Phosphorus-loaded coconut biochar: A novel strategy for cadmium remediation and soil fertility enhancement.

The management of cadmium (Cd) contamination in soils poses a significant environmental challenge. This study investigates the effectiveness of phosphorus (P)-loaded coconut biochar, synthesized at various pyrolysis temperatures (450°C, 500°C, 550°C, and 600°C), in immobilizing Cd and enhancing P availability in soil environments. The biochar underwent a series of treatments including activation and P enrichment, followed by incubation trials to evaluate its performance in Cd immobilization and P bioavailability enhancement across varying soil concentrations (0.5 %, 1.0 %, and 2.0 %) over time periods of 15, 30, and 45 days. Remediation progress was monitored using phytotoxicity assessments with radish (Raphanus sativus) root length as a bioindicator, supplemented by urease activity analyses. Notably, the activation process increased the P loading capacity of biochar produced at 450°C, 500°C, and 550°C by 54.6 %, 72.4 %, and 51.8 %, respectively, while reducing the P retention capacity of biochar prepared at 600°C by 31.0 %. The biochar activated at 550°C presented the highest efficiency in remediating Cd-contaminated soils. Key findings indicate that the enhanced specific surface area and oxygenated functional group content of the activated biochar facilitated Cd adsorption and P uptake. The P-loaded biochar exhibited a substantial adsorption capacity for Cd, particularly effective at lower concentrations, rendering it highly suitable for soil remediation purposes. Additionally, the study revealed that the application of biochar led to an increase in soil pH, resulting in precipitation of Cd as hydroxide species and formation of insoluble complexes with phosphate ions, thereby reducing its bioavailability. In summary, incorporating P-loaded biochar into soil significantly improved soil quality and enhanced Cd passivation in contaminated soils. The utilization of biochar produced at 550°C, which exhibited optimal performance, suggests a practical and sustainable approach for soil remediation. Future research endeavors should prioritize the refinement of the biochar production process to enhance cost-effectiveness while maintaining high P loading efficiency.

H3K18 lactylation accelerates liver fibrosis progression through facilitating SOX9 transcription.

Liver fibrosis is a significant health concern globally due to its association with severe liver conditions like cirrhosis and liver cancer. Histone lactylation has been implicated in the progression of hepatic fibrosis, but its specific role in liver fibrosis, particularly regarding H3K18 lactylation, remained unclear. To investigate this, we established in vivo and in vitro models of liver fibrosis using carbon tetrachloride (CCl4) injection in rats and stimulation of hepatic stellate cells (HSCs) with TGF-ß1, respectively. We found that histone lactylation, particularly H3K18 lactylation, was upregulated in both CCl4-induced rats and TGF-ß1-activated HSCs, indicating its potential involvement in liver fibrosis. Further experiments revealed that lactate dehydrogenase A (LDHA) knockdown inhibited H3K18 lactylation and had a beneficial effect on liver fibrosis by suppressing HSC proliferation, migration, and extracellular matrix (ECM) deposition. This suggests that H3K18 lactylation promotes liver fibrosis progression. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated that H3K18 lactylation facilitated the transcription of SOX9, a transcription factor associated with fibrosis. Importantly, overexpression of SOX9 counteracted the effects of LDHA silencing on activated HSCs, indicating that SOX9 is downstream of H3K18 lactylation in promoting liver fibrosis. In summary, this study uncovers a novel mechanism by which H3K18 lactylation contributes to liver fibrosis by activating SOX9 transcription. This finding opens avenues for exploring new therapeutic strategies for hepatic fibrosis targeting histone lactylation pathways.

Research Note: Effects of environmental sound stimulus on behavioral responses, cortisol levels, and horizontal immunity of transferred pullets.

The aim of this study was to investigate the effects of prolonged exposure to varying levels of music or noise on the behavioral, physiological, and immune responses of pullets following their transfer to an egg-laying facility. A total of 240 one-day-old Hy-Line Brown pullets were randomly assigned to five groups: 0 dB sound stimulation, low-decibel music (65-75 dB), high-decibel music (85-95 dB), low-decibel noise (65-75 dB), and high-decibel noise (85-95 dB) stimuli. Pullets received music or noise stimuli 10 h per d from 1-day-old to 16-wk-old and were then transferred to the egg-laying facility. The results indicated that feeding and drinking behaviors significantly decreased (P < 0.05), whereas feather pecking, aggression, and preening behaviors significantly increased (P < 0.05) in the pullets after transfer. Pullets also had higher serum cortisol (COR) levels (P < 0.05), whereas immunoglobulin Y (IgY), tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-1ß (IL-1ß), interleukin-2 (IL-2) and interleukin-6 (IL-6) levels significantly increased (P < 0.05). Low-decibel sound stimuli increased aggressive behavior and decreased pecking behavior (P < 0.05). High-decibel sound stimuli decreased feather pecking, cage pecking, aggression, and sham dustbathing behaviors (P < 0.05). In addition, a low-decibel sound stimulus decreased the serum COR content, and increased the serum IL-6 level in the transferred pullets. A high-decibel sound stimulus also induced shorter tonic immobility (TI) durations in pullets on d 7 after transport stress. Meanwhile, high-decibel sound stimulus decreased the serum IL-6 and TNF-α levels of pullets. In conclusion, the transfer has detrimental effects on the pullets. Long-term sound stimulation effectively mitigated the negative impact of transportation stress on pullets. Among them, the high-decibel sound stimulus showed more promise in relieving transport stress.

PI3K/AKT pathway modulation and cold acclimation alleviation concerning apoptosis and necroptosis in broiler thymus.

Moderate cold stimulation regulates the thymus's growth and function and facilitates cold acclimatization in broilers. However, the underlying mechanism remains unknown. To explore the possible mechanism of the thymus in cold-acclimated broilers against cold stress, 240 one-day-old Arbor Acres (AA) broilers were assigned to 2 groups randomly. The control group (C) was housed at conventional temperatures. The temperature during the first week was 33°C to 34°C. Between the ages of 8 and 32 d, the temperature was lowered by 1°C every 2 d, i.e., gradually from 32°C to 20°C, and then maintained at 20°C until 42 d of age. The cold-acclimated group (C-3) was housed at the same temperature as C from 1 to 7 d after birth. Between 8 and 42 d, the temperature of C-3 was 3°C colder than C. After 24 h exposure to acute cold stress (ACS) at 42 d, C and C-3 were named as S and S-3. The results showed that ACS was able to induce oxidation stress, modulate PI3K/AKT signal, and cause necroptosis and apoptosis in broiler thymus. By contrast, cold acclimation could alleviate apoptosis and necroptosis induced by cold stress via alleviating oxidative stress, efficiently activating the PI3K/AKT signal, as well as decreasing apoptotic and necrotic genes' levels. This study offers a novel theoretical basis for cold acclimation to improve the body's cold tolerance.

Application of metabolomics in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent malignancy affecting the head and neck region. The prognosis for OSCC patients remains unfavorable due to the absence of precise and efficient early diagnostic techniques. Metabolomics offers a promising approach for identifying distinct metabolites, thereby facilitating early detection and treatment of OSCC. OBJECTIVE: This review aims to provide a comprehensive overview of recent advancements in metabolic marker identification for early OSCC diagnosis. Additionally, the clinical significance and potential applications of metabolic markers for the management of OSCC are discussed. RESULTS: This review summarizes metabolic changes during the occurrence and development of oral squamous cell carcinoma and reviews prospects for the clinical application of characteristic, differential metabolites in saliva, serum, and OSCC tissue. In this review, the application of metabolomic technology in OSCC research was summarized, and future research directions were proposed. CONCLUSION: Metabolomics, detection technology that is the closest to phenotype, can efficiently identify differential metabolites. Combined with statistical data analyses and artificial intelligence technology, it can rapidly screen characteristic biomarkers for early diagnosis, treatment, and prognosis evaluations.

Comparing perioperative outcomes between regional anesthesia and general anesthesia in patients undergoing hip fracture surgery: a systematic review and meta-analysis.

PURPOSE: Nearly all patients with hip fractures undergo surgical treatment. The use of different anesthesia techniques during surgery may influence the clinical outcomes. The optimal anesthetic technique for patients undergoing hip fracture surgery is still controversial. We performed this updated systematic review and meta-analysis to compare clinical outcomes of patients undergoing hip fracture surgery with different anesthesia techniques. SOURCE: Articles published from 2000 to May 2023 were included from MEDLINE, Embase, Web of Science, and the Cochrane Library. We included randomized controlled trials and observational studies comparing general anesthesia (GA) with regional anesthesia (RA) for the outcomes of 30-day mortality, 90-day mortality, in-hospital mortality, perioperative complications, length of hospital stay, and length of surgery in patients undergoing hip fracture surgery. Subgroup analyses were performed for the outcomes based on study design (randomized controlled trials or observational studies). We used a random-effects model for all analyses. PRINCIPAL FINDINGS: In this meta-analysis, we included 12 randomized controlled trials. There was no difference in postoperative 30-day mortality between the two groups (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.44 to 1.74; I2 = 0%). The incidence of intraoperative hypotension was lower in patients who received RA vs GA (OR, 0.52; 95% CI, 0.38 to 0.72; I2 = 0%). No significant differences were observed in 90-day mortality, in-hospital mortality, postoperative delirium, pneumonia, myocardial infarction, venous thromboembolism, length of surgery, and length of hospital stay. CONCLUSION: In this updated systematic review and meta-analysis, RA did not reduce postoperative 30-day mortality in hip fracture surgery patients compared to GA. Fewer patients receiving RA had intraoperative hypotension than those receiving GA did. Apart from intraoperative hypotension, the data showed no differences in complications between the two anesthetic techniques. STUDY REGISTRATION: PROSPERO (CRD42023411854); registered 7 April 2023.

RéSUMé: OBJECTIF: Presque toutes les personnes ayant subi une fracture de la hanche se font opérer. L'utilisation de différentes techniques d'anesthésie pendant la chirurgie peut influencer les issues cliniques. La technique d'anesthésie optimale pour la patientèle bénéficiant de chirurgie de fracture de la hanche est encore controversée. Nous avons réalisé cette mise à jour par revue systématique et méta-analyse pour comparer les issues cliniques des personnes bénéficiant d'une chirurgie de fracture de la hanche avec différentes techniques d'anesthésie. SOURCES: Les articles publiés de 2000 à mai 2023 ont été inclus à partir des bases de données MEDLINE, Embase, Web of Science et Cochrane Library. Nous avons inclus des études randomisées contrôlées et des études observationnelles comparant l'anesthésie générale (AG) à l'anesthésie régionale (AR) pour les issues de mortalité à 30 jours, de mortalité à 90 jours, de mortalité intrahospitalière, de complications périopératoires, de durée de séjour à l'hôpital et de durée de la chirurgie pour les personnes bénéficiant d'une chirurgie de fracture de la hanche. Des analyses de sous-groupes ont été réalisées pour les issues en fonction de la méthodologie utilisée (étude randomisée contrôlée ou étude observationnelle). Un modèle à effets aléatoires a été utilisé pour toutes les analyses. CONSTATATIONS PRINCIPALES: Dans cette méta-analyse, nous avons inclus 12 études randomisées contrôlées. Il n'y avait pas de différence dans la mortalité postopératoire à 30 jours entre les deux groupes (rapport de cotes [RC], 0,88; intervalle de confiance à 95 % [IC], 0,44 à 1,74; I2 = 0 %). L'incidence d'hypotension peropératoire était plus faible chez les patient·es ayant reçu une AR vs une AG (RC, 0,52; IC 95 %, 0,38 à 0,72; I2 = 0 %). Aucune différence significative n'a été observée dans les issues de mortalité à 90 jours, de mortalité intrahospitalière, de delirium postopératoire, de pneumonie, d'infarctus du myocarde, de thromboembolie veineuse, de durée de la chirurgie, et de durée du séjour à l'hôpital. CONCLUSION: Dans cette revue systématique avec méta-analyse, l'anesthésie régionale n'a pas réduit la mortalité postopératoire à 30 jours chez les personnes ayant bénéficié d'une chirurgie de fracture de la hanche par rapport à l'anesthésie générale. Une proportion moindre de patient·es ayant reçu une AR présentaient une hypotension peropératoire par rapport aux personnes ayant reçu une AG. En dehors de l'hypotension peropératoire, les données n'ont montré aucune différence dans les complications entre les deux techniques anesthésiques. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42023411854); enregistrée le 7 avril 2023.

Long-term music stimulating alleviated the inflammatory responses caused by acute noise stress on the immune organs of broilers by NF-κB signaling pathway.

As an environmental enrichment, music can positively influence the immune function, while noise has an adverse effect on the physical and mental health of humans and animals. However, whether music-enriched environments mitigate noise-induced acute stress remains unclear. To investigate the anti-inflammatory effects of music on the immune organs of broiler chickens under conditions of early-life acute noise stress, 140 one-day-old white feather broilers (AA) were randomly divided into four groups: control (C), the music stimulation (M) group, the acute noise stimulation (N) group, the acute noise stimulation followed by music (NM) group. At 14 days of age, the N and NM groups received 120 dB noise stimulation for 10 min for one week. After acute noise stimulation, the NM group and M group were subjected to continuous music stimulation for 14 days (6 h per day, 60 dB). At 28 days of age, the body temperature of the chicks, the histopathological changes, quantification of ROS-positive density and apoptosis positivity in tissues of spleen, thymus, and bursa of Fabricius (BF) were measured. The results showed that acute noise stimulation led to an increase in the number and area of splenic microsomes and the cortex/medulla ratio of the detected immune organs. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of immune tissues of broilers in N group were decreased compared to the broilers in C group, while the mRNA levels of malondialdehyde (MDA), TNF-α, IL-1, and IL-1ß increased. In addition, the gene and protein expression levels of IKK, NF-κB, and IFN-γ of three immune organs from broilers in the N group were increased. Compared to the C and N group, chickens from the NM group showed a decrease in the number and area of splenic follicles, an increase in the activities of SOD and GSH-Px, and a decrease in the expression levels of MDA, TNF-α, IL-1, and IL-1ß. Therefore, a music-enriched environment can attenuate oxidative stress induced by acute noise stimulation, inhibiting the activation of the NF-κB signaling pathway and consequently alleviating the inflammatory response in immune organs.

LncRNA SNHG12 regulated by WTAP aggravated the oxygen-glucose deprivation/reperfusion-induced injury in bEnd.3 cell.

OBJECTIVES: Previous studies have identified abnormal expression of lncRNA SNHG12 in ischemic stroke, but the underlying molecular mechanism remains unclear. MATERIALS AND METHODS: Through database predictions, m6A methylation sites were found on SNHG12, suggesting post-transcriptional modification. To further elucidate the role of SNHG12 and m6A methyltransferase WTAP in oxygen-glucose deprivation/reperfusion (OGD/R)-induced damage in cerebral microvascular endothelial cells, we conducted investigations. Additionally, we examined the impact of m6A methyltransferase WTAP on SNHG12 expression. RESULTS: Overexpressing SNHG12 in bEnd.3 cells was found to inhibit cell proliferation and promote apoptosis, as well as activate the production of reactive oxygen species and inflammatory cytokines (E-selectin, IL-6 and MCP-1), along with angiogenic proteins (VEGFA and FGFb). Conversely, SNHG12 knockdown alleviated OGD/R-induced damage to BEnd.3 cells, resulting in improved cell proliferation, reduced apoptosis, decreased ROS and LDH production, as well as diminished expression of inflammatory cytokines (E-selectin, IL-6 and MCP-1) and angiogenic proteins (VEGFA and FGFb). Furthermore, WTAP was found to positively regulate SNHG12 expression, and WTAP knockdown in bEnd.3 cells under the OGD/R conditions inhibited cell proliferation, promoted apoptosis, and increased ROS and LDH production. CONCLUSION: These findings suggest that WTAP may play a crucial role in SNHG12-mediated OGD/R-induced damage in bEnd.3 cells. More molecular experiments are needed to further analyze its mechanism. Overall, our study helps to enrich our understanding of the dysregulation of SNHG12 in ischemic stroke.

Effects of intermittent cold stimulation on growth performance, meat quality, antioxidant capacity and liver lipid metabolism in broiler chickens.

Intermittent cold stimulation (ICS) enhances broilers' resistance to cold stress. Nonetheless, further research is needed to investigate the underlying mechanisms that enhance cold stress resistance. A total of 160 one-day-old male Ross 308 broilers were randomly divided into 2 groups (CC and CS5), with the CC group managing temperature according to the standard for broiler growth stages, while the CS5 group were subjected to cold stimulation at a temperature 3℃ lower than the CC group for 5 h, every 2 d from 15 to 35 d. Sampling was conducted at 36 d (36D), 50 d (50D) and after acute cold stress for 24 h (Y24). First, we examined the effects of ICS on broiler growth performance, meat quality, antioxidant capacity, and lipid metabolism. The results demonstrated that ICS enhanced the performance of broilers to a certain degree. Specifically, the average weight gain in the CS5 group was significantly higher than that of the CC group, and the feed conversion ratio significantly decreased compared to CC at 4 W and 6 W (P ≤ 0.05). Compared with the CC group, cold stimulation significantly reduced drip loss, shearing force, and yellowness (a* value) of chicken meat, while significantly increased redness (b* value) (P ≤ 0.05). At Y24, the levels of T-AOC and GSH-PX in the serum of the CS5 group were significantly higher than those of the CC group, while the level of MDA was significantly lower (P ≤ 0.05). The content of TG, FFA, and VLDL in the serum of the CS5 group was significantly elevated, whereas the level of TC and HDL was significantly lower (P ≤ 0.05). In addition, we further explored whether AMPK-mTOR pathway is involved in the regulation of changes in lipid metabolism and the possible regulatory mechanisms downstream of the signaling pathway. The results showed that ICS significantly upregulated the expression levels of AMPK mRNA and protein in the liver of the CS5 group at 36D and Y24, while significantly down-regulating mTOR (P ≤ 0.05). Compared with the CC group, ICS significantly down-regulated the mRNA expression levels of lipid synthesis and endoplasmic reticulum stress-related genes (SREBP1c, FAS, SCD, ACC, GRP78 and PERK) at 36D and Y24, while significantly up-regulating the mRNA expression levels of lipid decomposition and autophagy-related genes (PPAR and LC3) (P ≤ 0.05). In addition, at Y24, the protein expression levels of endoplasmic reticulum stress-related genes (GRP78) in the CS5 group were significantly lower, while autophagy-related genes (LC3 and ATG7) were significantly higher (P ≤ 0.05). ICS can affect meat quality and lipid metabolism in broilers, and when broilers are subjected to acute cold stress, broilers trained with cold stimulation have stronger lipid metabolism capacity.

The Application and Pitfalls of Immunohistochemical Markers in Challenging Diagnosis of Genitourinary Pathology.

CONTEXT.­: The morphologic features of different entities in genitourinary pathology overlap, presenting a diagnostic challenge, especially when diagnostic materials are limited. Immunohistochemical markers are valuable when morphologic features alone are insufficient for definitive diagnosis. The World Health Organization classification of urinary and male genital tumors has been updated for 2022. An updated review of immunohistochemical markers for newly classified genitourinary neoplasms and their differential diagnosis is needed. OBJECTIVE.­: To review immunohistochemical markers used in the diagnosis of genitourinary lesions in the kidney, bladder, prostate, and testis. We particularly emphasized difficult differential diagnosis and pitfalls in immunohistochemistry application and interpretation. New markers and new entities in the 2022 World Health Organization classifications of genitourinary tumors are reviewed. Recommended staining panels for commonly encountered difficult differential diagnoses and potential pitfalls are discussed. DATA SOURCES.­: Review of current literature and our own experience. CONCLUSIONS.­: Immunohistochemistry is a valuable tool in the diagnosis of problematic lesions of the genitourinary tract. However, the immunostains must be carefully interpreted in the context of morphologic findings with a thorough knowledge of pitfalls and limitations.

Coupled sorptive and oxidative antimony(III) removal by iron-modified biochar: Mechanisms of electron-donating capacity and reactive Fe species.

Sorption and oxidation are two potential pathways for the decontamination of trivalent antimony (Sb(III))-bearing water, using iron (Fe)-modified biochar (FeBC). Here we investigated the sorption and oxidation behavior of FeBC for Sb(III) in aqueous solutions. Results revealed that Sb(III) removal by FeBC was significantly improved showing the maximum Sb(III) sorption (64.0 mg g-1). Density functional theory (DFT) calculations indicated that magnetite (Fe3O4) in FeBC offered a sorption energy of -0.22 eV, which is 5 times that of non-modified biochar. With the addition of peroxymonosulfate (PMS), the sorption of Sb(III) on FeBC was 7 times higher than that on BC, indicating the sorption capacity of FeBC for Sb(III) could be substantially increased by adding oxidizing agents. Electrochemical analysis showed that Fe modification imparted FeBC higher electron-donating capacity than that of BC (0.045 v. s. 0.023 mmol e- (g biochar)-1), which might be the reason for the strong Sb(III) oxidation (63.6%) on the surface of FeBC. This study provides new information that is key for the development of effective biochar-based composite materials for the removal of Sb(III) from drinking water and wastewater. The findings from this study have important implications for protecting human health and agriculture.

Unintended consequences: Disrupting microbial communities of Nilaparvata lugens with non-target pesticides.

Insects are frequently exposed to a range of insecticides that can alter the structure of the commensal microbiome. However, the effects of exposure to non-target pesticides (including non-target insecticides and fungicides) on insect pest microbiomes are still unclear. In the present study, we exposed Nilaparvata lugens to three target insecticides (nitenpyram, pymetrozine, and avermectin), a non-target insecticide (chlorantraniliprole), and two fungicides (propiconazole and tebuconazole), and observed changes in the microbiome's structure and function. Our results showed that both non-target insecticide and fungicides can disrupt the microbiome's structure. Specifically, symbiotic bacteria of N. lugens were more sensitive to non-target insecticide compared to target insecticide, while the symbiotic fungi were more sensitive to fungicides. We also found that the microbiome in the field strain was more stable under pesticides exposure than the laboratory strain (a susceptible strain), and core microbial species g_Pseudomonas, s_Acinetobacter soli, g_Lactobacillus, s_Metarhizium minus, and s_Penicillium citrinum were significantly affected by specifically pesticides. Furthermore, the functions of symbiotic bacteria in nutrient synthesis were predicted to be significantly reduced by non-target insecticide. Our findings contribute to a better understanding of the impact of non-target pesticides on insect microbial communities and highlight the need for scientific and rational use of pesticides.

Childhood granulomatous periorificial dermatitis in 31 Chinese children successfully treated with oral roxithromycin.

Data regarding the treatment of childhood granulomatous periorificial dermatitis (CGPD) using oral therapies are limited. This study included 31 Chinese children with CGPD treated with oral roxithromycin. After 12 weeks of treatment, 90.3% of the patients recovered, and there were no severe adverse effects. Our results suggest that oral roxithromycin is an effective and safe treatment for CGPD.

Anthropogenic Activities Generate High-Refractory Black Carbon along the Yangtze River Continuum.

Combustion-driven particulate black carbon (PBC) is a crucial slow-cycling pool in the organic carbon flux from rivers to oceans. Since the refractoriness of PBC stems from the association of non-homologous char and soot, the composition and source of char and soot must be considered when investigating riverine PBC. Samples along the Yangtze River continuum during different hydrological periods were collected in this study to investigate the association and asynchronous combustion drive of char and soot in PBC. The results revealed that PBC in the Yangtze River, with higher refractory nature, accounts for 13.73 ± 6.89% of particulate organic carbon, and soot occupies 37.53 ± 11.00% of PBC. The preponderant contribution of fossil fuel combustion to soot (92.57 ± 3.20%) compared to char (27.55 ± 5.92%), suggested that fossil fuel combustion is a crucial driver for PBC with high soot percentage. Redundancy analysis and structural equation modeling confirmed that the fossil fuel energy used by anthropogenic activities promoting soot is the crucial reason for high-refractory PBC. We estimated that the Yangtze River transported 0.15-0.23 Tg of soot and 0.15-0.25 Tg of char to the ocean annually, and the export of large higher refractory PBC to the ocean can form a long-term sink and prolong the residence time of terrigenous carbon.

Bioinspired PROTAC-induced macrophage fate determination alleviates atherosclerosis.

Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque. The infiltration of proinflammatory M1 macrophages plays an essential role in the occurrence and development of atherosclerosis plaque. A recent study shows that TRIM24, an E3 ubiquitin ligase of a Trim family protein, acts as a valve to inhibit the polarization of anti-inflammatory M2 macrophages, and elimination of TRIM24 opens an avenue to achieve the M2 polarization. Proteolysis-targeting chimera (PROTAC) technology has emerged as a novel tool for the selective degradation of targeting proteins. But the low bioavailability and cell specificity of PROTAC reagents hinder their applications in treating atherosclerosis plaque. In this study we constructed a type of bioinspired PROTAC by coating the PROTAC degrader (dTRIM24)-loaded PLGA nanoparticles with M2 macrophage membrane (MELT) for atherosclerosis treatment. MELT was characterized by morphology, size, and stability. MELT displayed enhanced specificity to M1 macrophages as well as acidic-responsive release of dTRIM24. After intravenous administration, MELT showed significantly improved accumulation in atherosclerotic plaque of high fat and high cholesterol diet-fed atherosclerotic (ApoE-/-) mice through binding to M1 macrophages and inducing effective and precise TRIM24 degradation, thus resulting in the polarization of M2 macrophages, which led to great reduction of plaque formation. These results suggest that MELT can be considered a potential therapeutic agent for targeting atherosclerotic plaque and alleviating atherosclerosis progression, providing an effective strategy for targeted atherosclerosis therapy.

Intestinal obstruction caused by mesodiverticular band in children: a cohort study.

OBJECTIVE: To explore clinical characteristics, pathogenesis, diagnosis and treatment of intestinal obstruction due to mesodiverticular band (MDB) in children in a single center in China. METHODS: The clinical data of 20 children with acute intestinal obstruction due to MDB between 1998 and 2020 were retrospectively analyzed. RESULTS: The male-to-female ratio was 14:6 in 20 cases. Except one case of 7-month pregnant stillbirth, the cases were aged from 7 days to 14 years, at the median age of 4.31 years. The common symptoms were vomiting, abdominal pain and/or abdominal distension. About 40% (8/20) of patients had both MDB and Meckel's Diverticulum (MD), while 60% (12/20) of patients had MDB only. Only one case died because of total colonic aganglionosis, while other children recovered after surgery treatment. MDB led to the strangulation of necrotic bowel in six cases, intestinal perforation in one case, and intestinal rupture in one case. Pathologic examination showed thick-walled arteries and or thick venous vascular structures in the cord. All cases had no complications during 1-year follow-up. CONCLUSION: MDB results from the remnant of vitelline vessel, and often causes acute intestinal obstruction without special clinical symptoms. Unexplained abdominal pain and distension without surgery history should be paid attention, especially for strangulated intestinal obstruction. Timely surgical exploration is beneficial to avoid intestinal necrosis or even sudden death, and the pathological examination is important for the diagnosis.

The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells.

BACKGROUND: Testicular hypoplasia can affect the sexual and reproductive ability in adulthood, and even increase the risk of cancer. Abnormal development of the gubernaculum is one of the important factors of testicular hypoplasia. Therefore, a study of the structure and function of the gubernaculum is an important but neglected new breakthrough point for investigating the normal/abnormal development of the testis. Previous findings showed that Insulin like factor 3 (INSL3) is a key factor regulating the growth of gubernaculum, however, the mechanism by which INSL3 acts on the gubernaculum remains unknown. Therefore, we probed the mechanism associated with INSL3-induced the proliferation, migration, and apoptosis of gubernacular cells in mice. METHODS: A culture cell model of neonatal mice gubernaculum is established by INSL3 intervention. We blocked PLC/PKC signaling pathway with U73122 pretreat to investigate the role of the PLC/PKC signaling pathway. The changes of cell proliferation, migration, and apoptosis were detected by molecular biological methods. In addition, the levels of PCNA and F-action were detected by immunofluorescence and western blotting. RESULTS: We found that INSL3 can promote the proliferation and migration of gubernacular cells and inhibit their apoptosis, meanwhile, INSL3 significantly up-regulated PLC/PKC protein phosphorylation. However, treatment with the PLC/PKC signaling pathway inhibitor U73122 significantly inhibited these effects of INSL3. Besides, we found that INSL3 could up-regulate the protein expression level of PCNA and F-actin, while the PCNA and F-actin expression was significantly weakened after U73122 pretreatment. CONCLUSIONS: This research revealed that INSL3 binding to RXFP2 may up-regulate the expression levels of PCNA and F-actin by activating the PLC/PKC signaling pathway to promote the proliferation and migration of gubernacular cells. It suggests that the RXFP2-PLC/PKC axis may serve as a novel molecular mechanism by which INSL3 regulates growth of the gubernaculum.

Cyhalofop-butyl and pyribenzoxim-induced oxidative stress and transcriptome changes in the muscle of crayfish (Procambarus clarkii).

Cyhalofop-butyl and pyribenzoxim are commonly used herbicides in rice-crayfish co-culture fields. In actual production, weed control in paddy fields is inseparable from cyhalofop-butyl and pyribenzoxim, while its risk to P. clarkii is still unclear. The present study investigated the risk of acute and subchronic toxicity of cyhalofop-butyl and pyribenzoxim to P. clarkii. The results showed that cyhalofop-butyl and pyribenzoxim exposure for 28 days could accumulate in P. clarkii muscle and inhibit P. clarkii growth. Further research found that the malondialdehyde (MDA) level and glutathione-S-transferase (GST) activity in muscle of P. clarkii were significantly increased after exposure to cyhalofop-butyl and pyribenzoxim (4 days and 28 days), and the superoxide dismutase (SOD) and catalase (CAT) activities were significantly altered. Histological results also confirmed cyhalofop-butyl and pyribenzoxim-induced muscle damage in P. clarkii. Additionally, after 28 days exposure to 1.02 mg/L cyhalofop-butyl and 10.4 mg/L pyribenzoxim, transcriptome analysis identified 2029 and 4246 differentially expressed genes (DEGs), respectively. Exposure to 1.02 mg/L cyhalofop-butyl significantly altered metabolism-related pathways, such as drug metabolism-other enzymes, glutathione metabolism, drug metabolism-cytochrome P450, fatty acid biosynthesis and fatty acid degradation. While the pathways related to antioxidant system and nutrient substances synthesis and metabolic were significantly enriched after exposure to 10.4 mg/L pyribenzoxim. This research has significant implications for scientific and rational use of herbicides under rice-crayfish co-culture and will contribute to the development of the highly productive agricultural model.

Differentiation of benign and malignant breast lesions using diffusion-weighted imaging with a fractional-order calculus model.

PURPOSE: To assess the feasibility of using three diffusion parameters (D, ß, and µ) derived from fractional-order calculus (FROC) diffusion model for improving the differentiation between benign and malignant breast lesions. METHOD: In this prospective study, 103 patients with breast lesions were enrolled. All subjects underwent diffusion-weighted imaging (DWI) with 12b values. Inter-observer agreement with respect to quantification of parameters by two radiologists was assessed using intraclass coefficient. Conventional apparent diffusion coefficient (ADC) and three FROC model parameters D, ß, and µ were compared between the benign lesion and malignant lesion groups using the Mann-Whitney U test. Then, a comprehensive prediction model was created by using binary logistic regression. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the parameters using histopathological diagnosis as the reference standard. RESULTS: The FROC parameters and ADC all exhibited significant differences between benign lesions and malignant lesions (P＜0.001). Among the individual parameters, the sensitivity of µ was higher than ADC (95.92% for µ vs 91.84% for ADC), and the specificity of ß was higher than ADC (72.22% for ß vs 70.37% for ADC). The combination of ADC and FROC parameters (D and ß) generated the largest area under the ROC curve (0.841) when compared with individual parameters, indicating an improved performance for differentiating benign lesions from malignant lesions. CONCLUSIONS: This study demonstrated the feasibility of using the FROC diffusion model to improve the accuracy of identifying malignant breast lesions.