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Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored. [ABSTRACT FROM AUTHOR]

The proliferation of remote sensing image data in recent years has posed a pressing need for efficient compression techniques due to constrained transmission bandwidth. While lossless compression preserves image fidelity, it falls short of meeting real-time demands. Conversely, conventional lossy compression methods can attain high compression ratios for real-time applications, but often introduce issues like block artifacts, blurring, and distortions in the decompressed images. Hence, we propose the Global Feature-Assisted Segmentation Compression Network (GFSCompNet) as a solution for high compression ratio lossy compression. Initially, we design a segmentation network utilizing a dual-branch global feature-assisted segmentation approach to precisely detect small targets in remote sensing images. On the compression side of the network, we leverage an attention mechanism and code rate allocation technique to seamlessly merge the segmented small target information with the original image, thereby allocating a higher compression code rate to the small target region. Furthermore, a joint hyper-priority decoding and entropy coding estimation network is proposed to further remove the redundancy in the potential representation and improve the compression ratio. Experimental results conducted under conditions of high compression ratios and comparable bit rates demonstrate that our approach yields higher-quality reconstructed images compared to the JPEG algorithm and outperforms other deep learning-based image compression methods. Additionally, it effectively preserves small target information, thereby enhancing the interpretability of machine learning models. [ABSTRACT FROM AUTHOR]

High-purity ethylene production from CO2 electroreduction (CO2RR) is a coveted, yet arduous feat because the product stream comprises a blend of unreacted CO2, H2, and other off-target CO2 reduction products. Here we present an indirect reduction strategy for CO2-to-ethylene conversion, one that employs 2-bromoethanol (Br-EO) as a mediator. Br-EO is initially generated from CO2RR and subsequently undergoes reduction to ethylene without the need for energy-intensive separation steps. The optimized AC-Ag/C catalyst with Cl incorporation reduces the energy barrier of the debromination step during Br-EO reduction, and accelerates the mass-transfer process, delivering a 4-fold decrease of the relaxation time constant. Resultantly, AC-Ag/C achieved a FEethylene of over 95.0 ± 0.36% at a low potential of −0.08 V versus reversible hydrogen electrode (RHE) in an H-type cell with 0.5 M KCl electrolyte, alongside a near 100% selectivity within the range of −0.38 to −0.58 V versus RHE. Through this indirect strategy, the average ethylene purity within 6-hour electrolysis was 98.00 ± 1.45 wt%, at −0.48 V (vs RHE) from the neutralized electrolyte after CO2 reduction over the Cu/Cu2O catalyst in a flow-cell. Producing high-purity ethylene from direct CO2 electroreduction is challenging due to unwanted byproducts and unreacted CO2. Here, authors introduce an indirect method using 2-bromoethanol as a mediator, which reduces to ethylene with near-unity selectivity over an Ag catalyst. [ABSTRACT FROM AUTHOR]

Purpose: To predict severe inflammatory response after neoadjuvant radiochemotherapy in locally advanced rectal cancer (RC) patients using magnetic resonance imaging (MRI) radiomics models. Methods: This retrospective study included patients who underwent radical surgery for RC cancer after neoadjuvant radiochemotherapy between July 2017 and December 2019 at XXX Hospital. MRI radiomics features were extracted from T2WI images before (pre-nRCT-RF) and after (post-nRCT-RF) neoadjuvant radiochemotherapy, and the variation of radiomics features before and after neoadjuvant radiochemotherapy (delta-RF) were calculated. Eight, eight, and five most relevant features were identified for pre-nRCT-RF, post-nRCT-RF, and delta-RF, respectively. Results: Eighty-six patients were included and randomized 3:1 to the training and test set (n = 65 and n = 21, respectively). The prediction model based on delta-RF had areas under the curve (AUCs) of 0.80 and 0.85 in the training and test set, respectively. A higher rate of difficult operations was observed in patients with severe inflammation (65.5% vs. 42.9%, P = 0.045). Conclusion: The prediction model based on MRI delta-RF may be a useful tool for predicting severe inflammatory response after neoadjuvant radiochemotherapy in locally advanced RC patients. [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatase SHP2 activates RAS signaling, which is a novel target for colorectal cancer (CRC) therapy. However, SHP2 inhibitor monotherapy is ineffective for metastatic CRC and a combination therapy is required. In this study, we aimed to improve the antitumor efficacy of SHP2 inhibition and try to explore the resistance mechanism of SHP2 inhibitor. Results showed that WWP1 promoted the proliferation of CRC cells. Genetic or pharmacological inhibition of WWP1 enhanced the effect of SHP2 inhibitor in suppressing tumor growth in vitro and in vivo. WWP1 may mediate feedback reactivation of AKT signaling following SHP2 inhibition. Furthermore, nomogram models constructed with IHC expression of WWP1 and SHP2 greatly improved the accuracy of prognosis prediction for patients with CRC. Our findings indicate that WWP1 inhibitor I3C can synergize with SHP2 inhibitor and is expected to be a new strategy for clinical trials in treating advanced CRC patients. [ABSTRACT FROM AUTHOR]

Adaptation to different ecological niches is considered one of the main drivers of species diversification, also in cryptic species complexes, notwithstanding their morphological stasis. We here review all the published information on ecological differentiation within cryptic species complexes within the phylum Rotifera. We found 177 instances of cryptic species identified genetically, published in 101 papers. Only a subset of the papers contained available information on ecological differences and only for two of the 54 known complexes, namely Brachionus calyciflorus s.l. and Brachionus plicatilis s.l., sufficient data were available for analyses of ecological differences. For the B. calyciflorus complex, B. fernandoi consistently occurred at a significantly lower temperature than the other species in the complex; no differences were found for other environmental variables. For the B. plicatilis complex, B. paranguensis occurred in waters with higher pH than the other species; no differences were found for other environmental variables. These results, even if preliminary and based on scattered information, reveal that adaptation to different ecological niches exists also between closely related species. Our aim is to showcase this interesting field of research spurring further detailed studies to focus on the mechanisms of ecological speciation using rotifer cryptic species as a model system. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages play a crucial role in the tumor microenvironment. Tripartite motif 59 (TRIM59), a member of the tripartite motif (TRIM) family, is known to be associated with immunological diseases and macrophage activation. The functional and molecular mechanisms by which TRIM59 affects the occurrence and development of colorectal cancer (CRC) through macrophages are still not well understood. To address this, we generated macrophage-specific TRIM59 conditional knockout mice and utilized these mice to establish colitis-associated cancer and MC38 transplanted CRC models for further investigation. We found that the deficiency of TRIM59 in macrophages inhibited colorectal tumorigenesis in mice. This tumor-suppressive effect was achieved by promoting the activation of M1 macrophages via STAT1 signaling pathway. Further mechanistic studies revealed that TRIM59 could regulate macrophage polarization by ubiquitinating and degrading STAT1. These findings provide evidence that TRIM59 deficiency promotes M1 macrophage activation and inhibits CRC through the STAT1 signaling pathway, suggesting that the TRIM59/STAT1 signaling pathway may be a promising target for CRC. [ABSTRACT FROM AUTHOR]

Chloroaluminate ionic liquids selectively transform (waste) polyolefins into gasoline-range alkanes through tandem cracking-alkylation at temperatures below 100 °C. Further improvement of this process necessitates a deep understanding of the nature of the catalytically active species and the correlated performance in the catalyzing critical reactions for the tandem polyolefin deconstruction with isoalkanes at low temperatures. Here, we address this requirement by determining the nuclearity of the chloroaluminate ions and their interactions with reaction intermediates, combining in situ 27Al magic-angle spinning nuclear magnetic resonance spectroscopy, in situ Raman spectroscopy, Al K-edge X-ray absorption near edge structure spectroscopy, and catalytic activity measurement. Cracking and alkylation are facilitated by carbenium ions initiated by AlCl3-tert-butyl chloride (TBC) adducts, which are formed by the dissociation of Al2Cl7− in the presence of TBC. The carbenium ions activate the alkane polymer strands and advance the alkylation cycle through multiple hydride transfer reactions. In situ 1H NMR and operando infrared spectroscopy demonstrate that the cracking and alkylation processes occur synchronously; alkenes formed during cracking are rapidly incorporated into the carbenium ion-mediated alkylation cycle. The conclusions are further supported by ab initio molecular dynamics simulations coupled with an enhanced sampling method, and model experiments using n-hexadecane as a feed. The catalytic conversion of polyolefins into gasoline-range alkanes requires a comprehensive understanding of the catalytically active species and their corresponding performance. Here the authors tackle this need by examining the nuclearity of the chloroaluminate ions and their interactions with reaction intermediates. [ABSTRACT FROM AUTHOR]

Background: Despite adequate transurethral resection of the bladder tumor (TURBT) followed by intravesical bacillus-calmette guérin (BCG), high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is associated with high rates of recurrence and progression. Immune checkpoint inhibitors can improve antitumor activity in bladder cancer, but relevant evidence in HR-NMIBC is limited. Thus, we evaluated the efficacy and safety of the tislelizumab-based combination regimen in HR-NMIBC. Methods: A retrospective study included 21 patients diagnosed with HR-NMIBC between July 2020 and September 2022. All patients underwent TURBT followed by combination regimens of tislelizumab plus BCG with or without gemcitabine/cisplatin (GC) chemotherapy. Clinical Data on demographics and characteristics, treatment information, outcomes, and safety were collected and analyzed. Results: Among the 21 patients with HR-NMIBC, the median age was 63 years (range 39–85), with the majority of patients with stage T1 (16/21, 76.19%). The median treatment of tislelizumab was 5 cycles (range 1–12) and the median number of BCG instillations was 12 times (range 2–19). Of the 21 patients, 15 (71.43%) received combination chemotherapy with GC, with a median treatment of 2 cycles (range 0–7); others did not. Overall, after the median follow-up of 25 months (range 7–31), the estimated 2-year bladder recurrence-free survival rate was 78.64% (95% confidence intervals [CIs], 50.79–91.83%), 2-year cystectomy-free survival rate was 83.00% (95% CI 53.53–94.59%), and 2-year disease-free survival rate was 73.39% (95% CI 46.14–88.36%). Sixteen stage T1 patients achieved a distant metastasis-free survival rate of 95.45% (95% CI 71.87–99.34%) at 2 years. Fourteen (66.67%) patients experienced at least one treatment related-AEs (TRAEs), with 9.52% (2/21) of grade 3–4. Grade ≥ 3 TRAEs were hypophysitis (1/21, 4.76%) and myasthenia (1/21, 4.76%). No treatment-related deaths were observed. Conclusions: The study demonstrated promising clinical benefits and a manageable safety profile of tislelizumab-based combination regimen as a bladder-sparing treatment of HR-NMIBC. [ABSTRACT FROM AUTHOR]

In order to improve the accuracy of rockburst warning, it is necessary to accurately interpret the microseismic (MS) information obtained during the rockburst development process. However, the MS source location is very important for the interpretation of MS information, and the MS location method has an important impact on the location accuracy. To improve the location accuracy of MS sources, a location method considering diffraction in tunnel engineering is proposed. In this method, the shortest path length between the MS source and a sensor that does not cross the empty area of the excavated tunnel section replaces the straight path length between the MS source and the sensor for the location calculation, which can reduce the location error caused by propagation path length inaccuracy. To analyse the performance of this location method, a virtual MS source location simulation test and an in situ blasting point location test were carried out based on a tunnel project. The results show that the location method can well characterize the propagation path of MS source waves in a rock mass, thus making the location error smaller. During the in situ blasting point location test, the average absolute location error of point sources is approximately 8 m, and the average relative location error is approximately 6.72%. The location results can well meet the requirements of rockburst MS monitoring for location accuracy. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 μM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs. [ABSTRACT FROM AUTHOR]

Immunohistochemical analysis of platelet-derived growth factor receptor-α (PDGFR-α) was performed on human skin wounds obtained from forensic autopsy cases. Thirty human skin wounds were collected at different post-infliction intervals as follows: Group I, 4 h to 3 days (n = 16); Group II, 4 to 7 days (n = 7); Group III, 9 to 10 days (n = 3); and Group IV, 14 to 20 days (n = 4). Immunopositive reactions for PDGFR-α were not observed in the uninjured human skin specimens. In a semi-quantitative morphometrical analysis, the number of PDGFR-α-positive cells was observed increased in Group II, with the average number of PDGFR-α-positive cells being the highest in Group II. Additionally, in Group II, all specimens showed PDGFR-α-positive cells, with an average number of > 200 cells in five fields of view, suggesting a wound age of 4 to 7 days. Taken together, the immunohistochemical detection of PDGFR-α in human skin wounds can be a useful tool for wound age determination. [ABSTRACT FROM AUTHOR]

In this article, we study deformations of conjugate self-dual Galois representations. The study is twofold. First, we prove an R=T type theorem for a conjugate self-dual Galois representation with coefficients in a finite field, satisfying a certain property called rigid. Second, we study the rigidity property for the family of residue Galois representations attached to a symmetric power of an elliptic curve, as well as to a regular algebraic conjugate self-dual cuspidal representation. [ABSTRACT FROM AUTHOR]

Introduction: Isoniazid is a first-line antituberculosis agent with high variability, which would profit from individualized dosing. Concentrations of isoniazid at 2 h (C2h), as an indicator of safety and efficacy, are important for optimizing therapy. Objective: The objective of this study was to establish machine learning (ML) models to predict the C2h, that can be used for establishing an individualized dosing regimen in clinical practice. Methods: Published population pharmacokinetic (PopPK) models for adults were searched based on PubMed and ultimately four reliable models were selected for simulating individual C2h datasets under different conditions (demographics, genotype, ethnicity, etc.). Machine learning models were trained on simulated C2h obtained from the four PopPK models. Five different algorithms were used for ML model building to predict C2h. Real-world data were used for predictive performance evaluations. Virtual trials were used to compare ML-optimized doses with PopPK model-optimized doses. Results: Categorical boosting (CatBoost) exhibited the highest prediction ability. Target C2h can be predicted using the ML model combined with the dosing regimen and three covariates (N-acetyltransferase 2 [NAT2] genotypes, weight and race [Asians and Africans]). Real-world data validation results showed that the ML model can achieve an overall prediction accuracy of 93.4%. Using the final ML model, the mean absolute prediction error value decreased by 45.7% relative to the average of PopPK models. Using the ML-optimized dosing regimen, the probability of target attainment increased by 43.7% relative to the PopPK model-optimized dosing regimens. Conclusion: Machine learning models were developed with great predictive performance, which can be used to determine the individualized initial dose of isoniazid in adult patients. [ABSTRACT FROM AUTHOR]

Ratiometric fluorescence and colorimetric strategies for detecting activity of butyrylcholinesterase (BChE) in human serum were developed by using g-C3N4 nanosheets, silver ion (Ag+) and o-phenylenediamine (OPD) as chromogenic agents. The oxidation-reduction reaction of OPD and Ag+ generates 2,3-diaminophenazine (oxOPD). Under exciation at 370 nm, g-C3N4 nanosheets and oxOPD emit fluorescence at 440 nm (F440) and 560 nm (F560), respectively. Additionally, oxOPD exhibits quenching ability towards g-C3N4 nanosheets via photoinduced electron transfer (PET) process. Thiocholine (TCh), as a product of BChE-catalyzed hydrolysis reaction of butylthiocholine iodide (BTCh), can coordinate with Ag+ intensively, and consequently diminish the amount of free Ag+ in the testing system. Less amount of free Ag+ leads to less production of oxOPD, resulting in less fluorescence quenching towards g-C3N4 nanosheets as well as less fluorescence emission of oxOPD. Therefore, by using g-C3N4 nanosheets and oxOPD as fluorescence indicators, the intensity ratio of their fluorescence (F440/F560) was calculated and employed to evaluate the activity of BChE. Similarly, the color variation of oxOPD indicated by the absorbance at 420 nm (ΔA420) was monitored for the same purpose. These strategies were validated to be sensitive and selective for detecting BChE activity in human serum, with limits of detection (LODs) of 0.1 U L−1 for ratiometric fluorescence mode and 0.7 U L−1 for colorimetric mode. [ABSTRACT FROM AUTHOR]

A smartphone-based electrochemical aptasensing platform was developed for the point-of-care testing (POCT) of carcinoembryonic antigen (CEA) based on the ferrocene (Fc) and PdPt@PCN-224 dual-signal labeled strategy. The prepared PdPt@PCN-224 nanocomposite showed a strong catalytic property for the reduction of H2O2. Phosphate group-labeled aptamer could capture PdPt@PCN-224 by Zr–O–P bonds to form PdPt@PCN-224-P-Apt. Therefore, a dual signal labeled probe was formed by the hybridization between Fc-DNA and PdPt@PCN-224-P-Apt. The presence of CEA forced PdPt@PCN-224-P-Apt to leave the electrode surface due to the specific affinity, leading to the decrease of the reduction current of H2O2. At the same time, the Fc-DNA strand changed to hairpin structure, which made Fc closer to the electrode and resulted in the increase of the oxidation current of Fc. Thus, CEA can be accurately determined through both signals: the decrease of H2O2 reduction current and the increase of Fc oxidation current, which could avoid the false positive signal. Under the optimal conditions, the prepared aptasensor exhibited a wide linear range from 1 pg·mL−1 to 100 ng·mL−1 and low detection limits of 0.98 pg·mL−1 and 0.27 pg·mL−1 with Fc and PdPt@PCN-224 as signal labels, respectively. The aptasensor developed in this study has successfully demonstrated its capability to detect CEA in real human serum samples. These findings suggest that the proposed sensing platform will hold great potential for clinical tumor diagnosis and monitoring. [ABSTRACT FROM AUTHOR]

The dynamic regulation of circularly polarized luminescence (CPL) holds profound significance in various fields, such as high-level information storage and encryption. Here we developed a chiral amphiphilic molecule, CPSB-GLU-PEG350 (CGP), composed of aggregation-induced emission (AIE) chromophores (Z)-4-(1-cyano-2-phenylvinyl)benzoic acid (CPSB), a chiral linker Glutamic acid and polyethylene glycol (PEG) thermoresponsive segments. Within the self-assembled supramolecular system formed by CGP, we have achieved in-situ temperature-responsive chiral structures, facilitating the thermal control switch of the CPL signal. Molecular dynamics simulations demonstrate the distinct behaviors of AIE and PEG units during the temperature-variable assembly process. Furthermore, by co-assembling achiral dye molecules with CGP, we have expanded the color range of the temperature-responsive CPL assembly system in situ and confirmed the occurrence of circularly polarized-Förster resonance energy transfer (C-FRET) phenomenon in this process, which successfully enriched the strategies for in-situ CPL control in aqueous phases. In addition, the contactless radiative energy transfer of CPL can also be realized in this system, exhibiting more flexible temperature regulation of the CPL signal. This study provides a convenient and universal strategy for the construction of dynamically smart chiroptical materials. [ABSTRACT FROM AUTHOR]

The three-dimensional genome structure organized by CTCF is required for development. Clinically identified mutations in CTCF have been linked to adverse developmental outcomes. Nevertheless, the underlying mechanism remains elusive. In this investigation, we explore the regulatory roles of a clinically relevant R567W point mutation, located within the 11th zinc finger of CTCF, by introducing this mutation into both murine models and human embryonic stem cell-derived cortical organoid models. Mice with homozygous CTCFR567W mutation exhibit growth impediments, resulting in postnatal mortality, and deviations in brain, heart, and lung development at the pathological and single-cell transcriptome levels. This mutation induces premature stem-like cell exhaustion, accelerates the maturation of GABAergic neurons, and disrupts neurodevelopmental and synaptic pathways. Additionally, it specifically hinders CTCF binding to peripheral motifs upstream to the core consensus site, causing alterations in local chromatin structure and gene expression, particularly at the clustered protocadherin locus. Comparative analysis using human cortical organoids mirrors the consequences induced by this mutation. In summary, this study elucidates the influence of the CTCFR567W mutation on human neurodevelopmental disorders, paving the way for potential therapeutic interventions. Clinically identified mutations in CTCF have been linked to adverse developmental outcomes. Here, the authors explore the regulatory roles of the CTCFR567W point mutation, by introducing it into both murine models and human embryonic stem cell-derived cortical organoid models. [ABSTRACT FROM AUTHOR]

Peri-operative hemorrhagic shock and resuscitation (HSR), a severe traumatic stress, is closely associated with post-operative anxiety, depression, and cognitive dysfunction, subsequently causing a serious burden on families and society. Following the co-release of corticotropin-releasing factor and catecholamine, traumatic stress activates dopaminergic neurons, increasing the addictive behavior and neurocognitive impairment risks. This study investigates the association between cognitive dysfunction and dopaminergic neurons in the mPFC under HSR conditions. This study established an HSR model by bleeding and re-transfusion in the mice. After HSR exposure, a dopamine D1 receptor antagonist, SKF-83566, was administered intraperitoneally for three consecutive days. Novel object recognition (NOR), conditioned fearing (FC), and conditioned place preference (CPP) were used to assess cognitive changes 16 days after HSR exposure. Local field potential (LFP) in the mPFC was also investigated during the novel object exploration. Compared with the mice exposed to sham, there was a significant decrease in the object recognition index, a reduction in context- and tone-related freezing time, an increase in CPP values, a downregulation of β-power but upregulation of γ-power in the mPFC in the mice exposed to HSR. Moreover, the mice exposed to HSR showed significantly upregulated TH-positive cell number, cleaved caspase-1- and TH-positive cells, and interleukin (IL)-1β/18 expression in the mPFC compared with sham; SKF-83566 could partially reverse these alternations. The HSR caused excessive dopaminergic signaling and cognitive dysfunction in the mPFC, a condition that might be ameliorated using a dopamine D1 receptor inhibitor. [ABSTRACT FROM AUTHOR]

This article discusses a case report on the use of bispecific CAR-T cell therapy in a patient with refractory myasthenia gravis (MG), an autoimmune neuromuscular disorder. The patient experienced sustained disappearance of symptoms and anti-acetylcholine receptor antibodies after receiving the therapy. The study suggests that bispecific CAR-T cell therapy has the potential to be an effective treatment for MG and other diseases characterized by autoreactive B cells and autoantibodies. [Extracted from the article]

The Guangdong-Hong Kong-Macao Greater Bay Area (GBA) is threatened by potential tsunami hazards from the Littoral Fault Zone (LFZ) and the Manila subduction zone (MSZ), and may suffer huge damage because of its dense population, concentrated infrastructure, and low-lying coasts. Previous tsunami studies for the GBA made simple assumptions on the mechanisms of LFZ earthquakes, and used coarse bathymetry data in tsunami simulation, which limited the prediction of detailed tsunami hazard characteristics. In this paper, we develop a parallel dispersive tsunami model PCOMCOT to efficiently simulate dispersive, nonlinear, and breaking tsunami waves. We also construct large-scale and high-resolution bathymetry models for the GBA by correcting and integrating various data sources. Dynamic rupture simulation is performed for the LFZ to obtain a more reliable earthquake source model. We propose several representative earthquake scenarios for the LFZ and MSZ, and use PCOMCOT to calculate the resulting tsunami waves, currents, and inundation in the GBA. Our results indicate that if an Mw7.5 oblique-slip earthquake occurs in the LFZ off the Pearl River Estuary (PRE), the subsequent tsunami will primarily impact Hong Kong, causing maximum positive and negative waves of around 1 m and −2 m, respectively, along with slightly destructive currents (⩾1.5 m/s). An Mw9.0 MSZ megathrust earthquake can lead to widespread inundation with >1 m depth on the outlying islands of Macao and in the urban areas of Hong Kong around the Victoria Harbour. Besides, it will also cause catastrophic tsunami currents along the narrow waterways in Hong Kong and Macao, and the spatial distribution of strong currents (⩾3 m/s) shows a considerable discrepancy from the areas of serious inundation. Thus, more attention should be paid to the potential impacts of tsunami currents on the GBA. [ABSTRACT FROM AUTHOR]

Salmonella is considered as one of the most common zoonotic /foodborne pathogens in the world. The application of bacteriophages as novel antibacterial agents in food substrates has become an emerging strategy. Bacteriophages have the potential to control Salmonella contamination. We have isolated and characterized a broad-spectrum Salmonella phage, SP154, which can lyse 9 serotypes, including S. Enteritidis, S. Typhimurium, S. Pullorum, S. Arizonae, S. Dublin, S. Cholerasuis, S. Chester, S. 1, 4, [5], 12: i: –, and S. Derby, accounting for 81.9% of 144 isolates. SP154 showed a short latent period (40 min) and a high burst size (with the first rapid burst size at 107 PFUs/cell and the second rapid burst size at approximately 40 PFUs/cell). Furthermore, SP154 activity has higher survival rates across various environmental conditions, including pH 4.0–12.0 and temperatures ranging from 4 to 50 °C for 60 min, making it suitable for diverse food processing and storage applications. Significant reductions in live Salmonella were observed in different foods matrices such as milk and chicken meat, with a decrease of up to 1.9 log10 CFU/mL in milk contamination and a 1 log10 CFU/mL reduction in chicken meat. Whole genome sequencing analysis revealed that SP154 belongs to the genus Ithacavirus, subfamily Humphriesvirinae, within the family Schitoviridae. Phylogenetic analysis based on the terminase large subunit supported this classification, although an alternate tree using the tail spike protein gene suggested affiliation with the genus Kuttervirus, underscoring the limitations of relying on a single gene for phylogenetic inference. Importantly, no virulence or antibiotic resistance genes were detected in SP154. Our research highlights the potential of using SP154 for biocontrol of Salmonella in the food industry. [ABSTRACT FROM AUTHOR]

Integrating energy-storage devices (supercapacitors) and shape-deformation devices (actuators) advances the miniaturization and multifunctional development of soft robots. However, soft robots necessitate supercapacitors with high energy-storage performance and actuators with excellent actuation capability. Here, inspired by ant nests, we present a porous structure fabricated by MXene-graphene-methylcellulose (M-GMC) composite, which overcomes the self-stacking of MXene nanosheets and offers a larger specific surface area. The porous structure provides more channels and active sites for electrolyte ions, resulting in high energy storage performance. The areal capacitance of the M-GMC electrode reaches up to 787.9 mF·cm−2, significantly superior to that of the pristine MXene electrode (449.1 mF·cm−2). Moreover, the M-GMC/polyethylene bilayer composites with energy storage and multi-responsive actuation functions are developed. The M-GMC is used as the electrode and the polyethylene is used as the encapsulation layer of the quasi-solid-state supercapacitor. Meanwhile, the actuators fabricated by the bilayer composites can be driven by light or low voltage (≤ 9 V). The maximum bending curvature is up to 5.11 cm−1. Finally, a smart gripper and a fully encapsulated smart integrated circuit based on the M-GMC/polyethylene are designed. The smart gripper enables programmable control with multi-stage deformations. The applications realize the intelligence and miniaturization of soft robots. The ant-nest-inspired M-GMC composites would provide a promising development strategy for soft robots and smart integrated devices. [ABSTRACT FROM AUTHOR]

Existing research on non-suicidal self-injury (NSSI) among adolescents has primarily concentrated on general risk factors, leaving a significant gap in understanding the specific NSSI characteristics that predict diverse psychopathological outcomes. This study aims to address this gap by using Random Forests to discern the significant predictors of different clinical outcomes. The study tracked 348 adolescents (64.7% girls; mean age = 13.31, SD = 0.91) over 6 months. Initially, 46 characteristics of NSSI were evaluated for their potential to predict the repetition of NSSI, as well as depression, anxiety, and suicidal risks at a follow-up (T2). The findings revealed distinct predictors for each psychopathology. Specifically, psychological pain was identified as a significant predictor for depression, anxiety, and suicidal risks, while the perceived effectiveness of NSSI was crucial in forecasting its repetition. These findings imply that it is feasible to identify high-risk individuals by assessing key NSSI characteristics, and also highlight the importance of considering diverse NSSI characteristics when working with self-injurers. [ABSTRACT FROM AUTHOR]

Friction stir welding of aluminum alloy offers excellent joint quality, less residual stress and deformation, and high production efficiency when compared to conventional welding techniques. It is possible to optimize the welding process and raise the quality and efficiency of the welds by researching their nonlinear dynamic properties. In this study, a nonlinear dynamic model of friction stir welding of aluminum alloy was constructed by taking into account the flow of thermoplastic materials, time-varying upsetting force, and plastic metal friction model. The nonlinear behavior of the system was described by using bifurcation diagrams, Lyapunov exponent, time domain, fast Fourier transform (FFT) spectrum, phase plot and Poincare map. Moreover, the superharmonic resonance characteristics of the system were investigated using a multi-scale methodology, and the impact of displacement delay, displacement control, speed control, and system damping on the aluminum alloy friction stir welding system's oscillation mode were examined. According to the findings, the friction stir welding system of aluminum alloy possesses complex non-linear properties with the change of stirring pin rotation speed, feed speed and support stiffness. Furthermore, by choosing the right time delay parameters and boosting the damping, the system's stability can be enhanced. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess alterations in retinal vascular density in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients using optical coherence tomography angiography (OCTA) and investigate their association with MRI and cognitive features. Methods: Twenty-five patients with CADASIL and forty healthy controls were evaluated by Cirrus HD-OCT 5000 with AngioPlex OCTA to determine changes in macular retinal vasculature. Retinal vasculature parameters between two groups were compared. The MRI lesion burden and neuropsychological scales were also examined in patients. The association between OCTA parameters and MRI/cognitive features was evaluated using partial Spearman rank correlation. Results: The vessel density and perfusion density of whole image in macular region (vessel density: t = − 2.834, p = 0.005; perfusion density: t = − 2.691, p = 0.007) were significantly decreased in patients with CADASIL. Moreover, vessel density of whole image in macular region was negatively associated with Fazekas scores (ρ = − 0.457; p = 0.025) and the number of lacunar infractions (ρ = − 0.425, p = 0.038) after adjustment for age. Decreased macular vessel density and perfusion density of whole image were also associated with MoCA scores (vessel density: ρ = 0.542, p = 0.006; perfusion density: ρ = 0.478, p = 0.018) and other domain-specific neuropsychological tests (p < 0.05) after adjustment for age. Conclusion: Decreased retinal vascular density was associated with increased MRI lesion burden and cognitive impairment in patients with CADASIL. Our findings suggest that the degree of retinal vascular involvement, as demonstrated by OCTA, may be consistent with the severity of MRI lesions and the degree of cognitive impairment in patients. [ABSTRACT FROM AUTHOR]

There has been a growing interest in using Fiber Bragg Grating (FBG) sensors for the detection of humidity and water content due to their high sensitivity, ease of installation, multiplexing capability, reliability, and resistance to electromagnetic interference. Although, several studies and papers have been published on FBG sensors and their applications in various fields such as construction, geophysical, there is a lack of a consolidated review that specifically focuses on recent developments in agriculture with particular reference soil humidity and water content. Therefore, a comprehensive and up-to-date analysis of the advances, detection mechanisms, challenges, and potential future directions in this field is needed. This paper provides an in-depth analysis and summarizes the fundamental principles, advancements, methodologies, and recent research findings, highlighting the potential application in agriculture, development, challenges, and prospects for FBG-based humidity and water content detection. By utilizing the changes in FBG wavelength or amplitude caused by the presence of humidity, they provide an effective means for real-time monitoring and control of water content. However, challenges remain to be addressed, such as the need for accurate calibration and the potential for drift over time. In this review, we further discuss the strategies and techniques proposed to overcome the highlighted challenges, such as sensor packaging, signal processing algorithms, and calibration procedures, and suggest that further studies could be done to investigates the novel materials with enhanced sensitivity and selectivity, development of miniaturized and wireless FBG sensor system, as well as investigating multiplexing techniques for simultaneous measurement of multiple parameters. [ABSTRACT FROM AUTHOR]

The deep-learning protein structure prediction method AlphaFold2 has garnered enormous attention beyond the realm of structural biology, for its groundbreaking contribution to solving the "protein folding problem". In this perspective, we explore the connection between protein structure studies and environmental research, delving into the potential for addressing specific environmental challenges. Proteins are promising for environmental applications because of the functional diversity endowed by their structural complexity. However, structural studies on proteins with environmental significance remain scarce. Here, we present the opportunity to study proteins by advancing experimental determination and deep-learning prediction methods. Specifically, the latest progress in environmental research via cryogenic electron microscopy is highlighted. It allows us to determine the structure of protein complexes in their native state within cells at molecular resolution, revealing environmentally-associated structural dynamics. With the remarkable advancements in computational power and experimental resolution, the study of protein structure and dynamics has reached unprecedented depth and accuracy. These advancements will undoubtedly accelerate the establishment of comprehensive environmental protein structural and functional databases. Tremendous opportunities for protein engineering exist to enable innovative solutions for environmental applications, such as the degradation of persistent contaminants, and the recovery of valuable metals as well as rare earth elements. [ABSTRACT FROM AUTHOR]

Grey mould caused by Botrytis cinerea is a devastating disease responsible for large losses to agricultural production, and B. cinerea is a necrotrophic model fungal plant pathogen. Membrane proteins are important targets of fungicides and hotspots in the research and development of fungicide products. Wuyiencin affects the permeability and pathogenicity of B. cinerea, parallel reaction monitoring revealed the association of membrane protein Bcsdr2, and the bacteriostatic mechanism of wuyiencin was elucidated. In the present work, we generated and characterised ΔBcsdr2 deletion and complemented mutant B. cinerea strains. The ΔBcsdr2 deletion mutants exhibited biofilm loss and dissolution, and their functional activity was illustrated by reduced necrotic colonisation on strawberry and grape fruits. Targeted deletion of Bcsdr2 also blocked several phenotypic defects in aspects of mycelial growth, conidiation and virulence. All phenotypic defects were restored by targeted gene complementation. The roles of Bcsdr2 in biofilms and pathogenicity were also supported by quantitative real-time RT-PCR results showing that phosphatidylserine decarboxylase synthesis gene Bcpsd and chitin synthase gene BcCHSVII were downregulated in the early stages of infection for the ΔBcsdr2 strain. The results suggest that Bcsdr2 plays important roles in regulating various cellular processes in B. cinerea. Key points: • The mechanism of wuyiencin inhibits B. cinerea is closely associated with membrane proteins. • Wuyiencin can downregulate the expression of the membrane protein Bcsdr2 in B. cinerea. • Bcsdr2 is involved in regulating B. cinerea virulence, growth and development. [ABSTRACT FROM AUTHOR]

The Stöber method is a widely-used sol-gel route for synthesizing amorphous SiO2 colloids and conformal coatings. However, the material systems compatible with this method are still limited. Herein, we have extended the approach to metal-organic frameworks (MOFs) and coordination polymers (CPs) by mimicking the Stöber method. We introduce a general synthesis route to amorphous MOFs or CPs by making use of a base-vapor diffusion method, which allows to precisely control the growth kinetics. Twenty-four different amorphous CPs colloids were successfully synthesized by selecting 12 metal ions and 17 organic ligands. Moreover, by introducing functional nanoparticles (NPs), a conformal amorphous MOFs coating with controllable thickness can be grown on NPs to form core-shell colloids. The versatility of this amorphous coating technology was demonstrated by synthesizing over 100 core-shell composites from 20 amorphous CPs shells and over 30 different NPs. Besides, various multifunctional nanostructures, such as conformal yolk-amorphous MOF shell, core@metal oxides, and core@carbon, can be obtained through one-step transformation of the core@amorphous MOFs. This work significantly enriches the Stöber method and introduces a platform, enabling the systematic design of colloids exhibiting different level of functionality and complexity. What happens when the classical and famous Stöber method collides with popular Metal-Organic Frameworks and Coordination Polymers? The answer is Big Bang of the Amorphous Functional Colloids. [ABSTRACT FROM AUTHOR]

Off-line leachate collection from agricultural landscapes cannot guarantee precise evaluation of agricultural non-point source (ANPS) due to geospatial variations, time, and transportation from the field to the laboratory. Implementing an in-situ nitrogen and phosphorous monitoring system with a robust photochemical flow analysis is imperative for precision agriculture, enabling real-time intervention to minimize non-point source pollution and overcome the limitations posed by conventional analysis in laboratory. A reliable, robust and in-situ approach was proposed to monitor nitrogen and phosphorous for determining ANPS pollution. In this study, a home-made porous ceramic probe and the frequency domain reflectometer (FDR) based water content sensors were strategically placed at different soil depths to facilitate the collection of leachates. These solutions were subsequently analyzed by in-situ photochemical flow analysis monitoring system built across the field to estimate the concentrations of phosphorus and nitrogen. After applying both natural and artificial irrigation to the agricultural landscape, at least 10 mL of soil leachates was consistently collected using the porous ceramic probe within 20 min, regardless of the depth of the soil layers when the volumetric soil water contents are greater than 19%. The experimental results showed that under different weather conditions and irrigation conditions, the soil water content of 50 cm and 90 cm below the soil surface was 19.58% and 26.08%, respectively. The average concentrations of NH4+-N, NO3−-N, PO43− are 0.584 mg/L, 15.7 mg/L, 0.844 mg/L, and 0.562 mg/L, 16.828 mg/L and 0.878 mg/L at depths of 50 cm and 90 cm below the soil surface, respectively. Moreover, the comparison with conventional laboratory spectroscopic analysis confirmed R2 values of 0.9951, 0.9943, 0.9947 average concentration ranges of NH4+-N, NO3−-N, and PO43−, showcasing the accuracy and reliability of robust photochemical flow analysis in-situ monitoring system. The suggested monitoring system can be helpful in the assessment of soil nutrition for precision agriculture. [ABSTRACT FROM AUTHOR]

Bacterial biofilms commonly cause chronic and persistent infections in humans. Bacterial biofilms consist of an inner layer of bacteria and an autocrine extracellular polymeric substance (EPS). Biofilm dispersants (abbreviated as dispersants) have proven effective in removing the bacterial physical protection barrier EPS. Dispersants are generally weak or have no bactericidal effect. Bacteria dispersed from within biofilms (abbreviated as dispersed bacteria) may be more invasive, adhesive, and motile than planktonic bacteria, characteristics that increase the probability that dispersed bacteria will recolonize and cause reinfection. The dispersants should be combined with antimicrobials to avoid the risk of severe reinfection. Dispersant-based nanoparticles have the advantage of specific release and intense penetration, providing the prerequisite for further antibacterial agent efficacy and achieving the eradication of biofilms. Dispersant-based nanoparticles delivered antimicrobial agents for the treatment of diseases associated with bacterial biofilm infections are expected to be an effective measure to prevent reinfection caused by dispersed bacteria. Key points: • Dispersed bacteria harm and the dispersant's dispersion mechanisms are discussed. • The advantages of dispersant-based nanoparticles in bacteria biofilms are discussed. • Dispersant-based nanoparticles for cutting off reinfection in vivo are highlighted. [ABSTRACT FROM AUTHOR]

Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier. Nanomedicines between ~ 10 and 100 nm accumulate in many solid tumors by the enhanced permeability and retention effect, but it is controversial whether the effect can be exploited for treatment of brain tumors. PLX038A is a long-acting prodrug of the topoisomerase 1 inhibitor SN-38. It is composed of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release the SN-38. The prodrug was remarkably effective at suppressing growth of intracranial breast cancer and glioblastoma (GBM), significantly increasing the life span of mice harboring them. We addressed the important issue of whether the prodrug releases SN-38 systemically and then penetrates the brain to exert anti-tumor effects, or whether it directly penetrates the blood-tumor-brain-barrier and releases the SN-38 cargo within the tumor. We argue that the amount of SN-38 formed systemically is insufficient to inhibit the tumors, and show by PET imaging that a close surrogate of the 40 kDa PEG carrier in PLX038A accumulates and is retained in the GBM. We conclude that the prodrug penetrates the blood-tumor-brain-barrier, accumulates in the tumor microenvironment and releases its SN-38 cargo from within. Based on our results, we pose the provocative question as to whether the 40 kDa nanomolecule PEG carrier might serve as a "Trojan horse" to carry other drugs past the blood-tumor-brain-barrier and release them into brain tumors. [ABSTRACT FROM AUTHOR]

Optical resonators are indispensable tools in optical metrology that usually benefit from an evacuated and highly-isolated environment to achieve peak performance. Even in the more sophisticated design of Fabry-Perot (FP) cavities, the material choice limits the achievable quality factors. For this reason, monolithic resonators are emerging as promising alternative to traditional designs, but their design is still at preliminary stage and far from being optimized. Here, we demonstrate a monolithic FP resonator with 4.5 cm3 volume and 2 × 105 finesse. In the ambient environment, we achieve 18 Hz integrated laser linewidth and 7 × 10−14 frequency stability measured from 0.08 s to 0.3 s averaging time, the highest spectral purity and stability demonstrated to date in the context of monolithic reference resonators. By locking two separate lasers to distinct modes of the same resonator, a 96 GHz microwave signals is generated with phase noise -100 dBc/Hz at 10 kHz frequency offset, achieving orders of magnitude improvement in the approach of photonic heterodyne synthesis. The compact monolithic FP resonator is promising for applications in spectrally-pure, high-frequency microwave photonic references as well as optical clocks and other metrological devices. ©2024. All rights reserved. Optical resonators are essential tools for high precision metrology and applications where the spectral purity is highly demanded. Here, the authors demonstrate a monolithic resonator made of fused silica to support 18 Hz integrated laser linewidth in the ambient environment, and W-band microwave generation with low phase noise of -100 dBc/Hz at 10 kHz frequency offset. [ABSTRACT FROM AUTHOR]

Key message: The small-molecule glucosyltransferase loss-of-function mutant ugt76b1 exhibits both SID2- or NPR1-dependent and independent facets of enhanced plant immunity, whereupon FMO1 is required for the SID2 and NPR1 independence. The small-molecule glucosyltransferase UGT76B1 inactivates salicylic acid (SA), isoleucic acid (ILA), and N-hydroxypipecolic acid (NHP). ugt76b1 loss-of-function plants manifest an enhanced defense status. Thus, we were interested how UGT76B1 genetically integrates in defense pathways and whether all impacts depend on SA and NHP. We study the integration of UGT76B1 by transcriptome analyses of ugt76b1. The comparison of transcripts altered by the loss of UGT76B1 with public transcriptome data reveals both SA-responsive, ISOCHORISMATE SYNTHASE 1/SALICYLIC ACID INDUCTION DEFICIENT 2 (ICS1/SID2)- and NON EXPRESSOR OF PR GENES 1 (NPR1)-dependent, consistent with the role of UGT76B1 in glucosylating SA, and SA-non-responsive, SID2/NPR1-independent genes. We also discovered that UGT76B1 impacts on a group of genes showing non-SA-responsiveness and regulation by infections independent from SID2/NPR1. Enhanced resistance of ugt76b1 against Pseudomonas syringae is partially independent from SID2 and NPR1. In contrast, the ugt76b1-activated resistance is completely dependent on FMO1 encoding the NHP-synthesizing FLAVIN-DEPENDENT MONOOXYGENASE 1). Moreover, FMO1 ranks top among the ugt76b1-induced SID2- and NPR1-independent pathogen responsive genes, suggesting that FMO1 determines the SID2- and NPR1-independent effect of ugt76b1. Furthermore, the genetic study revealed that FMO1, ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), SID2, and NPR1 are required for the SA–JA crosstalk and senescence development of ugt76b1, indicating that EDS1 and FMO1 have a similar effect like stress-induced SA biosynthesis (SID2) or the key SA signaling regulator NPR1. Thus, UGT76B1 influences both SID2/NPR1-dependent and independent plant immunity, and the SID2/NPR1 independence is relying on FMO1 and its product NHP, another substrate of UGT76B1. [ABSTRACT FROM AUTHOR]

In this work, a hot extrusion forming process for magnesium (Mg) alloy square tubes, namely, tube-extrusion-continuous expending shear (TECES), was proposed. The thin-walled hollow square tube of Mg alloy with a thickness of 3 mm was successfully prepared by hot extrusion experiment. The evolution rules of effective stress, effective strain, and flow velocity in the process of tube forming were analyzed by numerical simulation, and the influence of different expanding ratios on tube forming was compared. The results show that the effective stress distribution of the tube is not uniform during the forming process, and the maximum stress appears at the first shear corner. In the shear deformation (SD) zone, there is a high strain zone at the corner of the square tube and outside the tube wall. As the tube is extruded, the uniformity of strain distribution in the deformation zone is improved. In the whole forming process, the flow rate of the tube increases first and then decreases, and the whole remains stable. As the expansion ratio increases when the expansion ratio is greater than 1.6, the resistance of plastic deformation increases, the fluidity of the metal becomes worse, and the formed tube cracks at the corner or is difficult to fill. When the expansion ratio is less than 1.6, the damage value area appears on the inner side of the tube wall, and the distribution uniformity is poor, which may lead to cracks or uneven thickness of the tube wall. The microstructure characterization of different deformation zones of the tube was carried out, and the results show that the TECES process can effectively refine the grain, and the average grain size of the formed tube is 10.1 μm. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. Methods: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan–Meier curve methods were used. Results: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. Conclusions: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS. [ABSTRACT FROM AUTHOR]

Purpose: TRPV1 is a nonselective Ca2+ channel protein that is widely expressed and plays an important role during the occurrence and development of many cancers. Activation of TRPV1 channels can affect tumour progression by regulating proliferation, apoptosis and migration. Some studies have also shown that activating TRPV1 can affect tumour progression by modulating tumour immunity. However, the effects of TRPV1 on the development of non-small cell lung cancer (NSCLC) have not been explored clearly. Method: The Cancer Genome Atlas (TCGA) database and spatial transcriptomics datasets from 10 × Genomics were used to analyze TRPV1 expression in various tumour tissues. Cell proliferation and apoptosis were examined by cell counting kit 8 (CCK8), colony formation, and flow cytometry. Immunohistochemistry, qPCR, and western blotting were used to determine the mRNA and protein expression levels of TRPV1 and other related molecules. Tumour xenografts in BALB/C and C57BL/6J mice were used to determine the effects of TRPV1 on NSCLC development in vivo. Neurotransmitter content was examined by LC-MS/MS, ELISA and Immunohistochemistry. Immune cell infiltration was assessed by flow cytometry. Results: In this study, we found that TRPV1 expression was significantly upregulated in NSCLC and that patients with high TRPV1 expression had a poor prognosis. TRPV1 knockdown can significantly inhibit NSCLC proliferation and induce cell apoptosis through Ca2+-IGF1R signaling. In addition, TRPV1 knockdown resulted in increased infiltration of CD4+ T cells, CD8+ T cells, GZMB+CD8+ T cells and DCs and decreased infiltration of immunosuppressive MDSCs in NSCLC. In addition, TRPV1 knockout effectively decreased the expression of M2 macrophage markers CD163 and increased the expression of M1-associated, costimulatory markers CD86. Knockdown or knockout of TRPV1 significantly inhibit tumour growth and promoted an antitumour immune response through supressing γ-aminobutyric acid (GABA) secretion in NSCLC. Conclusion: Our study suggests that TRPV1 acts as a tumour promoter in NSCLC, mediating pro-proliferative and anti-apoptotic effects on NSCLC through IGF1R signaling and regulating GABA release to affect the tumour immune response. [ABSTRACT FROM AUTHOR]

Electron powder bed fusion (EPBF), as one of the common additive manufacturing techniques, has received increasing attention. EPBF-processed Ti-6Al-4V is widely used in biomedical and aerospace industries. However, titanium alloys prepared by EPBF have large pores and poor corrosion resistance. Heat treatment is a simple and non-polluting way to improve material properties. However, the effect of heat treatment on the corrosion resistance of EPBF-processed Ti-6Al-4V alloy has not been thoroughly researched. In this paper, Ti-6Al-4V samples processed by EPBF were treated with different heat treatment methods. All corrosion tests were performed in 3.5 wt.% NaCl solution at ambient temperature. HT800 has the highest content of β phase, and the smallest grain boundary density, and therefore has the best corrosion resistance. The corrosion current of HT800 is reduced from 0.109 µA/cm2 unheated to 0.022 µA/cm2, a reduction of 79.82%. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia (SP) and intervertebral disc degeneration (IVDD) have a higher incidence in the elderly population. Previous studies have indicated a potential association between SP and IVDD. The objective of this study is to elucidate the potential causal relationship between sarcopenia-related traits and IVDD through Two-sample Mendelian randomization (MR) analysis. Methods: We utilized a genome-wide association study conducted on the European population to collect aggregated data on sarcopenia and IVDD. Inverse variance weighting was primarily employed, supplemented by MR Egger, weighted median, simple model, and weighted model methods. Additionally, sensitivity analysis was performed to assess the robustness of the findings. Results: Appendicular lean mass is positively associated with "Other intervertebral disc disorders" (OIDD) and "Prolapsed or slipped disc" (POSD) (OIDD: p = 0.002, OR = 1.120; POSD: p < 0.001, OR = 1.003), while grip strength (GS) is positively associated with POSD (left: p = 0.004, OR = 1.008; right: p < 0.001, OR = 1.010). It is worth mentioning that walking pace has significant causal relationship with "Low back pain" (LBP), "Lower back pain or/and sciatica" (LBPOAS), "Sciatica with lumbago" (SWL) and OIDD (LBP: p < 0.001, OR = 0.204; LBPOAS: p < 0.001, OR = 0.278; SWL: p = 0.003, OR = 0.249; OIDD: p < 0.001, OR = 0.256). Conclusion: The present study revealed the causal relationship between SP-related traits and IVDD and recommended to prevent and treat sarcopenia as a means of preventing IVDD in clinic practice. [ABSTRACT FROM AUTHOR]

A graphic processing unit (GPU)-accelerated implicit material point method (IMPM) is proposed in this paper, aiming at solving large-scale geotechnical engineering problems efficiently. The Cholesky decomposition direct solution method and the preconditioned conjugate gradient (PCG) iteration method are implemented to solve the governing equation implicitly. In order to build an efficient parallel computation framework, the sequential processes in these solution methods are optimized by adopting advancing parallel computational algorithms. The risk of data race during parallel computation is avoided using atomic operation. The GPU-accelerated IMPM is firstly tested by a 1-D compress column and cantilever beam simulation to validate the accuracy of the proposed IMPM. Then, the computational efficiency is tested using the sand column collapse simulation. The solution of the governing equation is the most time-consuming process, occupying more than 95% of the computational time. The PCG iteration method shows higher efficiency compared to Cholesky decomposition direct solution method. By analysing the memory usage, it is found that memory occupation is the primary limitation on the simulation scale of IMPM, especially using the Cholesky decomposition direct solution method. Finally, the GPU-accelerated IMPM is implemented in the simulation of the Xinmo landslide, showing high accuracy and computational efficiency. [ABSTRACT FROM AUTHOR]

Background: Guillain–Barré Syndrome (GBS) is caused by immunoglobulin G (IgG) autoantibodies. Efgartigimod, a human IgG antibody Fc fragment that acts as a natural ligand for the FcRn, can increase IgG degradation, which thus may be a promising therapeutic drug for GBS. Case presentation: The two patients presented with postinfectious and acute flaccid paralysis. On admission, they were bedridden. Nerve conduction studies indicated peripheral neuropathy. GBS was suspected and they are treated with two doses of efgartigimod (10 mg/kg) within 5 days. Their muscle strength improved gradually and 4 weeks after the initial dose, they could walk independently. Following the first dose, Patient 1 complaint of muscle soreness, which subsided the next morning. Patient 2 was intubated due to respiratory failure the day after the initial dose, and did not report other adverse effects. Discussion: In GBS patients, two doses of efgartigimod (10 mg/kg) were effective in rapidly improving muscle strength, with a satisfactory safety profile. The findings suggest a potential role for efgartigimod in modifying the disease process in GBS patients. Conclusion: Efgartigimod seems effective and safe in the treatment of GBS. This study indicates the potential role of efgartigimod as a novel treatment option for GBS. Well-designed clinical trials should be conducted. [ABSTRACT FROM AUTHOR]

Objective: This narrative review aimed to compile and summarize clinically relevant literature in radiation therapy and to discuss the potential in radioresistant and radiosensitive head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Google Scholar, PubMed, and the Cochrane Library were retrieved using combined key words such as "radiotherapy" and "head and neck cancer." Search strings additionally queried were "radioresistant," "radiosensitive," "head and neck region," "squamous cell carcinoma," in combination with Boolean operators 'AND' and 'OR.' Subsequently, the resulting publications were included for review of the full text. Results: Radiotherapeutic responses currently in clinical observation referred to HNSCC scoping were selected into this review. The compiled mechanisms were then detailed concerning on the clinical significance, biological characteristics, and molecular function. Conclusions: Brachytherapy or/and external-beam radiotherapy are crucial for treating HNSCC especially the early stage patients, but in some patients with locally advanced tumors, their outcome with radiation therapy is poor due to obvious radioresistance. The curative effects mainly depend on the response to radiation therapy so an updated review is needed to optimize further applications in HNSCC radiotherapy. [ABSTRACT FROM AUTHOR]

This article proposes a parameter extraction method suitable for Si substrate based GaN HEMT small signal equivalent circuit models. The proposed method is based on a swarm intelligence optimization algorithm, which improves efficiency and accuracy by introducing a slope penalty factor (SPF) method for the objective function, rather than simply minimizing the error between simulation and measurement. By using PSO, WOA, and PNC-WOA for validation, we have demonstrated the advantages of the SPF method in extracting small signal parameters using swarm intelligence optimization algorithms. It is suitable for complex small-signal models that can describe the GaN HEMT-on-Si substrates, even if working up to 40 GHz. [ABSTRACT FROM AUTHOR]