OliTag-seq enhances in cellulo detection of CRISPR-Cas9 off-targets.

The potential for off-target mutations is a critical concern for the therapeutic application of CRISPR-Cas9 gene editing. Current detection methodologies, such as GUIDE-seq, exhibit limitations in oligonucleotide integration efficiency and sensitivity, which could hinder their utility in clinical settings. To address these issues, we introduce OliTag-seq, an in-cellulo assay specifically engineered to enhance the detection of off-target events. OliTag-seq employs a stable oligonucleotide for precise break tagging and an innovative triple-priming amplification strategy, significantly improving the scope and accuracy of off-target site identification. This method surpasses traditional assays by providing comprehensive coverage across various sgRNAs and genomic targets. Our research particularly highlights the superior sensitivity of induced pluripotent stem cells (iPSCs) in detecting off-target mutations, advocating for using patient-derived iPSCs for refined off-target analysis in therapeutic gene editing. Furthermore, we provide evidence that prolonged Cas9 expression and transient HDAC inhibitor treatments enhance the assay's ability to uncover off-target events. OliTag-seq merges the high sensitivity typical of in vitro assays with the practical application of cellular contexts. This approach significantly improves the safety and efficacy profiles of CRISPR-Cas9 interventions in research and clinical environments, positioning it as an essential tool for the precise assessment and refinement of genome editing applications.

Homozygous variant in DRC3 (LRRC48) gene causes asthenozoospermia and male infertility.

Human infertility affects 10-15% of couples. Asthenozoospermia accounts for 18% of men with infertility and is a common male infertility phenotype. The nexin-dynein regulatory complex (N-DRC) is a large protein complex in the sperm flagellum that connects adjacent doublets of microtubules. Defects in the N-DRC can disrupt cilia/flagellum movement, resulting in primary ciliary dyskinesia and male infertility. Using whole-exome sequencing, we identified a pathological homozygous variant of the dynein regulatory complex subunit 3 (DRC3) gene, which expresses leucine-rich repeat-containing protein 48, a component of the N-DRC, in a patient with asthenozoospermia. The variant ENST00000313838.12: c.644dup (p. Glu216GlyfsTer36) causes premature translational arrest of DRC3, resulting in a dysfunctional DRC3 protein. The patient's semen count, color, and pH were normal according to the reference values of the World Health Organization guidelines; however, sperm motility and progressive motility were reduced. DRC3 protein was not detected in the patient's sperm and the ultrastructure of the patient's sperm flagella was destroyed. More importantly, the DRC3 variant reduced its interaction with other components of the N-DRC, including dynein regulatory complex subunits 1, 2, 4, 5, 7, and 8. Our data not only revealed the essential biological functions of DRC3 in sperm flagellum movement and structure but also provided a new basis for the clinical genetic diagnosis of male infertility.

Three novel er1 alleles and their functional markers for breeding resistance to powdery mildew (Erysiphe pisi) in pea.

Powdery mildew caused by Erysiphe pisi DC is a global notorious disease on peas. Deploying resistance pea cultivars is the most efficient and environmentally friendly method for the disease control. This study focuses on revealing the resistance genes in three pea germplasms and developing their functional markers for resistance breeding. The identification of resistance genes involved genetic mapping and the sequencing of the PsMLO1 gene. To confirm the hereditary in three reisistant germplasms, they were crossed with susceptible cultivars to generate F1, F2, and F2:3 populations. The F1 generation exhibited susceptibility to E. pisi, while segregation patterns in subsequent generations adhered to the 3:1 (susceptible: resistant) and 1:2:1 (susceptible homozygotes: heterozygotes: resistant homozygotes) ratios, indicating that powdery mildew resistance was governed by single recessive gene in each germplasm. Analysis of er1-linked markers and genetic mapping suggested that the resistance genes could be er1 alleles in these germplasms. The multiple clone sequencing results of the three homologous PsMLO1 genes showed they were novel er1 alleles, named er1-15, er1-16, and er1-17, respectively. The er1-15 and er1-16 were caused by 1-bp deletion at position 335 (A) and 429 (T) in exon 3, respectively, while er1-17 was caused a 1-bp insertion at position 248 in exon 3, causing a frame-shift mutation and premature termination of PsMLO1 protein translation. Their respective functional markers KASP-er1-15, KASP-er1-16 and KASP-er1-17 were successfully developed and validated in respective mapping populations and pea germplasms. These results provide valuable tools for pea breeding resistance to E pisi.

Metabolic profiling identifies Qrich2 as a novel glutamine sensor that regulates microtubule glutamylation and mitochondrial function in mouse sperm.

In our prior investigation, we discerned loss-of-function variants within the gene encoding glutamine-rich protein 2 (QRICH2) in two consanguineous families, leading to various morphological abnormalities in sperm flagella and male infertility. The Qrich2 knockout (KO) in mice also exhibits multiple morphological abnormalities of the flagella (MMAF) phenotype with a significantly decreased sperm motility. However, how ORICH2 regulates the formation of sperm flagella remains unclear. Abnormal glutamylation levels of tubulin cause dysplastic microtubules and flagella, eventually resulting in the decline of sperm motility and male infertility. In the current study, by further analyzing the Qrich2 KO mouse sperm, we found a reduced glutamylation level and instability of tubulin in Qrich2 KO mouse sperm flagella. In addition, we found that the amino acid metabolism was dysregulated in both testes and sperm, leading to the accumulated glutamine (Gln) and reduced glutamate (Glu) concentrations, and disorderly expressed genes responsible for Gln/Glu metabolism. Interestingly, mice fed with diets devoid of Gln/Glu phenocopied the Qrich2 KO mice. Furthermore, we identified several mitochondrial marker proteins that could not be correctly localized in sperm flagella, which might be responsible for the reduced mitochondrial function contributing to the reduced sperm motility in Qrich2 KO mice. Our study reveals a crucial role of a normal Gln/Glu metabolism in maintaining the structural stability of the microtubules in sperm flagella by regulating the glutamylation levels of the tubulin and identifies Qrich2 as a possible novel Gln sensor that regulates microtubule glutamylation and mitochondrial function in mouse sperm.

Embedding Quantum Many-Body Scars into Decoherence-Free Subspaces.

Quantum many-body scars are nonthermal excited eigenstates of nonintegrable Hamiltonians, which could support coherent revival dynamics from special initial states when scars form an equally spaced tower in the energy spectrum. For open quantum systems, engineering many-body scarred dynamics by a controlled coupling to the environment remains largely unexplored. Here, we provide a general framework to exactly embed quantum many-body scars into the decoherence-free subspaces of Lindblad master equations. The dissipative scarred dynamics manifest persistent periodic oscillations for generic initial states, and can be practically utilized to prepare scar states with potential quantum metrology applications. We construct the Liouvillian dissipators with the local projectors that annihilate the whole scar towers, and utilize the Hamiltonian part to rotate the undesired states out of the null space of dissipators. We demonstrate our protocol through several typical models hosting many-body scar towers and propose an experimental scheme to observe the dissipative scarred dynamics based on digital quantum simulations and resetting ancilla qubits.

Direct and Continuous Monitoring of Multicomponent Antibiotic Gentamicin in Blood at Single-Molecule Resolution.

Point-of-care monitoring of small molecules in biofluids is crucial for clinical diagnosis and treatment. However, the inherent low degree of recognition of small molecules and the complex composition of biofluids present significant obstacles for current detection technologies. Although nanopore sensing excels in the analysis of small molecules, the direct detection of small molecules in complex biofluids remains a challenge. In this study, we present a method for sensing the small molecule drug gentamicin in whole blood based on the mechanosensitive channel of small conductance in Pseudomonas aeruginosa (PaMscS) nanopore. PaMscS can directly detect gentamicin and distinguish its main components with only a monomethyl difference. The 'molecular sieve' structure of PaMscS enables the direct measurement of gentamicin in human whole blood within 10 min. Furthermore, a continuous monitoring device constructed based on PaMscS achieved continuous monitoring of gentamicin in live rats for approximately 2.5 h without blood consumption, while the drug components can be analyzed in situ. This approach enables rapid and convenient drug monitoring with single-molecule level resolution, which can significantly lower the threshold for drug concentration monitoring and promote more efficient drug use. Moreover, this work also lays the foundation for the future development of continuous monitoring technology with single-molecule level resolution in the living body.

Consolidating Organometallic Complex Ir-CA Empowers Mitochondria-Directed Chemotherapy against Resistant Cancer via Stemness and Metastasis Inhibition.

Cancer treatment has faced severe obstacles due to the smart biological system of cancer cells. Herein, we report a three-in-one agent Ir-CA via attenuation of cancer cell stemness with the down-regulated biomarker CD133 expression from the mitochondria-directed chemotherapy. Over 80% of Ir-CA could accumulate in mitochondria, result in severe mitochondrial dysfunctions, and subsequently initiate mitophagy and cell cycle arrest to kill cisplatin-resistant A549R cells. In vitro and in vivo antimetastatic experiments demonstrated that Ir-CA can effectively inhibit metastasis with down-regulated MMP-2/MMP-9. RNA seq analysis and Western blotting indicated that Ir-CA also suppresses the GSTP1 expression to decrease the intracellular Pt-GS adducts, resulting in the detoxification and resensitization to cisplatin of A549R cells. In vivo evaluation indicated that Ir-CA restrains the tumor growth and has minimal side effects and superior biocompatibility. This work not only provides the first three-in-one agent to attenuate cancer cell stemness and simultaneously realize anticancer, antimetastasis, and conquer metallodrug resistance but also demonstrates the effectiveness of the mitochondria-directed strategy in cancer treatment.

Direct single-molecule detection of CoA-SH and ATP by the membrane proteins TMEM120A and TMEM120B.

Membrane proteins are vital resources for developing biosensors. TMEM120A is a membrane protein associated with human pain transmission and lipid metabolism, and recent studies have demonstrated its ability to transport ions and bind to coenzyme A (COA-SH), indicating its potential to develop into a single-molecule sensor based on electrical methods. In this study, we investigated the ion transport properties of TMEM120A and its homolog TMEM120B on an artificial lipid bilayer using single-channel recording. The results demonstrate that both proteins can fuse into the lipid bilayer and generate stable ion currents under a bias voltage. Based on the stable ion transport capabilities of TMEM120A and TMEM120B, as well as the feature of TMEM120A binding with COA-SH, we developed these two proteins into a single-molecule sensor for detecting COA-SH and structurally similar molecules. We found that both COA-SH and ATP can reversibly bind to single TMEM120A and TMEM120B proteins embedded in the lipid bilayer and temporarily block ion currents during the binding process. By analyzing the current blocking signal, COA-SH and ATP can be identified at the single-molecule level. In conclusion, our work has provided two single-molecule biosensors for detecting COA-SH and ATP, offering insights for exploring and developing bio-inspired small molecule sensors.

Functional Upgrading of an Organo-Ir(III) Complex to an Organo-Ir(III) Prodrug as a DNA Damage-Responsive Autophagic Inducer for Hypoxic Lung Cancer Therapy.

The efficiency of nitrogen mustards (NMs), among the first chemotherapeutic agents against cancer, is limited by their monotonous mechanism of action (MoA). And tumor hypoxia is a significant obstacle in the attenuation of the chemotherapeutic efficacy. To repurpose the drug and combat hypoxia, herein, we constructed an organo-Ir(III) prodrug, IrCpNM, with the composition of a reactive oxygen species (ROS)-inducing moiety (Ir-arene fragment)-a hypoxic responsive moiety (azo linker)-a DNA-alkylating moiety (nitrogen mustard), and realized DNA damage response (DDR)-mediated autophagy for hypoxic lung cancer therapy for the first time. Prodrug IrCpNM could upregulate the level of catalase (CAT) to catalyze the decomposition of excessive H2O2 to O2 and downregulate the expression of the hypoxia-inducible factor (HIF-1α) to relieve hypoxia. Subsequently, IrCpNM initiates the quadruple synergetic actions under hypoxia, as simultaneous ROS promotion and glutathione (GSH) depletion to enhance the redox disbalance and severe oxidative and cross-linking DNA damages to trigger the occurrence of DDR-mediated autophagy via the ATM/Chk2 cascade and the PIK3CA/PI3K-AKT1-mTOR-RPS6KB1 signaling pathway. In vitro and in vivo experiments have confirmed the greatly antiproliferative capacity of IrCpNM against the hypoxic solid tumor. This work demonstrated the effectiveness of the DNA damage-responsive organometallic prodrug strategy with the microenvironment targeting system and the rebirth of traditional chemotherapeutic agents with a new anticancer mechanism.

Structural basis of the subcortical maternal complex and its implications in reproductive disorders.

The subcortical maternal complex (SCMC) plays a crucial role in early embryonic development. Malfunction of SCMC leads to reproductive diseases in women. However, the molecular function and assembly basis for SCMC remain elusive. Here we reconstituted mouse SCMC and solved the structure at atomic resolution using single-particle cryo-electron microscopy. The core complex of SCMC was formed by MATER, TLE6 and FLOPED, and MATER embraced TLE6 and FLOPED via its NACHT and LRR domains. Two core complexes further dimerize through interactions between two LRR domains of MATERs in vitro. FILIA integrates into SCMC by interacting with the carboxyl-terminal region of FLOPED. Zygotes from mice with Floped C-terminus truncation showed delayed development and resembled the phenotype of zygotes from Filia knockout mice. More importantly, the assembly of mouse SCMC was affected by corresponding clinical variants associated with female reproductive diseases and corresponded with a prediction based on the mouse SCMC structure. Our study paves the way for further investigations on SCMC functions during mammalian preimplantation embryonic development and reveals underlying causes of female reproductive diseases related to SCMC mutations, providing a new strategy for the diagnosis of female reproductive disorders.

Differential Modulation of Saliva-Derived Microcosm Biofilms by Antimicrobial Peptide LL-31 and D-LL-31.

Microbiome modulation, aiming to restore a health-compatible microbiota, is a novel strategy to treat periodontitis. This study evaluated the modulation effects of antimicrobial peptide LL-31 and its D-enantiomer (D-LL-31) on saliva-derived microcosm biofilms, spiked with or without Porphyromonas gingivalis. To this end, one-day-old biofilms were incubated for 24 h with biofilm medium alone, or medium containing 40 µM LL-31 or D-LL-31, after which biofilms were grown for 5 days. Biofilms were assessed at 1 day and 5 days after intervention for the total viable cell counts, dipeptidyl peptidase IV (DPP4) activity, P. gingivalis amount (by qPCR) and microbial composition (by sequencing). The results showed that D-LL-31, not LL-31, significantly reduced the total viable cell counts, the P. gingivalis amount, and the DPP4 activity of the biofilms spiked with P. gingivalis, but only at 1 day after intervention. In the biofilms spiked with P. gingivalis, D-LL-31 tended to reduce the α-diversity and the compositional shift of the biofilms in time as compared to the control and LL-31 groups. In conclusion, D-LL-31 showed a better performance than LL-31 in biofilm modulation. The biofilm modulation function of the peptides could be impaired when the biofilms were in a severely dysbiotic state.

Configured quantum reservoir computing for multi-task machine learning.

Amidst the rapid advancements in experimental technology, noise-intermediate-scale quantum (NISQ) devices have become increasingly programmable, offering versatile opportunities to leverage quantum computational advantage. Here we explore the intricate dynamics of programmable NISQ devices for quantum reservoir computing. Using a genetic algorithm to configure the quantum reservoir dynamics, we systematically enhance the learning performance. Remarkably, a single configured quantum reservoir can simultaneously learn multiple tasks, including a synthetic oscillatory network of transcriptional regulators, chaotic motifs in gene regulatory networks, and the fractional-order Chua's circuit. Our configured quantum reservoir computing yields highly precise predictions for these learning tasks, outperforming classical reservoir computing. We also test the configured quantum reservoir computing in foreign exchange (FX) market applications and demonstrate its capability to capture the stochastic evolution of the exchange rates with significantly greater accuracy than classical reservoir computing approaches. Through comparison with classical reservoir computing, we highlight the unique role of quantum coherence in the quantum reservoir, which underpins its exceptional learning performance. Our findings suggest the exciting potential of configured quantum reservoir computing for exploiting the quantum computation power of NISQ devices in developing artificial general intelligence.

New Interpretation of Neonatal Outcomes by Phenotypically Classified Preterm Syndrome: A Retrospective Cohort Study.

OBJECTIVE: The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology, classification, and diagnosis. This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes; to what extent would these outcomes be modified after the obstetric interventions, including use of glucocorticoid, magnesium sulfate, and progesterone. METHODS: This was a retrospective cohort study conducted at Tongji Hospital (composed of Main Branch, Optical Valley Branch and Sino-French New City Branch) in Wuhan. A total of 900 pregnant women and 1064 neonates were retrospectively enrolled. The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery, the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes, and to what extent these outcomes could be modified by obstetric interventions. RESULTS: Eight clusters were identified using two-step cluster analysis, including premature rupture of fetal membranes (PPROM) phenotype, abnormal amniotic fluid (AF) phenotype, placenta previa phenotype, mixed condition phenotype, fetal distress phenotype, preeclampsia-eclampsia & hemolysis, elevated liver enzymes, and low platelets syndrome (PE-E&HELLP) phenotype, multiple fetus phenotype, and no main condition phenotype. Except for no main condition phenotype, the other phenotypes were associated with one or more complications, which conforms to the clinical practice. Compared with no main condition phenotype, some phenotypes were significantly associated with short-term adverse neonatal outcomes. Abnormal AF phenotype, mixed condition phenotype, PE-E&HELLP phenotype, and multiple fetus phenotype were risk factors for neonatal small-for gestation age (SGA); placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min; mixed condition phenotype was associated with low APGAR scores, SGA, mechanical ventilation, and grade HI-W intraventricular hemorrhage (IVH); fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation; PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min, SGA and neonatal intensive care unit (NICU) admission; multiple fetus phenotype was not a risk factor for the outcomes included except for SGA. Not all neonates benefited from obstetric interventions included in this study. CONCLUSION: Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes. This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically, with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.

Cost-effectiveness analysis of sintilimab plus IBI305 versus sorafenib for unresectable hepatic cell carcinoma in China.

BACKGROUND: Sintilimab combined with IBI305 treatment regimen had potential clinical benefits than sorafenib in the first-line treatment of patients with unresectable hepatic cell carcinoma (HCC). However, whether sintilimab plus IBI305 has economic benefits in China remains unclear. METHODS: From the perspective of Chinese payers, we used the Markov model to simulate patients with HCC receiving treatment with sintilimab plus IBI305 and sorafenib. The transition probability between health states was estimated using the parametric survival model, and the cumulative medical costs and utility of the two treatment methods were estimated. Considering the incremental cost-effectiveness ratios (ICERs) as the evaluation index, sensitivity analyses were performed to explore the impact of uncertainty on the results. RESULTS: Compared to sorafenib, sintilimab plus IBI305 generated an additional $17552.17 and 0.33 quality-adjusted life years, resulting in an ICER of $52817.89. The analysis outcomes were most sensitive to the total cost of sintilimab plus IBI305. With a willingness-to-pay threshold of $38,334, sintilimab plus IBI305 showed a 1.28% probability of being cost-effective. The total cost of sintilimab plus IBI305 should be reduced by at least 31.9% to be accepted by Chinese payers. CONCLUSIONS: Regardless of whether the price of sintilimab plus IBI305 and sorafenib is covered by Medicare, sintilimab plus IBI305 is unlikely to be cost-effective for first-line treatment of patients with unresectable HCC.

Fungal mycobiome-mediated immune response: a non-negligible promoter in pancreatic oncogenesis and chemoresistance.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in humans due to late diagnosis and poor response to treatments. The tumor microenvironment (TME) of PDAC is characterized by a distinctive, suppressive immune profile, which inhibits the protective functions of anti-tumor immunity and thereby contributes to PDAC progression. Recently, the study of Alam et al. discovered for the first time that the intratumoral fungal mycobiome could contribute to the recruitment and activation of type 2 immune cells in the TME of PDAC via enhancing the secretion of a chemoattractant, interleukin (IL-) 33. In this article, we reviewed the important findings of this study. Together with our findings, we synthetically discussed the role of the fungal mycobiome in orchestrating the immune response and thereby modulating tumor progression.

Extracting Quantum Many-Body Scarred Eigenstates with Matrix Product States.

Quantum many-body scarred systems host nonthermal excited eigenstates immersed in a sea of thermal ones. In cases where exact expressions for these special eigenstates are not known, it is computationally demanding to distinguish them from their exponentially many thermal neighbors. We propose a matrix-product-state (MPS) algorithm, dubbed DMRG-S, to extract such states at system sizes far beyond the scope of exact diagonalization. Using this technique, we obtain scarred eigenstates in Rydberg-blockaded chains of up to 80 sites and perform a finite-size scaling study to address the lingering question of the stability for the Néel state revivals in the thermodynamic limit. Our method also provides a systematic way to obtain exact MPS representations for scarred eigenstates near the target energy without a priori knowledge. In particular, we find several new scarred eigenstates with exact MPS representations in kinetically constrained spin and clock models. The combination of numerical and analytical investigations in our work provides a new methodology for future studies of quantum many-body scars.

Deep quantum neural networks on a superconducting processor.

Deep learning and quantum computing have achieved dramatic progresses in recent years. The interplay between these two fast-growing fields gives rise to a new research frontier of quantum machine learning. In this work, we report an experimental demonstration of training deep quantum neural networks via the backpropagation algorithm with a six-qubit programmable superconducting processor. We experimentally perform the forward process of the backpropagation algorithm and classically simulate the backward process. In particular, we show that three-layer deep quantum neural networks can be trained efficiently to learn two-qubit quantum channels with a mean fidelity up to 96.0% and the ground state energy of molecular hydrogen with an accuracy up to 93.3% compared to the theoretical value. In addition, six-layer deep quantum neural networks can be trained in a similar fashion to achieve a mean fidelity up to 94.8% for learning single-qubit quantum channels. Our experimental results indicate that the number of coherent qubits required to maintain does not scale with the depth of the deep quantum neural network, thus providing a valuable guide for quantum machine learning applications with both near-term and future quantum devices.

Reflectance Confocal Microscopy and Dermoscopy For the Diagnosis and Treatment of Cutaneous Larva Migrans.

We describe a 39-year-old woman with a 1-month-old linear erythema diagnosed with cutaneous larva migrans by reflectance confocal microscopy (RCM). This case reveals that the great significance of diagnosing and treating cutaneous larva migrans (CLM) by RCM and dermoscopy, which might provide novel insights into dermatological clinical practice.

Structural basis of the substrate recognition and inhibition mechanism of Plasmodium falciparum nucleoside transporter PfENT1.

By lacking de novo purine biosynthesis enzymes, Plasmodium falciparum requires purine nucleoside uptake from host cells. The indispensable nucleoside transporter ENT1 of P. falciparum facilitates nucleoside uptake in the asexual blood stage. Specific inhibitors of PfENT1 prevent the proliferation of P. falciparum at submicromolar concentrations. However, the substrate recognition and inhibitory mechanism of PfENT1 are still elusive. Here, we report cryo-EM structures of PfENT1 in apo, inosine-bound, and inhibitor-bound states. Together with in vitro binding and uptake assays, we identify that inosine is the primary substrate of PfENT1 and that the inosine-binding site is located in the central cavity of PfENT1. The endofacial inhibitor GSK4 occupies the orthosteric site of PfENT1 and explores the allosteric site to block the conformational change of PfENT1. Furthermore, we propose a general "rocker switch" alternating access cycle for ENT transporters. Understanding the substrate recognition and inhibitory mechanisms of PfENT1 will greatly facilitate future efforts in the rational design of antimalarial drugs.

Molecular Analysis and Sex-specific Response of the Hepcidin Gene in Yellow Perch (Perca Flavescens) Following Lipopolysaccharide Challenge.

Hepcidin antimicrobial peptide (hamp) is active in teleosts against invading pathogens and plays important roles in the stress and immune responses of finfish. The response of hamp gene was studied in yellow perch (yp) (Perca flavescens) challenged with lipopolysaccharides to understand if this immunity response is sex-specifically different. The cloned hamp gene consists of an open-reading frame of 273 bp and encodes a deduced protein of 90 amino acids (a.a.), which includes a signal peptide of 24 a.a., a pro-domain of 40 a.a. and a mature peptide of 26 a.a. Yp hamp involves 8 cysteine residues with 4 disulfide bonds, and a protein with an internal alpha helix flanked with C- and N-terminal random coils was modeling predicted. RT-qPCR was used to analyze the relative abundances (RAs) of hamp mRNA in the livers of juvenile female and male yellow perch challenged with lipopolysaccharide. The expression levels of hamp were significantly elevated by 3 h (RA = 7.3) and then peaked by 6 h (RA = 29.4) post-treatment in females but the peak was delayed to 12 h (RA = 65.4) post-treatment in males. The peak mRNA level of challenged males was shown 7.6-fold higher than females. The post-treatment responses in both genders decreased to their lowest levels by 24 h and 48 h. Overall, female perch had an earlier but less-sensitive response to the lipopolysaccharide challenge than male.