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Abstract Background Currently, the synthesis of compounds based on microbial cell factories is rapidly advancing, yet it encounters several challenges. During the production process, engineered strains frequently encounter disturbances in the cultivation environment or the impact of their metabolites, such as high temperature, acid-base imbalances, hypertonicity, organic solvents, toxic byproducts, and mechanical damage. These stress factors can constrain the efficiency of microbial fermentation, resulting in slow cell growth, decreased production, significantly increased energy consumption, and other issues that severely limit the application of microbial cell factories. Results This study demonstrated that sterol engineering in Kluyveromyces marxianus, achieved by overexpressing or deleting the coding genes for the last five steps of ergosterol synthase (Erg2-Erg6), altered the composition and ratio of sterols in its cell membrane, and affected its multiple tolerance. The results suggest that the knockout of the Erg5 can enhance the thermotolerance of K. marxianus, while the overexpression of the Erg4 can improve its acid tolerance. Additionally, engineering strain overexpressed Erg6 improved its tolerance to elevated temperature, hypertonic, and acid. YZB453, obtained by overexpressing Erg6 in an engineering strain with high efficiency in synthesizing xylitol, produced 101.22 g/L xylitol at 45oC and 75.11 g/L xylitol at 46oC. Using corncob hydrolysate for simultaneous saccharification and fermentation (SSF) at 46oC that xylose released from corncob hydrolysate by saccharification with hemicellulase, YZB453 can produce 45.98 g/L of xylitol, saving 53.72% of the cost of hemicellulase compared to 42oC. Conclusions This study elucidates the mechanism by which K. marxianus acquires resistance to various antifungal drugs, high temperatures, high osmolarity, acidity, and other stressors, through alterations in the composition and ratio of membrane sterols. By employing sterol engineering, the fermentation temperature of this unconventional thermotolerant K. marxianus was further elevated, ultimately providing an efficient platform for synthesizing high-value-added xylitol from biomass via the SSF process at temperatures exceeding 45 °C.

Abstract Background Hylurgus ligniperda (Coleoptera: Curculionidae) is a worldwide forest quarantine pest. It is widely distributed, has many host tree species, and possesses strong adaptability. To explore its environmental adaptability and the related molecular mechanisms, we conducted chromosome-level genome sequencing and analyzed the transcriptome under different environmental factors, identifying key expressed genes. Results We employed PacBio, Illumina, and Hi-C sequencing techniques to assemble a 520 Mb chromosomal-level genome of H. ligniperda, obtaining an N50 of 39.97 Mb across 138 scaffolds. A total of 10,765 protein-coding genes were annotated after repeat masking. Fourteen chromosomes were identified, among which Hyli14 was determined to be the sex chromosome. Survival statistics were tested over various growth periods under high temperature and low humidity conditions. The maximum survival period of adults reached 292 days at 25 °C, 65% relative humidity. In comparison, the maximum survival period was 14 days under 35 °C, 65% relative humidity, and 106 days under 25°C, 40% relative humidity. This indicated that environmental stress conditions significantly reduced adults' survival period. We further conducted transcriptome analysis to screen for potentially influential differentially expressed genes, such as CYP450 and Histone. Subsequently, we performed gene family analysis to gain insights into their functions and interactions, such as CYP450 and Histone. CYP450 genes affected the detoxification metabolism of enzymes in the Cytochrome P450 pathway to adapt to different environments. Histone genes are involved in insect hormone biosynthesis and longevity-regulating pathways in H. ligniperda to adapt to environmental stress. Conclusions The genome at the chromosome level of H. ligniperda was assembled for the first time. The mortality of H. ligniperda increased significantly at 35 ℃, 65% RH, and 25 ℃, 40% RH. CYP450 and Histone genes played an important role in response to environmental stress. This genome offers a substantial genetic resource for investigating the molecular mechanisms behind beetle invasion and spread.

Objective: This study aimed to develop and evaluate a novel software tool for robust analysis of the Visually Enhanced Vestibular-Ocular Reflex (VVOR) and video head impulse test (vHIT) saccades. Methods: A retrospective study was conducted on 94 patients with Meniere's Disease (MD), unilateral vestibular hypofunction (UVH), and vestibular migraine (VM). The MATLAB-based VVOR Analysis System and Saccades All in One software were utilized for data processing. New techniques, VVOR_diff and VVOR_cycle, were deployed for saccade parameter extraction. Results: Saccade incidence rates, examined through vHIT, VVOR_diff, and VVOR_cycle, exhibited distinct patterns in MD, UVH, and VM patients. Frequent instances of multiple saccades within a single cycle were noted on the affected side in MD and UVH patients. Statistically significant differences in saccade gain and incidence rates between the affected and unaffected sides were evident in MD and UVH patients. Notably, high inter-method and intra-method correlations suggested consistency across different methods and potential interactions within one. Conclusion: The software proved effective in extracting saccades and reducing noise in VVOR data, thereby enhancing the evaluation of vestibular function and potentially improving diagnostic accuracy for vestibular disorders.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets epithelial cells in the respiratory tract, triggering an acute proinflammatory response and chronic lung inflammation. Probiotic supplementation has shown promise in reducing the nasopharyngeal SARS-CoV-2 viral load, diminishing symptom frequency and duration, and mitigating inflammation; thus, it is a potential strategy for treating coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 infection. In this study, we evaluated the effects of the oral administration of the Lactobacillus plantarum GUANKE strain, a gram-positive bacterium originally isolated from a healthy individual, on SARS-CoV-2 infection in a human ACE2 transgenic mouse model. We found that GUANKE significantly reduced inflammatory cell infiltration and pulmonary interstitial exudation in mice. The transcription of CCL2, TNFA, IL1B, IL6, and IL17C in the lungs was reduced. The protein levels of TNF-α, IL-1β, IL-6, and IL-17 in the lungs were significantly lower in GUANKE-treated mice than in control mice. The viral load in GUANKE-treated mice was lower than that in saline-treated mice, although this difference did not reach statistical significance. L. plantarum GUANKE can decrease SARS-CoV-2-induced lung inflammation in mice, suggesting its potential for use as an agent for treating SARS-CoV-2 infection.IMPORTANCEMost otherwise healthy individuals develop only mild or moderate symptoms of coronavirus disease 2019 (COVID-19) caused by current strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and virus replication is mainly confined to the upper respiratory tract; however, the virus can infect the lower respiratory tract and promote inflammation. Probiotic supplementation has been shown to reduce nasopharyngeal SARS-CoV-2 viral load, reduce the overall number and duration of symptoms, and attenuate inflammation in clinical trials. We showed that a novel L. plantarum GUANKE strain alleviated SARS-CoV-2-induced pneumonia in mice. The transcription and production of inflammatory cytokines were suppressed, and GUANKE moderately reduced the viral load. L. plantarum GUANKE has the potential to become a candidate drug for the treatment of COVID-19 or other viral respiratory infections.

Intelligent packaging film has received more and more attention because it can help consumers obtain more intuitive information about the packaging, provide better preservation and advanced convenience. In this study, black rice anthocyanin (BRA) was added into composite film formed by starch (S) and esterified starch (ES). As the BRA content increased, the thickness and the total color difference of the S/ES-BRA film increased. The opacity of S/ES-BRA film decreased relative to that of the film without BRA, but increased with the increase of anthocyanin. Compared with S/ES film, the elongation at break of S/ES-BRA0.5 film increased from 33.1 % to 45.4 %, and the tensile strength decreased from 7.3 to 5.8 MPa. S/ES-BRA film had response to different pH values and underwent color changes in different buffer solutions. Intelligent color changing packaging film will used to monitor food quality, water quality and soil properties.

Abstract Nucleic acid tests are essential for the accurate diagnosis and control of infectious diseases. However, current assays are not easily scalable for a large population, due to the requirement of laboratory settings or special equipment. Here, we developed an integrated box for instant nucleic acid screening which fully integrates nucleic acid release, amplification, and results visualization for self-service standalone test. Importantly, the operation of the box runs on a novel gamepad-like interface, which allows deployment of the box in home settings and operation by users without any prior professional training. The performance of the box is empowered by an RNA extraction-free sample inactivation process and nested recombinase polymerase amplification chemistry and exhibits sensitivity comparable to reverse transcription-quantitative polymerase chain reaction with high specificity for severe acute respiratory syndrome coronavirus 2 RNA in a reaction time of 30 minutes directly from fresh swab sample to results. These innovations make the box a novel platform for a convenient, accurate, and deployable point-of-care testing scheme.

Abstract Background Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. Methods We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. Results The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. Conclusion Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

Abstract Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT.

Extracellular vesicles (EVs) play an important role in normal life activities and disease treatment. In recent years, there have been abundant relevant studies focusing on EVs for cancer therapy and showing good performance on tumor inhibition. To enhance the effectiveness of EVs, EV analogs have been developed. This review summarizes the classification, origin, production, purification, modification, drug loading and cancer treatment applications of EVs and their analogs. Also, the characteristics of technologies involved are analyzed, which provides the basis for the development and application of biogenic vesicle-based drug delivery platform for cancer therapy. Meanwhile, challenges in translating these vesicles into clinic, such as limited sources, lack of production standards, and insufficient targeting and effectiveness are discussed. With ongoing exploration and clinical studies, EV-based drugs will make great contributions to cancer therapy.

Invasive Emerald Ash Borer (EAB) damage pose significant challenges for sustainable forest management, necessitating accurate mapping of damaged ash trees. Traditional change detection methods, using time-series imagery, are essential for monitoring forest disturbances but complicated by abnormal fluctuations in original time-series features. Tree phenology also complicates this process by masking the reflectance characteristics indicative of EAB infestation. To address these challenges, we propose an improved change detection method integrating patterns from host tree phenology and EAB life history. This improved method includes: (1) select the indices with time stability to enhance detection reliability by partial least squares method (PLS); (2) correction on negative change values before and positive change values after the phenological peak based on known patterns of tree phenology and EAB life history. Result confirms that this method effectively reflects the seasonal growth and decline dynamics of ash trees, revealing the impacts of phenology and EAB infestation. EAB-damaged trees exhibited slower growth in May and premature decline in July compared with healthy tree, with the damage severity influencing the rate of leaf decline. This proposed method achieved an overall accuracy of 53.4%-76.7% across different months for ash trees with health, light and severe damage. This study highlights the capabilities of integrating pest life history and phenology in change detection method and provide a new method to monitor individual tree health across large areas by high-resolution satellite imagery.

Abstract The climate commitment to achieving carbon neutrality before 2060 in China has been announced recently. In the context of pursuing carbon neutrality, sharing similar sources as greenhouse gases, aerosol particle and precursor emissions are projected to substantially decrease in China, which can potentially have a great impact on climate. Here, we investigate the effects of future aerosol reductions, because of achieving carbon neutrality, on solar and wind energy in China by using an earth system model. We show that significant reductions in aerosol emissions, particularly in eastern China, lead to increases in the surface downwelling shortwave radiation, surface air temperature and wind speed, which can further enhance the potential of solar and wind energy production. The findings underline that the pursuit of carbon neutrality can yield co‐benefits of not only mitigating climate change and air pollution but also fortifying the stability of renewable energy sources.

In northeast China, the invasive woodwasp., Sirex noctilio, attacks Pinus sylvestris var. mongolica Litv and often shares habitat with native Sirex nitobei. Previous research showed that S. noctilio can utilize the volatiles from its symbiotic fungus (A. areolatum IGS-BD) to locate host trees. Consequently, symbiotic fungi (A. areolatum IGS-D and A. chailletii) carried by S. nitobei may influence the behavioral selection of S. noctilio. This study aimed to investigate the impact of fungal odor sources on S. noctilio’s behavior in laboratory and field experiments. Our observations revealed that female woodwasps exhibited greater attraction toward the fungal volatiles of 14-day-old Amylostereum IGS-D in a “Y”-tube olfactometer and wind tunnel. When woodwasps were released into bolts inoculated separately with three strains in the field, females of S. noctilio exhibited a preference for those bolts pre-inoculated with A. areolatum IGS-BD. Gas chromatography–mass spectrometry (GC–MS) analysis revealed that the volatiles emitted by the two genotypes of A. areolatum were similar yet significantly distinct from those of Ampelopsis chailletii. Hence, we postulate that the existence of native A. areolatum IGS-D could potentially facilitate the colonization of S. noctilio in scenarios with minimal or no A. areolatum IGS-BD present in the host.

Abstract Background While liver cancer stem cells (CSCs) play a crucial role in hepatocellular carcinoma (HCC) initiation, progression, recurrence, and treatment resistance, the mechanism underlying liver CSC self-renewal remains elusive. We aim to characterize the role of Methyltransferase 16 (METTL16), a recently identified RNA N 6-methyladenosine (m6A) methyltransferase, in HCC development/maintenance, CSC stemness, as well as normal hepatogenesis. Methods Liver-specific Mettl16 conditional KO (cKO) mice were generated to assess its role in HCC pathogenesis and normal hepatogenesis. Hydrodynamic tail-vein injection (HDTVi)-induced de novo hepatocarcinogenesis and xenograft models were utilized to determine the role of METTL16 in HCC initiation and progression. A limiting dilution assay was utilized to evaluate CSC frequency. Functionally essential targets were revealed via integrative analysis of multi-omics data, including RNA-seq, RNA immunoprecipitation (RIP)-seq, and ribosome profiling. Results METTL16 is highly expressed in liver CSCs and its depletion dramatically decreased CSC frequency in vitro and in vivo. Mettl16 KO significantly attenuated HCC initiation and progression, yet only slightly influenced normal hepatogenesis. Mechanistic studies, including high-throughput sequencing, unveiled METTL16 as a key regulator of ribosomal RNA (rRNA) maturation and mRNA translation and identified eukaryotic translation initiation factor 3 subunit a (eIF3a) transcript as a bona-fide target of METTL16 in HCC. In addition, the functionally essential regions of METTL16 were revealed by CRISPR gene tiling scan, which will pave the way for the development of potential inhibitor(s). Conclusions Our findings highlight the crucial oncogenic role of METTL16 in promoting HCC pathogenesis and enhancing liver CSC self-renewal through augmenting mRNA translation efficiency.

The coronavirus disease of 2019 (COVID-19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can result in severe health complications. In addition to physical preventative measures, pharmaceutical intervention is also crucial. Numerous natural products from medicinal fungi have shown promise as potential antiviral drugs and may serve as a source of effective components with antiviral activity against SARS-CoV-2 and other coronaviruses. In this study, we developed a workflow that integrates viral infection inhibition assays at both cellular and molecular levels, as well as molecular separation and characterization, to screen and identify natural products with antiviral activity. Using this workflow, we screened 167 extracts extracted from 36 medicinal fungi using optimized extraction methods. We assessed the antiviral effects of these extracts by measuring their ability to inhibit SARS-CoV-2 infection and receptor binding domain - human angiotensin-converting enzyme 2 (RBD-hACE2) binding in vitro. Following charge- and size-based characterization of the active compounds through filtration and chromatographic fractionation, mass spectrometry characterization of the fractionated compounds revealed that the active components are polysaccharides and determined their monosaccharide residue composition. Our findings provide new insights into the antiviral potential of natural products and their screening strategies and may contribute to the development of effective antiviral therapeutics against COVID-19 and other diseases.

Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell responses, and 65.7% (23/35) had memory T-cell responses to VVT. Because of cross-immunity between the viruses, these findings can help guide mpox vaccination strategies in China.

Abstract Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

In this research, a variety of novel amphetamine derivatives were synthesized and assessed for their potential as multifaceted antidepressant agents. Among these compounds, compound 11b demonstrated potent inhibitory effects on both serotonin and noradrenaline transporters (SERT/NET) and high affinity for histamine H3 receptor (H3R), and displayed low affinity for off-target receptors (H1, α1) and hERG channels, which can reduce the prolongation of the QT interval. Molecular docking studies offered a rational binding model of compound 11b when it forms a complex with SERT, NET, and the histamine H3 receptor. In vivo behavioral studies, compound 11b dose-dependently reduced the immobility duration in the mouse FST and TST assays without a stimulatory effect on the locomotor activity. Furthermore, compound 11b had a favorable pharmacokinetic profile in rats. Thus, compound 11b has the potential to develop a novel class of drugs for the treatment of depression.

Dendroctonus valens is one of the main invasive pests in China, causing serious economic and ecological damage. Early detection and control of D. valens can help prevent further outbreaks. Based on unmanned aerial vehicle (UAV) thermal infrared and hyperspectral data, we compared the spectral characteristics of Pinus sylvestris var. mongolica in three states (healthy, early-infested, and dead), and constructed a classification model based on the random forest algorithm using four spectral datasets (reflectance, first derivative, second derivative, and spectral vegetation index) and one temperature parameter dataset. Our results indicated that the spectral differences between healthy and early-infested trees mainly occur in the near-infrared region, with dead trees showing different characteristics. While it was effective to distinguish healthy from early-infested trees using spectral data alone, the addition of a temperature parameter further improved classification accuracy across all datasets. The combination of the spectral vegetation index and temperature parameter achieved the highest accuracy at 93.75%, which is 3.13% higher than using the spectral vegetation index alone. This combination also significantly improved early detection precision by 13.89%. Our findings demonstrated the applicability of UAV-based thermal infrared and combined hyperspectral datasets in monitoring D. valens early-infested trees, providing important technical support for the scientific prevention and control of D. valens.

Sustainable forest management faces challenges from various biotic and abiotic stresses. The Asian longhorned beetle (ALB) and drought stress both induce water shortages in poplar trees, but require different management strategies. In northwestern China, ALB and drought stress caused massive mortality in poplar shelterbelts, which seriously affected the ecological functions of poplars. Developing a large-scale detection method for discriminating them is crucial for applying targeted management. This study integrated UAV-hyperspectral and LiDAR data to distinguish between ALB and drought stress in poplars of China’s Three-North Shelterbelt. These data were analyzed using a Partial Least Squares-Support Vector Machine (PLS-SVM). The results showed that the LiDAR metric (elev_sqrt_mean_sq) was key in detecting drought, while the hyperspectral band (R970) was key in ALB detection, underscoring the necessity of integrating both sensors. Detection of ALB in poplars improved when the poplars were well watered. The classification accuracy was 94.85% for distinguishing well-watered from water-deficient trees, and 80.81% for detecting ALB damage. Overall classification accuracy was 78.79% when classifying four stress types: healthy, only ALB affected, only drought affected, and combined stress of ALB and drought. The results demonstrate the effectiveness of UAV-hyperspectral and LiDAR data in distinguishing ALB and drought stress in poplar forests, which contribute to apply targeted treatments based on the specific stress in poplars in northwest China.

IntroductionThe drawbacks of using antibiotics as feed additives for blue foxes have gradually become apparent; moreover, thymol has wide-spectrum antimicrobial activity and has the potential to replace antibiotics in various animals. However, there are few reports on the effects of thymol on blue foxes.MethodsThis study aimed to investigate the effects of different concentrations of thymol on the growth performance, apparent nutrient digestibility, serum biochemical indicators, intestinal morphology, and gut microbiota of blue foxes. Twenty-four male blue foxes (120 ± 5 d) of similar weight (6.05 ± 0.16 kg) were randomly divided into 4 groups. 0, 100, 200, and 300 mg/kg thymol were added to the basal diets of groups C, L, M, and H, respectively.ResultsCompared with those in the C group, the addition of 100 mg/kg thymol to the diet significantly increased organic matter (OM) digestibility, crude protein (CP) digestibility, immunoglobulin (Ig) A, IgM, the VH of the duodenum, the CD of the jejunum, the VH of the ileum, and the VH/CD of the ileum (P < 0.05) and strongly significantly increased IgG (P < 0.01). The addition of 200 mg/kg thymol to the diet increased the VH/CD of the duodenum (P < 0.05). The addition of 300 mg/kg thymol to the diet significantly increased the VH and CD of the jejunum (P < 0.05). The addition of 200 mg/kg and 300 mg/kg thymol to the diets increased the final weight (FW) (P < 0.05). Adding 100 mg/kg thymol significantly increased the levels of interleukin-4 (IL-4) and catalase (CAT) compared with those in the other groups (P < 0.05). 16S rRNA gene detection revealed that thymol can change the abundances of Bifidobacterium, Fusobacterium, Allobaculum, Streptococcus, Megasphaera, and Lactobacillus in the gut.ConclusionThe addition of thymol to diets can increase the abundance of Bifidobacterium, Fusobacterium, and Allobaculum, which may contribute to improving the growth performance of blue foxes.

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

The pine wood nematode (PWN) is one of the most threatening pests of pine forests in China. An essential management response involves felling and removing the infested trees before the PWN can spread over large areas, but this requires early detection. In this study, we analyzed the temporal changes in the spectral signatures of healthy and infested trees throughout the entire growing season (May to October) using unmanned aerial vehicle (UAV) hyperspectral images (HSI). To explore the potential of these seasonal spectral changes in detecting PWN, we investigated the separability of healthy and infested trees using both absolute values and changes in values. A random forest (RF) classifier was applied to separate healthy and infested trees based on reflectances, derivatives, vegetation indices (VIs), and their seasonal change values. We obtained the following results: (1) the seasonal changes of tree crown spectra following a PWN infestation were similar to those observed using absolute spectral values, though the latter performed better in early detection; (2) in the early stage of infestation (June and July), the green and red-edge regions contained the most sensitive bands, whereas the near-infrared portion played a more important role in later stages; (3) derivatives achieved higher overall accuracy (OA) than the reflectance in the early stage of PWN infestation (June and July); (4) in June, the Pigment Specific Simple Ratio (PSSR) had the highest separability (OA = 0.77) for PWN infestation, followed by the Plant Senescence Reflectance Index (PSRI) and the Normalized Difference Red-edge Index (NDRE), both with a OA of 0.70. In July, PSRI, Red Edge Normalized Difference Vegetation Index (RENDVI), and the Modified Red Edge Simple Ratio (MRESR) had the highest OA of 0.77. These VIs were calculated based on the red-edge regions. In August, RENDVI achieved the best accuracy (0.87), followed by the Normalized Difference Vegetation Index (NDVI, OA = 0.83) and the Plant Stress Index (PSI, OA = 0.80). In September and October, PSRI, PSI, the Greenness Index (GI), and RENDVI showed the strongest separability (0.87 to 0.90). Similar results were obtained using change values of VIs. In June, RENDVI, PSI, and NDVI showed the highest accuracy (OA = 0.73). In July, MRESR had the best accuracy (0.77), followed by RENDVI (0.73) and PSI (0.73). In the late stage of PWN infestation, NDVI, PSRI, PSI, RENDVI, GI, and PSSR obtained the highest accuracies (0.83 to 0.93), surpassing the accuracy achieved using absolute spectra; (5) in RF classification model, seasonal variation values derived from reflectances, derivatives, and VIs performed well in the late stages of the PWN infestation (September and October) but were not as good as absolute values in the early and middle stages (June to August). Our study explored the potential of seasonal changes in UAV spectra for early detection of forest pests.

Abstract Sepsis poses a significant challenge in clinical management. Effective strategies targeting iron restriction, toxin neutralization, and inflammation regulation are crucial in combating sepsis. However, a comprehensive approach simultaneously targeting these multiple processes has not been established. Here, an engineered apoptotic extracellular vesicles (apoEVs) derived from macrophages is developed and their potential as multifunctional agents for sepsis treatment is investigated. The extensive macrophage apoptosis in a Staphylococcus aureus‐induced sepsis model is discovered, unexpectedly revealing a protective role for the host. Mechanistically, the protective effects are mediated by apoptotic macrophage‐released apoEVs, which bound iron‐containing proteins and neutralized α‐toxin through interaction with membrane receptors (transferrin receptor and A disintegrin and metalloprotease 10). To further enhance therapeutic efficiency, apoEVs are engineered by incorporating mesoporous silica nanoparticles preloaded with anti‐inflammatory agents (microRNA‐146a). These engineered apoEVs can capture iron and neutralize α‐toxin with their natural membrane while also regulating inflammation by releasing microRNA‐146a in phagocytes. Moreover, to exploit the microcosmic movement and rotation capabilities, erythrocytes are utilized to drive the engineered apoEVs. The erythrocytes‐driven engineered apoEVs demonstrate a high capacity for toxin and iron capture, ultimately providing protection against sepsis associated with high iron‐loaded conditions. The findings establish a multifunctional agent that combines natural and engineered antibacterial strategies.

Abstract To mitigate climate warming, many countries have committed to achieve carbon neutrality in the mid-21st century. Here, we assess the global impacts of changing greenhouse gases (GHGs), aerosols, and tropospheric ozone (O3) following a carbon neutrality pathway on climate and extreme weather events individually using the Community Earth System Model version 1 (CESM1). The results suggest that the future aerosol reductions significantly contribute to climate warming and increase the frequency and intensity of extreme weathers toward carbon neutrality and aerosol impacts far outweigh those of GHGs and tropospheric O3. It reverses the knowledge that the changing GHGs dominate the future climate changes as predicted in the middle of the road pathway. Therefore, substantial reductions in GHGs and tropospheric O3 are necessary to reach the 1.5 °C warming target and mitigate the harmful effects of concomitant aerosol reductions on climate and extreme weather events under carbon neutrality in the future.

Abstract Background Coronavirus disease 19 (COVID-19) is a major public health problem that cannot be ignored. As a widely used drug in the treatment of COVID-19, whether glucocorticoids may accelerate the clearance of COVID-19 is still not clear, and the glucocorticoids may improve the prognosis of patients is also controversial. Therefore, to explore the relationship between COVID-19 viral load and the use of glucocorticoids we designed this study. Methods Patients with COVID-19 infection who were admitted to the emergency department of Peking Union Medical College Hospital from the end of 2022 to early 2023 were enrolled in this study. Characteristics of baseline, clinical and laboratory evaluation especially immunological indicator and daily viral load were carefully collected. Kolmogorov–Smirnov test, Student’s t test, Mann–Whitney U test and proportional-hazards model (Cox model) were chosen as appropriate for comparison of variables. Results By comparing the daily COVID-19 viral load and prognosis of patients with and without glucocorticoid therapy, we found that glucocorticoids did not statistically enhance the clearance or replication of COVID-19, nor did it change the 28-days and in-hospital mortality. However, glucocorticoid therapy may be a favorable factor for COVID-19 negative conversion in Cox model. The inflammatory factors in patients with glucocorticoid therapy were significantly decreased. Conclusions We believe that the real effect of glucocorticoids may be to improve the destruction of host immune system caused by inflammatory storm through host immune regulation and then achieve the improvement of clinical symptoms.

Abstract As the in-depth expansion and integrated application of information technology, smart city is one of the important directions for nurturing breakthroughs in the new generation of information technology, and an important part of the development of global strategic emerging industries. In the context of world peace, the world economy is developing rapidly and the process of urbanization is accelerating. The construction of a city not only reflects the economic strength of the city, but also is closely related to the life of the citizens. Therefore, this paper aimed to explore a new way of urban cultural creative design. This paper focused on the application of human–computer interaction virtual reality (VR) technology in urban cultural creative design. For this reason, this paper designed an interactive and immersive urban design simulation platform based on VR technology. In order to choose the viewing angle freely and control the design module freely, this paper proposed improved gesture recognition algorithm and anti-collision algorithm. The algorithm designed in this paper can enable designers to have better presentation effects when working on the platform, making architectural design more intuitive. Experiments show that the average accuracy rate of the gesture recognition algorithm designed in this paper reaches 97.3%, which is 4.1% higher than that of the traditional algorithm; and when the anti-collision algorithm in this paper is set to the optimal parameters, the accuracy rate is as high as 95%. These results fully demonstrate that the human–computer interaction VR technology design platform proposed in this paper has good design performance and can be applied to urban cultural creative design.

Abstract A pediatric patient suffered from renal and hepatic abscesses (through hepatorenal space) and recovered by antibiotics and other therapies. By clinical analysis, the multi-organ abscesses might be caused by bloodstream-disseminated infection. In order to identify the pathogen, we collected kidney biopsy tissue, swabs, and plasma samples, and used metagenomics next-generation sequencing (mNGS) and some traditional methods. The results revealed that polymicrobial especially anaerobic bacteremia (Bacteroides fragilis, et al.) contributed to the abscess formation. What is more, systematic human adenovirus C (HAdV-C) infection was shown, and the virus was isolated. The titer of HAdV-2 neutralizing antibodies was 1/4 in the plasma after symptoms onset. Although the exact mechanism of HAdV-2 infection in multiple abscess formation has not been clarified, the case of multi-organ abscesses in the context of polymicrobial especially anaerobic bacteremia and HAdV infection in healthy children is infrequent.

Metformin is the initial medication recommended for the treatment of type 2 diabetes mellitus (T2DM). In addition to diabetes treatment, the function of metformin also can be anti-aging, antiviral, and anti-inflammatory. Nevertheless, further exploration is required to fully understand its mode of operation. Historically, the liver has been acknowledged as the main location where metformin reduces glucose levels, however, there is increasing evidence suggesting that the gastrointestinal tract also plays a significant role in its action. In the gastrointestinal tract, metformin effects glucose uptake and absorption, increases glucagon-like peptide-1 (GLP-1) secretion, alters the composition and structure of the gut microbiota, and modulates the immune response. However, the side effects of it cannot be ignored such as gastrointestinal distress in patients. This review outlines the impact of metformin on the digestive system and explores potential explanations for variations in metformin effectiveness and adverse effects like gastrointestinal discomfort.

The Hylurgini tribe (Coleoptera: Curculionidae: Scolytinae) comprises commercially significant bark beetles, including invasive species within the genera Dendroctonus and Hylurgus. These invasive species coexist with native Tomicus species of Hylurgini and cooperatively infest host trees in China. However, we lack sufficient mitochondrial genome data of Hylurgini to conduct phylogenetic studies, clarify the phylogenetic relationships of the above species, and improve the understanding of niche divergence and common hazards. Here, we sequenced and analyzed the mitochondrial genomes of seven Hylurgini species, including Dendroctonus valens, Hylurgus ligniperda, Hylurgus micklitzi, Tomicus piniperda, Tomicus brevipilosus, Tomicus minor and Tomicus yunnanensis. All sequenced mitochondrial genomes ranged from 15,339 bp to 17,545 bp in length, and their AT contents ranged from 73.24% to 78.81%. The structure of the seven mitochondrial genomes was consistent with that of ancestral insects. Based on 13 protein-coding genes from the reported mitochondrial genomes of 29 species of bark beetles, we constructed phylogenetic trees using maximum likelihood and Bayesian inference methods. The topology of the two phylogenetic trees was almost consistent. The findings elucidated the taxonomy classification of Hylurgini and the evolutionary connections of its sister taxa within the Scolytinae. This study offers insights for examining the evolutionary connections between invasive and native bark beetles, as well as the molecular identification and detection of newly invading species.

The gut microbiota undergoes substantial changes in COVID-19 patients; yet, the utility of these alterations as prognostic biomarkers at the time of hospital admission, and its correlation with immunological and hematological parameters, remains unclear. The objective of this study is to investigate the gut microbiota's dynamic change in critically ill patients with COVID-19 and evaluate its predictive capability for clinical outcomes alongside immunological and hematological parameters. In this study, anal swabs were consecutively collected from 192 COVID-19 patients (583 samples) upon hospital admission for metagenome sequencing. Simultaneously, blood samples were obtained to measure the concentrations of 27 cytokines and chemokines, along with hematological and biochemical indicators. Our findings indicate a significant correlation between the composition and dynamics of gut microbiota with disease severity and mortality in COVID-19 patients. Recovered patients exhibited a higher abundance of Veillonella and denser interactions among gut commensal bacteria compared to deceased patients. Furthermore, the abundance of gut commensal bacteria exhibited a negative correlation with the concentration of proinflammatory cytokines and organ damage markers. The gut microbiota upon admission showed moderate prognostic prediction ability with an AUC of 0.78, which was less effective compared to predictions based on immunological and hematological parameters (AUC 0.80 and 0.88, respectively). Noteworthy, the integration of these three datasets yielded a higher predictive accuracy (AUC 0.93). Our findings suggest the gut microbiota as an informative biomarker for COVID-19 prognosis, augmenting existing immune and hematological indicators.

Objective(s): Paraquat (PQ), a highly effective and rapidly non-selective herbicide, mainly targets the lungs and causes acute lung injury (ALI). So far, the scarcity of effective drug candidates against PQ-induced ALI remains a big challenge. Andrographolide (Andro), with its anti-inflammatory and antioxidant activities, has been demonstrated to alleviate ALI. Nevertheless, whether Andro could alleviate the PQ-mediated ALI remains unknown. Therefore, this study will explore the effects as well as the possible mechanism of Andro against ALI caused by PQ. Materials and Methods: C57BL/6J mice were injected with 20 mg/kg PQ intraperitoneally to establish an ALI model. PQ-treated MLE-12 cells were applied to a vitro model. Nuclear factor erythroid like-2 (Nrf2) was knocked out to explore the specific effects of the Nrf2/ Heme oxygenase-1 (OH-1) pathway in the protection of Andro against ALI caused by PQ.Results: Andro significantly reduced lung damage and the ratio of Wet/Dry (W/D) weight, decreased MDA, IL-6, IL-1β, and TNF-ɑ levels, reversed the decrease of CAT and SOD levels, and inhibited apoptosis caused by PQ. Andro obviously increased the ratio of Bcl-2/Bax while reducing caspase-3 and cleaved caspase-3 levels. Furthermore, Andro dramatically elevated the antioxidant proteins Nrf2, NQO-1, and HO-1 levels compared with the PQ group. This experiment demonstrated that Andro reduced ROS and inhibited apoptosis, induced by PQ in MLE-12 cells, by inducing Nrf2/HO-1 pathway activation.Conclusion: Andro effectively ameliorates oxidant stress and apoptosis in ALI caused by PQ, possibly through inducing Nrf2/HO-1 pathway activation.

Abstract Atopic dermatitis (AD) is a chronic and recurrent inflammation disease associated with immune dysfunction. The high level of reactive oxygen species (ROS) causes high oxidative stress and further results in the deterioration of AD. At the same time, the ROS produced by bacterial infection can further aggravate AD. Here, the prepared PVA-based hydrogel (Gel) has a high ROS scavenging ability, and the antibacterial agent Zn-MOF(ZIF-8) loaded into the hydrogel shows a lasting and effective antibacterial activity. Thus, a Zn-MOF hydrogel (Gel@ZIF-8) is prepared to regulate ROS-mediated inflammatory microenvironment. In vitro experiments show that Gel@ZIF-8 has good antibacterial effect and cell biocompatibility. In the AD-induced mouse model, Gel@ZIF-8 can significantly enhance the therapeutic effect, such as reduce the thickness of epidermis, the number of mast cells and IgE antibodies. The results indicate that the ROS-scavenging hydrogel could treat the AD by regulating the inflammatory microenvironment, providing a promising treatment for managing AD.

A large proportion of the insects which have invaded new regions and countries are emerging species, being found for the first time outside their native range. Being able to detect such species upon arrival at ports of entry before they establish in non-native countries is an urgent challenge. The deployment of traps baited with broad-spectrum semiochemical lures at ports-of-entry and other high-risk sites could be one such early detection tool. Rapid progress in the identification of semiochemicals for cerambycid beetles during the last 15 years has revealed that aggregation-sex pheromones and sex pheromones are often conserved at global levels for genera, tribes or subfamilies of the Cerambycidae. This possibly allows the development of generic attractants which attract multiple species simultaneously, especially when such pheromones are combined into blends. Here, we present the results of a worldwide field trial programme conducted during 2018–2021, using traps baited with a standardised 8-pheromone blend, usually complemented with plant volatiles. A total of 1308 traps were deployed at 302 sites covering simultaneously or sequentially 13 European countries, 10 Chinese provinces and some regions of the USA, Canada, Australia, Russia (Siberia) and the Caribbean (Martinique). We intended to test the following hypotheses: 1) if a species is regularly trapped in significant numbers by the blend on a continent, it increases the probability that it can be detected when it arrives in other countries/continents and 2) if the blend exerts an effective, generic attraction to multiple species, it is likely that previously unknown and unexpected species can be captured due to the high degree of conservation of pheromone structures within related taxa. A total of 78,321 longhorned beetles were trapped, representing 376 species from eight subfamilies, with 84 species captured in numbers greater than 50 individuals. Captures comprised 60 tribes, with 10 tribes including more than nine species trapped on different continents. Some invasive species were captured in both the native and invaded continents. This demonstrates the potential of multipheromone lures as effective tools for the detection of ‘unexpected’ cerambycid invaders, accidentally translocated outside their native ranges. Adding new pheromones with analogous well-conserved motifs is discussed, as well as the limitations of using such blends, especially for some cerambycid taxa which may be more attracted by the trap colour or other characteristics rather than to the chemical blend.

Background: Saccades are often observed on video head impulse tests (vHIT) in patients with Meniere's Disease (MD) and Vestibular Migraine (VM). However, their saccadic features are not fully described. Objective: This study aims to identify the saccades characteristics of MD and VM. Methods: 75 VM patients and 103 definite unilateral MD patients were enrolled in this study. First raw saccades were exported and analyzed. The VM patients were divided into left and right based on their ears, while the MD patients were separated into affected and unaffected subgroups based on their audiograms and symptoms. Results: The MD patients have more saccades on the affected side (85% vs. 69%), and saccade velocity is more consistent than the contralateral side (shown by the coefficient of variation). The saccades occurrence rates on both sides are similar in VM (77% vs. 76%), as are other saccadic parameters. The MD patients have more significant inter-aural differences than the VM patients, manifested in higher velocity (p-value 0.000), earlier arriving (p-value 0.010), and more time-domain gathered (p-value 0.003) on the affected side. Conclusions: Bilateral saccades are commonly observed in MD and VM. In contrast to MD, saccades on VM are subtle, scattered, and late-arrived. Furthermore, the MD patients showed inconsistent saccadic distribution with more velocity-uniform saccades on the affected side.

Abstract Background Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. Methods A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. Results Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06–92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p

With the emphasis placed by society on environmental resources, current petroleum-based packaging in the food industry can no longer meet people’s needs. However, new active packaging technologies have emerged, such as proteins, polysaccharides, and lipids, in which proteins are widely used for their outstanding gel film-forming properties. Most of the current literature focuses on research applications of single protein-based films. In this paper, we review the novel protein-based packaging technologies that have been used in recent years to categorize different proteins, including plant proteins (soybean protein isolate, zein, gluten protein) and animal proteins (whey protein isolate, casein, collagen, gelatin). The advances that have recently been made in protein-based active packaging technology can be understood by describing protein sources, gel properties, molding principles, and applied research. This paper presents the current problems and prospects of active packaging technology, provides new ideas for the development of new types of packaging and the expansion of gel applications in the future, and promotes the development and innovation of environmentally friendly food packaging.

Sirex noctilio, a European woodwasp, occasionally shares resources with the native S. nitobei and other colonizers in northeast China. The impact of its coexistence on individual species remains unclear. Random sampling was conducted to assess the patterns and extent of insect co-colonization across various spatial scales. Additionally, we analyzed wood sections to determine the density, adult size, and distribution of the two Sirex species. Spatial scales revealed negative associations (Asemum striatum and Phaenops sp.) and neutral ones (Ips acuminatus) between woodwasps and other co-colonizers. Clustering of woodwasps and Phaenops sp. occurred at a small scale (0–7.3 m). Regression analysis showed a positive correlation between the chance of woodwasp attacks and past attacks on the same host, with little impact from other colonization factors. The distribution and body size of S. noctilio within the tree appeared unaffected by S. nitobei’s presence. In the presence of S. noctilio, S. nitobei tended to lay eggs in damaged sections. At the stand level, the overall impact of S. noctilio on S. nitobei population density is likely positive because S. nitobei prefer weaker trees, a preference potentially influenced by initial attacks from S. noctilio on healthier hosts.

IntroductionAdding antibiotics to animal basal diets can improve growth and production performance. However, the use of antibiotics poses a potential threat to public health safety.MethodsThe study was conducted to investigate the effects of different levels of mannan oligosaccharides (MOS) on the fur quality, nutrient apparent digestibility, serum immunity, antioxidant status, intestinal morphology, and gut microbiota of fur-growing raccoon dogs. Divide 24 male raccoon dogs (120 ± 5 d) of similar weight (5.01 ± 0.52 kg) into 4 groups randomly. Add 0, 0.05, 0.1, and 0.2% MOS to the basal diets of groups C, L, M, and H, respectively.ResultsCompared to the C group, the addition of 0.05% and 0.1% MOS in the diet increased the apparent digestibility of crude protein (CP), Underfur length (UL), Guard hair length (GL), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels in the serum (p

ABSTRACTThe adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not BA.4/5 and induced neutralization against prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to prototype strain and Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine dose only. The breakthrough infection individuals produced stronger adaptive immunity than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adaptive immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. Omicron sublineages, especially for those emerged after BA.4/5 strain, evade NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.

Information transparency plays a vital role for developing capital markets. Using data of A-share listed companies from 2007 to 2020, this study examined the impact of customer concentration on corporate information transparency from a supply chain perspective. It suggests that a significant negative correlation exists between customer concentration and information transparency. Customer concentration affects the quality of corporate information disclosures. Through the mechanism test, the impact of customer concentration on corporate information transparency is based on the risk effect rather than the substitution effect of private information on public information. Research on regulatory effects points out that a poor internal information environment aggravates the negative relationship between customer concentration and information transparency. However, media supervision and a higher marketization process alleviate the adverse effects of customer concentration on information transparency. This study indicates that firms with a higher customer concentration have a higher risk of information disclosure, which provides a reference point for investors for making investment-related decisions and for the capital market supervision department for formulating information disclosure policies.

Abstract The profile of antibodies against antigenic epitopes of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) during neutralizing antibody (NAb) decay has not been clarified. Using a SARS‐CoV‐2 proteome microarray that contained viral antigenic peptides, we analyzed the characteristics of the humoral response in patients with coronavirus disease 19 (COVID‐19) in a longitudinal study. A total of 89 patients were recruited, and 226 plasma samples were serially collected in 2020. In the antigenic peptide microarray, the level of immunoglobulin G (IgG) antibodies against peptides within the S2 subunit (S‐82) and a conserved gene region in variants of interest, open reading frame protein 10 (ORF10‐3), were closely associated with the presence of SARS‐CoV‐2 NAbs. In an independent evaluation cohort of 232 plasma samples collected from 116 COVID‐19 cases in 2020, S82‐IgG titers were higher in NAbs‐positive samples (p = 0.002) than in NAbs‐negative samples using enzyme‐linked immunosorbent assay. We further collected 66 plasma samples from another cohort infected by Omicron BA.1 virus in 2022. Compared with the samples with lower S82‐IgG titers, NAb titers were significantly higher in the samples with higher S82‐IgG titers (p = 0.04). Our findings provide insights into the understanding of the decay‐associated signatures of SARS‐CoV‐2 NAbs.

Bactrocera dorsalis is a well-known invasive pest that causes considerable ecological and economic losses worldwild. Although it has a wide environmental tolerance, few studies have reported its mechanism of adaptation to multiple sub-lethal environmental stresses. In this study, 38, 41, 39 and 34 metabolites changed significantly in B. dorsalis under four sub-lethal stresses (heat, cold, desiccation and hypoxia), as found by the metabolomic method. Therein, lactic acid and pyruvic acid were induced, whereas metabolites in the tricarboxylic acid (TCA) cycle such as citric acid, α-ketoglutarate acid, malic acid and fumaric acid were reduced under at least one of the stresses. Enzyme activity and quantitative polymerase chain reaction (qPCR) analyses verified the repression of pyruvic acid proceeding into the TCA cycle. In addition, the levels of several cryoprotectants and membrane fatty acids in B. dorsalis were altered. The findings indicated that B. dorsalis has evolved shared metabolic pathways to adapt to heat, hypoxia and desiccation stresses, such as reducing energy consumption by activating the anaerobic glycolytic metabolism. Cryoprotectants and membrane fatty acids were produced to improve the efficiency of stress resistance. This study revealed the unique and generic crossed physiological mechanism of insects to adapt to various environmental stresses.

The use of sentinel woody plants in experimental plantings, Botanical Gardens and Arboreta has been experimentally validated as a tool for identifying possible unknown future threats prior to their introduction into new countries. Sentinel Plantings were recently established in Italy, France, Switzerland, China and South Africa, using a common experimental design. The plantings included various tree and shrub species of broadleaves and conifers. Two planting types were established, each with different objectives. In-patria plantings using native plants aim to estimate, in absence of any phytosanitary treatments, the associations and infestation rates of native insects susceptible to be exported to other countries with that particular commodity. Ex-patria plantings using non-native plants are relevant to identify native insect species capable of switching to the non-native plant that would otherwise be impossible to predict prior to its introduction. In the frame of the EU project HOMED, we have implemented this concept, widening the use of this tool simultaneously to many different countries and continents

We analyzed variations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome during a flight-related cluster outbreak of coronavirus disease 2019 (COVID-19) in Shenzhen, China, to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations (iSNVs) in a confined space. Thirty-three patients with COVID-19 were sampled, and 14 were resampled 3–31 days later. All 47 nasopharyngeal swabs were deep-sequenced. iSNVs and similarities in the consensus genome sequence were analyzed. Three SARS-CoV-2 variants of concern, Delta (n = 31), Beta (n = 1), and C.1.2 (n = 1), were detected among the 33 patients. The viral genome sequences from 30 Delta-positive patients had similar SNVs; 14 of these patients provided two successive samples. Overall, the 47 sequenced genomes contained 164 iSNVs. Of the 14 paired (successive) samples, the second samples (T2) contained more iSNVs (median: 3; 95% confidence interval [95% CI]: 2.77–10.22) than did the first samples (T1; median: 2; 95% CI: 1.63–3.74; Wilcoxon test, P = 0.021). 38 iSNVs were detected in T1 samples, and only seven were also detectable in T2 samples. Notably, T2 samples from two of the 14 paired samples had additional mutations than the T1 samples. The iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak event. Intra-host diversity increased gradually with time, and new site mutations occurred in vivo without a population transmission bottleneck. Therefore, we could not determine the generational relationship from the mutation site changes alone.

Abstract Background Central nervous system candidiasis due to Candida albicans (CNSC) in children is easily misdiagnosed and is associated with poor outcomes and a high mortality rate. There is no big data research or systematic review of CNSC. Methods Patients diagnosed as CNSC with positive culture results of Candida albicans in Beijing Children’s Hospital affiliated to Capital Medical University from March 2010 to March 2019 were included. Patients receiving immunosuppressive therapy or transplantation, or with malignant tumours were excluded. We analysed the clinical characteristics, follow-up results, drug susceptibility tests and whole-exome sequencing (WES) results. Results Thirty-three definitive patients were enrolled, including 22 males and 11 females. Twenty-five patients suffered from CNSC when they were less than 1 year old, and a total of 29 patients had high-risk factors. The main clinical manifestations were fever, convulsions, and positive neurological signs. Twenty-two patients had CNS infections alone, and 11 patients had CNS infections combined with invasive infections involving multiple sites. Twenty-seven cases had a positive CSF and/or blood culture at our hospital. All strains were susceptible to fluconazole, and 2 strains had intermediate susceptibility to voriconazole. As for amphotericin B, all the strains were wild type (WT). WES of 16 patients revealed 2 cases with CARD9 mutations, who suffered from recurrent onychomycosis or thrush before. Conclusion CNSC mostly existed in children younger than 1 year old, who all had underlying risk factors. CNSC patients with onset at an older age or with recurrent superficial fungal infections might have primary immunodeficiency.

The emergence of SARS-CoV-2 Omicron and other variants of concern (VOCs) has brought huge challenges to control the COVID-19 pandemic, calling for urgent development of effective vaccines and therapeutic drugs. In this study, we focused on characterizing the impacts of divergent VOCs on the antiviral activity of lipopeptide-based fusion inhibitors that we previously developed. First, we found that pseudoviruses bearing the S proteins of five VOCs (Alpha, Beta, Gamma, Delta, and Omicron) and one variant of interest (Lambda) exhibited greatly decreased infectivity relative to the wild-type (WT) strain or single D614G mutant, especially the Omicron pseudovirus. Differently, the most of variants exhibited an S protein with significantly enhanced cell fusion activity, whereas the S protein of Omicron still mediated decreased cell–cell fusion. Next, we verified that two lipopeptide-based fusion inhibitors, IPB02V3 and IPB24, maintained the highly potent activities in inhibiting various S proteins-driven cell fusion and pseudovirus infection. Surprisingly, both IPB02V3 and IPB24 lipopeptides displayed greatly increased potencies against the infection of authentic Omicron strain relative to the WT virus. The results suggest that Omicron variant evolves with a reduced cell fusion capacity and is more sensitive to the inhibition of fusion-inhibitory lipopeptides; thus, IPB02V3 and IPB24 can be further developed as potent, broad-spectrum antivirals for combating Omicron and the potential future outbreak of other emerging variants.

We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the Orf1ab and Spike genes was found.

Pigeon paramyxovirus type 1 (PPMV-1), an antigenic variant of avian paramyxovirus type 1 (APMV-1), mainly infects pigeons. PPMV-1 genotype VI is the dominant genotype infecting pigeons in China. Human infection of avian paramyxovirus was rarely reported, and usually developed mild symptoms, such as conjunctivitis. We detected PPMV-1 in the lower respiratory sample from a fatal case with severe pneumonia; this patient aged 64 years presented cough, fever, and haemoptysis for 8 days and was admitted to hospital on Dec 26, 2020. He developed acute respiratory distress syndrome and sepsis in the following days and died of multiple organ failure on Jan 7, 2021. Sputum and blood culture reported multidrug-resistant Acinetobacter baumannii (ABA) for samples collected on days 22 and 19 post-illness, respectively. However, clinical metagenomic sequencing further reported PPMV-1 besides ABA in the bronchoalveolar lavage fluid. The PPMV-1 genome showed 99.21% identity with a Chinese strain and belonged to VI genotype by BLAST analysis. Multiple basic amino acids were observed at the cleavage site of F protein (113RKKRF117), which indicated high virulence of this PPMV-1 strain to poultry. The patient had close contact with pigeons before his illness, and PPMV-1 nucleic acid was detected from the pigeon feather. PPMV antibody was also detected in the patient serum 20 days after illness. In conclusion, concurrent PPMV-1 genotype VI.2.1.1.2.2 and ABA infection were identified in a fatal pneumonia case, and cross-species transmission of PPMV-1 may occur between infected pigeons and the human being.