Artificial Multi-Stimulus-Responsive E-Skin Based on an Ionic Film with a Counter-Ion Exchange Reagent.

Sensing pressure and temperature are two important functions of human skin that integrate different types of tactile receptors. In this paper, a deformable artificial flexible multi-stimulus-responsive sensor is demonstrated that can distinguish mechanical pressure from temperature by measuring the impedance and the electrical phase at the same frequency without signal interference. The electrical phase, which is used for measuring the temperature, is totally independent of the pressure by controlling the surface micro-shapes and the ion content of the ionic film. By doping the counter-ion exchange reagent into the ionic liquid before pouring, the upper temperature measuring limit increases from 35 to 50 °C, which is higher than the human body temperature and the ambient temperature on Earth. The sensor shows high sensitivity to pressure (up to 0.495 kPa-1) and a wide temperature sensing range (-10 to 50 °C). A multimodal ion-electronic skin (IEM-skin) with an 8 × 8 multi-stimulus-responsive sensor array is fabricated and can successfully sense the distribution of temperature and pressure at the same time. Finally, the sensors are used for monitoring the touching motions of a robot-arm finger controlled by a remote interactive glove and successfully detect the touching states and the temperature changes of different objects.

Murine Inducible Nitric Oxide Synthase Expression Is Essential for Antifungal Defenses in Kidneys during Disseminated Cryptococcus deneoformans Infection.

Disseminated cryptococcosis has a nearly 70% mortality, mostly attributed to CNS infection, with lesser-known effects on other organs. Immune protection against Cryptococcus relies on Th1 immunity with M1 polarization, rendering macrophages fungicidal. The importance of M1-upregulated inducible NO synthase (iNOS) has been documented in pulmonary anticryptococcal defenses, whereas its role in disseminated cryptococcosis remains controversial. Here we examined the effect of iNOS deletion in disseminated (i.v.) C. deneoformans 52D infection, comparing wild-type (C57BL/6J) and iNOS-/- mice. iNOS-/- mice had significantly reduced survival and nearly 100-fold increase of the kidney fungal burden, without increases in the lungs, spleen, or brain. Histology revealed extensive lesions and almost complete destruction of the kidney cortical area with a loss of kidney function. The lack of fungal control was not due to a failure to recruit immune cells because iNOS-/- mice had increased kidney leukocytes. iNOS-/- mice also showed no defect in T cell polarization. We conclude that iNOS is critically required for local anticryptococcal defenses in the kidneys, whereas it appears to be dispensable in other organs during disseminated infection. This study exemplifies a unique phenotype of local immune defenses in the kidneys and the organ-specific importance of a single fungicidal pathway.

Modeling and Prediction of Thermal Deformation Errors in Fiber Optic Gyroscopes Based on the TD-Model.

For a fiber optic gyroscope, thermal deformation of the fiber coil can introduce additional thermal-induced phase errors, commonly referred to as thermal errors. Implementing effective thermal error compensation techniques is crucial to addressing this issue. These techniques operate based on the real-time sensing of thermal errors and subsequent correction within the output signal. Given the challenge of directly isolating thermal errors from the gyroscope's output signal, predicting thermal errors based on temperature becomes necessary. To establish a mathematical model correlating the temperature and thermal errors, this study measured synchronized data of phase errors and angular velocity for the fiber coil under various temperature conditions, aiming to model it using data-driven methods. However, due to the difficulty of conducting tests and the limited number of data samples, direct engagement in data-driven modeling poses a risk of severe overfitting. To overcome this challenge, we propose a modeling algorithm that effectively integrates theoretical models with data, referred to as the TD-model in this paper. Initially, a theoretical analysis of the phase errors caused by thermal deformation of the fiber coil is performed. Subsequently, critical parameters, such as the thermal expansion coefficient, are determined, leading to the establishment of a theoretical model. Finally, the theoretical analysis model is incorporated as a regularization term and combined with the test data to jointly participate in the regression of model coefficients. Through experimental comparative analysis, it is shown that, relative to ordinary regression models, the TD-model effectively mitigates overfitting caused by the limited number of samples, resulting in a substantial 58% improvement in predictive accuracy.

Multivalent butyrylcholinesterase inhibitor discovered by exploiting dynamic combinatorial chemistry.

In this study, we report the generation of a polymer-based dynamic combinatorial library (DCL) incorporating exchangeable side chains using acylhydrazone formation reaction. In combination with tetrameric butyrylcholinesterase (BChE), the most potent binding side chain was identified, and the information obtained was further used for the synthesis of a multivalent BChE inhibitor. In the in vitro biological evaluation, this multivalent inhibitor exhibited not only better inhibitory effect than the commercial reference but also high selectivity on BChE over acetylcholinesterase (AChE).

Identification and synthesis of an efficient multivalent E. coli heat labile toxin inhibitor __ A dynamic combinatorial chemistry approach.

A polymer based dynamic combinatorial library (DCL) was generated through condensation between aldehyde functionalized linear poly(glycidol) (APG) and galactose containing acylhydrazide derivatives. Pentameric E. coli heat labile enterotoxin B subunit (LTB) was subsequently applied to the DCL as external stimulus, resulting in amplification of a specific acylhydrazone side chain that was further used for the synthesis of a multivalent LTB inhibitor. In the in vitro biological evaluation, this inhibitor exhibited strong inhibition properties as well as low cytotoxicity.

Scavenger Receptor MARCO Orchestrates Early Defenses and Contributes to Fungal Containment during Cryptococcal Infection.

The scavenger receptor macrophage receptor with collagenous structure (MARCO) promotes protective innate immunity against bacterial and parasitic infections; however, its role in host immunity against fungal pathogens, including the major human opportunistic fungal pathogen Cryptococcus neoformans, remains unknown. Using a mouse model of C. neoformans infection, we demonstrated that MARCO deficiency leads to impaired fungal control during the afferent phase of cryptococcal infection. Diminished fungal containment in MARCO-/- mice was accompanied by impaired recruitment of Ly6Chigh monocytes and monocyte-derived dendritic cells (moDC) and lower moDC costimulatory maturation. The reduced recruitment and activation of mononuclear phagocytes in MARCO-/- mice was linked to diminished early expression of IFN-γ along with profound suppression of CCL2 and CCL7 chemokines, providing evidence for roles of MARCO in activation of the CCR2 axis during C. neoformans infection. Lastly, we found that MARCO was involved in C. neoformans phagocytosis by resident pulmonary macrophages and DC. We conclude that MARCO facilitates early interactions between C. neoformans and lung-resident cells and promotes the production of CCR2 ligands. In turn, this contributes to a more robust recruitment and activation of moDC that opposes rapid fungal expansion during the afferent phase of cryptococcal infection.

Structural and Comparative Analysis of the Complete Chloroplast Genome of Pyrus hopeiensis-"Wild Plants with a Tiny Population"-and Three Other Pyrus Species.

Pyrus hopeiensis is a valuable wild resource of Pyrus in the Rosaceae. Due to its limited distribution and population decline, it has been listed as one of the "wild plants with a tiny population" in China. To date, few studies have been conducted on P. hopeiensis. This paper offers a systematic review of P. hopeiensis, providing a basis for the conservation and restoration of P. hopeiensis resources. In this study, the chloroplast genomes of two different genotypes of P. hopeiensis, P. ussuriensis Maxin. cv. Jingbaili, P. communis L. cv. Early Red Comice, and P. betulifolia were sequenced, compared and analyzed. The two P. hopeiensis genotypes showed a typical tetrad chloroplast genome, including a pair of inverted repeats encoding the same but opposite direction sequences, a large single copy (LSC) region, and a small single copy (SSC) region. The length of the chloroplast genome of P. hopeiensis HB-1 was 159,935 bp, 46 bp longer than that of the chloroplast genome of P. hopeiensis HB-2. The lengths of the SSC and IR regions of the two Pyrus genotypes were identical, with the only difference present in the LSC region. The GC content was only 0.02% higher in P. hopeiensis HB-1. The structure and size of the chloroplast genome, the gene species, gene number, and GC content of P. hopeiensis were similar to those of the other three Pyrus species. The IR boundary of the two genotypes of P. hopeiensis showed a similar degree of expansion. To determine the evolutionary history of P. hopeiensis within the genus Pyrus and the Rosaceae, 57 common protein-coding genes from 36 Rosaceae species were analyzed. The phylogenetic tree showed a close relationship between the genera Pyrus and Malus, and the relationship between P. hopeiensis HB-1 and P. hopeiensis HB-2 was the closest.

Intracellular ß-glucosidases CEL1a and CEL1b are essential for cellulase induction on lactose in Trichoderma reesei.

Lactose (1,4-O-ß-d-galacto-pyranosyl-d-glucose) induces cellulolytic enzymes in Trichoderma reesei and is in fact one of the most important soluble carbon sources used to produce cellulases on an industrial level. The mechanism underlying the induction is, however, not fully understood. In this study, we investigated the cellular functions of the intracellular ß-glucosidases CEL1a and CEL1b in the induction of cellulase genes by lactose in T. reesei. We demonstrated that while CEL1a and CEL1b were functionally equivalent in mediating the induction, the simultaneous absence of these intracellular ß-glucosidases abolished cbh1 gene expression on lactose. d-Galactose restored the efficient cellulase gene induction in the Δcel1a strain independently of its reductive metabolism, but not in the Δcel1a Δcel1b strain. A further comparison of the transcriptional responses of the Δcel1a Δcel1b strain complemented with wild-type CEL1a or a catalytically inactive CEL1a version and the Δcel1a strain constitutively expressing CEL1a or the Kluyveromyces lactis ß-galactosidase LAC4 showed that both the CEL1a protein and its glycoside hydrolytic activity were indispensable for cellulase induction by lactose. We also present evidence that intracellular ß-glucosidase-mediated lactose induction is further conveyed to XYR1 to ensure the efficiently induced expression of cellulase genes.

Two major facilitator superfamily sugar transporters from Trichoderma reesei and their roles in induction of cellulase biosynthesis.

Proper perception of the extracellular insoluble cellulose is key to initiating the rapid synthesis of cellulases by cellulolytic Trichoderma reesei. Uptake of soluble oligosaccharides derived from cellulose hydrolysis represents a potential point of control in the induced cascade. In this study, we identified a major facilitator superfamily sugar transporter Stp1 capable of transporting cellobiose by reconstructing a cellobiose assimilation system in Saccharomyces cerevisiae. The absence of Stp1 in T. reesei resulted in differential cellulolytic response to Avicel versus cellobiose. Transcriptional profiling revealed a different expression profile in the Δstp1 strain from that of wild-type strain in response to Avicel and demonstrated that Stp1 somehow repressed induction of the bulk of major cellulase and hemicellulose genes. Two other putative major facilitator superfamily sugar transporters were, however, up-regulated in the profiling. Deletion of one of them identified Crt1 that was required for growth and enzymatic activity on cellulose or lactose, but was not required for growth or hemicellulase activity on xylan. The essential role of Crt1 in cellulase induction did not seem to rely on its transporting activity because the overall uptake of cellobiose or sophorose by T. reesei was not compromised in the absence of Crt1. Phylogenetic analysis revealed that orthologs of Crt1 exist in the genomes of many filamentous ascomycete fungi capable of degrading cellulose. These data thus shed new light on the mechanism by which T. reesei senses and transmits the cellulose signal and offers potential strategies for strain improvement.

Effect of long-term in-row branch covering on soil microorganisms in pear orchards.

Branches covering (BC) is a way to reuse the pruned branches and save the cost of ground cloth. This study investigated the effects of BC and ground-cloth covering on the soil microcosm environment by measuring the chemical properties and microbial communities at different soil depths for 6 years. The results revealed that BC significantly improved soil chemical properties, increased the abundance of bacterial microbial communities and the diversity and homogeneity of bacteria and fungi, while decreased the abundance of fungal microbial communities. There was a threshold value for the regulation of microbial communities by BC, which decreased the high-abundance communities (Proteobacteria, Ascomycota, etc.) and increased the low-abundance communities (Acidobacteriota, Basidiomycota, etc.). Fungi were more sensitive to BC than bacteria. The stability and homogeneity of microorganisms were stronger in the 15-25 cm soil layer. The bacterial phyla were dominated by Proteobacteria, with the top 10 phyla accounting for more than 80% of the relative abundance; the genera were dominated by MND1, with the top 10 genera accounting for about 10%. The fungal phyla were dominated by Ascomycota, with the top 10 phyla accounting for 50-90%; the genera were dominated by unidentified Pyronemataceae sp., with the top 10 genera accounting for 30-60%. The phyla that differed significantly between treatments were mainly Proteobacteria, Ascomycota, Acidobacteriota, and Basidiomycota. In addition, metabolism was the predominant function in bacteria, while Saprotroph was the predominant function in fungi. Bacteroidota correlated strongly with soil chemical properties and bacterial functions, while Chytridiomycota correlated strongly with soil chemical properties and Pathogen-Saprotroph-Symbiotroph. In conclusion, BC can improve soil nutrient content and optimize microbial community structure and function. Through initially assessing the effects of BC on soil nutrients and microorganisms in pear orchard rows, this study provides a reference for excavating key microorganisms and updating the soil row management model.

Astragalus polysaccharides ameliorate osteoarthritis via inhibiting apoptosis by regulating ROS-mediated ASK1/p38 MAPK signaling pathway targeting on TXN.

This research aims to explore the potential of astragalus polysaccharides (APS) in treating osteoarthritis. The primary component of APS extracted in this study was glucose, and noticeably it had a relatively high content of glucuronic acids. In vitro, APS reduced ROS levels, protected chondrocytes from apoptosis, and promoted collagen II expression by regulating ASK1 (apoptosis-signal-regulating kinase1)/p38 cell apoptosis pathway. Further co-immunoprecipitation and immunofluorescence localization experiments demonstrated that the thioredoxin (TXN) antioxidant system was responsible for its bioactivity. Moreover, TXN silencing remarkably blocked the protective effects of APS, indicating that APS inhibited chondrocyte apoptosis by targeting TXN. In vivo, APS effectively mitigated cartilage loss and chondrocyte apoptosis and decreased expressions of p-ASK1 and p-p38. Collectively, this research first demonstrated that APS could ameliorate osteoarthritis by ASK1/p38 signaling pathway through regulating thioredoxin. In conclusion, APS holds promise as a nutraceutical supplement for osteoarthritis in future drug development.

Batf3-dependent orchestration of the robust Th1 responses and fungal control during cryptococcal infection, the role of cDC1.

While type I conventional dendritic cells (cDC1s) are vital for generating adaptive immunity against intracellular pathogens and tumors, their role in defense against fungal pathogen Cryptococcus neoformans remains unclear. We investigated the role of the cDC1 subset in a fungus-restricting mouse model of cryptococcal infection. The cDC1 subset displayed a unique transcriptional signature with highly upregulated T-cell recruitment, polarization, and activation pathways compared to other DC subsets. Using Batf3-/- mice, which lack the cDC1 population, our results support that Batf3-dependent cDC1s are pivotal for the development of the effective immune response against cryptococcal infection, particularly within the lung and brain. Deficiency in Batf3 cDC1 led to diminished CD4 accumulation and decreased IFNγ production across multiple organs, supporting that cDC1s are a major driver of potent Th1 responses during cryptococcal infection. Consistently, mice lacking Batf3-cDC1 demonstrated markedly diminished fungicidal activity and weaker containment of the fungal pathogen. In conclusion, Batf3-dependent cDC1 can function as a linchpin in mounting Th1 response, ensuring effective fungal control during cryptococcal infection. Harnessing cDC1 pathways may present a promising strategy for interventions against this pathogen.IMPORTANCECryptococcus neoformans causes severe meningoencephalitis, accounting for an estimated 200,000 deaths each year. Central to mounting an effective defense against these infections is T-cell-mediated immunity, which is orchestrated by dendritic cells (DCs). The knowledge about the role of specific DC subsets in shaping anti-cryptococcal immunity is limited. Here, we demonstrate that Batf3 cDC1s are important drivers of protective Th1 CD4 T-cell responses required for clearance of cryptococcal infection. Deficiency of Batf3 cDC1 in the infected mice leads to significantly reduced Th1 response and exacerbated fungal growth to the point where depleting the remaining CD4 T cells no longer affects fungal burden. Unveiling this pivotal role of cDC1 in antifungal defense is likely to be important for the development of vaccines and therapies against life-threatening fungal pathogens.

Interlayer coupling modulated for thermoelectric transport characterization of black arsenic nanoscale devices.

Modulating interlayer coupling modes can effectively enhance the thermoelectric properties of nanomaterials or nanoscale devices. By using density functional theory combined with non-equilibrium Green's function method, we investigate the thermoelectric properties of zigzag-type black arsenic nanoscale devices with varying interlayer coupling modes. Our results show that altering the interlayer coupling mode significantly modulates the thermoelectric properties of the system. Specifically, we consider four coupling modes with different strengths, by modulating different interlayer overlap patterns. Notably, in the weaker interlayer coupling mode, the system exhibits enhanced thermoelectric properties due to increased interface phonon scattering, for example, the M4reaching a peak value of 2.23 atµ= -0.73 eV. Furthermore, we explore the temperature-dependent behavior of each coupling model. The results suggest that the thermoelectric characteristics are more sensitive to temperature variations in the weaker coupling modes. These insights provide valuable guidance for enhancing the thermoelectric performance of nanoscale devices through precise interlayer coupling modulation.

Simple Isopropanol-Assisted Direct Soft Imprint Lithography for Residue-Free Microstructure Patterning.

A direct soft imprint lithography was proposed to realize the direct fabrication of residue-free, well-shaped functional patterns through a single step. This imprint method requires only a simply prepared isopropanol-treated polydimethylsiloxane (PDMS) stamp without any additional resists. Residue-free Ag patterns were successfully fabricated on different substrates by directly imprinting the Ag ink with the isopropanol-treated PDMS stamp. Furthermore, the coffee-ring effect of the imprinting Ag patterns can be eliminated by optimizing the imprinting time, isopropanol-treating time, and imprinting temperatures. Studies show that the residual Ag ink in the contact region can be absorbed by the isopropanol-treated PDMS stamp due to the "like dissolves like" principle. Finally, this method was employed to fabricate the Ag electrodes for the thin-film transistors, attaining a mobility of ∼8 cm2 V-1 s-1, which is comparable to those with vacuum-processed electrodes. This process provides a simple, low-cost, residue-free, coffee-ring-free, and fast patterning method in the field of microelectronics.

Cryptococcus neoformans trehalose-6-phosphate synthase (tps1) promotes organ-specific virulence and fungal protection against multiple lines of host defenses.

Trehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for Cryptococcus neoformans and a promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion of host defenses during pulmonary and disseminated phases of infection. In the pulmonary infection model, TPS1-deleted (tps1Δ) Cryptococci are rapidly cleared by mouse lungs whereas TPS1-sufficent WT (H99) and revertant (tps1Δ:TPS1) strains expand in the lungs and disseminate, causing 100% mortality. Rapid pulmonary clearance of tps1Δ mutant is T-cell independent and relies on its susceptibility to lung resident factors and innate immune factors, exemplified by tps1Δ but not H99 inhibition in a coculture with dispersed lung cells and its rapid clearance coinciding with innate leukocyte infiltration. In the disseminated model of infection, which bypasses initial lung-fungus interactions, tps1Δ strain remains highly attenuated. Specifically, tps1Δ mutant is unable to colonize the lungs from the bloodstream or expand in spleens but is capable of crossing into the brain, where it remains controlled even in the absence of T cells. In contrast, strains H99 and tps1Δ:TPS1 rapidly expand in all studied organs, leading to rapid death of the infected mice. Since the rapid pulmonary clearance of tps1Δ mutant resembles a response to acapsular strains, the effect of tps1 deletion on capsule formation in vitro and in vivo was examined. Tps1Δ cryptococci form capsules but with a substantially reduced size. In conclusion, TPS1 is an important virulence factor, allowing C. neoformans evasion of resident pulmonary and innate defense mechanisms, most likely via its role in cryptococcal capsule formation.

Systematic Pharmacology and Experimental Validation to Reveal the Alleviation of Astragalus membranaceus Regulating Ferroptosis in Osteoarthritis.

Background: Astragalus membranaceus (AM) shows promise as a therapeutic agent for osteoarthritis (OA), a debilitating condition with high disability rates. OA exacerbation is linked to chondrocyte ferroptosis, yet the precise pharmacological mechanisms of AM remain unclear. Methods: We validated AM's protective efficacy in an anterior cruciate ligament transection (ACLT) mouse model of OA. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was utilized to identify AM's active components and their targets. FerrDb (a database for regulators and markers of ferroptosis and ferroptosis-disease associations) pinpointed ferroptosis-related targets, while GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), Therapeutic Target Database (TTD), and DrugBank sourced OA-related genes. Molecular docking analysis further validated these targets. Ultimately, the validation of the results was accomplished through in vitro experiments. Results: AM exhibited anabolic effects and suppressed catabolism in OA chondrocytes. Network pharmacology identified 19 common genes, and molecular docking suggested quercetin, an AM constituent, interacts with key proteins like HO-1 and NRF2 to inhibit chondrocyte ferroptosis. In vitro experiments confirmed AM's ability to modulate the NRF2/HO-1 pathway via quercetin, mitigating chondrocyte ferroptosis. Conclusion: This study elucidates how AM regulates chondrocyte ferroptosis, impacting OA progression, providing a theoretical basis and experimental support for AM's scientific application.

Preliminary investigation on the causes of red tides in Qinhuangdao coastal areas in 2022.

To explore the causes of red tides in Qinhuangdao coastal water, we conducted surveys on both water quality and red tides during April to September of 2022 and analyzed the relationships between main environmental factors and red tide organisms through the factor analysis and canonical correspondence analysis. The results showed that there were eight red tides along the coast of Qinhuangdao in 2022, with a cumulative blooming area of 716.1 km2. The red tides could be divided into three kinds based on the major blooming organisms and occurrence time, Noctiluca scintillans bloom, diatom-euglena (Skeletonema costatum, Eutreptiella gymnastica, Pseudo-nitzschia spp.) bloom, and dinoflagellate (Scrippsiella trochoidea and Ceratium furca) bloom. Seasonal factor played roles mainly during July to September, while inorganic nutrients including nitrogen and phosphorus influenced the blooms mainly in April and July. The canonical correspondence analysis suggested that N. scintillans preferred low temperature, and often bloomed with high concentrations of ammonium nitrogen and dissolved inorganic phosphorus. S. costatum, E. gymnastica, and Pseudo-nitzschia spp. could tolerate broad ranges of various environmental factors, but favored high temperature and nitrogen-rich seawater. C. furca and S. trochoidea had higher survival rate and competitiveness in phosphate-poor waters. Combined the results from both analyses, we concluded that the causes for the three kinds of red tide processes in Qinhuangdao coastal areas in 2022 were different. Adequate diet algae and appropriate water temperature were important factors triggering and maintaining the N. scintillans bloom. Suitable temperature, salinity and eutrophication were the main reasons for the diatom-euglena bloom. The abundant nutrients and seawater disturbance promoted the germination of S. trochoidea cysts, while phosphorus limitation caused the blooming organism switched to C. furca and maintained the bloom hereafter.

JAK/STAT Signaling Predominates in Human and Murine Fungal Post-infectious Inflammatory Response Syndrome.

Post-infection inflammatory syndromes have been increasingly recognized as a cause of host damage in a variety of infectious diseases including tuberculosis, bacterial meningitis, and COVID-19. Recently, a post-infectious inflammatory response syndrome (PIIRS) was described in non-HIV-infected cryptococcal fungal meningoencephalitis (CM) as a major cause of mortality. Inflammatory syndromes are particularly severe in neurological infections due to the skull's rigid structure which limits unchecked tissue expansion from inflammatory-induced edema. In the present studies, neurologic transcriptional pathway analysis utilizing a murine PIIRS model demonstrated a predominance of Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. JAK/STAT inhibitor treatment resulted in improvements in CNS damage markers, reductions in intrathecal CD44hiCD62lo CD4+ effector CD4+ T-cells and MHC II+ inflammatory myeloid cells, and weight gains in mice, the latter after treatment with antifungals. Based on these data, pathway-driven steroid-sparing human treatment for steroid-refractory PIIRS was initiated using short courses of the JAK/STAT inhibitor ruxolitinib. These were well tolerated and reduced activated HLA-DR+ CD4+ and CD8+ cells and inflammatory monocytes as well as improved brain imaging. Together, these findings support the role of JAK/STAT in PIIRS as well as further study of JAK/STAT inhibitors as potential adjunctive therapy for PIRS and other neural inflammatory syndromes.

The chemokine receptor CXCR3 promotes CD8+ T cell-dependent lung pathology during influenza pathogenesis.

The dual role of CD8+ T cells in influenza control and lung pathology is increasingly appreciated. To explore whether protective and pathological functions can be linked to specific subsets, we dissected CD8+ T responses in influenza-infected murine lungs. Our single-cell RNA-sequencing (scRNA-seq) analysis revealed notable diversity in CD8+ T subpopulations during peak viral load and infection-resolved state. While enrichment of a Cxcr3hi CD8+ T effector subset was associated with a more robust cytotoxic response, both CD8+ T effector and central memory exhibited equally potent effector potential. The scRNA-seq analysis identified unique regulons regulating the cytotoxic response in CD8+ T cells. The late-stage CD8+ T blockade in influenza-cleared lungs or continuous CXCR3 blockade mitigated lung injury without affecting viral clearance. Furthermore, adoptive transfer of wild-type CD8+ T cells exacerbated influenza lung pathology in Cxcr3-/- mice. Collectively, our data imply that CXCR3 interception could have a therapeutic effect in preventing influenza-linked lung injury.