Time-dependent proteomics and drug response in expanding cancer cells.

Cancer cell line is commonly used for discovery and development of anti-cancer drugs. It is generally considered that drug response remains constant for a certain cell line due to the identity of genetics thus protein patterns. Here, we demonstrated that cancer cells continued dividing even after reaching confluence, in that the proteomics was changed continuously and dramatically with strong relevance to cell division, cell adhesion and cell metabolism, indicating time-dependent intrinsically reprogramming of cells during expansion. Of note, the inhibition effect of most anti-cancer drugs was strikingly attenuated in culture cells along with cell expansion, with the strongest change at the third day when cells were still expanding. Profiling of an FDA-approved drug library revealed that attenuation of response with cell expansion is common for most drugs, an exception was TAK165 that was a selective inhibitor of mitochondrial respiratory chain complex I. Finally, we screened a panel of natural products and identified four pentacyclic triterpenes as selective inhibitors of cancer cells under prolonged growth. Taken together, our findings underscore that caution should be taken in evaluation of anti-cancer drugs using culture cells, and provide agents selectively targeting overgrowth cancer cells.

Pan-cancer prognosis, immune infiltration, and drug resistance characterization of lung squamous cell carcinoma tumor microenvironment-related genes.

Background: The tumor microenvironment (TME) plays an important role in cancer development; however, its implications in lung squamous cell carcinoma (LUSC) and pan-cancer have been poorly understood. Methods: In this study, The Cancer Genome Atlas (TCGA) and Estimation of Stromal and Immune cells in Malignant Tumor tissue using Expression Data (ESTIMATE) datasets were applied to identify differentially expressed genes. Additionally, online public databases were utilized for in-depth bioinformatics analysis of pan-cancer datasets to investigate the prognostic implications of TME-related genes further. Results: Our study demonstrated a significant association between stromal scores, immune scores, and specific clinical characteristics in LUSC patients. C3AR1, CSF1R, CCL2, CCR1, and CD14 were identified as prognostic genes related to the TME. All TME-related prognostic genes demonstrated varying degrees of correlation with immune infiltration subtypes and tumor cell stemness. Moreover, our study revealed that TME-related prognostic genes, particularly C3AR1 and CCR1, might contribute to drug resistance in cancer cells. Conclusions: The identified TME-related prognostic genes, particularly C3AR1 and CCR1, have potential implications for understanding and targeting drug resistance mechanisms in cancer cells.

Stair-stepped mandibulotomy: Clinical indication, surgery program design, and operation points.

For radical treatment of malignancies in the posterior region of the oral cavity and oropharynx, surgical exposure of the tumor by mandibulotomy is often required. Midline or paramedian vertical mandibulotomies are commonly performed in clinical practice, but these can damage the suprahyoid musculature and genioglossus, and weaken the swallowing and speech function of patients. Stair-stepped mandibulotomy is a new procedure, developed on the principles of functional surgery, that preserves the structure and function of the mandible whilst providing a clear field and avoiding damage to critical muscle attachments. Stair-stepped mandibulotomy is suitable for patients whose primary tumor is located in the middle and posterior part of the tongue or oropharynx, especially if the lesion involves extrinsic tongue muscles. In this case report, we draw on 2 cases of typical patients in our center to elaborate the surgery program design, operation points, advantages and disadvantages of stair-stepped mandibulotomy.

Phase distribution and circular dichroism switchable terahertz chiral metasurface.

Chiral metasurfaces have many applications in the terahertz (THz) band, but they still lack modulation flexibility and functionality expansion. This paper presents a terahertz chiral metasurface with switchable phase distribution and switchable circular dichroism (CD). The metasurface unit consists of a metallic inner ring embedded in vanadium oxide and a vanadium oxide outer ring, state switching by thermal control of vanadium oxide and a change in the frequency of the incident wave. Based on the switchable phase distribution, we designed a focusing vortex beam generator with adjustable focal lengths through simulation. Based on the switching CD capability, we simulate its mode switching in near-field imaging using numerical simulation, and innovatively propose an optical encryption method. Utilizing the chiral property, we also designed dual-channel switchable holographic imaging in the same frequency band, which combined with the state change of VO2 can realize a total of 4 holograms switching. Our proposed metasurface is expected to provide new ideas for the study of optical encryption and wavefront modulation of dynamics.

A scoring system to predict the technical difficulty of endoscopic resection for cardial submucosal tumors.

BACKGROUND AND AIM: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs. METHODS: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The ß coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute ß coefficient value. RESULTS: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively. CONCLUSIONS: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs.

The causal relationship between cathepsins and digestive system tumors: a Mendelian randomization study.

Background: Multiple studies have confirmed the significant role of cathepsins in the development and progression of digestive system tumors. However, further investigation is needed to determine the causal relationships. Methods: We conducted a two-sample bidirectional Mendelian randomization (MR) study using pooled data from a genome-wide association study (GWAS) to assess the causal associations between nine cathepsins (cathepsin B, E, F, G, H, L2, O, S, and Z) and six types of digestive system tumors, including hepatocellular carcinoma (HCC), pancreatic cancer (PCa), biliary tract cancer (BTC), colorectal cancer (CRC), gastric carcinoma (GC), and esophageal cancer (EC). We employed the following methods including inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran's Q, MR-PRESSO, MR-Egger intercept test and leave-one-out sensitivity analysis. The STROBE-MR checklist for the reporting of MR studies was used in this study. Results: The risk of HCC increased with high levels of cathepsin G (IVW: p = 0.029, odds ratio (OR) = 1.369, 95% confidence interval (CI) = 1.033-1.814). Similarly, BTC was associated with elevated cathepsin B levels (IVW: p = 0.025, OR = 1.693, 95% CI = 1.070-2.681). Conversely, a reduction in PCa risk was associated with increased cathepsin H levels (IVW: p = 0.027, OR = 0.896, 95% CI = 0.812-0.988). Lastly, high levels of cathepsin L2 were found to lower the risk of CRC (IVW: p = 0.034, OR = 0.814, 95% CI = 0.674-0.985). Conclusion: Our findings confirm the causal relationship between cathepsins and digestive system tumors, which can offer valuable insights for the diagnosis and treatment of digestive system tumors.

The relationship between social support and professional identity of health professional students from a two-way social support theory perspective: chain mediating effects of achievement motivation and meaning in life.

BACKGROUND: Studies has suggested that receiving social support improves the professional identity of health professional students. According to the two-way social support theory, social support includes receiving social support and giving social support. However, the effect of the two-way social support on health professional students' professional identity has not been clarified yet. METHODS: To explore the mechanism of how two-way social support affects health professional students' professional identity, an observational, cross-sectional study was conducted among a convenience and cluster sample of 1449 health professional students from two medical schools in western China. Measures included a short version of the two-way social support scale, a health professional students' professional identity questionnaire, an achievement motivation scale, and a meaning in life scale. Data were analyzed by use of SPSS26.0 software and PROCESSv4.0 plug-in. RESULTS: Receiving social support, giving social support, achievement motivation, meaning in life, and professional identity were positively correlated with each other. Receiving and giving social support not only directly predicted health professional students' professional identity, but also indirectly predicted health professional students' professional identity through the mediating roles of achievement motivation and meaning in life, and the chain mediating roles of achievement motivation and meaning in life, respectively. The effectiveness of predicting health professional students' professional identity varied among different types of two-way social support, which could be depicted as two-way social support > mainly giving social support > mainly receiving social support > low two-way social support. CONCLUSION: In the medical education, the awareness and ability of health professional students to receive and give social support should be strengthened. More attention should be drawn on the chain mediating effect of achievement motivation and meaning in life between two-way social support and professional identity. The current results shed new light on exploring effective ways of improving health professional students' professional identity, which suggested that more attention should be paid to the positive effects of mainly giving social support and two-way social support rather than only on the effects of receiving social support.

Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system.

BACKGROUND: The detailed transcriptomic profiles during human serotonin neuron (SN) differentiation remain elusive. The establishment of a reporter system based on SN terminal selector holds promise to produce highly-purified cells with an early serotonergic fate and help elucidate the molecular events during human SN development process. METHODS: A fifth Ewing variant (FEV)-EGFP reporter system was established by CRISPR/Cas9 technology to indicate SN since postmitotic stage. FACS was performed to purify SN from the heterogeneous cell populations. RNA-sequencing analysis was performed for cells at four key stages of differentiation (pluripotent stem cells, serotonergic neural progenitors, purified postmitotic SN and purifed mature SN) to explore the transcriptomic dynamics during SN differentiation. RESULTS: We found that human serotonergic fate specification may commence as early as day 21 of differentiation from human pluripotent stem cells. Furthermore, the transcriptional factors ZIC1, HOXA2 and MSX2 were identified as the hub genes responsible for orchestrating serotonergic fate determination. CONCLUSIONS: For the first time, we exposed the developmental transcriptomic profiles of human SN via FEV reporter system, which will further our understanding for the development process of human SN.

PANoptosis induced by inflammatory cytokines promotes salivary glands radiation injury.

OBJECTIVE: Salivary glands are frequently damaged in patients undergoing radiotherapy for head and neck cancer. Whether PANoptosis, which is characterized by pyroptosis, apoptosis, and necroptosis, occurs during radiation injury to the salivary glands and its role remain unclear. MATERIALS AND METHODS: Radiation-induced injury models of mouse submandibular gland, as well as primary acinar cells and HSG cell lines were established to determine the presence of radiation-induced PANoptosis. Several programmed cell death inhibitors, PFTα, disulfiram, Nec-1 and zVAD, were used to compare the effects of different cell death pathway on radiation injury. The LEGENDplex™ Human Inflammation Panel was used to characterize the inflammatory landscape secreted by salivary gland cells after radiotherapy. RESULTS: Single 15Gy or 8Gy radiotherapy triggered PANoptosis in mouse submandibular gland or salivary gland cells. Compared to the suppression of pyroptosis, apoptosis, or necroptosis alone, the inhibition of PANoptosis is more effective in preventing radiation injury to the salivary glands (p < 0.0001). The levels of multiple inflammatory cytokines were significantly up-regulated in the supernatants of HSG cells within 48 h after IR. Neutralizing inflammatory cytokines are capable of inhibiting salivary glands PANoptosis. CONCLUSIONS: Inhibition of PANoptosis induced by inflammatory cytokines can effectively prevent radiation injury of salivary glands.

Cytokine analysis of aqueous humor in patients with cytomegalovirus corneal endotheliitis.

PURPOSE: To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. METHODS: 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. RESULTS: All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). CONCLUSIONS: There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response.

Exploring prognostic microbiota markers in patients with endometrial carcinoma: Intratumoral insights.

Endometrial cancer, a leading gynecological malignancy, is profoundly influenced by the uterine microbiota, a key factor in disease prognosis and treatment. Our study underscores the distinct microbial compositions in endometrial cancer compared to adjacent non-cancerous tissues, revealing a dominant presence of p_Actinobacteria in cancerous tissues as opposed to p_Firmicutes in surrounding areas. Through comprehensive analysis, we identified 485 unique microorganisms in cancer tissues, 26 of which correlate with patient prognosis. Employing univariate Cox regression and LASSO regression analyses, we devised a microbial risk scoring model, effectively stratifying patients into high and low-risk categories, thereby providing predictive insights into their overall survival. We further developed a nomogram that incorporates the microbial risk score along with age, grade, and clinical stage, significantly enhancing the accuracy of our clinical prediction model for endometrial cancer. Moreover, our study delves into the differential immune landscapes of high-risk and low-risk patients. The low-risk group displayed a higher prevalence of activated B cells and increased T cell co-stimulation, indicative of a robust immune response. Conversely, high-risk patients showed elevated tumor immune dysfunction and exclusion scores, suggesting less favorable outcomes in immunotherapy. Notably, the efficacy of IPS-CTLA4 and PD1/PD-L1/PD-L2 blockers was substantially higher in the low-risk group, pointing to a more responsive immunotherapeutic approach. In summary, our research elucidates the unique microbial patterns in endometrial cancer and adjacent tissues, and establishes both a microbial risk score model and a clinical prediction nomogram. These findings highlight the potential of uterine microbiota as a biomarker for customizing treatment strategies, enabling precise interventions for high-risk patients while preventing overtreatment in low-risk cases. This study emphasizes the microbiota's role in tailoring immunotherapy, offering a novel perspective in the treatment and prognosis of endometrial cancer. Significantly, our study's expansive sample analysis from the TCGA-UCEC cohort, employing linear discriminant analysis effect size methodology, not only validates but also enhances our understanding of the microbiota's role in endometrial cancer, paving the way for novel diagnostic and therapeutic approaches in its management.

DCENet-based low-light image enhancement improved by spiking encoding and convLSTM.

The direct utilization of low-light images hinders downstream visual tasks. Traditional low-light image enhancement (LLIE) methods, such as Retinex-based networks, require image pairs. A spiking-coding methodology called intensity-to-latency has been used to gradually acquire the structural characteristics of an image. convLSTM has been used to connect the features. This study introduces a simplified DCENet to achieve unsupervised LLIE as well as the spiking coding mode of a spiking neural network. It also applies the comprehensive coding features of convLSTM to improve the subjective and objective effects of LLIE. In the ablation experiment for the proposed structure, the convLSTM structure was replaced by a convolutional neural network, and the classical CBAM attention was introduced for comparison. Five objective evaluation metrics were compared with nine LLIE methods that currently exhibit strong comprehensive performance, with PSNR, SSIM, MSE, UQI, and VIFP exceeding the second place at 4.4% (0.8%), 3.9% (17.2%), 0% (15%), 0.1% (0.2%), and 4.3% (0.9%) on the LOL and SCIE datasets. Further experiments of the user study in five non-reference datasets were conducted to subjectively evaluate the effects depicted in the images. These experiments verified the remarkable performance of the proposed method.

Clinical analysis of hyperbaric oxygen combined with subdural drilling and drainage in the management of subdural effusion type IV with intracranial infection in infant patients.

Background: To explore the therapeutic effect of hyperbaric oxygen combined with subdural drilling and drainage (SDD) on subdural effusion type IV with intracranial infection in infant patients. Methods: This retrospective controlled study included 328 infant patients with subdural effusion type 4 with intracranial infection between January 2005 and January 2023. 178 patients were treated by hyperbaric oxygen combined with SDD (group A). 142 cases were treated with SDD (group B). 97 infants were only received hyperbaric oxygen (group C). Clinical outcomes, the control time of intracranial infection, complications, and the degree of brain re-expansion after 6 months of treatment were compared among the three groups. According to the comprehensive evaluation of treatment effectiveness and imaging results, it is divided into four levels: cured, significantly effective, improved, and ineffective. Results: No patient died during follow-up. The three groups were similar regarding age, sex, the general information, and clinical symptoms (p > 0.05). All intracranial infections in the children were effectively controlled. There was no difference in infection control time between group A and group B, and there was no statistical significance. However, the control time of intracranial infection between the two groups was different from that of group C, which was statistically significant. Compared with group B and group C, the degree of brain re-expansion in group A has obvious advantages and significant differences. The effective rates of the three groups were 83.7%, 58.5%, and 56.7%, respectively. There were 28 cases of subcutaneous hydrops in group A and 22 cases of subcutaneous hydrops in group B after operation, and no other serious complications. Conclusion: The SDD is safe and effective for infant patients with intracranial infections through fluid replacement and intrathecal antibacterial. Hyperbaric oxygen is effective as an adjuvant therapy to promote brain re-expansion.

Fabrication and Characterization of Silicon-Based Antimonene Thin Film via Electron Beam Evaporation.

Antimonene has attracted much attention due to its excellent characteristics of high carrier mobility, thermoelectric properties and high stability. It has great application prospects in Q-switched lasers, laser protection and spintronics. At present, the epitaxy growth of antimonene mainly depends on molecular beam epitaxy. We have successfully prepared antimonene films on silicon, germanium/silicon substrates for the first time using electron beam evaporation coating and studied the effects of the deposition rate and substrate on the preparation of antimonene; film characterization was performed via confocal microprobe Raman spectroscopy, via X-ray diffraction and using a scanning electron microscope. Raman spectroscopy showed that different deposition rates can lead to the formation of different structures of antimonene, such as α phase and ß phase. At the same time, it was found that the growth of antimonene is also affected by different substrates and ion beams.

M2-type macrophage-targeted delivery of IKKß siRNA induces M2-to-M1 repolarization for CNV gene therapy.

Choroidal Neovascularization (CNV) is capable of inciting recurrent hemorrhage in the macular region, severely impairing patients' visual acuity. During the onset of CNV, infiltrating M2 macrophages play a crucial role in promoting angiogenesis. To control this disease, our study utilizes the RNA interference (RNAi)-based gene therapy to reprogram M2 macrophages to the M1 phenotype in CNV lesions. We synthesize the mannose-modified siRNA-loaded liposome specifically targeting M2 macrophages to inhibit the inhibitory kappa B kinase ß (IKKß) gene involved in the polarization of macrophages, consequently modulating macrophage polarization state. In vitro and in vivo, the mannose-modified IKKß siRNA-loaded liposome (siIKKß-ML) has been proven to effectively target M2 macrophages to repolarize them to M1 phenotype, and inhibit the progression of CNV. Collectively, our findings elucidate that siIKKß-ML holds the potential to control CNV by reprogramming the macrophage phenotype, indicating a promising therapeutic avenue for CNV management.

Endoscopic resection for calcifying fibrous tumors of the gastrointestinal tract.

BACKGROUND: Calcifying fibrous tumors (CFTs) are rare mesenchymal lesions that can occur in various sites throughout the body, including the tubular gastrointestinal (GI) tract. AIM: To analyze the clinical findings of 36 patients with GI tract CFTs to provide guidance for diagnosis and treatment. METHODS: This retrospective study included 36 patients diagnosed with CFTs of the GI tract. We collected demographic and clinical information and conducted regular follow-ups to assess for local recurrence. RESULTS: The stomach was the most commonly involved site, accounting for 72.2% of the 36 CFTs. Endoscopic mucosal resection (n = 1, 2.8%), endoscopic submucosal dissection (n = 14, 38.9%), endoscopic full-thickness resection (n = 16, 44.4%), and submucosal tunneling endoscopic resection (n = 5, 13.9%) were used to resect calcifying fibrous tumors. Overall, 34 (94.4%) CFTs underwent complete endoscopic resections with a mean procedure time of 39.8 ± 29.8 min. The average maximum diameter of the tumors was 10.6 ± 4.3 cm. No complications, such as bleeding or perforation, occurred during an average hospital stay of 2.9 ± 1.2 d. In addition, two patients developed new growth of CFTs near the primary tumor sites, and none of the patients developed distant metastases during the follow-up period. CONCLUSION: GI tract CFTs are rare and typically benign tumors that can be effectively managed with endoscopic procedures.

Modulating ß-catenin homeostasis for cancer therapy.

ß-Catenin is a well-established driver of many cancers; however, there are challenges in developing agents targeting ß-catenin for clinical use. Recent progress has indicated that most of the pathological changes in ß-catenin may be commonly caused by loss of protein homeostasis. Modulation of ß-catenin homeostasis, especially by hyperactivation of ß-catenin, potentially leads to robust antitumor outcomes. Here, we comprehensively dissect the protein homeostasis of ß-catenin in terms of time, compartmentalization, supramolecular assemblies, and dynamics, with emphasis on changes in ß-catenin homeostasis upon oncogenic mutations. We propose that altered ß-catenin homeostasis could be deleterious for ß-catenin-dependent cancers and that modulation of ß-catenin homeostasis offers a novel avenue for targeting ß-catenin for cancer therapy.

Endoscopic features and treatments of gastric cystica profunda.

BACKGROUND: Gastric cystica profunda (GCP) represents a rare condition characterized by cystic dilation of gastric glands within the mucosal and/or submucosal layers. GCP is often linked to, or may progress into, early gastric cancer (EGC). AIM: To provide a comprehensive evaluation of the endoscopic features of GCP while assessing the efficacy of endoscopic treatment, thereby offering guidance for diagnosis and treatment. METHODS: This retrospective study involved 104 patients with GCP who underwent endoscopic resection. Alongside demographic and clinical data, regular patient follow-ups were conducted to assess local recurrence. RESULTS: Among the 104 patients diagnosed with GCP who underwent endoscopic resection, 12.5% had a history of previous gastric procedures. The primary site predominantly affected was the cardia (38.5%, n = 40). GCP commonly exhibited intraluminal growth (99%), regular presentation (74.0%), and ulcerative mucosa (61.5%). The leading endoscopic feature was the mucosal lesion type (59.6%, n = 62). The average maximum diameter was 20.9 ± 15.3 mm, with mucosal involvement in 60.6% (n = 63). Procedures lasted 73.9 ± 57.5 min, achieving complete resection in 91.3% (n = 95). Recurrence (4.8%) was managed via either surgical intervention (n = 1) or through endoscopic resection (n = 4). Final pathology confirmed that 59.6% of GCP cases were associated with EGC. Univariate analysis indicated that elderly males were more susceptible to GCP associated with EGC. Conversely, multivariate analysis identified lesion morphology and endoscopic features as significant risk factors. Survival analysis demonstrated no statistically significant difference in recurrence between GCP with and without EGC (P = 0.72). CONCLUSION: The findings suggested that endoscopic resection might serve as an effective and minimally invasive treatment for GCP with or without EGC.

A metagenomic catalog of the early-life human gut virome.

Early-life human gut microbiome is a pivotal driver of gut homeostasis and infant health. However, the viral component (known as "virome") remains mostly unexplored. Here, we establish the Early-Life Gut Virome (ELGV), a catalog of 160,478 non-redundant DNA and RNA viral sequences from 8130 gut virus-like particles (VLPs) enriched or bulk metagenomes in the first three years of life. By clustering, 82,141 viral species are identified, 68.3% of which are absent in existing databases built mainly from adults, and 64 and 8 viral species based on VLPs-enriched and bulk metagenomes, respectively, exhibit potentials as biomarkers to distinguish infants from adults. With the largest longitudinal population of infants profiled by either VLPs-enriched or bulk metagenomic sequencing, we track the inherent instability and temporal development of the early-life human gut virome, and identify differential viruses associated with multiple clinical factors. The mother-infant shared virome and interactions between gut virome and bacteriome early in life are further expanded. Together, the ELGV catalog provides the most comprehensive and complete metagenomic blueprint of the early-life human gut virome, facilitating the discovery of pediatric disease-virome associations in future.

Diagnostic and therapeutic potentials of methyltransferase-like 3 in liver diseases.

Methyltransferase-like 3 (METTL3), a component of the RNA N6-methyladenosine (m6A) modification with a specific catalytic capacity, controls gene expression by actively regulating RNA splicing, nuclear export, stability, and translation, determines the fate of RNAs and assists in regulating biological processes. Studies conducted in recent decades have demonstrated the pivotal regulatory role of METTL3 in liver disorders, including hepatic lipid metabolism disorders, liver fibrosis, nonalcoholic steatohepatitis, and liver cancer. Although METTL3's roles in these diseases have been extensively investigated, the regulatory network of METTL3 and its potential applications remain unexplored. In this review, we provide a comprehensive overview of the roles and mechanisms of METTL3 implicated in these diseases, establish a regulatory network of METTL3, evaluate the potential for targeting METTL3 for diagnosis and treatment, and discuss avenues for future development and research. We found relatively upregulated expressions of METTL3 in these liver diseases, demonstrating its potential as a diagnostic biomarker and therapeutic target.