M1 Group Research Articles

Diagnostic value of exosomal N‐glycan profiles for microvascular invasion in hepatocellular carcinoma

AbstractBackgroundMicrovascular invasion (MVI) was a critical high‐risk factor for postoperative recurrence and adverse prognosis in patients with hepatocellular carcinoma (HCC), and there were no reliable non‐invasive pre‐operative diagnostic markers. The exosomal N‐glycan profile was closely related to the invasion and immune escape of HCC. Therefore, this article investigated the expression of N‐glycan profiles in serum exosomes of patients with HCC and its clinical significance for MVI.MethodsSerum samples from 210 patients with HCC were collected and randomly divided into modeling and validation cohorts. The abundances of N‐glycans in serum exosomes with different MVI grades were determined. A diagnostic model for MVI in HCC based on N‐glycosylation was constructed and the diagnostic value was analyzed.ResultsIn the modeling cohort, comparing groups M0 with M2, the area under the receiver operating characteristic (AUC) of the diagnostic model namely SUM (AUCSUM) was 0.861, the sensitivity of SUM was 92.68%, and the specificity of SUM was 79.41%, all of which were higher than the seven individual indexes (containing Peak 1, Peak 6, Peak 9, Peak 10, Peak 12, AFP, and PIVKA‐II). In the comparison between the M1 and M2 groups, the AUCSUM was 0.749, the sensitivity of SUM was 79.07%, and the specificity of SUM was 76.60%, all of which were higher than the seven individual indexes. When comparing the M0 and M1 groups, the AUCSUM was 0.712, the sensitivity of SUM was 88.57%, and the specificity of SUM was 65.00%. The AUCSUM and sensitivity of SUM were higher than the seven individual indexes and the specificity of SUM was slightly lower than that of AFP (68.18%) but higher than other individual indexes. The results of the validation cohort were similar to those of the modeling cohort.ConclusionThe SUM model of serum exosomes can serve as an auxiliary diagnostic index for MVI staging in patients with HCC.

Effects of repetitive transcranial magnetic stimulation at different targets on brain function in stroke patients: a randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) can improve post stroke motor function. However, there is little research on targets. The purpose of this study is to investigate the effects of rTMS therapy with different targets on post stroke motor function and neural plasticity. Fifty-four subjects were randomly divided into M1 (Primary motor area) group, SMA (supplementary motor area) group and Sham group, and were given 10 Hz on the affected M1 area, SMA area and sham stimulation rTMS. The primary outcomes included Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Fugl-Meyer Assessment Lower Extremity Scale (FMA-LE) and Berg balance scale (BBS). Secondary outcomes: amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were analyzed by functional magnetic resonance imaging (fMRI) to evaluate brain functional activation and functional connectivity changes. The 2-way repeated-measures ANOVA revealed a significant group × time interaction (F = 23.494, p < 0.001; F = 10.801, p < 0.001; F = 17.812, p < 0.001) in the FMA-UE, FMA-LE and BBS scores. Post hoc analysis indicated that 4 weeks of SMA rTMS resulted in an increase in FMA-UE, FMA-LE and BBS scores compared with Sham group (p = 0.006; p = 0.033; p = 0.012), SMA group was significantly increased in BBS compared with M1 group (p = 0.034). Moreover, there were significant effects of time in all 3 groups in the FMA-UE, FMA-LE and BBS scores (p < 0.001). In addition, the increase of ALFF in the supramarginal gyrus on the affected side was correlated with better FMA-UE recovery, the increase of ALFF in the middle temporal gyrus and the middle frontal gyrus on the affected side was positively correlated with the improvement of BBS, and the ALFF in the cerebellum on the healthy side was negatively correlated with the improvement of BBS. There was a positive correlation between FC (SMA - ipsilateral cerebellum) changes and BBS changes in SMA group. In conclusion, SMA-rTMS intervention has a better recovery effect on motor dysfunction after stroke than Sham-rTMS. SMA-rTMS led to similar improvement on motor function but significantly greater improvement on balance compared to M1-rTMS, and this may pave a new way for stroke rehabilitation. Registration number: ChiCTR2200060955, https://www.chictr.org.cn/.

Advancing microvascular invasion diagnosis: a multi-center investigation of novel MRI-based models for precise detection and classification in early-stage small hepatocellular carcinoma (≤ 3cm).

This study aimed to develop two preoperative magnetic resonance imaging (MRI) based models for detecting and classifying microvascular invasion (MVI) in early-stage small hepatocellular carcinoma (sHCC) patients. MVI is graded as M0 (no invasion), M1 (invasion of five or fewer vessels located within 1cm of the tumor's peritumoral region), and M2 (invasion of more than five vessels or those located more than 1cm from the tumor's surface). This study enrolled 395 early-stage sHCC (≤ 3cm) patients from three centers who underwent preoperative gadopentetate-enhanced MRI. From the first two centers, 310 patients were randomly divided into training (n = 217) and validation (n = 93) cohorts in a 7:3 ratio to develop the first model for predicting MVI presence. Among these, 153 patients with identified MVI were further divided into training (n = 112) and validation (n = 41) cohorts, using the same ratio, to construct the second model for MVI classification. An independent test cohort of 85 patients from the third center to validate both models. Univariate and multivariate logistic regression analyses identified independent predictors of MVI and its classification in the training cohorts. Based on these predictors, two nomograms were developed and assessed for their discriminative ability, calibration, and clinical usefulness. Besides, considering the two models are supposed applied in a serial fashion in the real clinical setting, we evaluate the performance of the two models together on the test cohorts by applying them simultaneously. Kaplan-Meier survival curve analysis was employed to assess the correlation between predicted MVI status and early recurrence, similar to the association observed with actual MVI status and early recurrence. The MVI detection nomogram, with platelet count (PLT), activated partial thromboplastin time (APTT), rim arterial phase hyperenhancement (Rim APHE) and arterial peritumoral enhancement, achieved area under the curve (AUC) of 0.827, 0.761 and 0.798 in the training, validation, and test cohorts, respectively. The MVI classification nomogram, integrating Total protein (TP), Shape, Arterial peritumoral enhancement and enhancement pattern, achieved AUC of 0.824, 0.772, and 0.807 across the three cohorts. When the two models were applied on the test cohorts in a serial fashion, they both demonstrated good performance, which means the two models had good clinical applicability. Calibration and decision curve analysis (DCA) results affirmed the model's reliability and clinical utility. Notably, early recurrence was more prevalent in the MVI grade 2 (M2) group compared to the MVI-absent and M1 groups, regardless of the actual or predicted MVI status. The nomograms exhibited excellent predictive performance for detecting and classifying MVI in patients with early-stage sHCC, particularly identifying high-risk M2 patients preoperatively.

Comparison of the efficacy of two preoxygenation techniques using oxygen reserve index.

Preoxygenation is very important to protect the patient from hypoxia before intubation. However, pulse oximetry has some limitations in detecting hypoxia. We aimed to compare the effectiveness of 2 preoxygenation techniques based on oxygen reserve index (ORI) levels. Twenty healthy male volunteers were included in the study. They inhaled 100% FiO2 oxygen administered at 5 L/min as the 1st technique (M1) with a ventilation mask as much as their tidal volumes for 3 min. The 2nd technique (M2) applied 100% FiO2 oxygen at 10 L/min flow using the same mask and 8 deep inspiratory volumes, which was aimed to be completed within 1 min. Maximum ORI levels, duration to reach that level, and time needed to reach the target ORI level (0.35) and return back to the "0" were measured. In the M1 group, ORI levels were significantly higher during and after 60 s, according to post hoc tests. In the M2 groups, ORI levels were significantly higher during and after the 4th inspiration, according to post hoc tests. Oxygen reserve index values at the 60th 2nd (M1) and 8th inspiration (M2) were compared as the 8th inspiration corresponded to the 60th second. The maximum ORI values were significantly lower in the M1 group compared to the M2 group (p < 0.001 and p = 0.006, respectively). Seven volunteers (36.8%) in the M1 group and 2 volunteers (10.5%) in the M2 group could not reach the target ORI (McNemar's test, test statistic 3.2, degrees of freedom (df) = 1, p = 0.063). The time to reach the target ORI value and to reach maximum ORI values was significantly longer in the M1 group than in the M2 group (p = 0.008 and p < 0.001, respectively). We observed that the 8-deep breath technique is more effective in preoxygenation compared to the 3-min tidal volume technique.

Tolerance and toxicity assessment of a novel methionine source, dipeptide Met-Met on common carp Cyprinus carpio

Methionine is the first-limiting essential amino acid in plant-based diet, and also is the most toxic amino acid. The study aimed to evaluate the tolerance and toxicity of a dipeptide DL-methionyl-DL-methionine (Met-Met) in the diet of common carp Cyprinus carpio. Five iso‑nitrogenous (∼ 380 g kg−1) and isoenergetic (∼185 MJ kg−1) diets were formulated including a positive control diet (100 g kg−1 fish meal, FM) supplemented with 3 g kg−1DL-Met and four low fish meal diets (40 g kg−1 fish meal), with 0 (M0), 3 (M3), 6 (M6), and 15 (M15) g kg−1 Met-Met being supplemented. The Met-Met supplementation levels of 6 and 15 g kg−1 were designed as the 2- and 5-fold of the optimal level (3 g kg−1) for the tolerance and toxicity assessment, respectively. After 10 weeks of feeding, the lowest growth performance was observed in the M0 group, as evidenced by the lowest weight gain rate and specific growth rate. Contents of protein and amino acid in whole-body, and retentions of nitrogen and amino acid were highest in the M6 group, while these values decreased in M15 group. Fish fed diet M15 showed lower levels of albumin, high density lipoprotein cholesterol (HDL), total cholesterol, alkaline phosphatase, and higher alanine aminotransferase, total bile acid, total antioxidant capacity (T-AOC) compared with M3. Fish fed diet M15 had lower levels of glucose, HDL, and higher T-AOC and malonaldehyde compared to M6. Genes related to bile acid metabolism (cyp8b1, rxrα, fxr), anti-inflammatory (tgfβ1, tgfβ2, il10), proinflammatory (tnfα, il1β, il17) were significantly down-regulated in the M15 group compared to M3. However, caspase-3 expression significantly up-regulated in the M15 group compared with M6. Increased signals of hepatic vacuolation and fibrosis were observed in the M0 and M15 groups. Besides M15 group showed higher expression of apoptosis signal marker, cleaved caspase-3 in hepatopancreas. This study clarified the safety margin of Met-Met was 2× dosage as 6 g kg−1, while 15 g kg−1 Met-Met caused deleterious consequences, manifested as the highly occurred of cholestatic liver disease.

Preliminary study of extracorporeal shock wave alleviating joint capsule fibrosis caused by internal bleeding of knee joint in rats

ABSTRACT Purpose Joint contracture is a common disease in clinical practice, joint bleeding is an important factor affecting the progression of joint contracture. This study aimed to explore the effect of extracorporeal shock wave on alleviating joint capsule fibrosis caused by intra-articular hemorrhage in rats. Methods Forty two SD rats were randomly divided into seven groups. Perform simple fixation and fixation after blood injection separately. Measure the range of motion of each group’s knee joints and calculate the corresponding degree of contraction. Use HE staining and Masson staining to detect the number of anterior joint capsule cells and collagen deposition. Detection of changes in Wnt1, β-catenin protein expression in joint capsule using Western blotting. Results Compared to group C, the degree of knee joint contracture in M1 and M2 groups of rats increased, and collagen deposition, cell number and Wnt1, β-catenin protein expression also increased accordingly. Compared to M1 and M2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, β-catenin protein expression were decreased, and the degree of joint contracture in NR1 and NR2 groups showed no significant improvement. Compared to NR1 and NR2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, β-catenin protein expression were decreased. Conclusions Both rat models of knee joint contracture were successful, and joint bleeding can exacerbate joint contracture. Extracorporeal shock waves alleviate joint capsule fibrosis caused by intra-articular bleeding in rats.

Synergistic and Antagonistic Activity of Selected Dietary Phytochemicals against Oxidative Stress-Induced Injury in Cardiac H9c2 Cells via the Nrf2 Signaling Pathway.

The antioxidant activities of lycopene (LY), lutein (LU), chlorogenic acid (CA), and delphinidin (DP) were tested in vitro on H9c2 cell-based models. Some indicators, such as the generation of reactive oxygen (ROS), the quantification of cell antioxidant activity (CAA), and the expressions of SOD, GSH-Px, and CAT, were calculated to examine their antioxidant interactions. From our results, the phytochemical mixtures (M1: CA-LU: F3/10, M2: DP-CA: F7/10, M3: DP-LY: F5/10) displayed strong synergistic effects based on the generation of ROS and the quantification of CAA. However, great antagonistic bioactivities were seen in the combinations of LY-LU: F5/10 (M4), CA-LU: F9/10 (M5), and DP-LY: F7/10 (M6). Western blotting analysis indicated that the possible mechanism underlying the synergistic antioxidant interactions among phytochemical combinations was to enhance the accumulation of Nrf2 in the nucleus and the expression of its downstream antioxidant enzymes, HO-1 and GCLC. The combinations (M1-M3 groups) showed significant protection against the loss of mitochondrial membrane potential than individual groups to avoid excessive ROS production. The M4-M6 groups exerted antagonistic protective effects compared with the individual groups. In addition, lutein and lycopene absorption was improved more because of the presence of chlorogenic acid and delphinidin in the M1 and M3 groups, respectively. However, delphinidin significantly reduced the cellular uptake of lycopene in the M6 group. It appeared that antioxidant interactions of phytochemical combinations may contribute to the restoration of cellular redox homeostasis and lead to an improvement in diet quality and collocation.

The impact of general anesthesia versus non-general anesthesia on thrombectomy outcomes by occlusion location: insights from the ETIS registry.

Identifying the optimal anesthetic technique for mechanical thrombectomy (MT) remains an unresolved issue. Prior research has not considered the influence of occlusion site when comparing general anesthesia (GA) with non-GA. This study evaluates the differential impacts of the anesthetic technique (GA vs non-GA) on outcomes according to the location of occlusion. This is a retrospective analysis of the ETIS (Endovascular Treatment in Ischemic Stroke) registry. Patients with anterior circulation large-vessel occlusion treated with MT were included. Patients were divided into groups according to the location of occlusion. Inverse propensity score weighting analysis was used. Among 2783 patients included in the propensity score analysis, 669 (24%) received GA. In the total cohort, GA was not associated with favorable outcome, excellent outcome, successful reperfusion, or complete reperfusion. GA was associated with higher odds of parenchymal hemorrhage (OR 1.42, 95% 1.05-1.92) but not symptomatic intracranial hemorrhage. GA was associated with Alberta Stroke Program Early CT Score progression (OR 1.36, 95% CI 1.11-1.68). In the internal carotid artery occlusion group, GA was associated with higher odds of mortality (OR 1.94, 95% CI 1.15-3.27). In the M1 group, GA was associated with lower odds of complications (OR 0.41, 95% CI 0.19-0.92). In the M2 group, GA was associated with successful reperfusion (OR 2.79, 95% CI 1.02-7.64). In addition, the complication rate was lower with GA (2.7% vs 7%), although the association was not significant in adjusted analysis. While GA and non-GA techniques did not differ significantly in functional outcomes, the influence of GA on angiographic and procedural safety outcomes was location dependent, underscoring the importance of a tailored anesthesia technique in MT procedures.

Comparative Analysis of Mechanical Thrombectomy Outcomes of Middle Cerebral Artery M1, M2 Superior, and M2 Inferior Occlusion Strokes

BackgroundThe M1 middle cerebral artery (MCA) commonly bifurcates into an M2 superior and an M2 inferior segment. However, MCA anatomy is highly variable rendering classification for mechanical thrombectomy (MT) trials difficult. Safety and effectiveness of M2 MCA stroke thrombectomy stratified by M2 MCA anatomy remains to be explored. MethodsLarge vessel occlusion strokes undergoing MT between 02/2016-08/2022 were reviewed (n=784). M1 (n=431) and M2 MCA (n=118) occlusions were assessed. Among M2 MCA occlusions only prototypical MCA bifurcation anatomy cases were included (n=99). Dominance was assessed based on angiography. Procedural and outcome data was compared between M1, M2 superior and M2 inferior MCA occlusions. ResultsBaseline demographics and periprocedural criteria of M2 superior (n=56) and M2 inferior (n=43) occlusion MTs were comparable. Among M2 inferior cases, the occluded branch was dominant in 41/43 (95.3%) but only in 37/56 (66.1%) among M2 superior cases (p<0.001). The 90-day favorable functional outcome (mRS 0-2) and mortality (mRS 6) rates were 60.0% and 8.9% in the M2 superior, 42.9% and 32.6% in the M2 inferior, and 44.1% and 26.0% in the M1 group (n=431). Compared to M2 superior, M2 inferior favorable outcome rates were lower (p=0.094) and mortality rates were higher (p=0.003) and resembled M1 outcome rates (p=0.750 and p=0.355, respectively). ConclusionIn setting of prototypical MCA bifurcation anatomy, thrombectomy of dominant M2 inferior occlusions had outcome rates like M1 occlusions. In contrast, M2 superior occlusions had significantly lower mortality rates and a trend towards better favorable functional outcome rates.

Immobilization of Heavy Metals by Phosphorus-solubilizing Bacteria and Inhibition of Cd and Pb Uptake by Wheat

Phosphorus-solubilizing microorganisms convert insoluble phosphorus in the soil into phosphorus that can be absorbed by plants. Soluble phosphate combines with heavy metals to form precipitation, reducing the content of available heavy metals, thereby reducing the absorption of heavy metals by crops, which plays an important role in the remediation of heavy metal-contaminated soil. The effects of the immobilization of Cd and Pb and the release of PO43- by the phosphorus-solubilizing bacterium Klebsiella sp. M2 were studied through solution culture experiments. In addition, the effects of strain M2 on wheat uptake of Cd and Pb and its microbiological mechanism were also explored through pot experiments. The results showed that strain M2 reduced the concentrations of Cd and Pb and increased the concentration of PO43- in the solution through cell wall adsorption and induced phosphate precipitation. Pot experiments showed that compared to those in the CK group and inactivated strain M2 group, inoculation with live strain M2 significantly increased （123%-293%） the contents of Ca2-P and Ca8-P in rhizosphere soil, decreased the content of DTPA-Cd （34.48%） and DTPA-Pb （36.72%） in wheat rhizosphere soil, and thus hindered the accumulation of Cd and Pb in wheat grains. Moreover, high-throughput sequencing results showed that strain M2 significantly increased the diversity of wheat rhizosphere bacterial communities； increased the relative abundance of Proteobacteria, Gemmatimonadetes, and Bacteroidota in wheat rhizosphere soil； and increased the proportion of heavy metal-immobilizing and phosphorus-promoting bacteria in wheat rhizosphere soil （mainly Sphingomonas, Nocardioides, Bacillus, Gemmatimonas, and Enterobacter）. These bacterial genera played an important role in immobilizing heavy metals and preventing wheat from absorbing heavy metals. These results provide bacterial resources and theoretical basis for the bioremediation of heavy metal-contaminated farmland.

Comparison of gut microbiota immunity and pathology in specific-pathogen-free chickens with glandular and muscular gastritis using different methods.

The objective of this study is to review different methods to screen for the optimal model for preventing and treating chicken glandular and muscular gastritis syndrome. Twenty-four 40-day-old specific pathogen-free (SPF) chickens were randomly allocated into four groups (N = 6): polyethylene glycol + ammonium chloride group (M1 group), acetic acid + rhubarb group (M2 group), polyethylene glycol + rhubarb group (M3 group), and control group. The control group had free access to water, while the remaining groups received different doses of molding reagents added to their drinking water. The animal models were assessed based on clinical manifestations, histopathology findings, serological analysis, and composition of intestinal microbiota to establish an optimal approach for constructing an avian model of glandular and muscular gastritis. The SPF chickens in each model group exhibited typical symptoms of glandular and muscular gastritis, poor spirit, yellow loose stools with undigested feed, and enlargement and ulceration of the glandular and muscular stomach. Among these groups, the M3 group had the highest incidence rate of 100%. Compared to the control group, the body weight and body temperature of the chicken in the three model groups were reduced, and the glandular and muscular stomachs and duodenum showed different degrees of bleeding, mucosal abscission, and other pathological injuries. Additionally, the levels of serum IL-2 and α-amylase activity decreased while the content of IL-4 increased. After conducting 16s rDNA sequencing, it was observed that the abundance of Bacteroides, Faecalibacterium, and Ruminococcaceae UCG-014 was significantly increased in the model group compared to the control group. Conversely, there was a notable decrease in the levels of Megamonas and Lactobacillus, which are speculated to be associated with arachidonic acid metabolism, the NF-κB signaling pathway, and TNF signaling pathways. The combination of polyethylene glycol and rhubarb emerged as the most effective method for establishing the glandular and muscular gastritis model in SPF chickens. This constructed chicken model displayed distinct signs of damage to the glandular and muscular stomach, inflammatory response, and disturbance in the intestinal flora, thereby providing a foundation for future research on the prevention and treatment of this syndrome.

Inactivated lactobacillus plantarum promoted growth performance, intestine health and antioxidant capacity of juvenile largemouth bass, Micropterus salmoides

To evaluate the effects of inactivated Lactobacillus plantarum (LPM) on carnivorous fish, juvenile largemouth bass [initial body mass: (5.62±0.13) g] were fed five isonitrogenous and isoenergetic diets containing 0 (M0), 200 (M1), 400 (M2), 600 (M3), and 800 (M4) mg/kg LPM for 8 weeks. The results showed that in terms of growth, weight gain rate (WGR) and specific growth rate (SGR) showed significant second-order polynomial trend with increasing LPM supplementation. WGR and SGR of the M3 group were significantly increased by 14.18% and 5.62%, respectively, compared with the M0 group. Significant linear and second order polynomial trends were observed for feed conversion ratio (FCR), protein efficiency ratio (PER) and protein deposition rate (PDR) with the increase in dietary LPM. FCR was significantly reduced by 8.9% in the M2 group compared to the M0 group. In terms of intestinal health, intestinal amylase, intestinal villi number, length and width showed significant second order polynomial trends with increasing LPM supplementation. Significant linear and second order polynomial trends were observed for intestinal lipase activity, liver crude fat content with increasing dietary LPM. Dietary LPM supplementation of 600 mg/kg significantly increased the abundance of beneficial bacteria. In terms of antioxidant capacity, with the increase of LPM supplemental level, superoxide dismutase activity, malondialdehyde content of serum and liver, and liver Cu/Zn-SOD, Keap-1 and TGF-β1 mRNA expression levels showed significant linear and second-order polynomial trend, and Nrf2 mRNA expression level showed a significant second-order polynomial trend. Overall, the appropriate level of LPM (400–600 mg/kg) promoted the growth performance and feed utilization of largemouth bass by increasing the abundance of intestinal bacteria, improving the activities of digestive enzymes and antioxidant enzymes, and up-regulating the mRNA expressions of genes related to antioxidants.

Phytostabilization of Heavy Metals and Fungal Community Response in Manganese Slag under the Mediation of Soil Amendments and Plants.

The addition of soil amendments and plants in heavy metal-contaminated soil can result in a significant impact on physicochemical properties, microbial communities and heavy metal distribution, but the specific mechanisms remain to be explored. In this study, Koelreuteria paniculata was used as a test plant, spent mushroom compost (SMC) and attapulgite (ATP) were used as amendments, and manganese slag was used as a substrate. CK (100% slag), M0 (90% slag + 5% SMC + 5% ATP) and M1 (90% slag + 5% SMC + 5% ATP, planting K. paniculata) groups were assessed in a pilot-scale experiment to explore their different impacts on phytoremediation. The results indicated that adding the amendments significantly improved the pH of the manganese slag, enhancing and maintaining its fertility and water retention. Adding the amendments and planting K. paniculata (M1) significantly reduced the bioavailability and migration of heavy metals (HMs). The loss of Mn, Pb and Zn via runoff decreased by 15.7%, 8.4% and 10.2%, respectively, compared to CK. K. paniculata recruited and enriched beneficial fungi, inhibited pathogenic fungi, and a more stable fungal community was built. This significantly improved the soil quality, promoted plant growth and mitigated heavy metal toxicity. In conclusion, this study demonstrated that the addition of SMC-ATP and planting K. paniculata showed a good phytostabilization effect in the manganese slag and further revealed the response process of the fungal community in phytoremediation.

Site Dependency of Anodal Transcranial Direct-Current Stimulation on Reaction Time and Transfer of Learning during a Sequential Visual Isometric Pinch Task.

Considering the advantages of brain stimulation techniques in detecting the role of different areas of the brain in human sensorimotor behaviors, we used anodal transcranial direct-current stimulation (a-tDCS) over three different brain sites of the frontoparietal cortex (FPC) in healthy participants to elucidate the role of these three brain areas of the FPC on reaction time (RT) during a sequential visual isometric pinch task (SVIPT). We also aimed to assess if the stimulation of these cortical sites affects the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: (1) left primary motor cortex (M1), (2) left dorsolateral prefrontal cortex (DLPFC), (3) left posterior parietal cortex (PPC), and (4) sham. A-tDCS (0.3 mA, 20 min) was applied concurrently with the SVIPT, in which the participants precisely controlled their forces to reach seven different target forces from 10 to 40% of the maximum voluntary contraction (MVC) presented on a computer screen with the right dominant hand. Four test blocks were randomly performed at the baseline and 15 min after the intervention, including sequence and random blocks with either hand. Our results showed significant elongations in the ratio of RTs between the M1 and sham groups in the sequence blocks of both the right-trained and left-untrained hands. No significant differences were found between the DLPFC and sham groups and the PPC and sham groups in RT measurements within the SVIPT. Our findings suggest that RT improvement within implicit learning of an SVIPT is not mediated by single-session a-tDCS over M1, DLPFC, or PPC. Further research is needed to understand the optimal characteristics of tDCS and stimulation sites to modulate reaction time in a precision control task such as an SVIPT.

Shift from Pro- to Anti-Inflammatory Phase in Pelvic Floor Muscles at Postpartum Matches Histological Signs of Regeneration in Multiparous Rabbits.

Background and Objectives: Pelvic floor muscles (PFM) play a core role in defecation and micturition. Weakening of PFM underlies urogynecological disorders such as pelvic organ prolapse and stress urinary incontinence. Vaginal delivery damages PFM. Muscle trauma implies an inflammatory response mediated by myeloid cells, essential for subsequent recovery. Molecular signaling characterizing the pro-inflammatory phase shifts M1 macrophages to M2 macrophages, which modulate muscle repair. The present study aimed to evaluate histological characteristics and the presence of M1 and M2 macrophages in bulbospongiosus (Bsm) and pubococcygeus muscles (Pcm). Materials and Methods: Muscles from young nulliparous (N) and multiparous rabbits on postpartum days three (M3) and twenty (M20) were excised and histologically processed to measure the myofiber cross-sectional area (CSA) and count the centralized myonuclei in hematoxylin-eosinstained sections. Using immunohistochemistry, M1 and M2 macrophages were estimated in muscle sections. Kruskal-Wallis or one-way ANOVA testing, followed by post hoc tests, were conducted to identify significant differences (p < 0.05). Results: The myofiber CSA of both the Bsm and Pcm of the M3 group were more extensive than those of the N and M20 groups. Centralized myonuclei estimated in sections from both muscles of M20 rabbits were higher than those of N rabbits. Such histological outcomes matched significant increases in HLA-DR immunostaining in M3 rabbits with the CD206 immunostaining in muscle sections from M20 rabbits. Conclusions: A shift from the pro- to anti-inflammatory phase in the bulbospongiosus and pubococcygeus muscles of multiparous rabbits matches with centralized myonuclei, suggesting the ongoing regeneration of muscles.

Larval biomass production from the co-digestion of mushroom root waste and soybean curd residues by black soldier fly larvae (Hermetia illucens L.).

People are increasingly using black soldier fly larvae (BSFL) as a sustainable waste management solution. They are high in protein and other essential nutrients, making them an ideal food source for livestock, poultry, and fish. Prior laboratory studies with BSFL developed on pure mushroom root waste (MRW) showed poor conversion efficiency compared to a regular artificial diet. Therefore, we mixed the nutrient-rich soybean curd residues (SCR) with MRW in different ratios (M2-M5). Pure mushroom root waste (M1, MRW 100%) had the lowest survival rate (86.2%), but it increased up to 96.9% with the SCR percentage increasing. M1 had the longest developmental period (31.1days) and the lowest BSFL weight (7.4g). However, the addition of SCR reduced the development time to 22.0 and 21.5days in M4 (MRW 40%, SCR 60%) and M5 (MRW 20%, SCR 80%), respectively, and improved the larval weight to 10.9g in M4 and 11.8g in M5. Other groups did not have as much feed conversion ratio (FCR) (8.4 for M4 and M5), bioconversion (M4 5.4%; M5 5.9%), or lipid content (M4 25.2%; M5 24.3%). These mixtures did.Compare this to M1. We observed better results, with no significant differences between the M4 and M5 groups and their parameters. In the present study, our main target was to utilize more MRW. Therefore, we preferred the M4 group in our nutritional and safety investigation and further compared it with the artificial diet (M7). The heavy metals and essential amino acids (histidine 3.6%, methionine 2.7%, and threonine 3.8%) required for human consumption compared to WHO/FAO levels showed satisfactory levels. Furthermore, fatty acids (capric acid 1.9%, palmitic acid 15.3%, oleic acid 17.3%, and arachidonic acid 0.3%) also showed higher levels in M4 than M7. The SEM images and FT-IR spectra from the residues showed that the BSFL in group M4 changed the structure of the compact fiber to crack and remove fibers, which made the co-conversion mixture better.

Activation of M2 macrophage autophagy by rapamycin increases the radiosensitivity of colorectal cancer xenografts.

Tumor-associated macrophages (TAMs) are intimately involved in cancer radiochemotherapy resistance. However, the mechanism by which macrophages affect radiosensitivity through autophagy remains unclear. The purpose of our study was to investigate how activating autophagy in type-II macrophages (M2) by using rapamycin (RAP) would affect the radiosensitivity of colorectal cancer (CRC) xenografts. A nude mouse CRC model was established by injecting LoVo CRC cells. After tumor formation, supernatant from M2 cells (autophagy-unactivated), autophagy-activated M2 cells, or autophagy-downregulated M2 cells was injected peritumorally. All tumor-bearing mice were irradiated with 8-Gy X-rays twice, and the radiosensitivity of CRC xenografts was analyzed in each group. The mass, volume, and microvessel density (MVD) of tumors in the autophagy-unactivated M2 group significantly increased; however, supernatant from M2 cells that were autophagy-activated by rapamycin significantly decreased tumor weight, volume, and MVD compared with negative control. Combining bafilomycin A1 (BAF-A1) with RAP treatment restored the ability of the M2 supernatant to increase tumor mass, volume, and MVD. Immunohistochemical and Western blot results showed that compared with the negative control group, supernatant from M2 cells that were not activated by autophagy downregulated the expression of Livin and Survivin in tumor tissues; activation of M2 autophagy further downregulated the protein levels. Therefore, autophagy-activated M2 supernatant can downregulate the expression of the antiapoptotic genes Livin and Survivin in CRC xenografts, improving the radiosensitivity of CRC by inducing apoptosis in combination with radiotherapy and inhibiting the growth of transplanted tumors.

Dietary supplementation of micelle silymarin enhances the antioxidant status, innate immunity, growth performance, resistance against Vibrio parahaemolyticus infection, and gut morphology in Pacific white shrimp (Litopenaeus vannamei)

Silymarin, a flavonoid compound derived from the milk thistle plant (Silybum marianum) is well-known for its hepatoprotective, antioxidant, immunomodulatory, and anti-inflammatory properties. Therefore, this study sought to evaluate the effect of silymarin and micelle silymarin (MS) supplementation on Pacific white shrimp (Litopenaeus vannamei). The experimental diets were formulated to include MS at levels of 0.25, 0.5, 1.0, 2.0, and 4.0 g/kg or silymarin at levels of 1.0 and 2.0 g/kg in the basal diet (Con, M0.25, M0.5, M1, M2, M4, S1 and S2, respectively). Juvenile shrimp (0.98 g) were fed with experimental diets (four replicates) for 42 days. The growth metrics were significantly (P < 0.05) increased in M0.25, M0.5, and M1 groups compared to the Con group. Feed conversion ratio decreased (P < 0.05) in M0.5, M1, and M2 groups, whereas the protein efficiency ratio increased (P < 0.05) in M0.5 and M1 groups compared to the Con group. Phenoloxidase, lysozyme, glutathione peroxidase, and superoxide dismutase activities were enhanced (P < 0.05), with the highest levels observed in the M0.5 group. Malondialdehyde level decreased (P < 0.05) in M1 and M2 groups compared to the Con group. Total protein increased (P < 0.05) in M0.25, M0.5 and S1 groups compared to the Con group. AST levels were significantly reduced (P < 0.05) in shrimp fed M0.5, M1, M2, M4, and S2 groups, and ALT levels decreased (P < 0.05) in M1 and S2 groups compared to Con group. Wall thickness was significantly higher (P < 0.05) in the M0.5 group, and villi length increased (P < 0.05) in M0.25, M0.5, and S1 groups. The resistance against Vibrio parahaemolyticus increased; however, no significant differences in cumulative survival were observed (P ˃ 0.05). Significantly higher (P < 0.05) proPO levels were observed in M0.5, M1, M2, M4, and S2 groups, whereas higher (P < 0.05) TLR-3 levels were observed in M1 and M2 groups compared to the Con group. TNF-α expression decreased (P < 0.05) in all other dietary treatments compared to the Con group. The findings suggest that dietary silymarin and MS can enhance growth, immune response, antioxidant capacity, gut morphology, and immune gene expression, while reducing lipid peroxidation and inflammation in Pacific white shrimp. The shrimp performance shows no significant difference between silymarin and MS groups at 1% and 2% levels. The optimal suggested inclusion level of MS in shrimp feed is 0.5–1.0 g/kg.

Prognosis and influencing factors of follicular thyroid cancer.

Follicular thyroid cancer (FTC) is prone to distant metastasis, and patients with distant metastasis often have poor prognosis. In this study, the impact of metastasis and other relevant factors on the prognosis of follicular thyroid carcinoma was examined. This was a retrospective study. Data were obtained from Zhejiang Cancer Hospital, Sun Yat-sen University Cancer Center and Hangzhou First People's Hospital affiliated with Zhejiang University School of Medicine, from January 2009 to June 2021 for 153 FTC patients. The patients were assigned into three groups according to their distant metastasis: distant metastasis at initial diagnosis (M1), distant metastasis during follow-up (M2), and no evidence of distant metastasis over the course of the study (M0). Data were collected and summarized on clinical data, laboratory parameters, imaging features, postoperative pathologic subtypes, and metastases. The Cox proportional hazard model was used to perform the univariate and multivariate analysis. Kaplan-Meier curves were used to evaluate cancer-specific survival (CSS). Based on metastasis, the patients were assigned into three groups, including 31 in the M1 group, 15 in the M2 group, and 107 in the M0 group. These individuals were followed up for an average of 5.9 years, and the group included 46 patients with distant metastasis (31 confirmed at diagnosis and 15 found during follow-up). Univariate Cox regression analysis showed that age, Hashimoto's thyroiditis (HT), surgery method, postoperative adjuvant therapy, histologic subtype, nodule size, calcification, TSH, and distant metastasis all impacted prognosis. Multivariate Cox regression analysis suggested that histologic subtype (widely invasive; HR: 7.440; 95% CI: 3.083, 17.954; p < 0.001), nodule size (≥40 mm; HR: 8.622; 95% CI: 3.181, 23.369; p < 0.001) and distant metastasis (positive; HR: 6.727; 95% CI: 2.488, 18.186; p < 0.001) were independent risk factors affecting the prognosis of follicular thyroid cancer. Histologic subtype, nodule size, and distant metastasis are important risk factors for the prognosis of follicular thyroid cancer. Patients with metastatic follicular thyroid cancer have a poor prognosis, especially with metastasis at the time of initial diagnosis. As a result, this group of patients requires individualized treatment and closer follow-up.

Biomechanical characteristics of a novel interspinous distraction fusion device in the treatment of lumbar degenerative diseases: a finite element analysis

BackgroundA novel interspinous distraction fusion (ISDF) device has been used to treat lumbar degenerative diseases. As a minimally invasive technique, ISDF differs from the traditional interspinous process distraction devices. Currently, biomechanical studies on ISDF are rare.ObjectiveTo investigate the biomechanical properties of the ISDF device (BacFuse) which is used to treat lumbar degenerative diseases.MethodsThree-dimensional L3-L5 models were created. The models were divided into four groups: intact (M1), local decompression alone (M2), internal fixation alone (M3) and local decompression combined with internal fixation (M4), based on different surgical procedures. Local laminectomy was performed to resect the lower part of the L4 lamina and the upper part of the L5 lamina at the right lamina of L4/5 in the M2 and M4 groups. After meshing the models elements, Abaqus were used to perform the finite element (FE) analysis. The intervertebral range of motion (ROM) was measured during flexion, extension, left lateral bending, right lateral bending, left rotation and right rotation under a follower load of 400 N with a 7.5Nm moment. The distributions of disc and facet joint stresses were observed and recorded. Spinal vertebral stress was compared, and internal fixation device stress was observed.ResultsThe ROM of L4/5 in M2 increased in flexion, extension, left lateral bending, right lateral bending, left rotation and right rotation compared with that in M1. In all motion directions, the ROM at L4/5 decreased, and the ROM at L3/4 increased after implantation of the ISDF device in M3 and M4 groups. The disc stress and facet joint stresses in the instrumented segment decreased after implantation of the ISDF device. The spinous process loaded a certain amount of stress in M3 and M4 groups. The spikes of the internal fixation device were loaded with the maximum stress.ConclusionBacFuse exhibited a reduction in intervertebral ROM, as well as decreased stress on the intervertebral disc and facet joint, while also demonstrating a discernible impact on the upper adjacent segment.