H2O2/acid self-supplying double-layer electrospun nanofibers based on ZnO2 and Fe3O4 nanoparticles for efficient catalytic therapy of wound infection.

Catalytic therapy based on nanozymes is promising for the treatment of bacterial infections. However, its therapeutic efficacy is usually restricted by the limited amount of hydrogen peroxide and the weak acidic environment in infected tissues. To solve these issues, we prepared polyvinyl alcohol (PVA)-polyacrylic acid (PAA)-iron oxide (Fe3O4)/polyvinyl alcohol (PVA)-zinc peroxide (ZnO2) double-layer electrospun nanofibers (PPF/PZ NFs). In this design, PVA serves as the carrier for ZnO2 nanoparticles (NPs), Fe3O4 NPs, and PAA. The double-layer structure of nanofibers can spatially separate the PAA and ZnO2 to avoid their reaction with each other during preparation and storage, while in the wet wound bed, PVA can dissolve and PAA can provide H+ ions to promote the generation of hydrogen peroxide and subsequent conversion to hydroxyl radicals for bacteria killing. In vitro experimental results demonstrated that PPF/PZ NFs can reduce the methicillin-resistant Staphylococcus aureus by 3.1 log (99.92%). Moreover, PPF/PZ NFs can efficiently treat the bacterial infection in a mouse wound model and promote wound healing with negligible toxicity to animals, indicating their potential use as "plug-and-play" antibacterial wound dressings. This work provides a novel strategy for the construction of double-layer electrospun nanofibers as catalytic wound dressings with hydrogen peroxide/acid self-supplying properties for the efficient treatment of bacterial infections.

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC.     Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

Evaluation of serological assays for the diagnosis of childhood tuberculosis disease: a study protocol.

BACKGROUND: Tuberculosis (TB) poses a major public health challenge, particularly in children. A substantial proportion of children with TB disease remain undetected and unconfirmed. Therefore, there is an urgent need for a highly sensitive point-of-care test. This study aims to assess the performance of serological assays based on various antigen targets and antibody properties in distinguishing children (0-18 years) with TB disease (1) from healthy TB-exposed children, (2) children with non-TB lower respiratory tract infections, and (3) from children with TB infection. METHODS: The study will use biobanked plasma samples collected from three prospective multicentric diagnostic observational studies: the Childhood TB in Switzerland (CITRUS) study, the Pediatric TB Research Network in Spain (pTBred), and the Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infections in children and adolescents (ProPAED) study. Included are children diagnosed with TB disease or infection, healthy TB-exposed children, and sick children with non-TB lower respiratory tract infection. Serological multiplex assays will be performed to identify M. tuberculosis antigen-specific antibody features, including isotypes, subclasses, Fc receptor (FcR) binding, and IgG glycosylation. DISCUSSION: The findings from this study will help to design serological assays for diagnosing TB disease in children. Importantly, those assays could easily be developed as low-cost point-of-care tests, thereby offering a potential solution for resource-constrained settings. GOV IDENTIFIER: NCT03044509.

A novel long non-coding RNA MIR4500HG003 promotes tumor metastasis through miR-483-3p-MMP9 axis in triple-negative breast cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is over 90% in BC patients, but once BC cells metastasis into distal organs, it is dramatically decreasing to less than 30%. Especially, triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. Understanding the underline mechanisms of TNBC metastasis is a critical issue. Non-coding RNAs, including of lncRNAs and microRNAs, are non-protein-coding transcripts and have been reported as important regulators in TNBC metastasis. However, the underline mechanisms for non-coding RNAs regulating TNBC metastasis remain largely unclear. Here, we found that lncRNA MIR4500HG003 was highly expressed in highly metastatic MDA-MB-231 TNBC cells and overexpression of MIR4500HG003 enhanced metastasis ability in vitro and in vivo and promoted MMP9 expression. Furthermore, we found MIR4500HG003 physically interacted with miR-483-3p and reporter assay showed miR-483-3p attenuated MMP9 expression. Importantly, endogenous high expressions of MIR4500HG003 were correlated with tumor recurrence in TNBC patients with tumor metastasis. Taken together, our findings suggested that MIR4500HG003 promotes metastasis of TNBC through miR-483-3p-MMP9 signaling axis and may be used as potential prognostic marker for TNBC patients.

Validation of Diagnostic Codes to Identify Glaucoma in Taiwan's Claims Data: A Multi-Institutional Study.

Background: Healthcare databases play a crucial role in improving our understanding of glaucoma epidemiology, which is the leading cause of irreversible blindness globally. However, the accuracy of diagnostic codes used in these databases to detect glaucoma is still uncertain. Aim: To assess the accuracy of ICD-9-CM and ICD-10-CM codes in identifying patients with glaucoma, including two distinct subtypes, primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Methods: We analyzed electronic medical records data from a 2% random sample of patients who newly underwent visual field examination in Taiwan's largest multi-institutional healthcare system from 2011 to 2020. The diagnosis of glaucoma was confirmed by two ophthalmologists, based on the glaucoma diagnostic criteria. The positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for ICD-9-CM codes 365.1X and 365.2X, and ICD-10-CM codes H4010X, H4011X, H4012X, H4020X, H4021X, H4022X, H4023X and H4024X for glaucoma were calculated. Results: We randomly selected 821 patients (mean age: 56.9 years old; female: 50.5%) from the original cohort of 41,050 newly receiving visual field examination in the study. Among 464 cases with an ICD-9-CM glaucoma code, the sensitivity, specificity, PPV and NPV for glaucoma were 86.5, 96.5, 91.9, and 90.9%, respectively. Among 357 cases with an ICD-10-CM glaucoma code, the sensitivity, specificity, PPV and NPV for glaucoma were 87.0, 92.8, 92.2 and 87.9%, respectively. The accuracy of diagnostic codes to identify POAG and PACG remained consistent. Conclusion: The diagnostic codes were highly reliable for identifying cases of glaucoma in Taiwan's routine healthcare practice. These results provide confidence when using ICD-9-CM and ICD-10-CM codes to define glaucoma cases in healthcare database research in Taiwan.

Deciphering the dual role of N-methyl-D-Aspartate receptor in postoperative cognitive dysfunction: A comprehensive review.

Postoperative cognitive dysfunction (POCD) is a common complication following surgery, adversely impacting patients' recovery, increasing the risk of negative outcomes, prolonged hospitalization, and higher mortality rates. The N-methyl-D-aspartate (NMDA) receptor, crucial for learning, memory, and synaptic plasticity, plays a significant role in the development of POCD. Various perioperative factors, including age and anesthetic use, can reduce NMDA receptor function, while surgical stress, inflammation, and pain may lead to its excessive activation. This review consolidates preclinical and clinical research to explore the intricate relationship between perioperative factors affecting NMDA receptor functionality and the onset of POCD. It discusses the influence of aging, anesthetic administration, perioperative injury, pain, and inflammation on the NMDA receptor-related pathophysiology of POCD. The comprehensive analysis presented aims to identify effective treatment targets for POCD, contributing to the improvement of patient outcomes post-surgery.

Molecular and functional characterization of a type-1 cystatin in amphioxus (Branchiostoma japonicum).

Cystatins comprise a vast superfamily of evolutionary conserved proteins, predominantly recognized for their roles as endogenous inhibitors by regulating the activity of cysteine proteases. Emerging lines of research evidence also provides insight into their alternative roles in a spectrum of biological and pathological processes, including neurodegenerative disorders, tumor progression, inflammatory diseases, and immune response. Nowadays, various type-1 cystatins (stefins) have been demonstrated among a variety of discovered vertebrate groups, while little is known about the related homologue in cephalochordate amphioxus, which are repositioned at the base of the chordate phylum. In the present study, a single type-1 cystatin homologue in Branchiostoma japonicum was first successfully cloned and designated as Bjcystatin-1. The deduced Bjcystatin-1 protein is structurally characterized by the presence of typical wedge-shaped cystatin features, including the 'QxVxG' and 'Px' motif, as well as the conserved N-terminal glycine residue. Phylogenomic analyses utilizing different cystatin counterparts affirmed the close evolutionary relationship of Bjcystatin-1 and type-1 cystatin homologue. Bjcystatin-1 was predominantly expressed in the gills and hind-gut in a tissue-specific pattern, and its expression was remarkably up-regulated in response to challenge with bacteria or their signature molecules LPS and LTA, suggesting the involvement in immune response. Additionally, the recombinant Bjcystatin-1 (rBjcystatin-1) protein showed significant inhibitory activity towards papain and binding ability to LPS and LTA, indicating its hypothesized role as a pattern recognition receptor in immune response. Subcellular localization results also showed that Bjcystatin-1 was located in the cytoplasm and nucleus, and its overexpression could attenuate the activation of LPS-induced nuclear transcription factors NF-κB. Taken together, our study suggests that amphioxus Bjcystatin-1 acts as a dual role in protease inhibitor and an immunocompetent factor, providing new insights into the immune defense effect of type-1 cystatin in amphioxus.

Xanthene-based near-infrared chromophores for high-contrast fluorescence and photoacoustic imaging of dipeptidyl peptidase 4.

Near-infrared (NIR) chromophores with analyte tunable emission and absorption properties are highly desirable for developing activatable fluorescence and photoacoustic (PA) probes for bioimaging and disease diagnosis. Here we engineer a class of new chromophores by extending the π-conjugation system of a xanthene scaffold at position 7 with different electron withdrawing groups. It is demonstrated that these chromophores exhibit pH-dependent transition from a spirocyclic "closed" form to a xanthene "open" form with remarkable changes in spectral properties. We further develop fluorescence and PA probes by caging the NIR xanthene chromophores with a dipeptidyl peptidase 4 (DPPIV) substrate. In vitro and live cell studies show that these probes allow activatable fluorescence and PA detection and imaging of DPPIV activity with high sensitivity, high specificity and fast response. Moreover, these two probes allow high-contrast and highly specific imaging of DPPIV activity in a tumour-bearing mouse model in vivo via systemic administration. This study highlights the potential of a xanthene scaffold as a versatile platform for developing high-contrast fluorescence and PA molecular probes.

Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity.

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).

An innovative microcoring technology: A novel approach to acne scar treatment.

BACKGROUND: Acne scars present a complex challenge in dermatology and cosmetics, despite advancements in technological interventions such as fractional lasers, microneedling, and surgical procedures. Effective treatment remains elusive for many individuals. OBJECTIVE: This study aims to evaluate the efficacy of rotational fractional resection using 1 mm diameter rotating scalpels as a primary treatment for icepick and boxcar scars on the cheeks and glabella region. METHODS: Three patients with acne scars underwent a single treatment session of rotational fractional resection. Evaluation occurred at the 2-month post-treatment mark to assess improvements in scar appearance and potential skin-related side effects. RESULTS: Following the treatment, significant improvements were observed in the targeted acne scars. Notable enhancements were noted without major skin-related adverse effects, except for minor suture marks. CONCLUSION: The outcomes of this study underscore the potential of rotational fractional resection as an innovative and effective approach in treating acne scars. This single-session cosmetic procedure shows promise in yielding lasting and quantifiable results, offering a hopeful solution for individuals seeking comprehensive acne scar treatment.

Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition: in vitro and in vivo study.

AIM: To provide the direct evidence for the crucial role of trimethylamine N-oxide (TMAO) in vascular permeability and endothelial cell dysfunction under diabetic condition. METHODS: The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells (HRMEC) under high glucose conditions was tested by a cell counting kit, wound healing, a transwell and a tube formation assay. The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction (RT-PCR). The expression of the cell junction was measured by Western blotting (WB) and immunofluorescence staining. In addition, two groups of rat models, diabetic and non-diabetic, were fed with normal or 0.1% TMAO for 16wk, and their plasma levels of TMAO, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were tested. The vascular permeability of rat retinas was measured using FITC-Dextran, and the expression of zonula occludens (ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining. RESULTS: TMAO administration significantly increased the cell proliferation, migration, and tube formation of primary HRMEC either in normal or high-glucose conditions. RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation, while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment. Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage, which were even higher in TMAO-feeding diabetic rats. Furthermore, TMAO administration increased the rat plasma levels of VEGF, IL-6 and TNF-α while decreasing the retinal expression levels of ZO-1 and claudin-5. CONCLUSION: TMAO enhances the proliferation, migration, and tube formation of HRMEC, as well as destroys their vascular integrity and tight connection. It also regulates the expression of VEGF, IL-6, and TNF-α.

Effects of ceramic thickness, ceramic translucency, and light transmission on light-cured bulk-fill resin composites as luting cement of lithium disilicate based-ceramics.

PURPOSE: To assess the effects of ceramic thickness, ceramic translucency, and light transmission on restorative composites used as luting cement for lithium disilicate-based ceramics. METHODS: Four luting types of cement were tested (n=8); a dual-cured resin cement (Multilink N), a light-cured conventional flowable composite (Tetric N-Flow), and two light-cured bulk-fill flowable composites (Tetric N-Flow Bulk Fill and X-tra base). The 20 s- or 40 s-light (1000 mW/cm2) was transmitted through 1- or 2-mm-thick high- or low-translucency (HT- or LT-) ceramic discs (IPS e.Max press) to reach the 1-mm-thick luting cement. Light transmitted to cement without ceramic served as a control. Vickers hardness number (VHN), flexural strength (FS), fractography, and degree of conversion (DC) were evaluated. One-way and multi-way analysis of variance was conducted to determine the effects of factors on VHN and FS. RESULTS: Ceramic thickness, light transmission time, and cement type significantly affected the VHN of the luting cement (P < .000). Only Multilink N (LT- and HT-1mm) and Tetric N-Flow (HT-1mm) reached 90% VHN of corresponding control by 20 s-light transmissions, but Tetric N-Flow exhibited lowest VHN and approximately 1/3-1/2 VHN of Multilink N (P < 0.05). X-tra base expressed superior physicochemical properties to Tetric N-Flow Bulk Fill (P < 0.05) and reached >90% VHN of control in all conditions with 40 s-light transmissions except for LT-2 mm. DC, FS, and fractography supported these findings. CONCLUSIONS: The light-cured bulk-fill composite served as a luting cement for lithium-disilicate-based ceramics in a product-dependent manner. Light transmission time is crucial to ensure sufficient luting cement polymerization.

Diverging Maternal and Cord Antibody Functions From SARS-CoV-2 Infection and Vaccination in Pregnancy.

Maternal immunity impacts the infant, but how is unclear. To understand the implications of the immune exposures of vaccination and infection in pregnancy for neonatal immunity, we evaluated antibody functions in paired peripheral maternal and cord blood. We compared those who in pregnancy received mRNA coronavirus disease 2019 (COVID-19) vaccine, were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the combination. We found that vaccination enriched a subset of neutralizing activities and Fc effector functions that was driven by IgG1 and was minimally impacted by antibody glycosylation in maternal blood. In paired cord blood, maternal vaccination also enhanced IgG1. However, Fc effector functions compared to neutralizing activities were preferentially transferred. Moreover, changes in IgG posttranslational glycosylation contributed more to cord than peripheral maternal blood antibody functional potency. These differences were enhanced with the combination of vaccination and infection as compared to either alone. Thus, Fc effector functions and antibody glycosylation highlight underexplored maternal opportunities to safeguard newborns.

Sex Differences and Discordance Between Symptoms and Signs of Dry Eye Disease.

PURPOSE: To examine the initial presenting symptoms in relation to sex and identify predictors of discordance between symptoms and signs of dry eye disease (DED) in Taiwan. DESIGN: Retrospective cross-sectional study. METHODS: This clinic-based cohort from a tertiary referral center in Taiwan included 1229 patients diagnosed with DED at Keelung Chang Gung Memorial Hospital in Taiwan between August 1, 2011, and July 31, 2018. Initial presenting symptoms were cross-sectionally and retrospectively collected. The composite score, indicating the discordance between symptoms and signs, was derived from the difference between the DED symptom severity score and the DED sign severity score. RESULTS: Of 1229 patients, 975 (79.3%) were female, with a mean age of 56.7 ± 14.9 years. Initial presenting symptoms didn't show significant sex differences (all P > .05). In multivariate analysis, predictors of higher symptom severity score than sign severity score included being female (P = .011) and having a surgical history of cataract (P = .037), pterygium, or conjunctivochalasis (P = .014). Conversely, older age (P < .001) and artificial tear use (P < .001) were significant predictors of a lower symptom severity score than sign severity score. CONCLUSIONS: Strong predictors of incongruity between DED symptoms and signs include age, gender, surgical history for cataract, pterygium or conjunctivochalasis, and artificial tear use. Ophthalmologists should prioritize symptoms for female patients and postsurgery cases. In addition, the absence of symptoms should not dismiss DED possibility in older adult patients and those using artificial tears. Notably, early recognition and enhancement of postoperative care can improve patient satisfaction and quality of life.

Repopulating Kupffer cells originate directly from hematopoietic stem cells.

BACKGROUND: Kupffer cells (KCs) originate from yolk-sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at a steady state and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adults remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. METHODS: We first traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate-mapping mouse models, respectively. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC-depletion in mice. Finally, we traced the fate of hematopoietic stem cells (HSCs) in an HSC-specific fate-mapping mouse model, in the context of chronic liver inflammation induced by repeated carbon tetrachloride treatment. RESULTS: By using fate-mapping mouse models, we found no evidence that repopulating KCs originate from preexisting KCs or MOs and found that in response to KC-depletion, HSCs proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Then, in the chronic liver inflammation context, we confirmed that repopulating KCs originated directly from HSCs. CONCLUSION: Taken together, these findings provided in vivo fate-mapping evidence that repopulating KCs originate directly from HSCs, which presents a completely novel understanding of the cellular origin of repopulating KCs and shedding light on the divergent roles of KCs in liver homeostasis and diseases.

Surface Roughness-Induced Changes in Important Physical Features of CoFeSm Thin Films on Glass Substrates during Annealing.

Co60Fe20Sm20 thin films were deposited onto glass substrates in a high vacuum setting. The films varied in thickness from 10 to 50 nm and underwent annealing processes at different temperatures: room temperature (RT), 100, 200, and 300 °C. Our analysis encompassed structural, magnetic, electrical, nanomechanical, adhesive, and optical properties in relation to film thickness and annealing temperature. X-ray diffraction (XRD) analysis did not reveal characteristic peaks in Co60Fe20Sm20 thin films due to insufficient growth-driving forces. Electrical measurements indicated reduced resistivity and sheet resistance with increasing film thickness and higher annealing temperatures, owing to hindered current-carrier transport resulting from the amorphous structure. Atomic force microscope (AFM) analysis showed a decrease in surface roughness with increased thickness and annealing temperature. The low-frequency alternating current magnetic susceptibility (χac) values increased with film thickness and annealing temperature. Nanoindentation analysis demonstrated reduced film hardness and Young's modulus with thicker films. Contact angle measurements suggested a hydrophilic film. Surface energy increased with greater film thickness, particularly in annealed films, indicating a decrease in contact angle contributing to this increase. Transmittance measurements have revealed intensified absorption and reduced transmittance with thicker films. In summary, the surface roughness of CoFeSm films at different annealing temperatures significantly influenced their magnetic, electrical, adhesive, and optical properties. A smoother surface reduced the pinning effect on the domain walls, enhancing the χac value. Additionally, diminished surface roughness led to a lower contact angle and higher surface energy. Additionally, smoother surfaces exhibited higher carrier conductivity, resulting in reduced electrical resistance. The optical transparency decreased due to the smoother surface of Co60Fe20Sm20 films.

Gut Microbiome-Estrobolome Profile in Reproductive-Age Women with Endometriosis.

Microbiota is associated with our bodily functions and microenvironment. A healthy, balanced gut microbiome not only helps maintain mucosal integrity, prevents translocation of bacterial content, and contributes to immune status, but also associates with estrogen metabolism. Gut dysbiosis and estrobolome dysfunction have hence been linked to certain estrogen-dependent diseases, including endometriosis. While prior studies on microbiomes and endometriosis have shown conflicting results, most of the observed microbial differences are seen in the genital tract. This case-control study of reproductive-age women utilizes their fecal and urine samples for enzymatic, microbial, and metabolic studies to explore if patients with endometriosis have distinguishable gut microbiota or altered estrogen metabolism. While gut ß-glucuronidase activities, microbial diversity, and abundance did not vary significantly between patients with or without endometriosis, fecal samples of patients with endometriosis were more enriched by the Erysipelotrichia class and had higher folds of four estrogen/estrogen metabolites. Further studies are needed to elucidate what these results imply and whether there indeed is an association or causation between gut microbiota and endometriosis.

Short-Term Outcomes Following Laparoscopic vs Open Pancreaticoduodenectomy in Patients With Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial.

Importance: The safety and efficacy of laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma remain controversial. Objective: To compare laparoscopic and open pancreaticoduodenectomy performed by experienced surgeons in patients with pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This was a noninferiority, open-label randomized clinical trial between September 20, 2019 and March 20, 2022, at 10 hospitals in China. A total of 412 adult patients were assessed for eligibility; 200 patients with histologically confirmed or clinically diagnosed pancreatic ductal adenocarcinoma who were eligible to undergo pancreaticoduodenectomy were enrolled. Study recruitment is complete, and follow-up is ongoing. This article reports prespecified early safety results from the trial. Interventions: Participants were randomized in a 1:1 ratio to undergo either laparoscopic or open pancreaticoduodenectomy, to be performed by experienced surgeons who had already performed at least 104 laparoscopic pancreaticoduodenectomy operations. Main Outcomes and Measures: The primary end point is 5-year overall survival, but the data for this end point are not yet mature; thus, secondary short-term outcomes, including operative findings, complications, mortality, and oncological results are reported here. The outcomes were analyzed according to a modified intention-to-treat and per-protocol principle. Results: Among 412 patients for eligibility, 200 patients were enrolled and randomly assigned 1:1 to have laparoscopic pancreaticoduodenectomy or open pancreaticoduodenectomy. The mean (SD) age was 61.3 (9.3) years, and 78 participants (39%) were female. Laparoscopic procedures had longer operative times (median [IQR], 330.0 [287.5-405.0] minutes vs 297.0 [245.0-340.0] minutes; P < .001). Patients in the laparoscopic group lost less blood than those in the open group (median [IQR], 145.0 [100.0-200.0] mL vs 200.0 [100.0-425.0] mL; P = .02). Ninety-day mortality occurred in 2 of 100 patients in the laparoscopic group and 0 of 100 patients in the open group. There was no difference in the rates of complications of the Clavien-Dindo grades III-IV (n = 17 [17.0%] vs n = 23 [23.0%]; P = .29), comprehensive complication index (median [IQR], 0.0 [0.0-22.6] vs 8.7 [0.0-26.2]; P = .79) or median (IQR) postoperative length of stay (14.0 [11.0-17.0] days vs 14.0 [12.0-18.5] days; P = .37) between the 2 groups. Conclusions and Relevance: Laparoscopic pancreaticoduodenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar short-term outcomes compared with open pancreaticoduodenectomy among patients with pancreatic ductal adenocarcinoma. Trial Registration: ClinicalTrials.gov Identifier: NCT03785743.

Comparisons of EQ-5D-Y and PedsQL in pediatric patients with mild-to-moderate chronic kidney disease in longitudinal analyses.

OBJECTIVE: To characterize longitudinal changes and correlations between the measures of EQ-5D-Y and generic PedsQL and their associations with clinical changes in children and adolescents with mild-to-moderate chronic kidney disease (CKD). METHODS: Participants were recruited from January 2017 to September 2021 in a medical center in Taiwan. Both instruments were administered in their initial visits and every 6-month subsequent visits. Spearman's Rho (ρ) was used to assess correlations between the scores of EQ-5D-Y and PedsQL measures in longitudinal changes. Cohen's effect size (ES) was used to evaluate the changes of scores/subscales over time. In addition, factors associated with longitudinal changes in the score/subscales were explored. RESULTS: A total of 121 participants were enrolled, and 83 with ≥ 3 HRQOL measures during the 3.5 years follow-up were assessed their changes of HRQOL measures. The correlations (ρ > 0.3) appeared between the changes in the visual analog scale (VAS) of EQ-5D-Y and emotional and social subscales of PedsQL. ES was small (< 0.5) in the VAS and level-sum-score (LSS) of EQ-5D-Y scores for the clinical changes in comorbidities, while some PedsQL subscales were medium to high (0.5-0.8 or > 0.8). Hypertension, mineral bone disorder/anemia, and hyperuricemia associated with the changes in both HRQOL scores were varied by their various domains. CONCLUSION: Both EQ-5D-Y and PedsQL of HRQOL measures were responsive to worsened childhood CKD-related comorbidities during the follow-up; however, convergent validity between them was limited in some domains. The LSS of EQ-5D-Y showed greater changes than the VAS by comorbidity status; further comparison with utility weight is needed to determine the better performance of EQ-5D-Y.

Metabolic Reprogramming by Ribitol Expands the Therapeutic Window of BETi JQ1 against Breast Cancer.

Many cancer patients still lack effective treatments, and pre-existing or acquired resistance limits the clinical benefit of even the most advanced medicines. Recently, much attention has been given to the role of metabolism in cancer, expanding from the Warburg effect to highlight unique patterns that, in turn, may improve diagnostic and therapeutic approaches. Our recent metabolomics study revealed that ribitol can alter glycolysis in breast cancer cells. In the current study, we investigate the combinatorial effects of ribitol with several other anticancer drugs (chrysin, lonidamine, GSK2837808A, CB-839, JQ1, and shikonin) in various breast cancer cells (MDA-MB-231, MCF-7, and T-47D). The combination of ribitol with JQ1 synergistically inhibited the proliferation and migration of breast cancer cells cell-type dependently, only observed in the triple-negative MDA-MB-231 breast cancer cells. This synergy is associated with the differential effects of the 2 compounds on expression of the genes involved in cell survival and death, specifically downregulation in c-Myc and other anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1), but upregulation in p53 and cytochrome C levels. Glycolysis is differentially altered, with significant downregulation of glucose-6-phosphate and lactate by ribitol and JQ1, respectively. The overall effect of the combined treatment on metabolism and apoptosis-related genes results in significant synergy in the inhibition of cell growth and induction of apoptosis. Given the fact that ribitol is a metabolite with limited side effects, a combined therapy is highly desirable with relative ease to apply in the clinic for treating an appropriate cancer population. Our results also emphasize that, similar to traditional drug development, the therapeutic potential of targeting metabolism for cancer treatment may only be achieved in combination with other drugs and requires the identification of a specific cancer population. The desire to apply metabolomic intervention to a large scope of cancer types may be one of the reasons identification of this class of drugs in a clinical trial setting has been delayed.