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Abstract Background Global warming-related temperature increases have a substantial effect on plant and human health. The Arabica coffee plant is susceptible to growing in many places across the world where temperatures are rising. This study examines how nanosilicon and seaweed extracts can improve Arabica coffee plant resilience during heat stress treatment (49.0 ± 0.3 °C) by maintaining mineral homeostasis and photosynthetic ability upon recovery. Results The principal component analysis arrangement of four treatments, nanosilicon (Si), seaweed extract (SWE), Si + SWE, and control (CT), showed each element ratio of magnesium, phosphorus, chloride, potassium, manganese, iron, copper, and zinc per silicon in ambient temperature and heat stress that found influenced upper shoot rather than basal shoot and root within 74.4% of largest feasible variance as first principal component. Magnesium and iron were clustered within the silicon group, with magnesium dominating and leading to a significant increase (p ≤ 0.05) in magnesium-to-silicon ratio in the upper shoot under heat conditions, especially in Si and Si + SWE treated plants (1.11 and 1.29 fold over SWE treated plant, respectively). The SWE and Si + SWE treated plants preserved chlorophyll content (15.01% and 28.67% over Si-treated plant, respectively) under heat stress, while the Si and Si + SWE treated plants restored photosynthetic efficiency (Fv/Fm) better than the SWE treated plant. Conclusions The concomitant of the Si + SWE treatment synergistically protected photosynthetic pigments and Fv/Fm by adjusting the magnesium-silicon homeostasis perspective in Arabica coffee to protect real-world agricultural practices and coffee cultivation under climate change scenarios.

During multiple field campaigns, small quasi-spherical ice crystals, commonly referred to as frozen droplets (FDs), and their aggregates (frozen-droplet aggregates, FDAs) have been identified as the predominant habits in the upper regions of deep convective clouds (DCCs) and their associated anvils. These findings highlight the significance of FDs and FDAs for understanding the microphysics and radiative properties of DCCs. Despite the prevalence of FDs and FDAs at the tops of DCCs where they directly contribute to cloud radiative effect, the detailed single-scattering properties (e.g., scattering-phase function P11 and asymmetry parameter g) of FDs and FDAs remain highly uncertain. This uncertainty is mainly due to insufficient in situ measurements and the resolution of cloud probes, which hinder the development of idealized shape models for FDs and FDAs. In this study, two shape models, the Gaussian random sphere (GS) and droxtal (DX), are proposed as possible representations for the shapes of FDs and FDAs measured in situ. A total of 120 individual models of GSs and 129 models of DXs were generated by varying their shapes. Furthermore, by attaching these individual models in both a homogeneous and heterogeneous manner, three different types and a total of 404 models of FDAs were created: (1) aggregates of GSs; (2) aggregates of DXs; and (3) combinations of GSs and DXs, which are called habit mixtures (HMs). The P11 and g values of the developed models were calculated using a geometric optics method at a wavelength of 0.80 µm and then compared with those obtained using a polar nephelometer (PN) during the CIRCLE-2 field campaign to assess the models. Both individual-component ice crystals (i.e., either GS or DX) and homogeneous-component aggregates (i.e., either aggregates of GSs or aggregates of DXs) showed substantial differences compared with the PN measurements, whereas the P11 of the HMs was found to most accurately match the P11 measured in situ, reducing the differences to +0.87 %, +0.88 %, and −5.37 % in the forward-, lateral-, and backward-scattering regions, respectively. The g value of the HMs was found to be 0.80, which falls within the range of the PN measurement (0.78 ± 0.04). The root-mean-square error for the HM was minimized to a value of 0.0427. It was shown that the novel HMs developed in this study demonstrated better performance than in previous research where HMs were developed indirectly by weighting the calculated P11 of shape models to interpret in situ measurement. The results of this study suggest potential implications for enhancing the calculation of single-scattering properties of ice crystals in DCCs.

Abstract Maternal nutrition significantly influences fetal development and postnatal outcomes. This study investigates the impact of maternal overfeeding during mid to late pregnancy on gene expression in the round and sirloin muscles of Hanwoo neonatal calves. Eight cows were assigned to either a control group receiving standard nutrition (100%) or a treated group receiving overnutrition (150%). After birth, tissue samples from the round and sirloin muscles of neonatal calves were collected and subjected to RNA sequencing to assess differentially expressed genes (DEGs). RNA sequencing identified 43 DEGs in round muscle and 15 in sirloin muscle, involving genes related to myogenesis, adipogenesis, and energy regulation. Key genes, including PPARGC1A, THBS1, CD44, JUND, CNN1, ENAH, and RUNX1, were predominantly downregulated. Gene ontology (GO) enrichment analyses revealed terms associated with muscle development, such as “biological regulation,” “cellular process,” and “response to stimulus.” Protein-protein interaction networks highlighted complex interactions among DEGs. Random Forest analysis identified ARC, SLC1A5, and GNPTAB as influential genes for distinguishing between control and treated groups. Overall, maternal overnutrition during mid-to-late pregnancy results in the downregulation of genes involved in muscle development and energy metabolism in neonatal Hanwoo calves. These findings provide insights into the molecular effects of maternal nutrition on muscle development.

Abstract The molecular characterization of genetically modified organisms (GMOs) is essential for ensuring safety and gaining regulatory approval for commercialization. According to CODEX standards, this characterization involves evaluating the presence of introduced genes, insertion sites, copy number, and nucleotide sequence structure. Advances in technology have led to the increased use of next-generation sequencing (NGS) over traditional methods such as Southern blotting. While both methods provide high reproducibility and accuracy, Southern blotting is labor-intensive and time-consuming due to the need for repetitive probe design and analyses for each target, resulting in low throughput. Conversely, NGS facilitates rapid and comprehensive analysis by mapping whole-genome sequencing (WGS) data to plasmid sequences, accurately identifying T-DNA insertion sites and flanking regions. This advantage allows for efficient detection of T-DNA presence, copy number, and unintended gene insertions without additional probe work. This paper reviews the current status of GMO genome characterization using NGS and proposes more efficient strategies for this purpose.

Abstract Uropygial gland secretions of birds consist of host and bacteria derived compounds and play a major sanitary and feather-protective role. Here we report on our microbiome studies of the New Guinean toxic bird Pachycephala schlegelii and the isolation of a member of the Amycolatopsis genus from the uropygial gland secretions. Bioactivity studies in combination with co-cultures, MALDI imaging and HR-MS/MS-based network analyses unveil the basis of its activity against keratinolytic bacteria and fungal skin pathogens. We trace the protective antimicrobial activity of Amycolatopsis sp. PS_44_ISF1 to the production of rifamycin congeners, ciromicin A and of two yet unreported compound families. We perform NMR and HR-MS/MS studies to determine the relative structures of six members belonging to a yet unreported lipopeptide family of pachycephalamides and of one representative of the demiguisins, a new hexapeptide family. We then use a combination of phylogenomic, transcriptomic and knock-out studies to identify the underlying biosynthetic gene clusters responsible for the production of pachycephalamides and demiguisins. Our metabolomics data allow us to map molecular ion features of the identified metabolites in extracts of P. schlegelii feathers, verifying their presence in the ecological setting where they exert their presumed active role for hosts. Our study shows that members of the Actinomycetota may play a role in avian feather protection.

Abstract Background Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. Methods This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC)

Abstract Background Research on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited. Methods Data from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed. Results During a median follow-up of 4.8 years (IQR 2.4–8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92–1.09), supplemental (HR 0.97, 95%CI 0.89–1.06) and total calcium intake (HR 0.99, 95%CI 0.88–1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene. Conclusion Calcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.

Background: Under nutrition and overweight in children co-exist in developing countries and may persist into adulthood. Interpretation of body mass index (BMI), a useful measure of nutritional status in children requires age related reference standards, many of which were developed from different international sources. It is necessary to determine which of these reference standards is most suitable for use in the assessment of BMI distribution among adolescents in Nigeria. Objective: To determine the prevalence of thinness, overweight and obesity using the World Health Organization (WHO), International Obesity Task Force (IOTF), and Centre for Disease Control (CDC) reference standards and assess their level of agreement amongst adolescents in Sokoto metropolis. Methods: 800 students were selected through multi-stage sampling technique from secondary schools. BMI was classified according to three reference standards (WHO, CDC, IOTF). Data was analysed with SPSS version 22. The level of agreement between the reference standards in diagnosing nutritional status was assessed using Kappa statistics. Level of significance was put at p< 0.05. Results: The prevalence rate of thinness was highest with the IOTF at 22.6% compared to 19.4%, and 19.6% by the WHO and CDC respectively. The prevalence rates of overweight and obesity were highest with the WHO reference standards at 7.0% and 1.3% followed by the IOTF (6.1%and 0.6%) and lowest with the CDC (5.8% and 0.3%). Substantial agreement was observed between WHO and IOTF (Kappa = 0.77), while the level of agreement was 0.68 for IOTF/CDC and 0.64 for WHO/CDC. All agreement statistics were significant (p < 0.001). Conclusion: The WHO and IOTF reference charts may be more suitable for our population.

Abstract Despite the growing interest in precision medicine-based therapies for Alzheimer's disease (AD), little research has been conducted on how individual AD risk factors influence changes in cognitive function following transcranial direct current stimulation (tDCS). This study evaluates the cognitive effects of sequential tDCS on 63 mild cognitive impairment (MCI) patients, considering AD risk factors such as amyloid-beta deposition, APOE ε4, BDNF polymorphism, and sex. Using both frequentist and Bayesian methods, we assessed the interaction of tDCS with these risk factors on cognitive performance. Notably, we found that amyloid-beta deposition significantly interacted with tDCS in improving executive function, specifically Stroop Word-Color scores, with strong Bayesian support for this finding. Memory enhancements were differentially influenced by BDNF Met carrier status. However, sex and APOE ε4 status did not show significant effects. Our results highlight the importance of individual AD risk factors in modulating cognitive outcomes from tDCS, suggesting that precision medicine may offer more effective tDCS treatments tailored to individual risk profiles in early AD stages.

Abstract Phenylpropanoids are naturally occurring secondary metabolites that exhibit various biological activities such as ultra-violet (UV) light protection and reactive-oxygen species (ROS) scavenging. In this study, we utilized a light-emitting diode (LED) based in-situ UV irradiation nuclear magnetic resonance (NMR) technique to monitor the photoisomerization reactions of these phenylpropanoids under UV irradiation in real-time. Through this approach, we measured the photochemical reaction rates and photostationary state (PSS) ratios of these molecules and observed distinct reaction rate and PSS ratio information depending on the variation of substituent groups in each phenylpropanoid molecule. We also evaluated the radical scavenging activity (RSA) for each photochemical product through diphenyl-1-picrylhydrazyl radical (DPPH) assay and 2,2’-azino-bis(3-ethylbenzenthiazoline-6-sulphonic acid) (ABTS) assay. We found that the photoisomerization product of caffeic acid can increase both DPPH and ABTS radical scavenging activities, and confirmed the enhanced ABTS radical scavenging ability of caffeic acid cis-isomer based on the online high-pressure liquid chromatography (HPLC)-ABTS analysis and the PSS ratio information of each isomer.

Abstract Windows provide access to daylight and outdoor views, influencing building design. Various glazing and window shade materials are used to mitigate glare, overheating and privacy issues, and they affect view clarity. Among them, we evaluated the effect of window films, electrochromic (EC) glass, and fabric shades on view clarity. We conducted an experiment with 50 participants using visual tests adapted from clinical vision tests (visual acuity, contrast sensitivity, color sensitivity) and images displayed on a computer monitor in a controlled laboratory. Window films and EC glass tints outperformed fabric shades in visual acuity, contrast sensitivity and view satisfaction with the exception of the darkest EC tint state and dark grey VLT 3% shade for color sensitivity and view satisfaction. The EC tints pose internal reflection issues and fabric shades are preferred for visual privacy. Window films and EC glass hinder participants’ blue–green color discrimination while fabric shades also decrease red–yellow color discrimination. Visual acuity predicts view satisfaction and contrast sensitivity is the strongest predictor for visual privacy. Generally, higher visible light transmittance and lower solar reflectance (darker color) enhance human visual performance. The proposed workflow provides an experimental procedure, identifies the primary variables and establishes a predictive framework for assessing view clarity of fenestration.

This research is important to understand the behavior of parents of Cerebral Palsy (CP) children by reducing the complexity in understanding knowledge and economic dimensions, thus providing a structured approach to identifying factors that influence the psychology of children with CP. This study aimed to identify and reduce the dimensions that influence the behavior of parents of children with CFA.This study aimed to reduce the socio-economic dimensions and knowledge of the behavior of parents of Cerebral Palsy (CP) children using CFA. A quantitative approach with a cross-sectional design was used in this study to comprehensively examine the behavior of parents of children with CP. Purposive sampling was used to select 200 participants from various backgrounds. The instrument used was a 28-item questionnaire which was distributed online to collect data. The questionnaire has gone through rigorous testing, including CFA, determinant KMO test, Bartlett test PCA, and grouping of variables based on identified factors.Research methods , a quantitative approach with cross-sectional design, and purposive sampling were used to select 200 parents of children with CP from various backgrounds. The instrument in the form of a questionnaire with 28 statement items was distributed online. Data analysis was carried out using CFA, including the determinant test, Kaiser-Meyer-Olkin (KMO) test, Bartlett test, Principal Components Analysis (PCA), and grouping variables based on factors. Research in Lampung shows that the number of boys with CP is slightly higher, with the majority aged 1-5 years. Factor analysis identified three main dimensions: parental knowledge about CP, family economic situation, and parental behavior. Better knowledge and a stable economic situation are positively correlated with better parental behavior in caring for children with CP. Many parents experience high levels of stress due to the physical, emotional, and financial burden of caring for a child with CP. The research conclusion shows that the 28 statement items were successfully reduced to three main dimensions (knowledge, economics, and behavior) which have a significant relationship in the care of children with CP. These findings suggest the need for interventions to increase parental knowledge about CP and family economic stability to increase parental participation in child care.Findings the sex distribution of children with cerebral palsy in Lampung showed a slight excess in the number of boys, with the majority of children being in the age range of 1-5 years. Factor analysis identified three main dimensions: parental knowledge of CP, family economic situation, and parental behavior, where better knowledge and stable economic situation positively correlated with better parental behavior in caring for children with CP. Many parents experience high levels of stress in caring for a child with CP because of the physical, emotional, and financial burden that the condition brings. In conclusion, the 28 items of the statement are reduced to 3 dimensions or factors, including knowledge, economics, and behavior. Each dimension has a relationship with each other significantly to the behavior of parents of CP children.

Kawasaki disease (KD) is an acute systemic vasculitis that mostly affects children less than 5years. Occasionally, it may presents with renal involvement of varying severity. In Nigeria and most of Africa, only a few cases of KD have been reported and these were among children within the typical age group. We report an unusual case of Kawasaki disease with renal manifestation in a 14 year old adolescent. Apart from the principal features of KD comprising of high grade fever, non purulent conjunctivitis, polymorphous rash, right sided cervical lymphadenitis and symmetrical desquamative lesions of the digits of the hands and feet; our patient also had renal involvement. The renal manifestations included mild periorbital edema, oliguria, hypertension (140/90mmHg), hematuria(++), proteinuria(++) and elevated serum urea and creatinine (8.3mmol/L and 1.9mg/dl respectively). He was managed with high dose aspirin at 80mg/kg/day. The dose was reduced (5mg/Kg/day) and subsequently stopped after serial echocardiography showed normal coronary arteries. Intravenous immune globuline (IVIG) could not be started due to non availability. Nevertheless, clinical signs resolved, renal function normalised after 6 weeks and echocardiographic picture did not deteriorate. Patient is currently on follow up at the paediatric cardiology clinic of UDUTH, Sokoto, Nigeria.. Conclusion: Kawasaki disease can occur even in older children and renal manifestation may be self limiting. This report highlights the need for high index of suspicion in all cases.

Background: Neonatal sepsis is a known leading cause of neonatal morbidity and mortality. Aim: To compare the efficacies of 96% methylated spirit and 4% chlorhexidine (CHX) gel in the treatment of umbilical stump of neonates. Method: This was a randomized, open labelled, parallel group trial of CHX gel and Methylated spirit for neonatal umbilical cord care in Jos, between 2/6/17 and 16/7/17. Inclusion criteria were term, newly born 0 to 6 hours old, with no known risk for sepsis and written informed parental consent. Eligible subjects were randomized to receive methylated spirit or 4% CHX gel. Outcome measures were cord separation time, omphalitis, neonatal sepsis and neonatal mortality by day 28. Results: A total sample of 51 of 58 met enrolment criteria. Thirtytwo (62.7%) where delivered in JUTH, 33(64.7%) were males with a mean birth weight of 3.7kg (CI 3.04 – 3.30). Mean cord separation times were 7.96 ± 4.07)days in the methylated spirit group vs 6.43 ± 3.13days in the CHX comparator group, (p=0.078). Omphalitis was0% vs2(8.3%) and NNS 2(7.4%)vs2(8.3%) in methylated spirit and CHX treatment groups respectively. There was 1(3.7%) mortality in the methylated spirit treatment group. Conclusion: Methylated spirit and 4% CHX gel have comparable umbilical stump treatment efficacy. Methylated spirit may be a safe alternative in clinical settings where topical 4% CHX gel is unavailable or unsafe.

Background: Severe neonatal jaundice remains common in Nigeria. Phototherapy is the most commonly used inhospital treatment for neonatal hyperbilirubinaemia. Objectives: To describe the availability and distribution of phototherapy services as an essential neonatal service in hospitals in Jos, North-Central Nigeria. Methods: This was a crosssectional study of all secondary and tertiary level health facilities in Jos-North, Jos-South and Jos- East Local government Areas (LGAs) between January and March 2015. Results: There were 30 (90.9%) secondary and three (9.1%) tertiary health facilities. Twenty – eight (84.8%) were privately owned. Fourteen (42.4%) of the 33 hospitals provided phototherapy services, of which 11 (78.6%) were private. Phototherapy services were available in all the tertiary facilities and in only 11 (36.7%) of the secondary level health facilities. Most (10; 71.4%) of the hospitals with phototherapy were located in Jos-North LGA. There were 38 phototherapy units in all the 14 hospitals that offered phototherapy, consisting of 8 (21.1%) light emitting diodes (LED) and 30(78.9%) conventional units of which 25(83.3%) were locally fabricated. In all the hospitals that provided phototherapy, jaundiced neonates were managed by physicians of whom only 12% were fulltime paediatricians. All hospitals that offered phototherapy had laboratory facilities to assay bilirubin. Conclusions: Phototherapy services in Jos, Nigeria are inadequate and are concentrated in the urban private sector. An increase in phototherapy services especially in secondary public facilities is needed.

Abstract Wild-simulated ginseng (WSG, Panax ginseng C.A. Meyer) is grown in mountainous forests, without the chemical treatment or installation of artificial facilities. This study aimed to investigate monthly changes in growth characteristics and ginsenoside contents in WSG to suggest the optimal harvest time. Four-year-old WSG were collected in the same area every month, and their growth characteristics and ginsenoside contents were measured. The growth characteristics of aerial and root parts were measured from May to July and from March to December, respectively. For the aerial part, most growth characteristics of WSG decreased over time, except for stem length. For the root part, rhizome length increased over time except for September, while the root diameter and weight of root part were mostly consistent. The root length increased by September, while the number of rootlets was the highest at May. At July, the total ginsenoside content of WSG was significantly the highest, while the total ginsenoside content at October was the lowest. This result was believed to be due to the F2, Rd, and Rg1 contents of the aerial part, rather than the root part. Also, based on these growths and the ginsenoside contents of WSG, the optimal harvest time for WSG is considered to be late spring–summer (May–July) when the aerial part can be identified.

Abstract Background Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. Results We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. Conclusions This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer.

Highlights In-depth review assesses III–V materials for efficient hydrogen generation and CO2 reduction in renewable energy technologies. Exploration of strategies for broad light absorption and increased efficiency in water splitting processes and CO2 reduction. Innovative electrode designs conclude the path for stable, large-scale implementation of clean energy systems.

Giulia Lanfranchi,1 Irene Paraboschi,2 Ugo Maria Pierucci,1 Guglielmo Mantica,3 Sara Costanzo,1 Federica Marinoni,1 Andrea Pansini,1 Giorgio Giuseppe Orlando Selvaggio,1 Gloria Pelizzo1,2 1Department of Pediatric Surgery, Buzzi Children’s Hospital, Milan, 20154, Italy; 2Department of Biomedical and Clinical Sciences “L Sacco”, University of Milano, Milan, 20157, Italy; 3Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, 16131, ItalyCorrespondence: Gloria Pelizzo, Department of Biomedical and Clinical Sciences “L Sacco”, University of Milan, Milan, 20157, Italy, Email gloria.pelizzo@unimi.itAim: To review our 10 years of experience with the endoscopic treatment of vesicoureteral reflux (VUR) in children, emphasizing the long-term efficacy of the “combined STING-HIT” technique.Materials and Methods: A retrospective study was performed including all children with symptomatic VUR undergoing the cystoscopic injection of bulking agents from January 2013 to December 2022 in our pediatric tertiary referral center. Three different endoscopic techniques were adopted: the “combined STING-HIT” technique, the STING technique, and the HIT technique. Treatment success was defined as symptom remission and VUR resolution on the voiding cystourethrogram (VCUG) performed at the 3-month follow-up.Results: In the study period, 140 (F:M = 64:76) patients and 228 ureters were treated at a median patient age of 3 (2.0– 6.0) years. After a single endoscopic treatment, VUR resolved in 203 (88%) ureters. The VUR resolution rate after a single endoscopic treatment was 95% (n=70/74) in case of I–II VUR, 88% (n=87/99) in case of III VUR; 83% (n=38/46) in case of IV VUR; 89% (n=8/9) in case of V VUR (p-value: 0.174). Overall, one or two endoscopic treatments succeeded in 219 (96%) ureters. The overall VUR resolution rate following one or two endoscopic treatments was 100% (74/74) in case of I–II VUR, 93% (n=92/99) in case of III VUR; 96% (n=44/46) in case of IV VUR; 100% (n=9/9) in case of V VUR (p-value: 0.083). Despite not being statistically significant, the VUR resolution rate was higher for the “combined STING-HIT” technique, both after one (92%: n=110/119; versus 85%; n=62/73 versus 86%; n=31/36; p-value: 0.225) or two (98%: n=116/119; versus 95%; n=69/73 versus 94%; n=34/36; p-value: 0.469) endoscopic treatments.Conclusion: The endoscopic approaches were highly successful for the treatment of VUR in children. The “combined STING-HIT” technique was a safe and effective procedure, being associated with the higher resolution rate.Keywords: vesicoureteral reflux, injection technique, endoscopic technique, pediatrics

In July 2022, stem rot symptom was found in a peony plant grown in a pot under a greenhouse at Jinju, Gyeongnam Province, South Korea. Two fungal species were isolated from the infected peony stems and cultured on 1/2-strength potato dextrose agar for identification. The morphological characteristics of the fungal isolates were examined, and nucleotide sequences of the internal transcribed spacer region, β-tubulin and translation elongation factor 1-α were analysed. The pathogenicity of the two isolates was confirmed in detached peony leaves, according to Koch's postulates. To our knowledge, this is the report of Neopestalotiopsis clavispora and Sclerotinia sclerotiorum as the causal agents of peony stem rots. Antifungal activity of chemical fungicide propineb and rhizobacterium Bacillus siamensis H30-3 was shown against the two plant pathogenic fungi N. clavispora and S. sclerotiorum. Unidentified diffusible and volatile compounds from B. siamensis H30-3 could suppress in vitro mycelial growths of N. clavispora JJ 8-2-1 and S. sclerotiorum JJ 8-2-2.

Background & objectives: Malaria remains a major public health concern in Nigeria and the vector (Anopheles species) can only be controlled effectively by having good knowledge of its composition and potential for disease transmission. This work aimed at surveying indoor malaria vectors and, Knowledge, Attitudes, and Practices (KAP) in relation to disease transmission in Toro LGA, Bauchi State, Nigeria. Methods: Mosquitoes were collected by Pyrethrum Spray Catch (PSC) between October and December 2019 and were morphologically identified using standard keys. Blood samples were collected from individuals who slept in the rooms where PSC was conducted. Thick and thin blood smears were made for malaria parasite examination. Questionnaires were administered to 120 participants for the KAP studies. Results: Ninety-seven Anopheles mosquitoes were collected and identified as Anopheles gambiae 76 (78.35%), An. funestus 20 (20.62%) and An. coustani 1(1.03%). The overall malaria prevalence was 15.8%. KAP studies revealed that measures and treatment-seeking behaviours against malaria varied significantly (P

Background and Objective The complex relationship between obstructive sleep apnea (OSA) and neurodegenerative diseases is increasingly being recognized. This study aims to elucidate the association between OSA and α-synucleinopathies, with a focus on Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), and dementia with Lewy bodies (DLB), highlighting the impact of demographic variables. Methods Employing a retrospective cohort approach, we analyzed 103785 patients diagnosed with OSA and their matched controls. The data were sourced from South Koreas National Health Insurance claims database spanning 2010 to 2019. Our investigation centered on the incidence of PD, PDD, and DLB among patients with OSA, utilizing chi-square tests, t-tests, and multivariable logistic regression to compute adjusted odds ratios (AOR). Additionally, we conducted a subgroup analysis focusing on variations by sex and age. Results The findings indicate that individuals suffering from OSA had a significantly elevated risk for PD (AOR = 2.166, 95% confidence interval [CI]: 1.840–2.549, p < 0.0001) and DLB (AOR = 4.001, 95% CI: 1.501–10.660, p = 0.0056). Subgroup analyses further highlighted that the association between PD, DLB, and OSA was markedly stronger in men and escalated in those above 60 years of age. Conclusions Our analysis establishes a substantial link between OSA and an increased likelihood of developing PD and DLB, emphasizing the vital role demographic factors play. These findings suggest the need for intensified surveillance and customized management strategies for OSA, particularly among individuals at heightened risk for neurodegenerative disorders. Additionally, this research lays the foundation for further studies into the progression and therapeutic interventions for these conditions.

Abstract Background Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed. Methods An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3. Considering the challenges of limited pharmaco-accessibility to the bladder due to its pathophysiological structure and the partially undruggable nature of target molecules, we designed a dual siRNA system targeting both mRNAs. Subsequently, this dual siRNA system was encoded into the adenovirus 5/3 (Ad 5/3) to enhance in vivo delivery efficiency. Results Gene-targeting efficacy was assessed using cells isolated from xenografted tumors using a single-cell analysis system. Our strategy demonstrated a balanced downregulation of mTOR and STAT3 at the single-cell resolution, both in vitro and in vivo. This approach reduced tumor growth in bladder cancer xenograft and orthotopic animal experiments. In addition, increased infiltration of CD8+ T cells was observed in a humanized mouse model. We provided helpful and safe tissue distribution data for intravesical therapy of siRNAs coding adenoviruses. Conclusions The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with “undruggability.” Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses. Graphical Abstract The current investigation introduces an innovative conceptualization of bispecific short hairpin RNA (bs_shRNA) tailored for the equilibrated modulation of dual genes within a singular cellular context. This novel bs_shRNA was loaded into the genome of an oncolytic adenovirus to augment the therapeutic efficacy of oncolytic viral interventions via the targeted inhibition of mTOR and STAT3 pathways. In addition, the administration of BSV significantly reduced the volume of bladder cancer tumors, concomitantly facilitating an enhanced recruitment of CD8+T lymphocytes in vivo.

Abstract The human oral microbiome may alter oral and systemic disease risk. Consuming high sugar content beverages (HSB) can lead to caries development by altering the microbial composition in dental plaque, but little is known regarding HSB-specific oral microbial alterations. Therefore, we conducted a large, population-based study to examine associations of HSB intake with oral microbiome diversity and composition. Using mouthwash samples of 989 individuals in two nationwide U.S. cohorts, bacterial 16S rRNA genes were amplified, sequenced, and assigned to bacterial taxa. HSB intake was quantified from food frequency questionnaires as low ( 3 servings/week). We assessed overall bacterial diversity and presence of specific taxa with respect to HSB intake in each cohort separately and combined in a meta-analysis. Consistently in the two cohorts, we found lower species richness in high HSB consumers (> 3 cans/week) (p = 0.027), and that overall bacterial community profiles differed from those of non-consumers (PERMANOVA p = 0.040). Specifically, presence of a network of commensal bacteria (Lachnospiraceae, Peptostreptococcaceae, and Alloprevotella rava) was less common in high compared to non-consumers, as were other species including Campylobacter showae, Prevotella oulorum, and Mycoplasma faucium. Presence of acidogenic bacteria Bifodobacteriaceae and Lactobacillus rhamnosus was more common in high consumers. Abundance of Fusobacteriales and its genus Leptotrichia, Lachnoanaerobaculum sp., and Campylobacter were lower with higher HSB consumption, and their abundances were correlated. No significant interaction was found for these associations with diabetic status or with microbial markers for caries (S. mutans) and periodontitis (P. gingivalis). Our results suggest that soft drink intake may alter the salivary microbiota, with consistent results across two independent cohorts. The observed perturbations of overrepresented acidogenic bacteria and underrepresented commensal bacteria in high HSB consumers may have implications for oral and systemic disease risk.

Background: H. pylori eradication is effective for gastric cancer prevention. Treatment failure is caused by increased antibiotic resistance. This study aimed to determine eradication rates and perform cost analysis between susceptibility-guided therapy and empirical treatment in patients with H. pylori treatment failure. Methods: This retrospective cohort study included patients with dyspepsia undergoing gastroscopy at tertiary care center in Thailand from March 2014 to October 2021. Treatment failure was defined as persistent H. pylori infection after ≥1 regimen completion. Early AST was defined as AST performed shortly after first-line treatment failure. Demographic data, AST results, eradication regimens, and medication costs were collected from database and reviewed. Results: Of 1080 patients with H. pylori infection, 315 had treatment failure (mean age 58.4 years; 44.4 % males). AST of 85 strains demonstrated resistance to levofloxacin (57.6 %), metronidazole (51.8 %), clarithromycin (44.7 %), and amoxicillin (4.7 %). In multivariate analysis, sequential therapy was significantly associated with treatment failure (OR 1.66; 95%CI 1.01–2.74, p = 0.045), whereas vonoprazan-containing therapy was related to treatment success (OR 1.60; 95%CI 1.04–2.48, p = 0.034). Medication nonadherence (OR 37.97; 95%CI 8.97–160.65, p

IntroductionCancer cachexia is associated with various metabolic mechanisms such as inflammatory response, insulin resistance, and increased muscle proteolysis. However, effective treatment methods have not yet been standardized. Chrysanthemum indicum L. (CI) is a perennial plant belonging to the Asteraceae family, and its flowers have been used for the treatment of headaches, colds, and rhinitis in Asia.MethodsThis study investigated the effect of CI on cancer cachexia. We subcutaneously injected CT26 colon cancer cells (5 × 105 cells/mouse) into the right flank of BALB/c mice. After 1 week, the mice were orally administered vehicle, CI (100 mg/kg), or Celecoxib (50 mg/kg) for 3 weeks.ResultsCI improved loss of body weight and impaired glucose tolerance, but celecoxib did not recover the body weight and glucose intolerance. CI not only improved the decreased myofiber diameters but also inhibited muscle protein degradation factors, MAFbx and MuRF1. CI also increased cellular membrane GLUT4 in CT26 conditioned medium-treated C2C12 myofibers and cancer cachexia-induced mice. Furthermore, we found that linarin, a constituent of CI, was responsible for the improvement of muscle atrophy.ConclusionOur findings indicate that CI can ameliorate muscle atrophy by improving glucose uptake, suggesting that CI could be a therapeutic agent for cancer cachexia.

Donation after circulatory death (DCD) heart transplantation is emerging as an alternative pathway to traditional donation after brain death (DBD) to expand the heart donor pool. Greater adoption of DCD heart allografts is hampered by the logistical and ethical constraints to perform invasive antemortem testing, thus limiting the capacity for the standard donor organ quality evaluation. Identification of the absence of coronary artery disease in patients at risk is an essential prerequisite for organ acceptance by an implant institution. This case presents a novel approach to the examination of coronary arteries in a cardiac allograft. We demonstrated that the coronary computed tomographic angiographic imaging of an ex-situ nonbeating cardiac allograft preserved after recovery in SherpaPak Cardiac Transport System is technically feasible. The images are of good quality and allow for three-dimensional reconstruction as well as quantification of coronary lesions.

Abstract Background The tumor microenvironment (TME) plays a critical role in cancer progression and response to immunotherapy. Immunotherapy targeting the immune system has emerged as a promising treatment modality, but challenges in understanding the TME limit its efficacy. Optical imaging strategies offer noninvasive, real‐time insights into the interactions between immune cells and the TME. Objective This review assesses the progress of optical imaging technologies in monitoring immunotherapy within the TME and explores their potential applications in clinical trials and personalized cancer treatment. Methods This is a comprehensive literature review based on the advances in optical imaging modalities including fluorescence imaging (FLI), bioluminescence imaging (BLI), and photoacoustic imaging (PAI). These modalities were analyzed for their capacity to provide high‐resolution, real‐time imaging of immune cell dynamics, tumor vasculature, and other critical components of the TME. Results Optical imaging techniques have shown significant potential in tracking immune cell infiltration, assessing immune checkpoint inhibitors, and visualizing drug delivery within the TME. Technologies like FLI and BLI are pivotal in tracking immune responses in preclinical models, while PAI provides functional imaging with deeper tissue penetration. The integration of these modalities with immunotherapy holds promise for improving treatment monitoring and outcomes. Conclusion Optical imaging is a powerful tool for understanding the complexities of the TME and optimizing immunotherapy. Further advancements in imaging technologies, combined with nanomaterial‐based approaches, could pave the way for enhanced diagnostic accuracy and therapeutic efficacy in cancer treatment.

Polyphenols have been well-established to exert sedative-hypnotic effects in psychopharmacology. Lime (Citrus aurantifolia) peel is rich in biologically active polyphenols; however, the effects of lime peel extract on sleep have not yet been demonstrated. A comparison was conducted in mice, between the sleep-promoting effects of a standardized lime peel supplement (SLPS) and a well-known hypnotic drug, zolpidem, and its hypnotic mechanism was investigated using in vivo and in vitro assays. The effects of SLPS on sleep were assessed using a pentobarbital-induced sleep test and sleep architecture analysis based on recording electroencephalograms and electromyograms. Additionally, a GABAA receptor binding assay, electrophysiological measurements, and in vivo animal models were used to elucidate the hypnotic mechanism. SLPS (200 and 400 mg/kg) was found to significantly decrease sleep latency and increase the amount of non-rapid eye movement sleep without altering delta activity. The hypnotic effects of SLPS were attributed to its flavonoid-rich ethyl acetate fraction. SLPS had a binding affinity to the GABA-binding site of the GABAA receptor and directly activated the GABAA receptors. The hypnotic effects and GABAA receptor activity of SLPS were completely blocked by bicuculline, a competitive antagonist of the GABAA receptor, in both in vitro and in vivo assays. To the best of our knowledge, this study is the first to demonstrate the hypnotic effects of SLPS, which acts via the GABA-binding site of the GABAA receptor. Our results suggest that lime peel, a by-product abundantly generated during juice processing, can potentially be used as a novel sedative-hypnotic.

Background: The number of multicultural adolescents is continuously increasing, and they tend to experience more psychological difficulties than their non-multicultural peers. Objective: This study investigates the mediating and moderating effects of parental support on the relationship between social withdrawal and life satisfaction among multicultural adolescents. Methods: This secondary data analysis utilized the Multicultural Children & Adolescents Panel Survey conducted by the National Youth Policy Institute. The analysis included data from 2018 and involved 1197 multicultural adolescents. The data were analyzed using the R-Statistics 4.1.1 program. Results: Social withdrawal and parental support had a detrimental impact on life satisfaction among multicultural adolescents. Parental support also played a partial mediating role in the connection between social support and life satisfaction. Furthermore, parental support was a moderating factor capable of mitigating the negative influence of social withdrawal on life satisfaction. Conclusion: Measures to reduce social withdrawal and increase parental support are very effective in improving the life satisfaction of multicultural adolescents. More focused professional intervention measures for social withdrawal and parental support must be considered when seeking and preparing support measures to improve the life satisfaction of multicultural adolescents.

Three-dimensional (3D) bioprinting has emerged as a promising strategy for fabricating complex tissue analogs with intricate architectures, such as vascular networks. Achieving this necessitates bioink formulations that possess highly printable properties and provide a cell-friendly microenvironment mimicking the native extracellular matrix. Rapid advancements in printing techniques continue to expand the capabilities of researchers, enabling them to overcome existing biological barriers. This review offers a comprehensive examination of ultraviolet-based 3D bioprinting, renowned for its exceptional precision compared to other techniques, and explores its applications in inducing angiogenesis across diverse tissue models related to hypoxia. The high-precision and rapid photocuring capabilities of 3D bioprinting are essential for accurately replicating the intricate complexity of vascular networks and extending the diffusion limits for nutrients and gases. Addressing the lack of vascular structure is crucial in hypoxia-related diseases, as it can significantly improve oxygen delivery and overall tissue health. Consequently, high-resolution 3D bioprinting facilitates the creation of vascular structures within three-dimensional engineered tissues, offering a potential solution for addressing hypoxia-related diseases. Emphasis is placed on fundamental components essential for successful 3D bioprinting, including cell types, bioink compositions, and growth factors highlighted in recent studies. The insights provided in this review underscore the promising prospects of leveraging 3D printing technologies for addressing hypoxia-related diseases through the stimulation of angiogenesis, complementing the therapeutic efficacy of cell therapy.

Warpage in semiconductor packages is a critical issue that affects their reliability and performance. This study aims to minimize the warpage of a bi-material dummy package by optimizing the post-mold curing (PMC) temperature profile. A warpage simulation model was developed considering the viscoelastic properties and cure shrinkage behavior of the epoxy molding compound (EMC). A compression molding monitoring system was also developed to analyze the cure behavior of the EMC. The gelation point of the EMC during compression molding was determined using a dielectric sensor, while cure shrinkage behaviors were analyzed using a fiber Bragg grating sensor. Viscoelastic properties were characterized through stress relaxation tests, and thermal properties were measured using three-dimensional digital image correlation. The developed simulation model was used to optimize the PMC temperature profile using a genetic algorithm. Experimental validation showed that the optimized temperature profile reduced the warpage from ∼1519 μm to 486 μm compared to a linear profile. The findings of this study have broader implications for the design and manufacturing of semiconductor packages, as the proposed approach can be applied to minimize warpage and improve package reliability.

With outstanding therapeutic potential in the tissue regeneration and anti-inflammation, mesenchymal stem cell-derived exosomes (MSC-EXOs) have emerged as a prominent therapeutic in recent. However, poor production yield and reproducibility have remained as significant challenges of their practical applications. To surmount these challenges, various alternative materials with stem cell-like functions, have been recently investigated, however, there has been no comprehensive analysis in these alternatives so far. Here, we discuss the recent progress of alternatives of MSC-EXOs, including exosomes and exosome-like nanovesicles from various biological sources such as plants, milk, microbes, and body fluids. Moreover, we extensively compare each alternative by summarizing their unique functions and mode of actions to suggest the expected therapeutic target and future directions for developing alternatives for MSC-EXOs.

BackgroundThe interrelation between infections, subjective cognitive decline (SCD), and dementia development is recognized, but not fully understood. This study explored the combined effect of specific infections and SCD on the risk of dementia.ObjectivesTo assess the influence of Helicobacter pylori, herpes simplex virus, varicella-zoster virus, and human papillomavirus on dementia risk in individuals with varying cognitive statuses, especially focusing on those with and without SCD.MethodsA cohort of 1,100,540 participants aged 66 years from the Korean National Health Insurance Service was divided into cognitively preserved (CP, n = 825,405) and SCD (n = 275,135) groups. This study analyzed the effects of single, dual, and triple infections on the risk of overall dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) using incidence rates and hazard ratios.ResultsThe SCD group consistently showed a doubled risk of dementia, particularly AD, regardless of the number of infections. In the initial data, both the presence and number of infections, especially in the CP group, were associated with an increased dementia incidence and risk; however, this correlation disappeared after adjusting for covariates, hinting at a possible protective effect.ConclusionOur findings emphasize that, while SCD is a steadfast risk factor for dementia, the role of infections is layered, subject to various influences, and requires more comprehensive exploration to fully understand their impact on dementia development.

Background: Several biologics have been developed and used to treat severe asthma. However, commercialized biologics have limitations in treating T2-low asthma because their main target is the T2 inflammation marker. Therefore, there is an unmet need for treating T2-low severe asthma. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is an auxiliary protein in the mammalian multi-aminoacyl-tRNA synthetase complex. AIMP1 also acts as a cytokine and induces the secretion of proinflammatory cytokines. Since anti-AIMP1 has been shown to reduce interleukin (IL)-6, tumor necrosis factor-α, and IL-17A levels in a mouse model, it could be effective in the treatment of T2-low severe asthma. Methods: Wild-type BALB/c mice were sensitized and challenged with intranasal inoculation of a crude HDM extract. Atliximab, a chimeric AIMP1 antibody, was administered once (20 μg, 40 μg, 100 μg) on Day 14. We evaluated airway hyperresponsiveness (AHR), performed cellular analyses of the bronchoalveolar lavage fluid (BALF), measured inflammatory cytokine levels, and examined peribronchial histological features. Results: Atliximab reduced AIMP1 levels in asthmatic mice in a dose-dependent manner. AHR and Inflammatory cells such as neutrophils and eosinophils in the BALF decreased in asthmatic mice treated with atliximab. The levels of IL-6, IL-13, and transforming growth factor-β (TGF-β) in the lung tissue decreased in asthmatic mice treated with a high dose of atliximab (100 μg). Atliximab also reduced goblet cell hyperplasia and peribronchial fibrosis. Conclusions: Atliximab improved asthmatic airway inflammation including neutrophilic inflammation in HDM-induced asthma mice. These data suggest that anti-AIMP1 plays an important role in the treatment of severe T2-low asthma.

Reliable estimates of how human activities may affect wildlife populations are critical for making scientifically sound resource management decisions. A significant issue in estimating the consequences of management, development, or conservation measures is the need to account for a variety of biotic and abiotic factors, such as land use and climate change, that interact over time altering wildlife habitats and populations. The snow leopard Panthera uncia (Schreber, 1775), as a vulnerable species, is extremely sensitive to indirect impacts of climate change. Given that it is highly difficult undertaking conservation measures on the entire range of snow leopards, identifying hotspots for conservation is necessary. This study was conducted in Bagrot and Haramosh valleys, in the Trans-Himalayan region, to evaluate the impacts of climate and human pressure on snow leopard habitat. Hybrid classification of Landsat satellite data for 2010 and 2020 was performed to elucidate land use changes that suggested a decrease in permanent snow by 10 % and 3 % in Haramosh and Bagrot while an increase in settlements cover by 16 % and 23 %, respectively. Life zone comparison for 2010 and 2020 using the Holdridge life zone (HLZ) classification system disclosed a change from three life zones to five life zones in Haramosh, and four life zones to five life zones in Bagrot, caused by a temperature increase of 2°C to 3°C, indicating that the area is becoming more and more suitable for settlements and less favorable for snow leopards. This study underlines again that mountainous regions are more vulnerable to the impacts of climate change. Warming weather is making survival more difficult for snow leopards. Although they are resilient to the direct effects of climate change, indirect impacts like avalanches, flash floods, urbanization, and human-wildlife conflict make them more vulnerable and threaten their survival. Thus, we recommend establishing further protected areas, better controlling illegal wildlife trade, and conducting genetic studies to understand impacts on snow leopards and rangeland management, livelihood improvement, and human-wildlife conflict reductions.

Young Woo Um,1 Inwon Park,1 Jae Hyuk Lee,1 Hee Eun Kim,1 Dongkwan Han,1 Seung Hyun Kang,1 Seonghye Kim,1 You Hwan Jo1– 3 1Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea; 2Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea; 3Disaster Medicine Research Center, Seoul National University Medical Research Center, Seoul, KoreaCorrespondence: Jae Hyuk Lee, Department of Emergency Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Korea, Tel +82-31-787-7579, Fax +82-31-787-4055, Email hyukmd@gmail.comPurpose: Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis.Patients and Methods: We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility.Results: Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028).Conclusion: The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility.Keywords: anti-bacterial agents, biomarkers, drug resistance, sepsis, triggering receptor expressed on myeloid cells-1

Abstract Ischemia-reperfusion injury (IRI) poses significant challenges across various organ systems, including the heart, brain, and kidneys. Exosomes have shown great potentials and applications in mitigating IRI-induced cell and tissue damage through modulating inflammatory responses, enhancing angiogenesis, and promoting tissue repair. Despite these advances, a more systematic understanding of exosomes from different sources and their biotransport is critical for optimizing therapeutic efficacy and accelerating the clinical adoption of exosomes for IRI therapies. Therefore, this review article overviews the administration routes of exosomes from different sources, such as mesenchymal stem cells and other somatic cells, in the context of IRI treatment. Furthermore, this article covers how the delivered exosomes modulate molecular pathways of recipient cells, aiding in the prevention of cell death and the promotions of regeneration in IRI models. In the end, this article discusses the ongoing research efforts and propose future research directions of exosome-based therapies. Graphical Abstract

Abstract Background Industrial biomanufacturing of value-added products using CO2 as a carbon source is considered more sustainable, cost-effective and resource-efficient than using common carbohydrate feedstocks. Cupriavidus necator H16 is a representative H2-oxidizing lithoautotrophic bacterium that can be utilized to valorize CO2 into valuable chemicals and has recently gained much attention as a promising platform host for versatile C1-based biomanufacturing. Since this microbial platform is genetically tractable and has a high-flux carbon storage pathway, it has been engineered to produce a variety of valuable compounds from renewable carbon sources. In this study, the bacterium was engineered to produce resveratrol autotrophically using an artificial phenylpropanoid pathway. Results The heterologous genes involved in the resveratrol biosynthetic pathway—tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), and stilbene synthase (STS) —were implemented in C. necator H16. The overexpression of acetyl-CoA carboxylase (ACC), disruption of the PHB synthetic pathway, and an increase in the copy number of STS genes enhanced resveratrol production. In particular, the increased copies of Vv STS derived from Vitis vinifera resulted a 2-fold improvement in resveratrol synthesis from fructose. The final engineered CR-5 strain produced 1.9 mg/L of resveratrol from CO2 and tyrosine via lithoautotrophic fermentation. Conclusions To the best of our knowledge, this study is the first to describe the valorization of CO2 into polyphenolic compounds by engineering a phenylpropanoid pathway using the lithoautotrophic bacterium C. necator H16, demonstrating the potential of this strain a platform for sustainable chemical production.

Abstract Potassium-competitive acid blockers (P-CABs) provide potent acid inhibition, yet studies on P-CAB-based quadruple therapy for H. pylori eradication are limited. We theorized that integrating bismuth subsalicylate into a quadruple therapy regimen could enhance eradication rates. However, data on the efficacy of vonoprazan bismuth quadruple therapy are notably scarce. Therefore, the aim of this study was to evaluate the efficacy of vonoprazan-based bismuth quadruple therapy in areas with high clarithromycin and levofloxacin resistance. This was a prospective, single-center, randomized trial conducted to compare the efficacy of 7-day and 14-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication between June 1, 2021, and March 31, 2022. Qualified patients were randomly assigned to the 7-day or 14-day regimen (1:1 ratio by computer-generated randomized list as follows: 51 patients for the 7-day regimen and 50 patients for the 14-day regimen). The regimens consisted of vonoprazan (20 mg) twice daily, bismuth subsalicylate (1024 mg) twice daily, metronidazole (400 mg) three times daily, and tetracycline (500 mg) four times daily. CYP3A4/5 genotyping and antibiotic susceptibility tests were also performed. Successful eradication was defined as 13negative C-UBTs 4 weeks after treatment. The primary endpoint was to compare the efficacy of 7-day and 14-day regimens as first-line treatments, which were assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary endpoints included adverse effects. A total of 337 dyspeptic patients who underwent gastroscopy were included; 105 patients (31.1%) were diagnosed with H. pylori infection, and 101 patients were randomly assigned to each regimen. No dropouts were detected. The antibiotic resistance rate was 33.3% for clarithromycin, 29.4% for metronidazole, and 27.7% for levofloxacin. The CYP3A4 genotype was associated with 100% rapid metabolism. The H. pylori eradication rates for the 7-day and 14-day regimens were 84.4%, 95% CI 74.3–94.2 and 94%, 95% CI 87.4–100, respectively (RR difference 0.25, 95% CI 0.03–0.53, p value = 0.11). Interestingly, the 14-day regimen led to 100% eradication in the clarithromycin-resistant group. Among the patients in the 7-day regimen group, only two exhibited resistance to clarithromycin; unfortunately, neither of them achieved a cure from H. pylori infection. The incidence of adverse events was similar in both treatment groups, occurring in 29.4% (15/51) and 28% (14/50) of patients in the 7-day and 14-day regimens, respectively. No serious adverse reactions were reported. In conclusion, 14 days of vonoprazan-based bismuth quadruple therapy is highly effective for H. pylori eradication in areas with high levels of dual clarithromycin and levofloxacin resistance.

Abstract The physiological changes caused by the decline in estrogen levels due to menopause are linked to an increased risk of depression. This study investigated the antidepressant effects of hyperoside (HYP), a natural flavonol glycoside, and its associated molecular mechanisms in primary hippocampal neurons and ovariectomized (OVX) mice. HYP treatment increased nitric oxide (NO) production and neuronal nitric oxide synthase (nNOS) expression in primary hippocampal neurons; additionally, it upregulated the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin receptor kinase B (TrkB). In OVX mice, HYP treatment significantly improved depression-like behaviors in an open field test to a level comparable to estrogen treatment. Furthermore, HYP treatment upregulated OVX-induced decreased nNOS expression and BDNF-TrkB signaling in the hippocampus. Therefore, this study suggests that HYP exhibits antidepressant potential by addressing estrogen deficiency-induced alterations, specifically by restoring nNOS expression, promoting NO production, and concurrently enhancing BDNF-TrkB signaling in OVX mice.

Abstract Piperine, an alkaloid compound in black pepper (Piper nigrum), has beneficial bioactivities. Specifically, piperine inhibits adipogenesis in 3T3-L1 cells by suppressing the transcriptional activity of PPARγ. Control of hair oiliness, which is related to adipogenic regulation, is important to prevent hair loss. Excessive sebum from the sebaceous gland (SG) can cause acne, folliculitis, or irritated skin by clogging pores. To investigate the in vivo function of piperine in SG, we used mice fed a high-fat diet (HFD). The HFD increased the size and Oil Red O (ORO) staining intensity of SG, which were significantly reduced by piperine. The HFD also upregulated the expression of sebocyte-associated genes, including PPARγ target genes, an effect reversed by piperine. In CD34/CD49f double-positive hair follicle bulge stem cells isolated from mouse vibrissae, piperine inhibited cellular adipogenesis, likely via transcriptional repression of related genes. Furthermore, piperine reduced the thickness of subcutaneous fat. In human dermal papilla cells, piperine inhibited cellular adipogenesis, as shown by the reduction in ORO staining and the downregulation of PPARγ target genes. In conclusion, piperine can be used to reduce hair greasiness by suppressing adipogenesis in hair stem cells.

Background/Aims: Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB). However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB. Methods : We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes. Results : A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (-0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15. Conclusion : s: BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.

Objective Ischemia-reperfusion (IR) injury is implicated in various clinical diseases. Kallistatin attenuates oxidative stress, and its deficiency has been associated with poor neurological outcomes after cardiac arrest. The present study investigated the antioxidant mechanism through which kallistatin prevents IR injury. Methods Human umbilical vein endothelial cells (HUVECs) were transfected with small interfering RNA (siRNA) targeting the human kallistatin gene (SERPINA4). Following SERPINA4 knockdown, the level of kallistatin expression was measured. To induce IR injury, HUVECs were exposed to 24 h of oxygen-glucose deprivation and reoxygenation (OGD/R). To evaluate the effect of SERPINA4 knockdown on OGD/R, cell viability and the concentration of kallistatin, endothelial nitric oxide synthase (eNOS) and total NO were measured. Results SERPINA4 siRNA transfection suppressed the expression of kallistatin in HUVECs. Exposure to OGD/R reduced cell viability, and this effect was more pronounced in SERPINA4 knockdown cells compared with controls. SERPINA4 knockdown significantly reduced kallistatin concentration regardless of OGD/R, with a more pronounced effect observed without OGD/R. Furthermore, SERPINA4 knockdown significantly decreased eNOS concentrations induced by OGD/R (P

Narcolepsy and attention deficit hyperactivity disorder (ADHD) are distinct neurobiological conditions characterized by overlapping symptoms, including excessive daytime sleepiness and cognitive dysfunction. Despite their differences in etiology and pathophysiology, recent studies have highlighted a potential association between the two disorders, with a significant prevalence of ADHD symptoms observed in narcolepsy patients. This narrative review explores the similarities and differences between narcolepsy and ADHD, focusing on their shared symptomatology, neurobiological mechanisms, challenges in diagnosis, and treatment implications. While both disorders exhibit disruptions in dopaminergic and noradrenergic neurotransmitter systems, differential diagnosis remains challenging due to overlapping clinical presentations. Polysomnography findings, such as appearance of sleep onset rapid eye movements in narcolepsy patients, provide important distinctions that enable accurate diagnosis. Treatment strategies often involve stimulant medications for symptom management; however, nonpharmacological interventions, such as cognitive behavioral therapy, have been shown to have the potential to improve patient outcomes. Clinicians must consider the possibility of coexisting narcolepsy in ADHD patients and vice versa to ensure appropriate treatment selection and optimal patient care. Further research is needed to refine diagnostic criteria, elucidate the complex interplay between the two disorders, and develop personalized therapeutic approaches. A multidisciplinary approach involving sleep specialists, neurologists, psychiatrists, and psychologists is essential to address the diverse biopsychosocial needs of patients with concurrent narcolepsy and ADHD.

Abstract Mitophagy induction upon mitochondrial stress is critical for maintaining mitochondrial homeostasis and cellular function. Here, we found that Mst1/2 (Stk3/4), key regulators of the Hippo pathway, are required for the induction of mitophagy under various mitochondrial stress conditions. Knockdown of Mst1/2 or pharmacological inhibition by XMU-MP-1 treatment led to impaired mitophagy induction upon CCCP and DFP treatment. Mechanistically, Mst1/2 induces mitophagy independently of the PINK1-Parkin pathway and the canonical Hippo pathway. Moreover, our results suggest the essential involvement of BNIP3 in Mst1/2-mediated mitophagy induction upon mitochondrial stress. Notably, Mst1/2 knockdown diminishes mitophagy induction, exacerbates mitochondrial dysfunction, and reduces cellular survival upon neurotoxic stress in both SH-SY5Y cells and Drosophila models. Conversely, Mst1 and Mst2 expression enhances mitophagy induction and cell survival. In addition, AAV-mediated Mst1 expression reduced the loss of TH-positive neurons, ameliorated behavioral deficits, and improved mitochondrial function in an MPTP-induced Parkinson’s disease mouse model. Our findings reveal the Mst1/2-BNIP3 regulatory axis as a novel mediator of mitophagy induction under conditions of mitochondrial stress and suggest that Mst1/2 play a pivotal role in maintaining mitochondrial function and neuronal viability in response to neurotoxic treatment.

Abstract This study investigates the suitability of the annealed approximation in high-dimensional systems characterized by dense networks with quenched link disorder, employing models of coupled oscillators. We demonstrate that dynamic equations governing dense-network systems converge to those of the complete-graph version in the thermodynamic limit, where link disorder fluctuations vanish entirely. Consequently, the annealed-network systems, where fluctuations are attenuated, also exhibit the same dynamic behavior in the thermodynamic limit. However, a significant discrepancy arises in the incoherent (disordered) phase wherein the finite-size behavior becomes critical in determining the steady-state pattern. To explicitly elucidate this discrepancy, we focus on identical oscillators subject to competitive attractive and repulsive couplings. In the incoherent phase of dense networks, we observe the manifestation of random irregular states. In contrast, the annealed approximation yields a symmetric (regular) incoherent state where two oppositely coherent clusters of oscillators coexist, accompanied by the vanishing order parameter. Our findings imply that the annealed approximation should be employed with caution even in dense-network systems, particularly in the disordered phase.

Abstract Background Multimer detection system-oligomeric amyloid-β (MDS-OAβ) is a measure of plasma OAβ, which is associated with Alzheimer’s disease (AD) pathology. However, the relationship between MDS-OAβ and disease severity of AD is not clear. We aimed to investigate MDS-OAβ levels in different stages of AD and analyze the association between MDS-OAβ and cerebral Aβ deposition, cognitive function, and cortical thickness in subjects within the AD continuum. Methods In this cross-sectional study, we analyzed a total 126 participants who underwent plasma MDS-OAβ, structural magnetic resonance image of brain, and neurocognitive measures using Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease, and cerebral Aβ deposition or amyloid positron emission tomography (A-PET) assessed by [18F] flutemetamol PET. Subjects were divided into 4 groups: N = 39 for normal control (NC), N = 31 for A-PET-negative mild cognitive impairment (MCI) patients, N = 30 for A-PET-positive MCI patients, and N = 22 for AD dementia patients. The severity of cerebral Aβ deposition was expressed as standard uptake value ratio (SUVR). Results Compared to the NC (0.803 ± 0.27), MDS-OAβ level was higher in the A-PET-negative MCI group (0.946 ± 0.137) and highest in the A-PET-positive MCI group (1.07 ± 0.17). MDS-OAβ level in the AD dementia group was higher than in the NC, but it fell to that of the A-PET-negative MCI group level (0.958 ± 0.103). There were negative associations between MDS-OAβ and cognitive function and both global and regional cerebral Aβ deposition (SUVR). Cortical thickness of the left fusiform gyrus showed a negative association with MDS-OAβ when we excluded the AD dementia group. Conclusions These findings suggest that MDS-OAβ is not only associated with neurocognitive staging, but also with cerebral Aβ burden in patients along the AD continuum.

Eva Futtrup Maksten,1,2,&ast; Rasmus Rask Kragh Jørgensen,1,2,&ast; Mathilde Selmar Pedersen,1,2 Kirsten Fonager,2,3 Rie Sander Bech,1,2 Ingolf Mølle,4 Andreas Due Ørskov,5 Claudia Schöllkopf,6 Ulrik Malthe Overgaard,6 Gunhild Nynke Thomsen,7 Tarec C El-Galaly,1,2 Marianne Tang Severinsen1,2 1Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; 2Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 3Department of Social Medicine, Aalborg University Hospital, Aalborg, Denmark; 4Department of Hematology, Aarhus University Hospital, Aarhus, Denmark; 5Department of Hematology, Zealand University Hospital, Roskilde, Denmark; 6Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark; 7Department of Hematology, Odense University Hospital, Odense, Denmark&ast;These authors contributed equally to this workCorrespondence: Eva Futtrup Maksten, Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Sdr. Skovvej 15, Aalborg, 9000, Denmark, Tel +45 97666864, Fax +45 97666323, Email efm@rn.dkPurpose: Most adult patients diagnosed with acute lymphoblastic leukemia (ALL) are below retirement age. The overall survival of patients with ALL has improved with implementation of high intensity pediatric-inspired treatment protocols. However, this treatment comes with a risk of long-term complications, which could affect the ability to work. The aim of this study was to investigate the risk of disability pension (DP) and return to work (RTW) for patients with ALL.Patients and Methods: Patients aged 18– 60 years diagnosed with ALL between 2005 and 2019 were identified in the Danish National Acute Leukemia Registry. Each patient was matched with five comparators from the general population on birth year, sex, and Charlson Comorbidity Index. The Aalen-Johansen estimator was used to calculate the cumulative risk of DP for patients and comparators from index date (defined as 1 year after diagnosis) with competing events (transplantation or relapse, death, retirement pension, or early retirement pension). Differences in cumulative incidences were calculated using Gray’s test. RTW was calculated as proportions one, three, and five years after the index date for patients holding a job before diagnosis.Results: A total of 154 patients with ALL and 770 matched comparators were included. The 5-year cumulative risk of DP was increased fivefold for patients with ALL compared with the general population. RTW was 41.7%, 65.7%, and 60.7% one, three, and five years after the index date, respectively.Conclusion: The risk of DP in patients with ALL increased significantly compared with the general population. Five years after the index date, RTW was 60.7% for patients with ALL.Keywords: acute lymphoblastic leukemia, disability pension, return to work

To actualize an advanced smart factory, personalized products are important to develop immediately during the design stage, particularly when producing novel shapes, which demands experts with many design experiments. This study proposes an automated 3D shape design system that actively evolves into new products quickly during the design stage. The framework consists of a series of 3D-generated using variational autoencoder, classification with 3D convolution neural network, and evaluation models by analyzing new shape similarity to existing shapes through an autoencoder. The main objective of this study is to optimize the generative design process, reduce the need for human intervention, and automate design novelty evaluation, thereby addressing a significant research gap. The proposed framework was applied to create a new chair design procedure wherein new 43 chairs were generated in a single iteration with 989 existing chair shapes. The proposed framework for generative design of 3D chairs introduces a novel, automated approach through a variational autoencoder model and 3D convolutional neural network, addressing a research gap by streamlining the generative design process, reducing the need for human intervention, and providing automated evaluation of design novelty.