Regulation of intracellular process by two-component systems: Exploring the mechanism of plasmid-mediated conjugative transfer.

Plasmid-mediated conjugative transfer facilitates the dissemination of antibiotic resistance, yet the comprehensive regulatory mechanisms governing this process remain elusive. Herein, we established pure bacteria and activated sludge conjugation system to investigate the regulatory mechanisms of conjugative transfer, leveraging metformin as an exogenous agent. Transcriptomic analysis unveiled that substantial upregulation of genes associated with the two-component system (e.g., AcrB/AcrA, EnvZ/Omp, and CpxA/CpxR) upon exposure to metformin. Furthermore, downstream regulators of the two-component system, including reactive oxygen species (ROS), cytoplasmic membrane permeability, and adenosine triphosphate (ATP) production, were enhanced by 1.7, 1.4 and 1.1 times, respectively, compared to the control group under 0.1 mg/L metformin exposure. Moreover, flow sorting and high-throughput sequencing revealed increased microbial community diversity among transconjugants in activated sludge systems. Notably, the antibacterial potential of human pathogenic bacteria (e.g., Bacteroides, Escherichia-Shigella, and Lactobacillus) was augmented, posing a potential threat to human health. Our findings shed light on the spread of antibiotic resistance bacteria and assess the ecological risks associated with plasmid-mediated conjugative transfer in wastewater treatment systems.

Ultrasound manifestations of primary intestinal non-Hodgkin lymphoma with liver metastasis in a child.

Non-Hodgkin lymphoma (NHL) is a highly aggressive malignant tumor arising in lymph nodes or extra-nodal lymphoid tissues, with an incidence of 8.3 per million. It accounts for approximately 7% of childhood and adolescent malignancies, second only to leukemia and brain tumors. Despite the gastrointestinal tract being the most common extra-nodal site involved by lymphoma, primary intestinal lymphoma (PIL) is rare and typically affects middle-aged men without specific clinical symptoms. Here, we present the case of a 2-year-old child indicative of PIL with the informed consent of the parents.

Trend of Mortality Due to Congenital Anomalies in Children Younger Than 5 Years in Eastern China, 2012-2021: Surveillance Data Analysis.

BACKGROUND: As one of the leading causes of child mortality, deaths due to congenital anomalies (CAs) have been a prominent obstacle to meet Sustainable Development Goal 3.2. OBJECTIVE: We conducted this study to understand the death burden and trend of under-5 CA mortality (CAMR) in Zhejiang, one of the provinces with the best medical services and public health foundations in Eastern China. METHODS: We used data retrieved from the under-5 mortality surveillance system in Zhejiang from 2012 to 2021. CAMR by sex, residence, and age group for each year was calculated and standardized according to 2020 National Population Census sex- and residence-specific live birth data in China. Poisson regression models were used to estimate the annual average change rate (AACR) of CAMR and to obtain the rate ratio between subgroups after adjusting for sex, residence, and age group when appropriate. RESULTS: From 2012 to 2021, a total of 1753 children died from CAs, and the standardized CAMR declined from 121.2 to 62.6 per 100,000 live births with an AACR of -9% (95% CI -10.7% to -7.2%; P<.001). The declining trend was also observed in female and male children, urban and rural children, and neonates and older infants, and the AACRs were -9.7%, -8.5%, -8.5%, -9.2%, -12%, and -6.3%, respectively (all P<.001). However, no significant reduction was observed in children aged 1-4 years (P=.22). Generally, the CAMR rate ratios for male versus female children, rural versus urban children, older infants versus neonates, and older children versus neonates were 1.18 (95% CI 1.08-1.30; P<.001), 1.20 (95% CI 1.08-1.32; P=.001), 0.66 (95% CI 0.59-0.73; P<.001), and 0.20 (95% CI 0.17-0.24; P<.001), respectively. Among all broad CA groups, circulatory system malformations, mainly deaths caused by congenital heart diseases, accounted for 49.4% (866/1753) of deaths and ranked first across all years, although it declined yearly with an AACR of -9.8% (P<.001). Deaths due to chromosomal abnormalities tended to grow in recent years, although the AACR was not significant (P=.90). CONCLUSIONS: CAMR reduced annually, with cardiovascular malformations ranking first across all years in Zhejiang, China. Future research and practices should focus more on the prevention, early detection, long-term management of CAs and comprehensive support for families with children with CAs to improve their survival chances.

Specific-CT brain template construction and retrospective dosimetric comparison study in brain for nasopharyngeal carcinoma patients treated with IMRT or VMAT.

The current Radiotherapy (RT) technology still inevitably irradiated normal brain tissue, causing implicit radiation-induced injury. This study investigates the precise localization and the corresponding radiation dosage of brain regions susceptible to damage in nasopharyngeal carcinoma (NPC) patients following RT. Utilizing the Advanced Normalization Tools (ANTs) package, a computed tomography (CT) brain template was created in the standard Montreal Neurological Institute (MNI) space, based on 803 Chinese NPC patients (T0~T4) who underwent RT. With this template, all patients' CT and RTdose data were registered to the MNI space, and the RTdose distribution characteristics in normal brain tissues were compared for NPC patients treated with Intensity-modulated radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), with patients' age and gender as covariates. Analysis of the average dosages indicated that certain areas within the Limbic, Temporal, and Posterior Lobes, the Brainstem, and the Cerebellum Posterior Lobe were exposed to doses exceeding 50 Gy. Inter-group analysis revealed that IMRT delivered higher doses than VMAT to brain regions anterior to the nasopharyngeal tumor, whereas VMAT affected the posterior regions more. Interestingly, VMAT showed a drawback in preserving the normal brain tissues for T4-stage patients. This revealed that the two treatment modalities have unique characteristics in preserving normal brain tissue, each with advantages. With better localization precision, the created CT brain template in MNI space may be beneficial for NPC patients' toxicity and dosimetric analyses.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

High expression of SRSF1 facilitates osteosarcoma progression and unveils its potential mechanisms.

BACKGROUND: SRSF1, a member of Serine/Arginine-Rich Splicing Factors (SRSFs), has been observed to significantly influence cancer progression. However, the precise role of SRSF1 in osteosarcoma (OS) remains unclear. This study aims to investigate the functions of SRSF1 and its underlying mechanism in OS. METHODS: SRSF1 expression level in OS was evaluated on the TCGA dataset, TAGET-OS database. qRT-PCR and Western blotting were employed to assess SRSF1 expression in human OS cell lines as well as the interfered ectopic expression states. The effect of SRSF1 on cell migration, invasion, proliferation, and apoptosis of OS cells were measured by transwell assay and flow cytometry. RNA sequence and bioinformatic analyses were conducted to elucidate the targeted genes, relevant biological pathways, and alternative splicing (AS) events regulated by SRSF1. RESULTS: SRSF1 expression was consistently upregulated in both OS samples and OS cell lines. Diminishing SRSF1 resulted in reduced proliferation, migration, and invasion and increased apoptosis in OS cells while overexpressing SRSF1 led to enhanced growth, migration, invasion, and decreased apoptosis. Mechanistically, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) revealed that the biological functions of SRSF1 were closely associated with the dysregulation of the protein targeting processes, location of the cytosolic ribosome, extracellular matrix (ECM), and proteinaceous extracellular matrix, along with the PI3K-AKT pathway, Wnt pathway, and HIPPO pathway. Transcriptome analysis identified AS events modulated by SRSF1, especially (Skipped Exon) SE events and (Mutually exclusive Exons) MXE events, revealing potential roles of targeted molecules in mRNA surveillance, RNA degradation, and RNA transport during OS development. qRT-PCR confirmed that SRSF1 knockdown resulted in the occurrence of alternative splicing of SRRM2, DMKN, and SCAT1 in OS. CONCLUSIONS: Our results highlight the oncogenic role of high SRSF1 expression in promoting OS progression, and further explore the potential mechanisms of action. The significant involvement of SRSF1 in OS development suggests its potential utility as a therapeutic target in OS.

Overlooked in-situ sulfur disproportionation fuels dissimilatory nitrate reduction to ammonium in sulfur-based system: Novel insight of nitrogen recovery.

Sulfur-based denitrification is a promising technology in treatments of nitrate-contaminated wastewaters. However, due to weak bioavailability and electron-donating capability of elemental sulfur, its sulfur-to-nitrate ratio has long been low, limiting the support for dissimilatory nitrate reduction to ammonium (DNRA) process. Using a long-term sulfur-packed reactor, we demonstrate here for the first time that DNRA in sulfur-based system is not negligible, but rather contributes a remarkable 40.5 %-61.1 % of the total nitrate biotransformation for ammonium production. Through combination of kinetic experiments, electron flow analysis, 16S rRNA amplicon, and microbial network succession, we unveil a cryptic in-situ sulfur disproportionation (SDP) process which significantly facilitates DNRA via enhancing mass transfer and multiplying 86.7-210.9 % of bioavailable electrons. Metagenome assembly and single-copy gene phylogenetic analysis elucidate the abundant genomes, including uc_VadinHA17, PHOS-HE36, JALNZU01, Thiobacillus, and Rubrivivax, harboring complete genes for ammonification. Notably, a unique group of self-SDP-coupled DNRA microorganism was identified. This study unravels a previously concealed fate of DNRA, which highlights the tremendous potential for ammonium recovery and greenhouse gas mitigation. Discovery of a new coupling between nitrogen and sulfur cycles underscores great revision needs of sulfur-driven denitrification technology.

Asymmetric chitosan-derivative/carboxymethylcellulose layer-by-layer film combining antimicrobial and vascular regeneration for the repair of infected wounds.

Bacterially infected wounds are a serious threat to patients' lives and health, and multifunctional dressings with antimicrobial properties and healing promotion are urgently needed. Thus, we used the cationic and anionic properties of chitosan (CS)-nerol (N) derivative (CSN) and carboxymethylcellulose (CMC) to prepare asymmetric layer-by-layer self-assembled (LBL) composite films (CSN-CMC LBL films) with antibacterial and healing properties using a spin-coating method. SEM images showed that the CSN-CMC LBL films had completely different degrees of roughness at the bottom (hydrophilic layer) and at the top (hydrophobic layer), with the roughness at the top increasing as the number of layers increased. The CSN and CMC were used to prepare asymmetric LBL films via the electrostatic attraction of -COO- and NH3+. In addition, adhesion and water contact angle tests showed that the CSN-CMC LBL films had enhanced tissue adhesion and good hydrophobicity. These materials had excellent antimicrobial activity and good biocompatibility. Importantly, the animal infection model results showed that CSN-CMC-8 LBL films effectively eliminated the infection in vivo, inhibited inflammation, promoted vascular regeneration, accelerated the epithelialization process, and achieved high quality healing. Overall, the CSN-CMC LBL films in this study showed considerable potential for application in infected wound healing.

Luminescence properties and energy transfer of broadband NIR phosphor Li2MgZrO4: 1.0%Cr3+, y%Yb3.

The discovery of high thermal stability, broad-band near-infrared (NIR) fluorescent phosphors holds significant potential in applications such as non-destructive testing, promoting plant growth, and night vision devices. In this study, a novel broad-band NIR phosphors Li2MgZrO4 (LMZ): 1.0 %Cr3+, y%Yb3+ were synthesized via a high-temperature solid-state reaction method, with the optimal doping concentration found to be y = 1.5. These phosphors exhibited broad NIR emission in the range of 700-1050 nm by effective energy transfer from Cr3+ to Yb3+. The maximum full width at half maximum (FWHM) of the Cr3+/Yb3+ co-doped LMZ phosphor is 270 nm. The thermal stability of the phosphors was improved with Yb3+ co-doping. Additionally, energy transfer from Cr3+ to Yb3+ was confirmed through luminescence spectra and lifetime analysis. Finally, NIR pc-LED devices composed of a 460 nm ultraviolet chip and LMZ: 1.0 %Cr3+, 1.5 %Yb3+ phosphors were fabricated, offering a highly promising source of invisible light. These results demonstrate the wide-ranging potential applications of this novel, high thermal stability, and ultra-broad NIR emitting fluorescent phosphor.

Cellulose Nanofibrils of High Immunoaffinity for Efficient Enrichment of Small Extracellular Vesicles.

Extracellular vesicles (EVs), crucial in facilitating the transport of diverse molecular cargoes for intercellular communication, have shown great potential in diagnostics, therapeutics, and drug delivery. The challenge of developing effective preparation methods for EVs is heightened by their intrinsic heterogeneity and complexity. Here, a novel strategy for high EV enrichment is developed by utilizing EV-affinitive-modified cellulose nanofibrils. Specifically, modified cellulose with rich carboxyl groups has outstanding dispersing properties, able to be dispersed into cellulose nanofibrils in solution. These cellulose nanofibrils are utilized as scaffolds for the immobilization of EV-affinitive antibody of CD63 by chemical conjugation. The CD63-modified nanofibrils demonstrate a superior EV capture efficiency of 86.4% compared with other reported methods. The high performance of this system is further validated by the efficient capture of EVs from biological blood plasma, allowing the detection of bioactive markers from EV-derived miRNAs and proteins. The authors envision that these modified cellulose nanofibrils of enhanced capability on EV enrichment will open new avenues in various biomedical applications.

Primary cardiac angiosarcoma: Imaging characterization.

This case report describes a 35-year-old female patient who presented with palpitations and shortness of breath. Imaging findings suggested a cardiac tumor, histopathology confirmed primary cardiac angiosarcoma. This tumor is highly aggressive, usually occurs in the right atrium, lacks specificity in clinical presentation, is prone to early metastasis, and has a poor prognosis. Echocardiography is the method of choice for early detection and is important in assessing tumor size, location, mode of attachment and whether cardiac function is impaired.

A Method of Reducing Salt Content in Fermented Soy Sauce Improves Its Flavor and Quality.

Most commercially available soy sauce is fermented by high-salt liquid-state (HS) fermentation, which has an excessive salt content and a long fermentation period. In this study, a new salt-reduced fermentation (SR) soy sauce technology involving multiple strains of bacteria was developed to reduce consumers' salt intake. The SR soy sauce was found to have an amino acid nitrogen content of 8.40 g/L and over 80 kinds of flavor substances, which were significantly higher than those of low-salt solid-state fermented soy sauce and approximately equal to HS soy sauce. Compared with HS soy sauce, the salt content of the SR soy sauce was reduced by 59.2%, achieving the salt reduction goal. The proportion of umami amino acids in SR soy sauce reached 32.0% of the total level, enhancing SR soy sauce's quality. Hence, the new fermentation process can decrease salt content and shorten fermentation time.

A case report of pediatric biliary botryoid rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children, and botryoid rhabdomyosarcoma (BRMS) represents a subtype of RMS. BRMS primarily occurs in infants, young children, and adolescent females, with a predilection for mucosa-lined hollow organs such as the bladder, vagina, bile duct, and so on. Its occurrence in the biliary tract is extremely rare. Due to the high malignancy and rapid metastasis of biliary botryoid rhabdomyosarcoma, early diagnosis and treatment are crucial for improving prognosis.

Pulmonary artery dissection secondary to ventricular septal defect and pulmonary valve stenosis.

The aortic short axis view demonstrated the widening of the pulmonary artery and the membrane-like echo in the pulmonary artery divided it into true lumen and false lumen. And the flow of the ruptured openings on the band-like echo was clearly revealed by Color Doppler.

Rhein potentiates doxorubicin in treating triple negative breast cancer by inhibiting cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs), one of the most abundant stromal cells in the tumor microenvironment, mediate desmoplastic responses. CAFs are major drivers for the failure of triple-negative breast cancer (TNBC) chemotherapy. It is well-documented that many traditional Chinese medicines (TCMs) exhibit potent anti-fibrotic effects based on their capacity to suppress the production of ECM proteins. Therefore, the combination of TCMs exhausting CAFs with chemotherapy is a potential regimen for treating TNBC. Here, TGF-ß was used to induce the transformation of NIH/3T3 cells into CAFs for screening TCMs to inhibit tumor fibrosis. After screening 11 candidate TCMs for inhibiting CAFs using the TMS method, rhein (Rhe) was found to strongly inhibit the proliferation of CAFs. Therefore, Rhe was chosen as a representative TCM to inhibit CAFs in TNBC. A 4T1Fluc/CAFs tumor sphere resembling the TME in vivo was constructed to explore the feasibility of inhibiting CAFs to sensitize DOX in treating TNBC. It was found that CAFs apparently hindered the penetration of DOX into 4T1Fluc/CAFs tumor spheres and decreased the the sensitivity of 4T1Fluc cells to DOX, while Rhe significantly restored the sensitivity of 4T1Fluc cells to DOX by inhibiting the proliferation of CAFs. Consistent with in vitro results, Rhe reversed the abnormal activation of CAFs and diminished the accumulation of collagen in 4T1Fluc mouse xenograft models. This removal of stromal barrier facilitated the antitumor efficacy of DOX. Altogether, this study demonstrated for the first time that Rhe could inhibit tumor tissue fibrosis and synergize DOX to treat TNBC.

3D Crown Ether Covalent Organic Framework as Interphase Layer toward High-Performance Lithium Metal Batteries.

The practical application of lithium (Li) metal batteries is inhibited by accumulative Li dendrites and continuous active Li consumption during cycling, which results in a low Coulombic efficiency and short lifetime. Constructing artificial solid-electrolyte interphase (SEI) layer in Li anode, such as 2D covalent organic frameworks (COFs), is an effective strategy to restrain the formation of Li dendrites and improve cycling performance. However, the exploration of 3D COFs as protecting layers is rarely reported, because of the preconception that the interconnect pores in 3D COFs eventually cause Li dendrites in disordered direction. 3D crown ether-based COF with ffc topology as interphase layer, in which the crown ether units are arranged in parallel and vertical orientation along the electrode, is demonstrated. The strong coupling effect between the crown ether and Li+ accelerates Li+ diffusion kinetics and enables homogeneous Li+ flux, resulting in a high Li+ transference number of 0.85 and smooth Li deposition in 3D direction. Li/COF-Cu cells display a lower Li-nucleation overpotential (17.4 mV) and high average Coulombic efficiency of ≈98.6% during 340 cycles with COF incorporation. This work gives a new insight into designing COFs for energy storage systems.

Solvent Effects on Metal-free Covalent Organic Frameworks in Oxygen Reduction Reaction.

Binding water molecules to polar sites in covalent organic frameworks (COFs) is inevitable, but the corresponding solvent effects in electrocatalytic process have been largely overlooked. Herein, we investigate the solvent effects on COFs for catalyzing the oxygen reduction reaction (ORR). Our designed COFs incorporated different kinds of nitrogen atoms (imine N, pyridine N, and phenazine N), enabling tunable interactions with water molecules. These interactions play a crucial role in modulating electronic states and altering the catalytic centers within the COFs. Among the synthesized COFs, the one with pyridine N atoms exhibits the highest activity, with characterized by a half-wave potential of 0.78 V and a mass activity of 0.32 A mg-1, which surpass those from other metal-free COFs. Theoretical calculations further reveal that the enhanced activity can be attributed to the stronger binding ability of *OOH intermediates to the carbon atoms adjacent to the pyridine N sites. This work sheds light on the significance of considering solvent effects on COFs in electrocatalytic systems, providing valuable insights into their design and optimization for improved performance.

Temperature, pH, and oxygen availability contributed to the functional differentiation of ancient Nitrososphaeria.

Ammonia-oxidizing Nitrososphaeria are among the most abundant archaea on Earth and have profound impacts on the biogeochemical cycles of carbon and nitrogen. In contrast to these well-studied ammonia-oxidizing archaea (AOA), deep-branching non-AOA within this class remain poorly characterized because of a low number of genome representatives. Here, we reconstructed 128 Nitrososphaeria metagenome-assembled genomes from acid mine drainage and hot spring sediment metagenomes. Comparative genomics revealed that extant non-AOA are functionally diverse, with capacity for carbon fixation, carbon monoxide oxidation, methanogenesis, and respiratory pathways including oxygen, nitrate, sulfur, or sulfate, as potential terminal electron acceptors. Despite their diverse anaerobic pathways, evolutionary history inference suggested that the common ancestor of Nitrososphaeria was likely an aerobic thermophile. We further surmise that the functional differentiation of Nitrososphaeria was primarily shaped by oxygen, pH, and temperature, with the acquisition of pathways for carbon, nitrogen, and sulfur metabolism. Our study provides a more holistic and less biased understanding of the diversity, ecology, and deep evolution of the globally abundant Nitrososphaeria.

Myxoma with rich blood supply in the left atrium.

Cardiac myxoma is the most common primary benign cardiac tumors, mostly found in the left atrium. It was previously reported that the main component of myxoma was myxoid stroma riched in acid-mucopolysaccharide, the blood vessels in which were sparsely distributed, being characterized as hypovascular tumor by contrast echocardiography (CE) and computed tomography angiography (CTA). There are few reports of myxoma with rich blood supply and we report one in the left atrium.

The effectiveness of interventions to reduce cancer-related stigma: An integrative review.

AIMS: The clinical significance of cancer-related stigma on patients' well-being has been widely established. Stigma can be perceived and internalised by cancer patients or implemented by the general population and healthcare workers. Various interventions have been carried out to reduce cancer-related stigma, but their effectiveness is not well-understood. This review aims to synthesise evidence on the effectiveness of interventions to reduce cancer-related stigma. DESIGN: An integrative review. METHODS: This integrative review combined both qualitative and quantitative studies and followed five steps to identify problems, search for the literature, appraise the literature quality, analyse data, and present data. Mixed Methods Appraisal Tool (version 2018) was applied to evaluate the quality of the included studies. DATA SOURCES: Databases included Web of Science, MEDLINE, SpringerLink, Wiley Online Journals, Cochrane Library, ScienceDirect, OVID, and China National Knowledge Infrastructure (from the inception of each database to 30 April 2021). RESULTS: Eighteen quantitative, six qualitative, and five mixed-methods studies were included in this review. Cultural factors should be considered when conducting interventions to reduce cancer-related stigma. For cancer patients, multi-component interventions have demonstrated a positive effect on their perceived stigma. For general population, interactive interventions show promise to reduce their implemented stigma towards cancer patients. For healthcare workers, there is a paucity of studies to reduce their implemented stigma. Existing studies reported inconclusive evidence, partially due to the lack of a robust study design with an adequate sample size. CONCLUSIONS: Multi-component and interactive interventions show promise to relieve cancer-related stigma. More methodologically robust studies should be conducted in different cultures to elucidate the most appropriate interventions for different populations to reduce cancer-related stigma. IMPLICATION FOR THE PROFESSION AND PATIENT CARE: These findings will facilitate healthcare workers to design and implement interventions to reduce cancer-related stigma, thus improving the quality of life for cancer patients. PATIENT AND PUBLIC CONTRIBUTION: No patient and public contribution.