Potential applications of single-incision laparoscopic totally preperitoneal hernioplasty.

BACKGROUND: The totally preperitoneal (TPP) approach is a new concept that was recently introduced. Although the TPP approach combined with single-incision laparoscopic hernia repair has its own advantages, there is little evidence reflecting the characteristics and feasibility of either approach. AIM: To analyze the potential applications of single-incision laparoscopic TPP (SIL-TPP) inguinal hernia hernioplasty for the treatment of inguinal hernias. METHODS: A total of 152 SIL-TPP surgeries were performed at the First Affiliated Hospital of Ningbo University from February 2019 to November 2022. A single-port, named Iconport, and standard laparoscopic instruments were used during the operation. Demographic data, intraoperative parameters and short-term postoperative outcomes were collected and retrospectively analyzed. RESULTS: The demographic data of 152 patients underwent SIL-TPP were shown in Table 1. The average age was 49.5 years (range from 21 to 81 years). The average body mass index was 27.7 kg/m2 (range from 17.7 kg/m2 to 35.6 kg/m2). SIL-TPP were conducted successfully in 147 patients. Three patients were converted to the SIL-transabdominal preperitoneal laparoscopic herniorrhaphy at the initial stage of the study due to a lack of experience. In 2 patients with incisional hernias, an auxiliary operation hole was added during the SIL-TPP procedure, as required for surgery. The mean operative time was 64.5 minutes (range: 36.0-110.0 minutes) for unilateral direct and femoral hernias and 81.6 minutes for indirect hernias (range: 40.0-150.0 minutes). The mean postoperative hospital stay was 3.4 days. CONCLUSION: SIL-TPP is feasible and has advantages for inguinal hernia repair. SIL-TPP has potential benefits for patients with various abdominal wall hernias. Consequently, doctors should be encouraged to actively apply the TPP approach combined with a single incision in their daily work.

Neuregulin 4 Attenuates Podocyte Injury and Proteinuria in Part by Activating AMPK/mTOR-Mediated Autophagy in Mice.

In this study, we investigate the effect of neuregulin 4 (NRG4) on podocyte damage in a mouse model of diabetic nephropathy (DN) and we elucidate the underlying molecular mechanisms. In vivo experiments were conducted using a C57BL/6 mouse model of DN to determine the effect of NRG4 on proteinuria and podocyte injury, and in vitro experiments were performed with conditionally immortalized mouse podocytes treated with high glucose and NRG4 to assess the protective effects of NRG4 on podocyte injury. Autophagy-related protein levels and related signaling pathways were evaluated both in vivo and in vitro. The involvement of the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was detected using chloroquine or AMPK inhibitors. The results showed that the AMPK/mTOR pathway was involved in the protective roles of NRG4 against high glucose-mediated podocyte injury. Also, NRG4 significantly decreased albuminuria in DN mice. PAS staining indicated that NRG4 mitigated glomerular volume and mesangium expansion in DN mice. Consistently, western blot and RT-PCR analyses confirmed that NRG4 decreased the expression of pro-fibrotic molecules in the glomeruli of DN mice. The immunofluorescence results showed that NRG4 retained expression of podocin and nephrin, whereas transmission electron microscopy revealed that NRG4 alleviated podocyte injury. In DN mice, NRG4 decreased podocyte apoptosis and increased expression of nephrin and podocin, while decreasing the expression of desmin and HIF1α. Overall, NRG4 improved albuminuria, glomerulosclerosis, glomerulomegaly, and hypoxia in DN mice. The in vitro experiments showed that NRG4 inhibited HG-induced podocyte injury and apoptosis. Furthermore, autophagy of the glomeruli decreased in DN mice, but reactivated following NRG4 intervention. NRG4 intervention was found to partially activate autophagy via the AMPK/mTOR signaling pathway. Consequently, when the AMPK/mTOR pathway was suppressed or autophagy was inhibited, the beneficial effects of NRG4 intervention on podocyte injury were diminished. These results indicate that NRG4 intervention attenuates podocyte injury and apoptosis by promoting autophagy in the kidneys of DN mice, in part, by activating the AMPK/mTOR signaling pathway.

Systematic Druggable Genome-Wide Mendelian Randomization Identifies Therapeutic Targets for Functional Outcome After Ischemic Stroke.

BACKGROUND: Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . METHODS AND RESULTS: Cis-expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3-6 versus 0-2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome-wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P<1.892×10-5) or poor functional outcome (modified Rankin Scale 3-6 versus 0-2, P<1.893×10-5). Steiger filtering analysis suggested potential directional stability (P<0.05). Colocalization analysis provided further support for the associations between genetically predicted expression of ABCC2, NRBP1, PI3, and SEMG1 with functional outcome after ischemic stroke. Furthermore, phenome-wide Mendelian randomization revealed additional beneficial indications and few potential safety concerns of therapeutics targeting ABCC2, NRBP1, PI3, and SEMG1, but the robustness of these results was limited by low power. CONCLUSIONS: The present study revealed 4 candidate therapeutic targets for improving functional outcome after ischemic stroke, while the underlying mechanisms need further investigation.

Contrastive learning based method for X-ray and CT registration under surgical equipment occlusion.

Deep learning-based 3D/2D surgical navigation registration techniques achieved excellent results. However, these methods are limited by the occlusion of surgical equipment resulting in poor accuracy. We designed a contrastive learning method that treats occluded and unoccluded X-rays as positive samples, maximizing the similarity between the positive samples and reducing interference from occlusion. The designed registration model has Transformer's residual connection (ResTrans), which enhances the long-sequence mapping capability, combined with the contrast learning strategy, ResTrans can adaptively retrieve the valid features in the global range to ensure the performance in the case of occlusion. Further, a learning-based region of interest (RoI) fine-tuning method is designed to refine the misalignment. We conducted experiments on occluded X-rays that contained different surgical devices. The experiment results show that the mean target registration error (mTRE) of ResTrans is 3.25 mm and the running time is 1.59 s. Compared with the state-of-the-art (SOTA) 3D/2D registration methods, our method offers better performance on occluded 3D/2D registration tasks.

Selective autophagy receptor p62/SQSTM1 inhibits TBK1-IRF7 innate immune pathway in triploid hybrid fish.

The production of type I interferon is tightly regulated to prevent excessive immune activation. However, the role of selective autophagy receptor SQSTM1 in this regulation in teleost remains unknown. In this study, we cloned the triploid fish SQSTM1 (3nSQSTM1), which comprises 1371 nucleotides, encoding 457 amino acids. qRT-PCR data revealed that the transcript levels of SQSTM1 in triploid fish were increased both in vivo and in vitro following spring viraemia of carp virus (SVCV) infection. Immunofluorescence analysis confirmed that 3nSQSTM1 was mainly distributed in the cytoplasm. Luciferase reporter assay results showed that 3nSQSTM1 significantly blocked the activation of interferon promoters induced by 3nMDA5, 3nMAVS, 3nTBK1, and 3nIRF7. Co-immunoprecipitation assays further confirmed that 3nSQSTM1 could interact with both 3nTBK1 and 3nIRF7. Moreover, upon co-transfection, 3nSQSTM1 significantly inhibited the antiviral activity mediated by TBK1 and IRF7. Mechanistically, 3nSQSTM1 decreased the TBK1 phosphorylation and its interaction with 3nIRF7, thereby suppressing the subsequent antiviral response. Notably, we discovered that 3nSQSTM1 also interacted with SVCV N and P proteins, and these viral proteins may exploit 3nSQSTM1 to further limit the host's antiviral innate immune responses. In conclusion, our study demonstrates that 3nSQSTM1 plays a pivotal role in negatively regulating the interferon signaling pathway by targeting 3nTBK1 and 3nIRF7.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

Allogeneic stem cell transplantation in de novo core-binding factor acute myeloid leukemia in first complete remission: data from the EBMT.

Core-binding factor acute myeloid leukemia (CBF-AML) represents 12-15% of all AML cases. Although CBF positivity infers a survival advantage, overall survival (OS) remains dismal. Treatment is with cytarabine/anthracycline-based chemotherapy induction followed by high-dose cytarabine (HiDAC) consolidation. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is reserved for relapse or for patients having not achieved MRD-negativity at high risk for relapse. The role of SCT in first complete remission (CR1) remains controversial and is considered in high risk conditions. In this retrospective, multi-national, European Society for Blood and Marrow Transplantation (EBMT)-based study, we identified 1901 patients with de novo CBF-AML who received an allo-SCT or autologous transplantation (ASCT) in CR1. 65.5% harbored t(8;21) and 34.4% inv(16). In this group, the majority (77%) were treated with allo-SCT in CR1. In multivariate analysis, treatment with allo-SCT was an independent and significant, negative predictor of NRM and OS (HR 4.26, p < 0.0001 and HR 1.67, p = 0.003) and among patients treated with allo-SCT, those treated with MSD had the best outcomes, comparable to those treated with ASCT. There was no interaction between the type of transplant and MRD status at time of SCT. In both, MRD-negative and MRD-positive groups, NRM was worse in the allo-SCT group (MRD-: 12.9% vs 5.2%, p = 0.007; MRD+: 10.6% vs 0%, p = 0.004). We therefore demonstrated that consolidation in CR1 with allo-SCT results in worse outcomes than ASCT. Whether consolidation with ASCT yields better outcomes than chemotherapy alone or chemotherapy in combination with Gemtuzumab Ozogamicin is yet to be investigated.

The profile and prognostic significance of bone marrow T-cell differentiation subsets in adult AML at diagnosis.

Background: T lymphocytes in tumor microenvironment play a pivotal role in the anti-tumor immunity, and the memory of T cells contributes to the long-term protection against tumor antigens. Compared to solid tumors, studies focusing on the T-cell differentiation in the acute myeloid leukemia (AML) bone marrow (BM) microenvironment remain limited. Patients and methods: Fresh BM specimens collected from 103 adult AML patients at diagnosis and 12 healthy donors (HDs) were tested T-cell differentiation subsets by multi-parameter flow cytometry. Results: CD4 and CD8 T-cell compartments had different constituted profiles of T-cell differentiated subsets, which was similar between AML patients and HDs. Compared to HDs, AML patients as a whole had a significantly higher proportion of CD8 effector T cells (Teff, P = 0.048). Moreover, the T-cell compartment of AML patients with no DNMT3A mutations skewed toward terminal differentiation at the expense of memory T cells (CD4 Teff: P = 0.034; CD8 Teff: P = 0.030; CD8 memory T: P = 0.017), whereas those with mutated DNMT3A had a decrease in CD8 naïve T (Tn) and CD4 effector memory T cells (Tem) as well as an increase in CD4 central memory T cells (Tcm) (P = 0.037, 0.053 and 0.053). Adverse ELN genetic risk correlated with a lower proportion of CD8 Tn. In addition, the low proportions of CD4 Tem and CD8 Tn independently predicted poorer relapse-free survival (RFS, HR [95%CI]: 5.7 (1.4-22.2), P = 0.017 and 4.8 [1.3-17.4], P = 0.013) and event-free survival (EFS, HR [95% CI]: 3.3 (1.1-9.5), P = 0.029; 4.0 (1.4-11.5), P = 0.010), respectively. Conclusions: AML patients had abnormal profiles of BM T-cell differentiation subsets at diagnosis, which was related to DNMT3A mutations. The low proportions of CD4 Tem and CD8 Tn predicted poor outcomes.

Clinical features and prognostic model for viral encephalitis after allogeneic haematopoietic stem cell transplantation.

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.

Spin-Mechanical Coupling in 2D Antiferromagnet CrSBr.

Spin-mechanical coupling is vital in diverse fields including spintronics, sensing, and quantum transduction. Two-dimensional (2D) magnetic materials provide a unique platform for investigating spin-mechanical coupling, attributed to their mechanical flexibility and novel spin orderings. However, studying their spin-mechanical coupling presents challenges in probing mechanical deformation and thermodynamic property changes at the nanoscale. Here we use nano-optoelectromechanical interferometry to mechanically detect the phase transition and magnetostriction effect in multilayer CrSBr, an air-stable antiferromagnet with large magnon-exciton coupling. The transitions among antiferromagnetism, spin-canted ferromagnetism, and paramagnetism are visualized. Nontrivial magnetostriction coefficient 2.3 × 10-5 and magnetoelastic coupling strength on the order of 106 J/m3 have been found. Moreover, we demonstrate the substantial tunability of the magnetoelastic constant by nearly 50% via gate-induced strain. Our findings demonstrate the strong spin-mechanical coupling in CrSBr and pave the way for developing sensitive magnetic sensing and efficient quantum transduction at the atomically thin limit.

A short-term functional recovery comparison of therapeutic plasma exchange and immunoadsorption in severe acute neuroimmune diseases.

OBJECTIVE: To compare the differential impact of recombinant protein A immunoadsorption (PAIA) or therapeutic plasma exchange (TPE) on neurological functional improvement and quality of life in patients afflicted with severe acute neuroimmune diseases, including Guillain-Barré syndrome (GBS), myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and anti-NMDA receptor encephalitis (NMDARE). METHODS: The retrospective study included 29 patients with moderate to severe disability (modified Rankin scale, mRS≥3) due to acute neuroimmune diseases at the second Xiangya hospital from January 2021 to January 2023. The clinical efficacy of PAIA and TPE in improving neurological function (ΔmRS≥1) and the difference in favorable functional outcomes (mRS 0-2) at three months were evaluated. The impact of both treatments on patients' health-related quality of life (HRQoL) was assessed using a visual analog scale (EQ-VAS) score ranging from 0 to 100. RESULTS: The findings revealed that the PAIA group exhibited a significantly higher rate of improvement in modified Rankin scale (mRS) scores (ΔmRS≥1) at the three-month follow-up compared to the TPE group (94.4 % vs. 54.5 %, p = 0.018). However, no statistically significant difference was observed between the two treatment modalities in terms of favorable neurological functional outcomes at the three-month mark. Furthermore, the PAIA group demonstrated a significantly higher EQ-VAS score at 14 days post-treatment compared to the TPE group (60.0 vs. 47.7, p = 0.017). CONCLUSION: In the short-term management of severe acute neuroimmune diseases, PAIA may present a greater probability of improving neurological function and facilitating an earlier enhancement of quality of life compared to TPE.

Oncoprotein-induced transcript 3 protein-enriched extracellular vesicles promotes NLRP3 ubiquitination to alleviate acute lung injury after cardiac surgery.

Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.

Coupling of ß-adrenergic and Hippo pathway signaling: Implications for heart failure pathophysiology and metabolic therapy.

Activation of the sympatho-ß-adrenergic receptor (ßAR) system is the hallmark of heart disease with adverse consequences that facilitate the onset and progression of heart failure (HF). Use of ß-blocking drugs has become the front-line therapy for HF. Last decade has witnessed progress in research demonstrating a pivotal role of Hippo pathway in cardiomyopathy and HF. Clinical studies have revealed myocardial Hippo pathway activation/YAP-TEAD1 inactivation in several types of human cardiomyopathy. Experimental activation of cardiac Hippo signaling or inhibition of YAP-TEAD1 have been shown to leads dilated cardiomyopathy with severe mitochondrial dysfunction and metabolic reprogramming. Studies have also convincingly shown that stimulation of ßAR activates cardiac Hippo pathway with inactivation of the down-stream effector molecules YAP/TAZ. There is strong evidence for the adverse consequences of the ßAR-Hippo signaling leading to HF. In addition to promoting cardiomyocyte death and fibrosis, recent progress is the demonstration of mitochondrial dysfunction and metabolic reprogramming mediated by ßAR-Hippo pathway signaling. Activation of cardiac ßAR-Hippo signaling is potent in downregulating a range of mitochondrial and metabolic genes, whereas expression of pro-inflammatory and pro-fibrotic factors are upregulated. Coupling of ßAR-Hippo pathway signaling is mediated by several kinases, mechanotransduction and/or Ca2+ signaling, and can be blocked by ß-antagonists. Demonstration of the converge of ßAR signaling and Hippo pathway bears implications for a better understanding on the role of enhanced sympathetic nervous activity, efficacy of ß-antagonists, and metabolic therapy targeting this pathway in HF. In this review we summarize the progress and discuss future research directions in this field.

MOCHA's advanced statistical modeling of scATAC-seq data enables functional genomic inference in large human cohorts.

Single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) is being increasingly used to study gene regulation. However, major analytical gaps limit its utility in studying gene regulatory programs in complex diseases. In response, MOCHA (Model-based single cell Open CHromatin Analysis) presents major advances over existing analysis tools, including: 1) improving identification of sample-specific open chromatin, 2) statistical modeling of technical drop-out with zero-inflated methods, 3) mitigation of false positives in single cell analysis, 4) identification of alternative transcription-starting-site regulation, and 5) modules for inferring temporal gene regulatory networks from longitudinal data. These advances, in addition to open chromatin analyses, provide a robust framework after quality control and cell labeling to study gene regulatory programs in human disease. We benchmark MOCHA with four state-of-the-art tools to demonstrate its advances. We also construct cross-sectional and longitudinal gene regulatory networks, identifying potential mechanisms of COVID-19 response. MOCHA provides researchers with a robust analytical tool for functional genomic inference from scATAC-seq data.

A case report on congenital hypothyroidism and alpha thalassemia in children with anemia and muscle damage as the main manifestation.

RATIONALE: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. PATIENT CONCERNS: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. DIAGNOSES: The child was diagnosed with CH with alpha thalassemia. INTERVENTIONS: The patient was treated with levothyroxine sodium and anemia correction. OUTCOMES: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CONCLUSIONS: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. LESSON: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.

Concept for power scaling by harmonic beam coaxial combination in an intra-cavity frequency doubling laser.

A new method of harmonic beam coaxial combination (HBCC) from two intra-cavity frequency doubling branches was demonstrated. Firstly, two identical nanosecond (ns) 532 nm green lasers with high power and good beam quality were created. Each green laser was constructed of an intra-cavity frequency doubling branch based on a laser diode (LD) end-pumped acousto-optical (AO) Q-switched 1064 nm Nd:YVO4 laser in a LiB3O5 (LBO) nonlinear crystal. Each branch generated about 45 W green output at a 50 kHz pulse repetition rate (PRR) with diffraction limited beam quality. The first green beam was injected into the LBO crystal in the second branch, and the pulses from the two branches did not exist simultaneously. Then, the HBCC was performed. Consequently, an 83 W combined green output power at 532 nm was obtained with a combination efficiency of 92.2%. The PRR of the HBCC pulse was doubled to be 100 kHz, with a pulse width of about 22 ns, corresponding to a single pulse energy of 0.83 mJ and a peak power of 37.73 kW. The combined beam quality factor was measured to be M x2 = 1.80 in the x direction and M y2 = 1.71 in the y direction, respectively. Moreover, many more beams could also be combined with this method for further scaling the green power.

View-shuffled clustering via the modified Hungarian algorithm.

In the majority of existing multi-view clustering methods, the prerequisite is that the data have the correct cross-view correspondence. However, this strong assumption may not always hold in real-world applications, giving rise to the so-called View-shuffled Problem (VsP). To address this challenge, we propose a novel multi-view clustering method, namely View-shuffled Clustering via the Modified Hungarian Algorithm (VsC-mH). Specifically, we first establish the cross-view correspondence of the shuffled data utilizing strategies of the global alignment and modified Hungarian algorithm (mH) based intra-category alignment. Subsequently, we generate the partition of the aligned data employing matrix factorization. The fusion of these two processes facilitates the interaction of information, resulting in improved quality of both data alignment and partition. VsC-mH is capable of handling the data with alignment ratios ranging from 0 to 100%. Both experimental and theoretical evidence guarantees the convergence of the proposed optimization algorithm. Extensive experimental results obtained on six practical datasets demonstrate the effectiveness and merits of the proposed method.

Structural characterization and immune activity evaluation of a polysaccharide from Lyophyllum Decastes.

An innovative acidic hydrolysate fingerprinting workflow was proposed for the characterization of Lyophyllum Decastes polysaccharide (LDP) by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The crude polysaccharides were firstly separated and purified by using DE-52 column and the BRT GPC purification system, respectively. The molecular weight and monosaccharide content of homogeneous polysaccharides were ascertained by utilizing HPGPC and ion chromatography separately. Secondly, the linkage of LDP was identified by methylation analysis and 1D/2D NMR spectra. The UPLC-MS/MS was used to scan and identify the acidic hydrolysate products of LDP using the PGC column. The oligosaccharides were collected by chromatography and identified by mass spectrometry. Thirdly, the expression of IL-1, IL-6, iNOS, TNF-α and IFNAR-I was measured in order to assess the immunological activity of LDP. Besides, the targeted receptors identification of polysaccharides was performed by screening the expression of TLRs family protein. The results showed that oligosaccharide fragments with different molecular weights can be obtained by partial hydrolysis, which further verified that the structures of LDP polysaccharides was a 1-6-linked ß-glucan. Moreover, the LDP polysaccharide can up-regulate the content of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I and plays an important immunoregulation role through TLRs family.

Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.

Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.

Sphingosine-1 phosphate receptor 1 (S1PR1) expression maintains stemness of acute myeloid leukemia stem cells.

Acute myeloid leukemia (AML) arises from leukemia stem cells (LSCs) and is maintained by cells which have acquired features of stemness. We compared transcription profiles of AML cells with/without stem cell features defined as in vitro clonogenicity and serial engraftment in immune-deficient mice xenograft model. We used multi-parameter flow cytometry (MPFC) to separate CD34+ bone marrow-derived leukemia cells into sphingosine-1 phosphate receptor 1 (S1PR1)+ and S1PR1- fractions. Cells in the S1PR1+ fraction demonstrated significantly higher clonogenicity and higher engraftment potential compared with those in the S1PR1- fraction. In contrast, CD34+ bone marrow cells from normal samples showed reduced clonogenicity in the S1PR1+ fraction compared with the S1PR1- fraction. Inhibition of S1PR1 expression in an AML cell line reduced the colony-forming potential of KG1 cells. Transcriptomic analyses and rescue experiments indicated PI3K/AKT pathway and MYBL2 are downstream mediators of S1PR1-associated stemness. These findings implicate S1PR1 as a functional biomarker of LSCs and suggest its potential as a therapeutic target in AML treatment.