Search

Fluoride-ion batteries (FIBs) offer a high theoretical energy density of 5000 W h L-1 and superior safety, but they face significant challenges such as electrode material dissolution and volume changes during cycling. Herein, this study presents an advanced interface engineering strategy to enhance the stability of the electrolyte--electrode interface. Through plasma treatment, substrate surface energy and adhesion are increased, while a co-deposition device generates a highenergy ion beam (Bi3+ and F-), depositing atoms densely and uniformly on CuF2 to form a protective layer. Additionally, regulating the BiOxFy crystal structure via controlled O2- ion injection optimizes F- transport and diffusion barriers. This modulation, driven by O-2p and F-2p electron density states, retards F- diffusion kinetics and mitigates volume changes in CuF2 during cycling. The resulting battery showed stable performance in N,N,N-dimethyl-N,N-dineopentylammonium fluoride liquid electrolyte at room temperature, including a specific capacity of 110 mA h g-1 and a fiftyfold longer cycling life than that of existing Cu@LaF3 core--shell batteries. Furthermore, X-ray absorption fine structure analysis reveals the pivotal role of a BiOF film in mitigating the lattice recombination effect by assimilating excess F-. These findings highlight the importance of this advanced interface strategy for advancements in FIBs. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system CNS characterized by demyelination, inflammation, and neurodegenerative changes, making it the most common nontraumatic disabling neurological disease in young adults. While current pharmacological treatments primarily target immunomodulation or immunosuppression, exercise is gaining increasing attention from the scientific community as an adjunctive therapy. This review explores the potential biological mechanisms of exercise in animal models of MS, focusing on its effects on neuroprotection and inflammation. The review examines how exercise inhibits pro-inflammatory microglial reactivity, stabilizes the blood–brain barrier, and enhances neurotrophic factor expression in animal studies. Future research directions are proposed by summarizing the evidence and limitations of existing animal models of MS, emphasizing the need to further validate these mechanisms in humans to better integrate exercise into the comprehensive management of MS. Additionally, investigating exercise-induced biomarkers for MS symptom reduction may provide a scientific basis for new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system CNS characterized by demyelination, inflammation, and neurodegenerative changes, making it the most common nontraumatic disabling neurological disease in young adults. While current pharmacological treatments primarily target immunomodulation or immunosuppression, exercise is gaining increasing attention from the scientific community as an adjunctive therapy. This review explores the potential biological mechanisms of exercise in animal models of MS, focusing on its effects on neuroprotection and inflammation. The review examines how exercise inhibits pro-inflammatory microglial reactivity, stabilizes the blood-brain barrier, and enhances neurotrophic factor expression in animal studies. Future research directions are proposed by summarizing the evidence and limitations of existing animal models of MS, emphasizing the need to further validate these mechanisms in humans to better integrate exercise into the comprehensive management of MS. Additionally, investigating exercise-induced biomarkers for MS symptom reduction may provide a scientific basis for new therapeutic strategies. [ABSTRACT FROM AUTHOR]

The Pinghu slope belt in the Xihu sag of the East China Sea Shelf Basin (ECSSB) is a crucial hydrocarbon production area in eastern China. However, due to the complex geological conditions, publications have lacked comprehensive research on the spatial-temporal coupling relationships of primary factors that impact hydrocarbon accumulation in the Pinghu slope belt. Furthermore, the hydrocarbon distribution patterns and the controlling factors across different study areas within the same slope belt are not yet fully understood. This study extensively utilized three-dimensional seismic data, well logging data, geochemical analysis, fluorescence analysis, and oil testing and production data to address these issues. Following a "stratification and differentiation" approach, the study identified seven distinct hydrocarbon migration and accumulation units (HMAU) in the Pinghu slope area based on the structural morphology characteristics, hydrocarbon source-reservoir-cap rock patterns, hydrocarbon migration pathways, and hydrocarbon supply range. Detailed analysis was conducted to examine the hydrocarbon distribution patterns and controlling factors within each migration and accumulation unit across different structural units, including high, medium, and low structural components. All data sources support a "southern-northern sub-area division, eastern-western sub-belt division, and variations in hydrocarbon accumulation" pattern in the Pinghu slope belt. The degree of hydrocarbon accumulation is controlled by the factors of structural morphology, hydrocarbon generation potential of source rocks, the spatial position of source slopes, fault sealing capacity, and sand body distribution. Furthermore, different coupling patterns of faults and sand bodies play a pivotal role in governing hydrocarbon enrichment systems across various migration and accumulation units. These observations indicate that three hydrocarbon accumulation patterns have been established within the slope belt, including near-source to far-source gentle slope with multiple hydrocarbon kitchens in the XP1-XP4 zones, near-source to middle-source gentle slope with dual-hydrocarbon kitchens in the XP5 zone, and near-source steep slope with a single hydrocarbon kitchen in the XP6-XP7 zones. These findings contribute to enhancing the theoretical system of hydrocarbon accumulation in the slope belt. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, characterized by high mortality and a poor prognosis. Despite various treatment methods, there has been limited improvement in the prognosis of ICH over the past decades. Therefore, it is imperative to identify a feasible treatment strategy for ICH. Mitochondria are organelles present in most eukaryotic cells and serve as the primary sites for aerobic respiration and energy production. Under unfavorable cellular conditions, mitochondria can induce changes in permeability through the opening of the mitochondrial permeability transition pore (mPTP), ultimately leading to mitochondrial dysfunction and contributing to various diseases. Recent studies have demonstrated that mPTP plays a role in the pathological processes associated with several neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke and ischemia-reperfusion injury, among others. However, there is limited research on mPTP involvement specifically in ICH. Therefore, this study comprehensively examines the pathological processes associated with mPTP in terms of oxidative stress, apoptosis, necrosis, autophagy, ferroptosis, and other related mechanisms to elucidate the potential mechanism underlying mPTP involvement in ICH. This research aims to provide novel insights for the treatment of secondary injury after ICH. [ABSTRACT FROM AUTHOR]

Benzene, a known toxic, carcinogenic, and pervasively present environmental pollutant, necessitates effective monitoring strategies to assess human exposure. S-Phenylmercapturic acid (S-PMA) is a specific biomarker for benzene exposure. This study presents a point-of-care testing (POCT) assay for the detection of S-PMA in human urine, integrating salt-induced phase separation (SIPS) with surface-enhanced Raman spectroscopy (SERS). S-PMA in human urine was first effectively separated using SIPS and then detected using a portable Raman spectrometer employing Au colloids as the SERS substrate. The POCT assay exhibited a clear correlation between the signal intensity and logarithmic concentration of S-PMA (0-5 ppm), demonstrating satisfactory recovery and reproducibility. Moreover, high-throughput fingerprint identification and quantitative analysis of S-PMA in urine were achieved within 10 min, with a detection limit as low as 1.06 ppb, by performing SIPS-SERS on 96-well plates. This POCT method holds promise for personal exposure assessment and may potentially aid in the prevention of benzene-induced diseases. [ABSTRACT FROM AUTHOR]

Objective: There is currently a lack of evidence in evidence-based medicine regarding acupuncture treatment for experimental intracerebral hemorrhage (ICH). The aim of this study was to systematically evaluate the efficacy of acupuncture treatment for experimental ICH based on neurological function scores and brain water content (BWC). Methods: Eight mainstream Chinese and English databases were searched. Outcome measures included neurological function scores and BWC, and subgroup analysis was conducted based on study characteristics. Results: A total of 32 studies were included. Meta-analysis results indicated that compared to the control group, the acupuncture group showed significant reductions in mNSS (MD = -3.16, p < 0.00001), Bederson score (MD = -0.99, p < 0.00001), Longa score (MD = -0.54, p < 0.0001), and brain water content (MD = -5.39, p < 0.00001). Subgroup analysis revealed that for mNSS, the autologous blood model (MD = -3.36) yielded better results than the collagenase model (MD = -0.92, p < 0.00001), and simple fixation (MD = -3.38) or no fixation (MD = -3.39) was superior to sham acupuncture (MD = -0.92, p < 0.00001). For BWC, the autologous blood model (MD = -7.73) outperformed the collagenase model (MD = -2.76, p < 0.00001), and GV20-GB7 (MD = -7.27) was more effective than other acupuncture points (MD = -2.92, p = 0.0006). Conclusion: Acupuncture significantly improves neurological deficits and brain edema in experimental ICH. Acupuncture at GV20 - GB7 is more effective than at other points. These findings support further studies to translate acupuncture into clinical treatment for human ICH. [ABSTRACT FROM AUTHOR]

A gel based on polyacrylamide, exhibiting delayed crosslinking characteristics, emerges as the preferred solution for mitigating degradation under conditions of high temperature and extended shear in ultralong wellbores. High viscosity/viscoelasticity of the fracturing fluid was required to maintain excellent proppant suspension properties before gelling. Taking into account both the cost and the potential damage to reservoirs, polymers with lower concentrations and molecular weights are generally preferred. In this work, the supramolecular action was integrated into the polymer, resulting in significant increases in the viscosity and viscoelasticity of the synthesized supramolecular polymer system. The double network gel, which is formed by the combination of the supramolecular polymer system and a small quantity of Zr-crosslinker, effectively resists temperature while minimizing permeability damage to the reservoir. The results indicate that the supramolecular polymer system with a molecular weight of (268-380) ×104 g/mol can achieve the same viscosity and viscoelasticity at 0.4 wt% due to the supramolecular interaction between polymers, compared to the 0.6 wt% traditional polymer (hydrolyzed polyacrylamide, molecular weight of 1078 ×104 g/mol). The supramolecular polymer system possessed excellent proppant suspension properties with a 0.55 cm/min sedimentation rate at 0.4 wt%, whereas the 0.6 wt% traditional polymer had a rate of 0.57 cm/min. In comparison to the traditional gel with a Zrcrosslinker concentration of 0.6 wt% and an elastic modulus of 7.77 Pa, the double network gel with a higher elastic modulus (9.00 Pa) could be formed only at 0.1 wt% Zr-crosslinker, which greatly reduced the amount of residue of the fluid after gel-breaking. The viscosity of the double network gel was 66 mPa s after 2 h shearing, whereas the traditional gel only reached 27 mPa s. [ABSTRACT FROM AUTHOR]

Developing highly efficient and low-cost photoelectrocatalyst for H2 evolution under visible-light irradiation is a key topic in the areas of energy and environment. In this work, we designed and deposited p-type semiconductor Cu3N onto 1D n-type rutile TiO2 nanorod array by the magnetron sputtering method. The formed TiO2/Cu3N p-n heterojunction not only exhibits a narrowed band gap from 3.09 eV for TiO2 to 2.01 eV for TiO2/Cu3N but also expands the light-response from UV to visiblelight region. In addition, the lifetime, separation and transfer of the photogenerated electron-hole pairs are efficiently prolonged and improved due to the build-in electric field at the interface of the TiO2/Cu3N p-n heterojunction. As a result, the photocurrent density under 4420 nm visible-light irradiation is enhanced for about 14.12 times, from 0.33 mA cm2 for TiO2 to 4.66 mA cm2 for TiO2/Cu3N at 0.97 V vs. RHE (reversible hydrogen electrode). Furthermore, the constructed TiO2/Cu3N heterojunction shows stable PEC H2 evolution performance, with the H2 production rate reaching 6.98 mmol cm2 h1 under 4420 nm visible-light irradiation. Our results suggest that the construction of nontoxic p-n heterojunction with suitable band gap should be a promising strategy to improve the photoelectrocatalytic performance of TiO2 and should be applied in other photoelectrocatalysts. [ABSTRACT FROM AUTHOR]

With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhagic stroke, characterized by acute hemorrhage in the brain, has a significant clinical prevalence and poses a substantial threat to individuals' well-being and productivity. Recent research has elucidated the role of gut microorganisms and their metabolites in influencing brain function through the microbiota-gut-brain axis (MGBA). This article provides a comprehensive review of the current literature on the common metabolites, short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), produced by gut microbiota. These metabolites have demonstrated the potential to traverse the blood-brain barrier (BBB) and directly impact brain tissue. Additionally, these compounds have the potential to modulate the parasympathetic nervous system, thereby facilitating the release of pertinent substances, impeding the buildup of inflammatory agents within the brain, and manifesting anti-inflammatory properties. Furthermore, this scholarly analysis delves into the existing dearth of investigations concerning the influence of gut microorganisms and their metabolites on cerebral functions, while also highlighting prospective avenues for future research. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) manifests precipitously and profoundly impairs the neurological function in patients who are aected. The etiology of subsequent injury post-ICH is multifaceted, characterized by the intricate interplay of various factors, rendering therapeutic interventions challenging. Astrocytes, a distinct class of glial cells, interact with neurons and microglia, and are implicated in a series of pathophysiological alterations following ICH. A comprehensive examination of the functions and mechanisms associated with astrocytic proteins may shed light on the role of astrocytes in ICH pathology and proer innovative therapeutic avenues for ICH managemen [ABSTRACT FROM AUTHOR]

Objective: Inflammation participates in the pathology and progression of secondary brain injury after intracerebral hemorrhage (ICH). This meta-analysis intended to explore the prognostic role of inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), white blood cell (WBC), and C-reactive protein (CRP) in ICH patients. Methods: Embase, PubMed, Web of Science, and Cochrane Library were searched until June 2023. Two outcomes, including poor outcome and mortality were extracted and measured. Odds ratio (OR) and 95% confidence interval (CI) were presented for outcome assessment. Results: Forty-six studies with 25,928 patients were included in this metaanalysis. The high level of NLR [OR (95% CI): 1.20 (1.13–1.27), p  <  0.001], WBC [OR (95% CI): 1.11 (1.02–1.21), p  =  0.013], and CRP [OR (95% CI): 1.29 (1.08–1.54), p  =  0.005] were related to poor outcome in ICH patients. Additionally, the high level of NLR [OR (95% CI): 1.06 (1.02–1.10), p  =  0.001], WBC [OR (95% CI): 1.39 (1.16–1.66), p  <  0.001], and CRP [OR (95% CI): 1.02 (1.01–1.04), p  =  0.009] were correlated with increased mortality in ICH patients. Nevertheless, PLR was not associated with poor outcome [OR (95% CI): 1.00 (0.99–1.01), p  =  0.749] or mortality [OR (95% CI): 1.00 (0.99–1.01), p  =  0.750] in ICH patients. The total score of risk of bias assessed by Newcastle-Ottawa Scale criteria ranged from 7–9, which indicated the low risk of bias in the included studies. Publication bias was low, and stability assessed by sensitivity analysis was good. Conclusion: This meta-analysis summarizes that the high level of NLR, WBC, and CRP estimates poor outcome and higher mortality in ICH patients. [ABSTRACT FROM AUTHOR]

The bone is one of the most commonly affected organs in sickle cell disease (SCD). Repeated ischemia, oxidative stress and inflammation within the bone is largely responsible for promoting bone pain. As more individuals with SCD survive into adulthood, they are likely to experience a synergistic impact of both aging and SCD on their bone health. As bone health deteriorates, bone pain will likely exacerbate. Recent mechanistic and observational studies emphasize an intricate relationship between bone remodeling and the peripheral nervous system. Under pathological conditions, abnormal bone remodeling plays a key role in the propagation of bone pain. In this review, we first summarize mechanisms and burden of select bone complications in SCD. We then discuss processes that contribute to pathological bone pain that have been described in both SCD as well as non-sickle cell animal models. We emphasize the role of bone-nervous system interactions and pitfalls when designing new therapies especially for the sickle cell population. Lastly, we also discuss future basic and translational research in addressing questions about the complex role of stress erythropoiesis and inflammation in the development of SCD bone complications, which may lead to promising therapies and reduce morbidity in this vulnerable population. [ABSTRACT FROM AUTHOR]

Compared to either HIV or hepatitis B virus (HBV) monoinfected individuals, HIV/HBV-coinfected individuals have a decreased probability of spontaneous HBV clearance and a greater risk of developing chronic liver damage and a faster progression to cirrhosis and hepatocellular carcinoma. This manuscript attempts to provide a comprehensive review of the landscape of current HIV/HBV coinfection research with a focus on the intricate interactions between these two viruses. Our review will help understand the disease dynamics of HIV/HBV coinfection and has important implications for designing public health strategies. [ABSTRACT FROM AUTHOR]

The development of aggregation-induced emission luminogens (AIEgens) with high brightness and efficient photodynamic therapy (PDT) is of great value for the precise diagnosis and treatment of cancers. In this contribution, two novel AIEgens, TBBCyP and TBTCyP with D-A-p-A structure, were designed and prepared based on molecular rational design of electron-donating receptors. Experimental and theoretical results indicated that both TBBCyP and TBTCyP own bright AIE feature, satisfy photos ability, and generate efficient singlet oxygen (1O2). Notably, TBBCyP exhibited brighter emission and higher 1O2 yield in compared with TBTCyP, which could be ascribed to its weaker twisted intramolecular charge transfer (TICT) effect and narrower singlet-triplet energy gap (ΔEST). Moreover, it was proved that TBBCyP and TBTCyP showed a great mitochondrial specificity and desired intracellular ROS productivity for realizing the effective mitochondria-targeted PDT of cancer cells. [ABSTRACT FROM AUTHOR]

Measurements of rice physical traits, such as length, width, and percentage of filled/unfilled grains, are essential steps of rice breeding. A new approach for measuring the physical traits of rice grains for breeding purposes was presented in this study, utilizing image processing techniques. Backlight photography was used to capture a grayscale image of a group of rice grains, which was then analyzed using a clustering algorithm to differentiate between filled and unfilled grains based on their grayscale values. The impact of backlight intensity on the accuracy of the method was also investigated. The results show that the proposed method has excellent accuracy and high efficiency. The mean absolute percentage error of the method was 0.24% and 1.36% in calculating the total number of grain particles and distinguishing the number of filled grains, respectively. The grain size was also measured with a little margin of error. The mean absolute percentage error of grain length measurement was 1.11%, while the measurement error of grain width was 4.03%. The method was found to be highly accurate, non-destructive, and costeffective when compared to conventional methods, making it a promising approach for characterizing physical traits for crop breeding. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is the most lethal type of stroke. Secondary injury from ICH determines the recovery, but there is still a lack of effective treatment. The identification of new therapeutic targets may address the current dilemma. The process of autophagy is mediated through the lysosomal pathway and is used to maintain cell homeostasis. Recent studies have advanced our knowledge of autophagy, and in particular its involvement in cell physiology and pathology. Autophagy involves multiple targets and signaling pathways and occurs in many brain cells. It also regulates oxidative stress and inflammation after ICH, both of which are important factors in secondary brain injury. An appropriate level of autophagy is protective in ICH, whereas excessive autophagy may be detrimental. In this review, we discuss the signaling pathways for autophagy in ICH and related factors that provide a theoretical basis for the discovery of new treatment targets. [ABSTRACT FROM AUTHOR]

Land-tenure security is integral to local communities' socioeconomic development. It has been a center of debate in academia and for legislators and advocates to implement reforms to enhance efficient and sustainable development in land management. Yet, knowledge gaps remain in how various contract-farming regimes contribute to land-improvement investment and technical efficiency. This study used a data set of 650 farm households collected through a two-stage stratified sampling to investigate the influence of three contract-farming regimes: long-term, medium-term, and short-term contracts, on the land-improvement investment, productivity, and technical efficiency of contract farmers in Punjab, Pakistan. The study used multivariate probit and ordinary least square regression models to examine the posit relationships. The findings highlight that farmers with long-term land contracts have higher per hectare yield, income and profit than those with medium-term and short-term contracts. The results confirm that farmers with medium- and long-term contracts tend to invest more in land-improvement measures, i.e., organic and green manure. Further, the study findings demonstrate that long-term land tenures are more effective when farmers make decisions regarding the on-farm infrastructure, like tube-well installation, tractor ownership, and holding farm logistics. Last, the study results confirm that long-term contracts are more robust regarding technical efficiency. Moreover, the findings support the Marshallian inefficiency hypothesis and extend the literature on contract farming, land-improvement investment, and land use policy, and offer coherent policy actions for stakeholders to improve farmers' productivity, technical efficiency, and income. [ABSTRACT FROM AUTHOR]

Introduction: To examine the burden of rheumatoid arthritis (RA) at the global, regional, and national levels in terms of sex, age, geographic distribution, and the Socio-demographic Index (SDI). Material and methods: Using Global Burden of Disease study data, the global incidence, disability-adjusted life years (DALYs), and estimated annual percentage change (EAPC) of RA from 1990 to 2019 were analysed. Results: From 1990 to 2019, the global RA incidence and DALYs increased by 6.47% and 1.15%, respectively. Moreover, both the global age-standardized incidence rate (EAPC = 0.30; 95% confidence interval (CI): 0.25-0.34) and DALYs (EAPC = 0.12; 95% CI: 0.08-0.17) increased. The age-standardized RA incidence was substantially higher in the high-SDI regions than in the other regions. By geographical region, the largest increases in the age-standardized RA incidence and DALYs were observed in Andean Latin America. By country, the largest increase in RA incidence was observed in Equatorial Guinea (EAPC = 1.78), followed by Bhutan (EAPC = 1.54) and Peru (EAPC = 1.53). The age-standardized RA incidence was lower in men than in women. Positive correlations were found between the EAPC of the age-standardized RA incidence and the SDI. Conclusions: Increasing trends in the age-standardized RA incidence and DALYs worldwide were shown. Future strategies for RA prevention should focus on women and older adults, as well as individuals from Andean Latin America, southern Latin America, central Asia, western sub-Saharan Africa, and other high-risk regions. [ABSTRACT FROM AUTHOR]

Pancreatic lipase (PL) is a well-known key target for the prevention and treatment of obesity. Human carboxylesterase 1A (hCES1A) has become an important target for the treatment of hyperlipidaemia. Thus, the discovery of potent dual-target inhibitors based on PL and hCES1A hold great potential for the development of remedies for treating related metabolic diseases. In this study, a series of natural triterpenoids were collected and the inhibitory effects of these triterpenoids on PL and hCES1A were determined using fluorescence-based biochemical assays. It was found that oleanolic acid (OA) and ursolic acid (UA) have the excellent inhibitory effects against PL and hCES1A, and highly selectivity over hCES2A. Subsequently, a number of compounds based on the OA and UA skeletons were synthesised and evaluated. Structure-activity relationship (SAR) analysis of these compounds revealed that the acetyl group at the C-3 site of UA (compound 41) was very essential for both PL and hCES1A inhibition, with IC50 of 0.75 µM and 0.014 µM, respectively. In addition, compound 39 with 2-enol and 3-ketal moiety of OA also has strong inhibitory effects against both PL and hCES1A, with IC50 of 2.13 µM and 0.055 µM, respectively. Furthermore, compound 39 and 41 exhibited good selectivity over other human serine hydrolases including hCES2A, butyrylcholinesterase (BChE) and dipeptidyl peptidase IV (DPP-IV). Inhibitory kinetics and molecular docking studies demonstrated that both compounds 39 and 41 were effective mixed inhibitors of PL, while competitive inhibitors of hCES1A. Further investigations demonstrated that both compounds 39 and 41 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. Collectively, we found two triterpenoid derivatives with strong inhibitory ability on both PL and hCES1A, which can be served as promising lead compounds for the development of more potent dual-target inhibitors targeting on PL and hCES1A. [ABSTRACT FROM AUTHOR]

Introduction: Radiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning. Methods: The dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation. We deployed a parabolic partial differential equation to account for the generalized radiation oxygen depletion, tissue oxygen diffusion, and metabolic processes to investigate oxygen distribution in 1D, 2D, and 3D solution space. Dose and dose rates, particle LET, vasculature spacing, and blood oxygen supplies were considered. Using a similar framework for the hypoxic reduction factor (HRF) developed previously, the FEDMF was derived as the ratio of the cumulative normoxic-equivalent dose (CNED) between CONV and UHDR deliveries. Results: Dynamic equilibrium between oxygen diffusion and tissue metabolism can result in tissue hypoxia. The hypoxic region displayed enhanced radioresistance and resulted in lower CNED under UHDR deliveries. In 1D solution, comparing 15 Gy proton dose delivered at CONV 0.5 and UHDR 125 Gy/s, 61.5% of the tissue exhibited ≥20% FEDMF at 175 mm vasculature spacing and 18.9 mM boundary condition. This percentage reduced to 34.5% and 0% for 8 and 2 Gy deliveries, respectively. Similar trends were observed in the 3D solution space. The FLASH versus CONV differential effect remained at larger vasculature spacings. A higher FLASH dose rate showed an increased region with ≥20% FEDMF. A higher LET near the proton Bragg peak region did not appear to alter the FLASH effect. Conclusion: We developed 1D, 2D, and 3D oxygen depletion simulation process to obtain the dynamic HRF and derive the proton FEDMF related to the dose delivery parameters and the local tissue vasculature information. The phenomenological model can be used to simulate or predict FLASH effects based on tissue vasculature and oxygen concentration data obtained from other experiments. [ABSTRACT FROM AUTHOR]

In developing countries, supply chains are rapidly transforming. However, smallholder farmers, in particular, have experienced mixed impacts in inclusion and exclusion from modern supply chains (MSCs). Therefore, by taking Pakistan's mandarin industry as a case, this study aims to analyze the farmers' efficiency and inclusiveness in modern supply chains and compare them across the farm size categories, i.e., small, medium, and large. For that purpose, cross-sectional data from 300 farmers were collected to test the posit objectives. The empirical investigation was made using the endogenous treatment effect model and the propensity score matching approach. Findings show that large farmers prefer to participate in MSCs, driven by contractors, processors or exporters. Conversely, the smallholders are more inclined to participate in the traditional supply chains (TSCs), driven by village vendors, local retailers/consumers, middlemen, and traditional fruit and vegetable markets. The results also revealed a positive connection between efficiency and farmers' inclusion in the MSC. Orchard size, education, off-farm income, and extension services positively impact profitability. In terms of an increase in farmers' profitability, the efficiency improvement can benefit the resource-poor smallholders who make up 74% of the total farmers in the sample. Therefore, these results are noteworthy for devising policy actions to facilitate smallholder inclusion in the modern agri-food supply chains to alleviate rural poverty and ensure farmers' wellbeing. [ABSTRACT FROM AUTHOR]

Purpose: Parkinson's disease (PD) is a serious neurodegenerative disease affecting the elderly. In general, the locomotion deficit, which seriously affects the daily life of patients with PD, usually occurs at a later stage. The mask face symptom meanwhile progressively worsens. However, facial muscle disorders and changes involved in the freezing mask are unclear. Method: In this study, we recruited 35 patients with PD and 26 age- and sex-balanced controls to undergo phonation tests, while the built-in camera on the laptop recorded their facial expressions during the whole pronunciation process. Furthermore, FaceReader (version 7.0; Noldus Information Technology, Wageningen, Netherlands) was used to analyze changes in PD facial landmark movement and region movement. Results: The two-tailed Student's t-test showed that the changes in facial landmark movement among 49 landmarks were significantly lower in patients with PD than in the control group (P < 0.05). The data on facial region movement revealed that the eyes and upper lip of patients with PD differed significantly from those in the control group. Conclusion: Patients with PD had defects in facial landmark movement and regional movement when producing a single syllable, double syllable, and multiple syllables, which may be related to reduced facial expressions in patients with PD. [ABSTRACT FROM AUTHOR]

Background: Associations between rheumatoid arthritis (RA) and reduced skeletal muscle have been studied, and we firstly reported myopenia independently predict one-year radiographic progression in RA. Myokine myostatin can negatively regulate skeletal muscle mass and promote osteoclast differentiation. However, there is no report about their relationships in RA patients. We firstly explored the relationship of serum myostatin and disease characteristics, as well as aggravated joint destruction during one-year follow-up. Methods: Consecutive RA patients were recruited from a real-world prospective cohort and completed at least one-year follow-up. Baseline serum level of myostatin was measured by enzyme-linked immunosorbent assay. Clinical data in RA patients as well as muscle index in both RA patients and healthy controls were collected. One-year radiographic progression as primary outcome was defined by a change in the total Sharp/van der Heijde modified score ≥0.5 units. Results: Totally 344 RA patients (age 47.9 ± 12.5 years, 84.0% female) and 118 healthy control subjects (age 42.8 ± 11.3 years, 74.6% female) were recruited. Compared with healthy controls, RA patients showed a higher level of serum myostatin at baseline (3.241 ± 1.679 ng/ml vs. 1.717 ± 0.872 ng/ml, P<0.001), although lower appendicular skeletal muscle mass index (ASMI, 6.0 ± 0.9 kg/m² vs. 6.5 ± 1.0 kg/m², P<0.001). In RA patients, those with high myostatin level showed a higher rate of radiographic progression than low myostatin group (45.3% vs. 18.6%, P<0.001). Furtherly, RA patients were stratified into four subgroups according to serum myostatin and myopenia. Compared with other three subgroups, RA patients with high myostatin overlapping myopenia had the highest rate of radiographic progression (67.2% vs. 10.3%-31.4%, P<0.001), as well as the lowest proportion of remission and the highest rate of physical dysfunction during one-year follow-up. After adjustment for confounding factors, high serum myostatin (AOR=3.451, 95%CI: 2.016-5.905) and myopenia (AOR=2.387, 95%CI: 1.416-4.022) at baseline were risk factors for one-year radiographic progression, especially for those with high myostatin overlapping myopenia (AOR=10.425, 95%CI: 3.959-27.450) as the highest-risk individuals among four subgroups. Significant synergistic interaction effect was observed between high myostatin and myopenia on one-year radiographic progression (AP=66.3%, 95%CI: 43.2%-89.3%). Conclusion: Myostatin is a novel predictor of aggravated joint destruction in RA patients which has synergistic interaction with myopenia for predicting value. [ABSTRACT FROM AUTHOR]

Variable application by wind is an efficient application technology recommended by the Food and Agriculture Organization (FAO) of the United Nations that can effectively improve the deposition effect of liquid medicine in a canopy and reduce droplet drift. In view of the difficulty of modelling wind forces in orchard tree canopies and the lack of a wind control model, the wind loss model for a canopy was studied. First, a three-dimensional wind measurement test platform was built for an orchard tree canopy. The orchard tree was located in three-dimensional space, and the inner leaf areas of the orchard tree canopy and the wind force in different areas were measured. Second, light detection and ranging (LiDAR) point cloud data of the orchard tree canopy were obtained by LiDAR scanning. Finally, classic regression, partial least squares regression (PLSR), and back propagation (BP) neural network algorithms were used to build wind loss models in the canopy. The research showed that the BP neural network algorithm can significantly improve the fitting accuracy of the model. Under different fan speeds of 1,381 r/min, 1,502 r/min, and 1,676 r/min, the coefficient of determination (R²) of the model were 81.78, 72.85, and 69.20%, respectively, which were 19.38, 7.55, and 12.3% higher than those of the PLSR algorithm and 21.48, 22.25, and 24.3% higher than those of multiple regression analysis. The comparison showed that the BP neural network algorithm obtains the highest model accuracy, but because the model is not intuitive, PLSR has the advantages of intuitive and simple models in the three algorithms. In practical applications, the wind loss model based on a BP neural network or PLSR can be selected according to the operational requirements and software and hardware conditions. This study can provide a basis for wind control in precise variable spraying and promote the development of wind control technologies. [ABSTRACT FROM AUTHOR]

In order to guarantee the accuracy of turntable angle measurement, a real-time compensation method for turntable positioning precision based on harmonic analysis is proposed in this paper. Firstly, the principle and feasibility of the real-time compensation method are analysed, and a detailed description of harmonic compensation is provided herein. Secondly, we analyse the relationships between the surface number of the polygon with the compensation order of the harmonic function and its corresponding compensation accuracy. The effects of the iterations number and the data width on calculation accuracy in the coordinate rotation digital computer (CORDIC) algorithm are analysed and the quantization models of the approximation error and rounding error of the CORDIC algorithm are established. Then, the calculation of the harmonic error function and real-time compensation processes are implemented on a field programmable gate array (FPGA) chip. The resource occupation and time delay of the phase angle calculation and the harmonic component calculation are discussed separately. Finally, the validity of the harmonic compensation method is proven through comparing the compensation effect with that of linear interpolation and the polynomial compensation method. The influences of the compensation order, the iterations number and the data width on the compensation results are demonstrated by simulation. A test platform with a laboratory-made FPGA circuit is built to evaluate the effect of real-time compensation with the harmonic function and the positioning error compensation can be performed within 760 ns. The results confirmed the effectiveness of the harmonic compensation method, revealing an improvement of the positioning precision from 54.21" to 1.63", equivalent to 96.99% reduction in positioning error. [ABSTRACT FROM AUTHOR]

Although highly active antiretroviral therapy has transformed HIV-1 infection into a manageable chronic disease, the development of an effective vaccine is still an important and challengeable research field of HIV-1 treatment. The challenge arises from an enormous diversity of HIV-1 strains and their rapid evolution ahead of effective immune responses. HIV-1 evasion from host immunity contributes to viral spread and pathogenesis, thus understanding the mechanisms of HIV-1 immune evasion is important. In this review, we summarized our present knowledge on the mechanisms how HIV-1 escapes immune responses. Such knowledge will help with the design of effective vaccines capable of inducing immune control of HIV-1. [ABSTRACT FROM AUTHOR]

[Objectives] To use poly (lactic-cc-glycolie acid) (PLGA) nanopaficles to improve the bioavailability and brain entrance capar billy of Salidroside (Sai). [Mettods] An emulsion solvent evaporation approach wat used to create PLGA nanoparticlee (Sal-NP). The preparation parameters were optimized using a single factor experiment. The particle size and zett potential were determined using the laser pafr tide analyzee, and the morphology of the nanoparticles wss observed using transmission electron microscopy. The encapsulation efficience and drug loading were determined using HPLC. Subsequently, the in vitro drug release was determined using a dynamic dialysii method, and the cellular uptake and cytotoxicity were determined using the bEnd3 cell model. [Results] The ultrasonic tirne and power for preparing Sal-NP were 6 min and 100 W, respectively. The size of the nanoparticles was 162. 0 ± 74. 86 nm, and the morphology of Sal-NP was spherical like. After 48 h, the cumulative release of Sal-NP was 62%, indicating that Sai showed a controlled release property in Sal-NP. Cellular uptake study showed that Oe PLGA nanopvticles remarkably increased the internalization than control group (P < 0.001). In addiâon, Sal-NPs were non-toxic te celis at concentrations ranging from 12. 5 te 100 "M. [Conclusions] PLGA nanoparCcles ii promising te be exploited in Alzheirner's disease research due to the increasing absorption and controlled release advantages for Sai. [ABSTRACT FROM AUTHOR]

Almost 40 years have passed since the first case of what is known as AIDS was documented. In these 40 years, AIDS has always been a research challenge and hot spot. Researchers and scientists have made tremendous progress in basic and clinical research on HIV. In particular, the widespread use of antiretroviral therapy (ART) has made it less of a deadly disease today and more of a manageable one. In the post- ART era when ART can significantly improve the immunity of people living with HIV (PLWH) and extend their life, the incidence of non-AIDS-defined cancers is greatly increased. Factors related to immunosuppression do not seem to explain this problem sufficiently. This suggests that besides immunosuppression, there are other mechanisms that may also contribute to the increased incidence of cancer in PLWH. Here, we summarized and discussed four possible mechanisms for the increased incidence of cancers in PLWH: immunosuppression, oncogenic viral infection, chronic infection, inflammatory damage, and the direct impact of HIV. [ABSTRACT FROM AUTHOR]

Copyright of INMATEH - Agricultural Engineering is the property of INMATEH - Agricultural Engineering and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Over time, the government of Pakistan introduced several strategies to deal with the issue of slums in its capital city, Islamabad. Contrary to the traditional strategies that primarily focus on the tenure security of occupants, the strategy of slum redevelopment is more composite. It involves the up-gradation of slums in their existing sites as well as the demolition of slums from the posh areas. The present study is first to empirically investigates the outcomes of the slums redevelopment policies on the value of adjacent residential properties. Using a rental valuation based hedonic price model, the study examined the spillover effects of an urban slum up-gradation and eviction projects on the nearby housing values. The results show that the redevelopment of slums reduces the adverse effects on residential value. It is essential for the urban planners to cautiously include the slum redevelopment projects spillover effects on the adjacent property value in different geographical locations, to maximize the net positive effects of improvements on the neighborhood. [ABSTRACT FROM AUTHOR]

At present, HIV-1 infection is treated with combined antiretroviral therapy (cART). cART greatly improves the life quality and outcome of infected individuals but cannot eradicate the virus from the hosts. Therefore, new treatment methods that can clear the virus are needed. In this review, we summarized four novel approaches that have the potentials to cure HIV infection, which are dendritic cell targeting, CCR5 editing, LASER ART and CRISPR-Cas9 dual therapy and broad neutralization antibodies. [ABSTRACT FROM AUTHOR]

This research investigation falls in the very few studies that seek the association between city development and sustainable urban planning. This study emphasized to examine and explore effects of urban village disamenity on Nanjing suburban and posh area property valuation. Globally, slums exist in almost every country; however, researchers focused less on slums' crumbled infrastructure, crimes, and other social problems; however, few kinds of research studies covered the adverse impact on the property value. This paper plans to seek the effects of rural area migrants on Nanjing City in response to the late 1970 economic reform implementation as they aimed to extract benefits of reforms offering enhanced economic opportunities, higher rate of income and employment, and comprehensive social benefits. This study examined the negativity of urban villages on the surrounding area valuation and its impact on residential properties. The results of this study specified an adverse effect of urban villages on the value of nearby apartments; however, residential units closer to these villages experienced the worst impact compared to the residential apartments located far away. The findings revealed that urban villages' neighborhood negatively influences home selling value when compared with other houses located far away. This study is helpful for government officials and policymakers to resolve urban villages' issues. [ABSTRACT FROM AUTHOR]

HIV-1 infection poses a major threat to the public health worldwide. The antiretroviral agents that are currently used to treat HIV-1 infection target viral reverse transcriptase, integrase and protease, or block the fusion of viral envelop and cell membrane. Studies have shown that the HIV-1 encoded protein Nef plays an important role in the pathogenesis of viral infection. Nef ensures efficient counterattack against host immune responses as well as long-term evasion of immune surveillance. In addition, Nef, expressing at a high level early in the viral life cycle, is required for maintaining a high viral load in the persistent infection in vivo and for full pathologic potential. Therefore, Nef may be an excellent target to treat HIV-1 infection. In this manuscript, we reviewed five potential Nef inhibitors, namely, DLC27-14, tightly bound hydroxypyrazole HIV-1 Nef inhibitor B9, 2c-like inhibitors, N-(3-aminoquinoxalin-2-yl)-4-chlorobenzenesulfonamide and compound 1[(7-oxo-7H-benzo[anthracene]-3-yl)amino]anthraquinone, and their working mechanisms. These drugs may be further developed into new regimens for the treatment of HIV-1 infection. [ABSTRACT FROM AUTHOR]

Context: Implantation is a reproductive bottleneck in women, regulated by fluctuations in ovarian steroid hormone concentrations. However, other nuclear receptor ligands are modifiers of endometrial differentiation leading to successful pregnancy. In the present study we analyzed the effects of peroxisome-proliferator-activated receptor β/δ (PPARβ/δ) activation on established cellular biomarkers of human endometrial differentiation (decidualization).Objective: The objective of this work is to test the effects of PPARβ/δ ligation on human endometrial cell differentiation.Design: Isolated primary human endometrial stromal cells (ESCs) were treated with synthetic (GW0742) or natural (all trans-retinoic acid, RA) ligands of PPARβ/δ, and also with receptor antagonists (GSK0660, PT-S58, and ST247) in the absence or presence of decidualizing hormones (10 nM estradiol, 100 nM progesterone, and 0.5 mM dibutyryl cAMP [3',5'-cyclic adenosine 5'-monophosphate]). In some cases interleukin (IL)-1β was used as an inflammatory stimulus. Time course and dose-response relationships were evaluated to determine effects on panels of well characterized in vitro biomarkers of decidualization.Results: PPARβ/δ, along with estrogen receptor α (ERα) and PR-A and PR-B, were expressed in human endometrial tissue and isolated ESCs. GW0742 treatment enhanced hormone-mediated ESC decidualization in vitro as manifested by upregulation of prolactin, insulin-like growth factor-binding protein 1, IL-11, and vascular endothelial growth factor (VEGF) secretion and also increased expression of ERα, PR-A and PR-B, and connexin 43 (Cx43). RA treatment also increased VEGF, ERα, PR-A, and PR-B and an active, nonphosphorylated isoform of Cx43. IL-1β and PPARβ/δ antagonists inhibited biomarkers of endometrial differentiation.Conclusion: Ligands that activate PPARβ/δ augment the in vitro expression of biomarkers of ESC decidualization. By contrast, PPARβ/δ antagonists impaired decidualization markers. Drugs activating these receptors may have therapeutic benefits for embryonic implantation. [ABSTRACT FROM AUTHOR]

Background: Birt-Hogg-Dubé Syndrome (BHDS) characterised by skin fibrofolliculomas, kidney tumour and pulmonary cysts/pneumothorax is caused by folliculin (FLCN) germline mutations. The pathology of both neoplasia and focused tissue loss of BHDS strongly features tissue-specific behaviour of the gene. Isolated cysts/pneumothorax is the most frequent atypical presentation of BHDS and often misdiagnosed as primary spontaneous pneumothorax (PSP). Deferential diagnosis of BHDS with isolated pulmonary presentation (PSP-BHD) from PSP is essential in lifelong surveillance for developing renal cell carcinoma.Methods: The expression profiles of microRNAs (miRNAs) in cystic lesions of PSP-BHD and PSP were determined via microarray. The selected upregulated miRNAs were further confirmed in the plasma of an expanded cohort of PSP-BHD patients by reverse transcription quantitative PCR (RT-qPCR). Their diagnostic accuracy was evaluated. Moreover, the cellular functions and targeted signalling pathways of FLCN-regulated miRNAs were assessed in various cell lines and in the lesion tissue contexts.Results: Cystic lesions of PSP-BHD and PSP showed different miRNAs profiles with a significant upregulation of miR-424-5p and let-7d-5p in PSP-BHD. The combination of the two effectively predicted BHDS patients. In vitro studies revealed a suppressive effect of FLCN on miR-424-5p and let-7d-5p expressions specifically in lung epithelial cells. The ectopic miRNAs triggered epithelial apoptosis and epithelial transition of mesenchymal cells and suppressed the reparative responses in cells and tissues with FLCN deficiency.Conclusion: The upregulation of miR-424-5p and let-7d-5p by FLCN deficiency occurred in epithelial cells and marked the PSP-BHD condition, which contributed to a focused degenerative pathology in the lung of PSP-BHD patients. [ABSTRACT FROM AUTHOR]

We have previously developed an rAAV2/HBoV1 vector in which a recombinant adeno-associated virus 2 (rAAV2) genome is pseudopackaged into a human bocavirus 1 (HBoV1) capsid. Recently, the production of rAAV2/HBoV1 in human embryonic kidney (HEK) 293 cells has been greatly improved in the absence of any HBoV1 nonstructural proteins (NS). This NS-free production system yields over 16-fold more vectors than the original production system that necessitates NS expression. The production of rAAV with infection of baculovirus expression vector (BEV) in the suspension culture of Sf9 insect cells is highly efficient and scalable. Since the replication of the rAAV2 genome in the BEV system is well established, we aimed to develop a BEV system to produce the rAAV2/HBoV1 vector in Sf9 cells. We optimized the usage of translation initiation signals of the HBoV1 capsid proteins (Cap), and constructed a BEV Bac-AAV2Rep-HBoV1Cap, which expresses the AAV2 Rep78 and Rep52 as well as the HBoV1 VP1, VP2, and VP3 at the appropriate ratios. We found that it is sufficient as a trans helper to the production of rAAV2/HBoV1 in Sf9 cells that were co-infected with the transfer Bac-AAV2ITR-GFP-luc that carried a 5.4-kb oversized rAAV2 genome with dual reporters. Further study found that incorporation of an HBoV1 small NS, NP1, in the system maximized the viral DNA replication and thus the rAAV2/HBoV1 vector production at a level similar to that of the rAAV2 vector in Sf9 cells. However, the transduction potency of the rAAV2/HBoV1 vector produced from BEV-infected Sf9 cells was 5–7-fold lower in polarized human airway epithelia than that packaged in HEK293 cells. Transmission electron microscopy analysis found that the vector produced in Sf9 cells had a high percentage of empty capsids, suggesting the pseudopackage of the rAAV2 genome in HBoV1 capsid is not as efficient as in the capsids of AAV2. Nevertheless, our study demonstrated that the rAAV2/HBoV1 can be produced in insect cells with BEVs at a comparable yield to rAAV, and that the highly efficient expression of the HBoV1 capsid proteins warrants further optimization. [ABSTRACT FROM AUTHOR]

Programmed death-ligand 1 (PD-L1) expression on tumor cells (TCs) by immunohistochemistry is rapidly gaining importance as a diagnostic for the selection or stratification of patients with nonsmall cell lung cancer (NSCLC) most likely to respond to singleagent checkpoint inhibitors. However, at least two distinct patterns of PD-L1 expression have been observed with potential biological and clinical relevance in NSCLC: expression on TC or on tumor-infiltrating immune cells (ICs). We investigated the molecular and cellular characteristics associated with PD-L1 expression in these distinct cell compartments in 4,549 cases of NSCLC. PDL1 expression on IC was more prevalent and likely reflected IFN- γ-induced adaptive regulation accompanied by increased tumorinfiltrating lymphocytes and effector T cells. High PD-L1 expression on TC, however, reflected an epigenetic dysregulation of the PDL1 gene and was associated with a distinct histology described by poor immune infiltration, sclerotic/desmoplastic stroma, and mesenchymal molecular features. Importantly, durable clinical responses to atezolizumab (anti-PD-L1) were observed in patients with tumors expressing high PD-L1 levels on either TC alone [40% objective response rate (ORR)] or IC alone (22%ORR). Thus, PD-L1 expression on TC or IC can independently attenuate anticancer immunity and emphasizes the functional importance of IC in regulating the antitumor T cell response. [ABSTRACT FROM AUTHOR]

This paper introduced the sources of total nitrogen pollutants in tannery wastewater, the status of the current total nitrogen treatment. Currently, there are two methods, clean production and biological treatment, to control the total nitrogen in tannery wastewater. And efficient biological treatment has become a research hotspot. Meanwhile, it was expounded for the research status of the application of a bioflocculation technique for removing total nitrogen pollutants from tannery wastewater. The component analysis indicated that the polysaccharide, protein, glycoprotein, glycosylamine, and lipids were found in the prepared bioflocculants. Furthermore, active component analysis results demonstrated that polysaccharide and protein were the active components for total nitrogen removal. Amount of studies on the action mechanisms of bioflocculants had established four theories for flocculation mechanisms, including adsorption and bridging theory, lectin hypothesis, cellulose fibril hypothesis, and chemical reaction hypothesis. The application of a bioflocculation technique in tannery wastewater treatment was proposed. [ABSTRACT FROM AUTHOR]