Preparation, structural characterization, and functional attributes of zein-lysozyme-κ-carrageenan ternary nanocomposites for curcumin encapsulation.

The low water solubility and inadequate bioavailability of curcumin significantly hinder its broad biological applications in the realms of food and medicine. There is limited information currently available regarding the particle characteristics and functional capabilities of zein-lysozyme-based nanomaterials. Thereby, the primary goal of the current work is to effectively develop innovative zein-lysozyme-κ-carrageenan complex nanocomposites (ZLKC) as a reliable carrier for curcumin encapsulation. As a result, ZLKC nanoparticles showed a smooth spherical nanostructure with improved encapsulation efficiency. Fourier-transform infrared, fluorescence spectroscopy, dissociation assay, and circular dichroism analysis revealed that hydrophobic and electrostatic interactions and hydrogen bonding were pivotal in the construction and durability of these composites. X-ray diffraction examination affirmed the lack of crystallinity in curcumin encapsulated within nanoparticles. The incorporation of κ-carrageenan significantly improved the physicochemical stability of ZLKC nanoparticles in diverse environmental settings. Additionally, ZLKC nanocomposites demonstrated enhanced antioxidant and antimicrobial properties, as well as sustained release characteristics. Therefore, these findings demonstrate the potential application of ZLKC nanocomposites as delivery materials for encapsulating bioactive substances.

Discovery and genetic characterization of novel paramyxoviruses from small mammals in Hubei Province, Central China.

Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

MyoVision-US: an Artificial Intelligence-Powered Software for Automated Analysis of Skeletal Muscle Ultrasonography.

Introduction/Aims: Muscle ultrasound has high utility in clinical practice and research; however, the main challenges are the training and time required for manual analysis to achieve objective quantification of morphometry. This study aimed to develop and validate a software tool powered by artificial intelligence (AI) by measuring its consistency and predictability of expert manual analysis quantifying lower limb muscle ultrasound images across healthy, acute, and chronic illness subjects. Methods: Quadriceps complex (QC [rectus femoris and vastus intermedius]) and tibialis anterior (TA) muscle ultrasound images of healthy, intensive care unit, and/or lung cancer subjects were captured with portable devices. Automated analyses of muscle morphometry were performed using a custom-built deep-learning model (MyoVision-US), while manual analyses were performed by experts. Consistency between manual and automated analyses was determined using intraclass correlation coefficients (ICC), while predictability of MyoVision -US was calculated using adjusted linear regression (adj.R 2 ). Results: Manual analysis took approximately 24 hours to analyze all 180 images, while MyoVision - US took 247 seconds, saving roughly 99.8%. Consistency between the manual and automated analyses by ICC was good to excellent for all QC (ICC:0.85-0.99) and TA (ICC:0.93-0.99) measurements, even for critically ill (ICC:0.91-0.98) and lung cancer (ICC:0.85-0.99) images. The predictability of MyoVision-US was moderate to strong for QC (adj.R 2 :0.56-0.94) and TA parameters (adj.R 2 :0.81-0.97). Discussion: The application of AI automating lower limb muscle ultrasound analyses showed excellent consistency and strong predictability compared with human analysis. Future work needs to explore AI-powered models for the evaluation of other skeletal muscle groups.

The superiority of hydrophilic polyurethane in comammox-dominant ammonia oxidation during low-strength wastewater treatment.

Carriers have been extensively employed to enhance nitrification performance during low-strength wastewater treatment by retaining slow-growing ammonia oxidizing microorganisms (AOMs). Still, there is a dearth of systematic understanding of biofilm properties and microbial community structure formed on different carriers. In this study, hydrophilic polyurethane foam (PUF) carriers were prepared and compared with five widely used commercial carriers, namely Kaldness 3, Biochip, activated carbon, volcanic rock, and zeolite. The results indicated that the biofilms formed on carriers enhanced microbial ammonia oxidation activity. Additionally, the biofilm developed on the PUF demonstrated the most superior performance among all selected carriers, not only exhibiting the highest abundant and the most active AOMs, with amoA gene abundance of 1.41 × 1013 copies/m3 and specific ammonia oxidation rate of 9.84 g NH+ 4-N/(m3 × h), but also possessing a compact structure, with 3.41 kg VSS/m3 and 46.83 mg extracellular polymeric substances/g VSS. The high-throughput sequencing analysis revealed that the comammox (CMX) Nitrospira dominated on biofilm due to the intrinsically low apparent half-saturation constant for substrate. A unique ecological community structure was established on PUF, characterized by low species diversity and high homogeneity in alignment with community characteristics of CMX. The biofilms on PUF contributed to the proliferation of CMX Nitrospira dominated by Nitrospira nitrosa, achieving the highest proportion among colonial three AOMs at 86.58 %. The appropriate average pore size, superior hydrophilicity, and large specific surface area of PUF carriers provided a robust foundation for the exceptional ammonia oxidation performance of the formed biofilms.

Efficacy of Natural Products in Preventing Oral Mucositis Resulting from Cancer Therapies: A Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Oral mucositis significantly compromises the quality of life for patients undergoing cancer therapies. This study aimed to evaluate the effectiveness of natural products in either preventing or alleviating oral mucositis resulting from cancer treatments. METHODS: A systematic review and network meta-analysis were conducted, sourcing data from the Cochrane Library, PubMed, Embase, Airiti Library, and Wan Fang Data Knowledge Service Platform until August 2023. The study was registered in PROSPERO (CRD42021285433). Confidence in Network Meta-Analysis (CINeMA) and R software 4.1.3 were used for analysis. RESULTS: From 1,556 identified articles, 36 randomized controlled trials (RCTs) were analyzed, involving 2,083 patients. Honey, notably, was found to significantly reduce the overall incidence of oral mucositis compared to standard care, with a relative risk (RR) of 0.80 (95% CI: 0.67-0.96). It was particularly effective against moderate-to-severe oral mucositis (grade ≥ 2), reducing incidence with RR of 0.48 (95% CI: 0.30-0.75) versus placebo and 0.56 (95% CI: 0.34-0.93) against standard care. Other natural products, including propolis, chamomile, and P. major L., also demonstrated significant efficacy in reducing the incidence of oral mucositis. Regarding pain relief, honey, and P. major L. emerged as effective, significantly reducing pain severity with a mean difference (MD) of -2.96 (95% CI: -3.80 to -1.94) compared to placebo. CONCUSSION: This network meta-analysis supports the use of honey, propolis, chamomile, and P. major L. as effective natural products in the prevention and treatment of oral mucositis among cancer patients. Specifically, honey is highlighted for its significant impact on reducing both the overall incidence and the severity of moderate-to-severe oral mucositis. By leveraging their anti-inflammatory and antioxidant properties, integrating these natural products into the standard care regimen could markedly improve the well-being of individuals undergoing cancer therapy.

Bilateral Production Shield Enabling Highly Efficient Perovskite Photovoltaics.

Enhancing the intrinsic stability of perovskite and through encapsulation to isolate water, oxygen, and UV-induced decomposition are currently common and most effective strategies in perovskite solar cells. Here, the atomic layer deposition process is employed to deposit a nanoscale (≈100 nm), uniform, and dense Al2O3 film on the front side of perovskite devices, effectively isolating them from the erosion caused by water and oxygen in the humid air. Simultaneously, nanoscale (≈100 nm) TiO2 films are also deposited on the glass surface to efficiently filter out the ultraviolet (UV) light in the light source, which induces degradation in perovskite. Ultimately, throughthe collaborative effects of both aspects, the stability of the devices is significantly improved under conditions of humid air and illumination. As a result, after storing the devices in ambient air for 1000 h, the efficiency only declines to 95%, and even after 662 h of UV exposure, the efficiency remains at 88%, far surpassing the performance of comparison devices. These results strongly indicate that the adopted Al2O3 and TiO2 thin films play a significant role in enhancing the stability of perovskite solar cells, demonstrating substantial potential for widespread industrial applications.

Efficacy and safety of adjunctive perampanel treatment in pediatric patients with epilepsy aged 4-12 years: a real-world study.

OBJECTIVE: To determine the efficacy and safety of perampanel (PER) as an adjunctive therapy in children aged 4-12 years with epilepsy. METHODS: We performed a non-randomized, open-label, placebo-uncontrolled, real-world self-controlled study that included 216 young children (aged 4-12 years) with epilepsy who received PER as adjunctive therapy at the children's hospital affiliated with Chongqing Medical University from July 4, 2020, to September 20, 2023. RESULTS: (1) The efficacy rates of adjunctive PER therapy at 3, 6, 9, and 12 months were 62.8%, 67.8%, 65.3%, and 61.2%, respectively. PER showed efficacy in alleviating focal seizures, generalized tonic-clonic seizures, myoclonic seizures, and absence seizures. The efficacy rates for variants of self-limited epilepsy with centrotemporal spikes (SeLECTS) and Lennox-Gastaut syndrome (LGS) were 89.5% and 66.7%, respectively. (2) Focal non-motor onset seizures with or without impaired awareness, focal to bilateral tonic-clonic seizures (FBTCS), LGS, variants of SeLECTS, the number of concomitant antiseizure medications (ASMs), a family history of epilepsy, and focal lesions on cranial magnetic resonance imaging were independent factors affecting efficacy. The order of PER addition did not affect efficacy. The retention rates at 3, 6, 9, and 12 months were 90.7%, 84.7%, 74.7%, 64.9%, respectively. (3) Adverse reactions occurred in 45 patients (45/216, 20.8%), with irritability/aggressive behavior (18/216, 8.3%) and somnolence (14/216, 6.5%) being the most common. Twelve patients (12/216, 5.6%) withdrew from the study because of adverse reactions. CONCLUSION: In young Chinese children with epilepsy, PER is effective, safe, and well-tolerated as an adjunctive therapy, making it a viable option for use with broad-spectrum ASMs.

Explaining the improving effect of dough crumb-sheet composite rolling on fresh noodle quality: From microstructure and moisture distribution perspective.

A new technique known as dough crumb-sheet composite rolling (DC-SCR) was used to improve the quality of fresh noodles. However, there is a dearth of theoretical investigations into the optimal selection of specific parameters for this technology, and the underlying mechanisms are not fully understood. Therefore, the effects of dough crumb addition times in DC-SCR on the texture, cooking, and eating quality of fresh noodles were first studied. Then, the underlying regulation mechanism of DC-SCR technology on fresh noodles was analyzed in terms of moisture distribution and microstructure. The study demonstrated that the most significant enhancement in the quality of fresh noodles was achieved by adding dough crumbs six times. Compared with fresh noodles made without the addition of dough crumbs, the initial hardness and chewiness of fresh noodles made by adding six times of dough crumbs increased by 25.32% and 46.82%, respectively. In contrast, the cooking time and cooking loss were reduced by 28.45% and 29.69%, respectively. This quality improvement in fresh noodles made by DC-SCR came from the microstructural differences of the gluten network between the inner and outer layers of the dough sheet. A dense structure on the outside and a loose structure on the inside could endow the fresh noodles made by DC-SCR with higher hardness, a shortened cooking time, and less cooking loss. This study would provide a theoretical and experimental basis for creating high-quality fresh noodles.

Widespread Adoption of Microincision Vitrectomy Surgery Improves Visual Outcomes in Endogenous Endophthalmitis with Poor Initial Vision: A 21-Year Experience in Taiwan.

PURPOSE: To review the presentation and visual prognostic factors of patients with endogenous endophthalmitis before and after the introduction of microincision vitrectomy surgery (MIVS), at a tertiary referral hospital in Taiwan, over a 21-year period. METHODS: We retrospectively analyzed medical records of patients diagnosed with endogenous endophthalmitis before and after the introduction of MIVS between January 2002 and December 2022. RESULTS: Data were collected from 147 patients. Diabetes mellitus was the most common comorbidity (59.9%). Liver abscess (32.7%) was the leading source of infection, followed by urinary tract infection (15.0%), and infective endocarditis (5.4%). Klebsiella pneumoniae (50.4%) was the most common pathogen, followed by Staphylococcus aureus (13.5%), and Candida albicans (8.3%). Poor initial visual acuity worse than counting fingers (CF) (p < 0.001) and diabetes mellitus (p = 0.008) were significantly associated with poor visual outcomes. In the treatment of 98 patients with poor initial visual acuity worse than CF, the proportion of vitrectomy surgeries performed increased from 13/56 (23.2%) to 24/42 (57.1%) (p = 0.001) after the introduction of MIVS. Final visual acuity of CF or better increased from 7/56 (12.5%) to 12/42 (28.6%) after the introduction of MIVS (p = 0.046). Vitrectomy was a better prognostic factor for final visual outcome in patients with poor initial visual acuity of worse than CF (p = 0.011) than other factors. CONCLUSION: In endogenous endophthalmitis patients presenting with poor initial visual acuity, vitrectomy was a better visual prognostic factor. MIVS has allowed more patients to undergo vitrectomy and improved visual outcomes.

Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.

Association between gut microbiota and central retinal artery occlusion: A two-sample Mendelian randomization study.

PURPOSE: The gut microbiota might be closely related to central retinal artery occlusion (CRAO), but the causality has not been well defined. Two-sample Mendelian randomization (MR) study was used to reveal the potential causal effect between the gut microbiota and CRAO. METHODS: Data for gut microbiota were obtained from the genome-wide association studies of the Dutch Microbiome Project (DMP) (n = 7738) and the MiBioGen consortium (n = 18,340), and data on CRAO were obtained from samples of FinnGen project (546 cases and 344,569 controls). Causalities of exposures and outcomes were explored mainly using the inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median (WM), simple mode, weighted mode, and MR Pleiotropy RESidual Sum and Outlier were simultaneously applied to validate the final results. RESULTS: We identified three microbial pathways (two risk factors/one protective factor) and seven microbial taxa (two risk factors/five protective factors) associated with CRAO in the DMP study. Based on the data from the MiBioGen consortium, we identified seven microbial taxa (two risk factors/five protective factors) associated with CRAO, including the Eubacterium genus, which was consistently identified as a risk factor in both the DMP and the MiBioGen consortium MR analyses. CONCLUSION: Our study implicates the potential causal effects of specific microbial taxa and pathways on CRAO, potentially providing new insights into the prevention and treatment of CRAO through specific gut microbial taxa and pathway. Since our conclusion is a hypothesis derived from secondary genome-wide association studies (GWAS) data analysis, further research is needed for confirmation.

Heat stress-induced oviposition behavioral change correlates with sperm damage in the pine sawyer beetle, Monochamus alternatus.

BACKGROUND: Global climate change is causing an increase in extreme high temperatures (EHTs), which subject insects to unprecedented stress. Behavior plasticity in response to EHTs, particularly oviposition behavior, is important for the persistence and outbreak of insect populations. Investigating the plasticity of oviposition behavior and its underlying mechanisms has theoretical importance to pest management, but knowledge gaps still remain. RESULTS: Herein, we characterized the reproductive traits of Monochamus alternatus, a dominant insect vector of the destructive pine wilt disease, including oviposition behavioral patterns, fecundity, offspring fitness and sperm viability, under simulated heatwave conditions in the laboratory. The results showed that (i) EHTs induced a novel oviposition behavior, whereby females deposited multiple eggs into a single groove rather than laying one egg per groove under normal condition; (ii) EHTs exerted stage- and sex-specific effects on fecundity, offspring fitness and sperm viability; and (iii) there was a significant correlation between frequency of the novel oviposition strategy and sperm viability. CONCLUSION: We hypothesized that this beetle pest has the ability to flexibly shift towards a low-cost oviposition strategy to counteract the fitness costs caused by heat stress. Taken together, these findings provide a theoretical foundation for personalized pest management strategies in the context of climate change. © 2024 Society of Chemical Industry.

Optimization of Composite Enzymatic Extraction, Structural Characterization and Biological Activity of Soluble Dietary Fiber from Akebia trifoliata Peel.

In order to reduce the waste of Akebia trifoliata peel and maximize its utilization, in this study, on the basis of a single-factor experiment and the response surface method, the optimum technological conditions for the extraction of soluble dietary fiber from Akebia trifoliata peel with the compound enzyme method were obtained. The chemical composition, physical and chemical properties, structural characterization and biological activity of the purified soluble dietary fiber (AP-SDF) from the Akebia trifoliata peel were analyzed. We discovered that that the optimum yield was 20.87% under the conditions of cellulase addition 600 U/g, enzymolysis time 100 min, solid-liquid ratio 1:24 g/mL and enzymolysis temperature 51 °C. At the same time, AP-SDF was a porous network structure cellulose type I acidic polysaccharose mainly composed of arabinoxylan (36.03%), galacturonic acid (27.40%) and glucose (19.00%), which possessed the structural characteristic peaks of the infrared spectra of polysaccharides and the average molecular weight (Mw) was 95.52 kDa with good uniformity. In addition, the AP-SDF exhibited high oil-holding capacity (15.11 g/g), good water-holding capacity and swelling capacity, a certain antioxidant capacity in vitro, hypoglycemic activity in vitro for α-glucosidase inhibition and hypolipidemic activity in vitro for the binding ability of bile acids and cholesterol. These results will provide a theoretical basis for the development of functional products with antioxidant, hypoglycemic and hypolipidemic effects, which have certain application value in related industries.

Contemporary Views of the Extraction, Health Benefits, and Industrial Integration of Rice Bran Oil: A Prominent Ingredient for Holistic Human Health.

Globally, 50% of people consume rice (Oryza sativa), which is among the most abundant and extensively ingested cereal grains. Rice bran is a by-product of the cereal industry and is also considered a beneficial waste product of the rice processing industry. Rice bran oil (RBO) is created from rice bran (20-25 wt% in rice bran), which is the outermost layer of the rice kernel; has a lipid content of up to 25%; and is a considerable source of a plethora of bioactive components. The main components of RBO include high levels of fiber and phytochemicals, including vitamins, oryzanols, fatty acids, and phenolic compounds, which are beneficial to human health and well-being. This article summarizes the stabilization and extraction processes of rice bran oil from rice bran using different techniques (including solvent extraction, microwaving, ohmic heating, supercritical fluid extraction, and ultrasonication). Some studies have elaborated the various biological activities linked with RBO, such as antioxidant, anti-platelet, analgesic, anti-inflammatory, anti-thrombotic, anti-mutagenic, aphrodisiac, anti-depressant, anti-emetic, fibrinolytic, and cytotoxic activities. Due to the broad spectrum of biological activities and economic benefits of RBO, the current review article focuses on the extraction process of RBO, its bioactive components, and the potential health benefits of RBO. Furthermore, the limitations of existing studies are highlighted, and suggestions are provided for future applications of RBO as a functional food ingredient.

Screening and optimization of shark nanobodies against SARS-CoV-2 spike RBD.

SARS-CoV-2 continues to threaten human health, antibody therapy is one way to control the infection. Because new SARS-CoV-2 mutations are constantly emerging, there is an urgent need to develop broadly neutralizing antibodies to block the viral entry into host cells. VNAR from sharks is the smallest natural antigen binding domain, with the advantages of small size, flexible paratopes, good stability, and low manufacturing cost. Here, we used recombinant SARS-CoV-2 Spike-RBD to immunize sharks and constructed a VNAR phage display library. VNAR R1C2, selected from the library, efficiently binds to the RBD domain and blocks the infection of ACE2-positive cells by pseudovirus. Next, homologous bivalent VNARs were constructed through the tandem fusion of two R1C2 units, which enhanced both the affinity and neutralizing activity of R1C2. R1C2 was predicted to bind to a relatively conserved region within the RBD. By introducing mutations at four key binding sites within the CDR3 and HV2 regions of R1C2, the affinity and neutralizing activity of R1C2 were significantly improved. Furthermore, R1C2 also exhibits an effective capacity of binding to the Omicron variants (BA.2 and XBB.1). Together, these results suggest that R1C2 could serve as a valuable candidate for preventing and treating SARS-CoV-2 infections.

Fe-Doped Ni2P/NiSe2 Composite Catalysts for Urea Oxidation Reaction (UOR) for Energy-Saving Hydrogen Production by UOR-Assisted Water Splitting.

The development of efficient urea oxidation reaction (UOR) catalysts helps UOR replace the oxygen evolution reaction (OER) in hydrogen production from water electrolysis. Here, we prepared Fe-doped Ni2P/NiSe2 composite catalyst (Fe-Ni2P/NiSe2-12) by using phosphating-selenizating and acid etching to increase the intrinsic activity and active areas. Spectral characterization and theoretical calculations demonstrated that electrons flowed through the Ni-P-Fe-interface-Ni-Se-Fe, thus conferring high UOR activity to Fe-Ni2P/NiSe2-12, which only needed 1.39 V vs RHE to produce the current density of 100 mA cm-2. Remarkably, this potential was 164 mV lower than that required for the OER under the same conditions. Furthermore, EIS demonstrated that UOR driven by the Fe-Ni2P/NiSe2-12 exhibited faster interfacial reactions, charge transfer, and current response compared to OER. Consequently, the Fe-Ni2P/NiSe2-12 catalyst can effectively prevent competition with OER and NSOR, making it suitable for efficient hydrogen production in UOR-assisted water electrolysis. Notably, when water electrolysis is operated at a current density of 40 mA cm-2, this UOR-assisted system can achieve a decrease of 140 mV in the potential compared to traditional water electrolysis. This study presents a novel strategy for UOR-assisted water splitting for energy-saving hydrogen production.

Humanization of a mouse anti-human complement C6 monoclonal antibody as a potential therapeutic for certain complement-mediated diseases.

The assembly of tissue-damaging membrane attack complexes (MACs; C5b-9) is a major mechanism by which excessive complement activation causes diseases. We previously developed a mouse anti-human C6 monoclonal antibody (mAb) 1C9 that selectively inhibits the assembly of MACs in human and non-human primates. In this project, we found that 1C9 also cross-reacted with rat and guinea pig C6, and determined its binding domains on C6 using different truncated C6 proteins. We then humanized the anti-C6 mAb by molecular modeling and complementarity-determining region grafting. After screening a library of 276 humanized variants with different combinations of humanized light and heavy chains in biophysical assays, we identified clone 3713 with the best developability profile, and an increased affinity against C6 when compared with the parental 1C9 mAb. This humanized 3713 mAb inhibited human, monkey, and rat complement-mediated hemolysis in vitro, and more importantly, it significantly reduced complement-mediated hemolysis in vivo in rats. These results demonstrated the successful humanization of the anti-C6 mAb and suggested that the humanized 3713 mAb could be further developed as a new therapeutic that selectively targets MAC for certain complement-mediated pathological conditions.

Proteomic profiling of tumor microenvironment and prognosis risk prediction in stage I lung adenocarcinoma.

OBJECTIVES: With the increasing popularity of CT screening, more cases of early-stage lung cancer are being diagnosed. However, 24.5% of stage I non-small-cell lung cancer (NSCLC) patients still experience treatment failure post-surgery. Biomarkers to predict lung cancer patients at high risk of recurrence are needed. MATERIALS AND METHODS: We collected protein mass spectrometry data from the Taiwan Lung Cancer Moonshot Project and performed bioinformatics analysis on proteins with differential expressions between tumor and adjacent normal tissues in 74 stage I lung adenocarcinoma (LUAD) cases, aiming to explore the tumor microenvironment related prognostic biomarkers. Findings were further validated in 6 external cohorts. RESULTS: The analysis of differentially expressed proteins revealed that the most enriched categories of diseases and biological functions were cellular movement, immune cell trafficking, and cancer. Utilizing proteomic profiling of the tumor microenvironment, we identified five prognostic biomarkers (ADAM10, MIF, TEK, THBS2, MAOA). We then developed a risk score model, which independently predicted recurrence-free survival and overall survival in stage I LUAD. Patients with high risk scores experienced worse recurrence-free survival (adjusted hazard ratio = 8.28, p < 0.001) and overall survival (adjusted hazard ratio = 6.88, p = 0.013). Findings had been also validated in the external cohorts. CONCLUSION: The risk score model derived from proteomic profiling of tumor microenvironment can be used to predict recurrence risk and prognosis of stage I LUAD.

Regulation of fatty acid delivery to metastases by tumor endothelium.

Tumor metastasis, the main cause of death in cancer patients, requires outgrowth of tumor cells after their dissemination and residence in microscopic niches. Nutrient sufficiency is a determinant of such outgrowth1. Fatty acids (FA) can be metabolized by cancer cells for their energetic and anabolic needs but impair the cytotoxicity of T cells in the tumor microenvironment (TME)2,3, thereby supporting metastatic progression. However, despite the important role of FA in metastatic outgrowth, the regulation of intratumoral FA is poorly understood. In this report, we show that tumor endothelium actively promotes tumor growth and restricts anti-tumor cytolysis by transferring FA into developing metastatic tumors. This process uses transendothelial fatty acid transport via endosome cargo trafficking in a mechanism that requires mTORC1 activity. Thus, tumor burden was significantly reduced upon endothelial-specific targeted deletion of Raptor, a unique component of the mTORC1 complex (RptorECKO). In vivo trafficking of a fluorescent palmitic acid analog to tumor cells and T cells was reduced in RptorECKO lung metastatic tumors, which correlated with improved markers of T cell cytotoxicity. Combination of anti-PD1 with RAD001/everolimus, at a low dose that selectively inhibits mTORC1 in endothelial cells4, impaired FA uptake in T cells and reduced metastatic disease, corresponding to improved anti-tumor immunity. These findings describe a novel mechanism of transendothelial fatty acid transfer into the TME during metastatic outgrowth and highlight a target for future development of therapeutic strategies.