The alterations of oral, airway and intestine microbiota in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Background: Increasing evidence indicates the microbial ecology of chronic obstructive pulmonary disease (COPD) is intricately associated with the disease's status and severity, and distinct microbial ecological variations exist between COPD and healthy control (HC). This systematic review and meta-analysis aimed to summarize microbial diversity indices and taxa relative abundance of oral, airway, and intestine microbiota of different stages of COPD and HC to make comparisons. Methods: A comprehensive systematic literature search was conducted in PubMed, Embase, the Web of Science, and the Cochrane Library databases to identify relevant English articles on the oral, airway, and intestine microbiota in COPD published between 2003 and 8 May 2023. Information on microbial diversity indices and taxa relative abundance of oral, airway, and intestine microbiota was collected for comparison between different stages of COPD and HC. Results: A total of 20 studies were included in this review, involving a total of 337 HC participants, 511 COPD patients, and 154 AECOPD patients. We observed that no significant differences in alpha diversity between the participant groups, but beta diversity was significantly different in half of the included studies. Compared to HC, Prevotella, Streptococcus, Actinomyces, and Veillonella of oral microbiota in SCOPD were reduced at the genus level. Most studies supported that Haemophilus, Lactobacillus, and Pseudomonas were increased, but Veillonella, Prevotella, Actinomyces, Porphyromonas, and Atopobium were decreased at the genus level in the airway microbiota of SCOPD. However, the abundance of Haemophilus, Lactobacillus and Pseudomonas genera exhibited an increase, whereas Actinomyces and Porphyromonas showed a decrease in the airway microbiota of AECOPD compared to HC. And Lachnospira of intestine microbiota in SCOPD was reduced at the genus level. Conclusion: The majority of published research findings supported that COPD exhibited decreased alpha diversity compared to HC. However, our meta-analysis does not confirm it. In order to further investigate the characteristics and mechanisms of microbiome in the oral-airway- intestine axis of COPD patients, larger-scale and more rigorous studies are needed. Systematic review registration: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42023418726.

Asiaticoside promoted ferroptosis and suppressed immune escape in gastric cancer cells by downregulating the Wnt/ß-catenin pathway.

BACKGROUND: Our previous study has revealed that asiaticoside (AC) promotes endoplasmic reticulum stress and antagonizes proliferation and migration of gastric cancer (GC) via miR-635/HMGA1 axis. However, the effect and mechanism of AC on other progressions of GC, such as ferroptosis and immune escape, are still unknown. METHODS: AGS and HGC27 cells were incubated with 1, 2 and 4 µM of AC for 24 h. Mice xenografted with AGS cells were intragastrically injected with AC. The effect and mechanism of AC on GC were determined by the measurement of the ferrous iron level, the ROS level and the glutathione peroxidase (GSH) content, flow cytometry, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and western blotting assays. RESULTS: AC increased the Fe2+ level and the ROS level, but decreased the expression of GPX4 and SLC7A11 and the GSH level. Besides, AC enhanced the percent of CD8+ T cells and the IFN-γ concentration, but reduced the PD-L1 expression and the IL-10 level. Mechanically, AC downregulated the relative levels of ß-catenin, active-ß-catenin, p-GSK3ß/GSK3ß, cyclin D1 and c-Myc in GC cells, which were rescued with the application of LiCl (an activator of Wnt/ß-catenin pathway) in AGS cells. Moreover, activation of Wnt/ß-catenin pathway by LiCl or the ß-catenin overexpression inverted the effect of AC on ferroptosis and immune escape in GC cells. In vivo, AC treatment declined the tumor size and weight, the level of GPX4, SLC7A11, PD-L1 and IFN-γ, and the expression of Wnt/ß-catenin pathway. CONCLUSION: AC enhanced ferroptosis and repressed immune escape by downregulating the Wnt/ß-catenin signaling in GC.

Enhanced biotoxicity by co-exposure of aged polystyrene and ciprofloxacin: the adsorption and its influence factors.

Microplastics (MPs), as emerging contaminants, usually experience aging processes in natural environments and further affect their interactions with coexisted contaminants, resulting in unpredictable ecological risks. Herein, the effect of MPs aging on their adsorption for coexisting antibiotics and their joint biotoxicity have been investigated. Results showed that the adsorption capacity of aged polystyrene (PS, 100 d and 50 d) for ciprofloxacin (CIP) was 1.10-4.09 times higher than virgin PS due to the larger BET surface area and increased oxygen-containing functional groups of aged PS. Following the increased adsorption capacity of aged PS, the joint toxicity of aged PS and CIP to Shewanella Oneidensis MR-1 (MR-1) was 1.03-1.34 times higher than virgin PS and CIP. Combined with the adsorption process, CIP posed higher toxicity to MR-1 compared to aged PS due to the rapid adsorption of aged PS for CIP in the first 12 h. After that, the adsorption process tended to be gentle and hence the joint toxicity to MR-1 was gradually dominated by aged PS. A similar transformation between the adsorption rate and the joint toxicity of PS and CIP was observed under different conditions. This study supplied a novel perception of the synergistic effects of PS aging and CIP on ecological health.

Carbonized cellulose microspheres loaded with Pd NPs as catalyst in p-nitrophenol reduction and Suzuki-Miyaura coupling reaction.

Catalytic reduction of p-nitrophenol is usually carried out using transition metal nanoparticles such as gold, palladium, silver and copper, especially palladium nanoparticles, which are characterized by fast reaction rate, high turnover frequency, good selectivity and high yield. However, the aggregation and precipitation of the metals lead to the decomposition of the catalyst, which results in a significant reduction of the catalytic activity. Therefore, the preparation of homogeneous stabilized palladium nanoparticle catalysts has been widely studied. Stabilized palladium nanoparticles mainly use synthetic polymers. Cellulose microspheres, as a natural polymer material with low cost and porous fiber network structure, are excellent carriers for stabilizing metal nanoparticles. Cellulose microspheres impregnated with palladium metal nanoparticles were carbonized to have a larger specific surface area and highly dispersed palladium nanoparticles, which exhibited excellent catalytic activity in the catalytic reduction of 4-nitrophenol. In this aspect, cellulose carbon-based microspheres Pd nanoparticles (Pd@CCM) catalysts were designed and characterized by SEM, TEM, EDS, XRD, FTIR, XPS, TGA, BET and so on. Furthermore, the catalytic performance of Pd@CCM catalysts were investigated via 4-nitrophenol reduction, which showed high catalytic activity. This catalyst also exhibited excellent catalytic performance in Suzuki-Miyaura coupling reaction. Linking aromatic monomer and benzene through Suzuki-Miyaura coupling was presented as an effective route to obtain polymeric substrate with low-cost and simple synthesis method. In addition, cellulose carbon-based microspheres Pd nanoparticles catalyst showed desirable recyclability with maintaining its catalytic activity even after five recycles. This work is highly suggestive on the heterogeneous catalysts design and application.

Highly stable Ag-doped Cu2O immobilized cellulose-derived carbon beads with enhanced visible-light photocatalytic degradation of levofloxacin.

Ag-doped Cu2O immobilized carbon beads (Ag/Cu2O@CB) based composite photocatalysts have been prepared for the removal of levofloxacin, an antibiotic, from water. The photocatalysts were prepared by the processes of chemical reduction and in-situ solid-phase precipitation. The composite photocatalyst was characterized by a porous and interconnected network structure. Ag nanoparticles were deposited on Cu2O particles to develop a metal-based semiconductor to increase the catalytic efficiency of the system and the separation efficiency of the photogenerated carriers. Cellulose-derived carbon beads (CBs) can also be used as electron storage libraries which can capture electrons released from the conduction band of Cu2O. The results revealed that the maximum catalytic degradation efficiency of the composite photocatalyst for the antibiotic levofloxacin was 99.02 %. The Langmuir-Hinshelwood model was used to study the reaction kinetics, and the process of photodegradation followed first-order kinetics. The maximum apparent rate was recorded to be 0.0906 min-1. The mass spectrometry technique showed that levofloxacin degraded into carbon dioxide and water in the presence of the photocatalyst. The results revealed that the easy-to-produce photocatalyst was stable and efficient in levofloxacin removing.

Effect of guar gum, gelatin, and pectin on moisture changes in freeze-dried restructured strawberry blocks.

This study aimed to investigate the effects of edible gum addition on moisture changes in freeze-dried restructured strawberry blocks (FRSB), which involved five groups: the control, 1.2% guar gum, 1.2% gelatin, 1.2% pectin, and the composite group with 0.5% guar gum, 0.5% gelatin, and 0.45% pectin. The results indicated that the drying rates of the five groups of FRSB presented similar early acceleration and later deceleration trends. Moisture content in FRSB was linearly predicted by peak area of low field nuclear magnetic resonance with R2 higher than 0.90 for all the five groups. The FRSB samples in the gelatin and composition groups formed a denser porous structure and had a lower hygroscopicity after four days of storage. This study provides a theoretical basis for controlling the processing of FRSB.

Spatiotemporal variations in soil pollution by polycyclic aromatic hydrocarbons over a 20-year economic boom in different districts of a heavy industrial city in North China.

Urbanization-related human activities, such as population aggregation, rapid industrial expansion, and intensified traffic, are key factors that impact local polycyclic aromatic hydrocarbon emissions and their associated health risks. Consequently, regions with varying degrees of urbanization within a megacity may exhibit diverse spatiotemporal patterns in the presence and distribution of soil polycyclic aromatic hydrocarbons, resulting in different levels of ecological risks for local inhabitants following the same period of development. In this study, we measured the concentrations of 16 polycyclic aromatic hydrocarbons in soil samples collected from industrial district and rural district in Tianjin (China) in 2018, and compared with polycyclic aromatic hydrocarbon data in 2001 from a previous study to characterize these regional variations in occurrence, source, and human risk of polycyclic aromatic hydrocarbons induced by urbanization with time and space. The results indicate the 20-year rapid urbanization and industrialization has differentially affected the composition, distribution and sources of polycyclic aromatic hydrocarbons in soils from different economic functional zones in Tianjin. Additionally, its impact on health risks in rural district appeared to be more significant than that in industrial district.

The weakened physiological functions of human serum albumin in presence of polystyrene nanoplastics.

Due to the widespread presence of nanoplastics (NPs) in daily essentials and drinking water, the potential adverse effects of NPs on human health have become a global concern. Human serum albumin (HSA), the most abundant and multi-functional protein in plasma, has been chosen to understand the biological effects of NPs after entering the blood. The esterase activity and the transport of bisphenol A in the presence of polystyrene nanoplastics (PSNPs) under physiological conditions (pH 4.0 and 7.4) have been investigated to evaluate the possible biological effects. The interactions between PSNPs and HSA have also been systematically studied by multispectral methods and dynamic light scattering techniques. The esterase activity of HSA presented a decreased trend with increasing PSNPs; conversely, higher permeabilities are accompanied by higher amounts of PSNPs. Compared with the unchanged hydrodynamic diameter and weaker interactions at pH 7.4, stronger binding between HSA and PSNPs at pH 4.0 led to a significant increase in the particle size of the PSNPs-HSA complex. The quenching mechanism belonged to the static quenching type. The electrostatic force is proposed to be the dominant factor for PSNPs binding to HSA. The work provides some information about the toxicity of NPs when exposed to humans.

Portable paper-based probe for on-site ratiometric fluorescence determination of total flavonol glycosides in plant extract using smartphone imaging.

A smartphone-assisted, paper-based ratio fluorescence probe is presented for the rapid, low-cost and on-site quantification of total flavonol glycosides in Ginkgo biloba extracts (GBE). The Al3+/Eu-MOF/paper-based probe utilizes lanthanide metal-organic framework (Ln-MOF) nanoparticles immobilized on Whatman filter paper along with Al3+ for detecting flavonols, which are the hydrolyzed products of flavonol glycosides. The color change of the paper-based fluorescence image from red to orange depends on the concentration of the target analyte in the sample solution. The smartphone equipped with a red, green, blue (RGB) color detector measured the fluorescence signal intensity on the paper substrate after adding flavonol. The analytical variables affecting the performance of the probe, including the addition sequence of the aluminum nitrate solution, its concentration, that of the Ln-MOF solution, the drying time of the paper probe, the reaction time and the sensitivity parameters of the mobile phone camera (ISO), were optimized. Under optimal conditions, the Al3+/Eu-MOF/paper-based probe has good linear response in the concentration range 7 ~ 80 µg mL- 1 and a lower detection limit of 2.07 µg mL- 1. The results obtained with the paper-based ratio fluorescence probe and smartphone combination were validated by comparing them with high-performance liquid chromatography (HPLC) measurements. This study provides a potential strategy for fabricating Al3+/Eu-MOF/paper-based probe used for total flavonol glycosides determination.

Allelopathy and Identification of Volatile Components from the Roots and Aerial Parts of Astragalus mongholicus Bunge.

The volatile compounds produced by plants play an important role in plant growth, plant communication, and resistance to biological and abiotic stresses. Astragalus membranaceus var. mongholicus (AM) is a perennial herbaceous plant (Leguminosae) that is widely cultivated in northwest China. The bioactive compounds in its root have shown various pharmacological activities. Root rot disease caused by Fusarium spp. often occurs in AM planting with increasing severity in continuous monoculture. It is currently still unclear what are the effects of the volatile compounds produced by fresh AM on itself, other crops cultivated on the same field after AM, pathogen, and rhizobia. In this study, we found that seed germination and seedling growth of AM, lettuce (Lactuca sativa L.), and wheat (Triticum aestivum L.) could be affected if they were in an enclosed space with fresh AM tissue. Additionally, 90 volatile compounds were identified by SPME-GC-MS from whole AM plant during the vegetative growth, 36 of which were specific to aerial parts of AM (stems and leaves, AMA), 17 to roots (AMR), and 37 were found in both AMA and AMR. To further identify the allelopathic effects of these volatile compounds, five compounds (1-hexanol, (E)-2-hexenal, (E,E)-2,4-decadienal, hexanal, and eugenol) with relatively high content in AM were tested on three receptor plants and two microorganisms. We found that (E,E)-2,4-decadienal and (E)-2-hexenal showed significant inhibitory effects on the growth of AM and lettuce. One-hexanol and hexanal suppressed the growth of wheat, while eugenol showed a similar effect on all three plant species. Moreover, the activities of these compounds were dose dependent. Notably, we discovered that (E)-2-hexenal and eugenol also inhibited the growth of the pathogen Fusarium solani by as high as 100%. Meanwhile, all five compounds tested suppressed the rhizobia Sinorhizobium fredii. In summary, this study furthered our understanding of the comprehensive allelopathic effects of the main volatile components of AM.

Comparison of the arsenic protective effects of four nanomaterials on pakchoi in an alkaline soil.

Accurately applying engineered nanoparticles (NPs) in farmland stress management is important for sustainable agriculture and food safety. We investigated the protective effects of four engineered NPs (SiO2, CeO2, ZnO, and S) on pakchoi under arsenic (As) stress using pot experiments. The results showed that CeO2, SiO2, and S NPs resulted in biomass reduction, while ZnO NPs (100 and 500 mg kg-1) significantly increased shoot height. Although 500 mg kg-1 S NPs rapidly dissolved to release SO42-, reducing soil pH and pore water As content and further reducing shoot As content by 21.6 %, the growth phenotype was inferior to that obtained with 100 mg kg-1 ZnO NPs, probably due to acid damage. The addition of 100 mg kg-1 ZnO NPs not only significantly reduced the total As content in pakchoi by 23.9 % compared to the As-alone treatment but also enhanced plant antioxidative activity by increasing superoxide dismutase (SOD) and peroxidase (POD) activities and decreasing malondialdehyde (MDA) content. ZnO NPs in soil might inhibit As uptake by roots by increasing the dissolved organic carbon (DOC) by 19.12 %. According to the DLVO theory, ZnO NPs were the most effective in preventing As in pore water from entering plant roots due to their smaller hydrated particle size. Redundancy analysis (RDA) further confirmed that DOC and SO42- were the primary factors controlling plant As uptake under the ZnO NP and S NP treatments, respectively. These findings provide an important basis for the safer and more sustainable application of NP-conjugated agrochemicals.

Time-delay control scheme with adaptive fixed-time convergent super-twisting fractional-order nonsingular terminal sliding mode for piezoelectric displacement amplifier.

Piezoelectric displacement amplifiers (PDAs) have been widely used in precision positioning fields. However, the inherent hysteresis and creep nonlinear effect of piezoelectric actuators (PEAs) and time-varying lumped disturbances bring extreme challenges to the precise motion control of PDAs. Although various control schemes based on PEAs have been developed and have shown significant results. However, due to the high sensitivity of precision positioning to environmental variations, the development and identification of accurate models and the control timeliness often become obstacles in engineering. To realize precise motion control of PDAs under complex lumped disturbances, a new time-delay control scheme (AFSTA-FONTSM) using an adaptive fixed-time convergent super-twisting algorithm (AFSTA) and a fractional-order nonsingular terminal sliding mode (FONTSM) is proposed. Specifically, the time-delay information obtained by time-delay estimation technology is used to estimate the lumped dynamic characteristic of the system, thus establishing a simple control framework without a system dynamic model. FONSTM is constructed as a sliding mode manifold, and satisfactory error dynamic characteristic is obtained. A new AFSTA is designed as the reaching law in the sliding mode phase. AFSTA has fixed-time convergence when the upper bound of lumped disturbances exists, which ensures the control timeliness. Benefiting from the newly designed adaptive algorithm, the upper bound value of lumped disturbances is no longer needed to determine the control gains, which effectively prevents overestimation of the control gains. Correspondingly, the convergence time of AFSTA is estimated, and the stability of the closed-loop system is analyzed by the Lyapunov theory. Three existing time-delay control schemes, namely MSTA-FONTSM, AMSTA-FONTSM, and ASTA-FONTSM are selected, and four scenes are designed for comparative experiments. The experimental results show that MSTA-FONTSM has the worst control performance among the four control schemes. For the step, and continuous cosine trajectories with periods of T = 1 s and T = 2 s, the root-mean-square error of the proposed AFSTA-FONTSM is reduced by 56.86%, 54.03%, and 50.24% compared with MSTA-FONTSM. For disturbance experiments under different loads, the control performance of the proposed AFSTA-FONTSM is still superior to the other three control schemes without load.

Low-frequency variability in theta activity modulates the attention-fluctuation across task and resting states.

Sustained attention is not constant but fluctuates influencing our task performance. Albeit intensive investigations, it remains unclear whether the attention-fluctuation during tasks is derived from its spontaneous fluctuation in the resting state. Here, we addressed this issue by investigating the attention-fluctuation in both task and resting states, through the EEG measurement of theta-variability. We found significant rest-task modulation of theta-variability, i.e., reduced theta-variability in the task state compared to the resting state. This task and rest modulation was manifested in the low-frequency of theta-variability (<0.1 Hz). Furthermore, the low-frequency theta-variability exhibited a significant rest-task correlation, however, only the low-frequency theta-variability in the task state but not in the resting state was correlated with the behavioral performance. These findings shed light on the low-frequency feature of attention-fluctuation, and advanced our understanding of sustained attention by suggesting that the theta-variability in low-frequencies was relevant to attention level in task state.

Role in post-translational modification of M2-type pyruvate kinase in tumorigenesis and development. / M2åž‹ä¸™é ®é ¸æ¿€é ¶ç¿»è¯‘åŽä¿®é¥°åœ¨è‚¿ç˜¤å‘ç”Ÿå’Œå‘å±•ä¸­çš„ä½œç”¨.

PKM2, also known as M2-type pyruvate kinase, has attracted significant attention due to its crucial role in glycolysis and its abnormal expression in various tumors. With the discovery of PKM2's non-metabolic functions, the transition between its pyruvate kinase activity (in the tetrameric form in the cytoplasm) and protein kinase activity (in the dimeric form in the nucleus) has once again made PKM2 a target of interest in cancer research. Studies have shown that PKM2 is a protein susceptible to various post-translational modifications, and different post-translational modifications play important regulatory roles in processes such as PKM2 cellular localization, structure, and enzyme activity conversion. In this review, we focused on the recent progress of multiple post-translational modifications of PKM2 and their important roles in tumor initiation and development. For example, phosphorylation and acetylation promote nuclear translocation by altering PKM2 cell localization; glycosylation and ubiquitination can promote the formation of dimer structure by affecting the structural transformation of PKM2; succinylation and redox modification promoted the enhancement of PKM2 kinase activity by affecting the transformation of kinase activity. Both changes affect the structure and cell localization of PKM2 and they play a role in promoting or inhibiting tumor development via altering its kinase activity.

Clinical utility of metagenomic next-generation sequencing in pathogen detection for lower respiratory tract infections and impact on clinical outcomes in southernmost China.

Background: Today, metagenomic next-generation sequencing (mNGS) has emerged as a diagnostic tool for infections. However, since Hainan has a complicated pathogen spectrum, the diagnostic value and impact on patient outcomes of mNGS in Hainan are to be explored. Methods: From April 2020 to October 2021, 266 suspected lower respiratory tract infections (LRTIs) patients in Hainan were enrolled, and specimens were collected before antibiotic treatment. Bronchoalveolar lavage fluid (BALF) samples were subjected to mNGS and culture to compare the diagnostic performance. Other conventional microbiological tests (CMT) were also performed. Patients' treatments and clinical outcomes were recorded, and the antibiotic resistance genes (ARGs) were detected via mNGS workflow. Results: The positive rate of mNGS outperformed that of culture (87.55% vs. 39.30%, p<0.001) and CMT (87.12% vs. 52.65%, p<0.001). Specifically, mNGS detected more P. aeruginosa (12.03% vs 9.02%, p<0.05), H. influenzae (9.77% vs 2.26%, p<0.001), Aspergillus fumigatus (3.00% vs 0.75%, p<0.05), Candida albicans (26.32% vs 7.52%, p<0.001) and uncommon pathogens. It also demonstrated great diagnostic advantages in Mycobacterium tuberculosis with 80% sensitivity and 97.4% specificity. Over half of the patients (147, 55.26%) had modified empirical treatment according to mNGS results and 89.12% of them responded well. For three deaths with modified treatment, multiple drug resistance was predicted by mNGS and confirmed by antibiotic susceptibility test. Conclusions: The application of mNGS can benefit clinics in pathogen identification and antimicrobial treatment stewardship. Physicians should be alert to some emerging uncommon pathogens, including Chlamydia Psittaci, Nocardia otitidiscaviarum, and rare NTM.

Experimental infection and co-infection with Chinese strains of Ehrlichia canis and Babesia vogeli in intact and splenectomized dogs: Insights on clinical, hematologic and treatment responses.

Animal infection models are crucial for studying various aspects of Ehrlichia canis infections. To understand the pathogenesis of the first Chinese isolate of E. canis and simulate the natural progression of canine ehrlichiosis, we developed a model with 18 Beagle dogs that consisted of E. canis initial infection (days 0-17), treatment with doxycycline or rifampicin (days 18-32), recovery (days 33-66), E. canis reinfection (days 67-91), and Babesia vogeli superinfection (days 92-116). We measured body weight and rectal temperature every other day, drew blood every 4 days for routine hematology and biochemistry tests, and for quantification of E. canis and B. vogeli by quantitative PCRs. In this study, the first isolate of E. canis from China was used to experimentally infect dogs, and the infected dogs exhibited clinical signs of acute severe ehrlichiosis, including high fever, loss of appetite, dehydration, and body weight loss, confirming the similar pathogenicity of E. canis in China as compared to isolates from other regions. Infection with E. canis and B. vogeli led to reduced body weight and fever in dogs. Doxycycline treatment led to absence of E. canis DNA in infected dogs, while rifampicin treatment lowered the blood E. canis copy number up to 1.5 folds. E. canis-free infected dogs after doxycycline treatment were successfully re-infected with E. canis, indicating dogs with antibodies are still at risk of re-infection. Super-infection with B. vogeli resulted in higher fever, more severe anemia, and a reduced number of platelets. Splenectomized dogs showed significantly higher E. canis numbers during recovery and re-infection than intact dogs. The histological changes were observed in brain, lung, kidney, liver and spleen of the infected dogs. The findings in this study provide insights into clinical and hematologic responses, as well as effective treatment options, for dogs infected with the first Chinese isolate of E. canis, and may contribute to our understanding of the diagnosis and prevention of tick-borne diseases in dogs, including canine monocytic ehrlichiosis.

Effects of Enteromorpha prolifera polysaccharides on growth performance, intestinal barrier function and cecal microbiota in yellow-feathered broilers under heat stress.

BACKGROUND: Global warming leading to heat stress (HS) is becoming a major challenge for broiler production. This study aimed to explore the protective effects of seaweed (Enteromorpha prolifera) polysaccharides (EPS) on the intestinal barrier function, microbial ecology, and performance of broilers under HS. A total of 144 yellow-feathered broilers (male, 56 days old) with 682.59 ± 7.38 g were randomly assigned to 3 groups: 1) TN (thermal neutral zone, 23.6 ± 1.8 °C), 2) HS (heat stress, 33.2 ± 1.5 °C for 10 h/d), and 3) HSE (HS + 0.1% EPS). Each group contained 6 replicates with 8 broilers per replicate. The study was conducted for 4 weeks; feed intake and body weights were measured at the end of weeks 2 and 4. At the end of the feeding trial, small intestine samples were collected for histomorphology, antioxidant, secretory immunoglobulin A (sIgA) content, apoptosis, gene and protein expression analysis; cecal contents were also collected for microbiota analysis based on 16S rDNA sequencing. RESULTS: Dietary EPS promoted the average daily gain (ADG) of broilers during 3-4 weeks of HS (P < 0.05). At the end of HS on broilers, the activity of total superoxide dismutase (T-SOD), glutathione S-transferase (GST), and the content of sIgA in jejunum were improved by EPS supplementation (P < 0.05). Besides, dietary EPS reduced the epithelial cell apoptosis of jejunum and ileum in heat-stressed broilers (P < 0.05). Addition of EPS in HS group broilers' diet upregulated the relative mRNA expression of Occludin, ZO-1, γ-GCLc and IL-10 of the jejunum (P < 0.05), whereas downregulated the relative mRNA expression of NF-κB p65, TNF-α and IL-1ß of the jejunum (P < 0.05). Dietary EPS increased the protein expression of Occludin and ZO-1, whereas it reduced the protein expression of NF-κB p65 and MLCK (P < 0.01) and tended to decrease the protein expression of TNF-α (P = 0.094) in heat-stressed broilers. Furthermore, the proportions of Bacteroides and Oscillospira among the three groups were positively associated with jejunal apoptosis and pro-inflammatory cytokine expression (P < 0.05) and negatively correlated with jejunal Occludin level (P < 0.05). However, the proportions of Lactobacillus, Barnesiella, Subdoligranulum, Megasphaera, Collinsella, and Blautia among the three groups were positively related to ADG (P < 0.05). CONCLUSIONS: EPS can be used as a feed additive in yellow-feathered broilers. It effectively improves growth performance and alleviates HS-induced intestinal injury by relieving inflammatory damage and improving the tight junction proteins expression. These beneficial effects may be related to inhibiting NF-κB/MLCK signaling pathway activation and regulation of cecal microbiota.

Impact of blood-brain barrier disruption on clinical features and treatment response in patients with newly diagnosed autoimmune encephalitis.

AIMS: Blood-brain barrier (BBB) breakdown is an essential mechanism in inflammatory diseases of the central nervous system. However, the association between BBB integrity and autoimmune encephalitis (AE) has not been investigated. Our study aimed to analyze this relationship in patients with AE between BBB integrity with clinical manifestations and therapeutic responses. METHODS: Our study enrolled 147 patients with AE who were newly diagnosed at the First Affiliated Hospital of Zhengzhou University between August 2015 and December 2021. Patients were classified into normal or damaged BBB groups based on cerebrospinal fluid (CSF) albumin/serum albumin (QAlb). To evaluate the severity of the illness, we used the modified Rankin Scale (mRS) and the Clinical Assessment Scale for Autoimmune Encephalitis (CASE). RESULTS: We found a higher proportion of males, higher CSF protein, immunoglobulin IgG, and 24-h intrathecal IgG synthesis rate in the damaged BBB group. The improvement rate was lower in the damaged BBB group, but we found that double- or triple-combination immunotherapy had better clinical outcomes than single immunotherapy. In addition, there was a positive correlation between the CASE score and mRS score, and a positive correlation between the CASE score or mRS score and QAlb on admission. CONCLUSIONS: BBB integrity is closely related to the clinical features and treatment responses of newly diagnosed AE. Patients with AE and a damaged BBB may benefit from combination immunotherapy.

Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disease that is mainly caused by PHOX2B mutations. The purpose of this study is to analyze and summarize the clinical and genetic characteristics of CCHS patients in the Chinese population from our study and previous literature. METHODS: The potential pathogenic gene mutations of CCHS were identified and verified by next generation sequencing combined with Sanger sequencing, fluorescent probe PCR and capillary electrophoresis. The clinical characteristics and gene mutations of CCHS cases in Chinese population were summarized from our study and previous literature to explore the genotype-phenotype correlations. RESULTS: We identified 48 CCHS cases including three new cases from our report in China. Overall, 77.1% of the patients had PHOX2B polyalanine repeat expansion mutations (PARMs), and the remaining 22.9% had 10 distinct PHOX2B non-polyalanine repeat expansion mutations (NPARMs). Compared to those with PARMs, patients with NPARMs were more likely to have premature birth (54.5% vs. 2.8%, p < 0.001) and lower birth weight (33.3% vs. 3.2%, p = 0.030), with statistical significance. The patients with PARMs were more likely to have cardiovascular defects (64.9% vs. 27.3%, p = 0.063), cerebral hemorrhage (29.7% vs. 9.1%, p = 0.322) and seizures (37.8% vs. 9.1%, p = 0.151) than those with NPARMs, with no statistical significance. CONCLUSIONS: CCHS patients with PHOX2B NPARMs were more likely to have premature birth and low birth weight, while PHOX2B PARMs tended to be positively associated with the risk of cardiovascular defects, cerebral hemorrhage and seizures in Chinese population.

Clinical Efficiency of Metagenomic Next-Generation Sequencing in Sputum for Pathogen Detection of Patients with Pneumonia According to Disease Severity and Host Immune Status.

Purpose: Severe pneumonia causes the highest mortality rate in immunocompromised patients. This study aimed to investigate the pathogen diagnostic efficacy of metagenomic next-generation sequencing (mNGS) using sputum sample in patients with pneumonia according to patients' disease severity and immune conditions. Patients and Methods: A total of 180 patients suffering from pneumonia were recruited, and sputum samples were collected in duplicate for pathogen detection by both conventional microbiological tests (CMT) and mNGS. Then, the performance of pathogen identification was examined between two methods, according to disease severity and patients' immune status. Results: In comparison to CMT, mNGS had higher positivity rates in all patients with pneumonia (85.0% vs 62.2%, P=9.445e-07). The most commonly detected microorganism in sputum of pneumonia patients was Acinetobacter baumannii (42/180, 23.3%) in bacterum level, Candida albicans in fungus level (44/180, 24.4%), and Human herpesvirus 1 (39/180, 27.5%) in virus level. However, for mNGS results, Candida albicans in 34.9% of positive patients, and Human herpesvirus 1 in 7.7% of positive cases were confirmed as pathogens causing pneumonia. Acinetobacter baumannii detected by mNGS in 75% of positive patients was diagnosed as pathogen of pneumonia. The microorganism profile of sputum mNGS differed according to disease severity and immune status of patients. Pneumocystis jirovecii was more likely to infect immunocompromised patients (P=0.002). Pseudomonas aeruginosa (14.8% vs 0.0%, P=0.008) and Human herpesvirus 1 (26.1% vs 5.3%, P=0.004) had higher infection rate in patients with severe pneumonia compared with non-severe cases. mNGS had overwhelming advantages over CMT in detecting a lot of microorganisms including Streptococcus pneumoniae, Enterococcus faecium, Pneumocystis jirovecii, and majority of viruses. Conclusion: mNGS is a complementary tool of CMT for detecting suspected pathogens for patients with lower respiratory infections. The interpretation of opportunistic pathogens identified by mNGS is challenging, and needs comprehensive consideration of sequencing data and clinical factors.