Transcriptome and metabolism study reveals impact of nitrogen fertilizer on triticale.

Autumn-sown forage triticale can effectively leverage the optimal light and heat conditions in Ningxia, a region that boasts an abundance of light and heat resources sufficient for a single seasonal crop, but limited for two seasons. This not only fully utilizes the limited growing season but also significantly improves grass yield and economic efficiency per unit area. To enhance triticale yield in low-light and low-temperature environments, we investigated the impact of applying different concentrations of nitrogen fertilizer on triticale forage yield. Our findings revealed that nitrogen fertilizer application significantly increased triticale biomass, with the N4 treatment group exhibiting the most profound effect. To further explore the mechanisms behind nitrogen fertilizer's regulation of triticale growth and development, we conducted transcriptomic and metabolomic studies. These studies revealed that nitrogen fertilizer application significantly heightened transcription activity and protein synthesis in triticale, fostering the development of its seeds. Additionally, appropriate concentrations of nitrogen fertilizer significantly promoted photosynthesis. Metabolomic analysis revealed that nitrogen fertilizer application increased the levels of proline and O-phosphoethanolamine, enhancing triticale's stress resistance and supporting its growth and development under adverse conditions.

Transcriptomics and metabolomics analyses of Rosa hybrida to identify heat stress response genes and metabolite pathways.

BACKGROUND: Global warming has greatly increased the impact of high temperatures on crops, resulting in reduced yields and increased mortality. This phenomenon is of significant importance to the rose flower industry because high-temperature stress leads to bud dormancy or even death, reducing ornamental value and incurring economic losses. Understanding the molecular mechanisms underlying the response and resistance of roses to high-temperature stress can serve as an important reference for cultivating high-temperature-stress-resistant roses. RESULTS: To evaluate the impact of high temperatures on rose plants, we measured physiological indices in rose leaves following heat stress. Protein and chlorophyll contents were significantly decreased, whereas proline and malondialdehyde (MDA) contents, and peroxidase (POD) activity were increased. Subsequently, transcriptomics and metabolomics analyses identified 4,652 common differentially expressed genes (DEGs) and 57 common differentially abundant metabolites (DAMs) in rose plants from four groups. Enrichment analysis showed that DEGs and DAMs were primarily involved in the mitogen-activated protein kinases (MAPK) signaling pathway, plant hormone signal transduction, alpha-linolenic acid metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis. The combined analysis of the DEGs and DAMs revealed that flavonoid biosynthesis pathway-related genes, such as chalcone isomerase (CHI), shikimate O-hydroxycinnamoyl transferase (HCT), flavonol synthase (FLS), and bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase (DFR), were downregulated after heat stress. Moreover, in the MAPK signaling pathway, the expression of genes related to jasmonic acid exhibited a decrease, but ethylene receptor (ETR/ERS), P-type Cu + transporter (RAN1), ethylene-insensitive protein 2/3 (EIN2), ethylene-responsive transcription factor 1 (ERF1), and basic endochitinase B (ChiB), which are associated with the ethylene pathway, were mostly upregulated. Furthermore, heterologous overexpression of the heat stress-responsive gene RcHSP70 increased resistance to heat stress in Arabidopsis thaliana. CONCLUSION: The results of this study indicated that the flavonoid biosynthesis pathway, MAPK signaling pathway, and plant hormones may be involved in high-temperature resistance in roses. Constitutive expression of RcHSP70 may contribute to increasing high-temperature tolerance. This study provides new insights into the genes and metabolites induced in roses in response to high temperature, and the results provide a reference for analyzing the molecular mechanisms underlying resistance to heat stress in roses.

Construction of a machine learning-based prediction model for unfavorable discharge outcomes in patients with ischemic stroke.

Background: Ischemic stroke is a common and serious disease with economic and healthcare burdens. Predicting the unfavorable discharge outcome of patients is essential for formulating appropriate treatment strategies and providing personalized care. Therefore, this study aims to establish and validate a prediction model based on machine learning methods to accurately predict the discharge outcome of ischemic stroke patients, providing valuable information for clinical decision making. Methods: The derivation data consisted of 964 patients from Guangdong Provincial People's Hospital and was used for training and internal validation. A favourable discharge outcome was defined as a National Institutes of Health Stroke Scale score of ≤1 or a decrease of ≥8 points compared to the admission score. A predictive model was created based on 88 medical characteristics gathered during the patient's initial admission, using nine machine learning algorithms. The model's predictive performance was compared using various evaluation metrics. The final model's feature importance was ranked and explained using the Shapley additive explanation method. Findings: The random forest model demonstrated the greatest discriminative ability among the nine machine learning models. We created an interpretable random forest model by ranking and reducing the features based on their importance, which included eight features. In internal validations, the final model accurately predicted the discharge outcomes of ischemic stroke with AUC values of 0.903 and has been translated into a convenient tool to facilitate its utility in clinical settings. Conclusions: Our explainable ML model was not only successfully developed to accurately predict discharge outcomes in patients with ischemic stroke and it mitigated the concern of the "black-box" issue with an undirect interpretation of the ML technique.

Covering corneal stromal lenticule for macular hole in pathological myopia.

AIM: To evaluate the clinical effect of a new surgery technique (covering corneal stromal lenticule, CSL) for macular hole (MH) in pathological myopia. METHODS: This was a prospective non-randomized series case study. Fourteen eyes of 14 patients whose axial length were more than 29 mm and suffered from MH and macular hole retinal detachment (MHRD) were included in this study. All cases were treated with 25-gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, covering CSL and C3F8 gas tamponade. These cases were followed for 6mo, and the best-corrected visual acuity (BCVA), healing status of MH, the reattached rate of retinal detachment (RD), and reoperation rate were analyzed. RESULTS: All cases were successfully performed the surgery and the postoperative follow-up was completed. After surgery, MHs were healed in all 14 eyes (100%, 14/14) after assessed by optical coherence tomography. The reattachment of retina was achieved in all 6 eyes (100%, 6/6) with MHRD. BCVA was improved in 12 eyes (85.71%, 12/14), and had no significant change in 2 eyes (14.29%, 2/14). The overall mean BCVA was improved from 1.80±0.77 to 0.82±0.46 logMAR (F=10.46, P<0.01). No serious complications occurred in all cases. CONCLUSION: The new surgery technique (covering CSL) has high reattached rate of RD and high healing rate of MH in pathological myopia in the preliminary study. And it can effectively improve the visual function of patients. This new technique offers meaningful new ideas for treating refractory MH in pathological myopia.

BSC2 modulates AmB resistance via the maintenance of intracellular sodium/potassium ion homeostasis in Saccharomyces cerevisiae.

Previous studies on BSC2 have shown that it enhances yeast cell resistance to AmB via antioxidation and induces multidrug resistance by contributing to biofilm formation. Herein, we found that BSC2 overexpression could reverse the sensitivity of pmp3Δ to AmB and help the tested strains restore the intracellular sodium/potassium balance under exposure to AmB. Meanwhile, overexpression of the chitin gene CHS2 could simulate BSC2 to reverse the sensitivity of pmp3Δ and nha1Δ to high salt or AmB. However, BSC2 overexpression in flo11Δ failed to induce AmB resistance, form biofilms, and affect cell wall biogenesis, while CHS2 overexpression compensated the resistance of flo11Δ to AmB. Additionally, BSC2 levels were positively correlated with maintaining cell membrane integrity under exposure to AmB, CAS, or a combination of both. BSC2 overexpression in nha1Δ exhibited a similar function of CHS2, which can compensate for the sensitivity of the mutant to high salt. Altogether, the results demonstrate for the first time that BSC2 may promote ion equilibrium by strengthening cell walls and inhibiting membrane damage in a FLO path-dependent manner, thus enhancing the resistance of yeast cells to AmB. This study also reveals the possible mechanism of antifungal drugs CAS and AmB combined to inhibit fungi.

Diagnosis and Management of Aggressive/Refractory Growth Hormone-Secreting Pituitary Neuroendocrine Tumors.

The majority of acromegaly and gigantism are caused by growth hormone-secreting pituitary neuroendocrine tumors (PitNETs). Most cases can be cured or controlled by surgery, medical therapy, and/or radiotherapy. However, a few of these tumors are resistant to traditional therapy and always have a poor prognosis. The title aggressive/refractory is used to differentiate them from pituitary carcinomas. To date, there is no definitive conclusion on how to diagnose aggressive/refractory growth hormone-secreting PitNETs, which may have slowed the process of exploring new therapeutical strategies. We summarized the literature described diagnosis and treatment of the disease. Potential disease markers and prospective therapies were also included.

Genomic Anatomy of Homozygous XX Females and YY Males Reveals Early Evolutionary Trajectory of Sex-determining Gene and Sex Chromosomes in Silurus Fishes.

Sex chromosomes display remarkable diversity and variability among vertebrates. Compared with research on the X/Y and Z/W chromosomes, which have long evolutionary histories in mammals and birds, studies on the sex chromosomes at early evolutionary stages are limited. Here, we precisely assembled the genomes of homozygous XX female and YY male Lanzhou catfish (Silurus lanzhouensis) derived from an artificial gynogenetic family and a self-fertilized family, respectively. Chromosome 24 (Chr24) was identified as the sex chromosome based on resequencing data. Comparative analysis of the X and Y chromosomes showed an approximate 320 kb Y-specific region with a Y-specific duplicate of anti-Mullerian hormone type II receptor (amhr2y), which is consistent with findings in 2 other Silurus species but on different chromosomes (Chr24 of Silurus meridionalis and Chr5 of Silurus asotus). Deficiency of amhr2y resulted in male-to-female sex reversal, indicating that amhr2y plays a male-determining role in S. lanzhouensis. Phylogenetic analysis and comparative genomics revealed that the common sex-determining gene amhr2y was initially translocated to Chr24 of the Silurus ancestor along with the expansion of transposable elements. Chr24 was maintained as the sex chromosome in S. meridionalis and S. lanzhouensis, whereas a sex-determining region transition triggered sex chromosome turnover from Chr24 to Chr5 in S. asotus. Additionally, gene duplication, translocation, and degeneration were observed in the Y-specific regions of Silurus species. These findings present a clear case for the early evolutionary trajectory of sex chromosomes, including sex-determining gene origin, repeat sequence expansion, gene gathering and degeneration in sex-determining region, and sex chromosome turnover.

Non-invasive imaging using a low-spatial-coherence multimode random polymer fiber laser.

Random lasers (RLs), with their low spatial coherence, are ideal illumination sources for speckle-free imaging. However, it is still challenging for RLs to maintain low spatial coherence with the need for integration and directionality. Here, a disordered multimode random polymer fiber laser (RPFL) is proposed and implemented as a low-spatial-coherence light source. Compared to typical multimode optical fibers, the number of accommodated modes is increased by about 11×, the speckle contrast is reduced to 0.013, and the spatial coherence factor is reduced to 0.08. The low-spatial-coherence property enables RPFL to produce significantly superior imaging quality in both speckle-free imaging and non-invasive imaging through opacity. This study provides a strategy for an integrated speckle-free imaging system and paves the way for non-invasive imaging.

Safety profiles of tetracycline-class drugs: a pharmacovigilance analysis of the FAERS database.

BACKGROUND: As synthesis technology advances, novel and efficient derivatives of tetracyclines are found. Three new antibiotics were approved within the past 18 years, and represent a new era in the use of tetracyclines. To gain further insight into adverse events linked to tetracyclines and better protect pediatric patients, ongoing monitoring of safety data is crucial. METHODS: The FAERS data from the first quarter of 2004 to the third quarter of 2023 in the AERSMine were extracted to conduct disproportionality analysis. The association between five tetracyclines and adverse events was evaluated using reporting odds ratio, and their risk factors were explored by multivariate logistic regression analysis. RESULTS: Our study showed that thyroid gland disorders had the strongest signal in children. Patients aged 12-18 and treatment with minocycline are risk factors for thyroid adverse events (12-18: OR = 10.727 [7.113-16.177], p < 0.0001; minocycline: OR = 17.025 [10.475-27.678], p < 0.0001). Second-generation tetracycline and third-generation tetracycline ADR patterns differed. Blood fibrinogen decreased and hypofibrinogenaemia was primarily reported with tigecycline and eravacycline. CONCLUSION: This study provided basic evidence for further research on tetracyclines-related adverse events. However, the safety of third-generation tetracycline in children requires additional validation through a large-scale prospective study.

Designing Symmetric Gradient Honeycomb Structures with Carbon-Coated Iron-Based Composites for High-Efficiency Microwave Absorption.

The impedance matching of absorbers is a vital factor affecting their microwave absorption (MA) properties. In this work, we controllably synthesized Material of Institute Lavoisier 88C (MIL-88C) with varying aspect ratios (AR) as a precursor by regulating oil bath conditions, followed by one-step thermal decomposition to obtain carbon-coated iron-based composites. Modifying the precursor MIL-88C (Fe) preparation conditions, such as the molar ratio between metal ions and organic ligands (M/O), oil bath temperature, and oil bath time, influenced the phases, graphitization degree, and AR of the derivatives, enabling low filler loading, achieving well-matched impedance, and ensuring outstanding MA properties. The MOF-derivatives 2 (MD2)/polyvinylidene Difluoride (PVDF), MD3/PVDF, and MD4/PVDF absorbers all exhibited excellent MA properties with optimal filler loadings below 20 wt% and as low as 5 wt%. The MD2/PVDF (5 wt%) achieved a maximum effective absorption bandwidth (EAB) of 5.52 GHz (1.90 mm). The MD3/PVDF (10 wt%) possessed a minimum reflection loss (RLmin) value of - 67.4 at 12.56 GHz (2.13 mm). A symmetric gradient honeycomb structure (SGHS) was constructed utilizing the high-frequency structure simulator (HFSS) to further extend the EAB, achieving an EAB of 14.6 GHz and a RLmin of - 59.0 dB. This research offers a viable inspiration to creating structures or materials with high-efficiency MA properties.

N-doped carbon layer cladded carbon sphere for broadband and boosted microwave attenuation capacity.

Structural construction and heteroatom doping are deemed effective strategies for designing a high-performance microwave absorbing composite to eliminate electromagnetic hazards. Herein, a series of core-shell structural carbon@N-doped carbon (C@NC) nanospheres were successfully fabricated without employing additional modifying agents and sophisticated operation. After incorporating them into a polyvinylidene fluoride (PVDF) matrix, the C@NC/PVDF composites possess tunable wave attenuation capacity obtained by regulating the coating layer thickness and filler loading. Benefitting from the design strategy of the core-shell structure and N-doped C, the C@NC-2/PVDF composites displayed the broadest effective absorption bandwidth of 6.29 GHz (11.71-18 GHz) under a filler content of only 10 wt% at 2.01 mm. Additionally, the minimum reflection loss value of C@NC-3/PVDF composites achieves -62.87 dB within the same mass ratio at a thickness of 2.35 mm. The excellent wave dissipation ability is attributed to the combination of optimized impedance matching and synergistically enhanced multiple loss mechanisms including conduction loss, interfacial polarization as well as dipolar polarization. This work offers a ponderable paradigm for the deeper exploitation of high-efficiency carbon absorbers.

Coupled single-cell and bulk RNA-seq analysis reveals the engulfment role of endothelial cells in atherosclerosis.

The clearance of apoptotic cell debris, containing professional phagocytosis and non-professional phagocytosis, is essential for maintaining the homeostasis of healthy tissues. Here, we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque. Single-cell RNA sequencing (RNA-seq) has revealed a unique endothelial cell subpopulation in atherosclerosis, which was strongly associated with vascular injury-related pathways. Moreover, integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1 (SR-B1) was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances. Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis. Furthermore, SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta. Overall, this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.

A comparative study of sampling methods in the detection of esophageal cancer-related microbiota.

Esophageal cancer (EC) is a multifaceted disease. Our understanding of the involvement of esophageal microbiota in its pathogenesis and progression is limited, which is due to the lack of proper endoscopic sampling methods. Hereby, we conducted a comparative analysis of paired samples obtained through endoscopic brushing and cytosponge, aiming at assessing the feasibility of using cytosponge as a minimally invasive sampling way for studying esophageal microbiota. Our findings suggest that cytosponge sampling yielded significantly superior community richness and diversity compared to endoscopic brushing in both controls (non-cancerous) and EC individuals. The analysis of beta-diversity revealed distinct microbial community pattern in the genus diversity between the two sampling methods, underscoring the importance of selecting appropriate sampling methods to effectively characterize the esophageal microbiota. Specifically, Lactococcus and Serratia showed higher abundance in the samples collected by endoscopic brushing, while Alloprevotella and Leptotrichia were more enriched in the samples collected by cytosponge. These differences in dominant microbes were associated with metabolic pathways that particularly were related to host inflammation, such as pyruvate and glucose metabolisms. Notably, the phylogenetic levels of the microbiota indicated varied explanatory power for different detection purposes. This study underscores the substantial impact of sampling method selection on the acquisition of esophageal microbiota associated with the EC development, encompassing considerations of both abundance and diversity. This highlights the significance of selecting an appropriate sampling method for investigating the esophageal microbial status and studying the micro-environment in EC-related individuals. IMPORTANCE: This study addresses a critical issue in esophageal cancer study by comparing two different sampling methods, endoscopic brushing and cytosponge, for investigating the esophageal microbiota. Our work highlights the suitability of the cytosponge technique as a minimally invasive sampling method for studying the esophageal microbiota and emphasizes the importance of selecting an appropriate sampling method to characterize the microbial community. Our findings have significant implications for advancing the understanding of the role of the esophageal microbiota in cancer development and will inform future research and clinical approaches in this field.

Effect of Pelvic Floor Function Exercises Based on the ERAS Concept on Lower Urinary Tract Symptoms after Radical Hysterectomy for Cervical Cancer: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to analyse the effect of pelvic floor function exercises based on the enhanced recovery after surgery (ERAS) concept on lower urinary tract symptoms after radical hysterectomy for cervical cancer. METHODS: The retrospective study was conducted using clinical data of patients admitted to our hospital from January 2021 to December 2022 and underwent radical hysterectomy for cervical cancer. In accordance with the nursing method, the patients were divided into the routine group (conventional care) and the ERAS pelvic floor function exercise group, for which ERAS concept-based pelvic floor function exercises were carried out on the basis of the former group. The confounders between the two groups were matched by propensity score, and the scores of urination, pelvic floor muscle strength, lower urinary tract symptoms and quality of life (QoL) were compared between the two groups after matching. RESULTS: A total of 180 patients were included in the study, of whom 60 patients were identified after propensity score matching, consisting of 30 patients each in the ERAS and routine groups. The baseline characteristics of the two groups were balanced, and the difference was not statistically significant (p > 0.05). Compared with the routine group, the observation group showed significantly shorter first spontaneous urination time, greater first urination volume (p < 0.05), better pelvic floor muscle strength, considerably lower urinary tract symptoms and better QoL at discharge and 3 months after discharge (p < 0.05). CONCLUSIONS: Pelvic floor function exercises based on the ERAS concept can relieve lower urinary tract symptoms, accelerate urination and improve pelvic floor muscle strength and QoL after radical hysterectomy for cervical cancer.

[A design of interactive review for computer aided diagnosis of pulmonary nodules based on active learning].

Automatic detection of pulmonary nodule based on computer tomography (CT) images can significantly improve the diagnosis and treatment of lung cancer. However, there is a lack of effective interactive tools to record the marked results of radiologists in real time and feed them back to the algorithm model for iterative optimization. This paper designed and developed an online interactive review system supporting the assisted diagnosis of lung nodules in CT images. Lung nodules were detected by the preset model and presented to doctors, who marked or corrected the lung nodules detected by the system with their professional knowledge, and then iteratively optimized the AI model with active learning strategy according to the marked results of radiologists to continuously improve the accuracy of the model. The subset 5-9 dataset of the lung nodule analysis 2016(LUNA16) was used for iteration experiments. The precision, F1-score and MioU indexes were steadily improved with the increase of the number of iterations, and the precision increased from 0.213 9 to 0.565 6. The results in this paper show that the system not only uses deep segmentation model to assist radiologists, but also optimizes the model by using radiologists' feedback information to the maximum extent, iteratively improving the accuracy of the model and better assisting radiologists.

Boosting antitumor efficacy of nanoparticles by modulating tumor mechanical microenvironment.

Nanoparticles have shown great potential for tumor targeting delivery via enhanced permeability and retention effect. However, the tumor mechanical microenvironment, characterized by dense extracellular matrix (ECM), high tumor stiffness and solid stress, leads to only 0.7% of administered dose accumulating in solid tumors and even fewer (∼0.0014%) reaching tumor cells, limiting the therapeutic efficacy of nanoparticles. Furthermore, the tumor mechanical microenvironment can regulate tumor cell stemness, promote tumor invasion, metastasis and reduce treatment efficacy. In this review, methods detecting the mechanical are introduced. Strategies for modulating the mechanical microenvironment including elimination of dense ECM by physical, chemical and biological methods, disruption of ECM formation, depletion or inhibition of cancer-associated fibroblasts, are then summarized. Finally, prospects and challenges for further clinical applications of mechano-modulating strategies to enhance the therapeutic efficacy of nanomedicines are discussed. This review may provide guidance for the rational design and application of nanoparticles in clinical settings.

Decoding the Qu-aroma of medium-temperature Daqu starter by volatilomics, aroma recombination, omission studies and sensory analysis.

Qu-aroma is of great significance for evaluation the quality of Daqu starter. This study aimed to decode the Qu-aroma of medium-temperature Daqu (MT-Daqu) via "top-down" and "bottom-up" approaches. Firstly, 52 aroma descriptors were defined to describe the MT-Daqu aroma by quantitative descriptive analysis. Secondly, 193 volatile organic compounds (VOCs) were identified from 42 MT-Daqu samples by HS-SPME-GC-MS, and 43 dominant VOCs were screened out by frequence of occurrence or abundance. By Thin Film (TF)-SPME-GC-O-MS, 27 odors and 90 VOCs were detected in MT-Daqu mixture, and 14 odor-active VOCs were screened out by odor intensity. Thirdly, a five-level MT-Daqu aroma wheel was constructed by matching 52 aroma descriptors and 37 aroma-active VOCs. Finally, Qu-aroma of MT-Daqu was reconstructed with 37 aroma-active VOCs and evaluated by omission experiments. Hereinto, 26 key aroma-active VOCs were determined by OAV value ≥1, including isovaleric acid, 1-hexanol, isovaleraldehyde, 2-octanone, trimethylpyrazine, γ-nonalactone, 4-vinylguaiacol, etc.

Differences in the Ability of Lactic Acid Bacteria To Prevent Acute Alcohol-Induced Liver Injury via the Gut Microbiota-Bile Acid-Liver Axis.

Probiotics can regulate gut microbiota and protect against acute alcohol-induced liver injury through the gut-liver axis. However, efficacy is strain-dependent, and their mechanism remains unclear. This study investigated the effect of lactic acid bacteria (LAB), including Lacticaseibacillus paracasei E10 (E10), Lactiplantibacillus plantarum M (M), Lacticaseibacillus rhamnosus LGG (LGG), Lacticaseibacillus paracasei JN-1 (JN-1), and Lacticaseibacillus paracasei JN-8 (JN-8), on the prevention of acute alcoholic liver injury in mice. We found that LAB pretreatment reduced serum alanine transaminase (ALT) and aspartate transaminase (AST) and reduced hepatic total cholesterol (TC) and triglyceride (TG). JN-8 pretreatment exhibited superior efficacy in improving hepatic antioxidation. LGG and JN-8 pretreatment significantly attenuated hepatic and colonic inflammation by decreasing the expression of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) and increasing the expression of interleukin 10 (IL-10). JN-1 and JN-8 pretreatments have better preventive effects than other LAB pretreatment on intestinal barrier dysfunction. In addition, the LAB pretreatment improved gut microbial dysbiosis and bile acid (BA) metabolic abnormality. All of the strains were confirmed to have bile salt deconjugation capacities in vitro, where M and JN-8 displayed higher activities. This study provides new insights into the prevention and mechanism of LAB strains in preventing acute alcoholic liver injury.

How to incorporate new agents into precise medicine for cholangiocarcinoma?

Cholangiocarcinoma, a rare and aggressive form of cancer originating from the bile ducts in the liver, poses a significant challenge for treatment. However, the emergence of precision medicine has brought newfound hope for more effective therapies. Several precision medicine approaches have demonstrated promise in the treatment of cholangiocarcinoma. One such approach is targeted therapy, which involves utilizing drugs that specifically target the genetic mutations or alterations present in the tumor cells. In the case of cholangiocarcinoma, mutations in the IDH1 and IDH2 genes are frequently observed. Immunotherapy is another precision medicine approach being explored for the treatment of cholangiocarcinoma. Immune checkpoint inhibitors like pembrolizumab and nivolumab can be used to bolster the body's immune response against cancer cells. While the response to immunotherapy can vary among individuals, studies have shown promising results, particularly in patients with high levels of tumor-infiltrating lymphocytes or microsatellite instability. Moreover, molecular profiling of cholangiocarcinoma tumors can play a crucial role in identifying potential targets for precision medicine. Through advanced next-generation sequencing techniques, specific gene alterations or dysregulations in pathways can be identified, potentially guiding treatment decisions. This personalized approach enables tailored treatment plans based on the unique genetic characteristics of each patient's tumor. In conclusion, the advent of precision medicine has opened up new avenues for the treatment of cholangiocarcinoma. Targeted therapy and immunotherapy have exhibited promising results, and further molecular profiling is expected to uncover additional therapeutic options. Such advancements represent a significant step forward in the quest to enhance outcomes for individuals affected by cholangiocarcinoma.