Interleukin-1 receptor 1 deficiency worsens hepatocellular carcinoma, while gemcitabine treatment alleviates the hepatocellular carcinoma-induced increase in intra-hepatic immune cells.

BACKGROUND AND AIM: Primary liver cancer, particularly hepatocellular carcinoma (HCC), represents a substantial global health challenge. Although immune checkpoint inhibitors are effective in HCC treatment, several patients still experience disease progression. Interleukin-1 (IL-1) regulates immunity and inflammation. We investigate the role of IL-1 in HCC development and progression and determine the potential therapeutic impact of gemcitabine in treating HCC. METHODS: Hydrodynamics-based transfection, employing the sleeping beauty transposase system, delivered surrogate tumor antigens, NRAS (NRAS proto-oncogene, GTPase), ShP53, and SB100 to C57BL/6 mice. A basic HCC mouse model was established. Pathogen-free animals were tested for serum and hepatotoxicity. The HCC prognosis was monitored using alanine aminotransferase and aspartate aminotransferase levels. Liver histology immunohistochemistry and mouse splenocyte/intra-hepatic immune cell flow cytometry were conducted. IL-1ß levels in human and mouse serum were assessed. RESULTS: Interleukin-1ß levels were elevated in patients with HCC compared with those in non-HCC controls. Hepatic IL-1ß levels were higher in HCC mouse models than those in non-HCC mice, suggesting localized hepatic inflammation. IL-1 receptor type 1 (IL-1R1) knockout (IL-1R1-/-) mice exhibited less severe HCC progression than that in wild-type mice, despite the high intra-hepatic IL-1ß concentration. IL-1R1-/- mice exhibited increased hepatic levels of myeloid-derived suppressor cells and regulatory T cells, which may exacerbate HCC. Gemcitabine significantly reduced the HCC tumor burden, improved liver conditions, and increased survival rates in HCC mouse models. Gemcitabine reduced the hepatic levels of myeloid-derived suppressor cells and regulatory T cells, potentially alleviating immune suppression in the liver. CONCLUSIONS: Targeting IL-1 or combining gemcitabine with immunotherapy is a promising approach for treating advanced-stage HCC.

Investigating developmental characteristics of biopsied blastocysts stratified by mitochondrial copy numbers using time-lapse monitoring.

BACKGROUND: For in vitro fertilization (IVF), mitochondrial DNA (mtDNA) levels in the trophectodermal (TE) cells of biopsied blastocysts have been suggested to be associated with the cells' developmental potential. However, scholars have reached differing opinions regarding the use of mtDNA levels as a reliable biomarker for predicting IVF outcomes. Therefore, this study aims to assess the association of mitochondrial copy number measured by mitoscore associated with embryonic developmental characteristics and ploidy. METHODS: This retrospective study analyzed the developmental characteristics of embryos and mtDNA levels in biopsied trophectodermal cells. The analysis was carried out using time-lapse monitoring and next-generation sequencing from September 2021 to September 2022. Five hundred and fifteen blastocysts were biopsied from 88 patients undergoing IVF who met the inclusion criteria. Embryonic morphokinetics and morphology were evaluated at 118 h after insemination using all recorded images. Blastocysts with appropriate morphology on day 5 or 6 underwent TE biopsy and preimplantation genetic testing for aneuploidy (PGT-A). Statistical analysis involved generalized estimating equations, Pearson's chi-squared test, Fisher's exact test, and Kruskal-Wallis test, with a significance level set at P < 0.05. RESULTS: To examine differences in embryonic characteristics between blastocysts with low versus high mitoscores, the blastocysts were divided into quartiles based on their mitoscore. Regarding morphokinetic characteristics, no significant differences in most developmental kinetics and observed cleavage dysmorphisms were discovered. However, blastocysts in mitoscore group 1 had a longer time for reaching 3-cell stage after tPNf (t3; median: 14.4 h) than did those in mitoscore group 2 (median: 13.8 h) and a longer second cell cycle (CC2; median: 11.7 h) than did blastocysts in mitoscore groups 2 (median: 11.3 h) and 4 (median: 11.4 h; P < 0.05). Moreover, blastocysts in mitoscore group 4 had a lower euploid rate (22.6%) and a higher aneuploid rate (59.1%) than did those in the other mitoscore groups (39.6-49.3% and 30.3-43.2%; P < 0.05). The rate of whole-chromosomal alterations in mitoscore group 4 (63.4%) was higher than that in mitoscore groups 1 (47.3%) and 2 (40.1%; P < 0.05). A multivariate logistic regression model was used to analyze associations between the mitoscore and euploidy of elective blastocysts. After accounting for factors that could potentially affect the outcome, the mitoscore still exhibited a negative association with the likelihood of euploidy (adjusted OR = 0.581, 95% CI: 0.396-0.854; P = 0.006). CONCLUSIONS: Blastocysts with varying levels of mitochondrial DNA, identified through biopsies, displayed similar characteristics in their early preimplantation development as observed through time-lapse imaging. However, the mitochondrial DNA level determined by the mitoscore can be used as a standalone predictor of euploidy.

Engineering an enzyme-like catalytic sensor for on-site dual-mode evaluation of total antioxidant capacity.

A novel Fe-MoOx nanozyme, engineered with enhanced peroxidase (POD)-like activity through strategic doping and the creation of oxygen vacancies, is introduced to catalyze the oxidation of TMB with high efficiency. Furthermore, Fe-MoOx is responsive to single electron transfer (SET) and hydrogen atom transfer (HAT) mechanisms related to antioxidants and can serve as a desirable nanozyme for total antioxidant capacity (TAC) determination. The TAC colorimetric platform can reach a low LOD of 0.512 µM in solution and 24.316 µM in the smartphone-mediated RGB hydrogel (AA as the standard). As proof of concept, the practical application in real samples was explored. The work paves a promising avenue to design diverse nanozymes for visual on-site inspection of food quality.

Yangonin, one of the kavalactones isolated from Piper methysticum G. Forst, acts through cannabinoid 1 (CB1) receptors to induce an intrathecal anti-hyperalgesia.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper methysticum G. Forst (Piperaceae) is traditionally consumed in Polynesian culture. The roots are used to produce an entheogenic drink and traditional medicine with sedative and anxiolytic properties. There is also evidence that it functions as a pain reliever. Kavalactones, its main active ingredients, exhibit psychoactive effects on the central nervous system. However, the active ingredients and pharmacological mechanisms underlying the analgesic effect of kavalactones are unclear. AIM OF THE STUDY: This study investigated the effects of kavain and yangonin on nociception, inflammatory hyperalgesia, and neuropathic mechanical allodynia at the spinal level. MATERIALS AND METHODS: Male Sprague-Dawley rats were administered kavain and yangonin (27.14 and 19.36 nmol/rat) via intrathecal injection. Tail-flick tests were performed to evaluate the anti-nociceptive properties. The efficacy of kavain and yangonin on inflammatory hyperalgesia was examined using a plantar test in rats with carrageenan-induced paw inflammation. The von Frey test was used to assess mechanical allodynia induced by partial sciatic nerve ligation. RESULTS: Intrathecal injection of yangonin demonstrated a relatively potent anti-nociceptive effect and attenuated carrageenan-induced hyperalgesia. These effects were completely reversed by the co-administration of PF 514273, a cannabinoid 1 (CB1) receptor antagonist. However, yangonin did not affect mechanical allodynia at the spinal level. Kavain, another abundant kavalactone, did not affect nociception, hyperalgesia, or mechanical allodynia at the spinal level. CONCLUSIONS: Overall, our study demonstrated that yangonin exerts anti-nociception and anti-inflammatory hyperalgesia effects via CB1 receptors at the spinal level. We identified a single kavalactone, yangonin, extracted from kava as a promising treatment for pain.

Intrauterine Infusion and Hysteroscopic Injection of Autologous Platelet-Rich Plasma for Patients with a Persistent Thin Endometrium: A Prospective Case-Control Study.

Objectives: To evaluate the effect of intrauterine infusion and hysteroscopic injection of autologous platelet-rich plasma (PRP) in patients with a persistent thin endometrium (EM) undergoing euploid frozen embryo transfer (EFET) cycles. Methods: This prospective case-control study enrolled 116 infertile women with thin EM (<7 mm) who underwent hormone replacement therapy (HRT) for EFET. These women had experienced at least one previous unsuccessful EFET cycle, which either resulted in the cancellation of the cycle or failure of pregnancy. A total of 55 women received an intrauterine infusion of PRP before FET, 38 received a hysteroscopic injection of PRP, and 23 received standard HRT treatment without PRP (control group). Only euploid embryos were transferred in these cycles. The primary outcomes were the implantation rate (IR) and clinical pregnancy rate (CPR) after EFET. Results: After receiving intrauterine infusion and hysteroscopic injection of PRP, 78.2% and 55.3% of patients, respectively, showed an EM thickness exceeding 7 mm, followed by embryo transfer. The hysteroscopic injection group demonstrated significantly higher IR (52%), a higher trend of CPR (52%), and a higher live birth rate (38%) than the control group (18%, 22%, and 4%). Conclusions: Intrauterine infusion and hysteroscopic injection of autologous PRP may be effective methods to increase EM thickness in HRT cycles. According to our results, both methods could increase EM thickness, while hysteroscopic injection appeared to provide more significant assistance in increasing IR, CPR, and live birth rate after EFET in patients with persistent thin EM.

Effectiveness of binaural beat music combined with rhythmical photic stimulation on older people with depressive symptoms in long-term care institution: a quasi-experimental pilot study.

BACKGROUND: Many older adults residing in long-term care often face issues like poor sleep, reduced vitality, and depression. Non-pharmacological approaches, specifically Binaural Beat Music (BBM) and Rhythmic Photic Stimulation (RPS), may alleviate these symptoms, yet their efficacy in this demographic has not been extensively explored. AIMS: This study investigated the effects of combined BBM and RPS interventions on sleep quality, vitality, and depression among older residents with depressive symptoms in long-term care facilities. METHODS: Using a quasi-experimental design, a total of 88 older adults with depressive symptoms from Taiwanese daytime care centers were divided into the BBM with RPS, and Sham groups (44 each). They underwent 20-minute daily sessions of their assigned treatment for two weeks. The BBM with RPS group listened to 10 Hz binaural beat music with 10 Hz photic stimulation glasses, and the Sham group received non-stimulating music and glasses. RESULTS: After the intervention, participants in the BBM with RPS groups showed significant improvements in vitality and depressive mood, with a notable increase in sympathetic nervous system activity. Conversely, the Sham group exhibited significant deterioration in vitality and mental health, with a significant increase in parasympathetic activity. Additionally, compared with the Sham group, the BBM and RPS groups showed significant improvements in vitality, mental health, and depression, with a significant increase in sympathetic nervous activity. CONCLUSION: The two-week intervention suggests that the combination of BBM and RPS, as a non-invasive intervention, can potentially improve vitality, mental health, and depressive mood among older adults in long-term care institutions.

Improved isoprene detection performance of Si-doped WO3 films deposited by sputtering and post-annealing.

Si-doped WO3 films were sputtered at room temperature and then annealed in air at 500 °C. The Si doping resulted in structural distortion from space group P21/n to Pc. A high density of pores with a diameter of ∼20 nm was observed in the films, which is ideal for gas sensing applications because of the easy diffusion of gas. Isoprene sensitivity, which is defined as the resistance ratio measured in pure air and in air containing 5 ppm isoprene, was greatly improved by the Si doping. The films containing 6.3 at% Si showed the highest sensitivity of 7.7 at a working temperature of 325 °C. However, despite a lower sensitivity of 6.9 measured at 350 °C, the films exhibited better gas selectivity for isoprene over a range of reference gases, including methanol, ethanol, acetone, CO and CO2. The response and recovery times of the films were very short, being less than 1.5 and 3.0 seconds, respectively. Detailed characterization with a range of techniques verified that the increase in gas sensitivity in the Si-doped films was related to better oxygen adsorbability as a consequence of an increase in positively-charged oxygen vacancies introduced by the aliovalent substitution of W6+ by Si4+.

Theoretical Analysis of GeSn Quantum Dots for Photodetection Applications.

GeSn alloys have recently emerged as complementary metal-oxide-semiconductor (CMOS)-compatible materials for optoelectronic applications. Although various photonic devices based on GeSn thin films have been developed, low-dimensional GeSn quantum structures with improved efficiencies hold great promise for optoelectronic applications. This study theoretically analyses Ge-capped GeSn pyramid quantum dots (QDs) on Ge substrates to explore their potential for such applications. Theoretical models are presented to calculate the effects of the Sn content and the sizes of the GeSn QDs on the strain distributions caused by lattice mismatch, the band structures, transition energies, wavefunctions of confined electrons and holes, and transition probabilities. The bandgap energies of the GeSn QDs decrease with the increasing Sn content, leading to higher band offsets and improved carrier confinement, in addition to electron-hole wavefunction overlap. The GeSn QDs on the Ge substrate provide crucial type-I alignment, but with a limited band offset, thereby decreasing carrier confinement. However, the GeSn QDs on the Ge substrate show a direct bandgap at higher Sn compositions and exhibit a ground-state transition energy of ~0.8 eV, rendering this system suitable for applications in the telecommunication window (1550 nm). These results provide important insights into the practical feasibility of GeSn QD systems for optoelectronic applications.

Examining the effects of binaural beat music on sleep quality, heart rate variability, and depression in older people with poor sleep quality in a long-term care institution: A randomized controlled trial.

OBJECTIVE: This study aimed to examine the effects of binaural beat music (BBM) on sleep quality, heart rate variability, and depression in older people with poor sleep quality in a long-term care institution. METHODS: A single-blind randomized controlled trial design was employed, and 64 older participants with poor sleep quality were recruited from a long-term care institution in Taiwan. Participants were randomized into the BBM group or control group and received 14 days of intervention. During the intervention period, participants in the experimental group listened to 20 min of Taiwanese Hokkien oldies embedded with BBM once in the morning and afternoon three times a week. Participants in the control group only listened to Taiwanese Hokkien oldies. Questionnaires and heart rate variability analysis were used to assess participants' sleep quality, heart rate variability, and depressive symptoms. RESULTS: Significant improvements were observed in sleep quality, along with an increase in heart rate variability means of heart rate and normal sinus beats, and a decrease in low-frequency normalized units and depression severity in the BBM group after the intervention. In the control group, effects on sleep quality were inconsistent, heart rate variability showed significant improvements in some autonomic nervous function regulation, and depression severity was significantly decreased. Furthermore, the BBM group showed a significant improvement in sleep quality and a significant reduction in sympathetic nervous activity compared with the control group. CONCLUSION: This study demonstrates that 14 days of BBM intervention, a non-invasive intervention, could improve sleep quality and depression in older people with poor sleep quality in long-term care institutions. Geriatr Gerontol Int 2024; 24: 297-304.

Development of a Silicone Rubber Mold with an Innovative Waterfall Cooling Channel.

A conformal cooling channel (CCC) follows the mold core or cavity profile to carry out uniform cooling in the cooling stage. However, the significant pressure drop along the cooling channels is a distinct disadvantage of the CCC. In this study, an innovative waterfall cooling channel (WCC) was proposed and implemented. The WCC cools the injected products via surface contact, replacing the conventional line contact to cool the injected products. The WCC was optimized using numerical simulation software. Silicone rubber molds with two kinds of cooling channels were designed and implemented. The cooling time of the molded part was evaluated using a low-pressure wax injection molding machine. The experimental results of the cooling time of the molded part were compared with the simulation results from numerical simulation software. The results showed that the optimal mesh element count was about 1,550,000 with a mesh size of 1 mm. The simulation software predicted the filling time of the water cup injection-molded product to be approximately 2.008 s. The cooling efficiency for a silicone rubber mold with a WCC is better than that of the silicone rubber mold with a CCC since the core and cavity cooling efficiency is close to 50%. The pressure drop of the WCC is smaller than that of the CCC, which reduces the pressure drop by about 56%. Taking a water cup with a mouth diameter of 70 mm, a height of 60 mm, and a thickness of 2 mm as an example, the experimental results confirmed that the use of the WCC can save the cooling time of the product by about 265 s compared with the CCC. This shows how a WCC can increase cooling efficiency by approximately 17.47%.

Microbial induced carbonate precipitation for remediation of heavy metals, ions and radioactive elements: A comprehensive exploration of prospective applications in water and soil treatment.

Improper disposal practices have caused environmental disruptions, possessing by heavy metal ions and radioactive elements in water and soil, where the innovative and sustainable remediation strategies are significantly imperative in last few decades. Microbially induced carbonate precipitation (MICP) has emerged as a pioneering technology for remediating contaminated soil and water. Generally, MICP employs urease-producing microorganisms to decompose urea (NH2CONH2) into ammonium (NH4+and carbon dioxide (CO2), thereby increasing pH levels and inducing carbonate precipitation (CO32-), and effectively removing remove contaminants. Nonetheless, the intricate mechanism underlying heavy metal mineralization poses a significant challenge, constraining its application in contaminants engineering, particularly in the context of prolonged heavy metal leaching over time and its efficacy in adverse environmental conditions. This review provides a comprehensive idea of recent development of MICP and its application in environmental engineering, examining metabolic pathways, mineral precipitation mechanisms, and environmental factors as well as providing future perspectives for commercial utilization. The use of ureolytic bacteria in MICP demonstrates cost-efficiency, environmental compatibility, and successful pollutant abatement over tradition bioremediation techniques, and bio-synthesis of nanoparticles. limitations such as large-scale application, elevated Ca2+levels in groundwater, and gradual contaminant release need to be overcome. The possible future research directions for MICP technology, emphasizing its potential in conventional remediation, CO2 sequestration, bio-material synthesis, and its role in reducing environmental impact for long-term economic benefits.

Intrathecal injections of angiotensin IV and oxytocin conjugates induce antihyperalgesia and antiallodynia in both sexes of rats.

Our previous studies have established that intrathecal oxytocin (OT) and angiotensin IV (Ang IV) injections induce antihyperalgesia and antiallodynia in rodents. Ang IV, a renin-angiotensin system hexapeptide, acts as an endogenous inhibitor that inhibits the oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP). The pain inhibitory effects by Ang IV were found to be through its inhibition on IRAP to potentiate the effect of OT. However, these effects were found to be with a significant sex difference, which could be partially due to the higher expression of IRAP at the spinal cords of female. Therefore, we synthesized Ang IV and OT conjugates connected with a peptide bond and tested for their effects on hyperalgesia and allodynia. Carrageenan-induced hyperalgesia and partial sciatic nerve ligation (PSNL) were performed using rat models. Conjugates Ang IV-OT (Ang IV at the N-terminal) and OT-Ang IV (OT at the N-terminal) were synthesized and intrathecally injected into male and female rats. Our results showed that Ang IV-OT exhibited prominent antihyperalgesia in male rats, particularly during hyperalgesia recovery, whereas OT-Ang IV was more effective during development stage. Ang IV-OT showed clear antihyperalgesia in female rats, but OT-Ang IV had no significant effect. Notably, both conjugates alleviated neuropathic allodynia in male rats; however, OT-Ang IV had no effect in female rats, whereas Ang IV-OT induced significant antiallodynia. In conclusion, Ang IV-OT has greater therapeutic potential for treating hyperalgesia and allodynia than OT-Ang IV. Its effects were not affected by sex, unlike those of OT and OT-Ang IV, extending its possible clinical applications.

Associations between the artificial intelligence scoring system and live birth outcomes in preimplantation genetic testing for aneuploidy cycles.

BACKGROUND: Several studies have demonstrated that iDAScore is more accurate in predicting pregnancy outcomes in cycles without preimplantation genetic testing for aneuploidy (PGT-A) compared to KIDScore and the Gardner criteria. However, the effectiveness of iDAScore in cycles with PGT-A has not been thoroughly investigated. Therefore, this study aims to assess the association between artificial intelligence (AI)-based iDAScore (version 1.0) and pregnancy outcomes in single-embryo transfer (SET) cycles with PGT-A. METHODS: This retrospective study was approved by the Institutional Review Board of Chung Sun Medical University, Taichung, Taiwan. Patients undergoing SET cycles (n = 482) following PGT-A at a single reproductive center between January 2017 and June 2021. The blastocyst morphology and morphokinetics of all embryos were evaluated using a time-lapse system. The blastocysts were ranked based on the scores generated by iDAScore, which were defined as AI scores, or by KIDScore D5 (version 3.2) following the manufacturer's protocols. A single blastocyst without aneuploidy was transferred after examining the embryonic ploidy status using a next-generation sequencing-based PGT-A platform. Logistic regression analysis with generalized estimating equations was conducted to assess whether AI scores are associated with the probability of live birth (LB) while considering confounding factors. RESULTS: Logistic regression analysis revealed that AI score was significantly associated with LB probability (adjusted odds ratio [OR] = 2.037, 95% confidence interval [CI]: 1.632-2.542) when pulsatility index (PI) level and types of chromosomal abnormalities were controlled. Blastocysts were divided into quartiles in accordance with their AI score (group 1: 3.0-7.8; group 2: 7.9-8.6; group 3: 8.7-8.9; and group 4: 9.0-9.5). Group 1 had a lower LB rate (34.6% vs. 59.8-72.3%) and a higher rate of pregnancy loss (26% vs. 4.7-8.9%) compared with the other groups (p < 0.05). The receiver operating characteristic curve analysis verified that the iDAScore had a significant but limited ability to predict LB (area under the curve [AUC] = 0.64); this ability was significantly weaker than that of the combination of iDAScore, type of chromosomal abnormalities, and PI level (AUC = 0.67). In the comparison of the LB groups with the non-LB groups, the AI scores were significantly lower in the non-LB groups, both for euploid (median: 8.6 vs. 8.8) and mosaic (median: 8.0 vs. 8.6) SETs. CONCLUSIONS: Although its predictive ability can be further enhanced, the AI score was significantly associated with LB probability in SET cycles. Euploid or mosaic blastocysts with low AI scores (≤ 7.8) were associated with a lower LB rate, indicating the potential of this annotation-free AI system as a decision-support tool for deselecting embryos with poor pregnancy outcomes following PGT-A.

Deep-learning model to improve histological grading and predict upstaging of atypical ductal hyperplasia / ductal carcinoma in situ on breast biopsy.

AIMS: Risk stratification of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), diagnosed using breast biopsy, has great clinical significance. Clinical trials are currently exploring the possibility of active surveillance for low-risk lesions, whereas axillary lymph node staging may be considered during surgical planning for high-risk lesions. We aimed to develop a machine-learning algorithm based on whole-slide images of breast biopsy specimens and clinical information to predict the risk of upstaging to invasive breast cancer after wide excision. METHODS AND RESULTS: Patients diagnosed with ADH/DCIS on breast biopsy were included in this study, comprising 592 (740 slides) and 141 (198 slides) patients in the development and independent testing cohorts, respectively. Histological grading of the lesions was independently evaluated by two pathologists. Clinical information, including biopsy method, lesion size, and Breast Imaging Reporting and Data System (BI-RADS) classification of ultrasound and mammograms, were collected. Deep DCIS consisted of three deep neural networks to evaluate nuclear grade, necrosis, and stromal reactivity. Deep DCIS output comprised five parameters: total patches, lesion extent, Deep Grade, Deep Necrosis, and Deep Stroma. Deep DCIS highly correlated with the pathologists' evaluations of both slide- and patient-level labels. All five parameters of Deep DCIS were significantly associated with upstaging to invasive carcinoma in subsequent wide excisional specimens. Using multivariate logistic regression, Deep DCIS predicted upstaging to invasive carcinoma with an area under the curve (AUC) of 0.81, outperforming pathologists' evaluation (AUC, 0.71 and 0.69). After including clinical and hormone receptor status information, performance further improved (AUC, 0.87). This combined model retained its predictive power in two subgroup analyses: the first subgroup included unequivocal DCIS (excluding cases of ADH and DCIS suspicious for microinvasion) (AUC, 0.83), while the second excluded cases of high-grade DCIS (AUC, 0.81). The model was validated in an independent testing cohort (AUC, 0.81). CONCLUSION: This study demonstrated that deep-learning models can refine histological evaluation of ADH and DCIS on breast biopsies, which may help guide future treatment planning.

Immunogenicity and safety of heterologous booster with protein-based COVID-19 vaccine (NVX-CoV2373) in healthy adults: A comparative analysis with mRNA vaccines.

BACKGROUND: Information on the protein-based severe acute respiratory syndrome (SARS-CoV-2) vaccine-NVX-CoV2373 (Novavax), as a heterologous booster remains limited. We investigated the immunogenicity and adverse events of NVX-CoV2373 as a second booster and compared them with those of mRNA vaccines in healthy adults. METHODS: Healthcare workers who had received an mRNA vaccine (mRNA-1273 or BNT-162b2) as the first booster (third dose) 12 weeks prior were recruited. Participants voluntarily received either NVX-CoV2373 or an mRNA vaccine as a second booster. Participants with a history of SARS-CoV-2 infection were excluded. The primary outcomes included serum anti-SARS-CoV-2 spike protein (SP) and neutralizing antibody titers against B.1.1.7 (Alpha), B.1.1.529 (Omicron) BA2, and BA5 variants on the 28th day after the boost. Secondary outcomes included new SARS-CoV-2 infections and adverse events reported during the study period. RESULTS: A total of 160 participants were enrolled in this study. Compared with the mRNA vaccination group (n = 59), the NVX-CoV2373 vaccination group (n = 101) had significantly lower anti-SARS-CoV-2 SP antibody titers and neutralizing antibody titers against all variants tested after the boost. During the study period, higher rates of new SARS-CoV-2 infections and a lower incidence of adverse events were observed in the NVX-CoV2373 vaccination group. No significant differences in cellular immune responses were observed between the two groups. CONCLUSION: Compared to a homologous mRNA booster vaccination, heterologous boosters with NVX-CoV2373 showed lower antibody responses, a higher incidence of new SARS-CoV-2 infections, and fewer adverse events.

Cadherin-13 Maintains Retinotectal Synapses via Transneuronal Interactions.

Maintaining precise synaptic contacts between neuronal partners is critical to ensure the proper functioning of the mammalian central nervous system (CNS). Diverse cell recognition molecules, such as classic cadherins (Cdhs), are part of the molecular machinery mediating synaptic choices during development and synaptic maintenance. Yet, the principles governing neuron-neuron wiring across diverse CNS neuron types remain largely unknown. The retinotectal synapses, connections from the retinal ganglion cells (RGCs) to the superior collicular (SC) neurons, offer an ideal experimental system to reveal molecular logic underlying synaptic choices and formation. This is due to the retina's unidirectional and laminar-restricted projections to the SC and the large databases of presynaptic RGC subtypes and postsynaptic SC neuronal types. Here, we focused on determining the role of Type II Cdhs in wiring the retinotectal synapses. We surveyed Cdhs expression patterns at neuronal resolution and revealed that Cdh13 is enriched in the wide-field neurons in the superficial SC (sSC). In either the Cdh13 null mutant or selective adult deletion within the wide-field neurons, there is a significant reduction of spine densities in the distal dendrites of these neurons in both sexes. Additionally, Cdh13 removal from presynaptic RGCs reduced dendritic spines in the postsynaptic wide-field neurons. Cdh13-expressing RGCs use differential mechanisms than αRGCs and On-Off Direction-Selective Ganglion Cells (ooDSGCs) to form specific retinotectal synapses. The results revealed a selective transneuronal interaction mediated by Cdh13 to maintain proper retinotectal synapses in vivo.

Reverse genetic study reveals the molecular targets of chordotonal organ TRPV channel modulators.

Insecticides have been widely used for the control of insect pests that have a significant impact on agriculture and human health. A better understanding of insecticide targets is needed for effective insecticide design and resistance management. Pymetrozine, afidopyropen and flonicamid are reported to target on proteins that located on insect chordotonal organs, resulting in the disruption of insect coordination and the inhibition of feeding. In this study, we systematically examined the susceptibility of six Drosophila melanogaster mutants (five transient receptor potential channels and one mechanoreceptor) to three commercially used insecticides, in order to identify the receptor subunits critical to the insect's response to insecticides. Our results showed that iav1, nan36aand wtrw1 mutants exhibited significantly reduced susceptibility to pymetrozine and afidopyropen, but not to flonicamid. The number of eggs produced by the three mutant females were significantly less than that of the w1118 strain. Meanwhile, the longevity of all male mutants and females of nan36a and wtrw1 mutants was significantly shorter than that of the w1118 strain as the control. However, we observed no gravitaxis defects in wtrw1 mutants and the anti-gravitaxis of wtrw1 mutants was abolished by pymetrozine. Behavioral assays using thermogenetic tools further confirmed the bioassay results and supported the idea that Nan as a TRPV subfamily member located in Drosophila chordotonal neurons, acting as a target of pymetrozine, which interferes with Drosophila and causes motor deficits with gravitaxis defects. Taken together, this study elucidates the interactions of pymetrozine and afidopyropen with TRPV channels, Nan and Iav, and TRPA channel, Wtrw. Our research provides another evidence that pymetrozine and afidopyropen might target on nan, iav and wtrw channels and provides insights into the development of sustainable pest management strategies.

Lunasin ameliorates glucose utilization in C2C12 myotubes and metabolites profile in diet-induced obese mice benefiting metabolic disorders.

AIMS: Obesity is the main cause of low-grade inflammation and oxidation, resulting in insulin resistance. This study aimed to investigate the effects of a seed peptide lunasin on glucose utilization in C2C12 myotubes and the metabolite profiles in obese mice. MAIN METHODS: C2C12 myotubes were challenged by palmitic acid (PA) to mimic the obese microenvironment and inflammation, cell vitality, and glucose utilization were determined. C57BL6/j mice were divided into low-fat diet (LF), high-fat diet (HF), and HF with intraperitoneally injected lunasin (HFL) groups. Glucose intolerance and metabolite profiles of the tissues were analyzed. KEY FINDINGS: In vitro, C2C12 myotubes treated with lunasin showed decreased proinflammatory cytokines and increased cell vitality under palmitic acid conditions. Lunasin improved glucose uptake and glucose transporter 4 expression by activating insulin receptor substrate-1 and AKT phosphorylation. Next-generation sequencing revealed that lunasin regulates genes expression by promoting insulin secretion and decreasing oxidative stress. In vivo, HF mice showed increased tricarboxylic acid cycle and uric acid metabolites but decreased bile acids metabolites and specific amino acids. Lunasin intervention improved glucose intolerance and modulated metabolites associated with increased insulin sensitivity and decreased metabolic disorders. SIGNIFICANCE: This study is the first to reveal that lunasin is a promising regulator of anti-inflammation, anti-oxidation, and glucose utilization in myotubes and ameliorating glucose uptake and metabolite profiles in obese mice, contributing to glucose homeostasis and benefiting metabolic disorders.

Insight interactions of engineered nanoparticles with aquatic higher plants for phytoaccumulation, phytotoxicity, and phytoremediation applications: A review.

With the growing age of human civilization, industrialization has paced up equally which is followed by the innovation of newer concepts of science and technology. One such example is the invention of engineered nanoparticles and their flagrant use in widespread applications. While ENPs serve their intended purposes, they also disrupt the ecological balance by contaminating pristine aquatic ecosystems. This review encompasses a comprehensive discussion about the potent toxicity of ENPs on aquatic ecosystems, with a particular focus on their impact on aquatic higher plants. The discussion extends to elucidating the fate of ENPs upon release into aquatic environments, covering aspects ranging from morphological and physiological effects to molecular-level phytotoxicity. Furthermore, this level of toxicity has been correlated with the determination of competent plants for the phytoremediation process towards the mitigation of this ecological stress. However, this review further illustrates the path of future research which is yet to be explored. Determination of the genotoxicity level of aquatic higher plants could explain the entire process comprehensively. Moreover, to make it suitable to be used in natural ecosystems phytoremediation potential of co-existing plant species along with the presence of different ENPs need to be evaluated. This literature will undoubtedly offer readers a comprehensive understanding of the stress induced by the irresponsible release of engineered nanoparticles (ENP) into aquatic environments, along with insights into the resilience characteristics of these pristine ecosystems.

Factors Affecting the Potential Efficacy of Intrauterine Platelet-Rich Plasma Infusion on Thin Endometrium in Women with Recurrent Implantation Failure.

Optimizing endometrial thickness (EMT) is crucial for successful embryo implantation, but enhancing thin endometrium remains a significant challenge. Platelet-rich plasma (PRP)-derived therapies have emerged as a promising approach in reproductive medicine due to their capacity to facilitate tissue repair and regeneration. This study aims to identify the risk factors associated with the failure of intrauterine PRP infusion for thin endometrium in women with recurrent implantation failure (RIF). We retrospectively reviewed data from 77 women with RIF, all exhibiting an EMT of <7 mm. These women underwent programmed hormone therapy for frozen embryo transfer (FET) and received two autologous intrauterine PRP infusions. Following intrauterine PRP-lysate (PL) infusions, the mean increase in EMT was 1.9 ± 1.2 mm, with EMT reaching 7 mm in 86% of the cases (66/77; average EMT, 8.3 mm). We identified an exceedingly thin EMT as a risk factor impacting the therapeutic efficacy in increasing EMT (p = 0.04, OR: 3.16; 95% CI: 1.03-9.67). Additionally, the number of previous uterine surgeries emerged as a prognostic factor for pregnancy failure following PL infusion (p = 0.02, OR: 2.02; 95% CI: 1.12-3.64). Our findings suggest that an extremely thin EMT and a history of numerous uterine surgeries can impede successful pregnancy, even when an optimal EMT is achieved following PRP infusion.