Spatial - temporal mapping of urine cadmium levels in China during 1980 - 2040: Dietary improvements lower exposure amid rising pollution.

Persistent cadmium exposure poses significant health risks to the Chinese population, underscored by its prevalence as an environmental contaminant. This study leverages a machine-learning model, fed with a comprehensive dataset of environmental and socio-economic factors, to delineate trends in cadmium exposure from 1980 to 2040. We uncovered that urinary cadmium levels peaked at 1.09 µg/g Cr in the mid-2000 s. Encouragingly, a decline is projected to 0.92 µg/g Cr by 2025, tapering further to 0.87 µg/g Cr by 2040. Despite this trend, regions heavily influenced by industrialization, such as Hunan and Guizhou, as well as industrial counties in Jilin, report stubbornly high levels of exposure. Our demographic analysis reveals a higher vulnerability among adults & adolescents over 14, with males displaying elevated cadmium concentrations. Alarmingly, the projected data suggests that by 2040, an estimated 41% of the population will endure exposure beyond the safety threshold set by the European Food Safety Authority. Our research indicates disproportionate cadmium exposure impacts, necessitating targeted interventions and policy reforms to protect vulnerable groups and public health in China.

Limestone water mixing process and hydrogen and oxygen stable isotope fractionation response under mining action.

North China type coalfield are gradually mining deep, and the mixing of groundwater is intensified. Hydrogen and oxygen isotopes are important elements for tracing groundwater movement. The fractionation response mechanism under mining conditions is not clear. In this paper, combined with numerical simulation, MixSIAR isotope mixing model and other methods, according to the δD, δ18O and hydrochemical information of various water bodies, the impact of coal mining on hydrogen and oxygen isotope fractionation is analyzed from multiple perspectives. The results show that summer soil water is the main source of recharge for limestone water, accounting for 30.7%-41.5%, and the Zhan River is the main source of recharge for limestone water. Before groundwater recharge, evaporation leads to the increase of δ18O in surface water by 0.31‰-5.58‰, water loss by 1.81%-28.00%, the increase of δ18O in soil water by 0.47‰-6.33‰, and water loss by 2.74%-35.80%. Compared with the coal mining layer, the degree of hydrogen and oxygen isotope drift and water-rock interaction in the coal mine stopping layer are significantly improved. The results of numerical simulation show that the pumping activity reduces the 18O concentration in the mining layer. The ion ratio is used as a new variable to eliminate the influence of water-rock interaction when calculating the mixing ratio. The results show that the limestone water is in a state of receiving external recharge, and mixing effect increases the δ18O in limestone water by 0.86‰ on average, and the δD increases by 0.72‰ on average. The research results explain the controlled process of hydrogen and oxygen isotope fractionation under mining conditions, which is of great significance to coal mine safety production.

LpNAC5 positively regulates drought, salt and alkalinity tolerance of Lilium pumilum.

NACs (NAM、ATAF1/2、CUC1/2), as a large family of plant transcription factors, are widely involved in abiotic stress responses. This study aimed to isolate and clone a novel stress-responsive transcription factor LpNAC5 from Lilium pumilum bulbs. Drought, salt, alkali, and ABA stresses induced the expression of LpNAC5. Transgenic tobacco plants overexpressing LpNAC5 were generated using the Agrobacterium-mediated method to understand the role of this factor in stress response. These plants exhibited increased tolerance to drought, salt, and alkali stresses. The tobacco plants overexpressing LpNAC5 showed strong drought, salt, and alkaline tolerance. Under the three abiotic stresses, the activities of antioxidant enzymes were enhanced, the contents of proline and chlorophyll increased, and the contents of malondialdehyde decreased. The functional analysis revealed that LpNAC5 enabled plants to positively regulate drought and salt stresses. These findings not only provided valuable insights into stress tolerance mechanisms in L. pumilum but also offered a potential genetic resource for breedi.

Research Note: Pharmacokinetics of bromhexine hydrochloride in broilers after single oral and intravenous administration.

The current study aimed to investigate the pharmacokinetics of bromhexine hydrochloride in broilers after single intravenous (IV) and oral (PO) administration at 2.5 mg/kg body weight (BW). The trial adopted a randomized, parallel-controlled design, where 20 twelve-wk-old broilers were randomly assigned to either the PO or IV group. Blood samples were collected at predetermined time points, and plasma was further separated for analysis. The bromhexine hydrochloride concentrations in plasma samples were determined using an ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method. Noncompartmental analysis (NCA) using Phoenix software was conducted to analyze the concentration versus time data of bromhexine hydrochloride in every chicken. Subsequently, the main pharmacokinetic parameters between the 2 groups were statistically analyzed using SPSS software. Results from NCA revealed that after oral administration at 2.5 mg/kg BW, bromhexine hydrochloride exhibited slow absorption, reaching an average peak concentration of 32.72 ng/mL at 1.78 h. However, incomplete absorption was observed, with an absolute bioavailability of only 20.06% ± 10.84%. Additionally, bromhexine hydrochloride displayed wide distribution, with a steady-state distribution volume (VSS) of 22.55 ± 13.45 L/kg, and slow elimination, with a clearance (Cl) of 1.52 ± 0.38 L/h/kg. Furthermore, gender effects were assessed on the pharmacokinetics of bromhexine hydrochloride in broilers, revealing better absorption in male broilers compared to females. This disparity may be attributed to the faster blood flow and richer blood volume typically found in male broilers.

Study on the thermal behaviour of spontaneous combustion of open-pit minerals.

To study thermal behaviour during spontaneous combustion of an open-pit coal mine, mixed slag (coal, oil shale, and coal gangue) was taken as the research object. Laser thermal conductivity analyser and differential scanning calorimetry were used to test thermophysical parameters and heat release characteristics of the minerals. The parameters can be employed to calculate the apparent activation energy using the Arrhenius equation and evaluate the thermal behaviour of open-pit mixed slag. The results indicate that thermophysical parameters have stage characteristics. Thermal diffusivity and thermal conductivity of minerals, especially mixed slag, have a strong correlation with temperature. Heat flow of minerals exhibits five characteristic stages, and heat flow of the samples is consistent with the change in heating rate. During the heating process, thermal diffusivity and heat flow of the mixed slag are between those of a single mineral. Except for the mixed slag at 15 and 20 °C/min, the initial exothermic temperature of the other samples is mainly concentrated at 50-80 °C. Thermal energy release of the sample is mainly concentrated in the accelerated exothermic stage and rapid exothermic stage. Thermal energy release of mixed slag in rapid exothermic stage is always greater than that in accelerated exothermic stage, and the proportion of thermal energy release in these two stages exceeds 98 %. The apparent activation energy during the accelerated exothermic stage is lower, making it easier to release heat, and rapid exothermic stage is relatively high, which can readily lead to heat accumulation. Thermal analysis reveals that the thermal behaviour of mixed slag is significantly different from that of a single mineral. Its unique exothermic characteristics can provide a more accurate theoretical basis for the prevention and control of environmental pollution caused by slag spontaneous combustion.

Clinical application of computed tomographic volumetric imaging in postoperative lung function assessment in patients with lung cancer.

BACKGROUND: To evaluate the effectiveness of the computed tomographic (CT) volumetric analysis in postoperative lung function assessment and the predicting value for postoperative complications in patients who had segmentectomy for lung cancer. METHODS: CT scanning and pulmonary function examination were performed for 100 patients with lung cancer. CT volumetric analyses were performed by specific software, for the volume of the inspiratory phase (Vin), the mean inspiratory lung density (MLDin), the volume of expiratory phase (Vex), and the mean lung density at expiratory phase (MLDex). Pulmonary function examination results and CT volumetric analysis results were used to predict postoperative lung function. The concordance and correlations of these values were assessed by Bland-Altman analysis and Pearson correlation analysis, respectively. Multivariate binomial logistic regression analysis was executed to assess the associations of CT data with complication occurrence. RESULTS: Correlations between CT scanning data and pulmonary function examination results were significant in both pre- and post-operation (0.8083 ≤ r ≤ 0.9390). Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the ratio of FVC and FEV1 estimated by CT volumetric analyses showed high concordance with those detected by pulmonary function examination. Preoperative (Vin-Vex) and (MLDex- MLDin) values were identified as predictors for post-surgery complications, with hazard ratios of 5.378 and 6.524, respectively. CONCLUSIONS: CT volumetric imaging analysis has the potential to determine the pre- and post-operative lung function, as well as to predict post-surgery complication occurrence in lung cancer patients with pulmonary lobectomy.

Mapping Blood Lead Levels in China during 1980-2040 with Machine Learning.

Lead poisoning is globally concerning, yet limited testing hinders effective interventions in most countries. We aimed to create annual maps of county-specific blood lead levels in China from 1980 to 2040 using a machine learning model. Blood lead data from China were sourced from 1180 surveys published between 1980 and 2022. Additionally, regional statistical figures for 15 natural and socioeconomic variables were obtained or estimated as predictors. A machine learning model, using the random forest algorithm and 2973 generated samples, was created to predict county-specific blood lead levels in China from 1980 to 2040. Geometric mean blood lead levels in children (i.e., age 14 and under) decreased significantly from 104.4 µg/L in 1993 to an anticipated 40.3 µg/L by 2040. The number exceeding 100 µg/L declined dramatically, yet South Central China remains a hotspot. Lead exposure is similar among different groups, but overall adults and adolescents (i.e., age over 14), females, and rural residents exhibit slightly lower exposure compared to that of children, males, and urban residents, respectively. Our predictions indicated that despite the general reduction, one-fourth of Chinese counties rebounded during 2015-2020. This slower decline might be due to emerging lead sources like smelting and coal combustion; however, the primary factor driving the decline should be the reduction of a persistent source, legacy gasoline-derived lead. Our approach innovatively maps lead exposure without comprehensive surveys.

Asparaginyl Endopeptidase-Mediated Peptide Cyclization for Phage Display.

We report here an enzymatic strategy for asparaginyl endopeptidase-mediated peptide cyclization. Incorporation of chloroacetyl groups into the recognition sequence of OaAEP1 enabled intramolecular cyclization with Cys residues. Combining this strategy and phage display, we identified nanomolar macrocyclic peptide ligands targeting TEAD4. One of the bicyclic peptides binds to TEAD4 with a KD value of 139 nM, 16 times lower than its linear analogue, demonstrating the utility of this platform in discovering high-affinity macrocyclic peptide ligands.

Transcriptomic profiling of Poa pratensis L. under treatment of various phytohormones.

Poa pratensis L. (Poaceae) is a valuable grass across the north hemisphere, inhabiting diverse environments with wide altitudinal span, where ubiquitous various kinds of stresses. Phytohormones would be helpful to improve tolerance to abiotic and biotic stresses, but the responses of transcriptome regulation of P. pratensis to exogenous phytohormones application remain unclear. In this study, we explored the alteration of plant physiological responses by the application of phytohormones. Aiming to achieve this knowledge, we got full-length transcriptome data 42.76 Gb, of which 74.9% of transcripts were completed. Then used 27 samples representing four treatments conducted at two time points (1 h and 6 h after application) to generate RNA-seq data. 371 and 907 common DEGs were identified in response to four phytohormones application, respectively, these DEGs were involved in "plant hormone signal transduction", "carbon metabolism" and "plant-pathogen interaction". Finally, P. pratensis basic research can gain valuable information regarding the responses to exogenous application of phytohormones in physiological indicators and transcriptional regulations in order to facilitate the development of new cultivars.

Tumor acidification and GSH depletion by bimetallic composite nanoparticles for enhanced chemodynamic therapy of TNBC.

Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.

Urinary cadmium levels in China (1982-2021): Regional trends and influential factors.

Despite the significant threat of cadmium exposure in China, a national-level assessment has been conspicuously absent. This study bridges this critical gap by collecting, geospatial analyzing and multivariable regression analyzing published studies on urinary cadmium levels in Chinese from 1982 to 2021. Our research reveals a notable decline trend in cadmium exposure among Chinese populations. However, this trend varies by region, age and gender group, higher levels are seen in the South (1.04 µg/g cr) compared to the North (0.48 µg/g cr), and in adults (1.08 µg/g cr) relative to children (0.33 µg/g cr), with higher levels being more pronounced in females (6.17 µg/g cr). Urinary cadmium is significantly correlated with rice consumption (P < 0.001), while mining activities have been identified as the dominant factor for cadmium exposure in most regions of China, a trend that is evident both in past decades and is expected to continue into the next decade. These findings underscore the need for region-specific environmental and public health strategies, designed to effectively address the distinct cadmium exposure risks in various regions and among different population groups, thus enhancing protection against the adverse effects of cadmium.

Comparison of gamithromycin residue depletion in yellow-feather and white-feather broilers after one single subcutaneous injection.

This study aimed to compare the residue depletion of gamithromycin in yellow-feather and white-feather broilers, using Sanhuang and Arbor Acres chickens as typical examples, respectively. Each breed (54 chickens) received a single subcutaneous dose of gamithromycin at 7.5 mg/kg bodyweight (BW). Tissues, including muscle, skin + fat, liver, kidney, and injection site, were collected at 6 h, 3, 5, 7, 10, 14, 21, 28, and 35 d postdrug administration. Gamithromycin concentrations in these tissues were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The kinetics of gamithromycin were analyzed in different tissues using a noncompartmental method in the Phoenix software. Differences were observed in gamithromycin concentrations and kinetic characteristics in both breeds of chickens, with higher residue concentrations and longer residue times found in yellow-feathered broilers. In Sanhuang broilers, the elimination rates of gamithromycin followed this order: injection site > muscle > liver > kidney > skin + fat. The corresponding elimination half-lives (t1/2λzs) in these samples were 1.22, 1.30, 1.71, 2.04, and 2.52 d, respectively. In contrast, in Arbor Acres broilers, a different order was noted: muscle > injection site > kidney > liver > skin + fat, with corresponding t1/2λzs of 1, 1.23, 1.88, 1.93, and 2.21 d, respectively. These differences may be related to variations in pigments in various tissues of chickens of the 2 breeds. However, further investigations are warranted to discern the underlying reasons.

In vitro antibacterial activity of danofloxacin against Escherichia coli in Gushi chickens and its residue depletion following multiple oral administration.

This study aimed to investigate the in vitro antibacterial activity of danofloxacin against Escherichia coli isolated from Gushi chickens, as well as the tissue distribution and residue depletion of danofloxacin in Gushi chickens following multiple oral administration. A total of 42 clinical E. coli strains were isolated from the cloaca of locally farmed Gushi chickens between August and October 2023. Then the minimum inhibitory concentration (MIC) of danofloxacin against these isolates was determined by broth microdilution method. Additionally, 42 healthy Gushi chickens were randomly divided into 6 groups, and danofloxacin was orally administered at a dose of 5 mg/kg body weight (BW) for 3 consecutive days. Plasma, intestinal content, and tissue samples, including muscle, skin + fat, liver, kidney, lung, and intestine, were collected at 4, 12, 24, 48, 72, and 120 h after the last administration. Danofloxacin concentrations in all samples were determined using a high-performance liquid chromatography (HPLC) method. The average concentration vs. time data were then subjected to noncompartmental analysis using Phoenix software, and withdrawal periods for danofloxacin in Gushi chickens were further determined with WT1.4 software, setting a 95% confidence interval. Results indicated a notable inhibitory effect of danofloxacin on E. coli, with an MIC50 of 0.5 µg/mL. Additionally, danofloxacin exhibited widespread distribution in Gushi chickens, detectable in all collected samples. Among all tissues, the liver exhibited the highest concentration, followed by the intestine. Even on the fifth day postadministration, danofloxacin persisted in skin + fat, liver, and lung. The elimination half-lives (t1/2λzs) of danofloxacin varied across samples: skin + fat (47.87 h), lung (30.61 h), liver (22.07 h), plasma (16.05 h), muscle (12.53 h), intestine (9.83 h), and kidney (6.34 h). Considering residue depletion and the maximum residue limit (MRL) of danofloxacin in poultry set by Chinese regulatory authorities, withdrawal periods for the kidney, muscle, liver, and skin + fat were determined as 1.03, 1.38, 3.34, and 5.85 d, respectively, rounded to a final withdrawal time of 6 d.

Photosensitive Hydrogels Encapsulating DPSCs and AgNPs for Dental Pulp Regeneration.

OBJECTIVE: Pulp regeneration with bioactive dentin-pulp complex has been a research hotspot in recent years. Stem cell therapy provided an interest strategy to regenerate the dental-pulp complex. Hence, this study aimed to evaluate the effects of photosensitive gelatin methacrylate (GelMA) hydrogel encapsulating dental pulp stem cells (DPSCs) and silver nanoparticles (AgNPs) for dental pulp regeneration in vitro. METHODS: First, the AgNPs@GelMA hydrogels were prepared by lithium phenyl-2,4,6-trimethyl-benzoyl phosphinate (LAP) initiation via blue-light emitting diode light. The physical and chemical properties of AgNPs@GelMA hydrogels were comprehensively analysed via scanning electron microscopy (SEM), and mechanical characterisation, such as swelling ability, degradation properties, and AgNP release profile. Then, AgNPs@GelMA hydrogels encapsulated DPSCs were used to establish an AgNPs@GelMA biomimetic complex, further analysing its biocompatibility, antibacterial properties, and angiogenic capacity in vitro. RESULTS: The results indicated that GelMA hydrogels demontrated optimal characteristics with a monomer:LAP ratio of 16:1. The physico-chemical properties of AgNPs@GelMA hydrogels did not change significantly after loading with AgNPs. There was no significant difference in AgNP release rate amongst different concentrations of AgNPs@GelMA hydrogels. Fifty to 200 µg/mL AgNPs@GelMA hydrogels could disperse E faecalis biofilm and reduce its metabolic activity . Furthermore, cell proliferation was arrested in 100 and 200 µg/mL AgNPs@GelMA hydrogels. The inhibition of 50 µg/mL AgNPs@GelMA hydrogels on E faecalis biofilm was above 50%, and the cell viability of the hydrogels was higher than 90%. The angiogenesis assay indicated that AgNPs@GelMA hydrogels encapsulating DPSCs could induce the formation of capillary-like structures and express angiogenic markers CD31, vascular endothelial growth factor , and von willebrand factor (vWF) in vitro. CONCLUSIONS: Results of this study indicate that 50 µg/mL AgNPs@GelMA hydrogels encapsulating DPSCs had significant antibacterial properties and angiogenic capacity, which could provide a significant experimental basis for the regeneration of the dentin-pulp complex.

Electrically Conductive Polymers for Additive Manufacturing.

The use of electrically conductive polymers (CPs) in the development of electronic devices has attracted significant interest due to their unique intrinsic properties, which result from the synergistic combination of physicochemical properties in conventional polymers with the electronic properties of metals or semiconductors. Most conventional methods adopted for the fabrication of devices with nonplanar morphologies are still challenged by the poor ionic/electronic mobility of end products. Additive manufacturing (AM) brings about exciting prospects to the realm of CPs by enabling greater design freedom, more elaborate structures, quicker prototyping, relatively low cost, and more environmentally friendly electronic device creation. A growing variety of AM technologies are becoming available for three-dimensional (3D) printing of conductive devices, i.e., vat photopolymerization (VP), material extrusion (ME), powder bed fusion (PBF), material jetting (MJ), and lamination object manufacturing (LOM). In this review, we provide an overview of the recent research progress in the area of CPs developed for AM, which advances the design and development of future electronic devices. We consider different AM techniques, vis-à-vis, their development progress and respective challenges in printing CPs. We also discuss the material requirements and notable advances in 3D printing of CPs, as well as their potential electronic applications including wearable electronics, sensors, energy storage and conversion devices, etc. This review concludes with an outlook on AM of CPs.

Preparation and application of biocontrol formulation of nematode-trapping fungus-Duddingtonia flagrans.

The use of nematophagous fungi as a biological control strategy for parasitic gastrointestinal nematodes (GINs) in livestock holds promise as an innovative alternative approach. This study aimed to evaluate the clinical efficacy of a lyophilized Duddingtonia flagrans preparation, utilized in association with the anthelmintics ivermectin or albendazole, to control GINs in Tibetan sheep on a farm based in Qinghai Province. The experimental design included five groups: D. flagrans lyophilized preparation group; D. flagrans+ ivermectin combination tablets treatment group (0.6 tablets for each 10 kg b.w. containing 106 chlamydospores of D. flagrans); D. flagrans+ albendazole combination capsules treatment group (5 capsules for each 10 kg b.w. containing 106 chlamydospores of D. flagrans); ivermectin group (0.2 mg/kg); albendazole group (15 mg/kg), and a control group; The effect of these strategies was evaluated through the analysis of feces collected directly from the animals in each group at 24 h, 48 h, 72 h,96 h and 120 h after administration, by estimating the counts of fecal egg count reduction percentage (FECR) and larval development reduction percentage (LDR). The combination of D. flagrans lyophilized preparation with either ivermectin or albendazole yielded fecal egg and larval reduction rates of up to 100% within 72 h after oral administration, outperforming the groups treated with a single anthelmintic. Moreover, the application of the lyophilized preparation of D. flagrans chlamydospores in isolation demonstrated an 89.8% larval reduction rate. The formulation containing D. flagrans showed high predatory capacity after passage through the gastrointestinal tract of sheep and was effective for controlling gastrointestinal nematodes, which greatly reduced the pollution of the grassland, and avoid reinfection.

Curcumin-loaded chitosan-based hydrogels accelerating S. aureus-infected wound healing.

The damaged skin for some reasons is vulnerable to invasion by bacteria and other harmful microorganisms, leading to delay of the wound healing. In order to promote the infected wound healing, curcumin was loaded with chitosan-based hydrogel was formed through phenylborate ester bonding and its properties and effects on the S. aureus-infected wound healing was tested. It was found the hydrogel showed good antioxidation on the intracellular reactive oxygen species, inhibition on the growth of S. aureus, and acceleration the infected skin healing. The ablity of hydrogel due to its regulating inflammation, promoting angiogenesis and collagen synthesis in the wound site. This research work suggested that the developed multifunctional hydrogel might be a beneficial treatment for the infected wound healing.

Effects of chitooligosaccharide on the in vitro antibacterial activity against avian Escherichia coli and the pharmacokinetics of florfenicol in healthy chickens.

This study investigates the combined effects of chitooligosaccharide (COS) and florfenicol (FLO) on the inhibition of Escherichia coli in vitro, as well as the pharmacokinetic interactions between these compounds in healthy chickens. The minimum inhibitory concentration (MIC) of COS and FLO alone and the fractional inhibitory concentration index (FICI) after combined treatment were determined using the broth microdilution method and checkerboard method, respectively. Additionally, we evaluated the pharmacokinetic interactions between the 2 types of COS and FLO in healthy chickens. Thirty chickens were randomly divided into 3 groups: Florfenicol group (30 mg/kg), COS J85 group (COS J85 20 mg/kg + florfenicol 30 mg/kg), COS H85 group (COS H85 20 mg/kg + florfenicol 30 mg/kg). Either FLO or COS was orally administered by gavage. The concentrations of FLO in chicken plasma were measured at different time points after the drug withdrawal using high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were calculated by a compartmental method. The results showed that COS J85 and COS H85, when combined with FLO, had FICI values of 0.1875 to 0.75 and 0.3125 to 1, respectively, indicating good synergistic or additive effects against Escherichia coli. The pharmacokinetics of FLO alone and in combination with COS followed a 1-compartment model with first-order absorption and elimination. Furthermore, the pharmacokinetic analysis revealed that the elimination half-life (t1/2ke) of florfenicol was significantly increased in the COS H85 group compared to oral administration of florfenicol alone (P < 0.05). Other pharmacokinetic parameters did not show significant changes (P > 0.05), except between the 2 combined treatment groups, where statistical differences were observed for various parameters, excluding the area under the concentration-time curve from the time of dosing to infinity (AUC) and peak concentration (Cmax).

Serum exosome-derived miR-146a-3p promotes macrophage M2 polarization in allergic rhinitis by targeting VAV3 via PI3K/AKT/mTOR pathway.

BACKGROUND: Our previous study showed that miR-146a-3p was elevated in serum exosomes of allergic rhinitis (AR) patients, but the underlying mechanisms were unclarified. This study was to investigate the impact of exosome-derived miR-146a-3p on macrophage polarization in the pathology of AR. METHOD: We detected the expression of miR-146a-3p in nasal tissues of AR patients and healthy controls (HCs), and investigated its correlation with macrophage polarization markers. The impact of miR-146a-3p derived from AR serum exosomes on macrophage polarization was examined. Transcriptome sequencing was performed on macrophages treated with a miR-146a-3p inhibitor, and target genes of miR-146a-3p were explored through a combination of bioinformatics analysis and experimental validation. RESULTS: The expressions of miR-146a-3p and macrophage polarization markers were increased in the AR nasal tissues, and a positive association was observed between the expressions of miR-146a-3p and the levels of CD163 and CD206. The AR serum exosomes could be uptake by macrophages, and promote M2 polarization and cytokine secretions. Mechanistically, miR-146a-3p regulation could impact both macrophage M2 polarization and cytokine secretion. Inhibition of miR-146a-3p altered the gene transcriptions within macrophages. Bioinformatics analysis and clinical pathological specimen research confirmed that VAV3 was a target gene of miR-146a-3p, and it exerted a detrimental effect on macrophage M2 polarization via the PI3K/AKT/mTOR pathway. Functional recovery experiments and dual-luciferase reporter gene assays confirmed that miR-146a-3p could selectively target and inhibit the expression of VAV3, thereby promoting macrophage M2 polarization through the PI3K/AKT/mTOR pathway. CONCLUSION: Serum exosome-derived miR-146a-3p facilitated macrophage M2 polarization in AR by targeting VAV3 through the PI3K/AKT/mTOR pathway. These findings implied that miR-146a-3p and VAV3 could serve as potential targets for the development of novel therapeutic strategies in AR management.

Concomitant Ipsilateral Knee Pain Is Associated With Worse Preoperative Functional Status and Short-Term Outcomes After Hip Arthroscopy in Patients With Femoroacetabular Impingement Syndrome.

PURPOSE: (1) To determine the effect of concomitant ipsilateral knee pain (IKP) on short-term outcomes after hip arthroscopic treatment of femoroacetabular impingement syndrome (FAIS) and (2) to determine whether IKP would improve with surgery. METHODS: Data between September 2021 and May 2022 were reviewed. Patients with a diagnosis of FAIS who underwent hip arthroscopy with a minimum of 1-year follow-up were included. The exclusion criteria were prior ipsilateral hip or knee surgery, hip Tönnis grade greater than 1, knee Kellgren-Lawrence grade greater than 2, hip conditions (avascular necrosis, Legg-Calvé-Perthes disease, pigmented villonodular synovitis, osteoid osteoma, synovial chondromatosis, and developmental dysplasia of the hip), and spine diseases. All patients underwent knee magnetic resonance imaging preoperatively. Preoperative and short-term (1-year) patient-reported outcomes were collected, consisting of the Hip Sports Activity Scale score, weekly sports participation, modified Harris Hip Score (mHHS), 12-component International Hip Outcome Tool (iHOT-12) score, and visual analog pain scale (VAS) scores for the hip and the ipsilateral knee. The percentages of patients achieving the minimal clinically important difference and patient acceptable symptom state (PASS) for the mHHS and iHOT-12 score were calculated. Multivariate regression analysis was performed to determine the effect of IKP severity on postoperative outcomes. Subgroup analysis was performed between patients with IKP alleviation and those without IKP alleviation. RESULTS: Among the 107 patients included, 47 presented with preoperative IKP. Compared with patients without IKP, the IKP cohort had comparable knee structural abnormalities (all with P > .05). Still, the IKP cohort showed inferior preoperative values for the mHHS (P = .003), iHOT-12 score (P = .016), hip VAS score (P = .001), and weekly sports participation (P = .039). Postoperatively, the IKP cohort had a lower mHHS (P = .046), lower iHOT-12 score (P = .037), and lower hip VAS score (P = .003) and were less likely to achieve the PASS for the mHHS (P = .021) and iHOT-12 score (P = .049). Patients with higher knee VAS scores were less likely to achieve the PASS for the mHHS (odds ratio, 0.61; P = .023). Within the IKP group, the knee VAS score improved from 2.3 to 1.0 (P < .001). Patients with alleviated IKP showed superior postoperative iHOT-12 scores (P = .038) compared with patients with persistent IKP. CONCLUSIONS: Concomitant IKP at baseline negatively affected preoperative status and short-term clinical outcomes after arthroscopic treatment of FAIS. Patients with IKP were less likely to meet clinical thresholds. Most patients achieved IKP alleviation postoperatively, which was associated with superior clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective cohort study.