Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison.

Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy option. Immune checkpoints are also important in tumor immunotherapy. Programmed cell death protein-1 (PD-1) is a widely acknowledged immune checkpoint target with effective anti-tumor activity. PD-1 inhibitors have demonstrated notable therapeutic efficacy in treating hematological and solid tumors; however, more than 50% of patients undergoing this treatment exhibit a poor response. However, ICI-based combination therapies (ICI combination therapies) have been demonstrated to synergistically increase anti-tumor effects and immune response rates. In this review, we compare the clinical efficacy and side effects of BSABs and ICI combination therapies in real-world tumor immunotherapy, aiming to provide evidence-based approaches for clinical research and personalized tumor diagnosis and treatment.

Transcriptomic responses of the liver of mandarin fish (Siniperca chuatsi) under hypoxic stress.

Environmental hypoxia is becoming more prevalent in aquatic environments of mandarin fish (Siniperca chuatsi) aquaculture because of eutrophication and climate change. Little information is available on the molecular mechanisms of the detrimental effects of hypoxia in this species. In this study, the authors assembled a transcriptome for mandarin fish exposed to lower oxygen conditions at different times (24 and 96 h). The antioxidant enzymatic activities of catalase, glutathione, superoxide dismutase, glutamic pyruvic transaminase and malondialdehyde significantly increased at 6 or 12 h but decreased after reaching a climax during 96 h hypoxia stress. The gene ontology study revealed 27,616 transcripts, whereas the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed 25 linked pathways. Significant changes in the expression of certain genes involved in protein processing in the endoplasmic reticulum, the calcium signalling system and inositol phosphate metabolism were discovered using the KEGG pathway analysis. In the liver, 97 genes were differentially expressed between the control and experimental groups. The expression level of 28 differentially expressed genes (DEGs) under different hypoxic stress conditions was detected using real-time PCR and compared to transcriptome sequencing results. The result showed that some genes in the experimental group associated with hypoxic stress, such as hif, ho-1a, ho-1b, igfbp1, hsp90α and hsp90 ß, were significantly upregulated compared with those in the control group. The large amount of transcriptome data from this research has enlarged the mandarin fish gene and genome bioinformation. The identified DEGs and pathways are useful in further studies of biological responses to hypoxia.

Dark/bright band of a melting layer detected by coherent Doppler lidar and micro rain radar.

Observation of a melting layer using a 1.55 µm coherent Doppler lidar (CDL) is first presented during a stratiform precipitation event. Simultaneous radar measurements are also performed by co-located 1.24 cm micro rain radar (MRR) and 10.6 cm Doppler weather radar (DWR). As a well-known bright band in radar reflectivity appears during precipitation, an interesting dark band about 160 m below that in lidar backscattering is observed. Due to the absorption effect, the backscattering from raindrops at 1.55 µm is found much weaker than that at short wavelengths usually used in direct detection lidars. However, the CDL provides additional Doppler information which is helpful for melting layer identification. For example, a spectrum bright band with broadened width and sign conversion of skewness is detected in this case. After a deep analysis of the power spectra, the aerosol and precipitation components are separated. The fall speed of hydrometeors given by CDL is found smaller than that of MRR, with the differences of approximately 0.5 m/s and 1.5 m/s for the snow and rainfall, respectively. To illustrate the influence of absorption effect, simulations of the backscatter coefficient and extinction coefficient of aerosol and rainfall are also performed at the wavelength range of 0.3 ∼ 2.2 µm using the Mie theory.

Delineating the role of cooperativity in the design of potent PROTACs for BTK.

Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that simultaneously bind to a target protein and an E3 ligase, thereby leading to ubiquitination and subsequent degradation of the target. They present an exciting opportunity to modulate proteins in a manner independent of enzymatic or signaling activity. As such, they have recently emerged as an attractive mechanism to explore previously "undruggable" targets. Despite this interest, fundamental questions remain regarding the parameters most critical for achieving potency and selectivity. Here we employ a series of biochemical and cellular techniques to investigate requirements for efficient knockdown of Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase essential for B cell maturation. Members of an 11-compound PROTAC library were investigated for their ability to form binary and ternary complexes with BTK and cereblon (CRBN, an E3 ligase component). Results were extended to measure effects on BTK-CRBN cooperative interactions as well as in vitro and in vivo BTK degradation. Our data show that alleviation of steric clashes between BTK and CRBN by modulating PROTAC linker length within this chemical series allows potent BTK degradation in the absence of thermodynamic cooperativity.

Transcriptome analysis of blood for the discovery of sex-related genes in ricefield eel Monopterus albus.

The blood acts as a transfer channel for a variety of factors in the whole body. The ricefield eel (Monopterus albus) is a protogynous hermaphrodite vertebrate. Until now, no research has reported an analysis of the blood transcriptome during the process of sexual development in the ricefield eel. In this study, the transcriptome sequencing of blood samples from male and female ricefield eels was completed with a total of 34.70 Gb clean data. The clean data of each sample all reached 5.23 GB, and the percent of the Q30 basic group was 88.62% and above. A total of 106,369 unigenes were obtained after assembly, including 13,296 unigenes with a length of more than 1 kb. Further functional annotation analysis showed that there are 28,522 unigenes that can be annotated. The annotations of genes with differential expression revealed that there were 563 genes with significant differential expression in the blood of male and female ricefield eels, including 91 upregulated genes and 472 downregulated genes. Among which, 14 genes may be closely related to sex differentiation, the qPCR was used to confirmed the expression pattern of those genes and result shown that 11 genes were downregulated and 3 genes were upregulated, consistent with the results of our RNA-Seq analysis. This blood transcript dataset will open future research avenues on ricefield eel sex development and differentiation.

Natural Product Bis-Intercalator Depsipeptides as a New Class of Payloads for Antibody-Drug Conjugates.

A potent class of DNA-damaging agents, natural product bis-intercalator depsipeptides (NPBIDs), was evaluated as ultrapotent payloads for use in antibody-drug conjugates (ADCs). Detailed investigation of potency (both in cells and via biophysical characterization of DNA binding), chemical tractability, and in vitro and in vivo stability of the compounds in this class eliminated a number of potential candidates, greatly reducing the complexity and resources required for conjugate preparation and evaluation. This effort yielded a potent, stable, and efficacious ADC, PF-06888667, consisting of the bis-intercalator, SW-163D, conjugated via an N-acetyl-lysine-valine-citrulline- p-aminobenzyl alcohol- N, N-dimethylethylenediamine (AcLysValCit-PABC-DMAE) linker to an engineered variant of the anti-Her2 mAb, trastuzumab, catalyzed by transglutaminase.

Effects of Rhizoma Alismatis extract on biochemical indices and adipose gene expression in oleic acid-induced hepatocyte injury in Jian carp (Cyprinus carpio var. Jian).

Fatty liver is an increasingly serious disease of fish in aquaculture. However, the mechanisms responsible for the occurrence of fatty liver remain unclear, and no effective methods for the prevention and treatment of this disease have yet been found. In the present study, we aimed to develop an in vitro model of hepatocyte injury using oleic acid as hepatotoxicant and evaluate the protective effects of Rhizoma Alismatis extract (RAE) in Jian carp using this model. Primary hepatocytes from Jian carp were isolated and purified and cultured in vitro. The result indicated that 0.4 mmol L-1 oleic acid and 48 h could be the optimal conditions to induce hepatocyte injury model in cultured hepatocytes. Hepatocytes were exposed to oleic acid, followed by the addition of RAE at 0, 1, 5, 10, 20, or 50 µg mL-1. The hepatocytes and supernatant were then analyzed. RAE suppressed oleic acid-induced elevations in aspartate aminotransferase, alanine aminotransferase, triglycerides, total cholesterol, lactate dehydrogenase, alkaline phosphatase, cholinesterase, malondialdehyde, γ-glutamyl transferase, cytochrome P450 1A, cytochrome P450 2E1, liver-type fatty acid binding protein, free fatty acid, fatty acid synthetase, and tumor necrosis factor-α (P < 0.01 or P < 0.05); reduced protein levels of cytochrome P450 1A, nuclear factor (NF)-κB p65, and NF-κB c-Rel; and inhibited cytochrome P4503A, NF-κB c-Rel, nuclear factor erythroid-related factor 2, peroxisome proliferator-activated receptor-α, and cytochrome P4501A mRNA levels. In conclusion, RAE exhibited a protective effect against hepatocyte injury in Jian carp. Further in vivo studies are needed to provide more evidence for the use of RAE as a hepatoprotective agent for the treatment of hepatocyte injury.

Anti-inflammatory and hepatoprotective effects of glycyrrhetinic acid on CCl4-induced damage in precision-cut liver slices from Jian carp (Cyprinus carpio var. jian) through inhibition of the nf-kƁ pathway.

In order to evaluate the antioxidant and anti-inflammatory effects of glycyrrhetinic acid (GA) on carbon tetrachloride (CCl4)-induced damage in precision-cut liver slices (PCLS) from Jian carp (Cyprinus carpio. Jian), an acute liver damage model was established in this study. The viability of PCLS, levels of anti-oxidases in liver homogenates, expression of inflammation-related genes including nuclear factor-κB (nf-κB)/c-rel, inducible nitric oxide synthase (inos), interleukin-1ß (il-1ß), interleukin-6 (il-6) and interleukin-8 (il-8), and protein levels of (nf-κB)/c-rel in liver tissues were measured. The results showed that pretreatment of PCLS with GA at 5 and 10 µg/mL for 6 h significantly inhibited the cytotoxicity of CCl4. GA attenuated CCl4-induced oxidative stress in PCLS through promoting the recovery of superoxide dismutase (SOD) and glutathione (GSH) levels, and inhibiting malondialdehyde (MDA) synthesis. In inflammatory response, GA at both 5 and 10 µg/mL significantly inhibited the increase in mRNA levels of inflammatory cytokines including nf-kƁ/c-rel, inos, il-1ß, il-6 and il-8, and the protein level of Nf-kƁ/C-rel induced by CCl4. Furthermore, treatment with pyrrolyl dithiocarbamate (PDTC, 4 µg/mL), an inhibitor of nuclear transcription factor nf-kB, significantly inhibited nf-kB levels, and transcription of downstream cytokines inos, il-1ß, il-6 and il-8, also the viability of PCLS was significantly increased. These results indicated that GA suppressed inflammation and reduced cytotoxicity by inhibiting the nf-kƁ signaling pathway, and plays a role in liver protection.

Identification and characterization of a LTR retrotransposon from the genome of Cyprinus carpio var. Jian.

A Ty3/gypsy-retrotransposon-type transposon was found in the genome of the Jian carp (Cyprinus carpio var. Jian) in a previous study (unpublished), and was designated a JRE retrotransposon (Jian retrotransposon). The full-length JRE retrotransposon is 5126 bp, which includes two long terminal repeats of 470 bp at the 5' end and 453 bp at the 3' end, and two open reading frames between them: 4203 bp encoding the group-specific antigen (GAG) and polyprotein (POL). The pol gene has a typical Ty3/gypsy retrotransposon structure, and the gene order is protease, reverse transcriptase, RNase H, and integrase (PR-RT-RH-IN). A phylogenetic analysis of the pol gene showed that it has similarities of 40.7, 40, and 32.8 %, to retrotransposons of Azumapecten farreri, Mizuhopecten yessoensis, and Xiphophorus maculatus, respectively. Therefore, JRE might belong to the JULE retrotransposon family. The copy number of the JRE transposon in the genome of the Jian carp is 124, determined with real-time quantitative PCR. The mRNA of the JRE retrotransposon is expressed in five Jian carp tissues, the liver, kidney, blood, muscle, and gonad, and slightly higher in the kidney and liver than in the other tissues.

Signal Analysis and Waveform Reconstruction of Shock Waves Generated by Underwater Electrical Wire Explosions with Piezoelectric Pressure Probes.

Underwater shock waves (SWs) generated by underwater electrical wire explosions (UEWEs) have been widely studied and applied. Precise measurement of this kind of SWs is important, but very difficult to accomplish due to their high peak pressure, steep rising edge and very short pulse width (on the order of tens of µs). This paper aims to analyze the signals obtained by two kinds of commercial piezoelectric pressure probes, and reconstruct the correct pressure waveform from the distorted one measured by the pressure probes. It is found that both PCB138 and Müller-plate probes can be used to measure the relative SW pressure value because of their good uniformities and linearities, but none of them can obtain precise SW waveforms. In order to approach to the real SW signal better, we propose a new multi-exponential pressure waveform model, which has considered the faster pressure decay at the early stage and the slower pressure decay in longer times. Based on this model and the energy conservation law, the pressure waveform obtained by the PCB138 probe has been reconstructed, and the reconstruction accuracy has been verified by the signals obtained by the Müller-plate probe. Reconstruction results show that the measured SW peak pressures are smaller than the real signal. The waveform reconstruction method is both reasonable and reliable.

Effects of curcumin on antioxidative activities and cytokine production in Jian carp (Cyprinus carpio var. Jian) with CCl4-induced liver damage.

We investigated the protective effects of curcumin on liver-damaged Cyprinus carpio var. Jian (Jian carp). The carp were fed 0.1%, 0.5%, or 1.0% curcumin for 60 days, then injected intraperitoneally with 30% carbon tetrachloride solution. Liver and blood samples were collected to measure the liver index, serum- and liver-associated enzymes, liver histology, nuclear factor-κB (NF-κB)/c-Rel, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-12 mRNA expression, and the level of NF-κB/c-Rel protein in the liver, and for a comet assay. We found that 0.5% and 1.0% curcumin significantly reduced the CCl(4)-induced increase in the liver index. The comet assay showed that the tail moment, olive tail moment, tail length, and tail DNA% improved in fish pretreated with 0.5 or 1.0% curcumin. CCl(4)-induced histological changes, including extensive hepatocyte degeneration, indistinct cell borders, nuclear condensation, and karyolysis were clearly reduced after treatment with 0.5% and 1.0% curcumin. Moreover, 0.5% and 1.0% curcumin significantly inhibited the CCl(4)-induced increase in serum glutamic oxaloacetic transaminase and promoted the restoration of superoxide dismutase in the liver; 1.0% curcumin significantly reduced serum glutamic pyruvic transaminase and lactate dehydrogenase and hepatic malondialdehyde, but significantly increased the total antioxidant capacity and glutathione levels in the liver. The CCl(4)-induced upregulation of NF-κB/c-Rel, IL-1ß, and TNF-α mRNAs and NF-κB/c-Rel protein levels was inhibited by 0.5% and 1.0% curcumin, and IL-12 mRNA was reduced by all three doses of curcumin. The effects of curcumin on the liver index, enzymes, histological changes, and cytokines were dose-dependent. Our results indicate that curcumin reduces CCl(4)-induced liver damage in Jian carp by upregulating antioxidative activities and inhibiting NF-κB, IL-1ß, TNF-α, and IL-12 expression.

Selectively targeting an inactive conformation of interleukin-2-inducible T-cell kinase by allosteric inhibitors.

ITK (interleukin-2-inducible T-cell kinase) is a critical component of signal transduction in T-cells and has a well-validated role in their proliferation, cytokine release and chemotaxis. ITK is an attractive target for the treatment of T-cell-mediated inflammatory diseases. In the present study we describe the discovery of kinase inhibitors that preferentially bind to an allosteric pocket of ITK. The novel ITK allosteric site was characterized by NMR, surface plasmon resonance, isothermal titration calorimetry, enzymology and X-ray crystallography. Initial screening hits bound to both the allosteric pocket and the ATP site. Successful lead optimization was achieved by improving the contribution of the allosteric component to the overall inhibition. NMR competition experiments demonstrated that the dual-site binders showed higher affinity for the allosteric site compared with the ATP site. Moreover, an optimized inhibitor displayed non-competitive inhibition with respect to ATP as shown by steady-state enzyme kinetics. The activity of the isolated kinase domain and auto-activation of the full-length enzyme were inhibited with similar potency. However, inhibition of the activated full-length enzyme was weaker, presumably because the allosteric site is altered when ITK becomes activated. An optimized lead showed exquisite kinome selectivity and is efficacious in human whole blood and proximal cell-based assays.

A two-terminal fault location method for gas switch prefire in linear transformer driver.

Large-scale linear transformer drivers (LTDs) are composed of numerous high-power gas switches, and switch prefire is a frequent operational fault. To detect and locate the faulty switch accurately and efficiently, a two-terminal location method is proposed. A B-dot sensor is integrated on the gas switch's shell to collect the discharging signal. All the B-dot sensors are connected in parallel through cables of equal length. The fault position can be determined by the time delay of the signals at the two terminals. A diode is inserted between the B-dot sensor's coil and the cable core to ensure low-loss transmission of the signal. Two methods are applied in fault location, including time-of-arrival (TOA) and time reversal (TR). For the TOA method, an energy criterion and a phase criterion are applied and compared. The accuracy of the energy criterion is greatly influenced by the signal-to-noise ratio, while the phase criterion requires a reasonable estimate of the actual delay to account for the impact of phase periodicity. The TR method based on a precise simulation model is established, which demonstrates high precision in location. The TR method has been tested and validated on a single stage LTD module. Moreover, the location method for double switches prefire is discussed theoretically. The method proposed in this paper will be helpful to improve the efficiency of the commissioning, operation, and maintenance of the large-scale LTD devices.

Fast and flexible solid-state linear transformer driver for plasma discharge based on metal oxide semiconductor field effect transistor.

A pulsed power supply with a short rise time and high repetition frequency is favorable to driving diffusive plasma for strongly oxidizing radical (O3, OH) generation and increasing the system's energy efficiency. In this paper, a 10-stage solid-state linear transformer driver (LTD) with a nanosecond rise time is developed to drive plasma for wastewater treatment. To decrease the rise time, a control system with low jitter is developed to improve the synchronization of pulses using an optocoupler isolation chip. A 10-stage LTD with a rise time of 6.2 ns is realized in the case that the rise time of the single-stage LTD is 5.4 ns. The results show that the LTD can generate pulses on a 300 Ω resistive load with a repetition frequency of 10 kHz, an amplitude of 8.80 kV, an overshoot less than 3.97%, and a reverse overshoot less than 4.82%. The rise time (6.2-33.0 ns), the pulse width (35.9-200.0 ns), and the fall time (10.5-27.6 ns) can be adjusted flexibly and independently by controlling the drive signals of metal oxide semiconductor field effect transistors. The pulsed generator is utilized to drive plasma in the needle-water electrode system. The preliminary experimental results show that the plasma includes abundant oxygen atoms and hydroxyl radicals with high activity, and it is suitable for wastewater treatment.

A repetitive frequency square wave generator based on Blumlein pulse forming network and pseudospark switch.

The Blumlein pulse forming network (PFN) has widely been used in pulsed power technology to generate square waves with short pulse widths. In this paper, we developed a repetitive frequency square wave generator based on Blumlein PFN and pseudospark switch (PSS). A Blumlein PFN with unequal capacitances has been proposed, and the PFN parameters have been optimized for better output waveforms. A single-gap PSS with a withstand voltage of 40 kV and a repetitive frequency of 100 Hz has been designed to switch the Blumlein PFN. The experiment results show that the square wave generator can output pulses with a voltage of 26 kV, a rise time of 25 ns, and a pulse width of 90 ns on a matched load of 11 Ω. It has operated steadily for 10 h with a repetitive frequency of 100 Hz, and the jitter remains at around 1 ns after 1.05 × 106 shots.

The numerical simulation of a four-stage linear transformer driver module based on the Preisach magnetic core model.

The use of linear transformer drivers (LTDs) is widely considered the most promising technological approach for the development of future pulsed-power accelerators. In large-scale pulsed-power accelerators, abnormal conditions like switch prefire can occur frequently during tests and normal operations due to the presence of a large number of switches. The diagnosis of such faults based on signature waveforms requires further investigation. According to previous research, the characteristics of the magnetic cores greatly influence the fault waveforms. In this paper, a full-cycle mathematical model of the magnetic core is established utilizing a classical Preisach model based on experimental results. This model is coupled with the LTD circuit model in simulations, and simulation results are obtained under the condition of switch prefire. The simulation results are in good agreement with the experimental results from a four-stage LTD module with a sharing shell and de-ionized water insulated transmission line. The magnetization process of the cores is also determined under prefire conditions. Analyses of the magnetization process indicate that the completely demagnetized core shows high permeability under positive excitation and that the permeability abruptly decreases as the excitation is reversed. The hysteresis characteristics result in a phenomenon in which the output voltage in the prefired stage is almost unipolar. Finally, the features of the fault voltages captured in the experiments are also explained.

High voltage nanosecond pulse generator based on pseudospark switch and diode opening switch.

With the development of technology, low-temperature plasma plays an increasingly important role in industrial applications. The industrial application of low-temperature plasma has the following requirements for plasma, high electron energy, low macroscopic temperature, and uniformity. Low-temperature plasma driven by nanosecond pulses reflects more significant advantages in these aspects compared to direct current plasma and alternating current plasma. In this paper, a simple topology is proposed, which is based on the pseudospark switch and the diode opening switch. A pulse generator is developed, which can eventually output pulses with an amplitude of 106 kV, a rise time of 15.5 ns, a pulse width of 46 ns, and a maximum repetition rate of 1 kHz on a 260 Ω resistive load. The pulse generator can successfully drive needle-plate discharge plasma in ambient air. It has excellent parameters, stability, compactness, and a long lifetime. The proposed topology may be helpful for nanosecond pulse generators with amplitude ranging from tens to hundreds of kilovolts, which could be widely used in industry.

Salvianolic Acid B Regulates Oxidative Stress, Autophagy and Apoptosis against Cyclophosphamide-Induced Hepatic Injury in Nile Tilapia (Oreochromis niloticus).

Salvianolic acid B (Sal B), as one of the main water-soluble components of Salvia miltiorrhizae, has significant pharmacological activities, including antioxidant, free radical elimination and biofilm protection actions. However, the protective effect of Sal B on Nile tilapia and the underlying mechanism are rarely reported. Therefore, the aim of this study was to evaluate the effects of Sal B on antioxidant stress, apoptosis and autophagy in Nile tilapia liver. In this experiment, Nile tilapia were fed diets containing sal B (0.25, 0.50 and 0.75 g·kg-1) for 60 days, and then the oxidative hepatic injury of the tilapia was induced via intrapleural injection of 50 g·kg-1 cyclophosphamide (CTX) three times. After the final exposure to CTX, the Nile tilapia were weighed and blood and liver samples were collected for the detection of growth and biochemical indicators, pathological observations and TUNEL detection, as well as the determination of mRNA expression levels. The results showed that after the CTX treatment, the liver was severely damaged, the antioxidant capacity of the Nile tilapia was significantly decreased and the hepatocyte autophagy and apoptosis levels were significantly increased. Meanwhile, dietary Sal B can not only significantly improve the growth performance of tilapia and effectively reduce CTX-induced liver morphological lesions, but can also alleviate CTX-induced hepatocyte autophagy and apoptosis. In addition, Sal B also significantly regulated the expression of genes related to antioxidative stress, autophagy and apoptosis pathways. This suggested that the hepatoprotective effect of Sal B may be achieved through various pathways, including scavenging free radicals and inhibiting hepatocyte apoptosis and autophagy.

Alleviative effects of astragaloside IV on cyclophosphamide-induced oxidative damage and immunosuppression in tilapia (Oreochromis niloticus).

Astragaloside IV (ASIV) has effects of antioxidation and immunologic enhancement. However, there are few reports on the application and potential mechanism of ASIV in aquaculture. In this study, we investigated the effect of ASIV on growth, antioxidation, and immune function of tilapia. Tilapia were fed a diet containing 0.1, 0.2, and 0.5 g·kg-1 ASIV for 60 days, followed by an intrapleural injection of 50 mg·kg-1 cyclophosphamide (CTX) to induce oxidative damage and immunosuppression. Then tilapia were weighed and blood, liver, spleen, kidney, and intestinal were collected. The results showed ASIV increased the final weight, relative weight rate, and specific growth rate of tilapia, reduce conversion ratio, and reduced the morphological lesions of tissues. Meanwhile, ASIV alleviated CTX-induced oxidative damage by improving antioxidant activity in serum and tissues and inhibiting lipid peroxidation. Additionally, ASIV attenuated the immunosuppression of tilapia caused by CTX, regulated immunochemical indexes in serum, increased the viability of peripheral blood leukocytes and head kidney macrophages, and restored respiratory burst activity (O2-) in head kidney macrophages and splenocytes. Furthermore, qPCR data showed ASIV up-regulated antioxidant-related gene expression of nrf2, ho-1, gpx3, and cat and immune-related gene expression including C3 and igm. In conclusion, ASIV as a feed additive can not only improve the growth performance but also enhance the antioxidant capacity and immune function of tilapia, which may be associated with the ability of ASIV to scavenge free radicals, reduce lipid peroxidation levels, and stabilize numbers of immune cells.

Handheld NIR-to-NIR Platform for on-site evaluating protective neutralizing antibody against SARS-CoV-2 ancestral strain and Omicron variant after vaccination or infection.

Lateral flow assays (LFAs) are promising points-of-care tests, playing a vital role in diseases screening, diagnosis and surveillance. However, development of portable, cheap, and smart LFAs platform for sensitive and accurate quantification of disease biomarkers in complex media is challenging. Here, a cheap handheld device was developed to realize on-site detection of disease biomarkers by Nd3+/Yb3+ co-doped near-infrared (NIR)-to-NIR downconversion nanoparticles (DCNPs) based LFA. Its sensitivity is at least 8-fold higher for detecting NIR light signal from Nd3+/Yb3+ co-doped nanoparticles than conventional expensive InGaAs camera based detection platform. Additionally, we enhance NIR quantum yield of Nd3+/Yb3+ co-doped nanoparticles up to 35.5% via simultaneous high dopant of sensitizer ions Nd3+ and emitter ions Yb3+. Combination of NIR-to-NIR handheld detection device and ultra-bright NIR emitting NaNbF4:Yb60%@NaLuF4 nanoparticle probe allows the detection sensitivity of SARS-CoV-2 ancestral strain and Omicron variants specific neutralizing antibodies LFA up to the level of commercial enzyme linked immunosorbent assay kit. Furthermore, by this robust method, enhanced neutralizing antibodies against SARS-CoV-2 ancestral strain and Omicron variants are observed in healthy participants with Ad5-nCoV booster on top of two doses of inactivated vaccine. This NIR-to-NIR handheld platform provides a promising strategy for on-site evaluating protective humoral immunity after SARS-CoV-2 vaccination or infection.