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Abstract This study aimed to investigate the changes in physical fitness and patient-reported outcomes as well as the correlation between these two factors in adult patients with newly diagnosed acute leukemia during chemotherapy. This was a longitudinal observational study. Patients were recruited from a tertiary hospital in China with a follow-up period of less than 90 days. Physical fitness was assessed using body mass index (BMI), mean skinfold thickness, waist-to-hip ratio, spirometry, mean grip strength, and flexibility at T1 (before chemotherapy), T2 (7–14 days after initial chemotherapy), and T3 (completely relieved or after two chemotherapy courses). A repeated-measures analysis of variance was used to analyze the physical fitness changes during follow-up. Multiple linear regression was used to analyze the factors influencing patient-reported outcomes. The study analyzed 121 patients. Changes in physical fitness during chemotherapy, including BMI, mean skinfold thickness, lung capacity and flexibility were not all equal at all three time points (F = 38.477, P

Abstract Influenza remains a severe respiratory illness that poses significant global health threats. Recent studies have identified distinct microbial communities within the respiratory tract, from nostrils to alveoli. This research explores specific anti-influenza respiratory microbes using a mouse model supported by 16S rDNA sequencing and untargeted metabolomics. The study found that transferring respiratory microbes from mice that survived H9N2 influenza to antibiotic-treated mice enhanced infection resistance. Notably, the levels of Aeromicrobium were significantly higher in the surviving mice. Mice pre-treated with antibiotics and then inoculated with Aeromicrobium camelliae showed reduced infection severity, as evidenced by decreased weight loss, higher survival rates, and lower lung viral titres. Metabolomic analysis revealed elevated LysoPE (16:0) levels in mildly infected mice. In vivo and in vitro experiments indicated that LysoPE (16:0) suppresses inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX2) expression, enhancing anti-influenza defences. Our findings suggest that Aeromicrobium camelliae could serve as a potential agent for influenza prevention and a prognostic marker for influenza outcomes.

Abstract Background Gut microbes are important regulators of host health and can also function as disease indicators. Lactiplantibacilllus plantarum(L. plantarum)used as express and delivery vaccines for mucosal immunity have been shown to activate specific immune responses in numerous studies. Results The interaction between recombinant L. plantarum and the gut microbiota was investigated in this study. The results indicated a change in the amount of gut OTU by recombinant L. plantarum. Recombinant L. plantarum dramatically boosted the species diversity of gut bacteria based on the Shannon-Wiener index. Beta diversity analysis showed that microbial structure was changed by recombinant L. plantarum. Furthermore, recombinant NC8 L. plantarum expressing a fusion between the P14.5 protein of the African swine fever virus and IL-33 enhanced the functions of gut bacteria in metabolism and immune regulation. Increased levels of IgG and IgG1 in serum and sIgA in feces, as well as enrichment of CD4+ T cells and IgA+ B cells, indicated that the gut microbiota exerted an immunomodulatory role when mediated by recombinant L. plantarum. Conclusions These results revealed that recombinant L. plantarum exerted its potential role in the gut microbiota and gut immunity.These fndings contribute to a broader understanding and utilization of L. plantarum bacteria in various therapeutic applications.

Abstract Background Chronic obstructive pulmonary disease (COPD) has become one of the major death-related causes. Chronic pulmonary heart disease (CPHD) is an adverse complication of COPD causing poor prognosis of patients. This study evaluated the role of lncRNA XIST in COPD and CPHD aiming to identify a potential biomarker for the screening and prediction of COPD. Methods The study enrolled 127 COPD patients, including 73 patients occurred CPHD with 76 healthy individuals as the control group. The expression of XIST was evaluated by PCR and compared between COPD patients with different severity, grades, and complications. The diagnostic and prognostic values of XIST in COPD and CPHD were assessed by ROC and Kaplan-Meier analyses. Results Significant upregulation of XIST was observed in the serum of COPD patients relative to healthy individuals, which distinguished COPD patients and showed a correlation with the respiratory and pulmonary function of COPD patients. COPD patients with acute exacerbations and CPHD showed a higher expression level. Increasing serum XIST discriminated COPD patients combined CPHD and positively correlated with right ventricular hypertrophy and pulmonary hypertension. Higher serum XIST levels could indicate the adverse 3-year prognosis of COPD patients, especially for COPD patients combined with CPHD. Conclusion Upregulated XIST served as a biomarker for screening COPD and predicting adverse prognosis of COPD and COPD patients with CPHD.

In order to evaluate the health of river ecosystems, it is essential to look at how macroinvertebrates are affected by changes in their habitat and how they react to environmental influences. This study focused on the Hulan River Basin, situated in a cold region, utilizing survey data on macroinvertebrates and water environmental factors collected in late April, late June, and late September of 2023. The research thoroughly analyzed the spatiotemporal distribution characteristics of macroinvertebrate functional feeding groups (FFGs) and their correlations with aquatic environmental factors, subsequently conducting a comprehensive biological assessment of water quality. The results indicated the collection of 88 taxonomic units (genus or species) of macroinvertebrates, belonging to 4 phyla, 14 orders, and 35 families. Among these, collector-gatherers were the most prevalent FFG, followed by scrapers, predators, and collector-filterers, with shredders being the least represented. Distinct seasonal variations in dominant macroinvertebrate species were observed, with Chironomus sp. being the annual dominant among collector-gatherers and Semisulcospira amurensis among scrapers. The PERMANOVA test revealed significant differences in the densities of macroinvertebrate FFGs between different river sections and highly significant differences between months. Redundancy Analysis (RDA) indicated that the influential environmental factors varied by month, with water temperature, dissolved oxygen, and total phosphorus being significant in April; ammonia in June; and dissolved oxygen, pH, and alkalinity in September. The ecosystem assessment of the Hulan River Basin based on FFG parameters showed that the upstream possesses robust capabilities for material cycling, longitudinal matter transport, and coastal material input, with the highest habitat stability. Temporally, parameters such as longitudinal transport capacity peaked in September, coinciding with the strongest habitat stability. The Hilsenhoff Biological Index and Shannon-Wiener Index assessments indicated water quality ranging from good to excellent in the upstream, moderate in the midstream, and moderate to poor in the downstream. Overall, the water quality in the upstream areas was superior to that in the midstream and downstream. This study demonstrates that macroinvertebrate FFGs are highly sensitive to human activities and agricultural pollution in the midstream and downstream areas of the Hulan River Basin. These findings provide valuable insights for the restoration of river ecosystems.

The proteins encoded by Influenza A virus (IAV) evade the innate immune system through diverse strategies to facilitate their replication. However, the regulatory mechanisms remain not fully understood. In this study, we identified that the H9N2 PB1 protein suppressed the activities of the IFN-β, ISRE, and NF-κB promoters. Furthermore, H9N2 PB1 inhibited the phosphorylation of IRF3, IκBα, and TBK1 and the secretion of IFN-β. The results demonstrated H9N2 PB1 as a negative regulator of the RIG-I signaling pathway. Subsequent investigations revealed a specific interaction between H9N2 PB1 and MAVS, which disturbed the stability of MAVS. Notably, we discovered that H9N2 PB1 exploited the function of TRIM25, leading to the autophagic degradation of MAVS through K48-linked polyubiquitination. In conclusion, we uncovered a negative regulatory axis consisting of H9N2 PB1-TRIM25-MAVS-IFN-I. These findings provide valuable insights into the molecular interactions involved in the regulation of the host's innate immune antiviral response by IAV.

Avian influenza virus (AIV) subtype H9N2 still poses a great threat to the poultry farming industry and public health worldwide, and the development of a new influenza vaccine that is safe and conservative and able to address influenza virus mutations is highly promising for application. HA2, the neck of the HA protein, and M2e, the extracellular N-terminal structural domain of the M2 protein, are conserved and effective protective antigens.In this study, the HA2 sequences were fused with three M2e copies (H9N2, H1N1 and H5N1) to the norovirus VP1 protein via the SpyTag-SpyCatcher platform to form self-assembled nanoparticles and display antigenic proteins on its surface, yielding pYL262. The chicken dendritic cells (DCs) targeting the nanobody phage-54 were then fused to HA2-3M2e to yield pYL327. Finally, a synthesized 20-repeat CpG adjuvant gene fragment was inserted into pYL327, resulting in the plasmid pYL331. All the constructed plasmids were then transformed into the sifA gene-deficient Salmonella vector χYL56 for oral immunization.The results showed that sifA-deficient Salmonella could efficiently increase antigen-specific mucosal sIgA antibody titers, especially in alveolar lavage samples, whereas the presence of the phage-54 nanobody could dramatically increase intracellular IFN-γ mRNA levels, indicating its ability to enhance the Th1-type immune response. Finally, the presence of the CpG adjuvant clearly increased T-cell proliferation and promoted DC activation, with elevated splenic TLR21 levels observed. Strikingly, after oral immunization with χYL56 (pYL331), chickens were protected against challenge with the G57 genotype H9N2 virus, which presented similar or even better levels of virus shedding and body weight gain compared with the commercial inactivated vaccine, providing a new option for controlling H9N2 virus infection in the future.

Objective To evaluate the applicability of a modified U-shaped forearm flap for the repair of small- and medium-sized defects in the oral and maxillary areas to provide a reference for clinicians. Methods This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ten patients with small- and medium-sized defects in the oral and maxillary areas underwent surgical repair using modified U-shaped forearm flaps. There were 8 males and 2 females aged 43-72 years. The donor site was apposed primarily after harvesting the modified U-shaped forearm skin flap. The flaps ranged from 6 cm × 4 cm to 8 cm × 5 cm in size. Six months after the operation, hand movements (finger extension, fist clenching, wrist rotation upward and wrist rotation downward), the forearm donor site, hand sensations and the satisfaction score for the postoperative quality of the scar at the donor site were evaluated (0 to 10; 0: very unattractive, 10: very satisfactory). Results A total of 10 patients with modified U-shaped forearm flaps survived. One patient developed venous crisis 24 hours after surgery and survived after surgical exploration. Delayed healing occurred at the donor site of the forearm in 1 patient, and the wounds at the donor site of the forearm in the other patients all healed in the first stage. One patient presented with dysesthesia in the hand 2 weeks after surgery and recovered within 3 months. Six months after surgery, all patients had no limited hand movement and no paresthesia at the forearm donor site or hand. The patients were basically satisfied with the appearance of the donor site,and the average satisfaction score of the subjective questionnaire was 8.4 points. Conclusion Modified U-shaped forearm flaps can directly close forearm donor site wounds, which avoids surgical trauma to the secondary donor site and significantly reduces related complications. Modified U-shaped forearm flaps provide an alternative to conventional forearm flaps for the repair of small- and medium-sized defects in the oral and maxillary areas.

Salmonella is a foodborne pathogen that causes disruption of intestinal mucosal immunity, leading to acute gastroenteritis in the host. In this study, we found that Salmonella Typhimurium (STM) infection of the intestinal tract of mice led to a significant increase in the proportion of Lacticaseibacillus, while the secretion of IL-22 from type 3 innate lymphoid cells (ILC3) increased significantly. Feeding Lacticaseibacillus rhamnosus GG (LGG) effectively alleviated the infection of STM in the mouse intestines. TLR2−/− mice experiments found that TLR2-expressing dendritic cells (DCs) are crucial for LGG‘s activation of ILC3. Subsequent in vitro experiments showed that heat-killed LGG (HK-LGG) could promote DCs to secrete IL-23, which in turn further promotes the activation of ILC3 and the secretion of IL-22. Finally, organoid experiments further verified that IL-22 secreted by ILC3 can enhance the intestinal mucosal immune barrier and inhibit STM infection. This study demonstrates that oral administration of LGG is a potential method for inhibiting STM infection.

The microbiota-associated factors that affect host susceptibility and adaptive immunity to influenza A virus (IAV) infection have not been fully elucidated. By comparing the microbiota composition between survivors and mice that succumbed to IAV strain PR8 infection, we identified that the commensal bacterium Blautia coccoides protects antibiotics (Abx)-treated or germ-free (GF) mice from PR8 infection by inducing functionally optimal virus-specific CD8+ T cell responses. Administration of exogenous acetate reproduced the protective effect of B. coccoides monocolonization in Abx and GF mice, enhancing oxidative phosphorylation and glycolysis as well as secretion of IFN-γ and granzyme B in virus-specific CD8+ T cells, dependent on GPR43 signaling and acetyl-CoA synthetase 2. Thus, we have demonstrated that microbiota-derived acetate possesses an antiviral effect that induces an optimal virus-specific CD8+ T cell response to IAV PR8 infection via GPR43-dependent metabolic reprogramming.

IntroductionPhytohormones play a crucial role in regulating the abscission of plant organs and tissues.MethodsIn this study, the ultrastructure of the sepals of Korla fragrant pears was observed using a transmission electron microscope, and high-performance liquid and gas chromatography were used to analyze the dynamic changes of phytohormones in the abscission zone during the calyx abscission process of Korla fragrant pears, and mass spectrometry imaging was applied to ascertain the spatial distribution of phytohormones.ResultsThe results revealed that the mitochondria in the abscission zone of the decalyx fruits were regularly distributed around the cell wall, and the chloroplasts were moderately present. In contrast, in the persistent calyx fruit, the corresponding parts of the abscission zone showed a scattered distribution of mitochondria within the cells, and there was a higher number of chloroplasts, which also contained starch granules inside. Mass spectrometry imaging revealed that ABA was enriched in the abscission zone of the decalyx fruit, and their ionic signal intensities were significantly stronger than those of the persistent calyx fruit. However, the ionic signal intensities of Indole-3-acetic acid (IAA) and Gibberellin A3 (GA3) of the persistent calyx fruit were significantly stronger than those in the abscission zone of the decalyx fruit and were concentrated in the persistent calyx fruit. 1-Aminocyclopropanecarboxylic Acid (ACC) did not show distinct regional distribution in both the decalyx and persistent calyx fruits. Furthermore, before the formation of the abscission zone, the levels of IAA, GA3, and zeatin (ZT) in the abscission zone of the decalyx fruits were significantly lower than those in the persistent calyx fruits by 37.9%, 57.7%, and 33.0%, respectively, while the levels of abscisic acid (ABA) and ethylene (ETH) were significantly higher by 21.9% and 25.0%, respectively. During the formation of the abscission zone, the levels of IAA, GA3, and ZT in the abscission zone of the decalyx fruits were significantly lower than those in the persistent calyx fruits by 41.7%, 71.7%, and 24.6%, respectively, while the levels of ABA and ETH were significantly higher by 15.2% and 80.0%, respectively. After the formation of the abscission zone, the levels of IAA and GA3 in the abscission zone of the decalyx fruits were lower than those in the persistent calyx fruits by 20.8% and 47.8%, respectively, while the levels of ABA and ETH were higher by 271.8% and 26.9%, respectively. In summary, during the calyx abscission process of Korla fragrant pears, IAA and GA3 in the abscission zone inhibited abscission, while ABA and ETH promoted calyx abscission. These research findings enrich the understanding of the regulatory mechanism of plant hormones on calyx abscission and provide a theoretical basis for the study of exogenous plant growth regulators for regulating calyx abscission in Korla fragrant pear.

Abstract Background Chicken coccidiosis is a protozoan disease that leads to considerable economic losses in the poultry industry. Live oocyst vaccination is currently the most effective measure for the prevention of coccidiosis. However, it provides limited protection with several drawbacks, such as poor immunological protection and potential reversion to virulence. Therefore, the development of effective and safe vaccines against chicken coccidiosis is still urgently needed. Methods In this study, a novel oral vaccine against Eimeria tenella was developed by constructing a recombinant Lactobacillus plantarum (NC8) strain expressing the E. tenella RON2 protein. We administered recombinant L. plantarum orally at 3, 4 and 5 days of age and again at 17, 18 and 19 days of age. Meanwhile, each chick in the commercial vaccine group was immunized with 3 × 102 live oocysts of coccidia. A total of 5 × 104 sporulated oocysts of E. tenella were inoculated in each chicken at 30 days. Then, the immunoprotection effect was evaluated after E. tenella infection. Results The results showed that the proportion of CD4+ and CD8+ T cells, the proliferative ability of spleen lymphocytes, inflammatory cytokine levels and specific antibody titers of chicks immunized with recombinant L. plantarum were significantly increased (P

Abstract The rational use and conversion of energy are the primary means for achieving the goal of carbon neutrality. MXenes can be used for photothermal conversion, but their opaque appearance limits wider applications. Herein, we successfully develop visible-light transparent and UV-absorbing polymer composite film by solution blending the MXene with polyethylene and then vacuum pressing. The resulting film could be quickly heated to 65 °C under 400 mW cm−2 light irradiation and maintained over 85% visible-light transmittance as well as low haze (

ABSTRACT E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Here, we systematically identify the E3 ligase ASB3 as a facilitative regulator in the development and progression of IBD. We observed that ASB3 exhibited significant upregulation in the lesions of patients with IBD. ASB3−/− mice are resistant to dextran sodium sulfate-induced colitis. IκBα phosphorylation levels and production of proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the colonic tissues of ASB3−/− mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotics removed the gut commensal microbiome. Mechanistically, ASB3 specifically catalyzes K48-linked polyubiquitination of TRAF6 in intestinal epithelial cells. In contrast, in ASB3-deficient organoids, the integrity of the TRAF6 protein is shielded, consequently decelerating the onset of intestinal inflammation. ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors’ production by disrupting TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis.IMPORTANCEUbiquitination is a key process that controls protein stability. We determined the ubiquitination of TRAF6 by ASB3 in intestinal epithelial cells during colonic inflammation. Inflammatory bowel disease patients exhibit upregulated ASB3 expression at focal sites, supporting the involvement of degradation of TRAF6, which promotes TLR-Myd88/TRIF-independent NF-κB aberrant activation and intestinal microbiota imbalance. Sustained inflammatory signaling in intestinal epithelial cells and dysregulated protective probiotic immune responses mediated by ASB3 collectively contribute to the exacerbation of inflammatory bowel disease. These findings provide insights into the pathogenesis of inflammatory bowel disease and suggest a novel mechanism by which ASB3 increases the risk of colitis. Our results suggest that future inhibition of ASB3 in intestinal epithelial cells may be a novel clinical strategy.

Abstract Mechanoluminescence (ML) sensing technologies open up new opportunities for intelligent sensors, self-powered displays and wearable devices. However, the emission efficiency of ML materials reported so far still fails to meet the growing application requirements due to the insufficiently understood mechano-to-photon conversion mechanism. Herein, we propose to quantify the ability of different phases to gain or lose electrons under friction (defined as triboelectric series), and reveal that the inorganic-organic interfacial triboelectricity is a key factor in determining the ML in inorganic-organic composites. A positive correlation between the difference in triboelectric series and the ML intensity is established in a series of composites, and a 20-fold increase in ML intensity is finally obtained by selecting an appropriate inorganic-organic combination. The interfacial triboelectricity-regulated ML is further demonstrated in multi-interface systems that include an inorganic phosphor-organic matrix and organic matrix-force applicator interfaces, and again confirmed by self-oxidization and reduction of emission centers under continuous mechanical stimulus. This work not only gives direct experimental evidences for the underlying mechanism of ML, but also provides guidelines for rationally designing high-efficiency ML materials.

Abstract Vaccination is still the most promising strategy for combating influenza virus pandemics. However, the highly variable characteristics of influenza virus make it difficult to develop antibody-based universal vaccines, until now. Lung tissue-resident memory T cells (TRM), which actively survey tissues for signs of infection and react rapidly to eliminate infected cells without the need for a systemic immune reaction, have recently drawn increasing attention towards the development of a universal influenza vaccine. We previously designed a sequential immunization strategy based on orally administered Salmonella vectored vaccine candidates. To further improve our vaccine design, in this study, we used two different dendritic cell (DC)-targeting strategies, including a single chain variable fragment (scFv) targeting the surface marker DC-CD11c and DC targeting peptide 3 (DCpep3). Oral immunization with Salmonella harboring plasmid pYL230 (S230), which displayed scFv-CD11c on the bacterial surface, induced dramatic production of spleen effector memory T cells (TEM). On the other hand, intranasal boost immunization using purified DCpep3-decorated 3M2e-ferritin nanoparticles in mice orally immunized twice with S230 (S230inDC) significantly stimulated the differentiation of lung CD11b+ DCs, increased intracellular IL-17 production in lung CD4+ T cells and elevated chemokine production in lung sections, such as CXCL13 and CXCL15, as determined by RNAseq and qRT‒PCR assays, resulting in significantly increased percentages of lung TRMs, which could provide efficient protection against influenza virus challenge. The dual DC targeting strategy, together with the sequential immunization approach described in this study, provides us with a novel “prime and pull” strategy for addressing the production of protective TRM cells in vaccine design.

Epidermoid cyst of the spleen is a rare disease, and relatively few cases were reported by literatures. Most published case reports provided inadequate information on the impact of splenic epidermoid cyst on tumor markers. A 32-year-old woman with a giant splenic epidermoid cyst was reported, for whom the serum concentration of a collection of tumor markers (CA19–9, CEA, CA125, CA242, and CA50) increased abruptly accompanied by left upper abdominal pain for 5 days. After comprehensive preoperative examination and multidisciplinary team discussion, we ruled out any concurrent malignancy and a laparoscopic total splenectomy was performed, during which the splenic cyst spontaneously ruptured unexpectedly. After surgery, the elevated serum tumor marker levels decreased sharply until reaching normal range 3 months later. Learning from the case, we conclude that interval monitoring of serum tumor markers is of critical value for patients with splenic epidermoid cyst. Abrupt elevation of tumor marker levels and abdominal pain may serve as signs of cyst rupture, which is strongly indicative of surgical intervention as soon as possible. Total removal of the splenic cyst is strongly suggested considering the recurrence and malignant potential of the splenic epidermoid cyst.

ABSTRACTEnterotoxigenic Escherichia coli (ETEC) is one of the major pathogens contributing to piglet diarrhea, with significant implications for both piglet health and the economic aspects of the livestock industry. SW207 is an isolate of Bacillus halotolerans isolated from the cold- and disease-resistant Leixiang pigs in Northeastern China. We have discovered that SW207 can survive in the pig’s gastrointestinal fluid and under conditions of high bile salt concentration, displaying potent antagonistic activity against ETEC. In this study, we established a weaned piglet diarrhea model infected with ETEC to investigate the role of SW207 in preventing diarrhea and improving intestinal health. Results indicate that SW207 upregulates the expression of tight junction proteins, including claudin-1, occludin, and zonula occludens-1, at both the transcriptional and translational levels. Furthermore, SW207 reduces serum endotoxin, D-lactic acid, and various oxidative stress markers while enhancing piglet mechanical barrier function. In terms of immune barrier, SW207 suppressed the activation of the TLR4/MyD88/NF-κB pathway, reducing the expression of various inflammatory factors and upregulating the expression of small intestine mucosal sIgA. Concerning the biological barrier, SW207 significantly reduces the content of E. coli in the intestines and promotes the abundance of beneficial bacteria, thereby mitigating the microbiota imbalance caused by ETEC. In summary, SW207 has the potential to prevent weaned piglet diarrhea caused by ETEC, alleviate intestinal inflammation and epithelial damage, and facilitate potential beneficial changes in the intestinal microbiota. This contributes to elucidating the potential mechanisms of host-microbe interactions in preventing pathogen infections.IMPORTANCEEnterotoxigenic Escherichia coli (ETEC) has consistently been one of the significant pathogens causing mortality in weaned piglets in pig farming. The industry has traditionally relied on antibiotic administration to control ETEC-induced diarrhea. However, the overuse of antibiotics has led to the emergence of drug-resistant zoonotic bacterial pathogens, posing a threat to public health. Therefore, there is an urgent need to identify alternatives to control pathogens and reduce antibiotic usage. In this study, we assessed the protective effect of a novel probiotic in a weaned piglet model infected with ETEC and analyzed its mechanisms both in vivo and in vitro. The study results provide theoretical support and reference for implementing interventions in the gut microbiota to alleviate early weaned piglet diarrhea and improve intestinal health.

ABSTRACTCanine distemper virus (CDV) poses a severe threat to both domesticated and wild animals, including multiple carnivores. With the continued expansion of its host range, there is an urgent need for the development of a safer and more effective vaccine. In this study, we developed subunit vaccines based on a bacterium-like particle (BLP) delivery platform containing BLPs-F and BLPs-H, which display the CDV F and H glycoprotein antigens, respectively, using the antigen-protein anchor fusions produced by a recombinant baculovirus insect cell expression system. The combination of BLPs-F and BLPs-H (CDV-BLPs), formulated with colloidal manganese salt [Mn jelly (MnJ)] adjuvant, triggered robust CDV-specific antibody responses and a substantial increase in the number of interferon gamma (IFN-γ)-secreting CD4+ and CD8+ T cells in mice. Dogs immunized intramuscularly with this vaccine not only produced CDV-specific IgG but also displayed elevated concentrations of IFN-γ and interleukin 6 in their serum, along with an increase of the CD3+CD4+ and CD3+CD8+ T cell subsets. Consequently, this heightened immune response provided effective protection against disease development and reduced viral shedding levels following challenge with a virulent strain. These findings suggest that this BLP-based subunit vaccine has the potential to become a novel canine distemper vaccine.IMPORTANCEMany sensitive species require a safe and effective distemper vaccine. Non-replicating vaccines are preferred. We constructed subunit particles displaying canine distemper virus (CDV) antigens based on a bacterium-like particle (BLP) delivery platform. The CDV-BLPs formulated with theMn jelly adjuvant induced robust humoral and cell-mediated immune responses to CDV in mice and dogs, thereby providing effective protection against a virulent virus challenge. This work is an important step in developing a CDV subunit vaccine.

Abstract Background Clinical decision-making involves ethical issues that become more and more complex. Nurse interns must be more skilled in making rational and timely decisions when facing ethical dilemmas. The contributing factors and their relationships that challenge ethical decision-making among nurse interns must be fully understood, as this level of knowledge can support the development of strategies and interventions that improve the ethical decision-making ability of nurse interns. Objective This study examined the relationships between moral courage, moral sensitivity, and ethical decision-making by nurse interns. In addition, we investigated whether moral sensitivity mediates the relationship between moral courage and ethical decision-making. Design A descriptive cross-sectional study using an online questionnaire. Setting The study sampled nurse interns from Class iii Grade A general hospitals in Sichuan Province, China. Participants A convenience sampling method was used to select 1334 nurse interns from March 2022 to May 2022. Methods A general information questionnaire, the Nurses’ Moral Courage Scale (NMCS), the Chinese Moral Sensitivity Questionnaire (MSQ), and the Judgement About Nursing Decision (JAND) were used for data collection. Data was processed and analysed using SPSS 26.0 and Amos 28.0. Data analysis included descriptive statistics, Pearson correlation analysis, and structural equation modelling. Results Moral courage was found to be positively correlated with ethical decision-making (P

Abstract The emulation of human multisensory functions to construct artificial perception systems is an intriguing challenge for developing humanoid robotics and cross‐modal human–machine interfaces. Inspired by human multisensory signal generation and neuroplasticity‐based signal processing, here, an artificial perceptual neuro array with visual‐tactile sensing, processing, learning, and memory is demonstrated. The neuromorphic bimodal perception array compactly combines an artificial photoelectric synapse network and an integrated mechanoluminescent layer, endowing individual and synergistic plastic modulation of optical and mechanical information, including short‐term memory, long‐term memory, paired pulse facilitation, and “learning‐experience” behavior. Sequential or superimposed visual and tactile stimuli inputs can efficiently simulate the associative learning process of “Pavlov's dog”. The fusion of visual and tactile modulation enables enhanced memory of the stimulation image during the learning process. A machine‐learning algorithm is coupled with an artificial neural network for pattern recognition, achieving a recognition accuracy of 70% for bimodal training, which is higher than that obtained by unimodal training. In addition, the artificial perceptual neuron has a low energy consumption of ∼20 pJ. With its mechanical compliance and simple architecture, the neuromorphic bimodal perception array has promising applications in large‐scale cross‐modal interactions and high‐throughput intelligent perceptions.

Beta-alanine is an important amino acid involved in several metabolic reactions in the body. The study aimed to investigate the effect of β-alanine supplementation on intestinal development and the immune performance of weaned piglets. Thirty-two 21-day-old healthy weaned piglets (half female and half male; Duroc × Landrace × Yorkshire) with an initial body weight of 8.11 ± 0.21 kg were randomly divided into 4 groups with 8 replicates of 1 pig each. The control group was fed a basal diet and the three experimental treatment groups were fed diets supplemented with 300, 600 and 1,200 mg/kg β-alanine, respectively. The trial lasted 28 days and the diets fed were divided into 2 phases: the late lactation period (day 1 to 14) and the nursery period (day 15 to 28), during which the weaned piglets had free access to food and water. The regulatory effects of β-alanine were further investigated in vitro using organoids obtained from the jejunum of piglets. In vivo, the addition of β-alanine to the diet had no significant effect on the growth performance of weaned piglets (P > 0.05), but significantly reduced serum levels of immunoglobulin G (IgG) (P

Programmed cell death (PCD) is common in plant growth and development, such as xylem development, organ senescence, and abscission. Calyx abscission in Korla fragrant pear contributes to fruit quality, while it was not clear whether PCD occurred during calyx abscission and which signals regulated the process. Therefore, it is imperative to clarify the process of PCD in the process of calyx abscission in Korla fragrant pear under natural conditions to enrich the mechanism of calyx abscission. The results showed that the total time of calyx abscission of Korla fragrant pear began from 6 days after pollination (DAP) to 13 DAP, and the peak of calyx abscission occurred 10 DAP. During the whole process of calyx abscission, PCD started 6 DAP. At 9 DAP, the degree of PCD deepened. At 12 DAP, the cells in the abscission zone showed asymmetry on both sides, the organelles in the distal cells of the abscission zone degraded into apoptotic fragments, and the protective layer of the normal development of cells located at the proximal end of the abscission zone region ended the PCD process. ETH concentrations in the abscission zone of the decalyx fruit were significantly higher than those of the persistent calyx fruits in each period during calyx abscission, and high levels of ethylene and hydrogen peroxide and low contents of the GA3, ZT, and hydroxyl radicals promoted calyx abscission before the formation of the abscission zone. At 3 DAP, the ethylene concentration (43.97 ppm) and H2O2 content (8.49 μmol/g) of decalyx fruit in the abscission zone were significantly higher than those of persistent calyx fruit by 67.69% and 27.86%, respectively; however, the GA3, ZT, and hydroxyl radicals showed the opposite. Overall, PCD in the abscission zone of decalyx fruits did occur during the calyx abscission of Korla fragrant pear, and ethylene and H2O2 might play major roles in initiating the PCD process during Korla fragrant pear calyx abscission.

Probiotics are beneficial for intestinal diseases. Research shows that probiotics can regulate intestinal microbiota and alleviate inflammation. Little research has been done on the effects of probiotics on colitis in mice. The purpose of this study was to investigate the inhibitory effect of the strains isolated and screened from the feces of healthy piglets on the enteritis of rocitrobacter. The compound ratio of isolated Lactobacillus L9 and Enterococcus faecalis L16 was determined, and the optimal compound ratio was selected according to acid production tests and bacteriostatic tests in vitro. The results showed that when the ratio of Lactobacillus L9 to Enterococcus faecalis L16 was 4:1, the pH value was the lowest, and the antibacterial diameter was the largest. Then, in animal experiments, flow cytometry was used to detect the number of T lymphocytes in the spleen and mesenteric lymph nodes of mice immunized with complex lactic acid bacteria. The results showed that the number of T lymphocytes in the spleen and mesenteric lymph nodes of mice immunized with complex lactic acid bacteria significantly increased, which could improve the cellular immunity of mice. The microbiota in mouse feces were sequenced and analyzed, and the results showed that compound lactic acid bacteria could increase the diversity of mouse microbiota. It stabilized the intestinal microbiota structure of mice and resisted the damage of pathogenic bacteria. The combination of lactic acid bacteria was determined to inhibit the intestinal colitis induced by Citrobacter, improve the cellular immune response of the body, and promote the growth of animals.

Thirty-six healthy 21-day-old weaned ternary piglets (Duroc × Landrace × Yorkshire) were randomly divided into two treatments with 18 replicates per treatment and one pig per replicate. The control group was fed with a basal diet and the test group was fed with diets supplemented with 1 kg/t tea residue. The test period was 28 days. The results are as follows: The addition of tea residue in the diet had no significant effect on the growth performance of weaned piglets (p > 0.05), but it could significantly reduce the diarrhea rate of piglets from 1 to 7 days and 1 to 28 days (p < 0.05). Compared with the control group, the dietary supplementation of tea residue had no significant effect on nutrient apparent digestibility, plasma biochemical indexes and plasma immune indexes (p > 0.05) but increased the content of glutathione in plasma (p < 0.05). Tea residue had no significant effect on the morphology of the jejunum and ileum of piglets (p > 0.05), but it could significantly reduce the content of chloride ions in feces (p < 0.05). Compared with the basal diet group, there was no significant difference in the relative expression of TMEM16A and CFTR mRNA in the colon of weaned piglets (p > 0.05). The whole-cell patch clamp recording showed that the TMEM16A and CFTR ion channels could be activated by ionomycin and forskolin, respectively. However, when HT-29 cells transfected with TMEM16A and CFTR channels were treated with tea residue extract, it could significantly inhibit the chloride current of the TMEM16A and CFTR ion channels (p < 0.05).

Abstract African swine fever virus (ASFV) is an important pathogen causing acute infectious disease in domestic pigs and wild boars that seriously endangers the global swine industry. As ASFV is structurally complex and encodes a large number of functional proteins, no effective vaccine has been developed to date. Thus, dissecting the mechanisms of immune escape induced by ASFV proteins is crucial. A previous study showed that the ASFV-encoded protein is an important factor in host immunity. In this study, we identified a negative regulator, MGF505-3R, that significantly downregulated cGAS/STING- and poly (dG:dC)-mediated IFN-β and interferon stimulation response element (ISRE) reporter activity and suppressed IFNB1 and IFIT2 mRNA levels. In addition, TBK1, IRF3 and IκBα phosphorylation levels were also inhibited. Mechanistically, MGF505-3R interacted with cGAS/TBK1/IRF3 and targeted TBK1 for degradation, thereby disrupting the cGAS-STING-mediated IFN-β signaling pathway, which appears to be highly correlated with autophagy. Knockdown MGF505-3R expression enhanced IFN-β and IL-1β production. Taken together, our study revealed a negative regulatory mechanism involving the MGF505-3R-cGAS-STING axis and provided insights into an evasion strategy employed by ASFV that involves autophagy and innate signaling pathways.

Abstract Background Common and frequent as acute pain is, it is often underestimated and undertreated in older people with dementia in nursing homes and inadequate pain management remains an issue. Methods The study is designed to be a randomized, sham-controlled trial and is underway in nursing homes located in China. A total of 206 dementia patients are being recruited from nursing homes in Yinchuan, China. They are randomly allocated to an intervention or a controlled group in a 1:1 ratio. The intervention group will be treated with true APP therapy, while the other group will receive APP at sham point stimulation therapy. The patients will be assessed at baseline (T0), at 5 min during performing the intervention (T1), and at 5 min after completion of the intervention (T2). The primary outcome is the level of pain relief at T1 and T2. Physiological parameters, side effects and additional use of analgesics during the procedure, satisfaction from caregivers, and acceptance of patients are evaluated as secondary outcomes. Discussion The results of this study are expected to verify the analgesic effect of APP for acute pain in patients with mild dementia in nursing homes. It has the potential to prompt APP therapy to be implemented widely in dementia patients with acute pain in nursing homes. Trial registration Chinese Clinical Trial Registry ChiCTR2100047932 . Registered on 27 June 2021. Currently, patient recruitment is ongoing. Recruitment is expected to take place from December 2020 to December 2021.

ABSTRACT The influenza virus continues to pose a great threat to public health due to the frequent variations in RNA viruses. Vaccines targeting conserved epitopes, such as the extracellular domain of the transmembrane protein M2 (M2e), a nucleoprotein, and the stem region of hemagglutinin proteins, have been developed, but more efficient strategies, such as nanoparticle-based vaccines, are still urgently needed. However, the labor-intensive in vitro purification of nanoparticles is still necessary, which could hinder the application of nanoparticles in the veterinary field in the future. To overcome this limitation, we used regulated lysis Salmonella as an oral vector with which to deliver three copies of M2e (3M2e-H1N1)-ferritin nanoparticles in situ and evaluated the immune response. Then, sequential immunization using Salmonella-delivered nanoparticles followed by an intranasal boost with purified nanoparticles was performed to further improve the efficiency. Compared with 3M2e monomer administration, Salmonella-delivered in situ nanoparticles significantly increased the cellular immune response. Additionally, the results of sequential immunization showed that the intranasal boost with purified nanoparticles dramatically stimulated the activation of lung CD11b dendritic cells (DCs) and elevated the levels of effector memory T (TEM) cells in both spleen and lung tissues as well as those of CD4 and CD8 tissue-resident memory T (TRM) cells in the lungs. The increased production of mucosal IgG and IgA antibody titers was also observed, resulting in further improvements to protection against a virus challenge, compared with the pure oral immunization group. Salmonella-delivered in situ nanoparticles efficiently increased the cellular immune response, compared with the monomer, and sequential immunization further improved the systemic immune response, as shown by the activation of DCs, the production of TEM cells and TRM cells, and the mucosal immune response, thereby providing us with a novel strategy by which to apply nanoparticle-based vaccines in the future. IMPORTANCE Salmonella-delivered in situ nanoparticle platforms may provide novel nanoparticle vaccines for oral administration, which would be beneficial for veterinary applications. The combination of administering Salmonella-vectored, self-assembled nanoparticles and an intranasal boost with purified nanoparticles significantly increased the production of effector memory T cells and lung resident memory T cells, thereby providing partial protection against an influenza virus challenge. This novel strategy could open a novel avenue for the application of nanoparticle vaccines for veterinary purposes.

At present, most studies have shown that probiotics have a positive regulatory effect on the nutritional metabolism of the body, but the mechanism is still unclear. Here, 48 piglets were divided into four groups. The control group was not fed probiotics, the Lac group was fed L. Rhamnosus GG ATCC53103, the Rha group was fed L. Plantarum JL01, and the mix group was fed two types of probiotics. Nitrogen metabolism and mRNA levels of mTOR and S6K in skeletal muscle were observed in each group. Then, metagenome and non-targeted metabonomics were used to observe the changes of intestinal microorganisms and plasma metabolites in portal channels after probiotics feeding. Finally, we combined the results of omics analysis to reveal the mechanism of probiotics on nitrogen metabolism in weaned piglets. The results showed that L. Rhmnosus GG ATCC53103 and L. Plantarum JL01 increased nitrogen apparent digestibility, nitrogen deposition rate, and nitrogen utilization rate of weaned piglets (P < 0.05); the relative expression of mTOR and SK6 mRNA in skeletal muscle increased significantly (P < 0.05). When L. rhamnosus GG ATCC53103 and L. plantarum JL01 were combined, we found that Clostridium and Prevotella significantly increased in the jejunum (P < 0.05). The relative abundance of Lactobacillus, Ruminococcus, Streptococcus, and Prevotella in the ileum increased significantly (P < 0.05). Compared with the control group, L-Tryptophan, 3-Phosphonyloxypyruvate, cis-Aconitate, and Carbamoyl phosphate were significantly increased in the mixed group portal vein. The result of the combinatorial analysis showed that the significantly increased microorganisms could encode the enzyme genes for the synthesis of L-Tryptophan, 3-Phosphonooxypyruvate, cis-Aconitate, and Carbamoyl phosphate. In summary, our results demonstrated that L. Rhamnosus GG ATCC53103 and L. Plantarum JL01 could stimulate the expression of skeletal muscle protein synthesis genes of weaned piglets by modulating the structure of the gut microbiota and its metabolites, thereby improving nitrogen metabolism in weaned piglets.

Abstract The type I interferon (IFN-I) signaling pathway is an important part of the innate immune response and plays a vital role in controlling and eliminating pathogens. African swine fever virus (ASFV) encodes various proteins to evade the host’s natural immunity. However, the molecular mechanism by which the ASFV-encoded proteins inhibit interferon production remains poorly understood. In the present study, ASFV MGF360-11L inhibited cGAS, STING, TBK1, IKKε, IRF7 and IRF3-5D mediated activation of the IFN-β and ISRE promoters, accompanied by decreases in IFN-β, ISG15 and ISG56 mRNA expression. ASFV MGF360-11L interacted with TBK1 and IRF7, degrading TBK1 and IRF7 through the cysteine, ubiquitin–proteasome and autophagy pathways. Moreover, ASFV MGF360-11L also inhibited the phosphorylation of TBK1 and IRF3 stimulated by cGAS-STING overexpression. Truncation mutation analysis revealed that aa 167-353 of ASFV MGF360-11L could inhibit cGAS-STING-mediated activation of the IFN-β and ISRE promoters. Finally, the results indicated that ASFV MGF360-11L plays a significant role in inhibiting IL-1β, IL-6 and IFN-β production in PAM cells (PAMs) infected with ASFV. In short, these results demonstrated that ASFV MGF360-11L was involved in regulating IFN-I expression by negatively regulating the cGAS signaling pathway. In summary, this study preliminarily clarified the molecular mechanism by which the ASFV MGF360-11L protein antagonizes IFN-I-mediated antiviral activity, which will help to provide new strategies for the treatment and prevention of ASF.

Rotavirus is one of the main pathogens that cause diarrhoea in young animals, and countless animals have died of rotavirus infection worldwide. Three strains of lactic acid bacteria isolated from Tibetan mushrooms were used to study the inhibition of rotavirus in vitro and in vivo. One part was to identify and study the biochemical and probiotic characteristics of three isolated lactic acid bacteria, and the other part was to evaluate the inhibitory effect on rotavirus via in vivo and in vitro experiments. The whole genome of the lactic acid bacteria with the best antiviral effect was sequenced, and the differences between them and the standard strains were analyzed by comparative genomic analysis, so as to provide a theoretical basis for exploring the antiviral effect of lactic acid bacteria.The three strains were identified as Pediococcus acidilactici, Lactobacillus casei and Lactobacillus paracasei. Pediococcus acidilactici showed good acid tolerance, bile salt tolerance, survival in artificial intestinal fluid, survival in gastric fluid and bacteriostasis. In in vitro experiments, pig intestinal epithelial cells cocultured with Pediococcus acidilactici exhibited reduced viral infection. In the in vivo experiment, the duodenum of mice fed Pediococcus acidilactici had extremely low numbers of virus particles. The total genome size was 2,026,809 bp, the total number of genes was 1988, and the total length of genes was 1,767,273 bp. The proportion of glycoside hydrolases and glycoside transferases in CAZy was 50.6 and 29.6%, respectively. The Metabolism function in KEEG had the highest number of Global and overview maps. Among the comparative genomes, Pediococcus acidilactici had the highest homology with GCF 000146325.1, and had a good collinearity with GCF 013127755.1, without numerous gene rearrangement events such as insertion, deletion, inversion and translocation. In conclusion, Pediococcus acidilactici was a good candidate strain for antiviral probiotics.

Abstract Mechanoluminescence, a smart luminescence phenomenon in which light energy is directly produced by a mechanical force, has recently received significant attention because of its important applications in fields such as visible strain sensing and structural health monitoring. Up to present, hundreds of inorganic and organic mechanoluminescent smart materials have been discovered and studied. Among them, strontium‐aluminate‐based materials are an important class of inorganic mechanoluminescent materials for fundamental research and practical applications attributed to their extremely low force/pressure threshold of mechanoluminescence, efficient photoluminescence, persistent afterglow, and a relatively low synthesis cost. This paper presents a systematic and comprehensive review of strontium‐aluminate‐based luminescent materials’ mechanoluminescence phenomena, mechanisms, material synthesis techniques, and related applications. Besides of summarizing the early and the latest research on this material system, an outlook is provided on its environmental, energy issue and future applications in smart wearable devices, advanced energy‐saving lighting and displays.

Mechanoluminescence (ML) materials, which directly convert mechanical energy into light emission, have emerged as an emerging class of light-emitting materials with various applications. Although significant progress has been made in the development of new ML materials and devices, their practical application is limited by their low intensity and homogenously structured host structures. Thus, multiple-structured host ML materials with high ML intensity and reproducibility are needed, particularly for wearable and printable ML light sources with high brightness. In this study, various Mn-doped ternary heterojunction ML materials, CaZnOS-ZnS-SrZnOS, are synthesised by high-temperature solid-phase reactions, and their luminescence properties are systematically tested. The result indicates that the ternary heterojunction materials have a higher ML intensity over 60 times stronger than the state-of-art SrZnOS: Mn2+, which is currently the brightest sample we have obtained. ML linearly depends on the magnitude of the applied force. Based on the synthesised ternary ML heterojunctions, repetitive self-driving luminescence of the zipper is achieved for the first time through powder modification and inlay; the clothes composed of our prepared zippers are pulled and bent when worn on the body to emit bright visible light. Additionally, a Velcro that can achieve light emission is developed; it provides a new idea for the development of wearable flexible self-luminous devices in the future. Simultaneously, movement-driven stress luminous printable objects that can be printed on the surface of various commodities or their packaging are demonstrated. The preparation of self-driven, battery-free, and electrode-free stress luminescence wearable low light sources has an important application trend, which can avoid the interference of the circuit and improve the stability of the devices, thus promising a wide range of applications in smart wear, energy-saving displays, safety and rescue, robotic skin, and information security.

Abstract Mechanoluminescent (ML) materials that directly convert mechanical energy into photon emission have emerged as promising candidates for various applications. Despite the recent advances in the development of both novel and conventional ML materials, the limited access to ML materials that simultaneously have the attributes of high brightness, low cost, self‐recovery, and stability, and the lack of appropriate designs for constructing ML devices represent significant challenges that remain to be addressed to boost the practical application of ML materials. Herein, ML hybrids derived from a natural source, waste eggshell, with the aforementioned attributes are demonstrated. The introduction of the eggshell not only enables the preparation of the hybrid in a simple and cost‐effective manner but also contributes to the homochromatism (red, green, or blue emission), high brightness, and robustness of the resultant ML hybrids. The significant properties of the ML hybrids, together with the proposed structural design, such as porosity or core–shell structure, could expedite a series of mechanic‐optical applications, including the self‐luminous shoes for the conversion of human motions into light and light generators that efficiently harvest water wave energy. The fascinating properties, versatile designs, and the efficient protocol of “turning waste into treasure” of the ML hybrids represent significant advances in ML materials, promising a leap to the practical applications of this flouring material family.

Background: Acupuncture and moxibustion have promising effects in managing primary dysmenorrhea. However, some evidence from clinical trials remains controversial due to methodological flaws in study designs that involve acupuncture and its related modalities and require urgent attention and dialogue. Methods: Allied and Complementary Medicine Database (AMED), Cochrane Library, Excerpta Medica database (EMBASE), PubMed, Web of Sciences, Chinese Biological Medicine (CBM), China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP), and Wanfang database were searched from their inception to July 2021. Data were extracted based on the types of study design, primary outcome measures, adverse events (AEs), and participants' subjective views. Results: Most studies (n = 282, 93 %) were published in Chinese and 21 (7 %) in English. Among these, there were 209 (69 %) randomized controlled trials (RCTs), 39 (13 %) non-randomized controlled trials (nRCTs), 30 (10 %) case-series reports, 15 (5 %) cohort studies, and 10 (3 %) case reports. The most frequent reported outcome was pain, followed by emotion, sleeping quality, quality of life, skin temperature, changes in brain function, uterine and ovarian blood flow, and reproductive endocrine level. AEs were reported in 37 studies with mild events, and all recovered without actions taken; 31 trials reported no AEs; 235 failed to report any AEs. One RCT found that the satisfaction rate of the intervention group was statistically significantly higher than the control group. Conclusion: Clinical studies on acupuncture and its related modalities face methodological challenges and require urgent attention. RCT with blinding and sham control might be the gold standard trial design. However, it may not be the most suitable research method for these modalities. We recommend using pragmatic RCTs in this field, where trial protocol registration on the trial registry platforms and detailed safety reporting should be mandatory.

Severe acute pancreatitis (SAP) is a critical illness characterized by a severe systemic inflammatory response resulting in persistent multiple organ failure and sepsis. The intestinal microbiome is increasingly appreciated to play a crucial role in modulation of AP disease outcome, but limited information is available about the identity and mechanism of action for specific commensal bacteria involved in AP-associated inflammation. Here we show that Bifidobacteria, particularly B. animalis, can protect against AP by regulating pancreatic and systemic inflammation in germ-free (GF) and oral antibiotic-treated (Abx) mouse models. Colonization by B. animalis and administration of its metabolite lactate protected Abx and GF mice from AP by reducing serum amylase concentration, ameliorating pancreatic lesions and improving survival rate after retrograde injection of sodium taurocholate. B. animalis relieved macrophage-associated local and systemic inflammation of AP in a TLR4/MyD88- and NLRP3/Caspase1-dependent manner through its metabolite lactate. Supporting our findings from the mouse study, clinical AP patients exhibited a decreased fecal abundance of Bifidobacteria that was inversely correlated with the severity of systemic inflammatory responses. These results may shed light on the heterogeneity of clinical outcomes and drive the development of more efficacious therapeutic interventions for AP, and potentially for other inflammatory disorders.

Macrophage polarization affects the progression of pathogenic bacterial infections. Lactobacillus is widely used to interact with macrophages and to exert specific immunomodulatory activities. In this study, we investigated the regulation of macrophage polarization against Salmonella enterica serotype Typhimurium (STM) by Lactobacillus plantarum JL01 (LP), to explore prevention and treatment strategies for salmonellosis. We assessed the in vitro differential polarization of RAW 264.7 macrophages and mouse bone marrow macrophages (BMMs) by LP against STM, by measuring protein and cytokine levels, and bactericidal activity. In addition, we assessed the protective effects of LP against STM by evaluating weight loss, survival, the burden of STM in tissues, the polarization of macrophages in the spleen and mesenteric lymph nodes (MLNs), intestinal histopathology, and cytokine production. LP slightly affected the polarization of RAW 264.7, a slight M1-skewing. LP promoted the RAW 264.7 bactericidal activity against STM. In BMMs, M1 polarization induced by LP was significantly lower than the M1-positive phenotype. The combination of LP with M1 synergistically improved M1 polarization and bactericidal activity against STM compared to the individual effects. LP promoted the activation of the NF-κB signaling pathway. Supplementation with the NF-κB inhibitor decreased M1 polarization induced by LP. We observed the protective effect of LP against STM in C57BL/6 mice, through a decrease in weight loss, mortality, STM burden in the liver, and promotion of macrophage M1 and M2 polarization in the spleen and MLNs; though M1 was higher, it did not cause inflammatory damage. In summary, LP can synergistically promote M1 polarization in combination with the M1 phenotype through the NF-κB signaling pathway and increases resistance against S. Typhimurium infection. These findings will lay the foundation for the prevention and treatment of S. Typhimurium infections in the future.