M2 macrophages promote PD-L1 expression in triple-negative breast cancer via secreting CXCL1.

BACKGROUND: M2 macrophages are known to play a significant role in the progression of triple-negative breast cancer (TNBC) by creating an immunosuppressive microenvironment. The aim of this study is to investigate the impact of M2 macrophages on TNBC and their correlation with programmed death-ligand 1 (PD-L1) expression. METHODS: We employed a co-culture system to analyze the role of the mutual regulation of M2 macrophages and TNBC cells. Employing a multifaceted approach, including bioinformatics analysis, Western blotting, flow cytometry analysis, ELISA, qRT-PCR, lentivirus infection, mouse models, and IHC, we aimed to elucidate the influence and mechanism of M2 macrophages on PD-L1 expression. RESULTS: The results showed a substantial infiltration of M2 macrophages in TNBC tissue, which demonstrated a positive correlation with PD-L1 expression. CXCL1 exhibited abnormally high expression in M2 macrophages and enhanced the expression of PD-L1 in TNBC cells. Notably, silencing CXCL1 or its receptor CXCR2 inhibited M2 macrophages-induced expression of PD-L1. Mechanistically, CXCL1 derived from M2 macrophages binding to CXCR2 activated the PI3K/AKT/NF-κB signaling pathway, resulting in increased PD-L1 expression in TNBC. CONCLUSION: Broadly speaking, these results provide evidence for the immunosuppressive role of M2 macrophages and CXCL1 in TNBC cells, indicating their potential as therapeutic biomarkers.

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods.

In accordance with the World Health Organization data, cancer remains at the forefront of fatal diseases. An upward trend in cancer incidence and mortality has been observed globally, emphasizing that efforts in developing detection and treatment methods should continue. The diagnostic path typically begins with learning the medical history of a patient; this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy. Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization. Thus, there is a need for novel cancer detection methods such as liquid biopsy, elastography, synthetic biosensors, fluorescence imaging, and reflectance confocal microscopy. Conventional therapeutic methods, although still common in clinical practice, pose many limitations and are unsatisfactory. Nowadays, there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy, exosome-based therapy, nanotechnology, dendritic cells, chimeric antigen receptors, immune checkpoint inhibitors, natural product-based therapy, tumor-treating fields, and photodynamic therapy. The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions. As evidenced, modern methods are not without drawbacks; there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity, specificity, safety, and efficacy. Nevertheless, an appropriate route has been taken, as confirmed by the approval of some modern methods by the Food and Drug Administration.

Impact of the gut microbiome on response and toxicity to chemotherapy in advanced esophageal cancer.

Objective: To identify the gut bacteria associated with chemotherapeutic outcomes, t characterized the gut microbiota in patients with esophageal squamous cell carcinoma (ESCC) in this prospective study. Design: Thirty-one patients with ESCC were enrolled. Chemotherapy was performed with paclitaxel and cisplatin (TP). Fecal samples were collected before and after treatment and analyzed using 16S rRNA sequencing. Results: The species with differences in baseline abundance between partial response (PR) and non-PR groups was identified as Bacteroides plebeius (P = 0.043). The baseline abundance of B. plebeius was higher in the responder (R, PR + stable disease (SD)) group (P = 0.045) than in the non-responder (NR). The abundance of B. ovatus was identified as a predictor for distinguishing patients with PR from those without PR (sensitivity, 83.3 %; specificity, 69.6 %). The abundance of B. plebeius was positively associated with the response to PR + SD (R) in predicting responders in the receiver operating characteristic (ROC) curve analysis (area under the ROC curve = 0.865, P = 0.041). The abundance of B. plebeius and B.uniform was a predictor of grade (G) 3-4 chemotherapy toxicities. The sensitivity and specificity of the established multi-analyte microbial predictive model demonstrated a better predictive ability than a single parameter (B. uniform or B. plebeius). Conclusion: The abundance of gut microbiota B. plebeius and B. ovatus are associated with the efficacy of TP chemotherapy in patients with ESCC. The abundance of B. plebeius and B.uniform may related to the toxicity of TP chemotherapy.

PRELP reduce cell stiffness and adhesion to promote the growth and metastasis of colorectal cancer cells by binding to integrin α5.

PRELP is thought to be an inhibitor of the development and progression of a variety of malignancies. Metastasis is a major cause of death in patients with colorectal cancer, but the mechanism underlying the role of PRELP in colorectal cancer metastasis remains poorly understood. In this study, we found that PRELP was significantly higher in metastatic tissues than in non-metastatic tissues of colorectal cancer and was closely associated with poor prognosis of colorectal cancer patients. PRELP promotes growth and metastasis of colorectal cancer cells. PRELP reduces cell stiffness and adhesion. PRELP promoted EMT in colorectal cancer cells and that PRELP bind to integrin α5 to activate the integrin α5/FAK/AKT signaling pathway. In conclusion, we demonstrate that PRELP is upregulated in metastatic colorectal cancer, providing a potential prognostic marker and therapeutic target for the clinical management of metastatic colorectal cancer from a biomechanical perspective.

Impact of visual and textural characteristics of street walls on stress recovery.

Rapid urbanization increases psychological stress among pedestrians, potentially heightening mental health disorders. This study examines the role of street walls' visual and textural characteristics in stress recovery, using Qingdao as a case study. Virtual reality is employed to simulate five distinct street walls: yellow mortar, brown stone, red brick, green plant, and white mortar. The stress recovery effectiveness of these walls was evaluated through psychological and physiological indicators from 48 young college students. Results indicated that street walls with warm tones, particularly brown stone, significantly aid stress recovery. Psychologically, Restorative Components Scale was highest for brown stone at 1.13. Physiologically, it was linked with notable reductions in diastolic and pulse pressure (decreases of 2.95 mmHg and 2.27 mmHg, respectively), and enhanced parasympathetic activity, as evidenced by the fastest decrease in low frequency/high frequency ratio (LF/HF), and increases in pNN50 and RR (0.14-2.01% and 1.57-11.81 ms, respectively). For urban design, the incorporation of warm-toned materials and natural elements like stone is recommended for their superior restorative benefits.

A pilot study on oral microbiome in electronic cigarettes consumers versus traditional cigarettes smokers.

Oral microorganisms are closely related to oral health, the occurrence of some oral diseases is associated with changes in the oral microbiota, and many studies have demonstrated that traditional smoking can affect the oral microbial community. However, due to the short time since the emergence of e-cigarettes, fewer studies are comparing oral microorganisms for users of e-cigarettes versus cigarettes. We collected saliva from 40 non-smokers (NS), 46 traditional cigarette smokers (TS), and 27 e-cigarette consumers (EC), aged between 18 and 35 years. We performed 16S rRNA gene sequencing on the saliva samples collected to study the effects of e-cigarettes versus traditional cigarettes on the oral microbiome. The results showed that compared with the NS group, the alpha diversity of oral flora in saliva was altered in the TS group, with no significant change in the e-cigarette group. Compared with the NS and EC groups, the relative abundance of Actinomyces and Prevotella was increased in the TS group. However, compared with the NS and TS groups, the relative abundance of Veillonella was increased, and the relative abundance of Porphyromonas and Peptostreptococcus was decreased in the EC group. These results showed that both e-cigarettes and traditional cigarettes could alter the structure and composition of oral microbiota. The use of traditional cigarettes promotes the growth of some anaerobic bacteria, which may contribute to dental decay and bad breath over time. E-cigarettes have a different effect on the structure and composition of the oral microbial community compared to conventional cigarettes. In order to better understand the effects of e-cigarettes and traditional cigarettes on users' mouths, future studies will investigate the relationship between diseases such as dental caries and periodontitis and changes in oral microbial species levels.

Multikingdom characterization of gut microbiota in patients with rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious and common extra-articular disease manifestation. Patients with RA-ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole-metagenome shotgun sequencing on fecal samples from 30 patients with RA-ILD, and 30 with RA-non-ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference-based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA-ILD and RA-non-ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA-ILD), Gemmiger formicilis, and Ruminococcus bromii (RA-non-ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA-ILD and RA-non-ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA-ILD and RA-non-ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research.

Assessing the efficacy of a graded pulmonary rehabilitation protocol in mechanically ventilated patients following brainstem hemorrhage.

BACKGROUND: The objective of this study is to assess the impact of an early-graded pulmonary rehabilitation training program on patients undergoing mechanical ventilation due to brainstem hemorrhage. METHODS: Eighty patients receiving mechanical ventilation due to brainstem hemorrhage at our hospital's neurosurgery department between August 2022 and October 2023 were enrolled as participants. A sampling table was generated based on the order of admission, and 80 random sequences were generated using SPSS software. These sequences were then sorted in ascending order, with the first half designated as the control group and the second half as the intervention group, each comprising 40 cases. The control group received standard nursing care for mechanical ventilation in brainstem hemorrhage cases, while the intervention group underwent early-graded pulmonary rehabilitation training in addition to standard care. This intervention was conducted in collaboration with a multidisciplinary respiratory critical care rehabilitation team. The study compared respiratory function indices, ventilator weaning success rates, ventilator-associated pneumonia incidence, mechanical ventilation duration, and patient discharge duration between the 2 groups. RESULTS: The comparison between patients in the observation group and the control group regarding peak expiratory flow and maximum inspiratory pressure on days 1, 3, 5, and 7 revealed statistically significant differences (P < .05). Additionally, there was a statistically significant interaction between the main effect of intervention and the main effect of time (P < .05). The success rate of ventilator withdrawal was notably higher in the observation group (62.5%) compared to the control group (32.5%), with a statistically significant difference (P < .05). Moreover, the incidence rate of ventilator-associated pneumonia was significantly lower in the observation group (2.5%) compared to the control group (17.5%) (P < .05). Furthermore, both the duration of mechanical ventilation and hospitalization were significantly shorter in the observation group compared to the control group (P < .05). CONCLUSION: Early-graded pulmonary rehabilitation training demonstrates effectiveness in enhancing respiratory function, augmenting the ventilator withdrawal success rate, and reducing both the duration of mechanical ventilation and hospitalization in mechanically ventilated patients with brainstem hemorrhage. These findings suggest the potential value of promoting the application of this intervention in clinical practice.

Association between thyroid autoimmunity and antinuclear antibody prevalence among pregnant women: a cross-sectional study in Qingdao, China.

Objective: To identify the relationship between thyroid autoimmunity and antinuclear antibody (ANA) prevalence in Chinese pregnant women. Methods: The study involved 1923 first-trimester women who were measured for thyroid stimulating hormone (TSH) level, thyroid autoantibodies (thyroperoxidase antibody [TPOAb] and thyroglobulin antibody [TgAb]) and ANA titer. Social demographic data were collected through standardized questionnaires. Results: In this study, 23.3% of pregnant women tested positive for TPOAb and 9.9% tested positive for TgAb. Women with a positive ANA were more likely to be TPOAb-positive or TgAb-positive than women with a negative ANA (adjusted odds ratio [AOR] 1.96, 95% confidence interval [CI] 1.47-2.62 for TPOAb [+]; AOR 3.12, 95% CI 2.18-4.48 for TgAb[+]). In addition, ANA titers were closely associated with thyroid autoimmunity. Women with an ANA titer of >1:320 had a significant higher risk of being TPOAb positive or TgAb positive (AOR 4.49, 95% CI 1.48-13.66 for TPOAb [+]; AOR 5.51, 95% CI 1.65-18.49 for TgAb [+]). The higher the ANA titer, the greater the risk of developing thyroid autoimmunity, especially for those with a high ANA titer. Conclusions: ANA positivity is strongly correlated with thyroid autoimmunity. Further study is warranted to clarify the causal relationship between thyroid autoimmunity and ANA in pregnant women.This research is essential to evaluate and predict the risk of co-existing autoimmune disorders,leading to improved care for pregnancy and neonatal health.

Mask-Guided Vision Transformer for Few-Shot Learning.

Learning with little data is challenging but often inevitable in various application scenarios where the labeled data are limited and costly. Recently, few-shot learning (FSL) gained increasing attention because of its generalizability of prior knowledge to new tasks that contain only a few samples. However, for data-intensive models such as vision transformer (ViT), current fine-tuning-based FSL approaches are inefficient in knowledge generalization and, thus, degenerate the downstream task performances. In this article, we propose a novel mask-guided ViT (MG-ViT) to achieve an effective and efficient FSL on the ViT model. The key idea is to apply a mask on image patches to screen out the task-irrelevant ones and to guide the ViT focusing on task-relevant and discriminative patches during FSL. Particularly, MG-ViT only introduces an additional mask operation and a residual connection, enabling the inheritance of parameters from pretrained ViT without any other cost. To optimally select representative few-shot samples, we also include an active learning-based sample selection method to further improve the generalizability of MG-ViT-based FSL. We evaluate the proposed MG-ViT on classification, object detection, and segmentation tasks using gradient-weighted class activation mapping (Grad-CAM) to generate masks. The experimental results show that the MG-ViT model significantly improves the performance and efficiency compared with general fine-tuning-based ViT and ResNet models, providing novel insights and a concrete approach toward generalizing data-intensive and large-scale deep learning models for FSL.

The role of a novel secretory peptidoglycan recognition protein with antibacterial ability from the Chinese Oak Silkworm Antheraea pernyi in humoral immunity.

Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors that play a critical role in the immune response of invertebrates and vertebrates. Herein, the short ApPGRP-D gene was cloned from the model lepidopteran Antheraea pernyi. Quantitative PCR (qPCR) confirmed that ApPGRP-D is an immune-related protein and that the expression of ApPGRP-D can be induced by microorganisms. ApPGRP-D is a broad-spectrum pattern recognition protein that activates the prophenoloxidase cascade activation system and promotes the agglutination of microbial cells. Likely due to its amidase activity, ApPGRP-D can inhibit the growth of E. coli and S. aureus. In addition, we demonstrated for the first time that zinc ions, as important metal coenzymes, could promote multiple functions of ApPGRP-D but not its amidase activity.

LINC02257 regulates colorectal cancer liver metastases through JNK pathway.

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood. Methods: To explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM. Results: Our findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM. Conclusions: Our study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC.

Texture improvement and in vitro digestion modulation of plant-based fish cake analogue by incorporating hydrocolloid blends.

Hydrocolloids have proven effective in improving the texture of surimi gels, yet their application in plant-based seafood analogues remains underexplored. This study aimed to develop a hydrocolloid blend comprising methylcellulose (MC), curdlan gum (CG), and high-acyl gellan gum (GG) to achieve a surimi-like texture in plant-based fish cakes (PBFC) made from brown rice and pea protein isolates. The research showcased that higher MC concentration boosted protein powder's heated oil holding capacity, while CG concentration increments lowered it. However, heated water holding capacity remained stable despite changes in MC and GG levels. Incorporating hydrocolloids elevated PBFC moisture content, decreasing expressible moisture and oil amounts with rising MC, CG and GG concentrations. PBFC hardness increased with higher hydrocolloid levels and was influenced by temperature, while springiness remained unaffected. GG helped maintain storage modulus (G') during PBFC cooling at higher concentrations, whereas the opposite effect was observed for MC. Analytically, higher MC concentrations reduced protein digestibility, while increased GG concentrations appeared to enhance it. Microstructural analysis corroborated these findings, with more protein aggregates in PBFC containing 3.8% MC and fewer in PBFCs with 6% CG and 3% GG. Consumer evaluations indicated that PBFC formulated with 1% MC, 3% CG, and 1.5% GG matched the springiness of commercial surimi-tofu fish cake, though it received slightly lower overall liking scores. In conclusion, the combined use of these three hydrocolloids demonstrated the potential to enhance the physical properties of PBFC and modify protein digestibility, offering insights into the development of innovative plant-based seafood analogues.

Association between hyperuricemia and chronic total coronary occlusion in non-chronic kidney disease populations: a cross-sectional study.

BACKGROUND: Chronic total coronary occlusion (CTO) is an extremely hazardous condition that leads to various clinical phenomena and complications and results in social and economic burdens. Hyperuricemia (HU) is often associated with atherosclerosis. Few studies, however, have investigated the risk of CTO in individuals with HU and the role of traditional cardiovascular risk factors in this setting. METHODS: A cohort of 1245 individuals without chronic kidney disease from southwest China who underwent coronary angiography between February 2018 and June 2021 were enrolled. CTO was defined as a total occlusion of any coronary artery or arteries for more than 3 months. HU was defined as a serum uric acid level of ≥420 µmol/L in men and ≥360 µmol/L in women. Univariate and multivariate logistic regression models and subgroup analyses were applied to assess the relationship between HU and CTO. RESULTS: After adjustment, HU was noted to be associated with a 1.47-fold increase in the risk of CTO [odds ratio (OR), 1.47; 95% confidence interval (CI), 1.06-2.58; P = 0.026]. As a continuous variable, uric acid was an independent predictor of CTO (OR, 1.002; 95% CI, 1.001-1.004; P = 0.047). Subgroup analyses showed that the risk of CTO was higher among individuals under 65 years of age (OR, 2.77; 95% CI, 1.3-5.89), nonobese individuals (OR, 1.9; 95% CI, 1.16-3.1), and those with dyslipidemia (OR, 1.8; 95% CI, 1.04-3.11), while sex, smoking, hypertension, and diabetes did not show similar effects. Interaction analyses revealed no interaction among subgroups. CONCLUSION: Among individuals residing in southwest China, HU was associated with an increased risk of CTO in non-CKD individuals, especially those under 65 years of age and nonobese and dyslipidemic individuals.

Whole-exome sequencing screening for candidate genes and variants associated with primary sporadic keratoconus in Chinese patients.

The pathogenesis of keratoconus (KC) is complex, and genetic factors play an important role. The purpose of this study was to screen and analyse candidate genes and variants in Chinese patients with primary sporadic KC. Whole-exome sequencing (WES) was performed to identify candidate genes and variants in 105 unrelated Chinese patients with primary sporadic KC. Through a series of screening processes, 54 candidate variants in 26 KC candidate genes were identified in 53 KC patients (53/105, 50.5%). These 54 candidate variants included 10 previously identified variants in 9 KC candidate genes and 44 novel variants in 20 KC candidate genes. The previously identified variants occurred in 25.7% (27/105) of patients. Of these, 4 variants (COL6A5, c.5014T > G; CAST, c.1814G > A; ZNF469, c.946G > A; and MPDZ, c.3836A > G) were identified for the first time in Chinese KC patients. The novel variants occurred in 33.3% (35/105) of patients. Of the 26 screened KC candidate genes, 11 KC candidate genes (CAT, COL12A1, FLG, HKDC1, HSPG2, PLOD1, ITGA2, TFAP2B, USH2A, WNT10A, and COL6A5) were found to be potentially pathogenic in Chinese KC patients for the first time. Gene Ontology (GO) biological process (BP) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the 26 KC candidate genes using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The results showed that the KC candidate genes were significantly enriched in biological processes such as collagen fibril organization and extracellular matrix (ECM) organization and in ECM-receptor interaction and protein digestion and absorption pathways. The results further expand the spectrum of KC candidate variants and provide a basis for further KC gene studies.

Ar/NH3 Plasma Etching of Cobalt-Nickel Selenide Microspheres Rich in Selenium Vacancies Wrapped with Nitrogen Doped Carbon Nanotubes as Highly Efficient Air Cathode Catalysts for Zinc-Air Batteries.

This work utilizes defect engineering, heterostructure, pyridine N-doping, and carbon supporting to enhance cobalt-nickel selenide microspheres' performance in the oxygen electrode reaction. Specifically, microspheres mainly composed of CoNiSe2 and Co9Se8 heterojunction rich in selenium vacancies (VSe·) wrapped with nitrogen-doped carbon nanotubes (p-CoNiSe/NCNT@CC) are prepared by Ar/NH3 radio frequency plasma etching technique. The synthesized p-CoNiSe/NCNT@CC shows high oxygen reduction reaction (ORR) performance (half-wave potential (E1/2) = 0.878 V and limiting current density (JL) = 21.88 mA cm-2). The JL exceeds the 20 wt% Pt/C (19.34 mA cm-2) and the E1/2 is close to the 20 wt% Pt/C (0.881 V). It also possesses excellent oxygen evolution reaction (OER) performance (overpotential of 324 mV@10 mA cm-2), which even exceeds that of the commercial RuO2 (427 mV@10 mA cm-2). The density functional theory calculation indicates that the enhancement of ORR performance is attributed to the synergistic effect of plasma-induced VSe· and the CoNiSe2-Co9Se8 heterojunction. The p-CoNiSe/NCNT@CC electrode assembled Zinc-air batteries (ZABs) show a peak power density of 138.29 mW cm-2, outperforming the 20 wt% Pt/C+RuO2 (73.9 mW cm-2) and other recently reported catalysts. Furthermore, all-solid-state ZAB delivers a high peak power density of 64.83 mW cm-2 and ultra-robust cycling stability even under bending.

Lactobacillus rhamnosus GG alleviates radiation-induced intestinal injury by modulating intestinal immunity and remodeling gut microbiota.

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy. In this study, we investigated the potential protective effect of Lactobacillus rhamnosus GG (LGG) on radiation-induced intestinal injury and its underlying mechanisms. Mice were assigned to a control group, a 10 Gy total abdominal irradiation (TAI) group, or a group pretreated with 108 CFU LGG for three days before TAI. Small intestine and gut microbiota were analyzed 3.5 days post-exposure. LGG intervention improved intestinal structure, reduced jejunal DNA damage, and inhibited the inflammatory cGAS/STING pathway. Furthermore, LGG reduced M1 proinflammatory macrophage and CD8+ T cell infiltration, restoring the balance between Th17 and Treg cells in the inflamed jejunum. LGG also partially restored the gut microbiota. These findings suggest the possible therapeutic radioprotective effect of probiotics LGG in alleviating radiation-induced intestinal injury by maintaining immune homeostasis and reshaping gut microbiota.

Synaptic alterations in pyramidal cells following genetic manipulation of neuronal excitability in monkey prefrontal cortex.

In schizophrenia, layer 3 pyramidal neurons (L3PNs) in the dorsolateral prefrontal cortex (DLPFC) are thought to receive fewer excitatory synaptic inputs and to have lower expression levels of activity-dependent genes and of genes involved in mitochondrial energy production. In concert, these findings from previous studies suggest that DLPFC L3PNs are hypoactive in schizophrenia, disrupting the patterns of activity that are crucial for working memory, which is impaired in the illness. However, whether lower PN activity produces alterations in inhibitory and/or excitatory synaptic strength has not been tested in the primate DLPFC. Here, we decreased PN excitability in rhesus monkey DLPFC in vivo using adeno-associated viral vectors (AAVs) to produce Cre recombinase-mediated overexpression of Kir2.1 channels, a genetic silencing tool that efficiently decreases neuronal excitability. In acute slices prepared from DLPFC 7-12 weeks post-AAV microinjections, Kir2.1-overexpressing PNs had a significantly reduced excitability largely attributable to highly specific effects of the AAV-encoded Kir2.1 channels. Moreover, recordings of synaptic currents showed that Kir2.1-overexpressing DLPFC PNs had reduced strength of excitatory synapses whereas inhibitory synaptic inputs were not affected. The decrease in excitatory synaptic strength was not associated with changes in dendritic spine number, suggesting that excitatory synapse quantity was unaltered in Kir2.1-overexpressing DLPFC PNs. These findings suggest that, in schizophrenia, the excitatory synapses on hypoactive L3PNs are weaker and thus might represent a substrate for novel therapeutic interventions. Significance Statement: In schizophrenia, dorsolateral prefrontal cortex (DLPFC) pyramidal neurons (PNs) have both transcriptional and structural alterations that suggest they are hypoactive. PN hypoactivity is thought to produce synaptic alterations in schizophrenia, however the effects of lower neuronal activity on synaptic function in primate DLPFC have not been examined. Here, we used, for the first time in primate neocortex, adeno-associated viral vectors (AAVs) to reduce PN excitability with Kir2.1 channel overexpression and tested if this manipulation altered the strength of synaptic inputs onto the Kir2.1-overexpressing PNs. Recordings in DLPFC slices showed that Kir2.1 overexpression depressed excitatory (but not inhibitory), synaptic currents, suggesting that, in schizophrenia, the hypoactivity of PNs might be exacerbated by reduced strength of the excitatory synapses they receive.

High-resolution short-term prediction of the COVID-19 epidemic based on spatial-temporal model modified by historical meteorological data.

In the global challenge of Coronavirus disease 2019 (COVID-19) pandemic, accurate prediction of daily new cases is crucial for epidemic prevention and socioeconomic planning. In contrast to traditional local, one-dimensional time-series data-based infection models, the study introduces an innovative approach by formulating the short-term prediction problem of new cases in a region as multidimensional, gridded time series for both input and prediction targets. A spatial-temporal depth prediction model for COVID-19 (ConvLSTM) is presented, and further ConvLSTM by integrating historical meteorological factors (Meteor-ConvLSTM) is refined, considering the influence of meteorological factors on the propagation of COVID-19. The correlation between 10 meteorological factors and the dynamic progression of COVID-19 was evaluated, employing spatial analysis techniques (spatial autocorrelation analysis, trend surface analysis, etc.) to describe the spatial and temporal characteristics of the epidemic. Leveraging the original ConvLSTM, an artificial neural network layer is introduced to learn how meteorological factors impact the infection spread, providing a 5-day forecast at a 0.01° × 0.01° pixel resolution. Simulation results using real dataset from the 3.15 outbreak in Shanghai demonstrate the efficacy of Meteor-ConvLSTM, with reduced RMSE of 0.110 and increased R 2 of 0.125 (original ConvLSTM: RMSE = 0.702, R 2 = 0.567; Meteor-ConvLSTM: RMSE = 0.592, R 2 = 0.692), showcasing its utility for investigating the epidemiological characteristics, transmission dynamics, and epidemic development.