A novel mesenchymal stem cell-targeting dual-miRNA delivery system based on aptamer-functionalized tetrahedral framework nucleic acids: Application to endogenous regeneration of articular cartilage.

Articular cartilage injury (ACI) remains one of the key challenges in regenerative medicine, as current treatment strategies do not result in ideal regeneration of hyaline-like cartilage. Enhancing endogenous repair via microRNAs (miRNAs) shows promise as a regenerative therapy. miRNA-140 and miRNA-455 are two key and promising candidates for regulating the chondrogenic differentiation of mesenchymal stem cells (MSCs). In this study, we innovatively synthesized a multifunctional tetrahedral framework in which a nucleic acid (tFNA)-based targeting miRNA codelivery system, named A-T-M, was used. With tFNAs as vehicles, miR-140 and miR-455 were connected to and modified on tFNAs, while Apt19S (a DNA aptamer targeting MSCs) was directly integrated into the nanocomplex. The relevant results showed that A-T-M efficiently delivered miR-140 and miR-455 into MSCs and subsequently regulated MSC chondrogenic differentiation through corresponding mechanisms. Interestingly, a synergistic effect between miR-140 and miR-455 was revealed. Furthermore, A-T-M successfully enhanced the endogenous repair capacity of articular cartilage in vivo and effectively inhibited hypertrophic chondrocyte formation. A-T-M provides a new perspective and strategy for the regeneration of articular cartilage, showing strong clinical application value in the future treatment of ACI.

Population structure and breed identification of Chinese indigenous sheep breeds using whole genome SNPs and InDels.

BACKGROUND: Accurate breed identification is essential for the conservation and sustainable use of indigenous farm animal genetic resources. In this study, we evaluated the phylogenetic relationships and genomic breed compositions of 13 sheep breeds using SNP and InDel data from whole genome sequencing. The breeds included 11 Chinese indigenous and 2 foreign commercial breeds. We compared different strategies for breed identification with respect to different marker types, i.e. SNPs, InDels, and a combination of SNPs and InDels (named SIs), different breed-informative marker detection methods, and different machine learning classification methods. RESULTS: Using WGS-based SNPs and InDels, we revealed the phylogenetic relationships between 11 Chinese indigenous and two foreign sheep breeds and quantified their purities through estimated genomic breed compositions. We found that the optimal strategy for identifying these breeds was the combination of DFI_union for breed-informative marker detection, which integrated the methods of Delta, Pairwise Wright's FST, and Informativeness for Assignment (namely DFI) by merging the breed-informative markers derived from the three methods, and KSR for breed assignment, which integrated the methods of K-Nearest Neighbor, Support Vector Machine, and Random Forest (namely KSR) by intersecting their results. Using SI markers improved the identification accuracy compared to using SNPs or InDels alone. We achieved accuracies over 97.5% when using at least the 1000 most breed-informative (MBI) SI markers and even 100% when using 5000 SI markers. CONCLUSIONS: Our results provide not only an important foundation for conservation of these Chinese local sheep breeds, but also general approaches for breed identification of indigenous farm animal breeds.

The function of juvenile-adult transition axis in female sexual receptivity of Drosophila melanogaster.

Female sexual receptivity is essential for reproduction of a species. Neuropeptides play the main role in regulating female receptivity. However, whether neuropeptides regulate female sexual receptivity during the neurodevelopment is unknown. Here, we found the peptide hormone prothoracicotropic hormone (PTTH), which belongs to the insect PG (prothoracic gland) axis, negatively regulated virgin female receptivity through ecdysone during neurodevelopment in Drosophila melanogaster. We identified PTTH neurons as doublesex-positive neurons, they regulated virgin female receptivity before the metamorphosis during the third-instar larval stage. PTTH deletion resulted in the increased EcR-A expression in the whole newly formed prepupae. Furthermore, the ecdysone receptor EcR-A in pC1 neurons positively regulated virgin female receptivity during metamorphosis. The decreased EcR-A in pC1 neurons induced abnormal morphological development of pC1 neurons without changing neural activity. Among all subtypes of pC1 neurons, the function of EcR-A in pC1b neurons was necessary for virgin female copulation rate. These suggested that the changes of synaptic connections between pC1b and other neurons decreased female copulation rate. Moreover, female receptivity significantly decreased when the expression of PTTH receptor Torso was reduced in pC1 neurons. This suggested that PTTH not only regulates female receptivity through ecdysone but also through affecting female receptivity associated neurons directly. The PG axis has similar functional strategy as the hypothalamic-pituitary-gonadal axis in mammals to trigger the juvenile-adult transition. Our work suggests a general mechanism underlying which the neurodevelopment during maturation regulates female sexual receptivity.

Epigenomic landscapes during prefrontal cortex development and aging in rhesus.

The prefrontal cortex (PFC) is essential for higher-level cognitive functions. How epigenetic dynamics participates in PFC development and aging is largely unknown. Here, we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging stages. The dynamics of chromatin states, including higher-order chromatin structure, chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription, participating in distinct processes of neurodevelopment. Dramatic changes of epigenetic signals occur around the birth stage. Notably, genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent promoters. We identified a cis-regulatory module and the transcription factors (TFs) associated with basal radial glia development, which was associated with large brain size in primates. These TFs include GLI3, CREB5 and SOX9. Interestingly, the genes associated with the basal radial glia (bRG)-associated cis-element module, such as SRY and SOX9, are enriched in sex differentiation. Schizophrenia-associated single nucleotide polymorphisms are more enriched in super enhancers (SEs) than typical enhancers, suggesting that SEs play an important role in neural network wiring. A cis-regulatory element of DBN1 is identified, which is critical for neuronal cell proliferation and synaptic neuron differentiation. Notably, the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging, which are associated with abnormal expression of aging-related genes and transposon activation, respectively. Collectively, our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

Promotion of osteochondral repair through immune microenvironment regulation and activation of endogenous chondrogenesis via the release of apoptotic vesicles from donor MSCs.

Utilizing transplanted human umbilical cord mesenchymal stem cells (HUMSCs) for cartilage defects yielded advanced tissue regeneration, but the underlying mechanism remain elucidated. Early after HUMSCs delivery to the defects, we observed substantial apoptosis. The released apoptotic vesicles (apoVs) of HUMSCs promoted cartilage regeneration by alleviating the chondro-immune microenvironment. ApoVs triggered M2 polarization in macrophages while simultaneously facilitating the chondrogenic differentiation of endogenous MSCs. Mechanistically, in macrophages, miR-100-5p delivered by apoVs activated the MAPK/ERK signaling pathway to promote M2 polarization. In MSCs, let-7i-5p delivered by apoVs promoted chondrogenic differentiation by targeting the eEF2K/p38 MAPK axis. Consequently, a cell-free cartilage regeneration strategy using apoVs combined with a decellularized cartilage extracellular matrix (DCM) scaffold effectively promoted the regeneration of osteochondral defects. Overall, new mechanisms of cartilage regeneration by transplanted MSCs were unconcealed in this study. Moreover, we provided a novel experimental basis for cell-free tissue engineering-based cartilage regeneration utilizing apoVs.

[Advances in clinical repair techniques for localized knee cartilage lesions].

Objective: To summarize the classic and latest treatment techniques for localized knee cartilage lesions in clinical practice and create a new comprehensive clinical decision-making process. Methods: The advantages and limitations of various treatment methods for localized knee cartilage lesions were summarized by extensive review of relevant literature at home and abroad in recent years. Results: Currently, there are various surgical methods for treating localized knee cartilage injuries in clinical practice, each with its own pros and cons. For patients with cartilage injuries less than 2 cm 2 and 2-4 cm 2 with bone loss are recommended to undergo osteochondral autograft (OAT) and osteochondral allograft (OCA) surgeries. For patients with cartilage injuries less than 2 cm 2 and 2-4 cm 2 without bone loss had treatment options including bone marrow-based techniques (micro-fracture and ogous matrix induced chondrogenesis), autologous chondrocyte implantation (ACI)/matrix-induced ACI, particulated juvenile allograft cartilage (PJAC), OAT, and OCA. For patients with cartilage injuries larger than 4 cm 2 with bone loss were recommended to undergo OCA. For patients with cartilage injuries larger than 4 cm 2 without bone loss, treatment options included ACI/matrix-induced ACI, OAT, and PJAC. Conclusion: There are many treatment techniques available for localized knee cartilage lesions. Treatment strategy selection should be based on the size and location of the lesion, the extent of involvement of the subchondral bone, and the level of evidence supporting each technique in the literature.

Improving multi-population genomic prediction accuracy using multi-trait GBLUP models which incorporate global or local genetic correlation information.

In the application of genomic prediction, a situation often faced is that there are multiple populations in which genomic prediction (GP) need to be conducted. A common way to handle the multi-population GP is simply to combine the multiple populations into a single population. However, since these populations may be subject to different environments, there may exist genotype-environment interactions which may affect the accuracy of genomic prediction. In this study, we demonstrated that multi-trait genomic best linear unbiased prediction (MTGBLUP) can be used for multi-population genomic prediction, whereby the performances of a trait in different populations are regarded as different traits, and thus multi-population prediction is regarded as multi-trait prediction by employing the between-population genetic correlation. Using real datasets, we proved that MTGBLUP outperformed the conventional multi-population model that simply combines different populations together. We further proposed that MTGBLUP can be improved by partitioning the global between-population genetic correlation into local genetic correlations (LGC). We suggested two LGC models, LGC-model-1 and LGC-model-2, which partition the genome into regions with and without significant LGC (LGC-model-1) or regions with and without strong LGC (LGC-model-2). In analysis of real datasets, we demonstrated that the LGC models could increase universally the prediction accuracy and the relative improvement over MTGBLUP reached up to 163.86% (25.64% on average).

Identification and Characterization of Three Novel Solemo-like Viruses in the White-Backed Planthopper, Sogatella furcifera.

Agricultural insects play a crucial role in transmitting plant viruses and host a considerable number of insect-specific viruses (ISVs). Among these insects, the white-backed planthoppers (WBPH; Sogatella furcifera, Hemiptera: Delphacidae) are noteworthy rice pests and are responsible for disseminating the southern rice black-streaked dwarf virus (SRBSDV), a significant rice virus. In this study, we analyzed WBPH transcriptome data from public sources and identified three novel viruses. These newly discovered viruses belong to the plant-associated viral family Solemoviridae and were tentatively named Sogatella furcifera solemo-like virus 1-3 (SFSolV1-3). Among them, SFSolV1 exhibited a prevalent existence in different laboratory populations, and its complete genome sequence was obtained using rapid amplification of cDNA ends (RACE) approaches. To investigate the antiviral RNA interference (RNAi) response in WBPH, we conducted an analysis of virus-derived small interfering RNAs (vsiRNAs). The vsiRNAs of SFSolV1 and -2 exhibited typical patterns associated with the host's siRNA-mediated antiviral immunity, with a preference for 21- and 22-nt vsiRNAs derived equally from both the sense and antisense genomic strands. Furthermore, we examined SFSolV1 infection and distribution in WBPH, revealing a significantly higher viral load of SFSolV1 in nymphs' hemolymph compared to other tissues. Additionally, in adult insects, SFSolV1 exhibited higher abundance in male adults than in female adults.

Complete genome sequence and genetic characterization of a novel segmented RNA virus infecting Nilaparvata lugens.

The brown planthopper (BPH), Nilaparvata lugens, is a significant agricultural pest capable of long-distance migration and transmission of viruses that cause severe disease in rice. In this study, we identified a novel segmented RNA virus in a BPH, and this virus exhibited a close relationship to members of a recently discovered virus lineage known as "quenyaviruses" within the viral kingdom Orthornavirae. This newly identified virus was named "Nilaparvata lugens quenyavirus 1" (NLQV1). NLQV1 consists of five positive-sense, single-stranded RNAs, with each segment containing a single open reading frame (ORF). The genomic characteristics and phylogenetic analysis support the classification of NLQV1 as a novel quenyavirus. Notably, all of the genome segments of NLRV contained the 5'-terminal sequence AUCUG. The characteristic virus-derived small interfering RNA (vsiRNA) profile of NLQV1 suggests that the antiviral RNAi pathway of the host BPH was activated in response to virus infection. These findings represent the first documented report of quenyaviruses in planthoppers, contributing to our understanding of quenyaviruses and expanding our knowledge of insect-specific viruses in planthoppers.

Finite element analysis of meniscus contact mechanical behavior based on kinematic simulation of abnormal gait.

The meniscus plays a crucial role in the proper functioning of the knee joint, and when it becomes damaged, partial removal or replacement is necessary to restore proper function. Understanding the stress and deformation of the meniscus during various movements is essential for developing effective materials for meniscus repair. However, accurately estimating the contact mechanics of the knee joint can be challenging due to its complex shape and the dynamic changes it undergoes during movement. To address this issue, the open-source software SCONE can be used to establish a kinematics model that monitors the different states of the knee joint during human motion and obtains relevant gait kinematics data. To evaluate the stress and deformation of the meniscus during normal human movement, values of different states in the movement gait can be selected for finite element analysis (FEA) of the knee joint. This analysis enables researchers to assess changes in the meniscus. To evaluate meniscus damage, it is necessary to obtain changes in its mechanical behavior during abnormal movements. This information can serve as a reference for designing and optimizing the mechanical performance of materials used in meniscus repair and replacement.

Palladium-catalyzed selective C-C bond cleavage of keto-vinylidenecyclopropanes: construction of structurally rich dihydrofurans and tetrahydrofurans.

Palladium-catalyzed selective cleavage of the distal C-C bond and proximal C-C bond of keto-vinylidenecyclopropanes by altering the sterically bulky phosphine ligands has been realized. The proximal C-C bond cleavage can be achieved by using dtbpf as a phosphine ligand, affording bicyclic products containing dihydrofuran skeletons in good yields along with broad substrate scope. In proximal C-C bond cleavage reactions, the eight-membered cyclic palladium intermediate plays a key role in the reaction. The [3 + 2] cycloaddition of keto-vinylidenecyclopropanes through the distal C-C bond cleavage can be effectively accomplished with t BuXPhos as a phosphine ligand and ZnCl2 as an additive, delivering bicyclic products containing tetrahydrofuran skeletons in good yields. The further transformation of these bicyclic products has been demonstrated, and the reaction mechanisms of two different C-C bond cleavage reactions have been investigated by control experiments and DFT calculations.

The larva and adult of Helicoverpa armigera use differential gustatory receptors to sense sucrose.

Almost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear. Helicoverpa armigera as a notorious crop pest worldwide mainly feeds on reproductive organs of many plant species in the larval stage, and its adult draws nectar. In this study, we determined that the sucrose sensory neurons located in the contact chemosensilla on larval maxillary galea were 100-1000 times more sensitive to sucrose than those on adult antennae, tarsi, and proboscis. Using the Xenopus expression system, we discovered that Gr10 highly expressed in the larval sensilla was specifically tuned to sucrose, while Gr6 highly expressed in the adult sensilla responded to fucose, sucrose and fructose. Moreover, using CRISPR/Cas9, we revealed that Gr10 was mainly used by larvae to detect lower sucrose, while Gr6 was primarily used by adults to detect higher sucrose and other saccharides, which results in differences in selectivity and sensitivity between larval and adult sugar sensory neurons. Our results demonstrate the sugar receptors in this moth are evolved to adapt toward the larval and adult foods with different types and amounts of sugar, and fill in a gap in sweet taste of animals.

Palladium catalyzed stereoselective intramolecular [3 + 2] cycloaddition reactions of (E) & (Z)-ene-vinylidenecyclopropanes.

A palladium-catalyzed ring-opening cyclization of (E) & (Z)-ene-vinylidenecyclopropanes has been developed via an intramolecular [3 + 2] cycloaddition process in the presence of a sterically bulky biaryl phosphine ligand, stereoselectively affording fused cis- & trans-bicyclo[4.3.0] skeletal products in good yields with a broad substrate scope and good functional tolerance. A plausible reaction mechanism was proposed on the basis of previous work and the DFT calculations.

Resequencing Analyses Revealed Genetic Diversity and Selection Signatures during Rabbit Breeding and Improvement.

Domestication has shaped the diverse characteristics of rabbits, including coat color, fur structure, body size, and various physiological traits. Utilizing whole-genome resequencing (DNBSEQ-T7), we analyzed the genetic diversity, population structure, and genomic selection across 180 rabbits from 17 distinct breeds to uncover the genetic basis of these traits. We conducted whole-genome sequencing on 17 rabbit breeds, identifying 17,430,184 high-quality SNPs and analyzing genomic diversity, patterns of genomic variation, population structure, and selection signatures related to coat color, coat structure, long hair, body size, reproductive capacity, and disease resistance. Through PCA and NJ tree analyses, distinct clusters emerged among Chinese indigenous rabbits, suggesting varied origins and domestication histories. Selective sweep testing pinpointed regions and genes linked to domestication and key morphological and economic traits, including those affecting coat color (TYR, ASIP), structure (LIPH), body size (INSIG2, GLI3), fertility (EDNRA, SRD5A2), heat stress adaptation (PLCB1), and immune response (SEC31A, CD86, LAP3). Our study identified key genomic signatures of selection related to traits such as coat color, fur structure, body size, and fertility; these findings highlight the genetic basis underlying phenotypic diversification in rabbits and have implications for breeding programs aiming to improve productive, reproductive, and adaptive traits. The detected genomic signatures of selection also provide insights into rabbit domestication and can aid conservation efforts for indigenous breeds.

Marker Density and Models to Improve the Accuracy of Genomic Selection for Growth and Slaughter Traits in Meat Rabbits.

The selection and breeding of good meat rabbit breeds are fundamental to their industrial development, and genomic selection (GS) can employ genomic information to make up for the shortcomings of traditional phenotype-based breeding methods. For the practical implementation of GS in meat rabbit breeding, it is necessary to assess different marker densities and GS models. Here, we obtained low-coverage whole-genome sequencing (lcWGS) data from 1515 meat rabbits (including parent herd and half-sibling offspring). The specific objectives were (1) to derive a baseline for heritability estimates and genomic predictions based on randomly selected marker densities and (2) to assess the accuracy of genomic predictions for single- and multiple-trait linear mixed models. We found that a marker density of 50 K can be used as a baseline for heritability estimation and genomic prediction. For GS, the multi-trait genomic best linear unbiased prediction (GBLUP) model results in more accurate predictions for virtually all traits compared to the single-trait model, with improvements greater than 15% for all of them, which may be attributed to the use of information on genetically related traits. In addition, we discovered a positive correlation between the performance of the multi-trait GBLUP and the genetic correlation between the traits. We anticipate that this approach will provide solutions for GS, as well as optimize breeding programs, in meat rabbits.

Whole transcriptome sequencing reveals key genes and ceRNA regulatory networks associated with pimpled eggs in hens.

Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.

Identify Candidate Genes Associated with the Weight and Egg Quality Traits in Wenshui Green Shell-Laying Chickens by the Copy Number Variation-Based Genome-Wide Association Study.

Copy number variation (CNV), as an essential source of genetic variation, can have an impact on gene expression, genetic diversity, disease susceptibility, and species evolution in animals. To better understand the weight and egg quality traits of chickens, this paper aimed to detect CNVs in Wenshui green shell-laying chickens and conduct a copy number variation regions (CNVRs)-based genome-wide association study (GWAS) to identify variants and candidate genes associated with their weight and egg quality traits to support related breeding efforts. In our paper, we identified 11,035 CNVRs in Wenshui green shell-laying chickens, which collectively spanned a length of 13.1 Mb, representing approximately 1.4% of its autosomal genome. Out of these CNVRs, there were 10,446 loss types, 491 gain types, and 98 mixed types. Notably, two CNVRs showed significant correlations with egg quality, while four CNVRs exhibited significant associations with body weight. These significant CNVRs are located on chromosome 4. Further analysis identified potential candidate genes that influence weight and egg quality traits, including FAM184B, MED28, LAP3, ATOH8, ST3GAL5, LDB2, and SORCS2. In this paper, the CNV map of the Wenshui green shell-laying chicken genome was constructed for the first time through population genotyping. Additionally, CNVRs can be employed as molecular markers to genetically improve chickens' weight and egg quality traits.

Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity.

Due to its unique structure, articular cartilage has limited abilities to undergo self-repair after injury. Additionally, the repair of articular cartilage after injury has always been a difficult problem in the field of sports medicine. Previous studies have shown that the therapeutic use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) has great potential for promoting cartilage repair. Recent studies have demonstrated that most transplanted stem cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are subsequently generated play crucial roles in tissue repair. Additionally, MSCs are known to exist under low-oxygen conditions in the physiological environment, and these hypoxic conditions can alter the functional and secretory properties of MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs that are isolated from adipose-derived MSCs cultured under hypoxic conditions (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than those that are isolated from cells cultured under normoxic conditions. Through in vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs exerted enhanced effects on stem cell proliferation, stem cell migration, and bone marrow derived macrophages (BMDMs) M2 polarization compared to ApoEVs. Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM scaffold provided mechanical support and created a microenvironment that was conducive to cartilage regeneration, and the H-ApoEVs further enhanced the regenerative capacity of endogenous stem cells and the immunomodulatory microenvironment of the joint cavity; thus, this approach significantly promoted cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery system based on a modified gelatine matrix/3D-printed ECM scaffold together with hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs and represents a promising approach for promoting cartilage regeneration.

A Countertraction Closed Reduction Technique in Minimally Invasive Fixation of Recent Type C Pelvic Ring Injuries.

OBJECTIVE: Closed reduction of pelvic injuries is a prerequisite and critical step in minimally invasive treatment. Achieving non-invasive closed reduction of pelvic injuries is a challenging clinical problem. This study demonstrated a non-invasive traction technique for closed reduction called countertraction closed reduction technique (CCRT) and evaluated its effectiveness for type C pelvic ring injuries. METHOD: The data of patients with unstable pelvic fractures treated with CCRT and minimally invasive fixation were retrospectively reviewed from January 2017 to February 2022. Sacroiliac screws were placed to fix the posterior pelvic ring, and internal or external fixation was used to fix the anterior pelvic ring. Operation time, intraoperative blood loss, duration of hospital stay, fracture union and postoperative complications were recorded. Fracture reduction quality was evaluated using the Matta scoring criteria. Functional recovery and general quality of life were evaluated using the Majeed functional scoring criteria. RESULTS: Thirteen patients (nine males and four females), with an average age of 49.6 years were treated with CCRT and followed up for a mean of 18.5 months. The average operation time was 137.2 minutes (range 92-195 minutes), the average intraoperative blood loss was 31.2 mL (range 10-120 mL) and the average duration of hospital stay was 14.3 days (range 4-32 days). All patients achieved bony union with an average union time of 11.9 weeks (range 10-16 weeks). According to the Matta radiographic criteria, the quality of fracture reduction was excellent in eight patients, good in four, and fair in one. The average Majeed functional score was 89.7 (range 78-100). The functional evaluation revealed that the outcomes were excellent in nine patients, and good in four patients. Complications included incision fat liquefaction in one patient, and heterotopic ossification in another patient. There were no surgical complications as a result of CCRT. CONCLUSION: CCRT is a non-invasive closed reduction method for minimally invasive fixation of fresh Tile C1 and C2 pelvic fractures. The advantages of CCRT combined with minimally invasive treatment include a small surgical incision, reduced intraoperative bleeding, satisfactory fracture reduction, bone healing and functional recovery.

ToxMPNN: A deep learning model for small molecule toxicity prediction.

Machine learning (ML) has shown a great promise in predicting toxicity of small molecules. However, the availability of data for such predictions is often limited. Because of the unsatisfactory performance of models trained on a single toxicity endpoint, we collected toxic small molecules with multiple toxicity endpoints from previous study. The dataset comprises 27 toxic endpoints categorized into seven toxicity classes, namely, carcinogenicity and mutagenicity, acute oral toxicity, respiratory toxicity, irritation and corrosion, cardiotoxicity, CYP450, and endocrine disruption. In addition, a binary classification Common-Toxicity task was added based on the aforementioned dataset. To improve the performance of the models, we added marketed drugs as negative samples. This study presents a toxicity predictive model, ToxMPNN, based on the message passing neural network (MPNN) architecture, aiming to predict the toxicity of small molecules. The results demonstrate that ToxMPNN outperforms other models in capturing toxic features within the molecular structure, resulting in more precise predictions with the ROC_AUC testing score of 0.886 for the Toxicity_drug dataset. Furthermore, it was observed that adding marketed drugs as negative samples not only improves the predictive performance of the binary classification Common-Toxicity task but also enhances the stability of the model prediction. It shows that the graph-based deep learning (DL) algorithms in this study can be used as a trustworthy and effective tool to assess small molecule toxicity in the development of new drugs.