Engineering strategies for enhanced 1', 4'-trans-ABA diol production by Botrytis cinerea.

BACKGROUND: Currently, industrial fermentation of Botrytis cinerea is a significant source of abscisic acid (ABA). The crucial role of ABA in plants and its wide range of applications in agricultural production have resulted in the constant discovery of new derivatives and analogues. While modifying the ABA synthesis pathway of existing strains to produce ABA derivatives is a viable option, it is hindered by the limited synthesis capacity of these strains, which hinders further development and application. RESULTS: In this study, we knocked out the bcaba4 gene of B. cinerea TB-31 to obtain the 1',4'-trans-ABA-diol producing strain ZX2. We then studied the fermentation broth of the batch-fed fermentation of the ZX2 strain using metabolomic analysis. The results showed significant accumulation of 3-hydroxy-3-methylglutaric acid, mevalonic acid, and mevalonolactone during the fermentation process, indicating potential rate-limiting steps in the 1',4'-trans-ABA-diol synthesis pathway. This may be hindering the flow of the synthetic pathway. Additionally, analysis of the transcript levels of terpene synthesis pathway genes in this strain revealed a correlation between the bchmgr, bcerg12, and bcaba1-3 genes and 1',4'-trans-ABA-diol synthesis. To further increase the yield of 1',4'-trans-ABA-diol, we constructed a pCBg418 plasmid suitable for the Agrobacterium tumefaciens-mediated transformation (ATMT) system and transformed it to obtain a single-gene overexpression strain. We found that overexpression of bchmgr, bcerg12, bcaba1, bcaba2, and bcaba3 genes increased the yield of 1',4'-trans-ABA-diol. The highest yielding ZX2 A3 strain was eventually screened, which produced a 1',4'-trans-ABA-diol concentration of 7.96 mg/g DCW (54.4 mg/L) in 144 h of shake flask fermentation. This represents a 2.1-fold increase compared to the ZX2 strain. CONCLUSIONS: We utilized metabolic engineering techniques to alter the ABA-synthesizing strain B. cinerea, resulting in the creation of the mutant strain ZX2, which has the ability to produce 1',4'-trans-ABA-diol. By overexpressing the crucial genes involved in the 1',4'-trans-ABA-diol synthesis pathway in ZX2, we observed a substantial increase in the production of 1',4'-trans-ABA-diol.

Characteristics of the gut microbiota and serum metabolites in postmenopausal women with reduced bone mineral density.

Introduction: Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women. Methods: In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis. Results: The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene. Discussion: Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis.

Highly oxidized guaiane 12(8),15(6)-dilactones with neuroprotective activities from the roots of Lindera aggregata (Sims) Kosterm.

In our search for neuroprotective agents, six previously undescribed highly oxidized guaiane sesquiterpenes, linderaggrols A-F (1-6), together with three known sesquiterpenes, were isolated from the roots of Lindera aggregata (Sims) Kosterm. Their structures including absolute configurations were established by a combination of NMR spectroscopic techniques and single crystal X-ray diffraction experiments. Compounds 1-6 represented the first instances of guaiane 12(8),15(6)-dilactones. Additionally, compound 6 possessed a rare 1,8-O-bridge. Neuroprotective effects against erastin-induced ferroptosis on HT-22 cells showed that some compounds demonstrated neuroprotective effects at 20.0 µM.

Functional and structural gradients reveal atypical hierarchical organization of Parkinson's disease.

Parkinson's disease (PD) patients exhibit deficits in primary sensorimotor and higher-order executive functions. The gradient reflects the functional spectrum in sensorimotor-associated areas of the brain. We aimed to determine whether the gradient is disrupted in PD patients and how this disruption is associated with treatment outcome. Seventy-six patients (mean age, 59.2 ± 12.4 years [standard deviation], 44 women) and 34 controls participants (mean age, 58.1 ± 10.0 years [standard deviation], 19 women) were evaluated. We explored functional and structural gradients in PD patients and control participants. Patients were followed during 2 weeks of multidisciplinary intensive rehabilitation therapy (MIRT). The Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) was administered to patients before and after treatment. We investigated PD-related alterations in the principal functional and structural gradients. We further used a support vector machine (SVM) and correlation analysis to assess the classification ability and treatment outcomes related to PD gradient alterations, respectively. The gradients showed significant differences between patients and control participants, mainly in somatosensory and visual networks involved in primary function, and higher-level association networks (dorsal attentional network (DAN) and default mode network (DMN)) related to motor control and execution. On the basis of the combined functional and structural gradient features of these networks, the SVM achieved an accuracy of 91.2% in discriminating patients from control participants. Treatment reduced the gradient difference. The altered gradient exhibited a significant correlation with motor improvement and was mainly distributed across the visual network, DAN and DMN. This study revealed damage to gradients in the brain characterized by sensorimotor and executive control deficits in PD patients. The application of gradient features to neurological disorders could lead to the development of potential diagnostic and treatment markers for PD.

Normal distribution of H3K9me3 occupancy co-mediated by histone methyltransferase BcDIM5 and histone deacetylase BcHda1 maintains stable ABA synthesis in Botrytis cinerea TB-31.

Abscisic acid (ABA) is a conserved and important "sesquiterpene signaling molecule" widely distributed in different organisms with unique biological functions. ABA coordinates reciprocity and competition between microorganisms and their hosts. In addition, ABA also regulates immune and stress responses in plants and animals. Therefore, ABA has a wide range of applications in agriculture, medicine and related fields. The plant pathogenic ascomycete B. cinerea has been extensively studied as a model strain for ABA production. Nevertheless, there is a relative dearth of research regarding the regulatory mechanism governing ABA biosynthesis in B. cinerea. Here, we discovered that H3K9 methyltransferase BcDIM5 is physically associated with the H3K14 deacetylase BcHda1. Deletion of Bcdim5 and Bchda1 in the high ABA-producing B. cinerea TB-31 led to severe impairment of ABA synthesis. The combined analysis of RNA-seq and ChIP-seq has revealed that the absence of BcDIM5 and BcHda1 has resulted in significant global deficiencies in the normal distribution and level of H3K9me3 modification. In addition, we found that the cause of the decreased ABA production in the ΔBcdim5 and ΔBchda1 mutants was due to cluster gene repression caused by the emergence of hyper-H3K9me3 in the ABA gene cluster. We concluded that the ABA gene cluster is co-regulated by BcDIM5 and BcHda1, which are essential for the normal distribution of the B. cinerea TB-31 ABA gene cluster H3K9me3. This work expands our understanding of the complex regulatory network of ABA biosynthesis and provides a theoretical basis for genetic improvement of high-yielding ABA strains.

Photo-crosslinked integrated triphasic scaffolds with gradient composition and strength for osteochondral regeneration.

Owing to the avascular and aneural nature of cartilage tissue and the complex, multilayered structure of osteochondral units, the repair of osteochondral defects poses significant challenges. Traditional monophasic scaffolds have difficulty meeting the repair requirements of both cartilage and bone tissues, whereas multiphasic scaffolds face the issue of interfacial integration. In this study, a triphasic methylpropenylated gelatin (GELMA) hydrogel scaffold was employed to repair osteochondral defects, in which three layers of hydrogel were covalently bonded through a sequential curing process. The upper layer of the scaffold was covalently bonded with chondroitin sulfate, promoting chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The middle and lower layers of the hydrogel introduced a gradient content of hydroxyapatite, forming a scaffold with gradient mechanical strength and effectively enhancing its angiogenic and osteogenic induction capabilities. Finally, the triphasic integrated scaffold cartilage and bone repair performance was evaluated using a rabbit knee joint defect model. The results demonstrated that the scaffold facilitated accelerated regeneration of osteochondral defects, thus providing a novel strategy for the treatment of osteochondral defects.

Photo-self-Fenton Reaction Mediated by Atomically Dispersed Ag-Co Photocatalysts toward Efficient Degradation of Organic Pollutants.

Achieving the complete mineralization of persistent pollutants in wastewater is still a big challenge. Here, we propose an efficient photo-self-Fenton reaction for the degradation of different pollutants using the high-density (Ag: 22 wt %) of atomically dispersed AgCo dual sites embedded in graphic carbon nitride (AgCo-CN). Comprehensive experimental measurements and density functional theory (DFT) calculations demonstrate that the Ag and Co dual sites in AgCo-CN play a critical role in accelerating the photoinduced charge separation and forming the self-Fenton redox centers, respectively. The bimetallic AgCo-CN exhibited excellent photocatalytic performance toward the phenol even under extreme conditions due to an efficient degradation pathway and in situ generation of the hydrogen peroxide producing the main active oxygen species (⋅OH and 1 O2 ) and showed long-term activity in a self-design photo-Filter reactor for the purification of the phenol. Our discoveries pave the way for the design of efficient single-atoms photocatalysts-based photo-self-Fenton reaction for recalcitrant pollutant treatment.

Analysis of the Potential Angiogenic Mechanisms of BuShenHuoXue Decoction against Osteonecrosis of the Femoral Head Based on Network Pharmacology and Experimental Validation.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease with a high disability rate. The clinical effect of BuShenHuoXue decoction (BSHX) for ONFH is satisfactory. We aimed to elucidate the potential angiogenic mechanisms of BSHX in a rat femoral osteonecrosis model and bone marrow mesenchymal stem cells (BMSCs). METHODS: With in vivo experiments, we established the steroid-induced osteonecrosis of the femoral head (SONFH) model using Sprague-Dawley (SD) rats (8-week-old). The rats were randomly divided into five group of 12 rats each and given the corresponding interventions: control, model (gavaged with 0.9% saline), BSHX low-, medium- and high-dose groups (0.132 3, 0.264 6, and 0.529 2 g/mL BSHX solution by gavage). After 12 weeks, haematoxylin and eosin (H&E) staining was preformed to evaluate rat osteonecrosis. the expression of angiogenic factors (CD31, VEGFA, KDR, VWF) in rat femoral head was detected by immunohistochemistry, qPCR and western blotting. In cell experiment, BMSCs were isolated and cultured in the femoral bone marrow cavity of 4-week-old SD rats. BMSCs were randomly divided into eight groups and intervened with different doses of BSHX-containing serum and glucocorticoids: control group (CG); BSHX low-, medium-, and high-dose groups (CG + 0.661 5, 1.323, and 2.646 g/kg BSHX gavage rat serum); dexamethasone (Dex) group; and Dex + BSHX low-, medium-, and high-dose groups (Dex + 0.661 5, 1.323, and 2.646 g/kg BSHX gavaged rat serum), the effects of BSHX-containing serum on the angiogenic capacity of BMSCs were examined by qPCR and Western blotting. A co-culture system of rat aortic endothelial cells (RAOECs) and BMSCs was then established. Migration and angiogenesis of RAOECs were observed using angiogenesis and transwell assay. Identification of potential targets of BSHX against ONFH was obtained using network pharmacology. RESULTS: BSHX upregulated the expression of CD31, VEGFA, KDR, and VWF in rat femoral head samples and BMSCs (p < 0.05, vs. control group or model group). Different concentrations of BSHX-containing serum significantly ameliorated the inhibition of CD31, VEGFA, KDR and VWF expression by high concentrations of Dex. BSHX-containing serum-induced BMSCs promoted the migration and angiogenesis of RAOECs, reversed to some extent the adverse effect of Dex on microangiogenesis in RAOECs, and increased the number of microangiogenic vessels. Furthermore, we identified VEGFA, COL1A1, COL3A1, and SPP1 as important targets of BSHX against ONFH. CONCLUSION: BSHX upregulated the expression of angiogenic factors in the femoral head tissue of ONFH model rats and promoted the angiogenic capacity of rat RAOECs and BMSCs. This study provides an important basis for the use of BSHX for ONFH prevention and treatment.

Combination of fractional carbon dioxide laser with recombinant human collagen in periocular skin rejuvenation.

BACKGROUND: The most visible sign of facial aging is often seen in the periocular area. However, periocular rejuvenation remains challenging due to the particularity of periocular anatomic locations. AIMS: We aimed to evaluate the efficacy and safety of the fractional-ablative CO2 laser-facilitated recombinant human collagen permeation in periocular rejuvenation. PATIENTS/METHODS: This 3-month prospective single-blinded and self-controlled trial enrolled 26 patients with periocular aging who underwent the treatments of fractional-ablative CO2 laser along with laser-facilitated recombinant human collagen permeation. Following the treatments, the patients were quantitatively assessed by various periocular skin aging indices before and after the treatment and monitored for any related adverse events. RESULTS: The patients showed significant improvements with the periocular skin aging indices 3 months after the treatments, which were detailed with a 47.3% decrease in lower eyelid skin rhytids, a 41.4% decrease in the lower eyelid skin texture, a 35.0% decrease in the static crow's feet, a 29.3% decrease in the amount of upper eyelid laxity, and a 20.2% increase in the MRD1 as compared with baseline (p < 0.05). Moreover, total skin thickness under ultrasound was increased in both upper and lower eyelids (5.6% and 3.3%, p < 0.05, respectively). Moreover, six patients (23.1%, 6/26) had erythema for 2 weeks, and two (2/26, 7.7%) had mild hyperpigmentation for 3 months. CONCLUSIONS: Fractional-ablative CO2 laser combined with laser-facilitated recombinant human collagen permeation can be a safe and effective treatment for periocular rejuvenation.

Restraint Stress, Foot Shock and Corticosterone Differentially Alter Autophagy in the Rat Hippocampus, Basolateral Amygdala and Prefrontal Cortex.

Autophagy is a conserved lysosomal degradation process that has recently been found to be associated with stress-related psychological diseases. However, previous studies have yielded inconsistent results regarding the effects of various stress patterns on autophagy in different brain regions. This discrepancy may arise from differences in autophagy flux across nuclei, the type of stress experienced, and the timing of autophagy assessment after stress exposure. In this study, we assessed autophagy flux in the rat hippocampus (HPC), medial prefrontal cortex (mPFC), and basal lateral amygdala (BLA) by quantifying protein levels of p-ULK1, LC3-I, LC3-II, and p62 via Western blot analysis at 15 min, 30 min, and 60 min following various stress paradigms: restraint stress, foot shock, single corticosterone injection, and chronic corticosterone treatment. We found that: (1) hippocampal autophagy decreased within 1 h of restraint stress, foot shock, and corticosterone injection, except for a transient increase at 30 min after restraint stress; (2) autophagy increased 1 h after restraint stress and corticosterone injection but decreased 1 h after foot shock in mPFC; (3) In BLA, autophagy increased 1 h after foot shock and corticosterone injection but decreased 1 h after restraint stress; (4) Chronic corticosterone increased autophagy in mPFC and BLA but had no effects in HPC. These findings suggest that stress regulates autophagy in a brain region- and stressor-specific manner within 1 h after stress exposure, which may contribute to the development of stress-related psychological disorders.

Knowledge mapping of programmed cell death in osteonecrosis of femoral head: a bibliometric analysis (2000-2022).

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common, refractory and disabling disease of orthopedic department, which is one of the common causes of hip pain and dysfunction. Recent studies have shown that much progress has been made in the research of programmed cell death (PCD) in ONFH. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hot spots of PCD in ONFH through bibliometrics. METHOD: The literature search related to ONFH and PCD was conducted on the Web of Science Core Collection (WoSCC) database from 2002 to 2021. The VOSviewers, "bibliometrix" R package and CiteSpace were used to conduct this bibliometric analysis. RESULTS: In total, 346 articles from 27 countries led by China and USA and Japan were included. The number of publications related to PCD in ONFH is increasing year by year. Shanghai Jiao Tong University, Xi An Jiao Tong University, Wuhan University and Huazhong University of Science and Technology are the main research institutions. Molecular Medicine Reports is the most popular journal in the field of PCD in ONFH, and Clinical Orthopaedics and Related Research is the most cocited journal. These publications come from 1882 authors among which Peng Hao, Sun Wei, Zhang Chang-Qing, Zhang Jian and Wang Kun-zheng had published the most papers and Ronald S Weinstein was cocited most often. Apoptosis, osteonecrosis, osteonecrosis of the femoral head, glucocorticoid and femoral head appeared are the main topics the field of PCD in ONFH. Autophagy was most likely to be the current research hot spot for PCD in ONFH. CONCLUSION: This is the first bibliometric study that comprehensively summarizes the research trends and developments of PCD in ONFH. This information identified recent research frontiers and hot directions, which will provide a reference for scholars studying PCD in ONFH.

Novel ecological implications of non-toxic Microcystis towards toxic ecotype in population-promoting toxic ecotype dominance at various N levels and cooperative defense against luteolin-stress.

Microcystin (MC)-producing (MC+) and MC-free (MC-) Microcystis always co-exist and interact during Microcystis-dominated cyanobacterial blooms (MCBs), where MC+Microcystis abundance and extracellular MC-content (EMC) determine the hazard extent of MCBs. The current study elucidated intraspecific interaction between MC+ and MC-Microcystis at various nitrogen (N) levels (0.5-50 mg/L) and how such N-mediated interaction impacted algicidal and EMC-inhibiting effect of luteolin, a natural bioalgicide. Conclusively, MC+ and MC-Microcystis were inhibited mutually at N-limitation (0.5 mg/L), which enhanced the algicidal and EMC-inhibiting effects of luteolin. However, at N-sufficiency (5-50 mg/L), MC-Microcystis promoted MC+ ecotype growth and dominance, and such intraspecific interaction induced the cooperative defense of two ecotypes, weakening luteolin's algicidal and EMC-inhibiting effects. Mechanism analyses further revealed that MC+Microcystis in luteolin-stress co-culture secreted exopolymeric substances (EPSs) for self-protection against luteolin-stress and also released more EMC to induce EPS-production by MC-Microcystis as protectants, thus enhancing their luteolin-resistance and promoting their growth. This study provided novel ecological implications of MC-Microcystis toward MC+ ecotype in terms of assisting the dominant establishment of MC+Microcystis and cooperative defense with MC+ ecotype against luteolin, which guided the application of bioalgicide (i.e. luteolin) for MCBs and MCs pollution mitigation in different eutrophication-degree waters.

Characterization and properties of manganese oxide film coated clinoptilolite as filter material in fixed-bed columns for removal of Mn(II) from aqueous solution.

A new filter material, manganese oxide film coated clinoptilolite (MOFCC), was characterized and introduced to explore the effect in treating high concentration of manganese (1.71-2.12 mg L-1) from aqueous solution in fixed-bed column. Adsorption behavior of Mn(II) can be approximately described with the Langmuir isotherm. During the continuous 30 days filtration experiment, the removal rate of Mn(II) has maintained to be above 95.51%, the accumulated removal amount (806.42 mg) is much higher than the theoretical adsorption capacity (89.71 mg), which indicated that the removal of manganese by MOFCC includes both adsorption and auto-catalytic oxidation process, and it does not require a start-up period. SEM, EDS, XPS, XRD, ZETA potential and BET analyses were used to observe the surface properties of MOFCC. The manganese oxide film of MOFCC exhibits in clusters, apparently on occupied surface, the main component of the manganese oxide film is (Na0.7Ca0.3)Mn7O14·2.8H2O, the specific surface area of MOFCC is 38.76 m2 g-1, and the pore size is concentrated in the range of 3-40 nm, within the mesoporous range mesopores. pHpzc (point of zero charge) value is about 2.36. The characteristics of MOFCC make it an excellent manganese removal filter material for water treatment plant. Therefore, there is a long-term practical significance to develop new system for deep removal of manganese based on MOFCC.

Recalcitrant nodular scabies showing excellent response to tofacitinib: five case reports.

Scabies is a contagious skin condition caused by Sarcoptes scabiei, and it is always associated with an intense, unbearable, nocturnal deteriorating itch. Its presentations include classic burrows, erythema, pruritic papules, pustules, vesicles, and inflammatory nodules, with diffuse or localized distribution on the finger webs, wrist flexors, elbows, axillae, buttocks, genitalia, and breasts. Nodular scabies is an uncommon clinical variant of scabies. Its management is still challenging for some patients up to date, although topical, intralesional or systemic corticosteroids, topical calcineurin inhibitors, and crotamiton as well as cryotherapy alone or in different combinations are used. We here report five male patients of nodular scabies, aged between 14 and 25 years, who had classical scabies that had been cured by sulfur ointment for at least 4 weeks except for their itching nodules, and their residual pruritic nodules also failed in previous treatments including antihistamines, topical applying and intralesional injection of steroids as well as topical tacrolimus in different combinations before being recruited to this study. The patients were administered tofacitinib 5 mg, twice a day, which led to excellent and rapid improvement for both lesions and symptoms after 1-4 weeks of treatment, respectively, without any associations. During 6 months of follow-up, only one had re-infection of scabies associated with nodules that were cured by sulfur ointment and tofacitinib again. No adverse reaction was observed. The present results suggested that tofacitinib might be a potential agent for nodular scabies with excellent response.

Analysis of influencing factors of job demands of healthcare workers working in mobile cabin hospitals in China.

AIM: To explore the job demands of healthcare workers (HCWs) working in mobile cabin hospitals in Shanghai and identify the influencing factors. DESIGN: The study had a cross-sectional design. METHODS: Using the convenience sampling method, we selected 1223 HCWs (medical team members) working in these mobile cabin hospitals during April-May 2022. The findings of the general information questionnaire and the hierarchy scale of job demands of HCWs working in mobile cabin hospitals were used for the investigation. RESULTS: The total score of job demands of the included HCWs was 132.26 ± 9.53; the average score of the items was 4.73 ± 0.34. Multivariate linear regression analyses showed that the following HCWs had significantly higher job demands: female HCWs and HCWs who received psychological training or intervention during the COVID-19 pandemic, were satisfied with the doctor/nurse-patient relationship, received support from family members/friends/colleagues, believed that the risk of working in mobile cabin hospitals was high, had adapted to the working environment of mobile cabin hospitals and had college/undergraduate level of education. They would benefit from increased social support and better training in terms of psychological coping mechanisms(both theoretical knowledge and applicable skills) and COVID-19 prevention,control and treatment abilities.

Variational Neural-Network Ansatz for Continuum Quantum Field Theory.

Physicists dating back to Feynman have lamented the difficulties of applying the variational principle to quantum field theories. In nonrelativistic quantum field theories, the challenge is to parametrize and optimize over the infinitely many n-particle wave functions comprising the state's Fock-space representation. Here we approach this problem by introducing neural-network quantum field states, a deep learning ansatz that enables application of the variational principle to nonrelativistic quantum field theories in the continuum. Our ansatz uses the Deep Sets neural network architecture to simultaneously parametrize all of the n-particle wave functions comprising a quantum field state. We employ our ansatz to approximate ground states of various field theories, including an inhomogeneous system and a system with long-range interactions, thus demonstrating a powerful new tool for probing quantum field theories.

The Effect of the Hip Flexion Angle in Osteonecrosis of the Femoral Head Based on China-Japan Friendship Hospital Classification - A Finite Element Study.

OBJECTIVE: The alteration in the mechanical environment of the necrotic area is the primary cause of the collapse observed in osteonecrosis of the femoral head (ONFH). This study aims to evaluate the biomechanical implications of the China-Japan Friendship Hospital (CJFH) classification system and hip flexion angles on the necrotic area in ONFH using finite element analysis (FEA). The goal is to provide valuable guidance for hip preservation treatments and serve as a reference for clinical diagnosis and therapeutic interventions. METHODS: Hip tomography CT scan data from a healthy volunteer was used to create a 3D model of the left hip. The model was preprocessed and imported into Solidworks 2018, based on the CJFH classification. Material parameters and boundary conditions were applied to each fractal model in ANSYS 21.0. Von Mises stresses were calculated, and maximum deformation values were obtained to evaluate the biomechanical effects of the load on the necrotic area and post-necrotic femur, as well as assess each fractal model's collapse risk. RESULTS: (1) At the same hip flexion angle, maximum deformation followed this order: M Type < C Type < L Type. The L3 type necrotic area experienced the most significant deformation at 0, 60, and 110° angles (1.121, 1.7913, and 1.8239 mm respectively). (2) Under the same CJFH classification, maximum deformation values increased with hip flexion angle (0 < 60 < 110°), suggesting a higher risk of collapse at larger angles. (3) Von Mises stress results showed that the maximum stress was not located in the necrotic area but near the inner and outer edge of the femoral neck, indicating decreased stiffness and strength of the subchondral bone after osteonecrosis. CONCLUSION: The study found that femoral head collapse risk was higher when the necrotic area was located in the lateral column under the same stress load and flexion angle. Mechanical properties of the necrotic area changed, resulting in decreased bone strength and stiffness. Large-angle hip flexion is more likely to cause excessive deformation of the necrotic area; thus, ONFH patients should reduce or avoid large-angle hip flexion during weight-bearing training in rehabilitation activities.

Plasma lipids, alcohol intake frequency and risk of Osteoarthritis: a Mendelian randomization study.

BACKGROUD: Plasma lipids and alcohol intake frequency have been reported to be associated with the risk of osteoarthritis (OA). However, it remains inconclusive whether plasma lipids and alcohol intake frequency play a role in the development of OA. METHODS: The study employed a comprehensive genome-wide association database to identify independent genetic loci strongly linked to plasma lipids and alcohol intake frequency, which were used as instrumental variables. The causal association between plasma lipids, alcohol intake frequency, and the risk of OA was then analyzed using two-sample Mendelian randomization methods such as inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), with odds ratios (ORs) as the evaluation criteria. RESULTS: A total of 392 SNPs were included as instrumental variables in this study, including 32 for total cholesterol (TC), 39 for triglycerides (TG), 170 for high-density lipoproteins (HDL), 60 for low-density lipoproteins (LDL), and 91 for alcohol intake frequency. Using the above two-sample Mendelian Randomization method to derive the causal association between exposure and outcome, with the IVW method as the primary analysis method and other MR analysis methods complementing IVW. The results of this study showed that four exposure factors were causally associated with the risk of OA. TC obtained a statistically significant result for IVW (OR = 1.207, 95% CI: 1.018-1.431, P = 0.031); TG obtained a statistically significant result for Simple mode (OR = 1.855, 95% CI: 1.107-3.109, P = 0.024); LDL obtained three statistically significant results for IVW, WME and Weighted mode (IVW: OR = 1.363, 95% CI: 1.043-1.781, P = 0.023; WME: OR = 1.583, 95% CI: 1.088-2.303, P = 0.016; Weighted mode: OR = 1.521, 95% CI: 1.062-2.178, P = 0.026). Three statistically significant results were obtained for alcohol intake frequency with IVW, WME and Weighted mode (IVW: OR = 1.326, 95% CI: 1.047-1.678, P = 0.019; WME: OR = 1.477, 95% CI: 1.059-2.061, P = 0.022; Weighted mode: OR = 1.641, 95% CI: 1.060-2.541, P = 0.029). TC, TG, LDL, and alcohol intake frequency were all considered as risk factors for OA. The Cochran Q test for the IVW and MR-Egger methods indicated intergenic heterogeneity in the SNPs contained in TG, HDL, LDL, and alcohol intake frequency, and the test for pleiotropy indicated a weak likelihood of pleiotropy in all causal analyses. CONCLUSIONS: The results of two-sample Mendelian randomization analysis showed that TC, TG, LDL, and alcohol intake frequency were risk factors for OA, and the risk of OA increased with their rise.