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Background: Osteonecrosis of the femoral head (ONFH) often affects young, active adults and leads to the destruction of the hip joint and disabling arthritis. Several procedures have been developed to prevent conversion to total hip arthroplasty (THA), especially in young patients who have a high rate of hip revision surgery. The aim of this long-term follow-up is to analyze the results of vascularized iliac bone flap transfer for ONFH treatment.Methods: We retrospectively reviewed 856 patients (1006 hips) who accepted hip-preserving surgery with vascularized iliac bone grafting due to ONFH (Ficat and Arlet stages II-IV) from January 1985 to December 2012 at our hospital. Radiographic assessment was performed with the Ficat and Arlet system, clinical assessment was performed with the Harris Hip Score system, and quality of life was evaluated with the 36-Item Short Form Survey. The hips included 575 stage II hips, 382 stage III hips, and 49 stage IV hips. We defined clinical failure as conversion to THA or any other hip-preserving surgery because of hip symptoms.Results: A total of 856 patients (1006 hips) were eventually followed up with an average time of 15 years (range 5-25). In total, 75 patients were lost to follow-up, and 105 hips were converted to THA. The average Harris Hip Score was 87.43 ± 6.42 points at the last follow-up, representing a great improvement compared to the 66.42 ± 6.52 points obtained preoperatively. The Kaplan-Meier survival analysis showed no difference in the 15-year survival rate between patients with stages II and III disease (using THA as an end point). However, the survival rate was lower for patients with stage IV disease than that for patients with stages II and III disease. The survival rate for patients in the glucocorticoid group was lower than that for patients in the idiopathic, alcoholic, and trauma groups. The Physical Component Summary scores ranged from 78 ± 10 to 85 ± 14 postoperatively compared to 30 ± 14 to 55 ± 15 preoperatively, and the postoperative Mental Component Summary scores (range from 34 ± 11 to 59 ± 12) were significantly higher than the preoperative scores (range from 72 ± 11 to 90 ± 10), representing great improvement in patient quality of life. Postoperative complications occurred in 86 patients (4.5%) during the follow-up, including 23 patients with deep venous thrombosis, 16 patients with meralgia paresthetica (which resolved), and 47 patients with secondary wound healing.Conclusion: The vascularized iliac bone flap grafting technique yields significant improvement (particularly in the precollapse disease stages in young patients) for restoration of the biomechanical support of the collapsed femoral head and reconstruction of the blood supply to the osteonecrotic area. This procedure allows these patients to avoid or delay the need for THA surgery. [ABSTRACT FROM AUTHOR]

The dorsal bed nucleus of stria terminalis (dBNST) is a pivotal hub for stress response modulation. Dysfunction of dopamine (DA) network is associated with chronic stress, but the roles of DA network of dBNST in chronic stress-induced emotional disorders remain unclear. We examine the role of dBNST Drd1+ and Drd2+ neurons in post-weaning social isolation (PWSI)-induced behavior deficits. We find that male, but not female, PWSI rats exhibit negative emotional phenotypes and the increase of excitability and E-I balance of dBNST Drd2+ neurons. More importantly, hypofunction of dBNST Drd2 receptor underlies PWSI-stress-induced male-specific neuronal plasticity change of dBNST Drd2+ neurons. Furthermore, chemogenetic activation of dBNST Drd2+ neurons is sufficient to induce anxiogenic effects, while Kir4.1-mediated chronic inhibition of dBNST Drd2+ neurons ameliorate PWSI-induced anxiety-like behaviors. Our findings reveal an important neural mechanism underlying PWSI-induced sex-specific behavioral abnormalities and potentially provide a target for the treatment of social stress-related emotional disorder. [Display omitted] • PWSI stress induces male-specific emotional and social dysfunction • Excitability of dBNST Drd2+, but not Drd1+, neurons of PWSI rats shows an increase • There is an enhancement of E:I balance of dBNST Drd2+ neurons in PWSI rats • Inhibition of dBNST Drd2+ neurons rescues anxiety-like phenotype caused by PWSI stress Zheng et al. find an important mechanism by which post-weaning social isolation stress induces male-specific anxiety-like behavior by the increase of the excitability of dBNST Drd2+, but not Drd1+, neurons and enhancement of E:I balance of dBNST Drd2+ neurons. [ABSTRACT FROM AUTHOR]

Abstract: The first-generation antihistamines are widely prescribed medications that relieve allergic reactions and urticaria by blocking the peripheral histamine H1 receptor. Overdose of these drugs often results in serious neuronal toxic effects, including seizures, convulsions and worsening of epileptic symptoms. The KCNQ/M K+ channel plays a crucial role in controlling neuron excitability. Here, we demonstrate that mepyramine and diphenhydramine, two structurally related first-generation antihistamines, can act as potent KCNQ/M channel blockers. Extracellular application of these drugs quickly and reversibly reduced KCNQ2/Q3 currents heterologously expressed in HEK293 cells. The current inhibition was concentration and voltage dependent. The estimated IC50 (12.5 and 48.1μM, respectively) is within the range of drug concentrations detected in poisoned patients (30–300μM). Both drugs shifted the I–V curve of KCNQ2/Q3 channel to more depolarized potentials and altered channel gating properties by prolonging activation and shortening deactivation kinetics. Mepyramine also inhibited the individual homomeric KCNQ1–4 and heteromeric KCNQ3/Q5 currents. Moreover, mepyramine inhibited KCNQ2/Q3 current in an outside-out patch excised from HEK293 cells and the inhibitory effect was neither observed when it was applied intracellularly nor affected by blocking phospholipase C (PLC) activity, indicating an extracellular and direct channel blocking mechanism. Finally, in cultured rat superior cervical ganglion (SCG) neurons, mepyramine reduced the M type K+ current in a concentration-dependent manner and led to marked membrane potential depolarization. It is likely that these effects may be involved in the adverse neuroexcitatory effects observed in patients experiencing an overdose of antihistamines. [Copyright &y& Elsevier]

Cooperation is common in nature and is pivotal to the development of human society. However, the details of how and why cooperation evolved remain poorly understood. Cross-species investigation of cooperation may help to elucidate the evolution of cooperative strategies. Thus, we design an automated cooperative behavioral paradigm and quantitatively examine the cooperative abilities and strategies of mice, rats, and tree shrews. We find that social communication plays a key role in the establishment of cooperation and that increased cooperative ability and a more efficient cooperative strategy emerge as a function of the evolutionary hierarchy of the tested species. Moreover, we demonstrate that single-unit activities in the orbitofrontal and prelimbic cortex in rats represent neural signals that may be used to distinguish between the cooperative and non-cooperative tasks, and such signals are distinct from the reward signals. Both signals may represent distinct components of the internal drive for cooperation. [Display omitted] • An automated task is designed for quantitatively assessing cooperative behavior • Social communication contributes to cooperative behavior • Cooperative ability increases as a function of the evolutionary hierarchy • Cooperation and reward are differentially represented in the brain Jiang et al. design an automated task and assess the cooperative behavior of three species of mammals. Increased cooperative ability and a more efficient cooperative strategy emerge as a function of evolutionary hierarchy of the tested species, and cooperation and reward are differentially represented in the brain. [ABSTRACT FROM AUTHOR]

Chronic pain, such as neuropathic pain, can lead to anxiety, depression, and other negative emotions, thereby forming comorbidities and increasing the risk of chronic pain over time. Both the infralimbic amygdala (IL) and the basolateral amygdala (BLA) are significantly associated with negative emotions and pain, and they are known to have reciprocal connections. However, the role of IL-BLA circuit pathways in neuropathic pain-induced anxiety and depression remains unexplored. Electroacupuncture (EA) is frequently employed in the treatment of chronic pain and emotional disorders. However, The mechanism by which EA mediates its analgesic and emotion-alleviating effects via the IL-BLA circuit remains uncertain. Here, we used chemogenetic manipulation combined with behavioral tests to detect pain induced anxiety-like and depression-like behaviors. We observed that activation of the IL-BLA circuit by chemogenetic activation induced depression-like behavior of mice. Additionally, we discovered that chemogenetic activation of the IL-BLA circuit successfully prevented the beneficial effects of EA on depression-like behavior brought on by chronic pain in mice with spared nerve injury (SNI). We discovered that SNI-induced depression-like behavior could be mitigated by inhibiting the circuit, and EA had a comparable depressive-relieving effect. Furthermore, the IL-BLA circuit's activation or inhibition had no effect on the anxiety-like feelings brought on by SNI. Overall, our findings identify a specific neural circuit that selectively regulates pain-induced depression-like emotions, without affecting pain-induced anxiety-like emotions. This discovery offers a precise target for future treatments of comorbid pain and depression and provides a plausible explanation for the efficacy of EA in treating depression-like emotions associated with chronic pain. • The ILCaMKIIα+-BLA circuit regulates pain and depressive-like emotions in chronic pain but does not affect anxiety-like emotions. • Chemogenetic inhibition of the circuit alleviates mechanical allodynia and depressive behaviors in SNI mice. • EA may reduce chronic pain and associated depressive symptoms by inhibiting the ILCaMKIIα+-BLA circuit. [ABSTRACT FROM AUTHOR]

• THRIL knockdown alleviated CLP-induced lung injury in mice. • THRIL knockdown alleviated CLP-induced inflammatory response of lung in mice. • THRIL knockdown inhibited LPS-induced inflammatory responses and apoptosis in MPVECs. • THRIL directly targets miR-424. • THRIL competitively binds miR-424 to up-regulate ROCK2. Here, we aimed to investigate the role of long noncoding RNA (lncRNA) THRIL in septic-induced acute lung injury. C57BL/6 mice were injected with Adenoviruses (Ad)-shTHRIL or negative control (NC) before caecal ligation and puncture (CLP) operation. MPVECs were transfected with Ad-shTHRIL or NC, followed by lipopolysaccharide (LPS) treatment. MiR-424 and Rho-associated kinase 2 (ROCK2) were predicted and verified as direct targets of THRIL and miR-424, respectively, by using dual-luciferase reporter assay. ROCK2 overexpression vector and shTHRIL were co-transfected into mouse pulmonary microvascular endothelial cells for 24 h before LPS treatment. Our results showed that THRIL was highly expressed in the lung of sepsis mice. CLP triggered severe lung injury and apoptosis in mice, which was abolished by THRIL knockdown. Moreover, CLP treatment visibly increased protein concentration, the number of total cell of neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF). Besides, elevated protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 were observed in both lung and BALF. However, inhibition of THRIL reduced the number of inflammatory cells and the production of pro-inflammatory cytokines in sepsis mouse model. The effect of THRIL on inflammatory response and apoptosis in the lung was confirmed in sepsis cell model. Moreover, mechanistic studies have shown that THRIL up-regulated ROCK2 level through sponging miR-424. Furthermore, ROCK2 overexpression reversed the inhibitory effects of THRIL knockdown on LPS-induced inflammatory response and apoptosis. Overall, in vivo and in vitro results suggested that THRIL accelerates sepsis-induced lung injury by sponging miR-424 and further restoring ROCK2. [ABSTRACT FROM AUTHOR]

[Display omitted] Allergic contact dermatitis (ACD) is a common skin disease featured with skin inflammation and a mixed itch/pain sensation. The itch/pain causes the desire to scratch, affecting both physical and psychological aspects of patients. Nevertheless, the mechanisms underlying itch/pain sensation of ACD still remain elusive. Here, we found that oxidative stress and oxidation-related injury were remarkably increased in the inflamed skin of a mouse model of ACD. Reducing oxidative stress significantly attenuated itch/pain-related scratching, allokonesis and skin inflammation. RNA-Sequencing reveals oxidative stress contributes to a series of skin biological processes, including inflammation and immune response. Attenuating oxidative stress reduces overproduction of IL-1β and IL-33, two critical cytokines involved in inflammation and pain/itch, in the inflamed skin of model mice. Exogenously injecting H 2 O 2 into the neck skin of naïve mice triggered IL-33 overproduction in skin keratinocytes and induced scratching, which was reduced in mice deficient in IL-33 receptor ST2. ACD model mice showed remarkable neutrophil infiltration in the inflamed skin. Blocking neutrophil infiltration reduced oxidative stress and attenuated scratching and skin inflammation. Therefore, our study reveals a critical contribution of neutrophil-derived oxidative stress to skin inflammation and itch/pain-related scratching of ACD model mice via mechanisms involving the triggering of IL-33 overproduction in skin keratinocytes. Targeting skin oxidative stress may represent an effective therapy for ameliorating ACD. [ABSTRACT FROM AUTHOR]

• A novel water-heat coupling model for water-saving irrigated rice fields was proposed. • Account for the drying-wetting soil water in the r c calculation and model deduction. • The model didn't consider the complex process of crop growth. • Water and heat components at hourly and daily scales were simulated successively. • The model was quite satisfactory in simulating various water and heat components. It is necessary to quantify the hydrothermal processes by develop a water-heat coupling model in rice fields where the transfer between water and energy is dramatically violent, under the circumstance that water-saving irrigation (WSI) was widely used in rice paddy due to the increasing water scarcity. Based on the theory of energy and water balance, considering the interaction of impedance near the ground, a simplified holistic recursive model of water-heat coupling was proposed in the soil–plant–atmosphere continuum (SPAC) system at hourly and daily scales, and the parameters were fitted based on water and energy balance components measured in WSI rice fields. The model, takes various soil moisture conditions into consideration, integrates all the terms in the surface energy balance and the water balance with conventional meteorological data as inputs. Additionally, the model accounts for the specific drying-wetting cycles condition for WSI rice field in the calculation of the canopy resistance (r c) and the recursive process. Variations in crop growth and meteorology were also considered. The results showed that the model performed well in simulating the water and heat fluxes, and temperature profiles during the growth of the rice. This is encouraging for modelling the response of hydrothermal process to drying-wetting cycles or irrigation regimes, which is help for improving the water use efficiency in rice field. Meanwhile, this study indicates that the systemic model is efficient and useful for a better understanding the interaction between hydrological and energy processes in the WSI rice ecosystem. [ABSTRACT FROM AUTHOR]

• Single entity collision electrochemistry for dynamic characterizing inorganic water pollutants. • Ultimate sensitivity of nano-impacts is sufficient for trace environmental concentration levels. • Single-entity measurement is more precise relative to averaged ensemble performance. • Nano-impacts to identify individual reactivity for predicting behavior of water pollutants. • Prospects for comprehensive analysis of target species and coupling with other techniques. In the context of aquatic environmental issues, dynamic analysis of nano-sized inorganic water pollutants has been one of the key topics concerning their seriously amplified threat to natural ecosystems and life health. Its ultimate challenge is to reach a single-entity level of identification especially towards substantial amount of inorganic pollutants formed as natural or manufactured nanoparticles (NPs), which enter the water environments along with the potential release of constituents or other contaminating species that may have coprecipitated or adsorbed on the particles' surface. Here, we introduced a 'nano-impacts' approach—single entity collision electrochemistry (SECE) promising for in-situ characterization and quantification of nano-sized inorganic pollutants at single-entity level based on confinement-controlled electrochemistry. In comparison with ensemble analytical tools, advantages and features of SECE point at understanding 'individual' specific fate and effect under its free-motion condition, contributing to obtain more precise information for 'ensemble' nano-sized pollutants on assessing their mixture exposure and toxicity in the environment. This review gives a unique insight about the single-entity collision measurements of various inorganic water pollutants based on recent trends and directions of state-of-the-art single entity electrochemistry, the prospects for exploring nano-impacts in the field of inorganic water pollutants measurements were also put forward. [Display omitted] [ABSTRACT FROM AUTHOR]

Excessive deposition of monosodium urate (MSU) crystal in the joint results in gout arthritis, which triggers severe pain and affects life quality. Oxidative stress is a pivotal mechanism that contributes to etiology of gout pain and inflammation. Here we investigated whether activating Nrf2, which plays important roles in regulating endogenous antioxidant response, would attenuate gout arthritis via promoting antioxidant signaling in joint tissues. Gout arthritis model was established by intra-articular injection of MSU (500 μg/ankle) into the right ankle joint of mouse. Pharmacologically activating Nrf2 by activator oltipraz (50, 100 or 150 mg/kg, intraperitoneal) at 1 h before and 5, 23, 47 h after model establishment dose-dependently inhibited joint inflammation, mechanical and heat hypersensitivities in model mice. Oltipraz (100 mg/kg) reversed gait impairments without altering locomotor activity and reduced neutrophil infiltrations in ankle joints. In vitro studies revealed oltipraz (25 μM) inhibited MSU-induced ROS production in mouse macrophages and improved mitochondrial bioenergetics impairments caused by MSU. In vivo ROS imaging combined with biochemical assays confirmed the antioxidant effects of oltipraz on model mice. Nrf2 activation inhibited pro-inflammatory cytokine overproduction in ankle joint and attenuated the overexpression and enhancement in TRPV1 channel in DRG neurons innervating hind limb. Therapeutic effects of oltipraz were abolished by inhibiting Nrf2 or in Nrf2 knockout mice. These results suggest pharmacologically activating Nrf2 alleviates gout pain, gait impairments, inflammation and peripheral sensitization via Nrf2-dependent antioxidant mechanism. Targeting Nrf2 may represent a novel treatment option for gout arthritis. [Display omitted] • Oltipraz relieves pain, inflammation and gait impairment in gout model mice. • Oltipraz inhibits inflammatory cell infiltration. • Oltipraz inhibits ROS production and TRPV1 overexpression. • Oltipraz's effects were abolished by antagonizing Nrf2 or in Nrf2 -/- mice. • Pharmacological targeting Nrf2 represents a new approach for gout management. [ABSTRACT FROM AUTHOR]

Developing metal-based nanocomposites as adsorbent for phosphorus (P) removal is a simple and effective strategy, while the separation of nanoscale adsorbents from water after adsorption is a tedious job. In this work, a novel Zr/Zn nanocomposite (Zr/Zn NCs) modified ceramsite (ZZMC) was synthesized to enhance P removal from agricultural drainage water. Characterization results showed that Zr/Zn NCs with fusiform nanostructures were uniformly loaded on the ceramsite, hence depending on the high mechanical strength and large size of ceramsite, the Zr/Zn NCs can be conveniently handled and separated after adsorption with P. The common issues of weak adsorption capacity and short using life related to ceramsite for P removal in wastewater were also significantly improved in complementarity combination with Zr/Zn NCs. The ZZMC exhibited higher P removal efficiency (>90%) at 5 mg-P L−1 in a wide pH range (5–9) than bulk ceramsite (<10%) and performed well when other ions were co-existed. For two real agricultural drainage water samples with total phosphorus (TP) of 0.526 mg-P L−1 and 0.865 mg-P L−1, the ZZMC demonstrated desirable adsorption performance not only for truly dissolved P (<3 kDa; >85%), but also for fine colloidal P (3 kDa–220 nm; 76.1%–79.1%) and medium colloidal P (220–450 nm; 80.7%–82.2%) within 30 adsorption cycles that included two-time regeneration treatments towards this material. Moreover, the adsorption capacity of TP by ZZMC after two regenerated treatments was more than 90% of that of fresh ZZMC. The results revealed the feasibility to remove different-sized P at low concentration for agricultural drainage water by ZZMC. [Display omitted] • P adsorption on ceramsite rose after Zr/Zn nanocomposites (NCs) modification. • ZZMC had high stable P adsorption efficiency (>90%) over a wide pH range. • ZZMC absorbed P by ligand exchange, electrostatic and Lewis acid-base interactions. • ZZMC can be easily separated, regenerated and reused. • ZZMC showed a potential for removing different-sized fractions of P. [ABSTRACT FROM AUTHOR]

Pain is a cardinal feature of many diseases. Chronic pain poses heavy burdens to the suffering patients, both physically and mentally. However, current mainstream medications for chronic pain, including opioids, antidepressants and non-steroid anti-inflammatory drugs are sometimes inefficient for chronic pain management and may cause side effects that limit long term usage. IL-33 belongs to IL-1 cytokine family and it exerts biological activities through binding to its specific receptor ST2. IL-33/ST2 signaling is very important in both innate and adaptive immunity. Emerging evidence indicates IL-33/ST2 signaling regulates pain in both immune and somatosensory systems through promoting neuro-immune or neuron-glia crosstalk, neuroinflammation and neuronal hyperexcitability. Some very latest studies indicate a vital part of IL-33/ST2 in mediating chronic itch. This work aims to overview the existing knowledge regarding the mechanisms of IL-33/ST2 involvement in pain and itch conditions, considering their potential similarities. We also summarized some key findings obtained from clinical studies. The targeting of IL-33/ST2 signaling holds promise for the development of novel therapeutic modalities in the management of pain and itch. [Display omitted] • IL-33 binds to its specific receptor ST2 to exert biological activities. • IL-33/ST2 is expressed in both immune and somatosensory system. • IL-33/ST2 modulates neuro-immune crosstalk and neuroinflammation. • IL-33/ST2 contributes to both pain and itch. • IL-33/ST2 may be a potential target for pain and itch management. [ABSTRACT FROM AUTHOR]

Phosphorus (P) availability and loss risk are linked to P species; however, their alternations in the soil amended with biochar-blended organic fertilizer is not well known, particularly under contrasting soil properties and land management. In this study, the variance of soil P species extracted by sequential chemical extraction (SCE) and 31P NMR techniques, as well as the degree of P saturation (DPS), were investigated throughout three paddy and three vegetable fields. These fields were amended with three different fertilizers at the same P application rate: chemical fertilizer (CF), organic fertilizer substitution (sheep manure/biogas slurry, SM/BS), and biochar-blended organic fertilizer substitution (BSM/BBS). Results showed that the BSM/BBS and SM increased the total P contents by 7.5% and 5.9% (TP) and available P contents by 30.1% and 19.2% (AP), but decreased the DPS values by 19.4% and 11.7%, compared to the CF treatment. Yet, the BS decreased the TP and AP contents but increased the DPS values across the experimental sites. In the BSM/BBS amended soils, high AP contents were due to the increased inorganic P (NaHCO 3 -P i), while the increased organic P (monoester and DNA) induced low DPS values and reduced soil P loss risk. Our study highlights that biochar-blended organic fertilizer is an effective agronomic way for improving P availability and decreasing P loss risk via the alteration of soil P species. [Display omitted] • High proportion of organic P and low P loss risk in the paddy fields. • Biochar addition increased stable P dissolution and organic P retention. • Biochar addition improved soil P availability and retention. [ABSTRACT FROM AUTHOR]

Recycling nutrients from the monosodium glutamate (MSG) wastewater as a low-cost fertilizer is a cleaner practice in the MSG industry. However, the potential of liquid organic fertilizer (LOF) recovered from MSG wastewater serving as a substitute for chemical fertilizer, improving crop yields, and mitigating reactive nitrogen emissions, has not been investigated. In a two-year paddy field experiment, the LOF recovered from the MSG wastewater was used as top dressing, following a multi-splits fertigation way, to evaluate its effects on rice yield, nitrogen use efficiency (NUE), NH 3 volatilization and nitrogen leaching losses. For top-dressed N, with local traditional top-dressing strategy (broadcast urea in three splits) as control (CF), LOF fertigated in seven splits (LOF 160 , totally 160 kg N ha−1) was set in 2017, and another two reduced N levels for LOF top-dressing (LOF 130 and LOF 100) were included in 2018. Compared with CF, the LOF 160 , LOF 130 and LOF 100 achieved similar rice yields and showed significant improvements in NUE (19.4%, 25.5% and 34.4%, respectively). Furthermore, due to the specific N forms and the implementation practice of more splits and low split-dosage, the LOF fertigation significantly decreased the cumulative NH 3 volatilization by 41.2%–67.7% and cumulative TDN leaching losses by 19.5%–44.1%. Although additional fertigation equipment investment is required, the LOF fertigation still improved the net economic benefits (NEB) by 10.4%–18.9% and the net economic and ecological benefit (NEEB) by 34.0%–54.9%, which primarily attributes to labor and fertilizer savings and the mitigation in environmental damage cost. This indicates that the use of recycled LOF as a substitute for chemical fertilizer can offer a promising option for delivering environmental and economic benefits of reduced chemical fertilizer use and industrial-agricultural pollution. [Display omitted] • Liquid organic fertilizer (LOF) increased N use efficiency while sustaining yield. • LOF applied in a more splits-lesser dosage way reduced volatile and leached N losses. • Application of LOF rich in organic N, did not increase dissolved organic N leaching. • LOF instead of urea increased the net economic and ecological benefit by 34.0%–54.9%. • LOF recycling builds a win-win nutrient loop between industry and agriculture. [ABSTRACT FROM AUTHOR]