Chemical structures of polyketides and alkaloids isolated from a culture of fungus Curvularia moringae.

Seven new polyketides [moringols I-VII (1-7)], a new alkaloid [moringamine I (8)], and seven known compounds (9-15) were isolated from the fungus Curvularia moringae JKYM-KR4. The planar chemical structures and relative configurations of the new compounds were elucidated by high-resolution mass spectrometry, 1D and 2D NMR spectroscopy, and DP4+ analysis using the calculated 13C NMR chemical shifts. For moringols I and II (1 and 2), the planar chemical structures and relative configurations were confirmed using X-ray crystallography. The absolute configurations of 1-6 and 8 were determined by ECD calculations. Among the isolated compounds, terpestacin (14) moderately inhibited the proliferation of HT-29 cells.

Risk factors for lenvatinib-induced palmar-plantar erythrodysesthesia syndrome in patients with hepatocellular carcinoma: A retrospective study.

AIM: Lenvatinib mesylate (LEN) is an oral tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). HCC treatment with LEN is associated with a very high incidence of adverse events. This study was aimed at investigating the incidence of LEN-induced palmar-planter erythrodysesthesia syndrome (PPES) and its relationship with patient demographics by analyzing clinical laboratory data of LEN-treated patients with HCC. METHODS: This was a single-centre, retrospective study of patients with HCC who received LEN between April 19, 2018, and September 30, 2020. The observation period was from 1 week before the start of LEN administration to 1 month after the end of administration. RESULTS: Overall, 75 patients with HCC were enrolled. LEN-induced PPES was found in 48.0% (36/75 patients). In these patients, alkaline phosphatase (ALP), γ-Glutamyl transpeptidase (γ-GTP) and monocytes (MONO) were significantly high (ALP: p = 1.32 × 10-3, γ-GTP: p = 4.25 × 10-3 and MONO: p = 0.013). The cut off values of ALP, γ-GTP and MONO for LEN-induced PPES were estimated at 573 U/L, 89 U/L, and 310 counts/µL, respectively. In the multivariate analysis, γ-GTP and MONO were independent risk factors for LEN-induced PPES. CONCLUSIONS: High γ-GTP and high MONO were risk factors for LEN-induced PPES.

Removal of tritiated water molecules by isotope exchange reaction between H2O vapor and tritium water.

Developing a cost-effective method for separating and concentrating tritium water (HTO) from light water (H2O) without consuming additional energy is crucial for achieving reliable and safe nuclear fission and fusion energy technologies. However, this presents a significant challenge because of the difficulties in obtaining basic information, such as the chemical and physical properties of HTO molecules. Here, we investigate the isotope exchange reaction (IER) between HTO molecules in H2O solution and H2O vapor in the atmosphere. The reduction and purification rates of HTO-containing water were measured by varying the system conditions, such as temperature (20-50 °C) and humidity (50 %-90 %), under an equilibrium state between the liquid phase (water) and vapor phase (air). Our findings indicate that the concentration of HTO in the solution can be significantly reduced by increasing H2O vapor in the atmosphere. This result can be quantitatively explained by considering the entropy of mixing between the solution and vapor phases. The results obtained here provide both basic understanding on the exchange process between liquid- and vapor-water molecules and a passive technology for treating HTO-containing water.

Clinical Efficacy of Therapeutic Agents for Clostridioides difficile Infection Based on Four Severity Classifications.

Japanese guidelines recommend metronidazole (MNZ) and vancomycin (VCM) for non-severe and severe cases of Clostridioides difficile infection (CDI), respectively. In the present study, we investigated the use of CDI antimicrobials and evaluated their clinical efficacy and validity using four severity classifications. A retrospective chart review was conducted using the data of 137 inpatients with initially positive C. difficile toxin test results and the initiation of CDI antimicrobials between April 2015 and March 2019. Patients treated with VCM or oral MNZ were included for clinical efficacy analysis of CDI antimicrobials and validation of severity classifications. The endpoints were CDI recurrence, 30-day mortality, and diarrhea cure rates. No significant differences were found between the VCM and oral MNZ groups in the CDI recurrence rate (10.4% vs. 12.7%, P = 0.707), 30-day mortality rate (12.5% vs. 5.6%, P = 0.162), and diarrhea cure rate (61.9% vs. 72.7%, P = 0.238), regardless of severity. Treatment with oral MNZ for non-severe cases was promising, confirming its usefulness according to Japanese guidelines. Further investigation of the clinical efficacy of oral MNZ in patients with first-episode CDI and evaluation of the preferred severity classification are warranted.

Antiproliferative Activities of Cynaropicrin and Related Compounds against Cancer Stem Cells.

Glioblastoma (GBM) has a high mortality rate despite the availability of various cancer treatment options. Although cancer stem cells (CSCs) have been associated with poor prognosis and metastasis, and play an important role in the resistance to existing anticancer drugs and radiation; no CSC-targeting drugs are currently approved in clinical practice. Therefore, the development of antiproliferative agents against CSCs is urgently required. In this study, we evaluated the antiproliferative activities of 21 sesquiterpenoids against human GBM U-251 MG CSCs and U-251 MG non-CSCs. Particularly, the guaianolide sesquiterpene lactone cynaropicrin (1) showed strong antiproliferative activity against U-251 MG CSCs (IC50 = 20.4 µM) and U-251 MG non-CSCs (IC50 = 10.9 µM). Accordingly, we synthesized six derivatives of 1 and investigated their structure-activity relationships. Most of the guaianolide sesquiterpene lactones with the α-methylene-γ-butyrolactone moiety showed antiproliferative activities against U-251 MG cells. We conclude that the 5,7,5-ring and the α-methylene-γ-butyrolactone moiety are both important for antiproliferative activities against U-251 MG cells. The results of this study suggest that the α,ß-unsaturated carbonyl moiety, which has recently become a research hotspot in drug discovery, is the active center of 1. Therefore, we consider 1 as a potential lead for developing novel drugs targeting CSCs.

Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7.

The Wnt/ß-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/ß-catenin signaling pathway, named LPD-01 (1), and 1 inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that 1 inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells. Therefore, we have attempted to identify the target proteins of 1 in HT-29 cells. Firstly, we investigated the effect on the expression levels of the Wnt/ß-catenin signaling pathway-related proteins. As a result, 1 inhibited the expression of target proteins of Wnt/ß-catenin signaling pathway (c-Myc and Survivin) and their genes, whereas the amount of transcriptional co-activator (ß-catenin) was not decreased, suggesting that 1 inhibited the Wnt/ß-catenin signaling pathway without affecting ß-catenin. Next, we investigated the target proteins of 1 using magnetic FG beads. Chemical pull-down assay combined with mass spectrometry suggested that 1 directly binds to importin7. As expected, 1 inhibited the nuclear translocation of importin7 cargoes such as Smad2 and Smad3 in TGF-ß-stimulated HT-29 cells. In addition, the knockdown of importin7 by siRNA reduced the expression of target genes of Wnt/ß-catenin signaling pathway. These results suggest that importin7 is one of the target proteins of 1 for inhibition of the Wnt/ß-catenin signaling pathway.

Resting-state brain activity distinguishes patients with generalised epilepsy from others.

PURPOSE: Epilepsy is a prevalent neurological disorder characterised by repetitive seizures. It is categorised into three types: generalised epilepsy (GE), focal epilepsy (FE), and combined generalised and focal epilepsy. Correctly subtyping the epilepsy is important to select appropriate treatments. The types are mainly determined (i.e., diagnosed) by their semiologies supported by clinical examinations, such as electroencephalography and magnetoencephalography (MEG). Although these examinations are traditionally based on visual inspections of interictal epileptic discharges (IEDs), which are not always visible, alternative analyses have been anticipated. We examined if resting-state brain activities can distinguish patients with GE, which would help us to diagnose the type of epilepsy. METHODS: The 5 min resting-state brain activities acquired using MEG were obtained retrospectively from 15 patients with GE. The cortical source of the activities was estimated at each frequency band from delta to high-frequency oscillation (HFO). These estimated activities were compared with reference datasets from 133 healthy individuals and control data from 29 patients with FE. RESULTS: Patients with GE showed larger theta in the occipital, alpha in the left temporal, HFO in the rostral deep regions, and smaller HFO in the caudal ventral regions. Their area under the curves of the receiver operating characteristic curves was around 0.8-0.9. The distinctive pattern was not found for data from FE. CONCLUSION: Patients with GE show distinctive resting-state brain activity, which could be a potential biomarker and used complementarily to classical analysis based on the visual inspection of IEDs.

[Exploration of Risk Factors of the Onset of Antibiotics-induced Acute Kidney Injury and Its Transfer to Chronic Kidney Disease Using the Medical Information Database].

Drug-induced acute kidney injury (AKI) is a serious adverse drug reaction, which results in a significant decline in renal function and is known to progress to chronic kidney disease (CKD). Therefore, appropriate drug therapy is important to avoid the risk of drug-induced AKI and CKD, which are serious concerns in clinical practice. In this study, using the medical information database of Hamamatsu University Hospital, we investigated the risk factors that accelerate the onset of drug-induced AKI or its progression to CKD in patients who received aminoglycoside antibiotics (AGs) or glycopeptide antibiotics (GPs), which are strongly associated with drug-induced AKI and CKD. We performed logistic regression analysis using patients' background, laboratory test results, and concomitant drug use, among other such factors as explanatory variables and drug-induced AKI or CKD onset as objective variables to explore the risk factors for drug-induced AKI and CKD. Our results showed that co-administration of amphotericin B, piperacillin-tazobactam and other AGs and GPs, increased serum creatinine (Scr) and chloride concentrations, serum lactate dehydrogenase activity, and decreased serum albumin concentration were risk factors for drug-induced AKI onset. Moreover, a reduced blood urea nitrogen : Scr ratio at drug-induced AKI onset served as a risk factor for CKD. These results suggest that careful monitoring of the aforementioned factors is important to ensure appropriate usage of these drugs in patients treated with AGs and GPs.

Cytotoxic activities of alkaloid constituents from the climbing stems and rhizomes of Sinomenium acutum against cancer stem cells.

From the methanolic extract of the climbing stems and rhizomes of Sinomenium acutum, two new aporphine analogues, acutumalkaloids I and II, were isolated together with fifteen known compounds including lysicamine. The chemical structures of the isolated new compounds were elucidated based on chemical/physicochemical evidence such as NMR and MS spectra. For acutumalkaloids I and II, the absolute configurations were established by comparison of experimental and predicted electronic circular dichroism (ECD) data. We compared anti-proliferative activities of isolated compounds with reported naturally occurring Wnt/ß-catenin pathway inhibitor, nuciferine. Among the isolated compounds, we found lysicamine have anti-proliferative activity against both of HT-29 human colon cancer cell line and its cancer stem cells (CSCs). The IC50 values of lysicamine against non-CSCs and its CSCs were lower than that of nuciferine. In addition, the results of western blotting analysis suggested that lysicamine inhibited the expression of Wnt/ß-catenin pathway target protein such as survivin. These results suggested that lysicamine show cytotoxic activity via inhibition of Wnt/ß-catenin pathway.

Risk Factors for Lenvatinib-Induced High-Grade Hypothyroidism in Patients with Hepatocellular Carcinoma: A Retrospective Study.

INTRODUCTION: Lenvatinib mesylate (LEN) is an orally administered tyrosine kinase inhibitor used for the treatment of various cancers, including hepatocellular carcinoma (HCC). HCC treatment with LEN is associated with a very high incidence of adverse events, especially hypothyroidism. This study investigated the incidence of hypothyroidism due to LEN and the relationships between hypothyroidism incidence and patient demographics by analyzing clinical laboratory data from HCC patients treated with LEN. METHODS: This was a single-center, retrospective study of HCC patients who received LEN between April 19, 2018, and September 30, 2020. The observation period was from 1 week before the start of LEN administration to 1 month after the end of administration. RESULTS: In total, 61 patients with HCC were enrolled. High-grade hypothyroidism (CTCAE Grade 2-3) was found in 36.1% (22/61 patients). In high-grade hypothyroidism, eosinophil (EOSINO) count was significantly low (p = 0.029). The cutoff value of EOSINO count was estimated to be approximately 150/µL. The adjusted odds ratios of high-grade hypothyroidism for current smoking and EOSINO count <150/µL were 0.237 (95% confidence interval: 0.063-0.893) and 4.219 (95% confidence interval: 1.119-15.92), respectively. CONCLUSION: The results showed that noncurrent smoking and EOSINO count <150/µL are risk factors for LEN-induced high-grade hypothyroidism.

Vancomycin Hydrochloride as a Risk Factor for Acute Kidney Injury: A Retrospective Study.

INTRODUCTION: The incidence of acute kidney injury (AKI) caused by vancomycin hydrochloride (VCM) was reported to be 5-43%. VCM-induced AKI was reported to be more likely to occur 4-17 days after initiating VCM treatment; however, it may occur earlier. The aim of this study was therefore to investigate risk factors for the development of AKI within two (AKI2days) and seven (AKI7days) days of VCM administration. METHODS: This was a single-center, retrospective study including patients who underwent VCM therapy between April 1, 2013, and December 31, 2019. AKI was evaluated based on the Kidney Disease: Improving Global Outcomes criteria. RESULTS: In total, 287 patients were enrolled. The incidence of VCM-induced AKI within 7 days was 10.8% (31/286 cases), and the incidence of AKI within 2 days was 5.9% (15/252 cases). Serum VCM trough concentrations and tazobactam-piperacillin (TZP) were shown to be a risk factor for VCM-induced AKI. The serum VCM trough concentration was 12.67 µg/mL within the 48 h threshold (AKI2days) and 19.03 µg/mL within the 7-day threshold (AKI7days). CONCLUSION: Our study demonstrated that high serum VCM trough concentrations and the combination of VCM and TZP were independent risk factors for VCM-induced AKI. Avoiding the concomitant use of TZP, or thorough monitoring of renal function with the concomitant use of TZP, may be helpful in reducing the occurrence of AKI. Furthermore, monitoring serum VCM trough concentrations within 2 days may effectively reduce the incidence of AKI.

Chemical Structures and Anti-proliferative Effects of Valeriana fauriei Constituents on Cancer Stem Cells.

We isolated the new sesquiterpenes, valerianaterpenes IV and V, and the new lignans valerianalignans I-III from the methanol extracts of the rhizomes and roots of Valeriana fauriei and elucidated their structures based on chemical and spectroscopic findings. The absolute configuration of valerianaterpene IV and valerianalignans I-III were established by comparing experimental and predicted electronic circular dichroism (ECD) data. Among the isolated compounds, valerianalignans I and II exerted anti-proliferative activity against human astrocytoma cells (U-251 MG) and their cancer stem cells (U-251 MG CSCs). Interestingly, valerianalignans I and II notably exerted anti-proliferative activities at lower concentrations against CSCs than non-CSCs, and the absolute configurations of these compounds affected their activities.

Antiproliferative Activities of Diterpenes from Leaves of Isodon trichocarpus against Cancer Stem Cells.

Two new diterpenes named trichoterpene I (1) and trichoterpene II (2) were isolated from the extract from the leaves of Isodon trichocarpus together with 19 known diterpenes. Their chemical structures were elucidated on the basis of chemical and physicochemical properties. Among them, oridonin (3), effusanin A (4), and lasiokaurin (9) with the α,ß-unsaturated carbonyl moiety showed antiproliferative activities against breast cancer MDA-MB-231 and human astrocytoma U-251 MG cells [i.e., non-cancer stem cells (non-CSCs)] and their cancer stem cells (CSCs) isolated by sphere formation. In particular, compound 4 (IC50 = 0.51 µM) showed a higher antiproliferative activity against MDA-MB-231 CSCs than against MDA-MB-231 non-CSCs. The antiproliferative activity toward CSCs of compound 4 was equal to adriamycin (positive control, IC50 = 0.60 µM).

Wavelength dependence of ultraviolet light inactivation for SARS-CoV-2 omicron variants.

Ultraviolet (UV) irradiation offers an effective and convenient method for the disinfection of pathogenic microorganisms. However, UV irradiation causes protein and/or DNA damage; therefore, further insight into the performance of different UV wavelengths and their applications is needed to reduce risks to the human body. In this paper, we determined the efficacy of UV inactivation of the SARS-CoV-2 omicron BA.2 and BA.5 variants in a liquid suspension at various UV wavelengths by the 50% tissue culture infection dose (TCID50) method and quantitative polymerase chain reaction (qPCR) assay. The inactivation efficacy of 220 nm light, which is considered safe for the human body, was approximately the same as that of health hazardous 260 nm light for both BA.2 and BA.5. Based on the inactivation rate constants determined by the TCID50 and qPCR methods versus the UV wavelength, the action spectra were determined, and BA.2 and BA.5 showed almost the same spectra. This result suggests that both variants have the same UV inactivation characteristics.

Multiple quantum interrogation to determine the position of an object in a serial array of ring resonators.

We propose quantum interaction-free measurements to determine not only whether an object exists, but also where it is situated among possible interrogation positions. In the first configuration, the object exists at one of several possible positions, and the other positions are empty. We regard this as multiple quantum trap interrogation. In the second configuration, the object does not exist in any possible interrogation position, but other positions are occupied by objects. We refer to this as multiple quantum loophole interrogation. It is possible to determine the position of a trap or loophole with almost 100% certainty, without any real interaction between the photon and the objects. We performed a preliminary experiment using a serial array of add-drop ring resonators and confirmed that multiple trap and loophole interrogations are possible. We discuss the detuning of resonators from the critical coupling condition, the loss effects in the resonator, the frequency detuning effect of incident light, and the effect of object semitransparency on the interrogation systems.

Bleeding events associated with recombinant human soluble thrombomodulin, classified according to renal function, in sepsis-induced disseminated intravascular coagulation.

OBJECTIVE: Recombinant human soluble thrombomodulin (rhsTM) is a therapeutic agent for sepsis-induced disseminated intravascular coagulation (DIC) and is associated with bleeding events. rhsTM is a renal excretion drug; however, information on the role of rhsTM in renal function is limited. MATERIALS AND METHODS: In this retrospective observational study, we assessed rhsTM-associated bleeding events according to the renal function of patients with sepsis-induced DIC. We analyzed the data of 79 patients administered a standard-dose of rhsTM for sepsis-induced DIC, at a single center. Patients were classified based on estimated glomerular filtration rate (eGFR). We measured fresh bleeding events following rhsTM administration, DIC score efficacy, and 28-day mortality. RESULTS: Fresh bleeding events were observed in 15 patients, with a significant difference in the eGFR, platelet count, and DIC scores. Furthermore, fresh bleeding events tended to increase with the deterioration of renal function (p = 0.039). The DIC scores in all renal function groups decreased after -rhsTM administration. Additionally, the 28-day mortality was less than 30% in all groups. CONCLUSION: Our results indicate that the effectiveness of the standard-dose of rhsTM is not related to renal function. However, standard-dose rhsTM therapy could potentially increase the risk of adverse bleeding events with severe renal function equivalent to G5.

Solid-State Far-Ultraviolet C Light Sources for the Disinfection of Pathogenic Microorganisms Using Graphene Nanostructure Field Emitters.

The ongoing global outbreak of coronavirus disease has necessitated the use of ultraviolet (UV) disinfection techniques to reduce viral transmission in public places. The previously used UV wavelength is harmful to the human body, the wavelength range from 200 to 235 nm, often referred to as far-UVC light, has attracted attention as a novel disinfection wavelength range that can be used in a safe manner. However, the currently used light sources have practical problems, such as an expensive cost, a low efficiency, and short lifetimes. Therefore, environmentally friendly solid-state light sources with a lower cost, higher efficiency, and longer lifetimes are demanded. Here, an efficient mercury-free far-UVC solid-state light source is presented. This light source demonstrates intense 230 nm emission with a narrow spectral width of 30 nm and a long lifetime of more than 1000 h. These characteristics can be achieved by graphene nanostructure field emitters and wide-bandgap magnesium aluminate phosphors. By using this light source, the efficient disinfection of Escherichia coli is demonstrated. The light sources presented here facilitate future technologies for preventing the spread of infectious diseases in a safe and convenient manner.

Plantainoside B in Bacopa monniera Binds to Aß Aggregates Attenuating Neuronal Damage and Memory Deficits Induced by Aß.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by dementia. The most characteristic pathological changes in AD brain include extracellular amyloid-ß (Aß) accumulation and neuronal loss. Particularly, cholinergic neurons in the nucleus basalis of Meynert are some of the first neuronal groups to degenerate; accumulating evidence suggests that Aß oligomers are the primary form of neurotoxicity. Bacopa monniera is a traditional Indian memory enhancer whose extract has shown neuroprotective and Aß-reducing effects. In this study, we explored the low molecular weight compounds from B. monniera extracts with an affinity to Aß aggregates, including its oligomers, using Aß oligomer-conjugated beads and identified plantainoside B. Plantainoside B exhibited evident neuroprotective effects by preventing Aß attachment on the cell surface of human induced pluripotent stem cell (hiPSC)-derived cholinergic neurons. Moreover, it attenuated memory impairment in mice that received intrahippocampal Aß injections. Furthermore, radioisotope experiments revealed that plantainoside B has affinity to Aß aggregates including its oligomers and brain tissue from a mouse model of Aß pathology. In addition, plantainoside B could delay the Aß aggregation rate. Accordingly, plantainoside B may exert neuroprotective effects by binding to Aß oligomers, thus interrupting the binding of Aß oligomers to the cell surface. This suggests its potential application as a theranostics in AD, simultaneously diagnostic and therapeutic drugs.

Azaphilones produced by Penicillium maximae with their cell death-inducing activity on Adriamycin-treated cancer cell.

BACKGROUND: Heat shock proteins (Hsps) are overexpressed in several tumors and contribute to cell proliferation, metastasis, and anticancer drug resistance. Therefore, Hsp inhibitors have enhanced cytotoxicity as chemotherapeutic agents and may be effective with a reduced dosage for tumor therapy to avoid side effects. RESULTS: Four new azaphilones, maximazaphilones I-IV (1-4), and three known compounds (5-7) have been isolated from the airborne-derived fungus Penicillium maximae. Inhibitory effects of isolated compounds against induction of Hsp105 were evaluated by the luciferase assay system using Hsp105 promoter. In this assay, 2-4, 6, and 7 significantly inhibited hsp105 promoter activity without cytotoxicity. In addition, all isolated compounds except for 5 significantly induced the death of Adriamycin (ADR)-treated HeLa cells. Interestingly, 1-4, 6, and 7 didn't show anti-proliferative and cell death-inducing activity without ADR. CONCLUSION: This study revealed the chemical structures of maximazaphilones I-IV (1-4) and the potency of azaphilones may be useful for cancer treatment and reducing the dose of anticancer agents. In addition, one of the mechanisms of cell death-inducing activity for 2-4, 6, and 7 was suggested to be inhibitory effects of Hsp105 expression.

Time-dose reciprocity mechanism for the inactivation of Escherichia coli explained by a stochastic process with two inactivation effects.

There is a great demand for developing and demonstrating novel disinfection technologies for protection against various pathogenic viruses and bacteria. In this context, ultraviolet (UV) irradiation offers an effective and convenient method for the inactivation of pathogenic microorganisms. The quantitative evaluation of the efficacy of UV sterilization relies on the simple time-dose reciprocity law proposed by Bunsen-Roscoe. However, the inactivation rate constants reported in the literature vary widely, even at the same dose and wavelength of irradiation. Thus, it is likely that the physical mechanism of UV inactivation cannot be described by the simple time-dose reciprocity law but requires a secondary inactivation process, which must be identified to clarify the scientific basis. In this paper, we conducted a UV inactivation experiment with Escherichia coli at the same dose but with different irradiances and irradiation durations, varying the irradiance by two to three orders of magnitude. We showed that the efficacy of inactivation obtained by UV-light emitting diode irradiation differs significantly by one order of magnitude at the same dose but different irradiances at a fixed wavelength. To explain this, we constructed a stochastic model introducing a second inactivation rate, such as that due to reactive oxygen species (ROS) that contribute to DNA and/or protein damage, together with the fluence-based UV inactivation rate. By solving the differential equations based on this model, the efficacy of inactivation as a function of the irradiance and irradiation duration under the same UV dose conditions was clearly elucidated. The proposed model clearly shows that at least two inactivation rates are involved in UV inactivation, where the generally used UV inactivation rate does not depend on the irradiance, but the inactivation rate due to ROS does depend on the irradiance. We conclude that the UV inactivation results obtained to date were simply fitted by one inactivation rate that superimposed these two inactivation rates. The effectiveness of long-term UV irradiation at a low irradiance but the same dose provides useful information for future disinfection technologies such as the disinfection of large spaces, for example, hospital rooms using UV light, because it can reduce the radiation dose and its risk to the human body.