Occurrence and management of the emerging pathogen Epicoccum sorghinum.

Epicoccum sorghinum is a notorious fungal pathogen that causes leaf spot symptoms on a wide range of plants, leading to devastating losses in crop production and quality. Here, all reports regarding the occurrence and management of E. sorghinum are covered for the first time. E. sorghinum has been detected in tropical and subtropical climate areas during the rainy season, mainly from March to August, since 2016. Although E. sorghinum shows broad host spectrum, the disease incidence is especially notorious in cereal crops and ornamental plants, suggesting that these plants are especially susceptible. Control methods based on synthetic fungicides, plant extracts, and microbial biocontrol agents have been reported. However, most agents were applied using only in vitro conditions, restricting the information about their actual applicability in field conditions. Additionally, E. sorghinum can colonize cereal grains and synthesize the carcinogenic mycotoxin tenuazonic acid, posing an enormous hazard for human health. Furthermore, although E. sorghinum is an emerging pathogen that is currently causing yield penalties in important crops, there is lack of information about its pathogenic mechanisms and virulence factors, and there is currently no commercial antifungal agent to manage E. sorghinum. Collectively, it is imperative to conduct in vivo studies to determine the efficacy of antifungal agents and the most effective methods of application in order to develop suitable management strategies against E. sorghinum.

Psychometric properties of anxiety sensitivity Index-3 among Chinese college students and its preliminary application among this population experiencing campus lockdown.

PURPOSE: Anxiety sensitivity (AS) refers to fear of anxiety-related sensory arousal and has been revealed to be associated with increased psychological distress and mental problems. Although Anxiety Sensitivity Index-3 (ASI-3) has been confirmed to be effective in evaluating this construct, whether it is consistently applicable in college students is still elusive. The present study aimed to examine the psychometric properties and measurement invariance of Chinese version of ASI-3 (C-ASI-3) among college students experiencing campus lockdown due to novel coronavirus disease 2019 (COVID-19) pandemic. METHODS: A total of 1532 Chinese college students (397, 25.9% males) aged between 16 and 25 were included in this study. Confirmatory factor analysis (CFA) was used to verify the factor structure of C-ASI-3. Multi-group CFA was conducted for analysis of measurement invariance with regard to gender. McDonald's omega values were computed for examination of scale reliability. For criterion, convergent, and divergent validity, average variance extracted (AVE) values for C-ASI-3 subscales, difference between square root of AVE for each factor and inter-factor correlation, as well as pearson correlation and partial correlation between the C-ASI-3 and other three scales, including the Depression, Anxiety, and Stress Scale-21 (DASS-21), the State-Trait Anxiety Inventory (STAI), and the Fear of COVID-19 scale (FCV-19 S) were evaluated. RESULTS: The C-ASI-3 presented a three-factor scale structure with fit indices being as follows: χ2/df = 11.590, CFI = 0.938, RMSEA = 0.083, SRMR = 0.042. Strict measurement invariance was reached across gender. Regarding convergent validity, the C-ASI-3 had a high correlation with the DASS-21 (r = 0.597, p < 0.01) and the STAI (r = 0.504, p < 0.01). All AVE values for C-ASI-3 subscales were above 0.5. In terms of divergent validity, the C-ASI-3 had medium correlation with the FCV-19 S (r = 0.360, p < 0.01). Square of root of AVE for each factor was higher that inter-factor correlation. McDonald's omega values of the three dimensions ranged from 0.898 ~ 0.958. CONCLUSION: The C-ASI-3 has acceptable psychometric properties among college students. College students with different gender have consistent understanding on the scale construct.

Nanostructures and multi-scale aggregation of high ion exchange capacity short-side-chain perfluorosulfonic acid dispersion.

Short-side-chain perfluorosulfonic acid (SSC-PFSA) ionomers with high ion-exchange-capacity are promising candidates for high-temperature proton exchange membranes (PEMs) and catalyst layer (CL) binders. The solution-casting method determines the importance of SSC-PFSA dispersion characteristics in shaping the morphology of PEMs and CLs. Therefore, a thorough understanding of the chain behavior of SSC-PFSA in dispersions is essential for fabricating high-quality PEMs and CLs. In this study, we have employed multiple characterization techniques, including dynamic light scatting (DLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscope (Cryo-TEM), to fully study the chain aggregation behaviors of SSC-PFSA in water-ethanol solvents and elucidate the concentration-dependent self-assembly process. In dilute dispersions (2 mg/mL), SSC-PFSA assembles into mono-disperse rod-like aggregates, featuring a twisted fluorocarbon backbone that forms a hydrophobic stem, and the sulfonic acid side chains extending outward to suit the hydrophilic environment. As the concentration increases, the radius of rod particles increases from 1.47 to 1.81 nm, and the mono-disperse rod particles first form a "end-to-end" configuration that doubles length (10 mg/mL), and then transform into a swollen network structure in semi-dilute dispersion (20 mg/mL). This work provides a well-established structure model for SSC-PFSA dispersions, which is the key nanostructure to be inherited by PEMs.

The effect of emotion regulation strategies on nomophobia in college students: The masking role of resilience.

College students have a high prevalence of nomophobia. However, research on the effects of emotion regulation and resilience on nomophobia in China is lacking. This research investigated how cognitive reappraisal and expressive suppression strategies directly and indirectly affect nomophobia through resilience. Therefore, from March to May 2023, 756 university student volunteers (21.4 % men) were selected from a university in northeastern China for a questionnaire survey. Our findings suggest that college students' resilience has a masking effect on the relationship between cognitive reappraisal and nomophobia and can attenuate the negative effect of the frequency of using cognitive reappraisal strategies on nomophobia. The frequency of expressive suppression strategies directly and positively affected nomophobia. Early psychological interventions targeting resilience might be potentially effective in alleviating nomophobia among college students.

Biocontrol Methods for the Management of Sclerotinia sclerotiorum in Legumes: A Review.

Sclerotinia sclerotiorum is an economically damaging fungal pathogen that causes Sclerotinia stem rot in legumes, producing enormous yield losses. This pathogen is difficult to control due to its wide host spectrum and ability to produce sclerotia, which are resistant bodies that can remain active for long periods under harsh environmental conditions. Here, the biocontrol methods for the management of S. sclerotiorum in legumes are reviewed. Bacillus strains, which synthesized lipopeptides and volatile organic compounds, showed high efficacies in soybean plants, whereas the highest efficacies for the control of the pathogen in alfalfa and common bean were observed when using Coniothyrium minitans and Streptomyces spp., respectively. The biocontrol efficacies in fields were under 65%, highlighting the lack of strategies to achieve a complete control. Overall, although most studies involved extensive screenings using different biocontrol agent concentrations and application conditions, there is a lack of knowledge regarding the specific antifungal mechanisms, which limits the optimization of the reported methods.

Loop PDE of viral capsid protein is involved in immune escape of the emerging novel variant infectious bursal disease virus.

Infectious bursa disease (IBD) is an acute, highly contactable, lethal, immunosuppressive infectious disease caused by the Infectious bursa disease virus (IBDV). Currently, the emerged novel variant IBDV (nVarIBDV) and the sustainedly prevalent very virulent IBDV (vvIBDV) are the two most prevalent strains of IBDV in China. The antigenic properties of the two prevalent strains differed significantly, which led to the escape of nVarIBDV from the immune protection provided by the existing vvIBDV vaccine. However, the molecular basis of the nVarIBDV immune escape remains unclear. In this study, we demonstrated, for the first time, that residues 252, 254, and 256 in the PDE of VP2 are involved in the immune escape of the emerging nVarIBDV. Firstly, the IFA-mediated antigen-antibody affinity assay showed that PBC and PDE of VP2 could affect the affinity of vvIBDV antiserum to VP2, of which PDE was more significant. The key amino acids of PDE influencing the antigen-antibody affinity were also identified, with G254N being the most significant, followed by V252I and I256V. Then the mutated virus with point or combined mutations was rescued by reverse genetics. it was further demonstrated that mutations of V252I, G254N, and I256V in PDE could individually or collaboratively reduce antigen-antibody affinity and interfere with antiserum neutralization, with G254N being the most significant. This study revealed the reasons for the widespread prevalence of nVarIBDV in immunized chicken flocks and provided innovative ideas for designing novel vaccines that match the antigen of the epidemic strain.

OASL suppresses infectious bursal disease virus replication by targeting VP2 for degrading through the autophagy pathway.

Infectious bursal disease (IBD) is an acute and fatal immunosuppressive disease caused by infectious bursal disease virus (IBDV). As an obligate intracellular parasite, IBDV infection is strictly regulated by host factors. Knowledge on the antiviral activity and possible mechanism of host factors might provide the theoretical basis for the prevention and control of IBD. In this study, RNA-sequencing results indicated that many host factors were induced by IBDV infection, among which the expression levels of OASL (2´,5´-oligadenylate synthetase-like protein) was significantly upregulated. OASL overexpression significantly inhibited IBDV replication, whereas OASL knockdown promoted IBDV replication. Interestingly, the antiviral ability of OASL was independent of its canonical enzymatic activity, i.e., OASL targeted viral protein VP2 for degradation, depending on the autophagy receptor p62/SQSTM1 in the autophagy pathway. Additionally, the 316 lysine (K) of VP2 was the key site for autophagy degradation, and its replacement with arginine disrupted VP2 degradation induced by OASL and enhanced IBDV replication. Importantly, our results for the first time indicate a unique and potent defense mechanism of OASL against double-stranded RNA virus by interaction with viral proteins, which leads to their degradation. IMPORTANCE: OASL (2´,5´-oligadenylate synthetase-like protein) exhibits broad-spectrum antiviral effects against single-stranded RNA viruses in mammals, potentially serving as a promising target for novel antiviral strategies. However, its role in inhibiting the replication of double-stranded RNA viruses (dsRNA viruses), such as infectious bursal disease virus (IBDV), in avian species remains unclear. Our findings indicated a unique and potent defense mechanism of OASL against dsRNA viruses. It has been previously shown in mammals that OASL inhibits virus replication through increasing interferon production. The groundbreaking aspect of our study is the finding that OASL has the ability to interact with IBDV viral protein VP2 and target it for degradation and thus exerts its antiviral effect. Our results reveal the interaction between avian natural antiviral immune response and IBDV infection. Our study not only enhances our understanding of bird defenses against viral infections but can also inform strategies for poultry disease management.

The first reported pulmonary nocardiosis caused by Nocardia gipuzkoensis resisted to trimethoprim/sulfamethoxazol (TMP-SMZ) in an immunocompetent patient.

OBJECTIVES: Nocardia gipuzkoensis was first described as a novel and distinct species in 2020 by Imen Nouioui and pulmonary nocardiosis associated with N. gipuzkoensis was once reported in two bronchiectasis patients. Noteworthy, both reported N. gipuzkoensis cases showed sensitivity to trimethoprim/sulfamethoxazol (TMP-SMZ), which are usually recommended for empirical therapy. METHODS: We reported the third case of N. gipuzkoensis infection in a 16-year-old girl with chief complaints of cough and persistent chest and back pain. No underlying immuno-suppressive conditions and glucocorticoid use was revealed. Patchy lesions next to the spine and located in the posterior basal segment of the lower lobes of the left lung were seen in thorax computed tomography (CT), but no pathogenic bacteria were detected according to routine laboratory testings. RESULTS: Metagenomic next-generation sequencing (mNGS) combined with whole-genome sequencing (WGS) was used to classified our isolate from bronchoalveolar lavage fluid (BALF) as N. gipuzkoensis. It is worth mentioning that drug susceptibility testing of our isolate showed resistance to TMP-SMZ, which was never reported before. The patient improved remarkably both clinically and radiographically according to the treatment with imipenem-cilastatin infusion alone. CONCLUSION: mNGS and WGS showed excellent performance in identifying the Nocardia genus to the species level and improving the detection rate of N. gipuzkoensis ignored by traditional culture. Different from previously reported cases, the N. gipuzkoensis infection case showed resistance to TMP-SMZ, which is an unprecedented finding and a crucial addition to our understanding of the antibacterial spectrum of N. gipuzkoensis. The successful treatment with imipenem-cilastatin infusion alone in this case is a testament to the importance of precise identification and tailored antibiotic therapy.

N123I mutation in the ALV-J receptor-binding domain region enhances viral replication ability by increasing the binding affinity with chNHE1.

The subgroup J avian leukosis virus (ALV-J), a retrovirus, uses its gp85 protein to bind to the receptor, the chicken sodium hydrogen exchanger isoform 1 (chNHE1), facilitating viral invasion. ALV-J is the main epidemic subgroup and shows noteworthy mutations within the receptor-binding domain (RBD) region of gp85, especially in ALV-J layer strains in China. However, the implications of these mutations on viral replication and transmission remain elusive. In this study, the ALV-J layer strain JL08CH3-1 exhibited a more robust replication ability than the prototype strain HPRS103, which is related to variations in the gp85 protein. Notably, the gp85 of JL08CH3-1 demonstrated a heightened binding capacity to chNHE1 compared to HPRS103-gp85 binding. Furthermore, we showed that the specific N123I mutation within gp85 contributed to the enhanced binding capacity of the gp85 protein to chNHE1. Structural analysis indicated that the N123I mutation primarily enhanced the stability of gp85, expanded the interaction interface, and increased the number of hydrogen bonds at the interaction interface to increase the binding capacity between gp85 and chNHE1. We found that the N123I mutation not only improved the viral replication ability of ALV-J but also promoted viral shedding in vivo. These comprehensive data underscore the notion that the N123I mutation increases receptor binding and intensifies viral replication.

G-site residue S67 is involved in the fungicide-degrading activity of a tau class glutathione S-transferase from Carica papaya.

Thiram is a toxic fungicide extensively used for the management of pathogens in fruits. Although it is known that thiram degrades in plant tissues, the key enzymes involved in this process remain unexplored. In this study, we report that a tau class glutathione S-transferase (GST) from Carica papaya can degrade thiram. This enzyme was easily obtained by heterologous expression in Escherichia coli, showed low promiscuity toward other thiuram disulfides, and catalyzed thiram degradation under physiological reaction conditions. Site-directed mutagenesis indicated that G-site residue S67 shows a key influence for the enzymatic activity toward thiram, while mutation of residue S13, which reduced the GSH oxidase activity, did not significantly affect the thiram-degrading activity. The formation of dimethyl dithiocarbamate, which was subsequently converted into carbon disulfide, and dimethyl dithiocarbamoylsulfenic acid as the thiram degradation products suggested that thiram undergoes an alkaline hydrolysis that involves the rupture of the disulfide bond. Application of the GST selective inhibitor 4-chloro-7-nitro-2,1,3-benzoxadiazole reduced papaya peel thiram-degrading activity by 95%, indicating that this is the main degradation route of thiram in papaya. GST from Carica papaya also catalyzed the degradation of the fungicides chlorothalonil and thiabendazole, with residue S67 showing again a key influence for the enzymatic activity. These results fill an important knowledge gap in understanding the catalytic promiscuity of plant GSTs and reveal new insights into the fate and degradation products of thiram in fruits.

Novel variations in TENT5D lead to teratozoospermia in infertile patients.

PURPOSE: Teratozoospermia is the main pathogenic factor of male infertility. However, the genetic etiology of teratozoospermia is largely unknown. This study aims to clarify the relationship between novel variations in TENT5D and teratozoospermia in infertile patients. MATERIALS AND METHODS: Two infertile patients were enrolled. Routine semen analysis of patients and normal controls was conducted with the WHO guidelines. Whole-exome sequencing (WES) was conducted to identify pathogenic variants in the two patients. Morphology and ultrastructure analysis of spermatozoa in the two patients was determined by Papanicolaou staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The functional effect of the identified variants was analyzed by immunofluorescence staining and western blotting. The expression of TENT5D in different germ cells was detected by immunofluorescence staining. RESULTS: Two new hemizygous variations, c.101C > T (p.P34L) and c.125A > T (p.D42V), in TENT5D were detected in two patients with male infertility. Morphology analysis showed abnormalities in spermatozoa morphology in the two patients, including multiple heads, headless, multiple tails, coiled, and/or bent flagella. Ultrastructure analysis showed that most of the spermatozoa exhibited missing or irregularly arranged '9+2' structures. Further functional experiments confirmed the abrogated TENT5D protein expression in patients. In addition, both p.P34L and p.D42V substitutions resulted in a conformational change of the TENT5D protein. We precisely analyzed the subcellular localization of TENT5D in germ cells in humans and mice. And we found that TENT5D was predominantly detected in the head and flagellum of elongating spermatids and epididymal spermatozoa. CONCLUSIONS: Our results showed further evidence of a relationship between TENT5D mutation and human male infertility, providing new genetic insight for use in the diagnosis and treatment of male infertility.

First Report of Penicillium oxalicum Causing Leaf Blight on 'Hongyang' Kiwifruit in China.

In September 2022, leaf blight symptoms (Fig. 1) were detected on six-year-old kiwi trees (Actinidia chinensis cv. 'Hongyang') in Xuzhou municipality (117.29º E, 34.23º N), Jiangsu Province. Early-stage disease symptoms included light brown necrotic lesions of irregular shape ranging in length from 0.2 to 2.4 cm, which turned into leaf blight after approximately 2 weeks. Those symptoms were similar to those previously reported during a Pestalotiopsis sp. infection on kiwi trees in Turkey (Karakaya 2001). Approximately 20% of the leaves from 300 trees examined in one kiwi orchard, 3000 m2 in size, showed the disease symptoms. Ten leading edges of symptomatic leaves were sterilized with 2% sodium hypochlorite for 1 min, rinsed twice with sterile ddH2O and cultured at 26ºC for 3 days on PDA medium containing 50 µg/ml chloramphenicol. The fungal colonies were collected, and the single spore isolation method was used to obtain four isolates. The obtained isolates showed white aerial mycelia that turned greyish after 2 days of cultivation on PDA medium at 26ºC. ITS (OR054113, OR054153-OR054155), TUB2 (OR060951-OR060953, OR249978), and CMD (OR255947-OR255950) genes were amplified using the ITS1/ITS4, BT2a/BT2b and CMD5/CMD6 primers, respectively (Visagie et al. 2014a). The obtained ITS, TUB2, and CMD sequences shared 99.81%-100%, 96.72%-96.96%, and 90.17%-92.58% homology compared to the ex-type strain P. oxalicum CBS 219.30 (MH855125, KF296462, and KF296367), while the obtained ITS and TUB2 sequences showed 99.62%-99.81%, and 96.46%-96.72% identity compared to the representative strain P. oxalicum DTO 179B9 (KJ775647 and KJ775140) (Visagie et al. 2014b). The sequences obtained also showed high homology compared to P. oxalicum HP7-1 (ITS: 99.81%-100% homology; TUB2: 98.98%-99.38% homology; CMD: 94.71%-95.10% homology) (Li et al. 2022). A molecular phylogenetic tree was constructed using MEGA X with representative Penicillium strains retrieved from GenBank (Fig. 2). Microscope observations revealed the presence of curved septate hyphae. Conidia were colorless, unicellular, and ellipsoidal (5-8 µm in length; > 2000 observations), whereas conidiophores were mainly monoverticillate (approximately 20% of the conidiophores were biverticillate) (50-70 µm in length; 43 observations) and contained cylindrical phialides (13-15 µm in length). These findings are consistent with P. oxalicum morphology (Wu et al. 2022; Zheng et al. 2023). The pathogenicity of the four isolates was screened using healthy non-detached 'Hongyang' kiwi leaves. Fifteen leaves from five different two-month-old trees were used for each isolate, with three repetitions. For inoculation, a 10 mL solution containing 1 × 106 spores/mL was sprayed on the leaves. Sterilized water was used in the control experiment, which was carried out using fifteen leaves from five different two-month-old trees, with three repetitions. Inoculated trees were stored at 26ºC and 60% relative humidity for 2 days. All the infected leaves had necrotic lesions and leaf blight symptoms comparable to those found in the field, but the control leaves had no lesions. The pathogen was recovered, and its identity was confirmed by ITS sequencing and morphology analysis, fulfilling Koch's postulates. P. oxalicum is a common cause of blue mould in postharvest fruits (Tang et al. 2020). P. oxalicum has been recently reported as the causal agent of leaf spot in pineapple (Wu et al. 2022; Zheng et al. 2023), and leaf blight on maize (Han et al. 2023). Although Alternaria sp., Glomerella cingulate, Pestalotiopsis sp., Phomopsis sp., and Phoma sp. were previously isolated from kiwi leaves with blight symptoms (Kim et al. 2017), this is the first report of P. oxalicum causing leaf blight on kiwi trees worldwide. P. oxalicum is a well-known source of mycotoxins, such as secalonic acid (Otero et al. 2020), indicating that its presence in kiwifruit orchards may pose a significant risk to human health. The discovery of this hazardous pathogen in kiwi trees must drive the development of management strategies. Kiwifruit is an important dietary source of vitamins, fiber, folate, and potassium, and China is the major producer of kiwifruit, with more than 1.2 million metric tons harvested in 2021. This report will help to generate a better understanding of the pathogens affecting kiwifruit orchards in China.

Risk factors, outcomes, and epidemiological and etiological study of hospitalized COVID-19 patients with bacterial co-infection and secondary infections.

BACKGROUND: As a common complication of viral respiratory tract infection, bacterial infection was associated with higher mortality and morbidity. Determining the prevalence, culprit pathogens, outcomes, and risk factors of co-infection and secondary infection occurring in hospitalized patients with coronavirus disease 2019 (COVID-19) will be beneficial for better antibiotic management. METHODS: In this retrospective cohort research, we assessed clinical characteristics, laboratory parameters, microbiologic results, and outcomes of laboratory-confirmed COVID-19 patients with bacterial co-infection and secondary infection in West China Hospital from 2022 December 2nd to 2023 March 15th. RESULTS: The incidence of bacterial co-infection and secondary infection, as defined by positive culture results of clinical specimens, was 16.3% (178/1091) and 10.1% (110/1091) respectively among 1091 patients. Acinetobacter, Klebsiella, and Pseudomonas were the most commonly identified bacteria in respiratory tract samples of COVID-19 patients. In-hospital mortality of COVID-19 patients with co-infection (17.4% vs 9.5%, p = 0.003) and secondary infection (28.2% vs 9.5%, p < 0.001) greatly exceeded that of COVID-19 patients without bacterial infection. Cardiovascular disease (1.847 (1.202-2.837), p = 0.005), severe COVID-19 (1.694 (1.033-2.778), p = 0.037), and critical COVID-19 (2.220 (1.196-4.121), p = 0.012) were proved to be risk factors for bacterial co-infection, while only critical COVID-19 (1.847 (1.202-2.837), p = 0.005) was closely related to secondary infection. CONCLUSIONS: Bacterial co-infection and secondary infection could aggravate the disease severity and worsen clinical outcomes of COVID-19 patients. Notably, only critical COVID-19 subtype was proved to be an independent risk factor for both co-infection and secondary infection. Therefore, standard empirical antibiotics was recommended for critically ill COVID-19 rather than all the inpatients according to our research.

Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner.

Viruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of host genes. During infection, viruses encode proteins with shutoff activity to globally inhibit host protein synthesis, which is an effective strategy for immune evasion. In this study, compelling evidence shows that infectious bursal disease virus (IBDV) infection triggers the suppression of host protein synthesis. Furthermore, using both in vitro and in vivo viral infection models, we have identified that IBDV specifically impedes the transcription of host genes via the shutoff activity of viral VP5, simultaneously conferring advantages to IBDV infection in these circumstances. The proposed mechanism suggests that VP5 competitively binds to RanBP1, disrupting the RanGDP/GTP gradient. This disruption interferes with cellular nucleocytoplasmic transport, impairing the nuclear import of proteins bearing nuclear localization signals. The nuclear transport of pivotal transcriptional regulatory factors, such as p65 and IFN regulatory factor 7, is also compromised, leading to the inhibition of pro-inflammatory cytokines and interferon expression. This newly discovered strategy employed by IBDV enables them to manipulate host gene expression, providing novel insights into how viruses evade host immune responses and establish infections.IMPORTANCEViruses manipulate host processes at various levels to regulate or evade both innate and adaptive immune responses, promoting self-survival and efficient transmission. The "host shutoff," a global suppression of host gene expression mediated by various viruses, is considered a critical mechanism for evading immunity. In this study, we have validated the presence of host shutoff during infectious bursal disease virus (IBDV) infection and additionally uncovered that the viral protein VP5 plays a pivotal role in inhibiting the overall synthesis of host proteins, including cytokines, through a transcription-dependent pathway. VP5 competitively binds with RanBP1, leading to disruption of the Ran protein cycle and consequently interfering with nucleocytoplasmic transport, which ultimately results in the suppression of host gene transcription. These findings unveil a novel strategy employed by IBDV to evade host innate immunity and rapidly establish infection. This study also suggests a novel supplement to understanding the pathway through which viruses inhibit host protein synthesis.

Prognostic Value of the Glasgow Prognostic Score in Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Meta-Analysis.

BACKGROUND: The Glasgow Prognostic Score (GPS) has proven to be a good biomarker for lung cancer prognosis. However, its usefulness in lung cancer patients receiving checkpoint inhibitor immunotherapy remains controversial. Therefore, we performed a meta-analysis to explore the prognostic value of the GPS in non-small cell lung cancer patients receiving immunotherapy. METHODS: PubMed, Web of Science, Scopus, and Embase were systematically searched for relevant studies up to May 31, 2023, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were merged to investigate the prognostic value of the GPS for overall survival (OS) and progression-free survival (PFS). RESULTS: Seven studies comprising 833 patients were included in the primary analysis, and the pooled results indicated that a higher baseline GPS was associated with poorer OS and PFS in non-small cell lung cancer patients treated with immune checkpoint inhibitors (ICIs) (OS: HR = 1.95, 95% CI: 1.47-2.58, p < 0.01; PFS: HR = 1.63, 95% CI: 1.26-2.11, p < 0.01). These findings were robust after subgroup and sensitivity analyses. CONCLUSIONS: The GPS can serve as a biomarker in non-small cell lung cancer patients receiving immunotherapy with significant prognostic value; however, these findings require more prospective evidence for validation.

Antifungal and elicitor activities of p-hydroxybenzoic acid for the control of aflatoxigenic Aspergillus flavus in kiwifruit.

Aspergillus flavus not only reduces kiwifruit production but also synthesizes carcinogenic aflatoxins, resulting in a relevant threat to human health. p-Hydroxybenzoic acid (pHBA) is one of the most abundant phenolics in kiwifruit. In this study, pHBA was found to reduce A. flavus mycelial growth by blocking the fungal mitotic exit network (MEN) and cytokinesis and to inhibit the biosynthesis of aflatoxins B1 and B2. The application of pHBA promoted the accumulation of endogenous pHBA and induced oxidative stress in A. flavus-infected kiwifruit, resulting in an increase in H2O2 content and catalase (CAT) and superoxide dismutase (SOD) activities. Preventive and curative treatments with 5 mM pHBA reduced A. flavus advancement by 46.1% and 68.0%, respectively. Collectively, the antifungal and elicitor properties of pHBA were examined for the first time, revealing new insights into the role of pHBA in the defense response of kiwifruit against A. flavus infection.

Association between pretreatment C-reactive protein level and survival in non-small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.

BACKGROUND: Current evidence suggests that C-reactive protein (CRP) levels may affect cancer prognosis. However, the effect of CRP has not been validated in immunotherapy recipients with non-small cell lung cancer (NSCLC). Therefore, we performed a meta-analysis to explore the prognostic value of CRP level in patients with NSCLC treated with immune checkpoint inhibitors. METHODS: PubMed, Web of Science, Embase, and Scopus databases were systematically retrieved for eligible publications, and hazard ratios (HRs) with corresponding 95% confidence intervals (95%CIs) were extracted and merged to evaluate the correlation between pretreatment CRP levels and overall survival (OS) and progression-free survival (PFS). Subgroup and sensitivity analyses were conducted to confirm these findings. RESULTS: Thirty-five cohorts consisting of 4698 patients were included in the primary analysis. Pooled results demonstrated that a higher pretreatment CRP level is associated with worse OS and PFS (OS: HR = 1.13, 95 %CI:1.09-1.18; PFS: HR = 1.16, 95 %CI:1.10-1.22). These findings remained robust after further statistical analyses. CONCLUSION: Pretreatment CRP level could be a promising biomarker for NSCLC immunotherapy. However, prospective studies are required to validate these findings.

Enterococcus faecium C171: Modulating the Immune Response to Acute Lethal Viral Challenge.

Commensal bacteria modulate acute immune responses to infection in hosts. In this study, Enterococcus faecium C171 was screened and isolated. This strain has similar basic characteristics to the reference probiotic, including strong anti-inflammatory and anti-infective effects. E. faecium C171 inhibits the production of pro-Caspase-1 and significantly reduces the production of interleukin-1ß (IL-1ß) in vitro. These reactions were confirmed using the Transwell system. Live E. faecium C171 mainly exerted an inhibitory effect on acute inflammation, whereas the anti-infective and immune-activating effects were primarily mediated by the E. faecium C171-produced bacterial extracellular vesicles (Efm-C171-BEVs). Furthermore, in the specific pathogen-free (SPF) chicken model, oral administration of E. faecium C171 increased the relative abundance of beneficial microbiota (Enterococcus and Lactobacillus), particularly Enterococcus, the most important functional bacteria of the gut microbiota. E. faecium C171 significantly inhibited the acute inflammatory response induced by a highly virulent infectious disease, and reduced mortality in SPF chickens by 75%. In addition, E. faecium C171 induced high levels of CD3+, CD4-, and CD8- immunoregulatory cells and CD8+ killer T cells, and significantly improved the proliferative activity of T cells in peripheral blood mononuclear cells, and the secretion of interferon-γ. These findings indicate that E. faecium C171 and Efm-C171-BEVs are promising candidates for adjuvant treatment of acute inflammatory diseases and acute viral infections.

A Novel Variant of Avian Reovirus Is Pathogenic to Vaccinated Chickens.

Avian reovirus (ARV) infections, characterized by severe arthritis, tenosynovitis, pericarditis, and poor weight gain, have become increasingly serious in recent years. The economic impact is significant as it causes growth inhibition and immunosuppression. Some commercial poultry in China have been widely vaccinated with available ARV vaccines; however, infections continue to occur even after vaccination. This study aimed to isolate a novel variant, ARV-SD19/11103, from the joint tissues of infected broiler chickens vaccinated with ARV vaccines in Shandong Province. Genetic evolution analysis of the major protective antigen σC gene in ARVs showed that ARV-SD19/11103 was located in the genotype cluster I but not in the same sub-cluster as the S1133 vaccine strain. The amino acid sequence similarity between SD19/11103 and vaccine strains S1133, 1733, and 2408 was <80%. After analyzing the amino acid sequences of the σC protein, 33 amino acid differences were found between the new variant isolate and the vaccine strains. This novel variant showed obvious pathogenicity in specific pathogen-free chicken embryos and chicks and could cause serious disease in chickens vaccinated with commercially available ARV vaccines. Cross-neutralization experiments further demonstrated a significant antigenic difference between the novel variant and genotype cluster I ARV strains. The novel variant strain isolated in this study provides an important theoretical basis for understanding the prevalence and genetic evolutionary characteristics of ARV variant strains in our country. This study identified the causes of ARVs circulating and emphasizes the needs for developing new vaccines against novel ARV variants.

Single-cell transcriptome analysis reveals cellular and molecular alterations in small cell lung cancer tumors following chemotherapy.

Chemotherapy is the standard therapy for small cell lung cancer (SCLC), but relapse is common and the 2-year survival rate remains low. Given the contribution of the tumor microenvironment (TME) to cancer development and response to treatment, we analyzed here how chemotherapy alters the TME in SCLC using single-cell RNA sequencing. The comparison between neuroendocrine cells and other epithelial cells in five chemotherapy-naive patients identified upregulation of Notch-inhibiting genes, such as DLL3 and HES6. Analysis of genes differentially expressed between five patients receiving chemotherapy and five treatment-naive patients in cells in the TME showed that chemotherapy promoted antigen presentation and senescence in neuroendocrine cells, upregulated ID1 to enhance angiogenic activities of stalk-like endothelial cells and strengthened vascular endothelial growth factor signaling in lymphatic endothelial cells. Chemotherapy also promoted the remodeling of extracellular matrix by fibroblasts and upregulated interferon-mediated antitumor immune responses by B and T cells. Our single-cell transcriptome analysis provides insights into how chemotherapy affects the TME in SCLC, which may guide efforts to make therapy more effective.