pH-mediated potentiation of gallium nitrate against Pseudomonas aeruginosa.

The emergence of multidrug-resistant Pseudomonas aeruginosa isolates is a growing concern for public health, necessitating new therapeutic strategies. Gallium nitrate [Ga(NO3)3], a medication for cancer-related hypercalcemia, has attracted great attention due to its ability to inhibit P. aeruginosa growth and biofilm formation by disrupting iron metabolism. However, the antibacterial efficacy of Ga(NO3)3 is not always satisfactory. It is imperative to investigate the factors that affect the bactericidal effects of Ga(NO3)3 and to identify new ways to enhance its efficacy. This study focused on the impact of pH on P. aeruginosa resistance to Ga(NO3)3, along with the underlying mechanism. The results indicate that acidic conditions could increase the effectiveness of Ga(NO3)3 against P. aeruginosa by promoting the production of pyochelin and gallium uptake. Subsequently, using glutamic acid, a clinically compatible acidic amino acid, the pH was significantly lowered and enhanced the bactericidal and inhibitory efficacy of Ga(NO3)3 against biofilm formation by P. aeruginosa, including a reference strain PA14 and several multidrug-resistant clinical isolates. Furthermore, we used an abscess mouse model to evaluate this combination in vivo; the results show that the combination of glutamic acid and Ga(NO3)3 significantly improved P. aeruginosa clearance. Overall, the present study demonstrates that acidic conditions can increase the sensitivity of P. aeruginosa to Ga(NO3)3. Combining glutamic acid and Ga(NO3)3 is a potential strategy for the treatment of P. aeruginosa infections.

Psilocybin for major depressive disorder: a systematic review of randomized controlled studies.

Objectives: The purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the effectiveness, safety, and tolerability of psilocybin in adult patients with major depressive disorder (MDD). Methods: A systematic search (up to September 14, 2023) was conducted for RCTs that examined the efficacy, safety, and tolerability of psilocybin in physically healthy adult patients with MDD. Three independent researchers extracted data from publications where the primary outcome was a change in depressive symptoms, and key secondary outcomes were changes in anxiety symptoms and suicidal ideation, discontinuation rates for any reason, and adverse drug reactions (ADRs). Results: Five RCTs with 472 adult patients with MDD on psilocybin (n = 274) and controls (n = 198) were included. Two of the five RCTs (40%) reported mixed results, while the other three (60%) found that psilocybin had a beneficial effect on MDD treatment. Four RCTs (80%) assessing the anxiolytic effects of psilocybin for treating MDD found that psilocybin was significantly more effective than the control group in improving anxiety symptoms. Psilocybin was more effective than the control group in improving suicidal ideation in one out of five RCTs. Discontinuation rates were similar for any reason between the psilocybin group (2-13%) and the control group (4-21%) (P > 0.05). Four RCTs (80%) reported ADRs in detail. The most common ADR in both groups was headache. Conclusion: Psilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD. The long-term efficacy and safety of psilocybin for MDD treatment needs to be further investigated in large RCTs.

The Efficacy of High-Fidelity Telesimulation in Preparing Nursing Students for Emergency and Critical Patient Care: A Prospective Study.

BACKGROUND: High-fidelity telesimulation can address the gap in nursing education caused by the pandemic by providing a simulated environment for students to practice skills that closely mimic real-life scenarios. PURPOSE: This study was designed to determine the effect of a high-fidelity telesimulation teaching program on emergency and critical patient care-related knowledge, self-confidence, and critical thinking skills in nursing students. METHODS: This randomized, single-blind controlled study was conducted on a sample of 84 nursing students who were evaluated using pretest and posttest measurements. The participants were randomized into a control group ( n = 43) and an experimental group ( n = 41). The control group received an in-person traditional teaching program, and the experimental group was taught using a high-fidelity telesimulation program. During the high-fidelity telesimulation, synchronous online tutorial learning and telesimulation were conducted every 100 and 300 minutes. The experimental group program included a lecture, simulation teaching videos, and demonstrations related to endotracheal intubation, 12-lead electrocardiography, protective clothing, and hybrid telesimulation learning. In each subgroup, the students executed a single high-fidelity telesimulation scenario in which they were assigned individual roles. The students in the other subgroups served as observers and engaged in the synchronous online debriefing. Teaching efficacy was evaluated using an objective structured clinical examination and a questionnaire designed for emergency and critical patient care. RESULTS: In the experimental group, levels of knowledge and self-confidence as well as critical thinking skills related to emergency and critical patient care were significantly higher than in the control group ( p < .05). CONCLUSIONS: High-fidelity telesimulation teaching is a feasible and reliable alternative to conventional in-person simulation for nursing students, particularly in situations where traditional clinical experiences are not possible.

Listening to Mom in the Neonatal Intensive Care Unit: A randomized trial of increased maternal speech exposure on white matter connectivity in infants born preterm.

Background: Early speech experiences have been proposed to contribute to the development of brain structures involved in processing spoken language. However, previous research has been limited to correlational studies. Here, we conducted an RCT with preterm neonates to determine whether increased exposure to maternal speech during NICU hospitalization is causally linked to structural white matter maturation. Methods: We enrolled 46 preterm neonates (24-31 weeks gestational age). Participants were randomly assigned to receive increased (T: n=21) or routine (C: n=25) exposure to mother's speech. The T-group heard 10-minute audio recordings of their mothers reading a children's story two times/hour between 10pm-6am, increasing speech exposure by 2.67 hours/day. At near-term-equivalent age, we obtained two high-angular resolution diffusion MRI (scan 1 bvalue=700, scan 2 bvalue=1500) and quantitative T1 relaxometry scans. We assessed mean diffusivity (MD), pre-registered primary outcome ( NCT02847689 ), of the left and right arcuate fasciculus, tracts implicated in language processing. Secondary outcomes included fractional anisotropy (FA) and R1 (1/T1). Findings: T- and C-groups were equivalent on medical and demographic variables. Compared to the C- group, the T-group demonstrated significantly lower MD in the left (scan 1: mean difference Δ = 0.11, 95% CI:0.03 - 0.19; scan 2: Δ = 0.13, 95% CI:0.04 - 0.21) but not right arcuate (scan 1: Δ = 0.06, 95% CI: -0.23 - 0.15; scan 2: Δ = 0.05, 95% CI:-0.05 - 0.13). The T-group also demonstrated significantly higher FA (scan 1: Δ = - 0.02, 95% CI:-0.04 - -0.00; scan 2: Δ = -0.03, 95% CI:-0.06 - -0.00) and R1 ( Δ = -0.02, 95% CI:-0.04 - -0.01) in the left but not right arcuate. Interpretation: Preterm neonates who experienced increased exposure to maternal speech during hospitalization demonstrated more mature microstructure of the left arcuate. Findings provide evidence for a causal link between speech experiences and brain development. Increasing speech exposure in the NICU may benefit preterm children. Research in Context Panel: Evidence before this study: Observational studies document the importance of early speech experience for language learning and brain development in term and preterm children. Children born preterm are at-risk for adverse language outcomes that have been attributed to alterations in brain development from limited exposure to speech in the neonatal intensive care unit (NICU). However, evidence that early speech experiences causally effect the development of brain structures relevant for language is lacking.Added value of this study: The Listening to Mom in NICU study is the first randomized controlled trial specifically designed to test the causal effects of maternal speech exposure on white matter brain development in neonates born preterm. This study demonstrates that speech experiences during neonatal development directly contribute to the maturation of the left arcuate fasciculus, a white matter tract implicated in language.Implications of all the available evidence: Study findings advance understandings for how early speech experiences contribute to neonatal brain development. This study also demonstrates that increasing exposure to speech via audio recordings among infants born preterm could serve as an inexpensive and scalable intervention to support recovery from alterations in brain development related to the NICU experience.

Contrast and Genomic Characterisation of Ancient and Recent Interspecific Introgression Between Deeply Diverged Moustache Toads (Leptobrachium).

Recent genomic analyses have provided new insights into the process of interspecific introgression and its consequences on species evolution. Most recent studies, however, focused on hybridization between recently radiated species, with few examining the genomic outcomes of ancient hybridization across deeply diverged species. Using whole genome data of moustache toads (Leptobrachium), we identified signals of three hybridization events among nine species that diverged at the Eocene. An ancient introgression from L. leishanense to the ancestral branch (C1) of L. liui introduced adaptive variants. The highly introgressed regions include genes with important functions in odorant detection and immune responses. These genes are preserved in all three descendent populations of L. liui_C1, and these regions likely have been positively selected over a long filtering process. A recent introgression occurred from L. huashen to L. tengchongense, with the introgressed regions being mostly neutral. Furthermore, one F1 hybrid individual was detected between sympatric L. ailaonicum and L. promustache. The signals of introgression largely disappeared after removing the hybrid individual, indicating an occasional hybridization but minimal introgression. Further examination of highly divergent but low introgressed genomic regions revealed both pre-mating isolation and genetic incompatibility as potential mechanisms of resisting introgression and maintaining species boundaries. Additionally, no large X-effect was found in these introgression events. Hybridization between deeply diverged amphibian species may be common, but detectable introgressions are likely less so, with recent introgression being mostly neutral and the rare ancient one potentially adaptive. Our findings complement recent genomic work, and together they provide a better understanding of the genomic characteristics of interspecific introgression and its significance in species adaptation and evolution.

Anti-Inflammatory and Antioxidant Effects of Irigenen Alleviate Osteoarthritis Progression through Nrf2/HO-1 Pathway.

BACKGROUND/OBJECTIVES: Osteoarthritis (OA) is a prevalent degenerative disease globally, characterized by cartilage degradation and joint dysfunction. Current treatments are insufficient for halting OA progression. Irigenin (IRI), a flavonoid extracted from natural plants with anti-inflammatory and antioxidant properties, has demonstrated potential in mitigating inflammation and oxidative stress in various diseases; however, its effects on OA remain unexplored. This study aims to evaluate the therapeutic effects of IRI on OA through in vivo and in vitro experiments and to elucidate the underlying molecular mechanisms. METHODS: In vitro, chondrocytes were exposed to hydrogen peroxide (H2O2) to induce an oxidative stress environment and were then treated with IRI. Western blotting, RT-qPCR, immunofluorescence staining assays, flow cytometry, and apoptosis assays were employed to assess the effects of IRI on chondrocyte matrix homeostasis, inflammatory response, and apoptosis. In vivo, an OA rat model was treated with regular IRI injections, and therapeutic effects were evaluated using micro-CT, histological staining, and immunohistochemistry assays. RESULTS: IRI treatment restored matrix homeostasis in chondrocytes and effectively suppressed H2O2-induced inflammation and apoptosis. Subsequent studies further revealed that IRI exerts its therapeutic effects by activating the Nrf2/HO-1 pathway. Inhibition of Nrf2 expression in chondrocytes partially blocked the anti-inflammatory and antioxidant effects of IRI. In the OA rat model, regular IRI injections effectively ameliorated cartilage degeneration. CONCLUSIONS: This study identifies IRI as a promising strategy for OA treatment by modulating inflammation and apoptosis through the Nrf2/HO-1 pathway.

Poly (lactic acid) electrospun nanofiber membranes: Advanced characterization for biomedical applications with drug loading performance studies.

Traditional dressings have shortcomings such as poor moisture absorption and easy to adhere, making the development of new dressings crucial. In this work, a PLA/PVP crosslinked drug-loaded nanofiber membrane was prepared through electrospinning and ultraviolet crosslinking, with poly (lactic acid) (PLA), polyvinylpyrrolidone (PVP), and salicylic acid (SA) as starting materials. The results demonstrated that the inclusion of PVP notably boosted the viscosity and conductivity of the blend spinning solution. The roughness of the fabricated fiber was elevated, and the diameter of the fibers was more uniform. Additionally, the incorporation of PVP not only enhanced the porosity of the fiber membrane but also effectively decreased its contact angle. Notably, when the PVP content reached 40 %, the contact angle underwent a substantial reduction, decreasing significantly from 125.4° to 82.2°. The SA drug-loaded fiber membrane exhibited a notable bacteriostatic effect against Escherichia coli and Staphylococcus aureus, with its release behavior adhering to Fick's diffusion law. In the cell viability experiment, the cell proliferation rate increased from 94 % to 129 % after 3 days. This shows that the prepared membrane has good antibacterial effect and cell compatibility, which provides a theoretical basis for the construction of a new medical dressing.

TRIM21 induces selective autophagic degradation of c-Myc and sensitizes regorafenib therapy in colorectal cancer.

Kirsten rat sarcoma virus (KRAS) mutation is associated with malignant tumor transformation and drug resistance. However, the development of clinically effective targeted therapies for KRAS-mutant cancer has proven to be a formidable challenge. Here, we report that tripartite motif-containing protein 21 (TRIM21) functions as a target of extracellular signal-regulated kinase 2 (ERK2) in KRAS-mutant colorectal cancer (CRC), contributing to regorafenib therapy resistance. Mechanistically, TRIM21 directly interacts with and ubiquitinates v-myc avian myelocytomatosis viral oncogene homolog (c-Myc) at lysine 148 (K148) via K63-linkage, enabling c-Myc to be targeted to the autophagy machinery for degradation, ultimately resulting in the downregulation of enolase 2 expression and inhibition of glycolysis. However, mutant KRAS (KRAS/MT)-driven mitogen-activated protein kinase (MAPK) signaling leads to the phosphorylation of TRIM21 (p-TRIM21) at Threonine 396 (T396) by ERK2, disrupting the interaction between TRIM21 and c-Myc and thereby preventing c-Myc from targeting autophagy for degradation. This enhances glycolysis and contributes to regorafenib resistance. Clinically, high p-TRIM21 (T396) is associated with an unfavorable prognosis. Targeting TRIM21 to disrupt KRAS/MT-driven phosphorylation using the antidepressant vilazodone shows potential for enhancing the efficacy of regorafenib in treating KRAS-mutant CRC in preclinical models. These findings are instrumental for KRAS-mutant CRC treatment aiming at activating TRIM21-mediated selective autophagic degradation of c-Myc.

Leader-Following Consensus of Linear Multiagent Systems With Aperiodically Sampled Outputs: A Distributed Impulsive-Observer-Based Approach.

This article studies the leader-following consensus problem for a class of linear multiagent systems over a directed graph with aperiodically sampled outputs. First, a novel distributed impulsive-observer-based consensus protocol is designed. This protocol requires only the output measurements at sporadic time instants for the observer and control gain design. Second, by using time-varying Lyapunov function techniques, sufficient conditions for exponential stability of a class of linear impulsive systems are established; subsequently, these stability results are applied for the distributed impulsive observer design. Different from the existing related works, the impulsive observer gain designed in this work is decoupled from the graph properties. As a result, once the impulsive observer gain is designed for one network topology, it can be directly used for other network topologies, as long as the graph properties and the dynamics of local agents satisfy certain conditions. Furthermore, the resilience of the designed protocol is tested under denial of service (DoS) attacks. It is shown that the protocol is robust with respect to low-frequency DoS attacks occurring in the observer communication network. Finally, two examples illustrating the validity and effectiveness of the proposed protocol are included.

Gut metagenome-derived image augmentation and deep learning improve prediction accuracy of metabolic disease classification.

In recent years, statistics and machine learning methods have been widely used to analyze the relationship between human gut microbial metagenome and metabolic diseases, which is of great significance for the functional annotation and development of microbial communities. In this study, we proposed a new and scalable framework for image enhancement and deep learning of gut metagenome, which could be used in the classification of human metabolic diseases. Each data sample in three representative human gut metagenome datasets was transformed into image and enhanced, and put into the machine learning models of logistic regression (LR), support vector machine (SVM), Bayesian network (BN) and random forest (RF), and the deep learning models of multilayer perceptron (MLP) and convolutional neural network (CNN). The accuracy performance of the overall evaluation model for disease prediction was verified by accuracy (A), accuracy (P), recall (R), F1 score (F1), area under ROC curve (AUC) and 10 fold cross-validation. The results showed that the overall performance of MLP model was better than that of CNN, LR, SVM, BN, RF and PopPhy-CNN, and the performance of MLP and CNN models was further improved after data enhancement (random rotation and adding salt-and-pepper noise). The accuracy of MLP model in disease prediction was further improved by 4%-11%, F1 by 1%-6% and AUC by 5%-10%. The above results showed that human gut metagenome image enhancement and deep learning could accurately extract microbial characteristics and effectively predict the host disease phenotype. The source code and datasets used in this study can be publicly accessed in https://github.com/HuaXWu/GM_ML_Classification.git.

Comparison of three-dimensional vs. two-dimensional assisted thoracoscopy for recurrent laryngeal nerve lymph nodes dissection in esophagectomy: a retrospective study.

BACKGROUND: This study aimed to explore the clinical value of 3D video-assisted thoracoscopic surgery in dissecting recurrent laryngeal nerve lymph nodes in patients undergoing minimally invasive esophagectomy. METHODS: A retrospective cohort study was conducted on 205 patients, including 120 males, who underwent esophagectomy from May 2018 to May 2020 in the Department of Thoracic Surgery at the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University. Perioperative parameters, including intraoperative blood loss, operation time, the number of dissected recurrent laryngeal nerve lymph nodes, the incidence and degree of postoperative recurrent laryngeal nerve injury, the volume of postoperative thoracic drainage, and postoperative complications, were compared between the 3D and 2D groups. RESULTS: There were no significant differences in the preoperative baseline data between these two groups (P > 0.05). The number of dissected recurrent laryngeal nerve lymph nodes in the 3D group was significantly higher than in the 2D group (P < 0.05). The operation times were significantly shorter in the 3D group than in the 2D group (P < 0.05). The volume of thoracic drainage in the first 2 days was significantly less in the 3D group than in the 2D group (P < 0.05). CONCLUSIONS: Compared to the 2D system, the application of 3D video-assisted thoracoscopic surgery in minimally invasive esophagectomy can increase the number of dissected recurrent laryngeal nerve lymph nodes and ensure safety. Additionally, it can reduce the duration of the operation, decrease early postoperative thoracic drainage volume, and promote patient recovery.

6:2 chlorinated polyfluoroalkyl ether sulfonate (F-53B) induced nephrotoxicity associated with oxidative stress, inflammation and fibrosis in mice.

6:2 Chlorinated polyfluoroalkyl ether sulfonate (trade name F-53B) is a substitute for perfluorooctane sulfonate (PFOS) used in the plating industry, and has been found in a range of environmental matrices and livings. There are numerous ways by which it is biotoxic to mammals. The kidneys are critical for maintaining homeostasis. However, little research has been conducted on how F-53B affects the kidneys. In this work, we investigated the renal toxicity of long-term oral F-53B treatment in C57BL/6J mice. Mice were allowed to drink F-53B freely at concentrations of 0, 0.057, 0.57, and 5.7 mg/L for 8 weeks. Renal oxidative stress, inflammation, and fibrosis were detected in mice exposed to F-53B, and the expression of related biochemical markers was significantly altered. Further investigations revealed that the TGF-ß1/Smad3 and NF-κB signaling pathways may be associated with F-53B-induced renal fibrotic damage and inflammation. Overall, this study suggested that F-53B causes renal injury possibly via oxidative stress, activating the TGF-ß1/Smad3 and NF-κB signaling pathways. This provides a foundation for further research into the harmful mechanism of F-53B in mammals.

Fecal Microbiota Transplantation Induced by Wumei Pills Improves Chemotherapy-Induced Intestinal Mucositis in BALB/c Mice by Modulating the TLR4/MyD88/NF-κB Signaling Pathway.

BACKGROUND: Our previous studies have found that Wumei Pills can regulate the intestinal flora to inhibit chemotherapy-induced intestinal mucositis (CIM). However, there is still insufficient evidence to confirm that intestinal flora is the main link in the regulation of CIM by Wumei Pills, and its downstream mechanism is still unclear. METHOD: We first obtained the signal pathway of the intervention of Wumei Pill on CIM through network pharmacological analysis and then transplanted the bacterial solution into CIM mice, combined with Western Blot, HE, ELISA and other biological technology-related proteins and inflammatory factors. RESULTS: It showed that 97 kinds of effective ingredients and 205 kinds of targets of Wumei pills were screened out and the potential mechanism of Wumei Pills on CIM may be the NF-κB signaling pathway. In contrast with the control group, the results displayed that the weight, food intake, and mice's colon length were apparently decreased in the 5-Fu group, while the diarrhea score was increased. However, FMT reversed this change, and the difference was statistically significant. Additionally, FMT could improve the pathological state of inflammatory cell infiltration in mice, reduce histopathological scores of colon and jejunum, decrease the expression levels of IL-1ß, MPO, TNF-α, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/ NF-κB and down-regulate protein expression, thereby exerting its anti-inflammatory activities. Further experiments have found that FMT could reverse the decreasing of tight junction proteins and mucins caused by 5-Fu, thereby repairing the intestinal mucosal barrier, and FMT could also increase the content of acetic acid, propanoic acid, and butanoic acid in the feces of 5-Fu group. CONCLUSION: FMT can defend the intestinal mucosal barrier integrality by increasing the content of exercise fatty acids, and its mechanism may be in connection with its inhibition of TLR4/My- D88/NF-κB signal pathway to relieve inflammation.

Silicon heterojunction back contact solar cells by laser patterning.

Back contact silicon solar cells, valued for their aesthetic appeal by removing grid lines on the sunny side, find applications in buildings, vehicles and aircrafts, enabling self-power generation without compromising appearance1-3. Patterning techniques arrange contacts on the shaded side of the silicon wafer, offering benefits for light incidence as well. However, the patterning process complicates production and causes power loss. Here we employ lasers to streamline back contact solar cell fabrication and enhance power conversion efficiency. Our approach produces the first silicon solar cell to exceed 27% efficiency. Hydrogenated amorphous silicon layers are deposited on the wafer for surface passivation and collection of light-generated carriers. A dense passivating contact, diverging from conventional technology practice, is developed. Pulsed picosecond lasers at different wavelengths are used to create back contact patterns. The developed approach is a streamlined process for producing high-performance back contact silicon solar cells, with a total effective processing time of about one-third that of emerging mainstream technology. To meet terawatt demand, we develop rare indium-less cells at 26.5% efficiency and precious silver-free cells at 26.2% efficiency. The integration of solar solutions in buildings and transportation is poised to expand with these technological advancements.

Bright dipolar excitons in twisted black phosphorus homostructures.

Bright dipolar excitons, which contain electrical dipoles and have high oscillator strength, are an ideal platform for studying correlated quantum phenomena. They usually rely on carrier tunneling between two quantum wells or two layers to hybridize with nondipolar excitons to gain oscillator strength. In this work, we uncovered a new type of bright infrared dipolar exciton by stacking 90°-twisted black phosphorus (BP) structures. These excitons, inherent to the reconstructed band structure, exhibit high oscillator strength. Most importantly, they inherit the linear polarization from BP, which allows light polarization to be used to select the dipole direction. Moreover, the dipole moment and resonance energy can be widely tuned by the thickness of the BP. Our results demonstrate a useful platform for exploring tunable correlated dipolar excitons.

Three Therapy Regimens and Their Cost-effectiveness for Girls With Central Precocious Puberty: A Real-World Clinical Study.

The objective of this study was to evaluate the effectiveness and cost-effectiveness of different therapy regimens for girls with central precocious puberty (CPP). This study retrospectively analyzed CPP girls from 2013 to 2021 and grouped them into GnRHa, Mixed, and GnRHa+GH based on therapy regimen. While comparing the differences among these groups, initial age and bone age of GnRHa group girls were significantly lower than Mixed and GnRHa+GH groups, but their growth level was significantly higher (P < .05). In the Mixed group, starting with GnRHa alone, the predicted adult height improvement (ΔPAH) decreased to -1.0 cm in the second year, prompting addition of growth hormone (GH) therapy in the third year, resulting in a ΔPAH increase to 3.0 cm. At therapy completion, final predicted adult heights (PAHs) were similar among the groups at 155.6 to 156.7 cm, with ΔPAH between 5.8 and 6.5 cm and no significant intergroup differences (P > .05). Younger CPP girls with greater height can begin therapy with GnRHa alone. Consideration of combining GH therapy depends on growth velocity and PAH during treatment.

27.09%-efficiency silicon heterojunction back contact solar cell and going beyond.

Crystalline-silicon heterojunction back contact solar cells represent the forefront of photovoltaic technology, but encounter significant challenges in managing charge carrier recombination and transport to achieve high efficiency. In this study, we produced highly efficient heterojunction back contact solar cells with a certified efficiency of 27.09% using a laser patterning technique. Our findings indicate that recombination losses primarily arise from the hole-selective contact region and polarity boundaries. We propose solutions to these issues and establish a clear relationship between contact resistivity, series resistance, and the design of the rear-side pattern. Furthermore, we demonstrate that the wafer edge becomes the main channel for current density loss caused by carrier recombination once electrical shading around the electron-selective contact region is mitigated. With the advanced nanocrystalline passivating contact, wafer edge passivation technologies and meticulous optimization of front anti-reflection coating and rear reflector, achieving efficiencies as high as 27.7% is feasible.

Calcium phosphate complex of recombinant human thrombomodulin promote bone formation in interbody fusion.

Interbody fusion is an orthopedic surgical procedure to connect two adjacent vertebrae in patients suffering from spinal disc disease. The combination of synthetic bone grafts with protein-based drugs is an intriguing approach to stimulate interbody bone growth, specifically in patients exhibiting restricted bone progression. Recombinant human thrombomodulin (rhTM), a novel protein drug characterized by its superior stability and potency, shows promise in enhancing bone formation. A composite bone graft, termed CaP-rhTM, has been synthesized, combining calcium phosphate (CaP) microparticles as a delivery vehicle for rhTM to facilitate interbody fusion.In vitrostudies have demonstrated that rhTM significantly promotes the proliferation and maturation of preosteoblasts at nanogram dosage, while exerting minimal impact on osteosarcoma cell growth. The expression levels of mature osteoblast markers, including osteocalcin, osteopontin, alkaline phosphatase, and calcium deposition were also enhanced by rhTM. In rat caudal disc model of interbody fusion, CaP-rhTM with 800 ng of drug dosage was implanted along with a polylactic acid cage, to ensure structural stability within the intervertebral space. Microcomputed tomography analyses revealed that from 8 to 24 weeks, CaP-rhTM substantially improves both bone volume and trabecular architecture, in addition to the textural integrity of bony endplate surfaces. Histological examination confirmed the formation of a continuous bone bridge connecting adjacent vertebrae. Furthermore, biomechanical assessment via three-point bending tests indicated an improved bone quality of the fused disc. This study has demostrated that rhTM exhibits considerable potential in promoting osteogenesis. The use of CaP-rhTM has also shown significant improvements in promoting interbody fusion.

Preclinical evaluation of a fully human, quadrivalent-hantavirus polyclonal antibody derived from a non-human source.

Hantaviruses are rodent-borne viruses that cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV) causing hantavirus pulmonary syndrome. In the Old World, major hantaviruses include Hantaan virus (HTNV) and Puumala virus (PUUV) causing hemorrhagic fever with renal syndrome. Here, we produced a pan-hantavirus therapeutic (SAB-163) comprised of fully human immunoglobulin purified from the plasma of transchromosomic bovines (TcB) vaccinated with hantavirus DNA plasmids coding for the major glycoproteins of ANDV, SNV, HTNV, and PUUV. SAB-163 has potent neutralizing antibodies (PRNT50 > 200,000) against the four targeted hantavirus and cross-neutralization against several other heterotypic hantaviruses. At a dosage of 10 mg/kg, SAB-163 is bioavailable in Syrian hamsters out to 70 days post-treatment with a half-life of 10-15 days. At this same dosage, SAB-163 administered 1 day before, or 5 days after exposure, protected all hamsters from lethal disease caused by ANDV. At a higher dose, partial but significant protection was achieved as late as day 6. SAB-163 also protected hamsters in the HTNV, PUUV, and SNV infection models when administered 1 day before or up to 3 days after challenge. This pan-hantavirus therapeutic is attractive because it is fully human, multi-targeted, safe, stable at 4°C, and effective in animal models. SAB-163 was evaluated for safety in GLP human tissue binding studies and a GLP rabbit toxicity study at 365 and 730 mg/kg and is investigational new drug enabled for phase 1 clinical trial(s). IMPORTANCE: This candidate polyclonal human IgG product was produced using synthetic gene-based vaccines and transgenic cows. Having now gone through cGMP production, GLP safety testing, and efficacy testing in animals, SAB-163 is the world's most advanced anti-hantavirus antibody-based medical countermeasure, aside from convalescent human plasma. Importantly, SAB-163 targets the most prevalent hantaviruses on four continents.

Synthesis of Indolyl Isothiocyanate and Its Inhibitory Activity against Fungi.

Based on previous research, this study synthesized 24 compounds by splicing the substructures of the indolyl group and the isothiocyanate group. Alternaria alternata, Phytophthora capsici, Botrytis cinerea, and Valsa mali were used to test the activity of the target compounds. At 100 µg/mL, compounds 8, 13, 14, and 17 exhibited excellent inhibitory effects of more than 80% on P. capsici, B. cinerea, and V. mail. The EC50 values of compounds 13 and 14 were 0.64 and 2.08 µg/mL, respectively. Potted antifungal activity demonstrated that compounds 13 and 14 had a protective effect of around 80% against B. cinerea at 200 µg/mL. Further physiological and biochemical studies on B. cinerea revealed that compound 13 thickened cell walls and caused mitochondrial vacuolization. Moreover, theoretical calculations indicated that the charge distribution of indolyl isothiocyanate compounds played a crucial role in the observed fungicidal activity. In summary, this study provided fundamental reference data for the derivative synthesis of these indolyl isothiocyanate compounds.