Lactobacillus helveticus attenuates alcoholic liver injury via regulation of gut microecology in mice.

Previous reports have demonstrated that alcohol consumption significantly reduces the abundance of Lactobacillus in the gut. In this study, we selected five species of the genus Lactobacillus, commonly found in fermented foods, and acknowledged them as safe, edible, and effective in preventing or treating certain diseases, to evaluate their effects on alcoholic liver disease (ALD). By comparing the liver damage indices in each group, we found that the type strain of Lactobacillus helveticus (LH, ATCC 15009) had the most marked alleviating effect on ALD-induced liver injury. Furthermore, experiments combining microbiomics and metabolomics were conducted to explore the mechanisms underlying the hepatoprotective effects of LH. Finally, we discovered that LH mitigated ethanol-induced liver steatosis and inflammation in ALD mice by altering the structure and function of the gut microbiome, increasing intestinal levels of short-chain fatty acids (SCFAs), and enhancing gut barrier integrity. These findings suggest a potential strategy for the clinical management of patients with ALD.

Co-Delivery of VEGF siRNA and THPP via Metal-Organic Framework Reverses Cisplatin-Resistant Non-Small Cell Lung Cancer and Inhibits Metastasis through a MUC4 Regulating Mechanism.

Cisplatin resistance significantly impacts the antitumor efficacy of cisplatin chemotherapy and contributes to poor prognosis, including metastasis. In this study, we present the utilization of metal-organic framework (MOF) nanoparticles as the therapeutic component and drug loading scaffold for implementing a ternary combination therapeutic strategy to combat cisplatin-resistant lung cancer and metastasis. Specifically, by engineering MOFs (Cis@MOF-siVEGF) through the self-assembly of THPP as photosensitizer for photodynamic therapy (PDT), along with the incorporation of cisplatin (DDP) and VEGF siRNA (siVEGF), we propose the leverage of photodynamic-induced oxidative damage and gene silencing of the angiogenic factor to reverse cisplatin resistance and sensitize therapeutic potency. Our findings demonstrated that the chemo/photodynamic/antiangiogenic triple combination therapy via Cis@MOF-siVEGF under irradiation effectively inhibits cisplatin-resistant tumor growth and induces abscopal effects. Importantly, molecular mechanistic exploration suggested that MUC4 exerted regulatory effects on governing cancer metastasis, thus representing a potential immunotherapeutic target for cancer intervention. Overall, our study creates a MOFs-based multicomponent delivery platform for complementary therapeutic modules with synergistically enhanced antitumor efficacy and sheds light on potential regulatory mechanisms on cisplatin-resistance cancers.

Christensenellaceae minuta modulates epithelial healing via PI3K-AKT pathway and macrophage differentiation in the colitis.

Ulcerative colitis (UC) is a chronic inflammatory disorder with an unsatisfactory cure rate and mucosal healing is a key treatment objective. Christensenellaceae minuta (C. minuta) has emerged as a next-generation of probiotic for maintaining intestinal health. We investigated the therapeutic efficacy of C. minuta in dextran sulfate sodium (DSS)-induced colitis, focusing on mucosal healing and the underlying mechanisms. C. minuta effectively alleviated colitis and promoted the regeneration of intestinal epithelial cells (IECs). Using 16S rRNA sequencing and metabolomics, we found that C. minuta administration increased beneficial bacteria, decreased pathogenic bacteria, and significantly elevated propionic acid levels. Additionally, C. minuta activated the PI3K-AKT pathway by upregulating systemic and local IGF-1 expression. Inhibiting the PI3K-AKT pathway reduced the therapeutic effects of C. minuta and impaired IEC regeneration. Furthermore, C. minuta promoted macrophage differentiation into the M2 phenotype and decreased proinflammatory factors. We propose that C. minuta alleviates colitis by regulating the gut microbiota, modulating macrophage differentiation, and enhancing mucosal healing by activating the PI3K-AKT pathway via IGF-1 secretion induced by short-chain fatty acids. Our findings provide evidence from animal experiments to support future clinical trials and the therapeutic translation of C. minuta.

A review of experimental Assessment Processes of material resistance to marine and freshwater biofouling.

Biofouling presents hazards to a variety of freshwater and marine underwater infrastructures and is one of the direct causes of species invasion. These negative impacts provide a unified goal for both industry practitioners and researchers: the development of novel antifouling materials to prevent the adhesion of biofouling. The prohibition of tributyltin (TBT) by the International Maritime Organization (IMO) in 2001 propelled the research and development of new antifouling materials. However, the evaluation process and framework for these materials remain incomplete and unsystematic. This mini-review starts with the classification and principles of new antifouling materials, discussing and summarizing the methods for assessing their biofouling resistance. The paper also compiles the relevant regulations and environmental requirements from different countries necessary for developing new antifouling materials with commercial potential. It concludes by highlighting the current challenges in antifouling material development and future outlooks. Systematic evaluation of newly developed antifouling materials can lead to the emergence of more genuinely applicable solutions, transitioning from merely laboratory products to materials that can be effectively used in real-world applications.

Sub-60-fs mode-locked Tm,Ho:CaYLuAlO4 laser at 2.05†µm.

Tm,Ho:CaYLuAlO4 (Tm,Ho:CALYLO) crystal has wide emission spectra both for π-polarization and σ-polarization, showing significant potential for the generation of ultrashort pulses. Here, a widely tunable and passively mode-locked laser operation based on Tm,Ho:CALYLO crystal under two polarizations was demonstrated for what we believe to be the first time ever. For π-polarization, a maximum output power of 1.52 W and a tuning range of 255.3 nm were achieved in the continuous wave (CW) regime. In the mode-locked regime, a pulse duration of 68 fs and an average output power of 228 mW were achieved upon GaSb-based semiconductor saturable absorber mirror (SESAM). As for σ-polarization, a broader tuning range of 267.1 nm was realized, leading to the shorter pulse duration of 58 fs at 79.7 MHz repetition rate.

Efficacy of immunotherapy in patients with oncogene-driven non-small-cell lung cancer: a systematic review and meta-analysis.

Background: Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene-positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC and concluded the efficacy of altered subtypes. Methods: A literature search was performed using PubMed, Web of Science, and Cochrane databases. The primary endpoints included the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients with oncogene-driven NSCLC. Results: In all, 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORRs in clinical trials treated with monoimmunotherapy of EGFR, ALK, and KRAS alteration were 6%, 0%, and 23%, respectively. In retrospective studies, the pooled ORRs of EGFR, ALK, KRAS, BRAF, MET, HER2, RET, and ROS1 alteration were 8%, 3%, 28%, 24%, 23%, 14%, 7%, and 8%, respectively. Among them, the pooled ORRs of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping, and MET-amplification were 33% 40%, 20%, 34%, 17%, and 60%, respectively. In addition, the pooled mPFS rates of EGFR, KRAS, MET, HER2, and RET alteration were 2.77, 3.24, 2.48, 2.31, and 2.68 months, while the pooled mOS rates of EGFR and KRAS alteration were 9.98 and 12.29 months, respectively. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months. Conclusions: EGFR-, ALK-, HER2-, RET-, and ROS1-altered NSCLC patients have poor reactivity to monoimmunotherapy but the efficacy of immune-based combined therapy is significantly improved. KRAS G12C mutation, BRAF non-V600E mutation, and MET amplification have better responses to immunotherapy, and more prospective studies are needed for further research.

Efficacy of immunotherapy in patients with oncogene-driven non-small cell lung cancer: a systematic review and meta analysis Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced NSCLC. However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC, and concluded the efficacy of altered subtypes. 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORR in clinical trials treated with monoimmunotherapy was of EGFR, ALK and KRAS alteration was 6%, 0%, and 23%, respectively. While in retrospective studies, the pooled ORR of EGFR, ALK, KRAS, BRAF, MET, HER2, RET and ROS1 alteration was 8%, 3%, 28%, 24%, 23%, 14%, 7% and 8%, respectively. Among them, the pooled ORR of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping and MET-amplification was 33% 40%, 20%, 34%, 17% and 60%, respectively. Additionally, the pooled mPFS of EGFR, KRAS, MET, HER2 and RET alteration was 2.77, 3.24, 2.48, 2.31 and 2.68 months, while the pooled mOS of EGFR and KRAS alteration was 9.98 and 12.29 months. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) was reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months. EGFR, ALK, HER2, RET and ROS1-altered NSCLC patients have poor reactivity to monoimmunotherapy, but the efficacy of immune-based combined therapy is significantly improved. KRAS G12C mutation, BRAF non-V600E mutation and MET amplification have better response to immunotherapy, and more prospective studies are needed for further research.

Effects of partial reduction of polystyrene micro-nanoplastics on the immunity, gut microbiota and metabolome of mice.

Microplastic (MP) and nanoplastic (NP) could cause gut microbiota alterations. Although micro/nanoplastic (MNP) degradation is attracting increasing scientific interest, the evaluation of MNP reduction in gut needs to be further investigated. This study aimed to determine whether partial reduction of polystyrene MNP in gut could affect the immunity, gut microbiota and metabolome of mice. Serum eotaxin/CCL11 was at a lower level in the mice exposed to 200 µg and 500 µg NP (i.e., 2NP and 5NP groups, respectively) compared to those exposed to 500 µg MP (i.e., 5 MP group), while serum IL-2 and IL-4 were both greater in the 5NP group compared to the 5 MP group. The gut bacterial alpha diversity, fungal diversity and evenness were all similar among the MNP and control groups. However, the gut fungal richness was greater in both the 5NP and 5 MP groups compared to the control group. The gut bacterial and fungal compositions were both different between the MNP and control groups. Multiple gut bacteria and fungi showed different levels between the 2NP and 5NP groups, as well as between the 2NP and 5 MP groups. Increased Staphylococcus and decreased Glomus were determined in the 2NP group compared to both the 5NP and 5 MP groups. A Lactobacillus phylotype was found as the sole gatekeeper in the bacterial network of the 2NP group, while a Bifidobacterium phylotype contributed most to the stability of the bacterial networks of both the 5NP and 5 MP groups. Multiple differential gut metabolic pathways were found between the 2NP and 5NP/5 MP groups, and mTOR signaling pathway was largely upregulated in the 2NP group compared to both the 5NP and 5 MP groups. The relevant results could help with the evaluation of partial reduction of MNP in gut.

Spectroscopy and efficient laser performances of a Tm,Ho:CaY0.9Lu0.1AlO4 crystal.

We report on the spectral properties and laser performances of a novel, to the best of our knowledge, Tm,Ho:CaY0.9Lu0.1AlO4 (Tm,Ho:CYLA) crystal. The polarized absorption spectra, luminescence spectra, and fluorescence lifetime are systematically investigated, presenting a broad and smooth luminescence band. Furthermore, a maximum continuous wave (CW) laser output power of 0.51 W at 2092 nm is obtained under an absorbed pump power of 2.89 W, corresponding to a slope efficiency of 20.4%. The beam quality factors (M2) are measured to be 1.04 in both the x and y axes. A tuning range of 123.4 nm, from 2017.8 nm to 2141.2 nm, is achieved in the CW regime by using a birefringent filter (BF). A stable passively Q switched Tm,Ho:CYLA laser employing Cr2+:ZnSe as a saturable absorber (SA) is realized for the first time, delivering the shortest pulse width of 560 ns with a transmittance of 1%. The results indicate that the Tm,Ho:CYLA crystal is an excellent laser medium for generating high-efficiency laser at ∼2 µm and has a potential in ultrafast laser generation.

Exploration on the first-line treatment of ERBB2-altered advanced non-small cell lung cancer: A multicenter retrospective study.

BACKGROUND: Although the treatment of ERBB2-altered non-small cell lung cancer (NSCLC) has been studied for many years, there are no comprehensive studies to evaluate the benefits of various therapies as first-line treatment. Through the development of immunotherapy, more and more different combination treatments were applicated in clinical practice, therefore, we conducted a multicenter retrospective study to evaluate the efficacy of different treatments. METHODS: We enrolled patients with ERBB2-altered NSCLC who had undergone at least one-line systemic anticancer treatment to evaluate the efficacy of first-line chemotherapy alone (Chemo), anti-ERBB2 tyrosine kinase inhibitor (TKI), chemotherapy plus immunotherapy (Chemo + Immuno), chemotherapy plus anti-angiogenesis therapy (Chemo + Antiangio) and chemotherapy combined with immunotherapy and anti-angiogenesis therapy (Chemo + Immuno + Antiangio). The clinical outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), one-year and three-year survival rate. RESULTS: We enroll 36 patients harboring ERBB2 mutation and 29 with ERBB2 amplification. The overall ORR was 30.8%, DCR was 69.2% and mPFS was 5.7 months. Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (7.8 vs 3.6 months, HR: 0.24, 95 %CI: 0.09-0.64, P = 0.002; 5.9 vs 3.6 months, HR: 0.36, 95 %CI: 0.15-0.88, P = 0.019; respectively), while there was no significant difference in mPFS between Chemo + Immuno or Chemo + Antiangio and Chemo (both P > 0.05), the mPFS of the first two was longer. For ERBB2-mutant patients, the mPFS was 5.9 months, and Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (12.9 vs 2.9 months, HR: 0.15, 95 %CI: 0.03-0.68, P = 0.005; 7.1 vs 2.9 months, HR: 0.50, 95 %CI: 0.29-0.88, P = 0.009, respectively). In the same therapies, patients with ERBB2 mutation or ERBB2 amplification showed no statistical significance in PFS (both P > 0.05). CONCLUSIONS: In the first-line treatment of ERBB2-altered NSCLC, chemotherapy combined with immunotherapy or anti-angiogenesis therapy may have greater survival benefits than ERBB2-target therapy, but the efficacy may not be better than that of chemotherapy.

[Effect of Different Antitumor Regimens on Incidence and Severity of Corona Virus 
Disease 2019 Pneumonia in Lung Cancer Patients: 
A Single-center Retrospective Study].

BACKGROUND: Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. METHODS: From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. RESULTS: (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. CONCLUSIONS: Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.

Clinical characteristics and targeted therapy of different gene fusions in non-small cell lung cancer: a narrative review.

Background and Objective: Lung cancer is the most fatal malignant tumor in the world. Since the discovery of driver genes, targeted therapy has been demonstrated to be superior to traditional chemotherapy and has revolutionized the therapeutic landscape of non-small cell lung cancer (NSCLC). The remarkable success of tyrosine kinase inhibitors (TKIs) in patients with epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions has shifted the treatment from platinum-based combination chemotherapy to targeted therapy. Although the incidence rate of gene fusion is low in NSCLC, it is of great significance in advanced refractory patients. However, the clinical characteristics and the latest treatment progress of patients with gene fusions in lung cancer have not been thoroughly explored. The objective of this narrative review was to summarize the latest research progress of targeted therapy for gene fusion variants in NSCLC to improve understanding for clinicians. Methods: We conducted a search of PubMed database and American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), and World Conference on Lung Cancer (WCLC) abstracts meeting proceedings from 1 January 2005 to 31 August 2022 with the following keywords "non-small cell lung cancer", "fusion", "rearrangement", "targeted therapy" and "tyrosine kinase inhibitor". Key Content and Findings: We comprehensively listed the targeted therapy of various gene fusions in NSCLC. Fusions of ALK, ROS proto-oncogene 1 (ROS1), and rearranged during transfection proto-oncogene (RET) are relatively more common than others (NTRK fusions, NRG1 fusions, FGFR fusions, etc.). Among ALK-rearranged NSCLC patients treated with crizotinib, alectinib, brigatinib, or ensartinib, the Asian population exhibited a slightly better effect than the non-Asian population in first-line therapy. It was revealed that ceritinib may have a slightly better effect in the non-Asian ALK-rearranged population as first-line therapy. The effect of crizotinib might be similar in Asians and non-Asians with ROS1-fusion-positive NSCLC in first-line therapy. The non-Asian population were shown to be more likely to be treated with selpercatinib and pralsetinib for RET-rearranged NSCLC than the Asian population. Conclusions: The present report summarizes the current state of fusion gene research and the associated therapeutic methods to improve understanding for clinicians, but how to better overcome drug resistance remains a problem that needs to be explored.

Airborne polystyrene microplastics and nanoplastics induce nasal and lung microbial dysbiosis in mice.

Microplastics (MP) and nanoplastics (NP) have been found in multiple environments and creatures. However, their effects on the airway microbiota still remain poorly understood. In this study, a series of bioinformatic and statistical analyses were carried out to explore the influence of airborne MP and NP on the nasal and lung microbiota in mice. Both MP and NP were capable of inducing nasal microbial dysbiosis, and MP had a stronger influence on the lung microbiota than NP. Multiple nasal and lung bacteria were associated with MP and NP groups, among which nasal Staphylococcus and lung Roseburia were most associated with MP group, while nasal Prevotella and lung unclassified_Muribaculaceae were most associated with NP group. The nasal Staphylococcus, lung Roseburia, lung Eggerthella and lung Corynebacterium were associated with both MP and NP groups, which were potential biomarkers of micro/nanoplastics-induced airway dysbiosis. SAR11_Clade_Ia and SAR11_Clade_II were associated with both nasal and lung microbiota in MP group, while no such bacterium was determined in NP group. The relevant results suggest that both airborne MP and NP could induce nasal and lung microbial dysbiosis, and the relevant preventative and curable strategies deserve further investigations.

Alterations of gut and oral microbiota in the individuals consuming take-away food in disposable plastic containers.

Microplastics (MP) and nanoplastics (NP) exist in the disposable plastic take-away containers. This study aims to determine the gut and oral microbiota alterations in the individuals frequently and occasionally consuming take-away food in disposable plastic containers (TFDPC), and explore the effect of micro/nanoplastics (MNP) reduction on gut microbiota in mice. TFDPC consumption are associated with greater presences of gastrointestinal dysfunction and cough. Both occasional and frequent consumers have altered gut and oral microbiota, and their gut diversity and evenness are greater than those of non-TFDPC consuming cohort. Multiple gut and oral bacteria are associated with TFDPC consumers, among which intestinal Collinsella and oral Thiobacillus are most associated with the frequent consumers, while intestinal Faecalibacterium is most associated with the occasional consumers. Although some gut bacteria associated with the mice treated with 500 µg NP and 500 µg MP are decreased in the mice treated with 200 µg NP, the gut microbiota of the three MNP groups are all different from the control group. This study demonstrates that TFDPC induces gut and oral microbiota alterations in the consumers, and partial reduction of the size and amount of MNP cannot rectify the MNP-induced gut microbial dysbiosis.

Ultrasound-Guided Dynamic Needle-Tip Positioning Method Is Superior to Conventional Palpation and Ultrasound Method in Arterial Catheterization.

Background: Dynamic needle-tip positioning (DNTP) was shown to improve arterial cannulation efficiency with fewer complications than conventional palpation and ultrasound methods by some studies. However, this is still controversial, and we performed this meta-analysis to comprehensively assess its value in arterial cannulation. Methods: A literature search of randomized controlled trials was conducted, and 11 studies were finally included. Efficiency outcomes (first-attempt success, overall success, and total cannulation time) and complications (hematoma, thrombosis, posterior wall puncture, and vasospasm) were separately analyzed. Subgroup analyses in different populations under cannulation were also performed. Results: DNTP was associated with increased first-attempt success (pooled RR = 1.792, p < 0.001), overall success (pooled RR = 1.368, p = 0.001), and decreased cannulation time (pooled SMD = −1.758, p = 0.001) than palpation. DNTP gained even more advantage in small children and infants. No significant difference in these outcomes between DNTP and conventional ultrasound method was detected. Fewer hematoma occurred in DNTP than palpation (pooled RR = 0.265, p < 0.001) or traditional ultrasound (pooled RR = 0.348, p < 0.001). DNPT was also associated with fewer posterior wall punctures (pooled RR = 0.495, p = 0.001) and vasospasm (pooled RR = 0.267, p = 0.007) than traditional ultrasound. Conclusions: DNTP was a better choice in artery cannulation than conventional palpation and ultrasound method, especially in small children and infants.

Multifield-Controlled Terahertz Hybrid Metasurface for Switches and Logic Operations.

Terahertz (THz) meta-devices are considered to be a promising framework for constructing integrated photonic circuitry, which is significant for processing the upsurge of data brought about by next-generation telecommunications. However, present active metasurfaces are typically restricted by a single external driving field, a single modulated frequency, fixed switching speed, and deficiency in logical operation functions which prevents devices from further practical applications. Here, to overcome these limitations, we propose a hybrid THz metasurface consisting of vanadium dioxide (VO2) and germanium (Ge) that enables electrical and optical tuning methods individually or simultaneously and theoretically investigate its performance. Each of the two materials is arranged in the meta-atom to dominate the resonance strength of toroidal or magnetic dipoles. Controlled by either or both of the external excitations, the device can switch on or off at four different frequencies, possessing two temporal degrees of freedom in terms of manipulation when considering the nonvolatility of VO2 and ultrafast photogenerated carriers of Ge. Furthermore, the "AND" and "OR" logic operations are respectively achieved at two adjacent frequency bands by weighing normalized transmission amplitude. This work may provide an auspicious paradigm of THz components, such as dynamic filters, multiband switches, and logical modulators, potentially promoting the design and implementation of multifunctional electro-optical devices in future THz computing and communication.

Alterations of gut microbiota in cirrhotic patients with spontaneous bacterial peritonitis: A distinctive diagnostic feature.

Background: Spontaneous bacterial peritonitis (SBP) is a severe infection in cirrhotic patients that requires early diagnosis to improve the long-term outcome. Alterations in the gut microbiota have been shown to correlate with the development and progression of liver cirrhosis. However, the relationship between SBP and gut microbiota remains unknown. Methods: In this study, we applied 16S rRNA pyrosequencing of feces to ascertain possible links between the gut microbiota and SBP. We recruited 30 SBP patients, 30 decompensated cirrhotic patients without SBP (NSBP) and 30 healthy controls. Metagenomic functional prediction of bacterial taxa was achieved using PICRUSt. Results: The composition of the gut microbiota in the SBP patients differed remarkably from that in the NSBP patients and healthy individuals. The microbial richness was significantly decreased, while the diversity was increased in the SBP patients. Thirty-four bacterial taxa containing 15 species, mainly pathogens such as Klebsiella pneumoniae, Serratia marcescens and Prevotella oris, were dominant in the SBP group, while 42 bacterial taxa containing 16 species, especially beneficial species such as Faecalibacterium prausnitzii, Methanobrevibacter smithii and Lactobacillus reuteri, were enriched in the NSBP group. Notably, we found that 18 gene functions of gut microbiota were different between SBP patients and NSBP patients, which were associated with energy metabolism and functional substance metabolism. Five optimal microbial markers were determined using a random forest model, and the combination of Lactobacillus reuteri, Rothia mucilaginosa, Serratia marcescens, Ruminococcus callidus and Neisseria mucosa achieved an area under the curve (AUC) value of 0.8383 to distinguish SBP from decompensated cirrhosis. Conclusions: We described the obvious dysbiosis of gut microbiota in SBP patients and demonstrated the potential of microbial markers as noninvasive diagnostic tools for SBP at an early stage.

Identification of a protective Bacteroides strain of alcoholic liver disease and its synergistic effect with pectin.

The depletion of Bacteroides in the gut is closely correlated with the progression of alcoholic liver disease (ALD). This study aimed to identify Bacteroides strains with protective effects against ALD and evaluate the synergistic effects of Bacteroides and pectin in this disease. Mice were fed Lieber-DeCarli alcohol diet to establish an experimental ALD model and pre-treated with 4 Bacteroides strains. The severity of the liver injury, hepatic steatosis, and inflammation was evaluated through histological and biochemical assays. We found that Bacteroides fragilis ATCC25285 had the best protective effects against ALD strains by alleviating both ethanol-induced liver injury and steatosis. B. fragilis ATCC25285 could counteract inflammatory reactions in ALD by producing short-chain fat acids (SCFAs) and enhancing the intestinal barrier. In the subsequent experiment, the synbiotic combination of B. fragilis ATCC25285 and pectin was evaluated and the underlying mechanisms were investigated by metabolomic and microbiome analyses. The combination elicited superior anti-ALD effects than the individual agents used alone. The synergistic effects of B. fragilis ATCC25285 and pectin were driven by modulating gut microbiota, improving tryptophan metabolism, and regulating intestinal immune function. Based on our findings, the combination of B. fragilis ATCC25285 and pectin can be considered a potential treatment for ALD. KEY POINTS: • B. fragilis ATCC25285 was identified as a protective Bacteroides strain against ALD. • The synbiotic combination of B. fragilis and pectin has better anti-ALD effects. • The synbiotic combination modulates gut microbiota and tryptophan metabolism.

Characteristics of the gut microbiota in Bifidobacterium catenulatum LI10 pretreated rats with lower levels of D-galactosamine-induced liver damage.

AIMS: Liver damage has caused great illness in human beings. Bifidobacterium catenulatum LI10 has been determined with protective effect against D-galactosamine-induced liver damage. However, due to the sample limitation, the individual difference in its protective effect was not determined. The current study was designed to characterize the gut microbiota of LI10-pretreated rats with lower levels of liver damage. METHODS AND RESULTS: A series of experiments and bioinformatic analyses were carried out. Two rat cohorts with different levels of liver damage were determined, that is, Non-Severe and Severe cohorts. Six out of the seven measured liver function variables were lower in the Non-Severe cohort, while four cytokine variables also yielded differences between the two cohorts. The Non-Severe and Severe cohorts were determined with distinct gut microbiota, among which ASV14_Parabacteroides and ASV7_Bacteroides were most associated with Non-Severe and Severe cohorts, respectively. Five phylotypes were determined as structural gatekeepers in the microbiota network of Non-Severe cohort, ASV135_Lachnospiraceae_NK4A136 of which contributed most to the stability of the network. CONCLUSIONS: The relevant findings suggest that some gut bacteria could benefit the protective effect of LI10 on lowering the severity of rat liver damage. SIGNIFICANCE AND IMPACT OF THE STUDY: The bacteria benefiting the protective effects of potential probiotics could be further investigated for future clinical application.

Microbial metabolites indole derivatives sensitize mice to D-GalN/LPS induced-acute liver failure via the Tlr2/NF-κB pathway.

Introduction: Acute liver failure (ALF) is a clinical condition with many causes, fast progression, and a poor prognosis. Previous research has indicated that microbial factors have a role in ALF, but a clear picture has yet to emerge. Methods: To investigate the specific involvement of microbial metabolites in ALF development, we pretreated D-GalN/LPS-induced ALF mice with indole derivatives, an influential class of gut microbial metabolites. Results: Contrary to their typical role as anti-inflammatory agents in the host, indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indolepropionic acid (IPA) gavage sensitize mice to D-GalN/LPS-induced-ALF with a rapid rise in serum transaminases and histologic lesion. For a clearer picture, we performed comprehensive analysis for the IAA therapy. IAA markedly amplified inflammatory response and cellular damage. The transcriptome analysis indicated the participation of the TNF-α/NF-κB signaling pathway. The structure of gut microbiota in ileum and the expression of Toll-like receptor 2 (Tlr2) in the liver were also significantly changed. Discussion: In conclusion, IAA pretreatment can exacerbate D-GalN/LPS-induced ALF via probable Tlr2/NF-κB pathway involvement and ileac dysbiosis characterized by enriched gram-positive genus with potential pathogenesis. Microbial metabolites IAA may aggravate individual susceptibility to D-GalN/LPS-induced ALF. Further investigation of the underlying mechanism is needed, and intervention with indole derivatives and related commensal species should be undertaken with caution.