Carbon Dot-Loaded Apoptotic Vesicles Improve the Liver Kupffer Cell-Mediated Antibacterial Effect to Synergistically Alleviate Sepsis.

Sepsis is a lethal systemic inflammatory disease against infection that lacks effective therapeutic approaches. Liver resident macrophage Kupffer cell (KC)-initiated bacterial clearance is crucial for the host to defend against infection. However, it remains unclear whether this process also governs the antibacterial therapy of sepsis that would be used to improve therapeutic outcomes. Here, we found that copper-doped carbon dots (Cu-CDs) exhibited superior antibacterial capabilities in vitro but displayed limited therapeutic effects in septic mice due to their limited ability to target the liver and restore KC antimicrobial capacity. Thus, we developed a composite nanodrug of copper-doped carbon dot-loaded apoVs (CC-apoVs) that combined the antibacterial ability of Cu-CDs and liver KC targeting features of apoV. Moreover, intravenous injection of CC-apoVs markedly alleviated the systemic infection and decreased the mortality of septic mice compared to Cu-CD and apoV infusion alone. Mechanistically, CC-apoV injection rescued impaired liver KCs during sepsis and enhanced their ability to capture and kill bloodborne bacteria. In addition, apoV-promoted macrophage killing of bacteria could be blocked by the inhibition of small GTPase Rab5. This study reveals a liver KC-targeted therapeutic strategy for sepsis and provides a nanodrug CC-apoV to improve the host antibacterial defense and amplify the therapeutic effect of the nanodrug.

Astragaloside IV attenuates renal tubule injury in DKD rats via suppression of CD36-mediated NLRP3 inflammasome activation.

Background: In recent years, diabetic kidney disease (DKD) has emerged as a prominent factor contributing to end-stage renal disease. Tubulointerstitial inflammation and lipid accumulation have been identified as key factors in the development of DKD. Earlier research indicated that Astragaloside IV (AS-IV) reduces inflammation and oxidative stress, controls lipid accumulation, and provides protection to the kidneys. Nevertheless, the mechanisms responsible for its protective effects against DKD have not yet been completely elucidated. Purpose: The primary objective of this research was to examine the protective properties of AS-IV against DKD and investigate the underlying mechanism, which involves CD36, reactive oxygen species (ROS), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1ß (IL-1ß). Methods: The DKD rat model was created by administering streptozotocin along with a high-fat diet. Subsequently, the DKD rats and palmitic acid (PA)-induced HK-2 cells were treated with AS-IV. Atorvastatin was used as the positive control. To assess the therapeutic effects of AS-IV on DKD, various tests including blood sugar levels, the lipid profile, renal function, and histopathological examinations were conducted. The levels of CD36, ROS, NLRP3, Caspase-1, and IL-1ß were detected using western blot analysis, PCR, and flow cytometry. Furthermore, adenovirus-mediated CD36 overexpression was applied to explore the underlying mechanisms through in vitro experiments. Results: In vivo experiments demonstrated that AS-IV significantly reduced hyperglycemia, dyslipidemia, urinary albumin excretion, and serum creatinine levels in DKD rats. Additionally, it improved renal structural abnormalities and suppressed the expression of CD36, NLRP3, IL-1ß, TNF-α, and MCP-1. In vitro experiments showed that AS-IV decreased CD36 expression, lipid accumulation, and lipid ROS production while inhibiting NLRP3 activation and IL-1ß secretion in PA-induced HK-2 cells. Conclusion: AS-IV alleviated renal tubule interstitial inflammation and tubule epithelial cell apoptosis in DKD rats by inhibiting CD36-mediated lipid accumulation and NLRP3 inflammasome activation.

Strategically reducing carbapenem-resistant Acinetobacter baumannii through PDCA cycle-driven antibiotic management.

PURPOSE: With the escalating global challenge of antibiotic resistance, particularly the resistance rate of Acinetobacter baumannii, the need to rationalize carbapenem antibiotic use in clinical settings has become paramount. Our study tapped into a fishbone diagram to uncover the irrationalities in applying these antibiotics and highlight potential influencing factors. METHODS: Based on these analyses, we initiated targeted intervention strategies. A PDCA cycle-based scientific management approach was implemented through the combined efforts of our antimicrobial stewardship team and relevant departments. RESULTS: Our study showed a significant post-intervention increase in the rational use of carbapenem antibiotics (P < 0.01) and a concurrent decrease in the detection of carbapenem-resistant Acinetobacter baumannii. CONCLUSION: Our findings underscore that carbapenem usage can be effectively minimized with the continuous refinements offered by the PDCA cycle, leading to a reduction in multidrug-resistant bacteria, thus fostering rational drug use in healthcare.

Characteristics of glucolipid metabolism and oxidative stress in breeding pigeons (Columba livia) during lactation.

Breeding pigeons is a fundamental source of profit in various enterprises but little is known on the metabolic laws governing their lactation. In this study, we analysed the metabolic profile of different sex of breeding pigeons (Columba livia, European pigeons, Mimas) during lactation. We found that male pigeons exhibited catabolism during lactation. Extension of lactation resulted in increased weight loss, then slow recovery of body weight. Conversely, the weight loss in female pigeons peaked on the seventh day of lactation. They then gradually recovered their body weight. Male pigeons showed more duration of combing, while female pigeons showed more duration of resting. In male pigeons, except for triglyceride (TG), which increased, blood lipid indexes barely changed during lactation. Conversely, in females, both TG and total cholesterol increased in middle and late lactation. The level of oxidative stress in female pigeons during lactation was higher than in males, lipid peroxide malondialdehyde, hydrogen peroxide (H2 O2 ), plasma calcium (Ca) and phosphorus (P) levels increased in late lactation. Levels of estradiol and progesterone in female pigeons increased during lactation, whereas those of luteotropic hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and testosterone gradually decreased. As per LC-MS spectra analysis, the differential metabolites in the plasma on the day of hatching and before laying in female pigeons in lactation were enriched in retrograde endocannabinoid signalling, α-linolenic acid, arachidonic acid, choline, glycerophospholipid metabolisms, and valine, leucine, and isoleucine degradations. Levels of fatty acids, amino acids, sphingomyelin and phosphatidylinositol related to the secretion of pigeon milk had reduced, whereas the levels of phosphatidylcholine, phosphatidylethanolamine, and TG, which are all related to egg production, had increased. In conclusion, our study systematically revealed the different metabolic characteristics of male and female breeding pigeons during lactation. This is useful for precision feeding of pigeons and applicable in nutritional interventions for improved production.

ASC-expressing pyroptotic extracellular vesicles alleviate sepsis by protecting B cells.

Pyroptosis is an inflammatory programmed cell death process characterized by membrane rupture. Interestingly, pyroptotic cells can generate plenty of nanosized vesicles. Non-inflammatory apoptotic cell death-derived apoptotic vesicles (apoVs) were systemically characterized and displayed multiple physiological functions and therapeutic potentials. However, the characteristics of pyroptotic cell-generated extracellular vesicles (EVs) are largely unknown. Here, we identified a group of pyroptotic EVs (pyroEVs) from in vitro cultured pyroptotic mesenchymal stem cells (MSCs), as well as from septic mouse blood. Compared with apoVs, pyroEVs express similar levels of annexin V, calreticulin, and common EV markers, but express a decreased level of apoptotic marker cleave caspase-3. PyroEVs, but not apoVs and exosomes, specifically express pyroptotic maker apoptosis-associated speck-like protein containing CARD (ASC). More importantly, MSC-derived pyroEVs protect B cells in the spleen and bone marrow to relieve inflammatory responses and enhance the survival rate of the septic mice. Mechanistically, pyroEV membrane-expressed ASC binds to B cells to repress cell death by repressing Toll-like receptor 4. This study uncovered the characteristics of pyroEVs and their therapeutic role in sepsis and B cell-mediated immune response.

Effects of granular feed on reproductive metabolism of breeding pigeons, intestinal development and microbiota of squab pigeons-A double-edged sword.

Pigeons like to eat raw grains, but meat pigeon enterprises often use compound feeds instead of raw grains to feed breeding pigeons to increase economic efficiency, which may change the pigeon's dietary behavior, and consequently lead to health and welfare problems. The purpose of this study was to investigate the effect of granular feeds on the health of high-yielding breeding pigeons and squabs in lactation. The results showed that, compared with raw grain group, the provision of granular feed resulted in lower total feed intake without affecting the weight of lactating breeding pigeons. Meanwhile, reproductive metabolism was improved and no oxidative stress was observed, which indicated that granular feeds had a positive effect on breeding pigeon's health. However, granular feed adversely affected jejunum development in squabs, compare wtih raw grain group, the growth rate of squab was reduced. Sequencing of the 16 s rRNA gene revealed that granular feed induced intestinal microbiota dysbiosis in the squabs. The use of granular feed reduced the relative abundance of gut microorganisms in functional categories related to lipid and energy metabolism, resulting in a decrease in the relative abundance of beneficial bacteria such as Bifidobacterium, Ligilactobacillus, Atopobium, and an increase in that of inflammation-related Limosilactobacillus, which likely inhibited squab intestinal development and growth. Although the use of granular feed can improve breeder metabolism, it affect the composition of the microbial community and gut development of squabs. Therefore, the use of granular feed in production should be more careful to avoid causing growth obstruction of squab.

Optimal dietary energy and protein levels for breeding pigeons in the winter "2 + 3" lactation pattern.

The nutritional requirements of breeding pigeons depend on their physiological period, breeding pattern, and environmental conditions. Despite works on reduced litter size in winter production to combat high mortality and the poor welfare of squabs, there are few studies on the related nutritional requirements of these pigeons. A total of 432 pairs of European Mimas pigeons were randomly divided into 9 groups in which 3 crude protein (CP) levels (15, 16.5, and 18%) and 3 metabolizable energy (ME) levels (12.2 MJ/kg, 12.4 MJ/kg, and 12.6 MJ/kg) were tested to determine the optimal energy and protein requirements of breeding pigeons in the winter "2 + 3" breeding pattern. The results showed that ME and CP levels had little effect on the body weight, feed intake, and egg quality of breeding pigeons during the lactation period. An 18% CP diet significantly increased the laying rate and hatchability (P < 0.05), but there was no difference in the laying rate with 18% CP and 16.5% CP during the whole reproductive cycle (P > 0.05). There was a significant interaction between ME and CP levels, and the laying interval of breeding pigeons in group 9 (18% CP; 12.6 MJ/kg) was significantly shortened (P < 0.05). For squabs, the ME level had no effect on growth performance, slaughter performance, or meat quality. The body weight of 21-day-old squabs in the 18% CP group increased by 3.16% compared with that of the 15% CP group, but there was no difference between the 18% CP and 16.5% CP groups. Compared with other experimental groups, group 7 (18% CP; 12.2 MJ/kg) had the fastest growth rate in squabs (P < 0.05), and the corresponding slaughter weight was also the heaviest (P < 0.05). We further found that the height of the squab intestinal epithelium was significantly increased in both the 16.5% CP and 18% CP groups of squabs (P < 0.01), but male breeding pigeons showed a certain degree of oxidative stress with an increase in CP level. In conclusion, the effects of 15 to 18% CP levels and 12.2 to 12.6 MJ/kg ME levels on the reproductive metabolism of breeding pigeons and the growth and development of squabs in the "2 + 3" breeding pattern during winter are small. For economic efficiency, we suggest that the CP level can be reduced to 16.5% while the ME level should not be less than 12.2 MJ/kg in practical production.

Effect of different dietary energy/protein ratios on growth performance, reproductive performance of breeding pigeons and slaughter performance, meat quality of squabs in summer.

Large-scale pigeon farming in China is gradually increasing. However, studies on the basic nutritional requirements of breeding pigeons during lactation, which greatly influence the productivity and economic benefits of pigeon breeding, remain scanty. The objective of this study was to determine the optimal dietary energy/protein ratio requirements for lactating pigeons in summer. A total of 576 pairs of Mimas breeding pigeons were randomly divided into 12 groups (n = 48 per treatment), and each pair bred 4 squabs. A two-way ANOVA design with different protein levels (15%, 16%, 17%, and 18%) for factor A and different energy levels (12.6 MJ/kg, 12.8 MJ/kg, and 13.0 MJ/kg) for factor B was used to design 12 groups of experimental diets for feeding. The experiment lasted for 28 d. We found that ME level had little effect on breeding pigeons, but the CP level and dietary energy/protein ratio significantly affected the reproductive and growth performance of the pigeons. The lowest total weight loss (P < 0.01), and the highest egg production (P < 0.01) were observed in group 11 (18% CP, 12.8 MJ/kg). It had no effect on egg quality. Both ME and CP levels significantly affected the growth performance, slaughter performance and meat quality of squabs, and there was a strong interaction between CP and ME. The fastest growth rate (P < 0.01) was observed in group 11 (18% CP, 12.8 MJ/kg). The best CP and ME combination for the eviscerated weight, pectoral muscle weight, organ weight, 45 min meat color (L⁎, a⁎, b⁎), pH, and muscle fiber characteristics were also group 11. Finally, the regression model revealed that the best dietary energy/protein ratio was 17.92 to 19.02 kcal/g for squabs and 16.72 kcal/g for the breeding pigeons. There was a strong interaction between energy and protein levels in breeding pigeons during the lactation period, and the best production performance was at 18% CP 12.8 MJ/kg. And this is recommended to be applied as the energy/protein ratio dietary requirement for breeding pigeons during lactation in the summer "2 + 4" pattern.

Metabolomics analysis of the effects of different litter size on reproductive metabolism and oxidative stress in breeding pigeon (Columba livia).

The pigeon breeding industry employs a high-rearing pattern to achieve economic benefits. However, too many squabs consume more energy of the breeding pigeons causing adverse effects on their breeding performance. To determine the optimal rearing patterns and the effects of different numbers of squabs on reproductive performance, oxidative stress, and glucolipid metabolism of lactating breeding pigeons in winter, three rearing patterns consisting of "2 + 2″, "2 + 3″ and "2 + 4" (a pair of breeding pigeons feeding two, three and four squabs, respectively) were adopted using European Mimas white pigeons breed. The feed intake, bodyweight loss, feed-to-meat ratio, and squab mortality were linearly increased with the number of squabs during lactation, while the bodyweight recovery rate and squab growth performance were significantly slowed down after lactation. Similarly, the laying rate was linearly decreased on days 16, 17, and 18 of lactation, with a similar pattern on the re-laying rate on days 11, 12, and 13 after first laying. In addition, the number of non-laying pigeons in the second batch was significantly increased, implying that the number of squabs significantly affected the reproductive performance of female pigeons. The eggshell weight and thickness in the "2 + 3″ group were significantly increased. However, the number of squabs in the "2 + 3″ group had no significant effect on plasma calcium (Ca) and phosphorus (P) levels. Analysis of the glucolipid metabolism index and oxidative stress level of pigeons further revealed that the contents of triglyceride (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) in the plasma of male pigeons were significantly decreased with the increase in the number of squabs, but there was no obvious oxidative stress. On the contrary, glucose (GLU), TG, malondialdehyde (MDA) in the plasma of female pigeons were significantly increased, total antioxidant capacity (T-AOC) were significantly decreased, implying that the female pigeons suffered more oxidative stress and more dramatic changes in glucolipid metabolism. Metabolomics revealed that the differential metabolites in the plasma of female pigeons in "2 + 2″, "2 + 3″, and "2 + 4″ groups were significantly enriched in the fatty acid, phospholipid, sphingolipid metabolism, and the Krebs cycle pathways, especially under "2 + 4″ rearing pattern. Overall, in female pigeons, the available lipids were reduced; hence, their body turned to sugar dysplasia and protein utilization mode, increasing the oxidative stress level and decreasing their reproductive performance. Therefore, an increased number of squabs significantly affects the body condition and reproductive performance of breeding pigeons. The "2 + 3″ rearing pattern is the most suitable for winter breeding pigeon production under the current nutrition level.

The difficulty of oral speech act production tasks in second language pragmatics testing.

This study examined the relative difficulty of oral speech act production tasks involving eight different types of speech acts for Chinese English as a foreign language (EFL) learners and the effects of three contextual variables, namely, power, social distance, and imposition, on such difficulty. Eight Oral Discourse Completion Task items, each representing a unique combination of the three contextual variables, were designed for each speech act. Eighty Chinese EFL learners responded to these items and their responses were rated for appropriateness by two native-speaking college English instructors. A Many-facet Rasch Measurement analysis suggested that the eight speech acts can be ordered by ascending difficulty as follows: Thank, Request, Suggestion, Disagreement, Invitation, Refusal, Offer, and Apology. Significant effects on performance scores were found for the interaction between each of the three contextual variables and speech act, and the specific effects observed varied by speech act. The implications of our findings for L2 pragmatics testing are discussed.

Apoptotic extracellular vesicles are metabolized regulators nurturing the skin and hair.

Over 300 billion of cells die every day in the human body, producing a large number of endogenous apoptotic extracellular vesicles (apoEVs). Also, allogenic stem cell transplantation, a commonly used therapeutic approach in current clinical practice, generates exogenous apoEVs. It is well known that phagocytic cells engulf and digest apoEVs to maintain the body's homeostasis. In this study, we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles. Mechanistically, apoEVs activate the Wnt/ß-catenin pathway to facilitate their metabolism in a wave-like pattern. The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension, which is associated with the mechanical force-regulated expression of DKK1 in circulation. Furthermore, we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/ß-catenin pathway in skin and hair follicle mesenchymal stem cells. This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.

Influence of TiCN addition on the microstructures and mechanical properties of the AZ31 alloy.

The microstructure and mechanical properties of extruded AZ31 + xTiCN (x = 0, 0.4, 0.8, 1.2 wt%) were investigated, and the strengthening mechanism was discussed. X-ray diffraction and energy dispersive spectroscopy (EDS) confirmed that the Al4C3 and Al2MgC2 duplex phase particles were generated in situ by TiCN and Al particles, which act as the nucleation precursors of Mg grains during solidification. The grain size decreased and then increased with increasing TiCN addition. The yield strength (YS) and ultimate tensile strength (UTS) increased with increasing TiCN addition reaching a maximum (217.5 MPa) at 0.4 wt%, and in contrast, the elongation index (EI) continuously decreased with increasing TiCN addition.

Cost-effectiveness of empagliflozin as a treatment for heart failure with reduced ejection fraction: an analysis from the Chinese healthcare perspective.

Background: The effect of empagliflozin on the cardiovascular outcome is consistent in heart failure with reduced ejection fraction (HFrEF) patients regardless of the presence or absence of diabetes. More evidence is needed regarding the cost-effectiveness of empagliflozin in HFrEF patients. This study sought to evaluate the economic outcomes of adding empagliflozin to the standard treatment for HFrEF patients from the perspective of the Chinese healthcare system, and thus to provide information for decision makers. Methods: Based on the EMPEROR-Reduced clinical trial and other published literature data, the direct medical costs and quality-adjusted life years (QALYs) of patients with HFrEF over a 15-year study period were simulated by a Markov model, and the incremental cost-effectiveness ratio (ICER) was calculated. The price of empagliflozin referred to the data released by Menet, the hospitalization expenses and utility values were derived from published studies in China. A one-way sensitivity analysis and probabilistic sensitivity analysis were conducted to evaluate the robustness of the model. Results: The results of the cost-effectiveness analysis showed that the cost of the combination arm was $5,220.98, with a utility of 4.86 QALYs, and the cost of the standard arm was $4,873.96, with a utility of 4.68 QALYs, which equated to an ICER of $1,893.59 per QALY gained. The subgroup analysis showed that patients with HFrEF and diabetes in empagliflozin group had a higher QALY (4.62 vs. 4.35) and a lower cost ($5,213.28 vs. $5,958.60) than standard group. The corresponding ICER for non-diabetic patients was $2,568.15 per QALY. Deterministic sensitivity analysis showed robust results. At the willingness-to-pay threshold of 3 times gross domestic product (GDP) per capita ($31,510.57), almost all of the scattered points in three scenarios were below the threshold line. Conclusions: At a willingness-to-pay threshold of $31,510.57, adding empagliflozin to standard treatment is a very cost-effective option for HFrEF patients with or without diabetes in China.

Electrostatic Charge-Mediated Apoptotic Vesicle Biodistribution Attenuates Sepsis by Switching Neutrophil NETosis to Apoptosis.

Mesenchymal stem cell (MSC) therapy can attenuate organ damage and reduce mortality in sepsis; however, the detailed mechanism is not fully elucidated. In this study, it is shown that MSC-derived apoptotic vesicles (apoVs) can ameliorate multiple organ dysfunction and improve survival in septic mice. Mechanistically, it is found that tail vein-infused apoVs mainly accumulate in the bone marrow of septic mice via electrostatic charge interactions with positively charged neutrophil extracellular traps (NETs). Moreover, apoVs switch neutrophils NETosis to apoptosis via the apoV-Fas ligand (FasL)-activated Fas pathway. In summary, these findings uncover a previously unknown role of apoVs in sepsis treatment and an electrostatic charge-directed target therapeutic mechanism, suggesting that cell death is associated with disease development and therapy.

Cladding Mode Fitting-Assisted Automatic Refractive Index Demodulation Optical Fiber Sensor Probe Based on Tilted Fiber Bragg Grating and SPR.

In the paper based on surface plasmon resonance (SPR) in a tilted fiber Bragg grating (TFBG), a novel algorithm is proposed, which facilitates demodulation of surrounding refractive index (SRI) via cladding mode interrogation and accelerates calibration and measurement of SRI. Refractive indices with a tiny index step of 2.2 × 10-5 are prepared by the dilution of glucose aqueous solution for the test and the calibration of this fiber sensor probe. To accelerate the calibration process, automatic selection of the most sensitive cladding mode is demonstrated. First, peaks of transmitted spectrum are identified and numbered. Then, sensitivities of several potentially sensitive cladding modes in amplitude adjacent to the left of the SPR area are calculated and compared. After that, we focus on the amplitudes of the cladding modes as a function of a SRI, and the highest sensitivity of -6887 dB/RIU (refractive index unit) is obtained with a scanning time of 15.77 s in the range from 1520 nm to 1620 nm. To accelerate the scanning speed of the optical spectrum analyzer (OSA), the wavelength resolution is reduced from 0.028 nm to 0.07 nm, 0.14 nm, and 0.28 nm, and consequently the scanning time is shortened to 6.31 s, 3.15 s, and 1.58 s, respectively. However, compared to 0.028 nm, the SRI sensitivity for 0.07 nm, 0.14 nm, and 0.28 nm is reduced to -5685 dB/RIU (17.5% less), -5415 dB/RIU (21.4% less), and -4359 dB/RIU (36.7% less), respectively. Thanks to the calculation of parabolic equation and weighted Gauss fitting based on the original data, the sensitivity is improved to -6332 dB/RIU and -6721 dB/RIU, respectively, for 0.07 nm, and the sensitivity is increased to -5850 dB/RIU and -6228 dB/RIU, respectively, for 0.14 nm.

Mesenchymal stem cells empower T cells in the lymph nodes via MCP-1/PD-L1 axis.

Mesenchymal stem cells (MSCs) are a type of immunosuppressive stromal cell found in multiple tissues and organs. However, whether MSCs possess immunosupportive characteristics remains unclear. In this study, we showed that the lymph nodes contain immunosupportive MSCs. They produce and secrete a high level of MCP-1 to promote T-cell proliferation and differentiation, in contrast to bone marrow MSCs (BMMSCs), which repress T-cell activation. Unlike BMMSCs, lymph node MSCs (LNMSCs) fail to respond to activated T-cell-induced production of PD-L1 to induce T-cell apoptosis. Mechanistically, MCP-1 activates phospho-Erk to sustain T-cell proliferation and activation while it represses NF-κB/PD-L1 pathway to avoid induction of T-cell apoptosis. Interestingly, inflammatory lymph node-derived LNMSCs abolish their immunosupportive function due to reduction of MCP-1 expression. Finally, we show that systemic infusion of LNMSCs rescues immunosuppression in cytoxan (CTX)-treated mice. This study reveals a previously unrecognized mechanism underlying MSC-based immunoregulation using the MCP-1/PD-L1 axis to energize T cells and suggests a potential to use MSCs to treat immunosuppressive disorders.

Proteomic analysis of MSC-derived apoptotic vesicles identifies Fas inheritance to ameliorate haemophilia a via activating platelet functions.

Apoptotic vesicles (apoVs) are apoptotic cell-derived nanosized vesicles that play a crucial role in multiple pathophysiological settings. However, their detailed characteristics, specific surface markers, and biological properties are not fully elucidated. In this study, we compared mesenchymal stem cell (MSC)-derived apoVs and exosomes from three different types of MSCs including human bone marrow MSCs (hBMSCs), human adipose MSCs (hASCs), and mouse bone marrow MSCs (mBMSCs). We established a unique protein map of MSC-derived apoVs and identified the differences between apoVs and exosomes in terms of functional protein cargo and surface markers. Furthermore, we identified 13 proteins specifically enriched in apoVs compared to exosomes, which can be used as apoV-specific biomarkers. In addition, we showed that apoVs inherited apoptotic imprints such as Fas to ameliorate haemophilia A in factor VIII knockout mice via binding to the platelets' FasL to activate platelet functions, and therefore rescuing the blood clotting disorder. In summary, we systemically characterized MSC-derived apoVs and identified their therapeutic role in haemophilia A treatment through a previously unknown Fas/FasL linkage mechanism.

Effectiveness of antiplatelet drugs for the prevention of diabetic nephropathy: A meta-analysis of randomized controlled trials
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AIMS: To evaluate the effects of antiplatelet drugs on proteinuria, renal function, and blood pressure (BP) in patients with diabetic nephropathy (DN). MATERIALS AND METHODS: A meta-analysis of randomized controlled trials (RCTs) was performed. Relevant RCTs were identified by a systematic search of the PubMed, Cochrane Library, and Embase databases. A random-effects model was applied to pool the results. RESULTS: Antiplatelet drugs significantly reduced urinary albumin excretion (weighted mean difference (WMD) = -69.25 mg/24, p = 0.005) and the urinary albumin/creatinine ratio (standardized mean difference (SMD) = -0.33, p = 0.009). However, renal function as reflected by the estimated glomerular filtration rate (WMD = -1.15 mL/min/1.73m2, p = 0.46) and BP (systolic BP: WMD = 1.53 mmHg, p = 0.35; diastolic BP: WMD = 0.40 mmHg, p = 0.70) were not significantly affected by antiplatelet drugs within 12 months of use (p > 0.05). CONCLUSION: Antiplatelet drugs may benefit patients with DN by reducing proteinuria. The long-term effects of antiplatelet drugs on the progression of DN warrant further evaluation.
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Compact Reconfigurable Antenna with an Omnidirectional Pattern and Four Directional Patterns for Wireless Sensor Systems.

A compact reconfigurable antenna with an omnidirectional mode and four directional modes is proposed. The antenna has a main radiator and four parasitic elements printed on a dielectric substrate. By changing the status of diodes soldered on the parasitic elements, the proposed antenna can generate four directional radiation patterns and one omnidirectional radiation pattern. The main beam directions of the four directional modes are almost orthogonal and the four directional beams can jointly cover a 360° range in the horizontal plane, i.e., the main radiation plane of omnidirectional mode. The whole volume of the antenna and the control network is approximately 0.70 λ × 0.53 λ × 0.02 λ, where λ is the wavelength corresponding to the center frequency. The proposed antenna has a simple structure and small dimensions under the requirement that the directional radiation patterns can jointly cover the main radiation plane of the omnidirectional mode, therefore, it can be used in smart wireless sensor systems for different application scenarios.

Sperm motility inversely correlates with seminal leptin levels in idiopathic asthenozoospermia.

BACKGROUND: Asthenozoospermia is one kind cause of male infertility. Nevertheless, no specific etiology can be identified by routine tests in some cases. Recently, it has been shown that leptin plays a critical role in male fertility. However, the link between leptin and sperm motility is yet to be determined. The aim of this study was to explore association between seminal and serum leptin levels and sperm motility in idiopathic asthenozoospermia. METHODS: Our study included 79 asthenozoospermic men and 77 normozoospermic men. Semen was assessed by volume, sperm concentration, motility and morphology. Serum gonadotropic and sex hormones were determined by a chemiluminescent assay. The leptin levels in serum and seminal plasma were detected with ELISA. RESULTS: The mean seminal leptin level in asthenozoospermic group was significantly higher than that in control group, but there was no significant difference in the serum leptin levels between these two groups. The serum leptin had no significant correlation with sperm motility. The seminal leptin had significantly negative correlation with sperm progressive motility and serum total testosterone. CONCLUSIONS: The findings indicate a pathophysiological relevance of seminal leptin in sperm motility.