Cytochrome P450 Mining for Bufadienolide Diversification.

Bufadienolides are a class of steroids with a distinctive α-pyrone ring at C17, mostly produced by toads and consisting of over 100 orthologues. They exhibit potent cardiotonic and antitumor activities and are active ingredients of the traditional Chinese medicine Chansu and Cinobufacini. Direct extraction from toads is costly, and chemical synthesis is difficult, limiting the accessibility of active bufadienolides with diverse modifications and trace content. In this work, based on the transcriptome and genome analyses, using a yeast-based screening platform, we obtained eight cytochrome P450 (CYP) enzymes from toads, which catalyze the hydroxylation of bufalin and resibufogenin at different sites. Moreover, a reported fungal CYP enzyme Sth10 was found functioning in the modification of bufalin and resibufogenin at multiple sites. A total of 15 bufadienolides were produced and structurally identified, of which six were first discovered. All of the compounds were effective in inhibiting the proliferation of tumor cells, especially 19-hydroxy-bufalin (2) and 1ß-hydroxy-bufalin (3), which were generated from bufalin hydroxylation catalyzed by CYP46A35. The catalytic efficiency of CYP46A35 was improved about six times and its substrate diversity was expanded to progesterone and testosterone, the common precursors for steroid drugs, achieving their efficient and site-specific hydroxylation. These findings elucidate the key modification process in the synthesis of bufadienolides by toads and provide an effective way for the synthesis of unavailable bufadienolides with site-specific modification and active potentials.

A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D.

Modulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here, we discover an aldo-keto reductase termed AKRtyl and present its three-level regulatory mechanism. Specifically, by combining steady-state and transient kinetics, X-ray crystallography and molecular dynamics simulation, we demonstrate that AKRtyl exhibits a positive synergy mediated by an unusual Monod-Wyman-Changeux (MWC) paradigm of allosteric regulation at low concentrations of the cofactor NADPH, but an inhibitory effect at high concentrations is observed. While the substrate tylosin binds at a remote allosteric site with positive cooperativity. We further reveal that these regulatory mechanisms are conserved in AKR12D subfamily, and that substrate cooperativity is common in AKRs across three kingdoms of life. This work provides an intriguing example for understanding complex allosteric regulatory networks.

Identification of an efficient phenanthrene-degrading Pseudarthrobacter sp. L1SW and characterization of its metabolites and catabolic pathway.

Phenanthrene, a typical chemical of polycyclic aromatic hydrocarbons (PAHs) pollutants, severely threatens health of wild life and human being. Microbial degradation is effective and environment-friendly for PAH removal, while the phenanthrene-degrading mechanism in Gram-positive bacteria is unclear. In this work, one Gram-positive strain of plant growth-promoting rhizobacteria (PGPR), Pseudarthrobacter sp. L1SW, was isolated and identified with high phenanthrene-degrading efficiency and great stress tolerance. It degraded 96.3% of 500 mg/L phenanthrene in 72 h and kept stable degradation performance with heavy metals (65 mg/L of Zn2+, 5.56 mg/L of Ni2+, and 5.20 mg/L of Cr3+) and surfactant (10 CMC of Tween 80). Strain L1SW degraded phenanthrene mainly through phthalic acid pathway, generating intermediate metabolites including cis-3,4-dihydrophenanthrene-3,4-diol, 1-hydroxy-2-naphthoic acid, and phthalic acid. A novel metabolite (m/z 419.0939) was successfully separated and identified as an end-product of phenanthrene, suggesting a unique metabolic pathway. With the whole genome sequence alignment and comparative genomic analysis, 19 putative genes associated with phenanthrene metabolism in strain L1SW were identified to be distributed in three gene clusters and induced by phenanthrene and its metabolites. These findings advance the phenanthrene-degrading study in Gram-positive bacteria and promote the practical use of PGPR strains in the bioremediation of PAH-contaminated environments.

O-methyltransferase-like enzyme catalyzed diazo installation in polyketide biosynthesis.

Diazo compounds are rare natural products possessing various biological activities. Kinamycin and lomaiviticin, two diazo natural products featured by the diazobenzofluorene core, exhibit exceptional potency as chemotherapeutic agents. Despite the extensive studies on their biosynthetic gene clusters and the assembly of their polyketide scaffolds, the formation of the characteristic diazo group remains elusive. L-Glutamylhydrazine was recently shown to be the hydrazine donor in kinamycin biosynthesis, however, the mechanism for the installation of the hydrazine group onto the kinamycin scaffold is still unclear. Here we describe an O-methyltransferase-like protein, AlpH, which is responsible for the hydrazine incorporation in kinamycin biosynthesis. AlpH catalyses a unique SAM-independent coupling of L-glutamylhydrazine and polyketide intermediate via a rare Mannich reaction in polyketide biosynthesis. Our discovery expands the catalytic diversity of O-methyltransferase-like enzymes and lays a strong foundation for the discovery and development of novel diazo natural products through genome mining and synthetic biology.

Polycyclic aromatic hydrocarbons exposure and plasma lncRNA signature: A profile and functional analysis.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants that pose detrimental effects on human health, and the exploration of the associations of PAHs exposure with long non-coding RNA (lncRNA) may provide novel clues to the underlying mechanisms. In the present study, we detected 10 urinary PAHs metabolites by GC-MS and plasma lncRNAs levels by Human LncRNA Array v4 among 230 participants from two panels (160 in the Shiyan panel and 70 in the Wuhan-Zhuhai panel). We applied linear regression models to assess the associations between PAHs metabolites and lncRNAs separately in each panel and combined the results using fixed-effect meta-analysis. To explore the potential origin of PAHs-related lncRNAs in plasma, we estimated their tissue-specificity and associations between lncRNAs levels in plasma and leukocytes. Leukocytes mRNA sequencing data and RNA binding proteins were utilized to explore implicated pathways of identified lncRNAs. We found that urinary 1-hydroxyphenanthrene (1-OH-Phe) was inversely associated with 8 lncRNAs and positively associated with 1 lncRNA, as well as 9-hydroxyphenanthrene (9-OH-Phe) was inversely associated with 11 lncRNAs (FDR < 0.1). Tissue specificity analysis using Genome Tissue Expression database suggested that several identified lncRNAs might specifically express in organs targeted by PAHs exposure (lung, liver, heart, kidney, and brain). Besides, plasma levels of 1-OH-Phe related ENSG00000260616 and 9-OH-Phe related STARD4-AS1 were inversely associated with their intra-leukocytes levels (P value < 0.05). Notably, STARD4-AS1 was positively associated with the expression levels of its neighboring protein-coding gene (CAMK4 and STARD4) in leukocytes and were involved in pathways related to cellular response to DNA damage, which we further confirmed using DNA damage biomarker, 8-hydroxydeoxyguanosine. Functional analysis also revealed vital pathways related to cytokine-mediated signaling and glucose homeostasis. Our findings provided novel insights into plausible biological mechanisms underlying the adverse effects of PAHs exposure.

C-N bond formation by a polyketide synthase.

Assembly-line polyketide synthases (PKSs) are molecular factories that produce diverse metabolites with wide-ranging biological activities. PKSs usually work by constructing and modifying the polyketide backbone successively. Here, we present the cryo-EM structure of CalA3, a chain release PKS module without an ACP domain, and its structures with amidation or hydrolysis products. The domain organization reveals a unique "∞"-shaped dimeric architecture with five connected domains. The catalytic region tightly contacts the structural region, resulting in two stabilized chambers with nearly perfect symmetry while the N-terminal docking domain is flexible. The structures of the ketosynthase (KS) domain illustrate how the conserved key residues that canonically catalyze C-C bond formation can be tweaked to mediate C-N bond formation, revealing the engineering adaptability of assembly-line polyketide synthases for the production of novel pharmaceutical agents.

The natural pyrazolotriazine pseudoiodinine from Pseudomonas mosselii 923 inhibits plant bacterial and fungal pathogens.

Natural products largely produced by Pseudomonads-like soil-dwelling microorganisms are a consistent source of antimicrobial metabolites and pesticides. Herein we report the isolation of Pseudomonas mosselii strain 923 from rice rhizosphere soils of paddy fields, which specifically inhibit the growth of plant bacterial pathogens Xanthomonas species and the fungal pathogen Magnaporthe oryzae. The antimicrobial compound is purified and identified as pseudoiodinine using high-resolution mass spectra, nuclear magnetic resonance and single-crystal X-ray diffraction. Genome-wide random mutagenesis, transcriptome analysis and biochemical assays define the pseudoiodinine biosynthetic cluster as psdABCDEFG. Pseudoiodinine biosynthesis is proposed to initiate from guanosine triphosphate and 1,6-didesmethyltoxoflavin is a biosynthetic intermediate. Transposon mutagenesis indicate that GacA is the global regulator. Furthermore, two noncoding small RNAs, rsmY and rsmZ, positively regulate pseudoiodinine transcription, and the carbon storage regulators CsrA2 and CsrA3, which negatively regulate the expression of psdA. A 22.4-fold increase in pseudoiodinine production is achieved by optimizing the media used for fermentation, overexpressing the biosynthetic operon, and removing the CsrA binding sites. Both of the strain 923 and purified pseudoiodinine in planta inhibit the pathogens without affecting the rice host, suggesting that pseudoiodinine can be used to control plant diseases.

Tabletop 360-Degree Three-Dimensional Light-Field Display Based on Viewpoint-Fitting Encoding Algorithm for Reducing Facet Braiding.

Since the effect of the facet braiding phenomenon, the display quality of reconstructed image degrades with increasing depth of field in tabletop three-dimensional light-field display. Here, to analysis the facet braiding, the imaging process of the tabletop 360-degree three-dimensional light-field display based on conical lens array is mathematically modeled. A viewpoint-fitting encoding algorithm is proposed to reduce the effect of the facet-braiding phenomenon and improve the range of depth of field, which is optimized to form the best synthetic encoded image by fitting the reconstructed image seen by the simulated human eye to the parallax image captured at the corresponding location. The effectiveness of the proposed optimization algorithm is verified by simulation analysis and optical experiments, respectively. In the experiment, the clear depth of field range of the display system is increased from 13 cm to 15 cm, and the visualization effect of the reconstructed three-dimensional image is enhanced.

Analysis of six cancer patients with persistent left superior vena cava identified during central venous access device placement via an intracavitary electrocardiogram.

Persistent left superior vena cava (PLSVC) is a rare congenital anomaly. PLSVC can be associated with clinically significant atrial septal defect (ASD) or ventricular septal defect (VSD). It is usually asymptomatic and accidentally detected during invasive procedures or imaging examinations. However, whether central venous access device (CVAD) can be placed and used in patients with PLSVC is controversial. A total of six patients were diagnosed with PLSVC and confirmed by chest CT among 3391 cancer patients who underwent CVAD placement via intracavitary electrocardiogram (IC-EKG) at the Venous Access Center (VAC) from May 2019 to December 2020. The CVADs (peripherally inserted central catheter in four patients and Ports in two patients) of these six patients were left in PLSVC. We analyzed changes in the P-wave in the IC-EKG during CVAD placement and the characteristics of the body surface electrocardiogram in these patients and discussed the catheter tip position in PLSVC. All six patients showed negative P-waves in lead II via IC-EKG from the beginning of catheterization: four patients showed negative P-waves and two showed biphasic P-waves in the body surface electrocardiogram (lead III) before catheterization. CVAD function was normal and no obvious complications were observed during the treatment of these patients. The total retention time of CVADs was 1537 days. For patients with a negative P-wave in lead II via IC-EKG during catheterization, especially in those with a negative or biphasic P-wave in lead III of the body surface electrocardiogram, PLSVC should be considered. CVAD insertion in patients with type I PLSVC is safe under certain conditions, with the proper tip position in the middle to lower part of PLSVC.

An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. S42.

Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. S42. The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. The new dimeric indole alkaloid via N-N linkage exhibits moderate antimicrobial activity.

Flavoprotein StnP2 Catalyzes the ß-Carboline Formation during the Streptonigrin Biosynthesis.

ß-Carboline (ßC) alkaloids constitute a large family of indole alkaloids that exhibit diverse pharmacological properties, such as antitumor, antiviral, antiparasitic, and antimicrobial activities. Here, we report that a flavoprotein StnP2 catalyzes the dehydrogenation at C1-N2 of a tetrahydro-ß-carboline (THßC) generating a 3,4-dihydro-ß-carboline (DHßC), and the DHßC subsequently undergoes a spontaneous dehydrogenation to ßC formation involved in the biosynthesis of the antitumor agent streptonigrin. Biochemical characterization showed that StnP2 catalyzed the highly regio- and stereo-selective dehydrogenation, and StnP2 exhibits promiscuity toward different THßCs. This study provides an alternative kind of enzyme catalyzing the biosynthesis of ßC alkaloids and enhances the importance of flavoproteins.

Circulating metals, leukocyte microRNAs and microRNA networks: A profiling and functional analysis in Chinese adults.

BACKGROUND: Metals in the human body represent both environmental exposure and nutritional status. Little is known about the miRNA signature in relation to circulating metals in humans. OBJECTIVES: To characterize metal-associated miRNAs in leukocytes, individually and collectively as networks. METHODS: In a panel of 160 Chinese adults, we measured 23 metals/metalloids in plasma, and sequenced miRNAs and mRNAs in leukocytes. We used linear regression to model the associations between ln-transformed metal concentrations and normalized miRNA levels adjusting for potential confounders. We inferred the enriched leukocyte subtypes for the identified miRNAs using an association approach. We utilized mRNA sequencing data to explore miRNA functions. We also constructed modules to identify metal-associated miRNA networks. RESULTS: We identified 55 metal-associated miRNAs at false discovery rate-adjusted P < 0.05. In particular, we found that lead, nickel, and vanadium were positively associated with potentially lymphocyte-enriched miR-142-3p, miR-150-3p, miR-28-5p, miR-361-3p, and miR-769-5p, and were inversely associated with potentially granulocyte-enriched let-7a/c/d-5p and miR-1294. Interestingly, the five lymphocyte-enriched miRNAs inhibited, whereas miR-1294 activated, ROS and DNA repair pathways. We further confirmed the findings using oxidative damage biomarkers. Next, we clustered co-expressed miRNAs into modules, and identified four miRNA modules that were associated with different metals. The identified modules represented miRNAs enriched in different leukocyte subtypes, and were involved in biological processes including hematopoiesis and immune response, mitochondrial functions, and response to the stimulus. CONCLUSIONS: At commonly exposed low levels, circulating metals were associated with distinct miRNA signatures in leukocytes. The identified miRNAs, individually or as regulatory networks, may provide a mechanistic link between metal exposure and pathophysiological changes in the immune system.

Investigation on Temperature Behavior for a GaAs E-pHEMT MMIC LNA.

In order to investigate the temperature behavior for monolithic microwave integrated circuits (MMICs) under alpine conditions, the performance parameters of a 0.4-3.8 GHz gallium arsenide (GaAs) enhancement pseudomorphic high-electron-mobility transistor (E-pHEMT) low-noise amplifier (LNA) are tested at different temperatures. The typical temperatures of -39.2 °C, -32.9 °C, -25.3 °C, -11.3 °C, -4.9 °C, 0 °C and 23 °C are chosen as the alpine condition. The major performance indexes including the direct current (DC) characteristics, S-parameters, stability, radio frequency (RF) output characteristics, output third-order intersection point (OIP3) and noise figure (NF), which were inspected and analyzed in detail. The results show that the DC characteristics, small-signal gain (S21), RF output characteristics and NF all deteriorate with the rising temperature due to the decrease in two-dimensional electron gas mobility (µ). Contrary to this trend, the special design makes stability and OIP3 increase. For further application of this MMIC LNA under alpine conditions, several measures can be utilized to remedy performance degradation. This paper can provide some significant engineering value for the reliable design of MMICs.

Spray-Coating Thick Films of All-Inorganic Halide Perovskites for Filterless Narrowband Photodetectors.

A significant challenge facing perovskite narrowband photodetectors is making high-quality and thick enough films. Here, we report a facile one-step spray-coating approach to deposit cesium lead halide perovskite thick films for filterless narrowband photodetectors, which exhibited a specific detectivity of 2.43 × 1010 Jones at 655 nm with an fwhm of 25 nm. We demonstrated that both substrate temperature and deposition time during the spray-coating process are key factors that govern the thickness and morphology of perovskite films. The photodetection behavior was dependent on the film thickness, and the narrowband photoresponse was recorded at a 3.9 µm thickness. We discovered that the internal electric field also plays a critical role in determining the narrowband photoresponse behavior. A distinct photoresponse behavior was observed when respectively applying a reverse bias and a forward bias, which is ascribed to the trade-off between the charge-trapping effect and charge extraction under the internal built-in electric field in different biased conditions. Through changing the halogen composition of perovskites from CsPbCl2Br to CsPbI2Br, the peak position of the narrowband spectral photoresponse was observed to shift from 460 to 660 nm. This study not only offers a controllable spray-coating approach to develop thick perovskite films but also provides an important guidance for the rational design of filterless narrowband photodetectors for practical applications in industrial control, visual imaging, and biological sensing.

A novel streptonigrin type alkaloid from the Streptomyces flocculus CGMCC 4.1223 mutant ΔstnA/Q2.

Streptonigrin (STN) is a highly functionalized aminoquinone alkaloid with broad and potent antitumor activities. Previously, the biosynthetic gene cluster of STN was identified in Streptomyces flocculus CGMCC 4.1223, revealing an α/ß-hydrolase (StnA) and a methyltransferase (StnQ2). In this work, a double mutant ΔstnA/Q2 was constructed by genetic manipulation and produced a novel derivative of STN, named as streptonigramide. Structure of streptonigramide was established by spectroscopic analyses. Its biosynthetic pathway has been proposed as well.

Ultrafast Single-Crystal-to-Single-Crystal Transformation from Metal-Organic Framework to 2D Hydroxide.

Single-crystal-to-single-crystal (SCSC) transformations have received considerable interest in crystal engineering, owing to providing a key platform for creating new materials. However, because of the limited tolerance of chemical bonds against the lattice strains, it is challenging to maintain the crystallinity when the structure changes dramatically. Here, a peculiar SCSC transformation from organic crystals to inorganic crystals, simultaneously achieving a drastic change in structure, connectivity, and dimension, is reported. As a demonstration, after reacting with liquid gallium, zeolitic imidazolate framework-8 (ZIF-8) can easily transform to 2D hydroxide single crystals. Interestingly, long-range ordered metallic atoms of hydroxide inherited from the ordered atomic arrangement of ZIF-8, but the connectivity is distinct. With good universality and extensibility, this transformation vastly expands the research scope of the SCSC transformations and provides a novel pathway for the synthesis of crystalline materials.

A comparative study on the tip position of peripherally inserted central catheter inserted at two forward P-wave amplitudes by intracavitary electrocardiogram in cancer patients.

BACKGROUND: This study aimed to compare the tip location of peripherally inserted central catheter (PICC) under two forward P-wave amplitudes (P-wave amplitude is the autonomous peak or P-wave amplitude is 50-80% of the QRS main wave) by intracavitary electrocardiogram (IC-EKG) to determine the PICC tip in optimal location thus avoiding catheter-related complications. METHODS: The data of 300 cancer patients with PICC insertion were collected retrospectively. For the observation group, the position of the catheter tip was left at the level when P wave amplitude was its autonomous peak (168 patients catheterized in 2018). While for the control group, the catheter tip was left at the level when the P wave amplitude was 50-80% of the QRS main wave (132 patients catheterized in 2017). Both groups of patients underwent the chest X-ray examination (CXR) after catheterization. The total compliance rate [PICC tip was located in the lower third of the Superior Vena Cava (SVC) and the Cavo-Atrial Junction (CAJ)], the optimal position compliance rate (PICC tip was located in the CAJ), and the incidence of the catheter tip malposition were compared between the two groups. The complications after catheterization including arrhythmia after catheterization within 24 hours, catheter-related thrombosis, catheter dysfunction, and catheter infection within 90 days were also compared. RESULTS: There was no difference in the total compliance rate of PICC tip position and the incidence of the catheter malposition in the two groups (P>0.05). But the optimal position compliance rate of the observation group was higher than that of the control group (P<0.05). There was no difference in the incidence of arrhythmia after catheterization within 24 hours of the two groups (P>0.05). The incidence of catheter-related thrombosis, catheter dysfunction, and catheter infection within 90 days in the observation group was lower than those in the control group (P<0.05). CONCLUSIONS: The PICC tip position at the autonomous peak of the P wave is significantly better than that at the P wave amplitude being 50-80% of the QRS main wave under the IC-EKG guidance for PICC insertion.

In Situ Investigation of the Motion Behavior of Graphene on Liquid Copper.

The in situ investigation of the dynamic growth process and novel assembly phenomena of graphene on liquid copper (Cu) is of great significance to deeply understand the special behavior of graphene and self-assembly mechanism. Here, the direct observation of the graphene growth and motion behavior on liquid Cu via in situ imaging is reported. Evidence of graphene movement on liquid Cu is offered and it is demonstrated that the translation and rotation behaviors of graphene are affected by the surface condition of liquid Cu. The self-assembly process of graphene array is also revealed by capturing the dynamic changes of graphene in real-time. Further analysis highlights the importance of surface energy of liquid Cu and the interaction between graphene building blocks during the self-assembling process. The growth parameters are also investigated to flexibly control the assembly configuration of graphene arrays. This work provides an insight into the mechanism of graphene motion and assembly behavior that can be used to guide the controllable manipulation of 2D materials and on-demand fabrication assembly structures with desired properties.

Association between ABO blood group and venous thrombosis related to the peripherally inserted central catheters in cancer patients.

OBJECTIVE: To evaluate the potential relation between the ABO blood group and the risk of venous thrombosis in cancer patients with peripherally inserted central catheters (PICCs). METHODS: The patients who underwent PICC catheterization in Beijing Cancer Hospital from January 2018 to October 2019 were retrospectively analyzed. The general information, disease diagnosis, catheterization situation, and complications were recorded for each patient. Further, the blood group status was identified using the hospital information systems. Logistic and Cox proportional hazard regression analyses were performed to identify the risk factors for symptomatic PICC-related thrombosis. RESULTS: Among the 2315 patients, 131 had symptomatic thrombosis after PICC catheterization. The incidence of symptomatic thrombosis was lower in patients with blood type O when compared with that in patients with blood types other than O. The history of venous thrombosis, tumor category, arm circumference, and insertion attempts are risk factors associated with the PICC-related venous thromboembolism (VTE). After multivariable adjustment, insertion attempts and the non-O blood type were observed to remain associated with thrombosis. CONCLUSION: The risk of PICC-related thrombosis in patients with non-O blood type is significantly higher than that in patients with blood type O.

The Influence of Venous Characteristics on Peripherally Inserted Central Catheter-Related Symptomatic Venous Thrombosis in Cancer Patients.

BACKGROUND: With increasing use, peripherally inserted central catheters (PICCs) are associated with the risk of venous thrombosis. Few studies have focused on the relationships between venous thrombosis and venous characteristics. This study aimed to identify effects of venous characteristics on symptomatic PICC-related venous thrombosis in cancer patients and explore the relationship between venous characteristics and blood flow velocity. METHODS: The data of patients who underwent placement of PICC were retrospectively studied between January 2015 and September 2017. Symptomatic PICC-related venous thrombosis was confirmed by ultrasound. Univariable, multivariable logistic regression analyses were performed to identify the risk factors associated with PICC-related venous thrombosis. In October 2017, 169 patients with PICCs were enrolled prospectively, and the relationships between blood flow velocity and venous characteristics were recorded and analyzed. RESULTS: A total of 2933 cancer patients were enrolled in this study; of these patients, 68 experienced symptomatic venous thrombosis. In the bivariate analysis, body mass index (BMI), history of venous thrombosis, triglycerides, tumor category, vessel diameter, vessel depth and arm circumference were associated with thrombosis. The multivariable analyses showed that arm circumference, vascular diameter, triglyceride level and tumor category were independent risk factors for thrombosis. Blood flow velocity was positively correlated with vessel depth and arm circumference but not with vessel diameter. CONCLUSION: Different venous characteristics can lead to different blood flow rates, which can affect the incidence of thrombosis. A vein depth of greater than 1.07cm or less than 0.57cm was associated with a higher incidence of PICC-related venous thrombosis, and the greater the arm circumference and vessel diameter, the greater the risk of venous thrombosis.