. The intermittent aeration resulted in partial increases in DO concentrations to 0.03-3.5 mg/L, which is expected to promote the removal of nitrogen compounds by the nitrification-anammox process. These groundbreaking results lay the foundation for self-sustaining wastewater treatment technologies.

Phylogenetic analyses of Chilomastix and Retortamonas species using in vitro excysted flagellates.

In vitro excystation of cysts of microscopically identified Chilomastix mesnili and Retortamonas sp. isolated from Japanese macaques and Retortamonas sp. isolated from small Indian mongooses could be induced using an established protocol for Giardia intestinalis and subsequently by culturing with H2S-rich Robinson's medium supplemented with Desulfovibrio desulfuricans. Excystation usually began 2 h after incubation in Robinson's medium. DNA was isolated from excysted flagellates after 4 h of incubation or from cultured excysted flagellates. Phylogenetic analysis based on their 18S rRNA genes revealed that two isolates of C. mesnili from Japanese macaques belonged to the same cluster as a C. mesnili isolate from humans, whereas a mammalian Retortamonas sp. isolate from a small Indian mongoose belonged to the same cluster as that of an amphibian Retortamonas spp. isolate from a 'poison arrow frog' [sequence identity to AF439347 (94.9%)]. These results suggest that the sequence homology of the 18S rRNA gene of the two C. mesnili isolates from Japanese macaques was similar to that of humans, in addition to the morphological similarity, and Retortamonas sp. infection of the amphibian type in the small Indian mongoose highlighted the possibility of the effect of host feeding habitats.

Dehalococcoides mccartyi strain NIT01 grows more stably in vessels made of pure titanium rather than the stainless alloy SUS304.

Advances in many isolation studies have revealed that pure Dehalococcoides grow stably, although the large-scale pure cultivation of Dehalococcoides has yet to be established. In this study, 7 L-culturing of Dehalococcoides mccartyi strain NIT01 was first performed using vessels made of glass and stainless alloy SUS304. All batches cultured in the glass vessel successfully dechlorinated >95% of 1 mM trichloroethene (TCE) to ethene (ETH), whereas only 5 out of 13 batches cultured in the SUS304 vessel did the same. The difference in dechlorination efficiency suggested the possible inhibition of dechlorination by SUS304. Also, the strain NIT01 showed long delays in dechlorination with pieces of SUS316, steel, and a repeatedly used SUS304, but not with titanium. The repeatedly used SUS304 cracked and increased the Fe2+ concentration to ≥76 µM. Dechlorination by this strain was also inhibited with ≥1000 µM Fe2+ and ≥23 µM Cr3+ but not with ≤100 µM Ni2+ , suggesting that Cr3+ eluted from solid stainless alloys inhibited the dechlorination. Culturing in a titanium vessel instead of a stainless alloy showed the complete dechlorination of 1 mM TCE within 12-28 days with a growth yield of 2.7 × 107 cells/µmol-released Cl- , even after repeating use of the vessels six times.

Soil organic matter and nutrient availability affect the applicability of low-carbon energy source in Dehalococcoides-augmented soil.

Dehalococcoides is a functional microorganism that completely dechlorinates trichloroethene (TCE). Augmentation with pure Dehalococcoides is important for reducing environmental disturbances that accompany bioaugmentation. However, the applicability of Dehalococcoides-bioaugmentation to contaminated soils is unclear. In this study, seven low-carbon energy sources (methanol, formate, acetate, ethanol, lactate, citrate, and benzoate) were used as electron donors for Dehalococcides to evaluate its applicability in remediating TCE-contaminated soils. Soil microcosms supplemented with ethanol, formate, or lactate showed relatively high dechlorination activity within 111-180 days. The functional gene profiles predicted by PICRUSt2 from 16 S rRNA gene sequences were similar in the proportions of dehydrogenases, which initiate electron donor oxidation, in all soils and did not seem to reflect Dehalococcoides-bioaugmentation applicability. Soils with higher organic matter content (>3.2%; dry weight base) and protein concentration (>1.6 µg/mL) supported complete dechlorination. These results suggest that organic matter and nutrient availability mainly affect successful TCE dechlorination in Dehalococcoides-augmented soils. The study offers significant experimental support for comprehending the suitability of low-carbon energy sources in successful bioaugmentation, aiming to mitigate environmental disturbances associated with the process.

Polyphasic Characterization of Geotalea uranireducens NIT-SL11 Newly Isolated from a Complex of Sewage Sludge and Microbially Reduced Graphene Oxide.

Graphene oxide (GO), a chemically oxidized sheet of graphite, has been used as a conductive carbon carrier of microbes to boost various bioelectrochemical reactions. However, the types of microbes that can reduce GO have rarely been investigated. In this study, a strain of GO-reducing bacteria, named NIT-SL11, which was obtained from a hydrogel of microbially reduced GO and anaerobic sludge that converts sewage to electricity, was phylogenically identified as a novel strain of Geotalea uraniireducens. Considering the current lack of information on the electrogenic ability of the bacterium and its physicochemical and chemotaxonomic characteristics, the polyphasic characterization of the Geotalea uraniireducens strain NIT-SL11 was performed. NIT-SL11 utilized various organic acids, such as lactate, benzoate, and formate, as electron donors and exhibited respiration using GO, electrodes, fumarate, and malate. The strain contained C16:1ω7c and C16:0 as the major fatty acids and MK-8 and 9 as the major respiratory quinones. The complete genome of NIT-SL11 was 4.7 Mbp in size with a G+C content of 60.9%, and it encoded 80 putative c-type cytochromes and 23 type IV pili-related proteins. The possible extracellular electron transfer (EET) pathways of the strain were the porin-cytochrome (Pcc) EET pathway and type IV pili-based pathway.

A program of successive gene expression in mouse one-cell embryos.

At the moment of union in fertilization, sperm and oocyte are transcriptionally silent. The ensuing onset of embryonic transcription (embryonic genome activation [EGA]) is critical for development, yet its timing and profile remain elusive in any vertebrate species. We here dissect transcription during EGA by high-resolution single-cell RNA sequencing of precisely synchronized mouse one-cell embryos. This reveals a program of embryonic gene expression (immediate EGA [iEGA]) initiating within 4 h of fertilization. Expression during iEGA produces canonically spliced transcripts, occurs substantially from the maternal genome, and is mostly downregulated at the two-cell stage. Transcribed genes predict regulation by transcription factors (TFs) associated with cancer, including c-Myc. Blocking c-Myc or other predicted regulatory TF activities disrupts iEGA and induces acute developmental arrest. These findings illuminate intracellular mechanisms that regulate the onset of mammalian development and hold promise for the study of cancer.

A Case of Neuroretinitis Following COVID-19 Vaccination.

PURPOSE: To present a case of neuroretinitis following an mRNA COVID-19 vaccination. CASE REPORT: A 78-year-old healthy woman was presented with blurry vision in her left eye 1 day after receiving the third dose of the Pfizer-BioNTech COVID-19 vaccine. The ocular examination revealed an optic disc swelling and retinal thickening of the macula with subretinal fluid in the left eye. The fluorescein angiography revealed hyperfluorescence of the left optic disc. The neuroretinitis resolved gradually after taking azithromycin and prednisolone orally. CONCLUSIONS: This is the first report of unilateral neuroretinitis following COVID-19 vaccination, implying a potential association between the mRNA vaccine and neuroretinitis.

Reduced graphene oxide increases cells with enlarged outer membrane of Citrifermentans bremense and exopolysaccharides secretion.

Conductive carbons can boost anaerobic microbial metabolism by assisting extracellular electron transfer (EET), and their chemistry affects microbial metabolism. Graphene oxide (GO), a chemically oxidized sheet of graphite, has been used in various bioelectrochemical systems, although its mechanism is rarely understood. This study revealed specific metabolic responses to reduced GO (rGO) in an electrogenic strain R4 of Citrifermentans bremense, recently renamed from "Geobacter bremensis," in comparison to that with graphite felt (GF). Specifically, the change in growth from planktonic cells to biofilm with an enlarged outer membrane. The mRNA profile supported the fact that rGO upregulated the 14 genes related to the exopolysaccharides (EPS) secretion and biofilm formation, which is more than that in GF (4 genes). While GF upregulated the 35 genes involved in cell motility, which is more than that in rGO (8 genes). The heme protein profile suggested that both carbons induced similar EET pathways involving OmcA/MtrC and OmcS; however, GO specifically induced PilQ. These findings show that the chemistry of conductive carbon differentiates metabolism, especially affecting cellular morphology or living form, rather than electron transfer metabolism.

Gene expression of axenically-isolated clinical Entamoeba histolytica strains and its impact on disease severity of amebiasis.

The severity of Entamoeba histolytica infection is determined by host immunology, pathogen virulence, and the intestinal environment. Conventional research for assessing pathogen virulence has been mainly performed using laboratory strains, such as a virulent HM-1: IMSS (HM-1) and an avirulent Rahman, under various artificial environmental conditions because of the difficulties of axenic isolation of the clinical strains. However, it is still unclear whether scientific knowledge based on laboratory strains are universally applicable to the true pathogenesis. Hereby, we performed transcriptomic analysis of clinical strains from patients with different degrees of disease severity, as well as HM-1 under different conditions. Even after several months of axenization, Clinical strains show the distinct profile in gene expression during in vitro passage, moreover, difference between any 2 of these strains was much greater than the changes on the liver challenge. Interestingly, 26 DEGs, which were closely related to the biological functions, were oppositely up- or down regulated between virulent Ax 19 (liver abscess) and avirulent Ax 11 (asymptomatic carrier). Additionally, RNAseq using laboratory strain (HM1) showed more than half of genes were differently expressed between continuously in vitro passaged HM1 (in vitro HM1) and periodically liver passaged HM1 (virulent HM1), which was much greater than the changes on the liver passage of virulent HM1. Also, transcriptomic analysis of a laboratory strain revealed that continuous environmental stress enhances its virulence via a shift in its gene expression profile. Changes in gene expression patterns on liver abscess formation were not consistent between clinical and laboratory strains.

Elevated ratio of serum anandamide to arachidonic acid intake in community-dwelling women with high depressive symptoms.

OBJECTIVES: The purpose of the present study was to investigate the serum levels of endocannabinoids (eCBs; anandamide: AEA and 2-arachidonoylglycerol: 2-AG) and daily intake of polyunsaturated fatty acids (PUFAs; arachidonic acid: ARA, docosahexaenoic acid: DHA, and eicosapentaenoic acid: EPA) among subjects with high and low depressive symptoms. METHODS: The participants comprised female community-dwellers aged 40 years or older in Japan. Among 208 females, fourteen participants with high depressive symptoms and ten participants with low depressive symptoms were selected for this study. The depressive symptoms were measured by the Japanese version of the Centre for Epidemiologic Studies Depression Scale (CES-D). The daily intake of PUFAs were assessed utilising the brief-type self-administered diet history questionnaire. The blood samples were analysed for AEA, 2-AG, and the CB receptor 1 gene (CNR1) single nucleotide polymorphism (SNP) rs806377. RESULTS: The ratio of AEA serum level to ARA intake (AEA/ARA) in high depressive participants was significantly higher compared with those in low depressive participants even after controlling for confounders, whereas there were no significant differences in the serum concentrations of eCBs, daily intake of PUFAs, as well as the CNR1 SNP (rs806377) between the high and low CES-D scored groups. CONCLUSION: The elevated level of AEA/ARA among high depressive participants suggests that the conversion rate of ARA to AEA may be accelerated in depressive individuals.

Formate: A promising electron donor to enhance trichloroethene-to-ethene dechlorination in Dehalococcoides-augmented groundwater ecosystems with minimal bacterial growth.

Various substrates have been used to stimulate habitat microbes in chloroethene-contaminated groundwater, however, the specific efficiency and minimum growth of microbes have rarely been studied. This study investigated the effects of seven substrates on trichloroethene (TCE) dechlorination by augmentation of groundwater with Dehalococcoides mccartyi NIT01 and its contribution to the microbial community. Three out of eight test groups completed dechlorination of 1 mM TCE-to-ethene in varying durations; groundwater supplemented with formate (FOR) required 78 days, whereas the microcosms with lactate (LAC) and citrate (CIT) required approximately twice as long (143 days). The calculated efficiency of how much produced H2 was used in dechlorination indicated a higher efficiency in FOR (36%) compared with LAC (1.9%) or CIT (2.9%). FOR showed lower microbial growth (3.4 × 105 copies/mL) than LAC (1.5 × 106) or CIT (4.4 × 106), and maintained a higher Shannon diversity index (5.65) than LAC (4.97) and CIT (4.30). The rapid and higher H2 transfer efficiency with lower bacterial growth by using formate was attributed to the slightly positive Gibbs free energy identified in H2 production requiring a H2-utilizer, lower carbon in the molecule, and adaptation to metabolic potential of the original groundwater microbiome. Formate is, therefore, a promising electron donor for rapid Dehalococcoides-augmented remediation with minimum bacterial growth. Sequential transferring of the FOR culture successfully maintained TCE-to-ethene dechlorination activity and enriched the members of genera Dehalococcoides (33%), Methanosphaerula (23%), Rectinema (13%), and Desulfitobacterium (5.6%). This suggests that formate is transferred to H2 and acetate, and provided to Dehalococcoides.

Screening and quantification of undeclared PGF2α analogs in eyelash-enhancing cosmetic serums using LC-MS/MS.

In recent years, cosmetics deemed equivalent to pharmaceutical products containing prostaglandin F2α (PGF2α) analogs have been distributed overseas in the form of eyelash serums that can be purchased via the internet. The purpose of this study was to investigate the presence or absence of PGF2α analogs in eyelash serums procured in Japan via the internet to elucidate the actual composition. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurement system was developed for the determination of 14 PGF2α analogs in cosmetic serums. In total, 64 eyelash serum samples were purchased from 34 websites. After pretreatment, eyelash serum samples were screened for PGF2α analogs using the LC-MS/MS system. Products containing PGF2α analogs were subjected to quantification of these compounds. Of the 64 products, four were found to contain bimatoprost, among which, three did not indicate their contents on their package labels. In contrast, no samples were found to contain latanoprost, travoprost, or tafluprost, which are prescribed for glaucoma treatment. Additionally, eight products contained other PGF2α analogs, which have not been used as pharmaceuticals. The ease of access to cosmetic serums containing PGF2α analogs via online purchases presents a risk of serious side effects, particularly when consumers are not informed of their contents on the packages. This issue requires serious consideration to avoid the incorporation of pharmaceutical substances into cosmetic products.

Simultaneous removal of organic matter and nitrogen compounds by partitioned aeration in a 226 L-scale microbial fuel cell.

Although microbial fuel cells (MFCs) have been widely studied as wastewater treatment technologies that convert organic matter to electricity, there are few reports of large-scale MFCs that treat both organic matter and nitrogen compounds. In this study, a 226 L reactor equipped with 27 MFC units was partially aerated at 10% of its total volume. The MFC unit consists of a cylindrical air core covered with a carbon-based air cathode, an anion exchange membrane, and a graphite non-woven fabric anode. The air-cathode MFC with 13 L min-1 aeration rate produced a current density of 0.0012-0.15 A m-2 with 40 to >93% biological oxygen demand (BOD) removal to have an effluent BOD of <5-36 mg L-1 at a hydraulic retention time (HRT) of 12-47 h. Meanwhile, 55 ± 17% of the total nitrogen (TN) was removed, resulting in 9.7 ± 3.8 mg L-1 TN in the effluent, although the TN removal was limited at ≥20 °C. The mono-exponential regression for BOD and TN (≥20 °C) estimated that an HRT of 21 h could meet the Japanese effluent quality standards of BOD and TN. Calculation of the total energy recovered via current generation and energy consumed by aeration suggested an energy consumption of 0.22 kW h m-3. Decreasing the aeration rate and HRT in the reactor would further reduce energy consumption and increase energy production.

Effectiveness of immunization activities on measles and rubella immunity among individuals in East Sepik, Papua New Guinea: A cross-sectional study.

Objectives: This study aimed to assess measles and rubella immunity by measuring virus-specific immunoglobulin G (IgG) prevalence among individuals and evaluate the effectiveness of recent supplementary immunization activities (SIAs) by comparing the antibody positivity rates of the SIA target age groups in 2015 with those in 2019 as measles and rubella are endemic in Papua New Guinea. Methods: A cross-sectional study. The measles- and rubella-specific IgG levels of patients aged ≥1 year at two clinics in East Sepik province, Papua New Guinea were assessed with commercially available virus-specific IgG EIA kits. Results: In total, 297 people participated in the study and 278 samples with sufficient volume, relevant information, and age inclusion criteria were analyzed. The overall IgG prevalence rates were 62.6% for measles and 82.0% for rubella. The age groups targeted in the 2019 SIAs had a higher IgG prevalence than those targeted in the 2015 SIAs for both the infectious diseases. Moreover, the IgG prevalence for rubella was higher than measles in these groups. Conclusions: The anti-measles and anti-rubella IgG prevalence in the target groups were lower than those required for herd immunity. The immunization program should be emphasized to eliminate measles and rubella. Further population-based studies are warranted.

Nano Pd doped Ni foam electrode stimulated electrochemical reduction of tetrabromobisphenol A: Optimization strategies and function mechanism.

Tetrabromobisphenol A (TBBPA), a hazardous and persistent flame retardant, has been widely detected in the natural aquatic system. The acceleration of reductive debromination (rate-limiting process) is vital during the decomposition and detoxification of TBBPA. This study achieved superior TBBPA electrochemical reductive debromination performance by nano Pd doped Ni foam electrode (4.8 times higher than Ni foam electrode). The optimal TBBPA reductive debromination performance was obtained under -1.2 V of cathode potential, 1.2 wt% of Pd loading, 10 mg L-1 of TBBPA and 100 mM of Na2SO4 as the electrolyte solution. UPLC-QTOF-MS verified that Br atoms in TBBPA were removed sequentially to form bisphenol A as the major product. Most TBBPA was reductively debrominated by atomic H* through indirect hydrodebromination, evidenced by the atomic H* quenching test. The higher solution conductivity and appropriate TBBPA concentration would contribute to the debromination efficiency. Excessive H2 generation whether by over negative potential or H atom richness electrolyte largely disturbed the reaction process and restricted the debromination. The improved generation of reductant (H*)adsPd was the most significant, while excessive Pd loading would make aggregation and limit the debromination efficiency. The study confirmed the optimization strategies of conditions for Pd/Ni foam electrode and revealed the related function mechanism for stimulating TBBPA electrochemical reduction, giving suggestions for the efficient removal of TBBPA in the aquatic environment.