De novo generation of SARS-CoV-2 antibody CDRH3 with a pre-trained generative large language model.

Artificial Intelligence (AI) techniques have made great advances in assisting antibody design. However, antibody design still heavily relies on isolating antigen-specific antibodies from serum, which is a resource-intensive and time-consuming process. To address this issue, we propose a Pre-trained Antibody generative large Language Model (PALM-H3) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 (CDRH3) with desired antigen-binding specificity, reducing the reliance on natural antibodies. We also build a high-precision model antigen-antibody binder (A2binder) that pairs antigen epitope sequences with antibody sequences to predict binding specificity and affinity. PALM-H3-generated antibodies exhibit binding ability to SARS-CoV-2 antigens, including the emerging XBB variant, as confirmed through in-silico analysis and in-vitro assays. The in-vitro assays validate that PALM-H3-generated antibodies achieve high binding affinity and potent neutralization capability against spike proteins of SARS-CoV-2 wild-type, Alpha, Delta, and the emerging XBB variant. Meanwhile, A2binder demonstrates exceptional predictive performance on binding specificity for various epitopes and variants. Furthermore, by incorporating the attention mechanism inherent in the Roformer architecture into the PALM-H3 model, we improve its interpretability, providing crucial insights into the fundamental principles of antibody design.

Identification of chitinase from Bacillus velezensis strain S161 and its antifungal activity against Penicillium digitatum.

Previous studies have demonstrated the presence of chitinase in Bacillus velezensis through extensive genomic sequencing and experimental analyses. However, the detailed structure, functional roles, and antifungal activity of these chitinases remain poorly characterized. In this study, genomic screening identified three genes-chiA, chiB, and lpmo10-associated with chitinase degradation in B. velezensis S161. These genes encode chitinases ChiA and ChiB, and lytic polysaccharide monooxygenase LPMO10. Both ChiA and ChiB contain two CBM50 binding domains and one catalytic domain, whereas LPMO10 includes a signal peptide and a single catalytic domain. The chitinases ChiA, its truncated variant ChiA2, and ChiB were heterologously expressed in Escherichia coli. The purified enzymes efficiently degraded colloidal chitin and inhibited the spore germination of Penicillium digitatum. Notably, even after losing one CBM50 domain, the resultant enzyme, consisting of the remaining CBM50 domain and the catalytic domain, maintained its colloidal chitin hydrolysis and antifungal activity, indicating commendable stability. These results underscore the role of B. velezensis chitinases in suppressing plant pathogenic fungi and provide a solid foundation for developing and applying chitinase-based biocontrol strategies.

Multi-objective double layer water optimal allocation and scheduling framework combing the integrated surface water - groundwater model.

Balancing the water consumption of agricultural and ecological is the key point of sustainable social and economic development in an inland river basin. The growth of desert riparian forests in inland river basins mainly depends on a certain phreatic water table depth (PWTD). The main object of this study was to allocate and schedule water resources to regulate the PWTD and satisfy agricultural water demand. Therefore, a multi-objective double layer optimal allocation and scheduling framework based on the computationally efficient integrated surface water-groundwater model (ISGWM), which can simulate the surface water processes, groundwater recharge and discharge processes, and PWTD changes, was constructed and applied to the mainstream of Tarim River Basin (TRB). The top layer model of the framework is an optimal ecological water allocation model, and its optimal allocation results are used as the initial solution of the bottom layer model. The results show that under 5 different inflow frequencies, the agricultural water shortage rate is 0, 17.38 %, 17.41 %, 14.06 %, and 19.94 %, respectively. The PWTD regulation has a great performance. After the optimal scheduling, the proportions of good growth of the control area behind the gate under different inflow frequencies were 98.18 %, 98.18 %, 98.18 %, 90.91 %, and 94.55 %. Agricultural water shortage is mainly due to the non-uniformity distribution of intra-annual inflow and the lack of controlling hydraulic engineering. The regulation of PWTD can guarantee the growth of desert riparian forests on both sides of the mainstream of TRB. Besides, we explored the feasibility of exploiting groundwater to supplement agricultural water consumption. The groundwater exploitation should be controlled within the scope of not causing excessive increase of PWTD (difference between PWTD and target depth <1 m), due to the groundwater exploitation to supplement agricultural water will lead to the increase of PWTD. Overall, this framework, which regulates the PWTD with the change of ecological water supply based on the ISGWM, provides a new idea for the allocation and scheduling of agricultural and ecological water resources in arid inland river basins. It also provides a new method for the coupled cooperative operation of surface water and groundwater.

Macro-characteristics and micro-mechanisms of Na2SO4 precipitation dissolved by KNO3 molten salt in a continuous supercritical water system.

This work aims to explore the ability of molten salt to solve salt deposition in supercritical water (SCW) related technologies including supercritical water oxidation and supercritical water gasification, with KNO3 and Na2SO4 as examples. In the pure KNO3 solution, the two-phase layering of high-density KNO3 molten salt (settling at the reactor bottom) and low-density saturated KNO3-SCW salt solution (flowing out at the top outlet of the reactor) was formed in a kettle-reactor with about 6.5 ratio of depth to inner diameter, thereby improving the accuracy of measured solubilities. The precipitation macro-characteristics of mixed KNO3 and Na2SO4 in SCW were investigated under different feed concentration conditions. The results showed that Na2SO4 deposition on the reactor sidewall could be reduced by more than 90 % when the mass ratio of KNO3 to Na2SO4 in the feed was only 0.167. No visible salt deposition was observed on the sidewall when the ratio was 0.374. All solid deposited salts were converted into the liquid molten salt as the ratio reached 3.341, and thus could easily flow out of the reactor, without plugging. 'Molten salt dissolution' mechanism may provide a more plausible explanation for mixed KNO3 and Na2SO4 in SCW. In addition, the precipitation micro-mechanisms of mixed KNO3 and Na2SO4, and the critical conditions of avoiding sidewall deposition and reactor plugging were proposed. This work is valuable for overcoming the salt deposition problem in SCW-related technologies.

Scalable multifunctional MOFs-textiles via diazonium chemistry.

Cellulose fiber-based textiles are ubiquitous in daily life for their processability, biodegradability, and outstanding flexibility. Integrating cellulose textiles with functional coating materials can unlock their potential functionalities to engage diverse applications. Metal-organic frameworks (MOFs) are ideal candidate materials for such integration, thanks to their unique merits, such as large specific surface area, tunable pore size, and species diversity. However, achieving scalable fabrication of MOFs-textiles with high mechanical durability remains challenging. Here, we report a facile and scalable strategy for direct MOF growth on cotton fibers grafted via the diazonium chemistry. The as-prepared ZIF-67-Cotton textile (ZIF-67-CT) exhibits excellent ultraviolet (UV) resistance and organic contamination degradation via the peroxymonosulfate activation. The ZIF-67-CT is also used to encapsulate essential oils such as carvacrol to enable antibacterial activity against E. coli and S. aureus. Additionally, by directly tethering a hydrophobic molecular layer onto the MOF-coated surface, superhydrophobic ZIF-67-CT is achieved with excellent self-cleaning, antifouling, and oil-water separation performances. More importantly, the reported strategy is generic and applicable to other MOFs and cellulose fiber-based materials, and various large-scale multi-functional MOFs-textiles can be successfully manufactured, resulting in vast applications in wastewater purification, fragrance industry, and outdoor gears.

Cluster Analysis of Cortical Amyloid Burden for Identifying Imaging-driven Subtypes in Mild Cognitive Impairment.

Over the past decade, Alzheimer's disease (AD) has become increasingly severe and gained greater attention. Mild Cognitive Impairment (MCI) serves as an important prodromal stage of AD, highlighting the urgency of early diagnosis for timely treatment and control of the condition. Identifying the subtypes of MCI patients exhibits importance for dissecting the heterogeneity of this complex disorder and facilitating more effective target discovery and therapeutic development. Conventional method uses clinical measurements such as cognitive score and neurophysical assessment to stratify MCI patients into two groups with early MCI (EMCI) and late MCI (LMCI), which shows their progressive stages. However, such clinical method is not designed to de-convolute the heterogeneity of the disorder. This study uses a data-driven approach to divide MCI patients into a novel grouping of two subtypes based on an amyloid dataset of 68 cortical features from positron emission tomography (PET), where each subtype has a homogeneous cortical amyloid burden pattern. Experimental evaluation including visual two-dimensional cluster distribution, Kaplan-Meier plot, genetic association studies, and biomarker distribution analysis demonstrates that the identified subtypes performs better across all metrics than the conventional EMCI and LMCI grouping.

Iterative Design of Near-Infrared Fluorescent Probes for Early Diagnosis of Alzheimer's Disease by Targeting Aß Oligomers.

Amyloid-ß oligomers (AßOs), crucial toxic proteins in early Alzheimer's disease (AD), precede the formation of Aß plaques and cognitive impairment. In this context, we present our iterative process for developing novel near-infrared fluorescent (NIRF) probes specifically targeting AßOs, aimed at early AD diagnosis. An initial screening identified compound 18 as being highly selective for AßOs. Subsequent analysis revealed that compound 20 improved serum stability while retaining affinity for AßOs. The most promising iteration, compound 37, demonstrated exceptional qualities: a high affinity for AßOs, emission in the near-infrared region, and good biocompatibility. Significantly, ex vivo double staining indicated that compound 37 detected AßOs in AD mouse brain and in vivo imaging experiments showed that compound 37 could differentiate between 4-month-old AD mice and age-matched wild-type mice. Therefore, compound 37 has emerged as a valuable NIRF probe for early detection of AD and a useful tool in exploring AD's pathological mechanisms.

[Exploring the Spatial and Temporal Trajectories of Land Use Carbon Emissions and Influencing Factors in the Aksu River Basin from 1990 to 2020].

Land use changes lead to changes in the functions of different types of carbon sources and sinks, which are key sources of carbon emissions. The study of carbon emissions and its influencing factors in the Aksu River Basin from the perspective of land use change is of great importance for the promotion of integrated protection and restoration of mountains, water, forests, fields, lakes, grasslands, sand, and ice in the basin and to help achieve the goal of carbon peaking and carbon neutrality. Based on four periods of land use data and socio-economic data from 1990 to 2020, the total carbon emissions from land use were measured, and the spatial and temporal trajectories of carbon emissions and their influencing factors were explored. The results showed that:① from 1990 to 2020, arable land, forest land, construction land, and unused land showed a general increasing trend, whereas grasslands and water areas showed a decreasing trend. The spatial change in land use types was mainly characterized by the conversion of grasslands and unused land into arable land, and 83.58 % of the arable land conversion areas were concentrated in the southwest of Wensu, Aksu, and the northern part of Awat. ② The total net carbon emissions in the basin showed a continuous growth trend from 1990 to 2020, with a cumulative increase of 14.78×104 t. The increase in arable land was a key factor causing an increase in net carbon emissions in the basin. ③ The spatial distribution pattern of land use carbon emissions in the basin was high in the middle and low in the fourth, with significant changes in net carbon emissions mainly in the southern part of Wensu, Aksu, Awat, and Alaer. ④ Human activities had the strongest driving effect on land use carbon emissions, with their effects gradually increasing from east to west. The contribution of average annual temperature to land use carbon emissions was mainly concentrated in the eastern part of Aksu and the northern part of Awat, whereas average annual rainfall had a strong inhibitory effect on the northern part of Wensu and the western part of Aheqi.

Deep Trans-Omic Network Fusion for Molecular Mechanism of Alzheimer's Disease.

Background: There are various molecular hypotheses regarding Alzheimer's disease (AD) like amyloid deposition, tau propagation, neuroinflammation, and synaptic dysfunction. However, detailed molecular mechanism underlying AD remains elusive. In addition, genetic contribution of these molecular hypothesis is not yet established despite the high heritability of AD. Objective: The study aims to enable the discovery of functionally connected multi-omic features through novel integration of multi-omic data and prior functional interactions. Methods: We propose a new deep learning model MoFNet with improved interpretability to investigate the AD molecular mechanism and its upstream genetic contributors. MoFNet integrates multi-omic data with prior functional interactions between SNPs, genes, and proteins, and for the first time models the dynamic information flow from DNA to RNA and proteins. Results: When evaluated using the ROS/MAP cohort, MoFNet outperformed other competing methods in prediction performance. It identified SNPs, genes, and proteins with significantly more prior functional interactions, resulting in three multi-omic subnetworks. SNP-gene pairs identified by MoFNet were mostly eQTLs specific to frontal cortex tissue where gene/protein data was collected. These molecular subnetworks are enriched in innate immune system, clearance of misfolded proteins, and neurotransmitter release respectively. We validated most findings in an independent dataset. One multi-omic subnetwork consists exclusively of core members of SNARE complex, a key mediator of synaptic vesicle fusion and neurotransmitter transportation. Conclusions: Our results suggest that MoFNet is effective in improving classification accuracy and in identifying multi-omic markers for AD with improved interpretability. Multi-omic subnetworks identified by MoFNet provided insights of AD molecular mechanism with improved details.

Learning With Noisy Labels Over Imbalanced Subpopulations.

Learning with noisy labels (LNL) has attracted significant attention from the research community. Many recent LNL methods rely on the assumption that clean samples tend to have a "small loss." However, this assumption often fails to generalize to some real-world cases with imbalanced subpopulations, that is, training subpopulations that vary in sample size or recognition difficulty. Therefore, recent LNL methods face the risk of misclassifying those "informative" samples (e.g., hard samples or samples in the tail subpopulations) into noisy samples, leading to poor generalization performance. To address this issue, we propose a novel LNL method to deal with noisy labels and imbalanced subpopulations simultaneously. It first leverages sample correlation to estimate samples' clean probabilities for label correction and then utilizes corrected labels for distributionally robust optimization (DRO) to further improve the robustness. Specifically, in contrast to previous works using classification loss as the selection criterion, we introduce a feature-based metric that takes the sample correlation into account for estimating samples' clean probabilities. Then, we refurbish the noisy labels using the estimated clean probabilities and the pseudo-labels from the model's predictions. With refurbished labels, we use DRO to train the model to be robust to subpopulation imbalance. Extensive experiments on a wide range of benchmarks demonstrate that our technique can consistently improve state-of-the-art (SOTA) robust learning paradigms against noisy labels, especially when encountering imbalanced subpopulations. We provide our code in https://github.com/chenmc1996/LNL-IS.

Physiological, molecular, and environmental insights into plant nitrogen uptake, and metabolism under abiotic stresses.

Nitrogen (N) as an inorganic macronutrient is inevitable for plant growth, development, and biomass production. Many external factors and stresses, such as acidity, alkalinity, salinity, temperature, oxygen, and rainfall, affect N uptake and metabolism in plants. The uptake of ammonium (NH4 +) and nitrate (NO3 -) in plants mainly depends on soil properties. Under the sufficient availability of NO3 - (>1 mM), low-affinity transport system is activated by gene network NRT1, and under low NO3 - availability (<1 mM), high-affinity transport system starts functioning encoded by NRT2 family of genes. Further, under limited N supply due to edaphic and climatic factors, higher expression of the AtNRT2.4 and AtNRT2.5T genes of the NRT2 family occur and are considered as N remobilizing genes. The NH4 + ion is the final form of N assimilated by cells mediated through the key enzymes glutamine synthetase and glutamate synthase. The WRKY1 is a major transcription factor of the N regulation network in plants. However, the transcriptome and metabolite profiles show variations in N assimilation metabolites, including glycine, glutamine, and aspartate, under abiotic stresses. The overexpression of NO3 - transporters (OsNRT2.3a and OsNRT1.1b) can significantly improve the biomass and yield of various crops. Altering the expression levels of genes could be a valuable tool to improve N metabolism under the challenging conditions of soil and environment, such as unfavorable temperature, drought, salinity, heavy metals, and nutrient stress.

Full-length transcriptome profiling of Acanthopanax gracilistylus provides new insight into the kaurenoic acid biosynthesis pathway.

Acanthopanax gracilistylus is a deciduous plant in the family Araliaceae, which is commonly used in Chinese herbal medicine, as the root bark has functions of nourishing the liver and kidneys, removing dampness and expelling wind, and strengthening the bones and tendons. Kaurenoic acid (KA) is the main effective substance in the root bark of A. gracilistylus with strong anti-inflammatory effects. To elucidate the KA biosynthesis pathway, second-generation (DNA nanoball) and third-generation (Pacific Biosciences) sequencing were performed to analyze the transcriptomes of the A. gracilistylus leaves, roots, and stems. Among the total 505,880 isoforms, 408,954 were annotated by seven major databases. Sixty isoforms with complete open reading frames encoding 11 key enzymes involved in the KA biosynthesis pathway were identified. Correlation analysis between isoform expression and KA content identified a total of eight key genes. Six key enzyme genes involved in KA biosynthesis were validated by real-time quantitative polymerase chain reaction. Based on the sequence analysis, the spatial structure of ent-kaurene oxidase was modeled, which plays roles in the three continuous oxidations steps of KA biosynthesis. This study greatly enriches the transcriptome data of A. gracilistylus and facilitates further analysis of the function and regulation mechanism of key enzymes in the KA biosynthesis pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01436-7.

Strong Interactions between Au Nanoparticles and BiVO4 Photoanode Boosts Hole Extraction for Photoelectrochemical Water Splitting.

Strong metal-support interaction (SMSI) is widely proposed as a key factor in tuning catalytic performances. Herein, the classical SMSI between Au nanoparticles (NPs) and BiVO4 (BVO) supports (Au/BVO-SMSI) is discovered and used innovatively for photoelectrochemical (PEC) water splitting. Owing to the SMSI, the electrons transfer from V4+ to Au NPs, leading to the formation of electron-rich Au species (Auδ-) and strong electronic interaction (i.e., Auδ--Ov-V4+), which readily contributes to extract photogenerated holes and promote charge separation. Benefitted from the SMSI effect, the as-prepared Au/BVO-SMSI photoanode exhibits a superior photocurrent density of 6.25 mA cm-2 at 1.23 V versus the reversible hydrogen electrode after the deposition of FeOOH/NiOOH cocatalysts. This work provides a pioneering view for extending SMSI effect to bimetal oxide supports for PEC water splitting, and guides the interfacial electronic and geometric structure modulation of photoanodes consisting of metal NPs and reducible oxides for improved solar energy conversion efficiency.

Synthesis of Spiro Polycyclic N-Heterocycles and Indolecarbazoles via Merging Oxidative Coupling and Cascade Palladium-Catalyzed Intramolecular Oxidative Cyclization.

We report a step-economic strategy for the direct synthesis of spiro polycyclic N-heterocycles and indolecarbazole-fused naphthoquinones by merging oxidative coupling and cascade palladium-catalyzed intramolecular oxidative cyclization. In the protocol, bi-indolylnaphthoquinones were first synthesized by oxidative coupling of indoles and naphthoquinones. Subsequent cascade palladium-catalyzed intramolecular oxidative cyclization of bi-indolylnaphthoquinones gave spiro polycyclic N-heterocycles and indolecarbazoles. The intramolecular oxidative cyclization approach could also be realized by the presence or absence of iron catalysts under standard conditions. This protocol is featured with moderate to excellent yields, a wide substrate scope, and divergent structures of products.

A signaling cascade mediating fruit trait development via phosphorylation-modulated nuclear accumulation of JAZ repressor.

It is generally accepted that jasmonate-ZIM domain (JAZ) repressors act to mediate jasmonate (JA) signaling via CORONATINE-INSENSITIVE1 (COI1)-mediated degradation. Here, we report a cryptic signaling cascade where a JAZ repressor, FvJAZ12, mediates multiple signaling inputs via phosphorylation-modulated subcellular translocation rather than the COI1-mediated degradation mechanism in strawberry (Fragaria vesca). FvJAZ12 acts to regulate flavor metabolism and defense response, and was found to be the target of FvMPK6, a mitogen-activated protein kinase that is capable of responding to multiple signal stimuli. FvMPK6 phosphorylates FvJAZ12 at the amino acid residues S179 and T183 adjacent to the PY residues, thereby attenuating its nuclear accumulation and relieving its repression for FvMYC2, which acts to control the expression of lipoxygenase 3 (FvLOX3), an important gene involved in JA biosynthesis and a diverse array of cellular metabolisms. Our data reveal a previously unreported mechanism for JA signaling and decipher a signaling cascade that links multiple signaling inputs with fruit trait development.

The genetic regulatory architecture and epigenomic basis for age-related changes in rattlesnake venom.

Developmental phenotypic changes can evolve under selection imposed by age- and size-related ecological differences. Many of these changes occur through programmed alterations to gene expression patterns, but the molecular mechanisms and gene-regulatory networks underlying these adaptive changes remain poorly understood. Many venomous snakes, including the eastern diamondback rattlesnake (Crotalus adamanteus), undergo correlated changes in diet and venom expression as snakes grow larger with age, providing models for identifying mechanisms of timed expression changes that underlie adaptive life history traits. By combining a highly contiguous, chromosome-level genome assembly with measures of expression, chromatin accessibility, and histone modifications, we identified cis-regulatory elements and trans-regulatory factors controlling venom ontogeny in the venom glands of C. adamanteus. Ontogenetic expression changes were significantly correlated with epigenomic changes within genes, immediately adjacent to genes (e.g., promoters), and more distant from genes (e.g., enhancers). We identified 37 candidate transcription factors (TFs), with the vast majority being up-regulated in adults. The ontogenetic change is largely driven by an increase in the expression of TFs associated with growth signaling, transcriptional activation, and circadian rhythm/biological timing systems in adults with corresponding epigenomic changes near the differentially expressed venom genes. However, both expression activation and repression contributed to the composition of both adult and juvenile venoms, demonstrating the complexity and potential evolvability of gene regulation for this trait. Overall, given that age-based trait variation is common across the tree of life, we provide a framework for understanding gene-regulatory-network-driven life-history evolution more broadly.

Efficiency of Protective Interventions on Irinotecan-Induced Diarrhea: A Systematic Review and Meta-Analysis.

BACKGROUND: Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID. METHOD: This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis. RESULT: The RR of high-grade diarrhea and all-grade diarrhea were 0.31 (I2 = 51%, 95% CI: 0.14-0.69; P = .004) and .76 (I2 = 65%, 95% CI: 0.62-0.93; P < .008) respectively, thus the use of intervention measures for preventing IID is effective, and the risk reduction of high-grade diarrhea was more significant. Subgroup analysis revealed that the monotherapy group (RR: 0.48, 95% CI: 0.21-1.13, I2 = 0%) and combination therapy group (RR: 0.14, 95% CI: 0.06-0.32, I2 = 0%) in the risk of high-grade diarrhea had no significant heterogeneity within the groups, and traditional herbal medicines (Kampo medicine Hangeshashin-to, PHY906 and hot ironing with Moxa Salt Packet on Tianshu and Shangjuxu) were effective preventive measures (RR:0.20, 95% CI: 0.07-0.60, I2 = 0%). The Jadad scores for traditional herbal medicines studies were 3, and the follow-up duration was only 2 to 6 weeks. CONCLUSION: This systematic review and meta-analysis suggest that preventive treatments significantly reduced the risk of high-grade and all-grade diarrhea, confirming the efficacy in the incidence and severity of IID, among which traditional herbal medicines (baicalin-containing) provided a protective effect in reducing the severity of IID. However, the traditional herbal medicines studies were of low quality. Combined irinotecan therapy can obtain better preventive effects than monotherapy of IID. These would be helpful for the prevention of IID in clinical practice.

Theoretical study of filtered and amplified PRBS phase modulation for SBS suppression in a 2.5†kW, 10†GHz monolithic fiber amplifier.

We report a theoretical and experimental study on stimulated Brillouin scattering (SBS) suppression in a monolithic fiber amplifier with filtered and amplified pseudo-random binary sequence (PRBS) phase modulation. Theoretically, we use a time-dependent three-wave coupled nonlinear system considering both active fiber and passive fiber to describe the acoustic phonon, laser, and Stokes characteristics in a fiber amplifier. The SBS threshold power after filtered PRBS phase modulation is numerically evaluated to obtain the optimal parameters, and the time-averaged distributions of the counter-pump power, laser power, and Stokes power at different positions along the fiber length of the fiber system are simulated. Also, we established a four-stage fiber amplifier system to verify our theory. The configuration of the fiber amplifier system includes a filtered and amplified PRBS phase-modulated single-frequency fiber laser, a three-stage pre-amplifier, and a counter-pumping main stage, subsequently. 2.5 kW output power with an FWHM linewidth of 9.63 GHz is accomplished by a domestic ytterbium-doped double-clad fiber with core/cladding diameters of 20.2/400  µm. The reflectivity of the main stage is 0.049‰ at the maximum output power, which indicates the proposed architecture is under the SBS threshold. The experiments verify the accuracy of the theoretical model, which provides a reliable reference for evaluating the SBS suppression capability of the high-power narrow-linewidth fiber amplifier phase modulated by the filtered and amplified PRBS signal.

[Occurrence Characteristic and Risk Assessment of Microplastics in Sishui River (Xingyang Section)].

Urban rivers are the main receptors and transporters of microplastic pollution. Understanding the occurrence and environmental risk of microplastics in urban rivers can provide theoretical basis for further control of microplastic pollution. The Sishui River, a tributary of the Yellow River, was selected as the research object. A total of nine water samples were collected from sewage outlets of the Sishui River (Xingyang section). The microplastics in the collected samples were characterized by their sizes, shapes, and colors using a microscope. It was found that microplastics were mostly in the form of transparent fibers and fragments in the water body of sewage outlets, of which the size below 500 µm was relatively high. In addition, PET and PE polymers were identified as the main types using a laser infrared imager. The correlation analysis showed that there was a significant correlation between the PET and PE, indicating that they were similar in origin. The results of the environmental risk assessment showed that the type of microplastics was the main factor affecting the assessment results, whereas the risk values of six sewage samples containing PVC were high. However, the value of pollution load index revealed a low risk level of pollutants in the study area.

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk in vitro and in vivo. ACNVax, combined with anti-PD-1, achieved long-term tumor remission (>200 days) with 80% complete response in mice with HER2+ breast cancer. ACNVax not only remodeled the tumor immune microenvironment but also induced a long-term immune memory, as evidenced by complete rejection of tumor rechallenge and a high level of antigen-specific memory B, CD4, and CD8 cells in mice (>200 days). This study provides a cancer vaccine design strategy, using B/CD4 T cell epitopes in an antigen clustered topography, to achieve long-term durable anticancer efficacy through promoting B/CD4 T cell crosstalk.