Enantioselective Synthesis of Bispiro[indanedione-oxindole-cyclopropane]s through Organocatalytic [2+1] Cycloaddition.

A series of compounds featuring a novel bispiro[indanedione-oxindole-cyclopropane] moiety have been synthesized through a squaramide-catalyzed [2+1] cycloaddition reaction. The tandem Michael-alkylation reaction of 2-arylidene-1,3-indanediones with 3-bromooxindoles furnished the cycloadducts in high yields with excellent diastereo- and enantioselectivities. The ammonium ylide in the catalytic process, as a key intermediate, was revealed by the high-resolution mass spectrometry study.

Regulation of PGC-1α of the Mitochondrial Energy Metabolism Pathway in the Gills of Indian Medaka (Oryzias dancena) under Hypothermal Stress.

Ectothermic fish exposure to hypothermal stress requires adjusting their metabolic molecular machinery, which was investigated using Indian medaka (Oryzias dancena; 10 weeks old, 2.5 ± 0.5 cm) cultured in fresh water (FW) and seawater (SW; 35‱) at room temperature (28 ± 1 °C). The fish were fed twice a day, once in the morning and once in the evening, and the photoperiod was 12 h:12 h light: dark. In this study, we applied two hypothermal treatments to reveal the mechanisms of energy metabolism via pgc-1α regulation in the gills of Indian medaka; cold-stress (18 °C) and cold-tolerance (extreme cold; 15 °C). The branchial ATP content was significantly higher in the cold-stress group, but not in the cold-tolerance group. In FW- and SW-acclimated medaka, the expression of genes related to mitochondrial energy metabolism, including pgc-1α, prc, Nrf2, tfam, and nd5, was analyzed to illustrate differential responses of mitochondrial energy metabolism to cold-stress and cold-tolerance environments. When exposed to cold-stress, the relative mRNA expression of pgc-1α, prc, and Nrf2 increased from 2 h, whereas that of tfam and nd5 increased significantly from 168 h. When exposed to a cold-tolerant environment, prc was significantly upregulated at 2 h post-cooling in the FW and SW groups, and pgc-1α was significantly upregulated at 2 and 12 h post-cooling in the FW group, while tfam and nd5 were downregulated in both FW and SW fish. Hierarchical clustering revealed gene interactions in the cold-stress group, which promoted diverse mitochondrial energy adaptations, causing an increase in ATP production. However, the cold-tolerant group demonstrated limitations in enhancing ATP levels through mitochondrial regulation via the PGC-1α energy metabolism pathway. These findings suggest that ectothermic fish may develop varying degrees of thermal tolerance over time in response to climate change. This study provides insights into the complex ways in which fish adjust their metabolism when exposed to cold stress, contributing to our knowledge of how they adapt.

Asymmetric Formal (3 + 2) Cyclocondensation of Coumarin-3-Formylpyrazoles as 3-Carbon Partners with 3-Hydroxyoxindoles via Esterification/Michael Addition Sequence.

The first enantioselective formal (3 + 2) cyclocondensation involving α,ß-unsaturated pyrazoleamides as 3-carbon partners was accomplished in a stepwise fashion. The stepwise esterification/Michael addition sequence is promoted by Zn(OTf)2 and quinine-squaramide derivative, respectively. The protocol enables access to spiro-fused pentacyclic spirooxindoles from coumarin-3-formylpyrazoles and 3-hydroxyoxindoles in good to satisfactory overall yields (up to 91%) with excellent dr (all cases >20:1 dr) and high ee values (up to 99%). Mechanistic investigations contributed to shedding light on the enantioselective event of the process.

Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense.

Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (±)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.

Organocatalytic Asymmetric Cyclopropanation of 3-Acylcoumarins with 3-Halooxindoles: Access to Spirooxindole-cyclopropa[c]coumarin Compounds.

A highly diastereo- and enantioselective cyclopropanation reaction of 3-acylcoumarins with 3-halooxindoles catalyzed by an organocatalyst through a [2 + 1] Michael/intramolecular cyclization process was developed. This scenario provides a facile strategy to access spirooxindole-cyclopropa[c]coumarin compounds bearing three continuous stereocenters, including two vicinal quaternary all-carbon stereocenters with high to excellent diastereo- and enantioselectivities. The HRMS study revealed the vital importance of the ammonium ylide intermediate in the catalytic process.

Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer.

Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

Lay abstract Previous evidence has indicated that the mRNA stem index (mRNAsi) is representative of the stemness of cancer stem cells (CSCs), whereas long noncoding RNAs (lncRNAs) may be crucial regulators in CSC phenotype. Nevertheless, the relationship between lncRNAs and mRNAsi in CRC is still unclear. Our results show that the mRNAsi was negatively related to pathological features and positively related to prognosis in CRC. Five mRNAsi-related lncRNAs were further identified and developed as a prognostic signature that could independently predict survival in CRC patients due to the five mRNAsi-related lncRNAs being involved in several pathways of CSCs and malignant cancer cell phenotypes, indicating the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

The Application of an Omentum Graft or Flap in Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) causes a primary injury at the lesion site and triggers a secondary injury and prolonged inflammation. There has been no definitive treatment till now. Promoting angiogenesis is one of the most important strategies for functional recovery after SCI. The omentum, abundant in blood and lymph vessels, possesses the potent ability of tissue regeneration. METHODS: The present work examines the efficacy of autologous omentum, either as a flap (with vascular connection intact) or graft (severed vascular connection), on spinal nerve regeneration. After contusive SCI in rats, a thin sheath of omentum was grafted to the injured spinal cord. RESULTS: Omental graft improved behavior scores significantly from the 3rd to 6th week after injury (6th week, 5.5 ± 0.5 vs. 8.6 ± 1.3, p < 0.05). Furthermore, the reduction in cavity and the preservation of class III ß-tubulin-positive nerve fibers in the injury area was noted. Next, the free omental flap was transposed to a completely transected SCI in rats through a pre-implanted tunnel. The flap remained vascularized and survived well several weeks after the operation. At 16 weeks post-treatment, SCI rats with omentum flap treatment displayed the preservation of significantly more nerve fibers (p < 0.05) and a reduced injured cavity, though locomotor scores were similar. CONCLUSIONS: Taken together, the findings of this study indicate that treatment with an omental graft or transposition of an omental flap on an injured spinal cord has a positive effect on nerve protection and tissue preservation in SCI rats. The current data highlight the importance of omentum in clinical applications.

Coumarin-3-formylpyrazoles as 3-carbon synthons in cyclocondensation for the synthesis of spiro-fused pentacyclic spirooxindoles.

Coumarin-3-formylpyrazoles have been synthesized and applied as 3-carbon synthons in reaction with 3-hydroxyoxindoles by using DABCO as the catalyst. A range of structurally diverse spiro-fused pentacyclic spirooxindoles, bearing a spirooxindole-γ-lactone and a 3,4-dihydrocoumarin substructure, could be smoothly obtained in good to excellent yields (up to 99%) with excellent diastereoselectivities (all cases >20 : 1 dr). The asymmetric version of this tandem reaction was preliminarily investigated by using chiral organocatalysts.

The Prognostic Value of a Pathologic Complete Response After Neoadjuvant Therapy for Digestive Cancer: Systematic Review and Meta-Analysis of 21 Studies.

BACKGROUND: Neoadjuvant therapy (NAT) before radical excision has become the preferred initial option for locally advanced digestive cancers such as esophageal cancer (EC), esophagogastric junction adenocarcinoma (EGJAC), gastric adenocarcinoma (GAC), rectal cancer (RC), and pancreatic cancer (PC). Although some patients reportedly achieve a pathologic complete response (pCR) after neoadjuvant therapy, the published data are inconsistent regarding whether pCR yields a survival benefit. The current meta-analysis was performed to assess the potential prognostic value of pCR after preoperative therapy for patients with digestive cancers. METHODS: An extensive electronic search in PubMed, Web of Science, and the Cochrane Library was performed for relevant articles, from which data relative to independent correlations of pCR with overall survival (OS) and disease-free survival (DFS) were extracted for analysis. A random-effects model was used to calculate the pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). RESULTS: The study identified 6780 patients who met the inclusion and exclusion criteria. The results showed that pCR was significantly correlated with better OS (HR, 0.50; 95% CI, 0.43-0.58; P < 0.001) and DFS (HR, 0.49; 95% CI, 0.40-0.60; P < 0.001) for the digestive cancer patients who achieved pCR than for those who did not achieve pCR. Subgroup analysis showed that the correlation of pCR with OS was significant in EC (HR, 0.57; 95% CI, 0.47-0.69; P < 0.001), EGJAC/GAC (HR, 0.38; 95% CI, 0.17-0.86; P = 0.02), RC (HR, 0.48; 95% CI, 0.28-0.81; P = 0.006), and PC (HR, 0.41; 95% CI, 0.17-0.97; P = 0.04). In addition, the survival benefit for pCR patients was of similar magnitude, irrespective of the type of study, type of NAT, or ethnicity. CONCLUSIONS: A pCR is correlated with favorable survival outcomes compared with a non-pCR for digestive cancer patients after NAT.

High ANKZF1 expression is associated with poor overall survival and recurrence-free survival in colon cancer.

Aim: To investigate the association and prognostic value of ANKZF1 gene for survival in colorectal cancer, the mechanism of ANKZF1 level alteration and correlated signaling pathways ANKZF1 is involved. Patients & methods: The Cancer Genome Atlas COREAD dataset was analyzed by bioinformatical investigation. Results: High ANKZF1 expression is associated with poor overall survival (hazard ratio [HR]: 2.094; 95% CI: 1.188-3.689; p = 0.011) and recurrence-free survival (HR: 1.762; 95% CI: 1.021-3.042; p = 0.042) in colon cancer. Bioinformatical analysis showed ANKZF1 was upregulated by amplification and exon expression. ANKZF1 was associated with angiogenesis and cancer signaling pathways. Conclusion: High ANKZF1 is an independent factor of poor survival (overall survival and recurrence-free survival) in colon cancer by taking part in angiogenesis and some cancer signaling pathways.

Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promising value for cancer therapy due to its capacity to induce apoptosis in cancer cells. Nevertheless, TRAIL therapy is greatly hampered by its resistance. Irigenin (Iri), isoflavonoids, can be isolated from the rhizome of Belamcanda chinensis, and has been shown anti-cancer properties. In this study, we explored if Iri could enhance TRAIL-regulated apoptosis in TRAIL resistant gastric cancer cells. Iri significantly potentiated TRAIL-triggered cytotoxicity. Iri alone and TRAIL alone showed no effective role in apoptosis induction, whereas combined treatment with Iri and TRAIL markedly induced apoptosis in cancer cells, as evidenced by the up-regulation of cleaved Caspase-8/-9/-3 and PARP. Additionally, the sensitization to TRAIL was along with the enhancement of pro-apoptotic proteins, including FAS-associated protein with death domain (FADD), death receptor 5 (DR5) and Bax. And suppressing FADD, DR5 and Bax by si RNA significantly reduced the apoptosis and enhanced the cell viability induced by the co-application of Iri and TRAIL. Moreover, the sensitization to TRAIL was accompanied by the decrease of Cellular-FLICE inhibitory protein (c-FLIP), Bcl-2 and Survivin. Additionally, Iri could sensitize TRAIL to produce reactive oxygen species (ROS). Pre-treatment of N-acetyl-cysteine (NAC), ROS scavenger, attenuated Iri plus TRAIL-induced apoptosis and improved cell viability. Finally, combination of Iri and TRAIL inhibited tumor growth in the xenograft model. Collectively, our present study gave new insights into the effects of Iri on potentiating TRAIL-sensitivity, and suggested that Iri could be a potential candidate for sensitizer of TRAIL-resistant cancer cell treatment.

Bhargavaea changchunensis sp. nov. isolated from soil in China.

A Gram-staining-positive, aerobic, rod-shaped (201802YP6T) bacteria was isolated from soil, Northeast of China. Growth occurred at 10-40 °C (optimum 25-30 °C), at pH 6.0-8.0 (optimum 7.0) and at 0-2% NaCl. Based on 16S rRNA gene sequence analysis, the nearest phylogenetic neighbors of strain 201802YP6T were identified as Bhargavaea cecembensis DSE10T (99.52%), Bhargavaea beijingensis ge10T (99.45%), Bhargavaea indica KJW98T (99.45%), Bhargavaea ullalensis ZMA19T (98.81%), and Bhargavaea ginsengi ge14T (98.76%). Levels of similarity among strain 201802YP6T and other Bhargavaea species were lower than 98.76%. GyrB amino acid sequence-based analysis supported the phylogenetic position and also distinguished strain 201802YP6T from the other species of the genus Bhargavaea. DNA-DNA hybridization values between strain 201802YP6T and B. cecembensis, B. beijingensis, B. indica, B. ullalensis, B. ginsengi were 43.5%, 43%, 32.5%, 30.5% and 20.4%, respectively. The DNA G + C content of strain 201802YP6T was 51.23 mol%. The average nucleotide identity (ANI) of the draft genome was 87.04% to B. cecembensis DSE10T. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, glycolipids, phosphatidylethanolamine, and phosphatidyllipid. The predominant menaquinone was MK-8. The major fatty acids were iso-C15:0 (39.91%), anteiso-C15:0 (28.86%), anteiso-C17:0 (6.30%) and C16:0 (6.13%). On the basis of the phylogenetic analysis, chemotaxonomic data, physiological characteristics and DNA-DNA hybridization data, strain 201802YP6T represents a novel species of the genus Bhargavaea, for which the name Bhargavaea changchunensis sp. nov. is proposed. The type strain is 201802YP6T (= CGMCC 1.13508T = KCTC 33975T).

SimBaby Plus Standardized Patient Teaching Model in the Teaching of Cases of Acute and Severe Bronchopneumonia in Infancy.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of SimBaby plus standardized patient (SP) teaching model in the simulation teaching of acute and severe bronchopneumonia in infancy. METHODS: A total of 40 students majoring in clinical medicine were assigned to either group A (SimBaby group, n = 20) or group B (SP + SimBaby group, n = 20). Medical students' expertise and their ability to apply the expertise on acute and severe bronchopneumonia in infancy were assessed using a scoring method, and the impact of the teaching model of SimBaby plus SP on medical students' comprehensive clinical capacity was assessed using a questionnaire. RESULTS: The SimBaby plus SP teaching model resulted in medical students' improvement in mastery and application of the knowledge on diagnostic accuracy, airway management, endotracheal intubation, and cardiac massage, enhancement of learning interest, learning initiative, and enthusiasm, as well as abilities in assessment of information, meta-analysis, linguistic organization and expression, communication, and clinical thinking. CONCLUSIONS: The SimBaby plus SP teaching model provided students with a real simulation-based teaching case of "interrogation-physical examination-operating practices" achieving satisfactory teaching outcome and also provided a reference case example for clinical teaching of other pediatric diseases.

The immunomodulator decoy receptor 3 improves locomotor functional recovery after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) causes loss of neurons and axons and results in motor and sensory function impairments. SCI elicits an inflammatory response and induces the infiltration of immune cells, predominantly macrophages, to the injured site. Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member (TNFRSF)-6B, is a pleiotropic immunomodulator capable of inducing macrophage differentiation into the M2 phenotype and enhancing angiogenesis. Because M2 macrophages are crucial for the recovery of impaired motor functions, we ask whether DcR3 is beneficial for the functional recovery of locomotion in Sprague-Dawley (SD) rats after SCI. METHODS: Contusion injury of the spinal cord was performed using a New York University impactor at the ninth thoracic vertebrae, followed by intrathecal injection of 15 µg recombinant protein comprising DcR3 (DcR3.Fc) in 5 µl of normal saline as the treatment, or 5 µl of normal saline as the control, into the injury epicenter. Functional recovery was evaluated using an open-field test weekly up to 6 weeks after injury. The cavity size and myelin sparing in the rostral-to-caudal region, including the epicenter of the injury, were then examined in SCI rats by histological staining. The expression of anti-inflammatory cytokines and the presence of M2 macrophages were determined by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry at 7 day after SCI. Statistical analysis was performed using a two-tailed Student's t test. RESULTS: Intrathecal administration of DcR3.Fc significantly improved locomotor function and reduced secondary injury with a smaller wound cavity and increased myelin sparing at the lesion site. Compared with the control group, DcR3.Fc-treated rats had increased vascularization at the injury epicenter along with higher levels of interleukin (IL)-4 and IL-10 and lower level of IL-1ß on DcR3.Fc-treated rats at day 7 after SCI. Moreover, higher levels of arginase I (Arg I) and CD206 (M2 macrophage markers) and RECA-1 (endothelial marker) were observed in the epicenter on day 7 after SCI by immunofluorescence staining. CONCLUSIONS: These results indicated that DcR3.Fc may promote the M2 macrophage infiltration and enhanced angiogenesis at the lesion site, thus preserving a greater amount of spinal cord tissues and enhancing functional recovery after SCI.

Adaptive divergence with gene flow in incipient speciation of Miscanthus floridulus/sinensis complex (Poaceae).

Young incipient species provide ideal materials for untangling the process of ecological speciation in the presence of gene flow. The Miscanthus floridulus/sinensis complex exhibits diverse phenotypic and ecological differences despite recent divergence (approximately 1.59 million years ago). To elucidate the process of genetic differentiation during early stages of ecological speciation, we analyzed genomic divergence in the Miscanthus complex using 72 randomly selected genes from a newly assembled transcriptome. In this study, rampant gene flow was detected between species, estimated as M = 3.36 × 10(-9) to 1.20 × 10(-6) , resulting in contradicting phylogenies across loci. Nevertheless, beast analyses revealed the species identity and the effects of extrinsic cohesive forces that counteracted the non-stop introgression. As expected, early in speciation with gene flow, only 3-13 loci were highly diverged; two to five outliers (approximately 2.78-6.94% of the genome) were characterized by strong linkage disequilibrium, and asymmetrically distributed among ecotypes, indicating footprints of diversifying selection. In conclusion, ecological speciation of incipient species of Miscanthus probably followed the parapatric model, whereas allopatric speciation cannot be completely ruled out, especially between the geographically isolated northern and southern M. sinensis, for which no significant gene flow across oceanic barriers was detected. Divergence between local ecotypes in early-stage speciation began at a few genomic regions under the influence of natural selection and divergence hitchhiking that overcame gene flow.

Theoretical investigation on action mechanism and mollifying efficacy of propellant stabilizers.

CONTEXT: This project performed quantum chemical computation, through kinetic and thermodynamic analyses to compare relative reactivity, reaction rate, and equilibrium composition from the possible pathways in connection with stabilizer-nitrodioxide reactions to determine the stability of the materials for practical application. Corresponding achievements have promoted the use of N-methyl-p-nitroaniline (MNA) and dinitrophenyl malonamide series (M3, M4, and M5) stabilizers as high priorities for selection. METHODS: The Gaussian 09 program (G09) (Frisch et al 2009) and density functional theory (DFT) calculations with the B3LYP/6-31G(d,p) function were performed to obtain related geometric and thermodynamic energy data for the molecular systems in this study. The synchronous transit-guided quasi-Newton method (STQN) (Peng and Schlegel Isr J Chem 33:49, 1993) was applied through the QST3 procedure to identify single imaginary frequency-valued transition-state species. The related reaction rate constant (k) and pre-exponential factor (A) were obtained, based on transition state theory (Su 2008), using Eqs. 11 and 12.

[Application of high hip center technique in total hip arthroplasty in patients with Crowe typeâ ¡and â ¢ developmental dysplasia of hip and severe hip osteoarthritis].

OBJECTIVE: To explore the clinical efficacy of high hip center technique total hip arthroplasty （THA） for Crowe Ⅱand Ⅲ developmental dysplasia of hip （DDH） and severe hip osteoarthritis （HOA）. METHODS: From January 2018 to January 2020, 74 patients with Crowe typeⅡand Ⅲ DDH and severe HOA were admitted, and 37 cases of anatomical hip center reconstruction were taken as control group, including 7 males and 30 females, aged from 42 to 65 years old with an average of （58.40±4.98） years old, body mass index （BMI） ranged from 18 to 29 kg·m-2 with an average of （23.02±2.21） kg·m-2. Thirty-seven routine high hip center technical reconstruction were performed as study group, including 5 males and 32 females, aged from 41 to 65 years old with an average of （57.31±5.42） years old, BMI ranged from 18 to 29 kg·m-2 with an average of （23.14±2.07） kg·m-2. The patients presented with hip pain, limited function and range of motion, and gait instability before surgery. All patients underwent THA, the control group underwent intraoperative anatomical hip center reconstruction, and the study group underwent intraoperative high hip joint reconstruction. The perioperative indicators of the two groups were compared. The hip joint function, balance function and gait of the patients were evaluated before surgery, 3 months, 6 months, and 12 months after surgery. The length difference of both lower limbs, horizontal distance of rotation center, vertical distance of rotation center and femoral eccentricity were measured before operation and 1 year after operation. The incidence of complications in the two groups during the operation and postoperative follow-up was counted. RESULTS: The operation time of the study group was shorter than that of the control group, and the intraoperative blood loss was less than that of the control group （P<0.05）. After 12-months follow-up, 1 was lost to followvup in study group and 2 were lost to follow-up in control group. The Harris scores and Berg balance scale（BBS）, pace, stride frequency and single step length in the study group were higher than those in the control group at 3 months and 6 months after operation （P<0.05）；there was no statistically significant difference between the two groups in the indexes 12 months after operation （P>0.05）. The vertical distance of the center of rotation of the study group was greater than that of the control group 12 months after operation （P<0.05）, and there was no significant difference in the length difference of the lower limbs, the horizontal distance of the center of rotation, and the femoral eccentricity between two groups （P>0.05）. There were no complications in either group. CONCLUSION: The long-term effects of THA in patients with DDH and severe HOA were similar between the two central hip reconstruction methods, and the safety was good, and the high hip central reconstruction technique could shorten the operation time and reduce the amount of intraoperative blood loss.At the same time, it has certain advantages in early recovery of hip joint function, balance function and walking function of patients.

A causal association between lipid-lowering medications and rotator cuff syndrome: a drug-targeted mendelian randomization study.

Background: Previous research has suggested that dyslipidemia may be a risk factor for rotator cuff syndrome (RCS), and lipid-lowering drugs may aid in its treatment, though conclusions have not been definitive. Mendelian randomization is a statistical method that explores the causal relationships between exposure factors and diseases. It overcomes the confounding issues inherent in traditional observational studies, thereby providing more reliable causal inferences. We employed this method to investigate whether hyperlipidemia is a risk factor for rotator cuff syndrome and whether lipid-lowering drugs can effectively treat this condition. Methods: Genetic variations linked to lipid traits low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) were acquired from the UK Biobank and the Global Lipids Genetics Consortium (GLGC). Data on genetic variation in rotator cuff syndrome were obtained from FinnGen, including 24,061 patients and 275,212 controls. In the next step, we carried out two-sample Mendelian randomization analyses to determine whether lipid traits correlate with rotator cuff syndrome risk. Additionally, we performed drug-target Mendelian randomization (MR) analyses on 10 drug targets related to rotator cuff syndrome. For the drug targets that showed significant results, further analysis was done using Summary-data-based Mendelian Randomization (SMR) and colocalization techniques. We performed a mediation analysis to identify potential mediators between HMG-CoA reductase (HMGCR) and RCS. Results: No causative link was established between these lipid traits and rotator cuff syndrome. However, a significant association has been identified where HMGCR inhibition corresponds to a reduced risk of rotator cuff disease (OR = 0.68, [95% CI, 0.56-0.83], p = 1.510 × 10-4). Additionally, enhanced expression of HMGCR in muscle tissues is also linked to a decreased risk of rotator cuff syndrome (OR = 0.88, [95% CI, 0.76-0.99], p = 0.03). Body mass index (BMI) mediated 22.97% of the total effect of HMGCR on RCS. Conclusion: This study does not support low-density LDL-C, TG, and TC as risk factors for rotator cuff syndrome. HMGCR represents a potential pharmaceutical target for preventing and treating rotator cuff syndrome. The protective action of statins on the rotator cuff syndrome might not be associated with their lipid-lowering properties.

Analysis of fluid force and flow fields during gliding in swimming using smoothed particle hydrodynamics method.

Gliding is a crucial phase in swimming, yet the understanding of fluid force and flow fields during gliding remains incomplete. This study analyzes gliding through Computational Fluid Dynamics simulations. Specifically, a numerical model based on the Smoothed Particle Hydrodynamics (SPH) method for flow-object interactions is established. Fluid motion is governed by continuity, Navier-Stokes, state, and displacement equations. Modified dynamic boundary particles are used to implement solid boundaries, and steady and uniform flows are generated with inflow and outflow conditions. The reliability of the SPH model is validated by replicating a documented laboratory experiment on a circular cylinder advancing steadily beneath a free surface. Reasonable agreement is observed between the numerical and experimental drag force and lift force. After the validation, the SPH model is employed to analyze the passive drag, vertical force, and pitching moment acting on a streamlined gliding 2D swimmer model as well as the surrounding velocity and vorticity fields, spanning gliding velocities from 1 m/s to 2.5 m/s, submergence depths from 0.2 m to 1 m, and attack angles from -10° to 10°. The results indicate that with the increasing gliding velocity, passive drag and pitching moment increase whereas vertical force decreases. The wake flow and free surface demonstrate signs of instability. Conversely, as the submergence depth increases, there is a decrease in passive drag and pitching moment, accompanied by an increase in vertical force. The undulation of the free surface and its interference in flow fields diminish. With the increase in the attack angle, passive drag and vertical force decrease whereas pitching moment increases, along with the alteration in wake direction and the increasing complexity of the free surface. These outcomes offer valuable insights into gliding dynamics, furnishing swimmers with a scientific basis for selecting appropriate submergence depth and attack angle.

Flushing emissions of methane and carbon dioxide from mangrove soils during tidal cycles.

Mangroves are transition areas connecting land, freshwater, and the ocean, where a great amount of organic carbon accumulates in the soil, forming a considerable carbon sink. However, the soil might also be a source of greenhouse gas (GHG) emissions. This study hypothesized that measuring GHG emissions solely during low tides can represent diurnal GHG emissions in mangroves. Methane (CH4) and carbon dioxide (CO2) emissions were quantified during tidal cycles using an ultraportable gas analyzer in Kandelia obovata (without pneumatophores) and Avicennia marina (with pneumatophores) mangroves in summer and fall. The results showed that the CH4 fluxes varied greatly during tidal cycles, from -1.25 to 96.24 µmol CH4 m-2 h-1 for K. obovata and from 2.86 to 2662.00 µmol CH4 m-2 h-1 for A. marina. The CO2 fluxes ranged from -4.23 to 20.65 mmol CO2 m-2 h-1 for K. obovata and from 0.09 to 24.69 mmol CO2 m-2 h-1 for A. marina. The diurnal variation in GHG levels in mangroves is predominantly driven by tidal cycles. The peak emissions of CH4 and CO2 were noted at the beginning of the flooding tide, rather than during daytime or nighttime. While the patterns of the CO2 fluxes during tidal cycles were similar between K. obovata and A. marina mangroves, their CH4 flux patterns during the tidal cycles differed. Possibly due to different transport mechanisms, CO2 emissions are primarily influenced by surface soils, whereas CH4 is predominantly emitted from deeper soils, thus being influenced by root structures. To reduce the uncertainty in measuring GHG emissions in mangrove soils during a tidal cycle, it is advisable to increase the number of GHG flux measurements during the period spanning 30 min before and after the beginning of the flooding and ebbing tides.