Search Results (36)

The ecological restoration of degraded sandy land in the Yarlung Zangbo River Valley is constrained by the metabolic functions of soil microorganisms. This study investigates the dynamic mechanisms of microbial elemental use efficiency in walnut plantations, with a focus on seasonal variations in soil chemical stoichiometry, extracellular enzyme activity, and microbial nutrient efficiency in rhizosphere and bulk soils. This paper explores the effects of conventional organic fertilizer (CF) and organic–inorganic compound fertilizer (OIF) on microbial nutrient use strategies and their seasonal dynamics. The results showed significant seasonal fluctuations in soil active nutrients and microbial biomass, while the total nutrient content remained stable. OIF enhanced microbial chemical stoichiometric homeostasis but simultaneously triggered a “carbon–phosphorus metabolic trade-off”, leading to a restraint of microbial carbon use efficiency (CUE) during the growing season. Microbial elemental use efficiency (EUE) exhibited clear seasonal differentiation: CUE was higher in summer, promoting biomass accumulation, whereas NUE and PUE increased in winter and spring, reflecting a nutrient conservation strategy. The EUE pathways were decoupled between rhizosphere and non-rhizosphere microenvironments. The rhizosphere was more directly driven by soil chemical stoichiometry and microbial biomass, while the non-rhizosphere was influenced by nutrient limitation states, represented by vector characteristics. This study provides insights into the seasonal adaptability and microenvironmental heterogeneity of microbial metabolism during the restoration of cold sandy land. It is suggested that future ecological management should focus on N-P balanced fertilization and consider the differential responses between rhizosphere and non-rhizosphere zones to enhance ecosystem productivity and soil carbon, nitrogen, and phosphorus sequestration potential. Full article

Background: Neuroinflammation and gut–brain axis (GBX) dysregulation are key pathological drivers of stress-related neuropsychiatric disorders. Zhi-Zi-Chi Decoction (ZZCD), a classic Traditional Chinese Medicine (TCM) formula, has been clinically used to alleviate mental disturbances via the TCM principle of “clearing heat and relieving restlessness.” Still, its modern neuroprotective mechanisms, especially its links to gut microbiota and central signaling pathways, remain incompletely elucidated. Purpose: This study aimed to systematically investigate the therapeutic effects of ZZCD on chronic restraint stress (CRS)-induced neurodysfunction in mice and clarify its mechanisms from the perspectives of TCM theory, material basis, gut microbiota–metabolite axis, and central signaling pathways. Method: CRS mice were treated with ZZCD or protocatechuic acid. Behavioral tests evaluated depression- and anxiety-like behaviors. UHPLC-Q-TOF/MS identified ZZCD’s chemical constituents; 16S rRNA sequencing and untargeted metabolomics analyzed gut microbiota and metabolite changes. Western blot, immunofluorescence, and proteomics examined neuroinflammation, microglial polarization, and signaling pathway activity (PI3K/Akt/mTOR, AMPK). Results: ZZCD reversed CRS-induced depression- and anxiety-like behaviors and suppressed neuroinflammation. Mechanistically, UHPLC-Q-TOF/MS identified 424 ZZCD constituents, with prenol lipids, organooxygen compounds, and flavonoids as the most abundant. ZZCD reversed CRS-induced imbalance in gut microbiota, reducing pro-inflammatory Prevotella and enriching beneficial Lactobacillus, and mediated the enrichment of the prebiotic metabolite PCA in colonic and serum samples, which crossed the blood–brain barrier (BBB) to exert neuroprotection. Additionally, ZZCD and PCA normalized the PI3K/Akt/mTOR pathway and activated AMPK, promoting M2 microglial polarization and restoring synaptic plasticity. Conclusions: ZZCD exerts antidepressant effects by a gut-microbiota-dependent modulation of PCA-PI3K/Akt/mTOR and AMPK dual axes that converts microglia from M1 to M2, providing ethnopharmacological evidence and a mechanistic rationale for its clinical application in major depressive disorder. Full article

Helicobacter pylori urease (HpU) plays a central role in bacterial survival and virulence by hydrolyzing urea into ammonia and carbon dioxide, neutralizing gastric acidity, and facilitating host colonization. The increasing prevalence of antibiotic resistance underscores the need for alternative strategies targeting essential bacterial enzymes such as urease. In this study, a multistage computational pipeline integrating pharmacophore modeling, machine learning (ML), ensemble docking, and enhanced molecular dynamics simulations were applied to identify novel triazole-based HpU inhibitors. Starting from over seven million compounds in the ZINC15 database, pharmacophore- and ML-based filters progressively reduced the chemical space to 7062 candidates. Ensemble docking across 25 conformational frames of HpU, followed by quantum-polarized ligand docking (QPLD), identified seven promising ligands exhibiting strong binding energies and stable metal coordination. Molecular dynamics (MD) simulations under progressively relaxed restraints revealed three highly stable complexes (CA1, CA3, and CA6). Subsequent well-tempered metadynamics (WT-MetaD) simulations reconstructed free-energy landscapes showing deep, localized basins for CA3 and CA6, comparable to the potent reference inhibitor DJM, supporting their potential as strong urease binders. Finally, unsupervised chemical space mapping using the UMAP algorithm positioned these candidates within molecular regions associated with potent urease inhibitors, further validating their structural coherence and pharmacophoric relevance. An ADMET assessment confirmed that the selected candidates exhibit physicochemical and early safety properties compatible with subsequent in vitro evaluation. This multilevel screening strategy demonstrates the power of combining ML-driven classification, ensemble docking, and enhanced sampling simulations to discover non-hydroxamic urease inhibitors. Although the current findings are computational, they provide a rational foundation for future in vitro validation and for expanding the discovery of triazole-based scaffolds targeting ureolytic enzymes. Full article

Baboons’ management requires chemical restraint. Three intramuscular sedative protocols in captive hamadryas baboons (Papio hamadryas) undergoing health-check and male vasectomy were compared. Animals were assigned to TZD_G (n = 17; tiletamine/zolazepam 3 mg/kg + dexmedetomidine 20 μg/kg), KDM_G (n = 23; ketamine 6 mg/kg + dexmedetomidine 30 μg/kg + methadone 0.2 mg/kg), or MDM_G (n = 9; midazolam 2 mg/kg + dexmedetomidine 60 μg/kg + methadone 0.2 mg/kg). Propofol was titrated intravenously for anaesthetic induction and maintenance. Sedation time and quality and cardiopulmonary parameters were recorded. Atipamezole (TZD_G 0.2 mg/kg, KDM_G 0.3 mg/kg, MDM_G 0.6 mg/kg) and flumazenil (MDM_G 0.02 mg/kg) were administered intramuscularly post-procedure. Recovery time and quality were recorded. Data were reported as median (interquartile range) or regression coefficient (B). Sedation was deepest in TZD_G (20, 20–20; KDM_G 20, 19–20; MDM_G 19, 15–20; p = 0.017). MDM_G had a significantly higher heart rate (B = 10.27, p = 0.001), respiratory rate (B = 9.09, p < 0.001), and lower end-tidal carbon dioxide (B = −3.00, p = 0.03) than TZD_G, while KDM_G had a lower respiratory rate than TZD_G (B = −3.67, p = 0.02) and a higher temperature (B = 1.66 p = 0.001). TZD_G showed the longest recovery (minutes: 19, 11.5–30; KDM_G: 6, 4–12; MDM_G: 4, 2.5–5; p < 0.001), while MDM_G the best recovery (0, 0–0; TZD_G: 9, 6–12; KDM_G: 0, 0–6; p < 0.001). TZD produced deepest sedation but bad recovery; KDM offered optimal sedation and recovery, and cardiopulmonary stability; MDM provided lighter sedation and excellent recovery. Full article

A multimodal approach is recommended to optimize perioperative pain control in animals, although opioid use in horses remains limited due to the risks of central nervous system (CNS) stimulation and reduced intestinal motility. A group of 19 healthy, male, mixed-breed horses were divided into two groups and medicated with acepromazine (0.05 mg kg⁻¹) and detomidine (10 µg kg⁻¹), with methadone (0.05 mg kg⁻¹) (ADM) or saline (ADS) administered intravenously (IV). Physiological variables, intestinal motility, gastric distention, and facial pain (EQUUS-FAP) were evaluated one day before (DB), before the surgical procedure (BS), and at 1, 2, 4, 6, and 8 h (T1h–T8h) after administration (ADM-ADS). Results are presented as means with standard deviation or medians with an interquartile range. Analysis of variance, the Mann–Whitney, and Durbin tests were applied (p < 0.05). Intestinal motility was reduced at T1h and T2h, returning to baseline by T6h and T8h in both groups. Ultrasonographic examination revealed reduced motility, with less significant changes in the left ventral colon (LVC), right ventral colon (RVC), and cecum. Gastric dilatation was more pronounced in the ADM group at T1, 4, 6, and 8h. EQUUS-FAP scores were significantly lower in ADM at T2, 4, and 6h. ADM protocol may aid chemical restraint and analgesia without increasing hypomotility. Full article

Nickel is used in aerospace, military, energy, and chemical sectors. Commercially pure (CP) Ni, and its alloys, including solid-solution strengthened (SSS), precipitation strengthened (PS), and specialty alloys (SA), are widely utilized, typically at elevated temperatures, in corrosive settings and in cryogenic milieu. Ni or Ni-based alloys frequently require welding realized, inter alia, via methods using electric arc and beam power. Tungsten inert gas (TIG) and Electron-beam welding (EBW) have been utilized most often. Friction stir welding (FSW) is the most promising solid-state welding technique for connecting Ni and its alloys. The primary weldability issues related to Ni and its alloys are porosity, as well as hot and warm cracking. CP Ni exhibits superior weldability. It is vulnerable to porosity and cracking during the solidification of the weld metal. Typically, SSS alloys demonstrate superior weldability when compared to PS Ni alloys; however, both types may experience weld metal solidification cracking, liquation cracking in the partially melted and heat-affected zones, as well as ductility-dip cracking (DDC). Furthermore, PS alloys are prone to strain-age cracking (SAC). The weldability of specialty Ni alloys is limited, and brazing might provide a solution. Employing appropriate filler metal, welding settings, and minimal restraint can reduce or avert cracking. Full article

In South Korea, issues have been raised regarding exposure to humidifier disinfectant products containing certain chemicals postulated to induce lung diseases in consumers. Several rodent studies utilizing whole-body inhalation, which comprises freely moving animals breathing through the nares, and intranasal instillation involving restraint, were conducted by various Korean Governmental Agencies on these products to investigate whether there is a causal relationship between these products and the development of lung diseases. In particular, the humidifier disinfectant product Kathon, containing chloromethylisothiazolinone and methylisothiazolinone (CMIT and MIT), when directly introduced into inhalation chambers at varying concentrations for up to 13 weeks, produced no significant histopathological alterations and no marked changes in pulmonary function parameters. Further, there was no evidence of cytotoxicity; total and differential cell counts did not differ from control. In addition, the levels of cytokine markers of inflammation were not markedly altered. In contrast to published papers utilizing intratracheal and intranasal instillation, where the animal is anesthetized and chemical bypasses the defense mechanisms in the respiratory tract, then reaches the pulmonary region, ignoring recommended dose levels was found to initiate fibrotic responses in mice and rats. However, the usefulness of experimental results to extrapolate to humans obtained following intratracheal and intranasal instillation studies is of limited value because the data generated did not use a realistic design and appropriate dosimetry. Therefore, these findings have significant drawbacks in their use to characterize an inhalation risk for pulmonary fibrosis in humans and cannot be used for the extrapolation of such risk to humans. It is thus evident that the inhalation data generated by the Korean Regulatory Agencies are more realistic and show that exposure to CMIT and MIT does not initiate pulmonary fibrosis. Although inhalation studies still do not fully replicate real-world human exposure scenarios and have limitations for direct extrapolation to humans, they are nevertheless more appropriate than intratracheal or intranasal instillation models. Full article

Jaguars play a crucial role in population control across multiple biomes. They are endangered and protected by in situ and ex situ conservation mechanisms to ensure their conservation. Cardiovascular diseases in wild mammals, including jaguars, often have unclear etiopathogenies, underscoring the need for research into novel hemodynamic parameters. This study evaluates the cardiovascular health of fifteen clinically healthy jaguars using conventional and Holter electrocardiography, non-invasive systemic blood pressure measurement, and echocardiography. Chemical restraint was achieved with medetomidine (0.08–0.1 mg/kg) and ketamine (5 mg/kg), with anesthesia reversed using atipamezole (0.25 mg/kg). The average heart rate was 72 ± 18 bpm, with sinus rhythm in ten animals and sinus arrhythmia in five. Six animals exhibited first and second-degree atrioventricular blocks, one had supraventricular complexes, and another had premature ventricular complexes. Non-invasive systolic blood pressure remained stable at 163 ± 29 mmHg during anesthesia. Echocardiographic examination revealed mitral, tricuspid, pulmonary, and aortic valve insufficiencies via color Doppler. The transmitral flow showed a normal E/A ratio and E` < A`, suggesting a pseudonormal ventricular filling pattern. No significant anesthetic complications were observed, affirming the protocol’s safety. This study provides valuable data, validating the anesthetic protocol and establishing reference cardiovascular values for jaguars, thus paving the way for future research in other veterinary species. Full article

Pulmonary function examinations are critical to assess respiratory disease severity in patients. In preclinical rodent models of viral respiratory infections, however, disease is frequently evaluated based on virological, pathological and/or surrogate clinical parameters, which are not directly associated with lung function. To bridge the gap between preclinical and clinical readouts, we aimed to apply unrestrained whole-body plethysmography (WBP) measurements in a SARS-CoV-2 Syrian hamster challenge model. While WBP measurements are frequently used for preclinical research in mice and rats, results from studies in hamsters are still limited. During unrestrained WBP measurements, we obtained highly variable breathing frequency values outside of the normal physiological range for hamsters. Importantly, we observed that animal movements were recorded as breaths during WBP measurements. By limiting animal movement through either mechanical or chemical restraint, we improved the reliability of the lung function readout and obtained breathing frequencies that correlated with clinical signs when comparing two different variants of SARS-CoV-2 post-inoculation. Simultaneously, however, new sources of experimental variation were introduced by the method of restraint, which demands further optimalization of WBP measurements in Syrian hamsters. We concluded that WBP measurements are a valuable refinement either in combination with video recordings or if average values of measurements lasting several hours are analyzed. Full article

Sex identification through coelioscopy is a minimally invasive surgical technique used to determine the sex of chelonians by directly visualizing their internal reproductive organs. An adequate anaesthesiologic plan is essential to guarantee patient immobilization and proper analgesia during the entire surgical procedure. In this study, we evaluated the effects of a combination of dexmedetomidine (0.05 mg/kg), midazolam (1 mg/kg), ketamine (8 mg/kg), and morphine (1 mg/kg) (DMKM) randomly delivered intramuscularly (IM) or subcutaneously (SC) in twenty-one Aldabra giant tortoise (Aldabrachelys gigantea) into the right antebrachium for celioscopic sex identification. Heart rate (HR), respiratory rate (RR), and body temperature (BT) were measured, along with the skeletal muscle tone of the thoracic and pelvic limbs, neck retraction reflex, palpebral reflex, and jaw tone every 15 min. The anaesthesiologic plan was considered to be adequate at the loss of the thoracic and pelvic limb retraction reflexes. After a 45 min interval, if the anaesthetic plan was deemed insufficient for the celioscopic procedure, a 5 mg/kg dose of propofol was administered intravenously into the subcarapacial venous plexus. At the end of the procedure, atipamezole (0.5 mg/kg) and flumazenil (0.05 mg/kg) were administered intramuscularly into the left antebrachium as reversal agents. Both HR and RR decreased from baseline to both 15 and 30 min. Due to the persistence of thoracic and pelvic limb retraction reflexes 45 min after DMKM administration, 6/11 (55%) cases in the SC group required the additional administration of propofol, in contrast to only 1/10 (10%) cases in the IM group (p = 0.05). The recovery times were comparable between the successfully induced animals in the IM and SC groups. In this study, the intramuscular administration of a DMKM combination quickly produced chemical restraint, suitable for celioscopic sex determination. Full article

Sterility mosaic disease (SMD) is a serious biotic restraint in pigeonpea-growing regions of the Indian subcontinent. Disease control using chemicals like acaricides is not economical or sustainable, pointing towards host plant resistance as the ideal strategy for its management. In this study, from preliminary screening of 75 pigeonpea germplasm accessions and breeding lines, 21 pigeonpea genotypes showing moderate resistance to SMD were selected and again assessed at two multi-environment locations during Kharif 2021/2022 and 2022/2023. Analysis of variance partitioned the variation between the main effects of genotype and genotype × environment (GGE). The results revealed a significant variation (p ˂ 0.05) in the SMD incidence between the tested genotypes, environment, and their interactions. Genotype variance contributed the greatest effect (63.56%) to the total variation and it represents the maximum disease variation. Furthermore, a significant positive correlation was found for the levels of SMD incidence between the test environments. We observed that SMD incidence had a high negative correlation with the maximum temperature (r = −0.933), and positively correlated with the rainfall (r = 0.502). Analysis of principal components 1 and 2 of the GGE explained 95.33% of the total variation and identified 10 genotypes (G1, G3, G4, G8, G10, G12, G13, G15, G20, and G21) showing moderate resistance stability across the environments. As new sources of resistance to SMD, these genotypes should be incorporated in pigeonpea breeding trials for further release. This research broadens the area of phenotyping and identifies stable resistance sources that can be used in future SMD resistance breeding projects. Full article

Falls are a major problem in hospitals, and physical or chemical restraints are commonly used to “protect” patients in hospitals and service users in hostels, especially elderly patients with dementia. However, physical and chemical restraints may be unethical, detrimental to mental health and associated with negative side effects. Building upon our previous development of the wandering behavior monitoring system “eNightLog”, we aimed to develop a non-contract restraint-free multi-depth camera system, “eNightTrack”, by incorporating a deep learning tracking algorithm to identify and notify about fall risks. Our system evaluated 20 scenarios, with a total of 307 video fragments, and consisted of four steps: data preparation, instance segmentation with customized YOLOv8 model, head tracking with MOT (Multi-Object Tracking) techniques, and alarm identification. Our system demonstrated a sensitivity of 96.8% with 5 missed warnings out of 154 cases. The eNightTrack system was robust to the interference of medical staff conducting clinical care in the region, as well as different bed heights. Future research should take in more information to improve accuracy while ensuring lower computational costs to enable real-time applications. Full article

In this work, catalytically significant states of the oncogenic G12C variant of KRAS, those of Mg²⁺-free and Mg²⁺-bound GDP-loaded forms, have been determined using CS-Rosetta software and NMR-data-driven molecular dynamics simulations. There are several Mg²⁺-bound G12C KRAS/GDP structures deposited in the Protein Data Bank (PDB), so this system was used as a reference, while the structure of the Mg²⁺-free but GDP-bound state of the RAS cycle has not been determined previously. Due to the high flexibility of the Switch-I and Switch-II regions, which also happen to be the catalytically most significant segments, only chemical shift information could be collected for the most important regions of both systems. CS-Rosetta was used to derive an “NMR ensemble” based on the measured chemical shifts, which, however, did not contain the nonprotein components of the complex. We developed a torsional restraint set for backbone torsions based on the CS-Rosetta ensembles for MD simulations, overriding the force-field-based parametrization in the presence of the reinserted cofactors. This protocol (csdMD) resulted in complete models for both systems that also retained the structural features and heterogeneity defined by the measured chemical shifts and allowed a detailed comparison of the Mg²⁺-bound and Mg²⁺-free states of G12C KRAS/GDP. Full article

Nuclear magnetic resonance (NMR) spectroscopy is a powerful method for studying the structure and dynamics of proteins in their native state. For high-resolution NMR structure determination, the collection of a rich restraint dataset is necessary. This can be difficult to achieve for proteins with high molecular weight or a complex architecture. Computational modeling techniques can complement sparse NMR datasets (<1 restraint per residue) with additional structural information to elucidate protein structures in these difficult cases. The Rosetta software for protein structure modeling and design is used by structural biologists for structure determination tasks in which limited experimental data is available. This review gives an overview of the computational protocols available in the Rosetta framework for modeling protein structures from NMR data. We explain the computational algorithms used for the integration of different NMR data types in Rosetta. We also highlight new developments, including modeling tools for data from paramagnetic NMR and hydrogen–deuterium exchange, as well as chemical shifts in CS-Rosetta. Furthermore, strategies are discussed to complement and improve structure predictions made by the current state-of-the-art AlphaFold2 program using NMR-guided Rosetta modeling. Full article

Complaints reflect a person’s or family’s experience within the aged care system and provide important insight into community expectations and consumer priorities. Crucially, when aggregated, complaints data can serve to indicate problematic trends in care provision. Our objective was to characterize the areas of medication management most frequently complained about in Australian residential aged care services from 1 July 2019 to 30 June 2020. A total of 1134 complaint issues specifically referenced medication use. Using content analysis, with a dedicated coding framework, we found that 45% of these complaints related to medicine administration processes. Three categories received nearly two thirds of all complaints: (1) not receiving medication at the right time; (2) inadequate medication management systems; and (3) chemical restraint. Half of the complaints described an indication for use. These were, in order of frequency: ‘pain management’, ‘sedation’, and ‘infectious disease/infection control’. Only 13% of medication-related complaints referred to a specific pharmacological agent. Opioids were the most common medication class referred to in the complaint dataset, followed by psychotropics and insulin. When compared to complaint data composition overall, a higher proportion of anonymous complaints were made about medication use. Residents were significantly less likely to lodge complaints about medication management, probably due to limited engagement in this part of clinical care provision. Full article