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Pulmonary arterial hypertension (PAH) is characterized by the severe obstruction of the small pulmonary arteries and concomitant high pulmonary arterial pressure, resulting in progressive right ventricular failure. Previously, we demonstrated that long-term interleukin (IL)-33 administration in mice induces severe occlusive medial hypertrophy of pulmonary arteries (PA) in the lungs, which is mediated by group 2 innate lymphoid cells (ILC2s). In response to IL-33, ILC2s accumulate around the blood vessels and produce IL-5, leading to perivascular eosinophil recruitment. In this study, we characterized IL-33-induced medial hypertrophy of PA. We demonstrated that long-term IL-33 administration causes an increase in right ventricular pressure. In IL-33-deficient mice, medial hypertrophy of PA mediated by eggs of Schistosoma mansoni was attenuated, accompanied by a partial reduction in ILC2s, eosinophils, and CD4 + T cells. In addition, proteomic analysis revealed dramatic changes in the urine samples from mice treated with IL-33 or S. mansoni eggs. Resistin-like alpha (RELMα), a pulmonary hypertension-related molecule, was commonly detected in the urine in both treatments. Large amounts of RELMα were observed in the lungs of the IL-33-treated mice. These observations suggest that IL-33-induced medial hypertrophy of PA is a useful model for studying the mechanism underlying the development of PAH and finding biomarkers to indicate the onset of PAH., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Masashi Ikutani reports financial support was provided by Hiroshima University. Shoichi Shimizu reports financial support was provided by University of Occupational and Environmental Health, Japan. Koki Okada reports financial support was provided by Hiroshima University. Koshi Imami reports financial support was provided by RIKEN. Tadakatsu Inagaki reports financial support was provided by National Cerebral and Cardiovascular Center Research Institute. Yoshikazu Nakaoka reports financial support was provided by National Cerebral and Cardiovascular Center Research Institute. Yoshio Osada reports financial support was provided by University of Occupational and Environmental Health, Japan. Susumu Nakae reports financial support was provided by Hiroshima University., (Copyright © 2024 Elsevier Inc. All rights reserved.)

SPring-8-II is a major upgrade project of SPring-8 that was inaugurated in October 1997 as a third-generation synchrotron radiation light source. This upgrade project aims to achieve three goals simultaneously: achievement of excellent light source performance, refurbishment of aged systems, and significant reduction in power consumption for the entire facility. A small emittance of 50 pm rad will be achieved by (1) replacing the existing double-bend lattice structure with a five-bend achromat one, (2) lowering the stored beam energy from 8 to 6 GeV, (3) increasing the horizontal damping partition number from 1 to 1.3, and (4) enhancing horizontal radiation damping by installing damping wigglers in long straight sections. The use of short-period in-vacuum undulators allows ultrabrilliant X-rays to be provided while keeping a high-energy spectral range even at the reduced electron-beam energy of 6 GeV. To reduce power consumption, the dedicated, aged injector system has been shut down and the high-performance linear accelerator of SACLA, a compact X-ray free-electron laser (XFEL) facility, is used as the injector of the ring in a time-shared manner. This allows the simultaneous operation of XFEL experiments at SACLA and full/top-up injection of the electron beam into the ring. This paper overviews the concept of the SPring-8-II project, the system design of the light source and the details of the accelerator component design., (open access.)

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection, and viral genes are poised to be transcribed in the latent chromatin. In the poised chromatins, KSHV latency-associated nuclear antigen (LANA) interacts with cellular chromodomain-helicase-DNA-binding protein 4 (CHD4) and inhibits viral promoter activation. CHD4 is known to regulate cell differentiation by preventing enhancers from activating promoters. Here, we identified a putative CHD4 inhibitor peptide (VGN73) from the LANA sequence corresponding to the LANA-CHD4 interaction surface. The VGN73 interacts with CHD4 at its PHD domain with a dissociation constant (K D ) of 14 nM. Pre-treatment with VGN73 enhanced monocyte differentiation into macrophages and globally altered the repertoire of activated genes in U937 cells. Furthermore, the introduction of the peptide into the cancer cells induced caspase-mediated CHD4 cleavage, triggered cell death, and inhibited tumor growth in a xenograft mouse model. The VGN73 may facilitate cell differentiation therapy., Competing Interests: Declaration of interests H.M., K.-H.W., and Y.I. filed provisional patents related to the VGN73 peptides utilization for therapeutics purposes through University of California Davis. M.S. and Y.I. are founders of VGN Bio, Inc. and are planning to further develop VGN73 as therapeutics tools., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Photosynthetic organisms have developed mechanisms to regulate light reactions in response to varying light conditions. Photosynthetic electron transport leads to the formation of a ΔpH across the thylakoid membrane, which is crucial for regulating electron transport. However, other pH modulators remain to be identified, particularly in cyanobacteria. In this study, we evaluated the potential involvement of six Na+/H+ antiporters (NhaS1-NhaS6) in control of pH in the cyanobacterium Synechocystis sp. PCC 6803. Synechocystis showed a strong requirement for Na+ at high light intensities, with ΔnhaS1 and ΔnhaS2 strains unable to grow under high light conditions. We analyzed Na+ efflux-driven H+-uptake activities of NhaS1-NhaS6 in inverted membranes of Escherichia coli. Biological fractionation and immunoelectron microscopy revealed that NhaS1 localizes to both the plasma and thylakoid membranes while NhaS2 localizes to the plasma membrane. Measurement of photosynthesis activity indicated that NhaS2 promotes ATP production and electron transport from PQ to P700. Measurements of pH outside of the cells and in the cytoplasm suggested that both NhaS1 and NhaS2 are involved in plasma membrane-mediated light-dependent H+ uptake and cytoplasmic acidification. NhaS1 and NhaS2 were also found to prevent photoinhibition under high light treatment. These results indicate that H+ transport mediated by NhaS1 and NhaS2 plays a role in regulating intracellular pH and maintaining photosynthetic electron transport., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Objective Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, increases the hemoglobin (Hb) levels in patients with chronic kidney disease (CKD). To date, limited clinical studies have focused on the excessive increase in the Hb levels in the early weeks after switching from erythropoiesis-stimulating agents (ESA) to roxadustat in adult non-dialysis patients. We conducted a retrospective study to examine whether early overshoot frequently occurs after switching to roxadustat. Methods This 8-week retrospective pilot study examined patients with anemic, non-dialyzed CKD who switched from ESA (darbepoetin or epoetin beta pegol) to roxadustat or continued ESA. The Hb levels >12.5 g/dL after starting our observation was defined as Hb overshoot. Patients: Twenty-three patients who switched to roxadustat (roxadustat group) and 63 who continued ESA (ESA group) were included. Results The baseline median estimated glomerular filtration rate and mean Hb levels were 15.7 mL/min/1.73 mShizuokax and 10.77 g/dL in roxadustat group and 15.2 mL/min/1.73 m 2 and 10.64 g/dL in ESA group, respectively. Eight patients (34.8%) in the roxadustat group and two patients (3.2%) in the ESA group had Hb overshoot within the 8-week visit (odds ratio: 20.2 [95% confidence interval 3.13-130.0, p<0.01] in the background adjusted model). Among the patients with Hb overshoot in the roxadustat group, the Hb levels were maintained close to baseline 4 weeks after roxadustat discontinuation. A younger age and higher baseline Hb and Hct levels were risk factors for Hb overshoot. Conclusions Hb overshoot was frequently observed in patients switched to roxadustat. Clinicians should be aware of Hb overshoot and emphasize the importance of early Hb level checks.

Background: The relationship between the combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) and prognosis in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) combination therapy with chemotherapy remains unclear. Thus, we investigated prognostic factors, including the COP-NLR, to identify patients who could benefit from the therapeutic efficacy of ICI combination therapy for advanced NSCLC. Furthermore, we evaluated the relationship between the COP-NLR score during ICI combination therapy and treatment response., Methods: We conducted a retrospective cohort study of 88 patients with NSCLC who initially received ICI combination therapy. The primary outcome was overall survival (OS). The prognostic factors were extracted using the Cox proportional hazards model. The relationship between COP-NLR score at 3 weeks after starting ICI combination therapy and a good response (complete response [CR] and partial response [PR]) to treatment was analyzed using the chi-square test., Results: The median OS was 15.7 months. In the multivariable analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, distant metastatic sites ≥2, and baseline COP-NLR scores of 1, 2 were extracted as significant poor prognostic factors. The proportion of patients with CR and PR in the 3-week COP-NLR score of 0 group was significantly higher than that in scores of 1, 2 group., Conclusions: Baseline COP-NLR, ECOG PS, and number of distant metastatic sites were prognostic factors in patients with NSCLC with ICI combination therapy. A lower 3-week COP-NLR was associated with a good response to treatment., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Similar to that in Europe and the United States, the need for forensic DNA identification in dogs is increasing in Japan. As few studies have used commercial genotyping kits, the effectiveness of the Canine Genotypes TM Panel 2.1 Kit for individual DNA identification in dogs bred in Japan was examined. We genotyped 150 unrelated dogs (50 Golden Retrievers, 50 Miniature Dachshunds, and 50 Shiba Inu) at 18 canine short tandem repeat loci by the Kit. The allele frequency, expected heterozygosity, observed heterozygosity, p-value, power of the discriminant, and of exclusion, polymorphic information content, and random matching probability were calculated for each marker. The random matching probability was subsequently estimated to be 4.394×10 -22 in the 150 dogs of the three pure-bred groups based on 18 STR loci; 3.257 × 10 -16 in the Golden Retriever, 3.933 × 10 -18 in the Miniature Dachshund, and 2.107 × 10 -18 in the Shiba Inu breeds. In addition, principal component analysis based on genotype data revealed the Golden Retrievers, Miniature Dachshunds, and Shiba Inus separated into three clusters. The results of the genotype analysis showed that the Canine Genotypes TM Panel 2.1 Kit could be useful for identity testing and tool of population study of canines in Japan., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus with a double-stranded DNA capable of establishing latent infection in the host cell. During latency, only a limited number of viral genes are expressed in infected host cells, and that helps the virus to evade host immune cell response. During primary infection, the KSHV genome is chromatinized and maintained as an episome, which is tethered to the host chromosome via Latency Associated Nuclear Antigen (LANA). The KSHV episome undergoes the same chromatin modification with the host cell chromosome and, therefore, is regulated by various epigenetic modifications, such as DNA methylation, histone methylation, and histone acetylation. The KSHV genome is also organized in a spatiotemporal manner by forming genomic loops, which enable simultaneous and coordinated control of dynamic gene transcription, particularly during the lytic replication phase. The genome-wide approaches and advancing bioinformatic tools have increased the resolution of studies on the dynamic transcriptional control and our understanding of KSHV latency-lytic switch regulation. We will summarize our current understanding of the epigenetic gene regulation on the KSHV chromatin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The clinically accepted planning target volume margin for radiation therapy to the paraortic nodal region in cervical cancer patients is 5 mm. However, the comprehensive alignment and variability from the pelvic bone to all lumbar vertebrae are undetermined. This study aims to quantify the residual setup errors between the pelvic bone and lumbar vertebrae and determine the optimal correction strategy for patients with cervical cancer., Materials and Methods: Fifteen patients underwent pretreatment mega-voltage computed tomography scans (375 total fractions). Residual setup errors and required margins for each lumbar vertebra were calculated based on registrations accounting for pelvic rotation and translation., Results: The systematic residual errors (1 SD) at L1, L2, L3, L4, and L5 using pelvic bone registration were 6.5, 4.9, 3.1, 1.5, and 0.6 mm in the anterior-posterior (AP) direction, 3.1, 2.3, 1.4, 0.6, and 0.3 mm in the right-left direction, and 2.7, 2.2, 1.7, 1.0, and 0.5 mm in the superior-inferior direction, respectively. The residual setup errors were the largest in the AP direction. Registration based on the pelvic bone required margins in the AP direction of 16.0, 12.1, 7.7, 3.6, and 1.3 mm for L1, L2, L3, L4, and L5, respectively, whereas registration based on L3 required margins of 8.8, 4.8, 4.4, 7.1, and 7.7 mm for L1, L2, L4, L5, and pelvic bone, respectively., Conclusions: Considerable local setup variability was found in patients with cervical cancer. After reviewing the corrective strategies, we determined that L3-based registration effectively minimized the required margins., Competing Interests: None., (© 2024 The Author(s).)

Decreased cough strength in myasthenia gravis (MG) leads to aspiration and increases the risk of MG crisis. The aim of this study was to clarify the reliability and validity of cough peak flow (CPF) measurements in MG. A total of 26 patients with MG who underwent CPF measurements using the peak flow meter by themselves were included. MG symptoms were evaluated by pulmonary function tests and clinical MG assessment scales before and after immune-treatments. The relationship between CPF and pulmonary function tests and MG comprehensive were assessed. The cut-off value of CPF for aspiration risk was determined and the area under the curve (AUC) was calculated. The intraclass correlation coefficient was more than 0.95 for pre-and post-treatment. Positive correlations were found between CPF and almost all spirometric values as well as between the differences of pre-and post-treatment in CPF and quantitative myasthenia gravis score. The CPF for identifying the aspiration risk was used to calculate the CPF cut-off value of 205 L/min with a sensitivity of 0.77, specificity of 0.90, and AUC of 0.85. The CPF, a convenient measure by patients themselves, has a high reliability in patients with MG, and is a useful biomarker reflecting MG symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In recent years, due to breeding improvements, strawberries with low anthocyanin content and a white rind are now available, and they are highly valued in the market. Strawberries with white skin color do not turn red when ripe, making it difficult to judge ripeness. The soluble solids content (SSC) is an indicator of fruit quality and is closely related to ripeness. In this study, visible-near-infrared (Vis-NIR) spectroscopy and near-infrared (NIR) spectroscopy are used for non-destructive evaluation of the SSC. Vis-NIR (500-978 nm) and NIR (908-1676 nm) data collected from 180 samples of "Tochigi iW1 go" white strawberries and 150 samples of "Tochigi i27 go" red strawberries are investigated. The white strawberry SSC model developed by partial least squares regression (PLSR) in Vis-NIR had a determination coefficient R 2 p of 0.89 and a root mean square error prediction (RMSEP) of 0.40%; the model developed in NIR showed satisfactory estimation accuracy with an R 2 p of 0.85 and an RMSEP of 0.43%. These estimation accuracies were comparable to the results of the red strawberry model. Absorption derived from anthocyanin and chlorophyll pigments in white strawberries was observed in the Vis-NIR region. In addition, a dataset consisting of red and white strawberries can be used to predict the pigment-independent SSC. These results contribute to the development of methods for a rapid fruit sorting system and the development of an on-site ripeness determination system.

The time for diabetic nephropathy (DN) to progress from mild to severe is long. Thus, methods to continuously repress DN are required to exert long-lasting effects mediated through epigenetic regulation. In this study, we demonstrated the ability of nicotinamide adenine dinucleotide (NAD) and its metabolites to reduce albuminuria through Sirt1- or Nampt-dependent epigenetic regulation. We previously reported that proximal tubular Sirt1 was lowered before glomerular Sirt1. Repressed glomerular Sirt1 was found to epigenetically elevate Claudin-1. In addition, we reported that proximal tubular Nampt deficiency epigenetically augmented TIMP-1 levels in Sirt6-mediated pathways, leading to type-IV collagen deposition and diabetic fibrosis. Altogether, we propose that the Sirt1/Claudin-1 axis may be crucial in the onset of albuminuria at the early stages of DN and that the Nampt/Sirt6/TIMP-1 axis promotes diabetic fibrosis in the middle to late stages of DN. Finally, administration of NMN, an NAD precursor, epigenetically potentiates the regression of the onset of DN to maintain Sirt1 and repress Claudin-1 in podocytes, suggesting the potential use of NAD metabolites as epigenetic medications for DN., (© 2024. The Authors.)

In recent years, the focus has shifted towards carbohydrate-based hydrogels and their eco-friendly preparation methods. This study involved an investigation into the treatment of wheat starch using dielectric barrier discharge (DBD) plasma technology over varying time gradients (0, 2, 5, 10, 15, and 20 min). The objective was to systematically examine the impact of different treatment durations on the physicochemical properties of wheat starch and the suitability of its gels for 3D printing. Morphology of wheat starch remained intact after DBD treatment. However, it led to a reduction in the amylose content, molecular weight, and crystallinity. This subsequently resulted in a decrease in the pasting temperature and viscosity. Moreover, the gels of the DBD-treated starch exhibited superior 3D printing performance. After a 2-min DBD treatment, the 3D printed samples of the wheat starch gel showed no significant improvements, as broken bars were evident on the surface of the 3D printed graphic, whereas DBD-20 showed better printing accuracy and surface structure, compared to the original starch without slumping. These results suggested that DBD technology holds potential for developing new starch-based gels with impressive 3D printing properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Obsessive slowness, a symptom of obsessive-compulsive disorder (OCD), is characterized by compulsive behavior and significant slowness of movement. Primary obsessive slowness (POS) is defined as a condition in which a series of actions are segmented, and the patient spends an unlimited amount of time performing each action while checking each action, resulting in cessation or slowness of movement. It is often difficult to treat POS with exposure and response prevention, which is considered effective in general OCD, and no treatment has been established. Here, we discuss the effectiveness of psychoeducation and modeling using video recordings in the treatment of POS., Case Presentation: We report a case of POS in a 19-year-old woman. Each action was subdivided and ordered, and the patient could not proceed to the next action without confirming that the previous step had been performed. Therefore, she could not live her daily life independently; for instance, toileting and bathing required more than 1 h, even with assistance. After more than 5 months of long-term treatment, including pharmacotherapy, psychoeducation, and modeling with video recordings, she recovered to live her daily life independently., Conclusion: Psychoeducation and behavioral therapy can effectively treat POS. Particularly, modeling with video recordings would be an easy-to-use option for POS treatment., (© 2024. The Author(s).)

The fidelity of vertical transmission is a critical factor in maintaining mutualistic associations with microorganisms. The obligate mutualism between termites and intestinal protist communities has been maintained for over 130 million years, suggesting the faithful transmission of diverse protist species across host generations. Although a severe bottleneck can occur when alates disperse with gut protists, how protist communities are maintained during this process remains largely unknown. In this study, we examined the dynamics of intestinal protist communities during adult eclosion and alate dispersal in the termite Reticulitermes speratus . We found that the protist community structure in last-instar nymphs differed significantly from that in workers and persisted intact during adult eclosion, whereas all protists disappeared from the gut during moults between worker stages. The number of protists in nymphs and alates was substantially lower than in workers, whereas the proportion of protist species exhibiting low abundance in workers was higher in nymphs and alates. Using a simulation-based approach, we demonstrate that such changes in the protist community composition of nymphs and alates improve the transmission efficiency of whole protist species communities. This study thus provides novel insights into how termites have maintained mutualistic relationships with diverse gut microbiota for generations., Competing Interests: We declare we have no conflict of interests., (© 2024 The Authors.)

Pulmonary arterial hypertension (PAH) is characterized by stenosis and occlusions of small pulmonary arteries, leading to elevated pulmonary arterial pressure and right heart failure. Although accumulating evidence shows the importance of interleukin (IL)-6 in the pathogenesis of PAH, the target cells of IL-6 are poorly understood. Using mice harboring the floxed allele of gp130 , a subunit of the IL-6 receptor, we found substantial Cre recombination in all hematopoietic cell lineages from the primitive hematopoietic stem cell level in SM22α-Cre mice. We also revealed that a CD4 + cell-specific gp130 deletion ameliorated the phenotype of hypoxia-induced pulmonary hypertension in mice. Disruption of IL-6 signaling via deletion of gp130 in CD4 + T cells inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and suppressed the hypoxia-induced increase in T helper 17 cells. To further examine the role of IL-6/gp130 signaling in more severe PH models, we developed Il6 knockout (KO) rats using the CRISPR/Cas9 system and showed that IL-6 deficiency could improve the pathophysiology in hypoxia-, monocrotaline-, and Sugen5416/hypoxia (SuHx)-induced rat PH models. Phosphorylation of STAT3 in CD4 + cells was also observed around the vascular lesions in the lungs of the SuHx rat model, but not in Il6 KO rats. Blockade of IL-6 signaling had an additive effect on conventional PAH therapeutics, such as endothelin receptor antagonist (macitentan) and soluble guanylyl cyclase stimulator (BAY41-2272). These findings suggest that IL-6/gp130 signaling in CD4 + cells plays a critical role in the pathogenesis of PAH., Competing Interests: Competing interests statement:Y.N. reports consulting fees from Chugai Pharmaceutical Co., Ltd. outside the submitted work; consulting fees from Janssen Pharmaceutical K.K. outside the submitted work.

Macrolide antibiotics such as clarithromycin (CLR) and azithromycin are the key drugs used in multidrug therapy for Mycobacterium avium complex (MAC) diseases. For these antibacterial drugs, drug susceptibility has been correlated with clinical response in MAC diseases. We have previously demonstrated the correlation between drug susceptibility and mutations in the 23S rRNA gene, which confers resistance to macrolides. Herein, we developed a rapid detection method using the amplification refractory mutation system (ARMS)-loop-mediated isothermal amplification (LAMP) technique to identify mutations in the 23S rRNA gene of M. avium . We examined the applicability of the ARMS-LAMP method to genomic DNA extracted from six genotypes of M. avium clinical isolates. The M. avium isolates were classified into 21 CLR-resistant and 9 CLR-susceptible strains based on the results of drug susceptibility tests; the 23S rRNA genes of these strains were sequenced and analyzed using the ARMS-LAMP method. Sequence analysis revealed that the 9 CLR-sensitive strains were wild-type strains, whereas the 21 CLR-resistant strains comprised 20 mutant-type strains and one wild-type strain. Using ARMS-LAMP, no amplification from genomic DNAs of the 10 wild-type strains was observed using the mutant-type mismatch primer sets (MTPSs); however, amplification from the 20 mutant-type strain DNAs was observed using the MTPSs. The rapid detection method developed by us integrates ARMS-LAMP with a real-time turbidimeter, which can help determine drug resistance in a few hours. In conclusion, ARMS-LAMP might be a new clinically beneficial technology for rapid detection of mutations.IMPORTANCEMultidrug therapy for pulmonary Mycobacterium avium complex disease is centered on the macrolide antibiotics clarithromycin and azithromycin, and resistance to macrolides is an important prognosticator for clinical aggravation. Therefore, it is important to develop a quick and easy method for detecting resistance to macrolides. Drug resistance is known to be correlated with mutations in macrolide resistance genes. We developed a rapid detection method using amplification refractory mutation system (ARMS)-loop-mediated isothermal amplification (LAMP) to identify a mutation in the 23S rRNA gene, which is a macrolide resistance gene. Furthermore, we examined the applicability of this method using M. avium clinical isolates. The rapid method developed by us for detection of the macrolide resistance gene by integrating ARMS-LAMP and a real-time turbidimeter can help in detection of drug resistance within a few hours. Since this method does not require expensive equipment or special techniques and shows high analytical speed, it would be very useful in clinical practice., Competing Interests: The authors declare no conflict of interest.

Porphyromonas gingivalis, a Gram-negative anaerobic bacillus, is the primary pathogen in periodontitis. Herein, we cultivated strains of oral bacteria, including P. gingivalis and the oral commensal bacteria Actinomyces viscosus and Streptococcus mutans, and recorded the infrared absorption spectra of the gases released by the cultured bacteria at a resolution of 0.5 cm -1 within the wavenumber range of 500-7500 cm -1 . From these spectra, we identified the infrared wavenumbers associated with characteristic absorptions in the gases released by P. gingivalis using a decision tree-based machine learning algorithm. Finally, we compared the obtained absorbance spectra of ammonia (NH 3 ) and carbon monoxide (CO) using the HITRAN database. We observed peaks at similar positions in the P. gingivalis gases, NH 3 , and CO spectra. Our results suggest that P. gingivalis releases higher amounts of NH 3 and CO than A. viscosus and S. mutans. Thus, combining Fourier transform infrared spectroscopy with machine learning enabled us to extract the specific wavenumber range that differentiates P. gingivalis from a vast dataset of peak intensity ratios. Our method distinguishes the gases from P. gingivalis from those of other oral bacteria and provides an effective strategy for identifying P. gingivalis in oral bacteria. Our proposed methodology could be valuable in clinical settings as a simple, noninvasive pathogen diagnosis technique., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

The palladium-catalyzed addition of trifluoroacetylsilanes to alkenes and allenes via the cleavage of the C-Si bonds is reported. When alkenes are used, cyclopropanation occurs to afford cyclopropane derivatives bearing CF 3 and siloxy groups with a high degree of stereoselectivity. When allenes are used, silylacylation occurs to form alkenylsilane derivatives bearing a trifluoroacetyl group at the allylic position with complete regioselectivity. Both reactions allow for highly atom-economical access to densely functionalized fluorinated organosilane derivatives using simple building blocks.

Mitochondria play a vital role in non-shivering thermogenesis in both brown and subcutaneous white adipose tissues (BAT and scWAT, respectively). However, specific regulatory mechanisms driving mitochondrial function in these tissues have been unclear. Here we demonstrate that prolonged activation of β-adrenergic signaling induces epigenetic modifications in scWAT, specifically targeting the enhancers for the mitochondria master regulator genes Pgc1a/b . This is mediated at least partially through JMJD1A, a histone demethylase that in response to β-adrenergic signals, facilitates H3K9 demethylation of the Pgc1a/b enhancers, promoting mitochondrial biogenesis and the formation of beige adipocytes. Disruption of demethylation activity of JMJD1A in mice impairs activation of Pgc1a/b driven mitochondrial biogenesis and limits scWAT beiging, contributing to reduced energy expenditure, obesity, insulin resistance, and metabolic disorders. Notably, JMJD1A demethylase activity is not required for Pgc1a/b dependent thermogenic capacity of BAT especially during acute cold stress, emphasizing the importance of scWAT thermogenesis in overall energy metabolism., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

The Kaposi's sarcoma-associated herpesvirus (KSHV) genome consists of an approximately 140-kb unique coding region flanked by 30-40 copies of a 0.8-kb terminal repeat (TR) sequence. A gene enhancer recruits transcription-related enzymes by having arrays of transcription factor binding sites. Here, we show that KSHV TR possesses transcription regulatory function with latency-associated nuclear antigen (LANA). Cleavage under targets and release using nuclease demonstrated that TR fragments were occupied by LANA-interacting histone-modifying enzymes in naturally infected cells. The TR was enriched with histone H3K27 acetylation (H3K27Ac) and H3K4 tri-methylation (H3K4me3) modifications and also expressed nascent RNAs. The sites of H3K27Ac and H3K4me3 modifications were also conserved in the KSHV unique region among naturally infected primary effusion lymphoma cells. KSHV origin of lytic replication (Ori-Lyt) showed similar protein and histone modification occupancies with that of TR. In the Ori-Lyt region, the LANA and LANA-interacting proteins colocalized with an H3K27Ac-modified nucleosome along with paused RNA polymerase II. The KSHV transactivator KSHV replication and transcription activator (K-Rta) recruitment sites franked the LANA-bound nucleosome, and reactivation evicted the LANA-bound nucleosome. Including TR fragments in reporter plasmid enhanced inducible viral gene promoter activities independent of the orientations. In the presence of TR in reporter plasmids, K-Rta transactivation was drastically increased, while LANA acquired the promoter repression function. KSHV TR, therefore, functions as an enhancer for KSHV inducible genes. However, in contrast to cellular enhancers bound by multiple transcription factors, perhaps the KSHV enhancer is predominantly regulated by the LANA nuclear body.IMPORTANCEEnhancers are a crucial regulator of differential gene expression programs. Enhancers are the cis-regulatory sequences determining target genes' spatiotemporal and quantitative expression. Here, we show that Kaposi's sarcoma-associated herpesvirus (KSHV) terminal repeats fulfill the enhancer definition for KSHV inducible gene promoters. The KSHV enhancer is occupied by latency-associated nuclear antigen (LANA) and its interacting proteins, such as CHD4. Neighboring terminal repeat (TR) fragments to lytic gene promoters drastically enhanced KSHV replication and transcription activator and LANA transcription regulatory functions. This study, thus, proposes a new latency-lytic switch model in which TR accessibility to the KSHV gene promoters regulates viral inducible gene expression., Competing Interests: The authors declare no conflict of interest.

Protein knockdown with an inducible degradation system is a powerful tool for studying proteins of interest in living cells. Here, we adopted the auxin-inducible degron (AID) approach to detail Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) function in latency maintenance and inducible viral lytic gene expression. We fused the mini-auxin-inducible degron (mAID) tag at the LANA N-terminus with KSHV bacterial artificial chromosome 16 recombination, and iSLK cells were stably infected with the recombinant KSHV encoding mAID-LANA. Incubation with 5-phenyl-indole-3-acetic acid, a derivative of natural auxin, rapidly degraded LANA within 1.5 h. In contrast to our hypothesis, depletion of LANA alone did not trigger lytic reactivation but rather decreased inducible lytic gene expression when we stimulated reactivation with a combination of ORF50 protein expression and sodium butyrate. Decreased overall lytic gene induction seemed to be associated with a rapid loss of KSHV genomes in the absence of LANA. The rapid loss of viral genomic DNA was blocked by a lysosomal inhibitor, chloroquine. Furthermore, siRNA-mediated knockdown of cellular innate immune proteins, cyclic AMP-GMP synthase (cGAS) and simulator of interferon genes (STING), and other autophagy-related genes rescued the degradation of viral genomic DNA upon LANA depletion. Reduction of the viral genome was not observed in 293FT cells that lack the expression of cGAS. These results suggest that LANA actively prevents viral genomic DNA from sensing by cGAS-STING signaling axis, adding novel insights into the role of LANA in latent genome maintenance.IMPORTANCESensing of pathogens' components is a fundamental cellular immune response. Pathogens have therefore evolved strategies to evade such cellular immune responses. KSHV LANA is a multifunctional protein and plays an essential role in maintaining the latent infection by tethering viral genomic DNA to the host chromosome. We adopted the inducible protein knockdown approach and found that depletion of LANA induced rapid degradation of viral genomic DNA, which is mediated by innate immune DNA sensors and autophagy pathway. These observations suggest that LANA may play a role in hiding KSHV episome from innate immune DNA sensors. Our study thus provides new insights into the role of LANA in latency maintenance., Competing Interests: The authors declare no conflict of interest.

Epstein-Barr virus (EBV) is a ubiquitous human lymphotropic herpesvirus that is causally associated with several malignancies. In addition to latent factors, lytic replication contributes to cancer development. In this study, we examined whether the lytic gene BNRF1, which is conserved among gamma-herpesviruses, has an important role in lymphomagenesis. We found that lymphoblastoid cell lines (LCLs) established by BNRF1-knockout EBV exhibited remarkably lower pathogenicity in a mice xenograft model than LCLs produced by wild-type EBV (LCLs-WT). RNA-seq analyses revealed that BNRF1 elicited the expression of interferon-inducible protein 27 (IFI27), which promotes cell proliferation. IFI27 knockdown in LCLs-WT resulted in excessive production of reactive oxygen species, leading to cell death and significantly decreased their pathogenicity in vivo. We also confirmed that IFI27 was upregulated during primary infection in B-cells. Our findings revealed that BNRF1 promoted robust proliferation of the B-cells that were transformed by EBV latent infection via IFI27 upregulation both in vitro and in vivo., Competing Interests: H.Kiyoi has received research funding from FUJIFILM, Kyowa-Kirin, Bristol-Myers Squibb, Otsuka, Perseus Proteomics, Daiichi Sankyo, Abbvie, CURED, Astellas Pharma, Chugai, Zenyaku Kogyo, Nippon Shinyaku, Eisai, Takeda, Sumitomo Dainippon Pharma, and Sanofi, in addition to honoraria from Abbvie, Chugai, Astellas Pharma, and Novartis. Other authors declare no competing financial interests., (Copyright: © 2024 Sagou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Farmers would be able to regulate fertilization and produce quality durian if they knew the nutrient concentration in durian leaves. A long period of time for traditional nutritional content determination is needed. Therefore, near-infrared spectroscopy is a good method for nondestructive and quick nutrient content evaluation. The leaf sample matrices (fresh leaves, dried ground leaves, and dried ground leaf pellets) were scanned by Fourier transform near-infrared (FT-NIR) with a wavelength of 12,500-3,600 cm -1 . Regression models were developed using partial least squares (PLS) with full wavelength, short wavelength, and selected wavelength by successive projections algorithm (SPA). In this study, the model for N and K concentration was acceptable and the prediction was considered good but for P content not had succeeded. As a result, the PLS-SPA model using fresh leaf samples for evaluating N content in durian leaves exhibited performance of r 2  = 0.852, SEP = 0.14%, RPD = 2.63 and bias = -0.020%. The PLS-SPA model using dried ground leaf samples for evaluating K content in durian leaves exhibited performance of r 2  = 0.820, SEP = 0.13%, RPD = 2.36 and bias = 0.006%. This research found that it is possible to apply NIR waves to predict N and K concentrations in durian leaves. It is not necessary to predict directly from the wavelengths associated with -N or -K bonds. Instead, NIR can measure them indirectly from the bonding of proteins, which are products formed by N and K. In addition, selecting the wavelength that is related to the value to be measured can produce results that are not significantly different from using full or short wavelengths. These models can assist farmers in rapidly predicting N and K content in durian leaves for immediate fertilizer adjustment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Panmanas Sirisomboon reports financial support was provided by National Research Council of Thailand (NRCT). Panmanas Sirisomboon reports financial support was provided by Agricultural Research Development Agency (Public Organization)., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Obturator hernia is a rare condition that commonly affects frail older women. A 54-year-old woman presented to our hospital with left hip joint pain. She had suffered a left pubic bone fracture and commenced maintenance hemodialysis. Pelvic computed tomography (CT) showed an incarcerated small intestine through the left obturator foramen, while abdominal CT showed marked intestinal dilatation. She underwent emergency laparotomy, and the incarcerated small intestine was found to be necrotic. Partial small intestinal resection and bilateral obturator hernioplasty were performed. Because obturator hernia is a potentially fatal condition, early detection and treatment are important.