MFG-E8 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells through GSK3ß/ß-catenin signaling pathway.

Fracture nonunion and bone defects are challenging for orthopedic surgeons. Milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein possibly secreted by macrophages in a fracture hematoma, participates in bone development. However, the role of MFG-E8 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. We investigated the osteogenic effect of MFG-E8 in vitro and in vivo. The CCK-8 assay was used to assess the effect of recombinant human MFG-E8 (rhMFG-E8) on the viability of hBMSCs. Osteogenesis was investigated using RT-PCR, Western blotting, and immunofluorescence. Alkaline phosphatase (ALP) and Alizarin red staining were used to evaluate ALP activity and mineralization, respectively. An enzyme-linked immunosorbent assay was conducted to evaluate the secretory MFG-E8 concentration. Knockdown and overexpression of MFG-E8 in hBMSCs were established via siRNA and lentivirus vector transfection, respectively. Exogenous rhMFG-E8 was used to verify the in vivo therapeutic effect in a tibia bone defect model based on radiographic analysis and histological evaluation. Endogenous and secretory MFG-E8 levels increased significantly during the early osteogenic differentiation of hBMSCs. Knockdown of MFG-E8 inhibited the osteogenic differentiation of hBMSCs. Overexpression of MFG-E8 and rhMFG-E8 protein increased the expression of osteogenesis-related genes and proteins and enhanced calcium deposition. The active ß-catenin to total ß-catenin ratio and the p-GSK3ß protein level were increased by MFG-E8. The MFG-E8-induced enhanced osteogenic differentiation of hBMSCs was partially attenuated by a GSK3ß/ß-catenin signaling inhibitor. Recombinant MFG-E8 accelerated bone healing in a rat tibial-defect model. In conclusion, MFG-E8 promotes the osteogenic differentiation of hBMSCs by regulating the GSK3ß/ß-catenin signaling pathway and so, is a potential therapeutic target.

Whole life exposure to low dose cadmium alters diet-induced NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a major global public health concern affecting more than 25% of the world's population. Although obesity and diabetes are major risk factors for NAFLD, they cannot account for all cases, indicating the importance of other factors such as environmental exposures. Cadmium (Cd) exposure is implicated in the development of NAFLD; however, the influence of early life, in utero Cd exposure on the development of diet-induced NAFLD is poorly understood. Therefore, we developed an in vivo, multiple-hit model to study the effect of whole-life, low dose Cd exposure on high fat diet (HFD)-induced NAFLD. Adult male and female C57BL/6 J mice fed normal diets (ND) were exposed to 0, 0.5 or 5 ppm Cd-containing drinking water for 14 weeks before breeding. At weaning, offspring were fed ND or HFD and continued on the same drinking water regimen as their parents for 24 weeks. Cd exposure at different concentrations differentially altered HFD-associated adverse health effects, including liver injury. HFD-induced increased body weight, decreased glucose tolerance. Liver injury and lipid deposition were exacerbated by 5 ppm Cd exposure but attenuated by 0.5 ppm Cd exposure. Further, HFD blunted the response of metallothionein, a major Cd detoxification protein, in mice exposed to 5 ppm Cd but enhanced the response in mice exposed to 0.5 ppm Cd, suggesting a possible mechanism for Cd alteration of HFD-induced NAFLD. These results confirm the multi-hit nature of NAFLD and show whole life, low dose Cd exposure alters HFD-induced NAFLD with outcomes dependent on Cd concentration.

Iodine Immobilized Metal-Organic Framework for NIR-Triggered Antibacterial Therapy on Orthopedic Implants.

Iodine has been known as an effective disinfectant with broad-spectrum antimicrobial potency yet without drug resistance risk when used in clinic. However, the exploration of iodine for antibacterial therapy in orthopedics remains sparse due to its volatile nature and poor solubility. Herein, leveraging the superior absorption capability of metal-organic frameworks (MOFs) and their inherent photocatalytic properties, iodine-loaded MOF surface is presented to realize responsive iodine release along with intracellular reactive oxygen species(ROS) oxidation under near-infrared (NIR) exposure to achieve synergistic antibacterial effect. Iodine is successfully loaded using vapor deposition process onto zeolitic imidazolate framework-8(ZIF-8), which is immobilized onto micro arc oxidized titanium via a hydrothermal approach. The combination of NIR-triggered iodine release and ZIF-8 mediated ROS oxidative stress substantially augments the antibacterial efficacy of this approach both in vitro and in vivo. Furthermore, this composite coating also supported osteogenic differentiation of bone marrow stromal cells, as well as improved osseointegration of coated implants using an intramedullary rat model, suggesting improvement of antibacterial efficacy does not impair osteogenic potential of the implants. Altogether, immobilization of iodine via MOF on orthopedic implants with synergistic antibacterial effect can be a promising strategy to combat bacterial infections.

Establishment of an immortalized cell line derived from the pupal ovary of Mythimna separata (Lepidoptera: Noctuidae) and identification of the cell source.

Determining the source of primary cells is conductive to enriching sufficient cells with immortal potential thereby improving the success rate of establishing cell lines. However, most of the existing insect cell lines are established by mixing and fragmentation of explants. At present, the origin of cell lines can only be determined according to the cultured tissues, so it is impossible to determine which cell types they come from. In this study, a new cell line designated IOZCAS-Myse-1 was generated from pupal ovaries of the migratory pest Mythimna separata by explant tissues to derive adherent cultures. This paper mainly shows the further descriptive information on the origin of primary cells in the process of ovarian tissue isolation and culture. Phospho-histone H3 antibody-labeled cells with mitotic activity showed that the rapidly developing somatic cells in vivo gradually stopped proliferation when cultured ex vivo. The primary cells dissociated outside the tissue originated from the lumen cells, rather than the germ cells or the follicular epithelium cells. The results suggest that the newly established cell line IOZCAS-Myse-1 had two possible sources. One is the mutation of lumen cells in the vitellarium, and the other is the stem cells with differentiation potential in the germarium of the ovarioles. Moreover, the newly established cell line is sensitive to the infection of Autographa californica multiple nucleopolyhedrovirus, responds to 20-hydroxyecdysone and has weak encapsulation ability. Therefore, the new cell line can be a useful platform for replication of viral insecticides, screening of hormone-based insecticides and immunology research.

Drought tolerance in Brassica napus is accompanied with enhanced antioxidative protection, photosynthetic and hormonal regulation at seedling stage.

Climate change, food insecurity, water scarcity, and population growth are some of today's world's frightening problems. Drought stress exerts a constant threat to field crops and is often seen as a major constraint on global agricultural productivity; its intensity and frequency are expected to increase in the near future. The present study investigated the effects of drought stress (15% w/v polyethylene glycol PEG-6000) on physiological and biochemical changes in five Brassica napus cultivars (ZD630, ZD622, ZD619, GY605, and ZS11). For drought stress induction, 3-week-old rapeseed oil seedlings were treated with PEG-6000 in full strength Hoagland nutrient solution for 7 days. PEG treatment significantly decreased the plant growth and photosynthetic efficiency, including primary photochemistry (Fv/Fm) of PSII, intercellular CO2 , net photosynthesis, chlorophyll contents, and water-use efficiency of all studied B. napus cultivars; however, pronounced growth retardations were observed in cultivar GY605. Drought-stressed B. napus cultivars also experienced a sharp rise in H2 O2 generation and malondialdehyde (MDA) content. Additionally, the accumulation of ROS was accompanied by increased activity of enzymatic antioxidants (superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, glutathione reductase, and monodehydroascorbate reductase), although the increase was more obvious in ZD622 and ZS11. Drought stress also caused an increased endogenous hormonal biosynthesis (abscisic acid, jasmonic acid, salicylic acid) and accumulation of total soluble proteins and proline content, but the extent varies in B. napus cultivars. These results suggest that B. napus cultivars have an efficient drought stress tolerance mechanism, as shown by improved antioxidant enzyme activities, photosynthetic and hormonal regulation.

Zinc protects against cadmium-induced toxicity in neonatal murine engineered cardiac tissues via metallothionein-dependent and independent mechanisms.

Cadmium (Cd) is a nonessential heavy metal and a prevalent environmental toxin that has been shown to induce significant cardiomyocyte apoptosis in neonatal murine engineered cardiac tissues (ECTs). In contrast, zinc (Zn) is a potent metallothionein (MT) inducer, which plays an important role in protection against Cd toxicity. In this study, we investigated the protective effects of Zn against Cd toxicity in ECTs and explore the underlying mechanisms. ECTs were constructed from neonatal ventricular cells of wild-type (WT) mice and mice with global MT gene deletion (MT-KO). In WT-ECTs, Cd (5-20 µM) caused a dose-dependent toxicity that was detected within 8 h evidenced by suppressed beating, apoptosis, and LDH release; Zn (50-200 µM) dose-dependently induced MT expression in ECTs without causing ECT toxicity; co-treatment of ECT with Zn (50 µM) prevented Cd-induced toxicity. In MT-KO ECTs, Cd toxicity was enhanced; but unexpectedly, cotreatment with Zn provided partial protection against Cd toxicity. Furthermore, Cd, but not Zn, significantly activated Nrf2 and its downstream targets, including HO-1; inhibition of HO-1 by a specific HO-1 inhibitor, ZnPP (10 µM), significantly increased Cd-induced toxicity, but did not inhibit Zn protection against Cd injury, suggesting that Nrf2-mediated HO-1 activation was not required for Zn protective effect. Finally, the ability of Zn to reduce Cd uptake provided an additional MT-independent mechanism for reducing Cd toxicity. Thus, Zn exerts protective effects against Cd toxicity for murine ECTs that are partially MT-mediated. Further studies are required to translate these findings towards clinical trials.

Serum uric acid level is associated with the incidence of heterotopic ossification following elbow trauma surgery.

BACKGROUND: Heterotopic ossification (HO) is a common complication after surgery for elbow trauma. Uric acid is the end product of purine metabolism and has several physiological and pathogenic roles. However, the relationship between HO and uric acid has not been explored. This retrospective study aimed to assess the relationship between HO and serum uric acid (SUA). MATERIAL AND METHODS: We retrospectively reviewed data from 155 patients undergoing elbow trauma surgery in our hospital between January 2013 and December 2018. One hundred patients were included according to the inclusion criteria. They were divided into 2 groups according to the presence or absence of HO, and the SUA level was compared between groups using the independent samples t test. The optimal prognostic cutoff value was obtained using the maximum value of the Youden index. RESULTS: The SUA level was significantly higher in the HO group than in the non-HO group (362.0 ± 87.4 µmol/L vs. 318.3 ± 87.0 µmol/L; P < .05). Using the maximum value of Youden index, 317.5 µmol/L was determined to be the optimal SUA cutoff value for the prediction of HO, with a sensitivity of 68.75% (95% confidence interval [CI], 54.67%-80.05%) and specificity of 55.77% (95% CI, 42.34%-68.40%). CONCLUSIONS: Our study was the first to find that the high SUA level is a risk factor for HO of the elbow joint after trauma. Moreover, 317.5 µmol/L is the SUA threshold predicting the occurrence and development of HO of the elbow, with high sensitivity and specificity.

Physiological and iTRAQ-Based Quantitative Proteomics Analysis of Methyl Jasmonate-Induced Tolerance in Brassica napus Under Arsenic Stress.

Brassica napus plants exposed to 200 µM arsenic (As) exhibited high-level of stress condition, which led to inhibited growth, enhanced lipid peroxidation, and disrupted cellular ultrastructures. Exogenous application of methyl jasmonate (MeJA) alleviated the As-induced oxidative stress and improved the plant growth and photosynthesis. In this study, changes in the B. napus leaf proteome are investigated in order to identify molecular mechanisms involved in MeJA-induced As tolerance. The study identifies 177 proteins that are differentially expressed in cultivar ZS 758; while 200 differentially expressed proteins are accumulated in Zheda 622, when exposed to As alone and MeJA+As treatments, respectively. The main objective was to identify the MeJA-regulated protein under As stress. Consistent with this, iTRAQ detected 61 proteins which are significantly accumulated in ZS 758 leaves treated with MeJA under As stress. While in Zheda 622, iTRAQ detected 49 MeJA-induced proteins under As stress. These significantly expressed proteins are further divided into five groups on the base of their function, that is, stress and defense, photosynthesis, carbohydrates and energy production, protein metabolism, and secondary metabolites. Taken together, this study sheds light on the molecular mechanisms involved in MeJA-induced As tolerance in B. napus leaves and suggests a more active involvement of MeJA in plant physiological processes.

Monotropein promotes angiogenesis and inhibits oxidative stress-induced autophagy in endothelial progenitor cells to accelerate wound healing.

Attenuating oxidative stress-induced damage and promoting endothelial progenitor cell (EPC) differentiation are critical for ischaemic injuries. We suggested monotropein (Mtp), a bioactive constituent used in traditional Chinese medicine, can inhibit oxidative stress-induced mitochondrial dysfunction and stimulate bone marrow-derived EPC (BM-EPC) differentiation. Results showed Mtp significantly elevated migration and tube formation of BM-EPCs and prevented tert-butyl hydroperoxide (TBHP)-induced programmed cell death through apoptosis and autophagy by reducing intracellular reactive oxygen species release and restoring mitochondrial membrane potential, which may be mediated viamTOR/p70S6K/4EBP1 and AMPK phosphorylation. Moreover, Mtp accelerated wound healing in rats, as indicated by reduced healing times, decreased macrophage infiltration and increased blood vessel formation. In summary, Mtp promoted mobilization and differentiation of BM-EPCs and protected against apoptosis and autophagy by suppressing the AMPK/mTOR pathway, improving wound healing in vivo. This study revealed that Mtp is a potential therapeutic for endothelial injury-related wounds.

Salidroside attenuates neuroinflammation and improves functional recovery after spinal cord injury through microglia polarization regulation.

Spinal cord injury (SCI) is a severe neurological disease; however, few drugs have been proved to treat SCI effectively. Neuroinflammation is the major pathogenesis of SCI secondary injury and considered to be the therapeutic target of SCI. Salidroside (Sal) has been reported to exert anti-inflammatory effects in airway, adipose and myocardial tissue; however, the role of Sal in SCI therapeutics has not been clarified. In this study, we showed that Sal could improve the functional recovery of spinal cord in rats as revealed by increased BBB locomotor rating scale, angle of incline, and decreased cavity of spinal cord injury and apoptosis of neurons in vivo. Immunofluorescence double staining of microglia marker and M1/M2 marker demonstrated that Sal could suppress M1 microglia polarization and activate M2 microglia polarization in vivo. To verify how Sal exerts its effects on microglia polarization and neuron protection, we performed the mechanism study in vitro in microglia cell line BV-2 and neuron cell line PC12. The results showed that Sal prevents apoptosis of PC12 cells in coculture with LPS-induced M1 BV-2 microglia, also the inflammatory secretion phenotype of M1 BV-2 microglia was suppressed by Sal, and further studies demonstrated that autophagic flux regulation through AMPK/mTOR pathway was involved in Sal regulated microglia polarization after SCI. Overall, our study illustrated that Sal could promote spinal cord injury functional recovery in rats, and the mechanism may relate to its microglia polarization modulation through AMPK-/mTOR-mediated autophagic flux stimulation.

Does Timing of Surgery Affect Treatment of the Terrible Triad of the Elbow?

BACKGROUND This study investigated the influence of surgical timing on the treatment of terrible triad of the elbow (TTE). MATERIAL AND METHODS After exclusion, 63 patients were enrolled in this study: 20 patients were classified into the emergency group (group A, within 24 h after injury), 26 into the early surgery group (group B, from 4 to 14 days after injury), and 17 into the delayed surgery group (group C, more than 14 days after injury). All patients underwent the same approach, and elbow motion and complication rates were recorded and compared. RESULTS Fifty-eight patients were followed up (mean 20.5±1.9 months), and 5 patients had lost partial final data. At 1 month after the operation, elbow motion in group A was higher than in group B and group C (P<0.01); however, 3 or more months later, there was no distinct difference between group A and group B (P>0.05), while both group A and group B showed better outcomes than group C at all time points (P<0.05). Moreover, group A and group B had better higher elbow motion, MEPS, excellent and good rate than group C at the final clinical visit (all P<0.05). No postoperative pain or complication rate differences were found among the 3 groups except for elbow stiffness (2 in group A, 3 in group B, and 7 in group C) (P<0.05) which required reoperation to enhance elbow function. CONCLUSIONS Emergency or early operation for TTE patients were more effective than delayed operation.

Selective toxicity of the mesoionic insecticide, triflumezopyrim, to rice planthoppers and beneficial arthropods.

The novel mesoionic insecticide triflumezopyrim was highly effective in controlling both imidacloprid-susceptible and resistant planthopper populations in Malaysia. However, the toxicity of triflumezopyrim to planthopper populations and their natural enemies has been under-investigated in China. In this study, the median lethal concentrations (LC50) of triflumezopyrim were determined in eight field populations of Nilaparvata lugens and one population of Sogatella furcifera from China under laboratory conditions. Triflumezopyrim showed higher toxicity to planthopper populations than the commonly-used insecticide, imidacloprid. Furthermore, the lethal effect of triflumezopyrim on eight beneficial arthropods of planthoppers was investigated in the laboratory and compared with three commonly-used insecticides, thiamethoxam, chlorpyrifos and abamectin. Triflumezopyrim was harmless to Anagrus nilaparvatae, Cyrtorhinus lividipennis and Paederus fuscipes, while thiamethoxam, chlorpyrifos and abamectin were moderately harmful or harmful to the insect parasitoid and predators. Triflumezopyrim and thiamethoxam were harmless to the predatory spiders Pirata subpiraticus, Ummeliata insecticeps, Hylyphantes graminicola and Pardosa pseudoannulata, and slightly harmful to Theridion octomaculatum. Chlorpyrifos caused slight to high toxicity to four spider species except U. insecticeps. Abamectin was moderately to highly toxic to all five spider species. Our results indicate that triflumezopyrim has high efficacy for rice planthoppers populations and is compatibile with their natural enemies in China.

Analysis of meteorological dryness/wetness features for spring wheat production in the Ili River basin, China.

Understanding the impacts of climate change on crop yield is important for improving crop growth and yield formation in northwestern China. In this study, we evaluated the relationship between meteorological dryness/wetness conditions and spring wheat yield in the Ili river basin (IRB). The climate and yield data from 1961 to 2013 were collected to analyze characteristics and correlations between these two variables using the standardized precipitation evapotranspiration index (SPEI), yield detrending method, modified Mann-Kendall test and Spearman correlation analysis. Main results were as follows: (1) correlations between monthly SPEI values (MSV) and climatic yield of spring wheat indicated that the dryness/wetness condition in May was a key factor affecting yield in the whole region; (2) although the MSV in May and yield fluctuated from negative to positive values in time, the severely and extremely dryness events were in good agreement with the higher yield losses; (3) each increase of 0.5 MSV in May promoted over 3% increase of yield in most part of IRB; however, the larger variability of MSV in May resulted in larger yield fluctuations; and (4) the Tibetan Plateau index in April showed significant correlations with the MSV in May and yield, which provided a precursory signal for decision-makers to better understand potential yield fluctuations.

Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation.

Cisplatin-loaded mesoporous polydopamine nanoparticles capped with MnO2 and coated with platelet membrane provide synergistic anti-tumor therapy.

A multifunctional nanoplatform was constructed in this work, with the goal of ameliorating the challenges faced with traditional cancer chemotherapy. Cisplatin (CP) was loaded into mesoporous polydopamine (mPDA) nanoparticles (NPs) with a drug loading of 15.8 ± 0.1 %, and MnO2 used as pore sealing agent. Finally, the NPs were wrapped with platelet membrane (PLTM). P-selectin on the PLTM can bind to CD44, which is highly expressed on the tumor cell membrane, so as to improve the targeting performance of the NPs. In addition, the CD47 on the PLTM can prevent the NPs from being phagocytosed by macrophages, which is conducive to immune escape. The final PLTM-CP@mPDA/MnO2 NPs were found to have a particle size of approximately 198 nm. MnO2 is degraded into Mn2+ in the tumor microenvironment, leading to CP release from the pores in the mPDA. CP both acts as a chemotherapy agent and can also increase the concentration of H2O2 in cells. Mn2+ can catalyze the conversion of H2O2 to OH, resulting in oxidative damage and chemodynamic therapy. In addition, Mn2+ can be used as a contrast agent in magnetic resonance imaging (MRI). In vitro and in vivo experiments were performed to explore the therapeutic effect of the NPs. When the concentration of CP is 30 µg/mL, the NPs cause approximately 50 % cell death. It was found that the PLTM-CP@mPDA/MnO2 NPs are targeted to cancerous cells, and in the tumor site cause extensive apoptosis. Tumor growth is thereby repressed. No negative off-target side effects were noted. MRI could be used to confirm the presence of the NPs in the tumor site. Overall, the nano-platform developed here provides cooperative chemotherapy and chemodynamic therapy, and can potentially be used for effective cancer treatment which could be monitored by MRI.

Nutritional composition analysis of meat from human lactoferrin transgenic bulls.

Transgenic technology has many potential advantages in food production. However, the transgenic technology process may influence the composition of food products derived from genetically engineered (GE) animals, which may be adverse to human health. Therefore, it is very important to research the compositions of GE animal products. Here, we analyzed the compositions of meat from the offspring of human lactoferrin (hLF) transgenic cows, which can express human lactoferrin proteins in their mammary gland. Six hLF transgenic bulls and three wide-type (WT) bulls, 10 months of age, were slaughtered for meat composition analysis. To determine the comparative health of hLF bulls for meat analysis, hematological analyses, organ/body weight analyses and pathology analyses were conducted. Results of the meat analysis show that there were no significant differences in the hematological parameters, organ/body weight ratios of hLF and WT bulls (P>0.05), and histopathological examination of the main organs of hLF bulls revealed no abnormalities. Nutrient parameters of meat compositions of hLF and WT bulls did not show any significant differences (P>0.05). All of these results suggest that the hLF transgene did not have an impact on the meat nutrient compositions of hLF bulls.

Deleveraging and decapacity: A comparative analysis of corporate capital allocation based on asset reversibility.

China's stimulus policies have caused overleveraging and overcapacity for the sustainable development of most industries (particularly high-pollution and energy-intensive industries). Thus, deleveraging and decapacity have become the two best options for the above industries to achieve long-term sustainable development. Based on China's A-share listed companies from 2009 to 2019, this study investigated the effect of deleveraging and decapacity on corporate capital allocation using fixed effects, propensity score matching (PSM) and difference-in-differences (DID). A homogeneity analysis of geographical and firm characteristics was also conducted. The results show that: (1) Deleveraging and decapacity can significantly increase financial capital allocation by 3.67%, and decapacity can increase investment-related capital allocation by 0.63%. This indicates asset allocation optimization for sustainable development. (2) High asset reversibility can weaken the effect of deleveraging on financial capital allocation while strengthening the effect of decapacity on capital investment. (3) The impact of deleveraging and decapacity may vary among companies due to heterogeneous asset reversibility resulting from geographical locations and technological intensities. Given the current global energy crisis, optimizing capital allocation has become essential in addressing resource shortages and achieving long-term sustainable development. This study may provide a reference for alleviating corporate capital misallocation.

Engineered Sensory Nerve Guides Self-Adaptive Bone Healing via NGF-TrkA Signaling Pathway.

The upstream role of sensory innervation during bone homeostasis is widely underestimated in bone repairing strategies. Herein, a neuromodulation approach is proposed to orchestrate bone defect healing by constructing engineered sensory nerves (eSN) in situ to leverage the adaptation feature of SN during tissue formation. NGF liberated from ECM-constructed eSN effectively promotes sensory neuron differentiation and enhances CGRP secretion, which lead to improved RAOECs mobility and osteogenic differentiation of BMSC. In turn, such eSN effectively drives ossification in vivo via NGF-TrkA signaling pathway, which substantially accelerates critical size bone defect healing. More importantly, eSN also adaptively suppresses excessive bone formation and promotes bone remodeling by activating osteoclasts via CGRP-dependent mechanism when combined with BMP-2 delivery, which ingeniously alleviates side effects of BMP-2. In sum, this eSN approach offers a valuable avenue to harness the adaptive role of neural system to optimize bone homeostasis under various clinical scenario.

Effects of whole-life exposure to low-dose cadmium with post-weaning high-fat diet on offspring testes in a male mouse model.

Although several studies have reported testicular impairments caused by cadmium (Cd) or obesity alone, the combined effect of Cd and obesity on the testes and its underlying mechanism remains unclear. We examined the combined effect of whole-life exposure to low-dose Cd started at preconception and post-weaning high-fat diet (HFD) on the testes of offspring mice. At weaning, male offspring parented with and without exposure to low-dose Cd were continued on the same drinking water regimen as their parents and fed with either a normal diet (ND) or HFD for 10 or 24 weeks. Whole-life exposure to Cd resulted in its accumulation in testes, and HFD induced obesity and lipid metabolism disorder. Exposure to Cd or HFD alone significantly decreased Johnsen scores, disrupted testicular structure, and increased germ cell apoptosis at both 10 and 24 weeks. However, co-exposure to Cd and HFD did not induce the toxic effects that were induced by either alone, as revealed by preserved testicular structure and spermatogenesis, lack of significant apoptosis, and increased cell proliferation. Mechanistically, the combined effects of low-dose Cd and HFD consumption were associated with the activation of the JAK/STAT pathway. These findings suggest that co-exposure to low-dose Cd and HFD did not cause Cd- or HFD-induced testicular injury, probably because of the activation of the JAK/STAT pathway to prevent germ cell apoptosis.

One-Pot Synthesis of Ag/Quaternary Ammonium Salt Co-Decorated Mesoporous Silica Nanoparticles for Synergistic Treatment of Cancer and Bacterial Infections.

Developing drug delivery nanosystems with both anticancer and antibacterial effects is of great clinical value. Herein, we report a facile approach to synthesize Ag and quaternary ammonium salt (QAS) co-decorated mesoporous silica nanoparticles (MSNs), namely, Ag/QAS-MSNs, for synergistic treatment of cancer and bacterial infections. In vitro studies demonstrated that Ag/QAS-MSNs not only had a strong antibacterial activity against the bacterial pathogens but also could efficiently induce cancer cell death through an apoptotic pathway. Moreover, in vivo combination therapy with Ag and QAS in Ag/QAS-MSNs was also tested in a nude mouse tumor model, and a significant synergistic anticancer effect, which is superior to that obtained by therapy with Ag-MSNs or QAS-MSNs alone, was achieved. Such excellent anticancer and antibacterial activity of Ag/QAS-MSNs could be attributed to the synergistic effect of Ag ions and QAS. Thus, Ag/QAS-MSNs have a promising future as potent anticancer agents with high antibacterial performance.