Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study.

Background: The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of population-level studies with providing robust evidence for establishing causality. This two-sample Mendelian randomization (MR) analysis aimed to investigate the causal relationship between the gut microbiota and IPF as well as lung function. Materials and methods: Adhering to Mendel's principle of inheritance, this MR analysis utilized summary-level data from respective genome-wide association studies (GWAS) involving 211 gut microbial taxa, IPF, and lung function indicators such as FEV1, FVC, and FEV1/FVC. A bidirectional two-sample MR design was employed, utilizing multiple MR analysis methods, including inverse variance-weighted (IVW), weighted median, MR-Egger, and weighted mode. Multivariable MR (MVMR) was used to uncover mediating factors connecting the exposure and outcome. Additionally, comprehensive sensitivity analyses were conducted to ensure the robustness of the results. Results: The MR results confirmed four taxa were found causally associated with the risk of IPF. Order Bifidobacteriales (OR=0.773, 95% CI: 0.610-0.979, p=0.033), Family Bifidobacteriaceae (OR=0.773, 95% CI: 0.610-0.979, p=0.033), and Genus RuminococcaceaeUCG009 (OR=0.793, 95% CI: 0.652-0.965, p=0.020) exerted protective effects on IPF, while Genus Coprococcus2 (OR=1.349, 95% CI: 1.021-1.783, p=0.035) promote the development of IPF. Several taxa were causally associated with lung function, with those in Class Deltaproteobacteria, Order Desulfovibrionales, Family Desulfovibrionaceae, Class Verrucomicrobiae, Order Verrucomicrobiales and Family Verrucomicrobiaceae being the most prominent beneficial microbiota, while those in Family Lachnospiraceae, Genus Oscillospira, and Genus Parasutterella were associated with impaired lung function. As for the reverse analysis, MR results confirmed the effects of FEV1 and FVC on the increased abundance of six taxa (Phylum Actinobacteria, Class Actinobacteria, Order Bifidobacteriales, Family Bifidobacteriaceae, Genus Bifidobacterium, and Genus Ruminiclostridium9) with a boosted level of evidence. MVMR suggested monounsaturated fatty acids, total fatty acids, saturated fatty acids, and ratio of omega-6 fatty acids to total fatty acids as potential mediating factors in the genetic association between gut microbiota and IPF. Conclusion: The current study suggested the casual effects of the specific gut microbes on the risk of IPF and lung function. In turn, lung function also exerted a positive role in some gut microbes. A reasonable dietary intake of lipid substances has a certain protective effect against the occurrence and progression of IPF. This study provides novel insights into the potential role of gut microbiota in IPF and indicates a possible gut microbiota-mediated mechanism for the prevention of IPF.

Impact of urban space on PM2.5 distribution: A multiscale and seasonal study in the Yangtze River Delta urban agglomeration.

Despite concerted efforts in emission control, air pollution control remains challenging. Urban planning has emerged as a crucial strategy for mitigating PM2.5 pollution. What remains unclear is the impact of urban form and their interactions with seasonal changes. In this study, base on the air quality monitoring stations in the Yangtze River Delta urban agglomeration, the relationship between urban spatial indicators (building morphology and land use) and PM2.5 concentrations was investigated using full subset regression and variance partitioning analysis, and seasonal differences were further analysed. Our findings reveal that PM2.5 pollution exhibits different sensitivities to spatial scales, with higher sensitivity to the local microclimate formed by the three-dimensional structure of buildings at the local scale, while land use exerts greater influence at larger scales. Specifically, land use indicators contributed sustantially more to the PM2.5 prediction model as buffer zone expand (from an average of 2.41% at 100 m range to 47.30% at 5000 m range), whereas building morphology indicators display an inverse trend (from an average of 13.84% at 100 m range to 1.88% at 5000 m range). These results enderscore the importance of considering building morphology in local-scale urban planning, where the increasing building height can significantly enhance the disperion of PM2.5 pollution. Conversely, large-scale urban planning should prioritize the mixed use of green spaces and construction lands to mitigate PM2.5 pollution. Moreover, the significant seasonal differences in the ralationship between urban spatical indicatiors and PM2.5 pollution were observed. Particularly moteworthy is the heightened association between forest, water indicators and PM2.5 concentrations in summer, indicating the urban forests may facilitate the formation of volatile compunds, exacerbating the PM2.5 pollution. Our study provides a theoretical basis for addressing scale-related challenges in urban spatial planning, thereby forstering the sustainable development of cities.

Sorting infrared optical vortices with a nonlinear angular lens.

Analogous to the regular lens, which spatially maps plane waves in the space domain to distinct points in the Fourier domain, the angular lens establishes the mapping relations between an angular mode and angular position, thus providing an effective toolkit for detecting an optical vortex. However, using the angular lens to sort infrared optical vortex modes via nonlinear optical processes remains relatively unexplored. Here, we design a nonlinear optical version of the angular lens to map the various infrared optical vortex modes to different angular positions in the visible region. We successfully sort nine infrared optical vortex modes of different topological charges with a visible camera, showing the cost-effective ability to sort infrared vortices compared to a relatively expensive infrared camera. Our scheme holds promise for infrared remote sensing, infrared vortex-encoded optical communications, and so on.

Low-Temperature Thermal Transport Characteristics in Epitaxial Bilayer Graphene Microbridges.

In this paper, we present a study of the thermal transport of epitaxial bilayer graphene microbridges. The thermal conductance of three graphene microbridges with different lengths was measured at different temperatures using Johnson noise thermometry. We find that with the decrease of the temperature, the thermal transport in the graphene microbridges switches from electron-phonon coupling to electron diffusion, and the switching temperature is dependent on the length of the microbridge, which is in good agreement with the simulation based on a distributed hot-spot model. Moreover, the electron-phonon thermal conductance has a temperature power law of T3 as predicted for pristine graphene and the electron-phonon coupling coefficient σep is found to be approximately 0.18 W/(m2 K4), corresponding to a deformation potential D of 55 eV. In addition, the electron diffusion in the graphene microbridges adheres to the Wiedemann-Franz law, requiring no corrections to the Lorentz number.

Progressively worsening ptosis in a woman: A case report.

Key Clinical Message: Filler injections into the upper eyelid may cause levator aponeurosis fibrosis and ptosis. This risk must be considered. When ptosis appears, treatment might be difficult. Understanding the upper eyelid anatomy and procedures is essential to prevent eyelid damage. Abstract: Ptosis is a prevalent condition in cosmetic surgery that occurs due to malfunction of the levator palpebrae superioris or insufficient Müller muscle action. It is characterized by the upper eyelid edge appearing lower than usual when seen at eye level. Ptosis may be categorized into congenital and acquired forms. The primary cause of congenital ptosis is attributed to abnormalities of the levator palpebrae superioris muscle or the motor nerve innervation that controls it. The condition arises from atypical development and malfunction of the oculomotor system. Acquired ptosis may be classified into many categories including traumatic, neurogenic, myogenic, senile, mechanical, and fake ptosis. Currently, there is little documentation of ptosis resulting from the degeneration of the aponeurosis of the muscle in the upper eyelid. We received a case of ptosis caused by fibrosis of the levator palpebrae superioris aponeurotic membrane. We used the technique of levator palpebrae superioris great advancement. The levator palpebrae superioris-Müller muscle was folded to create a stable composite construction via the levator palpebrae superioris high progress.

Correlation of TyG-BMI and TyG-WC with severity and short-term outcome in new-onset acute ischemic stroke.

Objectives: To research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke. Methods: Data of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyG-WC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome. Results: The study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of moderate-severe stroke [Q3: OR: 0.355, 95%CI (0.173-0.728), P = 0.005; Q4: OR: 0.140, 95%CI (0.056-0.351), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of short-term adverse outcomes [Q3: OR: 0.350, 95%CI (0.175-0.700), P = 0.003; Q4: OR: 0.178, 95%CI (0.071-0.451), P <0.001]. Conclusions: TyG-WC and TyG-BMI were correlated with the severity and short-term outcome of new-onset acute ischemic stroke. As TyG-WC and TyG-BMI increased, stroke severity decreased and short-term outcome was better.

Lab-on-Device Synthesis of Hierarchical Macro/Mesoporous WO3 Semiconducting Films for High-Performance H2S Sensing.

The performance consistency of the gas sensor is strongly dependent on the interface binding between the sensitive materials and the electrodes. Traditional powder coating methods can inevitably lead to differences in terms of substrate-film interface interaction and device performance, affecting the stability and lifetime. Thus, efficient growth of sensitive materials on device substrates is crucial and essential to enhance the sensing performance, especially for stability. Herein, hierarchically ordered macro/mesoporous WO3 films are in situ synthesized on the electrode via a facile soft/hard dual-template strategy. Orderly arrayed uniform polystyrene (PS) microspheres with tailored size (ca. 1.2 µm) are used as a hard template, and surfactant Pluronic F127 as a soft template can co-assemble with tungsten precursor into ordered mesostructure in the interstitials of PS colloidal crystal induced by solvent evaporation. Benefiting from its rich porosity and high stability, the macro/mesoporous WO3-based sensor shows high sensitivity (Rair/Rgas = 307), fast response/recovery speed (5/9 s), and excellent selectivity (SH2S/Smax > 7) toward 50 ppm H2S gas (a biomarker for halitosis). Significantly, the sensors exhibit an extended service life with a negligible change in sensing performance within 60 days. This lab-on-device synthesis provides a platform method for constructing stable nanodevices with good consistency and high stability, which are highly desired for developing high-performance sensors.

Natural plant medications for the treatment of retinal diseases: The blood-retinal barrier as a clue.

BACKGROUND: Retinal diseases significantly contribute to the global burden of visual impairment and blindness. The occurrence of retinal diseases is often accompanied by destruction of the blood‒retinal barrier, a vital physiological structure responsible for maintaining the stability of the retinal microenvironment. However, detailed summaries of the factors damage the blood‒retinal barrier and treatment methods involving natural plant medications are lacking. PURPOSE: To comprehensively summarize and analyze the protective effects of active substances in natural plant medications on damage to the blood-retina barrier that occurs when retinal illnesses, particularly diabetic retinopathy, and examine their medicinal value and future development prospects. METHODS: In this study, we searched for studies published in the ScienceDirect, PubMed, and Web of Science databases. The keywords used included natural plant medications, plants, natural herbs, blood retinal barrier, retinal diseases, diabetic retinopathy, age-related macular degeneration, and uveitis. Chinese herbal compound articles, non-English articles, warning journals, and duplicates were excluded from the analysis. RESULTS: The blood‒retinal barrier is susceptible to high glucose, aging, immune responses, and other factors that destroy retinal homeostasis, resulting in pathological changes such as apoptosis and increased vascular permeability. Existing studies have shown that the active compounds or extracts of many natural plants have the effect of repairing blood-retinal barrier dysfunction. Notably, berberine, puerarin, and Lycium barbarum polysaccharides exhibited remarkable therapeutic effects. Additionally, curcumin, astragaloside IV, hesperidin, resveratrol, ginsenoside Rb1, luteolin, and Panax notoginseng saponins can effectively protect the blood‒retinal barrier by interfering with distinct pathways. The active ingredients found in natural plant medications primarily repair the blood‒retinal barrier by modulating pathological factors such as oxidative stress, inflammation, pyroptosis, and autophagy, thereby alleviating retinal diseases. CONCLUSION: This review summarizes a series of plant extracts and plant active compounds that can treat retinal diseases by preventing and treating blood‒retinal barrier damage and provides reference for the research of new drugs for treating retinal diseases.

The mechanisms of yeast extracellular metabolites in stimulating microbial degradation of trichloroethylene: Physiological characteristics and omics analysis.

The biodegradation of Trichloroethylene (TCE) is limited by low microbial metabolic capacity but can be enhanced through biostimulation strategies. This study explored the physiological effects and potential molecular mechanisms of the yeast Yarrowia lipolytica extracellular metabolites (YEMs) on the degradation of TCE by Acinetobacter LT1. Results indicated that YEMs stimulated the efficiency of strain LT1 by 50.28%. At the physiological level, YEMs exhibited protective effects on cell morphology, reduced oxidative stress, lessened membrane damage, and enhanced energy production and conversion. Analysis of omics results revealed that the regulation of various metabolic pathways by YEMs improved the degradation of TCE. Furthermore, RT-qPCR showed that the genes encoding YhhW protein in TCE stress and YEMs stimulation groups were 1.72 and 3.22 times the control group, respectively. Molecular docking results showed that the conformation of YhhW after binding to TCE changed into a more active form, which enhanced enzyme activity. Therefore, it is speculated that YhhW is the primary degradative enzyme involved in the process of YEMs stimulating strain LT1 to degrade TCE. These results reveal how YEMs induce strain LT1 to enhance TCE degradation.

Genome-wide analysis of in vivo-evolved Candida auris reveals multidrug-resistance mechanisms.

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.

Coherent detection of the rotational Doppler effect measurement based on triple Fourier transform.

In recent years, the rotational Doppler effect (RDE) has been widely used in rotational motion measurement. However, the performance of existing detection systems based on the RDE are generally limited by the drastic reduction of signal-to-noise ratio (SNR) due to the influence of atmospheric turbulence, partial obscuration of the vortex beam (VB) during propagation, and misalignment between the optical axis of VB and the rotational axis of the object, which poses a challenge for practical applications. In this paper, we proposed a coherent detection method of the RDE measurement based on triple Fourier transform. First, the weak RDE signal in backscattered light is amplified by using the balanced homodyne detection method, and the amplified signal still retains the same characteristic of severe broadening in the frequency domain as the original signal. Furthermore, we proposed the triple Fourier transform to extract the broadened RDE frequency shift signal after the coherent amplification. The proposed method significantly improves the SNR of RDE measurement and facilitates the accurate extraction of rotational speed, which helps to further improve the RDE detection range and promote its practical application.

Gut-Derived Trimethylamine N-Oxide Promotes CCR2-Mediated Macrophage Infiltration in acute kidney injury.

BACKGROUND: Inflammation is crucial in the development of AKI and subsequent CKD following renal ischemia-reperfusion (IR) injury. Gut microbiota metabolites trigger inflammation and affect IR-induced renal damage. Yet, the driving factors and mechanisms are unclear. Trimethylamine N-oxide (TMAO), a gut-derived choline metabolite, is a strong pro-inflammatory factor that increases in patients with AKI and CKD. We hypothesized that TMAO can promote renal injury caused by IR. METHODS: Mice subjected to unilateral renal IR to induce AKI and CKD were fed a high-choline diet to observe the effects of TMAO on kidney inflammation, fibrosis, and macrophage dynamics. RESULTS: A choline-rich diet altered the gut microbiota and elevated TMAO levels, which exacerbated IR-induced AKI and subsequent CKD. Single-cell analysis identified a distinct subset of CCR2+ macrophages derived from monocytes as key responders to TMAO, intensifying immune cell interactions and worsening renal injury. TMAO promoted sustained CCR2 expression after IR, increasing macrophage infiltration. CCR2 deletion and antagonist RS-102895 improved TMAO-induced inflammation and fibrosis, alleviated renal injury induced by IR. CONCLUSIONS: Our study provides valuable insights into the link between TMAO and IR-incited renal inflammation and fibrosis, emphasizing the critical role of TMAO-mediated macrophage infiltration via CCR2 as a key therapeutic target in the acute and chronic phase after IR.

Real-time multilingual speech recognition and speaker diarization system based on Whisper segmentation.

This research presents the development of a cutting-edge real-time multilingual speech recognition and speaker diarization system that leverages OpenAI's Whisper model. The system specifically addresses the challenges of automatic speech recognition (ASR) and speaker diarization (SD) in dynamic, multispeaker environments, with a focus on accurately processing Mandarin speech with Taiwanese accents and managing frequent speaker switches. Traditional speech recognition systems often fall short in such complex multilingual and multispeaker contexts, particularly in SD. This study, therefore, integrates advanced speech recognition with speaker diarization techniques optimized for real-time applications. These optimizations include handling model outputs efficiently and incorporating speaker embedding technology. The system was evaluated using data from Taiwanese talk shows and political commentary programs, featuring 46 diverse speakers. The results showed a promising word diarization error rate (WDER) of 2.68% in two-speaker scenarios and 11.65% in three-speaker scenarios, with an overall WDER of 6.96%. This performance is comparable to that of non-real-time baseline models, highlighting the system's ability to adapt to various complex conversational dynamics, a significant advancement in the field of real-time multilingual speech processing.

Long-term use of etomidate disrupts the intestinal homeostasis and nervous system in mice.

Etomidate (ETO) is used as an anesthetic in surgery, but it is being abused in some populations. The damage caused by long-term intake of ETO to intestinal and brain functions is not yet clear, and it remains to be determined whether the drug affects the central nervous system through the gut-brain axis. This study aimed to investigate the neurotoxic and gastrointestinal effects of ETO at doses of 1 mg/kg and 3 mg/kg in mice over 14 consecutive days. The results showed that long-term injection of ETO led to drug resistance in mice, affecting their innate preference for darkness and possibly inducing dependence on ETO. The levels of 5-hydroxytryptamine in the brain, serum, and colon decreased by 37%, 51%, and 42% respectively, while the levels of γ-aminobutyric acid reduced by 38%, 52%, and 41% respectively. H&E staining revealed that ETO reduced goblet cells in the colon and damaged the intestinal barrier. The expression of tight junction-related genes Claudin4 and ZO-1 was downregulated. The intestinal flora changed, the abundance of Akkermansia and Lactobacillus decreased by 33% and 14%, respectively, while Klebsiella increased by 18%. TUNEL results showed that high-dose ETO increased apoptotic cells in the brain. The expression of Claudin1 in the brain was downregulated. Untargeted metabolomics analysis of the colon and brain indicated that ETO caused abnormalities in glycerophospholipid metabolism. Abnormal lipid metabolism might lead to the production or accumulation of lipotoxic metabolites, causing central nervous system diseases. ETO induced changes in the intestinal flora and metabolism, further affecting the central nervous system through the gut-brain axis. The study unveiled the detrimental effects on the brain and gastrointestinal system resulting from long-term intake of ETO, which holds significant implications for comprehending the adverse impact of ETO abuse on human health.

Selective Excitation of Exciton-Polariton Condensate Modes in an Annular Perovskite Microcavity.

Exciton-polariton systems composed of a light-matter quasi-particle with a light effective mass easily realize Bose-Einstein condensation. In this work, we constructed an annular trap in a halide perovskite semiconductor microcavity and observed the spontaneous formation of symmetrical petal-shaped exciton-polariton condensation in the annular trap at room temperature. In our study, we found that the number of petals of the petal-shaped exciton-polariton condensates, which is decided by the orbital angular momentum, is dependent on the light intensity distribution. Therefore, the selective excitation of perovskite microcavity exciton-polariton condensates under all-optical control can be realized by adjusting the light intensity distribution. This could pave the way to room-temperature topological devices, optical cryptographical devices, and new quantum gyroscopes in the exciton-polariton system.

In vitro modeling of recurrent Dermatofibrosarcoma Protuberans: Assessment of 5-aminolevulinic acid photodynamic therapy efficacy.

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. METHODS: This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. RESULTS: 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. CONCLUSIONS: The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence.

Assessment of Immune Status in Patients with Mismatch Repair Deficiency Endometrial Cancer.

Objective: This study introduced a novel subtype classification method for endometrial cancer (EC) with mismatch repair deficiency (MMRd) by employing immune status and prognosis as the foundational criteria. The goal was to enhance treatment guidance through precise subtype delineation. Methods: Study Cohort: This study encompassed a cohort of 119 patients diagnosed with MMRd-EC between 2015 and 2022. Analyses using t-tests and Mann-Whitney U-tests were performed to assess prognostic markers and peripheral blood immune cell profiles in patients with MutS deficiency (MutS-d) versus those with MutL deficiency (MutL-d). Logistic regression analysis was used to identify independent risk factors. Bioinformatics Analysis: An online database was used to assess the prognostic implications, immune cell infiltration, and immune checkpoint involvement associated with the deficiency of MutS versus MutL in EC. Results: Patients with MutL-d exhibited heightened risk factors, including elevated cancer grade and increased myometrial invasion, leading to poorer prognosis and shorter overall survival and progression-free survival. Regarding systemic immune status, patients with MutL-d demonstrated decreased peripheral blood lymphocyte percentage, lymphocyte count, and CD8+ T cell percentage. For local immunity, the infiltration of natural killer cells, CD8+ T cells, and cytotoxic T lymphocytes in the tumor tissue was reduced in patients with MutL-d. Additionally, patients with MutL-d exhibited lower expression of immune checkpoint markers. The composition of immune subtypes and survival outcomes also indicate that patients with MutL-d have a poorer immune status and prognosis than the patients with MutS-d. Conclusion: Patients with MMRd-EC can be subclassified according to MutS or MutL deficiency. Patients with MutS-d exhibited better immune status, prognosis, and immunotherapy benefits than those with MutL-d. These results can help guide patients to a more precise treatment.

Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study.

BACKGROUND: Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM: To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS: A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS: Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION: Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Spatial omics techniques and data analysis for cancer immunotherapy applications.

In-depth profiling of cancer cells/tissues is expanding our understanding of the genomic, epigenomic, transcriptomic, and proteomic landscape of cancer. However, the complexity of the cancer microenvironment, particularly its immune regulation, has made it difficult to exploit the potential of cancer immunotherapy. High-throughput spatial omics technologies and analysis pipelines have emerged as powerful tools for tackling this challenge. As a result, a potential revolution in cancer diagnosis, prognosis, and treatment is on the horizon. In this review, we discuss the technological advances in spatial profiling of cancer around and beyond the central dogma to harness the full benefits of immunotherapy. We also discuss the promise and challenges of spatial data analysis and interpretation and provide an outlook for the future.

The A2 haplotype of Echinococcus multilocularis is the predominant variant infecting humans and dogs in Yili Prefecture, Xinjiang.

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis, is an important zoonotic disease. Yili Prefecture in Xinjiang is endemic for AE, however the molecular variability of E. multilocularis in this region is poorly understood. In this study, 127 samples were used for haplotypes analysis, including 79 tissues from humans, 43 liver tissues from small rodents, and 5 fecal samples from dogs. Genetic variability in E. multilocularis was studied using complete sequences of the mitochondrial (mt) genes of cytochrome b (cob), NADH dehydrogenase subunit 2 (nad2), and cytochrome c oxidase subunit 1 (cox1), using a total of 3558 bp per sample. The Asia haplotype 2 (A2) was the dominant haplotype, with 72.15% (57/79) prevalence in humans, 2.33% (1/43) in small rodents, and 80.00% (4/5) in dogs, followed by A5, the second most common haplotype, which infected 27.91% (12/43) small rodents. Haplotype network analysis showed that all haplotypes clustered together with the Asian group. Pairwise fixation index (FST) values showed lower level of genetic differentiation between different regions within the country. Compared with the sequences of E. multilocularis from North America and Europe, all concatenated sequences isolated from Yili Prefecture were highly differentiated and formed a single population. The A2 haplotype, analyzed using the cob, nad2, and cox1 genes of E. multilocularis, is the predominant variant in humans and dogs in Yili Prefecture.