Dual-molecular targeting nanomedicine upregulates synergistic therapeutic efficacy in preclinical hepatoma models.

Advanced hepatocellular carcinoma (HCC) is one of the most challenging cancers because of its heterogeneous and aggressive nature, precluding the use of curative treatments. Sorafenib (SOR) is the first approved molecular targeting agent against the mitogen-activated protein kinase (MAPK) pathway for the noncurative therapy of advanced HCC; yet, any clinically meaningful benefits from the treatment remain modest, and are accompanied by significant side effects. Here, we hypothesized that using a nanomedicine platform to co-deliver SOR with another molecular targeting drug, metformin (MET), could tackle these issues. A micelle self-assembled with amphiphilic polypeptide methoxy poly(ethylene glycol)-block-poly(L-phenylalanine-co-L-glutamic acid) (mPEG-b-P(LP-co-LG)) (PM) was therefore designed for combinational delivery of two molecular targeted drugs, SOR and MET, to hepatomas. Compared with free drugs, the proposed, dual drug-loaded micelle (PM/SOR+MET) enhanced the drugs' half-life in the bloodstream and drug accumulation at the tumor site, thereby inhibiting tumor growth effectively in the preclinical subcutaneous, orthotopic and patient-derived xenograft hepatoma models without causing significant systemic and organ toxicity. Collectively, these findings demonstrate an effective dual-targeting nanomedicine strategy for treating advanced HCC, which may have a translational potential for cancer therapeutics. STATEMENT OF SIGNIFICANCE: Treatment of advanced hepatocellular carcinoma (HCC) remains a formidable challenge due to its aggressive nature and the limitations inherent to current therapies. Despite advancements in molecular targeted therapies, such as Sorafenib (SOR), their modest clinical benefits coupled with significant adverse effects underscore the urgent need for more efficacious and less toxic treatment modalities. Our research presents a novel nanomedicine platform that synergistically combines SOR with metformin within a specialized diblock polypeptide micelle, aiming to enhance therapeutic efficacy while reducing systemic toxicity. This innovative approach not only exhibits marked antitumor efficacy across multiple HCC models but also significantly reduces the toxicity associated with current treatments. Our dual-molecular targeting approach unveils a promising nanomedicine strategy for the molecular treatment of advanced HCC, potentially offering more effective and safer treatment alternatives with significant translational potential.

Integrated transcriptomic and metabolomic data reveal the cold stress responses molecular mechanisms of two coconut varieties.

Among tropical fruit trees, coconut holds significant edible and economic importance. The natural growth of coconuts faces a challenge in the form of low temperatures, which is a crucial factor among adverse environmental stresses impacting their geographical distribution. Hence, it is essential to enhance our comprehension of the molecular mechanisms through which cold stress influences various coconut varieties. We employed analyses of leaf growth morphology and physiological traits to examine how coconuts respond to low temperatures over 2-hour, 8-hour, 2-day, and 7-day intervals. Additionally, we performed transcriptome and metabolome analyses to identify the molecular and physiological shifts in two coconut varieties displaying distinct sensitivities to the cold stress. As the length of cold stress extended, there was a prominent escalation within the soluble protein (SP), proline (Pro) concentrations, the activity of peroxidase (POD) and superoxide dismutase (SOD) in the leaves. Contrariwise, the activity of glutathione peroxidase (GSH) underwent a substantial reduction during this period. The widespread analysis of metabolome and transcriptome disclosed a nexus of genes and metabolites intricately cold stress were chiefly involved in pathways centered around amino acid, flavonoid, carbohydrate and lipid metabolism. We perceived several stress-responsive metabolites, such as flavonoids, carbohydrates, lipids, and amino acids, which unveiled considerably, lower in the genotype subtle to cold stress. Furthermore, we uncovered pivotal genes in the amino acid biosynthesis, antioxidant system and flavonoid biosynthesis pathway that presented down-regulation in coconut varieties sensitive to cold stress. This study broadly enriches our contemporary perception of the molecular machinery that contributes to altering levels of cold stress tolerance amid coconut genotypes. It also unlocks several unique prospects for exploration in the areas of breeding or engineering, aiming to identifying tolerant and/or sensitive coconut varieties encompassing multi-omics layers in response to cold stress conditions.

A new technique of intramedullary elastic reduction of the "de-sharpened" Kirschner wire for the treatment of Gartland type III posterolateral displaced supracondylar fracture of the humerus in children.

OBJECTIVE: To compare the clinical effects of intramedullary elastic reduction of the "de-sharpened Kirschner wire and traditional three-dimensional manipulation in the treatment of Gartland type III posterolateral supracondylar fracture of the humerus in children. METHODS: A retrospective cohort analysis was made on 106 cases of Gartland type III posterolateral supracondylar fracture of the humerus treated in the Department of Orthopaedics of a Children's Hospital from March 2020 to March 2022. According to different surgical technology, the patients were divided into two groups: intramedullary elastic reduction of the de-sharpened Kirschner wire group (experimental group, n = 50) and traditional three-dimensional manipulation group (control group, n = 56). The surgical operating time, intraoperative fluoroscopy times, postoperative Baumann angle changes, postoperative elbow function Flynn score, and complications were collected and compared between the two groups. RESULTS: All the enrolled cases underwent surgery successfully and were followed-up at least 6 months. The surgical operating time of the experimental group was 32.88 ± 3.69 min and that of the control group was 45.56 ± 10.13 min, and the difference was statistically significant (P < 0.05). The intraoperative fluoroscopy times were 20.62 ± 5.41 times in the experimental group and 32.48 ± 8.20 times in the control group (P < 0.05). The change of Baumann angle in the experimental group after operation was 2.3 ± 1.3 and that in the control group was 6.0 ± 2.1 (P < 0.5). Elbow joint Flynn scoring standard to evaluate the curative effect: the excellent and good rate was 98.00% (49/50) in the experimental group and 92.86% (52/56) in the control group (P > 0.5). There were no complications such as osteomyelitis, compartment syndrome, iatrogenic vascular and nerve injury, and myositis ossificans in either group. CONCLUSIONS: Good functional outcome can be obtained with both intramedullary elastic reduction of the de-sharpened Kirschner wire and traditional three-dimensional manipulation for Gartland type III posterolateral displaced supracondylar fracture of the humerus in children; however, the former does not need repeated manipulation, and the operation time is shorter, the number of intraoperative fluoroscopy is less, and the recovery of the Baumann angle is better.

Comparative Transcriptome Analysis Provides Insights into the Effect of Epicuticular Wax Accumulation on Salt Stress in Coconuts.

The coconut is an important tropical economical crop and exhibits high tolerance to various types of salinity stress. However, little is known about the molecular mechanism underlying its salt tolerance. In this study, RNA-Seq was applied to examine the different genes expressed in four coconut varieties when exposed to a salt environment, resulting in the generation of data for 48 transcriptomes. Comparative transcriptome analysis showed that some genes involved in cutin and wax biosynthesis were significantly upregulated in salt treatment compared to the control, including CYP86A4, HTH, CER1, CER2, CER3, DCR, GPAT4, LTP3, LTP4, and LTP5. In particular, the expression of CER2 was induced more than sixfold, with an RPKM value of up to 205 ten days after salt treatment in Hainan Tall coconut, demonstrating superior capacity in salt tolerance compared to dwarf coconut varieties. However, for yellow dwarf and red dwarf coconut varieties, the expression level of the CER2 gene was low at four different time points after exposure to salt treatment, suggesting that this gene may contribute to the divergence in salt tolerance between tall and dwarf coconut varieties. Cytological evidence showed a higher abundance of cuticle accumulation in tall coconut and severe damage to cuticular wax in dwarf coconut.

Combined transcriptome and metabolome analysis of sugar and fatty acid of aromatic coconut and non-aromatic coconut in China.

Sugar and fatty acid content are among the important factors that contribute to the intensity of flavor in aromatic coconut. Gaining a comprehensive understanding of the sugar and fatty acid metabolites in the flesh of aromatic coconuts, along with identifying the key synthetic genes, is of significant importance for improving the development of desirable character traits in these coconuts. However, the related conjoint analysis of metabolic targets and molecular synthesis mechanisms has not been carried out in aromatic coconut until now. UPLC-MS/MS combined with RNA-Seq were performed in aromatic coconut (AC) and non-aromatic coconut (NAC) meat at 7, 9 and 11 months. The results showed that D-fructose in AC coconut meat was 3.48, 2.56 and 3.45 fold higher than that in NAC coconut meat. Similarly, D-glucose in AC coconut meat was 2.48, 2.25 and 3.91 fold higher than that in NAC coconut meat. The NAC coconut meat showed a 1.22-fold rise in the content of lauric acid compared to the AC coconut meat when it reached 11 months of age. Myristic acid content in NAC coconut meat was 1.47, 1.44 and 1.13 fold higher than that in AC coconut meat. The palmitic acid content in NAC coconut meat was 1.62 and 1.34 fold higher than that in AC coconut meat. The genes SPS, GAE, GALE, GLCAK, UGE, UGDH, FBP, GMLS, PFK, GPI, RHM, ACC, FabF, FatA, FabG, and FabI exhibited a negative correlation with D-fructose (r = -0.81) and D-glucose (r = -0.99) contents, while showing a positive correlation (r = 0.85-0.96) with lauric acid and myristic acid. Furthermore, GALE, GLCAK, FBP, GMLS, and ACC displayed a positive correlation (r = 0.83-0.94) with palmitic acid content. The sugar/organic acid ratio exhibited a positive correlation with SPS, GAE, UGE, FabF, FabZ and FabI.

Risk factor analysis of femoral avascular necrosis after operation for Tönnis grade IV developmental dysplasia of the hip.

PURPOSE: We explored the risk factors for avascular necrosis (AVN) after surgery using open reduction, pelvic osteotomy, and femoral osteotomy for Tönnis grade IV developmental dysplasia of the hip (DDH). METHODS: In this retrospective study, we collected data of patients with Tönnis grade IV DDH treated with open reduction and pelvic osteotomy combined with femoral osteotomy from January 2012 to May 2020. The patients were divided into the AVN group and non-AVN group using the Kalamchi-MacEwen classification system. The clinical and imaging data of the two groups were collected, and the possible risk factors were included in the analysis. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors and odds ratios of AVN. RESULTS: In all, 254 patients (mean age; 2.6±0.9 years, 278 hips) were included. The mean follow-up time was 3.8±1.5 years. A total of 89 hips (32%) were finally classified as AVN (Kalamchi-MacEwen II-IV). Univariate analysis showed significant associations with AVN for age (p=0.006), preoperative femoral neck anteversion (FAV) (p<0.001), femoral osteotomy length to dislocation height ratio (FDR) <1 (p<0.001), and the epiphyseal ossific nucleus diameter to the neck diameter ratio (ENR) <50% (p=0.009). Multivariate logistic regression analysis showed that only excessive preoperative FAV (OR: 1.04; 95% CI: 1.02-1.05; p<0.001) and FDR<1 (OR: 3.58; 95% CI: 2.03-6.31; p<0.001) were independent risk factors for femoral head necrosis. CONCLUSION: Excessive preoperative FAV and FDR<1 are important risk factors for femoral AVN after open reduction, pelvic osteotomy, and femoral osteotomy for Tönnis grade IV DDH. For children with DDH with high dislocation and excessive FAV, clinicians should fully evaluate their condition and design more personalized treatment programs to prevent AVN.

Widely targeted metabolomics combined with E-tongue and E-nose reveal dynamic changes of tender coconut water in responses to the infection of Ceratocystis paradoxa.

Ceratocystis paradoxa is a major cause of postharvest disease in tender coconuts worldwide. We conducted a comprehensive study using widely targeted metabolomics, electronic tongue (E-tongue), and electronic nose (E-nose) analyses to investigate the impacts of C. paradoxa invasion on the quality of tender coconut water (TCW) from fresh control (FC), uninoculated (UN), skin-inoculated (SI), and deep-inoculated (DI) nuts. DI exhibited significantly higher taste indicators associated with bitterness, saltiness, astringency aftertaste, and bitter aftertaste, as well as odor sensor values related to various compounds such as long-chain alkanes, hydrides, methane, organic sulfides, etc. Invasion of C. paradoxa into the endosperm altered the flavor characteristics of TCW mainly through the modulation of carbohydrate and secondary metabolite pathways. Furthermore, significant correlations were observed between the differentially expressed flavorful metabolites and the sensor indicators of the E-nose and E-tongue. These findings offer valuable insights into understanding the impact of C. paradoxa infection on coconuts.

Kirschner wire reconstruction of medial and lateral column periosteal hinge in the treatment of multidirectionally unstable supracondylar fracture of the humerus in children.

AIM AND OBJECTIVE: To compare the clinical effect of reconstruction of internal and lateral column periosteal hinge-assisted treatment with Kirschner wire and internal fixation with Kirschner wire in the treatment of multidirectional unstable supracondylar fractures of humerus in children. METHODS: A retrospective cohort study was conducted to analyze the clinical data of 48 patients (31 male, 17 female; mean age: 6.7 ± 2.4 years old) with multidirectionally unstable supracondylar fractures of the humerus treated in our Hospital from August 2020 to August 2022. Twenty-five cases were treated with Kirschner wire reconstruction of the internal and lateral column periosteal hinge assisted by closed reduction and Kirschner wire internal fixation (study group). Twenty-three cases were treated with closed reduction and Kirschner wire internal fixation (control group). The operation time, intraoperative fluoroscopy times, percentage of patients who underwent open reduction after failure of closed reduction, fracture healing time, Baumann angle (BA), shaft-condylar angle (SCA), range of motion (ROM), and Flynn score of elbow at the last follow-up were compared between two groups. Complications such as infection and irritation of Kirschner wire tail were observed in two groups 2 months after the operation. RESULTS: All patients were followed up for 10-22 months ([13.85 ± 2.89] months). The average operation time of the control group was 82.1 min, which was significantly longer than that of the study group 32.3 min (P < 0.05). The number of intraoperative fluoroscopy (29.4 ± 9.2) in the control group was significantly higher than that in the study group (15.2 ± 6.3) (P < 0.05). The incision rate of the control group was 17% while that of the study group was 0 (P < 0.05). According to Flynn score, the excellent and good rate of the elbow joint in the control group was 86.9% (20/23). The excellent and good rate of the elbow joint in the study group was 92.0% (23/25) (P > 0.05). There was no significant difference in fracture healing time, BA, SCA, and ROM between the two groups (P > 0.05). No infection or Kirschner wire tail irritation occurred in the two groups during the 2-month follow-up. CONCLUSION: Reconstruction of internal and lateral periosteal hinges with Kirscher wire has similar effects to closed reduction and Kirschner wire fixation in the treatment of multidirectionally unstable supracondylar fractures of the humerus in children, but it can shorten the operation time and reduce intraoperative fluoroscopy times and incision rate.

[Short-term effectiveness of ultrasound-guided Kirschner wire provocation technique in treatment of Salter-Harris types â and â ¡ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents].

Objective: To investigate the short-term effectiveness of ultrasound-guided closed reduction by Kirschner wire provocation technique in the treatment of Salter-Harris types Ⅰ and Ⅱ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents. Methods: Between May 2019 and May 2022, 41 patients with Salter Harris types Ⅰ and Ⅱ distal tibial epiphyseal fractures were admitted, all of whom had periosteal entrapment on preoperative MRI, and 38 cases (92.7%) were confirmed to have periosteal entrapment by intraoperative ultrasound. There were 24 males and 14 females, the age ranged from 6.8 to 15.7 years, with an average of 10.7 years; and there were 20 cases of Salter Harris type Ⅰ and 18 cases of type Ⅱ. The time from injury to operation was 22-76 hours, with an average of 28.4 hours. The preoperative imaging examination showed excellent alignment in 4 cases, good in 20 cases, and poor in 14 cases. The ultrasound guided Kirschner wire provocation technique for closed reduction and percutaneous Kirschner wire internal fixation were performed. The operation time, intraoperative fluoroscopy frequency, fracture healing time, and complications were recorded. Anteroposterior and lateral X-ray films of the affected ankle joint were taken before operation, at 3 months after operation, and at last follow-up to observe the healing of the fracture, and anteroposterior X-ray films of the whole length of both lower limbs were taken to evaluate the alignment of the force lines of the affected limbs. The range of motion (ROM), visual analogue scale (VAS) score, and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were used to evaluate ankle function. The mechanical lateral distal tibia angle (mLDTA) and the anatomic anterior distal tibia angle (aADTA) were measured. Results: The operation time ranged from 17 to 52 minutes, with an average of 22.6 minutes, and the intraoperative fluoroscopy frequency ranged from 3 to 11 times, with an average of 4.2 times. X-ray examination during operation and at 2 days after operation showed that anatomical reduction was achieved. All patients were followed up 10-24 months, with an average of 16.4 months. All fractures healed in 6.1-7.2 weeks, with an average of 6.3 weeks; no fracture displacement occurred, and the patients recovered to their pre-injury level of motion at 6 months after operation. Needle tail irritation occurred in 2 cases at 4 weeks after operation, and they recovered after symptomatic treatment. During the follow-up, there was no serious complication such as incision deep infection, bone nonunion, delayed union, and malunion. At last follow-up, the patients' alignment were all excellent, and the difference was significant when compared with preoperative one ( Z=-7.471, P<0.001). The VAS score, AOFAS ankle-hindfoot score, dorsiflexion-plantar flexion ROM, varus-valgus ROM, mLDTA, and aADTA significantly improved at 3 months after operation and last follow-up when compared with preoperative ones ( P<0.05). Conclusion: Ultrasound-guided closed reduction by Kirschner wire provocation technique for treating Salter-Harris types Ⅰ and Ⅱ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents is minimally invasive and safe.

Clinical effect of endovascular repair of complex aortic lesions using optimized Octopus surgery.

Objective: Complex aortic lesions, especially those involving branches of the visceral artery, remain a challenge to treat. A single-center study using the Octopus technique to evaluate the safety and short-term effects of endovascular repair of complex aortic lesions was reported and documented. Methods: The data of six cases who underwent optimized Octopus surgery in our center from August 2020 to February 2022 were analyzed retrospectively. The choice of operation scheme, operation time, operation complications, and follow-up data were analyzed among them. Results: The average age of the six patients undergoing optimized Octopus surgery was 55.1 ± 17.2 years. Two cases were diagnosed as pararenal aortic aneurysms; four cases were aortic dissection involving the visceral artery. All cases achieved technical success; all visceral arteries were reconstructed as planned. A total of 17 visceral arteries were planned to be reconstructed; five celiac arteries were embolized. Three cases of gutter endoleak were found during the operation without embolization but with follow-up observation. There were two cases of slight damage to renal function and two cases of perioperative death. Other complications, such as intestinal ischemia and spinal cord ischemia, did not occur. Follow-up ranged from 6 months to 30 months. One patient died of gastrointestinal bleeding 6 months after the operation. At the 6 months follow-up, computed tomographic angiography showed that all internal leaks had disappeared. The patency rate of the visceral artery was 100%, and no complications, such as stent displacement and occlusion, occurred during the follow-up period. Conclusion: With fenestrated and branched stent grafts technology not widely available, and off label use not a viable option, Octopus technology for treating complex aortic lesions should be considered. The Octopus technique is an up-and-coming surgical method, but we should recognize its operation difficulty, operation-related complications, and long-term prognosis. We should pay attention to and continue to optimize Octopus technology.

[Comparative study on effectiveness of ultrasound- and arthrography-assisted Kirschner wire fixation in treatment of Jakob type â ¡ lateral condylar humerus fractures in children].

Objective: To compare the effectiveness of ultrasound- and arthrography-assisted Kirschner wire fixation in the treatment of Jakob type Ⅱ lateral condylar humerus fracture (LCHF) in children. Methods: A clinical data of 101 children with Jakob type Ⅱ LCHF, who met the selection criteria and were admitted between April 2021 and April 2022, was retrospectively analyzed. Of them, 47 cases were treated with ultrasound-assisted Kirschner wire fixation (group A), and 54 cases with arthrography-assisted surgery (group B). There was no significant difference in gender, age, cause of injury, fracture side, and disease duration between groups (P>0.05). Intraoperative fluoroscopy times, operation time, and hospital stay, Flynn elbow joint function score, and postoperative complications were recorded and compared between groups. X-ray examination was performed to observe the healing of fracture, and measure the carrying angle and the shaft-condylar angle (SCA). Results: The success rate of closed reduction was significantly higher in group A than in group B (P<0.05), and the intraoperative fluoroscopy times was significantly less in group A than in group B (P<0.05). There was no significant difference in operation time and hospital stay between groups (P>0.05). All children in both groups were followed up 12-18 months, with an average of 13.6 months. X-ray reexamination showed that the fractures of both groups healed, and the difference in healing time was not significant (P>0.05). At last follow-up, there was no significant difference in carrying angle and SCA between unaffected side and affected side in both groups and between groups A and B in affected side (P>0.05). There was no significant difference in Flynn elbow joint function score between groups (P>0.05). There were 18 cases of lateral spurs formation in group A, 1 case of pinning infection and 26 cases of lateral spurs formation in group B, and there was no significant difference in the incidence of the above complications (P>0.05). Conclusion: Compared with the arthrography, the ultrasound-assisted Kirschner wire fixation in the treatment of Jakob type Ⅱ LCHF in children can avoid the open reduction and decrease the number of intraoperative fluoroscopy, and obtain the good effectiveness.

The impact of exosomes derived from distinct sources on rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that can induce joint deformities and functional impairment, significantly impacting the overall well-being of individuals. Exosomes, which are cellularly secreted vesicles, possess favorable biological traits such as biocompatibility, stability, and minimal toxicity. Additionally, they contain nucleic acids, lipids, proteins, amino acids, and metabolites, serving as mediators in cellular communication and information exchange. Recent studies have demonstrated the association between exosomes and the pathogenesis of RA. Exosomes derived from mesenchymal stem cells, dendritic cells, and neutrophils exert influence on the biological functions of immune cells and joint cells, however, the precise mechanism remains largely unclarified. This comprehensive review systematically analyzes and summarizes the biological characteristics and functionalities of exosomes derived from diverse cellular sources, thus establishing a scientific foundation for the utilization of exosomes as diagnostic targets and therapeutic modalities in the context of RA.

Human descending aorta injury caused by brucellosis: A case report.

BACKGROUND: Brucellosis is one of the most common zoonotic diseases in the world. Although cardiovascular complications of human brucellosis account for only 3% of morbidity, they are the leading cause of death. Peripheral vascular disease due to brucellosis is rare and under-reported in the literature. CASE PRESENTATION: Two patients with previous brucellosis, both of whom had been treated with anti-brucellosis, were admitted to vascular surgery for thoracic aortic ulcer and abdominal aortic pseudoaneurysm, respectively, with positive IgG antibody to brucellosis and negative IgM antibody to brucellosis, tube agglutination test, and blood culture. These 2 patients were successfully treated with aortic stent-graft implantation and followed up for 8 and 10 weeks without complications. CONCLUSIONS: Chronic damage to human blood vessels by brucellosis may not disappear with brucellosis treatment, and peripheral blood vessels should be examined annually in people previously diagnosed with brucellosis. Clinicians in related departments should pay attention to peripheral vascular complications of brucellosis.

Treatment of abdominal aortic pseudoaneurysm caused by brucellosis with endovascular aneurysm repair.

Peripheral vascular disease caused by brucellosis is rarely seen around the world; thus, it is easily ignored by patients and doctors, leading to a lack of corresponding screening and delayed comprehensive treatment. Currently, there is no standard or guideline for diagnosing and treating peripheral arterial disease caused by brucellosis. From June 2021 to December 2022, four cases of abdominal aortic pseudoaneurysm caused by brucellosis disease were treated with endovascular aneurysm repair This study reported treatment results as follows and reviewed the incidence, treatment, and prognosis of abdominal aortic pseudoaneurysm caused by brucellosis.

Genome-wide identification, classification and expression analysis of MYB gene family in coconut (Cocos nucifera L.).

MYB transcription factors regulate the growth, development, and secondary metabolism of plant species. To investigate the origin of color variations in coconut pericarp, we identified and analyzed the MYB gene family present in coconut. According to the sequence of MYB genes in Arabidopsis thaliana, homologous MYB gene sequences were found in the whole genome database of coconut, the conserved sequence motifs within MYB proteins were analyzed by Motif Elicitation (MEME) tool, and the sequences without conservative structure were eliminated. Additionally, we employed RNA-seq technology to generate gene expression signatures of the R2R3-MYB genes across distinctive coconut parts exhibiting diverse colors. To validate these profiles, we conducted quantitative PCR (qPCR). Through comprehensive genome-wide screening, we successfully identified a collection of 179 MYB genes in coconut. Subsequent phylogenetic analysis categorized these 179 coconut MYB genes into 4-subfamilies: 124 R2R3-MYB, 4 3R-MYB types, 4 4R-MYB type, and 47 unknown types. Furthermore, these genes were further divided into 34 subgroups, with 28 of these subgroups successfully classified into known subfamilies found in Arabidopsis thaliana. By mapping the CnMYB genes onto the 16 chromosomes of the coconut genome, we unveiled a collinearity association between them. Moreover, a preservation of gene structure and motif distribution was observed across the CnMYB genes. Our research encompassed a thorough investigation of the R2R3-MYB genes present in the coconut genome, including the chromosomal localization, gene assembly, conserved regions, phylogenetic associations, and promoter cis-acting elements of the studied genes. Our findings revealed a collection of 12 R2R3-MYB candidate genes, namely CnMYB8, CnMYB15, CnMYB27, CnMYB28, CnMYB61, CnMYB63, CnMYB68, CnMYB94, CnMYB101, CnMYB150, CnMYB153, and CnMYB164. These genes showed differential expressions in diverse tissues and developmental stages of four coconut species, such as CnMYB68, CnMYB101, and CnMYB28 exhibited high expression in majority of tissues and coconut species, while CnMYB94 and CnMYB164 showed lower expression. These findings shed light on the crucial functional divergence of CnMYB genes across various coconut tissues, suggesting these genes as promising candidate genes for facilitating color development in this important crop.

Mixed model-based deconvolution of cell-state abundances (MeDuSA) along a one-dimensional trajectory.

Deconvoluting cell-state abundances from bulk RNA-sequencing data can add considerable value to existing data, but achieving fine-resolution and high-accuracy deconvolution remains a challenge. Here we introduce MeDuSA, a mixed model-based method that leverages single-cell RNA-sequencing data as a reference to estimate cell-state abundances along a one-dimensional trajectory in bulk RNA-sequencing data. The advantage of MeDuSA lies primarily in estimating cell abundance in each state while fitting the remaining cells of the same type individually as random effects. Extensive simulations and real-data benchmark analyses demonstrate that MeDuSA greatly improves the estimation accuracy over existing methods for one-dimensional trajectories. Applying MeDuSA to cohort-level RNA-sequencing datasets reveals associations of cell-state abundances with disease or treatment conditions and cell-state-dependent genetic control of transcription. Our study provides a high-accuracy and fine-resolution method for cell-state deconvolution along a one-dimensional trajectory and demonstrates its utility in characterizing the dynamics of cell states in various biological processes.

An exploratory transmission mode of HIV/AIDS among older people based on data from multiple sources in China.

The HIV/AIDS cases and proportion in older people are continuously and rapidly increasing in China, especially in males. However, the transmission mechanism is not well understood. This study aims to explore the transmission mechanism of HIV/AIDS and potential ways to prevent or control HIV/AIDS transmission in a city in southwestern China. Data from multiple sources, including HIV/AIDS case reports in 2010-2020, a survey of HIV/AIDS cases in 2020, and sentinel surveillance data of female sex workers (FSWs) in 2016-2020 were analyzed. We explored the transmission mechanism of HIV/AIDS cases aged 50 years and older. In this city, the number of newly reported HIV/AIDS cases aged 50 years and older increased from 2010 to 2019, and decreased in 2020. The number of male and female cases aged 50 years and older both increased rapidly in 2017-2019, though the number of male cases was larger than that of female. The survey data showed that 84.7% of older male cases reported commercial sexual behavior, among whom 87.7% reported never using condom and 37.6% reported more than 10 times of commercial sexual behaviors in 1 year. In terms of price of sexual behavior, 68.3% of older male cases sought low-tier FSWs among whom the HIV/AIDS positive rate was 5.4% from the sentinel surveillance data. These results suggested HIV transmission between older men and low-tier FSWs through commercial sexual behavior. Among female cases aged 50 years and older, most reported non-marital and non-commercial heterosexual (60.5%) or regular sexual partner (31.4%) transmission, suggesting that they were infected by their spouse/regular sexual partner. Data of matched couples showed that most male cases had both marital sexual behavior and commercial sexual behavior, or acquired HIV through commercial sexual behavior, while most female cases had only marital sexual behavior. Based on these findings, we proposed a transmission mode of that local older male people and FSWs are transmitting bilaterally through commercial sexual behavior, and local older male people are spreading to local older female people through spouse or regular sexual partner route. By studying data from multiple sources, we explored the HIV transmission mode among older people. In the meantime, we found that marital status had a different impact on male and female old people in their sex behaviors.

Development of Intron Polymorphism Markers and Their Association With Fatty Acid Component Variation in Oil Palm.

Oil palm (Elaeis guineensis Jacq.) is a tropical woody oil crop of the palm family and is known as "the oil king of the world," but its palm oil contains about 50% palmitic acid, which is considered unhealthy for humans. Intron polymorphisms (IP) are highly efficient and easily examined molecular markers located adjacent to exon regions of functional genes, thus may be associated with targeted trait variation. In order to speed up the breeding of oil palm fatty acid composition, the current study identified a total of 310 introns located within 52 candidate genes involved in fatty acid biosynthesis in the oil palm genome. Based on the intron sequences, 205 primer pairs were designed, 64 of which showed polymorphism among 70 oil palm individuals. Phenotypic variation of fatty acid content in the 70 oil palm individuals was also investigated. Association analysis revealed that 13 IP markers were significantly associated with fatty acid content variation, and these IP markers were located on chromosomes 2, 5, 6, 8, 9, and 10 of oil palm. The development of such IP markers may be useful for the genetic improvement of fatty acid composition in oil palm.

Developing functional markers for vitamin E biosynthesis in oil palm.

Vitamin E is essential for human health and plays positive roles in anti-oxidation. Previously, we detected large variation in vitamin E content among 161 oil palm accessions. In this study, twenty oil palm accessions with distinct variation in vitamin E contents (171.30 to 1 258.50 ppm) were selected for genetic variation analysis and developing functional markers associated with vitamin E contents. Thirty-seven homologous genes in oil palm belonging to vitamin E biosynthesis pathway were identified via BLASTP analysis, the lengths of which ranged from 426 to 25 717 bp (average 7 089 bp). Multiplex PCR sequencing for the 37 genes found 1 703 SNPs and 85 indels among the 20 oil palm accessions, with 226 SNPs locating in the coding regions. Clustering analysis for these polymorphic loci showed that the 20 oil palm accessions could be divided into five groups. Among these groups, group I included eight oil palm accessions whose vitamin E content (mean value: 893.50 ppm) was far higher than other groups (mean value 256.29 to 532.94 ppm). Correlation analysis between the markers and vitamin E traits showed that 134 SNP and 7 indel markers were significantly (p < 0.05) related with total vitamin E content. Among these functional markers, the indel EgTMT-1-24 was highly correlated with variation in vitamin E content, especially tocotrienol content. Our study identified a number of candidate function associated markers and provided clues for further research into molecular breeding for high vitamin E content oil palm.

An integrated epigenomic-transcriptomic landscape of lung cancer reveals novel methylation driver genes of diagnostic and therapeutic relevance.

Background: Aberrant DNA methylation occurs commonly during carcinogenesis and is of clinical value in human cancers. However, knowledge of the impact of DNA methylation changes on lung carcinogenesis and progression remains limited. Methods: Genome-wide DNA methylation profiles were surveyed in 18 pairs of tumors and adjacent normal tissues from non-small cell lung cancer (NSCLC) patients using Reduced Representation Bisulfite Sequencing (RRBS). An integrated epigenomic-transcriptomic landscape of lung cancer was depicted using the multi-omics data integration method. Results: We discovered a large number of hypermethylation events pre-marked by poised promoter in embryonic stem cells, being a hallmark of lung cancer. These hypermethylation events showed a high conservation across cancer types. Eight novel driver genes with aberrant methylation (e.g., PCDH17 and IRX1) were identified by integrated analysis of DNA methylome and transcriptome data. Methylation level of the eight genes measured by pyrosequencing can distinguish NSCLC patients from lung tissues with high sensitivity and specificity in an independent cohort. Their tumor-suppressive roles were further experimentally validated in lung cancer cells, which depend on promoter hypermethylation. Similarly, 13 methylation-driven ncRNAs (including 8 lncRNAs and 5 miRNAs) were identified, some of which were co-regulated with their host genes by the same promoter hypermethylation. Finally, by analyzing the transcription factor (TF) binding motifs, we uncovered sets of TFs driving the expression of epigenetically regulated genes and highlighted the epigenetic regulation of gene expression of TCF21 through DNA methylation of EGR1 binding motifs. Conclusions: We discovered several novel methylation driver genes of diagnostic and therapeutic relevance in lung cancer. Our findings revealed that DNA methylation in TF binding motifs regulates target gene expression by affecting the binding ability of TFs. Our study also provides a valuable epigenetic resource for identifying DNA methylation-based diagnostic biomarkers, developing cancer drugs for epigenetic therapy and studying cancer pathogenesis.