Flexibility in coral-algal symbiosis is positively correlated with the host geographic range.

Generalists are thought to adapt to broader ecological conditions compared to less flexible specialists. However, few studies have systematically tested what ecological or life-history traits are associated with organisms' ecological flexibility. Here, we used stony corals to test the relative effects of host traits and ecological factors on corals' flexibility to form photosymbioses with algae. We analysed data from 211 stony coral species to test if coral's geographic distribution, depth range, symbiont transmission mode or colony morphology predict coral-algal flexibility. We report a novel positive correlation between coral-algal flexibility and coral species' geographic range. Symbiont transmission mode was also a predictor of flexibility, albeit the result is less robust against sampling bias. Coral depth range and morphology did not show significant effects. We highlight that host-symbiont dispersal abilities, interactions and evolutionary histories likely contribute to the observed patterns. We urge conservation efforts to consider the ecological implications of coral-algal flexibility.

Comparative transcriptomics revealed parallel evolution and innovation of photosymbiosis molecular mechanisms in a marine bivalve.

Photosymbioses between heterotrophic hosts and autotrophic symbionts are evolutionarily prevalent and ecologically significant. However, the molecular mechanisms behind such symbioses remain less elucidated, which hinders our understanding of their origin and adaptive evolution. This study compared gene expression patterns in a photosymbiotic bivalve (Fragum sueziense) and a closely related non-symbiotic species (Trigoniocardia granifera) under different light conditions to detect potential molecular pathways involved in mollusc photosymbiosis. We discovered that the presence of algal symbionts greatly impacted host gene expression in symbiont-containing tissues. We found that the host immune functions were suppressed under normal light compared with those in the dark. In addition, we found that cilia in the symbiont-containing tissues play important roles in symbiont regulation or photoreception. Interestingly, many potential photosymbiosis genes could not be annotated or do not exhibit orthologues in T. granifera transcriptomes, indicating unique molecular functions in photosymbiotic bivalves. Overall, we found both novel and known molecular mechanisms involved in animal-algal photosymbiosis within bivalves. Given that many of the molecular pathways are shared among distantly related host lineages, such as molluscs and cnidarians, it indicates that parallel and/or convergent evolution is instrumental in shaping host-symbiont interactions and responses in these organisms.

CXC chemokine receptor 7 ameliorates renal fibrosis by inhibiting ß-catenin signaling and epithelial-to-mesenchymal transition in tubular epithelial cells.

Renal fibrosis is a common feature of various chronic kidney diseases. However, the underlying mechanism remains poorly understood. The CXC chemokine receptor (CXCR) family plays a role in renal fibrosis; however, the detailed mechanisms have not been elucidated. In this study, we investigated the potential role of CXCR7 in mediating renal fibrosis. CXCR7 expression is decreased in unilateral ischemia-reperfusion injury (UIRI) and unilateral ureteral obstruction mouse models. Furthermore, CXCR7 was specifically expressed primarily in the Lotus Tetragonolobus Lectin-expressing segment of tubules, was slightly expressed in the peanut agglutinin-expressing segment, and was barely expressed in the Dolichos biflorus agglutinin-expressing segment. Administration of pFlag-CXCR7, an overexpression plasmid for CXCR7, significantly inhibited the activation of ß-catenin signaling and protected against the progression of epithelial-to-mesenchymal transition (EMT) and renal fibrosis in a UIRI mouse model. Using cultured HKC-8 cells, we found that CXCR7 significantly downregulated the expression of active ß-catenin and fibrosis-related markers, including fibronectin, Collagen I, and α-SMA. Furthermore, CXCR7 significantly attenuated TGF-ß1-induced changes in ß-catenin signaling, EMT and fibrosis. These results suggest that CXCR7 plays a crucial role in inhibiting the activation of ß-catenin signaling and the progression of EMT and renal fibrosis. Thus, CXCR7 could be a novel therapeutic target for renal fibrosis.

Treatment and Outcome of Supracondylar Humeral Fractures in Children Over 10 Years of Age at the Time of Injury: A Review of 60 Cases.

OBJECTIVES: To assess the treatment and outcomes of supracondylar humeral fractures (SHFs) in children older than 10 years of age at the time of injury. METHODS: The study analyzed clinical data from 60 patients who sustained SHF, all over the age of 10 years, were analyzed. The patients included 49 males and 11 females with a mean age of 10.9 ± 0.9 years (range, 10 to 14.5). All patients underwent surgical treatment under general anesthesia. Closed reduction (CR) and percutaneous fixation were the primary treatment, with open reduction and internal fixation being employed only in cases CR was unsuccessful. The study assessed the healing of fractures by measuring the radiographic angles, including the carrying angle (RCA), Baumann's angle (BA), and metaphyseal-diaphyseal angle (MDA) on anteroposterior radiographs of the elbow joint. In addition, the study evaluated whether the anterior humeral line (AHL) appropriately passed through the middle third of the capitellum. The final follow-up visit used the Mayo Elbow Performance Index score (MEPI) and Flynn's criteria to analyze the recovery of elbow function. RESULTS: There were 15 (25%) SHF type II, 17 (28.3%) type III and 28 (46.7%) type IV. Of the 60 patients, 56 (93.3%) underwent successful CR, whereas 4 (6.7%) required open reduction and internal fixation because of an unsuccessful CR. The final follow-up showed the average BA as 72° ± 5.3°, the average MDA as 88.3° ± 2.8°, and the average RCA as 9.6° ± 3.9°. The AHL bisected accurately the capitellum in 59 cases (98.3%). The average range of elbow flexion-extension was 146.6° ± 8.6°, whereas the average MEPI score was 99.9 ± 0.6; 98.3% (n=59) were rated as excellent and 1.7% (n=1) were rated as good. According to Flynn's criteria, 86.7% had an excellent outcome (n=52), 10% had a good outcome (n=6), and 3.3% had a poor outcome (n=2). Only 1 patient (1.7%) experienced redisplacement. Eight cases of nerve injury were reported, with 7 involving the radial nerve and 1 involving the ulnar nerve; all resolved spontaneously. CONCLUSIONS: CR and percutaneous fixation have been shown to be effective in treating SHF in 93.3% of children aged 10 years old and older at the time of injury, with favorable radiographic and functional outcomes and a low risk of secondary displacement. Open reduction should only be considered when CR is ineffective.

Early radiographic characteristics of the lateral talocalcaneal angle and its predictive significance for relapse in patients with idiopathic clubfoot treated with the Ponseti method.

In order to evaluate the early radiographic characteristics of the lateral talocalcaneal (L-TC) angle in patients with idiopathic clubfoot (ICF) and to investigate its prognostic significance for relapse after initial treatment with the Ponseti method. We retrospectively included 151 patients (96 males and 55 females; 227 feet) with ICF treated at our Institution between January 2005 and December 2014. The age at initial treatment was less than 6 months, and radiographs were obtained within 3 months of the Achilles tenotomy (mean age: 2.3 months; range: 0.77-6.8). All patients were followed up for at least 7 years (range, 7-18). The participants' feet were classified into three groups: relapsed (Group A), not relapsed (Group B), and normal foot groups which consisted of healthy feet in patients with unilateral ICF (Group C). All angle measurements were expressed in degrees. Forty-seven ICF feet in 33 patients relapsed, while 180 feet in 118 patients did not, and the age at relapse was 5.92±1.91 years. Seventy-five normal feet were included in Group C. The average L-TC angle in Group A and B patients was 33.57°±12.05° and 39.37°±12.55°, respectively, while Group C was 49.61°±9.11°. A significant difference was found among the three groups of patients (F=31.48, P<0.001). The L-TC angle cut-off value below which a recurrence could be predicted was 36.1° (sensitivity, 74.47%). The L-TC angle of ICF patients treated using the Ponseti method were reduced compared to normal feet. An L-TC angle of <36.1° has relative value in predicting ICF relapse. LEVEL OF EVIDENCE: III.

Morinda officinalis oligosaccharides mitigate depression-like behaviors in hypertension rats by regulating Mfn2-mediated mitophagy.

OBJECTIVE: Patients with hypertension have a risk of depression. Morinda officinalis oligosaccharides (MOOs) have anti-depressant properties. In this study, we aimed to determine whether MOOs can improve the symptoms of depression in individuals with hypertension. METHODS: Dahl salt-sensitive rats fed with a high-salt diet were stimulated by chronic unpredictable mild stress to mimic hypertension with depression. Primary astrocytes and neurons were isolated from these rats. Astrocytes underwent LPS stimulation to simulate the inflammatory astrocytes during depression. MOOs were administrated at 0.1 mg/g/day in vivo and 1.25, 2.5, and 5 mg/mL in vitro. Mitophagy was inhibited using 5 mM 3-methyladenine (3-MA). Astrocyte-mediated neurotoxicity was detected by co-culturing astrocytes and neurons. RESULTS: MOOs decreased systolic pressure, diastolic pressure, and mean arterial pressure, thereby improving depression-like behavior, including behavioral despair, lack of enthusiasm, and loss of pleasure during hypertension with depression. Furthermore, MOOs inhibited inflammation, astrocytic dysfunction, and mitochondrial damage in the brain. Then, MOOs promoted autophagosome and lysosome enriched in mitochondria in LPS-stimulated astrocytes. MOOs suppressed mitochondrial damage and the release of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß in astrocytes undergoing LPS stimulation. Importantly, MOOs rescued the impaired neurons co-cultured with astrocytes. The effects of MOOs on LPS-stimulated astrocytes were reversed by 3-MA. Finally, MOOs upregulated LPS-downregulated Mfn2 expression in astrocytes. Mfn2 inhibition partly reversed the effects of MOOs on hypertension with depression. Intriguingly, Mfn2 suppression activated PI3K/Akt/mTOR pathway during MOOs treatment. CONCLUSIONS: Astrocytes develop neuroinflammation in response to mitochondrial damage during hypertension with depression. MOOs upregulated Mfn2 expression to activate the PI3K/Akt/mTOR pathway-mediated mitophagy, thereby removing impaired mitochondria in astrocytes. HIGHLIGHTS: 1. MOOs have anti-hypertensive and anti-depressive properties. 2. MOOs inhibit inflammation and injury in astrocytes during hypertension with depression. 3. MOOs induce mitophagy activation in inflammatory astrocytes with mitochondrial damage. 4. MOOs upregulate Mfn2 expression in astrocytes. 5. Mfn2 activates mitophagy to resist mitochondrial damage in astrocytes.

Homologous proteins SAPCD2X1 and SAPCD2 have significantly different carcinogenic capacities in human colorectal cancer cells based on structural prediction and functional verification.

We discussed the expression and biological functions of the SAPCD2X1 protein in the HCT116 CRC cell line by bioinformatics analysis and prediction, and biological function verification. Spatial conformation models of SAPCD2X1 and SAPCD2 were predicted using the threading method, ensemble method, and several other protein structure prediction approaches. The conformational similarity between SAPCD2X1 and SAPCD2 was studied, and their functions were predicted. The biological experiments showed that SAPCD2X1 and SAPCD2 were overexpressed in CRC cells. SAPCD2X1-specific antibodies were prepared. The expressions of SAPCD2X1 and SAPCD2 were localized in cells using the immunofluorescence assay. The SAPCD2 and SAPCD2X1 overexpression models were validated using Western Blot and RT-qPCR. We successfully predicted the structures of the SAPCD2X1 and SAPCD2 proteins, and visualized them using the VDM software. It was predicted that the tertiary structure of SAPCD2X1 changed significantly compared with SAPCD2. Alteration of the biological functions of SAPCD2X1 was also predicted due to the changes in the spatial conformation of the protein. Anti-SAPCD2X1 antibody and SAPCD2X1-EGFP and SAPCD2-EGFP recombinant plasmids were established. The overexpression of the two proteins was induced in HCT116 cells using the recombinant plasmids, and verified by RT-qPCR and Western Blot. Meanwhile, the anti-SAPCD2X1 antibody was proved to have a high specificity. The immunofluorescence assay showed that SAPCD2X1 and SAPCD2 are mainly expressed in the cytoplasm. SAPCD2X1 and SAPCD2 exhibited significantly different biological functions in HCT116 cells. SAPCD2 is a carcinogenic protein, while SAPCD2X1 does not affect the proliferation, invasion, and migration of human CRC HCT116 cells.

Phosphocreatine addition to extender enhances the quality and antioxidant capacity of cryopreserved boar sperm.

Boar sperm are less resistant to drastic changes in the external environment during cryopreservation, mainly because their plasma membranes are rich in unsaturated fatty acids but lack cholesterol and are thus susceptible to lipid peroxidation caused by the attack of reactive oxygen species. This study evaluated the effect of adding phosphocreatine to cryopreservation extenders on boar sperm quality and antioxidant capacity. Different concentrations (0, 5.0, 7.5, 10.0 and 12.5 mmol/L) of phosphocreatine were added to the cryopreservation extender. After thawing, sperm were analysed for morphological parameters, kinetic parameters, acrosome integrity, membrane integrity, mitochondrial activity, DNA integrity and antioxidant enzyme activity. The results showed that 10.0 mmol/L phosphocreatine samples enhanced the boar sperm motility, viability, average path velocity, straight-line velocity, curvilinear velocity and beat cross frequency after cryopreservation and reduced the malformation rate compared to the control group (p < .05). The acrosome integrity, membrane integrity, mitochondrial activity and DNA integrity of boar sperm were higher than those of the control group after adding 10.0 mmol/L phosphocreatine to the cryopreservation extender (p < .05). Extenders containing 10.0 mmol/L phosphocreatine maintained high total antioxidant capacity; elevated the activities of catalase, glutathione peroxidase and superoxide dismutase; reduced malondialdehyde and H2 O2 content (p < .05). Therefore, adding phosphocreatine to the extender is potentially beneficial for boar sperm cryopreservation at an optimal 10.0 mmol/L concentration.

Computing Power Network: Multi-Objective Optimization-Based Routing.

This paper presents a novel routing planning method based on multi-objective optimization to tackle the routing problem in computing power networks. The proposed method aims to improve the performance and efficiency of routing by considering multiple objectives. In this study, we first model the computing power network and formulate the routing problem as a multi-objective optimization problem. To address this problem, we introduce a non-dominated sorting genetic algorithm incorporating a ratio parameter adjustment strategy based on reinforcement learning. Extensive simulations are conducted to evaluate the performance of the proposed routing algorithm. The results demonstrate significant client latency and cost reductions, highlighting the algorithm's effectiveness. By providing a comprehensive solution to the routing problem in computing power networks, this work contributes to the field by offering improved performance and efficiency. The proposed method's ability to optimize multiple objectives sets it apart from existing approaches, making it a valuable contribution to the research community.

PPARγ alleviates peritoneal fibrosis progression along with promoting GLUT1 expression and suppressing peritoneal mesothelial cell proliferation.

OBJECTIVE: Peritoneal fibrosis (PF) is commonly induced by bioincompatible dialysate exposure during peritoneal dialysis, but the underlying mechanisms remain elusive. This study aimed to investigate the roles of peroxisome proliferator-activated receptor gamma (PPARγ) in PF pathogenesis. METHODS: Rat and cellular PF models were established by high glucose dialysate and lipopolysaccharide treatments. Serum creatinine, urea nitrogen, and glucose contents were detected by ELISA. Histological evaluation was done through H&E and Masson staining. GLUT1, PPARγ, and other protein expression were measured by qRT-PCR, western blotting, and IHC. PPARγ and GLUT1 subcellular distribution were detected using confocal microscopy. Cell proliferation was assessed by MTT and Edu staining. RESULTS: Serum creatinine, urea nitrogen and glucose, and PPARγ and GLUT1 expression in rat PF model were reduced by PPARγ agonists Rosiglitazone or 15d-PGJ2 and elevated by antagonist GW9662. Rosiglitazone or 15d-PGJ2 repressed and GW9662 aggravated peritoneal fibrosis in rat PF model. PPARγ and GLUT1 were mainly localized in nucleus and cytosols of peritoneal mesothelial cells, respectively, which were reduced in cellular PF model, enhanced by Rosiglitazone or 15d-PGJ2, and repressed by GW9662. TGF-ß and a-SMA expression was elevated in cellular PF model, which was inhibited by Rosiglitazone or 15d-PGJ2 and promoted by GW9662. PPARγ silencing reduced GLUT1, elevated a-SMA and TGF-b expression, and promoted peritoneal mesothelial cell proliferation, which were oppositely changed by PPARγ overexpression. CONCLUSION: PPARγ inhibited high glucose-induced peritoneal fibrosis progression through elevating GLUT1 expression and repressing peritoneal mesothelial cell proliferation.

The pharmacological and pharmacokinetic properties of esculin: A comprehensive review.

Cortex fraxini is a widely used traditional Chinese medicine. Esculin is one of the main active ingredients of Cortex fraxini and has attracted more and more attention from scholars. The purpose of the review is to systematically review relevant studies on the pharmacological effects and pharmacokinetic characteristics of esculin to support its further application as therapeutic agents. Pharmacological studies have shown that the anti-inflammatory and anti-oxidative stress effects of esculin are outstanding. This indicates that esculin is promising to be used to treat a variety of diseases closely related to inflammation and oxidative damage. Esculin has anti-diabetic effect, which is closely related to improving pancreas damage, promoting insulin release, and enhancing glucose homeostasis. In addition, esculin has anti-cancer, antibiosis, anti-virus, neuroprotection, anti-thrombosis and treating eye diseases properties. Pharmacokinetic studies show that esculin can be quickly and evenly distributed in the body. However, the first pass effect of esculin is serious. In short, esculin is promising to treat many diseases, but further high quality studies are needed to firmly establish the clinical efficacy of esculin.

Modified Radiographic Classification System for Congenital Thumb Duplication: An Analysis of 2,300 Thumbs in 2,108 Children.

PURPOSE: The objectives of this study were to (1) evaluate the radiographic characteristics of children with congenital thumb duplication (CTD) seen in our institution between August 2015 and April 2021; (2) introduce a modified radiographic classification system (MCS) capable of including all cases of CTD based on their radiographic pathoanatomy; and (3) evaluate the inter- and intrarater reliability of the new classification system. METHODS: We retrospectively reviewed 2,108 patients with 2,300 CTDs. The MCS is based on the Wassel-Flatt and Chung et al classification systems and includes specific subtypes from the Rotterdam and modified Wassel-Flatt classifications. The MCS is characterized by 4 groups according to the anatomical morphology of the duplication: A (joint), B (epiphysis), C (bone), and D (soft tissues). Each group includes 4 subtypes according to the location of the CTD, with subtypes 1-3 extending from the distal phalanx to the metacarpal or interphalangeal joints, then to the carpometacarpal joint, and with subtype 4 only including the triphalangia of the main thumb. RESULTS: Among the 2,300 fingers, 360 (15.7%), 2 (0.1%), and 3 (0.1%) CTDs could not be classified according to the Wassel-Flatt, Chung et al, and Rotterdam classifications, respectively. According to the MCS, the 2 most common forms of CTD were A2 (680/2,300; 29.6%) and D2 (308/2,300; 13.4%). All cases could be classified according to this classification system. The MCS showed excellent intrarater (0.875) and interrater (0.851) reliability relative to the Wassel-Flatt (0.863 and 0.820, respectively), Chung et al (0.793 and 0.822, respectively), and Rotterdam (0.873 and 0.836, respectively) systems. CONCLUSIONS: The MCS is a potential radiographic classification for CTD that enables the classification of all patients and has excellent inter- and intrarater reliability. CLINICAL RELEVANCE: Existing classification systems do not allow classification of the full spectrum of CTD and are not always related to surgery, and some existing systems are complex, with many categories that are rarely encountered, or are difficult to use widely in clinical practice.

Closed reduction and percutaneous pinning versus open reduction and internal fixation for Jakob type 3 lateral condyle fractures in children.

PURPOSE: The management of type 3 lateral condyle fractures (LCFs) remains controversial. The main goal of this study was to evaluate the feasibility of closed reduction and percutaneous pinning (CRPP) in patients with type 3 LCFs and to assess the outcome of such injuries according to the type of treatment, CRPP, or open reduction and internal fixation (ORIF). METHODS: This is a retrospective review of prospectively enrolled children with type 3 LCF managed by CRPP or ORIF between 2018 and 2021. All patients were followed for at least 12 months. Patients were divided into two groups according to the type of treatment, CRPP or ORIF. Demographic characteristics were recorded for all patients. Standard radiographs were used to identify, evaluate, and classify each fracture and to detect the presence of other concomitant bone lesions. The clinical outcome was assessed according to the Hardacre et al. criteria. RESULTS: Seventy-eight children with type 3 LCF were included; 42 were treated by CRPP (53.8%) and 36 by ORIF (46.2%); the mean follow-up time was 17.7 months (range, 12.3-40.9). The baseline characteristics did not differ between the two groups of patients. Overall, successful CRPP could be achieved in 39 out of 42 patients (92.9%). The mean surgical time was 63.4 and 84.5 min in patients treated by CRPP and ORIF, respectively (p = 0.01). Fluoroscopy time was significantly shorter in patients managed by ORIF than in those treated by CRPP (12 versus 40 s, respectively; p < 0.001). Clinical outcome according to the Hardacre et al. criteria was excellent in 37 out of 39 (94.4%) and in 35 out of 36 patients (97.2%) treated by CRPP and ORIF, respectively (p = 0.09). CONCLUSIONS: CRPP management of paediatric type 3 LCF has clinical and radiographic outcomes similar to ORIF; if satisfactory reduction cannot be achieved by CRPP, conversion to ORIF should be considered.

To Angulate or Not to Angulate the Ulna during the Progressive Distraction Period Performed with a Monolateral External Fixator in Paediatric Patients with a Chronic Monteggia Fracture?

Background and Objectives: The purpose of this study was to compare the clinical and radiographic evolution of chronic Monteggia fractures (CMFs) treated by ulnar osteotomy and monolateral external fixators (MEFs) with or without angulation of the ulna during the distraction period. Materials and Methods: This retrospective study evaluated 20 children (14 boys and 6 girls) with CMFs. According to the strategy of ulnar lengthening, two groups of patients were identified: patients undergoing gradual lengthening with (Group A, n = 11) or without ulna angulation (Group B, n = 9). The mean age at the time of surgery was 7.7 years old (range, 5.4−12.9). The mean time from initial trauma to surgery was 26.3 months (range, 1−96), and the mean follow-up was 24.6 months (range, 5.5−45.4). Clinical outcomes were evaluated by Kim et al.'s Elbow Performance Score, while radiographic outcomes were assessed on plain radiographs. Results: Age at surgery, sex, laterality, time between trauma and surgery, and time of follow up in the two groups of patients showed no significant differences. The radial head was successfully reduced in 9 of 9 and 10 of 11 patients in Groups B and A, respectively (p = 1.00). The mean time to achieve radial head reduction was shorter in Group B (18.1 ± 5.3 days) than in Group A (39.2 ± 18.7 days; p = 0.004). The mean angulation of the ulna at the end of treatment was significantly lower in Group B (0.6° ± 1.1°) than in Group A (25.9° ± 6.3°; p < 0.0001). The average ulnar lengthening at the end of treatment in Group B (14.1 ± 5.8 mm) was, on average, 7.7 mm less than that in Group A (21.8 ± 9.7 mm; p = 0.05). The Kim et al. Elbow Performance Score at the last follow-up visit was comparable between the two groups of patients (p = 1.00). Conclusions: A shorter time to achieve radial head reduction and less deformity of the ulna can be expected in paediatric patients with CMFs undergoing intraoperative restoration of ulnar alignment and gradual lengthening without angulation postoperatively.

A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate.

Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by the formation of multiple benign cartilage-capped tumors, usually in the metaphyseal region of the long bones. Over 70% of HME cases arise from monoallelic mutations in either of the two genes encoding the heparan sulfate (HS) synthesis enzymes, ext1 and ext2. To identify more HME-associated mutations, genomic DNA from members of five independent consanguineous families with HME was sequenced with whole exome sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in ext2 was detected in all three affected members of family V. Further study showed that the novel mutation caused exon 7 of ext2 mRNA to be skipped during splicing and caused a frameshift after the codon for Arg360, which results in the appearance of new 43 codons, followed by a termination codon. Although the resulting truncated protein was still localized to the Golgi, similar to the full-length EXT2, its HS synthesis activity decreased by 40%. In this study, a novel splice site mutation in ext2 was identified and suggested to be a pathogenic mutation of HME, which may expand the genetic etiology spectrum of HME and may be helpful for clinical genetic counseling and prenatal diagnosis.

Shedding light: a phylotranscriptomic perspective illuminates the origin of photosymbiosis in marine bivalves.

BACKGROUND: Photosymbiotic associations between metazoan hosts and photosynthetic dinoflagellates are crucial to the trophic and structural integrity of many marine ecosystems, including coral reefs. Although extensive efforts have been devoted to study the short-term ecological interactions between coral hosts and their symbionts, long-term evolutionary dynamics of photosymbiosis in many marine animals are not well understood. Within Bivalvia, the second largest class of mollusks, obligate photosymbiosis is found in two marine lineages: the giant clams (subfamily Tridacninae) and the heart cockles (subfamily Fraginae), both in the family Cardiidae. Morphologically, giant clams show relatively conservative shell forms whereas photosymbiotic fragines exhibit a diverse suite of anatomical adaptations including flattened shells, leafy mantle extensions, and lens-like microstructural structures. To date, the phylogenetic relationships between these two subfamilies remain poorly resolved, and it is unclear whether photosymbiosis in cardiids originated once or twice. RESULTS: In this study, we establish a backbone phylogeny for Cardiidae utilizing RNASeq-based transcriptomic data from Tridacninae, Fraginae and other cardiids. A variety of phylogenomic approaches were used to infer the relationship between the two groups. Our analyses found conflicting gene signals and potential rapid divergence among the lineages. Overall, results support a sister group relationship between Tridacninae and Fraginae, which diverged during the Cretaceous. Although a sister group relationship is recovered, ancestral state reconstruction using maximum likelihood-based methods reveals two independent origins of photosymbiosis, one at the base of Tridacninae and the other within a symbiotic Fraginae clade. CONCLUSIONS: The newly revealed common ancestry between Tridacninae and Fraginae brings a possibility that certain genetic, metabolic, and/or anatomical exaptations existed in their last common ancestor, which promoted both lineages to independently establish photosymbiosis, possibly in response to the modern expansion of reef habitats.

Variables influencing the pelvic radiological evaluation in children with developmental dysplasia of the hip managed by closed reduction: a multicentre investigation.

PURPOSE: This study aims to evaluate (1) the probability to achieve normal pelvic radiographs in children with developmental dysplasia of the hip (DDH) treated by closed reduction and (2) the amount of time needed to achieve normal pelvic radiographs and to assess what factors influence both probability and time to achieve normal radiographic parameters following CR and spica cast immobilization for DDH. METHODS: We retrospectively reviewed 436 patients (393 girls, 43 boys; 507 hips) with DDH treated by closed reduction (CR). Tönnis grade, AVN, acetabular index (AI), centre-edge angle (CEA), and Severin radiographic grade were evaluated on plain radiographs. Criteria to rate pelvis radiographs as normal were established. Cox regression was used to evaluate the factors influencing the probability and the time to achieve normal radiographs. RESULTS: According to our criteria, 167 hips (32.9%) achieved normal radiographic parameters during follow-up. The overall amount of time to achieve normal pelvis radiographs was 36.1 ± 15.5 months. Patients older than 24 months of age at the time of CR needed longer time to achieve normal radiographic parameters (55.2 ± 28 months) compared with other age groups. Cox regression analysis suggested the overall cumulative probability of recovery increased by 46% at five years following CR, then it tended to plateau with an annual increase less than 5%. Age older than 24 months, bilateral dislocation, pre-operative AI greater than 40°, and AVN were risk factors for reduced probability of achieving normal radiographic parameters. CONCLUSIONS: The cumulative probability of achieving normal pelvis radiographs increases linearly during the first five years following CR, then it tends to plateau. Age older than 24 months and Tönnis grade III and IV are associated with longer time to achieve normal radiographic parameters. Age older than 24 months, bilateral dislocation, pre-operative AI greater than 40°, and AVN are risk factors for reduced probability of achieving normal radiographic parameters in children with DDH treated by closed means.

mTORC1 signaling is essential for neurofibromatosis type I gene modulated osteogenic differentiation of BMSCs.

Neurofibromatosis type I (NF1), which is caused by mutations in the NF1 gene, is a common autosomal dominant genetic disease leading to skeletal abnormalities. Both NF1 gene and mammalian target of rapamycin complex 1 (mTORC1) signaling are associated with the osteogenic differentiation of bone marrow stem cells (BMSCs). In this study, we hypothesized that mTORC1 signaling is involved in NF1-modulated osteoblast differentiation of BMSCs. Human BMSCs were cultured in an osteogenic induction medium. The expression of NF1 was either inhibited or overexpressed by transfecting NF1 with a specific small interfering RNA (siRNA) or pcDNA3.0 plasmid, respectively. In addition, an mTORC1 signaling inhibitor and agonist were used to investigate the effects of mTORC1 on NF1-modulated osteogenic differentiation of BMSCs. The results indicated that inhibiting the expression of NF1 with siRNA significantly decreased the mRNA levels of NF1, whereas overexpressing the expression of NF1 with pcDNA3.0 plasmid significantly increased the mRNA levels of NF1 at days 3, 7, 14 and 21 after culture. We observed reduced osteogenic differentiation and cell proliferation in the NF1-siRNA group and enhanced osteogenic differentiation and cell proliferation of BMSCs in the NF1-pcDNA3.0 group. The activity of mTORC1 signaling (p-mTORC1, p-S6K1, and p-4EBP1) was significantly upregulated in the NF1-siRNA group and significantly inhibited in the NF1-pcDNA3.0 group, 7 and 14 days after culture. The effects of NF1-siRNA and NF1-pcDNA3.0 on osteogenic differentiation of BMSCs and cell proliferation were reversed by mTORC1 inhibitor and agonist, respectively. In conclusion, NF1 modulates osteogenic differentiation and cell proliferation of human BMSCs and mTORC1 signaling is essential for this process.

HOXA9 rs3801776 G>A polymorphism increases congenital talipes equinovarus risk in a Chinese population.

BACKGROUND: Congenital talipes equinovarus (CTEV) is the most common congenital deformity in children, and muscular dysplasia plays a potential role in the etiology of CTEV. Notably, previous studies have found that HOXA9 rs3801776 and TPM2 rs2025126 genetic polymorphisms play important roles in regulating muscle development in Caucasian children; however, there is a lack of investigations conducted in Chinese children. METHODS: We conducted a hospital-based, case-control study of 189 children with CTEV and 457 CTEV-free children aiming to examine the associations between these two polymorphisms and CTEV susceptibility. The rs3801776 (G>A) and rs2025126 (G>A) polymorphisms were genotyped using TaqMan. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the associations between the selected polymorphisms and CTEV susceptibility. RESULTS: We found that rs3801776A was associated with increased CTEV risk (GA versus GG: adjusted OR = 1.81, 95% CI = 1.22-2.69, p = 0.0031; AA versus GG: adjusted OR = 2.19, 95% CI = 1.28-3.73, p = 0.0041; GA/AA versus GG: adjusted OR = 1.89, 95% CI = 1.29-2.76, p = 0.0010). In a stratified analysis, the risk effect of rs3801776 GA/AA was observed in both unilateral and bilateral patients. CONCLUSIONS: The present study suggests that the rs3801776 G>A polymorphism is associated with CTEV risk in Chinese children; however, this conclusion should be validated in larger studies.

Femoral anteversion does not predict redislocation in children with hip dysplasia treated by closed reduction.

PURPOSE: Increased femoral anteversion can be associated with hip instability, redislocation after closed reduction, and subsequent early degenerative arthritis. Our study compared proximal femoral anteversion of affected and unaffected sides of patients with unilateral developmental dysplasia of the hip (DDH) on two-dimensional computed tomography. The primary aim was to evaluate whether femoral anteversion at the time of treatment affected the outcome of patients with unilateral DDH treated by closed reduction. METHODS: A retrospective review of 89 patients (82 females; 53 left; mean age: 26.6 months) with unilateral DDH was performed. Anteversion angle (AA) of the femur and acetabular index (AI) of both affected (AAa; AIa) and unaffected (AAu; AIu) hips were measured on two-dimensional CT scan performed no more than seven days prior to the index surgical procedure. RESULTS: Among the 89 patients, 50 underwent closed reduction (56.2%), 38 underwent open reduction with or without pelvic osteotomy (42.7%), and one patient refused treatment (1.1%). Overall, the mean AAa was 28.1° ± 10.2° (range: 6.3°-54°) and mean AAu was 25.2° ± 9.9° (range: 1.9°-52.5°) (t = 3.2, p = 0.002). Tönnis type 2 hips did not show any statistically significant difference between AAa and AAu (p = 0.386), while Tönnis types 3 and 4 hips had significantly higher AAa than did AAu (t = 3.7, p = 0.001). There were significant correlations between age and AAa (coefficient = 0.4; p < 0.001) and AAu (coefficient = 0.304; p = 0.004). Correlation analysis showed that AIa did not improve with age in any Tönnis group (r: - 0.24, p = 0.823; F = 0.039, p = 0.962). AAa, AIa, AAD, AID, and Tönnis grade distribution were similar in patients with good (no redislocation) and poor outcomes (redislocation) (p > 0.05). CONCLUSION: In patients with unilateral DDH, anteversion angle (AA) was found to be significantly different between affected and unaffected sides. However, the difference had very limited or no clinical significance, as redislocation/sub-luxation was not influenced by AA values.