Monocytes release cystatin F dimer to associate with Aß and aggravate amyloid pathology and cognitive deficits in Alzheimer's disease.

BACKGROUND: Understanding the molecular mechanisms of Alzheimer's disease (AD) has important clinical implications for guiding therapy. Impaired amyloid beta (Aß) clearance is critical in the pathogenesis of sporadic AD, and blood monocytes play an important role in Aß clearance in the periphery. However, the mechanism underlying the defective phagocytosis of Aß by monocytes in AD remains unclear. METHODS: Initially, we collected whole blood samples from sporadic AD patients and isolated the monocytes for RNA sequencing analysis. By establishing APP/PS1 transgenic model mice with monocyte-specific cystatin F overexpression, we assessed the influence of monocyte-derived cystatin F on AD development. We further used a nondenaturing gel to identify the structure of the secreted cystatin F in plasma. Flow cytometry, enzyme-linked immunosorbent assays and laser scanning confocal microscopy were used to analyse the internalization of Aß by monocytes. Pull down assays, bimolecular fluorescence complementation assays and total internal reflection fluorescence microscopy were used to determine the interactions and potential interactional amino acids between the cystatin F protein and Aß. Finally, the cystatin F protein was purified and injected via the tail vein into 5XFAD mice to assess AD pathology. RESULTS: Our results demonstrated that the expression of the cystatin F protein was specifically increased in the monocytes of AD patients. Monocyte-derived cystatin F increased Aß deposition and exacerbated cognitive deficits in APP/PS1 mice. Furthermore, secreted cystatin F in the plasma of AD patients has a dimeric structure that is closely related to clinical signs of AD. Moreover, we noted that the cystatin F dimer blocks the phagocytosis of Aß by monocytes. Mechanistically, the cystatin F dimer physically interacts with Aß to inhibit its recognition and internalization by monocytes through certain amino acid interactions between the cystatin F dimer and Aß. We found that high levels of the cystatin F dimer protein in blood contributed to amyloid pathology and cognitive deficits as a risk factor in 5XFAD mice. CONCLUSIONS: Our findings highlight that the cystatin F dimer plays a crucial role in regulating Aß metabolism via its peripheral clearance pathway, providing us with a potential biomarker for diagnosis and potential target for therapeutic intervention.

Lab-on-Device Synthesis of Hierarchical Macro/Mesoporous WO3 Semiconducting Films for High-Performance H2S Sensing.

The performance consistency of the gas sensor is strongly dependent on the interface binding between the sensitive materials and the electrodes. Traditional powder coating methods can inevitably lead to differences in terms of substrate-film interface interaction and device performance, affecting the stability and lifetime. Thus, efficient growth of sensitive materials on device substrates is crucial and essential to enhance the sensing performance, especially for stability. Herein, hierarchically ordered macro/mesoporous WO3 films are in situ synthesized on the electrode via a facile soft/hard dual-template strategy. Orderly arrayed uniform polystyrene (PS) microspheres with tailored size (ca. 1.2 µm) are used as a hard template, and surfactant Pluronic F127 as a soft template can co-assemble with tungsten precursor into ordered mesostructure in the interstitials of PS colloidal crystal induced by solvent evaporation. Benefiting from its rich porosity and high stability, the macro/mesoporous WO3-based sensor shows high sensitivity (Rair/Rgas = 307), fast response/recovery speed (5/9 s), and excellent selectivity (SH2S/Smax > 7) toward 50 ppm H2S gas (a biomarker for halitosis). Significantly, the sensors exhibit an extended service life with a negligible change in sensing performance within 60 days. This lab-on-device synthesis provides a platform method for constructing stable nanodevices with good consistency and high stability, which are highly desired for developing high-performance sensors.

Association of Preoperative Subchondral Bone Marrow Oedema with Outcomes after Lateral Unicompartmental Knee Arthroplasty.

OBJECTIVE: To determine whether the presence of preoperative subchondral bone marrow oedema (SBME) is associated with inferior outcomes after lateral unicompartmental knee arthroplasty (LUKA). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Orthopaedic Surgery, Chongqing Orthopaedic Hospital of Traditional Chinese Medicine, Chongqing, China, from January 2019 to June 2022. METHODOLOGY: Data on patients treated with LUKA were obtained from the Medical Registry Database. Two groups were made based on the presence and absence of SBME on preoperative magnetic resonance imaging (MRI). The visual analogue scale (VAS), American Knee Society Scores (AKSS), and rate of patient satisfaction were compared between the two groups. RESULTS: A total of 20 patients treated with LUKA were reviewed. The SBME was present in 9 cases and absent in 11 cases. Patients with SBME had inferior scores at preoperative evaluation and at 1, 3, and 6 months postoperatively. However, there was no significant difference between the groups at the 12-month follow-up. Eight (88.9%) patients with SBME were satisfied with the LUKA surgery versus 9 (81.8%) patients without SBME, showing no significant differences between groups. CONCLUSION: Presence of preoperative SBME is associated with inferior functional outcomes after LUKA within six months of follow-up. KEY WORDS: Bone marrow, Oedema, Knee, Arthroplasty, Outcome, Patient satisfaction.

Causal relationship between dyslipidemia and risk of facial aging: Insights from Mendelian randomization in East Asian populations.

BACKGROUND: Emerging observational studies showed an association between dyslipidemia and aging. However, it remains unclear whether this association is causal, particularly in the case of Asians, which are aging more rapidly than other continents. Given the visible manifestations of aging often include changes in facial appearance, the objective of this study is to assess the causal relationship between dyslipidemia and facial aging in East Asian populations. METHODS: SNPs related to dyslipidemia in East Asian people such as Total cholesterol (TC), High-density-lipoprotein cholesterol (HDL), Low-density-lipoprotein cholesterol (LDL), and Triglyceride (TG) along with outcomes data on facial aging, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse variance weighted (IVW) method. RESULTS: Totally, 88 SNPs related to HDL among 70657 East Asian participants in GWAS. Based on the primary causal effects model using MR analyses with the IVW method, high HDL level was demonstrated as significantly related to the risk of facial aging (OR, 1.060; 95% CI, 1.005-1.119, p = 0.034), while high TC level (OR, 0.995; 95% CI, 0.920-1.076, p = 0.903), high LDL level (OR, 0.980, 95% CI, 0.924-1.041, p = 0.515), as well as high TG level (OR, 0.999, 95% CI, 0.932-1.071, p = 0.974), showed no significant correlation with facial aging. CONCLUSIONS: The two-sample MR analysis conducted in this study revealed a positive causal relationship between high HDL levels and facial aging. In contrast, facial aging demonstrated no significant correlation with high levels of TC, LDL, or TG. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding nutrition management to delay the aging process among old patients in East Asia.

Mapping of Long-Wavelength Phonon Contribution in the Thermal Transport of Alloyed Semiconductor Superlattices.

The mapping of long-wavelength phonons is important to understand and manipulate the thermal transport in multilayered structures, but it remains a long-standing challenge due to the collective behaviors of phonons. In this study, an experimental demonstration of mapping the long-wavelength phonons in an alloyed Al0.1Ga0.9As/Al0.9Ga0.1As superlattice system is reported. Multiple strategies to filter out the short- to mid-wavelength phonons are used. The phonon mean-free-path-dependent thermal transport properties directly demonstrate both the suppression effect of the ErAs nanoislands and the contribution of long-wavelength phonons. The contribution from phonons with mean free path longer than 1 µm is clearly demonstrated. A model based on the Boltzmann transport equation is proposed to calculate and describe the thermal transport properties, which depicts a clear physical picture of the transport mechanisms. This method can be extended to map different wavelength phonons and become a universal strategy to explore their thermal transport in various application scenarios.

Enhancing the activity and succinyl-CoA specificity of 3-ketoacyl-CoA thiolase Tfu_0875 through rational binding pocket engineering.

The 3-ketoacyl-CoA thiolase is the rate-limiting enzyme for linear dicarboxylic acids production. However, the promiscuous substrate specificity and suboptimal catalytic performance have restricted its application. Here we present both biochemical and structural analyses of a high-efficiency 3-ketoacyl-CoA thiolase Tfu_0875. Notably, Tfu_0875 displayed heightened activity and substrate specificity for succinyl-CoA, a key precursor in adipic acid production. To enhance its performance, a deep learning approach (DLKcat) was employed to identify effective mutants, and a computational strategy, known as the greedy accumulated strategy for protein engineering (GRAPE), was used to accumulate these effective mutants. Among the mutants, Tfu_0875N249W/L163H/E217L exhibited the highest specific activity (320% of wild-type Tfu_0875), the greatest catalytic efficiency (kcat/KM = 1.00 min-1mM-1), the highest succinyl-CoA specificity (KM = 0.59 mM, 28.1% of Tfu_0875) and dramatically reduced substrate binding energy (-30.25 kcal mol-1v.s. -15.94 kcal mol-1). A structural comparison between Tfu_0875N249W/L163H/E217L and the wild type Tfu_0875 revealed that the increased interaction between the enzyme and succinyl-CoA was the primary reason for the enhanced enzyme activity. This interaction facilitated rapid substrate anchoring and stabilization. Furthermore, a reduced binding pocket volume improved substrate specificity by enhancing the complementarity between the binding pocket and the substrate in stereo conformation. Finally, our rationally designed mutant, Tfu_0875N249W/L163H/E217L, increased the adipic acid titer by 1.35-fold compared to the wild type Tfu_0875 in shake flask. The demonstrated enzymatic methods provide a promising enzyme variant for the adipic acid production. The above effective substrate binding pocket engineering strategy can be beneficial for the production of other industrially competitive biobased chemicals when be applied to other thiolases.

A Review on the Carbonation of Steel Slag: Properties, Mechanism, and Application.

Steel slag is a by-product of the steel industry and usually contains a high amount of f-CaO and f-MgO, which will result in serious soundness problems once used as a binding material and/or aggregates. To relieve this negative effect, carbonation treatment was believed to be one of the available and reliable methods. By carbonation treatment of steel slag, the phases of f-CaO and f-MgO can be effectively transformed into CaCO3 and MgCO3, respectively. This will not only reduce the expansive risk of steel slag to improve the utilization of steel slag further but also capture and store CO2 due to the mineralization process to reduce carbon emissions. In this study, based on the physical and chemical properties of steel slag, the carbonation mechanism, factors affecting the carbonation process, and the application of carbonated steel slag were reviewed. Eventually, the research challenge was also discussed.

Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle.

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.

Pure separation of acetylene based on a sulfonic acid and amino group functionalized Zn-MOF.

The dual-ligand strategy was employed to synthesize a new microporous material, [Zn3(SNDC)(AmTAZ)3(H2O)]·H2O·CH3CN (1), incorporating sulfonic acid and amino groups for enhancing gas adsorption and separation. The activated 1 (named 1a) exhibited selective adsorption of acetylene over carbon dioxide and methane. Hence, the dual-ligand strategy optimized the pore environment and provided an effective approach for pure separation of gases.

Identification of a risk score model based on tertiary lymphoid structure-related genes for predicting immunotherapy efficacy in non-small cell lung cancer.

BACKGROUND: Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood. METHODS: TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease-free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP-counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C-MARK cohort. RESULTS: TLS-positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029). Both the TLS-positive and TLS-mature groups exhibited genes enrichment in immune activation pathways. The TLS-mature group showed more activated dendritic cell infiltration than the TLS-immature group. We screened TLS-related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five-genes (RGS8, RUF4, HLA-DQB2, THEMIS, and TRBV12-5) risk score model, the progression free survival (PFS) and OS of patients in the low-risk group were markedly superior to those in the high-risk group (p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor. CONCLUSIONS: Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS-related genes could predict the response to immunotherapy and is meaningful for clinical decision-making.

High Dietary Folic Acid Supplementation Reduced the Composition of Fatty Acids and Amino Acids in Fortified Eggs.

AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. RESULTS: Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. CONCLUSION: The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

Safety and efficacy of indocyanine green fluorescence imaging-guided laparoscopic para-aortic lymphadenectomy for left-sided colorectal cancer:A preliminary case-matched study.

AIM: This study is aimed to explore the safety and feasibility of indocyanine green (ICG) fluorescence imaging guidance in laparoscopic para-aortic lymph node (PALN) dissection for left-sided colorectal cancer (CRC) patients with clinically suspected PALN metastasis. METHOD: A total of 151 patients who underwent primary tumor resection and laparoscopic PALN dissection for left-sided CRC were included, with 20 patients in the ICG group and 131 patients in the non-ICG group. The surgical outcomes, postoperative complications, and pathological results, such as the number of harvested and metastatic lymph nodes were compared between groups after propensity score matching. RESULTS: Following propensity score matching, the ICG group had 20 patients, and the non-ICG group had 53 patients, and the two groups were similar in baseline characteristics. No significant differences were observed in overall intraoperative and postoperative complications between groups, except for chylous leakage, where the ICG group had a longer time to a normal diet. The number of harvested pericolic/perirectal and intermediate lymph nodes were comparable between the two groups, while the ICG group had a significantly higher number of total harvested lymph nodes (39 [14-78] vs. 29 [11-70], P = 0.001), inferior mesenteric artery lymph nodes (IMALN, 6 [0-17] vs. 3 [0-11], P = 0.006), and PALNs (9 [3-29] vs. 5 [1-37], P = 0.001). CONCLUSION: ICG fluorescence imaging could increase the retrieval of IMALN, PALN, and total lymph nodes, and potentially improve the completeness of laparoscopic PALN dissection in patients with left-sided CRC.

Polyvinyl alcohol as solid proton donor to modify g-C3N4via hydrogen bonding enabling efficient photocatalytic H2O2 production from H2O and O2.

Polyvinyl alcohol (PVA) was used as a solid proton donor to improve the photocatalytic performance of graphitic carbon nitride (CN) for hydrogen peroxide (H2O2) production. The modified CN (CN/PVA) was prepared by mixing CN and PVA at room temperature. The H2O2 production efficiency of CN/PVA was 5.65 times higher than that of CN in pure water. Photocurrent measurement, electrochemical impedance spectroscopy (EIS), and photoluminescence (PL) analysis proved that PVA increased charge separation of CN. X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared (FTIR) analyses further suggested that PVA acted as the proton donor during H2O2 production by interacting with CN via hydrogen bonds. The combination of the charge separation enhancer and proton donor from PVA promoted the sequential two-step single-electron reduction of O2 for H2O2 production. This study paves the way for the modification of g-C3N4 with hydroxyl-containing materials as solid proton donors for photocatalytic H2O2 production.

Choosing the Adaptive Cardiac Phase for Assessing Cardiac Dimensions Using Cardiac Computed Tomography for Heart Disease.

Background: Cardiac chamber dimensions and left ventricle (LV) wall thickness change with the cardiac cycle, in which researchers have set different time points for systole and diastole. OBJECTIVE: This study aimed to provide characteristics of normal heart and choose the correct cardiac cycle to measure maximum cardiac parameters for cardiovascular disease. METHODS: The parameters of left atrium (LA), LV, right atrium (RA), and right ventricle (RV), as well as the wall thickness of LV, were measured in different cardiac phases using cardiac computed tomography (CT). Then, their differences in different phases and the correlation between these parameters and traditional risk factors were analyzed. In addition, receiver operator characteristic curve (ROC) analyses was performed to estimate LA enlargement. RESULTS: The dimensions of LA and RA as well as the wall thickness of LV reached the maximum at the phase of 35% - 45%, while the dimensions of LV and RV reached the maximum at 95% - 5%. However, the changes of LA-B (antero-posterior diameter), LV-D1 (basal dimension), RA-B (minor dimension), and RV-D2 (mid cavity dimension) were relatively more stable than other diameters during the cardiac cycle. The maximum LA-B diameter, LV-D1 diameter, RA-B diameter, and RV-D2 diameter as well as the maximum interventricular septum thickness were acquired. Heart rate (HR) and smoking were potential indicators of LV-D2 (mid cavity dimension), while HR and LV myocardial mass were potential indicators of LV-D3 (apical-basal dimension). In phase 45%, the cut-off value of LA-B was 37.12 mm, with high sensitivity for predicting LA enlargement. CONCLUSION: Choosing the adaptive cardiac phase for evaluating cardiac chamber dimensions and wall thickness obtained by cardiac CT could provide a more accurate clinical measurement of the heart.

A Versatile Synthesis Platform Based on Polymer Cubosomes for a Library of Highly Ordered Nanoporous Metal Oxides Particles.

Polymer cubosomes (PCs) have well-defined inverse bicontinuous cubic mesophases formed by amphiphilic block copolymer bilayers. The open hydrophilic channels, large periods, and robust physical properties of PCs are advantageous to many host-guest interactions and yet not fully exploited, especially in the fields of functional nanomaterials. Here, the self-assembly of poly(ethylene oxide)-block-polystyrene block copolymers is systematically investigated and a series of robust PCs is developed via a cosolvent method. Ordered nanoporous metal oxide particles are obtained by selectively filling the hydrophilic channels of PCs via an impregnation strategy, followed by a two-step thermal treatment. Based on this versatile PC platform, the general synthesis of a library of ordered porous particles with different pore structures 3 ¯ $\bar{3}$ 3 ¯ $\bar{3}$ , tunable large pore size (18-78 nm), high specific surface areas (up to 123.3 m2 g-1 for WO3) and diverse framework compositions, such as transition and non-transition metal oxides, rare earth chloride oxides, perovskite, pyrochlore, and high-entropy metal oxides is demonstrated. As typical materials obtained via this method, ordered porous WO3 particles have the advantages of open continuous structure and semiconducting properties, thus showing superior gas sensing performances toward hydrogen sulfide.

Unraveling variations and enhancing prediction of successful sphincter-preserving resection for low rectal cancer: A post hoc analysis of the multicenter LASRE randomized clinical trial.

BACKGROUND: Accurate prediction of successful sphincter-preserving resection (SSPR) for low rectal cancer enables peer institutions to scrutinize their own performance and potentially avoid unnecessary permanent colostomy. The aim of this study is to evaluate the variation in SSPR and present the first artificial intelligence (AI) models to predict SSPR in low rectal cancer patients. STUDY DESIGN: This was a retrospective post hoc analysis of a multicenter, noninferiority randomized clinical trial (LASRE, NCT XXXXXX) conducted in 22 tertiary hospitals across China. A total of 604 patients who underwent neoadjuvant chemoradiotherapy (CRT) followed by radical resection of low rectal cancer were included as the study cohort, which was then split into a training set (67%) and a testing set (33%). The primary end point of this post hoc analysis was SSPR, which was defined as meeting all the following criteria: (1) sphincter-preserving resection; (2) complete or nearly complete TME, (3) a clear CRM (distance between margin and tumor of 1 mm or more), and (4) a clear DRM (distance between margin and tumor of 1 mm or more). Seven AI algorithms, namely, support vector machine (SVM), logistic regression (LR), extreme gradient boosting (XGB), light gradient boosting (LGB), decision tree classifier (DTC), random forest (RF) classifier, and multilayer perceptron (MLP), were employed to construct predictive models for SSPR. Evaluation of accuracy in the independent testing set included measures of discrimination, calibration, and clinical applicability. RESULTS: The SSPR rate for the entire cohort was 71.9% (434/604 patients). Significant variation in the rate of SSPR, ranging from 37.7% to 94.4%, was observed among the hospitals. The optimal set of selected features included tumor distance from the anal verge before and after CRT, the occurrence of clinical T downstaging, post-CRT weight and clinical N stage measured by magnetic resonance imaging. The 7 different AI algorithms were developed and applied to the independent testing set. The LR, LGB, MLP and XGB models showed excellent discrimination with AUROC values of 0.825, 0.819, 0.819 and 0.805, respectively. The DTC, RF and SVM models had acceptable discrimination with AUROC values of 0.797, 0.766 and 0.744, respectively. LR and LGB showed the best discrimination, and all 7 AI models had superior overall net benefits within the range of 0.3-0.8 threshold probabilities. Finally, we developed an online calculator based on the LGB model to facilitate clinical use. CONCLUSIONS: The rate of SSPR exhibits substantial variation, and the application of AI models has demonstrated the ability to predict SSPR for low rectal cancers with commendable accuracy.

Successful endovascular thrombectomy using solitaire FR stent with intermediate catheter assisting technique for acute persistent primitive trigeminal artery and basilar artery occlusion: A case report and literature review.

Background: The persistent primitive trigeminal artery (PPTA) is a persistent embryological carotid-basilar connection. Endovascular thrombectomy (EVT) for hypoplastic PPTA occlusion is a challenge. This case report aims to describe the successful recanalization of simultaneous occlusions in both the PPTA and basilar artery (BA) using the Solitaire FR (RECO SR)/Stent and Intermediate Catheter Assisting (SWIM) technique in a patient with acute cardiogenic cerebral embolism. To the best of our knowledge, this is the first report of such a case. Case Description: We present a case of a 70-year-old female patient who presented with acute right-sided hemiparesis and altered consciousness. Digital subtraction angiography confirmed the occlusion of both the distal portion of the PPTA and the BA. The patient underwent EVT using the SWIM technique, resulting in successful recanalization and significant improvement in the patient's condition. Conclusion: This case report demonstrates the successful application of the SWIM technique in achieving recanalization and improving outcomes in a patient with simultaneous occlusion of the acute PPTA and BA. These findings support the potential use of EVT in similar cases.

Methanooceanicella nereidis gen. nov., sp. nov., the first oceanic Methanocellaceae methanogen, isolated from potential methane hydrate bearing area offshore southwestern Taiwan.

A novel mesophilic, hydrogenotrophic methanogen, strain CWC-04T, was obtained from a sediment sample extracted from a gravity core retrieved at station 22 within the KP-9 area off the southwestern coast of Taiwan during the ORIII-1368 cruise in 2009. Cells of strain CWC-04T were rod-shaped, 1.4-2.9 µm long by 0.5-0.6 µm wide, and occurred singly. Strain CWC-04Tutilized formate, H2/CO2, 2-propanol/CO2 or 2-butanol/CO2 as catabolic substrates. The optimal growth conditions were 42 °C, 0.17 M NaCl and pH 5.35. The genomic DNA G+C content calculated from the genome sequence of strain CWC-04T was 46.19 mol%. Phylogenetic analysis of 16S rRNA gene revealed that strain CWC-04T is affiliated with the genus Methanocella. The 16S rRNA gene sequences similarities within strains Methanocella arvoryzae MRE50T, Methanocella paludicola SANAET and Methanocella conradii HZ254T were 93.7, 93.0 and 91.3 %, respectively. In addition, the optical density of CWC-04T culture dropped abruptly upon entering the late-log growth phase, with virus-like particles (150 nm in diameter) being observed on and around the cells. This observation suggests that strain CWC-04T harbours a lytic virus. Based on these phenotypic, phylogenetic and genomic results, we propose that strain CWC-04T represents a novel species of a novel genus in the family Methanocellaceae, for which the name Methanooceanicella nereidis gen. nov., sp. nov. is proposed. The type strain is CWC-04T (=BCRC AR10050T=NBRC 113165T).

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Rationally Engineering pH Adaptation of Acid-Induced Arginine Decarboxylase from Escherichia coli to Alkaline Environments to Efficiently Biosynthesize Putrescine.

Acid-induced arginine decarboxylase AdiA is a typical homo-oligomeric protein biosynthesizing alkaline nylon monomer putrescine. However, upon loss of the AdiA decamer oligomeric state at neutral and alkaline conditions the activity also diminishes, obstructing the whole-cell biosynthesis of alkaline putrescine. Here, a structure cohesion strategy is proposed to change the pH adaptation of AdiA to alkaline environments based on the rational engineering of meridional and latitudinal oligomerization interfaces. After integrating substitutions of E467K at the latitudinal interface and H736E at the meridional channel interface, the structural stability of AdiA decamer and its substrate transport efficiency at neutral and alkaline conditions are improved. Finally, E467K_H736E is well adapted to neutral and alkaline environments (pH 7.0-9.0), and its enzymatic activity is 35-fold higher than that of wild AdiA at pH 8.0. Using E467K_H736E in the putrescine synthesis pathway, the titer of putrescine is up to 128.9 g·L-1 with a conversion of 0.94 mol·mol-1 in whole-cell catalysis. Additionally, the neutral pH adaptation of lysine decarboxylase, with a decamer structure similar to AdiA, is also improved using this cohesion strategy, providing an option for pH-adaptation engineering of other oligomeric decarboxylases.