Single-cell exome sequencing reveals polyclonal seeding and TRPS1 mutations in colon cancer metastasis.

Liver metastasis remains the primary cause of mortality in patients with colon cancer. Identifying specific driver gene mutations that contribute to metastasis may offer viable therapeutic targets. To explore clonal evolution and genetic heterogeneity within the metastasis, we conducted single-cell exome sequencing on 150 single cells isolated from the primary tumor, liver metastasis, and lymphatic metastasis from a stage IV colon cancer patient. The genetic landscape of the tumor samples revealed that both lymphatic and liver metastases originated from the same region of the primary tumor. Notably, the liver metastasis was derived directly from the primary tumor, bypassing the lymph nodes. Comparative analysis of the sequencing data for individual cell pairs within different tumors demonstrated that the genetic heterogeneity of both liver and lymphatic metastases was also greater than that of the primary tumor. This finding indicates that liver and lymphatic metastases arose from clusters of circulating tumor cell (CTC) of a polyclonal origin, rather than from a single cell from the primary tumor. Single-cell transcriptome analysis suggested that higher EMT score and CNV scores were associated with more polyclonal metastasis. Additionally, a mutation in the TRPS1 (Transcriptional repressor GATA binding 1) gene, TRPS1 R544Q, was enriched in the single cells from the liver metastasis. The mutation significantly increased CRC invasion and migration both in vitro and in vivo through the TRPS1R544Q/ZEB1 axis. Further TRPS1 mutations were detected in additional colon cancer cases, correlating with advanced-stage disease and inferior prognosis. These results reveal polyclonal seeding and TRPS1 mutation as potential mechanisms driving the development of liver metastases in colon cancer.

Enhancing pakchoi cabbage yield and quality but reducing human-disease risk of bacterial community from wastewater irrigation by combined nanoscale zerovalent iron and nitrification inhibitor.

It was indispensable to seek effective and feasible measures to alleviate the adverse effects of wastewater irrigation. Nanoscale zerovalent iron (nZVI) and soil nitrogen management might enhance the vegetable yield and quality but mitigate the potential human-disease risks from wastewater irrigation. This study selected the nZVI and nitrification inhibitor as experimental objects. The planted pakchoi cabbage was irrigated with the tap water and wastewater and treated with nZVI and 3, 4-dimethylpyrazole phosphate (DMPP), respectively, the pakchoi cabbage yield and quality, soil enzyme activity and abiotic property, and human-disease risk of bacterial community were quantified. Compared with the control, the nZVI significantly enhanced the pakchoi cabbage yield by 51.5% but reduced the pakchoi cabbage nitrate content by 52.6% under wastewater irrigation condition. The nZVI alone had double-edged sword effects of increasing the pakchoi cabbage yield, reducing the pakchoi cabbage nitrate content and soil human-disease risk but inhibiting the system multifunctionality and soil bacterial community diversity and stability, under wastewater irrigation condition. The nZVI diminished human-disease risk via increasing the soil Firmicutes and Verrucomicrobiota ratios, and the extra DMPP could mitigate the negative effects of nZVI by increasing soil enzyme activity and stimulating soil Acidobacteria ratio. The combinations of nZVI and DMPP could not only enhance the pakchoi cabbage yield and quality but also reduce the human-disease risk of soil bacterial community from wastewater irrigation.

Gossypol derivate as a green anti-corrosion agent in the aqueous phase of crude oil.

Keeping recruitment of green and cost-effective solutions for environmental challenges in view, the current work was designed to solve the problems related to metal corrosion in the aqueous phases of crude oil in chemical industries. Green materials can play an important role in protecting metals from this corrosion. Hence, the green anti-corrosion material based upon gossypol derivate is suggested to solve the above problems. The electrochemical characteristics were appraised by cyclic voltammetry, electrochemical impedance spectroscopy, potentiodynamic polarization, and electrochemical noise methods. The thermodynamics were studied by gravimetric analyses. The surface morphology was scrutinized using scanning electron microscopy and energy-dispersive X-ray spectroscopy. Density functional theory and molecular dynamic simulations were exploited in theoretical analyses. The gossypol derivate is green, non-toxic, more efficient, non-volatile, and chemically stable anti-corrosion material for gas and oil industries. Carbon steel corrosion simulated in aqueous phases of crude oil (NaCl solutions (1.0 M) saturated with H2S and CO2) was maximally prohibited by forming a protective layer of binaphthalene. Its protection degree is 96.71% (at 100.0 mg/L/0.107 mM). The gossypol ring is a suitable core for preparing the next modification materials to protect against corrosion. The rigid adsorption progressed mainly via hydroxyl functional moieties. Compared to the inhibition behavior of the neutral form of gossypol, the optimized protonated form causes a greater inhibition.

Ultrasound-based histological differences in thickness between puffy eyelids and normal eyelids in Asian monolid women.

BACKGROUND: Upper eyelid tissue swelling is a common characteristic among Asian monolid individuals and is associated with a high incidence of complications following eyelid surgery. Currently, there is no precise definition for upper eyelid tissue swelling; thus, further research is required to elucidate the specific causes contributing to upper eyelid puffiness. METHOD: Between June 2023 and February 2024, we recruited 84 Asian monolid women categorized into groups based on the severity of upper eyelid tissue swelling: the puffy eyelid group and normal eyelid group. High-frequency ultrasound was employed to capture images of the upper eyelids and measure the thickness of various tissue layers. This study aimed to conduct a comparative analysis to identify the factors contributing to upper eyelid fullness, focusing on elucidating the underlying causes of this condition. RESULT: All volunteers underwent bilateral upper eyelid ultrasound imaging. Significant differences were observed in the thickness of subcutaneous fat, pre-tarsal fat, retro-orbicularis oculi fat (ROOF), and composite fat (ROOF and preaponeurotic fat) layer between the puffy and normal eyelid groups. However, no significant differences were found in skin thickness or orbicularis oculi muscle thickness. Additionally, no significant differences were observed in the thickness of various layers of the upper eyelid tissue between the left and right eyes in all participants. CONCLUSION: Thickening of the upper eyelid fat layer is a primary cause of upper eyelid puffiness. In upper blepharoplasty, targeted removal of preaponeurotic fat, ROOF, and pre-tarsal fat can achieve precise reduction to correct upper eyelid puffiness effectively.

Neuroendocrine Differentiation in Prostate Cancer Requires ASCL1.

Most patients with prostate adenocarcinoma develop resistance to therapies targeting the androgen receptor (AR). Consequently, a portion of these patients develop AR-independent neuroendocrine prostate cancer (NEPC), a rapidly progressing cancer with limited therapies and poor survival outcomes. Current research to understand the progression to NEPC suggests a model of lineage plasticity whereby AR-dependent luminal-like tumors progress towards an AR-independent NEPC state. Genetic analysis of human NEPC identified frequent loss of RB1 and TP53, and the loss of both genes in experimental models mediates the transition to a neuroendocrine lineage. Transcriptomics studies have shown that lineage transcription factors ASCL1 and NEUROD1 are present in NEPC. In this study, we modeled the progression of prostate adenocarcinoma to NEPC by establishing prostate organoids and subsequently generating subcutaneous allograft tumors from genetically-engineered mouse models harboring Cre-induced loss of Rb1 and Trp53 with Myc overexpression (RPM). These tumors were heterogeneous and displayed adenocarcinoma, squamous, and neuroendocrine features. ASCL1 and NEUROD1 were expressed within neuroendocrine-defined regions, with ASCL1 being predominant. Genetic loss of Ascl1 in this model did not decrease tumor incidence, growth, or metastasis; however, there was a notable decrease in neuroendocrine identity and an increase in basal-like identity. This study provides an in vivo model to study progression to NEPC and establishes the requirement for ASCL1 in driving neuroendocrine differentiation in prostate cancer.

Antimicrobial blue light inactivation of Pseudomonas aeruginosa: Unraveling the multifaceted impact of wavelength, growth stage, and medium composition.

Pseudomonas aeruginosa, a notable pathogen frequently associated with hospital-acquired infections, displays diverse intrinsic and acquired antibiotic resistance mechanisms, posing a significant challenge in infection management. Antimicrobial blue light (aBL) has been demonstrated as a potential alternative for treating P. aeruginosa infections. In this study, we investigated the impact of blue light wavelength, bacterial growth stage, and growth medium composition on the efficacy of aBL. First, we compared the efficacy of light wavelengths 405 nm, 415 nm, and 470 nm in killing three multidrug resistant clinical strains of P. aeruginosa. The findings indicated considerably higher antibacterial efficacy for 405 nm and 415 nm wavelength compared to 470 nm. We then evaluated the impact of the bacterial growth stage on the efficacy of 405 nm light in killing P. aeruginosa using a reference strain PAO1 in exponential, transitional, or stationary phase. We found that bacteria in the exponential phase were the most susceptible to aBL, followed by the transitional phase, while those in the stationary phase exhibited the highest tolerance. Additionally, we quantified the production of reactive oxygen species (ROS) in bacteria using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe and flow cytometry, and observed a positive correlation between aBL efficacy and ROS production. Finally, we determined the influence of growth medium on aBL efficacy. PAO1 was cultivated in brain heart infusion (BHI), Luria-Bertani (LB) broth or Casamino acids (CAA) medium, before being irradiated with aBL at 405 nm. The CAA-grown bacteria exhibited the highest sensitivity to aBL, followed by those grown in LB broth, and the BHI-grown bacteria demonstrated the lowest sensitivity. By incorporating FeCl3, MnCl2, ZnCl2, or the iron chelator 2,2'-bipyridine (BIP) into specific media, we discovered that aBL efficacy was affected by the iron levels in culture media.

Influences of Butylphthalide Injection in Combination with Edaravone on Clinical Efficacy and Cytokines in Elderly Acute Cerebral Infarction Patients.

Background: Acute cerebral infarction threatens human health and life safety. The edaravone is a new antioxidant and hydroxyl radical scavenger, which is used in the treatment of cardiovascular diseases. However, long-term use of edaravone is prone to drug resistance, resulting in limited therapeutic effect. Butylphthalein can improve collateral circulation, protect the integrity of vascular endothelial cells, improve vasospasm, increase blood perfusion in the ischemic area of brain tissue, and promote the recovery of cerebral nerve function. Objective: To measure the influences of butylphthalide injection in combination with edaravone on clinical efficacy and cytokines in elderly acute cerebral infarction patients, aiming to provide reference for the treatment of acute cerebral infarction. Design: This was a retrospective study. Setting: This study was performed in Yantaishan Hospital. Participants: A total of 168 elderly acute cerebral infarction patients who accepted therapy in our hospital from February 2022 to February 2023 were chosen and allocated into a combination group and a control group. Interventions: The control group accepted the edaravone injection treatment. The combination group was treated with edaravone injection combined with butylphthalide injection. Primary Outcome Measures: (1) Therapeutic effect (2) Cytokines (3) Vascular endothelial function (4) Oxidative stress (5) Degree of neurological impairment (6) Living ability. Results: The total effective rate in the combination group presented elevation when in contrast to the control group (P < .05). After therapy, the levels of cytokines in the combination group presented reduction relative to the control group (P < .05), nitric oxide level in the combination group presented elevation when in contrast to the control group (P < .05), vascular endothelial growth factor level in the combination group presented lessened relative to the control group (P < .05), glutathione peroxidase along with superoxide dismutase levels in the combination group presented higher relative to the control group (P < .05) and malondialdehyde level in the combination group presented lower relative to the control group (P < .05). After therapy, the National Institute of Stroke Scale score in the combination group presented reduced when compared with the control group (P < .05). In contrast, the activity of daily living score in the combination group presented higher relative to the control group (P < .05). Conclusion: Butylphthalide injection in combination with edaravone can effectively inhibit the inflammatory response and oxidative stress, promote vascular endothelial function, improve daily behavior ability as well as promote the neurological function of elderly acute cerebral infarction patients.

Comparative plastome analyses and evolutionary relationships of 25 East Asian species within the medicinal plant genus Scrophularia (Scrophulariaceae).

Backgroud: Scrophularia L., a genus of the Scrophulariaceae, is a group of important medicinal plants used for eliminating heat and detoxifying. East Asia has an abundance of potentially medicinal Scrophularia species, and it serves as a secondary diversity center of the genus. However, the genomic resources available for germplasm identification and pharmaceutical exploration of East Asian Scrophularia are insufficient, hindering its commercial and industrial development. Additionally, the interspecific relationships of most East Asian Scrophularia species remain unclear. Methods: In this study, we sequenced the leaves of 25 East Asian species of the genus Scrophularia, assembled and annotated the complete chloroplast genomes, and subsequently performed comparative and phylogenetic analyses on these genomes. Results and discussion: The conserved plastome length of these 25 species ranged from 151,582 bp to 153,239 bp, containing a total of 132 coding genes, including 18 duplicated genes and 114 unique genes. Through genome alignment of these 25 species, 38-53 repeated sequences and 7 shared SSRs were identified, along with regions with high nucleotide polymorphism (Pi), which could potentially serve as molecular markers for species identification. The genome structure, gene content, and arrangement showed conservation, while variations were observed in the IR boundary regions and IGS. Phylogenetic inferences based on whole plastomes or on coding sequences (CDS) only yielded congruent results. We categorized the 25 East Asian Scrophularia species into six distinct clades and further explored their interspecies relationships using morphological characteristics, such as flower color, the relative position of stamens and corolla, and plant height. This could lay a genetic basis for future resource development of Scrophularia in East Asia.

Inverse Identification of Constitutive Model for GH4198 Based on Genetic-Particle Swarm Algorithm.

A precise Johnson-Cook (J-C) constitutive model is the foundation for precise calculation of finite-element simulation. In order to obtain the J-C constitutive model accurately for a new cast and forged alloy GH4198, an inverse identification of J-C constitutive model was proposed based on a genetic-particle swarm algorithm. Firstly, a quasi-static tensile test at different strain rates was conducted to determine the initial yield strength A, strain hardening coefficient B, and work hardening exponent n for the material's J-C model. Secondly, a new method for orthogonal cutting model was constructed based on the unequal division shear theory and considering the influence of tool edge radius. In order to obtain the strain-rate strengthening coefficient C and thermal softening coefficient m, an orthogonal cutting experiment was conducted. Finally, in order to validate the precision of the constitutive model, an orthogonal cutting thermo-mechanical coupling simulation model was established. Meanwhile, the sensitivity of J-C constitutive model parameters on simulation results was analyzed. The results indicate that the parameter m significantly affects chip morphology, and that the parameter C has a notable impact on the cutting force. This study addressed the issue of missing constitutive parameters for GH4198 and provided a theoretical reference for the optimization and identification of constitutive models for other aerospace materials.

Identification of genetic basis of brain imaging by group sparse multi-task learning leveraging summary statistics.

Brain imaging genetics is an evolving neuroscience topic aiming to identify genetic variations related to neuroimaging measurements of interest. Traditional linear regression methods have shown success, but their reliance on individual-level imaging and genetic data limits their applicability. Herein, we proposed S-GsMTLR, a group sparse multi-task linear regression method designed to harness summary statistics from genome-wide association studies (GWAS) of neuroimaging quantitative traits. S-GsMTLR directly employs GWAS summary statistics, bypassing the requirement for raw imaging genetic data, and applies multivariate multi-task sparse learning to these univariate GWAS results. It amalgamates the strengths of conventional sparse learning methods, including sophisticated modeling techniques and efficient feature selection. Additionally, we implemented a rapid optimization strategy to alleviate computational burdens by identifying genetic variants associated with phenotypes of interest across the entire chromosome. We first evaluated S-GsMTLR using summary statistics derived from the Alzheimer's Disease Neuroimaging Initiative. The results were remarkably encouraging, demonstrating its comparability to conventional methods in modeling and identification of risk loci. Furthermore, our method was evaluated with two additional GWAS summary statistics datasets: One focused on white matter microstructures and the other on whole brain imaging phenotypes, where the original individual-level data was unavailable. The results not only highlighted S-GsMTLR's ability to pinpoint significant loci but also revealed intriguing structures within genetic variations and loci that went unnoticed by GWAS. These findings suggest that S-GsMTLR is a promising multivariate sparse learning method in brain imaging genetics. It eliminates the need for original individual-level imaging and genetic data while demonstrating commendable modeling and feature selection capabilities.

Reaction-Modulated Surface-Enhanced Raman Scattering Strategy for Stereoselective Differentiation and Identification of Amino Acids.

Surface-enhanced Raman scattering (SERS) sensing of racemates is a remarkably fascinating yet very sophisticated objective because of similar physicochemical features of enantiomers. Inspired by the enantiomeric selectivity of nucleophilic addition reaction (NAR) toward amino acids, we herein propose highly effective, robust SERS discrimination of d- and l-valine by synergizing asymmetric gold nanorods-embedded ZIF-8 nanoparticles (AGNZ) with NAR to engender stereoselective molecular fingerprint. Experimental and chemometric analyses disclose that enantioselectivity lies in dual aspects: (i) abundant interfacial cavities and 3D hot-spots in AGNZ offer necessary confined asymmetrical surroundings to trigger enantiospecific molecular adsorption and interaction affinity, and (ii) the specified NAR drags the racemates adjacent to the interfacial area of AGNZ for maximum analytes-substrate interaction. This strategy is universal and can be utilized for the recognition of different amino acid enantiomers. Importantly, multiple quantifications of the racemic ratio can be realized with superior prognostic performances. This synergizing strategy therefore provides a significant paradigm shift from traditional methods to realize highly effective SERS discrimination of racemates.

Challenges and improvements in HER2 scoring and histologic evaluation: insights from a national proficiency testing scheme for breast cancer diagnosis in China.

BACKGROUND: In 2022, our team launched the pioneering national proficiency testing (PT) scheme for the pathological diagnosis of breast cancer, rapidly establishing its credibility throughout China. Aiming to continuously monitor and improve the proficiency of Chinese pathologists in breast pathology, the second round of the PT scheme was initiated in 2023, which will expand the number of participating institutions, and will conduct a nationwide investigation into the interpretation of HER2 0, 1+, and 2+/FISH- categories in China. METHODS: The methodology employed in the current round of PT scheme closely mirrors that of the preceding cycle in 2022, which is designed and implemented according to the "Conformity assessment-General requirements for proficiency testing"(GB/T27043-2012/ISO/IEC 17043:2010). More importantly, we utilized a statistics-based method to generate assigned values to enhance their robustness and credibility. RESULTS: The final PT results, published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927 ), showed that all participants passed the testing. However, a few institutions demonstrated systemic biases in scoring HER2 0, 1+, and 2+/FISH- with accuracy levels below 59%, considered unsatisfactory. Especially, the concordance rate for HER2 0 cases was only 78.1%, indicating challenges in distinguishing HER2 0 from low HER2 expression. Meanwhile, areas for histologic type and grade interpretation improvement were also noted. CONCLUSIONS: Our PT scheme demonstrated high proficiency in diagnosing breast cancer in China. But it also identified systemic biases in scoring HER2 0, 1+, and 2+/FISH- at some institutions. More importantly, our study highlighted challenges in the evaluation at the extreme lower end of the HER2 staining spectrum, a crucial area for further research. Meanwhile, it also revealed the need for improvements in interpreting histologic types and grades. These findings strengthened the importance of robust quality assurance mechanisms, like the nationwide PT scheme conducted in this study, to maintain high diagnostic standards and identify areas requiring further training and enhancement.

Comparison of eliminating artificial hydronephrosis and creating artificial hydronephrosis in percutaneous nephrolithotomy in oblique supine position.

INTRODUCTION: The safety and effectiveness of percutaneous nephroscopic surgery without artificial hydronephrosis remain controversial, and there are few relevant studies. This retrospective study aimed to compare the efficacy of two different methods of eliminating and creating artificial hydronephrosis in percutaneous nephrolithotomy(PCNL) in the oblique supine position. METHODS: This is a retrospective study. A total of 162 patients who underwent PCNL in an oblique supine position at our hospital were divided into two groups according to the surgical method: the free artificial hydronephrosis group (Group A) and the artificial hydronephrosis group (Group B). Group A was directly treated with PCNL under ultrasound guidance and group B was treated with artificial hydronephrosis before PCNL. Several outcomes were measured, including operation time, stone clearance rate, and incidence of complications. RESULTS: The operation time in Group A lower than that in Group B, and the incidence of sepsis was significantly lower in group A than in Group B (P<0.05). There was no statistical difference in stone clearance rate, success rate of primary establishment of puncture channel, unilateral change in perioperative red blood cell count, change in perioperative renal function, and perioperative complications (except sepsis) between the two groups (P>0.05). CONCLUSION: For experienced physicians, percutaneous nephrolithotomy without artificial hydronephrosis in an oblique supine position can be attempted to reduce the number of surgical steps without affecting the stone clearance rate and increasing the occurrence of complications.

Machine learning-assisted optimization of food-grade spirulina cultivation in seawater-based media: From laboratory to large-scale production.

The shortage of food and freshwater sources threatens human health and environmental sustainability. Spirulina grown in seawater-based media as a healthy food is promising and environmentally friendly. This study used three machine learning techniques to identify important cultivation parameters and their hidden interrelationships and optimize the biomass yield of Spirulina grown in seawater-based media. Through optimization of hyperparameters and features, eXtreme Gradient Boosting, along with the recursive feature elimination (RFE) model demonstrated optimal performance and identified 28 important features. Among them, illumination intensity and initial pH value were critical determinants of biomass, which impacted other features. Specifically, high initial pH values (>9.0) mainly increased biomass but also increased nutrient sedimentation and ammonia (NH3) losses. Both batch and continuous additions could decrease nutrient losses by increasing their availability in the seawater-based media. When illumination intensity exceeded 200 µmol photons/m2/s, it amplified the growth of Spirulina by mitigating the light attenuation caused by a high initial inoculum level and counteracted the negative effect of low temperature (<25 °C). In large-scale cultivation, production efficiency would be reduced if illumination was not maintained at a high level. High salinity and sodium bicarbonate (NaHCO3) addition promoted carbohydrate accumulation, but suitable dilution could keep the required protein content in Spirulina with relatively low media and production costs. These findings reveal the interactive influence of cultivation parameters on biomass yield and help us determine the optimal cultivation conditions for large-scale cultivation of Spirulina-based seawater system based on a developed graphical user interface website.

Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukaemia cell growth.

The ten-eleven translocation (TET) family of dioxygenases maintain stable local DNA demethylation during cell division and lineage specification. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine is selectively enriched at specific genomic regions, such as enhancers, in a tissue-dependent manner. However, the mechanisms underlying this selectivity remain unresolved. Here we unveil a low-complexity insert domain within TET2 that facilitates its biomolecular condensation with epigenetic modulators, such as UTX and MLL4. This co-condensation fosters a permissive chromatin environment for precise DNA demethylation. Disrupting low-complexity insert-mediated condensation alters the genomic binding of TET2 to cause promiscuous DNA demethylation and genome reorganization. These changes influence the expression of key genes implicated in leukaemogenesis to curtail leukaemia cell proliferation. Collectively, this study establishes the pivotal role of TET2 condensation in orchestrating precise DNA demethylation and gene transcription to support tumour cell growth.

GOLM1 dictates acquired Lenvatinib resistance by a GOLM1-CSN5 positive feedback loop upon EGFR signaling activation in hepatocellular carcinoma.

Lenvatinib is a multiple receptor tyrosine kinases inhibitor (TKI) authorized for first-line treatment of hepatocellular carcinoma (HCC). However, Lenvatinib resistance is common in HCC clinical treatment, highlighting the urgent need to understand mechanisms of resistance. Here, we identified Golgi membrane protein 1 (GOLM1), a type II transmembrane protein originally located in the Golgi apparatus, as a novel regulator of Lenvatinib resistance. We found GOLM1 was overexpressed in Lenvatinib resistant human HCC cell lines, blood and HCC samples. Additionally, GOLM1 overexpression contributes to Lenvatinib resistance and HCC progression in vitro and in vivo. Mechanistically, GOLM1 upregulates CSN5 expression through EGFR-STAT3 pathway. Reversely, CSN5 deubiquitinates and stabilizes GOLM1 protein by inhibiting ubiquitin-proteasome pathway of GOLM1. Furthermore, clinical specimens of HCC showed a positive correlation between the activation of the GOLM1-EGFR-STAT3-CSN5 axis. Finally, GOLM1 knockdown was found to act in synergy with Lenvatinib in subcutaneous and orthotopic mouse model. Overall, these findings identify a mechanism of resistance to Lenvatinib treatment for HCC, highlight an effective predictive biomarker of Lenvatinib response in HCC and show that targeting GOLM1 may improve the clinical benefit of Lenvatinib.

Mapping cellular interactions from spatially resolved transcriptomics data.

Cell-cell communication (CCC) is essential to how life forms and functions. However, accurate, high-throughput mapping of how expression of all genes in one cell affects expression of all genes in another cell is made possible only recently through the introduction of spatially resolved transcriptomics (SRT) technologies, especially those that achieve single-cell resolution. Nevertheless, substantial challenges remain to analyze such highly complex data properly. Here, we introduce a multiple-instance learning framework, Spacia, to detect CCCs from data generated by SRTs, by uniquely exploiting their spatial modality. We highlight Spacia's power to overcome fundamental limitations of popular analytical tools for inference of CCCs, including losing single-cell resolution, limited to ligand-receptor relationships and prior interaction databases, high false positive rates and, most importantly, the lack of consideration of the multiple-sender-to-one-receiver paradigm. We evaluated the fitness of Spacia for three commercialized single-cell resolution SRT technologies: MERSCOPE/Vizgen, CosMx/NanoString and Xenium/10x. Overall, Spacia represents a notable step in advancing quantitative theories of cellular communications.

[Biomechanical study of three-dimensional printed filler block design in open wedge high tibial osteotomy].

The use of a filling block can improve the initial stability of the fixation plate in the open wedge high tibial osteotomy (OWHTO), and promote bone healing. However, the biomechanical effects of filling block structures and materials on OWHTO remain unclear. OWHTO anatomical filling block model was designed and built. The finite element analysis method was adopted to study the influence of six filling block structure designs and four different materials on the stress of the fixed plate, tibia, screw, and filling block, and the micro-displacement at the wedge gap of the OWHTO fixation system. After the filling block was introduced in the OWHTO, the maximum von Mises stress of the fixation plate was reduced by more than 30%, the maximum von Mises stress of the tibia decreased by more than 15%, and the lateral hinge decreased by 81%. When the filling block was designed to be filled in the posterior position of the wedge gap, the maximum von Mises stress of the fixation system was 97.8 MPa, which was smaller than other filling methods. The minimum micro-displacement of osteotomy space was -2.9 µm, which was larger than that of other filling methods. Compared with titanium alloy and tantalum metal materials, porous hydroxyapatite material could obtain larger micro-displacement in the osteotomy cavity, which is conducive to stimulating bone healing. The results demonstrate that OWHTO with a filling block can better balance the stress distribution of the fixation system, and a better fixation effect can be obtained by using a filling block filled in the posterior position. Porous HA used as the material of the filling block can obtain a better bone healing effect.