Exploring cross-modal plasticity in the auditory-visual cortex post cochlear implantation: implications for auditory and speech function recovery and mechanisms.

Objective: The aim of this is to explore changes in cross-modal reorganization within the auditory-visual cortex after cochlear implantation, examining their influence on auditory and speech functions along with their underlying mechanisms. Methods: Twenty prelingually deaf children who received cochlear implantation and rehabilitation training at our hospital between February 2022 and February 2023 comprised the prelingual deaf group. Simultaneously, 20 healthy children served as the control group. The prelingual deaf group underwent brain cortical activity assessment and evaluation of auditory-speech recovery pre-surgery, at postoperative weeks 1 and 2, and at months 1, 3, 6, 9, and 12. The control group underwent parallel assessments and evaluations. We analyzed the correlation between cortical activity in the auditory-visual cortex of patients and their auditory-speech functional recovery. Results: The group with prelingual deafness displayed elevated levels of auditory and visual cortical electromagnetic intensity compared to the control group, both prior to and 9 months after surgery. However, by the 12-month mark post-surgery, there was no discernible distinction between the two groups. Following surgery, the prelingually deaf group exhibited a progressive improvement in both Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR), initially lagging behind the control group. Notably, a negative correlation emerged between auditory and visual cortical electromagnetic intensity values and CAP/SIR scores at the 12-month post-surgery assessment. Conclusion: Cochlear implantation in prelingually deaf children results in elevated activity within the auditory and visual cortices, demonstrated by heightened electromagnetic intensity readings. Cross-modal reorganization is observed temporarily at 3 months post-surgery, which resolves to baseline levels by 12 months post-surgery. This phenomenon of reversal correlates with the restoration of auditory and speech functions in these children.

Multi-angle speed-of-sound imaging with sparse sampling to characterize medical tissue properties.

Medical Speed-of-sound (SoS) imaging, which can characterize medical tissue properties better by quantifying their different SoS, is an effective imaging method compared with conventional B-mode ultrasound imaging. As a commonly used diagnostic instrument, a hand-held array probe features convenient and quick inspection. However, artifacts will occur in the single-angle SoS imaging, resulting in indistinguishable tissue boundaries. In order to build a high-quality SoS image, a number of raw data are needed, which will bring difficulties to data storage and processing. Compressed sensing (CS) theory offers theoretical support to the feasibility that a sparse signal can be rebuilt with random but less sampling data. In this study, we proposed an SoS reconstruction method based on CS theory to process signals obtained from a hand-held linear array probe with a passive reflector positioned on the opposite side. The SoS reconstruction method consists of three parts. Firstly, a sparse transform basis is selected appropriately for a sparse representation of the original signal. Then, considering the mathematical principles of SoS imaging, the ray-length matrix is used as a sparse measurement matrix to observe the original signal, which represents the length of the acoustic propagation path. Finally, the orthogonal matching pursuit algorithm is introduced for image reconstruction. The experimental result of the phantom proves that SoS imaging can clearly distinguish tissues that show similar echogenicity in B-mode ultrasound imaging. The simulation and experimental results show that our proposed method holds promising potential for reconstructing precision SoS images with fewer signal samplings, transmission, and storage.

Early prediction of platelet recovery with immature platelet fraction in patients receiving hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is pivotal in treating hematologic disorders, yet it poses the risk of post-transplantation pancytopenia. Prophylactic platelet transfusions are often administered to mitigate this risk. Utilizing practical markers, such as immature platelet fraction (IPF), to predict hematopoietic recovery in advance could reduce unnecessary prophylactic transfusions. Our prospective study, involving 53 HSCT patients at Taipei Veterans General Hospital between September 2022 and May 2023, utilized the Sysmex XN analyzer to assess peripheral blood cell parameters. We investigated whether IPF could predict platelet recovery early, determined the optimal cut-off value, and compared platelet usage. Neutrophil and platelet engraftment occurred 10 (median; range: 10-12) and 15 (median; range: 15-18) days post-HSCT. Notably, 71.7% of patients exhibited an IPF increase exceeding 2% before platelet recovery. The optimal cut-off IPF on day 10 for predicting platelet recovery within five days was 2.15% (specificity 0.89, sensitivity 0.65). On average, patients received 3.89 units of post-transplantation platelet transfusion. Our results indicate that IPF serves as a predictive marker for platelet engraftment, peaking before the increase in platelet count. This insight aids clinicians in assessing the need for prophylactic platelet transfusions. Integrating reference IPF values alongside platelet counts enhances the accuracy of evaluating a patient's hematopoietic recovery status. Anticipating the timing of platelet recovery optimizes blood product usage and mitigates transfusion reaction risks.

Modulating Electrical Double Layers: Facile Approach for Promoting Noncovalent Interactions between Boron Nitride Nanosheets and Gold Nanoparticles.

Electrical double layer (EDL) plays a crucial role in colloidal chemistry, which can be modified by changing the pH and ionic strength of a solution. Even though EDL is well-recognized, there are limited studies exploring interactions between two-dimensional (2D) and zero-dimensional nanoparticles. Herein, we demonstrate a simple pH-based approach to control the EDL of boron nitride nanosheets (BNNSs) and gold nanoparticles (AuNPs) that plays a crucial role in their interaction, displaying a one-way gate effect. We observed that as the EDL decreases, AuNPs can come into closer interaction with BNNSs, and this also resulted in a deceleration of the aggregation process of AuNPs when functionalized with l-cysteine. This work provides a fundamental understanding of how modulation of the EDL of 2D nanomaterials can be achieved through functionalizing strategies.

Association of waist-to-hip ratio adjusted for body mass index with cognitive impairment in middle-aged and elderly patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. METHODS: A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. RESULTS: WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261-1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032-4.371, P for trend < 0.001). CONCLUSIONS: Our study illustrated that higher WHRadjBMI is likely to be associated with an increased risk of CI among patients with T2DM. These findings support the detrimental effects of excess visceral fat accumulation on cognitive function in middle-aged and elderly T2DM patients.

Dual ProGlide versus ProGlide and Angio-Seal for Femoral Access Hemostasis after Transcatheter Aortic Valve Replacement: A Randomized Comparative Trial.

BACKGROUND: Vascular complications increase morbidity and mortality after transcatheter aortic valve replacements(TAVR), often related to failures in vascular closure devices(VCD). We intended to compare the dual Perclose ProGlide(PP) strategy to the hybrid combination of PP and Angio-Seal(AS) for femoral access hemostasis after TAVR. METHODS: A randomized controlled trial with 257 patients comparing dual PP to one PP and one AS(AS+PP) for vascular closure after transfemoral TAVR was conducted. The primary endpoint was the composite of TAVR access site-related vascular complications and life-threatening type 2/3 or 1 bleeding according to VARC-3. Secondary endpoints included additional VCD use and significant peripheral ischemia related to arteriotomy closure within one year. Modified VCD failure, defined as failure to achieve hemostasis within 5 minutes or requiring additional endovascular maneuvers, was also recorded. RESULTS: The AS+PP combination yielded lower rates of the primary endpoint(18.2% vs 29.8%; p = 0.0381), vascular complication(18.2% vs 29.8%; p = 0.0381), additional VCD usage(0.8% vs 19.0%; p < 0.0001), and modified VCD failure(9.9% vs 33.1%; p < 0.0001) than the dual PP. Bleeding complication rates were similar between the two groups. Three-month follow-up vascular duplex tests showed similar common femoral artery(CFA) diameters and peak systolic velocities(PSV) between the two groups, but additional intervention had higher PSV and smaller CFA diameters than those without. CONCLUSIONS: The combined PP+AS for large-bore femoral access hemostasis following TAVR promises to be more effective and safer than dual PP in terms of vascular complications. Moreover, additional intervention for vascular complications resulted in smaller CFA diameters(ClinicalTrials.gov number, NCT05491070).

Bioaccessibility and bioavailability assessment of cadmium in rice: In vitro simulators with/without gut microbiota and validation through in vivo mouse and human data.

Assessing the bioaccessibility and bioavailability of cadmium (Cd) is crucial for effective evaluation of the exposure risk associated with intake of Cd-contaminated rice. However, limited studies have investigated the influence of gut microbiota on these two significant factors. In this study, we utilized in vitro gastrointestinal simulators, specifically the RIVM-M (with human gut microbial communities) and the RIVM model (without gut microbial communities), to determine the bioaccessibility of Cd in rice. Additionally, we employed the Caco-2 cell model to assess bioavailability. Our findings provide compelling evidence that gut microbiota significantly reduces Cd bioaccessibility and bioavailability (p<0.05). Notably, strong in vivo-in vitro correlations (IVIVC) were observed between the in vitro bioaccessibilities and bioavailabilities, as compared to the results obtained from an in vivo mouse bioassay (R2 = 0.63-0.65 and 0.45-0.70, respectively). Minerals such as copper (Cu) and iron (Fe) in the food matrix were found to be negatively correlated with Cd bioaccessibility in rice. Furthermore, the results obtained from the toxicokinetic (TK) model revealed that the predicted urinary Cd levels in the Chinese population, based on dietary Cd intake adjusted by in vitro bioaccessibility from the RIVM-M model, were consistent with the actual measured levels (p > 0.05). These results indicated that the RIVM-M model represents a potent approach for measuring Cd bioaccessibility and underscore the crucial role of gut microbiota in the digestion and absorption process of Cd. The implementation of these in vitro methods holds promise for reducing uncertainties in dietary exposure assessment.

The C-terminal amino acid motifs of NS1 protein affect the replication and virulence of naturally NS-truncated H1N1 canine influenza virus.

AbstractThe vast majority of data obtained from sequence analysis of influenza A viruses (IAVs) have revealed that nonstructural 1 (NS1) proteins from H1N1 swine, H3N8 equine, H3N2 avian and the correspondent subtypes from dogs have a conserved four C-terminal amino acid motif when independent cross-species transmission occurs between these species. To test the influence of the C-terminal amino acid motifs of NS1 protein on the replication and virulence of IAVs, we systematically generated 7 recombinants, which carried naturally truncated NS1 proteins, and their last four C-terminal residues were replaced with PEQK and SEQK (for H1N1), EPEV and KPEI (for H3N8) and ESEV and ESEI (for H3N2) IAVs. Another recombinant was generated by removing the C-terminal residues by reverse genetics. Remarkably, the ESEI and KPEI motifs circulating in canines largely contributed efficient replication in cultured cells and these had enhanced virulence. In contrast, the avian ESEV motif was only responsible for high pathogenicity in mice. We examined the effects of these motifs upon interferon (IFN) induction. The 7 mutant viruses replicated in vitro in an IFN-independent manner, and the canine SEQK motif was able to induced higher levels of IFN-ß in human cell lines. These findings shed further new light on the role of the four C-terminal residues in replication and virulence of IAVs and suggest that these motifs can modulate viral replication in a species-specific manner.

Laparoscopy combined with hysteroscopy in the treatment of Robert's uterus accompanied by adenomyosis: A case report.

BACKGROUND: Gynaecologists should be aware of a rare obstructive Mullerian duct abnormality like Robert's uterus and perform further surgery when necessary. CASE SUMMARY: We report a 41-year-old mother of two children with Robert's uterus who was examined and treated by laparoscopy and hysteroscopy. Unlike the existing cases reported in the literature, this patient had a late onset of Robert's uterus symptoms. Due to right tubal ectopic pregnancy 3 years previously, the patient was treated with right salpingectomy and left tubal ligation but suffered aggravated left lower abdominal pain. She was examined and treated by laparoscopy and hysteroscopy, and is completely asymptomatic at 5-year follow-up. CONCLUSION: The typical obstructive Mullerian abnormality requires further surgery. Combined laparoscopy and hysteroscopy is an effective, minimally invasive technique with better recovery outcomes than traditional transabdominal procedures.

Indole­3­propionic acid alleviates intestinal epithelial cell injury via regulation of the TLR4/NF­κB pathway to improve intestinal barrier function.

Indole­3­propionic acid (IPA), a product of Clostridium sporogenes metabolism, has been shown to improve intestinal barrier function. In the present study, in vitro experiments using NCM460 human colonic epithelial cells were performed to investigate how IPA alleviates lipopolysaccharide (LPS)­induced intestinal epithelial cell injury, with the aim of improving intestinal barrier function. In addition, the underlying mechanism was explored. NCM460 cell viability and apoptosis were measured using the Cell Counting Kit­8 assay and flow cytometry, respectively. The integrity of the intestinal epithelial barrier was evaluated by measuring transepithelial electrical resistance (TEER). The underlying molecular mechanism was explored using western blotting, immunofluorescence staining, a dual luciferase reporter gene assay and quantitative PCR. The results showed that 10 µg/ml LPS induced the most prominent decrease in cell viability after 24 h of treatment. By contrast, IPA effectively inhibited LPS­induced apoptosis in the intestinal epithelial cells. Additionally, >0.5 mM IPA improved intestinal barrier function by increasing TEER and upregulating the expression of tight junction proteins (zonula occludens­1, claudin­1 and occludin). Furthermore, IPA inhibited the release of pro­inflammatory cytokines (IL­1ß, IL­6 and TNF­α) in a dose­dependent manner and this was achieved via regulation of the Toll­like receptor 4 (TLR4)/myeloid differentiation factor 88/NF­κB and TLR4/TRIF/NF­κB pathways. In conclusion, IPA may alleviate LPS­induced inflammatory injury in human colonic epithelial cells. Taken together, these results suggest that IPA may be a potential therapeutic approach for the management of diseases characterized by LPS­induced intestinal epithelial cell injury and intestinal barrier dysfunction.

Interplay between Pro-inflammatory Mediators and Oxidative Stressinvolved Recurrent Chronic Heart Failure in Elderly Patients with Coronary Stents.

INTRODUCTION: Inflammation and oxidative stress are related to congestive heart failure in patients with coronary heart disease. OBJECTIVE: Chronic congestive heart failure is a serious stage of coronary artery disease and is mainly a disease of elderly people over the age of 65. Elderly heart failure patients are characterized by myocardial ischemia, and post-ischemic myocardial dysfunction. Oxidative Stress, inflammation, and immune response play important roles in the development of heart failure. We tried to examine the mutual triggering of oxidative stress (malondialdehyde), inflammatory cytokines (tumor necrosis factor-α and soluble tumor necrosis factor receptor-1/2), immune response (toll-like receptors 2,3,4), and high sensitivity C-reactive protein expression in elderly patients with recurrent congestive heart failure after coronary stenting and investigated the effect of interplay of these changes on onset and progression of recurrent congestive heart failure in elderly patients underwent coronary stent implantation. METHODS: A total of 726 patients were enrolled in this study. We determined the levels of malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF- α), soluble tumor necrosis factor receptor-1 and 2 (sTNFR-1/2) and toll-like receptor 2,3,4 (TLR2/3/4) in elderly patients with recurrent congestive heart failure after coronary artery stent implantation. RESULTS: Levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 were remarkably increased (p<0.01) in elderly patients with recurrent congestive heart failure after coronary artery stenting. The results indicated that these markers were closely correlated to each other and showed that these markers were associated with increased New York Heart Association functional classification and low left ventricular ejection fractions. Further analysis confirmed that the independent clinical risk factors for recurrent congestive heart failure were MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4. The interplay of oxidative stress, inflammatory cytokines and toll-like receptors, and hs-CRP expression levels was an important factor involved in recurrent congestive heart failure of elderly patients after coronary stenting. CONCLUSION: High levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 had an important implication for recurrent heart failure with increased New York Heart Association functional classification and low left ventricular ejection fractions. These eight factors amplified each other's positive effects and this interaction may be a key element of their roles in recurrent heart failure. The eight risk factors were inter-dependent and occurred simultaneously, and exerted detrimental effects forming a vicious circle. MDA may trigger the over-expressions of pro-inflammatory risk factors (hs-CRP, TNF-α, sTNFR-1, sTNFR-2) through the activation of TLRs as risk factors (TLR2, TLR3 and TLR4) contributing to the dysfunction of myocardial mitochondria, cardiomyocyte hypertrophy, maladaptive myocardial remodeling, myocardial interstitial fibrosis, cardiac systolic decrease and recurrent heart failure. These eight risk factors were the basis of the mechanisms of recurrent heart failure. Therefore, the mutual triggering of oxidative stress, inflammatory and toll-like receptor signaling pathways, and hs-CRP expression could play key roles in the development of recurrent congestive heart failure in elderly patients after coronary stenting.

Orbital Complication in the Setting of Cocaine Use: A Case Report and Review of Literature.

Orbital cellulitis is a common ophthalmologic consultation and has numerous risk factors; however, one that is seldomly encountered is chronic cocaine use. We describe a case of a 63-year-old man with a history of HIV and cocaine use who presented with OD pain, proptosis, and blurred vision. CT imaging revealed extensive erosions throughout the nasal septum, bilateral turbinates, ethmoid sinuses, and loss of the right medial orbital wall. The patient was treated empirically with broad-spectrum antibiotics, and a nasal biopsy and culture grew Staphylococcus aureus. After treatment with IV antibiotics, the patient's visual acuity returned to baseline with resolution of extraocular motility limitations. Although nasal erosions are a well-described sequela of cocaine use, full-thickness osseous defects of the orbital wall are rare and represent late-stage complications of cocaine-induced destructive midline lesions. Orbital cellulitis is a very rare complication in the setting of cocaine-induced destructive midline lesions. Clinicians should be aware of the link between cocaine use, rhino-orbital abnormalities, and orbital cellulitis.

The ideal range of laser hair removal for microtia patients undergoing two-stage ear reconstruction.

Although the technologies for auricular reconstruction in microtia have improved, issues such as low hairlines or excessive hair growth can still pose aesthetic problems for the reconstructed ear. Laser depilation has been reported as a solution for hair problems. However, few studies have discussed the appropriate region for hair removal. A retrospective analysis was performed on 276 patients with unilateral microtia who underwent the Nagata two-stage ear reconstruction. The gender ratio of male to female was 2.5 (198 males/78 females). Intense pulsed light depilation was used to remove hair. To determine the proper hair removal area, we measured the extent of hair removal. Before the first stage, the average vertical distance between the upper point (after localization) and hairline was 3.42 ± 4.75 mm (-10-20 mm). After the first stage, the average vertical distance between the upper point of the reconstructed ear and the hairline was 1.27 ± 2.41 mm (-10-15 mm). By using chi-square test to assess differences in hair removal success rates among various regions, we aimed to identify the suitable depilation region. Before the first stage, a depilation vertical distance ≥ 10 mm led to a 92.1% success rate. After the first stage surgery, among the patients needing additional hair removal, a vertical depilation distance ≥ 4 mm resulted in an 81.3% success rate. Based on our observation, we suggested that a depilation region of ≥ 10 mm (before the first surgery) or ≥ 4 mm (after the first surgery) would be the ideal range for laser hair removal.

Changes in the upper airway and its surrounding structures after bimaxillary surgery in patients with cleft-related Class III deformity.

OBJECTIVES: To compare upper airway changes following bimaxillary surgery for correction of Class III deformity between patients with unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) and to compare the preoperative and postoperative upper airway among patients with UCLP and BCLP to healthy controls. MATERIALS AND METHODS: Sixty adults with CLP-related skeletal Class III deformity (30 UCLP and 30 BCLP) who consecutively underwent bimaxillary surgery were studied retrospectively. Cone-beam computed tomography (CBCT) was performed before and after surgery to measure upper airway and movements of facial skeletal and surrounding structures. CBCT images from 30 noncleft skeletal Class I adults, matched by age, gender, and body mass index and without surgical intervention, served as controls. RESULTS: After surgery, the volume of the nasopharynx increased in patients with CLP (both P < .001). Patients with CLP did not differ from controls in postoperative volume of the nasopharynx or oropharynx. However, the nasal cavity differed significantly between patients with CLP and controls (P < .001). CONCLUSIONS: After bimaxillary surgery, the nasal cavity of patients with CLP differed significantly compared with the controls. Volumes of the nasopharynx and oropharynx did not differ between patients with CLP after surgery and controls.

Discovery and Evaluation of TLR-Targeted Immune Agonists.

Toll-like receptor (TLR) activation converts immunologically inactive tumors into immunologically active tumors by activating tumor residing antigen-presenting cells and recruitment of cytotoxic T lymphocytes. Targeted immune agonists (TIAs) are antibody drug conjugates with small-molecule TLR agonist payloads. The mechanism of action of TIAs involves tumor antigen recognition, Fcγ-receptor-dependent phagocytosis, and TLR-mediated activation to drive tumor killing by myeloid cells. Several new low DAR anti-HER2 TIAs conjugated with novel TLR7 or dual-TLR7/8 agonists with cleavable and noncleavable linkers were synthesized and profiled. In vitro studies demonstrated that these TIAs activate myeloid cells only in the presence of antigen-expressing cancer cells. Evaluation in ELISpot-based assays confirmed the low immunogenicity of these constructs. Systemic administration of the novel TIAs in tumor-bearing mice resulted in tumor reduction at low doses. These results provide a strong rationale for further development of the TIAs as a novel class of immunotherapeutics.

Irinotecan plus raltitrexed as second-line treatment in locally advanced or metastatic colorectal cancer patients: a prospective open-label, single-arm, multi-center, phase II study.

BACKGROUND: Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size. METHODS: This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety. RESULTS: A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1-61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1-5.7) and median overall survival was 13.1 months (95% CI 12.2-15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths. CONCLUSIONS: The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.

Effects of migratory birds activities on the stoichiometry of soil carbon, nitrogen and phosphorus in a Carex-dominated wetland of Poyang Lake.

Studying the stoichiometric characteristics of soil nutrients aids in evaluating soil quality and deciphering the coupling of soil nutrients. The influence of migratory bird activities on the dynamics of wetland soil nutrients and their stoichiometric remains unclear. We classified the central, peripheral and adjacent natural grassy areas as severe, mild, and no bird activity (control), respectively, in Donghu Carex meadow, a representative migratory bird habitat in Poyang Lake, based on flock characteristics and initial surveys. We analyzed the contents and stoichio-metry of soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) across soil depths of 0-100 cm under different intensities of migratory bird activities. The results showed that the activities of migratory birds significantly impacted nutrient levels exclusively within 0-30 cm soil. Mild activities markedly enhanced SOC and TN across 0-30 cm soil, while both mild and severe activities significantly raised TP within the same depth. For the 0-100 cm soil profiles, soil C/N ratios were 10.0, 10.8, and 9.9, C/P ratios were 23.5, 30.0, and 22.7, and N/P ratios were 2.3, 2.7, and 2.3 under no, mild, and severe bird activities, respectively. Further, mild activities of migratory birds significantly increased soil C/N, C/P and N/P ratios only within the 0-30 cm depth, while the stoichiometric ratios of all soil layer had no significant difference under severe bird activity. Soil stoichiometric ratios strongly correlated with physicochemical properties. SOC, TN, and TP primarily mediated the effects of migratory bird activity on soil carbon, nitrogen, and phosphorus stoichiometric ratios in Poyang Lake wetland. In conclusion, the influence of migratory bird activity on the stoichiometric ratios of soil carbon, nitrogen, and phosphorus in Poyang Lake wetland exhibited depth threshold (approximately 30 cm), aligning with the "Intermediate Distur-bance Hypothesis". These findings could provide a new perspective for the protection of wetlands and migratory birds.

The gut microbiome modulate response to immunotherapy in cancer.

Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors. Currently, clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of cancers. Preclinical investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy. Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells. Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies. Fecal microbial transplants, probiotics, dietary interventions, and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy. Ongoing clinical trials are evaluating these approaches. This review presents the recent advancements in understanding the dynamic interplay among the host immunity, the microbiome, and cancer immunotherapy, as well as strategies for modulating the microbiome, with a view to translating into clinical applications.

Structural analysis of the mitochondrial genome of Santalum album reveals a complex branched configuration.

BACKGROUND: Santalum album L. is an evergreen tree which is mainly distributes throughout tropical and temperate regions. And it has a great medicinal and economic value. RESULTS: In this study, the complete mitochondrial genome of S. album were assembled and annotated, which could be described by a complex branched structure consisting of three contigs. The lengths of these three contigs are 165,122 bp, 93,430 bp and 92,491 bp. We annotated 34 genes coding for proteins (PCGs), 26 tRNA genes, and 4 rRNA genes. The analysis of repeated elements shows that there are 89 SSRs and 242 pairs of dispersed repeats in S. album mitochondrial genome. Also we found 20 MTPTs among the chloroplast and mitochondria. The 20 MTPTs sequences span a combined length of 22,353 bp, making up 15.52 % of the plastome, 6.37 % of the mitochondrial genome. Additionally, by using the Deepred-mt tool, we found 628 RNA editing sites in 34 PCGs. Moreover, significant genomic rearrangement is observed between S. album and its associated mitochondrial genomes. Finally, based on mitochondrial genome PCGs, we deduced the phylogenetic ties between S. album and other angiosperms. CONCLUSIONS: We reported the mitochondrial genome from Santalales for the first time, which provides a crucial genetic resource for our study of the evolution of mitochondrial genome.

Serum taurine affects lung cancer progression by regulating tumor immune escape mediated by the immune microenvironment.

INTRODUCTION: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.