A Hybrid Nanoadjuvant Simultaneously Depresses PD-L1/TGF-ß1 and Activates cGAS-STING Pathway to Overcome Radio-Immunotherapy Resistance.

Currently, certain cancer patients exhibit resistance to radiotherapy due to reduced DNA damage under hypoxic conditions and acquired immune tolerance triggered by transforming growth factor-ß1 (TGF-ß1) and membrane-localized programmed death ligand-1 (PD-L1). Meanwhile, cytoplasm-distributed PD-L1 induces radiotherapy resistance through accelerating DNA damage repair (DDR). However, the disability of clinically used PD-L1 antibodies in inhibiting cytoplasm-distributed PD-L1 limits their effectiveness. Therefore, a nanoadjuvant is developed to sensitize cancer to radiotherapy via multi-level immunity activation through depressing PD-L1 and TGF-ß1 by triphenylphosphine-derived metformin, and activating the cGAS-STING pathway by generating Mn2+ from MnO2 and producing more dsDNA via reversing tumor hypoxia and impairing DDR. Thus, Tpp-Met@MnO2@Alb effectively enhances the efficiency of radiotherapy to inhibit the progression of irradiated local and abscopal tumors and tumor lung metastases, offering a long-term memory of antitumor immunity without discernible side effects. Overall, Tpp-Met@MnO2@Alb has the potential to be clinically applied for overcoming radio-immunotherapy resistance.

[Research progress of new multifunctional bone cement in bone tumor therapy].

Objective: The research progress of new multifunctional bone cement in bone tumor therapy in recent years was reviewed, in order to provide help for the future research of anti-tumor bone cement. Methods: The related literature on the treatment of bone tumors with new multifunctional bone cement at home and abroad in recent years was extensively reviewed and summarized. Results: The new multifunctional bone cements include those with the functions of photothermotherapy, magnetic thermotherapy, chemoradiotherapy, and antibacterial after operation, which are discussed from the aspects of anti-tumor, drug controlled release, and cytotoxicity. Controlled drug release has been achieved in multifunctional bone cements by adjusting heat and pH or incorporating particles such as chitosan oligosaccharides and γ-cyclodextrin. At present, multifunctional bone cement with hyperthermia, radiotherapy, and chemotherapy has effectively inhibited the local recurrence and distant metastasis of bone tumors. Broadening the application of bone cement for photothermal and magnetic thermal therapy to deeper bone tumors, investigating more precise controlled release of drug-loaded bone cement, and introducing nanoparticles with both thermal conversion and intrinsic enzymatic activities into bone cement for synergistic anti-tumor therapy are promising research directions. Conclusion: The new multifunctional bone cement inhibits bone tumor cells, promotes new bone formation in bone defects, and prevents incision infection after tumor resection. Certain progress has been made in anti-tumor, antibacterial, drug-controlled release, and reduction of cytotoxicity. Expanding the deeper application range of the new multifunctional bone cement, verifying the safety in clinical application, and focusing on the individualized treatment of the new multifunctional bone cement are the problems that need to be solved in the future.

[Progress in antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants].

Objective: To review antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants, so as to provide reference for subsequent research. Methods: The related research literature on antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants in recent years was reviewed, and the research progress was summarized based on different kinds of antibacterial substances and osteogenic active substances. Results: At present, the antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants includes: ① Combined coating strategy of antibiotics and osteogenic active substances. It is characterized in that antibiotics can be directly released around titanium-based implants, which can improve the bioavailability of drugs and reduce systemic toxicity. ② Combined coating strategy of antimicrobial peptides and osteogenic active substances. The antibacterial peptides have a wide antibacterial spectrum, and bacteria are not easy to produce drug resistance to them. ③ Combined coating strategy of inorganic antibacterial agent and osteogenic active substances. Metal ions or metal nanoparticles antibacterial agents have broad-spectrum antibacterial properties and various antibacterial mechanisms, but their high-dose application usually has cytotoxicity, so they are often combined with substances that osteogenic activity to reduce or eliminate cytotoxicity. In addition, inorganic coatings such as silicon nitride, calcium silicate, and graphene also have good antibacterial and osteogenic properties. ④ Combined coating strategy of metal organic frameworks/osteogenic active substances. The high specific surface area and porosity of metal organic frameworks can effectively package and transport antibacterial substances and bioactive molecules. ⑤ Combined coating strategy of organic substances/osteogenic active substancecs. Quaternary ammonium compounds, polyethylene glycol, N-haloamine, and other organic compounds have good antibacterial properties, and are often combined with hydroxyapatite and other substances that osteogenic activity. Conclusion: The factors that affect the antibacterial and osteogenesis properties of titanium-based implants mainly include the structure and types of antibacterial substances, the structure and types of osteogenesis substances, and the coating process. At present, there is a lack of clinical verification of various strategies for antibacterial/osteogenesis dual-functional surface modification of titanium-based implants. The optimal combination, ratio, dose-effect mechanism, and corresponding coating preparation process of antibacterial substances and bone-active substances are needed to be constantly studied and improved.

Sediment resuspension causes horizontal variations in the distributions of phosphorus (P) and P-inactivating materials with differing P immobilization in different sediment planes.

The importance of controlling internal phosphorus (P) pollution in lakes has been recognized by scientists, and the application of P-inactivating materials to immobilize sediment P is often considered. However, sediment resuspension, a typical physical process occurring in lakes, has been demonstrated to increase the uncertainty of immobilization. In this study, we explored the characteristics of P immobilization in the horizontal direction under the effects of resuspension using annular flume tests based on drinking water treatment residuals (DWTR). The results showed that resuspension caused the mobile P and bioavailable P to be heterogeneously distributed in sediment planes after DWTR addition, resulting in varying P immobilization efficiencies at different depths. In particular, the coefficient of variation was 14.2-24.5% for mobile P horizontally distributed in the planes, resulting in a range of mobile P decreasing efficiencies at 24.0-47.8%. Further analysis indicated that variations in horizontal distribution were typically due to the varied migration of particles of different sizes. Specifically, P immobilization in sediment planes at different depths was regulated by promoting the migration of <8 µm DWTR after relatively low-intensity disturbance (in surface 0-1 cm sediment). After relatively high-intensity disturbance (in the whole 0-3 cm sediment), immobilization in the horizontal direction was regulated by coupling the migration of >63 µm DWTR (to the bottom) with the mixing of <8 µm DWTR in the sediment plane at different depths. The varying horizontal distributions of total P, resulting from the migration of 16-32 µm sediment, could enhance the heterogeneities of the P immobilization. Thus, the particle size of materials and lake background conditions, for example, the hydrodynamic characteristics and P distributions in differently sized sediments, should be used as key bases to select or develop P-inactivating materials to design proper remediation strategies for controlling internal P pollution in lakes.

The analgesic effects of ß-elemene in rats with neuropathic pain by inhibition of spinal astrocytic ERK activation.

Neuropathic pain takes a heavy toll on individual well-being, while current therapy is far from desirable. Herein, we assessed the analgesic effect of ß-elemene, a chief component in the traditional Chinese medicine Curcuma wenyujin, and explored the underlying mechanisms at the level of spinal dorsal horn (SDH) under neuropathic pain. A spared nerve injury (SNI)-induced neuropathic pain model was established in rats. Intraperitoneal injection (i.p.) of ß-elemene was administered for 21 consecutive days. Mechanical allodynia was explored by von Frey filaments. The activation of the mitogen-activated protein kinase (MAPK) family (including ERK, p38, and JNK) in spinal neurons, astrocytes, and microglia was evaluated using immunostaining 29 days after SNI surgery. The expression of GFAP, Iba-1, p-ERK, p-JNK, and p-p38 within the SDH was measured using immunoblotting. The levels of proinflammatory cytokines (including TNF-α, IL-1ß, and IL-6) were measured with ELISA. The levels of oxidative stress indicators (including MDA, SOD, and GSH-PX) were detected using biochemical tests. Consecutive i.p. administration of ß-elemene relieved SNI-induced mechanical allodynia (with an EC50 of 16.40 mg/kg). SNI significantly increased the expression of p-ERK in spinal astrocytes but not microglia on day 29. ß-elemene reversed spinal astrocytic ERK activation and subsequent upregulation of proinflammatory cytokines in SNI rats, with no effect on the expression of p38 and JNK in spinal glia. ß-elemene also exerted antioxidative effects by increasing the levels of SOD and GSH-PX and decreasing the level of MDA. Our results suggest that SNI induces robust astrocytic ERK activation within the SDH in the late phase of neuropathic pain. ß-elemene exerts remarkable analgesic effects on neuropathic pain, possibly by inhibiting spinal astrocytic ERK activation and subsequent neuroinflammatory processes. Our findings suggest that ß-elemene might be a promising analgesic for the treatment of chronic pain.

Si@Ag@PEI substrate-based SERS sensor for rapid detection of illegally adulterated sulfur dioxide in traditional Chinese medicine.

The illegal adulteration of sulfur dioxide in natural healthcare products may lead to serious health problems, which raise an urgent demand of straightforward approach for detecting sulfur dioxide. In this paper, surface-enhanced Raman scattering (SERS) sensor with sample preparation apparatus for headspace adsorption of SO2 has been developed, which was successfully applied to detect illegal adulteration of sulfur dioxide in traditional Chinese medicine (TCM). Functional membrane substrate of Si@Ag@PEI composite was synthesized to enhance the adsorption and Raman signal of SO2. A 3D-printed headspace extraction device was designed to adsorbed SO2 by Si@Ag@PEI membrane after micro-extraction of TCM samples in 15 min. The content of sulfur dioxide was subsequently quantitatively measured by SERS sensor. The linear range of sensor is between 2.5 and 250 mg/kg with limit of detection of 0.25 mg/kg, which is lower than the strictest standard of Chinese Pharmacopoeia (10 mg/kg). The proposed approach was used to detect the SO2 residue in TCMs including ginseng, Salvia miltiorrhiza, and bitter almonds. The fabricated sensor exhibited satisfied sensitivity and stability, which provide a simple approach for on-site detection of illegal adulteration of sulfur dioxide.

Changes in Bone Mineral Density Following Conventional Oral Phosphonate Treatment of Hypophosphatemic Osteomalacia: A Non-Randomized Controlled Study.

PURPOSE: There are limited clinical studies aimed at solving the problem of the efficiency of conventional treatment with oral phosphate and calcitriol in adults with hypophosphatemic osteomalacia (HO). In addition, there still had no good non-hazardous markers to evaluate the severity of bone loss of osteomalacia before and after treatment. Therefore, the purpose of this study was to assess the efficacy of conventional treatment with a self-blended phosphate supplementation and calcitriol on patients with HO and whether bone mineral density (BMD) can be helpful for monitoring the efficacy. PATIENTS AND METHODS: A total of 21 HO patients and 105 healthy controls were enrolled. All patients were tested for serum biomarkers and BMD of the lumbar spine (L1-L4), femoral neck, and total left hip. After three years of treatment, 11 of 21 HO patients were recalled for BMD measurement. According to the administration of drugs, HO patients with calcium and calcitriol were divided into three phosphate treatment groups: patients in group A (n = 3) received continuous phosphate supplementation, patients in group B (n = 5) received intermittent phosphate supplementation and patients in group C (n = 3) received no phosphate supplementation. RESULTS: The diagnoses of 21 HO patients were 5 cases of hereditary hypophosphatemic rickets, 4 cases of Fanconi syndrome with the features of renal tubular acidosis and vitamin D deficiency, and 12 cases of hereditary vitamin D abnormality. The average initial serum phosphorus level of the patient group was approximately 50% lower than that of the control group. Lower BMD was significantly observed in the HO group than the control group at the lumbar spine and total hip. Continuous treatment with the phosphate supplement could increase BMD in the lumbar spine and total hip by 33.4-52.3% and in the femoral neck increased by 43.2-79.3% compared with baseline, and the effect appears to be continued once treatment is discontinued. CONCLUSION: These findings suggest that conventional therapy can improve bone mineral defects in patients with HO, especially in the femoral neck. Detection of BMD in HO patients is a good tool to assess the extent of bone defects and the therapeutic effect. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OOC-16010095. Registered 7 December 2016. Retrospectively registered.

Arvensic acids K and L, components of resin glycoside fraction from Convolvulus arvensis.

Alkaline hydrolysis of the resin glycoside fraction of the whole plants of Convolvulus arvensis gave two new glycosidic acids, named arvensic acids K and L (1 and 2). Their structures were characterized on the basis of spectroscopic data as well as chemical evidence. They possessed a same pentasaccharide chain, composed of one D-fucose, three D-glucose and one L-rhamnose units. The aglycone of compound 1 was identified to be rarely existing 11S-hydroxyheptadecanoic acid, while compound 2 possessed 11S-hydroxyhexadecanoic acid as the aglycone. Their cytotoxic and anti-migration activities were also evaluated.

Impact of pelvic floor ultrasound in diagnosis of postpartum pelvic floor dysfunction: A protocol of systematic review.

BACKGROUND: This study will appraise the impact of pelvic floor ultrasound (PFU) in diagnosis of postpartum pelvic floor dysfunction (PPPFD). METHODS: Studies that report the impact of PFU in diagnosis of PPPFD will be examined in Cochrane Library, MEDLINE, EMBASE, PSYCINFO, Scopus, Web of Science, Allied and Complementary Medicine Database, CNKI, and WANGFANG up to June 1, 2020. Grey literature sources will also be searched. All potential case-controlled studies (CCSs) exploring the impact of PFU in diagnosis of PPPFD will be considered for inclusion in this study. Data will be extracted from eligible CCSs for data pooling and meta-analysis. Whenever necessary, we will also perform summary effect size, heterogeneity across studies, study quality assessment, and reporting bias. RESULTS: The present study will estimate pooled outcome effects regarding the impact of PFU in diagnosis of PPPFD. CONCLUSION: This study may provide robust evidence to judge the impact of PFU on PPPFD SYSTEMATIC REVIEW REGISTRATION:: PROSPERO CRD42020187623.

Nanobubbles Water Curcumin Extract Reduces Injury Risks on Drop Jumps in Women: A Pilot Study.

PURPOSE: To verify the beneficial effects of Nanobubbles water curcumin extract (NCE) supplementation on health promotion and to demonstrate the application of NCE in reducing the risk of musculoskeletal injury. METHODS: In the current study, 12 females were randomly assigned to NCE (15g/day) and maltodextrin groups. Performance and related body composition were evaluated at 2 time points-presupplementation (pre-) and after 4 weeks of postsupplementation (post-). The posttest consists of a set of biochemical parameters for antifatigue activity and injury status evaluation. RESULTS: NCE group exhibited significantly lower levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), triglycerides (TG), and higher high-density lipoprotein (HDL) after a 4-week supplementation, compared with the placebo group. After a 15-minute session on the spinning bike, serum lactate and ammonia levels were decreased and glucose was economized in the NEC group. 4-week-NCE supplementation was also able to reduce the peak vertical ground reaction force (PVGRF) during drop jump. Therefore, the risk of musculoskeletal system in lower extremity could be reduced. CONCLUSION: We demonstrate that 4-week-NCE supplementation can also be used in explosiveness exercise for better physiological adaptation. Thus, NCE has potential for use with nutrient supplements toward a variety of benefits for athletics.

Photoacoustic-imaging-guided therapy of functionalized melanin nanoparticles: combination of photothermal ablation and gene therapy against laryngeal squamous cell carcinoma.

Multimodality therapy under imaging-guidance is significant to improve the accuracy of cancer treatment. In this study, a photoacoustic imaging (PAI)-guided anticancer strategy based on poly-l-lysine functionalized melanin nanoparticles (MNP-PLL) was developed to treat laryngeal squamous cell carcinoma (LSCC). As a promising alternative to traditional therapies for LSCC, MNP-PLL/miRNA nanoparticles were combined with photothermal ablation against primary tumors and miR-145-5p mediated gene therapy for depleting the metastatic potential of tumor cells. Furthermore, taking advantage of the photoacoustic properties of melanin, PAI guided therapy could optimize the time point of NIR irradiation to maximize the efficacy of photothermal therapy (PTT). The in vitro and in vivo results proved that the combined treatments displayed the most significant tumor suppression compared with monotherapy. By integrating thermo-gene therapies into a theranostic nanoplatform, the MNP-PLL/miR-145-5p nanoparticles significantly suppressed the LSCC progression, indicating their great potential use for cancer therapy.

US-guided microwave ablation for primary hyperparathyroidism: a safety and efficacy study.

OBJECTIVES: To evaluate the safety and efficacy of microwave ablation (MWA) with the assistance of continuous cool saline injection (CCSI) in patients with primary hyperparathyroidism (PHPT). METHODS: Between November 1, 2014, and February 29, 2016, 22 patients with PHPT were enrolled and treated with ultrasound-guided MWA assisted by CCSI. The levels of parathyroid hormone (PTH) and serum calcium were recorded before and after the MWA. Patients were divided into two groups (normalized and unnormalized groups) according to treatment efficacy. Fisher's exact test and the Mann-Whitney test were used to compare data between the two groups. Timing differences in serum PTH and calcium levels were analyzed with repeated measures analysis of variance. RESULTS: Normalized outcomes for both PTH and calcium levels were achieved in 19 of 22 (86.36%) patients with PHPT. In the normalized group, PTH levels remained normal for 12 months after MWA. PTH levels in the unnormalized group were outside the reference range at six of seven follow-ups within 12 months following MWA. By contrast, serum calcium levels gradually decreased in all patients in both groups. The mean serum PTH and mean calcium levels at 6 months after therapy were significantly lower than those before MWA (both p < 0.05). A transient voice change developed in eight patients. One patient experienced hypocalcaemia, which was corrected by oral calcium supplementation within 2 months. CONCLUSIONS: US-guided MWA assisted by CCSI is safe and effective for destroying parathyroid gland tissue and may serve as a therapeutic alternative for patients with PHPT. KEY POINTS: • Microwave ablation is a new option for patients with hypercalcemic or normocalcemic primary hyperparathyroidism. • Microwave ablation can decrease PTH and calcium levels with sustained efficacy in most patients. • Treatment is safe and causes only transient side effects.

Design of multi-drug combinations for poly-pharmacological effects using composition-activity relationship modeling and multi-objective optimization approach: Application in traditional Chinese medicine.

In recent years, multi-component therapies are increasingly utilized to treat complex diseases such as cancer, diabetes, and other chronic complex diseases. Here, we proposed the protocol for rational design of drug combination with poly-pharmacological effects by integration of design of experiments (DOE), computational modeling, and multiple-objective optimization algorithm. Here, we introduce a common workflow for modeling quantitative relationship of chemical composition and multiple activities of drug combinations. As an example, anti-oxidation, neuroprotective, and anti-platelet activities of three different salvia polyphenols were measured, which were mathematically represented by multivariant regression models to evaluate the effect of combination. In validation, the optimized combination which obtained by weighed-sum method showed good activities in all three models. Our results demonstrate that the multiple-objective optimization strategy is suitable to optimize the ratio of the compounds so to induce the best therapeutic action.

Arvensic acids A-D, novel heptasaccharide glycosidic acids as the alkaline hydrolysis products of crude resin glycosides from Convolvulus arvensis.

In this study, a resin glycoside fraction with cytotoxic activity was isolated from the alcoholic extract of C. arvensis whole plants. To describe the chemical feature of the resin glycosides, the fraction was alkaline hydrolyzed and four novel glycosidic acids, named arvensic acids A-D (1-4), were isolated. Their structures were thoroughly elucidated on the basis of spectroscopic data and chemical evidences. They all possess a same heptasacharride core, consisting of one D-fucose, two L-rhamnose and four d-glucose units. The difference among these glycosidic acids was placed on the aglycone, which is 12S-hydroxypentadecanoic acid for 1, 12S-hydroxyhexadecanoic acid for 2, 3S,12S-dihydroxypentadecanoic acid for 3, and 3S,12S- dihydroxyhexadecanoic acid for 4. These aglycones are rarely found in the structures of resin glycosides and are firstly identified in the genus Convolvulus.

Ultrasmall endogenous biopolymer nanoparticles for magnetic resonance/photoacoustic dual-modal imaging-guided photothermal therapy.

Multi-modal imaging-guided photothermal therapy (PTT) has aroused extensive attention in biomedical research recently because it can provide more comprehensive information for accurate diagnosis and treatment. In this research, the manganese ion chelated endogenous biopolymer melanin nanoparticles were successfully prepared for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging-guided PTT. The obtained nanoparticles with an ultrasmall size of about 3.2 nm exhibited negligible cytotoxicity, high relaxivity for MRI, an excellent photothermal effect and PA activity. Moreover, in vivo MRI and PAI results all demonstrated that the nanoparticles began to diffuse in the blood after intratumoral injection into tumor-bearing mice and could spread throughout the whole tumor region at 3 h, indicating the optimal treatment time. The subsequent photothermal therapy of cancer cells in vivo was carried out and the result showed that tumor growth could be effectively inhibited without inducing any observed side effects. Besides, melanin as an endogenous biopolymer has native biocompatibility and biodegradability, and it can be excreted through both renal and hepatobiliary pathways after treatment. Therefore, the melanin-Mn nanoparticles may assist in better indicating the optimal treatment time, monitoring the therapeutic process and enhancing the therapeutic effect and showed great clinical translation potential for cancer diagnosis and therapy.

Medicinal uses, pharmacology, and phytochemistry of Convolvulaceae plants with central nervous system efficacies: A systematic review.

Central nervous system (CNS) disorders play a major impact on individual lives and place a severe strain on health care resources. Convolvulaceae is a family comprising approximately 1,600-1,700 species grouped in 55-60 genera, and many species are reported to have an effect on CNS functions. A systematic review of the literature studies was carried out to summarize available evidences on Convolvulaceae plants with CNS efficacies. This review is based on various data sources such as Google Scholar, Web of Science, Scopus, PubMed, and Wanfang Data. A total of 200 related articles were included in this review. According to the research result, 54 Convolvulaceae species are suggested to display CNS efficacies historically, and 46 species have been evaluated for their CNS efficacies. In addition, 67 compounds from 16 Convolvulaceae species are recognized to possess CNS efficacies. Despite great progress made through pharmacology and phytochemistry studies on CNS active Convolvulaceae species, more exploratory research is needed to gain a better understanding of the CNS efficacies of this plant family.

Modeling the shape and composition of the human body using dual energy X-ray absorptiometry images.

There is growing evidence that body shape and regional body composition are strong indicators of metabolic health. The purpose of this study was to develop statistical models that accurately describe holistic body shape, thickness, and leanness. We hypothesized that there are unique body shape features that are predictive of mortality beyond standard clinical measures. We developed algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans into body thickness and leanness images. We performed statistical appearance modeling (SAM) and principal component analysis (PCA) to efficiently encode the variance of body shape, leanness, and thickness across sample of 400 older Americans from the Health ABC study. The sample included 200 cases and 200 controls based on 6-year mortality status, matched on sex, race and BMI. The final model contained 52 points outlining the torso, upper arms, thighs, and bony landmarks. Correlation analyses were performed on the PCA parameters to identify body shape features that vary across groups and with metabolic risk. Stepwise logistic regression was performed to identify sex and race, and predict mortality risk as a function of body shape parameters. These parameters are novel body composition features that uniquely identify body phenotypes of different groups and predict mortality risk. Three parameters from a SAM of body leanness and thickness accurately identified sex (training AUC = 0.99) and six accurately identified race (training AUC = 0.91) in the sample dataset. Three parameters from a SAM of only body thickness predicted mortality (training AUC = 0.66, validation AUC = 0.62). Further study is warranted to identify specific shape/composition features that predict other health outcomes.

Diurnal Variation of the Peripheral Cholinergic Antiinflammatory Function in Mice.

AIMS: Cholinergic antiinflammatory (CAI) pathway functions importantly in inflammation via α7 nicotinic acetylcholine receptors (α7nAChR). The present work tested circadian rhythm in peripheral CAI activity and validities of CAI activity and glucocorticoids in chronotherapy for lipopolysaccharide (LPS)-induced shock. METHODS: Vesicular acetylcholine transporter (VAChT) expressed in liver and kidney was examined every 3 h in C57BL/6 mice. Proinflammatory cytokines in serum and survival time in shock were monitored after LPS injection every 3 h. Mifepristone, antagonist of glucocorticoid receptors, and methyllycaconitine (MLA), antagonist of α7nAChR, were administrated before LPS to block antiinflammatory function of endogenous glucocorticoids and acetylcholine. RESULTS: Both levels of tumor necrosis factor α, interleukin 1ß, and interleukin 6 and mortality exhibited diurnal variations with prominent peaks when LPS was given at 15:00, and the minimum mortality occurred at 00:00. Expression of VAChT increased during resting period. MLA increased serum proinflammatory cytokines slightly, but not affected survival rate. Both differences in cytokines and in survival times between LPS injection at 15:00 and 00:00 were eliminated by mifepristone, but not by MLA. CONCLUSION: Peripheral CAI pathway exerts more powerful antiinflammatory effect during resting period. Glucocorticoids appear to be efficient in chronotherapy for septic shock.

Sodium Sulfide, a Hydrogen Sulfide-Releasing Molecule, Attenuates Acute Cerebral Ischemia in Rats.

AIMS: Acute cerebral ischemia may lead to ischemic stroke, which is a major cause of death and disability worldwide. Hydrogen sulfide (H2 S) functions importantly in mammalian systems. The present work was designed to study the effect of sodium sulfide, a donor of H2 S, on acute cerebral ischemia. METHODS: Acute cerebral focal ischemia was produced by middle cerebral artery occlusion (MCAO) in Sprague-Dawley (SD) rats. Bilateral vertebral arteries and common carotid arteries were blocked to establish cerebral global ischemia in SD rats. Acute cerebral anoxia was produced by hypobaric anoxia in C57BL/6 mice and hypoxic anoxia in SD rats. Nimodipine and aspirin were set as positive control separately. RESULTS: Infarct size after MCAO was decreased by sodium sulfide. Sodium sulfide improved cerebral energy metabolism after cerebral global ischemia and prolonged survival time of animals with acute cerebral anoxia. In addition, increased cerebral blood flow and decreased cerebrovascular resistance, blood viscosity, and thrombogenesis were observed in animals treated with sodium sulfide. In cultured neurons, sodium sulfide increased cell viability and decreased cell apoptosis induced by oxygen-glucose deprivation. CONCLUSION: Sodium sulfide, a H2 S donor, presents protective effect on acute cerebral ischemia, and might be a promising therapeutic drug.

Plants adapted to nutrient limitation allocate less biomass into stems in an arid-hot grassland.

Biomass allocation can exert a great influence on plant resource acquisition and nutrient use. However, the role of biomass allocation strategies in shaping plant community composition under nutrient limitations remains poorly addressed. We hypothesized that species-specific allocation strategies can affect plant adaptation to nutrient limitations, resulting in species turnover and changes in community-level biomass allocations across nutrient gradients. In this study, we measured species abundance and the concentrations of nitrogen and phosphorus in leaves and soil nutrients in an arid-hot grassland. We quantified species-specific allocation parameters for stems vs leaves based on allometric scaling relationships. Species-specific stem vs leaf allocation parameters were weighted with species abundances to calculate the community-weighted means driven by species turnover. We found that the community-weighted means of biomass allocation parameters were significantly related to the soil nutrient gradient as well as to leaf stoichiometry, indicating that species-specific allocation strategies can affect plant adaptation to nutrient limitations in the studied grassland. Species that allocate less to stems than leaves tend to dominate nutrient-limited environments. The results support the hypothesis that species-specific allocations affect plant adaptation to nutrient limitations. The allocation trade-off between stems and leaves has the potential to greatly affect plant distribution across nutrient gradients.