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Background/Aims: This study aimed to review the indications, methods, cooperation, complications, and outcomes of percutaneous endoscopic gastrostomy (PEG). Methods: Questionnaires were sent to 200 hospitals, of which 62 returned their questionnaires, with a response rate of approximately 30%. Descriptive statistics were calculated to analyze the responses to the questionnaires. Results: In 2019, a total of 1,052 PEGs were performed in 1,017 patients at 62 hospitals. The main group who underwent PEG was older adult patients with brain disease, particularly stroke. Nutritional supply was an important purpose of the PEG procedure. “The pull method” was the most commonly used for initial PEG insertion. The complications related to PEG were mostly mild, with leakage being the most common. Patients who underwent PEG procedures were primarily educated regarding the post-procedure management and complications related to PEG. Preoperative meetings were skipped at >50% of the institutions. Regarding the cooperation between the nutrition support team (NST) and the physician performing PEG, few endoscopists answered that they cooperated with NST before and after PEG. Moreover, the rate of NST certification obtained by physicians performing PEG and the frequency of attendance at NST-related conferences were relatively low. Conclusions: This study shows a similar trend to that found in the previous PEG guidelines. However, it covers new aspects, including team-based work for PEG procedure, nutrition support, and education for patients and guardians. Therefore, each medical institution needs to select an appropriate method considering the medical environment and doctor’s abilities.

Abstract Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV’s counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of the A3G-Vif complex and subsequent A3G ubiquitination in vitro and report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present an atomic model of the A3G-Vif interface, which assembles via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitro ubiquitination assays identify an adenine/guanine base preference for the interaction and a unique Vif-ribose contact. This establishes the biological significance of an RNA ligand. Further assessment of interactions between A3G, Vif, and RNA ligands show that the A3G-Vif assembly and subsequent ubiquitination can be controlled by amino acid mutations at the interface or by polynucleotide modification, suggesting that a specific chemical moiety would be a promising pharmacophore to inhibit the A3G-Vif interaction.

Objective This study was conducted to evaluate the effects of the supplementation of diets of broiler chickens with hot-melt extruded CuSO4 (HME-Cu) on their growth performance, nutrient digestibility, gut microbiota, small intestinal morphology, meat quality, and copper (Cu) bioavailability. Methods A total of 225 broilers (Ross 308), one-day old and initial weight 39.14 g, were weighed and distributed between 15 cages (15 birds per cage) in a completely randomized experimental design with 3 treatments (diets) and 5 replicates per treatment. Cages were allotted to three treatments including control (without supplemental Cu), IN-Cu (16 mg/kg of CuSO4), and HME-Cu (16 mg/kg of HME processed CuSO4). Results The HME-Cu treatment tended to increase the overall body weight gain (p

Immature poxviruses are characterized by nonicosahedral semiordered protein scaffolds critical for morphogenesis. Here, the authors use cryo-EM structures of Vaccinia virus D13 scaffold intermediates to explain their assembly mechanism.

Several studies have focused on Ca and P requirements for pigs. These requirements are estimated from their retention and bone formation. However, modern pig breeds have different responses to dietary Ca and P than traditional breeds, and their requirements are expected to change on an annual basis. Besides individual Ca and P needs, the Ca to P ratio (Ca/P) is an important factor in determining requirements. This study aimed to implement a linear and quadratic regression analysis to estimate Ca and P requirements based on average daily gain (ADG), apparent total tract digestibility (ATTD) of Ca (ATTD-Ca), ATTD of P (ATTD-P), and crude protein (CP) digestibility. Results show that Ca/P had linear and quadratic effects on ADG in the phytase-supplemented (PS) group in both the 6–11 kg and 11–25 kg categories. In the latter category, the CP digestibility was linearly increased in response to increasing Ca/P in the without-phytase (WP) group. In the 25–50 kg category, there was a linear response of ADG and linear and quadratic responses of CP digestibility to Ca/P in the PS group, while a linear and quadratic increase in CP digestibility and a quadratic effect on ATTD-Ca were observed in the WP group. In the 50–75 kg category, Ca/P had significant quadratic effects on ADG in the PS and WP groups, along with significant linear and quadratic effects on ATTD-Ca. In addition, Ca/P had significant quadratic effects on ATTD-P and led to a significant linear and quadratic increase in the CP digestibility in the WP group. In the 75–100 kg category, analysis showed a significant decrease in ATTD-Ca and ATTD-P in the PS and WP groups; in the latter, ATTD-P and ATTD-Ca were linearly decreased by increasing Ca/P. In conclusion, our equations predicted a higher Ca/P in the 6–25 kg bodyweight categories and a lower Ca/P in the 50-100 kg category than that recommended in the literature.

Efficient energy-level alignment is crucial for achieving high performance in organic electronic devices. Because the electronic structure of an organic semiconductor is significantly influenced by its molecular orientation, comprehensively understanding the molecular orientation and electronic structure of the organic layer is essential. In this study, we investigated the interface between a 1,4,5,8,9,11-hexaazatriphenylene hexacarbonitrile (HAT-CN) hole injection layer and a zinc-phthalocyanine (ZnPc) p-type organic semiconductor. To determine the energy-level alignment and molecular orientation, we conducted in situ ultraviolet and X-ray photoelectron spectroscopies, as well as angle-resolved X-ray absorption spectroscopy. We found that the HAT-CN molecules were oriented relatively face-on (40°) in the thin (5 nm) layer, whereas they were oriented relatively edge-on (62°) in the thick (100 nm) layer. By contrast, ZnPc orientation was not significantly altered by the underlying HAT-CN orientation. The highest occupied molecular orbital (HOMO) level of ZnPc was closer to the Fermi level on the 100 nm thick HAT-CN layer than on the 5 nm thick HAT-CN layer because of the higher work function. Consequently, a considerably low energy gap between the lowest unoccupied molecular orbital level of HAT-CN and the HOMO level of ZnPc was formed in the 100 nm thick HAT-CN case. This may improve the hole injection ability of the anode system, which can be utilized in various electronic devices.

Abstract During August 2020, we carried out a serological survey among students and employees at the Okinawa Institute of Science and Technology Graduate University (OIST), Japan, testing for the presence of antibodies against SARS-CoV-2, the causative agent of COVID-19. We used a FDA-authorized 2-step ELISA protocol in combination with at-home self-collection of blood samples using a custom low-cost finger prick-based capillary blood collection kit. Although our survey did not find any COVID-19 seropositive individuals among the OIST cohort, it reliably detected all positive control samples obtained from a local hospital and excluded all negatives controls. We found that high serum antibody titers can persist for more than 9 months post infection. Among our controls, we found strong cross-reactivity of antibodies in samples from a serum pool from two MERS patients in the anti-SARS-CoV-2-S ELISA. Here we show that a centralized ELISA in combination with patient-based capillary blood collection using as little as one drop of blood can reliably assess the seroprevalence among communities. Anonymous sample tracking and an integrated website created a stream-lined procedure. Major parts of the workflow were automated on a liquid handler, demonstrating scalability. We anticipate this concept to serve as a prototype for reliable serological testing among larger populations.

Background In foot and ankle infections, cases with apparent soft-tissue necrosis or purulent fluid collections definitely require surgical treatments. However, clinicians often have difficulty in determining whether to perform surgery in ambiguous cases without these findings. This study aimed to investigate the impact of the delta neutrophil index as a predictor of surgical treatment in patients with foot and ankle infections. Methods In total, 66 patients diagnosed with foot and ankle infections who underwent the delta neutrophil index test were retrospectively investigated. Medical records, including data on diabetes mellitus status, delta neutrophil index values, white blood cell count, polymorphonuclear leukocyte count, erythrocyte sedimentation rate, and C-reactive protein level, were retrospectively investigated. Logistic regression models were analyzed for the correlation between biomarkers, such as the delta neutrophil index and surgical treatment. The area under the curve was investigated to evaluate the cut-off value of the logistic model in predicting surgery. Results The relationship between the delta neutrophil index and surgical treatment was analyzed. The delta neutrophil index, adjusted for diabetes mellitus, was the best predictor of future surgical intervention. Based on the Youden index, the cutoff point (the equation’s adjusted by diabetes mellitus) for the prediction of surgical treatment was defined as a probability of 0.3, with sensitivity and specificity of 82.4% and 77.6%, respectively. Conclusions Based on the present study, the delta neutrophil index can help clinicians decide the appropriate surgical treatment for foot and ankle infections at the right time.

The reproductive performance of lactating sows was investigated by using different feeding methods including conventional feeding (CF, 3 times/d) or free feeding (FF), and different dietary energy level including low energy (LE: 3,300) or high energy (HE: 3,400 kcal/kg) during the hot season. A total of twenty-eight crossbred (Yorkshire × Landrace) sows were distributed into four treatments as a 2 × 2 factorial arrangement. Sows in the FF group showed lower body weight and backfat loss (p < 0.05) compared with the CF group. Backfat loss during lactation was lower (p < 0.05) in sows fed HE diet than in that fed LE diet. There were no significant differences in litter survival rate and weaning to estrus interval, but the litter weight at weaning was improved (p < 0.05) in FF and HE sows. Hence, it is concluded that using the free-feeding system or increased dietary energy density leads to improved sow performance during hot ambient temperature.

Category: Ankle, Orthosis, rehabilitation Introduction/Purpose: An axillary crutch is the most commonly used assistive device in foot and ankle patients who require nonweightbearing. On the other hand, its use frequently induces axillary or wrist pain and critical neurovascular injuries have been reported in several studies. Recently, knee walker was introduced, which minimized these weaknesses and yielded favorable results in some clinics. To the best of our knowledge, there have been no previous original article comparing the clinical results of the knee walker and axillary crutch in foot and ankle patients who require nonweightbearing. This study compared the clinical outcomes of patients using the knee walker and axillary crutch. Methods: A retrospective analysis was performed comparing the utility of a knee walker and axillary crutch as a nonweightbearing ambulatory aid for 62 foot and ankle patients treated between November 2016 and March 2018. A comparative study of the two orthosis could be performed because all the patients temporarily used an axillary crutch before or after the use of a knee walker. Jin Bae He Wheel Chair X 01 (JBH Medical Apparatus, Nanjing, China) was used for the knee walker and standard axillary crutch was used. A demographic study and comparative analysis based on the visual analogue scale (VAS) satisfaction score (0˜100), complications, and fall down history were evaluated. Furthermore, under the assumption of having retreatment, their preference of orthosis between the knee walker and axillary crutch was investigated. Results: The mean age of the patients was 36.5 and the mean duration of ambulation with a knee walker and axillary crutch were 5.2 and 2.4 weeks. The VAS satisfaction score of the knee walker and crutch was 88.8 and 27.5, respectively (p

Hypoxic conditions induce the activation of hypoxia-inducible factor-1α (HIF-1α) to restore the supply of oxygen to tissues and cells. Activated HIF-1α translocates into the nucleus and binds to hypoxia response elements to promote the transcription of target genes. Cathepsin L (CTSL) is a lysosomal protease that degrades cellular proteins via the endolysosomal pathway. In this study, we attempted to determine if CTSL is a hypoxia responsive target gene of HIF-1α, and decipher its role in melanocytes in association with the autophagic pathway. The results of our luciferase reporter assay showed that the expression of CTSL is transcriptionally activated through the binding of HIF1-α at its promoter. Under autophagy-inducing starvation conditions, HIF-1α and CTSL expression is highly upregulated in melan-a cells. The mature form of CTSL is closely involved in melanosome degradation through lysosomal activity upon autophagosome–lysosome fusion. The inhibition of conversion of pro-CTSL to mature CTSL leads to the accumulation of gp100 and tyrosinase in addition to microtubule-associated protein 1 light chain 3 (LC3) II, due to decreased lysosomal activity in the autophagic pathway. In conclusion, we have identified that CTSL, a novel target of HIF-1α, participates in melanosome degradation in melanocytes through lysosomal activity during autophagosome–lysosome fusion.

Abstracts: Air pollution, a global health concern, has been associated with adverse effects on human health. In particular, particulate matter (PM), which is a major contributor to air pollution, impacts various organ systems including the skins. In fact, PM has been suggested as a culprit for accelerating skin aging and pigmentation. In this study, using single-cell RNA sequencing, IL-24 was found to be highly upregulated among the differentially expressed genes commonly altered in keratinocytes and fibroblasts of ex vivo skins exposed to PM. It was verified that PM exposure triggered the expression of IL-24 in keratinocytes, which subsequently led to a decrease in type I procollagen expression and an increase in MMP1 expression in fibroblasts. Furthermore, long-term treatment of IL-24 induced cellular senescence in fibroblasts. Through high-throughput screening, we identified chemical compounds that inhibit the IL-24-STAT3 signaling pathway, with lovastatin being the chosen candidate. Lovastatin not only effectively reduced the expression of IL24 induced by PM in keratinocytes but also exhibited a capacity to restore the decrease in type I procollagen and the increase in MMP1 caused by IL-24 in fibroblasts. This study provides insights into the significance of IL-24, illuminating mechanisms behind PM-induced skin aging, and proposes IL-24 as a promising target to mitigate PM-associated skin aging.

We have determined the crystal structure of porcine quinolinate phosphoribosyltransferase (QAPRTase) in complex with nicotinate mononucleotide (NAMN), which is the first crystal structure of a mammalian QAPRTase with its reaction product. The structure was determined from protein obtained from the porcine kidney. Because the full protein sequence of porcine QAPRTase was not available in either protein or nucleotide databases, cDNA was synthesized using reverse transcriptase-polymerase chain reaction to determine the porcine QAPRTase amino acid sequence. The crystal structure revealed that porcine QAPRTases have a hexameric structure that is similar to other eukaryotic QAPRTases, such as the human and yeast enzymes. However, the interaction between NAMN and porcine QAPRTase was different from the interaction found in prokaryotic enzymes, such as those of Helicobacter pylori and Mycobacterium tuberculosis. The crystal structure of porcine QAPRTase in complex with NAMN provides a structural framework for understanding the unique properties of the mammalian QAPRTase active site and designing new antibiotics that are selective for the QAPRTases of pathogenic bacteria, such as H. pylori and M. tuberculosis.

Our work aimed to investigate the protective effects of saponin-based nanoemulsions of vitamin A and E against oxidative stress-induced cellular damage in AML-12 cells. Saponin nanoemulsions of vitamin A (SAN) and vitamin E (SEN) were prepared by high-pressure homogenization and characterized in terms of size, zeta potential, and polydispersity index. SEN and SAN protect AML-12 cells against oxidative stress-induced cellular damage more efficiently via scavenging reactive oxygen species (ROS), and reducing DNA damage, protein carbonylation, and lipid peroxidation. These results provide valuable information for the development of nanoemulsion-based delivery systems that would improve the antioxidant properties of vitamin A and E.

The MutS2 homologues have received attention because of their unusual activities that differ from those of MutS. In this work, we report on the functional characteristics and conformational diversities of Thermotoga maritima MutS2 (TmMutS2). Various biochemical features of the protein were demonstrated via diverse techniques such as scanning probe microscopy (SPM), ATPase assays, analytical ultracentrifugation, DNA binding assays, size chromatography, and limited proteolytic analysis. Dimeric TmMutS2 showed the temperature-dependent ATPase activity. The non-specific nicking endonuclease activities of TmMutS2 were inactivated in the presence of nonhydrolytic ATP (ADPnP) and enhanced by the addition of TmMutL. In addition, TmMutS2 suppressed the TmRecA-mediated DNA strand exchange reaction in a TmMutL-dependent manner. We also demonstrated that small-angle X-ray scattering (SAXS) analysis of dimeric TmMutS2 exhibited nucleotide- and DNA-dependent conformational transitions. Particularly, TmMutS2-ADPnP showed the most compressed form rather than apo-TmMutS2 and the TmMutS2-ADP complex, in accordance with the results of biochemical assays. In the case of the DNA-binding complexes, the stretched conformation appeared in the TmMutS2-four-way junction (FWJ)-DNA complex. Convergences of biochemical- and SAXS analysis provided abundant information for TmMutS2 and clarified ambiguous experimental results.

This study aimed to determine the optimal combination of three anti-infammatory materials [i.e., Cervus nippon Temminck (CT), Angelica gigas Nakai (AN), and Rehmannia glutinosa (RG)] for the strongest anti-infammatory potential. Eighteen combinations of the three materials were tested in LPS-stimulated RAW264.7 cells via assessing nitric oxide (NO). The best combination from in vitro studies was administered to LPS-treated C57BL/6J mice for fve days. Subsequently, plasma metabolites were profled by bioinformatics analyses and validations. As results, 2, 20, and 50 µg/mL of CT, AN, and RG (TM) were the most efective combination suppressing infammation. In mice, TM mitigated hepatic infammatory markers. Similarly, the metabolomics indicated that TM may suppress NF-κB signaling pathway, thereby alleviating hepatic infammation. TM also decreased systemic and hepatic pro-infammatory cytokines. Collectively, we found the optimal combination of TM for mitigating infammation; thus further studies on safety, mechanisms, and clinical models are warranted for human applications. [ABSTRACT FROM AUTHOR]

Filamentous fungal mycoproteins have gained increasing attention as sustainable alternatives to animal and plant-based proteins. This comprehensive review summarizes the nutritional characteristics, toxicological aspects, and healthpromoting effects of mycoproteins, focusing on those derived from filamentous fungi, notably Fusarium venenatum. Mycoproteins are characterized by their high protein content, and they have a superior essential amino acid profile compared to soybeans indicating excellent protein quality and benefits for human nutrition. Additionally, mycoproteins offer enhanced digestibility, further highlighting their suitability as a protein source. Furthermore, mycoproteins are rich in dietary fibers, which have been associated with health benefits, including protection against metabolic diseases. Moreover, their fatty acids profile, with significant proportions of polyunsaturated fatty acids and absence of cholesterol, distinguishes them from animal-derived proteins. In conclusion, the future of mycoproteins as a health-promoting protein alternative and the development of functional foods relies on several key aspects. These include improving the acceptance of mycoproteins, conducting further research into theirmechanisms of action, addressing consumer preferences and perceptions, and ensuring safety and regulatory compliance. To fully unlock the potential of mycoproteins and meet the evolving needs of a health-conscious society, continuous interdisciplinary research, collaboration among stakeholders, and proactive engagement with consumers will be vital. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are readily generated from the culture of mouse bone marrow (BM) treated with either granulocyte macrophage-colony stimulating factor (GM-CSF) or FMS-like tyrosine kinase 3 ligand (FLT3L). CD11c+MHCII+ or CD11c+MHCIIhicells are routinely isolated from those BM cultures and generally used as in vitro-generated DCs for a variety of experiments and therapies. Here, we examined CD11c+ cells in the BM culture with GM-CSF or FLT3L by staining with a monoclonal antibody 2A1 that is known to recognize mature or activated DCs. Most of the cells within the CD11c+MHCIIhi DC gate were 2A1+ in the BM culture with GM-CSF (GM-BM culture). In the BM culture with FLT3L (FL-BM culture), almost of all the CD11c+MHCIIhi cells were within the classical DC2 (cDC2) gate. The analysis of FL-BM culture revealed that a majority of cDC2-gated CD11c+MHCIIhi cells exhibited a 2A1- CD83- CD115+CX3CR1+ phenotype, and the others consisted of 2A1+CD83+CD115- CX3CR1- and 2A1- CD83- CD115- CX3CR1- cells. According to the antigen uptake and presentation, morphologies, and gene expression profiles, 2A1- CD83- CD115- CX3CR1- cells were immature cDC2s and 2A1+CD83+CD115- CX3CR1- cells were mature cDC2s. Unexpectedly, however, 2A1- CD83- CD115+CX3CR1+ cells, the most abundant cDC2-gated MHCIIhi cell subset in FL-BM culture, were non-DCs. Adoptive cell transfer experiments in the FL-BM culture confirmed that the cDC2-gated MHCIIhi non-DCs were precursors to cDC2s, i.e., MHCIIhi pre-cDC2s. MHCIIhi pre-cDC2s also expressed the higher [ABSTRACT FROM AUTHOR]